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Sample records for repayment programs lrp

  1. 76 FR 8748 - Loan Repayment Program for Repayment of Health Professions Educational Loans

    Science.gov (United States)

    2011-02-15

    ... Masters level. (f) Dentistry: DDS and DMD. (g) Dental Hygiene. (h) Pharmacy: B.S., Pharm.D. (i) Optometry... HUMAN SERVICES Indian Health Service Loan Repayment Program for Repayment of Health Professions... program in a health profession; or (B) Have a degree in a health profession and a license to practice in...

  2. 77 FR 3269 - Loan Repayment Program for Repayment of Health Professions Educational Loans; Announcement Type...

    Science.gov (United States)

    2012-01-23

    .... (i) Dental Hygiene. (j) Dental Assistant: Certified. (k) Pharmacy: B.S., Pharm.D. (l) Optometry: O.D...] Loan Repayment Program for Repayment of Health Professions Educational Loans; Announcement Type... program in a health profession; or (B) Have a degree in a health profession and a license to practice in...

  3. 78 FR 7787 - Loan Repayment Program for Repayment of Health Professions Educational Loans

    Science.gov (United States)

    2013-02-04

    ...: DDS and DMD. (i) Dental Hygiene. (j) Dental Assistant: Certified. (k) Pharmacy: B.S., Pharm.D. (l... HUMAN SERVICES Indian Health Service Loan Repayment Program for Repayment of Health Professions... program in a health profession; or (B) Have a degree in a health profession and a license to practice in...

  4. 75 FR 20239 - Veterinary Medicine Loan Repayment Program (VMLRP)

    Science.gov (United States)

    2010-04-19

    ... Research, Extension, and Teaching Policy Act of 1997 (NARETPA). This law established a new Veterinary... Food and Agriculture 7 CFR Part 3431 RIN 0524-AA43 Veterinary Medicine Loan Repayment Program (VMLRP... Veterinary Medicine Loan Repayment Program (VMLRP) authorized by the National Veterinary Medical Service Act...

  5. 75 FR 3193 - Application Package and Reporting Requirements for the Veterinary Medicine Loan Repayment Program...

    Science.gov (United States)

    2010-01-20

    ... Veterinary Medicine Loan Repayment Program (VMLRP) AGENCY: National Institute of Food and Agriculture, USDA... Veterinary Medicine Loan Repayment Program (VMLRP). This Notice initiates a 60-day comment period and... requirements for the Veterinary Medicine Loan Repayment Program (VMLRP) as authorized under section 1415A...

  6. 75 FR 22736 - Notice of Request for Applications for the Veterinary Medicine Loan Repayment Program

    Science.gov (United States)

    2010-04-30

    ... National Institute of Food and Agriculture Notice of Request for Applications for the Veterinary Medicine... . DATES: The FY 2010 Veterinary Medicine Loan Repayment Program (VMLRP) application package has been made... a new Veterinary Medicine Loan Repayment Program (7 U.S.C. 3151a) authorizing the Secretary...

  7. 77 FR 23461 - Notice of Request for Applications for the Veterinary Medicine Loan Repayment Program

    Science.gov (United States)

    2012-04-19

    ... National Institute of Food and Agriculture Notice of Request for Applications for the Veterinary Medicine...: The FY 2012 Veterinary Medicine Loan Repayment Program (VMLRP) application package will be available... a new Veterinary Medicine Loan Repayment Program (7 U.S.C. 3151a) authorizing the Secretary...

  8. Repayment Book. William D. Ford Federal Direct Loan Program.

    Science.gov (United States)

    Department of Education, Washington, DC.

    This booklet is intended to help individuals who received William D. Ford Federal Direct Loans as students manage the repayment process. Following an introduction, explanations are offered for how the principal balance of the loan is determined and how interest rates are applied. The following sections explain the four different repayment plans,…

  9. 76 FR 68126 - Solicitation of Input From Stakeholders Regarding the Veterinary Medicine Loan Repayment Program...

    Science.gov (United States)

    2011-11-03

    ...-AA43 Solicitation of Input From Stakeholders Regarding the Veterinary Medicine Loan Repayment Program... stakeholder input. SUMMARY: The National Institute of Food and Agriculture (NIFA) is soliciting stakeholder... the stakeholder input process, NIFA is inviting comments regarding the current procedures...

  10. 75 FR 77607 - Privacy Act of 1974; Proposed New System of Records; Veterinary Medicine Loan Repayment Program

    Science.gov (United States)

    2010-12-13

    ... Office of the Secretary Privacy Act of 1974; Proposed New System of Records; Veterinary Medicine Loan... of Agriculture system of records notice titled, ``Veterinary Medicine Loan Repayment Program Records... select applicants for the Veterinary Medicine Loan Repayment Program (VMLRP); (2) monitor loan...

  11. 77 FR 67330 - Solicitation of Input From Stakeholders Regarding the Veterinary Medicine Loan Repayment Program...

    Science.gov (United States)

    2012-11-09

    ... the Veterinary Medicine Loan Repayment Program (VMLRP) AGENCY: National Institute of Food and... and Agriculture (NIFA) is soliciting stakeholder input on the administration of the Veterinary... Research, Extension, and Teaching Policy Act of 1977 (7 U.S.C. 3151a). The purpose of this program is for...

  12. 78 FR 25417 - Notice of Request for Applications for the Veterinary Medicine Loan Repayment Program

    Science.gov (United States)

    2013-05-01

    ... National Institute of Food and Agriculture Notice of Request for Applications for the Veterinary Medicine...: The fiscal year (FY) 2013 Veterinary Medicine Loan Repayment Program (VMLRP) application package is..., Extension, and Teaching Policy Act of 1997 (NARETPA). This law established a new Veterinary Medicine...

  13. 76 FR 31299 - Request for Applications for the Veterinary Medicine Loan Repayment Program

    Science.gov (United States)

    2011-05-31

    ... National Institute of Food and Agriculture Request for Applications for the Veterinary Medicine Loan... National Institute of Food and Agriculture (NIFA) is announcing the release of the Veterinary Medicine Loan... 2011 Veterinary Medicine Loan Repayment Program (VMLRP) application package has been made available...

  14. 42 CFR 62.54 - What must applications for the State Loan Repayment Program contain?

    Science.gov (United States)

    2010-10-01

    ... accessibility of health care services in the State as measured by poverty levels, the percentage of the service... 42 Public Health 1 2010-10-01 2010-10-01 false What must applications for the State Loan Repayment Program contain? 62.54 Section 62.54 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND...

  15. 76 FR 23606 - Submission for OMB Review; Comment Request; National Institutes of Health Loan Repayment Programs

    Science.gov (United States)

    2011-04-27

    .... 288-5). The Contraception and Infertility Research LRP (CIR-LRP) is authorized by Section 487B of the... techniques or other forms of information technology. Direct Comments to OMB: Written comments and/or...

  16. Norrin, Frizzled4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization

    Science.gov (United States)

    Ye, Xin; Wang, Yanshu; Cahill, Hugh; Yu, Minzhong; Badea, Tudor C.; Smallwood, Philip M.; Peachey, Neal S.; Nathans, Jeremy

    2009-01-01

    SUMMARY Disorders of vascular structure and function play a central role in a wide variety of CNS diseases. Mutations in the Frizzled4 (Fz4) receptor, Lrp5 co-receptor, or Norrin ligand cause retinal hypovascularization, but the role of Norrin/Fz4/Lrp signaling in vascular development has not been defined. Using mouse genetic and cell culture models, we show that loss of Fz4 signaling in endothelial cells causes defective vascular growth, which leads to chronic but reversible silencing of retinal neurons. Loss of Fz4 in all endothelial cells disrupts the blood brain barrier in the cerebellum, while excessive Fz4 signaling disrupts embryonic angiogenesis. Sox17, a transcription factor that is up-regulated by Norrin/Fz4/Lrp signaling, plays a central role in inducing the angiogenic program controlled by Norrin/Fz4/Lrp. These experiments establish a cellular basis for retinal hypovascularization diseases due to insufficient Frizzled signaling, and they suggest a broader role for Frizzled signaling in vascular growth, remodeling, maintenance, and disease. PMID:19837032

  17. States' Experiences with Loan Repayment Programs for Health Care Professionals in a Time of State Budget Cuts and NHSC Expansion

    Science.gov (United States)

    Pathman, Donald E.; Morgan, Jennifer Craft; Konrad, Thomas R.; Goldberg, Lynda

    2012-01-01

    Purpose: The landscape of education loan repayment programs for health care professionals has been turbulent in recent years, with doubling of the funding for the National Health Service Corps (NHSC) and cuts in funding for some states' programs. We sought to understand how this turbulence is being felt within the state offices involved in…

  18. Service-linked scholarships, loans, and loan repayment programs for nurses in the southeast.

    Science.gov (United States)

    Thaker, Samir I; Pathman, Donald E; Mark, Barbara A; Ricketts, Thomas C

    2008-01-01

    A variety of public and private programs provide financial support for the costs of nurses' training in exchange for service commitments to work in rural, underserved, and other needy areas. Little is known about the number, size, and operations of these support-for-service programs for nurses. We identified and in this article describe such programs in eight southeastern states. Eligible programs were those that in 2004 paid for all or a portion of nurses' education costs in exchange for a period of clinical nursing service within one or more of the eight targeted states. Programs obligating nurses to a specific hospital, practice, or community or to teaching roles were excluded. Programs were identified through available compendia, online searches, and telephone contacts with program directors, nursing school administrators, and state officials. Additional data on eligible programs were gathered through telephone interviews and questionnaires mailed to program staff and from publicly available documents. Data were double coded, and qualitative and quantitative analyses were conducted. Twenty-four nursing support-for-service programs met our eligibility criteria in the eight-state region: nine scholarship programs; six loan repayment programs; five service-cancelable loan programs; two loan interest rate reduction programs; and two direct incentive programs. These programs had fiscal year 2004 budgets totaling approximately $28.8-31.8 million; collectively, they received approximately 11,700 applications from nurses, signed approximately 8,300 contracts, and had a combined field strength of approximately 4,900 nurses working to fulfill their program obligations. Individual states offered between zero and five eligible programs each. Support-for-service programs are a substantial component of federal and state nursing workforce distribution efforts in the Southeast. Future research should identify and describe these programs for other regions, measure outcomes, and

  19. 78 FR 63464 - William D. Ford Federal Direct Loan Program Repayment Plan Selection Form; Extension of Public...

    Science.gov (United States)

    2013-10-24

    ...On October 3, 2013 the U.S. Department of Education published a 30-day comment period notice in the Federal Register (Page 61347, Column 2) seeking public comment for an information collection entitled, ``William D. Ford Federal Direct Loan Program Repayment Plan Selection Form''. ED is extending the comment period to November 18, 2013 due to the public's inability to access the collection at......

  20. 24 CFR 954.500 - Repayment of investment.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Repayment of investment. 954.500... DEVELOPMENT INDIAN HOME PROGRAM Program Administration § 954.500 Repayment of investment. (a) HOME funds will be made available pursuant to a HOME Investment Partnership Agreement. The agreement ensures...

  1. 42 CFR 57.214 - Repayment of loans made after November 17, 1971, for failure to complete a program of study.

    Science.gov (United States)

    2010-10-01

    ..., adjusted annually for changes in the Consumer Price Index, and adjusted by the Secretary for use in this... undertakes to repay educational loans under section 722(k) of the Act, he or she will use the...

  2. 7 CFR 3431.13 - Terms of loan repayment and length of service requirements.

    Science.gov (United States)

    2010-01-01

    ...) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.13 Terms... service in a veterinary shortage situation, as determined by the Secretary, with a minimum of 3 years (and...

  3. 34 CFR 608.41 - What are the audit and repayment requirements?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What are the audit and repayment requirements? 608.41... PROGRAM What Conditions Must a Grantee Meet? § 608.41 What are the audit and repayment requirements? (a... the audit to the Secretary. (3) If a grantee is audited under Chapter 75 of Title 31 of the United...

  4. 34 CFR 682.102 - Obtaining and repaying a loan.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Obtaining and repaying a loan. 682.102 Section 682.102 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL FAMILY EDUCATION LOAN (FFEL) PROGRAM Purpose and Scope §...

  5. Como reembolsar sus prestamos para estudiantes (Repaying Your Student Loans).

    Science.gov (United States)

    Office of Federal Student Aid (ED), Washington, DC.

    This guide, written in Spanish, discusses how to repay student loans. Following a general introduction, the guide discusses the grace period before repayment and repayment requirements. Repayment plans are described for Perkins Loans, Direct Loans, and Federal Family Education Loans. Repayment options are discussed, including consolidation,…

  6. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis

    NARCIS (Netherlands)

    J.B.J. van Meurs (Joyce); T.A. Trikalinos (Thomas); S.H. Ralston (Stuart); S. Balcells (Susana); M.L. Brandi; K. Brixen (Kim); D.P. Kiel (Douglas); B.L. Langdahl (Bente); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); B. Obermayer-Pietsch (Barbara); C. Ohlsson (Claes); U. Pettersson (Ulrika); D.M. Reid (David); M.F. Rousseau (Francois); S. Scollen (Serena); W. Van Hul (Wim); L. Agueda (Lidia); K. Åkesson (Kristina); L.I. Benevolenskaya (Lidia); S.L. Ferrari (Serge); G. Hallmans (Göran); A. Hofman (Albert); L.B. Husted (Lise Bjerre); M. Kruk (Marcin); S. Kaptoge (Stephen); D. Karasik (David); M. Karlsson (Magnus); M. Lorentzon (Mattias); L. Masi (Laura); F.E. McGuigan; D. Mellström (Dan); L. Mosekilde (Leif); X. Nogues (Xavier); H.A.P. Pols (Huib); J. Reeve (Jonathan); W. Renner (Wilfried); F. Rivadeneira Ramirez (Fernando); N.M. van Schoor (Natasja); K. Weber (Kurt); J.P.A. Ioannidis (John); A.G. Uitterlinden (André)

    2008-01-01

    textabstractContext: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. Objective: To generate large-scale evidence

  7. Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis

    NARCIS (Netherlands)

    J.B.J. van Meurs (Joyce); T.A. Trikalinos (Thomas); S.H. Ralston (Stuart); S. Balcells (Susana); M.L. Brandi; K. Brixen (Kim); D.P. Kiel (Douglas); B.L. Langdahl (Bente); P. Lips (Paul); O. Ljunggren (Östen); R. Lorenc (Roman); B. Obermayer-Pietsch (Barbara); C. Ohlsson (Claes); U. Pettersson (Ulrika); D.M. Reid (David); M.F. Rousseau (Francois); S. Scollen (Serena); W. Van Hul (Wim); L. Agueda (Lidia); K. Åkesson (Kristina); L.I. Benevolenskaya (Lidia); S.L. Ferrari (Serge); G. Hallmans (Göran); A. Hofman (Albert); L.B. Husted (Lise Bjerre); M. Kruk (Marcin); S. Kaptoge (Stephen); D. Karasik (David); M. Karlsson (Magnus); M. Lorentzon (Mattias); L. Masi (Laura); F.E. McGuigan; D. Mellström (Dan); L. Mosekilde (Leif); X. Nogues (Xavier); H.A.P. Pols (Huib); J. Reeve (Jonathan); W. Renner (Wilfried); F. Rivadeneira Ramirez (Fernando); N.M. van Schoor (Natasja); K. Weber (Kurt); J.P.A. Ioannidis (John); A.G. Uitterlinden (André)

    2008-01-01

    textabstractContext: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population. Objective: To generate large-scale evidence

  8. Lrp4 in astrocytes modulates glutamatergic transmission.

    Science.gov (United States)

    Sun, Xiang-Dong; Li, Lei; Liu, Fang; Huang, Zhi-Hui; Bean, Jonathan C; Jiao, Hui-Feng; Barik, Arnab; Kim, Seon-Myung; Wu, Haitao; Shen, Chengyong; Tian, Yun; Lin, Thiri W; Bates, Ryan; Sathyamurthy, Anupama; Chen, Yong-Jun; Yin, Dong-Min; Xiong, Lei; Lin, Hui-Ping; Hu, Jin-Xia; Li, Bao-Ming; Gao, Tian-Ming; Xiong, Wen-Cheng; Mei, Lin

    2016-08-01

    Neurotransmission requires precise control of neurotransmitter release from axon terminals. This process is regulated by glial cells; however, the underlying mechanisms are not fully understood. We found that glutamate release in the brain was impaired in mice lacking low-density lipoprotein receptor-related protein 4 (Lrp4), a protein that is critical for neuromuscular junction formation. Electrophysiological studies revealed compromised release probability in astrocyte-specific Lrp4 knockout mice. Lrp4 mutant astrocytes suppressed glutamatergic transmission by enhancing the release of ATP, whose level was elevated in the hippocampus of Lrp4 mutant mice. Consequently, the mutant mice were impaired in locomotor activity and spatial memory and were resistant to seizure induction. These impairments could be ameliorated by blocking the adenosine A1 receptor. The results reveal a critical role for Lrp4, in response to agrin, in modulating astrocytic ATP release and synaptic transmission. Our findings provide insight into the interaction between neurons and astrocytes for synaptic homeostasis and/or plasticity.

  9. 7 CFR 1434.18 - Loan repayments.

    Science.gov (United States)

    2010-01-01

    ... repayment rate for marketing assistance loans for honey under this part will be in effect on a short-term... loan during the loan period at a rate that is the lesser of: (1) The principal, plus interest; or (2) The alternative repayment rate for honey as determined by the Secretary. (3) In the event of a severe...

  10. The Lrp family of transcriptional regulators

    NARCIS (Netherlands)

    Brinkman, A.B.; Ettema, T.J.G.; Vos, de W.M.; Oost, van der J.

    2003-01-01

    Genome analysis has revealed that members of the Lrp family of transcriptional regulators are widely distributed among prokaryotes, both bacteria and archaea. The archetype Leucine-responsive Regulatory Protein from Escherichia coli is a global regulator involved in modulating a variety of metabolic

  11. METHYLATION PATTERN OF LRP15 GENE IN LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate the methylation status of LRP15 gene in acute leukemia (AL) patients and its role in the tumorigenesis.Methods The methylation of LRP15 promoter and first exon of bone marrow mononuclear cells in 73 patients with AL, 10 with chronic leukemia (CL), 9 with hematological benign diseases, and 20 healthy transplantation donors was analyzed by using methylation specific polymerase chain reaction. The methylation of LRP15 gene promoter and first exon in COS7, K562, and HL60 cell lines was also assayed.Results No LRP15 gene promoter methylation was detected in COS7 cell line. LRP15 gene promoter was methylated in K562 and HL60 cell lines. No deletion of LRP15 gene was detected in all samples. In nearly all French-American-British leukemia subtypes, we found that frequency of LRP15 methylation in adult patients with AL was 71.23%( 52/73 ). There was no detectable methylation in any of the 20 healthy donors and 8 chronic myeloid leukemia patients.The difference in frequency of LRP15 methylation between AL patients and healthy donors or CL patients ( 10. 00%,1/10) was significant (P < 0. 01 ). Hypermethylation of LRP15 gene was found in 57. 14% (16/28) of newly diagnosed AL patients, 83.33% of relapsed AL patients respectively, which was significantly different ( P < 0. 05). We also demonstrated LRP15 methylation in 55.56% (5/9) adults with benign hematological diseases.Conclusions LRP15 methylation changes are common abnormalities in leukemia. LRP15 is postulated to be a tumor suppressor gene.

  12. Credit reporting, relationship banking, and loan repayment

    Directory of Open Access Journals (Sweden)

    Tahereh Shirzad Kebria

    2015-06-01

    Full Text Available This paper presents an empirical investigation to determine factors influencing on loan repayment in one of Iranian banks named Sepah Bank over the period 2012-2013. The study selects a sample of 290 bank’s customers who received loans and, using logistic regression technique, tries to find whether or not qualitative as well as quantitative characteristics of loan receivers influence on repayment of loans. The results indicate that history of outstanding debt as well as customers’ past experiences with banks had meaningful relationships with having bad credit and non-payment of loans. In our survey, having a bad credit in the past had positive relationship with non-payment of loans but long-term customers had negative relationship with non-payment of loans. In addition, working capital turnover ratio, cash ratio, total liabilities, current assets and loan value had significant impact on non-repayment of the loan facilities.

  13. Lrp6 is required for convergent extension during Xenopus gastrulation.

    Science.gov (United States)

    Tahinci, Emilios; Thorne, Curtis A; Franklin, Jeffrey L; Salic, Adrian; Christian, Kelly M; Lee, Laura A; Coffey, Robert J; Lee, Ethan

    2007-11-01

    Wnt signaling regulates beta-catenin-mediated gene transcription and planar cell polarity (PCP). The Wnt co-receptor, Lrp6, is required for signaling along the beta-catenin arm. We show that Lrp6 downregulation (by morpholino injection) or overexpression in Xenopus embryos disrupts convergent extension, a hallmark feature of Wnt/PCP components. In embryos with decreased Lrp6 levels, cells of the dorsal marginal zone (DMZ), which undergoes extensive cellular rearrangements during gastrulation, exhibit decreased length:width ratios, decreased migration, and increased numbers of transient cytoplasmic protrusions. We show that Lrp6 opposes Wnt11 activity and localizes to the posterior edge of migrating DMZ cells and that Lrp6 downregulation enhances cortical and nuclear localization of Dsh and phospho-JNK, respectively. Taken together, these data suggest that Lrp6 inhibits Wnt/PCP signaling. Finally, we identify the region of the Lrp6 protein with Wnt/PCP activity to a stretch of 36 amino acids, distinct from regions required for Wnt/beta-catenin signaling. We propose a model in which Lrp6 plays a critical role in the switch from Wnt/PCP to Wnt/beta-catenin signaling.

  14. 78 FR 23742 - Nomination Form of Veterinary Shortage Situations for the Veterinary Medicine Loan Repayment...

    Science.gov (United States)

    2013-04-22

    ... National Institute of Food and Agriculture Nomination Form of Veterinary Shortage Situations for the Veterinary Medicine Loan Repayment Program (VMLRP) AGENCY: National Institute of Food and Agriculture, USDA... Act of 1995, invites the general public to comment on an information collection for the...

  15. Ectodomains of the LDL receptor-related proteins LRP1b and LRP4 have anchorage independent functions in vivo.

    Directory of Open Access Journals (Sweden)

    Martin F Dietrich

    Full Text Available BACKGROUND: The low-density lipoprotein (LDL receptor gene family is a highly conserved group of membrane receptors with diverse functions in developmental processes, lipoprotein trafficking, and cell signaling. The low-density lipoprotein (LDL receptor-related protein 1b (LRP1B was reported to be deleted in several types of human malignancies, including non-small cell lung cancer. Our group has previously reported that a distal extracellular truncation of murine Lrp1b that is predicted to secrete the entire intact extracellular domain (ECD is fully viable with no apparent phenotype. METHODS AND PRINCIPAL FINDINGS: Here, we have used a gene targeting approach to create two mouse lines carrying internally rearranged exons of Lrp1b that are predicted to truncate the protein closer to the N-terminus and to prevent normal trafficking through the secretary pathway. Both mutations result in early embryonic lethality, but, as expected from the restricted expression pattern of LRP1b in vivo, loss of Lrp1b does not cause cellular lethality as homozygous Lrp1b-deficient blastocysts can be propagated normally in culture. This is similar to findings for another LDL receptor family member, Lrp4. We provide in vitro evidence that Lrp4 undergoes regulated intramembraneous processing through metalloproteases and gamma-secretase cleavage. We further demonstrate negative regulation of the Wnt signaling pathway by the soluble extracellular domain. CONCLUSIONS AND SIGNIFICANCE: Our results underline a crucial role for Lrp1b in development. The expression in mice of truncated alleles of Lrp1b and Lrp4 with deletions of the transmembrane and intracellular domains leads to release of the extracellular domain into the extracellular space, which is sufficient to confer viability. In contrast, null mutations are embryonically (Lrp1b or perinatally (Lrp4 lethal. These findings suggest that the extracellular domains of both proteins may function as a scavenger for

  16. College Student Debt and Anticipated Repayment Difficulty

    Science.gov (United States)

    Fox, Jonathan J.; Bartholomae, Suzanne; Letkiewicz, Jodi C.; Montalto, Catherine P.

    This study analyzes factors associated with anticipated difficulty with repayment of debt accumulated during college using a basic model of credit risk that includes socialization processes influencing college student financial decisions. The empirical analysis uses data from the 2010 Ohio Student Financial Wellness Study. Results provide evidence…

  17. Loan Officers’ Gender and Microfinance Repayment Rates

    NARCIS (Netherlands)

    Berg, van den Marrit; Lensink, Robert; Servin, Roselia

    2015-01-01

    This study examines the impact of loan officer characteristics on repayment rates of microfinance borrowers in Mexico applying multilevel analyses, with special attention to the impact of the gender of the loan officer on default rates. The results strongly suggest that loan officers play a cruci

  18. Loan Officers’ Gender and Microfinance Repayment Rates

    NARCIS (Netherlands)

    Berg, van den Marrit; Lensink, Robert; Servin, Roselia

    2015-01-01

    This study examines the impact of loan officer characteristics on repayment rates of microfinance borrowers in Mexico applying multilevel analyses, with special attention to the impact of the gender of the loan officer on default rates. The results strongly suggest that loan officers play a

  19. Collective strategic defaults: Bailouts and repayment incentives

    NARCIS (Netherlands)

    Vlahu, R.

    2008-01-01

    This paper shows that under a global games approach banks may be subject to risk of failure even when fundamentals are strong due to a coordination problem among debtors. As a result of collective strategic default a financially sound firm may claim inability to repay if it expects a sufficient numb

  20. Microcredit Loan Repayment Default among Small Scale ...

    African Journals Online (AJOL)

    2017-05-01

    May 1, 2017 ... macro level both variables depend on the state of the economy (systematic risk). At the micro level the ... policy implications are presented. Literature ... recovery rates was triggered by the advent of the new Basel Capital Accord. Also, most ...... repayment problem among microfinance borrowers in Malaysia.

  1. 34 CFR 674.33 - Repayment.

    Science.gov (United States)

    2010-07-01

    ... in proportion to the amount of principal advanced by each institution. (3) Minimum monthly repayment... teachout at another school as defined in 34 CFR 602.2 and administered in accordance with 34 CFR 602.207(b... discharged) that the borrower may have by contract or applicable law with respect to the loan or...

  2. Collective strategic defaults: Bailouts and repayment incentives

    NARCIS (Netherlands)

    Vlahu, R.

    2008-01-01

    This paper shows that under a global games approach banks may be subject to risk of failure even when fundamentals are strong due to a coordination problem among debtors. As a result of collective strategic default a financially sound firm may claim inability to repay if it expects a sufficient

  3. LRP2 mediates folate uptake in the developing neural tube.

    Science.gov (United States)

    Kur, Esther; Mecklenburg, Nora; Cabrera, Robert M; Willnow, Thomas E; Hammes, Annette

    2014-05-15

    The low-density lipoprotein (LDL) receptor-related protein 2 (LRP2) is a multifunctional cell-surface receptor expressed in the embryonic neuroepithelium. Loss of LRP2 in the developing murine central nervous system (CNS) causes impaired closure of the rostral neural tube at embryonic stage (E) 9.0. Similar neural tube defects (NTDs) have previously been attributed to impaired folate metabolism in mice. We therefore asked whether LRP2 might be required for the delivery of folate to neuroepithelial cells during neurulation. Uptake assays in whole-embryo cultures showed that LRP2-deficient neuroepithelial cells are unable to mediate the uptake of folate bound to soluble folate receptor 1 (sFOLR1). Consequently, folate concentrations are significantly reduced in Lrp2(-/-) embryos compared with control littermates. Moreover, the folic-acid-dependent gene Alx3 is significantly downregulated in Lrp2 mutants. In conclusion, we show that LRP2 is essential for cellular folate uptake in the developing neural tube, a crucial step for proper neural tube closure.

  4. Collective strategic defaults: Bailouts and repayment incentives

    OpenAIRE

    Vlahu, R.

    2008-01-01

    This paper shows that under a global games approach banks may be subject to risk of failure even when fundamentals are strong due to a coordination problem among debtors. As a result of collective strategic default a financially sound firm may claim inability to repay if it expects a sufficient number of other firms to do so as well, thus reducing bank's enforcement ability. This occurs in particular when financial environment is characterized by inadequate bankruptcy laws and poor quality of...

  5. 45 CFR 212.7 - Repayment to the United States.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Repayment to the United States. 212.7 Section 212... UNITED STATES CITIZENS RETURNED FROM FOREIGN COUNTRIES § 212.7 Repayment to the United States. (a) An..., any or all of the cost of such assistance to the United States, except insofar as it is...

  6. 7 CFR 1427.19 - Repayment of loans.

    Science.gov (United States)

    2010-01-01

    ... determined by CCC under § 1427.25, in effect on the day the repayment is received by the county office, loan... event that Thursday is a non-workday, such loan repayments will not be accepted beginning at 7 a.m...: (i) The tariff storage rate for the warehouse for the 2005 crop or, for any warehouse not...

  7. 5 CFR 179.306 - Written agreement for repayment.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Written agreement for repayment. 179.306 Section 179.306 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CLAIMS COLLECTION STANDARDS Administrative Offset § 179.306 Written agreement for repayment. A debtor who...

  8. Separating stimulus-driven and response-related LRP components with Residue Iteration Decomposition (RIDE).

    Science.gov (United States)

    Stürmer, Birgit; Ouyang, Guang; Zhou, Changsong; Boldt, Annika; Sommer, Werner

    2013-01-01

    When the lateralized readiness potential (LRP) is recorded in stimulus-response compatibility (SRC) tasks, two processes may overlap in the LRP, stimulus-driven response priming and activation based on response selection rules. These overlapping processes are hard to disentangle with standard analytical tools. Here, we show that Residue Iteration Decomposition (RIDE), based on latency variability, separates the overlapping LRP components from a Simon task into stimulus-driven and response-related components. SRC affected LRP amplitudes only in the stimulus-driven component, whereas LRP onsets were affected only in the response-locked component. Importantly, the compatibility effect in reaction times was more similar to the effect in the onsets of the RIDE-derived response-locked LRP component than in the unseparated LRP. Thus, RIDE-separated LRP components are devoid of distortions inherent to standard LRPs.

  9. LRP2 Acts as SHH Clearance Receptor to Protect the Retinal Margin from Mitogenic Stimuli.

    Science.gov (United States)

    Christ, Annabel; Christa, Anna; Klippert, Julia; Eule, J Corinna; Bachmann, Sebastian; Wallace, Valerie A; Hammes, Annette; Willnow, Thomas E

    2015-10-12

    During forebrain development, LRP2 promotes morphogen signaling as an auxiliary SHH receptor. However, in the developing retina, LRP2 assumes the opposing function, mediating endocytic clearance of SHH and antagonizing morphogen action. LRP2-mediated clearance prevents spread of SHH activity from the central retina into the retinal margin to protect quiescent progenitor cells in this niche from mitogenic stimuli. Loss of LRP2 in mice increases the sensitivity of the retinal margin for SHH, causing expansion of the retinal progenitor cell pool and hyperproliferation of this tissue. Our findings document the ability of LRP2 to act, in a context-dependent manner, as activator or inhibitor of the SHH pathway. Our current findings uncovered LRP2 activity as the molecular mechanism imposing quiescence of the retinal margin in the mammalian eye and suggest SHH-induced proliferation of the retinal margin as cause of the large eye phenotype observed in mouse models and patients with LRP2 defects.

  10. 34 CFR 685.211 - Miscellaneous repayment provisions.

    Science.gov (United States)

    2010-07-01

    ... Consolidation Loan, or a student Direct PLUS Loan, the Secretary may designate the income contingent repayment... Secretary's knowledge, the borrower (or the student on whose behalf a parent borrowed) provided false or...

  11. Factors Affecting Loan Utilization And Repayment Patterns By Small ...

    African Journals Online (AJOL)

    Factors Affecting Loan Utilization And Repayment Patterns By Small Holder Farmers ... 61.3% of the respondents had a minimum of secondary school education. ... Also, it can be inferred that effective utilization of loan is directly influenced by ...

  12. Lrp13 is a novel vertebrate lipoprotein receptor that binds vitellogenins in teleost fishes.

    Science.gov (United States)

    Reading, Benjamin J; Hiramatsu, Naoshi; Schilling, Justin; Molloy, Katelyn T; Glassbrook, Norm; Mizuta, Hiroko; Luo, Wenshu; Baltzegar, David A; Williams, Valerie N; Todo, Takashi; Hara, Akihiko; Sullivan, Craig V

    2014-11-01

    Transcripts encoding a novel member of the lipoprotein receptor superfamily, termed LDL receptor-related protein (Lrp)13, were sequenced from striped bass (Morone saxatilis) and white perch (Morone americana) ovaries. Receptor proteins were purified from perch ovary membranes by protein-affinity chromatography employing an immobilized mixture of vitellogenins Aa and Ab. RT-PCR revealed lrp13 to be predominantly expressed in striped bass ovary, and in situ hybridization detected lrp13 transcripts in the ooplasm of early secondary growth oocytes. Quantitative RT-PCR confirmed peak lrp13 expression in the ovary during early secondary growth. Quantitative mass spectrometry revealed peak Lrp13 protein levels in striped bass ovary during late-vitellogenesis, and immunohistochemistry localized Lrp13 to the oolemma and zona radiata of vitellogenic oocytes. Previously unreported orthologs of lrp13 were identified in genome sequences of fishes, chicken (Gallus gallus), mouse (Mus musculus), and dog (Canis lupus familiaris). Zebrafish (Danio rerio) and Nile tilapia (Oreochromis niloticus) lrp13 loci are discrete and share genomic synteny. The Lrp13 appears to function as a vitellogenin receptor and may be an important mediator of yolk formation in fishes and other oviparous vertebrates. The presence of lrp13 orthologs in mammals suggests that this lipoprotein receptor is widely distributed among vertebrates, where it may generally play a role in lipoprotein metabolism.

  13. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

    NARCIS (Netherlands)

    Baardman, Maria E.; Zwier, Mathijs V.; Wisse, Lambertus J.; Gittenberger-de Groot, Adriana C.; Kerstjens-Frederikse, Wilhelmina S.; Hofstra, Robert M. W.; Jurdzinski, Angelika; Hierck, Beerend P.; Jongbloed, Monique R. M.; Berger, Rolf M. F.; Plosch, Torsten; DeRuiter, Marco C.

    2016-01-01

    Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the

  14. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

    NARCIS (Netherlands)

    T. Baardman (Taco); M.V. Zwier (Mathijs V.); L.J. Wisse (Lambertus); A.C. Gittenberger-De Groot (Adriana); W.S. Kerstjens-Frederikse (Wilhelmina); R.M.W. Hofstra (Robert); A. Jurdzinski (Angelika); B.P. Hierck (Beerend); M.R.M. Jongbloed (Monique); R.M.F. Berger (Rolf); T. Plösch (Torsten); M.C. DeRuiter (Marco)

    2016-01-01

    textabstractLipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the

  15. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

    NARCIS (Netherlands)

    Baardman, Maria E.; Zwier, Mathijs V.; Wisse, Lambertus J.; Gittenberger-de Groot, Adriana C.; Kerstjens-Frederikse, Wilhelmina S.; Hofstra, Robert M. W.; Jurdzinski, Angelika; Hierck, Beerend P.; Jongbloed, Monique R. M.; Berger, Rolf M. F.; Plosch, Torsten; DeRuiter, Marco C.

    2016-01-01

    Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the cardiovascul

  16. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development

    NARCIS (Netherlands)

    T. Baardman (Taco); M.V. Zwier (Mathijs V.); L.J. Wisse (Lambertus); A.C. Gittenberger-De Groot (Adriana); W.S. Kerstjens-Frederikse (Wilhelmina); R.M.W. Hofstra (Robert); A. Jurdzinski (Angelika); B.P. Hierck (Beerend); M.R.M. Jongbloed (Monique); R.M.F. Berger (Rolf); T. Plösch (Torsten); M.C. DeRuiter (Marco)

    2016-01-01

    textabstractLipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts of Lrp2 knockout (KO) mice have not yet been investigated. We studied the

  17. Severe Cenani-Lenz syndrome caused by loss of LRP4 function.

    Science.gov (United States)

    Kariminejad, Ariana; Stollfuß, Barbara; Li, Yun; Bögershausen, Nina; Boss, Karin; Hennekam, Raoul C M; Wollnik, Bernd

    2013-06-01

    Limb patterning and growth are complex embryonic processes in which the elaborately orchestrated interplay of diverse endocrine and paracrine factors is crucial to limb integrity. LRP4 is a lipoprotein receptor known for its regulatory effects on LRP5- and LRP6-mediated Wnt signaling, a pathway that plays a pivotal role in limb development. Recessive mutations in LRP4 have been shown to cause Cenani-Lenz syndrome, which is characterized by severe limb malformations, an unusual face, and renal abnormalities. We report on a child with severe Cenani-Lenz syndrome caused by a novel homozygous nonsense mutation in LRP4. The severity of the phenotype in a patient with absent residual LRP4 function may point to a genotype-phenotype correlation.

  18. Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To explore the expression of leukemia related protein 16 (LRP16) in colorectal carcinoma, and analyze its correlation with clinicopathologic features and prognosis. METHODS: Immunohistochemistry for LRP16 was performed in 201 cases of colorectal carcinoma and 60 cases of distal normal mucosa. Medical records were reviewed and clinicopathological analysis was performed. RESULTS: LRP16 expression was detected in 117 of 201 cases of the colorectal carcinoma and in 21 cases of 60 distal normal mucosa. The ...

  19. LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State

    Directory of Open Access Journals (Sweden)

    Claus U. Pietrzik

    2017-04-01

    Full Text Available The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER leads to decreased APP cell surface levels and in turn, to reduced Aβ secretion. Here, we extended the biochemical and immunocytochemical analyses by showing via live cell imaging analyses in primary neurons that LRP1 and APP are transported only partly in common (one third but to a higher degree in distinct fast axonal transport vesicles. Interestingly, co-expression of LRP1 and APP caused a change of APP transport velocities, indicating that LRP1 recruits APP to a specific type of fast axonal transport vesicles. In contrast lowered levels of LRP1 facilitated APP transport. We further show that monomeric and dimeric APP exhibit similar transport characteristics and that both are affected by LRP1 in a similar way, by slowing down APP anterograde transport and increasing its endocytosis rate. In line with this, a knockout of LRP1 in CHO cells and in primary neurons caused an increase of monomeric and dimeric APP surface localization and in turn accelerated shedding by meprin β and ADAM10. Notably, a choroid plexus specific LRP1 knockout caused a much higher secretion of sAPP dimers into the cerebrospinal fluid compared to sAPP monomers. Together, our data show that LRP1 functions as a sorting receptor for APP, regulating its cell surface localization and thereby its processing by ADAM10 and meprin β, with the latter exhibiting a preference for APP in its dimeric state.

  20. LRP-1 ectodomain shedding as a post-transcriptional mechanism to regulate its endocytic activity

    OpenAIRE

    Selvais, Charlotte

    2010-01-01

    The low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1) is a type I integral membrane receptor that mediates endocytosis of a wide array of ligands. LRP-1-dependent endocytosis emerges as a main mechanism controlling the extracellular amounts of various matrix metalloproteinase (MMP) family members. The LRP-1-mediated internalization of MMP-2 was identified as a pivotal mechanism for controlling the extracellular activity of this proteinase. In particular, we have documented that...

  1. LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State.

    Science.gov (United States)

    Herr, Uta-Mareike; Strecker, Paul; Storck, Steffen E; Thomas, Carolin; Rabiej, Verena; Junker, Anne; Schilling, Sandra; Schmidt, Nadine; Dowds, C Marie; Eggert, Simone; Pietrzik, Claus U; Kins, Stefan

    2017-01-01

    The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER leads to decreased APP cell surface levels and in turn, to reduced Aβ secretion. Here, we extended the biochemical and immunocytochemical analyses by showing via live cell imaging analyses in primary neurons that LRP1 and APP are transported only partly in common (one third) but to a higher degree in distinct fast axonal transport vesicles. Interestingly, co-expression of LRP1 and APP caused a change of APP transport velocities, indicating that LRP1 recruits APP to a specific type of fast axonal transport vesicles. In contrast lowered levels of LRP1 facilitated APP transport. We further show that monomeric and dimeric APP exhibit similar transport characteristics and that both are affected by LRP1 in a similar way, by slowing down APP anterograde transport and increasing its endocytosis rate. In line with this, a knockout of LRP1 in CHO cells and in primary neurons caused an increase of monomeric and dimeric APP surface localization and in turn accelerated shedding by meprin β and ADAM10. Notably, a choroid plexus specific LRP1 knockout caused a much higher secretion of sAPP dimers into the cerebrospinal fluid compared to sAPP monomers. Together, our data show that LRP1 functions as a sorting receptor for APP, regulating its cell surface localization and thereby its processing by ADAM10 and meprin β, with the latter exhibiting a preference for APP in its dimeric state.

  2. LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes.

    Science.gov (United States)

    Borrell-Pages, Maria; Carolina Romero, July; Badimon, Lina

    2015-08-01

    Inflammation is triggered after invasion or injury to restore homeostasis. Although the activation of Wnt/β-catenin signaling is one of the first molecular responses to cellular damage, its role in inflammation is still unclear. It was our hypothesis that the low-density lipoprotein (LDL) receptor-related protein 5 (LRP5) and the canonical Wnt signaling pathway are modulators of inflammatory mechanisms. Wild-type (WT) and LRP5(-/-) mice were fed a hypercholesterolemic (HC) diet to trigger dislipidemia and chronic inflammation. Diets were supplemented with plant sterol esters (PSEs) to induce LDL cholesterol lowering and the reduction of inflammation. HC WT mice showed increased serum cholesterol levels that correlated with increased Lrp5 and Wnt/β-catenin gene expression while in the HC LRP5(-/-) mice Wnt/β-catenin pathway was shut down. Functionally, HC induced pro-inflammatory gene expression in LRP5(-/-) mice, suggesting an inhibitory role of the Wnt pathway in inflammation. Dietary PSE administration downregulated serum cholesterol levels in WT and LRP5(-/-) mice. Furthermore, in WT mice PSE increased anti-inflammatory genes expression and inhibited Wnt/β-catenin activation. Hepatic gene expression of Vldlr, Lrp2 and Lrp6 was increased after HC feeding in WT mice but not in LRP5(-/-) mice, suggesting a role for these receptors in the clearance of plasmatic lipoproteins. Finally, an antiatherogenic role for LRP5 was demonstrated as HC LRP5(-/-) mice developed larger aortic atherosclerotic lesions than WT mice. Our results show an anti-inflammatory, pro-survival role for LRP5 and the Wnt signaling pathway in peripheral blood leukocytes.

  3. LDL Receptor-Related Protein-1 (LRP1 Regulates Cholesterol Accumulation in Macrophages.

    Directory of Open Access Journals (Sweden)

    Anna P Lillis

    Full Text Available Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cell formation are incompletely understood. To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cell formation, but the in vivo contribution of the LDL receptor-related protein 1 (LRP1 to this process is not known [corrected]. To investigate the role of LRP1 in cholesterol accumulation in macrophages, we generated mice with a selective deletion of LRP1 in macrophages on an LDL receptor (LDLR-deficient background (macLRP1-/-. After feeding mice a high fat diet for 11 weeks, peritoneal macrophages isolated from Lrp+/+ mice contained significantly higher levels of total cholesterol than those from macLRP1-/- mice. Further analysis revealed that this was due to increased levels of cholesterol esters. Interestingly, macLRP1-/- mice displayed elevated plasma cholesterol and triglyceride levels resulting from accumulation of large, triglyceride-rich lipoprotein particles in the circulation. This increase did not result from an increase in hepatic VLDL biosynthesis, but rather results from a defect in catabolism of triglyceride-rich lipoprotein particles in macLRP1-/- mice. These studies reveal an important in vivo contribution of macrophage LRP1 to cholesterol homeostasis.

  4. ESTROGEN REGULATION OF LRP16 GENE EXPRESSION INVOLVES SP1 TRANSCRIPTION FACTOR

    Institute of Scientific and Technical Information of China (English)

    SI Yi-ling; HAN Wei-dong; ZhAO Ya-li; LI Qi; HAO Hao-jie; SONG Hai-jing; MU Yi-ming; YU Li

    2006-01-01

    Objective: To investigate the role of Sp1 as transcription factor required for transactivation of LRP16 gene by estrogen. Methods: Specific antibodies of Erα and Sp1 were used to precipitate the target DNA/protein complexes of MCF-7 cells at different time points after estrogen treatment (Chromatin immunoprecipitation assay), the promoter region of LRP16 gene was amplified by semi-nested polymerase chain reaction (snPCR). Small interfering RNA (siRNA) against Sp1 was transiently cotransfected with LRP16-Luc (containing the region from -213bp to -126bp of LRP16 gene promoter) in MCF-7 cells. The luciferase activities were measured by dual-luciferase assay. Results: The results of chromatin immunoprecipitation assay showed that Sp1 protein directly bound to the -213bp to -126bp region of LRP16 gene, and Erα could enhance the affinity of Sp1 to DNA. Sp1-siRNA specifically decreased the transactivation of LRP16-Luc by 17β-estradiol to 70-80%. Conclusion: The estrogen-induced transactivation of the human LRP16 gene was mediated by Sp1 protein. Moreover, the interactions of ER(/Sp1 functional complex with LRP16 promoter DNA were required for enhanced LRP16 gene transactivation.

  5. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development.

    Science.gov (United States)

    Baardman, Maria E; Zwier, Mathijs V; Wisse, Lambertus J; Gittenberger-de Groot, Adriana C; Kerstjens-Frederikse, Wilhelmina S; Hofstra, Robert M W; Jurdzinski, Angelika; Hierck, Beerend P; Jongbloed, Monique R M; Berger, Rolf M F; Plösch, Torsten; DeRuiter, Marco C

    2016-04-01

    Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts ofLrp2knockout (KO) mice have not yet been investigated. We studied the cardiovascular development ofLrp2KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. TheLrp2KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in theLrp2KO. This explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans withLRP2mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis.

  6. The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis

    DEFF Research Database (Denmark)

    Petersen, Steen V; Thøgersen, Ida B; Valnickova, Zuzana;

    2010-01-01

    In this study, we show that human extracellular superoxide dismutase (EC-SOD) binds to low-density lipoprotein receptor-related protein (LRP). This interaction is most likely responsible for the removal of EC-SOD from the blood circulation via LRP expressed in liver tissue. The receptor recogniti...

  7. Sa-Lrp from Sulfolobus acidocaldarius is a versatile, glutamine-responsive, and architectural transcriptional regulator.

    Science.gov (United States)

    Vassart, Amelia; Van Wolferen, Marleen; Orell, Alvaro; Hong, Ye; Peeters, Eveline; Albers, Sonja-Verena; Charlier, Daniel

    2013-02-01

    Sa-Lrp is a member of the leucine-responsive regulatory protein (Lrp)-like family of transcriptional regulators in Sulfolobus acidocaldarius. Previously, we demonstrated the binding of Sa-Lrp to the control region of its own gene in vitro. However, the function and cofactor of Sa-Lrp remained an enigma. In this work, we demonstrate that glutamine is the cofactor of Sa-Lrp by inducing the formation of octamers and increasing the DNA-binding affinity and sequence specificity. In vitro protein-DNA interaction assays indicate that Sa-Lrp binds to promoter regions of genes with a variety of functions including ammonia assimilation, transcriptional control, and UV-induced pili synthesis. DNA binding occurs with a specific affinity for AT-rich binding sites, and the protein induces DNA bending and wrapping upon binding, indicating an architectural role of the regulator. Furthermore, by analyzing an Sa-lrp deletion mutant, we demonstrate that the protein affects transcription of some of the genes of which the promoter region is targeted and that it is an important determinant of the cellular aggregation phenotype. Taking all these results into account, we conclude that Sa-Lrp is a glutamine-responsive global transcriptional regulator with an additional architectural role.

  8. MicroRNA-4739 regulates osteogenic and adipocytic differentiation of immortalized human bone marrow stromal cells via targeting LRP3

    DEFF Research Database (Denmark)

    Elsafadi, Mona; Manikandan, Muthurangan; Alajez, Nehad M

    2017-01-01

    3 (LRP3) in regulating the osteogenic and adipogenic differentiation of immortalized hBMSCs. Gene expression profiling revealed significantly higher LRP3 levels in the highly osteogenic hBMSC clone imCL1 than in the less osteogenic clone imCL2, as well as a significant upregulation of LRP3 during...

  9. 34 CFR 682.215 - Income-based repayment plan.

    Science.gov (United States)

    2010-07-01

    ... Income-based repayment plan. (a) Definitions. As used in this section— (1) Adjusted gross income (AGI... poverty guideline for the borrower's family size; or (ii) For a married borrower who files a joint Federal... of the difference between the borrower's and spouse's AGI, and 150 percent of the poverty guideline...

  10. 34 CFR 685.221 - Income-based repayment plan.

    Science.gov (United States)

    2010-07-01

    ... Income-based repayment plan. (a) Definitions. As used in this section— (1) Adjusted gross income (AGI... poverty guideline for the borrower's family size; or (ii) For a married borrower who files a joint Federal... of the difference between the borrower's and spouse's AGI, and 150 percent of the poverty guideline...

  11. 34 CFR 535.52 - What is the repayment schedule?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What is the repayment schedule? 535.52 Section 535.52 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF BILINGUAL EDUCATION AND MINORITY LANGUAGES AFFAIRS, DEPARTMENT OF EDUCATION BILINGUAL EDUCATION: GRADUATE...

  12. LRP-1 promotes cancer cell invasion by supporting ERK and inhibiting JNK signaling pathways.

    Directory of Open Access Journals (Sweden)

    Benoit Langlois

    Full Text Available BACKGROUND: The low-density lipoprotein receptor-related protein-1 (LRP-1 is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated. The lack of mechanistic insights into the intracellular signaling networks downstream of LRP-1 has prevented the understanding of its contribution towards cancer. METHODOLOGY/PRINCIPAL FINDINGS: Through a short-hairpin RNA-mediated silencing approach, we identified LRP-1 as a main regulator of ERK and JNK signaling in a tumor cell context. Co-immunoprecipitation experiments revealed that LRP-1 constitutes an intracellular docking site for MAPK containing complexes. By using pharmacological agents, constitutively active and dominant-negative kinases, we demonstrated that LRP-1 maintains malignant cells in an adhesive state that is favorable for invasion by activating ERK and inhibiting JNK. We further demonstrated that the LRP-1-dependent regulation of MAPK signaling organizes the cytoskeletal architecture and mediates adhesive complex turnover in cancer cells. Moreover, we found that LRP-1 is tethered to the actin network and to focal adhesion sites and controls ERK and JNK targeting to talin-rich structures. CONCLUSIONS: We identified ERK and JNK as the main molecular relays by which LRP-1 regulates focal adhesion disassembly of malignant cells to support invasion.

  13. Cellular cholesterol distribution influences proteolytic release of the LRP-1 ectodomain

    Directory of Open Access Journals (Sweden)

    Bassil eDEKKY

    2016-02-01

    Full Text Available Low-Density Lipoprotein Receptor-related Protein-1 (LRP-1 is a multifunctional matricellular receptor composed of a large ligand-binding subunit (515-kDa α-chain associated with a short trans-membrane subunit (85-kDa β-chain. LRP-1, which exhibits both endocytosis and cell signaling properties, plays a key role in tumor invasion by regulating the activity of proteinases such as matrix metalloproteinases (MMPs. LRP-1 is shed at the cell surface by proteinases such as membrane-type 1 MMP (MT1-MMP and a disintegrin and metalloproteinase-12 (ADAM-12. Here we show by using biophysical, biochemical and cellular imaging approaches that efficient extraction of cell cholesterol and increased LRP-1 shedding occur in MDA-MB-231 breast cancer cells but not in MDA-MB-435 cells. Our data show that cholesterol is differently distributed in both cell lines; predominantly intracellularly for MDA-MB-231 cells and at the plasma membrane for MDA-MB-435 cells. This study highlights the relationship between the rate and cellular distribution of cholesterol and its impact on LRP-1 shedding modulation. Altogether, our data strongly suggest that the increase of LRP-1 shedding upon cholesterol depletion induces a higher accessibility of the sheddase substrate, ie LRP-1, at the cell surface rather than an increase of expression of the enzyme.

  14. Sp1 and KLF15 regulate basal transcription of the human LRP5 gene

    Directory of Open Access Journals (Sweden)

    Zou Yongxin

    2010-02-01

    Full Text Available Abstract Background LRP5, a member of the low density lipoprotein receptor superfamily, regulates diverse developmental processes in embryogenesis and maintains physiological homeostasis in adult organisms. However, how the expression of human LRP5 gene is regulated remains unclear. Results In order to characterize the transcriptional regulation of human LRP5 gene, we cloned the 5' flanking region and evaluated its transcriptional activity in a luciferase reporter system. We demonstrated that both KLF15 and Sp1 binding sites between -72 bp and -53 bp contribute to the transcriptional activation of human LRP5 promoter. Chromatin immunoprecipitation assay demonstrated that the ubiquitous transcription factors KLF15 and Sp1 bind to this region. Using Drosophila SL2 cells, we showed that KLF15 and Sp1 trans-activated the LRP5 promoter in a manner dependent on the presence of Sp1-binding and KLF15-binding motifs. Conclusions Both KLF15 and Sp1 binding sites contribute to the basal activity of human LRP5 promoter. This study provides the first insight into the mechanisms by which transcription of human LRP5 gene is regulated.

  15. Knockdown of LRP/LR Induces Apoptosis in Breast and Oesophageal Cancer Cells.

    Science.gov (United States)

    Khumalo, Thandokuhle; Ferreira, Eloise; Jovanovic, Katarina; Veale, Rob B; Weiss, Stefan F T

    2015-01-01

    Cancer is a global burden due to high incidence and mortality rates and is ranked the second most diagnosed disease amongst non-communicable diseases in South Africa. A high expression level of the 37kDa/67kDa laminin receptor (LRP/LR) is one characteristic of cancer cells. This receptor is implicated in the pathogenesis of cancer cells by supporting tumor angiogenesis, metastasis and especially for this study, the evasion of apoptosis. In the current study, the role of LRP/LR on cellular viability of breast MCF-7, MDA-MB 231 and WHCO1 oesophageal cancer cells was investigated. Western blot analysis revealed that total LRP expression levels of MCF-7, MDA-MB 231 and WHCO1 were significantly downregulated by targeting LRP mRNA using siRNA-LAMR1. This knockdown of LRP/LR resulted in a significant decrease of viability in the breast and oesophageal cancer cells as determined by an MTT assay. Transfection of MDA-MB 231 cells with esiRNA-RPSA directed against a different region of the LRP mRNA had similar effects on LRP/LR expression and cell viability compared to siRNA-LAMR1, excluding an off-target effect of siRNA-LAMR1. This reduction in cellular viability is as a consequence of apoptosis induction as indicated by the exposure of the phosphatidylserine protein on the surface of breast MCF-7, MDA-MB 231 and oesophageal WHCO1 cancer cells, respectively, detected by an Annexin-V/FITC assay as well as nuclear morphological changes observed post-staining with Hoechst. These observations indicate that LRP/LR is crucial for the maintenance of cellular viability of breast and oesophageal cancer cells and recommend siRNA technology targeting LRP expression as a possible novel alternative technique for breast and oesophageal cancer treatment.

  16. LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APP.

    Science.gov (United States)

    Moir, Robert D; Tanzi, Rudolph E

    2005-04-01

    The pathogenesis of Alzheimer's disease (AD) involves the abnormal accumulation and deposition of beta-amyloid in cerebral blood vessels and in the brain parenchyma. Critical in modulating beta-amyloid deposition in brain is the flux of Abeta across the blood brain barrier. The low-density lipoprotein receptor-related protein (LRP), is a large endocytic receptor that mediates the efflux of Abeta out of brain and into the periphery. The first step in the LRP-mediated clearance of Abeta involves the formation of a complex between Abeta and the LRP ligands apolipoprotein E (apoE) or alpha(2)-macroglobulin (alpha(2)M). The Abeta/chaperone complexes then bind to LRP via binding sites on apoE or alpha(2)M. The efflux of Abeta/chaperone complexes out of the neuropil and into the periphery may be attenuated by LRP-ligands that compete with apoE or alpha(2)M for LRP binding. LRP is also the cell surface receptor for Kunitz Protease Inhibitor (KPI) containing isoforms of Abeta's parent protein, the amyloid protein precursor (APP). Protein and mRNA levels of KPI-containing APP isoforms (APP-KPI) are elevated in AD brain and are associated with increased Abeta production. In this study we show that soluble non-amyloidogenic APP-KPI can also inhibit the uptake of Abeta/alpha(2)M in a cell culture model of LRP mediated Abeta clearance. Clearance of Abeta/apoE complexes was not inhibited by APP-KPI. Our findings are consistent with studies showing that apoE and alpha(2)M have discrete binding sites on LRP. Most significantly, our data suggests that the elevated levels of APP-KPI in AD brain may attenuate the clearance of Abeta, the proteins own amyloidogenic catabolic product.

  17. Lrp4 modulates extracellular integration of cell signaling pathways in development.

    Directory of Open Access Journals (Sweden)

    Atsushi Ohazama

    Full Text Available The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway.

  18. LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways.

    Science.gov (United States)

    Kumar, Jitender; Swanberg, Maria; McGuigan, Fiona; Callreus, Mattias; Gerdhem, Paul; Akesson, Kristina

    2011-09-01

    Osteoporosis is a common complex disorder in postmenopausal women leading to changes in the micro-architecture of bone and increased risk of fracture. Members of the low-density lipoprotein receptor-related protein (LRP) gene family regulates the development and physiology of bone through the Wnt/β-catenin (Wnt) pathway that in turn cross-talks with the bone morphogenetic protein (BMP) pathway. In two cohorts of Swedish women: OPRA (n=1002; age 75 years) and PEAK-25 (n=1005; age 25 years), eleven single nucleotide polymorphisms (SNPs) from Wnt pathway genes (LRP4; LRP5; G protein-coupled receptor 177, GPR177) were analyzed for association with Bone Mineral Density (BMD), rate of bone loss, hip geometry, quantitative ultrasound and fracture. Additionally, interaction of LRP4 with LRP5, GPR177 and BMP2 were analyzed. LRP4 (rs6485702) was associated with higher total body (TB) and lumbar spine (LS) BMD in the PEAK-25 cohort (p=0.006 and 0.005 respectively), and interaction was observed with LRP5 (p=0.007) and BMP2 (p=0.004) for TB BMD. LRP4 also showed significant interaction with LRP5 for femoral neck (FN) and LS BMD in this cohort. In the OPRA cohort, LRP4 polymorphisms were associated with significantly lower fracture incidence overall (p=0.008-0.001) and fewer hip fractures (rs3816614, p=0.006). Significant interaction in the OPRA cohort was observed for LRP4 with BMP2 and GPR177 for FN BMD as well as for rate of bone loss at TB and FN (p=0.007-0.0001). In conclusion, LRP4 and interaction between LRP4 and genes in the Wnt and BMP signaling pathways modulate bone phenotypes including peak bone mass and fracture, the clinical endpoint of osteoporosis.

  19. Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies

    Science.gov (United States)

    Ettenberg, Seth A.; Charlat, Olga; Daley, Michael P.; Liu, Shanming; Vincent, Karen J.; Stuart, Darrin D.; Schuller, Alwin G.; Yuan, Jing; Ospina, Beatriz; Green, John; Yu, Qunyan; Walsh, Renee; Schmitz, Rita; Heine, Holger; Bilic, Sanela; Ostrom, Lance; Mosher, Rebecca; Hartlepp, K. Felix; Zhu, Zhenping; Fawell, Stephen; Yao, Yung-Mae; Stover, David; Finan, Peter M.; Porter, Jeffery A.; Sellers, William R.; Klagge, Ingo M.; Cong, Feng

    2010-01-01

    Disregulated Wnt/β-catenin signaling has been linked to various human diseases, including cancers. Inhibitors of oncogenic Wnt signaling are likely to have a therapeutic effect in cancers. LRP5 and LRP6 are closely related membrane coreceptors for Wnt proteins. Using a phage-display library, we identified anti-LRP6 antibodies that either inhibit or enhance Wnt signaling. Two classes of LRP6 antagonistic antibodies were discovered: one class specifically inhibits Wnt proteins represented by Wnt1, whereas the second class specifically inhibits Wnt proteins represented by Wnt3a. Epitope-mapping experiments indicated that Wnt1 class-specific antibodies bind to the first propeller and Wnt3a class-specific antibodies bind to the third propeller of LRP6, suggesting that Wnt1- and Wnt3a-class proteins interact with distinct LRP6 propeller domains. This conclusion is further supported by the structural functional analysis of LRP5/6 and the finding that the Wnt antagonist Sclerostin interacts with the first propeller of LRP5/6 and preferentially inhibits the Wnt1-class proteins. We also show that Wnt1 or Wnt3a class-specific anti-LRP6 antibodies specifically block growth of MMTV-Wnt1 or MMTV-Wnt3 xenografts in vivo. Therapeutic application of these antibodies could be limited without knowing the type of Wnt proteins expressed in cancers. This is further complicated by our finding that bivalent LRP6 antibodies sensitize cells to the nonblocked class of Wnt proteins. The generation of a biparatopic LRP6 antibody blocks both Wnt1- and Wnt3a-mediated signaling without showing agonistic activity. Our studies provide insights into Wnt-induced LRP5/6 activation and show the potential utility of LRP6 antibodies in Wnt-driven cancer. PMID:20713706

  20. Estrogen Receptor α(ERα) Target Gene LRP16 Interacts with ERα and Enhances Receptor's Transcriptional Activity

    Institute of Scientific and Technical Information of China (English)

    HAN Wei-dong; ZHAO Ya-li; WU Zhi-qing; MENG Yuan-guang; ZANG Li; MU Yi-ming

    2007-01-01

    Objective: It has been shown that LRP16 is an estrogen-induced gene through its receptor (Erα). Although there is evidence demonstrating that inhibition of LRP16 gene expression in MCF-7 human breast cancer cells partially attenuates its estrogen-responsiveness, the underlying molecular mechanism is still unclear. Here, the effect of LRP16 expression on the ER( signaling transduction was investigated. Methods: Cotransfection assays were used to measure the effect of LRP16 on ER(-mediated transcriptional activity. GST-pulldown and immunoprecipitation (CoIP) assays were employed to investigate the physical interaction of LRP16 and Erα. The mammalian two-hybrid method was used to map the functional interaction region. Results: the results of cotransfection assays demonstrated that the transcriptional activities of Erα were enhanced in a LRP16 dose-dependent manner in MCF-7 in the presence of estrogen, however, it was abolished in the absence of E2 in MCF-7 cells. The physical interaction of LRP16 and Erα proteins was confirmed by GST-pulldown in vitro and CoIP in vivo assays, which was enhanced by E2 but not dependent on its presence. Furthermore, the results of the mammalian two-hybrid assays indicated that the binding region of Erα to LRP16 located at the A/B AF-1 functional domain and E2 stimulated the binding of LRP16 to the full-length Erα molecule but not to the A/B region alone. Conclusion: These results support a role for estrogenically regulated LRP16 as an Erα coactivator, providing a positive feedback regulatory loop for Erα signal transduction. Based on this function of LRP16, we propose that Erα-positive breast cancer patients with high expression of LRP16 might benefit from targeting LRP16 therapy.

  1. Astrocytic LRP1 Mediates Brain Aβ Clearance and Impacts Amyloid Deposition.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Zhao, Na; Wang, Jian; Na, Wang; Cirrito, John R; Kanekiyo, Takahisa; Holtzman, David M; Bu, Guojun

    2017-03-08

    Accumulation and deposition of amyloid-β (Aβ) in the brain represents an early and perhaps necessary step in the pathogenesis of Alzheimer's disease (AD). Aβ accumulation leads to the formation of Aβ aggregates which may directly and indirectly lead to eventual neurodegeneration. While Aβ production is accelerated in many familial forms of early-onset AD, increasing evidence indicates that impaired clearance of Aβ is more evident in late-onset AD. To uncover the mechanisms underlying impaired Aβ clearance in AD, we examined the role of low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Although LRP1 has been shown to play critical roles in brain Aβ metabolism in neurons and vascular mural cells, its role in astrocytes, the most abundant cell type in the brain responsible for maintaining neuronal homeostasis, remains unclear. Here, we show that astrocytic LRP1 plays a critical role in brain Aβ clearance. LRP1 knockdown in primary astrocytes resulted in decreased cellular Aβ uptake and degradation. In addition, silencing of LRP1 in astrocytes led to down-regulation of several major Aβ-degrading enzymes, including matrix metalloproteases MMP2, MMP9 and insulin-degrading enzyme (IDE). More important, conditional knockout of the Lrp1 gene in astrocytes in the background of APP/PS1 mice impaired brain Aβ clearance, exacerbated Aβ accumulation and accelerated amyloid plaque deposition without affecting its production. Together, our results demonstrate that astrocytic LRP1 plays an important role in Aβ metabolism and that restoring LRP1 expression and function in the brain could be an effective strategy to facilitate Aβ clearance and counter amyloid pathology in AD.SIGNIFICANCE STATEMENTAstrocytes represent a major cell type regulating brain homeostasis; however, their roles in brain clearance of amyloid-β (Aβ) and underlying mechanism are not clear. In this study, we used both cellular models and conditional knockout mouse models to

  2. Targeting the LRP5 pathway improves bone properties in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Barber, Lauren A; Ayturk, Ugur M; Roberts, Heather J; Deal, Lauren E; Schwartz, Marissa A; Weis, MaryAnn; Eyre, David; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2014-10-01

    The cell surface receptor low-density lipoprotein receptor-related protein 5 (LRP5) is a key regulator of bone mass and bone strength. Heterozygous missense mutations in LRP5 cause autosomal dominant high bone mass (HBM) in humans by reducing binding to LRP5 by endogenous inhibitors, such as sclerostin (SOST). Mice heterozygous for a knockin allele (Lrp5(p.A214V) ) that is orthologous to a human HBM-causing mutation have increased bone mass and strength. Osteogenesis imperfecta (OI) is a skeletal fragility disorder predominantly caused by mutations that affect type I collagen. We tested whether the LRP5 pathway can be used to improve bone properties in animal models of OI. First, we mated Lrp5(+/p.A214V) mice to Col1a2(+/p.G610C) mice, which model human type IV OI. We found that Col1a2(+/p.G610C) ;Lrp5(+/p.A214V) offspring had significantly increased bone mass and strength compared to Col1a2(+/p.G610C) ;Lrp5(+/+) littermates. The improved bone properties were not a result of altered mRNA expression of type I collagen or its chaperones, nor were they due to changes in mutant type I collagen secretion. Second, we treated Col1a2(+/p.G610C) mice with a monoclonal antibody that inhibits sclerostin activity (Scl-Ab). We found that antibody-treated mice had significantly increased bone mass and strength compared to vehicle-treated littermates. These findings indicate increasing bone formation, even without altering bone collagen composition, may benefit patients with OI.

  3. LRP5 Signaling in Osteosarcomagenesis: a Cautionary Tale of Translation from Cell Lines to Tumors

    Directory of Open Access Journals (Sweden)

    Logan Horne

    2016-10-01

    Full Text Available Previous reports document expression of low-density lipoprotein receptor-related protein 5 (LRP5 in osteosarcoma (OS tissue. Expression of this Wnt receptor correlated with metastatic disease and poor disease-free survival. Forced expression of dominant-negative LRP5 (dnLRP5, which lacks the membrane binding domain of the native protein and therefore functions as a soluble receptor-sponge for Wnt ligands, reduced in vitro cellular invasion and in vivo xenograft tumor growth for osteosarcoma cell lines. Here, we use a genetically engineered mouse model of osteosarcomagenesis with and without expression of dnLRP5 to assess to what degree tumorigenesis is affected and whether Wnt/β-catenin signaling is circumvented or maintained. Each cohort of mice developed osteosarcoma at a similar ultimate prevalence, but after a slightly increased latency in those also expressing dnLRP5. On histology, there was no difference between groups, despite previous reports that the dnLRP5 osteosarcoma cells specifically undergo a mesenchymal-to-epithelial transition in vitro. Finally, immunohistochemistry showed the presence of cytosolic and nuclear β-catenin and nuclear Cyclin D1, markers consistent with preserved Wnt/β-catenin signaling despite constitutive blockade of the cell surface receipt of Wnt signaling ligand. These data suggest that canonical Wnt signaling plays a role in OS progression and that while blockade of singular nodes in signaling pathways can have dramatic effects on individual cell lines, real tumors readily evade such focused attacks.

  4. LRP1 controls biosynthetic and endocytic trafficking of neuronal prion protein

    DEFF Research Database (Denmark)

    Parkyn, Celia J; Vermeulen, Esmeralda G M; Mootoosamy, Roy C

    2008-01-01

    The trafficking of normal cellular prion protein (PrP(C)) is believed to control its conversion to the altered conformation (designated PrP(Sc)) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrP(C) on neurons is rapidly and consti......The trafficking of normal cellular prion protein (PrP(C)) is believed to control its conversion to the altered conformation (designated PrP(Sc)) associated with prion disease. Although anchored to the membrane by means of glycosylphosphatidylinositol (GPI), PrP(C) on neurons is rapidly...... required for this process. Moreover, sustained inhibition of LRP1 levels by siRNA leads to the accumulation of PrP(C) in biosynthetic compartments, with a concomitant lowering of surface PrP(C), suggesting that LRP1 expedites the trafficking of PrP(C) to the neuronal surface. PrP(C) and LRP1 can be co......-immunoprecipitated from the endoplasmic reticulum in normal neurons. The N-terminal domain of PrP(C) binds to purified human LRP1 with nanomolar affinity, even in the presence of 1 microM of the LRP-specific chaperone, receptor-associated protein (RAP). Taken together, these data argue that LRP1 controls both the surface...

  5. Truncating mutations in LRP4 lead to a prenatal lethal form of Cenani-Lenz syndrome.

    Science.gov (United States)

    Lindy, Amanda S; Bupp, Caleb P; McGee, Stephen J; Steed, Erin; Stevenson, Roger E; Basehore, Monica J; Friez, Michael J

    2014-09-01

    Cenani-Lenz syndrome (CLS) is an autosomal recessive skeletal dysplasia that results in malformations of the distal limb, renal anomalies, and characteristic facies. In 2010, this condition was found to be caused by mutations in LRP4, a member of the low-density lipoprotein family of receptors. LRP4 has been shown to antagonize LRP5/LRP6 activation of WNT and β-catenin signaling. Loss of LRP4 function leads to excessive Wnt and β-catenin signaling in the limb bud, which causes abnormal limb development. The large majority of patients with CLS reported in the literature have splicing and missense mutations, which result in syndactyly, oligodactyly, and minor renal malformations. More recently, a patient with CLS has been identified with a homozygous nonsense mutation and a more severe presentation of findings typically associated with this condition. Here we present two sibling fetuses with a prenatal lethal presentation of mesomelic limb reductions, oligosyndactyly, genitourinary malformation and compound heterozygosity for two novel truncating mutations in LRP4. These findings lend further support to the CLS genotype-phenotype correlation presented in recent publications.

  6. RAB8B Is Required for Activity and Caveolar Endocytosis of LRP6

    Directory of Open Access Journals (Sweden)

    Kubilay Demir

    2013-09-01

    Full Text Available Wnt/β-catenin signaling plays an important role in embryonic development and adult tissue homeostasis. When Wnt ligands bind to the receptor complex, LRP5/6 coreceptors are activated by phosphorylation and concomitantly endocytosed. In vertebrates, Wnt ligands induce caveolin-dependent endocytosis of LRP6 to relay signal downstream, whereas antagonists such as Dickkopf promote clathrin-dependent endocytosis, leading to inhibition. However, little is known about how LRP6 is directed to different internalization mechanisms, and how caveolin-dependent endocytosis is mediated. In an RNAi screen, we identified the Rab GTPase RAB8B as being required for Wnt/β-catenin signaling. RAB8B depletion reduces LRP6 activity, β-catenin accumulation, and induction of Wnt target genes, whereas RAB8B overexpression promotes LRP6 activity and internalization and rescues inhibition of caveolar endocytosis. In Xenopus laevis and Danio rerio, RAB8B morphants show lower Wnt activity during embryonic development. Our results implicate RAB8B as an essential evolutionary conserved component of Wnt/β-catenin signaling through regulation of LRP6 activity and endocytosis.

  7. Common Polymorphism in the LRP5 Gene May Increase the Risk of Bone Fracture and Osteoporosis

    Directory of Open Access Journals (Sweden)

    Guang-Yue Xu

    2014-01-01

    Full Text Available The low-density lipoprotein receptor-related protein 5 gene (LRP5 was identified to be linked to the variation in bone mineral density and types of bone diseases. The present study was aimed at examining the association of LRP5 rs3736228 C>T gene with bone fracture and osteoporosis by meta-analysis. A systematic electronic search of literature was conducted to identify all published studies in English or Chinese on the association of the LRP5 gene with bone fracture and osteoporosis risks. All analyses were calculated using the Version 12.0 STATA software. Odds ratios (ORs and their corresponding 95% confidence interval (95% CI were calculated. An updated meta-analysis was currently performed, including seven independent case-control studies. Results identified that carriers of rs3736228 C>T variant in the LRP5 gene were associated with an increased risk of developing osteoporosis and fractures under 4 genetic models but not under the dominant model (OR = 1.19, 95% CI = 0.97~1.46, and P=0.103. Ethnicity-subgroup analysis implied that LRP5 rs3736228 C>T mutation was more likely to develop osteoporosis and fractures among Asians and Caucasians in majority of subgroups. These results suggest that there is a modest effect of the LRP5 rs3736228 C>T on the increased susceptibility of bone fracture and osteoporosis.

  8. Congenital syndactyly in cattle: four novel mutations in the low density lipoprotein receptor-related protein 4 gene (LRP4

    Directory of Open Access Journals (Sweden)

    Höltershinken Martin

    2007-02-01

    Full Text Available Abstract Background Isolated syndactyly in cattle, also known as mulefoot, is inherited as an autosomal recessive trait with variable penetrance in different cattle breeds. Recently, two independent mutations in the bovine LRP4 gene have been reported as the primary cause of syndactyly in the Holstein and Angus cattle breeds. Results We confirmed the previously described LRP4 exon 33 two nucleotide substitution in most of the affected Holstein calves and revealed additional evidence for allelic heterogeneity by the identification of four new LRP4 non-synonymous point mutations co-segregating in Holstein, German Simmental and Simmental-Charolais families. Conclusion We confirmed a significant role of LRP4 mutations in the pathogenesis of congenital syndactyly in cattle. The newly detected missense mutations in the LRP4 gene represent independent mutations affecting different conserved protein domains. However, the four newly described LRP4 mutations do still not explain all analyzed cases of syndactyly.

  9. Convergent Signaling Pathways Controlled by LRP1 (Receptor-related Protein 1) Cytoplasmic and Extracellular Domains Limit Cellular Cholesterol Accumulation.

    Science.gov (United States)

    El Asmar, Zeina; Terrand, Jérome; Jenty, Marion; Host, Lionel; Mlih, Mohamed; Zerr, Aurélie; Justiniano, Hélène; Matz, Rachel L; Boudier, Christian; Scholler, Estelle; Garnier, Jean-Marie; Bertaccini, Diego; Thiersé, Danièle; Schaeffer, Christine; Van Dorsselaer, Alain; Herz, Joachim; Bruban, Véronique; Boucher, Philippe

    2016-03-04

    The low density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed cell surface receptor that protects from intracellular cholesterol accumulation. However, the underlying mechanisms are unknown. Here we show that the extracellular (α) chain of LRP1 mediates TGFβ-induced enhancement of Wnt5a, which limits intracellular cholesterol accumulation by inhibiting cholesterol biosynthesis and by promoting cholesterol export. Moreover, we demonstrate that the cytoplasmic (β) chain of LRP1 suffices to limit cholesterol accumulation in LRP1(-/-) cells. Through binding of Erk2 to the second of its carboxyl-terminal NPXY motifs, LRP1 β-chain positively regulates the expression of ATP binding cassette transporter A1 (ABCA1) and of neutral cholesterol ester hydrolase (NCEH1). These results highlight the unexpected functions of LRP1 and the canonical Wnt5a pathway and new therapeutic potential in cholesterol-associated disorders including cardiovascular diseases.

  10. 34 CFR 609.42 - What are the audit and repayment requirements?

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    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What are the audit and repayment requirements? 609.42... What Conditions Must a Grantee Meet? § 609.42 What are the audit and repayment requirements? (a)(1) A... two years, covering the period since the previous audit, and the grantee shall submit the audit to the...

  11. 26 CFR 31.6011(a)-3A - Returns of the railroad unemployment repayment tax.

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    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Returns of the railroad unemployment repayment... unemployment repayment tax. (a) Requirement—(1) Employers. Every rail employer (as defined in section 3323(a) and section 1 of the Railroad Unemployment Insurance Act) shall make a return of the tax imposed by...

  12. 42 CFR 433.140 - FFP and repayment of Federal share.

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    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false FFP and repayment of Federal share. 433.140 Section....140 FFP and repayment of Federal share. (a) FFP is not available in Medicaid payments if— (1) The... insurance contract limits or excludes payments if the individual is eligible for Medicaid. (b) FFP...

  13. 11 CFR 116.12 - Repayment of candidate loans of $250,000 or less.

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    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Repayment of candidate loans of $250,000 or less. 116.12 Section 116.12 Federal Elections FEDERAL ELECTION COMMISSION GENERAL DEBTS OWED BY CANDIDATES AND POLITICAL COMMITTEES § 116.12 Repayment of candidate loans of $250,000 or less. (a)...

  14. 42 CFR 57.310 - Repayment and collection of nursing student loans.

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    2010-10-01

    ... advance the borrower's knowledge of and strengthen his or her skills in the provision of nursing services... 42 Public Health 1 2010-10-01 2010-10-01 false Repayment and collection of nursing student loans... LOANS Nursing Student Loans § 57.310 Repayment and collection of nursing student loans. (a) Each...

  15. Antisense RNA controls LRP1 Sense transcript expression through interaction with a chromatin-associated protein, HMGB2.

    Science.gov (United States)

    Yamanaka, Yasunari; Faghihi, Mohammad Ali; Magistri, Marco; Alvarez-Garcia, Oscar; Lotz, Martin; Wahlestedt, Claes

    2015-05-12

    Long non-coding RNAs (lncRNAs), including natural antisense transcripts (NATs), are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of the majority of NATs remain largely unknown. Here, we identify a NAT of low-density lipoprotein receptor-related protein 1 (Lrp1), referred to as Lrp1-AS, that negatively regulates Lrp1 expression. We show that Lrp1-AS directly binds to high-mobility group box 2 (Hmgb2) and inhibits the activity of Hmgb2 to enhance Srebp1a-dependent transcription of Lrp1. Short oligonucleotides targeting Lrp1-AS inhibit the interaction of antisense transcript and Hmgb2 protein and increase Lrp1 expression by enhancing Hmgb2 activity. Quantitative RT-PCR analysis of brain tissue samples from Alzheimer's disease patients and aged-matched controls revealed upregulation of LRP1-AS and downregulation of LRP1. Our data suggest a regulatory mechanism whereby a NAT interacts with a ubiquitous chromatin-associated protein to modulate its activity in a locus-specific fashion.

  16. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage.

    Directory of Open Access Journals (Sweden)

    Nisha M Badders

    Full Text Available BACKGROUND: Ectopic Wnt signaling induces increased stem/progenitor cell activity in the mouse mammary gland, followed by tumor development. The Wnt signaling receptors, Lrp5/6, are uniquely required for canonical Wnt activity. Previous data has shown that the absence of Lrp5 confers resistance to Wnt1-induced tumor development. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that all basal mammary cells express Lrp5, and co-express Lrp6 in a similar fashion. Though Wnt dependent transcription of key target genes is relatively unchanged in mammary epithelial cell cultures, the absence of Lrp5 specifically depletes adult regenerative stem cell activity (to less than 1%. Stem cell activity can be enriched by >200 fold (over 80% of activity, based on high Lrp5 expression alone. Though Lrp5 null glands have apparent normal function, the basal lineage is relatively reduced (from 42% basal/total epithelial cells to 22% and Lrp5-/- mammary epithelial cells show enhanced expression of senescence-associated markers in vitro, as measured by expression of p16(Ink4a and TA-p63. CONCLUSIONS/SIGNIFICANCE: This is the first single biomarker that has been demonstrated to be functionally involved in stem cell maintenance. Together, these results demonstrate that Wnt signaling through Lrp5 is an important component of normal mammary stem cell function.

  17. Antisense RNA Controls LRP1 Sense Transcript Expression through Interaction with a Chromatin-Associated Protein, HMGB2

    Directory of Open Access Journals (Sweden)

    Yasunari Yamanaka

    2015-05-01

    Full Text Available Long non-coding RNAs (lncRNAs, including natural antisense transcripts (NATs, are expressed more extensively than previously anticipated and have widespread roles in regulating gene expression. Nevertheless, the molecular mechanisms of action of the majority of NATs remain largely unknown. Here, we identify a NAT of low-density lipoprotein receptor-related protein 1 (Lrp1, referred to as Lrp1-AS, that negatively regulates Lrp1 expression. We show that Lrp1-AS directly binds to high-mobility group box 2 (Hmgb2 and inhibits the activity of Hmgb2 to enhance Srebp1a-dependent transcription of Lrp1. Short oligonucleotides targeting Lrp1-AS inhibit the interaction of antisense transcript and Hmgb2 protein and increase Lrp1 expression by enhancing Hmgb2 activity. Quantitative RT-PCR analysis of brain tissue samples from Alzheimer’s disease patients and aged-matched controls revealed upregulation of LRP1-AS and downregulation of LRP1. Our data suggest a regulatory mechanism whereby a NAT interacts with a ubiquitous chromatin-associated protein to modulate its activity in a locus-specific fashion.

  18. LRP1 Downregulates the Alzheimer's β-Secretase BACE1 by Modulating Its Intraneuronal Trafficking(1,2,3).

    Science.gov (United States)

    Tanokashira, Daisuke; Motoki, Kazumi; Minegishi, Seiji; Hosaka, Ai; Mamada, Naomi; Tamaoka, Akira; Okada, Takashi; Lakshmana, Madepalli K; Araki, Wataru

    2015-01-01

    The β-secretase called BACE1 is a membrane-associated protease that initiates the generation of amyloid β-protein (Aβ), a key event in Alzheimer's disease (AD). However, the mechanism of intraneuronal regulation of BACE1 is poorly understood. Here, we present evidence that low-density lipoprotein receptor-related protein 1 (LRP1), a multi-functional receptor, has a previously unrecognized function to regulate BACE1 in neurons. We show that deficiency of LRP1 exerts promotive effects on the protein expression and function of BACE1, whereas expression of LRP-L4, a functional LRP1 mini-receptor, specifically decreases BACE1 levels in both human embryonic kidney (HEK) 293 cells and rat primary neurons, leading to reduced Aβ production. Our subsequent analyses further demonstrate that (1) both endogenous and exogenous BACE1 and LRP1 interact with each other and are colocalized in soma and neurites of primary neurons, (2) LRP1 reduces the protein stability and cell-surface expression of BACE1, and (3) LRP1 facilitates the shift in intracellular localization of BACE1 from early to late endosomes, thereby promoting lysosomal degradation. These findings establish that LRP1 specifically downregulates BACE1 by modulating its intraneuronal trafficking and stability through protein interaction and highlight LRP1 as a potential therapeutic target in AD.

  19. 78 FR 20466 - National Institutes of Health Loan Repayment Programs

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    2013-04-05

    ... nature, such as a physical or mental disability or terminal illness in the immediate family, which so... documentation as may be required, that the participant suffers from a permanent physical or mental disability...

  20. 77 FR 10455 - National Institutes of Health Loan Repayment Programs

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    2012-02-22

    ... with State and local government officials in the development of regulatory policies with federalism... contract and may be subject to assessment of monetary damages and penalties as defined by statute. Clinical... targeted toward a specific area (e.g., AIDS) or type of research (e.g., clinical research). The focus is...

  1. Osteoporosis-Pseudoglioma in a Mauritanian Child due to a Novel Mutation in LRP5

    Directory of Open Access Journals (Sweden)

    Noura Biha

    2016-01-01

    Full Text Available Osteoporosis-pseudoglioma (OPPG syndrome is a very rare autosomal recessive disorder, caused by mutations in the low-density lipoprotein receptor-related protein 5 (LRP5 gene. It manifests by severe juvenile osteoporosis with congenital or infancy-onset visual loss. We describe a case of OPPG due to novel mutation in LRP5 gene, occurring in a female Mauritanian child. This 10-year-old female child was born blind, and after then multiple fragility fractures appeared. PCR amplification and sequencing revealed a novel homozygous nonsense mutation in exon 10 of the LRP5 gene (c.2270G>A; pTrP757⁎; this mutation leads to the production of a truncated protein containing 757 amino acids instead of 1615, located in the third β-propeller domain of the LRP5 protein. Both parents were heterozygous for the mutation. This is the first case of the OPPG described in black Africans, which broadens the spectrum of LRP5 gene mutations in OPPG.

  2. Functional analysis LRP6 novel mutations in patients with coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Yujun Xu

    Full Text Available BACKGROUND: Genetic architecture of coronary artery disease (CAD is still to be defined. Since low density lipoprotein receptor-related protein 6 (LRP6 gene play critical roles in Wnt signal transduction which are important for vascular development and endodermis specification, we therefore resequenced it to search for mutations in CAD patients. METHODS: We systemically sequenced all the exons and promoter region of LRP6 gene in a sample of 380 early onset CAD patients and 380 control subjects in Chinese. RESULTS: In total, we identified 5 patient-specific mutations including K82N (two patients, S488Y (one patient, P1066T (two patients, P1206H (two patients and I1264V (one patient All these mutations located at the extracellular domain of LRP6 gene. In vitro functional analysis of patient-specific mutations demonstrated that these mutations resulted in a significant reduction in both protein level transporting to cell membrane and downstream Wnt signal activity. Furthermore, we found that LRP6 novel mutations attenuated proliferation and migration of human umbilical vein endothelial cells (HUVECs when compared with wild type (WT LRP6. CONCLUSION: Our results demonstrated that these loss-of-function variants might contribute to disease liability in a subset of CAD and defects in Wnt signal activation might be important contributing factors for the onset of CAD.

  3. Role of Wnt Co-receptor LRP6 in Triple Negative Breast Cancer Cell Migration and Invasion.

    Science.gov (United States)

    Ma, Jinlu; Lu, Wenyan; Chen, Dongquan; Xu, Bo; Li, Yonghe

    2017-03-01

    The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential Wnt co-receptor of the Wnt/β-catenin signaling pathway. Although studies have shown an increased expression of LRP6 in several types of cancer, its function in tumor development and progression remains to be elucidated. We herein demonstrated that LRP6 expression is up-regulated in human triple negative breast cancer (TNBC) patients and human TNBC cell lines, and that knockdown of LRP6 expression and treatment of recombinant Mesd protein (a specific inhibitor of LRP6) significantly decreased cell migration and invasion of TNBC MDA-MB-231 and BT549 cells. Interestingly, the effects of LRP6 knockdown and Mesd treatment on TNBC cell migration and invasion were more prominent than on TNBC cell proliferation/viability. Mechanistically, LRP6 knockdown and Mesd treatment inhibited Wnt/β-catenin signaling and decreased the expression of S100A4, a mediator of cancer metastasis and a specific target of Wnt/β-catenin signaling, in TNBC cells. Together, our data suggest that LRP6 promotes TNBC cell migration and invasion by regulating the expression and function of S100A4 via the Wnt/β-catenin signaling pathway. This article is protected by copyright. All rights reserved.

  4. Impaired LRP6-TCF7L2 Activity Enhances Smooth Muscle Cell Plasticity and Causes Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Roshni Srivastava

    2015-10-01

    Full Text Available Mutations in Wnt-signaling coreceptor LRP6 have been linked to coronary artery disease (CAD by unknown mechanisms. Here, we show that reduced LRP6 activity in LRP6R611C mice promotes loss of vascular smooth muscle cell (VSMC differentiation, leading to aortic medial hyperplasia. Carotid injury augmented these effects and led to partial to total vascular obstruction. LRP6R611C mice on high-fat diet displayed dramatic obstructive CAD and exhibited an accelerated atherosclerotic burden on LDLR knockout background. Mechanistically, impaired LRP6 activity leads to enhanced non-canonical Wnt signaling, culminating in diminished TCF7L2 and increased Sp1-dependent activation of PDGF signaling. Wnt3a administration to LRP6R611C mice improved LRP6 activity, led to TCF7L2-dependent VSMC differentiation, and rescued post-carotid-injury neointima formation. These findings demonstrate the critical role of intact Wnt signaling in the vessel wall, establish a causal link between impaired LRP6/TCF7L2 activities and arterial disease, and identify Wnt signaling as a therapeutic target against CAD.

  5. Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LRP2

    NARCIS (Netherlands)

    Zwier, Mathijs V; Baardman, Maria E; van Dijk, Theo H; Jurdzinski, Angelika; Wisse, Lambertus J; Bloks, Vincent W; Berger, Rolf M F; DeRuiter, Marco C; Groen, Albert K; Plösch, Torsten

    2016-01-01

    AIM: Lipoprotein related receptor protein type 2 (LRP2) is highly expressed on both yolk sac and placenta. Mutations in the corresponding gene are associated with severe birth defects in humans, known as Donnai-Barrow syndrome. We here characterized the contribution of LRP2 and maternal plasma chole

  6. Tyrosine-based signal mediates LRP6 receptor endocytosis and desensitization of Wnt/β-catenin pathway signaling.

    Science.gov (United States)

    Liu, Chia-Chen; Kanekiyo, Takahisa; Roth, Barbara; Bu, Guojun

    2014-10-03

    Wnt/β-catenin signaling orchestrates a number of critical events including cell growth, differentiation, and cell survival during development. Misregulation of this pathway leads to various human diseases, specifically cancers. Endocytosis and phosphorylation of the LDL receptor-related protein 6 (LRP6), an essential co-receptor for Wnt/β-catenin signaling, play a vital role in mediating Wnt/β-catenin signal transduction. However, its regulatory mechanism is not fully understood. In this study, we define the mechanisms by which LRP6 endocytic trafficking regulates Wnt/β-catenin signaling activation. We show that LRP6 mutant with defective tyrosine-based signal in its cytoplasmic tail has an increased cell surface distribution and decreased endocytosis rate. These changes in LRP6 endocytosis coincide with an increased distribution to caveolae, increased phosphorylation, and enhanced Wnt/β-catenin signaling. We further demonstrate that treatment of Wnt3a ligands or blocking the clathrin-mediated endocytosis of LRP6 leads to a redistribution of wild-type receptor to lipid rafts. The LRP6 tyrosine mutant also exhibited an increase in signaling activation in response to Wnt3a stimulation when compared with wild-type LRP6, and this activation is suppressed when caveolae-mediated endocytosis is blocked. Our results reveal molecular mechanisms by which LRP6 endocytosis routes regulate its phosphorylation and the strength of Wnt/β-catenin signaling, and have implications on how this pathway can be modulated in human diseases.

  7. APP interacts with LRP4 and agrin to coordinate the development of the neuromuscular junction in mice

    Science.gov (United States)

    Choi, Hong Y; Liu, Yun; Tennert, Christian; Sugiura, Yoshie; Karakatsani, Andromachi; Kröger, Stephan; Johnson, Eric B; Hammer, Robert E; Lin, Weichun; Herz, Joachim

    2013-01-01

    ApoE, ApoE receptors and APP cooperate in the pathogenesis of Alzheimer’s disease. Intriguingly, the ApoE receptor LRP4 and APP are also required for normal formation and function of the neuromuscular junction (NMJ). In this study, we show that APP interacts with LRP4, an obligate co-receptor for muscle-specific tyrosine kinase (MuSK). Agrin, a ligand for LRP4, also binds to APP and co-operatively enhances the interaction of APP with LRP4. In cultured myotubes, APP synergistically increases agrin-induced acetylcholine receptor (AChR) clustering. Deletion of the transmembrane domain of LRP4 (LRP4 ECD) results in growth retardation of the NMJ, and these defects are markedly enhanced in APP−/−;LRP4ECD/ECD mice. Double mutant NMJs are significantly reduced in size and number, resulting in perinatal lethality. Our findings reveal novel roles for APP in regulating neuromuscular synapse formation through hetero-oligomeric interaction with LRP4 and agrin and thereby provide new insights into the molecular mechanisms that govern NMJ formation and maintenance. DOI: http://dx.doi.org/10.7554/eLife.00220.001 PMID:23986861

  8. Thrombospondin 1 binding to calreticulin-LRP1 signals resistance to anoikis

    Science.gov (United States)

    Pallero, Manuel A.; Elzie, Carrie A.; Chen, Jiping; Mosher, Deane F.; Murphy-Ullrich, Joanne E.

    2008-01-01

    Anoikis, apoptotic cell death due to loss of cell adhesion, is critical for regulation of tissue homeostasis in tissue remodeling. Fibrogenesis is associated with reduced fibroblast apoptosis. The matricellular protein thrombospondin 1 (TSP1) regulates cell adhesion and motility during tissue remodeling and in fibrogenesis. The N-terminal domain of TSP1 binds to the calreticulin-LRP1 receptor co-complex to signal down-regulation of cell adhesion and increased cell motility through focal adhesion disassembly. TSP1 signaling through calreticulin-LRP1 activates cell survival signals such as PI3-kinase. Therefore, we tested the hypothesis that TSP1 supports cell survival under adhesion-independent conditions to facilitate tissue remodeling. Here, we show that platelet TSP1, its N-terminal domain (NoC1) as a recombinant protein, or a peptide comprising the calreticulin-LRP1 binding site [amino acids 17–35 (hep I)] in the N-terminal domain promotes fibroblast survival under anchorage-independent conditions. TSP1 activates Akt and decreases apoptotic signaling through caspase 3 and PARP1 in suspended fibroblasts. Inhibition of PI3K/Akt activity blocks TSP1-mediated anchorage-independent survival. Fibroblasts lacking LRP1 or expressing calreticulin lacking the TSP1 binding site do not respond to TSP1 with anchorage-independent survival. These data define a novel role for TSP1 signaling through the calreticulin/LRP1 co-complex in tissue remodeling and fibrotic responses through stimulation of anoikis resistance.—Pallero, M. A., Elzie, C. A., Chen, J., Mosher, D. F., Murphy-Ullrich, J. E. Thrombospondin 1 binding to calreticulin-LRP1 signals resistance to anoikis. PMID:18653767

  9. Keratin 18 attenuates estrogen receptor α-mediated signaling by sequestering LRP16 in cytoplasm

    Directory of Open Access Journals (Sweden)

    Si Yiling

    2009-12-01

    Full Text Available Abstract Background Oncogenesis in breast cancer is often associated with excess estrogen receptor α(ERα activation and overexpression of its coactivators. LRP16 is both an ERα target gene and an ERα coactivator, and plays a crucial role in ERα activation and proliferation of MCF-7 breast cancer cells. However, the regulation of the functional availability of this coactivator protein is not yet clear. Results Yeast two-hybrid screening, GST pulldown and coimmunoprecipitation (CoIP identified the cytoplasmic intermediate filament protein keratin 18 (K18 as a novel LRP16-interacting protein. Fluorescence analysis revealed that GFP-tagged LRP16 was primarily localized in the nuclei of mock-transfected MCF-7 cells but was predominantly present in the cytoplasm of K18-transfected cells. Immunoblotting analysis demonstrated that the amount of cytoplasmic LRP16 was markedly increased in cells overexpressing K18 whereas nuclear levels were depressed. Conversely, knockdown of endogenous K18 expression in MCF-7 cells significantly decreased the cytoplasmic levels of LRP16 and increased levels in the nucleus. CoIP failed to detect any interaction between K18 and ERα, but ectopic expression of K18 in MCF-7 cells significantly blunted the association of LRP16 with ERα, attenuated ERα-activated reporter gene activity, and decreased estrogen-stimulated target gene expression by inhibiting ERα recruitment to DNA. Furthermore, BrdU incorporation assays revealed that K18 overexpression blunted the estrogen-stimulated increase of S-phase entry of MCF-7 cells. By contrast, knockdown of K18 in MCF-7 cells significantly increased ERα-mediated signaling and promoted cell cycle progression. Conclusions K18 can effectively associate with and sequester LRP16 in the cytoplasm, thus attenuating the final output of ERα-mediated signaling and estrogen-stimulated cell cycle progression of MCF-7 breast cancer cells. Loss of K18 increases the functional availability

  10. INHIBITION OF PROLIFERATION OF HUMAN BREAST CANCER MCF-7 CELLS BY SMALL INTERFERENCE RNA AGAINST LRP16 GENE

    Institute of Scientific and Technical Information of China (English)

    韩为东; 赵亚力; 李琦; 母义明; 李雪; 宋海静; 陆祖谦

    2004-01-01

    Objective: Our previous studies have firstly demonstrated that 17(-E2 up-regulates LRP16 gene expression in human breast cancer MCF-7 cells, and ectopic expression of the LRP16 gene promotes MCF-7 cells proliferation. Here, the effects of the LRP16 gene expression on growth of MCF-7 human breast cancer cells and the mechanism were further studied by establishing two stably LRP16-inhibitory MCR-7 cell lines. Methods: Hairpin small interference RNA (siRNA) strategy, by which hairpin siRNA was released by U6 promoter and was mediated by pLPC-based retroviral vector, was adopted to knockdown endogenous LRP16 level in MCF-7 cells. And the hairpin siRNA against green fluorescence protein (GFP) was used as the negative control. The suppressant efficiency of the LRP16 gene expression was confirmed by Nothern blot. Cell proliferation assay and soft agar colony formation assay were used to determine the status of the cells proliferation. Cell cycle checkpoints including cyclin E and cyclin D1 were examined by Western blot. Results: The results from cell proliferation assays suggested that down-regulation of LRP16 gene expression is capable of inhibiting MCF-7 breast cancer cell growth and down-regulation of the LRP16 gene expression is able to inhibit anchorage-independent growth of breast cancer cells in soft agar. We also demonstrated that cyclin E and cyclin D1 proteins were much lower in the LRP16-inhibitory cells than in the control cells. Conclusion: These data suggest that LRP16 gene play an important role in MCF-7 cells proliferation by regulating the pathway of the G1/S transition and may function as an important modulator in regulating the process of tumorigenesis in human breast.

  11. Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo.

    Directory of Open Access Journals (Sweden)

    Hong Y Choi

    Full Text Available Lrp4 is a multifunctional member of the low density lipoprotein-receptor gene family and a modulator of extracellular cell signaling pathways in development. For example, Lrp4 binds Wise, a secreted Wnt modulator and BMP antagonist. Lrp4 shares structural elements within the extracellular ligand binding domain with Lrp5 and Lrp6, two established Wnt co-receptors with important roles in osteogenesis. Sclerostin is a potent osteocyte secreted inhibitor of bone formation that directly binds Lrp5 and Lrp6 and modulates both BMP and Wnt signaling. The anti-osteogenic effect of sclerostin is thought to be mediated mainly by inhibition of Wnt signaling through Lrp5/6 within osteoblasts. Dickkopf1 (Dkk1 is another potent soluble Wnt inhibitor that binds to Lrp5 and Lrp6, can displace Lrp5-bound sclerostin and is itself regulated by BMPs. In a recent genome-wide association study of bone mineral density a significant modifier locus was detected near the SOST gene at 17q21, which encodes sclerostin. In addition, nonsynonymous SNPs in the LRP4 gene were suggestively associated with bone mineral density. Here we show that Lrp4 is expressed in bone and cultured osteoblasts and binds Dkk1 and sclerostin in vitro. MicroCT analysis of Lrp4 deficient mutant mice revealed shortened total femur length, reduced cortical femoral perimeter, and reduced total femur bone mineral content (BMC and bone mineral density (BMD. Lumbar spine trabecular bone volume per total volume (BV/TV was significantly reduced in the mutants and the serum and urinary bone turnover markers alkaline phosphatase, osteocalcin and desoxypyridinoline were increased. We conclude that Lrp4 is a novel osteoblast expressed Dkk1 and sclerostin receptor with a physiological role in the regulation of bone growth and turnover, which is likely mediated through its function as an integrator of Wnt and BMP signaling pathways.

  12. 42 CFR 405.380 - Collection of past-due amounts on scholarship and loan programs.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Collection of past-due amounts on scholarship and... Suspension of Payment, Recovery of Overpayments, and Repayment of Scholarships and Loans Repayment of Scholarships and Loans § 405.380 Collection of past-due amounts on scholarship and loan programs. (a) Basis...

  13. Repayment flexibility can reduce financial stress: a randomized control trial with microfinance clients in India.

    Science.gov (United States)

    Field, Erica; Pande, Rohini; Papp, John; Park, Y Jeanette

    2012-01-01

    Financial stress is widely believed to cause health problems. However, policies seeking to relieve financial stress by limiting debt levels of poor households may directly worsen their economic well-being. We evaluate an alternative policy - increasing the repayment flexibility of debt contracts. A field experiment randomly assigned microfinance clients to a monthly or a traditional weekly installment schedule (N=200). We used cell phones to gather survey data on income, expenditure, and financial stress every 48 hours over seven weeks. Clients repaying monthly were 51 percent less likely to report feeling "worried, tense, or anxious" about repaying, were 54 percent more likely to report feeling confident about repaying, and reported spending less time thinking about their loan compared to weekly clients. Monthly clients also reported higher business investment and income, suggesting that the flexibility encouraged them to invest their loans more profitably, which ultimately reduced financial stress.

  14. Repayment flexibility can reduce financial stress: a randomized control trial with microfinance clients in India.

    Directory of Open Access Journals (Sweden)

    Erica Field

    Full Text Available Financial stress is widely believed to cause health problems. However, policies seeking to relieve financial stress by limiting debt levels of poor households may directly worsen their economic well-being. We evaluate an alternative policy - increasing the repayment flexibility of debt contracts. A field experiment randomly assigned microfinance clients to a monthly or a traditional weekly installment schedule (N=200. We used cell phones to gather survey data on income, expenditure, and financial stress every 48 hours over seven weeks. Clients repaying monthly were 51 percent less likely to report feeling "worried, tense, or anxious" about repaying, were 54 percent more likely to report feeling confident about repaying, and reported spending less time thinking about their loan compared to weekly clients. Monthly clients also reported higher business investment and income, suggesting that the flexibility encouraged them to invest their loans more profitably, which ultimately reduced financial stress.

  15. Structural basis of agrin-LRP4-MuSK signaling

    Energy Technology Data Exchange (ETDEWEB)

    Zong, Yinong; Zhang, Bin; Gu, Shenyan; Lee, Kwangkook; Zhou, Jie; Yao, Guorui; Figueiredo, Dwight; Perry, Kay; Mei, Lin; Jin, Rongsheng [Cornell; (GSHU); (Sanford-Burnham)

    2012-06-27

    Synapses are the fundamental units of neural circuits that enable complex behaviors. The neuromuscular junction (NMJ), a synapse formed between a motoneuron and a muscle fiber, has contributed greatly to understanding of the general principles of synaptogenesis as well as of neuromuscular disorders. NMJ formation requires neural agrin, a motoneuron-derived protein, which interacts with LRP4 (low-density lipoprotein receptor-related protein 4) to activate the receptor tyrosine kinase MuSK (muscle-specific kinase). However, little is known of how signals are transduced from agrin to MuSK. Here, we present the first crystal structure of an agrin-LRP4 complex, consisting of two agrin-LRP4 heterodimers. Formation of the initial binary complex requires the z8 loop that is specifically present in neuronal, but not muscle, agrin and that promotes the synergistic formation of the tetramer through two additional interfaces. We show that the tetrameric complex is essential for neuronal agrin-induced acetylcholine receptor (AChR) clustering. Collectively, these results provide new insight into the agrin-LRP4-MuSK signaling cascade and NMJ formation and represent a novel mechanism for activation of receptor tyrosine kinases.

  16. Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6 Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gwang-woong Go

    2015-06-01

    Full Text Available Low-density lipoprotein receptor-related protein 6 (LRP6 is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention.

  17. LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling

    Institute of Scientific and Technical Information of China (English)

    Changjun Li; Bart O Williams; Xu Cao; Mei Wan

    2014-01-01

    Lipoprotein receptor-related protein 6 (LRP6) plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells (MSCs), skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin1 MSCs by crossing nestin-Cre mice with LRP6flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin1 cells demonstrated reductions in body weight and body length at 1 and 3 months of age. Bone architecture measured by microCT (mCT) showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix1 osteoprogenitors and osteocalcin1 osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.

  18. Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance.

    Science.gov (United States)

    Tanahashi, Hiroshi; Tian, Qing-Bao; Hara, Yoshinobu; Sakagami, Hiroyuki; Endo, Shogo; Suzuki, Tatsuo

    2016-02-05

    Amniotic fluid volume during mid-to-late gestation depends mainly on the urine excretion from the foetal kidneys and partly on the fluid secretion from the foetal lungs during foetal breathing-like movements. Urine is necessary for foetal breathing-like movements, which is critical for foetal lung development. Bilateral renal agenesis and/or obstruction of the urinary tract lead to oligohydramnios, which causes infant death within a short period after birth due to pulmonary hypoplasia. Lrp4, which functions as an agrin receptor, is essential for the formation of neuromuscular junctions. Herein, we report novel phenotypes of Lrp4 knockout (Lrp4(-/-)) mice. Most Lrp4(-/-) foetuses showed unilateral or bilateral kidney agenesis, and Lrp4 knockout resulted in polyhydramnios. The loss of Lrp4 compromised foetal swallowing and breathing-like movements and downregulated the expression of aquaporin-9 in the foetal membrane and aquaporin-1 in the placenta, which possibly affected the amniotic fluid clearance. These results suggest that amniotic fluid removal was compromised in Lrp4(-/-) foetuses, resulting in polyhydramnios despite the impairment of urine production. Our findings indicate that amniotic fluid removal plays an essential role in regulating the amniotic fluid volume.

  19. LRP1 functions as an atheroprotective integrator of TGFbeta and PDFG signals in the vascular wall: implications for Marfan syndrome.

    Directory of Open Access Journals (Sweden)

    Philippe Boucher

    Full Text Available BACKGROUND: The multifunctional receptor LRP1 controls expression, activity and trafficking of the PDGF receptor-beta in vascular smooth muscle cells (VSMC. LRP1 is also a receptor for TGFbeta1 and is required for TGFbeta mediated inhibition of cell proliferation. METHODS AND PRINCIPAL FINDINGS: We show that loss of LRP1 in VSMC (smLRP(- in vivo results in a Marfan-like syndrome with nuclear accumulation of phosphorylated Smad2/3, disruption of elastic layers, tortuous aorta, and increased expression of the TGFbeta target genes thrombospondin-1 (TSP1 and PDGFRbeta in the vascular wall. Treatment of smLRP1(- animals with the PPARgamma agonist rosiglitazone abolished nuclear pSmad accumulation, reversed the Marfan-like phenotype, and markedly reduced smooth muscle proliferation, fibrosis and atherosclerosis independent of plasma cholesterol levels. CONCLUSIONS AND SIGNIFICANCE: Our findings are consistent with an activation of TGFbeta signals in the LRP1-deficient vascular wall. LRP1 may function as an integrator of proliferative and anti-proliferative signals that control physiological mechanisms common to the pathogenesis of Marfan syndrome and atherosclerosis, and this is essential for maintaining vascular wall integrity.

  20. Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5.

    Science.gov (United States)

    Downey, L M; Bottomley, H M; Sheridan, E; Ahmed, M; Gilmour, D F; Inglehearn, C F; Reddy, A; Agrawal, A; Bradbury, J; Toomes, C

    2006-09-01

    Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR. All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA). The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype. Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation.

  1. The LRP1-independent mechanism of PAI-1-induced migration in CpG-ODN activated macrophages.

    Science.gov (United States)

    Thapa, Bikash; Kim, Yeon Hyang; Kwon, Hyung-Joo; Kim, Doo-Sik

    2014-04-01

    CpG-oligodeoxynucleotides (CpG-ODNs) induces plasminogen activator inhibitor type-1 (PAI-1) expression in macrophages, leading to enhanced migration through vitronectin. However, the precise role of low-density lipoprotein receptor-related protein 1 (LRP1) in PAI-1 induced migration of macrophages in the inflammatory environment is not known. In this study, we elucidated a novel mechanism describing the altered role of LRP1 in macrophage migration depending on the activation state of the cells. Experimental evidence clearly shows that the blocking of LRP1 function inhibited the PAI-induced migration of resting RAW 264.7 cells through vitronectin but exerted a pro-migratory effect on CpG-ODN-activated cells. We also demonstrate that CpG-ODN downregulates the protein and mRNA levels of LRP1 both in vivo and in vitro, a function that depends on the NF-κB signaling pathway, resulting in reduced internalization of PAI-1. This work illustrates the distinct mechanism that PAI-1-induced migration of CpG-ODN-activated cells through vitronectin depends on the interaction of PAI-1 with vitronectin but not LRP1 unlike in the resting cells, where the migration is LRP1 dependent and vitronectin independent. In conclusion, our experimental results demonstrate the altered function of LRP1 in the migration of resting and activated macrophages in the context of microenvironmental extracellular matrix components.

  2. Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) C4408R Mutant Promotes Amyloid Precursor Protein (APP) α-Cleavage in Vitro.

    Science.gov (United States)

    Hou, Huayan; Habib, Ahsan; Zi, Dan; Tian, Kathy; Tian, Jun; Giunta, Brian; Sawmiller, Darrell; Tan, Jun

    2017-06-13

    Previous studies have demonstrated that the low-density lipoprotein receptor-related protein-1 (LRP1) plays conflicting roles in Alzheimer's disease (AD) pathogenesis, clearing β-amyloid (Aβ) from the brain while also enhancing APP endocytosis and resultant amyloidogenic processing. We have recently discovered that co-expression of mutant LRP1 C-terminal domain (LRP1-CT C4408R) with Swedish mutant amyloid precursor protein (APPswe) in Chinese hamster ovary (CHO) cells decreases Aβ production, while also increasing sAPPα and APP α-C-terminal fragment (α-CTF), compared with CHO cells expressing APPswe alone. Surprisingly, the location of this mutation on LRP1 corresponded with the α-secretase cleavage site of APP. Further experimentation confirmed that in CHO cells expressing APPswe or wild-type APP (APPwt), co-expression of LRP1-CT C4408R decreases Aβ and increases sAPPα and α-CTF compared with co-expression of wild-type LRP1-CT. In addition, LRP1-CT C4408R enhanced the unglycosylated form of LRP1-CT and reduced APP endocytosis as determined by flow cytometry. This finding identifies a point mutation in LRP1 which slows LRP1-CT-mediated APP endocytosis and amyloidogenic processing, while enhancing APP α-secretase cleavage, thus demonstrating a potential novel target for slowing AD pathogenesis.

  3. LRP4 mutations alter Wnt/beta-catenin signaling and cause limb and kidney malformations in Cenani-Lenz syndrome.

    Science.gov (United States)

    Li, Yun; Pawlik, Barbara; Elcioglu, Nursel; Aglan, Mona; Kayserili, Hülya; Yigit, Gökhan; Percin, Ferda; Goodman, Frances; Nürnberg, Gudrun; Cenani, Asim; Urquhart, Jill; Chung, Boi-Dinh; Ismail, Samira; Amr, Khalda; Aslanger, Ayca D; Becker, Christian; Netzer, Christian; Scambler, Pete; Eyaid, Wafaa; Hamamy, Hanan; Clayton-Smith, Jill; Hennekam, Raoul; Nürnberg, Peter; Herz, Joachim; Temtamy, Samia A; Wollnik, Bernd

    2010-05-14

    Cenani-Lenz syndrome (CLS) is an autosomal-recessive congenital disorder affecting distal limb development. It is characterized mainly by syndactyly and/or oligodactyly and is now shown to be commonly associated with kidney anomalies. We used a homozygosity-mapping approach to map the CLS1 locus to chromosome 11p11.2-q13.1. By sequencing candidate genes, we identified recessive LRP4 mutations in 12 families with CLS. LRP4 belongs to the low-density lipoprotein (LDL) receptor-related proteins (LRPs), which are essential for various developmental processes. LRP4 is known to antagonize LRP6-mediated activation of canonical Wnt signaling, a function that is lost by the identified mutations. Our findings increase the spectrum of congenital anomalies associated with abnormal lipoprotein receptor-dependent signaling.

  4. The genome-wide binding profile of the Sulfolobus solfataricus transcription factor Ss-LrpB shows binding events beyond direct transcription regulation.

    Science.gov (United States)

    Nguyen-Duc, Trong; van Oeffelen, Liesbeth; Song, Ningning; Hassanzadeh-Ghassabeh, Gholamreza; Muyldermans, Serge; Charlier, Daniel; Peeters, Eveline

    2013-11-25

    Gene regulatory processes are largely resulting from binding of transcription factors to specific genomic targets. Leucine-responsive Regulatory Protein (Lrp) is a prevalent transcription factor family in prokaryotes, however, little information is available on biological functions of these proteins in archaea. Here, we study genome-wide binding of the Lrp-like transcription factor Ss-LrpB from Sulfolobus solfataricus. Chromatin immunoprecipitation in combination with DNA microarray analysis (ChIP-chip) has revealed that Ss-LrpB interacts with 36 additional loci besides the four previously identified local targets. Only a subset of the newly identified binding targets, concentrated in a highly variable IS-dense genomic region, is also bound in vitro by pure Ss-LrpB. There is no clear relationship between the in vitro measured DNA-binding specificity of Ss-LrpB and the in vivo association suggesting a limited permissivity of the crenarchaeal chromatin for transcription factor binding. Of 37 identified binding regions, 29 are co-bound by LysM, another Lrp-like transcription factor in S. solfataricus. Comparative gene expression analysis in an Ss-lrpB mutant strain shows no significant Ss-LrpB-mediated regulation for most targeted genes, with exception of the CRISPR B cluster, which is activated by Ss-LrpB through binding to a specific motif in the leader region. The genome-wide binding profile presented here implies that Ss-LrpB is associated at additional genomic binding sites besides the local gene targets, but acts as a specific transcription regulator in the tested growth conditions. Moreover, we have provided evidence that two Lrp-like transcription factors in S. solfataricus, Ss-LrpB and LysM, interact in vivo.

  5. LRP-1 and LRP-2 receptors function in the membrane neuron. Trafficking mechanisms and proteolytic processing in Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Carlos eSpuch

    2012-07-01

    Full Text Available Low density lipoprotein receptor-related protein (LRP belongs to the low-density lipoprotein receptor family, generally recognized as cell surface endocytic receptors, which bind and internalize extracellular ligands for degradation in lysosomes. Neurons require cholesterol to function and keep the membrane rafts stable. Cholesterol uptake into the neuron is carried out by ApoE via LRPs receptors on the cell surface. In neurons the most important are LRP-1 and LRP-2, even it is thought that a causal factor in Alzheimer’s disease (AD is the malfunction of this process which cause impairment intracellular signalling as well as storage and/or release of nutrients and toxic compounds. Both receptors are multifunctional cell surface receptors that are widely expressed in several tissues including neurons and astrocytes. LRPs are constituted by an intracellular (ICD and extracellular domain (ECD. Through its ECD, LRPs bind at least 40 different ligands ranging from lipoprotein and protease inhibitor complex to growth factors and extracellular matrix proteins. These receptors has also been shown to interact with scaffolding and signalling proteins via its ICD in a phosphorylation-dependent manner and to function as a co-receptor partnering with other cell surface or integral membrane proteins. Thus, LRPs are implicated in two major physiological processes: endocytosis and regulation of signalling pathways, which are both involved in diverse biological roles including lipid metabolism, cell growth processes, degradation of proteases, and tissue invasion. Interestingly, LRPs were also localized in neurons in different stages, suggesting that both receptors could be implicated in signal transduction during embryonic development, neuronal outgrowth or in the pathogenesis of AD

  6. The bacterial two-hybrid system uncovers the involvement of acetylation in regulating of Lrp activity in Salmonella Typhimurium

    Directory of Open Access Journals (Sweden)

    Ran Qin

    2016-11-01

    Full Text Available Nε-lysine acetylation is an abundant and important Post-translational modification in bacteria. We used the bacterial two-hybrid system to screen the genome library of the Salmonella Typhimurium to identify potential proteins involved in acetyltransferase Pat - or deacetylase CobB-mediated acetylation. Then, the in vitro (deacetylation assays were used to validate the potential targets, such as STM14_1074, NrdF, RhaR. Lrp, a leucine-responsive regulatory protein and global regulator, was shown to interact with Pat. We further demonstrate that Lrp could be acetylated by Pat and deacetylated by NAD+-dependent CobB in vitro. Specifically, the conserved lysine residue 36 (K36 in helix-turn-helix (HTH DNA-binding domain of Lrp was acetylated. Acetylation of K36 impaired the function of Lrp through altering the affinity with the target promoter. The mutation of K36 in chromosome mimicking acetylation enhanced the transcriptional level of itself and attenuated the mRNA levels of Lrp-regulated genes including fimA, which was confirmed by yeast agglutination assay. These findings demonstrate that the acetylation regulates the DNA-binding activity of Lrp, suggesting that acetylation modification of transcription factors is a conserved regulatory manner to modulate gene expression in bacteria and eukaryotes.

  7. The matricellular receptor LRP1 forms an interface for signaling and endocytosis in modulation of the extracellular tumor environment

    Directory of Open Access Journals (Sweden)

    Bart eVan Gool

    2015-11-01

    Full Text Available The membrane protein low-density lipoprotein receptor related-protein 1 (LRP1 has been attributed a role in cancer. However, its presumably often indirect involvement is far from understood. LRP1 has both endocytic and signaling activities. As a matricellular receptor it is involved in regulation, mostly by clearing, of various extracellular matrix degrading enzymes including matrix metalloproteinases, serine proteases, protease-inhibitor complexes and the endoglycosidase heparanase. Furthermore, by binding extracellular ligands including growth factors and subsequent intracellular interaction with scaffolding and adaptor proteins it is involved in regulation of various signaling cascades. LRP1 expression levels are often downregulated in cancer and some studies consider low LRP1 levels a poor prognostic factor. On the contrary, upregulation in brain cancers has been noted and clinical trials explore the use of LRP1 as cargo receptor to deliver cytotoxic agents.This mini-review focuses on LRP1’s role in tumor growth and metastasis especially by modulation of the extracellular tumor environment. In relation to this role its diagnostic, prognostic and therapeutic potential will be discussed.

  8. The Wnt Co-Receptor Lrp5 Is Required for Cranial Neural Crest Cell Migration in Zebrafish.

    Directory of Open Access Journals (Sweden)

    Bernd Willems

    Full Text Available During vertebrate neurulation, cranial neural crest cells (CNCCs undergo epithelial to mesenchymal transition (EMT, delaminate from the neural plate border, and migrate as separate streams into different cranial regions. There, they differentiate into distinct parts of the craniofacial skeleton. Canonical Wnt signaling has been shown to be essential for this process at different levels but the involved receptors remained unclear. Here we show that the frizzled co-receptor low-density-lipoprotein (LDL receptor-related protein 5 (Lrp5 plays a crucial role in CNCC migration and morphogenesis of the cranial skeleton. Early during induction and migration of CNCCs, lrp5 is expressed ubiquitously but later gets restricted to CNCC derivatives in the ventral head region besides different regions in the CNS. A knock-down of lrp5 does not interfere with induction of CNCCs but leads to reduced proliferation of premigratory CNCCs. In addition, cell migration is disrupted as CNCCs are found in clusters at ectopic positions in the dorsomedial neuroepithelium after lrp5 knock-down and transient CRISPR/Cas9 gene editing. These migratory defects consequently result in malformations of the craniofacial skeleton. To date, Lrp5 has mainly been associated with bone homeostasis in mammals. Here we show that in zebrafish, lrp5 also controls cell migration during early morphogenetic processes and contributes to shaping the craniofacial skeleton.

  9. Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells.

    Science.gov (United States)

    Roy, Ananya; Coum, Antoine; Marinescu, Voichita D; Põlajeva, Jelena; Smits, Anja; Nelander, Sven; Uhrbom, Lene; Westermark, Bengt; Forsberg-Nilsson, Karin; Pontén, Fredrik; Tchougounova, Elena

    2015-09-15

    Glioblastoma (GBM) is a high-grade glioma with a complex microenvironment, including various inflammatory cells and mast cells (MCs) as one of them. Previously we had identified glioma grade-dependent MC recruitment. In the present study we investigated the role of plasminogen activator inhibitor 1 (PAI-1) in MC recruitment.PAI-1, a primary regulator in the fibrinolytic cascade is capable of forming a complex with fibrinolytic system proteins together with low-density lipoprotein receptor-related protein 1 (LRP1). We found that neutralizing PAI-1 attenuated infiltration of MCs. To address the potential implication of LRP1 in this process, we used a LRP1 antagonist, receptor-associated protein (RAP), and demonstrated the attenuation of MC migration. Moreover, a positive correlation between the number of MCs and the level of PAI-1 in a large cohort of human glioma samples was observed. Our study demonstrated the expression of LRP1 in human MC line LAD2 and in MCs in human high-grade glioma. The activation of potential PAI-1/LRP1 axis with purified PAI-1 promoted increased phosphorylation of STAT3 and subsequently exocytosis in MCs.These findings indicate the influence of the PAI-1/LRP1 axis on the recruitment of MCs in glioma. The connection between high-grade glioma and MC infiltration could contribute to patient tailored therapy and improve patient stratification in future therapeutic trials.

  10. The Wnt Co-Receptor Lrp5 Is Required for Cranial Neural Crest Cell Migration in Zebrafish.

    Science.gov (United States)

    Willems, Bernd; Tao, Shijie; Yu, Tingsheng; Huysseune, Ann; Witten, Paul Eckhard; Winkler, Christoph

    2015-01-01

    During vertebrate neurulation, cranial neural crest cells (CNCCs) undergo epithelial to mesenchymal transition (EMT), delaminate from the neural plate border, and migrate as separate streams into different cranial regions. There, they differentiate into distinct parts of the craniofacial skeleton. Canonical Wnt signaling has been shown to be essential for this process at different levels but the involved receptors remained unclear. Here we show that the frizzled co-receptor low-density-lipoprotein (LDL) receptor-related protein 5 (Lrp5) plays a crucial role in CNCC migration and morphogenesis of the cranial skeleton. Early during induction and migration of CNCCs, lrp5 is expressed ubiquitously but later gets restricted to CNCC derivatives in the ventral head region besides different regions in the CNS. A knock-down of lrp5 does not interfere with induction of CNCCs but leads to reduced proliferation of premigratory CNCCs. In addition, cell migration is disrupted as CNCCs are found in clusters at ectopic positions in the dorsomedial neuroepithelium after lrp5 knock-down and transient CRISPR/Cas9 gene editing. These migratory defects consequently result in malformations of the craniofacial skeleton. To date, Lrp5 has mainly been associated with bone homeostasis in mammals. Here we show that in zebrafish, lrp5 also controls cell migration during early morphogenetic processes and contributes to shaping the craniofacial skeleton.

  11. The Bacterial Two-Hybrid System Uncovers the Involvement of Acetylation in Regulating of Lrp Activity in Salmonella Typhimurium

    Science.gov (United States)

    Qin, Ran; Sang, Yu; Ren, Jie; Zhang, Qiufen; Li, Shuxian; Cui, Zhongli; Yao, Yu-Feng

    2016-01-01

    N𝜀-lysine acetylation is an abundant and important Post-translational modification in bacteria. We used the bacterial two-hybrid system to screen the genome library of the Salmonella Typhimurium to identify potential proteins involved in acetyltransferase Pat – or deacetylase CobB-mediated acetylation. Then, the in vitro (de)acetylation assays were used to validate the potential targets, such as STM14_1074, NrdF, RhaR. Lrp, a leucine-responsive regulatory protein and global regulator, was shown to interact with Pat. We further demonstrate that Lrp could be acetylated by Pat and deacetylated by NAD+-dependent CobB in vitro. Specifically, the conserved lysine residue 36 (K36) in helix-turn-helix (HTH) DNA-binding domain of Lrp was acetylated. Acetylation of K36 impaired the function of Lrp through altering the affinity with the target promoter. The mutation of K36 in chromosome mimicking acetylation enhanced the transcriptional level of itself and attenuated the mRNA levels of Lrp-regulated genes including fimA, which was confirmed by yeast agglutination assay. These findings demonstrate that the acetylation regulates the DNA-binding activity of Lrp, suggesting that acetylation modification of transcription factors is a conserved regulatory manner to modulate gene expression in bacteria and eukaryotes. PMID:27909434

  12. LRP2, an auxiliary receptor that controls sonic hedgehog signaling in development and disease.

    Science.gov (United States)

    Christ, Annabel; Herzog, Katja; Willnow, Thomas E

    2016-05-01

    To fulfill their multiple roles in organ development and adult tissue homeostasis, hedgehog (HH) morphogens act through their receptor Patched (PTCH) on target cells. However, HH actions also require HH binding proteins, auxiliary cell surface receptors that agonize or antagonize morphogen signaling in a context-dependent manner. Here, we discuss recent findings on the LDL receptor-related protein 2 (LRP2), an exemplary HH binding protein that modulates sonic hedgehog activities in stem and progenitor cell niches in embryonic and adult tissues. LRP2 functions are crucial for developmental processes in a number of tissues, including the brain, the eye, and the heart, and defects in this receptor pathway are the cause of devastating congenital diseases in humans. Developmental Dynamics 245:569-579, 2016. © 2016 Wiley Periodicals, Inc.

  13. 26 CFR 31.6302(c)-2A - Use of Government depositaries in connection with the railroad unemployment repayment tax.

    Science.gov (United States)

    2010-04-01

    ... with the railroad unemployment repayment tax. 31.6302(c)-2A Section 31.6302(c)-2A Internal Revenue...) § 31.6302(c)-2A Use of Government depositaries in connection with the railroad unemployment repayment...,000,000, such employer shall (except as provided below) deposit his undeposited railroad unemployment...

  14. 26 CFR 31.6071(a)-1A - Time for filing returns with respect to the railroad unemployment repayment tax.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Time for filing returns with respect to the railroad unemployment repayment tax. 31.6071(a)-1A Section 31.6071(a)-1A Internal Revenue INTERNAL REVENUE... filing returns with respect to the railroad unemployment repayment tax. (a) In general. Each return of...

  15. Implementations of the Best Practices in Repayment, the Way to Improve Collections of the Due Students' Loans in Tanzania

    Science.gov (United States)

    Nyahende, Veronica R.

    2016-01-01

    This study was designed to investigate the influence of the implementation of the best practices in repayment in the pre college preparation, in the in college period and in the after college period (the grace period and repayment) in increasing collections of the due students' loans. The study was geared towards achieving the following…

  16. Bili inhibits Wnt/beta-catenin signaling by regulating the recruitment of axin to LRP6.

    Directory of Open Access Journals (Sweden)

    Lorna S Kategaya

    Full Text Available BACKGROUND: Insights into how the Frizzled/LRP6 receptor complex receives, transduces and terminates Wnt signals will enhance our understanding of the control of the Wnt/ss-catenin pathway. METHODOLOGY/PRINCIPAL FINDINGS: In pursuit of such insights, we performed a genome-wide RNAi screen in Drosophila cells expressing an activated form of LRP6 and a beta-catenin-responsive reporter. This screen resulted in the identification of Bili, a Band4.1-domain containing protein, as a negative regulator of Wnt/beta-catenin signaling. We found that the expression of Bili in Drosophila embryos and larval imaginal discs significantly overlaps with the expression of Wingless (Wg, the Drosophila Wnt ortholog, which is consistent with a potential function for Bili in the Wg pathway. We then tested the functions of Bili in both invertebrate and vertebrate animal model systems. Loss-of-function studies in Drosophila and zebrafish embryos, as well as human cultured cells, demonstrate that Bili is an evolutionarily conserved antagonist of Wnt/beta-catenin signaling. Mechanistically, we found that Bili exerts its antagonistic effects by inhibiting the recruitment of AXIN to LRP6 required during pathway activation. CONCLUSIONS: These studies identify Bili as an evolutionarily conserved negative regulator of the Wnt/beta-catenin pathway.

  17. A Typology Framework of Loyalty Reward Programs

    Science.gov (United States)

    Cao, Yuheng; Nsakanda, Aaron Luntala; Mann, Inder Jit Singh

    Loyalty reward programs (LRPs), initially developed as marketing programs to enhance customer retention, have now become an important part of customer-focused business strategy. With the proliferation and increasing economy impact of the programs, the management complexity in the programs has also increased. However, despite widespread adoption of LRPs in business, academic research in the field seems to lag behind its practical application. Even the fundamental questions such as what LRPs are and how to classify them have not yet been fully addressed. In this paper, a comprehensive framework for LRP classification is proposed, which provides a foundation for further study of LRP design and planning issues.

  18. Impact of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) on glucose and lipid homeostasis

    DEFF Research Database (Denmark)

    Foer, D; Zhu, M; Cardone, R L

    2017-01-01

    potentially represents a target for drug discovery in type 2 diabetes and hyperlipidemia. Studies in animal models suggest a physiologic link between LRP5 and glucose and lipid homeostasis; however, whether it plays a similar role in humans is unclear. As current literature links loss-of-function LRP5...... kindreds with HBM-causing LRP5 mutations and included 9 males and 2 females. Two subjects that were being treated with insulin for type 2 diabetes were excluded from our analysis, as this would have obscured our ability to determine the impact of gain-of-function LRP5 mutations on glucose metabolism...

  19. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain-of-function mutations

    DEFF Research Database (Denmark)

    Galán-Díez, Marta; Isa, Adiba; Ponzetti, Marco;

    2016-01-01

    of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5...... patients showed normal hematopoiesis, normal percentage of myeloid cells, and lack of anemia. We conclude that Lrp5 GOF mutations do not activate β-catenin signaling in osteoblasts. As a result, myeloid lineage differentiation is normal in HBM patients and mice. This article is part of a Special Issue...

  20. Induction of the LRP16 gene by estrogen promotes the invasive growth of Ishikawa human endometrial cancer cells through the downregulation of E-cadherin

    Institute of Scientific and Technical Information of China (English)

    Yuan Guang Meng; Wei Dong Han; Ya Li Zhao; Ke Huang; Yi Ling Si; Zhi Qiang Wu; Yi Ming Mu

    2007-01-01

    LRP16 was previously identified as an estrogen-induced gene in breast cancer cells.The responsiveness of LRPl6to estrogen and its functional effects in endometrial cancer(EC)cells are still unclear.Here,we show that the mRNAlevel and promoter activity of the LRP16 gene were significantly increased by 17β-estradiol(E2)in estrogen receptorα(ERα)-positive Ishikawa human EC cells.Although the growth rate of Ishikawa cells was not obviously affected byectopic expression of LIP16,the results of a Transwell assay showed an approximate one-third increase of the invasivecapacity of LRP16-overexpressing cells.As a result of molecular screening,we observed that the expression of E-cadherin,an essential adhesion molecule associated with tumor metastasis,was repressed by LRP16.Further promoter analysesdemonstrated that LRP16 inhibited E-cadherin transactivation in a dose-dependent manner.However,the inhibition wasabolished by estrogen deprivation.indicating that the downregulation of E-cadherin transcription by LRP16 requiresERa mediation.Chromatin immunoprecipitation analyses revealed that the binding of ERa to the E-cadherin promoterwas antagonized by LRP16,suggesting that LRP16 could interfere with ERα-mediated transcription.These results sug-gest that the upregulation of LRP16 by estrogen could be involved in invasive growth by downregulating E-cadherin inhuman ECs.

  1. Dynamic repayment of mortgage loans: A solution for the low-income sector?

    Directory of Open Access Journals (Sweden)

    W.R. Gevers

    2003-12-01

    Full Text Available By using a dynamic instalment repayment plan to finance a mortgage loan rather than the usual fixed instalment financing, the threshold at which a prospective homeowner may enter the housing market may be lowered substantially. In this paper this method of financing will be evaluated to determine under which circumstances it could be used to help the low-income group to obtain housing, and also to highlight some of its deficiencies. Historic trends of income are also analysed to determine the income growth potential of the low-income sector. The income growth potential does not seem to distract from the potential of the dynamic repayment of mortgage loans.

  2. MANAGING NON-REPAYMENT RISK THROUGH GROUP-BASED LENDING IN MFIs

    OpenAIRE

    2009-01-01

    To analyze how MFIs are managing their non-repayment risk by using GBL approach. The deductive approach has been used in this study and the case study method is deployed. Khushhali Bank Limited, Pakistan has been taken for the subject MFI. The four inter-related theories have been taken into consideration, namely Portfolio, Principal-Agent, Contract and Transaction Cost Theories, to have a detailed literature review about the threat of non-repayment risk through GBL. The study chalked out a r...

  3. ANALYSIS OF INFLUENCE OF FINANCIAL SOCIAL LEARNING OPPORTUNITIES ON LOAN REPAYMENT BEHAVIOUR OF COOPERATOR BORROWERS IN ABIA STATE, NIGERIA

    Directory of Open Access Journals (Sweden)

    Christopher Ogbonna EMEROLE

    2014-12-01

    Full Text Available This study on analysis of influence of financial social learning opportunities on loan repayment behavior of cooperator borrowers was carried out in Abia State, Nigeria. It was the objectives of the study to relate social learning financial opportunities in cooperative societies and member borrowers budgeting and timely repayment of loans; and determine demographic, social learning and financial factors that influenced loan repayment by cooperator borrowers. Two-stage random sampling technique was used in selecting first, two of the three agricultural zones; and second two registered farmers’ multi-purpose agricultural cooperative societies. This was followed by purposive selection from registers of the chosen cooperative societies sixty cooperators who currently were repaying loans borrowed. Descriptive and inferential statistical techniques were used in analyzing the gathered cross sectional data. Results suggest important relationships between financial social learning opportunities in cooperative societies and borrowers’ budgeting and timely loan repayment behaviours. Attendance to meetings, discussions with fellow cooperators and meaningful observation on financial behaviour of members of cooperative societies had significant positive influences on conduct and performance loan beneficiaries. The number of times beneficiaries attended meeting since after loan(s were received; number of times they discussed loan matters with members before loan(s were received; and number of times they discussed loan repayment strategies with other cooperators after loans were received had positive influences on loan repayment behaviour of cooperator borrowers. Cooperator(s should participate in all union activities to truly belong and reap the benefits of being a member

  4. The Sulfolobus solfataricus Lrp-like protein LysM regulates lysine biosynthesis in response to lysine availability.

    Science.gov (United States)

    Brinkman, Arie B; Bell, Stephen D; Lebbink, Robert Jan; de Vos, Willem M; van der Oost, John

    2002-08-16

    Although the archaeal transcription apparatus resembles the eukaryal RNA polymerase II system, many bacterial-like regulators can be found in archaea. Particularly, all archaeal genomes sequenced to date contain genes encoding homologues of Lrp (leucine-responsive regulatory protein). Whereas Lrp-like proteins in bacteria are involved in regulation of amino acid metabolism, their physiological role in archaea is unknown. Although several archaeal Lrp-like proteins have been characterized recently, no target genes apart from their own coding genes have been discovered yet, and no ligands for these regulators have been identified so far. In this study, we show that the Lrp-like protein LysM from Sulfolobus solfataricus is involved in the regulation of lysine and possibly also arginine biosynthesis, encoded by the lys gene cluster. Exogenous lysine is the regulatory signal for lys gene expression and specifically serves as a ligand for LysM by altering its DNA binding affinity. LysM binds directly upstream of the TFB-responsive element of the intrinsically weak lysW promoter, and DNA binding is favored in the absence of lysine, when lysWXJK transcription is maximal. The combined in vivo and in vitro data are most compatible with a model in which the bacterial-like LysM activates the eukarya-like transcriptional machinery. As with transcriptional activation by Escherichia coli Lrp, activation by LysM is apparently dependent on a co-activator, which remains to be identified.

  5. 12 CFR 725.20 - Repayment, security and credit reporting agreements; other terms and conditions.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Repayment, security and credit reporting agreements; other terms and conditions. 725.20 Section 725.20 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS NATIONAL CREDIT UNION ADMINISTRATION CENTRAL...

  6. 76 FR 60527 - Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

    Science.gov (United States)

    2011-09-29

    ... Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract... region in the SUPPLEMENTARY INFORMATION section. FOR FURTHER INFORMATION CONTACT: Michelle Kelly, Water... for the delivery of project water for authorized uses in newspapers of general circulation in...

  7. 76 FR 44948 - Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

    Science.gov (United States)

    2011-07-27

    ...] [FR Doc No: 2011-18980] DEPARTMENT OF THE INTERIOR Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract Actions AGENCY: Bureau of Reclamation, Interior... Kelly, Water and Environmental Services Division, Bureau of Reclamation, P.O. Box 25007,...

  8. 76 FR 73674 - Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

    Science.gov (United States)

    2011-11-29

    ... Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract... region in the SUPPLEMENTARY INFORMATION section. FOR FURTHER INFORMATION CONTACT: Michelle Kelly, Water... for the delivery of project water for authorized uses in newspapers of general circulation in...

  9. Gender Issues in Microfinance and Repayment Performance: The Case of a Nicaraguan Microfinance Institution

    Directory of Open Access Journals (Sweden)

    Jimmy A. Saravia-Matus

    2012-04-01

    Full Text Available Conventional wisdom and increasing empirical evidence in microfinance hold that women are better risks than men. In the present work, a logit model ontrolling for a range of borrower and loan characteristics was carried out to assess the validity of this statement by comparing repayment rates. The study includes a sample of loans disbursed by a Nicaraguan microfinance institution during the years 2003-2004, a period characterized by high oil prices. A dichotomous dependent variable is created,taking the value of 1 if the credit turned out to be of the best quality i.e. an “A” credit by Nicaraguan regulations, and 0 otherwise. The dependent variable is regressed on variables summarizing the characteristics of the borrower and the loan to investigate the impact of gender on repayment performance. The results provide significant evidence that female client’s repayment performance is in fact better than that of male’s at the conventional levels of statistical significance. However, the results also show that the perceived difference in gender risk is lower than what popular wisdom would suggest when borrower characteristics and other exogenous economic variables are taken into account. With the present sample, we conclude that other characteristics of the borrower as well as changes in the economic environment can have a similar or larger impact on risk than gender when it comes to repayment performance.

  10. Entrepreneurial and business skills and loan repayment rates of microfinance clients in Ghana

    NARCIS (Netherlands)

    Agbeko, Daniel; Block, Vincent; Omta, Onno; Velde, van der G.

    2016-01-01

    Entrepreneurial and business skills are generally considered key to microbusiness success, hence to Microfinance Institution (MFI) clients’ loan repayment as well. However, empirical evidence is largely lacking, and where present, it is inconclusive on the importance of these skills for microfinance

  11. AHP 28: Too Much Loving-Kindness to Repay: Funeral Speeches of the Wenquan Pumi

    Directory of Open Access Journals (Sweden)

    Gerong Pincuo (kɛ́izoŋ pʰiŋtsʰu

    2013-12-01

    Full Text Available Two Pumi funeral speech rituals of the Wenquan Pumi area in northwestern Yunnan Province illustrate the traditional genre of speeches through their use of metaphor and parallellism. The speeches express the central concept of giving and repaying that plays an important role in strengthening social cohesion among Pumi relatives.

  12. 34 CFR 535.51 - What are the requirements for repayment of the fellowship?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What are the requirements for repayment of the fellowship? 535.51 Section 535.51 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF BILINGUAL EDUCATION AND MINORITY LANGUAGES AFFAIRS, DEPARTMENT OF EDUCATION...

  13. 34 CFR 535.55 - What is the length of the deferment of repayment?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What is the length of the deferment of repayment? 535.55 Section 535.55 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF BILINGUAL EDUCATION AND MINORITY LANGUAGES AFFAIRS, DEPARTMENT OF EDUCATION BILINGUAL...

  14. 34 CFR 535.56 - Under what circumstances is repayment waived?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Under what circumstances is repayment waived? 535.56 Section 535.56 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF BILINGUAL EDUCATION AND MINORITY LANGUAGES AFFAIRS, DEPARTMENT OF EDUCATION BILINGUAL EDUCATION:...

  15. 34 CFR 535.54 - Under what circumstances is repayment deferred?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Under what circumstances is repayment deferred? 535.54 Section 535.54 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF BILINGUAL EDUCATION AND MINORITY LANGUAGES AFFAIRS, DEPARTMENT OF EDUCATION BILINGUAL EDUCATION:...

  16. 12 CFR Appendix M2 to Part 226 - Actual Repayment Disclosures

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Actual Repayment Disclosures M2 Appendix M2 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... nearest whole year if the estimate contains a fractional year less than 0.5, and rounded up to the...

  17. 12 CFR Appendix M1 to Part 226 - Generic Repayment Estimates

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Generic Repayment Estimates M1 Appendix M1 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... rounded down to the nearest whole year if the estimate contains a fractional year less than 0.5,...

  18. 7 CFR 1703.309 - Terms of repayment of deferred loan payments.

    Science.gov (United States)

    2010-01-01

    ... deferment payment required. (e) The balance in a borrower's cushion of credit account shall not be reduced by the borrower below the level of the unpaid balance of the payment deferred. ... 7 Agriculture 11 2010-01-01 2010-01-01 false Terms of repayment of deferred loan payments. 1703...

  19. 42 CFR 57.312 - Repayment of loans for service in a shortage area.

    Science.gov (United States)

    2010-10-01

    ... migrant health center, a community health center, a nursing facility, a rural health clinic, or in a... 42 Public Health 1 2010-10-01 2010-10-01 false Repayment of loans for service in a shortage area. 57.312 Section 57.312 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN...

  20. 46 CFR 276.1 - Partial repayment-incidental domestic trading.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Partial repayment-incidental domestic trading. 276.1 Section 276.1 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING...—incidental domestic trading. In every instance where a vessel, with respect to which a...

  1. ANALYSIS OF MODELS OF EARLY DEBT REPAYMENT IN THE Generalized CREDIT TRANSACTIONS

    Directory of Open Access Journals (Sweden)

    2016-01-01

    Full Text Available This paper analyzes the patterns of early repayment in multi-period credit transactions. Considered one of the most common ways of conversion of unpaid interest for early repayment, so-called 78 rule. The relationship of this rule with the linear approximation of the exact value; redeemable debt is determined. The analysis of the maximum excess payment of interest on 78 rule. It has been shown how interest payment on 78 rule depended on the time of early repayment. Early repayment of debt is an agreement under which the borrower pays to the lender amount of money equal to the current balance (as of loan account. Then further regular payments cease and the contract terminates. However, the amount of outstanding debt is determined by the structure of prescription charges. So in the uniform schemes of repayment of consumer credit each payment contains the same part of principal amounts and the total interest. In case of early repayment the Bank loses a significant fraction of the expected interest payments. Therefore, in practice, often used so-called accelerated schemes of interest payments. One of them is 78 rule. Use the 78 rule is simple and straightforward. The name of the rule is due to the fact that the sum of the numbers 12 monthly payments is 78. In the schemes of consumer loan with a term of one year interest payment for the current month is equal to m/78 of the total amount of interest payments, where m is the number of remaining payments. The rule name is stored and in the more general case with an arbitrary number of payments. In general interest payment is determined by the relative weight of the total amount of interest in each payment. In uniform schemes it is constant. In accelerated with a particular speed decreases. Therefore, additional cash expenses by the 78 rule may be considered as additional penalties for early repayment of the debt. It this article is shown how this penalty depends on time before maturity. It is shown that

  2. Genetic Variants in LRP1 and ULK4 Are Associated with Acute Aortic Dissections.

    Science.gov (United States)

    Guo, Dong-Chuan; Grove, Megan L; Prakash, Siddharth K; Eriksson, Per; Hostetler, Ellen M; LeMaire, Scott A; Body, Simon C; Shalhub, Sherene; Estrera, Anthony L; Safi, Hazim J; Regalado, Ellen S; Zhou, Wei; Mathis, Michael R; Eagle, Kim A; Yang, Bo; Willer, Cristen J; Boerwinkle, Eric; Milewicz, Dianna M

    2016-09-01

    Acute aortic dissections are a preventable cause of sudden death if individuals at risk are identified and surgically repaired in a non-emergency setting. Although mutations in single genes can be used to identify at-risk individuals, the majority of dissection case subjects do not have evidence of a single gene disorder, but rather have the other major risk factor for dissections, hypertension. Initial genome-wide association studies (GWASs) identified SNPs at the FBN1 locus associated with both thoracic aortic aneurysms and dissections. Here, we used the Illumina HumanExome array to genotype 753 individuals of European descent presenting specifically with non-familial, sporadic thoracic aortic dissection (STAD) and compared them to the genotypes of 2,259 control subjects from the Atherosclerosis Risk in Communities (ARIC) study matched for age, gender, and, for the majority of cases, hypertension. SNPs in FBN1, LRP1, and ULK4 were identified to be significantly associated with STAD, and these results were replicated in two independent cohorts. Combining the data from all cohorts confirmed an inverse association between LRP1 rs11172113 and STAD (p = 2.74 × 10(-8); OR = 0.82, 95% CI = 0.76-0.89) and a direct association between ULK4 rs2272007 and STAD (p = 1.15 × 10(-9); OR = 1.35, 95% CI = 1.23-1.49). Genomic copy-number variation analysis independently confirmed that ULK4 deletions were significantly associated with development of thoracic aortic disease. These results indicate that genetic variations in LRP1 and ULK4 contribute to risk for presenting with an acute aortic dissection.

  3. Expression of multidrug resistance proteins, P-gp, MRP1 and LRP, in soft tissue sarcomas analysed according to their histological type and grade.

    NARCIS (Netherlands)

    Komdeur, R; Plaat, BE; Graaf, van der WT; Hoekstra, H.J.; Hollema, H; Berg, van den E; Zwart, N; Scheper, R.J.; Molenaar, W.M.

    2003-01-01

    0.0001). P-gp expression was most pronounced in malignant fibrous histiocytoma (MFH), but was low in leiomyosarcomas. MRP1 was expressed in most malignant peripheral nerve sheath tumours (MPNST). LRP was strongly expressed in MFH and unspecified sarcomas, but was low in liposarcomas. MRP1 and LRP ex

  4. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2

    DEFF Research Database (Denmark)

    Kozlova, Nina; Jensen, Jan Kristian; Chi, Tabughang Franklin

    2015-01-01

    Plasminogen activator inhibitor-1 (PAI-1) is the major and most specific acting urokinase (uPA) and tissue plasminogen activator (tPA) inhibitor. Apart from its function in the fibrinolytic system, PAI-1 was also found to contribute to processes like tissue remodelling, angiogenesis, and tumour...... progression. However, the role of PAI-1 in those processes remains largely controversial with respect to the influence of PAI-1 on cell signalling pathways. Although PAI-1 does not possess its own cellular receptor, it can be bound to low-density lipoprotein receptor-related protein 1 (LRP1) which...... was proposed to modulate the β-catenin pathway. Therefore, we used wild-type mouse embryonic fibroblasts (MEFs), and MEFs deficient of LRP1 to study PAI-1 as modulator of the β-catenin pathway. We found that PAI-1 influences MEF proliferation and motility in a LRP1-dependent manner and that β...

  5. Endocytic receptor LRP2/megalin-of holoprosencephaly and renal Fanconi syndrome.

    Science.gov (United States)

    Willnow, Thomas E; Christ, Annabel

    2017-08-01

    Megalin (or LRP2) is an endocytic receptor that plays a central role in embryonic development and adult tissue homeostasis. Loss of this receptor in congenital or acquired diseases results in multiple organ dysfunctions, including forebrain malformation (holoprosencephaly) and renal reabsorption defects (renal Fanconi syndrome). Here, we describe current concepts of the mode of receptor action that include co-receptors and a repertoire of different ligands, and we discuss how these interactions govern functional integrity of the kidney and the brain, and cause disease when defective.

  6. Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Taddei Kevin

    2010-01-01

    Full Text Available Abstract Background The low-density lipoprotein receptor related protein 1 (LRP1 has been implicated in Alzheimer's disease (AD but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1. Results We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP, which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b. Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression. Conclusions These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered

  7. Relationship between LRP6 polymorphisms and sudden cardiac death in patients with chronic heart failure in Chinese han population

    Institute of Scientific and Technical Information of China (English)

    GUO Qi; CHU Jian-min; REN Lan; CHEN Xu-hua; PU Jie-lin; ZHANG Shu

    2016-01-01

    AIM:Chronic heart failure (CHF), caused by ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM), is among the leading causes of mortality and morbidity worldwide .Low-density lipoprotein receptor-related protein 6 (LRP6) plays a criti-cal role in regulating Wnt signaling .Dysregulated Wnt signaling contributes to high incidence of arrhythmias .Thus, there might be an association between genetic variations of LRP6 and sudden cardiac death ( SCD) .The objective of the study was to examine the associ-ation between common variants of LRP6 and prognosis of CHF patients .METHODS:From July 2005 to December 2009, patients with CHF referred from 10 hospitals and participants without structural heart disease in China were undergone a prospective study .The sin-gle-nucleotide polymorphism rs 2302684 was selected to evaluate the effect of LRP6 polymorphisms on the survival of the patients .RE-SULTS:A total of 1 887 patients (1 437 with CHF and 450 in the control group)were finally enrolled for the analysis.During a medi-an follow-up of 61 months, a total of 546 (38.00%) patients died, including 201(36.81%) cases with SCD and 345 (63.19%) ca-ses with NSCD.No end point event occurred in the control group .Patients carrying A allele of rs2302684 had increased risks of all-cause death (PA in LRP6 is associated with an increased risk of all-cause death and SCD in patients with CHF in Chinese Han population , and the association is more prevalent in patients with CHF caused by ICM.Thus, LRP6 might be added as a novel predictor of SCD and could provide an attractive and direct therapeutic target in SCD prevention .

  8. An LRP5 receptor with internal deletion in hyperparathyroid tumors with implications for deregulated WNT/beta-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Peyman Björklund

    2007-11-01

    Full Text Available BACKGROUND: Hyperparathyroidism (HPT is a common endocrine disorder with incompletely understood etiology, characterized by enlarged hyperactive parathyroid glands and increased serum concentrations of parathyroid hormone and ionized calcium. We have recently reported activation of the Wnt signaling pathway by accumulation of beta-catenin in all analyzed parathyroid tumors from patients with primary HPT (pHPT and in hyperplastic parathyroid glands from patients with uremia secondary to HPT (sHPT. Mechanisms that may account for this activation have not been identified, except for a few cases of beta-catenin (CTNNB1 stabilizing mutation in pHPT tumors. METHODS AND FINDINGS: Reverse transcription PCR and Western blot analysis showed expression of an aberrantly spliced internally truncated WNT coreceptor low-density lipoprotein receptor-related protein 5 (LRP5 in 32 out of 37 pHPT tumors (86% and 20 out of 20 sHPT tumors (100%. Stabilizing mutation of CTNNB1 and expression of the internally truncated LRP5 receptor was mutually exclusive. Expression of the truncated LRP5 receptor was required to maintain the nonphosphorylated active beta-catenin level, transcription activity of beta-catenin, MYC expression, parathyroid cell growth in vitro, and parathyroid tumor growth in a xenograft severe combined immunodeficiency (SCID mouse model. WNT3 ligand and the internally truncated LRP5 receptor strongly activated transcription, and the internally truncated LRP5 receptor was insensitive to inhibition by DKK1. CONCLUSIONS: The internally truncated LRP5 receptor is strongly implicated in deregulated activation of the WNT/beta-catenin signaling pathway in hyperparathyroid tumors, and presents a potential target for therapeutic intervention.

  9. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2.

    Science.gov (United States)

    Kozlova, Nina; Jensen, Jan K; Chi, Tabughang Franklin; Samoylenko, Anatoly; Kietzmann, Thomas

    2015-05-01

    Plasminogen activator inhibitor-1 (PAI-1) is the major and most specific acting urokinase (uPA) and tissue plasminogen activator (tPA) inhibitor. Apart from its function in the fibrinolytic system, PAI-1 was also found to contribute to processes like tissue remodelling, angiogenesis, and tumour progression. However, the role of PAI-1 in those processes remains largely controversial with respect to the influence of PAI-1 on cell signalling pathways. Although PAI-1 does not possess its own cellular receptor, it can be bound to low-density lipoprotein receptor-related protein 1 (LRP1) which was proposed to modulate the β-catenin pathway. Therefore, we used wild-type mouse embryonic fibroblasts (MEFs), and MEFs deficient of LRP1 to study PAI-1 as modulator of the β-catenin pathway. We found that PAI-1 influences MEF proliferation and motility in a LRP1-dependent manner and that β-catenin is important for that response. In addition, expression of β-catenin and β-catenin-dependent transcriptional activity were induced by PAI-1 in wild type MEFs, but not in LRP1-deficient cells. Moreover, PAI-1-induced ERK1/2 activation was more prominent in the LRP1-deficient cells and interestingly knockdown of β-catenin abolished this effect. Together, the data of the current study show that PAI-1 can promote cell migration via LRP1-dependent activation of the β-catenin and ERK1/2 MAPK pathway which may be important in stage-specific treatment of human diseases associated with high PAI-1 levels.

  10. Prioritization of Factors Affecting the Delay or Inability to Repay Bank Facilities to Farmers

    Directory of Open Access Journals (Sweden)

    B. Maadanian

    2016-03-01

    Full Text Available Introduction: The role of credits in agricultural development is very important, especially after implementing land reform and converting subjects to a large class of small owners, the demand has been intensified. Seasonality of agricultural productions usually creates temporary vacuum among farmers payments and receipts, thus farmers need to save their previous incomes or seek financial help out of the sector in order to pay current expenses and investments in agriculture sector. Due to farmers low income, the saving possibility is low and therefore farmers are not in a situation that they can invest in agriculture sector from their savings or to purchase required inputs Materials and Methods: The aim of this study was to prioritize the factors affecting the delay and lack in repaying loans, therefore at first it should identify the payment factors. This means that one should find what factors are affecting the lack or delay in repayment of loans granted to farmers. So the factors affecting the delay or failure to repay the loans were identified by using the Delphi method and then prioritizing the factors will be discussed with regard to experts perspectives by using the analytical network process model. Analytical network process (ANP is one of the most efficient techniques for decision making with multiple criteria that it was proposed by Thomas Almaty for the first time in 1982 and as the developed form of AHP method. In cases where lower levels affect the upper levels or elements in a same level are not independent of each other, AHP method cannot be used. ANP technique is a more general form of AHP, but it does not require the hierarchical structure and therefore it show more complex relationships between different levels of decision in network form and it considers the interactions and feedbacks between criteria and alternatives. In fact the main objective of this process is to determine the overall impact of all factors in the face

  11. LRP-1-mediated intracellular antibody delivery to the Central Nervous System

    Science.gov (United States)

    Tian, Xiaohe; Nyberg, Sophie; S. Sharp, Paul; Madsen, Jeppe; Daneshpour, Nooshin; Armes, Steven P.; Berwick, Jason; Azzouz, Mimoun; Shaw, Pamela; Abbott, N. Joan; Battaglia, Giuseppe

    2015-07-01

    The blood-brain barrier (BBB) is by far the most important target in developing new approaches to improve delivery of drugs and diagnostic tools into the Central Nervous System (CNS). Here we report the engineering of pH- sensitive polymersomes (synthetic vesicles formed by amphiphilic copolymers) that exploit endogenous transport mechanisms to traverse the BBB, enabling delivery of large macromolecules into both the CNS parenchyma and CNS cells. We achieve this by targeting the Low Density Lipoprotein Receptor-Related Protein 1 (LRP-1) receptor. We show that LRP-1 is associated with endothelial transcytosis that does not involve acidification of cargo in membrane-trafficking organelles. By contrast, this receptor is also associated with traditional endocytosis in CNS cells, thus aiding the delivery of relevant cargo within their cytosol. We prove this using IgG as a model cargo, thus demonstrating that the combination of appropriate targeting combined with pH-sensitive polymersomes enables the efficient delivery of macromolecules into CNS cells.

  12. Gateway技术构建转基因重组质粒pRP.EX3d-EF1A-LRP16-His-IRES-eGFP%Application of gateway technology in construction of recombinant transgenic vector pRP. EX3d-EF1A-LRP16-His-IRES-eGFP

    Institute of Scientific and Technical Information of China (English)

    柏苗苗; 王春萌; 伍志强; 梅倩; 李小雷; 李祥; 赵亚力; 韩为东

    2014-01-01

    Objective To lay the foundation for establishing transgenic mice by constructing recombinant transgenic vector pRP. EX3d-EF1A-LRP16-His-IRES-eGFP. Methods The attB1- LRP16-His-attB2 was amplified by overlap PCR. The LRP16 gene was cloned into pDown vector via BP reaction and transmitted into pRP.EX3d vector via LR reaction with pDown-LRP16-His, pUp-EF1A, pTail-IRES-eGFP and PRP. Des3d. The recombinant plasmid was transformed into Stbl3 cells and screened using the ampicillin (AMP) resistance gene. Positive clones were confirmed by PCR and DNA sequencing, respectively. Results Sequencing and restriction endonuclease showed that the recombinant vector pRP.EX3d-EF1A-LRP16-His-IRES-eGFP was successfully constructed. Conclusion The successfully constructed recombinant vector pRP.EX3d-EF1A-LRP16-His-IRES-eGFP can be used in establishing LRP16 transgenic mice.%目的:构建转基因重组质粒pRP.EX3d-EF1A-LRP16-His-IRES-eGFP,为转基因鼠的建立奠定基础。方法利用重叠PCR技术扩增attB1-LRP16-His-attB2,经BP反应,将LRP16基因插入到载体pDown上,pUp-EF1A、pDown-LRP16-His、pTail-IRES-eGFP和PRP.Des3d经LR反应,将LRP16转移到pRP.EX3d上,转化Stbl3细胞,用氨苄西林进行抗性筛选,经PCR鉴定后将阳性克隆送测序。结果测序及酶切结果验证获得正确的pRP.EX3d-EF1A-LRP16-His-IRES-eGFP重组质粒。结论成功构建pRP.EX3d-EF1A-LRP16-His-IRES-eGFP重组质粒,可用于下一步LRP16转基因小鼠的构建。

  13. Triglyceride-rich lipoprotein metabolism in unique VLDL receptor, LDL receptor, and LRP triple-deficient mice

    NARCIS (Netherlands)

    Espirito Santo, S.M.S.; Rensen, P.C.N.; Goudriaan, J.R.; Bensadoun, A.; Bovenschen, N.; Voshol, P.J.; Havekes, L.M.; Vlijmen, B.J.M. van

    2005-01-01

    The very low density lipoprotein receptor (VLDLR), low density lipoprotein receptor (LDLR), and low density lipoprotein receptor-related protein (LRP) are the three main apolipoprotein E-recognizing endocytic receptors involved in the clearance of triglyceride (TG)-rich lipoproteins from plasma.

  14. Expression of LRP1 by human osteoblasts: a mechanism for the delivery of lipoproteins and vitamin K1 to bone

    DEFF Research Database (Denmark)

    Niemeier, Andreas; Kassem, Moustapha; Toedter, Klaus

    2005-01-01

    Accumulating clinical and experimental data show the importance of dietary lipids and lipophilic vitamins, such as vitamin K1, for bone formation. The molecular mechanism of how they enter the osteoblast is unknown. Here we describe the expression of the multifunctional LRP1 by human osteoblasts...

  15. The Sulfolobus solfataricus Lrp-like protein LysM regulates lysine biosynthesis in response to lysine availability

    NARCIS (Netherlands)

    Brinkman, A.B.; Bell, S.D.; Lebbink, R.J.; Vos, de W.M.; Oost, van der J.

    2002-01-01

    Although the archaeal transcription apparatus resembles the eukaryal RNA polymerase II system, many bacterial-like regulators can be found in archaea. Particularly, all archaeal genomes sequenced to date contain genes encoding homologues of Lrp (leucine-responsive regulatory protein). Whereas

  16. PAI-1 modulates cell migration in a LRP1-dependent manner via β-catenin and ERK1/2

    DEFF Research Database (Denmark)

    Kozlova, Nina; Jensen, Jan Kristian; Chi, Tabughang Franklin

    2015-01-01

    of β-catenin abolished this effect. Together, the data of the current study show that PAI-1 can promote cell migration via LRP1-dependent activation of the β-catenin and ERK1/2 MAPK pathway which may be important in stage-specific treatment of human diseases associated with high PAI-1 levels....

  17. The Global Regulators Lrp, LeuO, and HexA Control Secondary Metabolism in Entomopathogenic Bacteria.

    Science.gov (United States)

    Engel, Yvonne; Windhorst, Carina; Lu, Xiaojun; Goodrich-Blair, Heidi; Bode, Helge B

    2017-01-01

    Photorhabdus luminescens TTO1 and Xenorhabdus nematophila HGB081 are insect pathogenic bacteria and producers of various structurally diverse bioactive natural products. In these entomopathogenic bacteria we investigated the role of the global regulators Lrp, LeuO, and HexA in the production of natural products. Lrp is a general activator of natural product biosynthesis in X. nematophila and for most compounds in TTO1. Microarray analysis confirmed these results in X. nematophila and enabled the identification of additional biosynthesis gene clusters (BGC) regulated by Lrp. Moreover, when promoters of two X. nematophila BGC were analyzed, transcriptional activation by Lrp was observed. In contrast, LeuO in X. nematophila and P. luminescens has both repressing and activating features, depending on the natural product examined. Furthermore, heterologous overexpression of leuO from X. nematophila in the closely related Xenorhabdus szentirmaii resulted in overproduction of several natural products including novel compounds. The presented findings could be of importance for establishing a tool for overproduction of secondary metabolites and subsequent identification of novel compounds.

  18. LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

    Directory of Open Access Journals (Sweden)

    Timo Grimmer

    2014-01-01

    Discussion: In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD.

  19. Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2

    DEFF Research Database (Denmark)

    Johanns, Manuel; Lemoine, Pascale; Janssens, Virginie

    2017-01-01

    Matrix metalloproteinases (MMPs) are regulated at multiple transcriptional and post-transcriptional levels, among which receptor-mediated endocytic clearance. We previously showed that low-density lipoprotein receptor-related protein-1 (LRP-1) mediates the clearance of a complex between the zymogen...

  20. Survey and Thought on Graduates’ Repayment Awareness of Student Loan in Agricultural Universities and Colleges

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    To find out graduates’ repayment awareness of student loan,we conducted a questionnaire survey for those graduates who applied for student loan in Zhongkai University of Agriculture and Engineering.The survey has following results.First,the national student loan plays an important role in assisting poor students in finishing their study.Second,graduates value social function of personal credit.Third,trustworthiness education activities carried out by colleges and universities are effective.Fourth,economic income is a major factor of graduates repaying capital with interest.Fifth,bank’s student loan management system is not perfect.Sixth,the national student loan system remains to be improved.In line with these results,we put forward five countermeasures and suggestions:strengthen the trustworthiness education of students;standardize the credit investigation management of students’ personal credit;establish student information management mechanism;standardize banks’ payment reminder administration behavior;and perfect national student loan system.

  1. Lrp of Corynebacterium glutamicum controls expression of the brnFE operon encoding the export system for L-methionine and branched-chain amino acids.

    Science.gov (United States)

    Lange, Christian; Mustafi, Nurije; Frunzke, Julia; Kennerknecht, Nicole; Wessel, Mirja; Bott, Michael; Wendisch, Volker F

    2012-04-30

    Corynebacterium glutamicum possesses export systems for various amino acids including BrnFE, a two-component export system for L-methionine and the branched-chain amino acids L-valine, L-isoleucine and L-leucine. A gene for a putative transcriptional regulator of the Lrp family is transcribed divergently to the brnFE operon and is required for L-isoleucine export. By comparing global gene expression changes due to L-isoleucine addition we revealed increased brnFE expression in response to L-isoleucine in C. glutamicum wild type but not in an lrp deletion mutant. ChIP-to-chip analysis, band shift experiments and DNAse footprint analysis demonstrated that Lrp binds to the intergenic region between lrp and brnF. Expression analysis of transcriptional fusions with the lrp and brnFE promoters indicated that branched-chain amino acids and L-methionine when added to the growth medium stimulated brnFE expression in the order L-leucine > L-methionine > L-isoleucine > L-valine and that Lrp was required for activation of brnFE expression. Thus, regulation of brnFE by Lrp ensures that BrnFE is synthesized only if its substrate amino acids accumulate in cells which is commensurate with its role to counteract such situations of metabolic imbalance.

  2. Missense Mutations in LRP5 Associated with High Bone Mass Protect the Mouse Skeleton from Disuse- and Ovariectomy-Induced Osteopenia

    Science.gov (United States)

    Niziolek, Paul J.; Bullock, Whitney; Warman, Matthew L.; Robling, Alexander G.

    2015-01-01

    The low density lipoprotein receptor-related protein-5 (LRP5), a co-receptor in the Wnt signaling pathway, modulates bone mass in humans and in mice. Lrp5 knock-out mice have severely impaired responsiveness to mechanical stimulation whereas Lrp5 gain-of-function knock-in and transgenic mice have enhanced responsiveness to mechanical stimulation. Those observations highlight the importance of Lrp5 protein in bone cell mechanotransduction. It is unclear if and how high bone mass-causing (HBM) point mutations in Lrp5 alter the bone-wasting effects of mechanical disuse. To address this issue we explored the skeletal effects of mechanical disuse using two models, tail suspension and Botulinum toxin-induced muscle paralysis, in two different Lrp5 HBM knock-in mouse models. A separate experiment employing estrogen withdrawal-induced bone loss by ovariectomy was also conducted as a control. Both disuse stimuli induced significant bone loss in WT mice, but Lrp5 A214V and G171V were partially or fully protected from the bone loss that normally results from disuse. Trabecular bone parameters among HBM mice were significantly affected by disuse in both models, but these data are consistent with DEXA data showing a failure to continue growing in HBM mice, rather than a loss of pre-existing bone. Ovariectomy in Lrp5 HBM mice resulted in similar protection from catabolism as was observed for the disuse experiments. In conclusion, the Lrp5 HBM alleles offer significant protection from the resorptive effects of disuse and from estrogen withdrawal, and consequently, present a potential mechanism to mimic with pharmaceutical intervention to protect against various bone-wasting stimuli. PMID:26554834

  3. Missense Mutations in LRP5 Associated with High Bone Mass Protect the Mouse Skeleton from Disuse- and Ovariectomy-Induced Osteopenia.

    Science.gov (United States)

    Niziolek, Paul J; Bullock, Whitney; Warman, Matthew L; Robling, Alexander G

    2015-01-01

    The low density lipoprotein receptor-related protein-5 (LRP5), a co-receptor in the Wnt signaling pathway, modulates bone mass in humans and in mice. Lrp5 knock-out mice have severely impaired responsiveness to mechanical stimulation whereas Lrp5 gain-of-function knock-in and transgenic mice have enhanced responsiveness to mechanical stimulation. Those observations highlight the importance of Lrp5 protein in bone cell mechanotransduction. It is unclear if and how high bone mass-causing (HBM) point mutations in Lrp5 alter the bone-wasting effects of mechanical disuse. To address this issue we explored the skeletal effects of mechanical disuse using two models, tail suspension and Botulinum toxin-induced muscle paralysis, in two different Lrp5 HBM knock-in mouse models. A separate experiment employing estrogen withdrawal-induced bone loss by ovariectomy was also conducted as a control. Both disuse stimuli induced significant bone loss in WT mice, but Lrp5 A214V and G171V were partially or fully protected from the bone loss that normally results from disuse. Trabecular bone parameters among HBM mice were significantly affected by disuse in both models, but these data are consistent with DEXA data showing a failure to continue growing in HBM mice, rather than a loss of pre-existing bone. Ovariectomy in Lrp5 HBM mice resulted in similar protection from catabolism as was observed for the disuse experiments. In conclusion, the Lrp5 HBM alleles offer significant protection from the resorptive effects of disuse and from estrogen withdrawal, and consequently, present a potential mechanism to mimic with pharmaceutical intervention to protect against various bone-wasting stimuli.

  4. Strong effect of SNP rs4988300 of the LRP5 gene on bone phenotype of Caucasian postmenopausal women.

    Science.gov (United States)

    Horváth, Péter; Balla, Bernadett; Kósa, János P; Tóbiás, Bálint; Szili, Balázs; Kirschner, Gyöngyi; Győri, Gabriella; Kató, Karina; Lakatos, Péter; Takács, István

    2016-01-01

    The purpose of this study was to identify relationships between single nucleotide polymorphisms (SNPs) in the genes of the Wnt pathway and bone mineral density (BMD) of postmenopausal women. We chose this pathway due to its importance in bone metabolism that was underlined in several studies. DNA samples of 932 Hungarian postmenopausal women were studied. First, their BMD values at different sites (spine, total hip) were measured, using a Lunar Prodigy DXA scanner. Thereafter, T-score values and the patients' body mass indices (BMIs) were calculated, while information about the fracture history of the sample population was also collected. We genotyped nine SNPs of the following three genes: LRP5, GPR177, and SP7, using a Sequenom MassARRAY Analyzer 4 instrument. The genomic DNA samples used for genotyping were extracted from the buccal mucosa of the subjects. Statistical analyses were carried out using the SPSS 21 and R package. The results of this analysis showed a significant association between SNP rs4988300 of the LRP5 gene and total hip BMD values. We could not reveal any associations between the markers of GPR177, SP7, and bone phenotypes. We found no effect of these genotypes on fracture risk. We could demonstrate a significant gene-gene interaction between two SNPs of LRP5 (rs4988300 and rs634008, p = 0.009) which was lost after Bonferroni correction. We could firmly demonstrate a significant association between rs4988300 of the LRP5 gene and bone density of the hip on the largest homogeneous postmenopausal study group analyzed to date. Our finding corroborates the relationship between LRP5 genotype and bone phenotype in postmenopausal women, however, the complete mechanism of this relationship requires further investigations.

  5. Performance of Loan Repayment Determinants in Ethiopian Micro Finance - An Analysis

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    Shaik Abdul Majeeb PASHA

    2014-05-01

    Full Text Available Micro finance involves the provision of micro-credit, savings, and other services to the poor that are excluded by the commercial banks for collateral and other reasons. Microfinance is relatively new to Ethiopia and came to existence during 1994-95. Out of which Sidama Micro Finance Institution (SMFI is one among 31Micro Finance Institutions (MFIs to serve needy people in Ethiopia. Based on this researchers’ intended to study major socio- economic factors and loan related factors that determines loan repayment performance of borrowers in SMFI. In fact, the identifying and analyzing such determining factors of loan repayment rate is vital in the achievement of profitability and sustainability of MFIs. In this connection, researchers’ collected data from primary and secondary resources and analyzed by using Binary logistic model is used. Through the study 14 determinants’ are selected for evaluation, out of which 9 variables are significant and remaining insignificant are found. Based on the analysis, researchers are recommended that proper training should be provided, reasonable amount of loan which should be useful to their business. Further, more age people and well business experience people can able to repay their loan amount` timely to micro finance institution.

  6. Determinants of Repayment of Loan Beneficiaries of Micro Finance Institutions in Southeast States of Nigeria

    Directory of Open Access Journals (Sweden)

    Eugene Chukwuemeka Okorji

    2012-09-01

    Full Text Available The study investigated the loan repayment, its determinantsand socio-economic characteristics of microfinance loanbeneficiaries in the Southeast states of Nigeria. It was carriedout in three states of the five southeast states. Using a multistagesampling technique, a total of 144 loan beneficiaries in thethree segments of MFIs, namely; formal (commercial and developmentbanks; semi-formal (NGOs-MFIs and informal(ROSCAS, “Isusu” and co-operative societies were randomlyselected and interviewed in the three states. An ordinary leastsquare (OLS multiple regression analysis was carried out toisolate and examine the determinants of loan repayment fromthe respondents’ perspective. Results showed that beneficiarieshad low level of education, operated enterprises at a relativelysmall scale, had large family size and were of middle age.Further, it was found out that the majority of the respondentswere involved in farming enterprise (crop and poultry eventhough trading was the most prominent single non-farmingenterprise (trading, processing and artisanship. The result affirmedthat the informal sector respondents recorded the bestrepayment rate, followed by the respondents of semi-formaland the banks brought the rear. Outstanding among the determinantsof loan repayments from the respondents’ perspectivewere; loan size, level of education, experience, profitabilityand portfolio diversity. These, therefore deserve special attentionin loan administration of MFIs.

  7. A multi-institutional survey of newer surgery faculty on the impacts of education debt and debt repayment strategies.

    Science.gov (United States)

    Swanson, Jennifer A; Melin, M Mark; D'Cunha, Jonathan; Radosevich, David M; Farley, David R; Schmitz, Constance C

    2013-01-01

    The cost associated with becoming a physician is significant, and studies have shown that surgeons, in particular, accrue higher debts than matched controls from other specialties, and the public. These findings, along with the current era of economic turmoil, prompted our investigation into the effects of educational debt on the career, family and lifestyle choices of recently graduated surgeons. Our goal was to query young surgical faculty about the education debt carried, the burden it presents as they embark on a career, and the financial management strategies employed to pay down their debt. This study is a one-time, cross-sectional survey of regular and adjunct faculty from the University of Minnesota and the Mayo Clinic-Rochester. Participation was voluntary and responses were collected anonymously via SurveyMonkey. Respondents were sorted into two groups: those with and without education debt at the time of residency graduation. We compared these groups on a number of variables. Of the 111 respondents (111/152, 73% response rate), 69 (62.2%) carried debt at the time of graduation from residency. The median educational debt at graduation was $100,000, and surgeons with educational debt carried a significantly higher burden of consumer and total debt than those without educational debt at graduation (p revenue sources (faculty, clinical), debt repayment strategies, and overall training on financial matters early in their residency. Copyright © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  8. Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR.

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    Katia Cortese

    Full Text Available BACKGROUND: The urokinase receptor (uPAR/CD87 is highly expressed in malignant tumours. uPAR, as a GPI anchored protein, is preferentially located at the cell surface, where it interacts with its ligands urokinase (uPA and the extracellular matrix protein vitronectin, thus promoting plasmin generation, cell-matrix interactions and intracellular signalling events. Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have found that along with the ligand-induced down-regulation, uPAR also internalizes and recycles constitutively through a second pathway that is independent of LRP-1 and clathrin but shares some properties with macropinocytosis. The ligand-independent route is amiloride-sensitive, does not require uPAR partitioning into lipid rafts, is independent of the activity of small GTPases RhoA, Rac1 and Cdc42, and does not require PI3K activity. Constitutively endocytosed uPAR is found in EEA1 positive early/recycling endosomes but does not reach lysosomes in the absence of ligands. Electron microscopy analysis reveals the presence of uPAR in ruffling domains at the cell surface, in macropinosome-like vesicles and in endosomal compartments. CONCLUSIONS/SIGNIFICANCE: These results indicate that, in addition to the ligand-induced endocytosis of uPAR, efficient surface expression and membrane trafficking might also be driven by an uncommon macropinocytic mechanism coupled with rapid recycling to the cell surface.

  9. Large repayments of premium subsidies may be owed to the IRS if family income changes are not promptly reported.

    Science.gov (United States)

    Jacobs, Ken; Graham-Squire, Dave; Gould, Elise; Roby, Dylan

    2013-09-01

    Subsidies for health insurance premiums under the Affordable Care Act are refundable tax credits. They can be taken when taxes are filed or in advance, as reductions in monthly premiums that must be reconciled at tax filing. Recipients who take subsidies in advance will receive tax refunds if their subsidies were too small but will have to make repayments if their subsidies were too high. We analyzed predicted repayments and refunds for people receiving subsidies, using California as a case study. We found that many families could owe large repayments to the Internal Revenue Service at their next tax filing. If income changes were reported and credits adjusted in a timely manner throughout the tax year, the number of filers owing repayments would be reduced by 7-41 percent and the median size of repayments reduced by as much as 61 percent (depending on the level of changes reported and the method used to adjust the subsidy amounts). We recommend that the health insurance exchanges mandated by the Affordable Care Act educate consumers about how the subsidies work and the need to promptly report income changes. We also recommend that they provide tools and assistance to determine the amount of subsidies that enrollees should take in advance.

  10. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of l-alanine in Escherichia coli.

    Science.gov (United States)

    Ihara, Kohei; Sato, Kazuki; Hori, Hatsuhiro; Makino, Yumiko; Shigenobu, Shuji; Ando, Tasuke; Isogai, Emiko; Yoneyama, Hiroshi

    2017-04-01

    The alaE gene in Escherichia coli encodes an l-alanine exporter that catalyzes the active export of l-alanine using proton electrochemical potential. In our previous study, alaE expression was shown to increase in the presence of l-alanyl-l-alanine (Ala-Ala). In this study, the global regulator leucine-responsive regulatory protein (Lrp) was identified as an activator of the alaE gene. A promoter less β-galactosidase gene was fused to an alaE upstream region (240 nucleotides). Cells that were lacZ-deficient and harbored this reporter plasmid showed significant induction of β-galactosidase activity (approximately 17-fold) in the presence of 6 mM l-alanine, l-leucine, and Ala-Ala. However, a reporter plasmid possessing a smaller alaE upstream region (180 nucleotides) yielded transformants with strikingly low enzyme activity under the same conditions. In contrast, lrp-deficient cells showed almost no β-galactosidase induction, indicating that Lrp positively regulates alaE expression. We next performed an electrophoretic mobility shift assay (EMSA) and a DNase I footprinting assay using purified hexahistidine-tagged Lrp (Lrp-His). Consequently, we found that Lrp-His binds to the alaE upstream region spanning nucleotide -161 to -83 with a physiologically relevant affinity (apparent KD, 288.7 ± 83.8 nM). Furthermore, the binding affinity of Lrp-His toward its cis-element was increased by l-alanine and l-leucine, but not by Ala-Ala and d-alanine. Based on these results, we concluded that the gene expression of the alaE is regulated by Lrp in response to intracellular levels of l-alanine, which eventually leads to intracellular homeostasis of l-alanine concentrations.

  11. Foxg1-Cre Mediated Lrp2 Inactivation in the Developing Mouse Neural Retina, Ciliary and Retinal Pigment Epithelia Models Congenital High Myopia.

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    Olivier Cases

    Full Text Available Myopia is a common ocular disorder generally due to increased axial length of the eye-globe. Its extreme form high myopia (HM is a multifactorial disease leading to retinal and scleral damage, visual impairment or loss and is an important health issue. Mutations in the endocytic receptor LRP2 gene result in Donnai-Barrow (DBS and Stickler syndromes, both characterized by HM. To clearly establish the link between Lrp2 and congenital HM we inactivated Lrp2 in the mouse forebrain including the neural retina and the retinal and ciliary pigment epithelia. High resolution in vivo MRI imaging and ophthalmological analyses showed that the adult Lrp2-deficient eyes were 40% longer than the control ones mainly due to an excessive elongation of the vitreal chamber. They had an apparently normal intraocular pressure and developed chorioretinal atrophy and posterior scleral staphyloma features reminiscent of human myopic retinopathy. Immunomorphological and ultrastructural analyses showed that increased eye lengthening was first observed by post-natal day 5 (P5 and that it was accompanied by a rapid decrease of the bipolar, photoreceptor and retinal ganglion cells, and eventually the optic nerve axons. It was followed by scleral thinning and collagen fiber disorganization, essentially in the posterior pole. We conclude that the function of LRP2 in the ocular tissues is necessary for normal eye growth and that the Lrp2-deficient eyes provide a unique tool to further study human HM.

  12. Immunization with Individual Proteins of the Lrp/AsnC Family Induces Protection Against Brucella melitensis 16M Challenges in Mice

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    Xinhui eWang

    2015-10-01

    Full Text Available Brucellosis is one of the most common zoonoses worldwide. Subunit vaccines are promising for the prevention of human brucellosis. In our previous protective antigen screening studies, we identified a new protective antigen, BMEI0357, which belongs to the Lrp/asnC protein family, a conserved transcriptional regulator in bacteria that is absent in eukaryotes. In the present study, the Brucella genome annotation was screened and a total of 6 proteins were identified as members of the Lrp/AsnC family. Lrp/AsnC proteins have 2 domains that are conserved among the family members. However, sequence similarities between these proteins ranged from 9% to 50%, indicating high sequence heterogeneity. To test whether proteins of this family have similar characteristics, all 6 proteins were cloned and expressed in Escherichia coli. The recombinant proteins were purified and their protective efficacy was evaluated in BALB/c mice challenged with Brucella melitensis 16M. The results show that all 6 Lrp/AsnC proteins could induce a protective immune response against Brucella melitensis 16M. Antibodies against the Lrp/AsnC proteins were detected in the immunized mice. However, levels of antibodies against these proteins were relatively variable in human brucellosis sera. Taken together, our results show that these 6 proteins of the Lrp/AsnC family in Brucella could induce protective immune responses in mice.

  13. Foxg1-Cre Mediated Lrp2 Inactivation in the Developing Mouse Neural Retina, Ciliary and Retinal Pigment Epithelia Models Congenital High Myopia

    Science.gov (United States)

    Obry, Antoine; Santin, Mathieu D.; Ben-Yacoub, Sirine; Pâques, Michel; Amsellem-Levera, Sabine; Bribian, Ana; Simonutti, Manuel; Augustin, Sébastien; Debeir, Thomas; Sahel, José Alain; Christ, Annabel; de Castro, Fernando; Lehéricy, Stéphane; Cosette, Pascal; Kozyraki, Renata

    2015-01-01

    Myopia is a common ocular disorder generally due to increased axial length of the eye-globe. Its extreme form high myopia (HM) is a multifactorial disease leading to retinal and scleral damage, visual impairment or loss and is an important health issue. Mutations in the endocytic receptor LRP2 gene result in Donnai-Barrow (DBS) and Stickler syndromes, both characterized by HM. To clearly establish the link between Lrp2 and congenital HM we inactivated Lrp2 in the mouse forebrain including the neural retina and the retinal and ciliary pigment epithelia. High resolution in vivo MRI imaging and ophthalmological analyses showed that the adult Lrp2-deficient eyes were 40% longer than the control ones mainly due to an excessive elongation of the vitreal chamber. They had an apparently normal intraocular pressure and developed chorioretinal atrophy and posterior scleral staphyloma features reminiscent of human myopic retinopathy. Immunomorphological and ultrastructural analyses showed that increased eye lengthening was first observed by post-natal day 5 (P5) and that it was accompanied by a rapid decrease of the bipolar, photoreceptor and retinal ganglion cells, and eventually the optic nerve axons. It was followed by scleral thinning and collagen fiber disorganization, essentially in the posterior pole. We conclude that the function of LRP2 in the ocular tissues is necessary for normal eye growth and that the Lrp2-deficient eyes provide a unique tool to further study human HM. PMID:26107939

  14. Association of common polymorphisms in the LRP6 gene with sporadic coronary artery disease in a Chinese population

    Institute of Scientific and Technical Information of China (English)

    WANG Hui; LIU Qi-ji; CHEN Min-zhi; LI Li; ZHANG Kai; CHENG Guang-hui; MA Long; GONG Yao-qin

    2012-01-01

    Background Genetic factors contribute to the development of coronary artery disease (CAD).Recently,a missense mutation in the low density lipoprotein receptor related protein 6 (LRP6) gene,encoding low density lipoprotein receptor related protein 6,has been implicated in an autosomal dominant form of early-onset CAD.The aim of this study was to determine whether the common variants in LRP6 are associated with sporadic CAD in Chinese.Methods A total of 766 CAD patients and 806 healthy controls were included in this study.The presence of angiographic CAD was determined by coronary angiographic analysis.Six signal nucleotide polymorphisms (SNPs) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.Results A significant association was detected between rs11054731 in LRP6 intron 2 and CAD in our cohort (P=0.001).The CC genotype and C allele frequency in the case group were 52% and 72%.Using a dominant model of inheritance,the C allele of rs11054731 was shown to be an independent risk factor for CAD with an OR of 1.45 (95% CI:1.19-1.77,P=0.0002).With the stratification according to the number of affected coronary arteries,an association was observed between rs11054731 and CAD (P=0.0002).No significant association was observed between any other SNPs and the risk of CAD.Conclusion The C allele of the rs11054731 within the LRP6 gene was associated with increased risk and extent of CAD in Chinese.

  15. Cenani-Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation.

    Science.gov (United States)

    Khan, Tahir Naeem; Klar, J; Ali, Zafar; Khan, F; Baig, S M; Dahl, N

    2013-07-01

    Cenani-Lenz syndrome (CLS) is a rare autosomal recessive developmental disorder of the limbs. The disorder is characterized by complete syndactyly with metacarpal fusions and/or oligodactyly sometimes accompanied by radioulnar synostosis. The clinical expression is variable and kidney agenesis/hypoplasia, craniofacial dysmorphism and teeth abnormalities are frequent features as well as lower limb involvement. CLS was recently associated with mutations in the low-density lipoprotein receptor-related protein 4 (LRP4) gene and dysregulated canonical WNT signaling. We have identified a large consanguineous Pakistani pedigree with 9 members affected by CLS. The affected individuals present with a consistent expression of the syndrome restricted to the limbs and kidneys. Symptoms from the lower limb are mild or absent and there were no radioulnar synostosis or craniofacial involvement. Genetic analysis using autozygosity mapping and sequencing revealed homozygosity for a novel missense mutation c.2858T > C (p.L953P) in the LRP4 gene. The mutation is located in a region encoding the highly conserved low-density lipoprotein receptor repeat class B domain of LRP4. Our findings add to the genotype-phenotype correlations in CLS and support kidney anomalies as a frequent associated feature.

  16. A gene panel, including LRP12, is frequently hypermethylated in major types of B-cell lymphoma.

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    Nicole Bethge

    Full Text Available Epigenetic modifications and DNA methylation in particular, have been recognized as important mechanisms to alter gene expression in malignant cells. Here, we identified candidate genes which were upregulated after an epigenetic treatment of B-cell lymphoma cell lines (Burkitt's lymphoma, BL; Follicular lymphoma, FL; Diffuse large B-cell lymphoma, DLBCL activated B-cell like, ABC; and germinal center like, GCB and simultaneously expressed at low levels in samples from lymphoma patients. Qualitative methylation analysis of 24 candidate genes in cell lines revealed five methylated genes (BMP7, BMPER, CDH1, DUSP4 and LRP12, which were further subjected to quantitative methylation analysis in clinical samples from 59 lymphoma patients (BL, FL, DLBCL ABC and GCB; and primary mediastinal B-cell lymphoma, PMBL. The genes LRP12 and CDH1 showed the highest methylation frequencies (94% and 92%, respectively. BMPER (58%, DUSP4 (32% and BMP7 (22%, were also frequently methylated in patient samples. Importantly, all gene promoters were unmethylated in various control samples (CD19+ peripheral blood B cells, peripheral blood mononuclear cells and tonsils as well as in follicular hyperplasia samples, underscoring a high specificity. The combination of LRP12 and CDH1 methylation could successfully discriminate between the vast majority of the lymphoma and control samples, emphasized by receiver operating characteristic analysis with a c-statistic of 0.999. These two genes represent promising epigenetic markers which may be suitable for monitoring of B-cell lymphoma.

  17. Linear dynamic model of production-inventory with debt repayment: optimal management strategies

    CERN Document Server

    Tuchnolobova, Ekaterina; Vasilieva, Olga

    2012-01-01

    In this paper, we present a simple microeconomic model with linear continuous-time dynamics that describes a production-inventory system with debt repayment. This model is formulated in terms of optimal control and its exact solutions are derived by prudent application of the maximum principle under different sets of initial conditions (scenarios). For a potentially profitable small firm, we also propose some alternative short-term control strategies resulting in a positive final profit and prove their optimality. Practical implementation of such strategies is also discussed.

  18. Recombinant Expression of the Full-length Ectodomain of LDL Receptor-related Protein 1 (LRP1) Unravels pH-dependent Conformational Changes and the Stoichiometry of Binding with Receptor-associated Protein (RAP).

    Science.gov (United States)

    De Nardis, Camilla; Lössl, Philip; van den Biggelaar, Maartje; Madoori, Pramod K; Leloup, Nadia; Mertens, Koen; Heck, Albert J R; Gros, Piet

    2017-01-20

    LDL receptor-related protein 1 (LRP1) is a highly modular protein and the largest known mammalian endocytic receptor. LRP1 binds and internalizes many plasma components, playing multiple crucial roles as a scavenger and signaling molecule. One major challenge to studying LRP1 has been that it is difficult to express such a large, highly glycosylated, and cysteine-rich protein, limiting structural studies to LRP1 fragments. Here, we report the first recombinant expression of the complete 61 domains of the full-length LRP1 ectodomain. This advance was achieved with a multistep cloning approach and by using DNA dilutions to improve protein yields. We investigated the binding properties of LRP1 using receptor-associated protein (RAP) as a model ligand due to its tight binding interaction. The LRP1 conformation was studied in its bound and unbound state using mass spectrometry, small-angle X-ray scattering, and negative-stain electron microscopy at neutral and acidic pH. Our findings revealed a pH-dependent release of the ligand associated with a conformational change of the receptor. In summary, this investigation of the complete LRP1 ectodomain significantly advances our understanding of this important receptor and provides the basis for further elucidating the mechanism of action of LRP1 in a whole and integrated system. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Generation of a Potent Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Antagonist by Engineering a Stable Form of the Receptor-associated Protein (RAP) D3 Domain.

    Science.gov (United States)

    Prasad, Joni M; Migliorini, Mary; Galisteo, Rebeca; Strickland, Dudley K

    2015-07-10

    The low density lipoprotein receptor-related protein 1 (LRP1) is a member of the low density lipoprotein receptor family and plays important roles in a number of physiological and pathological processes. Expression of LRP1 requires the receptor-associated protein (RAP), a molecular chaperone that binds LRP1 and other low density lipoprotein receptor family members in the endoplasmic reticulum and traffics with them to the Golgi where the acidic environment causes its dissociation. Exogenously added RAP is a potent LRP1 antagonist and binds to LRP1 on the cell surface, preventing ligands from binding. Following endocytosis, RAP dissociates in the acidic endosome, allowing LRP1 to recycle back to the cell surface. The acid-induced dissociation of RAP is mediated by its D3 domain, a relatively unstable three-helical bundle that denatures at pH RAP D3 domain. By combining this disulfide bond with elimination of key histidine residues, we generated a stable RAP molecule that is resistant to both pH- and heat-induced denaturation. This molecule bound to LRP1 with high affinity at both neutral and acidic pH and proved to be a potent inhibitor of LRP1 function both in vitro and in vivo, suggesting that our stable RAP molecule may be useful in multiple pathological settings where LRP1 blockade has been shown to be effective. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Generation of a Potent Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Antagonist by Engineering a Stable Form of the Receptor-associated Protein (RAP) D3 Domain*

    Science.gov (United States)

    Prasad, Joni M.; Migliorini, Mary; Galisteo, Rebeca; Strickland, Dudley K.

    2015-01-01

    The low density lipoprotein receptor-related protein 1 (LRP1) is a member of the low density lipoprotein receptor family and plays important roles in a number of physiological and pathological processes. Expression of LRP1 requires the receptor-associated protein (RAP), a molecular chaperone that binds LRP1 and other low density lipoprotein receptor family members in the endoplasmic reticulum and traffics with them to the Golgi where the acidic environment causes its dissociation. Exogenously added RAP is a potent LRP1 antagonist and binds to LRP1 on the cell surface, preventing ligands from binding. Following endocytosis, RAP dissociates in the acidic endosome, allowing LRP1 to recycle back to the cell surface. The acid-induced dissociation of RAP is mediated by its D3 domain, a relatively unstable three-helical bundle that denatures at pH RAP D3 domain. By combining this disulfide bond with elimination of key histidine residues, we generated a stable RAP molecule that is resistant to both pH- and heat-induced denaturation. This molecule bound to LRP1 with high affinity at both neutral and acidic pH and proved to be a potent inhibitor of LRP1 function both in vitro and in vivo, suggesting that our stable RAP molecule may be useful in multiple pathological settings where LRP1 blockade has been shown to be effective. PMID:26013822

  1. ERK/MAPK activation involves hypoxia-induced MGr1-Ag/37LRP expression and contributes to apoptosis resistance in gastric cancer.

    Science.gov (United States)

    Liu, Lili; Zhang, Hongbo; Sun, Li; Gao, Yuqi; Jin, Haifeng; Liang, Shuhui; Wang, Yanxia; Dong, Mingqing; Shi, Yongquan; Li, Zhichao; Fan, Daiming

    2010-08-15

    We previously demonstrated that hypoxia increased the hypoxia-inducible factor (HIF-1)-dependent MGr1-Ag/37LRP expression, which enhanced adhesion of gastric cancer cells to laminin, inhibited drug-induced apoptosis and caused cell adhesion-mediated drug resistance (CAM-DR). Here, we investigated the role of extracellular-regulated kinase (ERK) 1/2 in the signaling mechanisms underlying these events. We found that hypoxia activated ERK activity in vitro and in vivo. Overexpression of mitogen-activated protein kinase (MAPK) kinase (MEK), which preferentially activated ERK, mimics, in a nonadditive way, hypoxia-induced activity of MGr1-Ag/37LRP promoter and expression of MGr1-Ag/37LRP. Furthermore, U0126, the MEK inhibitor, inhibited hypoxia- and MEK-induced MGr1-Ag/37LRP promoter activity in a dose-dependent manner. MEK inhibition also reversed hypoxia- and MEK-induced HIF-1 protein and its activity in a dose-dependent manner. We also investigated reactive oxygen species signaling this response. Exogenous addition of H(2)O(2) was sufficient to activate ERK in a dose-dependent profile. Reactive oxygen species scavengers of H(2)O(2) significantly inhibited hypoxia-induced ERK or HIF-1 activation and sequential expression of MGr1-Ag/37LRP. We also investigated the signaling in hypoxia-induced cell adhesion and apoptosis induced by vincristine. Hypoxia significantly enhanced adhesion of SGC7901 cells to laminin in a time-dependent manner, which might be inhibited by the MEK inhibitor U0126 and MGr1-Ag/37LRP siRNA. Consistent with results of adhesion assay, hypoxia-resistant apoptosis might be reversed by U0126 in a dose-dependent manner. Our results suggest that hypoxia-elicited MGr1-Ag/37LRP expression activated by HIF-1 depends on ERK activation. These events are dependent of reactive oxygen intermediates.

  2. Multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP and lung resistance protein (LRP gene expression in childhood acute lymphoblastic leukemia

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    Elvis Terci Valera

    Full Text Available CONTEXT: Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Expression of genes for the multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP, and lung resistance protein (LRP may confer the phenotype of resistance to the treatment of neoplasias. OBJECTIVE: To analyze the expression of the MDR-1, MRP and LRP genes in children with a diagnosis of acute lymphoblastic leukemia via the semiquantitative reverse transcription polymerase chain reaction (RT-PCR, and to determine the correlation between expression and event-free survival and clinical and laboratory variables. DESIGN: A retrospective clinical study. SETTING: Laboratory of Pediatric Oncology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. METHODS: Bone marrow aspirates from 30 children with a diagnosis of acute lymphoblastic leukemia were assessed for the expression of messenger RNA for the MDR-1, MRP and LRP genes by semi-quantitative RT-PCR. RESULTS: In the three groups studied, only the increased expression of LRP was related to worsened event-free survival (p = 0.005. The presence of the common acute lymphoblastic leukemia antigen (CALLA was correlated with increased LRP expression (p = 0.009 and increased risk of relapse or death (p = 0.05. The relative risk of relapse or death was six times higher among children with high LRP expression upon diagnosis (p = 0.05, as confirmed by multivariate analysis of the three genes studied (p = 0.035. DISCUSSION: Cell resistance to drugs is a determinant of the response to chemotherapy and its detection via RT-PCR may be of clinical importance. CONCLUSIONS: Evaluation of the expression of genes for resistance to antineoplastic drugs in childhood acute lymphoblastic leukemia upon diagnosis, and particularly the expression of the LRP gene, may be of clinical relevance, and should be the

  3. The Effect of Social Capital on Customer’s Repayment Rate at Islamic Microfinance Institution

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    Jaenal Effendi

    2016-07-01

    Full Text Available The potency of Micro and Small Enterprises (MSEs in Indonesia which is great, is not directly proportional to the ease of getting capital from formal financial institutions such as banks because it is not bankable. Meanwhile, microfinance institutions (MFIs that provide financing to the MSEs are currently thriving. This condition exposes the existence of factors that cause the MFIs continuesly providing financing to MSEs which are not bankable. This research aims to analyze the effect of social capital toward the repayment rate of Islamic MFIs’ customers. The methods used in this research was the logistic regression. The results showed variable relationship with BMT employees, relations with other customers, and Islamic recitation had positive and significant effect toward the repayment rate of the customer. While recommendations, membership status, and travel time from home to the BMT had negative and significant effect.  Variable outside the social capital indicator which is income rate had no significant effect.DOI: 10.15408/aiq.v8i2.2631

  4. Do student loans delay marriage? Debt repayment and family formation in young adulthood

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    Robert Bozick

    2014-06-01

    Full Text Available Background: With increasing levels of student loan debt, the path to economic stability may be less smooth than it was for earlier generations of college graduates. This paper explores this emerging trend by assessing whether or not student loan debt influences family formation. Objective: The objective of this study is to examine whether student loan debt delays marriage in young adulthood, whether or not the relationship between student loan debt and marriage differs for women and for men, and if this relationship attenuates during the years immediately after college graduation. Methods: We estimate a series of discrete-time hazard regression models predicting the odds of first marriage as a function of time-varying student loan debt balance, using a nationally representative sample of bachelor's degree recipients from the 1993 Baccalaureate and Beyond Longitudinal Study (N = 9,410. Results: We find that the dynamics of loan repayment are related to marriage timing for women, but not for men. Specifically, an increase of $1,000 in student loan debt is associated with a reduction in the odds of first marriage by two percent a month among female bachelor degree recipients during the first four years after college graduation. This relationship attenuates over time. Conclusions: Our study lends support to the proposition that the financial weight of monthly loan repayments impedes family formation in the years immediately following college graduation -- however, only for women. This finding questions traditional models of gender specialization in family formation that emphasize the economic resources of men.

  5. 26 CFR 1.592-1 - Repayment of certain loans by mutual savings banks, building and loan associations, and...

    Science.gov (United States)

    2010-04-01

    ... banks, building and loan associations, and cooperative banks. 1.592-1 Section 1.592-1 Internal Revenue... (CONTINUED) Mutual Savings Banks, Etc. § 1.592-1 Repayment of certain loans by mutual savings banks, building and loan associations, and cooperative banks. There is deductible, under section 592, from the...

  6. 7 CFR 3.42 - Debtor rights to inspect or copy records, submit repayment proposals, or request administrative...

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Debtor rights to inspect or copy records, submit repayment proposals, or request administrative review. 3.42 Section 3.42 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Administrative Offset § 3.42 Debtor rights to inspect or copy...

  7. 46 CFR 308.526 - Certificate for repayment of decrease of collateral deposit fund, Form MA-306.

    Science.gov (United States)

    2010-10-01

    ... deposit fund, Form MA-306. 308.526 Section 308.526 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF... Insurance § 308.526 Certificate for repayment of decrease of collateral deposit fund, Form MA-306. The..., Form MA-306, may be obtained from the American War Risk Agency or MARAD....

  8. 78 FR 33395 - Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2013-William D. Ford...

    Science.gov (United States)

    2013-06-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2013--William D. Ford Federal...- 800-877-8339. SUPPLEMENTARY INFORMATION: Under the William D. Ford Federal Direct Loan (Direct...

  9. 77 FR 30266 - Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2012; William D. Ford...

    Science.gov (United States)

    2012-05-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2012; William D. Ford Federal... the ICR plan formula for 2012. Under the William D. Ford Federal Direct Loan (Direct Loan)...

  10. 77 FR 20796 - Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2011; William D. Ford...

    Science.gov (United States)

    2012-04-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF EDUCATION Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2011; William D. Ford Federal... the ICR plan formula for 2011. Under the William D. Ford Federal Direct Loan (Direct Loan)...

  11. 12 CFR 313.48 - Special review of repayment agreement or salary offset due to changed circumstances.

    Science.gov (United States)

    2010-01-01

    ... for special review, the employee shall submit to the Director a detailed statement and supporting... current salary offset or payments result in extreme financial hardship to the employee. (d) The Director... request a special review by the Director of the amount of the salary offset or voluntary repayment,...

  12. Expression of Lung Resistance Protein (LRP) Gene in Hepatocellular Carcinoma and Its Significance%原发性肝细胞癌肺耐药蛋白LRP基因表达及其意义

    Institute of Scientific and Technical Information of China (English)

    王百林; WANG Bailin; 陈孝平; CHEN Xiaoping; 翟淑萍; ZHAI Shuping; YANG Haiyan; ZHONG Yong; MENG Lei; ZHAO Wentao

    2004-01-01

    Objective: To study the multidrug resistance (MDR) mechanism of lung resistance protein (LRP) gene in hepatocellular carcinoma (HCC), and the relations among the expression of the LRP gene adjuvant chemotherapy after resection of HCC. Methods: The expression of the LRP gene encoding LRP and mRNA LRP was detected in tissues from 54 untreated patients with HCC, adjacent tissues from 24 patients with HCC and archival paraffin-embedded tissues from 12 patients with posthepatitic cirrhosis. The relationship between the LRP gene expression and the change of AFP level was analyzed in the 24 postoperative HCC patients whose AFP was measured after 2 weeks. All of the HCC patients were followed up. Results: The percentage of positive expression of LRP and mRNA LRP in the 3tissues was 61.1%, 33.3%, 16.7%, and 75.9%, 37.5%, 33.3% respectively. There was significant difference between the untreated HCC tissue and other tissues (P<0.05). No difference existed between the LRP gene expression and clinicopathologic findings, age, sex, and tumor size (P>0.05), but the expression was related to the degree of differentiation of HCC (P<0.05). The effective rate of AFP in the LRP gene positive expression group or in postoperative chemotherapeutic patients was very lower than that in the negative group (P<0.05). Although the mean survival time of postoperative HCC patients in negative LRP gene expression group was longer than that of positive group, there was no difference between them (P<0.05).Conclusion: LRP gene expression is related to MDR of HCC and initiates the intrinsic MDR. Detection of LRP gene expression is of great guiding significance in accessing chemotherapeutic resistance of HCC.As an index to chemotherapy of HCC, detection of LRP expression provides evidence for making individual chemotherapeutic treatment,and reversing MDR in HCC. Although LRP gene expression correlates with the tumor differential degree (P<0.05), it perhaps does not relate with the

  13. 42 CFR 62.1 - What is the scope and purpose of the National Health Service Corps scholarship program?

    Science.gov (United States)

    2010-10-01

    ... Health Service Corps scholarship program? 62.1 Section 62.1 Public Health PUBLIC HEALTH SERVICE... SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.1 What is the scope and purpose of the National Health Service Corps scholarship program? These regulations apply...

  14. Lrp4 regulates initiation of ureteric budding and is crucial for kidney formation--a mouse model for Cenani-Lenz syndrome.

    Directory of Open Access Journals (Sweden)

    Courtney M Karner

    Full Text Available BACKGROUND: Development of the kidney is initiated when the ureteric bud (UB branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation. METHODS AND PRINCIPAL FINDINGS: We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. CONCLUSION: Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4(-/- mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidney malformations in humans and mice.

  15. Structure of the Dual-Mode Wnt Regulator Kremen1 and Insight into Ternary Complex Formation with LRP6 and Dickkopf.

    Science.gov (United States)

    Zebisch, Matthias; Jackson, Verity A; Zhao, Yuguang; Jones, E Yvonne

    2016-09-01

    Kremen 1 and 2 have been identified as co-receptors for Dickkopf (Dkk) proteins, hallmark secreted antagonists of canonical Wnt signaling. We present here three crystal structures of the ectodomain of human Kremen1 (KRM1ECD) at resolutions between 1.9 and 3.2 Å. KRM1ECD emerges as a rigid molecule with tight interactions stabilizing a triangular arrangement of its Kringle, WSC, and CUB structural domains. The structures reveal an unpredicted homology of the WSC domain to hepatocyte growth factor. We further report the general architecture of the ternary complex formed by the Wnt co-receptor Lrp5/6, Dkk, and Krm, determined from a low-resolution complex crystal structure between β-propeller/EGF repeats (PE) 3 and 4 of the Wnt co-receptor LRP6 (LRP6PE3PE4), the cysteine-rich domain 2 (CRD2) of DKK1, and KRM1ECD. DKK1CRD2 is sandwiched between LRP6PE3 and KRM1Kringle-WSC. Modeling studies supported by surface plasmon resonance suggest a direct interaction site between Krm1CUB and Lrp6PE2.

  16. The Research on the Relationship of RAGE, LRP-1, and Aβ Accumulation in the Hippocampus, Prefrontal Lobe, and Amygdala of STZ-Induced Diabetic Rats.

    Science.gov (United States)

    Ma, Lou-Yan; Fei, Yu-Lang; Wang, Xiao-Ye; Wu, Song-Di; Du, Jun-Hui; Zhu, Mei; Jin, Long; Li, Ming; Li, Hai-Long; Zhai, Jia-Jia; Ji, Lu-Peng; Ma, Ran-Ran; Liu, Song-Fang; Li, Mo; Ma, Li; Ma, Xiao-Rui; Qu, Qiu-Min; Lv, Ya-Li

    2017-05-01

    Diabetes mellitus (DM) has been regarded as an important risk factor for Alzheimer's disease (AD), and diabetic patients and animals have shown cognitive dysfunction. More research has shown that the amyloid-β (Aβ), which is a hallmark of AD, was found deposited in the hippocampus of diabetic rats. This Aβ accumulation is regulated by the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP-1). However, the expression of RAGE and LRP-1 in diabetic rats is not very clear. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether the expression of RAGE and LRP-1 is related to Aβ1-42 deposition at the hippocampus, prefrontal lobe, and amygdala in DM. We found that diabetic rats had longer escape latency and less frequency of entrance into the target zone than that of the control group (P RAGE increased (P RAGE positively (P RAGE, and LRP-1 were not changed in the amygdala between the diabetic rats and the control group. These findings indicated that upregulating RAGE and/or downregulating LRP-1 at the hippocampus and the prefrontal lobe contributed to the Aβ1-42 accumulation and then further promoted the cognitive impairment of diabetic rats.

  17. 42 CFR 62.11 - When can a scholarship program payment obligation be discharged in bankruptcy?

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false When can a scholarship program payment obligation... HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.11 When can...

  18. 42 CFR 62.6 - How will individuals be selected to participate in the scholarship program?

    Science.gov (United States)

    2010-10-01

    ... the scholarship program? 62.6 Section 62.6 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.6 How will...

  19. 42 CFR 62.3 - Who is eligible to apply for a scholarship program award?

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible to apply for a scholarship program... FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.3 Who is eligible to apply for a scholarship...

  20. 42 CFR 62.5 - How is application made for a scholarship program award?

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false How is application made for a scholarship program... FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.5 How is application made for a scholarship...

  1. 75 FR 59058 - Competitive and Noncompetitive Non-Formula Federal Assistance Programs-Specific Administrative...

    Science.gov (United States)

    2010-09-27

    ... the Veterinary Medicine Loan Repayment Program (VMLRP) authorized under section 1415A of the National...-Formula Federal Assistance Programs--Specific Administrative Provisions for the New Era Rural Technology... administrative requirements for the New Era Rural Technology Competitive Grants Program (RTP) to supplement...

  2. Gateway技术构建转基因重组质粒pRP.EX3d-EF1A-LRP16-His-IRES-eGFP

    Institute of Scientific and Technical Information of China (English)

    柏苗苗; 王春萌; 伍志强; 梅倩; 李小雷; 李祥; 赵亚力; 韩为东

    2014-01-01

    目的:构建转基因重组质粒pRP.EX3d-EF1A-LRP16-His-IRES-eGFP,为转基因鼠的建立奠定基础。方法利用重叠PCR技术扩增attB1-LRP16-His-attB2,经BP反应,将LRP16基因插入到载体pDown上,pUp-EF1A、pDown-LRP16-His、pTail-IRES-eGFP和PRP.Des3d经LR反应,将LRP16转移到pRP.EX3d上,转化Stbl3细胞,用氨苄西林进行抗性筛选,经PCR鉴定后将阳性克隆送测序。结果测序及酶切结果验证获得正确的pRP.EX3d-EF1A-LRP16-His-IRES-eGFP重组质粒。结论成功构建pRP.EX3d-EF1A-LRP16-His-IRES-eGFP重组质粒,可用于下一步LRP16转基因小鼠的构建。

  3. Too Much Loving-Kindness to Repay: Funeral Speeches of the Wenquan Pumi

    Directory of Open Access Journals (Sweden)

    Gerong Pincuo

    2013-12-01

    Full Text Available Two Pumi funeral speech rituals of the Wenquan Pumi area in northwestern Yunnan Province illustrate the traditional genre of speeches through their use of metaphor and parallellism. The speeches express the central concept of giving and repaying that plays an important role in strengthening social cohesion among Pumi relatives. This study introduces two interlinear Pumi (autonym ʈʰɔ́ŋmə 'White People' funeral speeches from the Wenquan area of Southwest China that provide readers insight into the structure of the language and the beauty of its verbal art, something that is easily lost in translation. Due to China's push for rapid modernization, many minority languages are under great pressure – some are already disappearing. A record of traditional verbal art in its original language is thus valuable for language and culture documentation.

  4. 雌激素调控子宫内膜癌Ishikawa细胞中LRP16基因表达及其意义%Expression regulation of LRP16 gene by 17β-estradiol and its significance in human endometrial cancer Ishikawa cells

    Institute of Scientific and Technical Information of China (English)

    孟元光; 韩为东; 黄柯; 伍志强; 赵亚力; 母义明; 宋磊

    2006-01-01

    目的:探讨子宫内膜癌Ishikawa细胞中雌激素(E2)对LRP16基因表达的调控作用,LRP16基因过表达对Ishikawa细胞增殖及侵袭生长能力的影响以及可能的分子机制. 方法:采用Northern blot方法检测细胞中LRP16基因mRNA表达水平. 双荧光报告系统检测相对荧光素酶活性. 胎盘蓝死活细胞计数方法观察LRP16过表达对Ishikawa细胞增殖的影响,Matrigel包被的Transwell方法观察LRP16 过表达对Ishikawa细胞侵袭生长能力的影响. Western blot方法检测Ishikawa细胞中的蛋白水平. 结果:雌二醇诱导了Ishikawa细胞中LRP16基因mRNA水平表达上调;而ICI 182 780则Ishikawa细胞中LRP16 mRNA水平下调. 增加ERα表达量促使Ishikawa细胞中LRP16基因上调. pGL3-S5与ERα共转染Ishikawa细胞的相对荧光素酶活性较单纯pGL3-S5转染组细胞升高30倍. 我们没有观察到LRP16基因过表达对Ishikawa细胞的促增殖效应. Transwell结果显示LRP16基因过表达Ishikawa细胞的侵袭率较对照组细胞增加了30%. LRP16基因过表达的Ishikawa细胞中E-钙粘合素的mRNA以及蛋白水平较对照组细胞下调了3倍,而没有检测到MMP2,MMP9以及CD44蛋白水平的变化. 结论:我结果表明E2通过激活ERα上调子宫内膜癌Ishikawa细胞中LRP16基因mRNA水平,LRP16表达水平依赖于雌激素. LRP16基因表达上调没有促进子宫内膜癌细胞的增殖,但可能通过抑制E-钙粘合素表达水平增加了细胞的侵袭能力.

  5. Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor

    DEFF Research Database (Denmark)

    Kristensen, Torsten; Moestrup, Søren Kragh; Gliemann, Jørgen;

    1990-01-01

    The human placental receptor (α2MR) for α2-macroglobulin-proteinase complexes contains 3 polypeptides of approx. 500 kDa, 85 kDa, and 40 kDa. N-terminal sequence analysis of the 500 kDa and 85 kDa polypeptides, analysis of a random selection of peptides covering 536 residues from these polypeptides......, and analysis of a 1772 bp cDNA encoding part of the 500 kDa polypeptide provide evidence that the 500 kDa and 85 kDa chains are the α- and β-subunits, respectively, of a recently cloned hepatic membrane protein, termed the low density lipoprotein receptor related protein (LRP) (Herz, J., Hamann, U., Rogne, S......., Myklebost, O., Gausepohl, H. and Stanley, K.K. (1988) EMBO J. 7, 4119-4127; Herz, J., Kowal, R.C., Goldstein, J.L. and Brown, M.S. (1990) EMBO J. 9, 1769-1776). N-terminal sequence analysis of the 40 kDa polypeptide shows that it is of distinct genetic origin. It is suggested that LRP is the functional...

  6. 42 CFR 62.7 - What will an individual be awarded for participating in the scholarship program?

    Science.gov (United States)

    2010-10-01

    ... participating in the scholarship program? 62.7 Section 62.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.7 What will...

  7. 42 CFR 62.8 - What does an individual have to do in return for the scholarship program award?

    Science.gov (United States)

    2010-10-01

    ... the scholarship program award? 62.8 Section 62.8 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.8 What does...

  8. Direct PLUS Loan Basics: Parent Loans for Students. William D. Ford Federal Direct Loan Program.

    Science.gov (United States)

    Department of Education, Washington, DC.

    The Direct PLUS Loan is one of the low-interest loans provided by the William D. Ford Federal Direct Loan Program. The U.S. Department of Education delivers loan proceeds through the student's school, and parents are responsible for repaying the Department. This booklet answers parents' questions about the loan program, including: (1) Am I…

  9. Repayment of Short Term Loans in the Formal Credit Market: The Role of Accessibility to Credit from InformalSources

    OpenAIRE

    Manojit Bhattacharjee; Meenakshi Rajeev

    2012-01-01

    This paper is an attempt to link the problem of non-repayment in the formal credit market with the accessibility to credit from informal sources. In many developing countries a well established network of informal lenders continues to prevail in spite of various formal lending programmes implemented by the government. Scholars often dealt with how the poorer households become the victim of usurious rates of interest charged by informal lenders and lose their valuable properties. We however sh...

  10. Polymorphisms in the Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5) Gene Are Associated with Peak Bone Mass in Non-sedentary Men

    DEFF Research Database (Denmark)

    Brixen, K; Beckers, S; Peeters, A

    2007-01-01

    PURPOSE: To investigate the impact of the Ala1330Val (rs3736228, exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men. METHODS: The Odense Androgen Study (OAS) is a population-based study...

  11. In vitro discrimination of the role of LRP1 at the BBB cellular level: focus on brain capillary endothelial cells and brain pericytes.

    Science.gov (United States)

    Candela, Pietra; Saint-Pol, Julien; Kuntz, Mélanie; Boucau, Marie-Christine; Lamartiniere, Yordenca; Gosselet, Fabien; Fenart, Laurence

    2015-01-12

    Several studies have demonstrated that the blood-brain barrier (BBB) (dynamic cellular complex composed by brain capillary endothelial cells (BCECs) and surrounded by astrocytic end feet and pericytes) regulates the exchanges of amyloid β (Aβ) peptide between the blood and the brain. Deregulation of these exchanges seems to be a key trigger for the brain accumulation of Aβ peptide observed in Alzheimer's disease (AD). Whereas the involvement of receptor for advanced glycation end-products in Aβ peptide transcytosis has been demonstrated in our laboratory, low-density lipoprotein receptor's role at the cellular level needs to be clarified. For this, we used an in vitro BBB model that consists of a co-culture of bovine BCECs and rat glial cells. This model has already been used to characterize low-density lipoprotein receptor-related peptide (LRP)'s involvement in the transcytosis of molecules such as tPA and angiopep-2. Our results suggest that Aβ peptide efflux across the BCEC monolayer involves a transcellular transport. However, the experiments with RAP discard an involvement of LRP family members at BCECs level. In contrast, our results show a strong transcriptional expression of LRP1 in pericytes and suggest its implication in Aβ endocytosis. Moreover, the observations of pericytes contraction and local downregulation of LRP1 in response to Aβ treatment opens up perspectives for studying this cell type with respect to Aβ peptide metabolism and AD. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Connection between Proliferation Rate and Temozolomide Sensitivity of Primary Glioblastoma Cell Culture and Expression of YB-1 and LRP/MVP.

    Science.gov (United States)

    Moiseeva, N I; Susova, O Yu; Mitrofanov, A A; Panteleev, D Yu; Pavlova, G V; Pustogarov, N A; Stavrovskaya, A A; Rybalkina, E Yu

    2016-06-01

    Glioblastomas (GBL) are the most common and aggressive brain tumors. They are distinguished by high resistance to radiation and chemotherapy. To find novel approaches for GBL classification, we obtained 16 primary GBL cell cultures and tested them with real-time PCR for mRNA expression of several genes (YB-1, MGMT, MELK, MVP, MDR1, BCRP) involved in controlling cell proliferation and drug resistance. The primary GBL cultures differed in terms of proliferation rate, wherein a group of GBL cell cultures with low proliferation rate demonstrated higher resistance to temozolomide. We found that GBL primary cell cultures characterized by high proliferation rate and lower resistance to temozolomide expressed higher mRNA level of the YB-1 and MDR1 genes, whereas upregulated expression of MVP/LRP mRNA was a marker in the group of GBL with low proliferation rate and high resistance. A moderate correlation between expression of YB-1 and MELK as well as YB-1 and MDR1 was found. In the case of YB-1 and MGMT expression, no correlation was found. A significant negative correlation was revealed between mRNA expression of MVP/LRP and MELK, MDR1, and BCRP. No correlation in expression of YB-1 and MVP/LRP genes was observed. It seems that mRNA expression of YB-1 and MVP/LRP may serve as a marker for GBL cell cultures belonging to distinct groups, each of which is characterized by a unique pattern of gene activity.

  13. Integration of regulatory signals through involvement of multiple global regulators: control of the Escherichia coli gltBDF operon by Lrp, IHF, Crp, and ArgR

    Directory of Open Access Journals (Sweden)

    Mishra Pankaj K

    2007-01-01

    Full Text Available Abstract Background The glutamate synthase operon (gltBDF contributes to one of the two main pathways of ammonia assimilation in Escherichia coli. Of the seven most-global regulators, together affecting expression of about half of all E. coli genes, two were previously shown to exert direct, positive control on gltBDF transcription: Lrp and IHF. The involvement of Lrp is unusual in two respects: first, it is insensitive to the usual coregulator leucine, and second, Lrp binds more than 150 bp upstream of the transcription starting point. There was indirect evidence for involvement of a third global regulator, Crp. Given the physiological importance of gltBDF, and the potential opportunity to learn about integration of global regulatory signals, a combination of in vivo and in vitro approaches was used to investigate the involvement of additional regulatory proteins, and to determine their relative binding positions and potential interactions with one another and with RNA polymerase (RNAP. Results Crp and a more local regulator, ArgR, directly control gltBDF transcription, both acting negatively. Crp-cAMP binds a sequence centered at -65.5 relative to the transcript start. Mutation of conserved nucleotides in the Crp binding site abolishes the Crp-dependent repression. ArgR also binds to the gltBDF promoter region, upstream of the Lrp binding sites, and decreases transcription. RNAP only yields a defined DNAse I footprint under two tested conditions: in the presence of both Lrp and IHF, or in the presence of Crp-cAMP. The DNAse I footprint of RNAP in the presence of Lrp and IHF is altered by ArgR. Conclusion The involvement of nearly half of E. coli's most-global regulatory proteins in the control of gltBDF transcription is striking, but seems consistent with the central metabolic role of this operon. Determining the mechanisms of activation and repression for gltBDF was beyond the scope of this study. However the results are consistent with a

  14. Rapid hepatic clearance of full length CCN-2/CTGF: a putative role for LRP1-mediated endocytosis.

    Science.gov (United States)

    Gerritsen, K G F; Bovenschen, N; Nguyen, T Q; Sprengers, D; Koeners, M P; van Koppen, A N; Joles, J A; Goldschmeding, R; Kok, R J

    2016-12-01

    CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min). Immunosorbent assay and immunostaining showed that CCN-2 distributed mainly to the liver and was taken up by hepatocytes. Steady state clearance in rats, determined by continuous infusion of CCN-2, was fast (45 mL/kg/min). Renal CCN-2 clearance, determined by arterial and renal vein sampling, accounted for only 12 % of total clearance. Co-infusion of CCN-2 with receptor-associated protein (RAP), an antagonist of LDL-receptor family proteins, showed that RAP prolonged CCN-2 half-life and completely prevented CCN-2 internalization by hepatocytes. This suggests that hepatic uptake of CCN-2 is mediated by a RAP-sensitive mechanism most likely involving LRP1, a member of the LDL-receptor family involved in hepatic clearance of various plasma proteins. Surface plasmon resonance binding studies confirmed that CCN-2 is an LRP1 ligand. Co-infusion of CCN-2 with an excess of the heparan sulphate-binding protamine lowered the large initial distribution volume of CCN-2 by 88 % and reduced interstitial staining of CCN-2, suggesting binding of CCN-2 to heparan sulphate proteoglycans (HSPGs). Protamine did not affect clearance rate, indicating that RAP-sensitive clearance of CCN-2 is HSPG independent. In conclusion, unlike its amino-terminal fragment which is cleared by the kidney, full length CCN-2 is primarily eliminated by the liver via a fast RAP-sensitive, probably LRP1-dependent

  15. Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Erickson Michelle A

    2011-10-01

    Full Text Available Abstract Background Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. However, very little is known about their immune activities or their roles in neuroinflammation. Here, we focused on the immunological profile of brain pericytes in culture in the quiescent and immune-challenged state by studying their production of immune mediators such as nitric oxide (NO, cytokines, and chemokines. We also examined the effects of immune challenge on pericyte expression of low density lipoprotein receptor-related protein-1 (LRP-1, a protein involved in the processing of amyloid precursor protein and the brain-to-blood efflux of amyloid-β peptide. Methods Supernatants were collected from primary cultures of mouse brain pericytes. Release of nitric oxide (NO was measured by the Griess reaction and the level of S-nitrosylation of pericyte proteins measured with a modified "biotin-switch" method. Specific mitogen-activated protein kinase (MAPK pathway inhibitors were used to determine involvement of these pathways on NO production. Cytokines and chemokines were analyzed by multianalyte technology. The expression of both subunits of LRP-1 was analyzed by western blot. Results Lipopolysaccharide (LPS induced release of NO by pericytes in a dose-dependent manner that was mediated through MAPK pathways. Nitrative stress resulted in S-nitrosylation of cellular proteins. Eighteen of twenty-three cytokines measured were released constitutively by pericytes or with stimulation by LPS, including interleukin (IL-12, IL-13, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, eotaxin, chemokine (C-C motif ligand (CCL-3, and CCL-4. Pericyte expressions of both subunits of

  16. Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor

    DEFF Research Database (Denmark)

    Kristensen, T; Moestrup, Søren Kragh; Gliemann, Jørgen;

    1990-01-01

    these polypeptides, and analysis of a 1772 bp cDNA encoding part of the 500 kDa polypeptide provide evidence that the 500 kDa and 85 kDa chains are the alpha- and beta-subunits, respectively, of a recently cloned hepatic membrane protein, termed the low density lipoprotein receptor related protein (LRP) (Herz, J......The human placental receptor (alpha 2MR) for alpha 2-macroglobulin-proteinase complexes contains 3 polypeptides of approx. 500 kDa, 85 kDa, and 40 kDa. N-terminal sequence analysis of the 500 kDa and 85 kDa polypeptides, analysis of a random selection of peptides convering 536 residues from...

  17. Deferred Cost Recovery for Higher Education: Student Loan Programs in Developing Countries. World Bank Discussion Papers, No. 137.

    Science.gov (United States)

    Albrecht, Douglas; Ziderman, Adrian

    This study analyzes the experience of existing higher education student loan programs in developing countries in order to understand their role in fostering cost recovery. Detailed financial analyses of 24 loan programs shows that present value of the repayments collected constitutes a small percentage of the loan value disbursed. In general,…

  18. Up-regulation of hepatic low-density lipoprotein receptor-related protein 1: a possible novel mechanism of antiatherogenic activity of hydroxymethylglutaryl-coenzyme A reductase inhibitor Atorvastatin and hepatic LRP1 expression.

    Science.gov (United States)

    Moon, Jae Hoon; Kang, Saet Byol; Park, Jong Suk; Lee, Byung Wan; Kang, Eun Seok; Ahn, Chul Woo; Lee, Hyun Chul; Cha, Bong Soo

    2011-07-01

    Low-density lipoprotein receptor-related protein 1 (LRP1) binds to apolipoprotein E and serves as a receptor for remnant lipoproteins in the liver, thus playing an important role in clearing these atherogenic particles. In this study, we investigated the effect of atorvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, on hepatic LRP1 expression. We used HepG2 and Hep3B cells for in vitro study, and Otsuka Long-Evans Tokushima fatty and Sprague-Dawley rats for in vivo study. We used relatively high pharmacologic dose of atorvastatin in this study (in vitro, 0.5 μmol/L in culture media, for 48 hours; in vivo, 20 mg/[kg d], for 6 weeks). Atorvastatin increased LRP1 and low-density lipoprotein (LDL) receptor expression in HepG2 and Hep3B cells and induced hepatic LRP1 and LDL receptor expression in chow diet-fed Sprague-Dawley rats and high-fat diet-fed Otsuka Long-Evans Tokushima fatty rats. Atorvastatin decreased intracellular sterol level and increased the amount of the nuclear form of sterol response element-binding protein-2 (SREBP-2) in both HepG2 and Hep3B cells as well as in two animal models. Treatment of HepG2 cells with LDL increased intracellular sterol level and reduced LRP1, LDL receptor, and SREBP-2. When SREBP-2 in HepG2 cells was knocked down by small interfering RNA, the induction of LRP1 expression by atorvastatin did not take place. In conclusion, up-regulation of hepatic LRP1 might be a novel mechanism by which statin treatment decreases remnant lipoproteins. In addition, SREBP-2 acts as a mediator of atorvastatin-induced up-regulation of hepatic LRP1. Future studies using standard doses of atorvastatin in humans are needed to elucidate clinical relevance of these findings.

  19. Mode of Repayment for Student Loan Based on Sinking Fund%基于偿债基金的助学贷款偿还模式

    Institute of Scientific and Technical Information of China (English)

    周明法; 吴琼; 王金亮

    2014-01-01

    The traditional repayment methods of students ’ loan are still applied nowadays by Chinese Government, namely, the method of equal repayment in each term of the partial sum of the principal and interest, and the method of equal repayment in each term of the partial amount of loan principal itself. The borrowers have the greatest pressure at the very time when they begin to repay, since the burden rates reduce gradually in both cases. There is no flexibility in that the borrowers have to pay each term a fixed amount of money.This paper introduces a new method of establishing a repayment fund and analyze it ’s the merits and defects. Furthermore, it also discuss the modes of equal repayment in each of the partial sum of the principal plus interest, equal repayment in each term of the partial amount of loan principal itself, and increasing repay-ment with a fixed ratio, which are all based on the repayment fund. The first two modes mentioned above can offer more flexibility for both the creditors and debtors, since the banks can encourage the action of saving and earlier repayment of the loan by the rising deposit interest rate of the fund, thus it can enhance the bank ’s control of situations and can lower the violation rate of the loan repayment. Moreover, they go seamless well with the current policy and have very strong operability, because only a repayment fund is needed for every borrower. Theoretical analyses reveal that the concrete increasing rate burden repayment method has extra advantages in giving the debt-or the right of choosing the burden rate to balance the repayment burden according to the ability of the borrowers, which can arrive at a desirable situation with a low repayment burden at period-beginning and high one at the period-ending. Therefore, the violation rate of the loan can be lowered obviously by changing the repayment mode ruled by the banks. As a result, the method of increasing burden rate based on repayment fund is suitable for

  20. 76 FR 35318 - Competitive and Noncompetitive Nonformula Federal Assistance Programs-Administrative Provisions...

    Science.gov (United States)

    2011-06-17

    ... Veterinary Medicine Loan Repayment Program (VMLRP) authorized under section 1415A of the National... demonstration of biofuels and biobased products; and the methods, practices, and technologies for the production... The objectives of BRDI are to develop (a) technologies and processes necessary for abundant...

  1. Mutations in zebrafish lrp2 result in adult-onset ocular pathogenesis that models myopia and other risk factors for glaucoma.

    Directory of Open Access Journals (Sweden)

    Kerry N Veth

    2011-02-01

    Full Text Available The glaucomas comprise a genetically complex group of retinal neuropathies that typically occur late in life and are characterized by progressive pathology of the optic nerve head and degeneration of retinal ganglion cells. In addition to age and family history, other significant risk factors for glaucoma include elevated intraocular pressure (IOP and myopia. The complexity of glaucoma has made it difficult to model in animals, but also challenging to identify responsible genes. We have used zebrafish to identify a genetically complex, recessive mutant that shows risk factors for glaucoma including adult onset severe myopia, elevated IOP, and progressive retinal ganglion cell pathology. Positional cloning and analysis of a non-complementing allele indicated that non-sense mutations in low density lipoprotein receptor-related protein 2 (lrp2 underlie the mutant phenotype. Lrp2, previously named Megalin, functions as an endocytic receptor for a wide-variety of bioactive molecules including Sonic hedgehog, bone morphogenic protein 4, retinol-binding protein, vitamin D-binding protein, and apolipoprotein E, among others. Detailed phenotype analyses indicated that as lrp2 mutant fish age, many individuals--but not all--develop high IOP and severe myopia with obviously enlarged eye globes. This results in retinal stretch and prolonged stress to retinal ganglion cells, which ultimately show signs of pathogenesis. Our studies implicate altered Lrp2-mediated homeostasis as important for myopia and other risk factors for glaucoma in humans and establish a new genetic model for further study of phenotypes associated with this disease.

  2. Pregnancy-associated osteoporosis with a heterozygous deactivating LDL receptor-related protein 5 (LRP5) mutation and a homozygous methylenetetrahydrofolate reductase (MTHFR) polymorphism.

    Science.gov (United States)

    Cook, Fiona J; Mumm, Steven; Whyte, Michael P; Wenkert, Deborah

    2014-04-01

    Pregnancy-associated osteoporosis (PAO) is a rare, idiopathic disorder that usually presents with vertebral compression fractures (VCFs) within 6 months of a first pregnancy and delivery. Spontaneous improvement is typical. There is no known genetic basis for PAO. A 26-year-old primagravida with a neonatal history of unilateral blindness attributable to hyperplastic primary vitreous sustained postpartum VCFs consistent with PAO. Her low bone mineral density (BMD) seemed to respond to vitamin D and calcium therapy, with no fractures after her next successful pregnancy. Investigation of subsequent fetal losses revealed homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated both with fetal loss and with osteoporosis (OP). Because her neonatal unilateral blindness and OP were suggestive of loss-of-function mutation(s) in the gene that encodes LDL receptor-related protein 5 (LRP5), LRP5 exon and splice site sequencing was also performed. This revealed a unique heterozygous 12-bp deletion in exon 21 (c.4454_4465del, p.1485_1488del SSSS) in the patient, her mother and sons, but not her father or brother. Her mother had a normal BMD, no history of fractures, PAO, ophthalmopathy, or fetal loss. Her two sons had no ophthalmopathy and no skeletal issues. Her osteoporotic father (with a family history of blindness) and brother had low BMDs first documented at ages ∼40 and 32 years, respectively. Serum biochemical and bone turnover studies were unremarkable in all subjects. We postulate that our patient's heterozygous LRP5 mutation together with her homozygous MTHFR polymorphism likely predisposed her to low peak BMD. However, OP did not cosegregate in her family with the LRP5 mutation, the homozygous MTHFR polymorphism, or even the combination of the two, implicating additional genetic or nongenetic factors in her PAO. Nevertheless, exploration for potential genetic contributions to PAO may explain part of the pathogenesis of this

  3. Prognostic significance of miR-23b in combination with P-gp, MRP and LRP/MVP expression in non-small cell lung cancer.

    Science.gov (United States)

    Janikova, M; Zizkova, V; Skarda, J; Kharaishvili, G; Radova, L; Kolar, Z

    2016-01-01

    Recently, miR-23b has emerged as a promising new cancer biomarker but its role in lung cancer has not been established yet. Patients still do not respond well to available treatments, probably due to expression of multidrug resistance (MDR) proteins, such as P-gp, MRP and LRP/MVP. The aim of this study was to determine the role of miR-23b in non-small cell lung cancer (NSCLC) and its relationship to the patient outcome together with MDR transporter proteins. We immunohistochemically evaluated expression of P-gp, MRP and LRP/MVP and quantified the relative levels of miR-23b in 62 NSCLC patients´ samples. The prognostic significance of miR-23b and MDR proteins was tested by Kaplan-Meier and Cox-regression analysis. Our results showed that miR-23b is mostly downregulated in NSCLC samples (57/62) and that its upregulation in tumors is connected with longer progression-free survival (PFS; P = 0.065) and overall survival (OS; P = 0.048). The Cox proportional hazard model revealed that the risk of death or relapse in NSCLC patients with miR-23b downregulation increases together with LRP/MVP expression and both risks decrease with miR-23b upregulation (HRPFS = 4.342, PPFS = 0.022; HROS = 4.408, POS = 0.015). Our findings indicate that miR-23b, especially in combination with LRP/MVP expression, might serve as a suitable prognostic biomarker for NSCLC patients.

  4. Seed-Specific Expression of a Lysine-Rich Protein Gene, GhLRP, from Cotton Significantly Increases the Lysine Content in Maize Seeds

    Directory of Open Access Journals (Sweden)

    Jing Yue

    2014-03-01

    Full Text Available Maize seed storage proteins are a major source of human and livestock consumption. However, these proteins have poor nutritional value, because they are deficient in lysine and tryptophan. Much research has been done to elevate the lysine content by reducing zein content or regulating the activities of key enzymes in lysine metabolism. Using the naturally lysine-rich protein genes, sb401 and SBgLR, from potato, we previously increased the lysine and protein contents of maize seeds. Here, we examined another natural lysine-rich protein gene, GhLRP, from cotton, which increased the lysine content of transgenic maize seeds at levels varying from 16.2% to 65.0% relative to the wild-type. The total protein content was not distinctly different, except in the six transgenic lines. The lipid and starch levels did not differ substantially in Gossypium hirsutum L. lysine-rich protein (GhLRP transgenic kernels when compared to wild-type. The agronomic characteristics of all the transgenic maize were also normal. GhLRP is a high-lysine protein candidate gene for increasing the lysine content of maize. This study provided a valuable model system for improving maize lysine content.

  5. Seed-specific expression of a lysine-rich protein gene, GhLRP, from cotton significantly increases the lysine content in maize seeds.

    Science.gov (United States)

    Yue, Jing; Li, Cong; Zhao, Qian; Zhu, Dengyun; Yu, Jingjuan

    2014-03-27

    Maize seed storage proteins are a major source of human and livestock consumption. However, these proteins have poor nutritional value, because they are deficient in lysine and tryptophan. Much research has been done to elevate the lysine content by reducing zein content or regulating the activities of key enzymes in lysine metabolism. Using the naturally lysine-rich protein genes, sb401 and SBgLR, from potato, we previously increased the lysine and protein contents of maize seeds. Here, we examined another natural lysine-rich protein gene, GhLRP, from cotton, which increased the lysine content of transgenic maize seeds at levels varying from 16.2% to 65.0% relative to the wild-type. The total protein content was not distinctly different, except in the six transgenic lines. The lipid and starch levels did not differ substantially in Gossypium hirsutum L. lysine-rich protein (GhLRP) transgenic kernels when compared to wild-type. The agronomic characteristics of all the transgenic maize were also normal. GhLRP is a high-lysine protein candidate gene for increasing the lysine content of maize. This study provided a valuable model system for improving maize lysine content.

  6. Salinomycin suppresses LRP6 expression and inhibits both Wnt/β-catenin and mTORC1 signaling in breast and prostate cancer cells.

    Science.gov (United States)

    Lu, Wenyan; Li, Yonghe

    2014-10-01

    Emerging evidence indicates that activation of Wnt/β-catenin signaling at the cell surface results in inhibition of glycogen synthase kinase 3β (GSK3β), leading to activation of mTORC1 signaling in cancer cells. The low density lipoprotein receptor-related protein-6 (LRP6) is an essential Wnt co-receptor for Wnt/β-catenin signaling. Salinomycin is a novel small molecule inhibitor of LRP6. In the present study, we found that LRP6 overexpression induced mTORC1 signaling activation in cancer cells, and that salinomycin was not only a potent Wnt/β-catenin signaling inhibitor, but also a strong mTORC1 signaling antagonist in breast and prostate cancer cells. Mechanistically, salinomycin activated GSK3β in cancer cells. Moreover, salinomycin was able to suppress the expression of cyclin D1 and survivin, two targets of both Wnt/β-catenin and mTORC1 signaling, in prostate and breast cancer cells, and displayed remarkable anticancer activity. Our results present novel mechanisms underlying salinomycin-mediated cancer cell death.

  7. 小鼠LRP16基因打靶载体的构建和同源重组型胚胎干细胞筛选%Construction of a LRP16 gene targeting vector and screening of homologously recombinant clone of embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    伍志强; 韩为东; 赵亚力; 司艺玲; 母义明; 孟元光; Masatoshi Nomura

    2008-01-01

    BACKGROUND: Previous studies have demonstrated that LRP16 is an estrogen-responsive gene. Its expression level is strongly associated with the proliferation and invasive growth of human breast cancer cells.OBJECTIVE: To construct a LRP16 targeting vector and screen mouse embryonic stem cell clones with homolougous recombination of an inactive LRP16 gene.DESIGN: Constructing an inserting inactivation target by inserting SA-RIES-β geo expression cassette.SETTING: Bioregulatory Laboratory of the Third Medical Department of Kyushu University in Japan and Department of Molecular Biology, General Hospital of Chinese PLA.MATERIALS: The materials used here were mainly provided by the Bioregulatory Laboratory, the Third Medical Department of Kyushu University in Japan. The mouse genomic library in pBeloBAC11 Vector was purchased from lnvitrogen Corp. The competent TopF10 was purchased from Beijing Tiangen Biotech Corp. pcDNA3.1(+) vector was kept in our laboratory. Mouse ES cells were provided by Kyushu University.METHODS: The experiment was performed in Kyushu University and Department of Molecular Biology of PLA General Hospital from November 2004 to May 2005. Targeting sequence of LRP16 gene was obtained from 129 mouse genomic Bacterial Artificial Chromosomes library based on polymerase chain reaction (PCR) screening. The SA-RIES-β geo fragment was inserted within LRP16 fifth exon to inactivate LRP16. ES cells were screened with G418 and the homologously recombinant clone was identified by Southern blot analysis.MAIN OUTCOME MEASURES: Clones with homologous recombination.RESULTS: The LRP16 fragment including exon 5 to 11 was subcloned into the pBluescript SK Ⅱvector. Restriction map demonstrated that the SA-IRES-β geo fragment was correctly inserted into the LRP16 fifth exon. Southern blot results showed that there was an ES clone with targeting sequence homologously inserted.CONCLUSION: A LRP16 gene targeting vector is constructed and a homologous recombinant is

  8. Evidence that the newly cloned low-density-lipoprotein receptor related protein (LRP) is the alpha 2-macroglobulin receptor

    DEFF Research Database (Denmark)

    Kristensen, T; Moestrup, Søren Kragh; Gliemann, Jørgen;

    1990-01-01

    The human placental receptor (alpha 2MR) for alpha 2-macroglobulin-proteinase complexes contains 3 polypeptides of approx. 500 kDa, 85 kDa, and 40 kDa. N-terminal sequence analysis of the 500 kDa and 85 kDa polypeptides, analysis of a random selection of peptides convering 536 residues from...... these polypeptides, and analysis of a 1772 bp cDNA encoding part of the 500 kDa polypeptide provide evidence that the 500 kDa and 85 kDa chains are the alpha- and beta-subunits, respectively, of a recently cloned hepatic membrane protein, termed the low density lipoprotein receptor related protein (LRP) (Herz, J......., Hamann, U., Rogne, S., Myklebost, O., Gausepohl, H. and Stanley, K.K. (1988) EMBO J. 7, 4119-4127; Herz, J., Kowal, R.C., Goldstein, J.L. and Brown, M.S. (1990) EMBO J. 9, 1769-1776). N-terminal sequence analysis of the 40 kDa polypeptide shows that it is of distinct genetic origin. It is suggested...

  9. Dimerization leads to changes in APP (amyloid precursor protein) trafficking mediated by LRP1 and SorLA.

    Science.gov (United States)

    Eggert, Simone; Gonzalez, A C; Thomas, C; Schilling, S; Schwarz, S M; Tischer, C; Adam, V; Strecker, P; Schmidt, V; Willnow, T E; Hermey, G; Pietrzik, C U; Koo, E H; Kins, Stefan

    2017-08-10

    Proteolytic cleavage of the amyloid precursor protein (APP) by α-, β- and γ-secretases is a determining factor in Alzheimer's disease (AD). Imbalances in the activity of all three enzymes can result in alterations towards pathogenic Aβ production. Proteolysis of APP is strongly linked to its subcellular localization as the secretases involved are distributed in different cellular compartments. APP has been shown to dimerize in cis-orientation, affecting Aβ production. This might be explained by different substrate properties defined by the APP oligomerization state or alternatively by altered APP monomer/dimer localization. We investigated the latter hypothesis using two different APP dimerization systems in HeLa cells. Dimerization caused a decreased localization of APP to the Golgi and at the plasma membrane, whereas the levels in the ER and in endosomes were increased. Furthermore, we observed via live cell imaging and biochemical analyses that APP dimerization affects its interaction with LRP1 and SorLA, suggesting that APP dimerization modulates its interplay with sorting molecules and in turn its localization and processing. Thus, pharmacological approaches targeting APP oligomerization properties might open novel strategies for treatment of AD.

  10. 20 CFR 1002.264 - Is the employee allowed to repay a previous distribution from a pension benefits plan upon being...

    Science.gov (United States)

    2010-04-01

    ... distribution from a pension benefits plan upon being reemployed? 1002.264 Section 1002.264 Employees' Benefits... and Benefits Pension Plan Benefits § 1002.264 Is the employee allowed to repay a previous distribution from a pension benefits plan upon being reemployed? Yes, provided the plan is a defined benefit plan...

  11. The High Affinity Binding Site on Plasminogen Activator Inhibitor-1 (PAI-1) for the Low Density Lipoprotein Receptor-related Protein (LRP1) Is Composed of Four Basic Residues.

    Science.gov (United States)

    Gettins, Peter G W; Dolmer, Klavs

    2016-01-08

    Plasminogen activator inhibitor 1 (PAI-1) is a serpin inhibitor of the plasminogen activators urokinase-type plasminogen activator (uPA) and tissue plasminogen activator, which binds tightly to the clearance and signaling receptor low density lipoprotein receptor-related protein 1 (LRP1) in both proteinase-complexed and uncomplexed forms. Binding sites for PAI-1 within LRP1 have been localized to CR clusters II and IV. Within cluster II, there is a strong preference for the triple CR domain fragment CR456. Previous mutagenesis studies to identify the binding site on PAI-1 for LRP1 have given conflicting results or implied small binding contributions incompatible with the high affinity PAI-1/LRP1 interaction. Using a highly sensitive solution fluorescence assay, we have examined binding of CR456 to arginine and lysine variants of PAI-1 and definitively identified the binding site as composed of four basic residues, Lys-69, Arg-76, Lys-80, and Lys-88. These are highly conserved among mammalian PAI-1s. Individual mutations result in a 13-800-fold increase in Kd values. We present evidence that binding involves engagement of CR4 by Lys-88, CR5 by Arg-76 and Lys-80, and CR6 by Lys-69, with the strongest interactions to CR5 and CR6. Collectively, the individual binding contributions account quantitatively for the overall PAI-1/LRP1 affinity. We propose that the greater efficiency of PAI-1·uPA complex binding and clearance by LRP1, compared with PAI-1 alone, is due solely to simultaneous binding of the uPA moiety in the complex to its receptor, thereby making binding of the PAI-1 moiety to LRP1 a two-dimensional surface-localized association.

  12. Receptor-associated protein (RAP) has two high-affinity binding sites for the low-density lipoprotein receptor-related protein (LRP): consequences for the chaperone functions of RAP.

    Science.gov (United States)

    Jensen, Jan K; Dolmer, Klavs; Schar, Christine; Gettins, Peter G W

    2009-06-26

    RAP (receptor-associated protein) is a three domain 38 kDa ER (endoplasmic reticulum)-resident protein that is a chaperone for the LRP (low-density lipoprotein receptor-related protein). Whereas RAP is known to compete for binding of all known LRP ligands, neither the location, the number of binding sites on LRP, nor the domains of RAP involved in binding is known with certainty. We have systematically examined the binding of each of the three RAP domains (D1, D2 and D3) to tandem and triple CRs (complement-like repeats) that span the principal ligand-binding region, cluster II, of LRP. We found that D3 binds with low nanomolar affinity to all (CR)2 species examined. Addition of a third CR domain increases the affinity for D3 slightly. A pH change from 7.4 to 5.5 gave only a 6-fold increase in Kd for D3 at 37 degrees C, whereas temperature change from 22 degrees C to 37 degrees C has a similar small effect on affinity, raising questions about the recently proposed D3-destabilization mechanism of RAP release from LRP. Surprisingly, and in contrast to literature suggestions, D1 and D2 also bind to most (CR)2 and (CR)3 constructs with nanomolar affinity. Although this suggested that there might be three high-affinity binding sites in RAP for LRP, studies with intact RAP showed that only two binding sites are available in the intact chaperone. These findings suggest a new model for RAP to function as a folding chaperone and also for the involvement of YWTD domains in RAP release from LRP in the Golgi.

  13. The Farmers Perception on Effectiveness of Private Forest Revolving Fund Distribution and Factors Affecting its Repayment: Case in South Lampung District, Lampung Province

    Directory of Open Access Journals (Sweden)

    Sanudin

    2016-04-01

    Full Text Available Commercial s are ed providing for forest plantation development bank not interest in fund community based . - Therefore, in this case, non bank institutions such Forest Development Funding Center (pusat pembiayaan pembangunan hutan, PPPH private forest are highly required. This paper is aimed to find out the effectiveness of revolving fund and factors affecting its repayment distribution . The research was conducted during September–December 2014 in Private Forest Farmer Groups in Katibung Sub-District South Lampung Dist 3 , , rict Lampung Province. The data was collected through household surveys and in-depth interviews. The household surveys were done using structured questionnaires that included questions related to: characteristics of the borrowers, characteristics of private forest, characteristics of loan, and household perceptions on private forest revolving fund Household perceptions on private forest revolving fund are loan . pre requirement, loan procedure, realization, interest rate, , and repayment procedure The effectiveness of private forest length of repayment periode . revolving fund d t and factors affecting repayment of loan was analyzed by istribution was analyzed by liker scale logistic regression. ult private forest revolving fund in The res showed that: 1 three private forest farmer groups in Katibung Sub-District, South Lampung effective District was 2 income from non-private forest and amount of loan , are factors affecting repayment of private forest revolving fund, 3 faced private forest revolving f the problem in und distribution PPPH private could be overcame by maximizing the role of field officers in assisting and facilitating forest revolving fund ors debit candidate.

  14. Effects of neoadjuvant chemotherapy on the quantitative expression of P-gp, LRP, MRP, GST-π in NSCLC and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    XIANG Fenggang; YU Wenjuan; SHEN Yi; WU Cuijiao; WANG Yuewei

    2007-01-01

    Background and objective Neoadjuvant chemotherapy (NACT) plays an important role in systemic chemotherapy for non-small cell lung cancer (NSCLC). P-glycoprotein (P-gp), lung resistance related protein (LRP), multidrug resistance-associated protein (MRP) and glutathione S-transferase (GST-π) may be associated to drug resisitance to chemotherapy in NSCLC. The aim of this study is to investigate the expressions of P-gp, LRP, MRP and GST-π in samples from NSCLC patients before and after treatment with NACT, and their quantitative changes, so that to evaluate the influence of NACT on drug resistance to chemotherapy of NSCLC. Methods Total 92 specimens from 72 cases of NSCLC, including 52 samples of surgery excision from non-NACT-treated patients and 20 paired samples before and after NACT from the same patient,were studied. The expression of P-gp, LRP, MRP and GST-π was detected with tissue chip technique and immunohistochemistry. The quantitative analysis was carried out by computer image analysis system. Results In the samples before NACT, the positive rate of P-gp, LRP, MRP, GST-π expression was 66.67% (48/72),72.22% (52/72), 81.94% (59/72), 83. 33% (60/72), respectively. The expressive intensity of P-gp, LRP and GST-π was significantly stronger in adenocarcinoma than that in squamous cell carcinoma (P<0.05, P<0.001, P<0.001, respectively); there was no significant difference in the expression of MRP between adenocarcinoma and squamous cell carcinoma (P>0.05). In samples after treatment with NACT, the expression of P-gp, GST-π demonstrated by average optical density (AOD) and integral optical density (IOD) were significantly higher (P<0.05, P<0.001 respectively) than that in biopsied samples taken before NACT; The change in expression of P-gp, GST-π was also showed difference by different histopathological types, differentiations, ages, sizes, clinical stages as well as lymph node metastasis or not (P<0. 05 or P<0. 001). There was no

  15. Expression of P-gp, MRP, LRP, GST-π and TopoIIα and intrinsic resistance in human lung cancer cell lines.

    Science.gov (United States)

    Wang, Jiarui; Zhang, Jinhui; Zhang, Lichuan; Zhao, Long; Fan, Sufang; Yang, Zhonghai; Gao, Fei; Kong, Ying; Xiao, Gary Guishan; Wang, Qi

    2011-11-01

    This study aimed to determine the relationship between the endogenous levels of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione-s-transferase-π (GST‑π) and topoisomerase IIα (TopoIIα) and intrinsic drug resistance in four human lung cancer cell lines, SK-MES-1, SPCA-1, NCI-H-460 and NCI-H-446, of different histological types. The expression of P-gp, MRP, LRP, GST-π and TopoIIα was measured by immunofluorescence, Western blotting and RT-PCR. Drug resistance to cisplatin, doxorubicin and VP-16 was determined using MTT assays. The correlation between expression of the resistance-related proteins and their roles in the resistance to drugs in these cancer cell lines was analyzed. We found that the endogenous levels of P-gp, MRP, LRP, GST-π and TopoIIα in the four cell lines varied. The level of GST-π in the SK-MES-1 cells was the highest, whereas the level of P-gp in the SPCA-1 cells was the lowest. The chemoresistance to cisplatin, doxorubicin and VP-16 in the four cell lines was different. The SPCA-1 cell line was most resistance to cisplatin; SK-MES-1 was most resistance to VP-16; whereas SK-MES-1 was most sensitive to doxorubicin. There was a positive correlation between GST-π expression and resistance to cisplatin, between TopoIIα expression and resistance to VP-16; and a negative correlation was noted between TopoIIα expression and resistance to doxorubicin. In summary, the endogenous expression of P-gp, MRP, LRP, GST-π and TopoIIα was different in the four human lung cancer cell lines of different histological types, and this variance may be associated with the variation in chemosensitivity to cisplatin, doxorubicin and VP-16. Among the related proteins, GST-π may be useful for the prediction of the intrinsic resistance to cisplatin, whereas TopoIIα may be useful to predict resistance to doxorubicin and VP-16 in human lung cancer cell lines.

  16. The rLrp of Mycobacterium tuberculosis inhibits proinflammatory cytokine production and downregulates APC function in mouse macrophages via a TLR2-mediated PI3K/Akt pathway activation-dependent mechanism.

    Science.gov (United States)

    Liu, Yuan; Li, Jia-Yun; Chen, Su-Ting; Huang, Hai-Rong; Cai, Hong

    2016-11-01

    We demonstrate that Mycobacterium tuberculosis recombinant leucine-responsive regulatory protein (rLrp) inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α), interleukin-6, and interleukin-12 production and blocks the nuclear translocation of subunits of the nuclear-receptor transcription factor NF-κB (Nuclear factor-kappa B). Moreover, rLrp attenuated LPS-induced DNA binding and NF-κB transcriptional activity, which was accompanied by the degradation of inhibitory IκBα and a consequent decrease in the nuclear translocation of the NF-κB p65 subunit. RLrp interfered with the LPS-induced clustering of TNF receptor-associated factor 6 and with interleukin-1 receptor-associated kinase 1 binding to TAK1. Furthermore, rLrp did not attenuate proinflammatory cytokines or the expression of CD86 and major histocompatibility complex class-II induced by interferon-gamma in the macrophages of Toll-like receptor 2 deletion (TLR2(-/-)) mice and in protein kinase b (Akt)-depleted mouse cells, indicating that the inhibitory effects of rLrp were dependent on TLR2-mediated activation of the phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. RLrp could also activate the PI3K/Akt pathway by stimulating the rapid phosphorylation of PI3K, Akt, and glycogen synthase kinase 3 beta in macrophages. In addition, 19 amino acid residues in the N-terminus of rLrp were determined to be important and required for the inhibitory effects mediated by TLR2. The inhibitory function of these 19 amino acids of rLrp raises the possibility that mimetic inhibitory peptides could be used to restrict innate immune responses in situations in which prolonged TLR signaling has deleterious effects. Our study offers new insight into the inhibitory mechanisms by which the TLR2-mediated PI3K/Akt pathway ensures the transient expression of potent inflammatory mediators.

  17. Study on correlation among expression of LRP and platinum resistance and prognosis in advanced non-small cell lung cancer%晚期非小细胞肺癌组织中 LRP 表达与铂类耐药性及预后的相关性研究

    Institute of Scientific and Technical Information of China (English)

    刘琼; 黄昌杰; 黄文锋; 湛永滋; 黄剑锋; 王湘萍

    2014-01-01

    目的探讨晚期非小细胞肺癌(NSCLC)组织中肺耐药蛋白(LRP)的表达与铂类化疗耐药及其预后的关系。方法采用免疫组织化学SP法对89例晚期NSCLC碏块进行免疫组织化学染色,检测LRP的表达水平,并分析其与患者的性别、年龄、吸烟史、组织分型、分化程度、远处转移、淋巴结转移及含铂化疗方案疗效的关系。结果在NSCLC患者组织中,LRP的阳性表达率为77.5%,与年龄、吸烟史、组织分型、分化程度和淋巴结转移无关( P均>0.05),而LRP表达阳性组和阴性组的含铂类方案化疗疗效、有效率、总反应率、无进展生存时间和总生存时间比较差异无统计学意义( P均>0.05)。女性患者肿瘤组织LRP表达阳性率(95.5%)高于男性患者(71.6%)(P=0.043);在远处转移的患者中,LPR阳性表达率为87.3%,而无远处转移的患者LRP阳性表达率为61.8%,差异有统计学意义( P=0.005)。结论 LRP基因的阳性表达与远处转移有关,且LRP阳性表达患者无疾病进展时间及总生存时间均低于LRP阴性表达患者,提示其可能作为判断预后指标。%Objective To study the expression of lung resistance protein (LRP) in non-small cell Lung Cancer(NSCLC) and its correlation with Platium resistance and prognosis .Methods The expression of LRP in 89 NSCLC patients was detected by the way of immunohistochemical method .The relationship between LRP and clinico-pathological feature and the others (age, sex, smoking history, histological type, differentiation, distant metastasis, lymphatic metastasis and so on ) were studied .Results In the tissues of patients with NSCLC , the positive express-ing rate of LRP was 77.5%, and was not related with age , sex, smoking history, histological type, differentiation, distant metastasis , lymphatic metastasis ( P>0.05 ) .In the platinum contained chemotherapy regimens , there were not

  18. Practical Problems of Giving Opinions by Regional Chambers of Accounting on the Possibility of Repayment of Obligations in Local Government Units

    Directory of Open Access Journals (Sweden)

    Marcin Tyniewicki

    2014-06-01

    Full Text Available Opinions of the regional accounting chambers on the possibility of repayment of the credit, loan or redemption of the securities by local government units have some specific features compared with the other opinions concerning the financial management of the local government. Firstly, they are only issued at the request of the unit that they concerned. Secondly, for the reason they relate to public debt issues, to some extent their content may be similar or “partial reproduction” of the standpoint of the regional chamber of accounting within already issued opinions referring to acts on budgetary planning process in local government units. The purpose of this article is to assess the legitimacy of issuing such opinions and to identify the relationship between the ordinances (resolutions on the possibility of repayment of the credit, loan or redemption of the securities and provisions of local government budget.

  19. BarR, an Lrp-type transcription factor in Sulfolobus acidocaldarius, regulates an aminotransferase gene in a β-alanine responsive manner.

    Science.gov (United States)

    Liu, Han; Orell, Alvaro; Maes, Dominique; van Wolferen, Marleen; Lindås, Ann-Christin; Bernander, Rolf; Albers, Sonja-Verena; Charlier, Daniel; Peeters, Eveline

    2014-05-01

    In archaea, nothing is known about the β-alanine degradation pathway or its regulation. In this work, we identify and characterize BarR, a novel Lrp-like transcription factor and the first one that has a non-proteinogenic amino acid ligand. BarR is conserved in Sulfolobus acidocaldarius and Sulfolobus tokodaii and is located in a divergent operon with a gene predicted to encode β-alanine aminotransferase. Deletion of barR resulted in a reduced exponential growth rate in the presence of β-alanine. Furthermore, qRT-PCR and promoter activity assays demonstrated that BarR activates the expression of the adjacent aminotransferase gene, but only upon β-alanine supplementation. In contrast, auto-activation proved to be β-alanine independent. Heterologously produced BarR is an octamer in solution and forms a single complex by interacting with multiple sites in the 170 bp long intergenic region separating the divergently transcribed genes. In vitro, DNA binding is specifically responsive to β-alanine and site-mutant analyses indicated that β-alanine directly interacts with the ligand-binding pocket. Altogether, this work contributes to the growing body of evidence that in archaea, Lrp-like transcription factors have physiological roles that go beyond the regulation of α-amino acid metabolism.

  20. RACE技术在钓取白血病相关基因LRP16全长cDNA中的应用

    Institute of Scientific and Technical Information of China (English)

    韩为东; 于力; 等

    2001-01-01

    LRP16是我们应用甲基化敏感的限制性界标基因组扫描(restrection landmark genomic scanning,RLGS)技术时发现的一个与白血病复发相关的新基因。为钓取这一新基因的全长cDNA,本实验采用cDNA末端快速扩增法(rapid amplification of cDNA end,RACE)。通过对RACE法若干步骤进行优化,克隆得到了LRP16基因cDNA的5’-与3’-非翻译区,进而获得其全长及完整的开放阅读框架,并作为新基因被GenBank收录。上述结果表明,RACE技术是钓取未知基因全长cDNA敏感而快速的方法,尤其是对5’-及3’-非翻译区的钓取更具有实用性。

  1. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pires, L.A. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Hegg, R. [Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Freitas, F.R.; Tavares, E.R.; Almeida, C.P. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Baracat, E.C. [Departamento de Ginecologia, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Maranhão, R.C. [Laboratório de Metabolismo de Lípides, Instituto do Coração, Faculdade de Medicina, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP (Brazil); Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-05-04

    Low-density lipoprotein (LDL) receptors are overexpressed in most neoplastic cell lines and provide a mechanism for the internalization and concentration of drug-laden nanoemulsions that bind to these receptors. The aim of the present study was to determine whether the administration of standard chemotherapeutic schemes can alter the expression of LDL and LDL receptor-related protein 1 (LRP-1) receptors in breast carcinoma. Fragments of tumoral and normal breast tissue from 16 consecutive volunteer women with breast cancer in stage II or III were obtained from biopsies before the beginning of neoadjuvant chemotherapy and after chemotherapy, from fragments excised during mastectomy. Tissues were analyzed by immunohistochemistry for both receptors. Because complete response to treatment was achieved in 4 patients, only the tumors from 12 were analyzed. Before chemotherapy, there was overexpression of LDL receptor in the tumoral tissue compared to normal breast tissue in 8 of these patients. LRP-1 receptor overexpression was observed in tumors of 4 patients. After chemotherapy, expression of both receptors decreased in the tumors of 6 patients, increased in 4 and was unchanged in 2. Nonetheless, even when chemotherapy reduced receptors expression, the expression was still above normal. The fact that chemotherapy does not impair LDL receptors expression supports the use of drug carrier systems that target neoplastic cells by the LDL receptor endocytic pathway in patients on conventional chemotherapy.

  2. A low-pH medium in vitro or the environment within a macrophage decreases the transcriptional levels of fimA, fimZ and lrp in Salmonella enterica serovar Typhimurium

    Indian Academy of Sciences (India)

    Ke-Chuan Wang; Yuan-Hsun Hsu; Yi-Ning Huang; Ter-Hsin Chen; Jiunn-Horng Lin; Shih-Ling Hsuan; Maw-Sheng Chien; Wei-Cheng Lee; Kuang-Sheng Yeh

    2013-09-01

    Many Salmonella Typhimurium isolates produce type 1 fimbriae and exhibit fimbrial phase variation in vitro. Static broth culture favours the production of fimbriae, while solid agar medium inhibits the generation of these appendages. Little information is available regarding whether . Typhimurium continues to produce type 1 fimbriae during in vivo growth. We used a type 1 fimbrial phase-variable strain . Typhimurium LB5010 and its derivatives to infect RAW 264.7 macrophages. Following entry into macrophages, . Typhimurium LB5010 gradually decreased the transcript levels of fimbrial subunit gene fimA, positive regulatory gene fimZ, and global regulatory gene lrp. A similar decrease in transcript levels was detected by RT-PCRwhen the pH of static brothmediumwas shifted frompH 7 to amore acidic pH 4. A fimA-deleted strain continued to multiply within macrophages as did the parental strain. An lrp deletion strain was unimpaired for in vitro growth at pH 7 or pH 4, while a strain harboring an lrp-containing plasmid exhibited impaired in vitro growth at pH 4. We propose that acidic medium, which resembles one aspect of the intracellular environment in a macrophage, inhibits type 1 fimbrial production by down-regulation of the expression of lrp, fimZ and fimA.

  3. A low-pH medium in vitro or the environment within a macrophage decreases the transcriptional levels of fimA, fimZ and lrp in Salmonella enterica serovar Typhimurium.

    Science.gov (United States)

    Wang, Ke-Chuan; Hsu, Yuan-Hsun; Huang, Yi-Ning; Chen, Ter-Hsin; Lin, Jiunn-Horng; Hsuan, Shih-Ling; Chien, Maw-Sheng; Lee, Wei-Cheng; Yeh, Kuang-Sheng

    2013-09-01

    Many Salmonella Typhimurium isolates produce type 1 fimbriae and exhibit fimbrial phase variation in vitro. Static broth culture favours the production of fimbriae, while solid agar medium inhibits the generation of these appendages. Little information is available regarding whether S. Typhimurium continues to produce type 1 fimbriae during in vivo growth. We used a type 1 fimbrial phase-variable strain S. Typhimurium LB5010 and its derivatives to infect RAW 264.7 macrophages. Following entry into macrophages, S. Typhimurium LB5010 gradually decreased the transcript levels of fimbrial subunit gene fimA, positive regulatory gene fimZ, and global regulatory gene lrp. A similar decrease in transcript levels was detected by RT-PCRwhen the pH of static brothmediumwas shifted frompH 7 to amore acidic pH 4. A fimA-deleted strain continued to multiply within macrophages as did the parental strain. An lrp deletion strain was unimpaired for in vitro growth at pH 7 or pH 4, while a strain harboring an lrp-containing plasmid exhibited impaired in vitro growth at pH 4. We propose that acidic medium, which resembles one aspect of the intracellular environment in a macrophage, inhibits type 1 fimbrial production by down-regulation of the expression of lrp, fimZ and fimA.

  4. Association of type 2 diabetes mellitus with the interaction between low-density lipoprotein receptor-related protein 5 (LRP5) polymorphisms and overweight and obesity in rural Chinese adults.

    Science.gov (United States)

    Zhang, Lu; Wang, Jinjin; Zhang, Ming; Wang, Guo'an; Shen, Yanxia; Wu, Dongting; Wang, Chongjian; Li, Linlin; Ren, Yongcheng; Wang, Bingyuan; Zhang, Hongyan; Yang, Xiangyu; Zhao, Yang; Han, Chengyi; Zhou, Junmei; Pang, Chao; Yin, Lei; Zhao, Jingzhi; Luo, Xinping; Hu, Dongsheng

    2017-01-09

    Low-density lipoprotein receptor-related protein 5 (LRP5) plays an important role in glucose and cholesterol metabolism. The present cohort study evaluated associations of LRP5 variants with the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. In all, 7751 subjects aged ≥18 years without T2DM underwent genotyping at baseline; 6326 subjects (81.62%) were followed-up, and 5511 with a clear disease outcome were eligible for analysis. The same questionnaire was administered and the same anthropometric and blood biochemical examinations were performed at baseline and follow-up. Association analysis was performed for five single nucleotide polymorphisms and haplotypes of LRP5. Cox proportional hazards testing of three different genetic models found no significant association between T2DM and LRP5 after adjusting for potential risk factors (P > 0.05). However, the incidence of T2DM in subjects with LRP5 mutational genotypes was higher in the overweight/obese than normal weight population. Under the dominant model, the risk of T2DM was increased with an interaction between rs11228303 and the waist-to-height ratio adjusted for baseline age, sex, and family history of T2DM (synergy index [SI] = 4.172; 95% confidence interval [CI] 1.014-17.166)], and body mass index (SI = 3.237; 95% CI 1.102-9.509). Furthermore, the A allele of rs3758644 was related to decreased fasting plasma insulin and homeostatic model assessment of β-cell function levels, whereas the T allele of rs12363572 was related to increased high-density lipoprotein cholesterol levels in new-onset diabetes patients (P < 0.05). The risk of T2DM may be associated with interactions between the LRP5 gene and overweight and obesity. Polymorphisms of LRP5 are related to β-cell function and lipid metabolism. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  5. 成人急性白血病GST-π与LRP基因的RQ-PCR检测及其临床意义%RQ-PCR Detection of GST-π and LRP Genes in Adult Acute Leukemia and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    王静; 肖镇

    2012-01-01

    本研究通过对急性白血病(AL)患者外周血谷胱甘肽-S-转移酶-π(GST-π)和肺耐药相关蛋白(lung resistance-related protein,LRP)基因的检测,探讨两种基因与患者多药耐药性的关系.采用实时荧光定量逆转录-聚合酶链反应(RQ-PCR)检测44例AL患者及27例正常人外周血单个核细胞GST-π与LRP基因的表达.结果表明,GST-π基因水平在初治组和难治组与完全缓解组之间均有极显著性差异(P<0.01).LPR基因水平在初治组与难治组,完全缓解组与难治组均有极显著性差异(P≤0.01).GST-π与LRP基因之间无相关性.GST-π及LRP基因表达在不同外周血白细胞计数组、不同临床分型组( ALL、ANLL)之间的差异均不显著.结论:GST-π和LRP基因通过不同机制引起多药耐药,二者联合检测较单独测定某一基因对白血病评定预后更具临床意义.外周血白细胞计数、白血病分型可能与GST-π和LRP基因的表达无关.%This study was aimed to detect the glutathion S-transferase-iT ( GST-ir) and lung resistance-related protein (LRP) genes and to investigate their relationship with multidrug resistance (MDR) of patients with acute leukemia(AL). Real-time fluorescent quantitative reverse transcription polymerase chain reaction (RQ-PCR) was used to detect the expression of GST-tt and LRP genes in peripheral blood mononuclear cells from 44 AL patients and 27 normal subjects. The results showed that the significant difference in GST-tt expression level was found between newly diagnosed patients and complete remission patients and between refractory patients and complete remission patients (P < 0. 01), while expression level of LRP genes showed obvious difference (P≤0. 01) between newly diagnosed patients and refractory patients and between complete remission patients and refractory patients. Statistical analysis indicated that there was no correlation between GST-tt gene and LRP gene. The expression of GST-tt and LRP genes

  6. ANALISIS EFEKTIVITAS PEMBERIAN PINJAMAN PROGRAM PEMBIAYAAN UMKM OLEH KOPERASI

    Directory of Open Access Journals (Sweden)

    Hadi Ismanto

    2014-10-01

    Full Text Available Abstrak: Analisis Efektivitas Pemberian Pinjaman Program Pembiayaan UMKM Oleh Koperasi. Program Pembiayaan memiliki peran yang penting bagi UMKM, namun sering menghadapi masalah penunggakan dan kemacetan pembayaran angsuran. Penelitian ini berupaya untuk mengetahui sebab-sebab tidak lancarnya pengembalian Program Pembiayaan UJKS sehingga diharapkan dapat menyusun strategi yang lebih baik lagi dalam menyeleksi calon peminjam agar angka pinjaman bermasalah dapat ditekan. Populasi dalam penelitian ini adalah semua UMKM yang menjadi Peminjam (peminjam program pembiayaan UJKS Mitra Usaha dan masih tergolong aktif hingga bulan November 2013 dan telah memperoleh fasilitas pembiayaan sekurang-kurangnya enam bulan berjalan. Penelitian ini menemukan bahwa faktor-faktor yang berpengaruh positif terhadap tingkat pengembalian pinjaman (lancar atau menunggak adalah omzet usaha, lama usaha dan nilai plafon pinjaman. Hal ini dapat dijadikan bahan pertimbangan bagi UJKS dalam menjalankan program pembiayaan sehingga menjadi lebih efektif dalam menjalankannya.   Kata Kunci: UMKM, UJKS, Program Pembiayaan, Lancar, dan Macet.   Abstract: Effectiveness Analysis of SMEs Financing Program by Cooperative. Financing programs have an important role to SMEs, but often face the problem of repayment failures and installment payments. This study examines the causes of saving and loan cooperatives’ repayment problems. The population of this study is all SMEs borrowing from Mitra Usaha saving and loan cooperative. Furthermore these SMEs must be categorized as active SMEs until November 2013 and they had been receiving loan for at least six months. The study found that the variables such as: the length of the business, the business volume, and the value of the loan have a positive impact on repayment rate.   Keywords: SMEs, Saving and Loan Cooperative, Financing Program

  7. Verification of predicted alternatively spliced Wnt genes reveals two new splice variants (CTNNB1 and LRP5 and altered Axin-1 expression during tumour progression

    Directory of Open Access Journals (Sweden)

    Reich Jens G

    2006-06-01

    Full Text Available Abstract Background Splicing processes might play a major role in carcinogenesis and tumour progression. The Wnt pathway is of crucial relevance for cancer progression. Therefore we focussed on the Wnt/β-catenin signalling pathway in order to validate the expression of sequences predicted as alternatively spliced by bioinformatic methods. Splice variants of its key molecules were selected, which may be critical components for the understanding of colorectal tumour progression and may have the potential to act as biological markers. For some of the Wnt pathway genes the existence of splice variants was either proposed (e.g. β-Catenin and CTNNB1 or described only in non-colon tissues (e.g. GSK3β or hitherto not published (e.g. LRP5. Results Both splice variants – normal and alternative form – of all selected Wnt pathway components were found to be expressed in cell lines as well as in samples derived from tumour, normal and healthy tissues. All splice positions corresponded totally with the bioinformatical prediction as shown by sequencing. Two hitherto not described alternative splice forms (CTNNB1 and LRP5 were detected. Although the underlying EST data used for the bioinformatic analysis suggested a tumour-specific expression neither a qualitative nor a significant quantitative difference between the expression in tumour and healthy tissues was detected. Axin-1 expression was reduced in later stages and in samples from carcinomas forming distant metastases. Conclusion We were first to describe that splice forms of crucial genes of the Wnt-pathway are expressed in human colorectal tissue. Newly described splicefoms were found for β-Catenin, LRP5, GSK3β, Axin-1 and CtBP1. However, the predicted cancer specificity suggested by the origin of the underlying ESTs was neither qualitatively nor significant quantitatively confirmed. That let us to conclude that EST sequence data can give adequate hints for the existence of alternative splicing

  8. Pulsed electromagnetic fields improve bone microstructure and strength in ovariectomized rats through a Wnt/Lrp5/β-catenin signaling-associated mechanism.

    Science.gov (United States)

    Jing, Da; Li, Feijiang; Jiang, Maogang; Cai, Jing; Wu, Yan; Xie, Kangning; Wu, Xiaoming; Tang, Chi; Liu, Juan; Guo, Wei; Shen, Guanghao; Luo, Erping

    2013-01-01

    Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and β-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/β-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.

  9. The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD

    Directory of Open Access Journals (Sweden)

    Jeong Byung-Hoon

    2011-08-01

    Full Text Available Abstract Background Although polymorphisms of PRNP, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s modulating susceptibility to prion disease. Ribosomal protein SA (RPSA, also called 37 kDa laminin receptor precursor (LRP/67 kDa laminin receptor (LR, acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR. Methods To identify other susceptibility genes involved in prion disease, we performed genetic analysis of RPSA. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on RPSA by direct sequencing or restriction fragment length polymorphism (RFLP analysis. Results We observed four single nucleotide polymorphisms (SNPs, including -8T>C (rs1803893 in the 5'-untranslated region (UTR of exon 2, 134-32C>T (rs3772138 in the intron, 519G>A (rs2269350 in the intron and 793+58C>T (rs2723 in the intron on the RPSA. The 519G>A (at codon 173 is located in the direct PrP binding site. The genotypes and allele frequencies of the RPSA polymorphisms showed no significant differences between the controls and sporadic CJD patients. Conclusion These results suggest that these RPSA polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of RPSA gene with sporadic CJD.

  10. 34 CFR 674.34 - Deferment of repayment-Federal Perkins loans, NDSLs and Defense loans.

    Science.gov (United States)

    2010-07-01

    ... and in attendance as a regular student in at least a half-time course of study at an eligible... graduate fellowship program approved by the Secretary; (iii) Engaged in graduate or post-graduate... least a half-time regular student for a full academic year and intends to enroll as at least a...

  11. 77 FR 27467 - Proposed Information Collection; Request for Public Comment: Indian Health Service Loan Repayment...

    Science.gov (United States)

    2012-05-10

    ... for education expenses that meet program criteria and who are qualified and willing to serve at, often..., and the individual agrees to work at an IHS location and provide health services to American Indian... location according to vacancy rates for that fiscal year and also considers whether the location is in...

  12. RACE技术在钓取白血病相关基因LRP16 全长cDNA中的应用%The Application of RACE Technique to Clone the Full-Length cDNA of A Novel Leukemia Associated Gene LRP16

    Institute of Scientific and Technical Information of China (English)

    韩为东

    2001-01-01

    LRP16是我们应用甲基化敏感的限制性界标基因组扫描(restriction landmark genomicscanning,RLGS)技术时发现的一个与白血病复发相关的新基因.为钓取这一新基因的全长cDNA,本实验采用了cDNA末端快速扩增法(rapid amplification of cDNA end,RACE).通过对RACE法若干步骤进行优化,克隆得到了LRP16基因cDNA的5′-与3′-非翻译区,进而获得其全长及完整的开放阅读框架,并作为新基因被GenBank收录.上述结果表明,RACE技术是钓取未知基因全长cDNA敏感而快速的方法,尤其是对5′-及3′-非翻译区的钓取更具有实用性.

  13. 耐药相关蛋白P-gp、MRP、LRP在非小细胞肺癌组织中的表达及意义%The expression and significance of the multidrug resistance-related proteins P-gp, MRP and LRP in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To explore the expression and significance of the multidrug resistance-related proteins P-glycoprotein (P-gp), multidrug resistance-related protein (MRP), lung resistance protein (LRP) in human non-small cell lung cancer (NSCLC) tissues and paratumor tissues. Methods: Immunohistochemistry (IHC) was used to examine the expression level of proteins P-gp, MRP and LRP in 43 samples of NSCLC and 15 samples of paratumor tissues. Results: The expression rates of P-gp, MRP and LRP in 43 tumor tissues were 74.42% (32/43), 67.44% (29/43) and 88.37% (38/43), respectively, while in 15 paratumor tissues were 13.33% (2/15), 20.00% (3/15) and 6.67% (1/15), respectively. There was significant difference in the expression of proteins (P-gp, MRP and LRP) between lung cancer tissues and paratumor tissues (P < 0.05). The expression of proteins P-gp, LRP in lung adenocarcinoma were higher than that in other pathological carcinomas (P < 0.05). The expression of protein MRP was not related to pathological type, clinical stage and classification of histodifferentiation (P >0.05). Conclusion: Multidrug resistance is more common in NSCLC. The proteins of P-gp, MRP and LRP participated in the formation of multidrug resistance in lung cancer. Detection of multidrug resistance-related proteins in lung cancer tissues may be useful to choice drugs.

  14. Purification, crystallization and preliminary X-ray crystallographic analysis of ST1022, a putative member of the Lrp/AsnC family of transcriptional regulators isolated from Sulfolobus tokodaii strain 7

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Noboru; Kumarevel, Thirumananseri, E-mail: tskvel@spring8.or.jp; Matsunaga, Emiko; Shinkai, Akeo [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Kuramitsu, Seiki [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Department of Biological Sciences, Graduate School of Science, Osaka University, Tayonaka, Osaka 560-0043 (Japan); Yokoyama, Shigeyuki, E-mail: tskvel@spring8.or.jp [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Genomic Sciences Center, Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2007-11-01

    A putative member of the Lrp/AsnC family of transcriptional regulators, ST1022 from S. tokodaii strain 7, has been purified and crystallized in the absence and presence of the effector l-glutamine. A molecular-replacement solution was found using the FL11 transcriptional regulator from Pyrococcus sp. OT3 as a model and structural refinement is under way. The Lrp/AsnC family of transcriptional regulators, also known as feast/famine transcriptional regulators, are widely distributed among bacteria and archaea. This family of proteins are likely to be involved in cellular metabolism, with exogenous amino acids functioning as effectors. Here, the crystallization and preliminary X-ray diffraction analysis of ST1022, a member of the Lrp/AsnC family of proteins, is reported with and without exogenous glutamine as the effector molecule. The crystals of native ST1022 and of the putative complex belong to the tetragonal space group I422, with unit-cell parameters a = b = 103.771, c = 73.297 Å and a = b = 103.846, c = 73.992 Å, respectively. Preliminary X-ray diffraction data analysis and molecular-replacement solution revealed the presence of one monomer per asymmetric unit.

  15. A common LRP4 haplotype is associated with bone mineral density and hip geometry in men-Data from the Odense Androgen Study (OAS)

    DEFF Research Database (Denmark)

    Boudin, Eveline; Steenackers, Ellen; Freitas, Fenna de;

    2013-01-01

    6485702 and BMD at all sites except the lumbar spine. The most significant association was found with whole body BMD (p=4.7×10(-5)). In addition, we found these two polymorphisms to be associated with different geometry parameters especially of the femoral shaft. Analysis of the two associated SNPs.......05) and non-synonymous coding polymorphisms located in the extracellular region of the LRP4 protein: rs3816614 (A/g), rs2306029 (G/a), rs2306033 (C/t) and rs6485702 (G/a) (large and small characters indicate major and minor alleles, respectively). Bone mineral density (BMD) measurements of the hip, the spine...... and whole body as well as different hip geometry parameters were available for a total of 1404 Danish men from two age groups ([20-29 years]: n=804; [60-74 years]: n=600). Using linear regression analysis adjusted for age, height and weight, we found significant associations between both rs2306029 and rs...

  16. A Microfinance Program Targeting People Living with HIV in Uganda: Client Characteristics and Program Impact.

    Science.gov (United States)

    Linnemayr, Sebastian; Buzaalirwa, Lydia; Balya, James; Wagner, Glenn

    2016-09-14

    HIV has disproportionately affected economically vulnerable populations. HIV medical care, including antiretroviral therapy, successfully restores physical health but can be insufficient to achieve social and economic health. It may therefore be necessary to offer innovative economic support programs such as providing business training and microcredit tailored to people living with HIV/AIDS. However, microfinance institutions have shown reluctance to reach out to HIV-infected individuals, resulting in nongovernment and HIV care organizations providing these services. The authors investigate the baseline characteristics of a sample of medically stable clients in HIV care who are eligible for microcredit loans and evaluate their business and financial needs; the authors also analyze their repayment pattern and how their socioeconomic status changes after receipt of the program. The authors find that there is a significant unmet need for business capital for the sample under investigation, pointing toward the potentially beneficial role of providing microfinance and business training for clients in HIV care. HIV clients participating in the loans show high rates of repayment, and significant increases in (disposable) income, as well as profits and savings. The authors therefore encourage other HIV care providers to consider providing their clients with such loans.

  17. Watchdogs Prod Debt Repayment

    Institute of Scientific and Technical Information of China (English)

    REN WEI

    2006-01-01

    @@ As of the end of September, 102 publicly traded firms on the Shanghai and Shenzhen stock exchanges were still owed a total of 25.4 billion yuan (US$3.2 billion) by their parents or affiliates, even though the securities watchdogs have been pushing for the payback since June. On June 1, the two bourses made public the names of listed firms whose funds were misused by their shareholders and affiliates. At that time,a combined 33.6 billion yuan (US$4.2 billion)worth of funds were misused by major share owners or affiliated firms.

  18. Secure Repayable Storage System

    Science.gov (United States)

    Alkharobi, T. M.

    This paper proposes a method to create a system that allows data to be stored in several locations in secure and reliable manner. The system should create several shares from the data such that only pre-specified subsets of these shares can be used to retrieve the original data. The shares then will be distributed to shareholders over a local and/or wide area network. The system should allow requesting some/all shares from shareholders and using them to rebuild the data.

  19. 7 CFR 3431.23 - Service to Federal Government in emergency situations.

    Science.gov (United States)

    2010-01-01

    ...) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.23...

  20. 7 CFR 3431.24 - Reporting requirements, monitoring, and close-out.

    Science.gov (United States)

    2010-01-01

    ...) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.24...

  1. Looking for new measures of local government debt. Case study of an example of repayment period of communes of Kujawsko-Pomorskie voivodeship in the years 2002–2015

    Directory of Open Access Journals (Sweden)

    Daniel Jurewicz

    2017-03-01

    Full Text Available The debt of local government units is, to a large extent, the sum of repayment of commitments contracted to carry out investment projects. It is not surprising that in the literature of the subject local government debt is presented mainly as good, profitable or constructive. Commitment to repayment obligations is always associated with the possibility of an occurrence of negative effects which often appear to be underestimated. In numerous scientific and public publications, the indebtedness of the Polish self-governments is assessed first of all by the prism of its relation to earned incomes. However, it is imperative to look for metrics and data sources to look at this debt from new perspectives. The purpose of this study is to present the results of research conducted in the communes of the Kujawsko-Pomorskie voivodeship using new measures of their debt.

  2. miR-30e-5p and miR-15a Synergistically Regulate Fatty Acid Metabolism in Goat Mammary Epithelial Cells via LRP6 and YAP1

    Directory of Open Access Journals (Sweden)

    Zhi Chen

    2016-11-01

    Full Text Available MicroRNA (miRNA regulates the expression of genes and influences a series of biological processes, including fatty acid metabolism. We screened the expression of miRNA in goat mammary glands during peak-lactation and non-lactating (“dry” periods, and performed an in vitro study with goat mammary epithelial cells (GMEC prior to sequencing analysis. Results illustrated that miR-30e-5p and miR-15a were highly expressed. Utilizing a luciferase reporter assay and Western blot, low-density lipoprotein receptor-related protein 6 (LRP6 and Yes associated protein 1 (YAP1 genes were demonstrated to be a target of miR-30e-5p and miR-15a in GMEC. Moreover, we demonstrated that the overexpression of miR-30e-5p and miR-15a in GMEC promoted fat metabolism while their knockdown impaired fat metabolism. These findings extend the discovery of a key role of miR-30e-5p and miR-15a in mediating adipocyte differentiation by suggesting a role in promoting milk fat synthesis. In conclusion, our findings indicate that miR-30e-5p, together with miR-15a, represses expression of LRP6 and promotes fat metabolism in GMEC. The data expanded our knowledge on the function of miRNAs in milk fat metabolism and synthesis in ruminant mammary cells.

  3. 78 FR 35429 - Ability-to-Repay and Qualified Mortgage Standards Under the Truth in Lending Act (Regulation Z)

    Science.gov (United States)

    2013-06-12

    ..., and with an interest subsidy for the LMI consumer, resulting in a graduated monthly payment between... coincided with increasing unemployment, falling home values, and the onset of subprime ARM resets. As a... Unemployment Program, and Supplemental Directive 12-02 (Mar. 9, 2012), expanding HAMP eligibility. MHA programs...

  4. Syndecan-1 (CD138 modulates triple-negative breast cancer stem cell properties via regulation of LRP-6 and IL-6-mediated STAT3 signaling.

    Directory of Open Access Journals (Sweden)

    Sherif A Ibrahim

    Full Text Available Syndecan-1 (CD138, a heparan sulfate proteoglycan, acts as a coreceptor for growth factors and chemokines and is a molecular marker associated with epithelial-mesenchymal transition during development and carcinogenesis. Resistance of Syndecan-1-deficient mice to experimentally-induced tumorigenesis has been linked to altered Wnt-responsive precursor cell pools, suggesting a potential role of Syndecan-1 in breast cancer cell stem function. However, the precise molecular mechanism is still elusive. Here, we decipher the functional impact of Syndecan-1 knockdown using RNA interference on the breast cancer stem cell phenotype of human triple-negative MDA-MB-231 and hormone receptor-positive MCF-7 cells in vitro employing an analytical flow cytometric approach. Successful Syndecan-1 siRNA knockdown was confirmed by flow cytometry. Side population measurement by Hoechst dye exclusion and Aldehyde dehydrogenase-1 activity revealed that Syndecan-1 knockdown in MDA-MB-231 cells significantly reduced putative cancer stem cell pools by 60% and 27%, respectively, compared to controls. In MCF-7 cells, Syndecan-1 depletion reduced the side population by 40% and Aldehyde dehydrogenase-1 by 50%, repectively. In MDA-MB-231 cells, the CD44(+CD24(-/low phenotype decreased significantly by 6% upon siRNA-mediated Syndecan-1 depletion. Intriguingly, IL-6, its receptor sIL-6R, and the chemokine CCL20, implicated in regulating stemness-associated pathways, were downregulated by >40% in Syndecan-1-silenced MDA-MB-231 cells, which showed a dysregulated response to IL-6-induced shifts in E-cadherin and vimentin expression. Furthermore, activation of STAT-3 and NFkB transcription factors and expression of a coreceptor for Wnt signaling, LRP-6, were reduced by >45% in Syndecan-1-depleted cells compared to controls. At the functional level, Syndecan-1 siRNA reduced the formation of spheres and cysts in MCF-7 cells grown in suspension culture. Our study demonstrates the

  5. Syndecan-1 (CD138) modulates triple-negative breast cancer stem cell properties via regulation of LRP-6 and IL-6-mediated STAT3 signaling.

    Science.gov (United States)

    Ibrahim, Sherif A; Hassan, Hebatallah; Vilardo, Laura; Kumar, Sampath Katakam; Kumar, Archana Vijaya; Kelsch, Reinhard; Schneider, Cornelia; Kiesel, Ludwig; Eich, Hans Theodor; Zucchi, Ileana; Reinbold, Rolland; Greve, Burkhard; Götte, Martin

    2013-01-01

    Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a coreceptor for growth factors and chemokines and is a molecular marker associated with epithelial-mesenchymal transition during development and carcinogenesis. Resistance of Syndecan-1-deficient mice to experimentally-induced tumorigenesis has been linked to altered Wnt-responsive precursor cell pools, suggesting a potential role of Syndecan-1 in breast cancer cell stem function. However, the precise molecular mechanism is still elusive. Here, we decipher the functional impact of Syndecan-1 knockdown using RNA interference on the breast cancer stem cell phenotype of human triple-negative MDA-MB-231 and hormone receptor-positive MCF-7 cells in vitro employing an analytical flow cytometric approach. Successful Syndecan-1 siRNA knockdown was confirmed by flow cytometry. Side population measurement by Hoechst dye exclusion and Aldehyde dehydrogenase-1 activity revealed that Syndecan-1 knockdown in MDA-MB-231 cells significantly reduced putative cancer stem cell pools by 60% and 27%, respectively, compared to controls. In MCF-7 cells, Syndecan-1 depletion reduced the side population by 40% and Aldehyde dehydrogenase-1 by 50%, repectively. In MDA-MB-231 cells, the CD44(+)CD24(-/low) phenotype decreased significantly by 6% upon siRNA-mediated Syndecan-1 depletion. Intriguingly, IL-6, its receptor sIL-6R, and the chemokine CCL20, implicated in regulating stemness-associated pathways, were downregulated by >40% in Syndecan-1-silenced MDA-MB-231 cells, which showed a dysregulated response to IL-6-induced shifts in E-cadherin and vimentin expression. Furthermore, activation of STAT-3 and NFkB transcription factors and expression of a coreceptor for Wnt signaling, LRP-6, were reduced by >45% in Syndecan-1-depleted cells compared to controls. At the functional level, Syndecan-1 siRNA reduced the formation of spheres and cysts in MCF-7 cells grown in suspension culture. Our study demonstrates the viability of flow

  6. THE ACCOUNTING OF THE PLEDGED ASSETS PASSED TO THE LICENSED BANKS FROM THE REPUBLIC OF MOLDOVA FOR THE REPAYMENT OF THE GRANTED LOAN

    Directory of Open Access Journals (Sweden)

    Tatiana ŞEVCIUC

    2014-06-01

    Full Text Available In banking practice the pledge plays an important role, it is often used to denote the pledge agreement, as well asthe real right that is the result of the pledge agreement conclusion and the good that is the object of the pledge. Thepledge is the only real security interest in the range of bank guarantees. Actually, each obligation can beguaranteed by the pledging. Assets diversification and trade needs have led to the development of a new pledgeform. Anyway, regardless of the number and content of the economic material, the licensed banks from the Republicof Moldova attach importance to the correctness of pledge accounting taking into account the deadline. Thus, thisresearch aims to present the accounting of the pledged assets passed to the licensed banks from the Republic ofMoldova for the repayment of the granted loan, taking into account the enforcement of the obligation secured by thepledge deadline, the right to possession of the pledged asset and not the least of its value. In the research there wasmainly used the method of monographic study applying elements of observation, selection, induction and deduction.

  7. Impact of genetic variants of IL-6, IL6R, LRP5, ESR1 and SP7 genes on bone mineral density in postmenopausal Mexican-Mestizo women with obesity.

    Science.gov (United States)

    Méndez, Juan Pablo; Rojano-Mejía, David; Coral-Vázquez, Ramón Mauricio; Coronel, Agustín; Pedraza, Javier; Casas, María José; Soriano, Ruth; García-García, Eduardo; Vilchis, Felipe; Canto, Patricia

    2013-10-10

    Since obesity and osteoporosis present a high genetic predisposition and polymorphisms of IL-6, IL6R, LRP5, ESR1 and SP7 may influence the risk of both diseases, the aim of this study was to analyze the possible association of polymorphisms in these genes, as well as their haplotypes, with BMD variations in postmenopausal Mexican-Mestizo women with grade 2 or grade 3 obesity. One hundred eighty unrelated postmenopausal women with grade 2 or grade 3 obesity were included. BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Rs1800795 of IL-6, rs2228145 of IL6R, rs3736228 of LRP5, rs9340799 (XbaI) and rs2234693 (PvuII), of ESR1, rs10876432 and rs2016266, of SP7 (and their haplotypes), were studied by real-time PCR allelic discrimination. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r(2), and haplotype analysis was conducted. Using WHO criteria, 54.5% had grade 2 obesity, and 45.5% had grade 3 obesity. Regarding DXA results, 11.1% women had osteoporosis, 41.7% had osteopenia, and 47.2% had normal BMD. Genotype and haplotype analysis showed no significant differences with BMD variations at the lumbar spine, total hip or femoral neck. We did not find a significant association between the polymorphisms analyzed or their haplotypes and BMD variations in postmenopausal women with obesity. The higher BMD observed in women with obesity could be the result of an adaptive response to the higher loading of the skeleton. © 2013 Elsevier B.V. All rights reserved.

  8. 以PPP模式运作的银行贷款还款来源分析%Source analysis of the bank loan repayment in the operation of PPP model

    Institute of Scientific and Technical Information of China (English)

    张明

    2015-01-01

    Local government debt management standards,PPP mode(the government and social capital cooperation mode)will become an important channel for the transformation of local government functions,will also change the local government of the original financing model,PPP project loans will become focus of commercial banks further wrestling,expand their business at the same time,the commercial banks are also not neglect asset quality requirements. Around the PPP project loan repayment sources,respectively from the first repayment and the second source of repayment of PPP project loans in the process of the core elements of the analysis,to ensure the quality and safety of credit assets,and promote the healthy operation of PPP project,to alleviate the pressure on local government debt.%地方政府债务规范性管理后,PPP模式(政府与社会资本合作模式)将成为地方政府职能转型的重要渠道,也将改变地方政府原有的融资模式,PPP项目贷款将成为各家商业银行进一步角力的重点,在业务拓展的同时,商业银行同样不能忽视对资产质量的要求. 围绕PPP项目贷款还款来源,分别从第一还款和第二还款来源出发,分析PPP项目贷款过程中的核心要点,确保信贷资产质量安全,推进PPP项目健康运营,缓解地方政府债务压力.

  9. On Debt Repayment of Urban Rail Transit Construction Projects%城市轨道交通建设项目债务偿还方式思考

    Institute of Scientific and Technical Information of China (English)

    马季华

    2013-01-01

    Low-fare policy of urban rail transit results in project construction fund essentially relying on the city government subsidies. The principal of the loans should be paid in annual installments and the interests are also to be paid by amortization. Compared with principal repayment with grace period, annual amortization has stronger binding effect on companies so that they can act according to their capabilities, control risks and apportion their debt burdens. It is a safe and fair long-term mechanism for investment and financing.%城市轨道交通的低票价政策决定了项目建设资金最终依靠城市政府投入与个人住房采取按揭贷款“超前消费”的模式类似,城市轨道交通建设项目适合采取借钱“超前建设”的模式.建议城市轨道交通建设项目的债务实行本金按年分期偿还的方式,即不但利息要按年支付,本金也要按年分期偿还.本金按年分期偿还方式与本金设置宽限期偿还方式相比,具有更强的约束性,有利于实现量力而行、控制风险和均衡负担,是安全、公平的投融资长效机制.

  10. 阿尔茨海默病患者精神行为障碍与ApoE、LRP基因多态性的关联性分析%The Correlation Analysis of AD Patients’ Mental and Behavioral Disorders and ApoE and LRP Gene Polymorphism

    Institute of Scientific and Technical Information of China (English)

    董翔

    2013-01-01

      目的探讨阿尔茨海默病(AD)患者精神行为障碍与 ApoE、LRP 基因多态性的关联性分析。方法收集2010年8月至2012年10月 AD 患者80例,正常对照者80例。结果ε4/4在偏执和妄想观念、幻觉及行为紊乱、攻击方面与其他基因型差异有统计学意义, AD 患者 ApoE 基因频率分布与正常对照组比较,差异有统计学意义(P <0.05)。两组 LRP 的基因型频率和等位基因频率差异无统计学意义(P >0.05)。结论 AD 患者精神行为障碍与 ApoE 基因频率多态性存在一定联系,ApoEε4是 AD 的风险基因,LRP 基因多态性和 AD 的关系有待进一步研究探讨。%Objective To study the Alzheimer's disease (AD) patients mental and behavioral disorders and ApoE gene polymorphism and LRP the correlation analysis. Methods Collect in August 2010 to October 2012 AD patients in 80 cases, 80 cases of normal controls, the AD disease pathology behavior rating scale (BEHAVE - AD) behavior evaluation, the spirit of PLR in ApoE and LRP gene parting. Results In the ApoE gene type, ε 4/4 in paranoid and delusion concept, illusion and behavior disorders, attack and other genotype difference have statistical significance, in patients with AD ApoE gene frequency distribution and the normal control group, the difference is statistically significant (P0.05) in patients with AD. Conclusion Mental and behavioral disorders and ApoE gene frequency polymorphism there is contact, ApoE epsilon4 AD is the risk of LRP gene, gene polymorphism and AD relationship needs further study.

  11. FLT3-ITD and MLL-PTD influence the expression of MDR-1, MRP-1, and BCRP mRNA but not LRP mRNA assessed with RQ-PCR method in adult acute myeloid leukemia.

    Science.gov (United States)

    Nasilowska-Adamska, Barbara; Solarska, Iwona; Paluszewska, Monika; Malinowska, Iwona; Jedrzejczak, Wieslaw W; Warzocha, Krzysztof

    2014-04-01

    Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and mixed-lineage leukemia gene-partial tandem duplication (MLL-PTD) are aberrations associated with leukemia which indicate unsatisfactory prognosis. Downstream regulatory targets of FLT3-ITD and MLL-PTD are not well defined. We have analyzed the expression of MDR-1, multidrug resistant protein-1 (MRP-1), breast cancer resistance protein (BCRP), and lung resistance protein (LRP) messenger RNA (mRNA) in relation to the mutational status of FLT3-ITD and MLL-PTD in 185 acute myeloid leukemia (AML) adult patients. The real-time quantitative polymerase chain reaction method was performed to assess the expression of the MDR-1, MRP-1, BCRP, and LRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule. Significantly higher expressions of MDR-1 mRNA were found in patients who did not harbor FLT3-ITD (0.20 vs. 0.05; p = 0.0001) and MRP-1 mRNA in patients with this mutation (0.96 vs. 0.70; p = 0.002) and of BCRP mRNA in patients with MLL-PTD (0.61 vs. 0.38; p = 0.03). In univariate analysis, the high expression of MDR-1 mRNA (≥0.1317) negatively influenced the outcome of induction therapy (p = 0.05), whereas the high expression of BCRP mRNA (≥1.1487) was associated with a high relapse rate (RR) (p = 0.013). We found that the high expression of MDR-1 (≥0.1317), MRP-1 (≥0.8409), and BCRP mRNA (≥1.1487) significantly influenced disease-free survival (DFS; p = 0.059, 0.032, and 0.009, respectively) and overall survival (0.048, 0.014, and 0.059, respectively). Moreover, a high expression of BCRP mRNA (≥1.1487) proved to be an independent prognostic factor for RR (p = 0.01) and DFS (p = 0.002) in multivariate analysis. The significant correlation between the expression of MDR-1, MRP-1, and BCRP mRNA and FLT3-ITD or MLL-PTD in AML patients requires further investigation.

  12. 对银行贷款中“借新还旧”所涉及相关问题的研究%On"Making New Bank Loans for Repaying the Old" Involved Related Problems

    Institute of Scientific and Technical Information of China (English)

    刘永淳

    2012-01-01

    "借新还旧"是近年来商业银行信贷业务中经常采用的一种操作形式,这种方式有利于商业银行顺利完成收贷任务,克服诉讼时效的法律限制,进一步明确了债权债务关系,有效弱化了即期贷款风险。在存在种种优点的同时,"借新还旧"在一定程度上对信用产生了负面影响,进一步弱化了企业的信用观念,掩盖了资产质量的真实状况,推迟了信贷风险的暴露时间,隐含着相当的法律风险。本文通过对"借新还旧"业务操作中出现的法律及风险问题的探讨,提出了防范"借新还旧"业务风险的一些具体建议。%In recent years, "making new loans for repaying the old" has been a frequently used operation form in commercial bank credit business. This way is advantageous to successfully complete the task of recovering loans and overcome the action limitation of legal restrictions for the cotnmercial bank, which further clarifies the relationship between creditor and debtor and weakens demand loan risk effectively. But meanwhile, to a certain extent, "making new loans for repaying the old" has a r, egative impact on the credit, such as further weakening the enterprise credit concept, hiding the true state of the assets quality, deferring credit risk exposure specific suggestions on guardin time, implying considerable legal risk. This article puts forward to some g against "making new loans for repaying the old" business risks through the discussion on the emerging legal and risk problems of its operations.

  13. 血脑屏障RAGE/LRP1转运体及神经血管单元与阿尔茨海默病关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    王浩[1; 杜贯涛[2; 刘广军[2; 洪浩[1

    2015-01-01

    血脑屏障(blood-brain barrier,BBB)是介于外周和中枢神经系统之间的一道生理屏障,对维持中枢神经系统的稳态起着重要作用。研究表明,血脑屏障与阿尔茨海默病(Alzheimer’s disease,AD)的发生发展密切相关。该文重点论述血脑屏障晚期糖基化终产物受体(receptor for advanced glycation end products,RAGE)/低密度脂蛋白受体相关蛋白1(low density lipoprotein receptor-related protein 1,LRP1)受体转运系统及以血脑屏障为核心组分的神经血管单元(neurovascular unit,NVU)介导的中枢β-淀粉样蛋白(β-amyloid protein,Aβ)水平调控与AD发病机制的关系,为AD防治提供新思路。

  14. Evaluation of Brazilian family farming program: a study on the intention of repaingy the agricultural credit / Avaliação do programa nacional de fortalecimento da agricultura familiar: a intenção de pagamento do crédito

    Directory of Open Access Journals (Sweden)

    Mardonio Rique Dias (in memoriam

    2009-01-01

    Full Text Available This publication is part of a major study (Thesis. In that thesis it was analyzed the intention of Pronaf's beneficiaries to repay the credit they have received. The Pronaf is a line of credit for small farmers implemented by the Brazilian Federal Government in 1996. Ajzen's Theory of Planned Behavior (1991 was used to evaluate the beneficiaries' intention in paying what they owned. In order to accomplish this evaluation, two studies were conducted. The first one (Preliminary Study focused on the small farmer's beliefs about the program operation. The second (Main Study focused on the measurement of these beliefs. Two beneficiary groups participated of the studies: Group A (agrarian reform settlers and Group B (small farmers. According to Ajzen's model, for the participants of the Group A, the Attitude, the Normative belief (subjective norm component and the Subjective Norm were positive significant predictors of the Intention to repay the credit. For the Group B, the Attitude, Behavioral belief (attitude component, Normative belief (subjective norm component and Control belief (perceived behavioral control component were positive significant predictors of the Intention to repay the credit. The Perceived behavioral control did not influence directly the behavioral Intention, but this variable indirectly predicts the target behavior.

  15. Repayment and Donation: Loyalty of Changlu Salt Merchants to the Emperor in Qing Dynasty%报效与捐输:清代芦商的急公好义

    Institute of Scientific and Technical Information of China (English)

    王宏斌

    2012-01-01

    在清代,除了“盐课”之外,盐商还要在国家急需时,以报效和捐输的名义,交纳数额巨大的银两,堤内损失堤外补,盐商在“报效”和“捐输”一定数额的银两之后,可以得到一定的政治和经济回报。“报效”和“捐输”,尽管从形式上说同是盐商向国家情愿缴纳大批款项,而在名义上却是不同的。二者既有联系又有区别。报效的对象是“国家庆典和大工大役”,得到的政治回报一般是“给予实职官阶,铨补班次”。%In Qing Dynasty, besides "salt tax", salt merchants had to donate a huge amount of taels of silver to the government in its urgent need. What they lost in donation was compensated from salt price increase. After repayment or donation, they were rewarded with some political and economic interests. Repayment and donation were related but different. They were the same in handing in a large amount of money to the government, but different in names; the objects of donation were "national celebrations and large projects" and generally the political reward was "official positions of real power".

  16. 76 FR 11946 - Emergency Homeowners' Loan Program

    Science.gov (United States)

    2011-03-04

    ..., deed of trust, executor land sales contract, conditional sales contract, or other form of security and... mortgage payments; (e) Have a reasonable likelihood to resume full monthly mortgage payments, and repay...

  17. The Investigations on the Current Status of Enterprises’and Individual Evasion of Repayment of Bank Loans in Zhenjiang City and Some Reflections---A Case of A City of Jiangsu Province%对当前镇江市企业及个人逃废银行债务的调查与思考--以江苏省某市为例

    Institute of Scientific and Technical Information of China (English)

    侯瑞

    2016-01-01

    受宏观经济下行压力加大、企业资产负债率上升、局部地区金融生态环境恶化等多因素影响,2014年以来某市企业及个人逃废银行债务的事件屡有发生,严重损害了商业银行等相关方的利益。本文对江苏省某市辖内企业及个人逃废银行债务的情况进行了调查,总结分析了企业及个人逃废银行债务的原因,介绍了银行防范企业逃废债务、加强内部风险管控的主要举措,并就当前企业及个人逃废银行债务事件中值得关注的问题提出了政策建议。%Affected by the increase of the downward pressure of the macro-economy, the rise of the ratio of liabilities to assets of enterprises, the deterioration of the financial ecological environment of local regions and other factors, events like enterprises’and in-dividual evasion of repayment of bank loans in one city since 2014 have occurred frequently, seriously injuring the benefits of stake-holders such as commercial banks. The paper investigates enterprises’ and individual evasion of repayment of bank loans in one city of Jiangsu province, summarizes the causes, introduces the major measures on preventing enterprises’ and individual evasion of re-payment of bank loans and strengthening the internal risk control, and puts forward policy suggestions on issues worthy of attention in current events of enterprises’and individual evasion of repayment of bank loans.

  18. Assessing the impact of microfinance programming on children: an evaluation from post-tsunami Aceh.

    Science.gov (United States)

    Stark, Lindsay; Kassim, Nafessa; Sparling, Thalia; Buscher, Dale; Yu, Gary; Boothby, Neil

    2015-04-01

    This paper presents an evaluation of the long-term impact of microfinance programmes on Acehnese children during the post-tsunami recovery. The study, conducted from June to August 2010, examined the impact of microfinance programming six years after the tsunami. The sample consisted of 185 microfinance participants, with a comparison group of 192 individuals who did not participate in microfinance programmes. All respondents were parents, interviewed through a structured survey. The study used four child protection indicators-diet, health, childcare and education-in contrast to traditional repayment rate indicators. The primary results were insignificant with respect to all four child protection indicators, suggesting that, with respect to these indicators, there was no long-term difference between the impact of microfinance on beneficiaries' children and non-beneficiaries' children. These findings signify a need for microfinance actors to move beyond traditional indicators of economic success to evaluate the social changes microfinance programmes are presumed to effect.

  19. 7 CFR 3431.11 - Application.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.11 Application. Individuals who meet the eligibility...

  20. 7 CFR 3431.18 - Service agreement.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.18 Service agreement. (a) The service...

  1. 7 CFR 3431.10 - Eligibility to participate.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.10 Eligibility to participate. To be...

  2. 敲低低密度脂蛋白受体相关蛋白1抑制C3H10T1/2多潜能干细胞定向成脂%Knock Down of Low Density Lipoprotein Receptor-related Protein 1(Lrp1) by RNAi Inhibits The Commitment of C3H10T1/2 Pluripotent Stem Cells to Preadipocyte

    Institute of Scientific and Technical Information of China (English)

    陈婧文; 郭亮

    2012-01-01

    C3H10T1/2多潜能干细胞成脂过程分为定向和分化两个阶段,骨形成蛋白4(BMP4)可以诱导其定向成前脂肪细胞.已有的研究表明,脂肪组织特异性敲除低密度脂蛋白受体相关蛋白1 (Lrp1)的小鼠体重减轻,脂肪组织含量减少,揭示此基因对成脂具有重要作用.然而,目前尚不清楚Lrp1是否在成脂定向过程中发挥作用.采用小干扰RNA技术(RNAi),在体外水平研究低密度脂蛋白Lrp1对C3H10T1/2多潜能干细胞成脂定向的作用.分别在C3H10T1/2成脂的定向期和脂滴成熟期敲低Lrp1,通过显微镜下观察、油红O染色、Western blotting等实验证实,定向期而非脂滴成熟期敲低Lrp1显著抑制C3H10T1/2多潜能干细胞成脂.BMP4通过激活下游Smad1/5/8信号通路发挥作用,而敲低Lrp1显著抑制BMP4诱导的Smad1/5/8磷酸化.这些结果说明:敲低Lrp1通过下调Smad信号通路,抑制BMP4诱导的C3H10T1/2多潜能干细胞成脂定向.%The adipocyte development process of C3H10T1/2 pluripotent stem cells includes two stages: the commitment stage and the differentiation stage. There are evidences that BMP4 commits C3H10T1/2 cells into preadipocytes. Previous studies have shown that mice lacking adipocyte Lrpl(adLrpl-/-) displays reduced body weight and smaller fat stores which highlights the important role of Lrpl in adipogenesis. However, little is known about the role of Lrpl in preadipocyte commitment. RNAi was used to study the effect of low density lipoprotein receptor-related protein l(Lrpl) on commitment of C3H10T1/2 to preadipocyte. Through microscopic examination, Oil red O staining, Western blotting, it is demonstrated that Lrpl RNAi inhibits C3H10T1/2 adipogenesis in commitment stage, rather than in lipid maturation period. BMP4 signals through Smadl/5/8 and Lrpl RNAi significantly suppresses the BMP4-triggered phosphorylation of Smadl/5/8. These data suggest that Lrpl RNAi has inhibitory effects on the BMP4-induced of C3H10T1

  3. 34 CFR 674.5 - Federal Perkins Loan program cohort default rate and penalties.

    Science.gov (United States)

    2010-07-01

    ... students at the institution enter repayment on a loan received for attendance at the institution, the... loan received for attendance at the institution, the “cohort default rate” means the percentage of those current and former students who entered repayment on loans received for attendance at that...

  4. Effect of Electroacupuncture on Learning-memory Ability,and Aβ and LRP 1 Immunoactivity in Hippocampal Suicus Microvesseis in APP Transgenic Mice%电针对淀粉样前体蛋白转基因小鼠海马微血管淀粉样沉积的影响及其与低密度脂蛋白相关受体1的关系

    Institute of Scientific and Technical Information of China (English)

    薛卫国; 张忠; 许红; 吴海霞; 白丽敏

    2011-01-01

    目的:探讨电针治疗阿尔茨海默病的可能作用机制.方法:将13月龄的淀粉样前体蛋白(APP)转基因小鼠随机分为模型组和电针治疗组,以相同月龄和背景的C 57 BL/6小鼠作对照组.电针治疗组取"百会""涌泉"穴,每次留针15 min,隔日1次,针刺3个月.以Lashley Ⅲ水迷宫测定各组小鼠的学习记忆能力,以免疫组化方法检测海马B淀粉样蛋白(amyloid β protein,Aβ)、低密度脂蛋白相关受体1(low density lipoprotein receptor-related protein 1,LRP 1)的表达.结果:模型组水迷宫游出时间较对照组延长(P<0.05),海马沟微血管壁Aβ1-42表达的累积吸光度较对照组升高(P<0.01),海马沟微血管壁LRP 1表达较对照组减低(P<0.01);而电针治疗组的水迷宫游出时间明显低于模型组,海马沟微血管壁Aβ1-42表达低于模型组,海马沟微血管壁LRP 1表达高于模型组(均P<0.05).结论:电针治疗可能通过提高脑微血管壁Aβ受体LRP 1的清除转运能力,降低APP转基因鼠脑微血管壁的Aβ沉积,从而改善其学习、记忆能力.%Objective To investigate the effect of electroacupuncture (EA) of “Baihui” (GV20) and “Yongquan” (KI1) on the expression of amyloid β protein (Aβ) and low density lipoprotein (LDL) receptor-related protein 1 (LRP 1 ) in the hippocampal sulcus microvessels in amyloid precursor protein (APP) 695 V 717 Ⅰ transgenic mice, so as to study its mechanism under lying relief of Alzheimer Disease (AD). Methods Twelve APP 695 V 717 Ⅰ transgenic mice were randomly divided into model group and EA group. Six C 57 BL/6 mice were used as the control group. EA (2 Hz/100 Hz, 3-5 mA) was applied to “Baihui”(GV 20) and “Yongquan” (KI1) for 15 min, once every other day for three months. The learning-memory ability of mice was detected by using Lashley Ⅲ water maze system. The expression level of Aβ1-42, and LRP 1 in the hippocampal sulcus microvessels were measured by immunohistochemistry

  5. Nurse-midwives in federally funded health centers: understanding federal program requirements and benefits.

    Science.gov (United States)

    Carter, Martha

    2012-01-01

    Midwives are working in federally funded health centers in increasing numbers. Health centers provide primary and preventive health care to almost 20 million people and are located in every US state and territory. While health centers serve the entire community, they also serve as a safety net for low-income and uninsured individuals. In 2010, 93% of health center patients had incomes below 200% of the Federal Poverty Guidelines, and 38% were uninsured. Health centers, including community health centers, migrant health centers, health care for the homeless programs, and public housing primary care programs, receive grant funding and enjoy other benefits due to status as federal grantees and designation as federally qualified health centers. Clinicians working in health centers are also eligible for financial and professional benefits because of their willingness to serve vulnerable populations and work in underserved areas. Midwives, midwifery students, and faculty working in, or interacting with, health centers need to be aware of the regulations that health centers must comply with in order to qualify for and maintain federal funding. This article provides an overview of health center regulations and policies affecting midwives, including health center program requirements, scope of project policy, provider credentialing and privileging, Federal Tort Claims Act malpractice coverage, the 340B Drug Pricing Program, and National Health Service Corps scholarship and loan repayment programs.

  6. 7 CFR 3431.15 - Qualifying loans.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.15 Qualifying loans. (a) General. Loan repayments provided...

  7. Development, validation and operating room-transfer of a six-step laparoscopic training program for the vesicourethral anastomosis.

    Science.gov (United States)

    Klein, Jan; Teber, Dogu; Frede, Tom; Stock, Christian; Hruza, Marcel; Gözen, Ali; Seemann, Othmar; Schulze, Michael; Rassweiler, Jens

    2013-03-01

    Development and full validation of a laparoscopic training program for stepwise learning of a reproducible application of a standardized laparoscopic anastomosis technique and integration into the clinical course. The training of vesicourethral anastomosis (VUA) was divided into six simple standardized steps. To fix the objective criteria, four experienced surgeons performed the stepwise training protocol. Thirty-eight participants with no previous laparoscopic experience were investigated in their training performance. The times needed to manage each training step and the total training time were recorded. The integration into the clinical course was investigated. The training results and the corresponding steps during laparoscopic radical prostatectomy (LRP) were analyzed. Data analysis of corresponding operating room (OR) sections of 793 LRP was performed. Based on the validity, criteria were determined. In the laboratory section, a significant reduction of OR time for every step was seen in all participants. Coordination: 62%; longitudinal incision: 52%; inverted U-shape incision: 43%; plexus: 47%. Anastomosis catheter model: 38%. VUA: 38%. The laboratory section required a total time of 29 hours (minimum: 16 hours; maximum: 42 hours). All participants had shorter execution times in the laboratory than under real conditions. The best match was found within the VUA model. To perform an anastomosis under real conditions, 25% more time was needed. By using the training protocol, the performance of the VUA is comparable to that of an surgeon with experience of about 50 laparoscopic VUA. Data analysis proved content, construct, and prognostic validity. The use of stepwise training approaches enables a surgeon to learn and reproduce complex reconstructive surgical tasks: eg, the VUA in a safe environment. The validity of the designed system is given at all levels and should be used as a standard in the clinical surgical training in laparoscopic reconstructive urology.

  8. On Optimization of Schooling Loaning,Repayment Mechanisms for Helping Poor College Students in China%我国大学生助学贷款还款机制优化的研究

    Institute of Scientific and Technical Information of China (English)

    裴智民

    2014-01-01

    National student loan is a kind of bank loan operated by the bank,the administrative departments of ed-ucation and students whose families are poor and in need of help.This policy has helped many poor college students in China since 1999 .However,because of various reasons,the loan risk has also emerged.Part of the students had defaulted on their loans and rejected debt after graduation.This phenomenon has led to the bank′s credit crunch,rejection.To ensure that students loan has an effective operation mechanism,we must rely on the cooperation among the government,banks,colleges,students,parents and employers,so as to optimize student loaning and repayment mechanisms and provide good economic guarantee for cultivating talents.%国家助学贷款是由银行、教育行政部门与学生共同操作的专门帮助贫困家庭学生的银行贷款。1999年我国大学生助学贷款政策实施以来,助推许多家庭经济困难的学生完成了学业。但由于种种原因,部分大学生毕业以后拖欠贷款甚至逃债,导致了银行惜贷、拒贷等现象。要保证大学生助学贷款还款机制的有效运行,有赖于政府、银行、高校、学生、家长和用人单位等多方面的协同配合,进一步完善和健全大学生助学贷款还款机制,方能为国家培养优秀人才提供良好的经济保障。

  9. 44 CFR 206.367 - Loan repayment.

    Science.gov (United States)

    2010-10-01

    ... outstanding cash from the actual date of its disbursement by the Treasury. (2) The interest amount due will be... interest, P=the principal amount disbursed; R=the interest rate of the loan; and, T=the outstanding term in... be added to the unpaid balance of the loan, bear interest at the same rate as the loan, and...

  10. 44 CFR 206.377 - Loan repayment.

    Science.gov (United States)

    2010-10-01

    ... Assistant Administrator for the Disaster Assistance Directorate. Interest will accrue on outstanding cash..., where I = the amount of simple interest, P = the principal amount disbursed; R = the interest rate of... rate as the loan, and be immediately due without demand. (6) In the event of default on this note...

  11. Program specialization

    CERN Document Server

    Marlet, Renaud

    2013-01-01

    This book presents the principles and techniques of program specialization - a general method to make programs faster (and possibly smaller) when some inputs can be known in advance. As an illustration, it describes the architecture of Tempo, an offline program specializer for C that can also specialize code at runtime, and provides figures for concrete applications in various domains. Technical details address issues related to program analysis precision, value reification, incomplete program specialization, strategies to exploit specialized program, incremental specialization, and data speci

  12. Quasiconvex Programming

    OpenAIRE

    Eppstein, David

    2004-01-01

    We define quasiconvex programming, a form of generalized linear programming in which one seeks the point minimizing the pointwise maximum of a collection of quasiconvex functions. We survey algorithms for solving quasiconvex programs either numerically or via generalizations of the dual simplex method from linear programming, and describe varied applications of this geometric optimization technique in meshing, scientific computation, information visualization, automated algorithm analysis, an...

  13. Program Perancangan Kegiatan Kredit Mikro (Dana Bergulir Bagi Mahasiswa di Perguruan Tinggi

    Directory of Open Access Journals (Sweden)

    Lasminasih Lasmi

    2016-01-01

    Full Text Available Design Program of Microcredit Activity (Revolving FundFor Students in Higher Education. Systems design of microcredit is generally conducted by financial institutions of which credit is mostly provided for private sectors, both large and small medium Enterprises (SMEs. However, credit for new entrepreneurs, especially for college students, who want to start a business has never been provided formally due to numerous factors and among others is because of the absence of collateral. Meanwhile, in order to stimulate the eagerness of running a business, credit is inevitably essential. Hence, this study is proposing a comprehensive systems design to overcome any potential problems between new entreprenurs in getting credit from financial intitutions. This systems design handles a series of processes in granting credit which starts from screening and selecting business proposals. When the proposals are accepted and the credit is granted, then they will get processes of mentoring, training, exhibition and finally process of monitoring through financial reports. Also there will be internet facility of integrated microcredit information system to ease communication between the new entrepreneurs, mentors and financial institutions. This systems design can enhance success for the new entrepreneurs and diminish any potential risks of unable to repay the credit. So when the business starts to grow, they can apply for bigger credit.DOI: 10.15408/ess.v5i1.2329

  14. Program Fullerene

    DEFF Research Database (Denmark)

    Wirz, Lukas; Peter, Schwerdtfeger,; Avery, James Emil

    2013-01-01

    Fullerene (Version 4.4), is a general purpose open-source program that can generate any fullerene isomer, perform topological and graph theoretical analysis, as well as calculate a number of physical and chemical properties. The program creates symmetric planar drawings of the fullerene graph, an......-Fowler, and Brinkmann-Fowler vertex insertions. The program is written in standard Fortran and C++, and can easily be installed on a Linux or UNIX environment....

  15. Effective Programming

    DEFF Research Database (Denmark)

    Frost, Jacob

    To investigate the use of VTLoE as a basis for formal derivation of functional programs with effects. As a part of the process, a number of issues central to effective formal programming are considered. In particular it is considered how to develop a proof system suitable for pratical reasoning......, how to implement this system in the generic proof assistant Isabelle and finally how to apply the logic and the implementation to programming....

  16. Programming F#

    CERN Document Server

    Smith, Chris

    2009-01-01

    Why learn F#? This multi-paradigm language not only offers you an enormous productivity boost through functional programming, it also lets you develop applications using your existing object-oriented and imperative programming skills. With Programming F#, you'll quickly discover the many advantages of Microsoft's new language, which includes access to all the great tools and libraries of the .NET platform. Learn how to reap the benefits of functional programming for your next project -- whether it's quantitative computing, large-scale data exploration, or even a pursuit of your own. With th

  17. Programming Interactivity

    CERN Document Server

    Noble, Joshua

    2009-01-01

    Make cool stuff. If you're a designer or artist without a lot of programming experience, this book will teach you to work with 2D and 3D graphics, sound, physical interaction, and electronic circuitry to create all sorts of interesting and compelling experiences -- online and off. Programming Interactivity explains programming and electrical engineering basics, and introduces three freely available tools created specifically for artists and designers: Processing, a Java-based programming language and environment for building projects on the desktop, Web, or mobile phonesArduino, a system t

  18. 7 CFR 4279.43 - Certified Lender Program.

    Science.gov (United States)

    2010-01-01

    ... cash flow analysis, history of debt repayment, necessity of any debt refinancing, and the credit... complete financial statements; and completion by the Agency of the environmental analysis. The Agency may... lender will provide a written certification to this effect along with a statistical analysis of its...

  19. 76 FR 75427 - Farm Loan Programs Loan Making Activities

    Science.gov (United States)

    2011-12-02

    ...; (6) Obtain from the buyer a current balance sheet, income statement, cash flow budget, and any... direct and guaranteed loans as required by the Food, Conservation, and Energy Act of 2008 (the 2008 Farm..., buyers with an Agency approved repayment plan under this section will supply the Agency a current...

  20. 77 FR 42085 - Federal Perkins Loan Program, Federal Family Education Loan Program, and William D. Ford Federal...

    Science.gov (United States)

    2012-07-17

    ... of the annual poverty guideline amount for the borrower's State and family size. Borrowers who repay... borrower's AGI and 150 percent of the annual poverty guideline amount for the borrower's State and family....221(a)(4) would reflect the statutory definition of ``new borrower'' for purposes of the changes to...

  1. Computer Programs.

    Science.gov (United States)

    Anderson, Tiffoni

    This module provides information on development and use of a Material Safety Data Sheet (MSDS) software program that seeks to link literacy skills education, safety training, and human-centered design. Section 1 discusses the development of the software program that helps workers understand the MSDSs that accompany the chemicals with which they…

  2. Choreographic Programming

    DEFF Research Database (Denmark)

    Montesi, Fabrizio

    , as they offer a concise view of the message flows enacted by a system. For this reason, in the last decade choreographies have been used in the development of programming languages, giving rise to a programming paradigm that in this dissertation we refer to as Choreographic Programming. Recent studies show...... sessions; it remains thus unclear whether choreographies can still guarantee safety when dealing with such nontrivial features. This PhD dissertation argues for the suitability of choreographic programming as a paradigm for the development of safe distributed systems. We proceed by investigating its...... foundations and application. To this aim, we provide three main contributions. The first contribution is the development of a formal model for choreographic programming that supports asynchrony, mobility, modularity, and multiparty sessions. In the model, choreographies are projected to distributed endpoint...

  3. 78 FR 61347 - Agency Information Collection Activities; Submission to the Office of Management and Budget for...

    Science.gov (United States)

    2013-10-03

    ... and Approval; Comment Request; William D. Ford Federal Direct Loan Program Repayment Plan Selection... notice will be considered public records. Title of Collection: William D. Ford Federal Direct...

  4. 7 CFR 1735.61 - Approval criteria.

    Science.gov (United States)

    2010-01-01

    ... AGRICULTURE GENERAL POLICIES, TYPES OF LOANS, LOAN REQUIREMENTS-TELECOMMUNICATIONS PROGRAM Mortgage Controls... economic and loan-repayment feasibility characteristics of the proposed system are satisfactory; (2...

  5. Programming Python

    CERN Document Server

    Lutz, Mark

    2011-01-01

    If you've mastered Python's fundamentals, you're ready to start using it to get real work done. Programming Python will show you how, with in-depth tutorials on the language's primary application domains: system administration, GUIs, and the Web. You'll also explore how Python is used in databases, networking, front-end scripting layers, text processing, and more. This book focuses on commonly used tools and libraries to give you a comprehensive understanding of Python's many roles in practical, real-world programming. You'll learn language syntax and programming techniques in a clear and co

  6. Overseas programs

    Science.gov (United States)

    1983-06-01

    Subprograms of the Overseas Program of the Australian Bureau of Mineral Resources are presented and discussed. Topics addressed in the subprograms include volcanology, the geology and geophysics of Southwest Pacific island arcs and structural basins, and antarctic paleomagnetism and geology.

  7. Linear programming

    CERN Document Server

    Solow, Daniel

    2014-01-01

    This text covers the basic theory and computation for a first course in linear programming, including substantial material on mathematical proof techniques and sophisticated computation methods. Includes Appendix on using Excel. 1984 edition.

  8. SPOT Program

    Science.gov (United States)

    Smith, Jason T.; Welsh, Sam J.; Farinetti, Antonio L.; Wegner, Tim; Blakeslee, James; Deboeck, Toni F.; Dyer, Daniel; Corley, Bryan M.; Ollivierre, Jarmaine; Kramer, Leonard; Zimmerman, Patrick L.; Khatri, Reshma

    2010-01-01

    A Spacecraft Position Optimal Tracking (SPOT) program was developed to process Global Positioning System (GPS) data, sent via telemetry from a spacecraft, to generate accurate navigation estimates of the vehicle position and velocity (state vector) using a Kalman filter. This program uses the GPS onboard receiver measurements to sequentially calculate the vehicle state vectors and provide this information to ground flight controllers. It is the first real-time ground-based shuttle navigation application using onboard sensors. The program is compact, portable, self-contained, and can run on a variety of UNIX or Linux computers. The program has a modular objec-toriented design that supports application-specific plugins such as data corruption remediation pre-processing and remote graphics display. The Kalman filter is extensible to additional sensor types or force models. The Kalman filter design is also strong against data dropouts because it uses physical models from state and covariance propagation in the absence of data. The design of this program separates the functionalities of SPOT into six different executable processes. This allows for the individual processes to be connected in an a la carte manner, making the feature set and executable complexity of SPOT adaptable to the needs of the user. Also, these processes need not be executed on the same workstation. This allows for communications between SPOT processes executing on the same Local Area Network (LAN). Thus, SPOT can be executed in a distributed sense with the capability for a team of flight controllers to efficiently share the same trajectory information currently being computed by the program. SPOT is used in the Mission Control Center (MCC) for Space Shuttle Program (SSP) and International Space Station Program (ISSP) operations, and can also be used as a post -flight analysis tool. It is primarily used for situational awareness, and for contingency situations.

  9. Integer programming

    CERN Document Server

    Conforti, Michele; Zambelli, Giacomo

    2014-01-01

    This book is an elegant and rigorous presentation of integer programming, exposing the subject’s mathematical depth and broad applicability. Special attention is given to the theory behind the algorithms used in state-of-the-art solvers. An abundance of concrete examples and exercises of both theoretical and real-world interest explore the wide range of applications and ramifications of the theory. Each chapter is accompanied by an expertly informed guide to the literature and special topics, rounding out the reader’s understanding and serving as a gateway to deeper study. Key topics include: formulations polyhedral theory cutting planes decomposition enumeration semidefinite relaxations Written by renowned experts in integer programming and combinatorial optimization, Integer Programming is destined to become an essential text in the field.

  10. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Safety Conference Registry Login SCR Training and Testing Cancer Cancer Programs Cancer Programs Overview of Cancer Programs Cancer Programs News American Joint Committee on ...

  11. Programming Algol

    CERN Document Server

    Malcolme-Lawes, D J

    2014-01-01

    Programming - ALGOL describes the basics of computer programming using Algol. Commands that could be added to Algol and could increase its scope are described, including multiplication and division and the use of brackets. The idea of labeling or naming a command is also explained, along with a command allowing two alternative results. Most of the important features of Algol syntax are discussed, and examples of compound statements (that is, sets of commands enclosed by a begin ... end command) are given.Comprised of 11 chapters, this book begins with an introduction to the digital computer an

  12. Programming Interactivity

    CERN Document Server

    Noble, Joshua

    2012-01-01

    Ready to create rich interactive experiences with your artwork, designs, or prototypes? This is the ideal place to start. With this hands-on guide, you'll explore several themes in interactive art and design-including 3D graphics, sound, physical interaction, computer vision, and geolocation-and learn the basic programming and electronics concepts you need to implement them. No previous experience is necessary. You'll get a complete introduction to three free tools created specifically for artists and designers: the Processing programming language, the Arduino microcontroller, and the openFr

  13. Discussion on Promoting the Normal Repayment Behavior of Loans Students:Tips of the 9-year 0 Malicious Loan Defaults%促进大学生正常履行贷款合同的实践探讨--连续九年零恶意贷款违约率的心得体会

    Institute of Scientific and Technical Information of China (English)

    张秒高; 黄晓清

    2016-01-01

    At present, the national student loan defaults occasionally happen, that cause adverse impact on the major measures of the student financial aid. Therefore, the performance of contract is an important content of the loan. Based on the practice of 0 malicious loan defaults in recent 9 years, the author continuously demonstrates the cycle of practice-summary-practice and puts forward a set of effective loan work management mechanism. Specific contents as follows: ① Pay special attention to the data verification and feedback before the loan and protect students' privacy and self-esteem. ② Do a good job of the interpretation during the loan and the reimbursement pep rally after the loan to inspire the student to perform the contract payments consciousness. ③ Promote the mental health and growth of the loans students to improve the repayment ability of the contract. ④ Promote the employment of the loans students to promote reimbursement practices. Many links are closely linkaged to jointly promote the normal repayment behavior of loans students so as to form the benign atmosphere and circulation pattern of the reimbursement and guarantee 0 malicious defaults.%当前国家助学贷款违约现象时有发生,对于该助学助困的重大措施造成了不良的影响。因此,保证合同履行就成了贷款重要内容。笔者根据连续9年0恶意贷款违约率的实践,持续进行实践-理论总结-实践的循环论证,提出了一套有效的贷款工作管理机制。具体内容如下:①亲力抓好贷款的贷前资料审核和反馈,保护好学生的隐私和自尊心;②做好贷中合同解读和贷后还款动员会,启发学生履行合同的还款意识;③促进贷款学生的心理健康和成长成才,提高履行合同的还款能力;④促进贷款学生的就业,以就业促进还款实践。多环节紧扣联动,共同促进了贷款学生的正常还款行为,从而形成了良性的还款

  14. 75 FR 28262 - Office of the Director, National Institutes of Health; Notice of Meeting

    Science.gov (United States)

    2010-05-20

    ... Group for Human Embryonic Stem Cell Review; (3) Work Group on Outside Awards for NIH Employees. Place... Assistance Program Nos. 93.14, Intramural Research Training Award; 93.22, Clinical Research Loan Repayment Program for Individuals from Disadvantaged Backgrounds; 93.232, Loan Repayment Program for...

  15. 7 CFR 3431.22 - Waiver.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.22 Waiver. (a) A program participant may seek a waiver or...

  16. 7 CFR 3431.21 - Breach.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.21 Breach. (a) General. If a program participant fails to...

  17. Design of the LRP airfoil series using 2D CFD

    DEFF Research Database (Denmark)

    Zahle, Frederik; Bak, Christian; Sørensen, Niels N.;

    2014-01-01

    This paper describes the design and wind tunnel testing of a high-Reynolds number, high lift airfoil series designed for wind turbines. The airfoils were designed using direct gradient- based numerical multi-point optimization based on a Bezier parameterization of the shape, coupled to the 2D Nav...

  18. ORGEL program

    Energy Technology Data Exchange (ETDEWEB)

    none

    1963-09-01

    Parameter optimization studies for an ORGEL power plant are reported, and the ESSOR test reactor used in the program is described. Research at Ispra in reactor physics, technology, metallurgy, heat transfer, chemistry, and physical chemistry associated with ORGEL development is also summarized. (D.C.W.)

  19. Constraint Programming versus Mathematical Programming

    DEFF Research Database (Denmark)

    Hansen, Jesper

    2003-01-01

    Constraint Logic Programming (CLP) is a relatively new technique from the 80's with origins in Computer Science and Artificial Intelligence. Lately, much research have been focused on ways of using CLP within the paradigm of Operations Research (OR) and vice versa. The purpose of this paper...

  20. Linear programming

    CERN Document Server

    Karloff, Howard

    1991-01-01

    To this reviewer’s knowledge, this is the first book accessible to the upper division undergraduate or beginning graduate student that surveys linear programming from the Simplex Method…via the Ellipsoid algorithm to Karmarkar’s algorithm. Moreover, its point of view is algorithmic and thus it provides both a history and a case history of work in complexity theory. The presentation is admirable; Karloff's style is informal (even humorous at times) without sacrificing anything necessary for understanding. Diagrams (including horizontal brackets that group terms) aid in providing clarity. The end-of-chapter notes are helpful...Recommended highly for acquisition, since it is not only a textbook, but can also be used for independent reading and study. —Choice Reviews The reader will be well served by reading the monograph from cover to cover. The author succeeds in providing a concise, readable, understandable introduction to modern linear programming. —Mathematics of Computing This is a textbook intend...

  1. Prolog programming

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, M.

    1986-01-01

    A volume in the Artificial Intelligence Texts series, this book teaches Prolog programming by following a series of sample programs. New concepts are introduced step-by-step in order to present solutions to problems, each problem being chosen so that its solution exposes one of the features of Prolog. The examples are chosen from areas which are of practical use to readers, such as data base query, expert system design, natural language interfacing, knowledge representation, computer simulation, and planning of problem solving. Contents: Prolog as a database query language; Writing an expert system; Natural language processing; Knowledge representation; List processing and pattern matching; Planning, problem solving and simulation; Extending Prolog; A model of Prolog virtual machine.

  2. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Accreditation Program for Breast Centers About NAPBC Accreditation Education NAPBC Standards News Cancer Cancer Programs Cancer Programs ... Program for Hospitals Trauma Systems Consultation Program Trauma Education Trauma Systems Conference Publications and Posters Injury Prevention ...

  3. Optimalisasi Harga Penjualan Perumahan dengan Metode Goal Programming (Studi Kasus: Golden Gindi Residence Kota Bima Nusa Tenggara Barat

    Directory of Open Access Journals (Sweden)

    Lilik Ika Rahmawati

    2013-06-01

    Full Text Available This research aims to determine the minimum selling price of each type of house using the method of goal programming, so that the developer  get profit  in appropriate with the targets set. Goal Programming method is one of the method of solving linear programming to solve the problems that include multiple targets. The result of the research showed: (1 the minimum salling price type of house 36/150 is Rp. 56.371.450,-; (2 type 45/150 is Rp. 77.261.250,-; (3 type 52/150 is Rp. 84.221.445,56. To calculate monthly installment purchase of a home within 5 years and 10 years using Capital Recovery Factor (CRF method with annual interest of 11.5%. In order to obtain the amount of monthly loan installments within 5 years with 60 time installments for the type 36/150 is Rp. 930.250 , type 45/150 is Rp. 1.275.000 and type 52/150 is Rp. 1.389.800. By using the same method obtained the amount of monthly installments within 10 years with 120 installments for the type 36/150 is Rp. 549.900, type 45/150 is Rp. 815.300 and type 52/150 is Rp. 888.800 . Optimal selling price obtained was lower than the selling price from the developer, so the developer need to consider again the results obtained for the salling price of homes. The calculation of credit installments depending on the amount of interest and repayment period, so not become burden for the customers.

  4. Optimalisasi Harga Penjualan Perumahan dengan Metode Goal Programming (Studi Kasus: Golden Gindi Residence Kota Bima Nusa Tenggara Barat

    Directory of Open Access Journals (Sweden)

    Lilik Ika Rahmawati

    2015-06-01

    Full Text Available This research aims to determine the minimum selling price of each type of house using the method of goal programming, so that the developer  get profit  in appropriate with the targets set. Goal Programming method is one of the method of solving linear programming to solve the problems that include multiple targets. The result of the research showed: (1 the minimum salling price type of house 36/150 is Rp. 56.371.450,-; (2 type 45/150 is Rp. 77.261.250,-; (3 type 52/150 is Rp. 84.221.445,56. To calculate monthly installment purchase of a home within 5 years and 10 years using Capital Recovery Factor (CRF method with annual interest of 11.5%. In order to obtain the amount of monthly loan installments within 5 years with 60 time installments for the type 36/150 is Rp. 930.250 , type 45/150 is Rp. 1.275.000 and type 52/150 is Rp. 1.389.800. By using the same method obtained the amount of monthly installments within 10 years with 120 installments for the type 36/150 is Rp. 549.900, type 45/150 is Rp. 815.300 and type 52/150 is Rp. 888.800 . Optimal selling price obtained was lower than the selling price from the developer, so the developer need to consider again the results obtained for the salling price of homes. The calculation of credit installments depending on the amount of interest and repayment period, so not become burden for the customers.

  5. Programming Razor

    CERN Document Server

    Chadwick, Jess

    2011-01-01

    Take Razor for a test drive and discover first hand how this scripting syntax simplifies the way you create dynamic, data-driven websites. With this concise guide, you'll work with Razor syntax by building example websites with Microsoft WebMatrix and ASP.NET MVC. You'll quickly learn how Razor lets you combine code and content in a fluid and expressive manner on Windows-based servers. Programming Razor also explores components of the Razor API, and shows you how Razor templates are turned into rendered HTML. By the end of this book, you'll be able to create Razor-based websites with custom

  6. Programming Pig

    CERN Document Server

    Gates, Alan

    2011-01-01

    This guide is an ideal learning tool and reference for Apache Pig, the open source engine for executing parallel data flows on Hadoop. With Pig, you can batch-process data without having to create a full-fledged application-making it easy for you to experiment with new datasets. Programming Pig introduces new users to Pig, and provides experienced users with comprehensive coverage on key features such as the Pig Latin scripting language, the Grunt shell, and User Defined Functions (UDFs) for extending Pig. If you need to analyze terabytes of data, this book shows you how to do it efficiently

  7. Geothermal Technologies Program Overview - Peer Review Program

    Energy Technology Data Exchange (ETDEWEB)

    Milliken, JoAnn [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States)

    2011-06-06

    This Geothermal Technologies Program presentation was delivered on June 6, 2011 at a Program Peer Review meeting. It contains annual budget, Recovery Act, funding opportunities, upcoming program activities, and more.

  8. 75 FR 63143 - Solicitation of Input From Stakeholders Regarding Administration of the Veterinary Medicine Loan...

    Science.gov (United States)

    2010-10-14

    ... Administration of the Veterinary Medicine Loan Repayment Program (VMLRP) AGENCY: National Institute of Food and... Veterinary Medicine Loan Repayment Program (VMLRP) authorized under section 1415A of the National..., veterinary services in veterinarian shortage situations. As part of the stakeholder input process, NIFA is...

  9. 75 FR 59679 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2010-09-28

    ...: Veterinary Medicine Loan Repayment Program Application. OMB Control Number: 0524-0047. Summary of Collection... established a new Veterinary Medicine Loan Repayment Program (VMLRP) (7 U.S.C. 3151a) authorizing the... other technological collection techniques or other forms of information technology should be...

  10. 75 FR 23664 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2010-05-04

    ... Extension Service Title: Veterinary Medicine Loan Repayment Program (VMLRP) Shortage Situation. OMB Control... Teaching Policy Act of 1997. This law established a new Veterinary Medicine Loan Repayment Program (VMLRP..., mechanical, or other technological collection techniques or other forms of information technology should...

  11. 7 CFR 3431.8 - Purpose and scope.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.8 Purpose and scope. (a) Purpose. The regulations of this...

  12. 7 CFR 3431.12 - Selection of applicants.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.12 Selection of applicants. (a) Review of...

  13. 7 CFR 3431.20 - Administration.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.20 Administration. The VMLRP will be administered by CSREES...

  14. 7 CFR 3431.9 - Eligibility to apply.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.9 Eligibility to apply. (a) General. To...

  15. 7 CFR 3431.14 - Priority.

    Science.gov (United States)

    2010-01-01

    ... Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.14 Priority. Pursuant to NVMSA, the Secretary will give...

  16. 7 CFR 3431.19 - Payment and tax liability.

    Science.gov (United States)

    2010-01-01

    ... Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.19 Payment and tax liability. (a) Loan...

  17. 7 CFR 3431.17 - VMLRP service agreement offer.

    Science.gov (United States)

    2010-01-01

    ....17 Agriculture Regulations of the Department of Agriculture (Continued) COOPERATIVE STATE RESEARCH, EDUCATION, AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM Administration of the Veterinary Medicine Loan Repayment Program § 3431.17 VMLRP service agreement offer. The...

  18. Telemedicine Program

    Science.gov (United States)

    1996-01-01

    Since the 1970s, NASA has been involved in the research and demonstration of telemedicine for its potential in the care of astronauts in flight and Earth-bound applications. A combination of NASA funding, expertise and off-the-shelf computer and networking systems made telemedicine possible for a medically underserved hospital in Texas. Through two-way audio/video relay, the program links pediatric oncology specialists at the University of Texas Health Science Center in San Antonio to South Texas Hospital in Harlingen, providing easier access and better care to children with cancer. Additionally, the hospital is receiving teleclinics on pediatric oncology nursing, family counseling and tuberculosis treatment. VTEL Corporation, Sprint, and the Healthcare Open Systems and Trials Consortium also contributed staff and hardware.

  19. Program Logics for Homogeneous Meta-programming

    Science.gov (United States)

    Berger, Martin; Tratt, Laurence

    A meta-program is a program that generates or manipulates another program; in homogeneous meta-programming, a program may generate new parts of, or manipulate, itself. Meta-programming has been used extensively since macros were introduced to Lisp, yet we have little idea how formally to reason about meta-programs. This paper provides the first program logics for homogeneous meta-programming - using a variant of MiniML_e^{square} by Davies and Pfenning as underlying meta-programming language. We show the applicability of our approach by reasoning about example meta-programs from the literature. We also demonstrate that our logics are relatively complete in the sense of Cook, enable the inductive derivation of characteristic formulae, and exactly capture the observational properties induced by the operational semantics.

  20. Two years into the storm over pricing to and collecting from the uninsured--a hospital valuation expert examines the risk/return dynamics and asks: would fair pricing and fair medical debt repayment plans increase yields to hospitals and simultaneously mitigate these controversies?

    Science.gov (United States)

    Unland, James J

    2005-01-01

    As the controversies over 501(c)(3) "charitable" hospitals' pricing, collections, and charity care practices that emerged in the winter and spring of 2003 continue unabated--now involving government officials from city councils and county boards to state attorneys general and Congress as well as numerous class action lawsuits--a hospital valuation expert and risk analyst looks at the fundamental economic and strategic issues, concluding that the risk/return dynamics are out of whack in that hospitals are facing mushrooming, multifaceted troubles over what has been a very low net yield patient population. After interviewing patient account representatives at hospitals and conducting other research, this analyst asks: Should attention have been focused at the national and state hospital association levels in 2003 to take steps to increase the net yield to hospitals from the uninsured population through more equitable pricing and better medical debt repayment terms, steps that might have mitigated these controversies? Many hospitals and hospital associations have been so intent on proving hospitals' legal right to charge "list price" to and sue the uninsured that they have overlooked a simple yet effective business premise that many hospital patient accounts representatives already fully know: Fair pricing and fair payment terms are actually good business. The author asserts that the controversies that emerged in 2003 actually represented a significant opportunity that, with a different approach, would likely have resulted in hospitals being able to collect significantly more money from the uninsured population while, at the same time, lessening or even avoiding the destructive ramifications that have occurred in the form of investigations, legislation, and lawsuits. To realize higher net yields from the uninsured, highly specific leadership steps need to be taken uniquely at national and state "association" levels in order to avoid the negative financial consequences

  1. Stop smoking support programs

    Science.gov (United States)

    Smokeless tobacco - stop smoking programs; Stop smoking techniques; Smoking cessation programs; Smoking cessation techniques ... It is hard to quit smoking if you are acting alone. Smokers may have a ... of quitting with a support program. Stop smoking programs ...

  2. Functional Python programming

    CERN Document Server

    Lott, Steven

    2015-01-01

    This book is for developers who want to use Python to write programs that lean heavily on functional programming design patterns. You should be comfortable with Python programming, but no knowledge of functional programming paradigms is needed.

  3. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  4. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Quality Improvement Program About Standards Apply Participant Use Data File (PUF) Resources & FAQs Find a MBSAQIP Center ... Programs BleedingControl.org Trauma Quality Programs National Trauma Data Bank Trauma Quality Improvement Program Mentoring for Excellence ...

  5. North Carolina used-motor-oil re-refining program. Topical report 2. Economics and logistics: startup experience and operating projections

    Energy Technology Data Exchange (ETDEWEB)

    1982-07-01

    This is the second in a planned series of topical reports on a program to develop and demonstrate a state-operated re-refining system for used engine oil. The North Carolina Oil Re-Refining Facility, using a 2,000,000 gallon input per year PROP plant, was installed in late 1980. During the first year of startup operation ending December 31, 1981, approximately 137,000 gallons were produced. This was much less than expected due to many impediments; however, product quality has consistently been excellent. Capital costs to date total about $2.3 million, and it is projected that an additional $1.5 million of equipment upgrading and facility expansion/improvements will be needed before the plant will produce satisfactorily. For the first year, based on normal accrual accounting, operating costs exceeded revenues by about $350,000 and the negative cash flow was about $346,000. After upgrading, however, it is expected the plant will generate revenues sufficient to repay the investment within ten years, even assuming that the selling price of re-refined oil will not inflate faster than the cost of producing it. This report also contains sections reporting on the logistics of oil pickup and delivery and also brief descriptions of information forms and procedures developed for the facility.

  6. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Programming for Young Fellows Programming for International Surgeons Leadership Opportunities Leadership Opportunities Leadership Opportunities Leadership & Advocacy Summit ...

  7. 76 FR 5774 - Planning and Establishment of Consumer Operated and Oriented Plan Program; Request for Comments...

    Science.gov (United States)

    2011-02-02

    ... reserve requirements, solvency regulations, and requisite surplus note arrangements that must be..., how should HHS take into consideration state reserve requirements? 2. What factors will determine the... (repayable in 15 years) to assist such issuers in meeting State solvency requirements. The Secretary must...

  8. 77 FR 3121 - Program Integrity: Gainful Employment-Debt Measures; Correction

    Science.gov (United States)

    2012-01-23

    ... regulations, the errors resulting from this misapplication. We do not change the regression analysis model... retention rates. Correcting this language does not change the regression analysis model itself or the... in repayment rates.'' On page 34461, second column, first full paragraph, we correct the phrase...

  9. 13 CFR 120.398 - America's Recovery Capital (ARC) Loan Program.

    Science.gov (United States)

    2010-01-01

    ... assistance to swimming pools. (2) Going Concern is a small business concern actively engaging in business... of repayment, taking into consideration the following: (1) Character, reputation, and credit history... business that includes the nature and history of the business, current and historical financial statements...

  10. Behavioral program synthesis with genetic programming

    CERN Document Server

    Krawiec, Krzysztof

    2016-01-01

    Genetic programming (GP) is a popular heuristic methodology of program synthesis with origins in evolutionary computation. In this generate-and-test approach, candidate programs are iteratively produced and evaluated. The latter involves running programs on tests, where they exhibit complex behaviors reflected in changes of variables, registers, or memory. That behavior not only ultimately determines program output, but may also reveal its `hidden qualities' and important characteristics of the considered synthesis problem. However, the conventional GP is oblivious to most of that information and usually cares only about the number of tests passed by a program. This `evaluation bottleneck' leaves search algorithm underinformed about the actual and potential qualities of candidate programs. This book proposes behavioral program synthesis, a conceptual framework that opens GP to detailed information on program behavior in order to make program synthesis more efficient. Several existing and novel mechanisms subs...

  11. System programming languages

    OpenAIRE

    ŠMIT, MATEJ

    2016-01-01

    Most operating systems are written in the C programming language. Similar is with system software, for example, device drivers, compilers, debuggers, disk checkers, etc. Recently some new programming languages emerged, which are supposed to be suitable for system programming. In this thesis we present programming languages D, Go, Nim and Rust. We defined the criteria which are important for deciding whether programming language is suitable for system programming. We examine programming langua...

  12. Purely Functional Structured Programming

    OpenAIRE

    Obua, Steven

    2010-01-01

    The idea of functional programming has played a big role in shaping today's landscape of mainstream programming languages. Another concept that dominates the current programming style is Dijkstra's structured programming. Both concepts have been successfully married, for example in the programming language Scala. This paper proposes how the same can be achieved for structured programming and PURELY functional programming via the notion of LINEAR SCOPE. One advantage of this proposal is that m...

  13. Lippincott Basic Reading Program.

    Science.gov (United States)

    Monterey Peninsula Unified School District, Monterey, CA.

    This program, included in "Effective Reading Programs...," serves 459 students in grades 1-3 at 15 elementary schools. The program employs a diagnostic-prescriptive approach to instruction in a nongraded setting through the use of the Lippincott Basic Reading program. When a child enters the program, he is introduced to a decoding…

  14. Programing Structural Synthesis System

    Science.gov (United States)

    Rogers, James L., Jr.

    1986-01-01

    Program aids research in analysis and optimization. Programing Structural Synthesis System (PROSSS2) developed to provide structural-synthesis capability by combining access to SPAR with CONMIN program and set of interface procedures. SPAR is large general-purpose finite-element structural-analysis program, and CONMIN is large general-purpose optimization program. PROSSS2 written in FORTRAN IV for batch execution.

  15. Structured Programming: An Introduction.

    Science.gov (United States)

    Moulton, Peter

    Designed for use by computer programming teachers, this booklet presents the concepts of structured programming and provides examples of how to implement this methodology, which provides a systematic way of organizing programs so that even large and complex programs are easier to understand and modify than unstructured programs. After a brief…

  16. 78 FR 69391 - Submission for OMB Review; Comment Request

    Science.gov (United States)

    2013-11-19

    ... institution confirms the loan status and certification and mails the form back to the Military Service...-372-0493. SUPPLEMENTARY INFORMATION: Title, Associated Form and OMB Number: DOD Loan Repayment Program... Military Services are authorized to repay student loans for individuals who meet certain criteria and...

  17. 34 CFR 611.45 - Under what circumstances does the Secretary discharge a scholarship recipient's obligation to...

    Science.gov (United States)

    2010-07-01

    ... scholarship recipient's obligation to repay for failure to meet the service obligation? 611.45 Section 611.45... EDUCATION, DEPARTMENT OF EDUCATION TEACHER QUALITY ENHANCEMENT GRANTS PROGRAM Scholarships § 611.45 Under what circumstances does the Secretary discharge a scholarship recipient's obligation to repay...

  18. 7 CFR 1951.230 - Transfer of security and assumption of loans.

    Science.gov (United States)

    2010-01-01

    ... 103-354 program in the area. (3) Transfers to eligible applicants will receive preference over... changed, the new repayment period may not exceed the lesser of the repayment period for a new loan of the..., Federal Collection Policies for Consumer or Commercial Debts,” with the applicant, and the form must...

  19. Energy Technology Programs: program summaries for 1979

    Energy Technology Data Exchange (ETDEWEB)

    1979-12-01

    The Energy Technology Programs in the BNL Department of Energy and Environment cover a broad range of activities, namely: electrochemical research, chemical energy storage, chemical heat pumps, solar technology, fossil technology, catalytic systems development, space-conditioning technology, and technical support/program management. Summaries of the individual tasks associated with these activities along with publications, significant accomplishments, and program funding levels are presented.

  20. TEN MASTER TEACHER AND PROGRAM AWARD PROGRAMS.

    Science.gov (United States)

    KOVACH, EDITH M.A.

    IN 1966 THE AMERICAN CLASSICAL LEAGUE HONORED THREE TEACHERS WITH ITS MASTER SECONDARY SCHOOL LATIN TEACHER AND PROGRAM AWARD. AMONG THE 32 PROGRAMS CITED FOR RECOGNITION, TEN (INCLUDING THOSE OF THE AWARD WINNERS) POSSESS CLEARLY INNOVATIVE FEATURES. IN BRIEF THEY FEATURE (1) A FIFTH YEAR ADVANCED PLACEMENT PROGRAM, LATIN AS INTRODUCTORY TO…

  1. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Safety Resources About the Patient Education Program The Recovery Room Choosing Wisely Educational Programs Educational Programs Educational ... and practice the skills needed for optimal postoperative recovery. The kit supports the entire surgical team with ...

  2. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Trauma Quality Programs National Trauma Data Bank Trauma Quality Improvement Program Mentoring for Excellence in Trauma Surgery Advanced Trauma Life Support Verification, Review, and Consultation Program for Hospitals ...

  3. [Theme: Horticulture Programs.

    Science.gov (United States)

    Henderson, Jan; And Others

    1982-01-01

    A series of articles discusses requirements for optimum growth of horticulture education programs. Includes beginning a program, simulating working conditions, the need for mechanical skills, starting a business, and other areas to be considered for a successful horticultural program. (JOW)

  4. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Conference Publications and Posters National Trauma System Injury Prevention and Control Quality and Safety Conference Quality and ... Safety Resources About the Patient Education Program The Recovery Room Choosing Wisely Educational Programs Educational Programs Educational ...

  5. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Education Trauma Systems Conference Publications and Posters Injury Prevention and Control Strong for Surgery Strong for Surgery ... Safety Resources About the Patient Education Program The Recovery Room Choosing Wisely Educational Programs Educational Programs Educational ...

  6. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Accreditation Program for Breast Centers About NAPBC Accreditation Education NAPBC Standards News Quality in Geriatric Surgery Coalition ... Program for Hospitals Trauma Systems Consultation Program Trauma Education Achieving Zero Preventable Deaths Conference Publications and Posters ...

  7. Health Programs for Veterans

    Science.gov (United States)

    ... Health Administration » Health Programs for Veterans Veterans Health Administration Health Programs for Veterans Beyond the doctors and nurses who ... Veterans Plain Language Surviving Spouses & Dependents Adaptive Sports Program ... Veterans Health Administration Veterans Benefits Administration National Cemetery ...

  8. 自发自还背景下我国地方政府债券信用风险研究%A Study on the Credit Risk of Local Government Bonds in the Back-ground of Self-issuance and Self-repayment

    Institute of Scientific and Technical Information of China (English)

    刘亚; 刘阿钢; 赵继志; 郑杰

    2015-01-01

    在地方政府债券自发自还的背景下,研究我国地方政府市政债券信用风险,对于相关监管部门确定省、市层级合理适度的市政债券发行额度和规模,对于市政债券的发行者以及投资者准确评估市政债券信用风险,确保市政债券安全有效地发行具有重要意义。文章通过引入奈特不确定性因素期权定价理论的相关思想,构建了市政债券信用风险模型。研究结果表明在考虑奈特不确定性背景下,当债务规模占可担保财政收入80%以下时,理论违约概率趋近于零,当债务规模达到可担保财政收入80%以上之后,理论违约概率对债务规模的敏感性突然放大。据此文章得出结论:在考虑奈特不确定性因素的背景下,违约率与奈特不确定性因子存在正相关关系;市政债券规模需严格控制。%In the background of self-issuance and self-repayment of the local government bonds,to study on the credit risk of local municipal bonds in our country,has great significance for the rele-vant regulatory authorities to determine the provincial and city level reasonably moderate issuance scale,and for the issuers and investors to access the credit risk of municipal bonds reasonably and accurately,thus to ensure that municipal bonds can be issued safely and effectively. This pa-per constructs a credit risk model of municipal bonds by introducing the ideas of option pricing un-der Knightian uncertainty theory. The research results show that under Knightian uncertainty, when the debt scale is below 80% of the fiscal revenues that can be guaranty,the theoretical de-fault probability is close to zero;but when the debt scale exceeds 80% of the fiscal revenues that can be guaranty,the sensitivity of default probability to debt scale amplifies suddenly. So this pa-per concludes that there exists a positive correlation between the default rate and Knightian un-certainty factors with considering

  9. 34 CFR 685.209 - Income contingent repayment plan.

    Science.gov (United States)

    2010-07-01

    ... Consumer Price Index (as determined by the Secretary) between December 1995 and the December next preceding... table reflecting changes based on inflation. This revised table is developed by changing each of the...

  10. 34 CFR 682.209 - Repayment of a loan.

    Science.gov (United States)

    2010-07-01

    .... (3) The lender may not charge an additional insurance premium or Federal default fee on the loan, but... refinancing lender may charge the borrower an insurance premium on a loan made under paragraph (f)(1) of this... certify to the matters described in that paragraph, provide the requesting lender and the guarantor on...

  11. 42 CFR 60.11 - Terms of repayment.

    Science.gov (United States)

    2010-10-01

    ...) Accreditation Council for Graduate Medical Education. (ii) Council on Optometric Education. (iii) Commission on... Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS HEALTH EDUCATION ASSISTANCE... Podiatry Education. (vi) American Council on Pharmaceutical Education. (vii) Council on Education...

  12. Code it right or repay: place-of-service compliance.

    Science.gov (United States)

    Schaum, Kathleen D

    2012-05-01

    All physicians/practitioners/suppliers should download and read CMS Transmittal 2407 in its entirety. In addition, a precise process to inform billers of the exact location where each wound care service was performed should be established. Billers should enter the correct POS code on every claim submitted to Medicare. Because the physician/practitioner/supplier is ultimately responsible for all claims submitted with the provider number, you should conduct internal audits of submitted claims to be certain that the POS code has been appropriately assigned and matches the actual location where your service was performed. If the internal audit identifies noncompliance with the POS code policy, correct your process and consider self-reporting the billing errors to Medicare. If the internal audit identifies compliance with the POS code policy, celebrate with your team!

  13. 7 CFR 1421.10 - Loan repayment rates.

    Science.gov (United States)

    2010-01-01

    ... for long grain rice and medium grain rice. (1) The prevailing world market price for long grain and... prevailing world market price for a class of rice will be determined by CCC based upon a review of prices at which rice is being sold in world markets and a weighting of such prices through the use of...

  14. 7 CFR 1721.106 - Repayment of deferred payments.

    Science.gov (United States)

    2010-01-01

    ... energy project(s), distributed generation project(s), and the contribution(s)-in-aid of construction. An... period starting with the next payment (November if paying on a monthly basis). When a Borrower defers...

  15. LANL Meteorology Program

    Energy Technology Data Exchange (ETDEWEB)

    Dewart, Jean Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-02-09

    The goal of the Meteorology Program is to provide all routine meteorology measurements for LANL operational requirements. This report discusses the program, its routine operations, and other services.

  16. An Evaluation of Micro-Credit Programs in Bosnia and Herzegovina Using Porter’s Diamond Model

    Directory of Open Access Journals (Sweden)

    Mohammad HAMAD

    2013-11-01

    Full Text Available The effective design and delivery of a microcredit program is difficult under any circumstance. Similarly, the task of microcredit institutions in Bosnia and Herzegovina that provide financial stability to its most impoverished members is very much complicated. The purpose of this paper is to explore competitive advantages that microcredit industry in Bosnia and Herzegovina has by using Porter's diamond model. The demonstration of the Diamond Model is used to explain the competitive advantage that the microcredit industry has in Bosnia and Herzegovina. To analyze the competitive advantages, secondary data were used from various institutional and governmental resources .The findings reflect that the meaningful objectives were set out by microcredit institutions in the country including objectively verifiable indicators of achievements. Among peers in Kosovo and in other Balkan regions (Albania, Croatia, Macedonia, Montenegro, Serbia, as well as peers similar in size and market outreach from Eastern Europe and Central Asia (ECA, the Bosnian microcredit institutions are some of the most highly leveraged. There is a clear upward trend in the median indicator for portfolio at risk between 2006 and 2008. The inflationary pressures that started at the end of 2007 in BH as well as the repercussions of the global 2008/2009 financial crisis have affected the repayment capacity of clients. From a policy perspective, the results suggest that in order to improve efficiency in the microcredit sector, and in the financial sector as a whole, a unified banking agency for the country must be established. Despite being hopeful for future, this doesn't seem likely to happen until the Bosnian Constitution is amended sometime in the future.

  17. The Cybernetic Writing Program.

    Science.gov (United States)

    Lowe, Kelly Fisher

    This paper looks at the role of a Writing Program Administrator, and applies the idea of a cybernetic system to the administration of the program. In this cybernetic model, the Writing Program Administrator (WPA) works as both a problem solver and problem causer, with the responsibility of keeping the program in proper balance. A cybernetic…

  18. Stochastic Constraint Programming

    OpenAIRE

    Walsh, Toby

    2009-01-01

    To model combinatorial decision problems involving uncertainty and probability, we introduce stochastic constraint programming. Stochastic constraint programs contain both decision variables (which we can set) and stochastic variables (which follow a probability distribution). They combine together the best features of traditional constraint satisfaction, stochastic integer programming, and stochastic satisfiability. We give a semantics for stochastic constraint programs, and propose a number...

  19. Viking Lander reliability program

    Science.gov (United States)

    Pilny, M. J.

    1978-01-01

    The Viking Lander reliability program is reviewed with attention given to the development of the reliability program requirements, reliability program management, documents evaluation, failure modes evaluation, production variation control, failure reporting and correction, and the parts program. Lander hardware failures which have occurred during the mission are listed.

  20. Laser Programs Highlights 1998

    Energy Technology Data Exchange (ETDEWEB)

    Lowdermilk, H.; Cassady, C.

    1999-12-01

    This report covers the following topics: Commentary; Laser Programs; Inertial Confinement Fusion/National Ignition Facility (ICF/NIF); Atomic Vapor Laser Isotope Separation (AVLIS); Laser Science and Technology (LS&T); Information Science and Technology Program (IS&T); Strategic Materials Applications Program (SMAP); Medical Technology Program (MTP) and Awards.

  1. Software for PROM Programing

    Science.gov (United States)

    Goolsby, C. W.

    1985-01-01

    Driver program allows for programing, reading, and verification of various PROM's. Manual entry of data to DATA/I/O PROM Programmer timeconsuming and error-prone. Driver program combines file management capability of EXORCISOR with flexibility of DATA I/O system. Provides user with way of reading, programing and verifying PROM's storing data on disk, modifying files and printing data.

  2. Generating Consistent Program Tutorials

    DEFF Research Database (Denmark)

    Vestdam, Thomas

    2002-01-01

    In this paper we present a tool that supports construction of program tutorials. A program tutorial provides the reader with an understanding of an example program by interleaving fragments of source code and explaining text. An example program can for example illustrate how to use a library...

  3. Light water reactor program

    Energy Technology Data Exchange (ETDEWEB)

    Franks, S.M.

    1994-12-31

    The US Department of Energy`s Light Water Reactor Program is outlined. The scope of the program consists of: design certification of evolutionary plants; design, development, and design certification of simplified passive plants; first-of-a-kind engineering to achieve commercial standardization; plant lifetime improvement; and advanced reactor severe accident program. These program activities of the Office of Nuclear Energy are discussed.

  4. Developing Parallel Programs

    Directory of Open Access Journals (Sweden)

    Ranjan Sen

    2012-09-01

    Full Text Available Parallel programming is an extension of sequential programming; today, it is becoming the mainstream paradigm in day-to-day information processing. Its aim is to build the fastest programs on parallel computers. The methodologies for developing a parallelprogram can be put into integrated frameworks. Development focuses on algorithm, languages, and how the program is deployed on the parallel computer.

  5. [PIC Program Evaluation Forms.

    Science.gov (United States)

    Short, N. J.

    These 4 questionnaires are designed to elicit teacher and parent evaluations of the Prescriptive Instruction Center (PIC) program. Included are Teacher Evaluation of Program Effectiveness (14 items), M & M Evaluation of Program Implementation (methods and materials specialists; 11 items), Teacher Evaluation of Program Effectiveness--Case Study…

  6. C++ Programming Language

    Science.gov (United States)

    Shaykhian, Gholam Ali

    2007-01-01

    C++ Programming Language: The C++ seminar covers the fundamentals of C++ programming language. The C++ fundamentals are grouped into three parts where each part includes both concept and programming examples aimed at for hands-on practice. The first part covers the functional aspect of C++ programming language with emphasis on function parameters and efficient memory utilization. The second part covers the essential framework of C++ programming language, the object-oriented aspects. Information necessary to evaluate various features of object-oriented programming; including encapsulation, polymorphism and inheritance will be discussed. The last part of the seminar covers template and generic programming. Examples include both user defined and standard templates.

  7. Introduction to parallel programming

    CERN Document Server

    Brawer, Steven

    1989-01-01

    Introduction to Parallel Programming focuses on the techniques, processes, methodologies, and approaches involved in parallel programming. The book first offers information on Fortran, hardware and operating system models, and processes, shared memory, and simple parallel programs. Discussions focus on processes and processors, joining processes, shared memory, time-sharing with multiple processors, hardware, loops, passing arguments in function/subroutine calls, program structure, and arithmetic expressions. The text then elaborates on basic parallel programming techniques, barriers and race

  8. Technology Commercialization Program 1991

    Energy Technology Data Exchange (ETDEWEB)

    1991-11-01

    This reference compilation describes the Technology Commercialization Program of the Department of Energy, Defense Programs. The compilation consists of two sections. Section 1, Plans and Procedures, describes the plans and procedures of the Defense Programs Technology Commercialization Program. The second section, Legislation and Policy, identifies legislation and policy related to the Program. The procedures for implementing statutory and regulatory requirements are evolving with time. This document will be periodically updated to reflect changes and new material.

  9. Multiobjective programming and planning

    CERN Document Server

    Cohon, Jared L

    2004-01-01

    This text takes a broad view of multiobjective programming, emphasizing the methods most useful for continuous problems. It reviews multiobjective programming methods in the context of public decision-making problems, developing each problem within a context that addresses practical aspects of planning issues. Topics include a review of linear programming, the formulation of the general multiobjective programming problem, classification of multiobjective programming methods, techniques for generating noninferior solutions, multiple-decision-making methods, multiobjective analysis of water reso

  10. The impact of a microfinance program on client perceptions of the quality of care provided by private sector midwives in Uganda.

    Science.gov (United States)

    Agha, Sohail; Balal, Asma; Ogojo-Okello, Francis

    2004-12-01

    To assess the impact of a microfinance program that provided business skills training and revolving loans to private sector midwives on perceived quality of services and client loyalty. A quasi-experimental study with a pretest, posttest design was used to evaluate the impact of the intervention. Exit interviews were conducted at 15 clinics that received the intervention and 7 clinics that did not. Baseline exit interviews were conducted between November and December 2000. Five days of business skills training were provided to midwives, and loans (averaging $454) were given during January and February 2001. A follow-up clinic visit was made to assess whether midwives were implementing what was emphasized during the training. The loans were to be repaid with interest within 6 to 12 months, at an interest rate that is standard within the local commercial market. For those who repaid the first set of loans (11 clinics), a second set of loans (averaging $742) was provided after June 2001. Follow-up exit interviews were conducted at the same clinics between February and March 2002. We assessed the effect of the intervention at both clinic and client levels. T-tests, the analysis of variance, and multivariate logistic regression analysis were conducted. These findings should be interpreted cautiously since secular trends were observed during the study period. The intervention was associated with improvement in clients' perceptions of the quality of care received at intervention clinics. The intervention was also associated with a higher level of client loyalty. The enthusiastic response of midwives and the high loan repayment rate indicate that midwives were very receptive to the microfinance program. Overall, these findings suggest that microfinance may have an important role in strengthening private sector health services by increasing private providers' business skills and clients' satisfaction with services.

  11. Programming Models in HPC

    Energy Technology Data Exchange (ETDEWEB)

    Shipman, Galen M. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-06-13

    These are the slides for a presentation on programming models in HPC, at the Los Alamos National Laboratory's Parallel Computing Summer School. The following topics are covered: Flynn's Taxonomy of computer architectures; single instruction single data; single instruction multiple data; multiple instruction multiple data; address space organization; definition of Trinity (Intel Xeon-Phi is a MIMD architecture); single program multiple data; multiple program multiple data; ExMatEx workflow overview; definition of a programming model, programming languages, runtime systems; programming model and environments; MPI (Message Passing Interface); OpenMP; Kokkos (Performance Portable Thread-Parallel Programming Model); Kokkos abstractions, patterns, policies, and spaces; RAJA, a systematic approach to node-level portability and tuning; overview of the Legion Programming Model; mapping tasks and data to hardware resources; interoperability: supporting task-level models; Legion S3D execution and performance details; workflow, integration of external resources into the programming model.

  12. On finitely recursive programs

    CERN Document Server

    Baselice, Sabrina; Criscuolo, Giovanni

    2009-01-01

    Disjunctive finitary programs are a class of logic programs admitting function symbols and hence infinite domains. They have very good computational properties, for example ground queries are decidable while in the general case the stable model semantics is highly undecidable. In this paper we prove that a larger class of programs, called finitely recursive programs, preserves most of the good properties of finitary programs under the stable model semantics, namely: (i) finitely recursive programs enjoy a compactness property; (ii) inconsistency checking and skeptical reasoning are semidecidable; (iii) skeptical resolution is complete for normal finitely recursive programs. Moreover, we show how to check inconsistency and answer skeptical queries using finite subsets of the ground program instantiation. We achieve this by extending the splitting sequence theorem by Lifschitz and Turner: We prove that if the input program P is finitely recursive, then the partial stable models determined by any smooth splittin...

  13. Analyzing Array Manipulating Programs by Program Transformation

    Science.gov (United States)

    Cornish, J. Robert M.; Gange, Graeme; Navas, Jorge A.; Schachte, Peter; Sondergaard, Harald; Stuckey, Peter J.

    2014-01-01

    We explore a transformational approach to the problem of verifying simple array-manipulating programs. Traditionally, verification of such programs requires intricate analysis machinery to reason with universally quantified statements about symbolic array segments, such as "every data item stored in the segment A[i] to A[j] is equal to the corresponding item stored in the segment B[i] to B[j]." We define a simple abstract machine which allows for set-valued variables and we show how to translate programs with array operations to array-free code for this machine. For the purpose of program analysis, the translated program remains faithful to the semantics of array manipulation. Based on our implementation in LLVM, we evaluate the approach with respect to its ability to extract useful invariants and the cost in terms of code size.

  14. Learning Programming Using MATLAB

    CERN Document Server

    Sayood, Khalid

    2007-01-01

    This book is intended for anyone trying to learn the fundamentals of computer programming. The chapters lead the reader through the various steps required for writing a program, introducing the MATLABr(R) constructs in the process. MATLABr(R) is used to teach programming because it has a simple programming environment. It has a low initial overhead which allows the novice programmer to begin programming immediately and allows the users to easily debug their programs. This is especially useful for people who have a "mental block" about computers. Although MATLABr(R) is a high-level la

  15. National Toxicology Program

    Science.gov (United States)

    ... to Main Navigation Skip to Site Sidebar National Toxicology Program http://ntp.niehs.nih.gov Home Testing ... NTP Cell Phone Radiofrequency Radiation Studies The National Toxicology Program (NTP) has been conducting experiments in rats ...

  16. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Associate Fellows Residents Medical Students Affiliate Members ACS Insurance Programs ACS Discount Programs FACS Resources Career Connection ... and Awards Overview Scholarships, Fellowships, and Awards Overview Health Policy Scholarships Scholarships for International Surgeons Research Scholarships ...

  17. HUD Program Income Limits

    Data.gov (United States)

    Department of Housing and Urban Development — Income limits used to determine the income eligibility of applicants for assistance under three programs authorized by the National Housing Act. These programs are...

  18. LOADING SIMULATION PROGRAM C

    Data.gov (United States)

    U.S. Environmental Protection Agency — LSPC is the Loading Simulation Program in C++, a watershed modeling system that includes streamlined Hydrologic Simulation Program Fortran (HSPF) algorithms for...

  19. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Profession Member Benefits About Member Benefits About Member Benefits Fellows (US and Canada) International Fellows Associate Fellows Residents Medical Students Affiliate Members ACS Insurance Programs ACS Discount Programs ...

  20. Kickstarting Choreographic Programming

    OpenAIRE

    Montesi, Fabrizio

    2015-01-01

    We present an overview of some recent efforts aimed at the development of Choreographic Programming, a programming paradigm for the production of concurrent software that is guaranteed to be correct by construction from global descriptions of communication behaviour.

  1. Modeling EERE deployment programs

    Energy Technology Data Exchange (ETDEWEB)

    Cort, K. A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hostick, D. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Belzer, D. B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Livingston, O. V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2007-11-01

    The purpose of the project was to identify and characterize the modeling of deployment programs within the EERE Technology Development (TD) programs, address possible improvements to the modeling process, and note gaps in knowledge for future research.

  2. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Downloads NSQIP in the Literature Newsroom Contact Us Hospital Compare Quality and Safety Conference Registry Login SCR ... Life Support Verification, Review, and Consultation Program for Hospitals Trauma Systems Consultation Program Trauma Education Achieving Zero ...

  3. ICASE Computer Science Program

    Science.gov (United States)

    1985-01-01

    The Institute for Computer Applications in Science and Engineering computer science program is discussed in outline form. Information is given on such topics as problem decomposition, algorithm development, programming languages, and parallel architectures.

  4. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Associate Fellows Residents Medical Students Affiliate Members ACS Insurance Programs ACS Discount Programs FACS Resources Career Connection ... Downloads NSQIP in the Literature Newsroom Contact Us Hospital Compare Quality and Safety Conference Registry Login SCR ...

  5. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... ACS Insurance Programs ACS Discount Programs FACS Resources Career Connection Update Your Profile Member Communities Leadership Opportunities ... Disaster Management and Emergency Preparedness Rural Trauma Team Development Course Trauma Evaluation and Management Trauma CME Nora ...

  6. Software Acquisition Program Dynamics

    Science.gov (United States)

    2011-10-24

    techniques to avoid these problems The Objective • Improve acquisition program staff decision-making, and thus improve acquisition program outcomes...classroom training, eLearning , certification, and more—to serve the needs of customers and partners worldwide.

  7. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... You Want to Be a Surgeon Resident Resources Teaching Resources Online Guide to Choosing a Surgical Residency ... Ostomy Home Skills Program Ostomy Home Skills Program Adult Ostomy Pediatric Ostomy Programa de Destrezas para manejo ...

  8. Radiologic Technology Program Standards.

    Science.gov (United States)

    Georgia Univ., Athens. Dept. of Vocational Education.

    This publication contains statewide standards for the radiologic technology program in Georgia. The standards are divided into 12 categories; Foundations (philosophy, purpose, goals, program objectives, availability, evaluation); Admissions (admission requirements, provisional admission requirements, recruitment, evaluation and planning); Program…

  9. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Care Organizations Other Publications Surgery Workforce Policy Program Current Projects Journal Publications from Surgery Workforce Policy Program ... ACS ACS and Veterans Diversity at ACS Benefits Current Openings Newsroom Newsroom Newsroom Press Releases Media Resources ...

  10. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Opportunities Leadership Opportunities Leadership & Advocacy Summit Get Involved in ACS Surgeons as Leaders Course Webinars for Surgeons ... Quality Programs Overview About Quality Programs ACS Leadership in Quality ACS Leadership in Quality Inspiring Quality Initiative ...

  11. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Be a YFA Leader Meetings and Events YFA Mentor Programs Top 10 Reasons to Participate Resources Webinars ... National Trauma Data Bank Trauma Quality Improvement Program Mentoring for Excellence in Trauma Surgery Advanced Trauma Life ...

  12. Nonflammable Clothing Development Program

    Science.gov (United States)

    Johnston, Richard; Radnofsky, Matthew I.

    1968-01-01

    Protective clothing is of major importance in our space program. The authors discuss the requirements, selection, and testing of materials considered for use in the program. The various types of garments worn by astronauts and support personnel are briefly described.

  13. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Participate in Improvement Activities How to Participate in Cost Federal Legislation Federal Legislation Federal Legislation Health Care ... Care Organizations Other Publications Surgery Workforce Policy Program Current Projects Journal Publications from Surgery Workforce Policy Program ...

  14. Parallel programming with PCN

    Energy Technology Data Exchange (ETDEWEB)

    Foster, I.; Tuecke, S.

    1991-12-01

    PCN is a system for developing and executing parallel programs. It comprises a high-level programming language, tools for developing and debugging programs in this language, and interfaces to Fortran and C that allow the reuse of existing code in multilingual parallel programs. Programs developed using PCN are portable across many different workstations, networks, and parallel computers. This document provides all the information required to develop parallel programs with the PCN programming system. In includes both tutorial and reference material. It also presents the basic concepts that underly PCN, particularly where these are likely to be unfamiliar to the reader, and provides pointers to other documentation on the PCN language, programming techniques, and tools. PCN is in the public domain. The latest version of both the software and this manual can be obtained by anonymous FTP from Argonne National Laboratory in the directory pub/pcn at info.mcs.anl.gov (c.f. Appendix A).

  15. Veterans Choice Program

    Data.gov (United States)

    Department of Veterans Affairs — If you are already enrolled in VA health care, the Choice Program allows you to receive health care within your community. Using this program does NOT impact your...

  16. Early Retirement Programs.

    Science.gov (United States)

    Everett, Peter W.

    1984-01-01

    Early retirement programs offer individuals an alternative to the work ethic while allowing them to maintain job security. Examples are given of several early, partial, and phased retirement programs currently being used in universities and public school systems. (DF)

  17. Quality program plan

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, D.P.

    1977-07-15

    This report describes a quality program plan for the Mound laboratory. Areas include variation engineering, technical manual process control systems, process performance data, product index system, promotional marketing program, quality engineering staff, ultimate use education, and management reporting.

  18. Entrez Programming Utilities

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Entrez Programming Utilities (E-utilities) are a set of eight server-side programs that provide a stable interface into the Entrez query and database system at...

  19. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Improvement Program Mentoring for Excellence in Trauma Surgery Advanced Trauma Life Support Verification, Review, and Consultation Program ... Education Achieving Zero Preventable Deaths Trauma Systems Conference Advanced Surgical Skills for Exposure in Trauma Advanced Trauma ...

  20. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... and Safety Conference Registry Login SCR Training and Testing Cancer Cancer Programs Cancer Programs Overview of Cancer ... and FAQs Features of the SSR CMS Merit-Based Incentive Payment System MOC Part 4 and Recertification ...

  1. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Other Publications Surgery Workforce Policy Program Current Projects Journal Publications from Surgery Workforce Policy Program AMA House ... the ACS Catalog Find a Product Contribute Education Journal of the American College of Surgeons About JACS ...

  2. Crab Rationalization Permit Program

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Crab Rationalization Program (Program) allocates BSAI crab resources among harvesters, processors, and coastal communities. The North Pacific Fishery Management...

  3. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Accreditation Program for Breast Centers About NAPBC Accreditation Education NAPBC Standards News Quality in Geriatric Surgery Coalition ... 4 and Recertification SSR Login MIPS Resources and Education Quality and Safety Conference Trauma Trauma Programs Trauma ...

  4. Building Technologies Program Multi-Year Program Plan Program Portfolio Management 2008

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2008-01-01

    Building Technologies Program Multi-Year Program Plan 2008 for program portfolio management, including the program portfolio management process, program analysis, performance assessment, stakeholder interactions, and cross-cutting issues.

  5. Reactive Programming in Java

    CERN Document Server

    CERN. Geneva

    2017-01-01

    Reactive Programming in gaining a lot of excitement. Many libraries, tools, and frameworks are beginning to make use of reactive libraries. Besides, applications dealing with big data or high frequency data can benefit from this programming paradigm. Come to this presentation to learn about what reactive programming is, what kind of problems it solves, how it solves them. We will take an example oriented approach to learning the programming model and the abstraction.

  6. Acquisition Support Program Overview

    Science.gov (United States)

    2016-06-30

    Principles of Effective Acquisition © 2006 by Carnegie Mellon University page 31 Summary The SEI, through the Acquisition Support Program , works directly...2006 by Carnegie Mellon University page 1 Acquisition Support Program Overview Brian Gallagher Director, Acquisition Support Program 9 March, 2006...MAR 2006 2. REPORT TYPE 3. DATES COVERED 00-00-2006 to 00-00-2006 4. TITLE AND SUBTITLE Acquisition Support Program Overview 5a. CONTRACT

  7. Joint Program Management Handbook

    Science.gov (United States)

    1994-12-01

    the Engieermg and Manufacuring Devopment Phase. Nfilestoae HI- Develommen Annros Devopment approval marks a significant step for any program, but it is...to review concept formulaton. Systems Engilneertn As with service programs, systems engineering in joint program management is an essential tool . I...MANAGEMENT HANDBOOK On=e wd Umawtaiutt As discussed in Chapter 7, systems analysis of relationships is a usef tool for joint program managers. The joint

  8. Photovoltaic systems. Program summary

    Energy Technology Data Exchange (ETDEWEB)

    None

    1978-12-01

    Each of the Department of Energy's Photovoltaic Systems Program projects funded and/or in existence during fiscal year 1978 (October 1, 1977 through September 30, 1978) are described. The project sheets list the contractor, principal investigator, and contract number and funding and summarize the programs and status. The program is divided into various elements: program assessment and integration, research and advanced development, technology development, system definition and development, system application experiments, and standards and performance criteria. (WHK)

  9. The robot programming network

    OpenAIRE

    Cervera Mateu, Enric; Martinet, Philippe; Marín Prades, Raúl; Moughlbay, Amine A.; Pascual del Pobil Ferré, Ángel; Alemany, Jaime; Esteller Curto, Roger; Casañ Núñez, Gustavo Adolfo

    2016-01-01

    The Robot Programming Network (RPN) is an initiative for creating a network of robotics education laboratories with remote programming capabilities. It consists of both online open course materials and online servers that are ready to execute and test the programs written by remote students. Online materials include introductory course modules on robot programming, mobile robotics and humanoids, aimed to learn from basic concepts in science, technology, engineering, and math...

  10. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... Ostomy Home Skills Program Ostomy Home Skills Program Adult Ostomy Pediatric Ostomy Programa de Destrezas para manejo Doméstico de Ostomía Ostomy Home Skills Program Adult Ostomy Pediatric Ostomy Programa de Destrezas para manejo ...

  11. Special Milk Program

    Science.gov (United States)

    US Department of Agriculture, 2009

    2009-01-01

    The Special Milk Program provides milk to children in schools, child care institutions and eligible camps that do not participate in other Federal child nutrition meal service programs. The program reimburses schools and institutions for the milk they serve. In 2008, 4,676 schools and residential child care institutions participated, along with…

  12. Gifted Program Evaluation

    Science.gov (United States)

    Neumeister, Kristie Speirs; Burney, Virginia Hays

    2012-01-01

    Faced with significant budget challenges, many districts cannot afford to hire an outside consultant to conduct a formal evaluation of their gifted programs. As an interim solution, districts may wish to conduct their own in-house program evaluation. "Gifted Program Evaluation: A Handbook for Administrators and Coordinators" is designed to assist…

  13. Customer Service Programming

    Science.gov (United States)

    1982-01-01

    Use of computer program STRCMACS has enabled Illinois Bell Telephone, a subsidiary of American Telephone and Telegraph to cut software development costs about 10 percent by reducing program maintenance and by allowing the department to bring other software into operation more quickly. It has also been useful in company training of programming staff.

  14. Pressure simulation program

    NARCIS (Netherlands)

    Knoll, B.; Phaff, J.C.; Gids, W.F. de

    1995-01-01

    A computer program has been developed to predict the wind pressure coefficients Cp on facades and roofs of block shaped buildings. The program is based on fits of measured data, including wind shielding by obstacles and terrain roughness. Main advantages of the program are: it needs no expertise of

  15. Linear Projective Program Syntax

    NARCIS (Netherlands)

    Bergstra, J.A.; Bethke, I.

    2004-01-01

    Based on an extremely simple program notation more advanced program features can be developed in linear projective program syntax such as conditional statements, while loops, recursion, use of an evaluation stack, object classes, method calls etc. Taking care of a cumulative and bottom up

  16. Programming Agents with Emotions

    NARCIS (Netherlands)

    Dastani, Mehdi; Floor, Chr.; Meyer, John-Jules Charles

    2014-01-01

    In this paper we show how a cognitive agent programming language can be endowed with ways to program emotions. In particular we show how the programming language 2APL can be augmented so that it can work together with the computational emotion model ALMA to deal with appraisal, emotion/mood generati

  17. Mini Project Programming Exams

    DEFF Research Database (Denmark)

    Nørmark, Kurt; Thomsen, Lone Leth; Torp, Kristian

    2008-01-01

    A number of different types of final programming exams used or considered at the Department of Computer Science, Aalborg University, are identified and analyzed. Based on this analysis, a new type of programming exam is introduced called a Mini Project Programming (MIP) exam. MIP is a group-based...... of MIP is how to detect fraud....

  18. College Outcomes Evaluation Program.

    Science.gov (United States)

    Hollander, T. Edward

    Guidelines and implementation options for a program to evaluate the outcomes of collegiate education in New Jersey are discussed. A good program must seek to: (1) maintain public confidence; (2) nuture institutional autonomy and individual diversity; and (3) stimulate educational excellence. College outcomes that the program should cover are:…

  19. Programming the BBC micro

    CERN Document Server

    Ferguson, John D; Macari, Louie; Williams, Peter H

    1983-01-01

    Programming the BBC Micro is a 12-chapter book that begins with a description of the BBC microcomputer, its peripheral, and faults. Subsequent chapters focus on practice in programming, program development, graphics, words, numbers, sound, bits, bytes, and assembly language. The interfacing, file handling, and detailed description of BBC microcomputer are also shown.

  20. The Zero Program

    Science.gov (United States)

    Roland, Erling; Midthassel, Unni Vere

    2012-01-01

    Zero is a schoolwide antibullying program developed by the Centre for Behavioural Research at the University of Stavanger, Norway. It is based on three main principles: a zero vision of bullying, collective commitment among all employees at the school using the program, and continuing work. Based on these principles, the program aims to reduce…

  1. Language Program Evaluation

    Science.gov (United States)

    Norris, John M.

    2016-01-01

    Language program evaluation is a pragmatic mode of inquiry that illuminates the complex nature of language-related interventions of various kinds, the factors that foster or constrain them, and the consequences that ensue. Program evaluation enables a variety of evidence-based decisions and actions, from designing programs and implementing…

  2. Maine's Employability Skills Program

    Science.gov (United States)

    McMahon, John M.; Wolffe, Karen E.; Wolfe, Judy; Brooker, Carrie

    2013-01-01

    This Practice Report describes the development and implementation of the "Maine Employability Skills Program," a model employment program developed by the Maine Division for the Blind and Visually Impaired (DBVI). The program was designed to support the efforts of the chronically unemployed or underemployed. These consumers were either…

  3. Technical Program, 1974,

    Science.gov (United States)

    proposed AGARD Technical Program and Budget for 1974. The report reflects the program that was unanimously approved by the AGARD National Delegates Board...required to support the proposed 1974 AGARD technical program is presented in Section 3. The separate publications summary shown in Section 4 identifies by

  4. Certification Programs for Citrus

    Science.gov (United States)

    Citrus certification programs designed to ensure that healthy plants of the highest genetic potential are being planted in the field are the basic building block of an integrated pest management program. Certification programs began for citrus began with the discovery that the diseases were graft t...

  5. Employment and Training Programs.

    Science.gov (United States)

    Minnesota State Office of the Legislative Auditor, St. Paul. Program Evaluation Div.

    This report examines the effectiveness of employment and training programs in Minnesota and discusses the impact of the 1985 Jobs Bill state legislation. Chapter 1 provides an introduction to Minnesota's programs and to studies of employment and training programs conducted nationwide. Chapter 2 studies the use of Job Training Partnership Act funds…

  6. Scallop License Limitation Program (SLLP) Permit Program

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — A federal Scallop License Limitation Program (SLLP) license is required onboard any vessel deployed in scallop fisheries in Federal waters off Alaska (except for...

  7. Clean Coal Technology Programs: Program Update 2009

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-10-01

    The purpose of the Clean Coal Technology Programs: Program Update 2009 is to provide an updated status of the U.S. Department of Energy (DOE) commercial-scale demonstrations of clean coal technologies (CCT). These demonstrations have been performed under the Clean Coal Technology Demonstration Program (CCTDP), the Power Plant Improvement Initiative (PPII), and the Clean Coal Power Initiative (CCPI). Program Update 2009 provides: (1) a discussion of the role of clean coal technology demonstrations in improving the nation’s energy security and reliability, while protecting the environment using the nation’s most abundant energy resource—coal; (2) a summary of the funding and costs of the demonstrations; and (3) an overview of the technologies being demonstrated, along with fact sheets for projects that are active, recently completed, or recently discontinued.

  8. Weatherization and Intergovernmental Program - Weatherization Assistance Program

    Energy Technology Data Exchange (ETDEWEB)

    None

    2010-06-01

    The U.S. Department of Energy’s (DOE) Weatherization Assistance Program reduces energy costs for low-income households by increasing the energy efficiency of their homes, while ensuring their health and safety.

  9. Fuels from biomass program. Program summary

    Energy Technology Data Exchange (ETDEWEB)

    None

    1978-01-01

    An overview of the ongoing research, development, and demonstration efforts of the period Oct. 1, 1976--Sept. 30, 1977 is presented. Accomplishments are highlighted and plans for continued activities are included. Discussion is presented under the following section headings: the Fuels from Biomass Program; organizational and functional responsibilities; program funding; fiscal year 1977 summary tables; current projects: production and collection of biomass and conversion of biomass; bibliography; index of contractors; and, appendix--unsolicited proposal requirements. (JGB)

  10. C++ how to program

    CERN Document Server

    Deitel, Paul J

    2014-01-01

    This best-selling comprehensive text is aimed at readers with little or no programming experience. It teaches programming by presenting the concepts in the context of full working programs and takes an early-objects approach. The authors emphasize achieving program clarity through structured and object-oriented programming, software reuse and component-oriented software construction. The Ninth Edition encourages students to connect computers to the community, using the Internet to solve problems and make a difference in our world. All content has been carefully fine-tuned in response to a team of distinguished academic and industry reviewers.

  11. Programming in COBOL

    CERN Document Server

    Lancaster, G T

    2014-01-01

    Programming in COBOL is a simple yet concise how-to book that teaches the programming language in a short yet effective step-by-step manner, which can be easily understood by anyone with sufficient knowledge in information technology. Covering first the advantages of COBOL over other programming languages, the book discusses COBOL's divisions - identification, environment, procedure, and data, and then describes the testing of the COBOL source programs and program questions. The book is valuable for those who wish to learn basic COBOL language, but do not have the time to take manufacturers' o

  12. Choosing the Right Program

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Given the transient nature of the job market, fewer companies are willing to fund the better quality international or global programs, programs that can clearly add value for those focusing on a career in China. "The connection between the pricing point and the perceived value is missing, even when the same program, quality and degree are twice as much in the US. There is absolutely a disconnection between the local market and the high-end foreign or joint programs," says Ira Cohen, Rutgers International Executive MBA Program China director.

  13. Programming for microprocessors

    CERN Document Server

    Colin, Andrew John Theodore

    1979-01-01

    Programming for Microprocessors deals with the basics of programming for microprocessors and contains practical aids to programming. Topics covered range from assembly language and microprocessor design to the Motorola 6800, programming techniques, control of peripheral devices, and high-level languages. Emphasis is given to the computer-like aspects of microprocessors. This text is comprised of 12 chapters; the first of which provides a general overview of microprocessors, differences between hardwired and programmed devices, and different kinds of microprocessors. The reader is then introduc

  14. Beginning programming for dummies

    CERN Document Server

    Wang, Wallace

    2011-01-01

    Do you think the programmers who work at your office are magical wizards who hold special powers that manipulate your computer? Believe it or not, anyone can learn how to write programs, and it doesn't take a higher math and science education to start. Beginning Programming for Dummies shows you how computer programming works without all the technical details or hard programming language. It explores the common parts of every computer programming language and how to write for multiple platforms like Windows, Mac OS X, or Linux. This easily accessible guide provides you with the tools

  15. Avaliação do programa nacional de fortalecimento da agricultura familiar: a intenção de pagamento do crédito Evaluation of Brazilian family farming program: a study on the intention of repaingy the agricultural credit

    Directory of Open Access Journals (Sweden)

    Francisco Eduardo de Castro Rocha

    2009-01-01

    Full Text Available Esta publicação faz parte de um estudo maior (Tese. Nela analisou-se a intenção de pagamento do crédito no contexto da avaliação do Programa Nacional de Fortalecimento da Agricultura Familiar (Pronaf na Paraíba. A pesquisa foi executada com base na opinião dos beneficiários do Grupo A (Assentados e B (Agricultores familiares em duas etapas: (a preliminar, para o levantamento de crenças e informações e (b principal, para a medição dessas crenças. Para avaliar a intenção de pagamento, foi empregado o modelo Teórico da Ação Planejada de Ajzen (1991. Com base nesse modelo, a Atitude, a Crença normativa (componente da norma subjetiva e a Norma Subjetiva foram, para o Grupo A, as variáveis preditoras que explicaram a Intenção de pagamento de crédito. Para o Grupo B, as dimensões Atitude, Crença comportamental (componente da atitude, Crença normativa (componente da norma subjetiva e a crença de controle (componente da percepção de controle influenciaram a Intenção do pagamento de crédito. A Percepção de controle não influenciou diretamente a Intenção comportamental, mas indiretamente essa variável é preditora do Comportamento-alvo.This publication is part of a major study (Thesis. In that thesis it was analyzed the intention of Pronaf's beneficiaries to repay the credit they have received. The Pronaf is a line of credit for small farmers implemented by the Brazilian Federal Government in 1996. Ajzen's Theory of Planned Behavior (1991 was used to evaluate the beneficiaries' intention in paying what they owned. In order to accomplish this evaluation, two studies were conducted. The first one (Preliminary Study focused on the small farmer's beliefs about the program operation. The second (Main Study focused on the measurement of these beliefs. Two beneficiary groups participated of the studies: Group A (agrarian reform settlers and Group B (small farmers. According to Ajzen's model, for the participants of the

  16. Programming Community Resources; A Training Program For Alcohol Program Administrators.

    Science.gov (United States)

    National Center for Alcohol Education, Arlington, VA.

    This guide is designed to upgrade and/or develop the assessment and negotiation skills of management personnel who are involved in developing and coordinating resources among community agencies to provide comprehensive services for individuals with alcohol problems. This training program addresses the following topics: (1) community assessment;…

  17. Variational Program Inference

    CERN Document Server

    Harik, Georges

    2010-01-01

    We introduce a framework for representing a variety of interesting problems as inference over the execution of probabilistic model programs. We represent a "solution" to such a problem as a guide program which runs alongside the model program and influences the model program's random choices, leading the model program to sample from a different distribution than from its priors. Ideally the guide program influences the model program to sample from the posteriors given the evidence. We show how the KL- divergence between the true posterior distribution and the distribution induced by the guided model program can be efficiently estimated (up to an additive constant) by sampling multiple executions of the guided model program. In addition, we show how to use the guide program as a proposal distribution in importance sampling to statistically prove lower bounds on the probability of the evidence and on the probability of a hypothesis and the evidence. We can use the quotient of these two bounds as an estimate of ...

  18. Computer network programming

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, J.Y. [California Polytechnic State Univ., San Luis Obispo, CA (United States)

    1996-12-31

    The programs running on a computer network can be divided into two parts, the Network Operating System and the user applications. Any high level language translator, such as C, JAVA, BASIC, FORTRAN, or COBOL, runs under NOS as a programming tool to produce network application programs or software. Each application program while running on the network provides the human user with network application services, such as remote data base search, retrieval, etc. The Network Operating System should provide a simple and elegant system interface to all the network application programs. This programming interface may request the Transport layer services on behalf of a network application program. The primary goals are to achieve programming convenience, and to avoid complexity. In a 5-layer network model, the system interface is comprised of a group of system calls which are collectively known as the session layer with its own Session Protocol Data Units. This is a position paper discussing the basic system primitives which reside between a network application program and the Transport layer, and a programming example of using such primitives.

  19. Radioisotope Power Systems Program: A Program Overview

    Science.gov (United States)

    Hamley, John A.

    2016-01-01

    NASA's Radioisotope Power Systems (RPS) Program continues to plan, mature research in energy conversion, and partners with the Department of Energy (DOE) to make RPS ready and available to support the exploration of the solar system in environments where the use of conventional solar or chemical power generation is impractical or impossible to meet potential future mission needs. Recent programs responsibilities include providing investment recommendations to NASA stakeholders on emerging thermoelectric and Stirling energy conversion technologies and insight on NASA investments at DOE in readying a generator for the Mars 2020 mission. This presentation provides an overview of the RPS Program content and status and the approach used to maintain the readiness of RPS to support potential future NASA missions.

  20. Site Support Program Plan Infrastructure Program

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-26

    The Fiscal Year 1996 Infrastructure Program Site Support Program Plan addresses the mission objectives, workscope, work breakdown structures (WBS), management approach, and resource requirements for the Infrastructure Program. Attached to the plan are appendices that provide more detailed information associated with scope definition. The Hanford Site`s infrastructure has served the Site for nearly 50 years during defense materials production. Now with the challenges of the new environmental cleanup mission, Hanford`s infrastructure must meet current and future mission needs in a constrained budget environment, while complying with more stringent environmental, safety, and health regulations. The infrastructure requires upgrading, streamlining, and enhancement in order to successfully support the site mission of cleaning up the Site, research and development, and economic transition.

  1. Site Support Program Plan Infrastructure Program

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-26

    The Fiscal Year 1996 Infrastructure Program Site Support Program Plan addresses the mission objectives, workscope, work breakdown structures (WBS), management approach, and resource requirements for the Infrastructure Program. Attached to the plan are appendices that provide more detailed information associated with scope definition. The Hanford Site`s infrastructure has served the Site for nearly 50 years during defense materials production. Now with the challenges of the new environmental cleanup mission, Hanford`s infrastructure must meet current and future mission needs in a constrained budget environment, while complying with more stringent environmental, safety, and health regulations. The infrastructure requires upgrading, streamlining, and enhancement in order to successfully support the site mission of cleaning up the Site, research and development, and economic transition.

  2. Test-driven programming

    Science.gov (United States)

    Georgiev, Bozhidar; Georgieva, Adriana

    2013-12-01

    In this paper, are presented some possibilities concerning the implementation of a test-driven development as a programming method. Here is offered a different point of view for creation of advanced programming techniques (build tests before programming source with all necessary software tools and modules respectively). Therefore, this nontraditional approach for easier programmer's work through building tests at first is preferable way of software development. This approach allows comparatively simple programming (applied with different object-oriented programming languages as for example JAVA, XML, PYTHON etc.). It is predictable way to develop software tools and to provide help about creating better software that is also easier to maintain. Test-driven programming is able to replace more complicated casual paradigms, used by many programmers.

  3. Programming in Biomolecular Computation

    DEFF Research Database (Denmark)

    Hartmann, Lars; Jones, Neil; Simonsen, Jakob Grue

    2010-01-01

    Our goal is to provide a top-down approach to biomolecular computation. In spite of widespread discussion about connections between biology and computation, one question seems notable by its absence: Where are the programs? We introduce a model of computation that is evidently programmable......, by programs reminiscent of low-level computer machine code; and at the same time biologically plausible: its functioning is defined by a single and relatively small set of chemical-like reaction rules. Further properties: the model is stored-program: programs are the same as data, so programs are not only...... in a strong sense: a universal algorithm exists, that is able to execute any program, and is not asymptotically inefficient. A prototype model has been implemented (for now in silico on a conventional computer). This work opens new perspectives on just how computation may be specified at the biological level....

  4. Programming Scala Scalability = Functional Programming + Objects

    CERN Document Server

    Wampler, Dean

    2009-01-01

    Learn how to be more productive with Scala, a new multi-paradigm language for the Java Virtual Machine (JVM) that integrates features of both object-oriented and functional programming. With this book, you'll discover why Scala is ideal for highly scalable, component-based applications that support concurrency and distribution. Programming Scala clearly explains the advantages of Scala as a JVM language. You'll learn how to leverage the wealth of Java class libraries to meet the practical needs of enterprise and Internet projects more easily. Packed with code examples, this book provides us

  5. Akamai Internship Program

    Science.gov (United States)

    2015-04-17

    AFRL-OSR-VA-TR-2015-0094 AKAMAI INTERNSHIP PROGRAM Lisa Hunter UNIVERSITY OF HAWAII SYSTEMS Final Report 04/17/2015 DISTRIBUTION A: Distribution...YYYY) 08-04-2015 2. REPORT TYPE Final 3. DATES COVERED (From - To) Jan 2010 - Dec 2014 4. TITLE AND SUBTITLE Akamai Internship Program 5a...DISTRIBUTION/AVAILABILITY STATEMENT Distribution A Public release 13. SUPPLEMENTARY NOTES none 14. ABSTRACT The Akamai Internship Program

  6. ON NONDETERMINISTIC DYNAMIC PROGRAMMING

    OpenAIRE

    2008-01-01

    R. Bellman left a lot of research problems in his work “Dynamic Programming" (1957). Having received ideas from Bellman, S. Iwamoto has extracted, out of his problems, a problem on nondeterministic dynamic programming (NDP). Instead of stochastic dynamic programming which has been well studied, Iwamoto has opened a gate to NDP. This report presents speci_c optimal solutions for NDPs on continuous state and decision spaces.

  7. Los Alamos Programming Models

    Energy Technology Data Exchange (ETDEWEB)

    Bergen, Benjamin Karl [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-07-07

    This is the PDF of a powerpoint presentation from a teleconference on Los Alamos programming models. It starts by listing their assumptions for the programming models and then details a hierarchical programming model at the System Level and Node Level. Then it details how to map this to their internal nomenclature. Finally, a list is given of what they are currently doing in this regard.

  8. Meteorological Monitoring Program

    Energy Technology Data Exchange (ETDEWEB)

    Hancock, H.A. Jr. [ed.; Parker, M.J.; Addis, R.P.

    1994-09-01

    The purpose of this technical report is to provide a comprehensive, detailed overview of the meteorological monitoring program at the Savannah River Site (SRS) near Aiken, South Carolina. The principle function of the program is to provide current, accurate meteorological data as input for calculating the transport and diffusion of any unplanned release of an atmospheric pollutant. The report is recommended for meteorologists, technicians, or any personnel who require an in-depth understanding of the meteorological monitoring program.

  9. Privacy Training Program

    Science.gov (United States)

    Recognizing that training and awareness are critical to protecting agency Personally Identifiable Information (PII), the EPA is developing online training for privacy contacts in its programs and regions.

  10. Revealing the programming process

    DEFF Research Database (Denmark)

    Bennedsen, Jens; Caspersen, Michael Edelgaard

    2005-01-01

    One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because the textb......One of the most important goals of an introductory programming course is that the students learn a systematic approach to the development of computer programs. Revealing the programming process is an important part of this; however, textbooks do not address the issue -- probably because...... the textbook medium is static and therefore ill-suited to expose the process of programming. We have found that process recordings in the form of captured narrated programming sessions are a simple, cheap, and efficient way of providing the revelation.We identify seven different elements of the programming...... process for which process recordings are a valuable communication media in order to enhance the learning process. Student feedback indicates both high learning outcome and superior learning potential compared to traditional classroom teaching....

  11. Veterinary Services Program

    Data.gov (United States)

    Federal Laboratory Consortium — Mission:To provide quality veterinary medical care and environmental enrichment programs for all animals, representing nine different species.To provide guidance for...

  12. Joint Robotics Program

    Science.gov (United States)

    2008-04-23

    Åèìáëáíáçå= oÉëÉ~êÅÜ=póãéçëáìã= JOINT ROBOTICS PROGRAM Published: 23 April 2008 by Joel Brown and Paul Varian 5th Annual Acquisition Research...3. DATES COVERED 00-00-2008 to 00-00-2008 4. TITLE AND SUBTITLE Joint Robotics Program 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM...ëóåÉêÖó=Ñçê=áåÑçêãÉÇ=ÅÜ~åÖÉ=======- 464 - = = Joint Robotics Program Presenter: Joel Brown, Defense Acquisition University Author: Paul Varian

  13. Practical C programming

    CERN Document Server

    Oualline, Steve

    1997-01-01

    There are lots of introductory C books, but this is the first one that has the no-nonsense, practical approach that has made Nutshell Handbooks® famous. C programming is more than just getting the syntax right. Style and debugging also play a tremendous part in creating programs that run well and are easy to maintain. This book teaches you not only the mechanics of programming, but also describes how to create programs that are easy to read, debug, and update. Practical rules are stressed. For example, there are fifteen precedence rules in C (&& comes before || comes before ?:). The practi

  14. Surface-Shading Program

    Science.gov (United States)

    Plessel, Todd

    1991-01-01

    Surface Shading computer program, SURF, developed in support of work of Computational Fluid Dynamics (CFD). Part of CFD graphics software. Accepts input in form of grid and solution files otherwise normally fed to Ames Research Center's version of PLOT3D software from "flow solver" programs. Interactively creates wire-frame, shaded, and function-map parts viewed and then transferred to Ames Research Graphic (ARCGRAPH) standard files, animated with GAS (COSMIC Program ARC-12379). Written in C programming language and requires Silicon Graphics "include" files (e.g., stdio.h, gl.h).

  15. Construction program management

    CERN Document Server

    Delaney, Joseph

    2013-01-01

    Although construction is one of the largest industries in the United States, it lags behind other industries in its implementation of modern management techniques such as those contained in the Standard for Program Management (the Standard) by the Project Management Institute (PMI(R)). Construction Program Management details the successful use of the PMI(R) approach for the construction of capital programs. It demonstrates, through case studies, how implementation of PMI's set of tools and techniques can improve the chances of program success. Exploring tactical and strategic management method

  16. An extended day program

    Directory of Open Access Journals (Sweden)

    Ševkušić-Mandić Slavica G.

    2002-01-01

    Full Text Available The paper presents the results of a pilot project evaluation, carried out as an action investigation whose aim was to provide a better quality extended day for primary school students. The project included the training of teachers involved in extended day program, designing of special activities performed by teachers with children once a week as well as changes and equipping of premises where children stay. The aims of the program were conception and performance of activities in a less formal way than during regular instructional days, linking of learning at school and acquired knowledge to everyday experiences, and work on contents contributing to the development of child's interests and creativity. The program was accomplished in a Belgrade primary school during the 2001/2002 academic year, comprising students of 1st and 2nd grades (N=77. The effects of the program were monitored throughout the academic year (observation and teachers' reports on accomplished workshops and at the end of the academic year (teachers and students' opinions of the program, academic achievement and creativity of students attending the extended day program compared with students not attending it. Findings about positive effects of the program on students' broadening of interests and willingness to express themselves creatively, indicate unequivocally that there is a need for developing special extended day programs. The extended day program is an opportunity for school to exert greater educational influence that has yet to be tapped.

  17. Small engine technology programs

    Science.gov (United States)

    Niedzwiecki, Richard W.

    1990-01-01

    Described here is the small engine technology program being sponsored at the Lewis Research Center. Small gas turbine research is aimed at general aviation, commuter aircraft, rotorcraft, and cruise missile applications. The Rotary Engine program is aimed at supplying fuel flexible, fuel efficient technology to the general aviation industry, but also has applications to other missions. The Automotive Gas Turbine (AGT) and Heavy-Duty Diesel Transport Technology (HDTT) programs are sponsored by DOE. The Compound Cycle Engine program is sponsored by the Army. All of the programs are aimed towards highly efficient engine cycles, very efficient components, and the use of high temperature structural ceramics. This research tends to be generic in nature and has broad applications. The HDTT, rotary technology, and the compound cycle programs are all examining approaches to minimum heat rejection, or 'adiabatic' systems employing advanced materials. The AGT program is also directed towards ceramics application to gas turbine hot section components. Turbomachinery advances in the gas turbine programs will benefit advanced turbochargers and turbocompounders for the intermittent combustion systems, and the fundamental understandings and analytical codes developed in the research and technology programs will be directly applicable to the system projects.

  18. Transit Benefit Program Data -

    Data.gov (United States)

    Department of Transportation — This data set contains information about any US government agency participating in the transit benefits program, funding agreements, individual participating Federal...

  19. Ostomy Home Skills Program

    Medline Plus

    Full Text Available ... CME Accreditation CME Joint Providership Program Verification of Knowledge and Skills ... Practice Management Workshops Patients and Family Patient Education Patient Education ...

  20. Sandia Laboratories energy programs

    Energy Technology Data Exchange (ETDEWEB)

    Lundergan, C.D.; Mead, P.L.; Gillespie, R.S. (eds.)

    1977-03-01

    As one of the multiprogram laboratories of the Energy Research and Development Administration, Sandia Laboratories applies its resources to a number of nationally important programs. About 75 percent of these resources are applied to research and development for national security programs having to do primarily with nuclear weapons--the principal responsibility of the Laboratories. The remaining 25 percent are applied to energy programs and energy-related activities, particularly those requiring resources that are also used in nuclear weapon and other national security programs. Examples of such energy programs and activities are research into nuclear fusion, protection of nuclear materials from theft or diversion, and the disposal of radioactive waste. A number of technologies and disciplines developed for the weapon program are immediately applicable for the development of various energy sources. Instruments developed to detect, measure, and record the detonation of nuclear devices underground, now being used to support the development of in-situ processing of coal and oil shale, are examples. The purpose of this report is to provide an overview of these and other energy programs being conducted by these laboratories in the development of economical and environmentally acceptable alternative energy sources. Energy programs are undertaken when they require capabilities used at the Laboratories for the weapon program, and when they have no adverse effect upon that primary mission. The parallel operation of weapon and energy activities allows optimum use of facilities and other resources.