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

Science.gov (United States)

2013-04-22

... DEPARTMENT OF AGRICULTURE National Institute of Food and Agriculture Nomination Form of Veterinary Shortage Situations for the Veterinary Medicine Loan Repayment Program (VMLRP) AGENCY: National Institute... information collection for the Veterinary Medicine Loan Repayment Program (VMLRP). This notice initiates a 30...

Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

Science.gov (United States)

Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.

2016-01-01

Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

A Comparison of the J-1 Visa Waiver and Loan Repayment Programs in the Recruitment and Retention of Physicians in Rural Nebraska.

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Opoku, Samuel T; Apenteng, Bettye A; Lin, Ge; Chen, Li-Wu; Palm, David; Rauner, Thomas

2015-01-01

There is a dearth of literature evaluating the effectiveness of programs aimed at recruiting and retaining physicians in rural Nebraska. Taking advantage of the Nebraska Health Professional Tracking System, this study attempts to comparatively assess the effectiveness of the J-1 visa waiver and state loan repayment programs in the recruitment and retention of physicians in rural Nebraska. A mixed methods approach was used. We tracked 240 physicians who enrolled in the J-1 visa waiver and state loan repayment programs between 1996 and 2012 until 2013. In addition, key informant interviews were conducted to obtain perspectives on the recruitment and retention of physicians in rural Nebraska through the 2 programs. Results from multilevel survival regression analysis indicated that physicians enrolled in the J-1 visa waiver program were more likely to leave rural Nebraska when compared with those enrolled in the state loan repayment program. Participants in the qualitative study, however, cautioned against declaring one program as superior over the other, given that the 2 programs addressed different needs for different communities. In addition, results suggested that fostering the integration of physicians and their families into rural communities might be a way of enhancing retention, regardless of program. The findings from this study highlight the complexity of recruitment and retention issues in rural Nebraska and suggest the need for more holistic and family-centered approaches to addressing these issues. © 2015 National Rural Health Association.

LRP-1: Functions, Signaling and Implications in Kidney and Other Diseases

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Ling Lin

2014-12-01

Full Text Available Low-density lipoprotein (LDL-related protein-1 (LRP-1 is a member of LDL receptor family that is implicated in lipoprotein metabolism and in the homeostasis of proteases and protease inhibitors. Expression of LRP-1 is ubiquitous. Up-regulation of LRP-1 has been reported in numerous human diseases. In addition to its function as a scavenger receptor for various ligands, LRP-1 has been shown to transduce multiple intracellular signal pathways including mitogen-activated protein kinase (MAPK, Akt, Rho, and the integrin signaling. LRP-1 signaling plays an important role in the regulation of diverse cellular process, such as cell proliferation, survival, motility, differentiation, and transdifferentiation, and thus participates in the pathogenesis of organ dysfunction and injury. In this review, we focus on the current understanding of LRP-1 signaling and its roles in the development and progression of kidney disease. The role and signaling of LRP-1 in the nervous and cardiovascular systems, as well as in carcinogenesis, are also briefly discussed.

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... AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS NONRECOURSE MARKETING ASSISTANCE LOAN AND LDP REGULATIONS FOR HONEY § 1434.18 Loan repayments. (a) A honey producer may repay a nonrecourse marketing assistance...

Binding of alpha2ML1 to the low density lipoprotein receptor-related protein 1 (LRP1 reveals a new role for LRP1 in the human epidermis.

Directory of Open Access Journals (Sweden)

Marie-Florence Galliano

Full Text Available BACKGROUND: The multifunctional receptor LRP1 has been shown to bind and internalize a large number of protein ligands with biological importance such as the pan-protease inhibitor alpha2-macroglobulin (alpha2M. We recently identified Alpha2ML1, a new member of the alpha2M gene family, expressed in epidermis. alpha2ML1 might contribute to the regulation of desquamation through its inhibitory activity towards proteases of the chymotrypsin family, notably KLK7. The expression of LRP1 in epidermis as well as its ability to internalize alpha2ML1 was investigated. METHODS AND PRINCIPAL FINDINGS: In human epidermis, LRP1 is mainly expressed within the granular layer of the epidermis, which gathers the most differentiated keratinocytes, as shown by immunohistochemistry and immunofluorescence using two different antibodies. By using various experimental approaches, we show that the receptor binding domain of alpha2ML1 (RBDl is specifically internalized into the macrophage-like cell line RAW and colocalizes with LRP1 upon internalization. Coimmunoprecipitation assays demonstrate that RBDl binds LRP1 at the cell surface. Addition of RAP, a universal inhibitor of ligand binding to LRP1, prevents RBDl binding at the cell surface as well as internalization into RAW cells. Silencing Lrp1 expression with specific siRNA strongly reduces RBDl internalization. CONCLUSIONS AND SIGNIFICANCE: Keratinocytes of the upper differentiated layers of epidermis express LRP1 as well as alpha2ML1. Our study also reveals that alpha2ML1 is a new ligand for LRP1. Our findings are consistent with endocytosis by LRP1 of complexes formed between alpha2ML1 and proteases. LRP1 may thus control desquamation by regulating the biodisponibility of extracellular proteases.

Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/β-catenin signalling

Science.gov (United States)

Chen, Qing; Su, Yi; Wesslowski, Janine; Hagemann, Anja I; Ramialison, Mirana; Wittbrodt, Joachim; Scholpp, Steffen; Davidson, Gary

2014-01-01

Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) function as transmembrane receptors to transduce Wnt signals. A key mechanism for signalling is Wnt-induced serine/threonine phosphorylation at conserved PPPSPxS motifs in the LRP6 cytoplasmic domain, which promotes pathway activation. Conserved tyrosine residues are positioned close to all PPPSPxS motifs, which suggests they have a functional significance. Using a cell culture-based cDNA expression screen, we identified the non-receptor tyrosine kinases Src and Fer as novel LRP6 modifiers. Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly. In contrast to the known PPPSPxS Ser/Thr kinases, tyrosine phosphorylation by Src and Fer negatively regulates LRP6-Wnt signalling. Epistatically, they function upstream of β-catenin to inhibit signalling and in agreement with a negative role in regulating LRP6, MEF cells lacking these kinases show enhanced Wnt signalling. Wnt3a treatment of cells enhances tyrosine phosphorylation of endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and disrupts LRP6 signalosome formation. Interestingly, CK1γ inhibits Fer-induced LRP6 phosphorylation, suggesting a mechanism whereby CK1γ acts to de-represses inhibitory LRP6 tyrosine phosphorylation. We propose that LRP6 tyrosine phosphorylation by Src and Fer serves a negative regulatory function to prevent over-activation of Wnt signalling at the level of the Wnt receptor, LRP6. Subject Categories Membrane & Intracellular Transport; Post-translational Modifications, Proteolysis & Proteomics PMID:25391905

LRP1B, BRD2 and CACNA1D: new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia.

Science.gov (United States)

Houde, Andrée-Anne; Ruchat, Stephanie-May; Allard, Catherine; Baillargeon, Jean-Patrice; St-Pierre, Julie; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Hivert, Marie-France; Bouchard, Luigi

2015-10-01

To assess the associations between gestational diabetes mellitus (GDM) and DNA methylation levels at genes related to energy metabolism. Ten loci were selected from our recent epigenome-wide association study on GDM. DNA methylation levels were quantified by bisulfite pyrosequencing in 80 placenta and cord blood samples (20 exposed to GDM) from an independent birth cohort (Gen3G). We did not replicate association between DNA methylation and GDM. However, in normoglycemic women, glucose levels were associated with DNA methylation changes at LRP1B and BRD2 and at CACNA1D and LRP1B gene loci in placenta and cord blood, respectively. These results suggest that maternal glucose levels, within the normal range, are associated with DNA methylation changes at genes related to energy metabolism and previously associated with GDM. Maternal glycemia might thus be involved in fetal metabolic programming.

Unimpaired dendritic cell functions in MVP/LRP knockout mice.

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Mossink, Marieke H; de Groot, Jan; van Zon, Arend; Fränzel-Luiten, Erna; Schoester, Martijn; Scheffer, George L; Sonneveld, Pieter; Scheper, Rik J; Wiemer, Erik A C

2003-09-01

Dendritic cells (DCs) act as mobile sentinels of the immune system. By stimulating T lymphocytes, DCs are pivotal for the initiation of both T- and B-cell-mediated immune responses. Recently, ribonucleoprotein particles (vaults) were found to be involved in the development and/or function of human DCs. To further investigate the role of vaults in DCs, we examined the effects of disruption of the major vault protein (MVP/LRP) on the development and antigen-presenting capacity of DCs, using our MVP/LRP knockout mouse model. Mononuclear bone marrow cells were isolated from wild-type and knockout mice and stimulated to differentiate to DCs. Like human DCs, the wild-type murine DC cultures strongly expressed MVP/LRP. Nevertheless, the MVP/LRP-deficient DCs developed normally and showed similar expression levels of several DC surface markers. No differences were observed in in vitro studies on the antigen uptake and presenting capacities of the wild-type and MVP/LRP knockout DCs. Moreover, immunization of the MVP/LRP-deficient mice with several T-cell antigens led to responses similar to those observed in the wild-type mice, indicating that the in vivo DC migration and antigen-presentation capacities are intact. Moreover, no differences were observed in the induction of the T cell-dependent humoral responses and orally induced peripheral T-cell tolerance. In conclusion, vaults are not required for primary DC functions. Their abundance in DCs may, however, still reflect basic roles in myeloid cell proliferation and DC development.

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.

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

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

SET-LRP of the Hydrophobic Biobased Menthyl Acrylate.

Science.gov (United States)

Bensabeh, Nabil; Ronda, Joan C; Galià, Marina; Cádiz, Virginia; Lligadas, Gerard; Percec, Virgil

2018-04-09

Cu(0) wire-catalyzed single electron transfer-living radical polymerization (SET-LRP) of (-)-menthyl acrylate, a biobased hydrophobic monomer, was investigated at 25 °C in ethanol, isopropanol, ethyl lactate, 2,2,2-trifluoroethanol (TFE), and 2,2,3,3-tetrafluoropropanol (TFP). All solvents are known to promote, in the presence of N ligands, the mechanistically required self-regulated disproportionation of Cu(I)Br into Cu(0) and Cu(II)Br 2 . Both fluorinated alcohols brought out their characteristics of universal SET-LRP solvents and showed the proper polarity balance to mediate an efficient polymerization of this bulky and hydrophobic monomer. Together with the secondary alkyl halide initiator, methyl 2-bromopropionate (MBP), and the tris(2-dimethylaminoethyl)amine (Me 6 -TREN) ligand, TFE and TPF mediated an efficient SET-LRP of MnA at room temperature that proceeds through a self-generated biphasic system. The results presented here demonstrate that Cu(0) wire-catalyzed SET-LRP can be used to target polyMnA with different block lengths and narrow molecular weight distribution at room temperature. Indeed, the use of a combination of techniques that include GPC, 1 H NMR, MALDI-TOF MS performed before and after thioetherification of bromine terminus via "thio-bromo" click chemistry, and in situ reinitiation copolymerization experiments supports the near perfect chain end functionality of the synthesized biobased hydrophobic polymers. These results expand the possibilities of SET-LRP into the area of renewable resources where hydrophobic compounds are widespread.

42 CFR 57.1513 - Repayment.

Science.gov (United States)

2010-10-01

... to Assist in Construction of Teaching Facilities for Health Profession Personnel § 57.1513 Repayment... 42 Public Health 1 2010-10-01 2010-10-01 false Repayment. 57.1513 Section 57.1513 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS GRANTS FOR CONSTRUCTION OF TEACHING...

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

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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,…

Major vault protein/lung resistance-related protein (MVP/LRP) expression in nervous system tumors.

Science.gov (United States)

Sasaki, Tsutomu; Hankins, Gerald R; Helm, Gregory A

2002-01-01

Lung resistance-related protein (LRP) was identified as the major vault protein (MVP), the main component of multimeric vault particles. It functions as a transport-associated protein that can be associated with multidrug resistance. In previous studies, expression of MVP/LRP has been documented in tumors of various types. In general, good correlations have been reported for expression of MVP/LRP and decreased sensitivity to chemotherapy and poor prognosis. MVP/LRP expression has been documented in glioblastomas, but its expression in nervous system tumors in general has not been well characterized. Immunohistochemistry using anti-human MVP/LRP antibody (LRP-56) was performed on formalin-fixed, paraffin-embedded archival tissue from 69 primary central nervous system tumors. Expression of MVP/LRP was observed in 81.2% (56/69) of primary nervous system tumors, including astrocytomas (11/13), oligodendrogliomas (1/2), oligoastrocytomas (5/5), ependymoma (1/1), meningiomas (35/45), schwannomas (2/2), and neurofibroma (1/1). Various degrees and distributions of immunoreactivity to MVP/ LRP were observed. Neither the presence nor the degree of immunoreactivity to MVP/LRP showed any correlation with either tumor grade or the presence of brain invasion.

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

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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.

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...

Detection of the Mr 110,000 lung resistance-related protein LRP/MVP with monoclonal antibodies.

Science.gov (United States)

Schroeijers, A B; Scheffer, G L; Reurs, A W; Pijnenborg, A C; Abbondanza, C; Wiemer, E A; Scheper, R J

2001-11-01

The Mr 110,000 lung resistance-related protein (LRP), also termed the major vault protein (MVP), constitutes >70% of subcellular ribonucleoprotein particles called vaults. Overexpression of LRP/MVP and vaults has been linked directly to MDR in cancer cells. Clinically, LRP/MVP expression can be of value to predict response to chemotherapy and prognosis. Monoclonal antibodies (MAbs) against LRP/MVP have played a critical role in determining the relevance of this protein in clinical drug resistance. We compared the applicability of the previously described MAbs LRP-56, LMR-5, LRP, 1027, 1032, and newly isolated MAbs MVP-9, MVP-16, MVP-18, and MVP-37 for the immunodetection of LRP/MVP by immunoblotting analysis and by immunocyto- and histochemistry. The availability of a broader panel of reagents for the specific and sensitive immunodetection of LRP/MVP should greatly facilitate biological and clinical studies of vault-related MDR.

Immunization with Recombinantly Expressed LRP4 Induces Experimental Autoimmune Myasthenia Gravis in C57BL/6 Mice.

Science.gov (United States)

Ulusoy, Canan; Çavuş, Filiz; Yılmaz, Vuslat; Tüzün, Erdem

2017-07-01

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), characterized with muscle weakness. While MG develops due to acetylcholine receptor (AChR) antibodies in most patients, antibodies to muscle-specific receptor tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4) may also be identified. Experimental autoimmune myasthenia gravis (EAMG) has been previously induced by both LRP4 immunization and passive transfer of LRP4 antibodies. Our aim was to confirm previous results and to test the pathogenic effects of LRP4 immunization in a commonly used mouse strain C57BL/6 (B6) using a recombinantly expressed human LRP4 protein. B6 mice were immunized with human LRP4 in CFA, Torpedo Californica AChR in CFA or only CFA. Clinical and pathogenic aspects of EAMG were compared among groups. LRP4- and AChR-immunized mice showed comparable EAMG clinical severity. LRP4-immunized mice displayed serum antibodies to LRP4 and NMJ IgG and complement factor C3 deposits. IgG2 was the dominant anti-LRP4 isotype. Cultured lymph node cells of LRP4- and AChR-immunized mice gave identical pro-inflammatory cytokine (IL-6, IFN-γ and IL-17) responses to LRP4 and AChR stimulation, respectively. Our results confirm the EAMG-inducing action of LRP4 immunization and identify B6 as a LRP4-EAMG-susceptible mouse strain. Demonstration of complement fixing anti-LRP4 antibodies in sera and complement/IgG deposits at the NMJ of LRP4-immunized mice indicates complement activation as a putative pathogenic mechanism. We have thus developed a practical LRP4-induced EAMG model using a non-conformational protein and a widely available mouse strain for future investigation of LRP4-related MG.

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.

Prolonged Stationary-Phase Incubation Selects for lrp Mutations in Escherichia coli K-12

Science.gov (United States)

Zinser, Erik R.; Kolter, Roberto

2000-01-01

Evolution by natural selection occurs in cultures of Escherichia coli maintained under carbon starvation stress. Mutants of increased fitness express a growth advantage in stationary phase (GASP) phenotype, enabling them to grow and displace the parent as the majority population. The first GASP mutation was identified as a loss-of-function allele of rpoS, encoding the stationary-phase global regulator, ςS (M. M. Zambrano, D. A. Siegele, M. A. Almirón, A. Tormo, and R. Kolter, Science 259:1757–1760, 1993). We now report that a second global regulator, Lrp, can also play a role in stationary-phase competition. We found that a mutant that took over an aged culture of an rpoS strain had acquired a GASP mutation in lrp. This GASP allele, lrp-1141, encodes a mutant protein lacking the critical glycine in the turn of the helix-turn-helix DNA-binding domain. The lrp-1141 allele behaves as a null mutation when in single copy and is dominant negative when overexpressed. Hence, the mutant protein appears to retain stability and the ability to dimerize but lacks DNA-binding activity. We also demonstrated that a lrp null allele generated by a transposon insertion has a fitness gain identical to that of the lrp-1141 allele, verifying that cells lacking Lrp activity have a competitive advantage during prolonged starvation. Finally, we tested by genetic analysis the hypothesis that the lrp-1141 GASP mutation confers a fitness gain by enhancing amino acid catabolism during carbon starvation. We found that while amino acid catabolism may play a role, it is not necessary for the lrp GASP phenotype, and hence the lrp GASP phenotype is due to more global physiological changes. PMID:10894750

7 CFR 773.19 - Interest rate, terms, security requirements, and repayment.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Interest rate, terms, security requirements, and... SERVICE AGENCY, DEPARTMENT OF AGRICULTURE SPECIAL PROGRAMS SPECIAL APPLE LOAN PROGRAM § 773.19 Interest rate, terms, security requirements, and repayment. (a) Interest rate. The interest rate will be fixed...

7 CFR 1980.424 - Term of loan repayment.

Science.gov (United States)

2010-01-01

... scheduled for payment as agreed upon by the lender and applicant but on terms that reasonably assure repayment of the loan. However, the first installment to include a repayment of principal may be scheduled... collateral obsolescence prior to full repayment of the indebtedness. The loan file must be documented to...

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.

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.

Immunization of mice with LRP4 induces myasthenia similar to MuSK-associated myasthenia gravis.

Science.gov (United States)

Mori, Shuuichi; Motohashi, Norio; Takashima, Rumi; Kishi, Masahiko; Nishimune, Hiroshi; Shigemoto, Kazuhiro

2017-11-01

Since the first report of experimental animal models of myasthenia gravis (MG) with autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), there have not been any major reports replicating the pathogenicity of anti-LRP4 antibodies (Abs). Recent clinical studies have cast doubt on the specificity and pathogenicity of anti-LRP4 antibodies for MG, highlighting the need for further research. In this study, we purified antigens corresponding to the extracellular region of human LRP4 stably expressed with chaperones in 293 cells and used these antigens to immunize female A/J mice. Immunization with LRP4 protein caused mice to develop myasthenia having similar electrophysiological and histological features as are observed in MG patients with circulating Abs against muscle-specific kinase (MuSK). Our results clearly demonstrate that active immunization of mice with LRP4 proteins causes myasthenia similar to the MG induced by anti-MuSK Abs. Further experimental and clinical studies are required to prove the pathogenicity of anti-LRP4 Abs in MG patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

42 CFR 57.314 - Repayment of loans made after November 17, 1971, for failure to complete a program of study. 2

Science.gov (United States)

2010-10-01

..., EDUCATIONAL IMPROVEMENTS, SCHOLARSHIPS AND STUDENT LOANS Nursing Student Loans § 57.314 Repayment of loans..., medical, or financial difficulties. The Secretary will only repay education loans made after November 17...

Are Debt Repayment Incentives Undermined by Foreign Aid?

DEFF Research Database (Denmark)

Bjørnskov, Christian; Schröder, Philipp

2013-01-01

This paper investigates the effects of inflows of foreign aid on the debt repayment behavior of developing countries. The paper first delineates the overall incentives to committing to timely debt repayment in a war of attrition-type model. A set of panel estimates including 93 developing countries...... shows that foreign aid is strongly negatively associated with repayment incentives. The findings pertain to both total debt service and service on publically guaranteed debt. A set of conditional estimates suggest that the main findings generalize to the majority of developing countries...

Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

Science.gov (United States)

Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

2015-04-08

Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

5 CFR 179.306 - Written agreement for repayment.

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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 admits...

Are Debt Repayment Incentives Undermined by Foreign Aid?

DEFF Research Database (Denmark)

Bjørnskov, Christian; Schröder, Philipp J.H.

This paper investigates the effects of inflows of foreign aid on the debt repayment behaviour of developing countries. The paper first delineates the overall incentives to committing to timely repayment in a war of attrition-type model. A set of panel estimates including 93 developing countries...... shows that foreign aid is strongly negatively associated with repayment incentives. The findings pertain to both total debt service and service on publically guaranteed debt. Only countries that tend to vote predominantly with the US in the UN General Assembly are not significantly discouraged from...... servicing their debt by inflows of foreign aid....

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. © 2014 American Society for Bone and Mineral Research.

34 CFR 609.42 - 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? 609.42 Section 609.42 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STRENGTHENING HISTORICALLY BLACK GRADUATE INSTITUTIONS PROGRAM What Conditions Must a Grantee...

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

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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.

Mesd Is a Universal Inhibitor of Wnt Co-receptor LRP5/6 and Blocks Wnt/β-catenin Signaling in Cancer Cells†

Science.gov (United States)

Lu, Wenyan; Liu, Chia-Chen; Thottassery, Jaideep V.; Bu, Guojun; Li, Yonghe

2010-01-01

Mesd is a specialized chaperone for the low-density lipoprotein receptor-related protein-5 (LRP5) and LRP6. In our previous studies, we found that Mesd binds to mature LRP6 on the cell surface and blocks the binding of Wnt antagonist Dickkopf-1(Dkk1) to LRP6. Herein, we demonstrated that Mesd also binds to LRP5 with a high affinity, and is a universal inhibitor of LRP5/6 ligands. Mesd not only blocks Wnt antagonists Dkk1 and Sclerostin binding to LRP5/6, but also inhibits Wnt3A and Rspondin1-induced Wnt/β-catenin signaling in LRP5/6 expressing cells. We also found that Mesd, Dkk1 and Sclerostin compete with one another for binding to LRP5 and LRP6 at the cell surface. More importantly, we demonstrated that Mesd is able to suppress LRP6 phosphorylation and Wnt/β-catenin signaling in prostate cancer PC-3 cells, and inhibits PC-3 cell proliferation. Our results indicate that recombinant Mesd protein is a useful tool for studying Wnt/β-catenin signaling on the cell surface, and has a potential therapeutic role in Wnt-dependent cancers. PMID:20446724

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 Section 608.41 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STRENGTHENING HISTORICALLY BLACK COLLEGES AND UNIVERSITIES PROGRAM What Conditions Must a Grante...

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...... Navier-Stokes flow solver EllipSys2D. The resulting airfoils, the LRP2-30 and LRP2-36, achieve both higher operational lift coefficients and higher lift to drag ratios compared to the equivalent FFA-W3 airfoils....

Design of the LRP airfoil series using 2D CFD

International Nuclear Information System (INIS)

Zahle, Frederik; Bak, Christian; Sørensen, Niels N; Vronsky, Tomas; Gaudern, Nicholas

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 Navier-Stokes flow solver EllipSys2D. The resulting airfoils, the LRP2-30 and LRP2-36, achieve both higher operational lift coefficients and higher lift to drag ratios compared to the equivalent FFA-W3 airfoils

Mutant LRP6 Impairs Endothelial Cell Functions Associated with Familial Normolipidemic Coronary Artery Disease

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Jian Guo

2016-07-01

Full Text Available Mutations in the genes low-density lipoprotein (LDL receptor-related protein-6 (LRP6 and myocyte enhancer factor 2A (MEF2A were reported in families with coronary artery disease (CAD. We intend to determine the mutational spectrum of these genes among hyperlipidemic and normolipidemic CAD families. Forty probands with early-onset CAD were recruited from 19 hyperlipidemic and 21 normolipidemic Chinese families. We sequenced all exons and intron-exon boundaries of LRP6 and MEF2A, and found a novel heterozygous variant in LRP6 from a proband with normolipidemic CAD. This variant led to a substitution of histidine to tyrosine (Y418H in an evolutionarily conserved domain YWTD in exon 6 and was not found in 1025 unrelated healthy individuals. Co-segregated with CAD in the affected family, LRP6Y418H significantly debilitated the Wnt3a-associated signaling pathway, suppressed endothelial cell proliferation and migration, and decreased anti-apoptotic ability. However, it exhibited no influences on low-density lipoprotein cholesterol uptake. Thus, mutation Y418H in LRP6 likely contributes to normolipidemic familial CAD via impairing endothelial cell functions and weakening the Wnt3a signaling pathway.

Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

Science.gov (United States)

Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J; Herz, Joachim; Muglia, Louis J; Bu, Guojun

2011-01-11

Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

Directory of Open Access Journals (Sweden)

Qiang Liu

2011-01-01

Full Text Available Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

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

2009-08-01

Full Text Available 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.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.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.

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.

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 recognition...

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

2009-11-01

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.

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

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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.

45 CFR 33.8 - Voluntary repayment agreement in lieu of salary offset.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Voluntary repayment agreement in lieu of salary... SALARY OFFSET § 33.8 Voluntary repayment agreement in lieu of salary offset. (a)(1) In response to the... notice of intent to offset. An employee who wishes to repay the debt without salary offset shall also...

[Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma].

Science.gov (United States)

Li, Le; Su, Li-ping; Ma, Li; Zhao, Jin; Zhu, Lei; Zhou, Yong-an

2009-03-01

To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma. mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed. (1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01). The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

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

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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.

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

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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.

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

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Philippe Boucher

2007-05-01

Full Text Available 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.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.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.

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 determined...

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...

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

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Mona Elsafadi

2017-04-01

Full Text Available Understanding the regulatory networks underlying lineage differentiation and fate determination of human bone marrow stromal cells (hBMSC is a prerequisite for their therapeutic use. The goal of the current study was to unravel the novel role of the low-density lipoprotein receptor-related protein 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 the osteogenic induction of the imCL1 clone. Data from functional and gene expression assays demonstrated the role of LRP3 as a molecular switch promoting hBMSC lineage differentiation into osteoblasts and inhibiting differentiation into adipocytes. Interestingly, microRNA (miRNA expression profiling identified miR-4739 as the most under-represented miRNA (−36.11 fold in imCL1 compared to imCL2. The TargetScan prediction algorithm, combined with functional and biochemical assays, identified LRP3 mRNA as a novel target of miR-4739, with a single potential binding site for miR-4739 located in the LRP3 3′ UTR. Regulation of LRP3 expression by miR-4739 was subsequently confirmed by qRT-PCR, western blotting, and luciferase assays. Over-expression of miR-4739 mimicked the effects of LRP3 knockdown on promoting adipogenic and suppressing osteogenic differentiation of hBMSCs. Hence, we report for the first time a novel biological role for the LRP3/hsa-miR-4739 axis in balancing osteogenic and adipocytic differentiation of hBMSCs. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.

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

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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.

Structural insight into gene transcriptional regulation and effector binding by the Lrp/AsnC family

NARCIS (Netherlands)

Thaw, P.; Sedelnikova, S.E.; Muranova, T.; Wiese, S.; Ayora, S.; Alonso, J.C.; Brinkman, A.B.; Akerboom, A.P.; Oost, van der J.; Rafferty, J.B.

2006-01-01

The Lrp/AsnC family of transcriptional regulatory proteins is found in both archaea and bacteria. Members of the family influence cellular metabolism in both a global (Lrp) and specific (AsnC) manner, often in response to exogenous amino acid effectors. In the present study we have determined both

LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

Science.gov (United States)

Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-11-14

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.

Science.gov (United States)

Rebelo, Thalia M; Vania, Leila; Ferreira, Eloise; Weiss, Stefan F T

2018-07-01

The 37 kDa/67 kDa laminin receptor (LRP/LR) is over-expressed in tumor cells and has been implicated in several tumourigenic processes such as metastasis and telomerase activation, however, more importantly the focus of the present study is on the maintenance of cellular viability and the evasion of apoptosis. The aim of the study was to investigate the role of LRP/LR on the cellular viability of early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and western blot analysis revealed that A375SM cells contain more cell-surface and total LRP/LR levels in comparison to the A375 cells, respectively. In order to determine the effect of LRP/LR on cell viability and apoptosis, LRP was down-regulated via siRNA technology. MTT assays revealed that LRP knock-down led to significant reductions in the viability of A375 and A375SM cells. Confocal microscopy indicated nuclear morphological changes suggestive of apoptotic induction in both cell lines and Annexin-V FITC/PI assays confirmed this observation. Additionally, caspase-3 activity assays revealed that apoptosis was induced in both cell lines after siRNA-mediated down-regulation of LRP. Caspase-8 and -9 activity assays suggested that post LRP knock-down; A375 cells undergo apoptosis solely via the extrinsic pathway, while A375SM cells undergo apoptosis via the intrinsic pathway. siRNAs mediated LRP knock-down might represent a powerful alternative therapeutic strategy for the treatment of malignant melanoma through the induction of apoptosis. Copyright © 2018. Published by Elsevier Inc.

Down-regulation of LRP1B in colon cancer promoted the growth and migration of cancer cells.

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Wang, Zhiqiang; Sun, Peng; Gao, Chun; Chen, Ji; Li, Jun; Chen, Zhonghao; Xu, Ming; Shao, Jun; Zhang, Yunpeng; Xie, Jiang

2017-08-01

Aberrant activation of beta-catenin/TCF signaling is one of the hallmarks of colon cancer. It is of great interest to study the mechanism for the regulation of beta-catenin/TCF signaling. In this study, it was found that LRP1B was down-regulated in colon cancer tissues and inhibited the growth, migration and metastasis of colon cancer cells. The molecular mechanism study revealed that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling. Taken together, our study demonstrated the suppressive roles of LRP1B in the progression of colon cancer, implicating that restoring the function of LRP1B would be a promising strategy for the treatment of colon cancer. Copyright © 2017. Published by Elsevier Inc.

Thailand's Student Loans Fund: Interest Rate Subsidies and Repayment Burdens

Science.gov (United States)

Chapman, Bruce; Lounkaew, Kiatanantha; Polsiri, Piruna; Sarachitti, Rangsit; Sitthipongpanich, Thitima

2010-01-01

Government student loan schemes typically have implicit interest rate subsidies which, while these are a cost to taxpayers, they have the benefit of diminishing repayment burdens for graduates. Our goal is to illustrate the extent of both interest rate subsidies and repayment burdens with respect to Thailand's Student Loans Fund (SLF), using…

Wise regulates bone deposition through genetic interactions with Lrp5.

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Ellies, Debra L; Economou, Androulla; Viviano, Beth; Rey, Jean-Philippe; Paine-Saunders, Stephenie; Krumlauf, Robb; Saunders, Scott

2014-01-01

In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development.

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

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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.

Crystallization and quaternary structure analysis of an Lrp-like regulatory protein from the hyperthermophile Pyrococcus furiosus

NARCIS (Netherlands)

Sedelnikova, S.E.; Smits, S.H.J.; Leonard, P.M.; Brinkman, A.B.; Oost, van der J.; Rafferty, J.B.

2001-01-01

The LrpA transcriptional regulator from Pyrococcus furiosus, a member of the leucine-responsive regulatory protein (Lrp) family, has been crystallized by the hanging-drop method of vapour diffusion using ammonium sulfate as the precipitant. The crystals belong to the tetragonal system and are in

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

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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.

Wnt isoform-specific interactions with coreceptor specify inhibition or potentiation of signaling by LRP6 antibodies.

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Yan Gong

Full Text Available β-Catenin-dependent Wnt signaling is initiated as Wnt binds to both the receptor FZD and coreceptor LRP5/6, which then assembles a multimeric complex at the cytoplasmic membrane face to recruit and inactivate the kinase GSK3. The large number and sequence diversity of Wnt isoforms suggest the possibility of domain-specific ligand-coreceptor interactions, and distinct binding sites on LRP6 for Wnt3a and Wnt9b have recently been identified in vitro. Whether mechanistically different interactions between Wnts and coreceptors might mediate signaling remains to be determined. It is also not clear whether coreceptor homodimerization induced extracellularly can activate Wnt signaling, as is the case for receptor tyrosine kinases. We generated monoclonal antibodies against LRP6 with the unexpected ability to inhibit signaling by some Wnt isoforms and potentiate signaling by other isoforms. In cell culture, two antibodies characterized further show reciprocal activities on most Wnts, with one antibody antagonizing and the other potentiating. We demonstrate that these antibodies bind to different regions of LRP6 protein, and inhibition of signaling results from blocking Wnt binding. Antibody-mediated dimerization of LRP6 can potentiate signaling only when a Wnt isoform is also able to bind the complex, presumably recruiting FZD. Endogenous autocrine Wnt signaling in different tumor cell lines can be either antagonized or enhanced by the LRP6 antibodies, indicating expression of different Wnt isoforms. As anticipated from the roles of Wnt signaling in cancer and bone development, antibody activities can also be observed in mice for inhibition of tumor growth and in organ culture for enhancement of bone mineral density. Collectively, our results indicate that separate binding sites for different subsets of Wnt isoforms determine the inhibition or potentiation of signaling conferred by LRP6 antibodies. This complexity of coreceptor-ligand interactions may

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

DEFF Research Database (Denmark)

Galan-Diez, 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...... mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation...... of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM...

Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1.

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Tachibana, Masaya; Shinohara, Mitsuru; Yamazaki, Yu; Liu, Chia-Chen; Rogers, Justin; Bu, Guojun; Kanekiyo, Takahisa

2016-03-01

Apolipoprotein E (apoE) plays a critical role in maintaining synaptic integrity by transporting cholesterol to neurons through the low-density lipoprotein receptor related protein-1 (LRP1). Bexarotene, a retinoid X receptor (RXR) agonist, has been reported to have potential beneficial effects on cognition by increasing brain apoE levels and lipidation. To investigate the effects of bexarotene on aging-related synapse loss and the contribution of neuronal LRP1 to the pathway, forebrain neuron-specific LRP1 knockout (nLrp1(-/-)) and littermate control mice were administered with bexarotene-formulated diet (100mg/kg/day) or control diet at the age of 20-24 months for 8 weeks. Upon bexarotene treatment, levels of brain apoE and ATP-binding cassette sub-family A member 1 (ABCA1) were significantly increased in both mice. While levels of PSD95, glutamate receptor 1 (GluR1), and N-methyl-d-aspartate receptor NR1 subunit (NR1), which are key postsynaptic proteins that regulate synaptic plasticity, were decreased with aging, they were restored by bexarotene treatment in the brains of control but not nLrp1(-/-) mice. These results indicate that the beneficial effects of bexarotene on synaptic integrity depend on the presence of neuronal LRP1. However, we also found that bexarotene treatment led to the activation of glial cells, weight loss and hepatomegaly, which are likely due to hepatic failure. Taken together, our results demonstrate that apoE-targeted treatment through the RXR pathway has a potential beneficial effect on synapses during aging; however, the therapeutic application of bexarotene requires extreme caution due to its toxic side effects. Copyright © 2015 Elsevier Inc. All rights reserved.

Deficiency in LRP6-Mediated Wnt Signaling Contributes to Synaptic Abnormalities and Amyloid Pathology in Alzheimer’s Disease

OpenAIRE

Liu, Chia-Chen; Tsai, Chih-Wei; Deak, Ferenc; Rogers, Justin; Penuliar, Michael; Sung, You Me; Maher, James N.; Fu, Yuan; Li, Xia; Xu, Huaxi; Estus, Steven; Hoe, Hyang-Sook; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

2014-01-01

Alzheimer’s disease (AD) is an age-related neurological disorder characterized by synaptic loss and dementia. The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential co-receptor for Wnt signaling and its genetic variants have been linked to AD risk. Here we report that neuronal LRP6-mediated Wnt signaling is critical for synaptic function and cognition. Conditional deletion of Lrp6 gene in mouse forebrain neurons leads to age-dependent deficits in synaptic integrity and ...

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

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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

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

Science.gov (United States)

Galán-Díez, Marta; Isa, Adiba; Ponzetti, Marco; Nielsen, Morten Frost; Kassem, Moustapha; Kousteni, Stavroula

2016-03-01

Osteoblasts are emerging regulators of myeloid malignancies since genetic alterations in them, such as constitutive activation of β-catenin, instigate their appearance. The LDL receptor-related protein 5 (LRP5), initially proposed to be a co-receptor for Wnt proteins, in fact favors bone formation by suppressing gut-serotonin synthesis. This function of Lrp5 occurring in the gut is independent of β-catenin activation in osteoblasts. However, it is unknown whether Lrp5 can act directly in osteoblast to influence other functions that require β-catenin signaling, particularly, the deregulation 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 mutation, we show here that Lrp5 GOF mutations in both humans and mice do not activate β-catenin signaling in osteoblasts. Consistent with a lack of β-catenin activation in their osteoblasts, Lrp5(A214V) mice have normal trilinear hematopoiesis. In contrast to leukemic mice with constitutive activation of β-catenin in osteoblasts (Ctnnb1(CAosb)), accumulation of early myeloid progenitors, a characteristic of AML, myeloid-blasts in blood, and segmented neutrophils or dysplastic megakaryocytes in the bone marrow, are not observed in Lrp5(A214V) mice. Likewise, peripheral blood count analysis in HBM 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 entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza. Published

Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population.

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Zheng Dong

Full Text Available Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately; however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009. In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A decreased the risk of gout (OR = 0.77, P = 0.015, whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020. The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.

Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population.

Science.gov (United States)

Dong, Zheng; Zhao, Dongbao; Yang, Chengde; Zhou, Jingru; Qian, Qiaoxia; Ma, Yanyun; He, Hongjun; Ji, Hengdong; Yang, Yajun; Wang, Xiaofeng; Xu, Xia; Pang, Yafei; Zou, Hejian; Jin, Li; Wang, Jiucun

2015-01-01

Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.

Haemorrhagic snake venom metalloproteases and human ADAMs cleave LRP5/6, which disrupts cell-cell adhesions in vitro and induces haemorrhage in vivo.

Science.gov (United States)

Seo, Tadahiko; Sakon, Taketo; Nakazawa, Shiori; Nishioka, Asuka; Watanabe, Kohei; Matsumoto, Kaori; Akasaka, Mari; Shioi, Narumi; Sawada, Hitoshi; Araki, Satohiko

2017-06-01

Snake venom metalloproteases (SVMPs) are members of the a disintegrin and metalloprotease (ADAM) family of proteins, as they possess similar domains. SVMPs are known to elicit snake venom-induced haemorrhage; however, the target proteins and cleavage sites are not known. In this work, we identified a target protein of vascular apoptosis-inducing protein 1 (VAP1), an SVMP, relevant to its ability to induce haemorrhage. VAP1 disrupted cell-cell adhesions by relocating VE-cadherin and γ-catenin from the cell-cell junction to the cytosol, without inducing proteolysis of VE-cadherin. The Wnt receptors low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are known to promote catenin relocation, and are rendered constitutively active in Wnt signalling by truncation. Thus, we examined whether VAP1 cleaves LRP5/6 to induce catenin relocation. Indeed, we found that VAP1 cleaved the extracellular region of LRP6 and LRP5. This cleavage removes four inhibitory β-propeller structures, resulting in activation of LRP5/6. Recombinant human ADAM8 and ADAM12 also cleaved LRP6 at the same site. An antibody against a peptide including the LRP6-cleavage site inhibited VAP1-induced VE-cadherin relocation and disruption of cell-cell adhesions in cultured cells, and blocked haemorrhage in mice in vivo. Intriguingly, animals resistant to the effects of haemorrhagic snake venom express variants of LRP5/6 that lack the VAP1-cleavage site, or low-density lipoprotein receptor domain class A domains involved in formation of the constitutively active form. The results validate LRP5/6 as physiological targets of ADAMs. Furthermore, they indicate that SVMP-induced cleavage of LRP5/6 causes disruption of cell-cell adhesion and haemorrhage, potentially opening new avenues for the treatment of snake bites. © 2017 Federation of European Biochemical Societies.

Influence of l-Leucine and l-Alanine on Lrp Regulation of foo, Coding for F1651, a Pap Homologue

OpenAIRE

Berthiaume, Frédéric; Crost, Cécile; Labrie, Vincent; Martin, Christine; Newman, Elaine B.; Harel, Josée

2004-01-01

The foo operon encodes F1651 fimbriae that belong to the P-regulatory family and are synthesized by septicemic Escherichia coli. Using an Lrp-deficient host and the lrp gene cloned under the arabinose pBAD promoter, we demonstrated that foo was transcribed proportionally to the amount of Lrp synthesized. l-Leucine and l-alanine decreased drastically the steady-state transcription of foo and modified phase variation, independently of the presence of FooI. Specific mutations in the C-terminal r...

Association between LRP1 C766T polymorphism and Alzheimer's disease susceptibility: a meta-analysis.

Science.gov (United States)

Wang, Yun; Liu, Shengyuan; Wang, Jingjing; Zhang, Jie; Hua, Yaqiong; Li, Hua; Tan, Huibiao; Kuai, Bin; Wang, Biao; Sheng, Sitong

2017-08-16

Low density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer's disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case-control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817-1.037, P = 0.172). In subgroup analysis, significant decreased AD susceptibility was found among Asian population in allele model (T versus C: OR = 0.786, 95% CI = 0.635-0.974, P = 0.028) and dominant model (TT + CT versus CC: OR = 0.800, 95% CI = 0.647-0.990, P = 0.040). Moreover, T allele of LRP1 C766T was statistically associated with late onset of AD (LOAD) (T versus C: OR = 0.858, 95% CI = 0.748-0.985, P = 0.029; TT + CT versus CC: OR = 0.871, 95% CI = 0.763-0.994, P = 0.040). In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.

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

... DEPARTMENT OF EDUCATION Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2013--William D. Ford Federal Direct Loan Program Catalog of Federal Domestic Assistance (CFDA) Number... free, at 1- 800-877-8339. SUPPLEMENTARY INFORMATION: Under the William D. Ford Federal Direct Loan...

Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women.

Science.gov (United States)

Giroux, S; Elfassihi, L; Cole, D E C; Rousseau, F

2008-12-01

Replication is a critical step to validate positive genetic associations. In this study, we tested two previously reported positive associations. The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated. This result is in line with results from large consortiums such as Genomos. However, the estrogen-related receptor alpha (ESRRA) repeat in the promoter is not replicated although the polymorphism studied was functional and could have been a causative variant. We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample. For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels. We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645). The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.

44 CFR 206.367 - Loan repayment.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Loan repayment. 206.367 Section 206.367 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... interest, P=the principal amount disbursed; R=the interest rate of the loan; and, T=the outstanding term in...

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

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

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...

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

... IMPROVEMENTS, SCHOLARSHIPS AND STUDENT LOANS Health Professions Student Loans § 57.214 Repayment of loans made... complete these studies, taking into account such factors as academic, medical, or financial difficulties...

Is self-repayment of the nuclear fuel cycle plants profitable for national economy?

International Nuclear Information System (INIS)

Shevelev, Ya.V.

1991-01-01

The nuclear fuel cycle (NFC) plants should not be repaying in the optimal plan of nuclear economy development. Their losses are overlapped by superprofits of energy consumers. The loss in the national economy resulting from compulsory conversion of the NFC plants to self-repayment is estimated. 12 refs

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

... DEPARTMENT OF EDUCATION Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2012; William D. Ford Federal Direct Loan Program AGENCY: Federal Student Aid, Department of Education... announces the annual updates to the ICR plan formula for 2012. Under the William D. Ford Federal Direct Loan...

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

... DEPARTMENT OF EDUCATION Annual Updates to the Income Contingent Repayment (ICR) Plan Formula for 2011; William D. Ford Federal Direct Loan Program AGENCY: Federal Student Aid, Department of Education... announces the annual updates to the ICR plan formula for 2011. Under the William D. Ford Federal Direct Loan...

Rapid analysis of adulterations in Chinese lotus root powder (LRP) by near-infrared (NIR) spectroscopy coupled with chemometric class modeling techniques.

Science.gov (United States)

Xu, Lu; Shi, Peng-Tao; Ye, Zi-Hong; Yan, Si-Min; Yu, Xiao-Ping

2013-12-01

This paper develops a rapid analysis method for adulteration identification of a popular traditional Chinese food, lotus root powder (LRP), by near-infrared spectroscopy and chemometrics. 85 pure LRP samples were collected from 7 main lotus producing areas of China to include most if not all of the significant variations likely to be encountered in unknown authentic materials. To evaluate the model specificity, 80 adulterated LRP samples prepared by blending pure LRP with different levels of four cheaper and commonly used starches were measured and predicted. For multivariate quality models, two class modeling methods, the traditional soft independent modeling of class analogy (SIMCA) and a recently proposed partial least squares class model (PLSCM) were used. Different data preprocessing techniques, including smoothing, taking derivative and standard normal variate (SNV) transformation were used to improve the classification performance. The results indicate that smoothing, taking second-order derivatives and SNV can improve the class models by enhancing signal-to-noise ratio, reducing baseline and background shifts. The most accurate and stable models were obtained with SNV spectra for both SIMCA (sensitivity 0.909 and specificity 0.938) and PLSCM (sensitivity 0.909 and specificity 0.925). Moreover, both SIMCA and PLSCM could detect LRP samples mixed with 5% (w/w) or more other cheaper starches, including cassava, sweet potato, potato and maize starches. Although it is difficult to perform an exhaustive collection of all pure LRP samples and possible adulterations, NIR spectrometry combined with class modeling techniques provides a reliable and effective method to detect most of the current LRP adulterations in Chinese market. Copyright © 2013 Elsevier Ltd. All rights reserved.

Agricultural credit repayment in Finoteselam town, northwestern ...

African Journals Online (AJOL)

... of loans to consumption ends. Family planning, creating enabling conditions for insurance markets, and enhancing labour markets are areas of policy concerns that could further improve loan repayment performances. Key words: Agricultural credit, determinants, microfinance, ACSI, northwestern Ethiopia, Finoteselam ...

75 FR 15453 - Central Valley Project Improvement Act, Westlands Water District Drainage Repayment Contract

Science.gov (United States)

2010-03-29

... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Central Valley Project Improvement Act, Westlands Water District Drainage Repayment Contract AGENCY: Bureau of Reclamation, Interior. ACTION: Notice of Proposed Repayment Contract. SUMMARY: The Bureau of Reclamation will be initiating negotiations with the...

Interaction between LRP5 and periostin gene polymorphisms on serum periostin levels and cortical bone microstructure.

Science.gov (United States)

Pepe, J; Bonnet, N; Herrmann, F R; Biver, E; Rizzoli, R; Chevalley, T; Ferrari, S L

2018-02-01

We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women. In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005). These results suggest that periostin expression is genetically modulated, particularly by polymorphisms

22 CFR 309.18 - Voluntary repayment agreements as an alternative to salary offset.

Science.gov (United States)

2010-04-01

... to salary offset. 309.18 Section 309.18 Foreign Relations PEACE CORPS DEBT COLLECTION Salary Offset § 309.18 Voluntary repayment agreements as an alternative to salary offset. (a) In response to a notice of intent, an employee may propose a written agreement to repay the debt as an alternative to salary...

28 CFR 32.36 - Payment and repayment.

Science.gov (United States)

2010-07-01

....36 Judicial Administration DEPARTMENT OF JUSTICE PUBLIC SAFETY OFFICERS' DEATH, DISABILITY, AND EDUCATIONAL ASSISTANCE BENEFIT CLAIMS Educational Assistance Benefit Claims § 32.36 Payment and repayment. (a... from the eligible educational institution as to the claimant's full-, three-quarter-, half-, or less...

miR-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of LRP5 and β-catenin.

Directory of Open Access Journals (Sweden)

Tianhao Sun

Full Text Available Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p targeted low-density lipoprotein receptor-related protein 5 (LRP5, a co-receptor of the Wnt signaling pathways, and β-catenin as determined by luciferase activity assay, and it decreased the expression levels of LRP5 and β-catenin. Thirdly, the decline of protein levels of β-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric assay. Additionally, all the parameters including the relative bone volume from μCT measurement suggested that LRP5 knockout in mice resulted in a looser and worse-connected trabeculae. The mRNA levels of important negative modulators relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Last but not least, the expression levels of LRP5 increased during the osteogenesis of MC3T3-E1, while the levels of β-catenin decreased in bone tissues from osteoporotic patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by targeting LRP5 and β-catenin. In addition, loss of functions of LRP5 damaged bone formation in vivo. Clinically, miR-375-3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in osteoporosis

The impact of LRP5 polymorphism (rs556442) on calcium homeostasis, bone mineral density, and body composition in Iranian children.

Science.gov (United States)

Ashouri, Elham; Meimandi, Elham Mahmoodi; Saki, Forough; Dabbaghmanesh, Mohammad Hossein; Omrani, Gholamhossein Ranjbar; Bakhshayeshkaram, Marzieh

2015-11-01

Failure to achieve optimal bone mass in childhood is the primary cause of decreased adult bone mineral density (BMD) and increased bone fragility in later life. Activating and inactivating LRP5 gene mutations has been associated with extreme bone-related phenotypes. Our aim was to investigate the role of LRP5 polymorphism on BMD, mineral biochemical parameters, and body composition in Iranian children. This cross-sectional study was performed on 9-18 years old children (125 boys, 137 girls). The serum level of calcium, phosphorous, alkaline phosphatase, and vitamin D parameters were checked. The body composition and BMD variables were measured by the Hologic system DXA. The rs566442 (V1119V) coding polymorphism in exon 15 of LRP5 was performed using PCR-RFLP method. Linear regression analysis, with adjustment for age, gender, body size parameters, and pubertal status was used to determine the association between LRP5 polymorphism (rs556442) and bone and body composition parameters. The allele frequency of the rs566442 gene was 35.5 % A and 63.9 % G. Our study revealed that LRP5 (rs556442) has not any significant influence on serum calcium, phosphorus, 25OHvitD, and serum alkaline phosphatase (P > 0.05). Total lean mass was greater in GG genotype (P = 0.028). Total body less head area (P = 0.044), spine BMD (P = 0.04), and total femoral BMC (P = 0.049) were lower in AG heterozygote genotype. This study show LRP5 polymorphism may associate with body composition and BMD in Iranian children. However, further investigations should be done to evaluate the role of other polymorphism.

38 CFR 1.990 - Written agreement to repay debt as alternative to salary offset.

Science.gov (United States)

2010-07-01

... repay debt as alternative to salary offset. 1.990 Section 1.990 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS GENERAL PROVISIONS Salary Offset Provisions § 1.990 Written agreement to repay debt as alternative to salary offset. (a) Notification by employee. The employee may propose, in...

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

Science.gov (United States)

2010-04-01

... 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...

Student Loan Default and Repayment in Kentucky

Science.gov (United States)

Kentucky Council on Postsecondary Education, 2016

2016-01-01

As college costs continue to rise, student loan default and repayment are issues of increasing concern to students and families, colleges and universities, and state and federal governments. Helping students borrow responsibly and manage their debt are vitally important to maintaining college access and affordability and increasing the education…

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...... to impaired glucose and lipid metabolism, we hypothesized that individuals with an HBM-causing mutation in LRP5 would exhibit improved glucose and lipid homeostasis. Since studies in animal models have suggested that Wnt signaling augments insulin secretion, we also examined the effect of Wnt signaling...... on glucose-stimulated insulin secretion on human pancreatic islets. METHODS: This was a matched case-control study. We used several methods to assess glucose and lipid metabolism in 11 individuals with HBM-causing mutations in LRP5. Affected study participants were recruited from previously identified...

Evaluation Of Loan Disbursement And Repayment Of Supervised ...

African Journals Online (AJOL)

Evaluation Of Loan Disbursement And Repayment Of Supervised Credit ... bank as regard to loan supervision was scored low as a result of low rate of loan recovery, ... strategy to recover outstanding debts and reduce interest charge on loans.

Who borrows and who may not repay?

Czech Academy of Sciences Publication Activity Database

Bičáková, Alena; Prelcová, Zuzana; Pašaličová, R.

2011-01-01

Roč. 9, č. 2 (2011), s. 10-13 ISSN 1803-7089 Institutional research plan: CEZ:MSM0021620846 Keywords : household credit * debt burden * repayment Subject RIV: AH - Economics http://www.cnb.cz/miranda2/export/sites/www.cnb.cz/en/research/research_publications/erb/download/ERB_No2_2011.pdf

7 CFR 1421.10 - Loan repayment rates.

Science.gov (United States)

2010-01-01

... grain rice, medium grain rice, and confectionery and each other kind of sunflower seed (other than oil... determined by the Secretary) that is calculated based on average market prices for the loan commodity during... and announce repayment rates under paragraphs (a)(2) and (a)(3) of this section based upon market...

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

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.

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 K D , 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. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Genetic interaction between Lrp6 and Wnt5a during mouse development

Czech Academy of Sciences Publication Activity Database

Andersson, E.; Bryjová, Lenka; Biris, K.; Yamaguchi, T.P.; Arenas, E.; Bryja, Vítězslav

2010-01-01

Roč. 239, č. 1 (2010), s. 237-245 ISSN 1058-8388 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Wnt 5a * Lrp6 * somitogenesis Subject RIV: BO - Biophysics Impact factor: 2.864, year: 2010

10 CFR 603.575 - Repayment of Federal cost share.

Science.gov (United States)

2010-01-01

... Business Evaluation Accounting, Payments, and Recovery of Funds § 603.575 Repayment of Federal cost share. In accordance with the Energy Policy Act of 2005 (Public Law 109-58), section 988(e), the contracting...

The Roles of the Wnt-Antagonists Axin and Lrp4 during Embryogenesis of the Red Flour Beetle Tribolium castaneum.

Science.gov (United States)

Prühs, Romy; Beermann, Anke; Schröder, Reinhard

2017-10-15

In both vertebrates and invertebrates, the Wnt-signaling pathway is essential for numerous processes in embryogenesis and during adult life. Wnt activity is fine-tuned at various levels by the interplay of a number of Wnt-agonists (Wnt ligands, Frizzled-receptors, Lrp5/6 coreceptors) and Wnt-antagonists (among them Axin, Secreted frizzled and Lrp4) to define anterior-posterior polarity of the early embryo and specify cell fate in organogenesis. So far, the functional analysis of Wnt-pathway components in insects has concentrated on the roles of Wnt-agonists and on the Wnt-antagonist Axin. We depict here additional features of the Wnt-antagonist Axin in the flour beetle Tribolium castaneum . We show that Tc-axin is dynamically expressed throughout embryogenesis and confirm its essential role in head development. In addition, we describe an as yet undetected, more extreme Tc-axin RNAi-phenotype, the ectopic formation of posterior abdominal segments in reverse polarity and a second hindgut at the anterior. For the first time, we describe here that an lrp4 ortholog is involved in axis formation in an insect. The Tribolium Lrp4 ortholog is ubiquitously expressed throughout embryogenesis. Its downregulation via maternal RNAi results in the reduction of head structures but not in axis polarity reversal. Furthermore, segmentation is impaired and larvae develop with a severe gap-phenotype. We conclude that, as in vertebrates, Tc-lrp4 functions as a Wnt-inhibitor in Tribolium during various stages of embryogenesis. We discuss the role of both components as negative modulators of Wnt signaling in respect to axis formation and segmentation in Tribolium .

Characterization of an Lrp/AsnC family regulator SCO3361, controlling actinorhodin production and morphological development in Streptomyces coelicolor.

Science.gov (United States)

Liu, Jing; Li, Jie; Dong, Hong; Chen, Yunfu; Wang, Yansheng; Wu, Hang; Li, Changrun; Weaver, David T; Zhang, Lixin; Zhang, Buchang

2017-07-01

Lrp/AsnC family regulators have been found in many bacteria as crucial regulators controlling diverse cellular processes. By genomic alignment, we found that SCO3361, an Lrp/AsnC family protein from Streptomyces coelicolor, shared the highest similarity to the SACE_Lrp from Saccharopolyspora erythraea. Deletion of SCO3361 led to dramatic reduction in actinorhodin (Act) production and delay in aerial mycelium formation and sporulation on solid media. Dissection of the mechanism underlying the function of SCO3361 in Act production revealed that it altered the transcription of the cluster-situated regulator gene actII-ORF4 by directly binding to its promoter. SCO3361 was an auto-regulator and simultaneously activated the transcription of its adjacent divergently transcribed gene SCO3362. SCO3361 affected aerial hyphae formation and sporulation of S. coelicolor by activating the expression of amfC, whiB, and ssgB. Phenylalanine and cysteine were identified as the effector molecules of SCO3361, with phenylalanine reducing the binding affinity, whereas cysteine increasing it. Moreover, interactional regulation between SCO3361 and SACE_Lrp was discovered for binding to each other's target gene promoter in this work. Our findings indicate that SCO3361 functions as a pleiotropic regulator controlling secondary metabolism and morphological development in S. coelicolor.

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

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

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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

Improving Navy Recruiting with the New Planned Resource Optimization Model With Experimental Design (PROM-WED)

Science.gov (United States)

2017-03-01

GUI graphical user interface HumRRO Human Resources Research Organization JPM Job Performance Measurement/Enlistment Standards LRP loan repayment... management system… for all appropriated funding” (Tomasini, n.d.). The DOD’s strategy, force structure, and allocation of resources are all delineated...Alexandria, Va. Human Resources Research Organization. Microsoft Excel, Version 15.0.4849.1003 [Computer software] (2013). Redmond, WA: Microsoft

LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women.

Science.gov (United States)

Giroux, Sylvie; Elfassihi, Latifa; Cardinal, Guy; Laflamme, Nathalie; Rousseau, François

2007-05-01

Bone mineral density has a strong genetic component but it is also influenced by environmental factors making it a complex trait to study. LRP5 gene was previously shown to be involved in rare diseases affecting bone mass. Mutations associated with gain-of-function were described as well as loss-of-function mutations. Following this discovery, many frequent LRP5 polymorphisms were tested against the variation of BMD in the normal population. Heel bone parameters (SOS, BUA) were measured by right calcaneal QUS in 5021 healthy French-Canadian women and for 2104 women, BMD evaluated by DXA at two sites was available (femoral neck (FN) and lumbar spine (LS)). Among women with QUS measures and those with DXA measures, 26.5% and 32.8% respectively were premenopausal, 9.2% and 10.7% were perimenopausal and 64.2% and 56.5% were postmenopausal. About a third of the peri- and postmenopausal women never received hormone therapy. Two single nucleotide coding polymorphisms (Val667Met and Ala1330Val) in LRP5 gene were genotyped by allele-specific PCR. All bone measures were tested individually for associations with each polymorphism by analysis of covariance with adjustment for non genetic risk factors. Furthermore, haplotype analysis was performed to take into account the strong linkage disequilibrium between the two polymorphisms. The two LRP5 polymorphisms were found to be associated with all five bone measures (L2L4 and femoral neck DXA as well as heel SOS, BUA and stiffness index) in the whole sample. Premenopausal women drove the association as expected from the proposed role of LRP5 in peak bone mass. Our results suggest that the Val667Met polymorphism is the causative variant but this remains to be functionally proven.

34 CFR 31.10 - Request for repayment agreement.

Science.gov (United States)

2010-07-01

.... (b) In the agreement, the Secretary and the employee may agree to satisfaction of the debt from... Education Office of the Secretary, Department of Education SALARY OFFSET FOR FEDERAL EMPLOYEES WHO ARE... repayment agreement. (a) The Secretary does not initiate an offset under this part if the employee agrees in...

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

Science.gov (United States)

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Certificate for repayment of decrease of collateral... TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.526 Certificate for repayment of decrease of collateral deposit fund, Form MA-306. The...

The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo

Czech Academy of Sciences Publication Activity Database

Bryja, Vítězslav; Andersson, E.R.; Schambony, A.; Esner, M.; Bryjová, Lenka; Biris, K.K.; Hall, A.C.; Kraft, B.; Čajánek, L.; Yamaguchi, T.P.; Buckingham, M.; Arenas, E.

2009-01-01

Roč. 20, č. 3 (2009), s. 924-936 ISSN 1059-1524 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : non-canonical Wnt signaling * Lrp5/6 * mouse Subject RIV: BO - Biophysics Impact factor: 5.979, year: 2009

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...... in vitro and in vivo. We provide evidence that LRP1 plays an important role in the uptake of postprandial lipoproteins and vitamin K1 by human osteoblasts....

Novel Mutation of LRP6 Identified in Chinese Han Population Links Canonical WNT Signaling to Neural Tube Defects.

Science.gov (United States)

Shi, Zhiwen; Yang, Xueyan; Li, Bin-Bin; Chen, Shuxia; Yang, Luming; Cheng, Liangping; Zhang, Ting; Wang, Hongyan; Zheng, Yufang

2018-01-15

Neural tube defects (NTDs), the second most frequent cause of human congenital abnormalities, are debilitating birth defects due to failure of neural tube closure. It has been shown that noncanonical WNT/planar cell polarity (PCP) signaling is required for convergent extension (CE), the initiation step of neural tube closure (NTC). But the effect of canonical WNT//β-catenin signaling during NTC is still elusive. LRP6 (low density lipoprotein receptor related proteins 6) was identified as a co-receptor for WNT/β-catenin signaling, but recent studies showed that it also can mediate WNT/PCP signaling. In this study, we screened mutations in the LRP6 gene in 343 NTDs and 215 ethnically matched normal controls of Chinese Han population. Three rare missense mutations (c.1514A>G, p.Y505C); c.2984A>G, p.D995G; and c.4280C>A, p.P1427Q) of the LRP6 gene were identified in Chinese NTD patients. The Y505C mutation is a loss-of-function mutation on both WNT/β-catenin and PCP signaling. The D995G mutation only partially lost inhibition on PCP signaling without affecting WNT/β-catenin signaling. The P1427Q mutation dramatically increased WNT/β-catenin signaling but only mildly loss of inhibition on PCP signaling. All three mutations failed to rescue CE defects caused by lrp6 morpholino oligos knockdown in zebrafish. Of interest, when overexpressed, D995G did not induce any defects, but Y505C and P1427Q caused more severe CE defects in zebrafish. Our results suggested that over-active canonical WNT signaling induced by gain-of-function mutation in LRP6 could also contribute to human NTDs, and a balanced WNT/β-catenin and PCP signaling is probably required for proper neural tube development. Birth Defects Research 110:63-71, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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 construction...

34 CFR 686.43 - Obligation to repay the grant.

Science.gov (United States)

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Obligation to repay the grant. 686.43 Section 686.43 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION TEACHER EDUCATION ASSISTANCE FOR COLLEGE AND HIGHER EDUCATION (TEACH...

Determinants of rural bank loan repayment capacity among farmers ...

African Journals Online (AJOL)

This study examined the determinants of the Nigeria Agricultural Cooperative and Rural Development Bank (NACRDB) repayment by farmers in Yewa division of Ogun State. Primary data collected through scheduled interview with the help of a structured questionnaire as well as secondary data were used for this purpose.

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

African Journals Online (AJOL)

The study identified factors affecting loan utilization and repayment patterns by small holder farmers of the Nigerian Agricultural Co-operative and Rural Development Bank (NACRDB) Osogbo branch in Osun State. Two Local Government Areas with large number of loan beneficiaries from 2003 to 2008 in NACRDB were ...

Key factors for loan repayment of micro entrepreneurs in Ghana

NARCIS (Netherlands)

Agbeko, Daniel

2017-01-01

This thesis examines the extent to what corporate social responsibility (CSR) strategies, entrepreneurial and business skills and programmes for training and monitoring improve microbusiness performance and loan repayment rates:

‘To what extent do corporate social responsibility

11 CFR 9007.5 - Petitions for rehearing; stays of repayment determinations.

Science.gov (United States)

2010-01-01

... CAMPAIGN FUND: GENERAL ELECTION FINANCING EXAMINATIONS AND AUDITS; REPAYMENTS § 9007.5 Petitions for... Commission's decision on a petition for rehearing under paragraph (a) of this section or, if no petition for...

Analysis of borrowing and repayment of credit among livestock ...

African Journals Online (AJOL)

This study examined borrowing and repayment of credit among livestock farmers in Cross River State, Nigeria. Data for the study was obtained from the Bank of Agriculture (BOA), Calabar. Descriptive statistics such as percentage count, mean and tables were employed in the analysis. It was discovered that BOA in ...

Expression of multidrug resistance-related protein (MRP-1), lung resistance-related protein (LRP) and topoisomerase-II (TOPO-II) in Wilms' tumor: immunohistochemical study using TMA methodology.

Science.gov (United States)

Fridman, Eduard; Skarda, Jozef; Pinthus, Jonatan H; Ramon, Jonathan; Mor, Yoran

2008-06-01

MRP-1, LRP and TOPO-II are all associated with protection of the cells from the adverse effects of various chemotherapeutics. The aim of this study was to measure the expression of these proteins in Wilms' tumor (WT). TMA block was constructed from 14 samples of WT's and from xenografts derived from them. Sections of the TMA were used for immunostaining against MRP-1, LRP and TOPO-IIa. All normal kidneys expressed MRP-1 but were either weakly or negatively stained for LRP and TOPO-IIa. In WT samples, MRP-1 was universally expressed, exclusively in the tubular component, while there was no expression of LRP and TOPO-IIa showed heterogeneous distribution. The xenografts varied in their MRP-1 and TOPO-IIa expression and exhibited weak/negative staining of LRP. This study shows that although all the proteins evaluated, had different expression patterns in the tumor samples, the most prominent changes in expression were found for MRP-1. The exact clinical implications of these changes in expression and their relevance to the resistance of these tumors to chemotherapy requires further investigation. The finding of different expression profiles for the multidrug resistance proteins in the original WT's and their xenografts suggests that the results of animal cancer models may be difficult to interpret.

Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6.

Science.gov (United States)

Guidato, Sonia; Itasaki, Nobue

2007-10-15

The Wnt signaling pathway is tightly regulated by extracellular and intracellular modulators. Wise was isolated as a secreted protein capable of interacting with the Wnt co-receptor LRP6. Studies in Xenopus embryos revealed that Wise either enhances or inhibits the Wnt pathway depending on the cellular context. Here we show that the cellular localization of Wise has distinct effects on the Wnt pathway readout. While secreted Wise either synergizes or inhibits the Wnt signals depending on the partner ligand, ER-retained Wise consistently blocks the Wnt pathway. ER-retained Wise reduces LRP6 on the cell surface, making cells less susceptible to the Wnt signal. This study provides a cellular mechanism for the action of Wise and introduces the modulation of cellular susceptibility to Wnt signals as a novel mechanism of the regulation of the Wnt pathway.

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.

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

... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Repayment of certain loans by mutual savings 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...

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.

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...

Determinants Of Loan Repayment Ability Of Farmers In Kogi State ...

African Journals Online (AJOL)

This study evaluates socio-economic factors that could predict repayment ability, quantify the effects of those factors and device a method to curb or manage default in agriculture and/or other credit lending. Data for the analysis were obtained by interviewing a sample of loan beneficiary farmers cooperative society members ...

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

Osteoporosis is a common disease characterized by an increased susceptibility to fracture. It is a complex disorder resulting from the interaction of several polymorphisms in different genes and environmental factors. Since we recently reported a role for low density lipoprotein-related protein...... (LRP)-4 in monogenic disorders with bone overgrowth, we now wanted to evaluate whether genetic variation in the LRP4 gene has an effect on the susceptibility to osteoporosis in a population based cohort from the Odense Androgen Study. We chose to genotype four common (minor allele frequency (MAF)≥0.......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...

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...

Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6

Czech Academy of Sciences Publication Activity Database

Červenka, I.; Wolf, J.; Mašek, J.; Krejčí, Pavel; Wilcox, W. R.; Kozubík, Alois; Schulte, G.; Gutkind, J.S.; Bryja, Vítězslav

2011-01-01

Roč. 31, č. 1 (2011), s. 179-189 ISSN 0270-7306 R&D Projects: GA ČR(CZ) GC204/09/J030 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : WNT RECEPTOR ACTIVATION * BETA-CATENIN * CORECEPTOR LRP6 Subject RIV: BO - Biophysics Impact factor: 5.527, year: 2011

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.

7 CFR 771.9 - Interest rates, terms, security requirements, and repayment.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Interest rates, terms, security requirements, and... Interest rates, terms, security requirements, and repayment. (a) Interest rate. The interest rate will be fixed for the term of the loan. The rate will be established by FSA, based upon the cost of Government...

Financial Management: Emergency Steel Loan Guarantee Program

National Research Council Canada - National Science Library

2001-01-01

In a February 1, 2001 letter, you expressed concerns about repayments of federally guaranteed loans by borrowers under the Emergency Steel Loan Guarantee Program and the effect of the program on the U.S. steel industry...

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

Science.gov (United States)

2010-10-01

... exercise of due diligence, a school must follow procedures which are at least as extensive and effective as... 42 Public Health 1 2010-10-01 2010-10-01 false Repayment and collection of nursing student loans. 57.310 Section 57.310 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

Regulation of Expression of Uropathogenic Escherichia coli Nonfimbrial Adhesin TosA by PapB Homolog TosR in Conjunction with H-NS and Lrp

Science.gov (United States)

Engstrom, Michael D.

2016-01-01

Urinary tract infections (UTIs) are a major burden to human health. The overwhelming majority of UTIs are caused by uropathogenic Escherichia coli (UPEC) strains. Unlike some pathogens, UPEC strains do not have a fixed core set of virulence and fitness factors but do have a variety of adhesins and regulatory pathways. One such UPEC adhesin is the nonfimbrial adhesin TosA, which mediates adherence to the epithelium of the upper urinary tract. The tos operon is AT rich, resides on pathogenicity island aspV, and is not expressed under laboratory conditions. Because of this, we hypothesized that tosA expression is silenced by H-NS. Lrp, based on its prominent function in the regulation of other adhesins, is also hypothesized to contribute to tos operon regulation. Using a variety of in vitro techniques, we mapped both the tos operon promoter and TosR binding sites. We have now identified TosR as a dual regulator of the tos operon, which could control the tos operon in association with H-NS and Lrp. H-NS is a negative regulator of the tos operon, and Lrp positively regulates the tos operon. Exogenous leucine also inhibits Lrp-mediated tos operon positive regulation. In addition, TosR binds to the pap operon, which encodes another important UPEC adhesin, P fimbria. Induction of TosR synthesis reduces production of P fimbria. These studies advance our knowledge of regulation of adhesin expression associated with uropathogen colonization of a host. PMID:26755158

5 CFR 179.209 - Voluntary repayment agreement as alternative to salary offset.

Science.gov (United States)

2010-01-01

... alternative to salary offset. 179.209 Section 179.209 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CLAIMS COLLECTION STANDARDS Salary Offset § 179.209 Voluntary repayment agreement as alternative to salary offset. (a)(1) In response to a notice of intent, an employee may propose...

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, and...

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 nearest...

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

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.

Characterization of the Interaction of Sclerostin with the Low Density Lipoprotein Receptor-related Protein (LRP) Family of Wnt Co-receptors

Czech Academy of Sciences Publication Activity Database

Holdsworth, G.; Slocombe, P.; Doyle, C.; Sweeney, B.; Veverka, Václav; Le Riche, K.; Franklin, R. J.; Compson, J.; Brookings, D.; Turner, J.; Kennedy, J.; Garlish, R.; Shi, J.; Newnham, L.; McMillan, D.; Muzylak, M.; Carr, M. D.; Henry, A. J.; Ceska, T.; Robinson, M. K.

2012-01-01

Roč. 287, č. 32 (2012), s. 26464-26477 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z40550506 Keywords : Wnt pathway * LRP * sclerostin Subject RIV: CE - Biochemistry Impact factor: 4.651, year: 2012

The effects of musical training on movement pre-programming and re-programming abilities: an event-related potential investigation.

Science.gov (United States)

Anatürk, Melis; Jentzsch, Ines

2015-03-01

Two response precuing experiments were conducted to investigate effects of musical skill level on the ability to pre- and re-programme simple movements. Participants successfully used advance information to prepare forthcoming responses and showed response slowing when precue information was invalid rather than valid. This slowing was, however, only observed for partially invalid but not fully invalid precues. Musicians were generally faster than non-musicians, but no group differences in the efficiency of movement pre-programming or re-programming were observed. Interestingly, only musicians exhibited a significant foreperiod lateralized readiness potential (LRP) when response hand was pre-specified or full advance information was provided. These LRP findings suggest increased effector-specific motor preparation in musicians than non-musicians. However, here the levels of effector-specific preparation did not predict preparatory advantages observed in behaviour. In sum, combining the response precuing and ERP paradigms serves a valuable tool to examine influences of musical training on movement pre- or re-programming processes. Copyright © 2015 Elsevier B.V. All rights reserved.

The impact of training and monitoring on loan repayment of microfinance debtors in Ghana

NARCIS (Netherlands)

Agbeko, Daniel; Blok, Vincent; Omta, S.W.F.; Velde, van der G.

2017-01-01

Microbusiness entrepreneurs training and monitoring programmes are widely recognized as key to loan repayment performance of microfinance institution (MFI) loan clients in developing countries. Empirical evidence is, however, largely lacking and where present, not consistent. The present paper

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.

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

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 LIQUIDITY...

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.

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

Science.gov (United States)

2011-07-27

... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract Actions AGENCY: Bureau of Reclamation, Interior. ACTION: Notice. SUMMARY... SUPPLEMENTARY INFORMATION section. FOR FURTHER INFORMATION CONTACT: Michelle Kelly, Water and Environmental...

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

75 FR 42774 - Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

Science.gov (United States)

2010-07-22

... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract Actions AGENCY: Bureau of Reclamation, Interior. ACTION: Notice. SUMMARY... region in the SUPPLEMENTARY INFORMATION section. FOR FURTHER INFORMATION CONTACT: Michelle Kelly, Water...

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

Science.gov (United States)

2011-11-29

... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract Actions AGENCY: Bureau of Reclamation, Interior. ACTION: Notice. SUMMARY... INFORMATION CONTACT: Michelle Kelly, Water and Environmental Resources Division, Bureau of Reclamation, P.O...

75 FR 82066 - Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

Science.gov (United States)

2010-12-29

... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract Actions AGENCY: Bureau of Reclamation, Interior. ACTION: Notice. SUMMARY... CONTACT: Michelle Kelly, Water and Environmental Services Division, Bureau of Reclamation, P.O. Box 25007...

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

Science.gov (United States)

2011-09-29

... DEPARTMENT OF THE INTERIOR Bureau of Reclamation Status Report of Water Service, Repayment, and Other Water- Related Contract Actions AGENCY: Bureau of Reclamation, Interior. ACTION: Notice. SUMMARY... CONTACT: Michelle Kelly, Water and Environmental Resources Division, Bureau of Reclamation, P.O. Box 25007...

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.

p38 MAP kinase is required for Wnt3a-mediated osterix expression independently of Wnt-LRP5/6-GSK3β signaling axis in dental follicle cells

International Nuclear Information System (INIS)

Sakisaka, Yukihiko; Kanaya, Sousuke; Nakamura, Takashi; Tamura, Masato; Shimauchi, Hidetoshi; Nemoto, Eiji

2016-01-01

Wnt3a is a secreted glycoprotein that activates the glycogen synthase kinase-3β (GSK3β)/β-catenin signaling pathway through low-density-lipoprotein receptor-related protein (LRP)5/6 co-receptors. Wnt3a has been implicated in periodontal development and homeostasis, as well as in cementum formation. Recently, we have reported that Wnt3a increases alkaline phosphatase expression through the induction of osterix (Osx) expression in dental follicle cells, a precursor of cementoblasts. However, the molecular mechanism by which Wnt3a induces Osx expression is still unknown. In this study, we show that Wnt3a-induced Osx expression was inhibited in the presence of p38 mitogen-activated protein kinase (MAPK) inhibitors (SB203580 and SB202190) at gene and protein levels, as assessed by real-time PCR and immunocytohistochemistry, respectively. Pretreatment of cells with Dickkopf-1, a potent canonical Wnt antagonist binding to LRP5/6 co-receptors, did not influence Wnt3a-mediated p38 MAPK phosphorylation, suggesting that Wnt3a activates p38 MAPK through LRP5/6-independent signaling. On the other hand, pretreatment with p38 MAPK inhibitors had no effects on the phosphorylated status of GSK3β and β-catenin as well as β-catenin nuclear translocation, but inhibited Wnt3a-mediated β-catenin transcriptional activity. These findings suggest that p38 MAPK modulates canonical Wnt signaling at the β-catenin transcriptional level without any crosstalk with the Wnt3a-mediated LRP5/6-GSK3β signaling axis and subsequent β-catenin nuclear translocation. These findings expand our knowledge of the mechanisms controlling periodontal development and regeneration. - Highlights: • Wnt3a induces Osx expression via p38 MAPK signaling in dental follicle cells. • p38 MAPK has no crosstalk with Wnt3a-mediated LRP5/6 and GSK3β signaling. • p38 MAPK is required for Wnt signaling at the β-catenin transcriptional level.

7 CFR 3.80 - Written agreement to repay debts as alternative to salary offset.

Science.gov (United States)

2010-01-01

... salary offset. 3.80 Section 3.80 Agriculture Office of the Secretary of Agriculture DEBT MANAGEMENT Federal Salary Offset § 3.80 Written agreement to repay debts as alternative to salary offset. (a) Notification by employee. The employee may propose, in response to a Notice of Intent to Offset Salary, a...

24 CFR 17.133 - Written agreement to repay debt as alternative to salary offset.

Science.gov (United States)

2010-04-01

... alternative to salary offset. 17.133 Section 17.133 Housing and Urban Development Office of the Secretary... the Government Salary Offset Provisions § 17.133 Written agreement to repay debt as alternative to salary offset. (a) Notification by employee. The employee may propose, in response to a Notice of Intent...

20 CFR 361.10 - Written agreement to repay debt as alternative to salary offset.

Science.gov (United States)

2010-04-01

... alternative to salary offset. 361.10 Section 361.10 Employees' Benefits RAILROAD RETIREMENT BOARD INTERNAL... EMPLOYEES § 361.10 Written agreement to repay debt as alternative to salary offset. (a) Notification by... debt as an alternative to salary offset. Any employee who wishes to do this must submit a proposed...

77 FR 72960 - William D. Ford Federal Direct Loan Program

Science.gov (United States)

2012-12-07

... Federal Direct Loan Program AGENCY: Office of Postsecondary Education, Department of Education. ACTION... document to establish the date for the early implementation of William D. Ford Federal Direct Loan (Direct Loan) program regulations that establish a new income-contingent repayment plan based on the President...

76 FR 12127 - Emergency Homeowners' Loan Program: Announcement of Activation of Program and Availability of...

Science.gov (United States)

2011-03-04

... are not limited to: Developing and disseminating program marketing materials; Providing an overview of... sale, deed-in-lieu of foreclosure, or traditional sale of home. B. Intermediary to Perform Funds... modification, short sale, deed-in-lieu of foreclosure, or traditional sale of home. 2. Repayment of Emergency...

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

Directory of Open Access Journals (Sweden)

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

78 FR 72109 - Quarterly Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

Science.gov (United States)

2013-12-02

... continues negotiations on an operations, maintenance and replacement transfer contract with the Navajo... Status Report of Water Service, Repayment, and Other Water-Related Contract Actions AGENCY: Bureau of... individual contract actions may be published in the Federal Register and in newspapers of general circulation...

78 FR 46365 - Quarterly Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

Science.gov (United States)

2013-07-31

..., Colorado, New Mexico, Texas, Utah, and Wyoming: Contracts for extraordinary maintenance and replacement... Status Report of Water Service, Repayment, and Other Water-Related Contract Actions AGENCY: Bureau of... individual contract actions may be published in the Federal Register and in newspapers of general circulation...

78 FR 72111 - Quarterly Status Report of Water Service, Repayment, and Other Water-Related Contract Actions

Science.gov (United States)

2013-12-02

...: Reclamation continues negotiations on an operations, maintenance and replacement transfer contract with the... Status Report of Water Service, Repayment, and Other Water-Related Contract Actions AGENCY: Bureau of... individual contract actions may be published in the Federal Register and in newspapers of general circulation...

Prognostic implications of the nuclear localization of Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: their correlation with activated Akt, LRP/MVP and P-glycoprotein expression.

Science.gov (United States)

Oda, Yoshinao; Ohishi, Yoshihiro; Basaki, Yuji; Kobayashi, Hiroaki; Hirakawa, Toshio; Wake, Norio; Ono, Mayumi; Nishio, Kazuto; Kuwano, Michihiko; Tsuneyoshi, Masazumi

2007-07-01

The nuclear localization of Y-box-binding protein-1 (YB-1) is known to be a poor prognostic factor in several human malignancies, including ovarian carcinoma. Following on from our basic study dealing with microarray analyses of YB-1-associated gene expression in ovarian cancer cells, we examined whether nuclear localization of YB-1 is associated with the expression of CXCR4, a vault protein named lung resistance-related vault protein (LRP/MVP), phosphorylated Akt (p-Akt) or P-glycoprotein (P-gp) in human ovarian carcinoma. Fifty-three surgically resected ovarian carcinomas treated with paclitaxel and carboplatin were examined immunohistochemically for nuclear YB-1 expression and intrinsic expression of p-Akt, P-gp, LRP/MVP and CXCR4. Nuclear expression of YB-1 demonstrated significant correlation with p-Akt, P-gp and LRP expression, but no relationship with CXCR4 expression. By multivariate analysis, only YB-1 nuclear expression and CXCR4 expression were independent prognostic factors with regard to overall survival. These results indicate that YB-1 nuclear expression and CXCR4 expression are important prognostic factors in ovarian carcinoma.

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.

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

International Nuclear Information System (INIS)

Nakano, Noboru; Kumarevel, Thirumananseri; Matsunaga, Emiko; Shinkai, Akeo; Kuramitsu, Seiki; Yokoyama, Shigeyuki

2007-01-01

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

Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy

International Nuclear Information System (INIS)

Schneider, José; Gonzalez-Roces, Severino; Pollán, Marina; Lucas, Raul; Tejerina, Armando; Martin, Miguel; Alba, Alfonso

2001-01-01

Axillary node status after induction chemotherapy for locally advanced breast cancer has been shown on multivariate analysis to be an independent predictor of relapse. However, it has been postulated that responders to induction chemotherapy with a clinically negative axilla could be spared the burden of lymphadenectomy, because most of them will not show histological nodal invasion. P-glycoprotein expression in the rescue mastectomy specimen has finally been identified as a significant predictor of patient survival. We studied the expression of the genes encoding multidrug resistance associated protein (MDR1) and lung cancer associated resistance protein (LRP) in formalin-fixed, paraffin-embedded tumor samples from 52 patients treated for locally advanced breast cancer by means of induction chemotherapy followed by rescue mastectomy. P-glycoprotein expression was assessed by means of immunohistochemistry before treatment in 23 cases, and by means of reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) after treatment in 46 (6 failed). LRP expression was detected by means of immunohistochemistry, with the LRP-56 monoclonal antibody, in 31 cases before treatment. Immunohistochemistry for detecting the expression of c-erb-B2, p53, Ki67, estrogen receptor and progesterone receptor are routinely performed in our laboratory in every case, and the results obtained were included in the study. All patients had received between two and six cycles of standard 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy, with two exceptions [one patient received four cycles of a docetaxel-adriamycin combination, and the other four cycles of standard cyclophosphamide-methotrexate-5-fluorouracil (CMF) polychemotherapy]. Response was assessed in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST). By these, 2 patients achieved a complete clinical response, 37 a partial response, and the remaining 13 showed stable disease. This makes a

The Influence of Macroeconomic Trends on the Repayment of Loans by Households: Evidence from the Federation of Bosnia and Herzegovina and Policy Reccomendations

Directory of Open Access Journals (Sweden)

Pašić Sanela

2016-04-01

Full Text Available This paper explores the influence of macroeconomic indicators, namely GDP growth, the Consumer Price Index and the unemployment rate on the quality of loan repayments by households in the banking market of the Federation of Bosnia and Herzegovina. Potential influence is observed over a period of fourteen years at the level of nonperforming household loans using regression analysis. The authors aim to determine whether macroeconomic forces actually influence loan repayment, and if so how and what can be done by banks to utilize this information in order to reduce future credit losses, and by the government to maintain the stability of the banking sector.

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

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.

78 FR 6407 - Ability-to-Repay and Qualified Mortgage Standards Under the Truth in Lending Act (Regulation Z)

Science.gov (United States)

2013-01-30

..., and child support; (7) the monthly debt-to-income ratio or residual income; and (8) credit history... concerns were heightened as mortgage delinquencies and foreclosure rates increased dramatically, caused in... to repay.\\6\\ Subprime products were sold primarily to consumers with poor or no credit history...

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

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

... other evidence of repayment ability.\\3\\ \\2\\ Inside Mortg. Fin., The 2011 Mortgage Market Statistical..., refinancing became more difficult and delinquency rates on subprime and Alt-A products increased dramatically... peaked at 2.5 percent in late 2007.\\5\\ As the economy worsened, the rates of serious delinquency (90 or...

Low-density Lipoprotein Receptor-related Protein-1 (LRP1) Mediates Autophagy and Apoptosis Caused by Helicobacter pylori VacA*

OpenAIRE

Yahiro, Kinnosuke; Satoh, Mamoru; Nakano, Masayuki; Hisatsune, Junzo; Isomoto, Hajime; Sap, Jan; Suzuki, Hidekazu; Nomura, Fumio; Noda, Masatoshi; Moss, Joel; Hirayama, Toshiya

2012-01-01

In Helicobacter pylori infection, vacuolating cytotoxin (VacA)-induced mitochondrial damage leading to apoptosis is believed to be a major cause of cell death. It has also been proposed that VacA-induced autophagy serves as a host mechanism to limit toxin-induced cellular damage. Apoptosis and autophagy are two dynamic and opposing processes that must be balanced to regulate cell death and survival. Here we identify the low-density lipoprotein receptor-related protein-1 (LRP1) as the VacA rec...

77 FR 10455 - National Institutes of Health Loan Repayment Programs

Science.gov (United States)

2012-02-22

... science or clinical research parameters and is not targeted toward a specific area (e.g., AIDS) or type of..., whether the time is spent on research, teaching, patient care, or other activities. Living Expenses: Means...) Primary Care Loan (PCL) Program, and (10) Public Health Service Scholarship (PHS) Program; (d) For...

78 FR 20466 - National Institutes of Health Loan Repayment Programs

Science.gov (United States)

2013-04-05

... science or clinical research parameters and is not targeted toward a specific area (e.g., AIDS) or type of..., whether the time is spent on research, teaching, patient care, or other activities. Living expenses means... Shortage Area Scholarship Program, (9) Primary Care Loan (PCL) Program, and (10) Public Health Service...

The DNA-recognition mode shared by archaeal feast/famine-regulatory proteins revealed by the DNA-binding specificities of TvFL3, FL10, FL11 and Ss-LrpB

Science.gov (United States)

Yokoyama, Katsushi; Nogami, Hideki; Kabasawa, Mamiko; Ebihara, Sonomi; Shimowasa, Ai; Hashimoto, Keiko; Kawashima, Tsuyoshi; Ishijima, Sanae A.; Suzuki, Masashi

2009-01-01

The DNA-binding mode of archaeal feast/famine-regulatory proteins (FFRPs), i.e. paralogs of the Esherichia coli leucine-responsive regulatory protein (Lrp), was studied. Using the method of systematic evolution of ligands by exponential enrichment (SELEX), optimal DNA duplexes for interacting with TvFL3, FL10, FL11 and Ss-LrpB were identified as TACGA[AAT/ATT]TCGTA, GTTCGA[AAT/ATT]TCGAAC, CCGAAA[AAT/ATT]TTTCGG and TTGCAA[AAT/ATT]TTGCAA, respectively, all fitting into the form abcdeWWWedcba. Here W is A or T, and e.g. a and a are bases complementary to each other. Apparent equilibrium binding constants of the FFRPs and various DNA duplexes were determined, thereby confirming the DNA-binding specificities of the FFRPs. It is likely that these FFRPs recognize DNA in essentially the same way, since their DNA-binding specificities were all explained by the same pattern of relationship between amino-acid positions and base positions to form chemical interactions. As predicted from this relationship, when Gly36 of TvFL3 was replaced by Thr, the b base in the optimal DNA duplex changed from A to T, and, when Thr36 of FL10 was replaced by Ser, the b base changed from T to G/A. DNA-binding characteristics of other archaeal FFRPs, Ptr1, Ptr2, Ss-Lrp and LysM, are also consistent with the relationship. PMID:19468044

13 CFR 120.1881 - How are payments on the Collateral allocated between the SISMBD borrower and repayment of the...

Science.gov (United States)

2010-01-01

... are payments on the Collateral allocated between the SISMBD borrower and repayment of the SISMBD Loan? Unless otherwise provided in the Loan Agreements for a particular SISMBD Loan, any payment on Collateral... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false How are payments on the Collateral...

Peripheral administration of antisense oligonucleotides targeting the amyloid-β protein precursor reverses AβPP and LRP-1 overexpression in the aged SAMP8 mouse brain.

Science.gov (United States)

Erickson, Michelle A; Niehoff, Michael L; Farr, Susan A; Morley, John E; Dillman, Lucy A; Lynch, Kristin M; Banks, William A

2012-01-01

The senescence accelerated mouse-prone 8 (SAMP8) mouse model of Alzheimer's disease has a natural mutation leading to age-related increases in the amyloid-β protein precursor (AβPP) and amyloid-β (Aβ) in the brain, memory impairment, and deficits in Aβ removal from the brain. Previous studies show that centrally administered antisense oligonucleotide directed against AβPP can decrease AβPP expression and Aβ production in the brains of aged SAMP8 mice, and improve memory. The same antisense crosses the blood-brain barrier and reverses memory deficits when injected intravenously. Here, we give 6 μg of AβPP or control antisense 3 times over 2 week intervals to 12 month old SAMP8 mice. Object recognition test was done 48 hours later, followed by removal of whole brains for immunoblot analysis of AβPP, low-density lipoprotein-related protein-1 (LRP-1), p-glycoprotein (Pgp), receptor for advanced glycation endproducts (RAGE), or ELISA of soluble Aβ(40). Our results show that AβPP antisense completely reverses a 30% age-associated increase in AβPP signal (p < 0.05 versus untreated 4 month old SAMP8). Soluble Aβ(40) increased with age, but was not reversed by antisense. LRP-1 large and small subunits increased significantly with age (147.7%, p < 0.01 and 123.7%, p < 0.05 respectively), and AβPP antisense completely reversed these increases (p < 0.05). Pgp and RAGE were not significantly altered with age or antisense. Antisense also caused improvements in memory (p < 0.001). Together, these data support the therapeutic potential of AβPP antisense and show a unique association between AβPP and LRP-1 expression in the SAMP8 mouse.

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.

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...

75 FR 69454 - Emergency Homeowners' Loan Program: Notice of Allocation of Funding for Substantially Similar...

Science.gov (United States)

2010-11-12

... assistance and provide security for such repayment by recordation of a HUD mortgage as a junior lien on the... current first lien mortgage loan payments for which the homeowner remains responsible. IV. Submission of.... Nondiscrimination and Civil Rights Requirements States operating existing programs that provide substantially...

76 FR 16598 - Agency Information Collection Activities: Proposed Collection; Comment Request-Supplemental...

Science.gov (United States)

2011-03-24

... States have reported as disqualified. One of the factors used by a State agency to determine the...: Proposed Collection; Comment Request--Supplemental Nutrition Assistance Program Repayment Demand and... Assistance Program Repayment Demand and Program Disqualification. OMB Number: 0584-0492. Form Number: None...

Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP.

Science.gov (United States)

Nikopoulos, Konstantinos; Venselaar, Hanka; Collin, Rob W J; Riveiro-Alvarez, Rosa; Boonstra, F Nienke; Hooymans, Johanna M M; Mukhopadhyay, Arijit; Shears, Deborah; van Bers, Marleen; de Wijs, Ilse J; van Essen, Anthonie J; Sijmons, Rolf H; Tilanus, Mauk A D; van Nouhuys, C Erik; Ayuso, Carmen; Hoefsloot, Lies H; Cremers, Frans P M

2010-06-01

Wnt signaling is a crucial component of the cell machinery orchestrating a series of physiological processes such as cell survival, proliferation, and migration. Among the plethora of roles that Wnt signaling plays, its canonical branch regulates eye organogenesis and angiogenesis. Mutations in the genes encoding the low density lipoprotein receptor protein 5 (LRP5) and frizzled 4 (FZD4), acting as coreceptors for Wnt ligands, cause familial exudative vitreoretinopathy (FEVR). Moreover, mutations in the gene encoding NDP, a ligand for these Wnt receptors, cause Norrie disease and FEVR. Both FEVR and Norrie disease share similar phenotypic characteristics, including abnormal vascularization of the peripheral retina and formation of fibrovascular masses in the eye that can lead to blindness. In this mutation update, we report 21 novel variants for FZD4, LRP5, and NDP, and discuss the putative functional consequences of missense mutations. In addition, we provide a comprehensive overview of all previously published variants in the aforementioned genes and summarize the phenotypic characteristics in mouse models carrying mutations in the orthologous genes. The increasing molecular understanding of Wnt signaling, related to ocular development and blood supply, offers more tools for accurate disease diagnosis that may be important in the development of therapeutic interventions.

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

International Nuclear Information System (INIS)

Pires, L.A.; Hegg, R.; Freitas, F.R.; Tavares, E.R.; Almeida, C.P.; Baracat, E.C.; Maranhão, R.C.

2012-01-01

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

Does the group leader matter? The impact of monitoring activities and social ties of group leaders on the repayment performance of groupbased lending Eritrea

NARCIS (Netherlands)

Hermes, Niels; Lensink, Robert; Mehrteab, Habteab T.

2005-01-01

This paper analyzes whether the effects of monitoring and social ties of the group leader and other group members on repayment performance of groups differ, using data from an extensive questionnaire held in Eritrea among participants of 102 groups. We hypothesize that the monitoring activities and

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.

78 FR 52896 - Submission for OMB Review; Comment Request

Science.gov (United States)

2013-08-27

... development, facilitate learning and engage youth in the work of their community to enhance the quality of... Agriculture Title: Veterinary Medicine Loan Repayment Program (VMLRP) Shortage Situation. OMB Control Number... process to designate veterinarian shortage situations for the Veterinary Medicine Loan Repayment Program...

Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR.

Science.gov (United States)

Jeong, Ji-A; Hyun, Jaekyung; Oh, Jeong-Il

2015-10-01

In the presence of alanine, AldR, which belongs to the Lrp/AsnC family of transcriptional regulators and regulates ald encoding alanine dehydrogenase in Mycobacterium smegmatis, changes its quaternary structure from a homodimer to an octamer with an open-ring conformation. Four AldR-binding sites (O2, O1, O4, and O3) with a consensus sequence of GA/T-N2-NWW/WWN-N2-A/TC were identified upstream of the M. smegmatis ald gene by means of DNase I footprinting analysis. O2, O1, and O4 are required for the induction of ald expression by alanine, while O3 is directly involved in the repression of ald expression. In addition to O3, both O1 and O4 are also necessary for full repression of ald expression in the absence of alanine, due to cooperative binding of AldR dimers to O1, O4, and O3. Binding of a molecule of the AldR octamer to the ald control region was demonstrated to require two AldR-binding sites separated by three helical turns between their centers and one additional binding site that is in phase with the two AldR-binding sites. The cooperative binding of AldR dimers to DNA requires three AldR-binding sites that are aligned with a periodicity of three helical turns. The aldR gene is negatively autoregulated independently of alanine. Comparative analysis of ald expression of M. smegmatis and Mycobacterium tuberculosis in conjunction with sequence analysis of both ald control regions led us to suggest that the expression of the ald genes in both mycobacterial species is regulated by the same mechanism. In mycobacteria, alanine dehydrogenase (Ald) is the enzyme required both to utilize alanine as a nitrogen source and to grow under hypoxic conditions by maintaining the redox state of the NADH/NAD(+) pool. Expression of the ald gene was reported to be regulated by the AldR regulator that belongs to the Lrp/AsnC (feast/famine) family, but the underlying mechanism was unknown. This study revealed the regulation mechanism of ald in Mycobacterium smegmatis and

Local and Regional Food Aid Procurement: An Assessment of Experience in Africa and Elements of Good Donor Practice

OpenAIRE

Tschirley, David L.; del Castillo, Anne Marie

2008-01-01

This Policy Synthesis is a summary of a longer report that discusses the procurement of food aid within the country or region where it is needed. Referred to as local and regional procurement – LRP – this practice has become a major element in multilateral food aid response over the past decade1. The paper examines the relevance and the rationale for using LRP, reviews the efficiency of World Food Program (WFP) LRP activities in Africa relative to inkind food aid and to prices in the markets ...

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

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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

Proteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6.

Science.gov (United States)

Weekes, Michael P; Antrobus, Robin; Talbot, Suzanne; Hör, Simon; Simecek, Nikol; Smith, Duncan L; Bloor, Stuart; Randow, Felix; Lehner, Paul J

2012-03-02

The endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins. To identify a more comprehensive repertoire of proteins whose cell surface expression is dependent on gp96, we developed plasma membrane profiling (PMP), a technique that combines SILAC labeling with selective cell surface aminooxy-biotinylation. This approach allowed us to compare the relative abundance of plasma membrane (PM) proteins on gp96-deficient versus gp96-reconstituted murine pre-B cells. Analysis of unfractionated tryptic peptides initially identified 113 PM proteins, which extended to 706 PM proteins using peptide prefractionation. We confirmed a requirement for gp96 in the cell surface expression of certain TLRs and integrins and found a marked decrease in cell surface expression of four members of the extended LDL receptor family (LDLR, LRP6, Sorl1 and LRP8) in the absence of gp96. Other novel gp96 client proteins included CD180/Ly86, important in the B-cell response to lipopolysaccharide. We highlight common structural motifs in these client proteins that may be recognized by gp96, including the beta-propeller and leucine-rich repeat. This study therefore identifies the extended LDL receptor family as an important new family of proteins whose cell surface expression is regulated by gp96.

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.

Specific deletion of LDL receptor-related protein on macrophages has skewed in vivo effects on cytokine production by invariant natural killer T cells.

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Roman Covarrubias

Full Text Available Expression of molecules involved in lipid homeostasis such as the low density lipoprotein receptor (LDLr on antigen presenting cells (APCs has been shown to enhance invariant natural killer T (iNKT cell function. However, the contribution to iNKT cell activation by other lipoprotein receptors with shared structural and ligand binding properties to the LDLr has not been described. In this study, we investigated whether a structurally related receptor to the LDLr, known as LDL receptor-related protein (LRP, plays a role in iNKT cell activation. We found that, unlike the LDLr which is highly expressed on all immune cells, the LRP was preferentially expressed at high levels on F4/80+ macrophages (MΦ. We also show that CD169+ MΦs, known to present antigen to iNKT cells, exhibited increased expression of LRP compared to CD169- MΦs. To test the contribution of MΦ LRP to iNKT cell activation we used a mouse model of MΦ LRP conditional knockout (LRP-cKO. LRP-cKO MΦs pulsed with glycolipid alpha-galactosylceramide (αGC elicited normal IL-2 secretion by iNKT hybridoma and in vivo challenge of LRP-cKO mice led to normal IFN-γ, but blunted IL-4 response in both serum and intracellular expression by iNKT cells. Flow cytometric analyses show similar levels of MHC class-I like molecule CD1d on LRP-cKO MΦs and normal glycolipid uptake. Survey of the iNKT cell compartment in LRP-cKO mice revealed intact numbers and percentages and no homeostatic disruption as evidenced by the absence of programmed death-1 and Ly-49 surface receptors. Mixed bone marrow chimeras showed that the inability iNKT cells to make IL-4 is cell extrinsic and can be rescued in the presence of wild type APCs. Collectively, these data demonstrate that, although MΦ LRP may not be necessary for IFN-γ responses, it can contribute to iNKT cell activation by enhancing early IL-4 secretion.

Agrin-LRP4-MuSK signaling as a therapeutic target for myasthenia gravis and other neuromuscular disorders.

Science.gov (United States)

Ohno, Kinji; Ohkawara, Bisei; Ito, Mikako

2017-10-01

Signal transduction at the neuromuscular junction (NMJ) is compromised in a diverse array of diseases including myasthenia gravis, Lambert-Eaton myasthenic syndrome, Isaacs' syndrome, congenital myasthenic syndromes, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Except for sarcopenia, all are orphan diseases. In addition, the NMJ signal transduction is impaired by tetanus, botulinum, curare, α-bungarotoxin, conotoxins, organophosphate, sarin, VX, and soman to name a few. Areas covered: This review covers the agrin-LRP4-MuSK signaling pathway, which drives clustering of acetylcholine receptors (AChRs) and ensures efficient signal transduction at the NMJ. We also address diseases caused by autoantibodies against the NMJ molecules and by germline mutations in genes encoding the NMJ molecules. Expert opinion: Representative small compounds to treat the defective NMJ signal transduction are cholinesterase inhibitors, which exert their effects by increasing the amount of acetylcholine at the synaptic space. Another possible therapeutic strategy to enhance the NMJ signal transduction is to increase the number of AChRs, but no currently available drug has this functionality.

Super Energy Savings Performance Contracts: Federal Energy Management Program (FEMP) Program Overview (revision)

International Nuclear Information System (INIS)

Pitchford, P.

2001-01-01

This four-page publication describes the U.S. Department of Energy's (DOE's) streamlined energy savings performance contracting, or ''Super ESPC,'' process, which is managed by DOE's Federal Energy Management Program (FEMP). Under a Super ESPC, a qualifying energy service company (ESCO) from the private sector pays for energy efficiency improvements or advanced renewable energy technologies (e.g., photovoltaic systems, wind turbines, or geothermal heat pumps, among others) for a facility of a government agency. The ESCO is then repaid over time from the agency's resulting energy cost savings. Delivery orders under these contracts specify the level of performance (energy savings) and the repayment schedule; the contract term can be up to 25 years, although many Super ESPCs are for about 10 years or less

7 CFR 766.351 - Liquidation.

Science.gov (United States)

2010-01-01

... not otherwise fully repay or sell loan security to repay a deceased borrower's FLP loans, the Agency... SPECIAL PROGRAMS DIRECT LOAN SERVICING-SPECIAL Loan Liquidation § 766.351 Liquidation. (a) General. (1) When a borrower cannot or will not meet a loan obligation, the Agency will consider liquidating the...

The Model For Linking Savings And Credit Groups With Banks In ...

African Journals Online (AJOL)

The linkage program will greatly be enhanced if the design of the linkage encourages joint liability in loan repayment and if the savings instrument is adequately flexible such that groups can use part of the mandatory savings to repay loans when group income falls short of the group's financial obligations. Key Words: ...

45 CFR 2540.660 - If the final decision determines that I received a financial benefit improperly, will I be...

Science.gov (United States)

2010-10-01

... financial benefit improperly, will I be required to repay that benefit? 2540.660 Section 2540.660 Public... determines that I received a financial benefit improperly, will I be required to repay that benefit? If it is determined that you received a financial benefit improperly, you may be required to reimburse the program for...

75 FR 54005 - Conservation Loan Program

Science.gov (United States)

2010-09-03

... reduced application exemption. This is necessary to fully assess the problem and correct any delinquency... capital and collateral position, but these criteria, which indicate a solid past history of debt repayment...

75 FR 8974 - Office of the Director, National Institutes of Health; Notice of Meeting

Science.gov (United States)

2010-02-26

... Effectiveness; NIH Intramural Research Program; and Substance Use, Abuse, and Addiction. The Board will also... Research Loan Repayment Program; 93.187, Undergraduate Scholarship Program for Individuals from...

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.

24 CFR 570.489 - Program administrative requirements.

Science.gov (United States)

2010-04-01

... to 24 CFR part 597, subpart B. Such exclusion shall not apply if CDBG funds are used to repay the... purchase orders and contracts include any clauses required by Federal statutes, executive orders and...

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.

Modeling a four-layer location-routing problem

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Mohsen Hamidi

2012-01-01

Full Text Available Distribution is an indispensable component of logistics and supply chain management. Location-Routing Problem (LRP is an NP-hard problem that simultaneously takes into consideration location, allocation, and vehicle routing decisions to design an optimal distribution network. Multi-layer and multi-product LRP is even more complex as it deals with the decisions at multiple layers of a distribution network where multiple products are transported within and between layers of the network. This paper focuses on modeling a complicated four-layer and multi-product LRP which has not been tackled yet. The distribution network consists of plants, central depots, regional depots, and customers. In this study, the structure, assumptions, and limitations of the distribution network are defined and the mathematical optimization programming model that can be used to obtain the optimal solution is developed. Presented by a mixed-integer programming model, the LRP considers the location problem at two layers, the allocation problem at three layers, the vehicle routing problem at three layers, and a transshipment problem. The mathematical model locates central and regional depots, allocates customers to plants, central depots, and regional depots, constructs tours from each plant or open depot to customers, and constructs transshipment paths from plants to depots and from depots to other depots. Considering realistic assumptions and limitations such as producing multiple products, limited production capacity, limited depot and vehicle capacity, and limited traveling distances enables the user to capture the real world situations.

Navigated Pattern Laser System versus Single-Spot Laser System for Postoperative 360-Degree Laser Retinopexy.

Science.gov (United States)

Kulikov, Alexei N; Maltsev, Dmitrii S; Boiko, Ernest V

2016-01-01

Purpose . To compare three 360°-laser retinopexy (LRP) approaches (using navigated pattern laser system, single-spot slit-lamp (SL) laser delivery, and single-spot indirect ophthalmoscope (IO) laser delivery) in regard to procedure duration, procedural pain score, technical difficulties, and the ability to achieve surgical goals. Material and Methods . Eighty-six rhegmatogenous retinal detachment patients (86 eyes) were included in this prospective randomized study. The mean procedural time, procedural pain score (using 4-point Verbal Rating Scale), number of laser burns, and achievement of the surgical goals were compared between three groups (pattern LRP (Navilas® laser system), 36 patients; SL-LRP, 28 patients; and IO-LRP, 22 patients). Results . In the pattern LRP group, the amount of time needed for LRP and pain level were statistically significantly lower, whereas the number of applied laser burns was higher compared to those in the SL-LRP group and in the IO-LRP group. In the pattern LRP, SL-LRP, and IO-LRP groups, surgical goals were fully achieved in 28 (77.8%), 17 (60.7%), and 13 patients (59.1%), respectively ( p > 0.05). Conclusion . The navigated pattern approach allows improving the treatment time and pain in postoperative 360° LRP. Moreover, 360° pattern LRP is at least as effective in achieving the surgical goal as the conventional (slit-lamp or indirect ophthalmoscope) approaches with a single-spot laser.

Federal Student Loan Programs

Science.gov (United States)

Federal Student Aid, US Department of Education, 2014

2014-01-01

For those needing a loan to attend college, think federal aid first. Federal student loans usually offer borrowers lower interest rates and have more flexible repayment terms and options than private student loans. This brief report answers the following questions about federal aid: (1) What is a federal student loan?; (2) What is a private…

LDL receptor-related protein 1 regulates the abundance of diverse cell-signaling proteins in the plasma membrane proteome.

Science.gov (United States)

Gaultier, Alban; Simon, Gabriel; Niessen, Sherry; Dix, Melissa; Takimoto, Shinako; Cravatt, Benjamin F; Gonias, Steven L

2010-12-03

LDL receptor-related protein 1 (LRP1) is an endocytic receptor, reported to regulate the abundance of other receptors in the plasma membrane, including uPAR and tissue factor. The goal of this study was to identify novel plasma membrane proteins, involved in cell-signaling, that are regulated by LRP1. Membrane protein ectodomains were prepared from RAW 264.7 cells in which LRP1 was silenced and control cells using protease K. Peptides were identified by LC-MS/MS. By analysis of spectral counts, 31 transmembrane and secreted proteins were regulated in abundance at least 2-fold when LRP1 was silenced. Validation studies confirmed that semaphorin4D (Sema4D), plexin domain-containing protein-1 (Plxdc1), and neuropilin-1 were more abundant in the membranes of LRP1 gene-silenced cells. Regulation of Plxdc1 by LRP1 was confirmed in CHO cells, as a second model system. Plxdc1 coimmunoprecipitated with LRP1 from extracts of RAW 264.7 cells and mouse liver. Although Sema4D did not coimmunoprecipitate with LRP1, the cell-surface level of Sema4D was increased by RAP, which binds to LRP1 and inhibits binding of other ligands. These studies identify Plxdc1, Sema4D, and neuropilin-1 as novel LRP1-regulated cell-signaling proteins. Overall, LRP1 emerges as a generalized regulator of the plasma membrane proteome.

Lower rates, better service, accelerated debt repayment: how best to sell a minority interest in Hydro One

International Nuclear Information System (INIS)

2002-01-01

The sale of a minority stake in the provincially-owned, integrated electricity transmission and distribution company Hydro One is being contemplated by the Ontario government. Several options are open to the government to complete this sale, such as an income trust, an Initial Public Offering (IPO), straight sale of 49.9 per cent or less, and the separation and sale of the distribution operations. Some issues must be considered before proceeding with the divestiture: service quality and the current structure of the distribution sector in Ontario, the distribution and transmission rates, fostering competition in distribution, regulatory costs, tax leakage/stranded debt repayment, maximization of value to the province, public/stakeholder acceptance, foreign versus domestic ownership, accountability to consumers, and the policies/requirements of interconnected markets. The aim in the divestiture is to ensure customers in Ontario benefit from lower distribution rates, higher quality services, enhanced local accountability, a more efficient electricity industry, and accelerated stranded debt payoff. As a result, the Electricity Distributors Association is proposing that the government separate Hydro One's transmission and distribution. The rationale for the proposal was discussed in the paper, stressing the importance of making the decision now

The low-density lipoprotein receptor-related protein 10 is a negative regulator of the canonical Wnt/β-catenin signaling pathway

International Nuclear Information System (INIS)

Jeong, Young-Hee; Sekiya, Manami; Hirata, Michiko; Ye, Mingjuan; Yamagishi, Azumi; Lee, Sang-Mi; Kang, Man-Jong; Hosoda, Akemi; Fukumura, Tomoe; Kim, Dong-Ho; Saeki, Shigeru

2010-01-01

Wnt signaling pathways play fundamental roles in the differentiation, proliferation and functions of many cells as well as developmental, growth, and homeostatic processes in animals. Low-density lipoprotein receptor (LDLR)-related protein (LRP) 5 and LRP6 serve as coreceptors of Wnt proteins together with Frizzled receptors, triggering activation of canonical Wnt/β-catenin signaling. Here, we found that LRP10, a new member of the LDLR gene family, inhibits the canonical Wnt/β-catenin signaling pathway. The β-catenin/T cell factor (TCF) transcriptional activity in HEK293 cells was activated by transfection with Wnt3a or LRP6, which was then inhibited by co-transfection with LRP10. Deletion of the extracellular domain of LRP10 negated its inhibitory effect. The inhibitory effect of LRP10 was consistently conserved in HEK293 cells even when GSK3β phosphorylation was inhibited by incubation with lithium chloride and co-transfection with constitutively active S33Y-mutated β-catenin. Nuclear β-catenin accumulation was unaffected by LRP10. The present studies suggest that LRP10 may interfere with the formation of the β-catenin/TCF complex and/or its binding to target DNA in the nucleus, and that the extracellular domain of LRP10 is critical for inhibition of the canonical Wnt/β-catenin signaling pathway.

76 FR 31312 - Federal Family Education Loan Program

Science.gov (United States)

2011-05-31

... activities are encouraged to include in their proposals pricing strategies that include leveraging activities... intervention strategies, chose a more appropriate repayment plan for their financial situation. These types of... capacity to develop, implement, and evaluate a strategy to perform one or more of the GA Responsibility...

Amygdala α-Synuclein Pathology in the Population-Based Vantaa 85+ Study.

Science.gov (United States)

Raunio, Anna; Myllykangas, Liisa; Kero, Mia; Polvikoski, Tuomo; Paetau, Anders; Oinas, Minna

2017-01-01

We investigated the frequency of Lewy-related pathology (LRP) in the amygdala among the population-based Vantaa 85+ study. Data of amygdala samples (N = 304) immunostained with two α-synuclein antibodies (clone 42 and clone 5G4) was compared with the previously analyzed LRP and AD pathologies from other brain regions. The amygdala LRP was present in one third (33%) of subjects. Only 5% of pure AD subjects, but 85% of pure DLB subjects had LRP in the amygdala. The amygdala LRP was associated with dementia; however, the association was dependent on LRP on other brain regions, and thus was not an independent risk factor. The amygdala-predominant category was a rare (4%) and heterogeneous group.

Leakage resilient password systems

CERN Document Server

Li, Yingjiu; Deng, Robert H

2015-01-01

This book investigates tradeoff between security and usability in designing leakage resilient password systems (LRP) and introduces two practical LRP systems named Cover Pad and ShadowKey. It demonstrates that existing LRP systems are subject to both brute force attacks and statistical attacks and that these attacks cannot be effectively mitigated without sacrificing the usability of LRP systems. Quantitative analysis proves that a secure LRP system in practical settings imposes a considerable amount of cognitive workload unless certain secure channels are involved. The book introduces a secur

New Insights into the Roles of Megalin/LRP2 and the Regulation of its Functional Expression

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María-Paz Marzolo

2011-01-01

Full Text Available Since the discovery of the low-density lipoprotein receptor (LDLR and its association with familial hypercholesterolemia in the early 1980s, a family of structurally related proteins has been discovered that has apolipoprotein E as a common ligand, and the broad functions of its members have been described. LRP2, or megalin, is a member of the LDLR family and was initially called gp330. Megalin is an endocytic receptor expressed on the apical surface of several epithelial cells that internalizes a variety of ligands including nutrients, hormones and their carrier proteins, signaling molecules, morphogens, and extracellular matrix proteins. Once internalized, these ligands are directed to the lysosomal degradation pathway or transported by transcytosis from one side of the cell to the opposite membrane. The availability of megalin at the cell surface is controlled by several regulatory mechanisms, including the phosphorylation of its cytoplasmic domain by GSK3, the proteolysis of the extracellular domain at the cell surface (shedding, the subsequent intramembrane proteolysis of the transmembrane domain by the gamma-secretase complex, and exosome secretion. Based on the important roles of its ligands and its tissue expression pattern, megalin has been recognized as an important component of many pathological conditions, including diabetic nephropathy, Lowe syndrome, Dent disease, Alzheimer's disease (AD and gallstone disease. In addition, the expression of megalin and some of its ligands in the central and peripheral nervous system suggests a role for this receptor in neural regeneration processes. Despite its obvious importance, the regulation of megalin expression is poorly understood. In this review, we describe the functions of megalin and its association with certain pathological conditions as well as the current understanding of the mechanisms that underlie the control of megalin expression.

Patients With High Bone Mass Phenotype Exhibit Enhanced Osteoblast Differentiation and Inhibition of Adipogenesis of Human Mesenchymal Stem Cells

DEFF Research Database (Denmark)

Qiu, Weimin; Andersen, Tom; Bollerslev, Jens

2007-01-01

in iliac crest bone biopsies from patients with the HBM phenotype and controls. We also used retrovirus-mediated gene transduction to establish three different human mesenchymal stem cell (hMSC) strains stably expressing wildtype LRP5 (hMSC-LRP5WT), LRP5T244 (hMSC-LRP5T244, inactivation mutation leading...... to osteoporosis), or LRP5T253 (hMSC-LRP5T253, activation mutation leading to high bone mass). We characterized Wnt signaling activation using a dual luciferase assay, cell proliferation, lineage biomarkers using real-time PCR, and in vivo bone formation. Results: In bone biopsies, we found increased trabecular...... mineralized bone when implanted subcutaneously with hydroxyapatite/tricalcium phosphate in SCID/NOD mice. Conclusions: LRP5 mutations and the level of Wnt signaling determine differentiation fate of hMSCs into osteoblasts or adipocytes. Activation of Wnt signaling can thus provide a novel approach to increase...

34 CFR 674.33 - Repayment.

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2010-07-01

... to provide educational instruction in all programs, as determined by the Secretary; (B) “School... Income Protection Allowance for the current award year for a family of four with one in college. (B) For... Protection Allowance for the current award year for a family with one in college and equal in size to that of...

Low density lipoprotein receptor-related protein 1 expression correlates with cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy patients

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Cal Roi

2012-08-01

Full Text Available Abstract Our hypothesis was that overexpression of certain lipoprotein receptors might be related to lipid accumulation in the human ischemic myocardium. Intramyocardial lipid overload contributes to contractile dysfunction and arrhythmias in cardiomyopathy. Thus, the purpose of this study was to assess the effect of hypercholesterolemic LDL and hypertrigliceridemic VLDL dose on LRP1 expression in cardiomyocytes, as well as the potential correlation between LRP1 expression and neutral lipid accumulation in the left ventricle tissue from ischemic cardiomyopathy patients. Cell culture experiments include control and LRP1-deficient cardiomyocytes exposed to lipoproteins under normoxic and hypoxic conditions. Explanted hearts from 18 ICM patients and eight non-diseased hearts (CNT were included. Low density lipoprotein receptor-related protein 1 (LRP1, very low density lipoprotein receptor (VLDLR and low density lipoprotein receptor (LDLR expression was analyzed by real time PCR and Western blotting. Cholesteryl ester (CE, triglyceride (TG and free cholesterol (FC content was assess by thin layer chromatography following lipid extraction. Western blotting experiments showed that protein levels of LRP1, VLDLR and HIF-1α were significantly upregulated in ischemic hearts. Immunohistochemistry and confocal microscopy analysis showed that LRP1 and HIF-1α were upregulated in cardiomyocytes of ICM patients. In vitro studies showed that VLDL, LDL and hypoxia exerted an upregulatory effect on LRP1 expression and that LRP1 played a major role in cholesteryl ester accumulation from lipoproteins in cardiomyocytes. Myocardial CE accumulation strongly correlated with LRP1 levels in ischemic hearts. Taken together, our results suggest that LRP1 upregulation is key for myocardial cholesterol ester accumulation in ischemic human hearts and that LRP1 may be a target to prevent the deleterious effects of myocardial cholesterol accumulation in ischemic cardiomyopathy.

78 FR 70311 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

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2013-11-25

... of Committee: National Institute of Child Health and Human Development Special Emphasis Panel; Male..., Contraception and Infertility Loan Repayment Program, National Institutes of Health, HHS). Dated: November 19...

77 FR 58855 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

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2012-09-24

... Institute of Child Health and Human Development Special Emphasis Panel; Male Germline. Date: October 17..., Center for Medical Rehabilitation Research; 93.209, Contraception and Infertility Loan Repayment Program...

Carbon debt of Conservation Reserve Program (CRP) grasslands converted to bioenergy production.

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Gelfand, Ilya; Zenone, Terenzio; Jasrotia, Poonam; Chen, Jiquan; Hamilton, Stephen K; Robertson, G Philip

2011-08-16

Over 13 million ha of former cropland are enrolled in the US Conservation Reserve Program (CRP), providing well-recognized biodiversity, water quality, and carbon (C) sequestration benefits that could be lost on conversion back to agricultural production. Here we provide measurements of the greenhouse gas consequences of converting CRP land to continuous corn, corn-soybean, or perennial grass for biofuel production. No-till soybeans preceded the annual crops and created an initial carbon debt of 10.6 Mg CO(2) equivalents (CO(2)e)·ha(-1) that included agronomic inputs, changes in C stocks, altered N(2)O and CH(4) fluxes, and foregone C sequestration less a fossil fuel offset credit. Total debt, which includes future debt created by additional changes in soil C stocks and the loss of substantial future soil C sequestration, can be constrained to 68 Mg CO(2)e·ha(-1) if subsequent crops are under permanent no-till management. If tilled, however, total debt triples to 222 Mg CO(2)e·ha(-1) on account of further soil C loss. Projected C debt repayment periods under no-till management range from 29 to 40 y for corn-soybean and continuous corn, respectively. Under conventional tillage repayment periods are three times longer, from 89 to 123 y, respectively. Alternatively, the direct use of existing CRP grasslands for cellulosic feedstock production would avoid C debt entirely and provide modest climate change mitigation immediately. Incentives for permanent no till and especially permission to harvest CRP biomass for cellulosic biofuel would help to blunt the climate impact of future CRP conversion.

An empirical analysis of the cost of rearing dairy heifers from birth to first calving and the time taken to repay these costs.

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Boulton, A C; Rushton, J; Wathes, D C

2017-08-01

Rearing quality dairy heifers is essential to maintain herds by replacing culled cows. Information on the key factors influencing the cost of rearing under different management systems is, however, limited and many farmers are unaware of their true costs. This study determined the cost of rearing heifers from birth to first calving in Great Britain including the cost of mortality, investigated the main factors influencing these costs across differing farming systems and estimated how long it took heifers to repay the cost of rearing on individual farms. Primary data on heifer management from birth to calving was collected through a survey of 101 dairy farms during 2013. Univariate followed by multivariable linear regression was used to analyse the influence of farm factors and key rearing events on costs. An Excel spreadsheet model was developed to determine the time it took for heifers to repay the rearing cost. The mean±SD ages at weaning, conception and calving were 62±13, 509±60 and 784±60 days. The mean total cost of rearing was £1819±387/heifer with a mean daily cost of £2.31±0.41. This included the opportunity cost of the heifer and the mean cost of mortality, which ranged from £103.49 to £146.19/surviving heifer. The multivariable model predicted an increase in mean cost of rearing of £2.87 for each extra day of age at first calving and a decrease in mean cost of £6.06 for each percentile increase in time spent at grass. The model also predicted a decrease in the mean cost of rearing in autumn and spring calving herds of £273.20 and £288.56, respectively, compared with that in all-year-round calving herds. Farms with herd sizes⩾100 had lower mean costs of between £301.75 and £407.83 compared with farms with economic analysis suggest that management decisions on key reproduction events and grazing policy significantly influence the cost of rearing and the time it takes for heifers to start making a profit for the farm.

Impaired LDL receptor-related protein 1 translocation correlates with improved dyslipidemia and atherosclerosis in apoE-deficient mice.

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Philip L S M Gordts

Full Text Available OBJECTIVE: Determination of the in vivo significance of LDL receptor-related protein 1 (LRP1 dysfunction on lipid metabolism and atherosclerosis development in absence of its main ligand apoE. METHODS AND RESULTS: LRP1 knock-in mice carrying an inactivating mutation in the NPxYxxL motif were crossed with apoE-deficient mice. In the absence of apoE, relative to LRP1 wild-type animals, LRP1 mutated mice showed an increased clearance of postprandial lipids despite a compromised LRP1 endocytosis rate and inefficient insulin-mediated translocation of the receptor to the plasma membrane, likely due to inefficient slow recycling of the mutated receptor. Postprandial lipoprotein improvement was explained by increased hepatic clearance of triglyceride-rich remnant lipoproteins and accompanied by a compensatory 1.6-fold upregulation of LDLR expression in hepatocytes. One year-old apoE-deficient mice having the dysfunctional LRP1 revealed a 3-fold decrease in spontaneous atherosclerosis development and a 2-fold reduction in LDL-cholesterol levels. CONCLUSION: These findings demonstrate that the NPxYxxL motif in LRP1 is important for insulin-mediated translocation and slow perinuclear endosomal recycling. These LRP1 impairments correlated with reduced atherogenesis and cholesterol levels in apoE-deficient mice, likely via compensatory LDLR upregulation.

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

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2010-05-20

... discussion are: (1) NIH Director's Report; (2) Work Group for Human Embryonic Stem Cell Review; (3) Work... available. (Catalogue of Federal Domestic Assistance Program Nos. 93.14, Intramural Research Training Award; 93.22, Clinical Research Loan Repayment Program for Individuals from Disadvantaged Backgrounds; 93...

PENGARUH PROGRAM SERTIFIKASI TANAH TERHADAP AKSES PERMODALAN BAGI USAHA MIKRO DAN KECIL STUDI KASUS PROGRAM SERTIFIKASI TAHUN 2008 DI KABUPATEN KULON PROGO

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Istikomah Istikomah

2013-04-01

Full Text Available This paper discusses influence of land certification program on Micro and Small Enterprises (MSEs to access capital through the identification of factors that influence the decision of micro and small entrepreneurs (MSEs in the use of Certificate of Land Ownership (SHM as collateral and identification of the influence of certificate program to increase total loans granted to MSEs as the land owner. The identification of the factors that influence the decision of MSEs in the use of SHM as loan collateral (Y1, use binary logit regression analysis with independent variable including credit application purposes (X1, the suitability of the number of credits earned by the required amount (X2, the preception of lending procedures financial institutions (X3, perceptions of ability to repay the loan (X4, the age of the respondent (X5, sex (X6, the education level of respondents (X7, MSEs participation in MSE land certificate program (X8 and the amount of labor (X9. Meanwhile, the identification of the factors that affect the increase in lending financial in the factors that affect the increase in lending financial institution (Y2 uses multiple linear regression analysis with the independent variables include omzet (X1, the use of certificates as collateral (X2, MSEs perception of the analysis applied to financial institutions (X3, the age of respondents (X4, sex (X5, educational level (X6, and participation in the program MSEs land certificate MSE (X7.

Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice.

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Kawaguchi, Takumi; Ueno, Takato; Nogata, Yoichi; Hayakawa, Masako; Koga, Hironori; Torimura, Takuji

2017-02-01

Whole-wheat intake is known to reduce the risk of metabolic syndrome. However, the active component remains unclear. Recently, we identified bioactive peptides [leucine-arginine-proline (LRP) and leucine-glutamine‑proline (LQP)] from wheat bran autolytic hydrolysate. The present study aimed to investigate the effects of LRP and LQP on non-alcoholic steatohepatitis (NASH) in a mouse model. We also evaluated the effects of these peptides on oxidative stress and on the AMP-activated protein kinase (AMPK) signaling pathway, two major pathogenic factors of NASH. Seven‑week-old male C57BL/6 mice were fed a high-fat diet for 10 weeks and administered water supplemented with 0.05% LRP, 0.20% LRP, 0.05% LQP, or 0.20% LQP (each n=5) or distilled water (control; n=5) ad libitum. Oxidative stress was evaluated by measuring the serum levels of diacron reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP). Hepatic expression of phosphorylated AMPK and phosphorylated acetyl-CoA carboxylase (ACC) were evaluated by immunoblotting. The result showed that non‑alcoholic fatty liver disease activity score was significantly decreased in all types of treatment. Serum d-ROM levels were significantly decreased in the 0.20% LRP group, but not in the 0.05% LRP, 0.05% LQP, and 0.20% LQP groups. Serum BAP levels were significantly increased in the 0.05% LRP and 0.20% LRP groups, but not in the 0.05% LQP and 0.20% LQP groups. Immunoblotting analysis revealed that the expression of phospho-AMPK was increased whereas that of phospho-ACC was decreased in the 0.20% LQP group. In conclusion, we demonstrated that both LRP and LQP alleviated the severity of NASH in a high-fat diet-induced NASH mouse model. In addition, we showed that LRP and LQP modulated oxidative stress and upregulated AMPK/ACC, respectively. Thus, LRP and LQP may constitute clinically applicable therapeutic agents for NASH.

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

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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. © 2012 by the American College of Nurse-Midwives.

Expression of LDL receptor-related proteins (LRPs in common solid malignancies correlates with patient survival.

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Steven L Gonias

Full Text Available LDL receptor-related proteins (LRPs are transmembrane receptors involved in endocytosis, cell-signaling, and trafficking of other cellular proteins. Considerable work has focused on LRPs in the fields of vascular biology and neurobiology. How these receptors affect cancer progression in humans remains largely unknown. Herein, we mined provisional databases in The Cancer Genome Atlas (TCGA to compare expression of thirteen LRPs in ten common solid malignancies in patients. Our first goal was to determine the abundance of LRP mRNAs in each type of cancer. Our second goal was to determine whether expression of LRPs is associated with improved or worsened patient survival. In total, data from 4,629 patients were mined. In nine of ten cancers studied, the most abundantly expressed LRP was LRP1; however, a correlation between LRP1 mRNA expression and patient survival was observed only in bladder urothelial carcinoma. In this malignancy, high levels of LRP1 mRNA were associated with worsened patient survival. High levels of LDL receptor (LDLR mRNA were associated with decreased patient survival in pancreatic adenocarcinoma. High levels of LRP10 mRNA were associated with decreased patient survival in hepatocellular carcinoma, lung adenocarcinoma, and pancreatic adenocarcinoma. LRP2 was the only LRP for which high levels of mRNA expression correlated with improved patient survival. This correlation was observed in renal clear cell carcinoma. Insights into LRP gene expression in human cancers and their effects on patient survival should guide future research.

The low-density lipoprotein receptor-related protein 1 and amyloid-β clearance in Alzheimer’s disease

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Takahisa eKanekiyo

2014-05-01

Full Text Available Accumulation and aggregation of amyloid-β (Aβ peptides in the brain trigger the development of progressive neurodegeneration and dementia associated with Alzheimer’s disease (AD. Perturbation in Aβ clearance, rather than Aβ production, is likely the cause of sporadic, late-onset AD, which accounts for the majority of AD cases. Since cellular uptake and subsequent degradation constitute a major Aβ clearance pathway, the receptor-mediated endocytosis of Aβ has been intensely investigated. Among Aβ receptors, the low-density lipoprotein receptor-related protein 1 (LRP1 is one of the most studied receptors. LRP1 is a large endocytic receptor for more than 40 ligands, including apolipoprotein E (apoE, α2-macroglobulin and Aβ. Emerging in vitro and in vivo evidence demonstrates that LRP1 is critically involved in brain Aβ clearance. LRP1 is highly expressed in a variety of cell types in the brain including neurons, vascular cells and glial cells, where LRP1 functions to maintain brain homeostasis and control Aβ metabolism. LRP1-mediated endocytosis regulates cellular Aβ uptake by binding to Aβ either directly or indirectly through its co-receptors or ligands. Furthermore, LRP1 regulates several signaling pathways, which also likely influences Aβ endocytic pathways. In this review, we discuss how LRP1 regulates the brain Aβ clearance and how this unique endocytic receptor participates in AD pathogenesis. Understanding of the mechanisms underlying LRP1-mediated Aβ clearance should enable the rational design of novel diagnostic and therapeutic strategies for AD.

24 CFR 941.501 - HUD review of PHA performance; sanctions.

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2010-04-01

... repay HUD for amounts awarded under the development programs that were improperly expended; (e) Types of... it an opportunity, within a prescribed period of time, to present any arguments or additional facts...

77 FR 9674 - Eunice Kennedy Shriver National Institute of Child Health and Human Development; Notice of Closed...

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2012-02-17

..., ``Male Reproduction.'' Date: March 14, 2012. Time: 2 p.m. to 4 p.m. Agenda: To review and evaluate grant..., Center for Medical Rehabilitation Research; 93.209, Contraception and Infertility Loan Repayment Program...

Progressive Supranuclear Palsy

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... Disorders (NORD) 55 Kenosia Avenue Danbury, CT 06810 orphan@rarediseases.org https://rarediseases.org/ Tel: 203-744- ... Overview Loan Repayment Programs Administrative Supplements Peer Review Process Review Committees Application Support Library Clinical Research Next ...

Mucolipidoses

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... Disorders (NORD) 55 Kenosia Avenue Danbury, CT 06810 orphan@rarediseases.org https://rarediseases.org/ Tel: 203-744- ... Overview Loan Repayment Programs Administrative Supplements Peer Review Process Review Committees Application Support Library Clinical Research Next ...

Tuberous Sclerosis

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... Disorders (NORD) 55 Kenosia Avenue Danbury, CT 06810 orphan@rarediseases.org https://rarediseases.org/ Tel: 203-744- ... Overview Loan Repayment Programs Administrative Supplements Peer Review Process Review Committees Application Support Library Clinical Research Next ...

Post-Polio Syndrome

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... PPS is unknown but experts have offered several theories to explain the phenomenon—ranging from the fatigue ... New Investigators Grant Application Overview Loan Repayment Programs Administrative Supplements Peer Review Process Review Committees Application Support ...

The expression and significance of P-glycoprotein, lung resistance protein and multidrug resistance-associated protein in gastric cancer

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Li Yan

2009-11-01

Full Text Available Abstract Background To detect the expression of multidrug resistance molecules P-glycoprotein (P-gp, Lung resistnce protein (LRP and Multidrug resistance-associated protein (MRP and analyze the relationship between them and the clinico-pathological features. Methods The expressions of P-gp, LRP and MRP in formalin-fixed paraffin-embedded tissue sections from 59 gastric cancer patients were determined by a labbelled Streptavidin-Peroxidase (SP immunohistochemical technique, and the results were analyzed in correlation with clinicopathological data. None of these patients received chemotherapy prior to surgery. Results The positive rates of P-gp, LRP, MRP were 86.4%, 84.7% and 27.1%, respectively. The difference between the positive rate of P-gp and MRP was significant statistically, as well as the difference between the expression of MRP and LRP. No significant difference was observed between P-gp and LRP, but the positively correlation between the expression of P-gp and LRP had been found. No significant correlation between the expression of P-gp, LRP, MRP and the grade of differentiation were observed. The expression of P-gp was correlated with clinical stages positively (r = 0.742, but the difference with the expression of P-gp in different stages was not significant. Conclusion The expressions of P-gp, LRP and MRP in patients with gastric cancer without prior chemotherapy are high, indicating that innate drug resistance may exist in gastric cancer.

Oncological outcomes of high-risk prostate cancer patients between robot-assisted laparoscopic radical prostatectomy and laparoscopic radical prostatectomy in Taiwan

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Chieh-Chun Liao

2018-01-01

Full Text Available Objective: To compare pathological and oncological outcomes between robotic-assisted laparoscopic radical prostatectomy (RaLRP and laparoscopic radical prostatectomy (LRP among high-risk prostate cancer patient in a tertiary center in Taiwan. Materials and methods: From November 2003 to October 2013, 129 high-risk prostate cancer patients receiving minimally-invasive radical prostatectomy were included. The Kaplan–Meier analysis was used for measuring biochemical recurrence-free survival (BFS. Multivariate logistic regression models and Cox proportional hazards regression models were used to determine predictors of positive surgical margin and BFS. Results: Among the 129 high-risk prostate cancer patients included, 80 (62% patients received LRP and 49 (38% patients received RaLRP. There was no significant difference of positive surgical margin and biochemical recurrence rate between RaLRP and LRP group (P = 0.802 and 0.292. Higher pathological T stage predicted an increased likelihood of positive margins (OR = 3.44, 95% CI [1.45, 8.18], P = 0.005. Higher initial PSA level (HR = 2.88, 95% CI [1.04, 7.94], P = 0.041 and positive surgical margin (HR = 2.55, 95% CI [1.20, 5.44], P = 0.015 were poor prognostic factors for BFS. Conclusion: RaLRP can be considered among high-risk prostate cancer in Asian people with comparable oncological outcomes to LRP. Higher pathological T stage was associated with increased likelihood of positive margins, patients with higher iPSA level and positive surgical margin had worsen biochemical recurrence-free survival.

7 CFR 3560.409 - Subordinations or junior liens against security property.

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2010-01-01

... program requirements or to operate and manage the housing project in a manner consistent with program... specific amount. (4) The subordination or junior lien must not adversely impact the Agency's ability to... condition and the borrower's ability to repay the Agency loan being secured by the property. (3) The action...

Guide to Direct Consolidation Loans.

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Department of Education, Washington, DC.

Intended for financial aid counselors, this document provides guidelines to the Federal Direct Consolidation Loan Program for borrowers who are in school, as well as those in repayment, or in default. An introductory section explains the basics of the consolidated loan program, loan categories, and interest rates. Next, standards for borrower…

7 CFR 771.2 - Abbreviations and definitions.

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2010-01-01

... payment means a payment derived from the sale of property serving as security for a loan, such as real... include a modification of the interest rate and/or repayment terms of the loan. Security means assets... AGRICULTURE SPECIAL PROGRAMS BOLL WEEVIL ERADICATION LOAN PROGRAM § 771.2 Abbreviations and definitions. The...

Wnt-1 Signaling in Mammary Carcinogenesis

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2000-04-01

and the notochord (4), Wnt-5A/LRP6 or LRP6 (higher doses) alone induced trunk axis duplication with muscle and neural tissues but lacking head or the... notochord (Fig. lb). It remains unclear whether this is due to quantitative or qualitative differences between Wnt-5a/LRP6 and Wnt-5a/hFz5 co...2 ng) or Wnt-5a (20 pg) plus LRP6 (100 pg) induced trunk axis duplication lacking head and the notochord . Top: the whole embryo phenotype at stage 40

Scientists Take a Close-Up of Key Pain-Sensing Molecule

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... 12, 2018 NIH-funded researchers and Google show machine learning can be applied to biomedical research NIH-supported ... Considerations Apply for Funding New Investigators Grant Application Overview Loan Repayment Programs Administrative Supplements Peer Review Process ...

Mitogen-activated protein kinase signaling pathways promote low-density lipoprotein receptor-related protein 1-mediated internalization of beta-amyloid protein in primary cortical neurons.

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Yang, Wei-Na; Ma, Kai-Ge; Qian, Yi-Hua; Zhang, Jian-Shui; Feng, Gai-Feng; Shi, Li-Li; Zhang, Zhi-Chao; Liu, Zhao-Hui

2015-07-01

Mounting evidence suggests that the pathological hallmarks of Alzheimer's disease (AD) are caused by the intraneuronal accumulation of beta-amyloid protein (Aβ). Reuptake of extracellular Aβ is believed to contribute significantly to the intraneuronal Aβ pool in the early stages of AD. Published reports have claimed that the low-density lipoprotein receptor-related protein 1 (LRP1) mediates Aβ1-42 uptake and lysosomal trafficking in GT1-7 neuronal cells and mouse embryonic fibroblast non-neuronal cells. However, there is no direct evidence supporting the role of LRP1 in Aβ internalization in primary neurons. Our recent study indicated that p38 MAPK and ERK1/2 signaling pathways are involved in regulating α7 nicotinic acetylcholine receptor (α7nAChR)-mediated Aβ1-42 uptake in SH-SY5Y cells. This study was designed to explore the regulation of MAPK signaling pathways on LRP1-mediated Aβ internalization in neurons. We found that extracellular Aβ1-42 oligomers could be internalized into endosomes/lysosomes and mitochondria in cortical neurons. Aβ1-42 and LRP1 were also found co-localized in neurons during Aβ1-42 internalization, and they could form Aβ1-42-LRP1 complex. Knockdown of LRP1 expression significantly decreased neuronal Aβ1-42 internalization. Finally, we identified that p38 MAPK and ERK1/2 signaling pathways regulated the internalization of Aβ1-42 via LRP1. Therefore, these results demonstrated that LRP1, p38 MAPK and ERK1/2 mediated the internalization of Aβ1-42 in neurons and provided evidence that blockade of LRP1 or inhibitions of MAPK signaling pathways might be a potential approach to lowering brain Aβ levels and served a potential therapeutic target for AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic and Phenotypic Analysis of Lateral Root Development in Arabidopsis thaliana.

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Napsucialy-Mendivil, Selene; Dubrovsky, Joseph G

2018-01-01

Root system formation to a great extent depends on lateral root (LR) formation. In Arabidopsis thaliana, LRs are initiated within a parent root in pericycle that is an external tissue of the stele. LR initiation takes place in a strictly acropetal pattern, whereas posterior lateral root primordium (LRP) formation is asynchronous. In this chapter, we focus on methods of genetic and phenotypic analysis of LR initiation, LRP morphogenesis, and LR emergence in Arabidopsis. We provide details on how to make cleared root preparations and how to identify the LRP stages. We also pay attention to the categorization of the LRP developmental stages and their variations and to the normalization of the number of LRs and LRPs formed, per length of the primary root, and per number of cells produced within a root. Hormonal misbalances and mutations affect LRP morphogenesis significantly, and the evaluation of LRP abnormalities is addressed as well. Finally, we deal with various molecular markers that can be used for genetic and phenotypic analyses of LR development.

Downregulation of the non-integrin laminin receptor reduces cellular viability by inducing apoptosis in lung and cervical cancer cells.

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Kiashanee Moodley

Full Text Available The non-integrin laminin receptor, here designated the 37-kDa/67-kDa laminin receptor (LRP/LR, is involved in many physiologically relevant processes, as well as numerous pathological conditions. The overexpression of LRP/LR on various cancerous cell lines plays critical roles in tumour metastasis and angiogenesis. This study investigated whether LRP/LR is implicated in the maintenance of cellular viability in lung and cervical cancer cell lines. Here we show a significant reduction in cellular viability in the aforementioned cell lines as a result of the siRNA-mediated downregulation of LRP. This reduction in cellular viability is due to increased apoptotic processes, reflected by the loss of nuclear integrity and the significant increase in the activity of caspase-3. These results indicate that LRP/LR is involved in the maintenance of cellular viability in tumorigenic lung and cervix uteri cells through the blockage of apoptosis. Knockdown of LRP/LR by siRNA might represent an alternative therapeutic strategy for the treatment of lung and cervical cancer.

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.

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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.

Characterization of wise protein and its molecular mechanism to interact with both Wnt and BMP signals.

Science.gov (United States)

Lintern, Katherine B; Guidato, Sonia; Rowe, Alison; Saldanha, José W; Itasaki, Nobue

2009-08-21

Cross-talk of BMP and Wnt signaling pathways has been implicated in many aspects of biological events during embryogenesis and in adulthood. A secreted protein Wise and its orthologs (Sostdc1, USAG-1, and Ectodin) have been shown to modulate Wnt signaling and also inhibit BMP signals. Modulation of Wnt signaling activity by Wise is brought about by an interaction with the Wnt co-receptor LRP6, whereas BMP inhibition is by binding to BMP ligands. Here we have investigated the mode of action of Wise on Wnt and BMP signals. It was found that Wise binds LRP6 through one of three loops formed by the cystine knot. The Wise deletion construct lacking the LRP6-interacting loop domain nevertheless binds BMP4 and inhibits BMP signals. Moreover, BMP4 does not interfere with Wise-LRP6 binding, suggesting separate domains for the physical interaction. Functional assays also show that the ability of Wise to block Wnt1 activity through LRP6 is not impeded by BMP4. In contrast, the ability of Wise to inhibit BMP4 is prevented by additional LRP6, implying a preference of Wise in binding LRP6 over BMP4. In addition to the interaction of Wise with BMP4 and LRP6, the molecular characteristics of Wise, such as glycosylation and association with heparan sulfate proteoglycans on the cell surface, are suggested. This study helps to understand the multiple functions of Wise at the molecular level and suggests a possible role for Wise in balancing Wnt and BMP signals.

Coexpression of multidrug resistance involve proteins: a flow cytometric analysis.

Science.gov (United States)

Boutonnat, J; Bonnefoix, T; Mousseau, M; Seigneurin, D; Ronot, X

1998-01-01

Cross resistance to multiple natural cytotoxic products represents a major obstacle in myeloblastic acute leukaemia (AML). Multidrug resistance (MDR) often involves overexpression of plasma membrane drug transporter P-glycoprotein (PGP) or the resistance associated protein (MRP). Recently, a protein overexpressed in a non-PGP MDR lung cancer cell line and termed lung resistance related protein (LRP) was identified. These proteins are known to be associated with a bad prognosis in AML. We have developed a triple indirect labelling analysed by flow cytometry to detect the coexpression of these proteins. Since no cell line expressing all three antigens is known, we mixed K562 cells (resistant to Adriblastine, PGP+, MRP-, LRP-) with GLC4 cells (resistant to Adriblastine, PGP-, MRP+, LRP+) to create a model system to test the method. The antibodies used were UIC2 for PGP, MRPm6 for MRP and LRP56 for LRP. They were revealed by Fab'2 coupled with Fluoresceine-isothiocyanate, Phycoerythrin or Tricolor with isotype specificity. Cells were fixed and permeabilized after PGP labelling because MRPm6 and LRP56 recognize intracellular epitopes. PGP and LRP were easily detected. MRP is expressed at relatively low levels and was more difficult to detect because in the triple labelling the non specific staining was higher than in a single labelling. Despite the increased background in the triple labelling we were able to detect coexpression of PGP, MRP, LRP by flow cytometry. This method appears to be very useful to detect coexpression of markers in AML. Such coexpression could modify the therapeutic approach with revertants.

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

Science.gov (United States)

2010-04-19

... past due in its payment schedule as determined by the lending institution. Debt threshold means the... lending institutions by an agency of the United States or the State in which the lender has its principal... health animal experts in the State in the nomination process. Sec. 3431.6 Review of nominations. (a) Peer...

nilR is necessary for co-ordinate repression of Xenorhabdus nematophila mutualism genes.

Science.gov (United States)

Cowles, Charles E; Goodrich-Blair, Heidi

2006-11-01

The bacterial mutualist Xenorhabdus nematophila colonizes a specific region of its nematode host Steinernema carpocapsae. We previously reported the identification of a chromosomal locus encoding three X. nematophila genes of unknown function, nilA, B and C, that are each necessary for colonization. Subsequent work indicated the global regulator Lrp is a repressor of nilC: nilC transcription is elevated in an lrp mutant and Lrp interacts directly with the nilC promoter. In this manuscript, we report the identification of an additional gene, nilR, required for repression of nilC transcription. We show that nilR and lrp mutants also have elevated expression of nilA and nilB, demonstrating that nilA, B and C are co-ordinately regulated. nil gene expression is derepressed most strongly when both nilR and lrp are lacking, suggesting NilR and Lrp synergistically repress nil transcription. NilR contains a helix-turn-helix-type DNA binding domain and likely acts directly at promoters. A comparison of the wild type and nilR proteomes indicates that NilR, unlike Lrp, regulates a small number of genes. Finally, X. nematophila carrying an ectopic copy of nilR colonizes at approximately 60-fold lower levels than the control strain, suggesting that derepression of nil gene expression is necessary for nematode colonization.

7 CFR 3431.3 - Definitions and acronyms.

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2010-01-01

...: (i) The prescription, dispensing, administration, or application of any drug, medicine, biologic..., AND EXTENSION SERVICE, DEPARTMENT OF AGRICULTURE VETERINARY MEDICINE LOAN REPAYMENT PROGRAM... other species as determined by the Secretary. Food supply veterinary medicine means all aspects of...

77 FR 28607 - Agency Information Collection Activities: Proposed Collection: Comment Request

Science.gov (United States)

2012-05-15

... of automated collection techniques or other forms of information technology. Proposed Project... Administration (HRSA) Faculty Loan Repayment Program, degree-trained health professionals from disadvantaged... notice. Dated: May 9, 2012. Reva Harris, Acting Director, Division of Policy and Information Coordination...

The p38 mitogen-activated protein kinase signaling pathway is involved in regulating low-density lipoprotein receptor-related protein 1-mediated β-amyloid protein internalization in mouse brain.

Science.gov (United States)

Ma, Kai-Ge; Lv, Jia; Hu, Xiao-Dan; Shi, Li-Li; Chang, Ke-Wei; Chen, Xin-Lin; Qian, Yi-Hua; Yang, Wei-Na; Qu, Qiu-Min

2016-07-01

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Recently, increasing evidence suggests that intracellular β-amyloid protein (Aβ) alone plays a pivotal role in the progression of AD. Therefore, understanding the signaling pathway and proteins that control Aβ internalization may provide new insight for regulating Aβ levels. In the present study, the regulation of Aβ internalization by p38 mitogen-activated protein kinases (MAPK) through low-density lipoprotein receptor-related protein 1 (LRP1) was analyzed in vivo. The data derived from this investigation revealed that Aβ1-42 were internalized by neurons and astrocytes in mouse brain, and were largely deposited in mitochondria and lysosomes, with some also being found in the endoplasmic reticulum. Aβ1-42-LRP1 complex was formed during Aβ1-42 internalization, and the p38 MAPK signaling pathway was activated by Aβ1-42 via LRP1. Aβ1-42 and LRP1 were co- localized in the cells of parietal cortex and hippocampus. Furthermore, the level of LRP1-mRNA and LRP1 protein involved in Aβ1-42 internalization in mouse brain. The results of this investigation demonstrated that Aβ1-42 induced an LRP1-dependent pathway that related to the activation of p38 MAPK resulting in internalization of Aβ1-42. These results provide evidence supporting a key role for the p38 MAPK signaling pathway which is involved in the regulation of Aβ1-42 internalization in the parietal cortex and hippocampus of mouse through LRP1 in vivo. Copyright © 2016 Elsevier Ltd. All rights reserved.

EVALUASI PROGRAM PENGENTASAN KEMISKINAN (Studi Kasus Pemberdayaan Ekonomi pada Program Nasional Pemberdayaan Masyarakat (PNPM Mandiri Perkotaan di Kelurahan Perwira Kecamatan Bekasi Utara Kota Bekasi Jawa Barat

Directory of Open Access Journals (Sweden)

Ari Saptono

2013-08-01

Full Text Available This research is to evaluate the process of economy empowerment on PNPM Mandiri Perkotaan in Officer North Bekasi with targeted research that examines the implementation of economic development programs related to community participation, community capacity building, as well as assessing the degree of empowerment community. Model of evaluation which is used in this research is CIPP evaluation. In general, this evaluation model consists of four evaluation objectives, namely: Context Evaluation, Input Evaluation, Process Evaluation, Product evaluation. Research results showed: there is no standard criteria or indicators to determine the receivers of loan; achievement rate in providing infrastructure BKM is 42.85%, it’s in moderate category; staffing is in accordance with the procedures set out in the guidelines; public institutions is fully established. People's understanding of revolving loans varies. Public participation has achieve minimum target of 40%. The quantity of training which can improve skill must be increased since skills owned by the members are expected can increase family income through home businesses. Perwira District has not develop partnership yet with external party such as: bank, corporate, and higher education institution. This economy empowerment program has satisfactory result, indicated by: 93% of repayment rate, 2,63% of loans at risk , 211,36% cost coverage ratio, and 6,54% return on investment.

Neuronal low-density lipoprotein receptor-related protein 1 binds and endocytoses prion fibrils via receptor cluster 4

DEFF Research Database (Denmark)

Jen, Angela; Parkyn, Celia J; Mootoosamy, Roy C

2010-01-01

For infectious prion protein (designated PrP(Sc)) to act as a template to convert normal cellular protein (PrP(C)) to its distinctive pathogenic conformation, the two forms of prion protein (PrP) must interact closely. The neuronal receptor that rapidly endocytoses PrP(C) is the low......-density lipoprotein receptor-related protein 1 (LRP1). We show here that on sensory neurons LRP1 is also the receptor that binds and rapidly endocytoses smaller oligomeric forms of infectious prion fibrils, and recombinant PrP fibrils. Although LRP1 binds two molecules of most ligands independently to its receptor...... both prion and LRP1 biology....

Modulation of β-catenin signaling by glucagon receptor activation.

Directory of Open Access Journals (Sweden)

Jiyuan Ke

Full Text Available The glucagon receptor (GCGR is a member of the class B G protein-coupled receptor family. Activation of GCGR by glucagon leads to increased glucose production by the liver. Thus, glucagon is a key component of glucose homeostasis by counteracting the effect of insulin. In this report, we found that in addition to activation of the classic cAMP/protein kinase A (PKA pathway, activation of GCGR also induced β-catenin stabilization and activated β-catenin-mediated transcription. Activation of β-catenin signaling was PKA-dependent, consistent with previous reports on the parathyroid hormone receptor type 1 (PTH1R and glucagon-like peptide 1 (GLP-1R receptors. Since low-density-lipoprotein receptor-related protein 5 (Lrp5 is an essential co-receptor required for Wnt protein mediated β-catenin signaling, we examined the role of Lrp5 in glucagon-induced β-catenin signaling. Cotransfection with Lrp5 enhanced the glucagon-induced β-catenin stabilization and TCF promoter-mediated transcription. Inhibiting Lrp5/6 function using Dickkopf-1(DKK1 or by expression of the Lrp5 extracellular domain blocked glucagon-induced β-catenin signaling. Furthermore, we showed that Lrp5 physically interacted with GCGR by immunoprecipitation and bioluminescence resonance energy transfer assays. Together, these results reveal an unexpected crosstalk between glucagon and β-catenin signaling, and may help to explain the metabolic phenotypes of Lrp5/6 mutations.

Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.

Science.gov (United States)

Wang, Zhongxiao; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Favazza, Tara L; Morss, Peyton C; Saba, Nicholas J; Fredrick, Thomas W; He, Xi; Akula, James D; Chen, Jing

2016-10-01

Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Loss of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 Confers Resistance to the Antiatherogenic Effects of Tumor Necrosis Factor-α Inhibition.

Science.gov (United States)

Zhu, Lin; Giunzioni, Ilaria; Tavori, Hagai; Covarrubias, Roman; Ding, Lei; Zhang, Youmin; Ormseth, Michelle; Major, Amy S; Stafford, John M; Linton, MacRae F; Fazio, Sergio

2016-08-01

Antiatherosclerotic effects of tumor necrosis factor-α (TNF-α) blockade in patients with systemic inflammatory states are not conclusively demonstrated, which suggests that effects depend on the cause of inflammation. Macrophage LRP1 (low-density lipoprotein receptor-related protein 1) and apoE contribute to inflammation through different pathways. We studied the antiatherosclerosis effects of TNF-α blockade in hyperlipidemic mice lacking either LRP1 (MΦLRP1(-/-)) or apoE from macrophages. Lethally irradiated low-density lipoprotein receptor (LDLR)(-/-) mice were reconstituted with bone marrow from either wild-type, MΦLRP1(-/-), apoE(-/-) or apoE(-/-)/MΦLRP1(-/-)(DKO) mice, and then treated with the TNF-α inhibitor adalimumab while fed a Western-type diet. Adalimumab reduced plasma TNF-α concentration, suppressed blood ly6C(hi) monocyte levels and their migration into the lesion, and reduced lesion cellularity and inflammation in both wild-type→LDLR(-/-) and apoE(-/-)→LDLR(-/-) mice. Overall, adalimumab reduced lesion burden by 52% to 57% in these mice. Adalimumab reduced TNF-α and blood ly6C(hi) monocyte levels in MΦLRP1(-/-)→LDLR(-/-) and DKO→LDLR(-/-) mice, but it did not suppress ly6C(hi) monocyte migration into the lesion or atherosclerosis progression. Our results show that TNF-α blockade exerts antiatherosclerotic effects that are dependent on the presence of macrophage LRP1. © 2016 American Heart Association, Inc.

Rational design of DKK3 structure-based small peptides as antagonists of Wnt signaling pathway and in silico evaluation of their efficiency.

Directory of Open Access Journals (Sweden)

Mansour Poorebrahim

Full Text Available Dysregulated Wnt signaling pathway is highly associated with the pathogenesis of several human cancers. Dickkopf proteins (DKKs are thought to inhibit Wnt signaling pathway through binding to lipoprotein receptor-related protein (LRP 5/6. In this study, based on the 3-dimensional (3D structure of DKK3 Cys-rich domain 2 (CRD2, we have designed and developed several peptide inhibitors of Wnt signaling pathway. Modeller 9.15 package was used to predict 3D structure of CRD2 based on the Homology modeling (HM protocol. After refinement and minimization with GalaxyRefine and NOMAD-REF servers, the quality of selected models was evaluated utilizing VADAR, SAVES and ProSA servers. Molecular docking studies as well as literature-based information revealed two distinct boxes located at CRD2 which are actively involved in the DKK3-LRP5/6 interaction. A peptide library was constructed conducting the backrub sequence tolerance scanning protocol in Rosetta3.5 according to the DKK3-LRP5/6 binding sites. Seven tolerated peptides were chosen and their binding affinity and stability were improved by some logical amino acid substitutions. Molecular dynamics (MD simulations of peptide-LRP5/6 complexes were carried out using GROMACS package. After evaluation of binding free energies, stability, electrostatic potential and some physicochemical properties utilizing computational approaches, three peptides (PEP-I1, PEP-I3 and PEP-II2 demonstrated desirable features. However, all seven improved peptides could sufficiently block the Wnt-binding site of LRP6 in silico. In conclusion, we have designed and improved several small peptides based on the LRP6-binding site of CRD2 of DKK3. These peptides are highly capable of binding to LRP6 in silico, and may prevent the formation of active Wnt-LRP6-Fz complex.

78 FR 15022 - Office of the Director, National Institutes of Health; Notice of Meeting

Science.gov (United States)

2013-03-08

... on: the epidemiology, diagnosis, assessment, treatment, and prevention of Neuro-AIDS and HIV... increasing vulnerability to Neuro-AIDS; CNS compartmentalization and challenges for an HIV cure; CNS... Nos. 93.14, Intramural Research Training Award; 93.22, Clinical Research Loan Repayment Program for...

75 FR 12766 - National Center on Minority Health and Health Disparities; Notice of Closed Meetings

Science.gov (United States)

2010-03-17

... Health and Health Disparities; Notice of Closed Meetings Pursuant to section 10(d) of the Federal... and Health Disparities Special Emphasis Panel Loan Repayment Program for Health Disparities Research... Review, National Center on Minority Health and Health Disparities, 6707 Democracy Boulevard, Suite 800...

25 CFR 166.910 - What happens if I do not fulfill my obligation to the BIA?

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2010-04-01

... GRAZING PERMITS Agriculture Education, Education Assistance, Recruitment, and Training § 166.910 What... under agriculture education programs with an obligated service requirement, and who does not accept employment or unreasonably terminates employment must repay us in accordance with the following table: If you...

78 FR 45515 - Agency Information Collection Activities; Comment Request; William D. Ford Federal Direct Loan...

Science.gov (United States)

2013-07-29

... DEPARTMENT OF EDUCATION [Docket No.: ED-2013-ICCD-0099] Agency Information Collection Activities; Comment Request; William D. Ford Federal Direct Loan Program Repayment Plan Selection Form AGENCY... notice will be considered public records. Title of Collection: William D. Ford Federal Direct Loan...

75 FR 9421 - National Center on Minority Health and Health Disparities; Notice of Closed Meeting

Science.gov (United States)

2010-03-02

... Health and Health Disparities; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Health Disparities Special Emphasis Panel; Loan Repayment Program for Health Disparities Research..., National Center on Minority Health and Health Disparities, 6707 Democracy Boulevard, Suite 800, Bethesda...

50 CFR 600.1104 - Bering Sea and Aleutian Islands (BSAI) crab species fee payment and collection system.

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2010-10-01

... endorsement for Norton Sound red king. More specifically, the reduction endorsement fisheries, and the crab... COMMERCE MAGNUSON-STEVENS ACT PROVISIONS Specific Fishery or Program Fishing Capacity Reduction Regulations....1012 of subpart L, establish: (i) The borrower's obligation to repay a reduction loan, and (ii) The...

12 CFR 614.4150 - Lending policies and loan underwriting standards.

Science.gov (United States)

2010-01-01

... determining that an applicant has the operational, financial, and management resources necessary to repay the debt from cashflow (2) That are appropriate for each loan program and the institution's risk-bearing... loan underwriting standards. Under the policies of its board, each institution shall adopt written...

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.

Business planning for university health science programs: a case study.

Science.gov (United States)

Austin, Michael; Milos, Nadine; Raborn, G Wayne

2002-02-01

Many publicly funded education programs and organizations have developed business plans to enhance accountability. In the case of the Department of Dentistry at the University of Alberta, the main impetus for business planning was a persistent deficit in the annual operating fund since a merger of a stand-alone dental faculty with the Faculty of Medicine. The main challenges were to balance revenues with expenditures, to reduce expenditures without compromising quality of teaching, service delivery and research, to maintain adequate funding to ensure future competitiveness, and to repay the accumulated debt owed to the university. The business plan comprises key strategies in the areas of education, clinical practice and service, and research. One of the strategies for education was to start a BSc program in dental hygiene, which was accomplished in September 2000. In clinical practice, a key strategy was implementation of a clinic operations fee, which also occurred in September 2000. This student fee helps to offset the cost of clinical practice. In research, a key strategy has been to strengthen our emphasis on prevention technologies. In completing the business plan, we learned the importance of identifying clear goals and ensuring that the goals are reasonable and achievable; gaining access to high-quality data to support planning; and nurturing existing positive relationships with external stakeholders such as the provincial government and professional associations.

Low-Density Lipoprotein Receptor–Related Protein-1 Is a Therapeutic Target in Acute Myocardial Infarction

Directory of Open Access Journals (Sweden)

Stefano Toldo, PhD

2017-10-01

Full Text Available Low-density lipoprotein receptor–related protein-1 (LRP1 is a ubiquitous membrane receptor functioning as a scavenger and regulatory receptor, inducing anti-inflammatory and prosurvival signals. Based on the known structure–activity of the LRP1 receptor binding site, the authors synthesized a small peptide (SP16. SP16 induced a >50% reduction in infarct size (p < 0.001 and preservation of left ventricular systolic function (p < 0.001, and treatment with an LRP1 blocking antibody eliminated the protective effects of SP16. In conclusion, LRP1 activation with SP16 given within 30 min of reperfusion during experimental acute myocardial infarction leads to a cardioprotective signal reducing infarct size and preservation of cardiac systolic function.

78 FR 1216 - Office of the Director, National Institutes of Health; Notice of Meeting

Science.gov (United States)

2013-01-08

... highly pathogenic avian influenza H5N1 strains that have the potential to be transmissible through.... Individuals who plan to attend and need special assistance, such as sign language interpretation or other..., Intramural Research Training Award; 93.22, Clinical Research Loan Repayment Program for Individuals from...

A System Dynamics Model for Integrated Decision Making ...

Science.gov (United States)

EPA’s Sustainable and Healthy Communities Research Program (SHC) is conducting transdisciplinary research to inform and empower decision-makers. EPA tools and approaches are being developed to enable communities to effectively weigh and integrate human health, socioeconomic, environmental, and ecological factors into their decisions to promote community sustainability. To help achieve this goal, EPA researchers have developed systems approaches to account for the linkages among resources, assets, and outcomes managed by a community. System dynamics (SD) is a member of the family of systems approaches and provides a framework for dynamic modeling that can assist with assessing and understanding complex issues across multiple dimensions. To test the utility of such tools when applied to a real-world situation, the EPA has developed a prototype SD model for community sustainability using the proposed Durham-Orange Light Rail Project (D-O LRP) as a case study.The EPA D-O LRP SD modeling team chose the proposed D-O LRP to demonstrate that an integrated modeling approach could represent the multitude of related cross-sectoral decisions that would be made and the cascading impacts that could result from a light rail transit system connecting Durham and Chapel Hill, NC. In keeping with the SHC vision described above, the proposal for the light rail is a starting point solution for the more intractable problems of population growth, unsustainable land use, environmenta

49 CFR 260.9 - Loan terms.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Loan terms. 260.9 Section 260.9 Transportation... TRANSPORTATION REGULATIONS GOVERNING LOANS AND LOAN GUARANTEES UNDER THE RAILROAD REHABILITATION AND IMPROVEMENT FINANCING PROGRAM Overview § 260.9 Loan terms. The maximum repayment period for direct loans and guaranteed...

43 CFR 431.7 - Administration and management of the Colorado River Dam Fund.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Administration and management of the... management of the Colorado River Dam Fund. Reclamation is responsible for the repayment of the Project and... Federal law. (b) Appropriations for the visitor facilities program and any other purposes authorized by...

Indians' Problems in Acquiring Development Capital. Four Corners Agriculture and Forestry Development Study. Special Report No. 11.

Science.gov (United States)

Fuller, Stephen W.

The difficulty with which American Indians acquire equity capital and an examination of selected Federal programs which make this type of credit available to this minority group are discussed in this report. Specifically, collateral, fractional heirship, ownership of chattels, managerial training, repayment, and servicing of loans are discussed as…

77 FR 58775 - Second Fishing Capacity Reduction Program for the Longline Catcher Processor Subsector of the...

Science.gov (United States)

2012-09-24

... long-line catcher processors harvesting non-pollock groundfish were required to pay and forward a fee... seller reports when a person fails either to pay or to collect the loan repayment fee (2 hours). These... Act, or whether a discrepancy in the name appearing on LLP Licenses and other documents was material...

Shoot-supplied ammonium targets the root auxin influx carrier AUX1 and inhibits lateral root emergence in Arabidopsis

KAUST Repository

Li, Baohai; Li, Qing; Su, Yanhua; Chen, Hao; Xiong, Liming; Mi, Guohua; Kronzucker, Herbert J.; Shi, Weiming

2011-01-01

. In this study, we show that SSA significantly affects lateral root (LR) development. We show that SSA inhibits lateral root primordium (LRP) emergence, but not LRP initiation, resulting in significantly impaired LR number. We show that the inhibition

Incentive-Compatible Sovereign Debt

DEFF Research Database (Denmark)

Bersem, Mario R. C.

This paper presents a theory of sovereign borrowing and lending when there is no court to enforce repayment obligations. Specifically, I extend the costly state verification approach in financial contracting to include an ex-post repayment decision in which the borrower repays creditors to avoid...

7 CFR 3431.17 - VMLRP service agreement offer.

Science.gov (United States)

2010-01-01

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

75 FR 26260 - National Center for Complementary & Alternative Medicine; Notice of Closed Meeting

Science.gov (United States)

2010-05-11

... Complementary & Alternative Medicine; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory..., Research and Training in Complementary and Alternative Medicine, National Institutes of Health, HHS) [[Page... Alternative Medicine Special Emphasis Panel; Loan Repayment Program. Date: May 17, 2010. Time: 8 a.m. to 5 p.m...

Direct Lending Works.

Science.gov (United States)

Riley, Richard W.

1997-01-01

In its third year, direct lending is working well for college students and administration. It is a simpler, faster, more efficient way of getting loan funds to students that cuts out financial middlemen. It helps students manage their finances better when repaying loans, promotes competition, stimulates program innovation, leads to greater…

7 CFR 765.205 - Subordination of liens.

Science.gov (United States)

2010-01-01

... AGRICULTURE SPECIAL PROGRAMS DIRECT LOAN SERVICING-REGULAR Protecting the Agency's Security Interest § 765.205..., expenses, and debt repayment plan; and (6) Verification of all debts. (b) Real estate security. For loans... loan security will be increased by an amount at least equal to the advance to be made under the...

75 FR 70003 - Agency Information Collection Activities: Comment Request

Science.gov (United States)

2010-11-16

... offered by foreign governments and by absorbing credit risks that the private sector will not accept, Ex.... Under the Working Capital Guarantee Program, Ex-Im Bank provides repayment guarantees to lenders on... guaranteed by Ex-Im Bank the guaranteed lender may seek payment by the submission of a claim. This collection...

76 FR 5374 - Agency Information Collection Activities: Comment Request

Science.gov (United States)

2011-01-31

... offered by foreign governments and by absorbing credit risks that the private sector will not accept, Ex.... Under the Working Capital Guarantee Program, Ex-Im Bank provides repayment guarantees to lenders on... guaranteed by Ex-Im Bank the guaranteed lender may seek payment by the submission of a claim. This collection...

12 CFR 717.30 - Obtaining or using medical information in connection with a determination of eligibility for credit.

Science.gov (United States)

2010-01-01

... current and that the consumer has no delinquencies in her repayment history. If the existing debt were... health, condition or history, type of treatment, or prognosis into account as part of any such... use information about: (A) The dollar amount, repayment terms, repayment history, and similar...

12 CFR 222.30 - Obtaining or using medical information in connection with a determination of eligibility for credit.

Science.gov (United States)

2010-01-01

... current and that the consumer has no delinquencies in her repayment history. If the existing debt were... health, condition or history, type of treatment, or prognosis into account as part of any such... use information about: (A) The dollar amount, repayment terms, repayment history, and similar...

12 CFR 334.30 - Obtaining or using medical information in connection with a determination of eligibility for credit.

Science.gov (United States)

2010-01-01

... current and that the consumer has no delinquencies in her repayment history. If the existing debt were... health, condition or history, type of treatment, or prognosis into account as part of any such... use information about: (A) The dollar amount, repayment terms, repayment history, and similar...

12 CFR 571.30 - Obtaining or using medical information in connection with a determination of eligibility for credit.

Science.gov (United States)

2010-01-01

... current and that the consumer has no delinquencies in her repayment history. If the existing debt were... health, condition or history, type of treatment, or prognosis into account as part of any such... use information about: (A) The dollar amount, repayment terms, repayment history, and similar...

12 CFR 232.3 - Financial information exception for obtaining and using medical information.

Science.gov (United States)

2010-01-01

... that the debt is current and that the consumer has no delinquencies in her repayment history. If the..., mental, or behavioral health, condition or history, type of treatment, or prognosis into account as part... example, to obtain and use information about: (i) The dollar amount, repayment terms, repayment history...

A research on personal credit rating under big-data

Science.gov (United States)

Chen, Yong; Nie, Erbao; Chen, Shaozhen

2018-04-01

Solvency mainly discover the availability and fluctuations of one's cashflow, to reveal the reasons for one's balance and future trends, as well as to determine one's ability to obtain funds to repay debt and the flow Release space. the intention to repay reflects the debtor's decision which is made after weighting the benefits and cost of repaying the principal and interest. examining the repaying willingness reveals the debtor's passion to repay the outstanding obligations and the new debt, then based on which we can determine the security of principal and interest payment. risk preference is to examine individual's exact demand for credit, and the adjusting degree between the demand and the solvency, to derive the agent cost and the coverage rate of the new-issued debt.

42 CFR 405.374 - Opportunity for rebuttal.

Science.gov (United States)

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Opportunity for rebuttal. 405.374 Section 405.374 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM FEDERAL HEALTH INSURANCE FOR THE AGED AND DISABLED Suspension of Payment, Recovery of Overpayments, and Repayment of Scholarships and...

78 FR 13359 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

Science.gov (United States)

2013-02-27

... Science AIDS Research (R24). Date: March 21-22, 2013. Time: 8:00 a.m. to 5:00 p.m. Agenda: To review and... Domestic Assistance Program Nos. 93.864, Population Research; 93.865, Research for Mothers and Children; 93.929, Center for Medical Rehabilitation Research; 93.209, Contraception and Infertility Loan Repayment...

Structures and Interactions of Proteins in the Brain

DEFF Research Database (Denmark)

Nielsen, Lau Dalby

The protein low density lipoprotein receptor related protein 1 (LRP1) plays multiple roles in the biology of amyloid β peptide (Aβ) and Alzheimer’s disease. LRP1 is very important for clearance of Aβ both in the brain and by facilitating Aβ export over the blood brain barrier. In spite of the app......The protein low density lipoprotein receptor related protein 1 (LRP1) plays multiple roles in the biology of amyloid β peptide (Aβ) and Alzheimer’s disease. LRP1 is very important for clearance of Aβ both in the brain and by facilitating Aβ export over the blood brain barrier. In spite...... coding for Arc protein has been domesticated from the same branch of genes that has given rise to retroviruses. We show that even despite the large evolutional distance between Arc and retroviruses. Despite large evolutionary distance Arc still self-assemble into higher order structures that resembles...

Grafting of functional methacrylate polymer brushes by photoinduced SET-LRP

Czech Academy of Sciences Publication Activity Database

Vorobii, M.; Pop-Georgievski, Ognen; de los Santos Pereira, Andres; Kostina, N. Yu.; Jezorek, R.; Sedláková, Zdeňka; Percec, V.; Rodriguez-Emmenegger, C.

2016-01-01

Roč. 7, č. 45 (2016), s. 6934-6945 ISSN 1759-9954 R&D Projects: GA ČR(CZ) GJ15-09368Y Grant - others:OPPK(XE) CZ.2.16/3.1.00/21545 Program:OPPK Institutional support: RVO:61389013 Keywords : photo-induced polymerization * polymer brushes * spatial control Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.375, year: 2016

Maternal-fetal cholesterol transport in the second half ofmouse pregnancy does not involve LDL receptor-related protein 2

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

AimLDL receptor-related 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 cholesterol

78 FR 38420 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Science.gov (United States)

2013-06-26

... subtracting an LRP value to a security's last sale price. The Exchange sets and disseminates a specific LRP... Exchange is increasing the highest price per share at which automatic execution is available, the Exchange...-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate Effectiveness of...

Maternal-fetal cholesterol transport in the second half of mouse pregnancy does not involve LDL receptor-related protein 2.

Science.gov (United States)

Zwier, M V; Baardman, M E; van Dijk, T H; Jurdzinski, A; Wisse, L J; Bloks, V W; Berger, R M F; DeRuiter, M C; Groen, A K; Plösch, T

2017-08-01

LDL receptor-related 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 cholesterol availability to maternal-fetal cholesterol transport and fetal cholesterol levels in utero in mice. Lrp2 +/- mice were mated heterozygously to yield fetuses of all three genotypes. Half of the dams received a 0.5% probucol-enriched diet during gestation to decrease maternal HDL cholesterol. At E13.5, the dams received an injection of D7-labelled cholesterol and were provided with 1- 13 C acetate-supplemented drinking water. At E16.5, fetal tissues were collected and maternal cholesterol transport and fetal synthesis quantified by isotope enrichments in fetal tissues by GC-MS. The Lrp2 genotype did not influence maternal-fetal cholesterol transport and fetal cholesterol. However, lowering of maternal plasma cholesterol levels by probucol significantly reduced maternal-fetal cholesterol transport. In the fetal liver, this was associated with increased cholesterol synthesis rates. No indications were found for an interaction between the Lrp2 genotype and maternal probucol treatment. Maternal-fetal cholesterol transport and endogenous fetal cholesterol synthesis depend on maternal cholesterol concentrations but do not involve LRP2 in the second half of murine pregnancy. Our results suggest that the mouse fetus can compensate for decreased maternal cholesterol levels. It remains a relevant question how the delicate system of cholesterol transport and synthesis is regulated in the human fetus and placenta. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

A Literature-Based Analysis of the Learning Curves of Laparoscopic Radical Prostatectomy

Directory of Open Access Journals (Sweden)

Daniel W. Good

2014-05-01

Full Text Available There is a trend for the increased adoption of minimally invasive techniques of radical prostatectomy (RP – laparoscopic (LRP and robotic assisted (RARP – from the traditional open radical retropubic prostatectomy (ORP, popularised by Partin et al. Recently there has been a dramatic expansion in the rates of RARP being performed, and there have been many early reports postulating that the learning curve for RARP is shorter than for LRP. The aim of this study was to review the literature and analyse the length of the LRP learning curves for the various outcome measures: perioperative, oncologic, and functional outcomes. A broad search of the literature was performed in November 2013 using the PubMed database. Only studies of real patients and those from 2004 until 2013 were included; those on simulators were excluded. In total, 239 studies were identified after which 13 were included. The learning curve is a heterogeneous entity, depending entirely on the criteria used to define it. There is evidence of multiple learning curves; however the length of these is dependent on the definitions used by the authors. Few studies use the more rigorous definition of plateauing of the curve. Perioperative learning curve takes approximately 150-200 cases to plateau, oncologic curve approximately 200 cases, and the functional learning curve up to 700 cases to plateau (700 for potency, 200 cases for continence. In this review, we have analysed the literature with respect to the learning curve for LRP. It is clear that the learning curve is long. This necessitates centralising LRP to high volume centres such that surgeons, trainees, and patients are able to utilise the benefits of LRP.

Financial sustainability in savings and credit programmes.

Science.gov (United States)

Havers, M

1996-05-01

This article provides a framework for determining, justifying, and improving financial sustainability of savings and credit programs. Credit programs have income from interest and fees. Income must pay for the cost of funds, loan write-offs, operating costs, and inflation. Reference is made to Otero and Rhyne's four levels of self-sufficiency in credit programs. The Grameen Bank is an example of Level 3 and most credit unions are level 4. Nongovernmental groups in the United Kingdom are level 1 or 2. Experience has shown that removal of subsidies did not affect the quality of services or shift benefits away from the poor. Success in serving poorer people better is attributed 1) to more money being available for lending under tighter management practices, 2) to greater openness to a variety of clients from removal of subsidy restrictions, 3) to a shift to higher interest rates that eliminate richer borrowers, and 4) to a shift to serious collection of loans which is a disincentive to more privileged borrowers. Percentages of loan loss, administration costs, cost of funds, and inflation are useful in measuring the sustainability of credit programs. Interest and fee income must also be measured. Fee repayment rates do not have a common definition of arrears, default, and write-off. A simple measure is the percentage of total costs covered by income. The World Bank recommends the Subsidy Dependence Index. Women tend to be better at repaying loans. Loan size should be related to borrowers' ability to handle the amount of the loan. Low and subsidized interest rates deter depositors and attract richer borrowers. Poorer borrowers are attracted by access to credit and not the cost of credit. Interest rates should be based on market rates. The loan payment should be no longer than necessary. Small groups of borrowers can guarantee each others loans. Group-based loan schemes work best. NGOs must project an image of being serious about loan collections and must take action

Origins of the protein synthesis cycle

Science.gov (United States)

Fox, S. W.

1981-01-01

Largely derived from experiments in molecular evolution, a theory of protein synthesis cycles has been constructed. The sequence begins with ordered thermal proteins resulting from the self-sequencing of mixed amino acids. Ordered thermal proteins then aggregate to cell-like structures. When they contained proteinoids sufficiently rich in lysine, the structures were able to synthesize offspring peptides. Since lysine-rich proteinoid (LRP) also catalyzes the polymerization of nucleoside triphosphate to polynucleotides, the same microspheres containing LRP could have synthesized both original cellular proteins and cellular nucleic acids. The LRP within protocells would have provided proximity advantageous for the origin and evolution of the genetic code.

Common Genetic Variation in the DKK1 Gene is Associated with Hip Axis Length but not with Bone Mineral Density and Bone Turnover Markers in Young Adult Men: Results from the Odense Androgen Study

DEFF Research Database (Denmark)

Piters, Elke; Balemans, Wendy; Nielsen, Torben Leo

2010-01-01

LRP5 was recently confirmed as an important susceptibility gene for osteoporosis. Our objective was to evaluate the effect of DKK1 polymorphisms on bone mineral density (BMD), hip geometry, and bone turnover. DKK1 is a secreted protein that binds to LRP5/6 receptors and inhibits canonical Wnt...

Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling

NARCIS (Netherlands)

Janda, Claudia Y.; Dang, Luke T.; You, Changjiang; Chang, Junlei; Lau, Wim De; Zhong, Zhendong A.; Yan, Kelley S.; Marecic, Owen; Siepe, DIrk; Li, Xingnan; Moody, James D.; Williams, Bart O.; Clevers, Hans; Piehler, Jacob; Baker, David; Kuo, Calvin J.; Garcia, K. Christopher

2017-01-01

Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19

Seventeen copies of the human 37 kDa laminin receptor precursor/p40 ribosome-associated protein gene are processed pseudogenes arisen from retropositional events

DEFF Research Database (Denmark)

Jackers, P; Clausse, N; Fernandez, M

1996-01-01

A cDNA coding for a 37 kDa polypeptide has been identified in several species as both the potential precursor of the 67 kDa laminin receptor (37LRP) and a putative ribosome-associated protein (p40). Interestingly, increased expression of this polypeptide (37LRP/p40) is consistently observed...

Smooth muscle LDL receptor-related protein-1 deletion induces aortic insufficiency and promotes vascular cardiomyopathy in mice.

Directory of Open Access Journals (Sweden)

Joshua E Basford

Full Text Available Valvular disease is common in patients with Marfan syndrome and can lead to cardiomyopathy. However, some patients develop cardiomyopathy in the absence of hemodynamically significant valve dysfunction, suggesting alternative mechanisms of disease progression. Disruption of LDL receptor-related protein-1 (Lrp1 in smooth muscle cells has been shown to cause vascular pathologies similar to Marfan syndrome, with activation of smooth muscle cells, vascular dysfunction and aortic aneurysms. This study used echocardiography and blood pressure monitoring in mouse models to determine whether inactivation of Lrp1 in vascular smooth muscle leads to cardiomyopathy, and if so, whether the mechanism is a consequence of valvular disease. Hemodynamic changes during treatment with captopril were also assessed. Dilation of aortic roots was observed in young Lrp1-knockout mice and progressed as they aged, whereas no significant aortic dilation was detected in wild type littermates. Diastolic blood pressure was lower and pulse pressure higher in Lrp1-knockout mice, which was normalized by treatment with captopril. Aortic dilation was followed by development of aortic insufficiency and subsequent dilated cardiomyopathy due to valvular disease. Thus, smooth muscle cell Lrp1 deficiency results in aortic dilation and insufficiency that causes secondary cardiomyopathy that can be improved by captopril. These findings provide novel insights into mechanisms of cardiomyopathy associated with vascular activation and offer a new model of valvular cardiomyopathy.

Reversal of cisplatin resistance in non-small cell lung cancer stem cells by Taxus chinensis var.

Science.gov (United States)

Jiang, Y Q; Xu, X P; Guo, Q M; Xu, X C; Liu, Q Y; An, S H; Xu, J L; Su, F; Tai, J B

2016-09-02

Drug resistance in cells is a major impedance to successful treatment of lung cancer. Taxus chinensis var. inhibits the growth of tumor cells and promotes the synthesis of interleukins 1 and 2 and tumor necrosis factor, enhancing immune function. In this study, T. chinensis var.-induced cell death was analyzed in lung cancer cells (H460) enriched for stem cell growth in a defined serum-free medium. Taxus-treated stem cells were also analyzed for Rhodamine 123 (Rh-123) expression by flow cytometry, and used as a standard functional indicator of MDR. The molecular basis of T. chinensis var.-mediated drug resistance was established by real-time PCR analysis of ABCC1, ABCB1, and lung resistance-related protein (LRP) mRNA, and western blot analysis of MRP1, MDR1, and LRP. Our results revealed that stem cells treated with higher doses of T. chinensis var. showed significantly lower growth inhibition rates than did H460 cells (P var. and cisplatin was also significantly inhibited (P var. (P var.-treated stem cells showed significant downregulation of the ABCC1, ABCB1, and LRP mRNA and MRP1, MDR1, and LRP (P var.-mediated downregulation of MRP1, MDR1, and LRP might contribute to the reversal of drug resistance in non-small cell lung cancer stem cells.

Using social impact borrowing to expand preschool through third grade programs in urban public schools.

Science.gov (United States)

Temple, Judy A; Reynolds, Arthur J

Budget constraints and difficulty raising taxes limit school districts from expanding education programming even when research shows that additional expenditures would generate economic benefits that are greater than costs. Recently, coalitions of private investors, philanthropists, education practitioners, and government finance analysts have emerged to create opportunities to expand education services that promise high rates of social net benefits without raising taxes or reducing other expenditures. These collaborators have a strong interest in obtaining careful estimates of educational program effectiveness. We describe the use of social-impact borrowing to increase access to the Child-Parent Center preschool-through-third-grade intervention for at-risk students in the Chicago Public School District. The partners include the city, school district, investors, nonprofit organizations, and a university. The key to the feasibility of social-impact borrowing is the ability to document that early intervention can reduce the need for later special-education services. With the help of private investors and nonprofit organizations, it is possible for public school districts to finance services with funds from private sources and use future cost savings to repay this debt. We discuss how social-impact borrowing is being used in Chicago and in Salt Lake County as the nation's first two instances of using pay-for-performance social-impact borrowing to support early education.

The LDL Receptor-Related Protein 1: At the Crossroads of Lipoprotein Metabolism and Insulin Signaling

Directory of Open Access Journals (Sweden)

Dianaly T. Au

2017-01-01

Full Text Available The metabolic syndrome is an escalating worldwide public health concern. Defined by a combination of physiological, metabolic, and biochemical factors, the metabolic syndrome is used as a clinical guideline to identify individuals with a higher risk for type 2 diabetes and cardiovascular disease. Although risk factors for type 2 diabetes and cardiovascular disease have been known for decades, the molecular mechanisms involved in the pathophysiology of these diseases and their interrelationship remain unclear. The LDL receptor-related protein 1 (LRP1 is a large endocytic and signaling receptor that is widely expressed in several tissues. As a member of the LDL receptor family, LRP1 is involved in the clearance of chylomicron remnants from the circulation and has been demonstrated to be atheroprotective. Recently, studies have shown that LRP1 is involved in insulin receptor trafficking and regulation and glucose metabolism. This review summarizes the role of tissue-specific LRP1 in insulin signaling and its potential role as a link between lipoprotein and glucose metabolism in diabetes.

A heuristic algorithm for a multi-product four-layer capacitated location-routing problem

Directory of Open Access Journals (Sweden)

Mohsen Hamidi

2014-01-01

Full Text Available The purpose of this study is to solve a complex multi-product four-layer capacitated location-routing problem (LRP in which two specific constraints are taken into account: 1 plants have limited production capacity, and 2 central depots have limited capacity for storing and transshipping products. The LRP represents a multi-product four-layer distribution network that consists of plants, central depots, regional depots, and customers. A heuristic algorithm is developed to solve the four-layer LRP. The heuristic uses GRASP (Greedy Randomized Adaptive Search Procedure and two probabilistic tabu search strategies of intensification and diversification to tackle the problem. Results show that the heuristic solves the problem effectively.

Denying Loan Access: The Student-Level Consequences When Community Colleges Opt out of the Stafford Loan Program. A CAPSEE Working Paper

Science.gov (United States)

Wiederspan, Mark

2015-01-01

The degree to which students are able to make adequate repayments on their student loans and avoid default is of special concern for colleges. If too many former students go into default, the college will face sanctions by the federal government and lose eligibility to provide currently enrolled students federal financial aid, such as the Pell…

The impact of bladder neck sparing on urinary continence during laparoscopic radical prostatectomy; Results from a high volume centre

Directory of Open Access Journals (Sweden)

Ali Serdar Gozen

2017-10-01

Full Text Available Objective: To evaluate the effects of bladder neck reconstruction techniques on early continence after laparoscopic radical prostatectomy (LRP. Materials and methods: This non-randomized retrospective study analyzed prospectively collected data concerning LRP. In total, 3107 patients underwent LRP between March 1999 and December 2016. Exclusion criteria were preoperative urinary incontinence, previous history of external beam radiotherapy, co-morbities which may affect urinary continence such as diabetes mellitus and/or neurogenic disorders, irregular followup, and follow-up shorter than 24 months. All patients were divided into one of three groups, posterior reconstruction being performed in Group 1 (n = 112, anterior reconstruction in Group 2 (n = 762, and bladder neck sparing (BNS in Group 3 (n = 987. Demographic and pre-, peri-, and postoperative data were collected. Multivariate analyses were performed to determine factors affecting early continence after LRP. Results: 1861 patients were enrolled in the study. The mean follow-up period was 48.12 ± 29.8 months, and subjects’ mean age was 63.6 ± 6.2 years. There was no significant difference among the groups in terms of demographic or preoperative data. Postoperative data, including oncological outcomes, were similar among the groups. The level of early continence was higher in Group 3 than in the other groups (p < 0.001. Multivariate analyses identified BNS and age as parameters significantly affecting early continence levels after LRP (p < 0.001 and p < 0.001, respectively. Bladder neck reconstruction provided less earlier continence than BNS.

Formation of the 67-kDa laminin receptor by acylation of the precursor.

Science.gov (United States)

Butò, S; Tagliabue, E; Ardini, E; Magnifico, A; Ghirelli, C; van den Brûle, F; Castronovo, V; Colnaghi, M I; Sobel, M E; Ménard, S

1998-06-01

Even though the involvement of the 67-kDa laminin receptor (67LR) in tumor invasiveness has been clearly demonstrated, its molecular structure remains an open problem, since only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated so far. A pool of recently obtained monoclonal antibodies directed against the recombinant 37LRP molecule was used to investigate the processing that leads to the formation of the 67-kDa molecule. In soluble extracts of A431 human carcinoma cells, these reagents recognize the precursor molecule as well as the mature 67LR and a 120-kDa molecule. The recovery of these proteins was found to be strikingly dependent upon the cell solubilization conditions: the 67LR is soluble in NP-40-lysis buffer whereas the 37LRP is NP-40-insoluble. Inhibition of 67LR formation by cerulenin indicates that acylation is involved in the processing of the receptor. It is likely a palmitoylation process, as indicated by sensitivity of NP-40-soluble extracts to hydroxylamine treatment. Immunoblotting assays performed with a polyclonal serum directed against galectin3 showed that both the 67- and the 120-kDa proteins carry galectin3 epitopes whereas the 37LRP does not. These data suggest that the 67LR is a heterodimer stabilized by strong intramolecular hydrophobic interactions, carried by fatty acids bound to the 37LRP and to a galectin3 cross-reacting molecule.

Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6.

Science.gov (United States)

Johnson, Bryce G; Ren, Shuyu; Karaca, Gamze; Gomez, Ivan G; Fligny, Cécile; Smith, Benjamin; Ergun, Ayla; Locke, George; Gao, Benbo; Hayes, Sebastian; MacDonnell, Scott; Duffield, Jeremy S

2017-06-01

Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ β -catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis. Copyright © 2017 by the American Society of Nephrology.

Identification of the receptor scavenging hemopexin-heme complexes

DEFF Research Database (Denmark)

Hvidberg, Vibeke; Maniecki, Maciej B; Jacobsen, Christian

2005-01-01

and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons......, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin......-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation....

Determinants of Financial Sustainability for Farm Credit Applications—A Delphi Study

Directory of Open Access Journals (Sweden)

Johannes I. F. Henning

2016-01-01

Full Text Available Farmers use credit from commercial credit providers to finance production activities. Commercial credit providers have to predict the financial sustainability of the enterprise to ensure that the borrower will have the ability to repay the loan. A Delphi study was conducted to explore what factors are used as indicators of loan-repayment ability of farmers. The objective was not only to identify factors that are currently considered, but also to identify other personal attributes that may improve the accuracy in predicting the repayment ability of potential borrowers. The Delphi was applied to a panel consisting of nine credit analysts and credit managers from a commercial credit provider in South Africa. The results indicate that the current and past financial performance, account standing, collateral, and credit record of the farm are very important in the assessment of applications in terms of financial performance. Experience and the success factors compared to competitors were found to be important, while age and education/qualification are regarded as less important in predicting repayment ability. The results also show that, although not currently objectively included in credit evaluations, credit analysis regards leadership and human relations; commitment and confidence; internal locus of control; self-efficacy; calculated risk taking; need for achievement; and opportunity seeking as important indicators of the ability of potential borrows to repay their loans. Thus, credit analysts and managers also regard management abilities and entrepreneurial characteristics of potential borrowers to be good indicators of repayment ability. Results from this research provide new indicator factors that can be used to extend existing credit evaluation instruments in order to more accurately predict repayment ability.

Nanobody®-based chromatin immunoprecipitation/micro-array analysis for genome-wide identification of transcription factor DNA binding sites

Science.gov (United States)

Nguyen-Duc, Trong; Peeters, Eveline; Muyldermans, Serge; Charlier, Daniel; Hassanzadeh-Ghassabeh, Gholamreza

2013-01-01

Nanobodies® are single-domain antibody fragments derived from camelid heavy-chain antibodies. Because of their small size, straightforward production in Escherichia coli, easy tailoring, high affinity, specificity, stability and solubility, nanobodies® have been exploited in various biotechnological applications. A major challenge in the post-genomics and post-proteomics era is the identification of regulatory networks involving nucleic acid–protein and protein–protein interactions. Here, we apply a nanobody® in chromatin immunoprecipitation followed by DNA microarray hybridization (ChIP-chip) for genome-wide identification of DNA–protein interactions. The Lrp-like regulator Ss-LrpB, arguably one of the best-studied specific transcription factors of the hyperthermophilic archaeon Sulfolobus solfataricus, was chosen for this proof-of-principle nanobody®-assisted ChIP. Three distinct Ss-LrpB-specific nanobodies®, each interacting with a different epitope, were generated for ChIP. Genome-wide ChIP-chip with one of these nanobodies® identified the well-established Ss-LrpB binding sites and revealed several unknown target sequences. Furthermore, these ChIP-chip profiles revealed auxiliary operator sites in the open reading frame of Ss-lrpB. Our work introduces nanobodies® as a novel class of affinity reagents for ChIP. Taking into account the unique characteristics of nanobodies®, in particular, their short generation time, nanobody®-based ChIP is expected to further streamline ChIP-chip and ChIP-Seq experiments, especially in organisms with no (or limited) possibility of genetic manipulation. PMID:23275538

Aggregate Uncertainty, Money and Banking

OpenAIRE

Hongfei Sun

2006-01-01

This paper studies the problem of monitoring the monitor in a model of money and banking with aggregate uncertainty. It shows that when inside money is required as a means of bank loan repayment, a market of inside money is entailed at the repayment stage and generates information-revealing prices that perfectly discipline the bank. The incentive problem of a bank is costlessly overcome simply by involving inside money in repayment. Inside money distinguishes itself from outside money by its ...

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.

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.

Analysis of a two-domain binding site for the urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex in low-density-lipoprotein-receptor-related protein.

Science.gov (United States)

Andersen, O M; Petersen, H H; Jacobsen, C; Moestrup, S K; Etzerodt, M; Andreasen, P A; Thøgersen, H C

2001-07-01

The low-density-lipoprotein-receptor (LDLR)-related protein (LRP) is composed of several classes of domains, including complement-type repeats (CR), which occur in clusters that contain binding sites for a multitude of different ligands. Each approximately 40-residue CR domain contains three conserved disulphide linkages and an octahedral Ca(2+) cage. LRP is a scavenging receptor for ligands from extracellular fluids, e.g. alpha(2)-macroglobulin (alpha(2)M)-proteinase complexes, lipoprotein-containing particles and serine proteinase-inhibitor complexes, like the complex between urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor-1 (PAI-1). In the present study we analysed the interaction of the uPA-PAI-1 complex with an ensemble of fragments representing a complete overlapping set of two-domain fragments accounting for the ligand-binding cluster II (CR3-CR10) of LRP. By ligand blotting, solid-state competition analysis and surface-plasmon-resonance analysis, we demonstrate binding to multiple CR domains, but show a preferential interaction between the uPA-PAI-1 complex and a two-domain fragment comprising CR domains 5 and 6 of LRP. We demonstrate that surface-exposed aspartic acid and tryptophan residues at identical positions in the two homologous domains, CR5 and CR6 (Asp(958,CR5), Asp(999,CR6), Trp(953,CR5) and Trp(994,CR6)), are critical for the binding of the complex as well as for the binding of the receptor-associated protein (RAP) - the folding chaperone/escort protein required for transport of LRP to the cell surface. Accordingly, the present work provides (1) an identification of a preferred binding site within LRP CR cluster II; (2) evidence that the uPA-PAI-1 binding site involves residues from two adjacent protein domains; and (3) direct evidence identifying specific residues as important for the binding of uPA-PAI-1 as well as for the binding of RAP.

A variable neighborhood descent based heuristic to solve the capacitated location-routing problem

Directory of Open Access Journals (Sweden)

M. S. Jabal-Ameli

2011-01-01

Full Text Available Location-routing problem (LRP is established as a new research area in the context of location analysis. The primary concern of LRP is on locating facilities and routing of vehicles among established facilities and existing demand points. In this work, we address the capacitated LRP which arises in many practical applications within logistics and supply chain management. The objective is to minimize the overall system costs which include the fixed costs of opening depots and using vehicles at each depot site, and the variable costs associated with delivery activities. A novel heuristic is proposed which is based on variable neighborhood descent (VND algorithm to solve the resulted problem. The computational study indicates that the proposed VND based heuristic is highly competitive with the existing solution algorithms in terms of solution quality.

The lifetime cost to English students of borrowing to invest in a medical degree: a gender comparison using data from the Office for National Statistics.

Science.gov (United States)

Ercolani, Marco G; Vohra, Ravinder S; Carmichael, Fiona; Mangat, Karanjit; Alderson, Derek

2015-04-21

To evaluate this impact on male and female English medical graduates by estimating the total time and amount repaid on loans taken out with the UK's Student Loans Company (SLC). UK. 4286 respondents with a medical degree in the Labour Force Surveys administered by the Office for National Statistics (ONS) between 1997 and 2014. Age-salary profiles were generated to estimate the repayment profiles for different levels of initial graduate debt. 2195 female and 2149 male medical graduates were interviewed by the ONS. Those working full-time (73.1% females and 96.1% males) were analysed in greater depth. Following standardisation to 2014 prices, average full-time male graduates earned up to 35% more than females by the age of 55. The initial graduate debt from tuition fees alone amounts to £39,945.69. Owing to interest charges on this debt the average full-time male graduate repays £57,303 over 20 years, while the average female earns less and so repays £61,809 over 26 years. When additional SLC loans are required for maintenance, the initial graduate debt can be as high as £81,916 and, as SLC debt is written off 30 years after graduation, the average female repays £75,786 while the average male repays £110,644. Medical graduates on an average salary are unlikely to repay their SLC debt in full. This is a consequence of higher university fees and as SLC debt is written off 30 years after graduation. This results in the average female graduate repaying more when debt is low, but a lower amount when debt is high compared to male graduates. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Regulation of neuronal APL-1 expression by cholesterol starvation.

Directory of Open Access Journals (Sweden)

Mary Wiese

Full Text Available BACKGROUND: Alzheimer's disease (AD is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP. While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD, sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1, and lrp-1 (lipoprotein receptor-related protein 1, suggesting a potential interaction between apl-1 and cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot. CONCLUSIONS: Our results show that cholesterol and lrp-1 are involved in the regulation of synaptic transmission, similar to apl-1. Both are able to modulate APL-1 protein levels in neurons, however cholesterol changes do not affect global apl-1 transcription or APL-1 protein indicating the changes are specific to neurons. Thus, regulation of synaptic transmission and molting by LRP-1 and cholesterol may be mediated by their ability to control APL-1 neuronal protein expression.

Learning curve of robot-assisted laparoscopic radical prostatectomy for a single experienced surgeon: comparison with simultaneous laparoscopic radical prostatectomy.

Science.gov (United States)

Ku, Ja Yoon; Ha, Hong Koo

2015-04-01

Despite the large number of analytical reports regarding the learning curve in the transition from open to robot-assisted radical prostatectomy (RARP), few comparative results with laparoscopic radical prostatectomy (LRP) have been reported. Thus, we evaluated operative and postoperative outcomes in RARP versus 100 simultaneously performed LRPs. A single surgeon had performed more than 1,000 laparoscopic operations, including 415 cases of radical nephrectomy, 85 radical cystectomies, 369 radical prostatectomies, and treatment of 212 other urological tumors, since 2009. We evaluated operative (operation time, intraoperative transfusion, complications, hospital stay, margin status, pathological stage, Gleason score) and postoperative (continence and erectile function) parameters in initial cases of RARP without tutoring compared with 100 recently performed LRPs. Mean operation time and length of hospital stay for RARP and LRP were 145.5±43.6 minutes and 118.1±39.1 minutes, and 6.4±0.9 days and 6.6±1.1 days, respectively (p=0.003 and p=0.721). After 17 cases, the mean operation time for RARP was similar to LRP (less than 2 hours). Positive surgical margins in localized cancer were seen in 11.1% and 8.9% of cases in RARP and LRP, respectively (p=0.733). At postoperative 3 months, sexual intercourse was reported in 14.0% and 12.0%, and pad-free continence in 96.0% and 81.0% in patients with RARP and LRP, respectively (p=0.796 and p=0.012). Previous large-volume experience of LRPs may shorten the learning curve for RARP in terms of oncological outcome. Additionally, previous experience with laparoscopy may improve the functional outcomes of RARP.

Activated α2 -Macroglobulin Induces Mesenchymal Cellular Migration Of Raw264.7 Cells Through Low-Density Lipoprotein Receptor-Related Protein 1.

Science.gov (United States)

Ferrer, Darío G; Dato, Virginia Actis; Fincati, Javier R Jaldín; Lorenc, Valeria E; Sánchez, María C; Chiabrando, Gustavo A

2017-07-01

Distinct modes of cell migration contribute to diverse types of cell movements. The mesenchymal mode is characterized by a multistep cycle of membrane protrusion, the formation of focal adhesion, and the stabilization at the leading edge associated with the degradation of extracellular matrix (ECM) components and with regulated extracellular proteolysis. Both α 2 -Macroglobulin (α 2 M) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1), play important roles in inflammatory processes, by controlling the extracellular activity of several proteases. The binding of the active form of α 2 M (α 2 M*) to LRP1 can also activate different signaling pathways in macrophages, thus inducing extracellular matrix metalloproteinase-9 (MMP-9) activation and cellular proliferation. In the present study, we investigated whether the α 2 M*/LRP1 interaction induces cellular migration of the macrophage-derived cell line, Raw264.7. By using the wound-scratch migration assay and confocal microscopy, we demonstrate that α 2 M* induces LRP1-mediated mesenchymal cellular migration. This migration exhibits the production of enlarged cellular protrusions, MT1-MMP distribution to these leading edge protrusions, actin polymerization, focal adhesion formation, and increased intracellular LRP1/β1-integrin colocalization. Moreover, the presence of calphostin-C blocked the α 2 M*-stimulated cellular protrusions, suggesting that the PKC activation is involved in the cellular motility of Raw264.7 cells. These findings could constitute a therapeutic target for inflammatory processes with deleterious consequences for human health, such as rheumatoid arthritis, atherosclerosis and cancer. J. Cell. Biochem. 118: 1810-1818, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Thermo-mechanical behaviour of FBTR reactor vessel due to natural convection in cover gas space

International Nuclear Information System (INIS)

Srinivasan, G.; Varadarajan, S.; Kapoor, R.P.

1988-01-01

Fast Breeder Test Reactor is a 40 MW(t), loop type sodium cooled reactor, similar in design to Rapsodie. The Reactor Assembly, which is the heart of FBTR, comprises the Reactor Vessel (RV) housed in a safety vessel within a concrete cell (A1 Cell). The RV which supports the core is shielded at the top by two rotatable plugs which are stacked with layers of borated graphite and steel. The smaller plug (SRP), is mounted excentric to the larger one (LRP). A nominal annular gap of 16 mm is provided between RV and LRP and between LRP and SRP to enable free rotation of the plugs. Stainless Steel insulation is fixed inside the steel vessel, to avoid overheating of the A1 Cell concrete. The core is supported by the Grid Plate (GP), bolted to the RV. During preheating, sodium charging and isothermal runs upto 350 0 C, temperature asymmetries were noticed in the reactor vessel wall in the cover gas space. This was attributable to convection currents in the annulus between RV and LRP. The asymmetries also resulted in a lateral shift of the grid plate. This paper discusses our experience in suppressing these convection currents, and minimising the grid plate shift

Cisplatin induces expression of drug resistance-related genes through c-jun N-terminal kinase pathway in human lung cancer cells.

Science.gov (United States)

Xu, Li; Fu, Yingya; Li, Youlun; Han, Xiaoli

2017-08-01

Change of multidrug resistance-related genes (e.g., lung resistance protein, LRP) and overexpression of anti-apoptotic genes (Bcl-2, Bcl-Xl, XIAP, Survivin) are responsible for cisplatin resistance. In our study, we investigated the mechanism by which cisplatin induces LRP, Bcl-2, Bcl-xL, XIAP, and Survivin expression in human lung adenocarcinoma A549 cells and human H446 small cell lung cancer cells at mRNA and protein levels. In our study, cell proliferation was assessed with CCK-8 assays, and cell apoptosis was assessed with flow cytometric analysis and Annexin-V/PI staining. qPCR was used to complete RNA experiments. Protein expression was assessed with Western blotting. Cisplatin increased Bcl-2, LRP, and Survivin expression, but decreased Bcl-xL and XIAP expression in a dose-dependent manner. Preincubation with JNK-specific inhibitor, SP600125, significantly inhibited these genes' expression at mRNA and protein levels, enhanced chemosensitivity of lung cancer cells to cisplatin, and promoted cisplatin-induced apoptosis. Our data suggest that the JNK signaling pathway plays an important role in cisplatin resistance. Lung resistance protein (LRP) and anti-apoptotic genes (Bcl-2, Bcl-Xl, XIAP, Survivin) are involved in the process. The results reminded us of a novel therapy target for lung cancer treatment.

29 CFR 4047.5 - Repayment of PBGC payments of guaranteed benefits.

Science.gov (United States)

2010-07-01

... from its single-employer insurance fund (the fund established pursuant to ERISA section 4005(a)) to pay... owed to the plan, the liquidity of plan assets, the interests of the single-employer insurance program...

Financing physical therapy doctoral education: methods used by entry-level students and the financial impact after graduation.

Science.gov (United States)

Thompson, Kris; Coon, Jill; Handford, Leandrea

2011-01-01

With the move to the doctor of physical therapy (DPT) degree and increasing tuition costs, there is concern about financing entry-level education. The purposes of this study were to identify how students finance their DPT education and to describe the financial impact after graduation. A written survey was used to collect data on financing DPT education, student debt, and the financial impact on graduates. There were 92 subjects who had graduated from one program. Frequencies as well as nonparametric statistics using cross-tabulations and chi-squared statistics were calculated. The response rate was 55%. Of the respondents, 86% had student loans, 66% worked during school, 57% received some family assistance, and 21% had some scholarship support. The amount of monthly loan repayment was not statistically related to the ability to save for a house, the ability to obtain a loan for a house or car, or the decision to have children. Saving for the future (p = 0.016) and lifestyle choices (p = 0.035) were related to the amount of monthly loan repayment. Major sources of funding were student loans, employment income, and/or family assistance. Respondent's ability to save for the future and lifestyle choices were negatively impacted when loan debt increased. Physical therapist education programs should consider offering debt planning and counseling.

An Adaptive Tabu Search Heuristic for the Location Routing Pickup and Delivery Problem with Time Windows with a Theater Distribution Application

Science.gov (United States)

2006-08-01

including approximations of delivery costs. The solution of a sub-problem provides input for another sub-problem. Perl (1983) and Perl and Daskin (1985...developed in this section represents a modification and combination of both the three-layer location routing formulation of Perl and Daskin (1985) and the...1985) LRP formulation to create the LPDPTW. 4.2.1 Generalization of the LRP Perl and Daskin (1985) utilize a fixed charge location problem as the

Other people’s money: essays on capital market frictions

NARCIS (Netherlands)

Bersem, M.R.C.

2012-01-01

This dissertation investigates capital market frictions across three themes. The first theme is sovereign debt. Recent experience in the EU shows that it can be complex to enforce the repayment promises of states. Furthermore, governments are better informed about their repayment capacity than

Modernization of WWER-1000 radiation monitoring systems

Energy Technology Data Exchange (ETDEWEB)

Smith, T [General Atomics, San Diego, CA (United States)

1996-12-31

A modernization scheme of the radiation monitoring system for WWER-1000 is proposed. It has a purpose to comply with international standards and to reduce operational and maintenance cost by deleting obsolete components and reducing the number of detector channels. Detailed layouts of I/C system architecture, digital radiation monitoring system (DRAMS) architecture and LRP block diagram are presented. If planned and implemented properly, this program can provide cost savings by reducing time required to access and display data and maintenance cost by deleting obsolete parts and decreasing the number of detector channels. 3 figs.

Modernization of WWER-1000 radiation monitoring systems

International Nuclear Information System (INIS)

Smith, T.

1995-01-01

A modernization scheme of the radiation monitoring system for WWER-1000 is proposed. It has a purpose to comply with international standards and to reduce operational and maintenance cost by deleting obsolete components and reducing the number of detector channels. Detailed layouts of I/C system architecture, digital radiation monitoring system (DRAMS) architecture and LRP block diagram are presented. If planned and implemented properly, this program can provide cost savings by reducing time required to access and display data and maintenance cost by deleting obsolete parts and decreasing the number of detector channels. 3 figs

Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjögren's syndrome.

Science.gov (United States)

Johar, Angad S; Mastronardi, Claudio; Rojas-Villarraga, Adriana; Patel, Hardip R; Chuah, Aaron; Peng, Kaiman; Higgins, Angela; Milburn, Peter; Palmer, Stephanie; Silva-Lara, Maria Fernanda; Velez, Jorge I; Andrews, Dan; Field, Matthew; Huttley, Gavin; Goodnow, Chris; Anaya, Juan-Manuel; Arcos-Burgos, Mauricio

2015-06-02

Multiple autoimmune syndrome (MAS), an extreme phenotype of autoimmune disorders, is a very well suited trait to tackle genomic variants of these conditions. Whole exome sequencing (WES) is a widely used strategy for detection of protein coding and splicing variants associated with inherited diseases. The DNA of eight patients affected by MAS [all of whom presenting with Sjögren's syndrome (SS)], four patients affected by SS alone and 38 unaffected individuals, were subject to WES. Filters to identify novel and rare functional (pathogenic-deleterious) homozygous and/or compound heterozygous variants in these patients and controls were applied. Bioinformatics tools such as the Human gene connectome as well as pathway and network analysis were applied to test overrepresentation of genes harbouring these variants in critical pathways and networks involved in autoimmunity. Eleven novel and rare functional variants were identified in cases but not in controls, harboured in: MACF1, KIAA0754, DUSP12, ICA1, CELA1, LRP1/STAT6, GRIN3B, ANKLE1, TMEM161A, and FKRP. These were subsequently subject to network analysis and their functional relatedness to genes already associated with autoimmunity was evaluated. Notably, the LRP1/STAT6 novel mutation was homozygous in one MAS affected patient and heterozygous in another. LRP1/STAT6 disclosed the strongest plausibility for autoimmunity. LRP1/STAT6 are involved in extracellular and intracellular anti-inflammatory pathways that play key roles in maintaining the homeostasis of the immune system. Further; networks, pathways, and interaction analyses showed that LRP1 is functionally related to the HLA-B and IL10 genes and it has a substantial impact within immunological pathways and/or reaction to bacterial and other foreign proteins (phagocytosis, regulation of phospholipase A2 activity, negative regulation of apoptosis and response to lipopolysaccharides). Further, ICA1 and STAT6 were also closely related to AIRE and IRF5, two very

Tonoplast aquaporins facilitate lateral root emergence

DEFF Research Database (Denmark)

Reinhardt, Hagen; Hachez, Charles; Bienert, Manuela Désirée

2016-01-01

Aquaporins (AQPs) are water channels allowing fast and passive diffusion of water across cell membranes. It was hypothesized that AQPs contribute to cell elongation processes by allowing water influx across the plasma membrane and the tonoplast to maintain adequate turgor pressure. Here, we report...... mutants showed no or minor reduction in growth of the main root. This phenotype was due to the retardation of LRP emergence. Live cell imaging revealed that tight spatiotemporal control of TIP abundance in the tonoplast of the different LRP cells is pivotal to mediating this developmental process. While...... lateral root emergence is correlated to a reduction of AtTIP1;1 and AtTIP1;2 protein levels in LRPs, expression of AtTIP2;1 is specifically needed in a restricted cell population at the base, then later at the flanks, of developing LRPs. Interestingly, the LRP emergence phenotype of the triple tip mutants...

IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway

International Nuclear Information System (INIS)

Ozeki, Nobuaki; Hase, Naoko; Hiyama, Taiki; Yamaguchi, Hideyuki; Kawai, Rie; Kondo, Ayami; Nakata, Kazuhiko; Mogi, Makio

2014-01-01

We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into α2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1β was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1β increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3 mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1β-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1β-induced proliferation of ES cell-derived odontoblast-like cells. - Highlights: • IL-1β induces Wnt5, Lrp5/Fzd9 and MMP-3 in ES cell-derived odontoblast-like cells. • IL-1β-induced Wnt5 expression results in increased cell proliferation. • Exogenous Wnt5 increases MMP-3 activity and cell proliferation. • Exogenous Wnt5 rescues IL-1β-driven proliferation with anti-Wnt5 siRNA suppression. • IL-1β-induced cell proliferation involves Wnt5, Lrp5, and MMP-3 sequentially

IL-1β-induced, matrix metalloproteinase-3-regulated proliferation of embryonic stem cell-derived odontoblastic cells is mediated by the Wnt5 signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Ozeki, Nobuaki; Hase, Naoko; Hiyama, Taiki; Yamaguchi, Hideyuki; Kawai, Rie [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650 (Japan)

2014-10-15

We previously established a method for differentiating induced pluripotent stem cells and embryonic stem (ES) cells into α2 integrin-positive odontoblast-like cells. We also reported that interleukin (IL)-1β induces matrix metalloproteinase (MMP)-3-regulated cell proliferation and suppresses apoptosis in these cells, suggesting that MMP-3 plays a potentially unique physiological role in the regeneration of odontoblast-like cells. Here, we examined whether up-regulation of MMP-3 activity by IL-1β was mediated by Wnt signaling and led to increased proliferation of odontoblast-like cells. IL-1β increased mRNA and protein levels of Wnt5a, Wnt5b and the Wnt receptor Lrp5. Exogenous Wnt5a and Wnt5b were found to increase MMP-3 mRNA, protein and activity, and interestingly the rate of proliferation in these cells. Treatment with siRNAs against Wnt5a, Wnt5b and Lrp5 suppressed the IL-1β-induced increase in MMP-3 expression and suppressed cell proliferation, an effect rescued by application of exogenous Wnt5. These results demonstrate the sequential involvement of Wnt5, Lrp5 and MMP-3 in effecting IL-1β-induced proliferation of ES cell-derived odontoblast-like cells. - Highlights: • IL-1β induces Wnt5, Lrp5/Fzd9 and MMP-3 in ES cell-derived odontoblast-like cells. • IL-1β-induced Wnt5 expression results in increased cell proliferation. • Exogenous Wnt5 increases MMP-3 activity and cell proliferation. • Exogenous Wnt5 rescues IL-1β-driven proliferation with anti-Wnt5 siRNA suppression. • IL-1β-induced cell proliferation involves Wnt5, Lrp5, and MMP-3 sequentially.

Robot-assisted radical prostatectomy has lower biochemical recurrence than laparoscopic radical prostatectomy: Systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Seon Heui Lee

2017-05-01

Full Text Available Purpose: To assess the effectiveness and safety of robot-assisted radical prostatectomy (RARP versus laparoscopic radical prostatectomy (LRP in the treatment of prostate cancer. Materials and Methods: Existing systematic reviews were updated to investigate the effectiveness and safety of RARP. Electronic databases, including Ovid MEDLINE, Ovid Embase, the Cochrane Library, KoreaMed, Kmbase, and others, were searched through July 2014. The quality of the selected systematic reviews was assessed by using the revised assessment of multiple systematic reviews (R-Amstar and the Cochrane Risk of Bias tool. Meta-analysis was performed by using Revman 5.2 (Cochrane Community and Comprehensive Meta-Analysis 2.0 (CMA; Biostat. Cochrane Q and I2 statistics were used to assess heterogeneity. Results: Two systematic reviews and 16 additional studies were selected from a search performed of existing systematic reviews. These included 2 randomized controlled clinical trials and 28 nonrandomized comparative studies. The risk of complications, such as injury to organs by the Clavien-Dindo classification, was lower with RARP than with LRP (relative risk [RR], 0.44; 95% confidence interval [CI], 1.23–0.85; p=0.01. The risk of urinary incontinence was lower (RR, 0.43; 95% CI, 0.31–0.60; p<0.000001 and the potency rate was significantly higher with RARP than with LRP (RR, 1.38; 95% CI, 1.11–1.70; I2 =78%; p=0.003. Regarding positive surgical margins, no significant difference in risk between the 2 groups was observed; however, the biochemical recurrence rate was lower after RARP than after LRP (RR, 0.59; 95% CI, 0.48–0.73; I2 =21%; p<0.00001. Conclusions: RARP appears to be a safe and effective technique compared with LRP with a lower complication rate, better potency, a higher continence rate, and a decreased rate of biochemical recurrence.

Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early Differentiation of Human Neural Stem Cells.

Science.gov (United States)

Bengoa-Vergniory, Nora; Gorroño-Etxebarria, Irantzu; López-Sánchez, Inmaculada; Marra, Michele; Di Chiaro, Pierluigi; Kypta, Robert

2017-10-01

Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by expression of the genes DCX, NEUROD1, and NGN1, suggesting ROR2 signals normally prevent differentiation. Silencing of the other Wnt receptors singly did not affect Wnt-3a-induced neuronal differentiation. However, pairwise silencing of ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal differentiation, as detected by reductions in the expression of neuronal genes and immunocytochemical detection of DCX, NEUROD1 and DCX. Ectopic expression of these receptors in HEK 293 cells increased ATF2-dependent transcription. In addition, ROR1 coimmunoprecipitated with FZD4 and LRP6 in transfected HEK 293 cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected L cells. Wnt-3a did not appear to affect these interactions but did alter the interactions between LRP6 and FZD4/5. Together, these observations highlight roles for ROR1, LRP6, FZD4, and FZD5 in neural stem cell differentiation and provide support for a model in which dynamic interactions among these receptors mediate Wnt-3a activation of ATF2 signaling.

38 CFR 36.4319 - Servicer loss-mitigation options and incentives.

Science.gov (United States)

2010-07-01

... options or alternatives to foreclosure completed: repayment plans, special forbearance agreements, loan modifications, compromise sales, and deeds-in-lieu of foreclosure. Only one incentive payment will be made with.... (b) The amount of the incentive payment is as follows: Tier ranking One Two Three Four Repayment Plan...

Strategic loan defaults and coordination : An experimental analysis

NARCIS (Netherlands)

Trautmann, S.T.; Vlahu, R.

2013-01-01

This paper experimentally studies the impact of bank and borrower fundamentals on loan repayment. We find that solvent borrowers are more likely to default strategically when the bank’s expected strength is low, although loan repayment is a Pareto dominant Nash equilibrium. Borrowers are also less

EFEKTIVITAS PIDANA PEMBAYARAN UANG PENGGANTI DALAM TINDAK PIDANA KORUPSI (Studi Putusan Tindak Pidana Korupsi di Pengadilan Negeri Purwokerto

Directory of Open Access Journals (Sweden)

Ade Paul Lukas

2010-05-01

Full Text Available This punishment is proved not effective because there were only two person punished who repaid. The rest failed to do so due either to lack of money or liquid assets. Instead they signed a letter stating their inability to repay the corrupted money and their readiness to undergo subsidiary punishment. The verdicts of Purwokerto regential Court against corruption act during the period between 2004 through 2008 stated that the punished were given additional punishment to repay the corrupted money but not all of them were punished with such additional punishment. The punishment given was without the obligation to repay and verdict of not guilty. There was constraint from the legal aspect. The constraining factors were the difficulty the public attorney faced in tracing the wealth obtained from corruption. There was also the unawareness of the society to report corruption act.  Keyword : Legal effectiveness, Repay the corrupted money, Corruption

Shoot-supplied ammonium targets the root auxin influx carrier AUX1 and inhibits lateral root emergence in Arabidopsis

KAUST Repository

Li, Baohai

2011-03-24

Deposition of ammonium (NH4 +) from the atmosphere is a substantial environmental problem. While toxicity resulting from root exposure to NH4 + is well studied, little is known about how shoot-supplied ammonium (SSA) affects root growth. In this study, we show that SSA significantly affects lateral root (LR) development. We show that SSA inhibits lateral root primordium (LRP) emergence, but not LRP initiation, resulting in significantly impaired LR number. We show that the inhibition is independent of abscisic acid (ABA) signalling and sucrose uptake in shoots but relates to the auxin response in roots. Expression analyses of an auxin-responsive reporter, DR5:GUS, and direct assays of auxin transport demonstrated that SSA inhibits root acropetal (rootward) auxin transport while not affecting basipetal (shootward) transport or auxin sensitivity of root cells. Mutant analyses indicated that the auxin influx carrier AUX1, but not the auxin efflux carriers PIN-FORMED (PIN)1 or PIN2, is required for this inhibition of LRP emergence and the observed auxin response. We found that AUX1 expression was modulated by SSA in vascular tissues rather than LR cap cells in roots. Taken together, our results suggest that SSA inhibits LRP emergence in Arabidopsis by interfering with AUX1-dependent auxin transport from shoot to root. © 2011 Blackwell Publishing Ltd.

Cardiac protein expression patterns are associated with distinct inborn exercise capacity in non-selectively bred rats

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L.P. Ribeiro

2018-01-01

Full Text Available In the present study, we successfully demonstrated for the first time the existence of cardiac proteomic differences between non-selectively bred rats with distinct intrinsic exercise capacities. A proteomic approach based on two-dimensional gel electrophoresis coupled to mass spectrometry was used to study the left ventricle (LV tissue proteome of rats with distinct intrinsic exercise capacity. Low running performance (LRP and high running performance (HRP rats were categorized by a treadmill exercise test, according to distance run to exhaustion. The running capacity of HRPs was 3.5-fold greater than LRPs. Protein profiling revealed 29 differences between HRP and LRP rats (15 proteins were identified. We detected alterations in components involved in metabolism, antioxidant and stress response, microfibrillar and cytoskeletal proteins. Contractile proteins were upregulated in the LVs of HRP rats (α-myosin heavy chain-6, myosin light chain-1 and creatine kinase, whereas the LVs of LRP rats exhibited upregulation in proteins associated with stress response (aldehyde dehydrogenase 2, α-crystallin B chain and HSPβ-2. In addition, the cytoskeletal proteins desmin and α-actin were upregulated in LRPs. Taken together, our results suggest that the increased contractile protein levels in HRP rats partly accounted for their improved exercise capacity, and that proteins considered risk factors to the development of cardiovascular disease were expressed in higher amounts in LRP animals.

5 CFR 1630.11 - Requirements for requests to amend records.

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2010-01-01

..., investment allocation, interfund transfers, loans, loan repayments, and withdrawals Write to TSP record..., retirement code, address, loan repayments, the amount of participant's contribution, amount of the Government... listed in § 1630.4. The words “Privacy Act—Request to Amend Record” should be written on the letter and...

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

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2010-07-01

..., except for a residency program in dentistry. (3) The institution of higher education at which the... or state public assistance program, such as Aid to Families with Dependent Children, Supplemental... is determined by counting the borrower, the borrower's spouse, and the borrower's children, including...

26 CFR 1.46-3 - Qualified investment.

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2010-04-01

... section 593 applies, regulated investment companies or real estate investment trusts subject to taxation... the utility facilities is advanced by Y under a contract providing that X will repay the advances over... repayable by X even though the full amount advanced by Y has not been repaid. Assuming that the utility...

7 CFR 773.6 - Eligibility requirements.

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2010-01-01

... Nationalization Act. For a business entity applicant, the majority of the business entity must be owned by members... information; and (g) The individual or business entity loan applicant and all entity members must have acceptable credit history demonstrated by debt repayment. A history of failure to repay past debts as they...

An adaptive large neighborhood search heuristic for Two-Echelon Vehicle Routing Problems arising in city logistics

Science.gov (United States)

Hemmelmayr, Vera C.; Cordeau, Jean-François; Crainic, Teodor Gabriel

2012-01-01

In this paper, we propose an adaptive large neighborhood search heuristic for the Two-Echelon Vehicle Routing Problem (2E-VRP) and the Location Routing Problem (LRP). The 2E-VRP arises in two-level transportation systems such as those encountered in the context of city logistics. In such systems, freight arrives at a major terminal and is shipped through intermediate satellite facilities to the final customers. The LRP can be seen as a special case of the 2E-VRP in which vehicle routing is performed only at the second level. We have developed new neighborhood search operators by exploiting the structure of the two problem classes considered and have also adapted existing operators from the literature. The operators are used in a hierarchical scheme reflecting the multi-level nature of the problem. Computational experiments conducted on several sets of instances from the literature show that our algorithm outperforms existing solution methods for the 2E-VRP and achieves excellent results on the LRP. PMID:23483764

Cross-talk between insulin and Wnt signaling in preadipocytes

DEFF Research Database (Denmark)

Palsgaard, Jane; Emanuelli, Brice; Winnay, Jonathon N

2012-01-01

and appears to be due to an inducible interaction between LRP5 and the insulin receptor as demonstrated by co-immunoprecipitation. These data demonstrate that Wnt and insulin signaling pathways exhibit cross-talk at multiple levels. Wnt induces phosphorylation of Akt, ERK1/2, and GSK3β, and this is dependent...... and LRP6 and with and without knock-out of insulin and IGF-1 receptors. We find that Wnt stimulation leads to phosphorylation of insulin signaling key mediators, including Akt, GSK3β, and ERK1/2, although with a lower fold stimulation and slower time course than observed for insulin. These Wnt effects...... are insulin/IGF-1 receptor-dependent and are lost in insulin/IGF-1 receptor double knock-out cells. Conversely, in LRP5 knockdown preadipocytes, insulin-induced phosphorylation of IRS1, Akt, GSK3β, and ERK1/2 is highly reduced. This effect is specific to insulin, as compared with IGF-1, stimulation...

An adaptive large neighborhood search heuristic for Two-Echelon Vehicle Routing Problems arising in city logistics.

Science.gov (United States)

Hemmelmayr, Vera C; Cordeau, Jean-François; Crainic, Teodor Gabriel

2012-12-01

In this paper, we propose an adaptive large neighborhood search heuristic for the Two-Echelon Vehicle Routing Problem (2E-VRP) and the Location Routing Problem (LRP). The 2E-VRP arises in two-level transportation systems such as those encountered in the context of city logistics. In such systems, freight arrives at a major terminal and is shipped through intermediate satellite facilities to the final customers. The LRP can be seen as a special case of the 2E-VRP in which vehicle routing is performed only at the second level. We have developed new neighborhood search operators by exploiting the structure of the two problem classes considered and have also adapted existing operators from the literature. The operators are used in a hierarchical scheme reflecting the multi-level nature of the problem. Computational experiments conducted on several sets of instances from the literature show that our algorithm outperforms existing solution methods for the 2E-VRP and achieves excellent results on the LRP.

Data on proteins of lysenin family in coelomocytes of Eisenia andrei and E. fetida obtained by tandem mass spectrometry coupled with liquid chromatography

Directory of Open Access Journals (Sweden)

Bianka Swiderska

2016-12-01

Full Text Available The data described are related to the article “Lysenin family proteins in earthworm coelomocytes – comparative approach” (B. Swiderska, S. Kedracka-Krok, T. Panz, A.J. Morgan, A. Falniowski, P.Grzmil, B. Plytycz, 2016 [1]. Lysenin family proteins were identified based on unique peptides sequenced by tandem mass spectrometry coupled with liquid chromatography (LC-MS/MS in lumbricid earthworms Eisenia andrei and E. fetida, the latter with or without the MUG-like fluorophore. Lysenin and lysenin-related protein 2 (LRP-2, fetidin were identified in all 9 investigated specimens of Eisenia sp. LRP-1 was identified in 5 of 6 specimens of E. fetida, while LRP-3 was present in 2 of 3 investigated specimens of E. andrei. Here, the detailed characteristics of identified peptides unique to the particular members of lysenin family present in each particular earthworm specimen was provided. The information concerning mass to charge ratio, retention time, modifications and score of unique peptides was given.

A “Partnership” for the Professional Development of Librarian Researchers

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Pamela Carson

2014-09-01

Full Text Available In this article the authors introduce the Librarians’ Research Partnership (LRP, founded in 2013, at McGill and Concordia University Libraries. The Partnership was inspired by the Canadian Association of Research Libraries’ Librarians’ Research Institute (CARL LRI which was attended by three of the authors in 2012 and is described here from the point of view of the participants. The authors touch upon the research culture at McGill and Concordia Libraries and discuss barriers and supports for research as prominent themes in the literature on the research role of Canadian academic librarians. The formation of the LRP and the eight subsequent meetings are explained in detail, as well as the factors that made the LRP a successful initiative between the two universities: physical proximity, similarity of working environments, and common organizational culture. The article also includes a discussion of how the LRP’s philosophy might diverge from that of the LRI.

The multiligand α₂-macroglobulin receptor/low density lipoprotein receptor-related protein

DEFF Research Database (Denmark)

Gliemann, Jørgen; Nykjær, Anders; Petersen, Claus Munck

1994-01-01

The fusion of separate lines of research has greatly helped in elucidating the function of the giant members of the low density lipoprotein (LDL) receptor (LDLR) supergene family. The cDNA encoding a large protein structurally closely related to LDLR, and hence named LDLR-related protein (LRP......), was cloned by Herz et al. in 1988.'Evidence was provided demonstrating that LRP can function as a receptor for chylomicron remnants@-migrating very low density lipoproteins (P-VLDL) rich in apolipoprotein E (apoE)?' The a2-macroglobulin (a2M) receptor (a2MR) was purified from rat livep and human p l a~e n t...... from the observation that affinity-purified a2MR/LRP contains a 40-kDa5.8 or 39-kDa6.' protein, designated a2MRAP, in addition to the a2MFULRP a- and P-chains. cDNA cloning" disclosed the 323-residue protein as both the human homologue of mouse heparin binding protein 44 (see reference 11) and...

QCD and Hadron Physics

Energy Technology Data Exchange (ETDEWEB)

Brodsky, Stanley J.; Deshpande, Abhay L.; Gao, Haiyan; McKeown, Robert D.; Meyer, Curtis A.; Meziani, Zein-Eddine; Milner, Richard G.; Qiu, Jianwei; Richards, David G.; Roberts, Craig D.

2015-02-26

This White Paper presents the recommendations and scientific conclusions from the Town Meeting on QCD and Hadronic Physics that took place in the period 13-15 September 2014 at Temple University as part of the NSAC 2014 Long Range Planning process. The meeting was held in coordination with the Town Meeting on Phases of QCD and included a full day of joint plenary sessions of the two meetings. The goals of the meeting were to report and highlight progress in hadron physics in the seven years since the 2007 Long Range Plan (LRP07), and present a vision for the future by identifying the key questions and plausible paths to solutions which should define the next decade. The introductory summary details the recommendations and their supporting rationales, as determined at the Town Meeting on QCD and Hadron Physics, and the endorsements that were voted upon. The larger document is organized as follows. Section 2 highlights major progress since the 2007 LRP. It is followed, in Section 3, by a brief overview of the physics program planned for the immediate future. Finally, Section 4 provides an overview of the physics motivations and goals associated with the next QCD frontier: the Electron-Ion-Collider.

20 CFR 416.1901 - Scope of subpart S.

Science.gov (United States)

2010-04-01

... to the State (or a political subdivision of the State) as repayment for interim assistance it gave... you must have given written authorization for us to repay the State (or a political subdivision of the... State. (4) Appeals. Sections 416.1920 through 416.1922 describe your appeal rights in the State and in...

Flexible Micro Finance Program: Effectiveness and Efficiency to Reach the Extreme Poor

Directory of Open Access Journals (Sweden)

Meherun AHMED

2017-11-01

Full Text Available Following widespread criticisms of the conventional MFI framework, Plan Bangladesh, an INGO devised a flexible credit scheme characterized by door to door collection of deposits and loan repayments on a day to day basis. The scheme departs from the joint liability mechanism practiced by traditional MFIs in an effort to disburse services to the ultra poor, who are often excluded by community screening mechanisms as well as service providers. This paper aims to test the viability of a flexible scheme offering products developed through participatory market research targeted at individuals. We find the scheme to be highly effective, enhancing income of ultra poor households as well as providing adequate leverage for asset accumulation.

Shamba Maisha: A pilot study assessing impacts of a micro-irrigation intervention on the health and economic wellbeing of HIV patients

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Onjolo Elijah

2010-05-01

Full Text Available Abstract Background HIV/AIDS negatively impacts poverty alleviation and food security, which reciprocally hinder the rapid scale up and effectiveness of HIV care programs. Nyanza province has the highest HIV prevalence (15.3%, and is the third highest contributor (2.4 million people to rural poverty in Kenya. Thus, we tested the feasibility of providing a micro-irrigation pump to HIV-positive farmers in order to evaluate its impact on health and economic advancement among HIV-positive patients and their families. Methods Thirty HIV-positive patients enrolled in the Family AIDS Care and Education Services (FACES program in Kisumu, Kenya were provided a micro-financed loan to receive an irrigation pump and farming guidance from KickStart, the developer of the pump. Economic data, CD4 counts, household health and loan repayment history were collected 12 months after the pumps were distributed. Results Mean annual family income increased by $1,332 over baseline. CD4 counts did not change significantly. Though income increased, only three (10% participants had paid off more than a quarter of the loan. Conclusions We demonstrated the feasibility of an income-generating micro-irrigation intervention among HIV-positive patients and the collection of health and economic data. While family income improved significantly, loan repayment rates were low- likely complicated by the drought that occurred in Kenya during the intervention period.

Shamba Maisha: a pilot study assessing impacts of a micro-irrigation intervention on the health and economic wellbeing of HIV patients.

Science.gov (United States)

Pandit, Jay A; Sirotin, Nicole; Tittle, Robin; Onjolo, Elijah; Bukusi, Elizabeth A; Cohen, Craig R

2010-05-11

HIV/AIDS negatively impacts poverty alleviation and food security, which reciprocally hinder the rapid scale up and effectiveness of HIV care programs. Nyanza province has the highest HIV prevalence (15.3%), and is the third highest contributor (2.4 million people) to rural poverty in Kenya. Thus, we tested the feasibility of providing a micro-irrigation pump to HIV-positive farmers in order to evaluate its impact on health and economic advancement among HIV-positive patients and their families. Thirty HIV-positive patients enrolled in the Family AIDS Care and Education Services (FACES) program in Kisumu, Kenya were provided a micro-financed loan to receive an irrigation pump and farming guidance from KickStart, the developer of the pump. Economic data, CD4 counts, household health and loan repayment history were collected 12 months after the pumps were distributed. Mean annual family income increased by $1,332 over baseline. CD4 counts did not change significantly. Though income increased, only three (10%) participants had paid off more than a quarter of the loan. We demonstrated the feasibility of an income-generating micro-irrigation intervention among HIV-positive patients and the collection of health and economic data. While family income improved significantly, loan repayment rates were low- likely complicated by the drought that occurred in Kenya during the intervention period.

Modelos matemáticos para estimar as exigências de lisina digestível para aves de corte ISA Label Mathematical models to estimate digestible lysine of ISA Label broilers

Directory of Open Access Journals (Sweden)

Jefferson Costa de Siqueira

2009-09-01

Full Text Available O objetivo neste estudo foi avaliar diferentes modelos ajustados às respostas de ganho de peso obtidas em experimento com aves da linhagem ISA Label no período de 1 a 28 dias de idade. Foram utilizados 480 pintos de ambos os sexos, distribuídos em delineamento inteiramente casualizado, em arranjo fatorial 4 X 2 (níveis de lisina X sexo, com três repetições, com 20 aves por unidade experimental. Uma ração basal foi formulada para atender às exigências das aves, exceto em lisina. Essa ração foi suplementada com L-lisina HCl em substituição ao ácido L-glutâmico, resultando em rações experimentais isonitrogênicas e isoenergéticas contendo 0,85; 0,97; 1,09 e 1,21% de lisina digestível. As respostas de ganho de peso foram ajustadas de acordo com os níveis de lisina da ração pelos modelos Linear Reponse Plateau (LRP, segmentado de duas inclinações, polinomial quadrático e exponencial. A primeira intersecção da equação quadrática com o platô do LRP também foi utilizado para estimar o nível ótimo. Os níveis de lisina digestível estimados pelos modelos LRP, segmentado e quadrático, foram 0,999; 1,010 e 1,116%, respectivamente. Na combinação do modelo quadrático com o LRP, a estimativa da exigência de lisina digestível foi de 1,041%. O modelo exponencial proporcionou estimativa de 1,066%, considerando 95% da resposta assintótica. Com base nos custos com alimentação, esse mesmo modelo gerou estimativas de 1,000 e 1,030% quando o custo do quilograma de L-lisina HCl foi R$ 8,50 e R$ 6,50, respectivamente. Considerando as limitações de cada um dos modelos propostos, o procedimento para estimar as exigências de lisina digestível pela primeira intersecção da equação quadrática com o platô do LRP foi o mais adequado para melhorar o ganho de peso das aves quando variáveis econômicas não foram consideradas.The objective of this study was to evaluate different models in the adjustment of weight gain (WG

Economic Cost and Benefits of Subsidizing Western Credits to the East,

Science.gov (United States)

1984-07-01

these reports it is possible to calculate the scheduled repayments and deter- mine the extent to which these repayments were not made. Table 5...It was bleved tha in am of sp- MOM dfficultee, the Soviet would aasf their satllfML Th& ocabld uubftf hrtbyo tho ouhl dis dited b nosut expesLne .4. p

The Looming Student Loan Default Crisis Is Worse than We Thought. Evidence Speaks Reports, Vol 2, #34

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Scott-Clayton, Judith

2018-01-01

This report analyzes new data on student debt and repayment, released by the U.S. Department of Education in October 2017. Previously available data have been limited to borrowers only, follow students for a relatively short period (3-5 years) after entering repayment, and had only limited information on student characteristics and experiences.…

5 CFR 1655.17 - Prepayment.

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2010-01-01

... participant may repay a loan in full, without a penalty, at any time before the declaration of a taxable... means receipt by the TSP record keeper of a payment, by personal check or guaranteed funds made payable... returns a loan check to the TSP record keeper, it will be treated as a repayment; however, additional...

43 CFR 424.1 - Regulations.

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2010-10-01

... provisions of Article 34 and 25 of repayment contract I1r-1534, dated September 20, 1948, between the United... supplemented, Articles 34, and 25 of the Repayment Contract I1r-1534 dated Sept. 20, 1948, between the United... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Regulations. 424.1 Section 424.1 Public...

Exogenous DKK-3/REIC inhibits Wnt/β-catenin signaling and cell proliferation in human kidney cancer KPK1.

Science.gov (United States)

Xu, Jiaqi; Sadahira, Takuya; Kinoshita, Rie; Li, Shun-Ai; Huang, Peng; Wada, Koichiro; Araki, Motoo; Ochiai, Kazuhiko; Noguchi, Hirofumi; Sakaguchi, Masakiyo; Nasu, Yasutomo; Watanabe, Masami

2017-11-01

The third member of the Dickkopf family (DKK-3), also known as reduced expression in immortalized cells (REIC), is a tumor suppressor present in a variety of tumor cells. Regarding the regulation of the Wnt/β-catenin signaling pathway, exogenous DKK-1 and DKK-2 are reported to inhibit Wnt signaling by binding the associated effectors. However, whether exogenous DKK-3 inhibits Wnt signaling remains unclear. A recombinant protein of human full-length DKK-3 was used to investigate the exogenous effects of the protein in vitro in KPK1 human renal cell carcinoma cells. It was demonstrated that the expression of phosphorylated (p-)β-catenin (inactive form as the transcriptional factor) was increased in KPK1 cells treated with the exogenous DKK-3 protein. The levels of non-p-β-catenin (activated form of β-catenin) were consistently decreased. It was revealed that the expression of transcription factor (TCF) 1 and c-Myc, the downstream transcription factors of the Wnt/β-catenin signaling pathway, was inhibited following treatment with DKK-3. A cancer cell viability assay confirmed the anti-proliferative effects of exogenous DKK-3 protein, which was consistent with a suppressed Wnt/β-catenin signaling cascade. In addition, as low-density lipoprotein receptor-related protein 6 (LRP6) is a receptor of DKK-1 and DKK-2 and their interaction on the cell surface inhibits Wnt/β-catenin signaling, it was examined whether the exogenous DKK-3 protein affects LRP6-mediated Wnt/β-catenin signaling. The LRP6 gene was silenced and the effects of DKK-3 on the time course of the upregulation of p-β-catenin expression were subsequently analyzed. Notably, LRP6 depletion elevated the base level of p-β-catenin; however, there was no significant effect on its upregulation course or expression pattern. These findings indicate that exogenous DKK-3 upregulates p-β-catenin and inhibits Wnt/β-catenin signaling in an LRP6-independent manner. Therefore, exogenous DKK-3 protein may inhibit

Genetic predictors of recovery in low back and lumbar radicular pain.

Science.gov (United States)

Bjorland, Siri; Røe, Cecilie; Moen, Aurora; Schistad, Elina; Mahmood, Aqsa; Gjerstad, Johannes

2017-08-01

Previous data suggest that persistent back pain may be associated with genetic variability. In this study, we assessed the correlation between 8 genetic polymorphisms (VDR, COL11, MMP1, MMP9, IL-1α, IL-1RN, OPRM1, COMT) and pain recovery in patients with low back pain (LBP) and lumbar radicular pain (LRP). In total, 296 patients with LBP or LRP were followed for 5 years. The patients underwent standardized clinical examination and completed pain and function questionnaires. Univariate linear regression associations with P values pain intensity at baseline, age, sex, smoking, body mass index, and LBP or LRP. Pain intensity at 5-year follow-up was associated with VDR rs731236 (B = -0.5, 95% confidence interval [CI] -0.9 to -0.1, P = 0.017), MMP9 rs17576 (B = 0.5, 95% CI 0.1-0.9, P = 0.022), and OPRM1 rs1799971 (B = -0.8, 95% CI -1.4 to -0.2, P = 0.006) in the univariate analyses. MMP9 rs17576 and OPRM1 rs1799971 remained significant (B = 0.4, 95% CI 0.05-0.8, P = 0.026 and B = -0.8, 95% CI -1.3 to -0.2, P = 0.007) in the multivariable model. Thus, the data demonstrated that the rare allele of MMP9 rs17576 was associated with poor pain recovery, whereas the rare allele of OPRM1 rs1799971 was associated with better pain recovery at 5-year follow-up in the LBP and LRP patients. In particular, the present study suggested that the OPRM1 rs179971 A>G in men was associated with better long-term pain recovery. In men, the OPRM1 rs1799971 explained 4.7% of the variance of pain intensity. We conclude that the MMP9 rs17576 and OPRM1 rs1799971 genotypes may affect 5-year recovery in patients with LBP and LRP.

Cognitive-behavioral therapy induces sensorimotor and specific electrocortical changes in chronic tic and Tourette's disorder.

Science.gov (United States)

Morand-Beaulieu, Simon; O'Connor, Kieron P; Sauvé, Geneviève; Blanchet, Pierre J; Lavoie, Marc E

2015-12-01

Tic disorders, such as the Gilles de la Tourette syndrome and persistent tic disorder, are neurodevelopmental movement disorders involving impaired motor control. Hence, patients show repetitive unwanted muscular contractions in one or more parts of the body. A cognitive-behavioral therapy, with a particular emphasis on the psychophysiology of tic expression and sensorimotor activation, can reduce the frequency and intensity of tics. However, its impact on motor activation and inhibition is not fully understood. To study the effects of a cognitive-behavioral therapy on electrocortical activation, we recorded the event-related potentials (ERP) and lateralized readiness potentials (LRP), before and after treatment, of 20 patients with tic disorders and 20 healthy control participants (matched on age, sex and intelligence), during a stimulus-response compatibility inhibition task. The cognitive-behavioral therapy included informational, awareness training, relaxation, muscle discrimination, cognitive restructuration and relapse prevention strategies. Our results revealed that prior to treatment; tic patients had delayed stimulus-locked LRP onset latency, larger response-locked LRP peak amplitude, and a frontal overactivation during stimulus inhibition processing. Both stimulus-locked LRP onset latency and response-locked LRP peak amplitude normalized after the cognitive behavioral therapy completion. However, the frontal overactivation related to inhibition remained unchanged following therapy. Our results showed that P300 and reaction times are sensitive to stimulus-response compatibility, but are not related to tic symptoms. Secondly, overactivity of the frontal LPC and impulsivity in TD patients were not affected by treatment. Finally, CBT had normalizing effects on the activation of the pre-motor and motor cortex in TD patients. These results imply specific modifications of motor processes following therapy, while inhibition processes remained unchanged. Given

The cost-effectiveness of three interventions for providing preventive services to low-income children.

Science.gov (United States)

Johnson, Ben; Serban, Nicoleta; Griffin, Paul M; Tomar, Scott L

2017-12-01

We evaluated the impact of loan repayment programmes, revising Medicaid fee-for-service rates, and changing dental hygienist supervision requirements on access to preventive dental care for children in Georgia. We estimated cost savings from the three interventions of preventive care for young children after netting out the intervention cost. We used a regression model to evaluate the impact of changing the Medicaid reimbursement rates. The impact of supervision was evaluated by comparing general and direct supervision in school-based dental sealant programmes. Federal loan repayments to dentists and school-based sealant programmes (SBSPs) had lower intervention costs (with higher potential cost savings) than raising the Medicaid reimbursement rate. General supervision had costs 56% lower than direct supervision of dental hygienists for implementing a SBSP. Raising the Medicaid reimbursement rate by 10 percentage points would improve utilization by Loan repayment could serve almost 13 000 children for a cost of $400 000 and a potential cost saving of $176 000. The three interventions all improved met need for preventive dental care. Raising the reimbursement rate alone would marginally affect utilization of Medicaid services but would not substantially increase acceptance of Medicaid by providers. Both loan repayment programmes and amending supervision requirements are potentially cost-saving interventions. Loan repayment programmes provide complete care to targeted areas, while amending supervision requirements of dental hygienists could provide preventive care across the state. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Government Shutdown: Operations of Department of Defense During a Lapse in Appropriations

Science.gov (United States)

2011-04-01

proactive in working with creditors to reschedule debt repayments under these circumstances… c. Military personnel: During a shutdown of DoD activities due...creditors to reschedule debt repayments under these circumstances. The key point that both the creditor and the soldier should remember is that the...including Uniformed Services Treatment Facilities) including doctors, nurses , medical technicians, dentists, and essential support personnel (cooks

Sequential induction of auxin efflux and influx carriers regulates lateral root emergence.

Science.gov (United States)

Péret, Benjamin; Middleton, Alistair M; French, Andrew P; Larrieu, Antoine; Bishopp, Anthony; Njo, Maria; Wells, Darren M; Porco, Silvana; Mellor, Nathan; Band, Leah R; Casimiro, Ilda; Kleine-Vehn, Jürgen; Vanneste, Steffen; Sairanen, Ilkka; Mallet, Romain; Sandberg, Göran; Ljung, Karin; Beeckman, Tom; Benkova, Eva; Friml, Jiří; Kramer, Eric; King, John R; De Smet, Ive; Pridmore, Tony; Owen, Markus; Bennett, Malcolm J

2013-10-22

In Arabidopsis, lateral roots originate from pericycle cells deep within the primary root. New lateral root primordia (LRP) have to emerge through several overlaying tissues. Here, we report that auxin produced in new LRP is transported towards the outer tissues where it triggers cell separation by inducing both the auxin influx carrier LAX3 and cell-wall enzymes. LAX3 is expressed in just two cell files overlaying new LRP. To understand how this striking pattern of LAX3 expression is regulated, we developed a mathematical model that captures the network regulating its expression and auxin transport within realistic three-dimensional cell and tissue geometries. Our model revealed that, for the LAX3 spatial expression to be robust to natural variations in root tissue geometry, an efflux carrier is required--later identified to be PIN3. To prevent LAX3 from being transiently expressed in multiple cell files, PIN3 and LAX3 must be induced consecutively, which we later demonstrated to be the case. Our study exemplifies how mathematical models can be used to direct experiments to elucidate complex developmental processes.

Introduction of N-cadherin-binding motif to alginate hydrogels for controlled stem cell differentiation.

Science.gov (United States)

Lee, Jae Won; An, Hyoseok; Lee, Kuen Yong

2017-07-01

Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif. In vitro changes in the morphology and differentiation of mouse bone marrow stromal cells (D1 stem cells) cultured in LRP5-alginate hydrogels were investigated. LRP5-alginate gels successfully induced stem cell aggregation and enhanced chondrogenic differentiation of D1 stem cells, compared to RGD-alginate gels, at low cell density. This approach to tailoring synthetic biomimetic ECMs using cell-cell interaction motifs may be critical in tissue engineering approaches using stem cells. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Laparoscopic radical prostatectomy: omitting a pelvic drain

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David Canes

2008-03-01

Full Text Available PURPOSE: Our goal was to assess outcomes of a selective drain placement strategy during laparoscopic radical prostatectomy (LRP with a running urethrovesical anastomosis (RUVA using cystographic imaging in all patients. Materials and Methods: A retrospective chart review was performed for all patients undergoing LRP between January 2003 and December 2004. The anastomosis was performed using a modified van Velthoven technique. A drain was placed at the discretion of the senior surgeon when a urinary leak was demonstrated with bladder irrigation, clinical suspicion for a urinary leak was high, or a complex bladder neck reconstruction was performed. Routine postoperative cystograms were obtained. RESULTS: 208 patients underwent LRP with a RUVA. Data including cystogram was available for 206 patients. The overall rate of cystographic urine leak was 5.8%. A drain was placed in 51 patients. Of these, 8 (15.6% had a postoperative leak on cystogram. Of the 157 undrained patients, urine leak was radiographically visible in 4 (2.5%. The higher leak rate in the drained vs. undrained cohort was statistically significant (p = 0.002. Twenty-four patients underwent pelvic lymph node dissection (8 drained, 16 undrained. Three undrained patients developed lymphoceles, which presented clinically on average 3 weeks postoperatively. There were no urinomas or hematomas in either group. CONCLUSIONS: Routine placement of a pelvic drain after LRP with a RUVA is not necessary, unless the anastomotic integrity is suboptimal intraoperatively. Experienced clinical judgment is essential and accurate in identifying patients at risk for postoperative leakage. When suspicion is low, omitting a drain does not increase morbidity.

Labelling of leucocytes with colloidal technetium-99m-SnF2: an investigation of the labelling process by autoradiography

International Nuclear Information System (INIS)

Puncher, M.R.B.; Blower, P.J.

1995-01-01

Autoradiography of smears and frozen sections of labelled cell suspensions was used to study the distribution of radioactivity in and among blood cells labelled in either whole blood or leucocyte-rich plasma (LRP) with technetium-99m-SnF 2 colloid. The tracer proved selective for neutrophils: the labelling probability (relative to that for erythrocytes) for each cell type in LRP (mean of five samples) was: neutrophils, 9.4; lymphocytes, 3.7; monocytes, 3.0; eosinophils 1.4; erythrocytes, 1.0. When labelling was carried out in whole blood (five samples), 74.5%±8.3% of the cell-bound radioactivity was bound to erythrocytes, 13.6%±6.5% to neutrophils, and 11.9%±2.1% to lymphocytes, whereas in LRP (in which the leucocytes were only slightly outnumbered by erythrocytes), 76.5%±14.9% of radioactivity was neutrophil bound. Labelled cells in smear autoradiographs exhibited two distinct silver grain patterns, ''diffuse'', consistent with an intracellular radioactive particle (in neutrophils), and ''focal'', consistent with a cell surface-adhering particle in direct contact with the emulsion (in other leucocyte types and erythrocytes). The phagocytic inhibitor cytochalasin B neither reduced the proportion of labelled neutrophils nor altered the labelling pattern. Neutrophils were able to scavenge radioactivity from the surface of erythrocytes. It is concluded that neutrophils bind 99m Tc-SnF 2 intracellularly by phagocytosis, with high affinity; other cells become labelled at the cell surface reversibly and with lower affinity. This selectivity is high enough to permit predominantly leucocyte labelling in LRP but not in whole blood. (orig.)

Labelling of leucocytes with colloidal technetium-99m-SnF{sub 2}: an investigation of the labelling process by autoradiography

Energy Technology Data Exchange (ETDEWEB)

Puncher, M.R.B. [Biological Lab., Canterbury Univ. (United Kingdom); Blower, P.J. [Nuclear Medicine Dept., Kent and Canterbury Hospital, Canterbury (United Kingdom)

1995-02-01

Autoradiography of smears and frozen sections of labelled cell suspensions was used to study the distribution of radioactivity in and among blood cells labelled in either whole blood or leucocyte-rich plasma (LRP) with technetium-99m-SnF{sub 2} colloid. The tracer proved selective for neutrophils: the labelling probability (relative to that for erythrocytes) for each cell type in LRP (mean of five samples) was: neutrophils, 9.4; lymphocytes, 3.7; monocytes, 3.0; eosinophils 1.4; erythrocytes, 1.0. When labelling was carried out in whole blood (five samples), 74.5%{+-}8.3% of the cell-bound radioactivity was bound to erythrocytes, 13.6%{+-}6.5% to neutrophils, and 11.9%{+-}2.1% to lymphocytes, whereas in LRP (in which the leucocytes were only slightly outnumbered by erythrocytes), 76.5%{+-}14.9% of radioactivity was neutrophil bound. Labelled cells in smear autoradiographs exhibited two distinct silver grain patterns, ``diffuse``, consistent with an intracellular radioactive particle (in neutrophils), and ``focal``, consistent with a cell surface-adhering particle in direct contact with the emulsion (in other leucocyte types and erythrocytes). The phagocytic inhibitor cytochalasin B neither reduced the proportion of labelled neutrophils nor altered the labelling pattern. Neutrophils were able to scavenge radioactivity from the surface of erythrocytes. It is concluded that neutrophils bind {sup 99m}Tc-SnF{sub 2} intracellularly by phagocytosis, with high affinity; other cells become labelled at the cell surface reversibly and with lower affinity. This selectivity is high enough to permit predominantly leucocyte labelling in LRP but not in whole blood. (orig.)

Site-specific O-glycosylation of members of the low-density lipoprotein receptor superfamily enhances ligand interactions

DEFF Research Database (Denmark)

Wang, Shengjun; Mao, Yang; Narimatsu, Yoshiki

2018-01-01

in the LA linker regions of VLDLR, LRP1, and LRP2 (Megalin) from both cell lines and rat organs. Using a panel of gene-edited isogenic cell line models, we demonstrate that GalNAc-T11-mediated LDLR and VLDLR O-glycosylation is not required for transport and cell surface expression and stability...... of these receptors, but markedly enhances LDL and VLDL binding and uptake. Direct ELISA-based binding assays with truncated LDLR constructs revealed that O-glycosylation increased affinity for LDL by approximately 5-fold. The molecular basis for this observation is currently unknown, but these findings open up new...

Does fellowship pay: what is the long-term financial impact of subspecialty training in pediatrics?

Science.gov (United States)

Rochlin, Jonathan M; Simon, Harold K

2011-02-01

To (1) analyze the financial returns of fellowship training in pediatrics and to compare them with those generated from a career in general pediatrics and (2) evaluate the effects of including the newly enacted federal loan-repayment program and of changing the length of fellowship training. Although the choice to enter fellowship is based on many factors, economic considerations are important. We are not aware of any study that has focused on the financial impact of fellowship training in pediatrics. Using standard financial techniques, we estimated the financial returns that a graduating pediatric resident might anticipate from additional fellowship training followed by a career as a pediatric subspecialist and compared them with the returns that might be expected from starting a career as a general pediatrician immediately after residency. The financial returns of pediatric fellowship training varied greatly depending on which subspecialty fellowship was chosen. Pursuing a fellowship in most pediatric subspecialties was a negative financial decision when compared with pursuing no fellowship at all and practicing as a general pediatrician. Incorporating the federal loan-repayment program targeted toward pediatric subspecialists and decreasing the length of fellowship training from 3 to 2 years would substantially increase the financial returns of the pediatric subspecialties. Pediatric subspecialization yielded variable financial returns. The results from this study can be helpful to current pediatric residents as they contemplate their career options. In addition, our study may be valuable to policy makers evaluating health care reform and pediatric workforce-allocation issues.

The Planning and Scheduling of HST: Improvements and Enhancements since Launch

Science.gov (United States)

Taylor, D. K.; Chance, D. R.; Jordan, I. J. E.; Patterson, A. P.; Stanley, M.; Taylor, D. C.

2001-12-01

The planning and scheduling (P&S) systems used in operating the Hubble Space Telescope (HST) have undergone such substantial and pervasive re-engineering that today they dimly resemble those used when HST was launched. Processes (i.e., software, procedures, networking, etc.) which allow program implementation, the generation of a Long Range Plan (LRP), and the scheduling of science and mission activities have improved drastically in nearly 12 years, resulting in a consistently high observing efficiency, a stable LRP that principal investigators can use, exceptionally clean command loads uplinked to the spacecraft, and the capability of a very fast response time due to onboard anomalies or targets of opportunity. In this presentation we describe many of the systems which comprise the P&S ("front-end") system for HST, how and why they were improved, and what benefits have been realized by either the HST user community or the STScI staff. The systems include the Guide Star System, the Remote Proposal Submission System - 2 (RPS2), Artificial Intelligence (AI) planning tools such as Spike, and the science and mission scheduling software. We also describe how using modern software languages such as Python and better development practices allow STScI staff to do more with HST (e.g., to handle much more science data when ACS is installed) without increasing the cost to HST operations.

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

Science.gov (United States)

2010-10-01

... rates of infant mortality, low birth weight, geographic barriers and other indicators; (3) A proposal... accessibility of health care services in the State as measured by poverty levels, the percentage of the service...

AcEST: DK943939 [AcEST

Lifescience Database Archive (English)

Full Text Available YMU02A01NGRL0004_H07 354 Adiantum capillus-veneris mRNA. clone: YMU02A01NGRL0004_H0...7. 5' end sequence. DK943939 - Show DK943939 Clone id YMU02A01NGRL0004_H07 Library YMU02 Length 354 Definiti...on Adiantum capillus-veneris mRNA. clone: YMU02A01NGRL0004_H07. 5' end sequence. Accession DK943939 Tissue t... of protein database search programs, Nucleic Acids Res. 25:3389-3402. Query= DK943939|Adiantum capillus-ven... CYA LHPRAVNCRKK CGH+N+LRP KK++ Sbjct: 1 IIEPSLRQLAQKYNCDKMICRKCYARLHPRAVNCRKKKCGHTNNLRPKKKVK 52 TrEMBL (release 39

Návratné zdroje financování územní samosprávy

OpenAIRE

Kalužová, Jana

2009-01-01

The diploma thesis deals with the financial resources of municipal authorities with the intention on so called repayable financial resources. Repayable financial resources represent significant component for financing short-term and long-term projects of municipal authorities and serve as an important financial instrument for the development of municipal territory. The aim of the thesis is to evaluate forms and potentials of using repayabe financial resources by municipal authorities and also...

Multiple Criteria Decision Making Combined with VRP: A Categorized Bibliographic Study

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Yahia Zare Mehrjerdi

2015-08-01

Full Text Available In this research author reviews references related to the topic of multi criterion (goal programming, multiple objective linear and nonlinear programming, bi-criterion programming, Multi Attribute Decision Making, Compromise Programming, Surrogate Worth Trade-off Method and various versions of vehicle routing problem (VRP, Multi depot VRP (MDVRP, VRP with time windows (VRPWTW, Stochastic VRP (SVRP, Capacitated VRP (CVRP, Fuzzy VRP (FVRP, Location VRP (LVRP, Backhauling VRP(BHVRP, Facility Location VRP (FLVRP, and Inventory control VRP (ICVRP. Although, VRP is a research area with rich research works and powerful researchers there found only 81 articles that relates various vehicle routing type problems with various multiple objectives techniques. This author found that there is no research done in some areas of VRP (i.e., FVRP, ICVRP, LRP and CVRP. It is interesting to see that this research area was completely an unattractive to master students (with zero research reported and a somewhat attractive area to doctoral students (with 6 researches reported. Among the many multi criterion programming techniques available only three of them (goal programming, bi-criterion programming, linear and nonlinear multi objective programming are being employed to solve the problem.

Managing Assets Of Agricultural Property Of The National Treasury In The Context Of State Aid Granted By The Agricultural Property Agency

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Lizińska Wiesława

2015-09-01

Full Text Available This study covers the issue of activities of the Agricultural Property Agency in terms of state aid in the form of non-repayable financial aid, with the following specific objectives: determining the scale and diversity of state aid granted by the APA (including the local branch in Olsztyn, evaluating the current technical condition of some of the assets and their condition upon being handed over by the APA, determining their importance, main problems associated with resources which are taken over, identifying and assessing the importance of actions which encourage communes to take over property still held by the APA, assessing the scale and procedure of aid granted in the opinion of representatives of APA units. The article makes use of information obtained from the local branch of the APA in Olsztyn in the years 2003-2014. A direct survey among the entities was taken. The survey questionnaire was sent in 2014 to all communes (gminas of the Province (Voivodeship of Warmia and Mazury (116 units. Completed questionnaires were returned by 73 representatives of the communes. A total of PLN 327.1 million was allotted in the Agency’s financial plans for the program of non-repayable financial aid during the period from 2009 to 2014. Approximately 81.6% of PLN 164.4 million granted by the local branch of the APA in Olsztyn, was granted to units of the public finance sector. As was shown in the survey conducted among representatives of local governments, the interest of communes in taking over assets still held by2 the local branch of the APA in Olsztyn could be increased by limiting the number of tenants who do not pay the rent regularly and by increasing the amount of non-repayable financial aid. It is possible to carry out the latter action, but the former could prove to be extremely difficult.

Seminal vesicle sparing laparoscopic radical prostatectomy using a low-energy source: Better continence and potency

Directory of Open Access Journals (Sweden)

Shrenik J Shah

2009-01-01

Full Text Available Objectives: Ongoing with the newer developments in laparoscopic radical prostatectomy (LRP, we report our experience in a consecutive series of 42 patients with a mean 18-month follow-up. We also studied the use of a low-energy source, especially in the region of the prostatic apex and the neurovascular bundle and evaluated its outcome on continence and potency. Materials and Methods: Between November 2003 and December 2008, 50 patients aged 50-80 yrs underwent LRP with vesicourethral anastomosis and of these, 42 patients who had a minimum follow-up of 3 months were selected for the study. Of these, the initial 16 patients were operated by the routine method and the 26 patients operated in the later part of our experience were operated upon using a minimal energy source. Results: The mean follow-up was 18 months (range 3-60. Continence was evaluated at 1, 3, 6, and 12 months. Eleven of the 16 patients in Group I were continent as compared with 21 of 26 patients in Group II. The difference in continence rates was mainly due to less use of electrocautery and harmonic scalpel at the bladder neck. Of the eight patients who were potent pre-operatively in Group I, four remained potent 3 months after LRP. In Group II, 20 of the 26 patients were potent pre-operatively and 16 remained potent 3 months after LRP. Conclusions: Use of a low-energy source at the bladder neck and neurovascular bundle, sparing of seminal vesicle, and leaving behind a long, healthy stump of the urethra during apical dissection, is associated with better continence and potency without compromising oncological outcome.

Expression of Multidrug Resistance-Associated Markers, Their Relation to Quantitative Pathologic Tumour Characteristics and Prognosis in Advanced Ovarian Cancer

Directory of Open Access Journals (Sweden)

Mariël Brinkhuis

2002-01-01

Full Text Available Mean nuclear area has been consistently shown by different researchers to be a strong and independent prognostic factor in advanced ovarian carcinoma. However, the biological background of the prognostic value of nuclear area remains unclear. Others have found that the multidrug‐resistance (MDR related protein LRP has strong prognostic value. In the present study we have analysed whether the mean nuclear area and LRP are related in tumour tissue of the ovary obtained at the debulking operation before the administration of chemotherapy in 40 patients. The mitotic activity index, volume percentage epithelium, standard deviation of nuclear area and the other MDR‐related proteins P‐glycoprotein (JSB‐1, MRK‐16 and MRP have been investigated additionally for correlations and prognostic value. No correlations were found between the morphometrical features and MDR‐related proteins. Mean nuclear area tended to be larger in LRP positive tumours, but the correlation was not significant. In multivariate analysis LRP‐protein expression and mean nuclear area had independent prognostic value. Further studies are required to elucidate the biological background of the strong prognostic value of mean nuclear area in advanced ovarian cancer.

TMEM59 potentiates Wnt signaling by promoting signalosome formation.

Science.gov (United States)

Gerlach, Jan P; Jordens, Ingrid; Tauriello, Daniele V F; van 't Land-Kuper, Ineke; Bugter, Jeroen M; Noordstra, Ivar; van der Kooij, Johanneke; Low, Teck Y; Pimentel-Muiños, Felipe X; Xanthakis, Despina; Fenderico, Nicola; Rabouille, Catherine; Heck, Albert J R; Egan, David A; Maurice, Madelon M

2018-04-09

Wnt/β-catenin signaling controls development and adult tissue homeostasis by regulating cell proliferation and cell fate decisions. Wnt binding to its receptors Frizzled (FZD) and low-density lipoprotein-related 6 (LRP6) at the cell surface initiates a signaling cascade that leads to the transcription of Wnt target genes. Upon Wnt binding, the receptors assemble into large complexes called signalosomes that provide a platform for interactions with downstream effector proteins. The molecular basis of signalosome formation and regulation remains elusive, largely due to the lack of tools to analyze its endogenous components. Here, we use internally tagged Wnt3a proteins to isolate and characterize activated, endogenous Wnt receptor complexes by mass spectrometry-based proteomics. We identify the single-span membrane protein TMEM59 as an interactor of FZD and LRP6 and a positive regulator of Wnt signaling. Mechanistically, TMEM59 promotes the formation of multimeric Wnt-FZD assemblies via intramembrane interactions. Subsequently, these Wnt-FZD-TMEM59 clusters merge with LRP6 to form mature Wnt signalosomes. We conclude that the assembly of multiprotein Wnt signalosomes proceeds along well-ordered steps that involve regulated intramembrane interactions. Copyright © 2018 the Author(s). Published by PNAS.

EFEKTIVITAS PIDANA PEMBAYARAN UANG PENGGANTI DALAM TINDAK PIDANA KORUPSI (Studi Putusan Tindak Pidana Korupsi di Pengadilan Negeri Purwokerto

Directory of Open Access Journals (Sweden)

Ade Paul Lukas

2010-05-01

Full Text Available This punishment is proved not effective because there were only two person punished who repaid. The rest failed to do so due either to lack of money or liquid assets. Instead they signed a letter stating their inability to repay the corrupted money and their readiness to undergo subsidiary punishment. The verdicts of Purwokerto regential Court against corruption act during the period between 2004 through 2008 stated that the punished were given additional punishment to repay the corrupted money but not all of them were punished with such additional punishment. The punishment given was without the obligation to repay and verdict of not guilty. There was constraint from the legal aspect. The constraining factors were the difficulty the public attorney faced in tracing the wealth obtained from corruption. There was also the unawareness of the society to report corruption act.

KEWIRAUSAHAAN DI PERGURUAN TINGGI MENYIAPKAN ENTREPRENEUR UNGGUL

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Margunani Margunani

2015-02-01

Full Text Available Product or service Wira New Business (WUB generated the students have the advantage of science and technology. Independent entrepreneurs from universities that produce the products / services can be developed through the science and technology-based business consulting to experts, research and laboratories on campus. Readiness is integrated and holistic childbirth entrepreneurs from universities, superior, has a broader and more adaptative insight. Entrepreneurship lecture testruktur, entrepreneurial practices chance divasilitasi Entrepreneurship Student Creativity Program (PKM-K through a grant to try to try. Student Entrepreneurial Program (PMW which provide more opportunities, where students who tried because of limited funds got very soft loan (without interest. Useful for students to practice managing capital / funding from outside to study the production, trade, repay, and so on.

HECS System Changes: Impact on Students

OpenAIRE

Gillian Beer; Bruce Chapman

2004-01-01

This paper examines the impact of changes to Australia’s student financing system on various hypothetical students who choose the Government’s proposed deferred payment options, HECS-HELP and FEE-HELP. The present values of their HECS repayments under the existing (2004) system are compared with the present values of repayments under various alternative systems. These alternative systems relate to increasing the HECS charge by 25 per cent for HECS-HELP students and introducing a fee paid with...

Amyloid-beta transporter expression at the blood-CSF barrier is age-dependent

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Pascale Crissey L

2011-07-01

Full Text Available Abstract Background Age is the major risk factor for many neurodegenerative diseases, including Alzheimer's disease (AD. There is an accumulation of amyloid-beta peptides (Aβ in both the AD brain and the normal aging brain. Clearance of Aβ from the brain occurs via active transport at the blood-brain barrier (BBB and blood-cerebrospinal fluid barrier (BCSFB. With increasing age, the expression of the Aβ efflux transporters is decreased and the Aβ influx transporter expression is increased at the BBB, adding to the amyloid burden in the brain. Expression of the Aβ transporters at the choroid plexus (CP epithelium as a function of aging was the subject of this study. Methods This project investigated the changes in expression of the Aβ transporters, the low density lipoprotein receptor-related protein-1 (LRP-1, P-glycoprotein (P-gp, LRP-2 (megalin and the receptor for advanced glycation end-products (RAGE at the BCSFB in Brown-Norway/Fischer rats at ages 3, 6, 9, 12, 20, 30 and 36 months, using real time RT-PCR to measure transporter mRNA expression, and immunohistochemistry (IHC to measure transporter protein in isolated rat CP. Results There was an increase in the transcription of the Aβ efflux transporters, LRP-1 and P-gp, no change in RAGE expression and a decrease in LRP-2, the CP epithelium influx transporter, at the BCSFB with aging. Decreased Aβ42 concentration in the CP, as measured by quantitative IHC, was associated with these Aβ transporter alterations. Conclusions Age-dependent alterations in the CP Aβ transporters are associated with a decrease in Aβ42 accumulation in the CP, and are reciprocal to the changes seen in these transporters at the BBB, suggesting a possible compensatory role for the BCSFB in Aβ clearance in aging.

[Study of anatomy of the lateral attachment of the renal fascia in adult with multidetector computed tomography].

Science.gov (United States)

Qi, Rui; Zhou, Xianping; Yu, Jianqun; Chen, Weixia; Li, Zhenlin; Zhang, Chunle

2012-08-01

The present paper is aimed to observe the lateral attachment of the renal fascia (RF) in vivo with multidetector computed tomography (MDCT) scanning, and to discuss its diagnostic value. 121 healthy adults were adopted into this experiment. All images were obtained with MDCT and double phase enhancement scanning. Then we observed the lateral attachment of RF. In addition, we mad a fresh body specimen as anatomical basis. The study found that above the renal hilar plane (RHP), the anterior renal fascia laterally fused with the peritoneum of the liver on the right and the peritoneum of the spleen on the left,and the posterior renal fascia fused with the subdiaphragmatic fascia. The lateral attachment of the RF at the RHP and the lower renal pole(LRP)is divided into three types. The RF in Type I is about 47.9% (58/121) at the left RHP, while about 33.9% (41/121) at the right RHP. At the LRP of the kidney is about 55.3% (67/121) on the left, and about 42.1% (51/121) on the right. The RF in Type I is about 38.8% (47/121) on the left side at the RHP, about 26.4% (32/121) on the right side. At the LRP, left side about 27.3% (33/121), right side about 13.3%(16/121). The RF in Type III at the RHP is 13.3% (16/121) on the left side, and on the right side is about 39.7% (48/121). At the LRP, it is about 17.4% (21/121) on the left side, and about 44.6% (54/121) on the right side. MDCT can display the lateral attachment of the RF better as well as the outside connection of the retroperitoneal space.

High-definition resolution three-dimensional imaging systems in laparoscopic radical prostatectomy: randomized comparative study with high-definition resolution two-dimensional systems.

Science.gov (United States)

Kinoshita, Hidefumi; Nakagawa, Ken; Usui, Yukio; Iwamura, Masatsugu; Ito, Akihiro; Miyajima, Akira; Hoshi, Akio; Arai, Yoichi; Baba, Shiro; Matsuda, Tadashi

2015-08-01

Three-dimensional (3D) imaging systems have been introduced worldwide for surgical instrumentation. A difficulty of laparoscopic surgery involves converting two-dimensional (2D) images into 3D images and depth perception rearrangement. 3D imaging may remove the need for depth perception rearrangement and therefore have clinical benefits. We conducted a multicenter, open-label, randomized trial to compare the surgical outcome of 3D-high-definition (HD) resolution and 2D-HD imaging in laparoscopic radical prostatectomy (LRP), in order to determine whether an LRP under HD resolution 3D imaging is superior to that under HD resolution 2D imaging in perioperative outcome, feasibility, and fatigue. One-hundred twenty-two patients were randomly assigned to a 2D or 3D group. The primary outcome was time to perform vesicourethral anastomosis (VUA), which is technically demanding and may include a number of technical difficulties considered in laparoscopic surgeries. VUA time was not significantly shorter in the 3D group (26.7 min, mean) compared with the 2D group (30.1 min, mean) (p = 0.11, Student's t test). However, experienced surgeons and 3D-HD imaging were independent predictors for shorter VUA times (p = 0.000, p = 0.014, multivariate logistic regression analysis). Total pneumoperitoneum time was not different. No conversion case from 3D to 2D or LRP to open RP was observed. Fatigue was evaluated by a simulation sickness questionnaire and critical flicker frequency. Results were not different between the two groups. Subjective feasibility and satisfaction scores were significantly higher in the 3D group. Using a 3D imaging system in LRP may have only limited advantages in decreasing operation times over 2D imaging systems. However, the 3D system increased surgical feasibility and decreased surgeons' effort levels without inducing significant fatigue.

Increasing educational indebtedness influences medical students to pursue specialization: a military recruitment potential?

Science.gov (United States)

Bale, Asha G; Coutinho, Karl; Swan, Kenneth G; Heinrich, George F

2013-02-01

Cost of medical education and student indebtedness has increased dramatically. This study surveyed medical students on educational debt, educational costs, and whether indebtedness influenced career choice. Responses should impact (1) Department of Defense (DoD) recruitment of physicians and (2) future of primary care. The authors surveyed 188 incoming medical students (University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Class of 2012) concerning educational indebtedness, perceptions about educational costs, and plans regarding loan repayment. Data were analyzed and expressed as mean +/- standard error. Students with loans anticipated their medical educational costs to be $155,993. 62% felt costs were "exorbitant," and 28% "appropriate." 64% planned to specialize, whereas only 9% chose primary care. 28% of students planning specialization said income potential influenced their decision. 70% of students said cost was a factor in choosing New Jersey Medical School over a more expensive school. Students anticipated taking about 10 years to repay loans. As medical educational costs and student indebtedness rise, students are choosing less costly education and career paths with higher potential future earnings. These trends will negatively impact health care availability, accessibility, and cost. DoD programs to provide financial assistance in exchange for military service are not well publicized. These findings should increase DoD recruitment opportunities.

Classification of European Union countries according to a household debt level and structure

Directory of Open Access Journals (Sweden)

Zbigniew Gołaś

2011-01-01

Full Text Available In the article were shown the results of cross-sectional and dynamic analysis of diversification of the level and structure of household debt and the problems with its repayment in the EU countries over the period 2005-2009. In the article the multidimen-sional methods of data analysis (cluster analysis – k-means method which enabled to classify the households in the EU according to the characteristics that were used describe its debt. Moreover, in order to determine the quantitative relationships between the level of household debt, and between the frequency of occurring the problem with debt repayment, the tools of correlation and regression analysis were used. In the article were shown the results of cross-sectional and dynamic analysis of diversification of the level and structure of household debt and the problems with its repayment in the EU countries over the period 2005-2009. In the article the multidimen-sional methods of data analysis (cluster analysis – k-means method which enabled to classify the households in the EU according to the characteristics that were used describe its debt. Moreover, in order to determine the quantitative relationships between the level of household debt, and between the frequency of occurring the problem with debt repayment, the tools of correlation and regression analysis were used.

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

Science.gov (United States)

2010-01-20

... following methods: Federal eRulemaking Portal: http://www.regulations.gov . Follow the instructions for... Leader, Veterinary Science; National Institute of Food and Agriculture; U.S. Department of Agriculture..., Extension, and Teaching Policy Act of 1977 (NARETPA). This information collection applies to Subpart B of 7...

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

Science.gov (United States)

2011-11-03

...: Paper, disk or CD-ROM submissions should be submitted to VMLRP, Policy and Oversight Division, National... a veterinarian's student loan debt per year if the veterinarian commits to at least three years to... passed into law adding section 1415A to the National Agricultural Research, Extension, and Teaching...

Selling an Energy Efficiency Loan Portfolio in Oregon: Resale of the Craft3 loan portfolio to Self-Help Credit Union

Energy Technology Data Exchange (ETDEWEB)

Thompson, Peter; Borgeson, Merrian; Kramer, Chris; Zimring, Mark; Goldman, Charles

2014-05-30

Under the Clean Energy Works (CEW) program, Craft3 developed a loan product that widened access to financing for homeowners, offered long term funding, and collected repayments through the customer?s utility bill. The program?s success led Craft3 to pursue the sale of the loan portfolio to both mitigate its own risks and replenish funds for lending. This sale breaks new ground for energy efficiency finance and is notable as it was completed even with many novel program design elements. It replenished Craft3?s program capital and uncovered some valuable lessons that may facilitate future transactions. However, the lack of data history and the unproven nature of the loan portfolio meant that Craft3 had to limit the risk of losses to Self-Help, the purchaser of the portfolio. It remains to be seen whether this experience will pave the way for more sales of on-bill energy efficiency loan portfolios. This case study illustrates how certain program design decisions can sometimes both facilitate programmatic objectives and possibly present challenges for the sale of a portfolio of energy efficiency loans.

The role of lenders' trust in determining borrowing conditions for sovereign debt: An analysis of one-period government bonds with default risk

OpenAIRE

Guo, Yanling

2015-01-01

In this paper, the author considers the sovereign debt in the form of one-period government bonds with default risk, which can be purchased by and traded among domestic and foreign investors. She shows that the weight assigned to the lenders' interest by the borrowing government at the time of debt repayment, which captures the lenders' trust in the government's propensity to repay the debt and is denoted as », also determines the default risk: a higher » means a lower default risk ceteris pa...

The Speed of Visual Attention and Motor-Response Decisions in Adult Attention-Deficit/Hyperactivity Disorder

DEFF Research Database (Denmark)

Cross-Villasana, Fernando; Finke, Kathrin; Hennig-Fast, Kristina

2015-01-01

Abstract Background: Adults with Attention Deficit/Hyperactivity Disorder (ADHD) exhibit slowed reaction times (RTs) in various attention tasks. The exact origins of this slowing, however, have not been yet established. Potential candidates are early sensory processes mediating the deployment...... of focal-attention, stimulus-response translation processes deciding upon the appropriate motor-response, and motor processes generating the response. Methods: We combined mental chronometry (RT) measures of adult ADHD (n = 15) and healthy control (n = 15) participants with their lateralized event...... (sLRP) and response events (rLRP) were used to index the times taken for response selection and production, respectively. To assess the clinical relevance of ERPs, a correlation analysis between neural measures and subjective current and retrospective ADHD symptom ratings was performed. Results: ADHD...

The effectiveness of reintegrative shaming and restorative justice conferences: focusing on juvenile offenders' perceptions in Australian reintegrative shaming experiments.

Science.gov (United States)

Kim, Hee Joo; Gerber, Jurg

2012-10-01

This article examines the effectiveness of diversionary restorative justice (RJ) conferences through the eyes of juvenile offenders. In Australia, Reintegrative Shaming Experiments (RISE) are based on Braithwaite's theory of reintegrative shaming. Previous studies, although showing that RISE reported high levels of victim satisfaction and positive changes in the attitudes of offenders, also demonstrated that it has different outcomes for juvenile offenders depending on the type of offense with which they were charged. However, the effectiveness of RISE in terms of the offenders' perceptions has not been addressed, and the impact of the offenders' perceptions about RISE still remains under investigation. Using Australian data from RISE between 1995 and 1999, this article examines juvenile offenders' perceptions on preventing reoffending, repaying the victim and society, and the degree of repentance. The data were taken from interviews with juvenile offenders to measure their perceptions after the court or RISE processing. A comparison of standard court processing effects and RISE on juvenile offending, including property crime, shoplifting, and violent offenses, was undertaken. The results from this study were somewhat inconsistent with previous research. In this study, there was no significant relationship between RJ conference and the offenders' own perceptions on the prevention of future offending. However, it was found that there were treatment effects on repaying the victim, repaying society, and the degree of feeling repentance, and that younger offenders wanted to repay the victim/society and feel repentance.

An Adaptive Tabu Search Heuristic for the Location Routing Pickup and Delivery Problem with Time Windows with a Theater Distribution Application

National Research Council Canada - National Science Library

Burks, Jr, Robert E

2006-01-01

.... The location routing problem (LRP) is an extension of the vehicle routing problem where the solution identifies the optimal location of the depots and provides the vehicle schedules and distribution routes...

Do Tax Incentives for Saving in Pension Accounts Cause Debt Accumulation?

DEFF Research Database (Denmark)

Yde Andersen, Henrik

2018-01-01

This paper applies a quasi-experimental research design on a Danish 2010 policy that reduced tax incentives for saving in annuity pension schemes to show significant substitution of savings from retirement accounts to gross debt repayments. We find that for every 1 Danish currency unit reduction...... in retirement savings 31 cents goes to debt repayments. Taking into account all types of savings, we find full crowding-out. Consistent with previous findings, we document that the effect is driven by a minority, about 23 percent, who actively rebalance their savings....

The great exterminator of children.

Science.gov (United States)

Logie, D

1992-05-30

Time is running out. Major contributors to declines in the health of Brazilian children, particularly street children, are the international debt crisis, the reverse flow of capital from the South to the North, and economic adjustment policies. There are medical consequences and an ecological debt. There is a question about the merits of having the poor pay for the folly of bad, past government decisions. All the major charities campaigned against repayment of debt. Banks are only exposed to 3% of their total assets in Third World debt, and are receiving tax relief for non repayment. Austerity programs have meant cuts in health and education, and diversion of food, wages, and welfare to producing exports in order to repay the debt. The message is earn more and spend less. The poor are hit the hardest, particularly by rising food prices. Diseases which were though to be eradicated are coming back. After decades of economic advances, countries are slipping back into mass poverty. Cuts in food subsidies or health care and family planning affect women and overpopulation. Land is being usurped from peasant farmers and tropical forests destroyed; urbanization has led to abandonment of 8 million children on the streets. The 1989 Brady plan suggests trading commercial debt for lower priced bonds which could be purchased by big business or even by the country itself. The deals tend to be complex. So far only 6 countries have benefited. Another proposal is English Prime Minister John Major's Trinidad Terms of September 1990, which is directed to low income country debtors. In December 1991 the UK cancelled 50% of the debt to the poorest countries over the next 3 years. The US and Australia have set up rescheduling agreements. World Bank debt is still in question. Commercial banks should also make an offer of relief. It is suggested that doctors unite in an organization called Physicians Against International Debt-PAID to lobby banks, governments, and the international

DAMPAK TERUKUR FASILITAS KREDIT USAHA MIKRO POLA TANGGUNGRENTENG SEBAGAI ALAT PEMBETUK LENDING MODEL BAGI USAHA MIKRO PEMULA DAN PROGRAM PENDANAAN BERKELANJUTAN

Directory of Open Access Journals (Sweden)

Sunardi Sunardi

2016-10-01

Full Text Available The objectives of this research are to examine the revenue impact and the repayment capacity of working modal credit facility for Small Medium Eterprises by using joint liability. This research used a correlational ap-proach and purposive sampling technique with several criteria such as: (1 Small Medium Eterprises should have 5 (five people minimally; (2 Small Medium Eterprises have been guided by a university; (3 Small Medium Eterprises have got a loan from a bank. The result of this research shows that the revenue and the rep6ayment capacity from the fourth Small Medium Eterprises have increased. The highest revenue is ob-tained from Batik sector and the lowest revenue is obtained from convection sector.

Pre-movement planning processes in people with congenital mirror movements.

Science.gov (United States)

Franz, E A; Fu, Y

2017-10-01

Pre-movement processes were investigated in people with Congenital mirrormovement (CMM), a rare disorder in which bilateral movement (mirroring) occurs in the upper distal extremities (primarily the hands and fingers) during intended unilateral movements. Abnormal density of ipsilateral corticospinal projections is an established hallmark of CMM. This study tested whether the Lateralised Readiness Potential (LRP), which reflects movement planning and readiness, is also abnormal in people with CMM. Twenty-eight neurologically-normal controls and 8 people with CMM were tested on a unimanual Go/No-go task while electroencephalography (EEG) was recorded to assess the LRP. No significant group differences were found in reaction time (RT). However, significantly smaller LRP amplitudes were found, on average, in the CMM group compared to Controls at central-motor (C3,C4) sites in stimulus-locked and response-locked epochs; similar group differences were also found at further frontal sites (F3,F4) during response-locked epochs. Abnormal brain activity in pre-movement processes associated with response planning and preparation is present in people with CMM. Aberrant bilateral activity during pre-movement processes is clearly implicated; whether part of the etiology of CMM, or as a mechanism of neuro-compensation, is not yet known. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

Science.gov (United States)

Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Abdullah, Maizaton Atmadini; Basri, Hamidon

2017-11-01

Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue. Copyright © 2017 Elsevier

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.

Modelling Monetary and Fiscal Governance in the Wake of the Sovereign Debt Crisis in Europe

Directory of Open Access Journals (Sweden)

Bodo Herzog

2016-05-01

Full Text Available This paper analyzes different government debt relief programs in the European Monetary Union. I build a model and study different options ranging from debt relief to the European Stability Mechanism (ESM. The analysis reveals the following: First, patient countries repay debt, while impatient countries more likely consume and default. Second, without ESM loans, indebted countries default anyway. Third, if the probability to be an impatient government is high, then the supply of loans is constrained. In general, sustainable and unsustainable governments should be incentivized differently especially in a supranational monetary union. Finally, I develop policy recommendations for the ongoing debate in the Eurozone.

Interleukin-1 Acts via the JNK-2 Signaling Pathway to Induce Aggrecan Degradation by Human Chondrocytes.

Science.gov (United States)

Ismail, Heba M; Yamamoto, Kazuhiro; Vincent, Tonia L; Nagase, Hideaki; Troeberg, Linda; Saklatvala, Jeremy

2015-07-01

Aggrecan enables articular cartilage to bear load and resist compression. Aggrecan loss occurs early in osteoarthritis and rheumatoid arthritis and can be induced by inflammatory cytokines such as interleukin-1 (IL-1). IL-1 induces cleavage of specific aggrecans characteristic of the ADAMTS proteinases. The aim of this study was to identify the intracellular signaling pathways by which IL-1 causes aggrecan degradation by human chondrocytes and to investigate how aggrecanase activity is controlled by chondrocytes. We developed a cell-based assay combining small interfering RNA (siRNA)-induced knockdown with aggrecan degradation assays. Human articular chondrocytes were overlaid with bovine aggrecan after transfection with siRNAs against molecules of the IL-1 signaling pathway. After IL-1 stimulation, released aggrecan fragments were detected with AGEG and ARGS neoepitope antibodies. Aggrecanase activity and tissue inhibitor of metalloproteinases 3 levels were measured by enzyme-linked immunosorbent assay. Low-density lipoprotein receptor-related protein 1 (LRP-1) shedding was analyzed by Western blotting. ADAMTS-5 is a major aggrecanase in human chondrocytes, regulating aggrecan degradation in response to IL-1. The tumor necrosis factor receptor-associated 6 (TRAF-6)/transforming growth factor β-activated kinase 1 (TAK-1)/MKK-4 signaling axis is essential for IL-1-induced aggrecan degradation, while NF-κB is not. Of the 3 MAPKs (ERK, p38, and JNK), only JNK-2 showed a significant role in aggrecan degradation. Chondrocytes constitutively secreted aggrecanase, which was continuously endocytosed by LRP-1, keeping the extracellular level of aggrecanase low. IL-1 induced aggrecanase activity in the medium in a JNK-2-dependent manner, possibly by reducing aggrecanase endocytosis, because IL-1 caused JNK-2-dependent shedding of LRP-1. The signaling axis TRAF-6/TAK-1/MKK-4/JNK-2 mediates IL-1-induced aggrecanolysis. The level of aggrecanase is controlled by its

Plasminogen activator inhibitor-2 polymorphism associates with recurrent coronary event risk in patients with high HDL and C-reactive protein levels.

Directory of Open Access Journals (Sweden)

James P Corsetti

Full Text Available The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C and C-reactive protein (CRP and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2 were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1, a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095 and LRP-1 (LRP1, rs1800156 as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272, p22phox (CYBA, rs4673, and thrombospondin-4 (THBS4, rs1866389. Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014 along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked

Prepayment risk, impact on credit products

Directory of Open Access Journals (Sweden)

Dan Costin NIŢESCU

2012-08-01

Full Text Available Credit pricing is always an important aspect of operations of banks, as loans are generally two thirds of bank assets. Therefore, the study of factors influencing a bank customer behavior and their impact on early repayment of loans may have a significant influence in reducing the risk assumed by such unexpected operations.Objective analysis of prepayment risk is to estimate the probability of repayment to better manage its manifestation. The existence of potential customers that use this option exposes the bank to a number of risks, such as interest rate risk, the maturity mismatch risk and liquidity risk.Proper evaluation and forecasting the evolution of this risk can bring great benefits for a credit institution in the management of loan products and customer relationship: lower risk of over-ensure against fixed rate mortgage, a better management of short-term and long term liquidity needs (thus reducing the risk of over-financing can offer customers more competitive pricing (achieved by reducing funding costs due to better assessment and management of risks involved early repayment.

Beauty premium: Event-related potentials evidence of how physical attractiveness matters in online peer-to-peer lending.

Science.gov (United States)

Jin, Jia; Fan, Bonai; Dai, Shenyi; Ma, Qingguo

2017-02-15

Although it is well known that attractiveness-based impressions affect the labor market, election outcomes and many other social activities, little is known about the role physical attractiveness plays in financial transactions. With the development of online finance, peer-to-peer lending has become one of the most important ways in which businesses or individuals raise capital. However, because of information asymmetry, the lender must decide whether or not to lend money to a stranger based on limited information, resulting in their decision being influenced by many other factors. In the current study, we investigated how potential borrowers' facial attractiveness influenced lenders' attitudes toward borrowers' repayment behavior at the brain level by using event-related potentials. At the priming stage, photos of attractive borrowers induced smaller N200 amplitude than photos of unattractive borrowers. Meanwhile, at the feedback stage, compared with the condition of repaying on time, breach of repayment from unattractive borrowers induced larger feedback-related negativity (FRN) amplitude, which was a frontal-central negative deflection and would be enhanced by the unexpected outcome. Furthermore, smaller P300 amplitude was also elicited by the condition of not repaying on time. These differences in the FRN and P300 amplitudes were not observed between negative and positive feedback from attractive borrowers. Therefore, our findings suggest that the beauty premium phenomenon is present in online peer-to-peer lending and that lenders were more tolerant toward attractive borrowers' dishonest behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Reconciliation as a tool for decision making within decision tree related to insolvency problems

Directory of Open Access Journals (Sweden)

Tomáš Poláček

2016-05-01

Full Text Available Purpose of the article: The paper draws on the results of previous studies recoverability of creditor’s claims, where it was research from debtor’s point of view and his/her debts on the Czech Republic financial market. The company, which fell into a bankruptcy hearing, has several legislatively supported options how to deal with this situation and repay creditors money. Each of the options has been specified as a variant of a decisionmaking tree. This paper is focused on third option of evaluation – The reconciliation. The heuristic generates all missing information items. The result is then focused on the comparison and evaluation of the best ways to repay the debt, also including solution for the future continuation of the company currently in liquidation and quantification of percentage refund of creditors claim. A realistic case study is presented in full details. Further introduction of decision making with uncerteinties in insolvency proceedings. Methodology/methods: Solving within decision tree with partially ignorance of probability using reconciliation. Scientific aim: Comparison and evaluation of the best ways to repay the debt, also including solution for the future continuation of the company currently in liquidation and quantification of percentage refund of creditors claim. Findings: Predictions of future actions in dealing with insolvency act and bankruptcy hearing, quicker and more effective agreeing on compromises among all creditors and debtor. Conclusions: Finding a best way and solution of repayment and avoiding of termination for both of interested parties (creditor and debtor.

Predictive factors from videourodynamic study for delayed urinary continence after laparoscopic radical prostatectomy

Directory of Open Access Journals (Sweden)

Kuan-Tang Huang

2015-03-01

Conclusion: Preoperative small bladder capacity at FS, large prostate, and BOO are predicting factors of SUI at 6 months after LRP. Baseline DO and BOO did not have an impact on postoperative urgency or UUI.

42 CFR 62.23 - How will individuals be selected to participate in the Loan Repayment Program?

Science.gov (United States)

2010-10-01

... practice experience and other criteria related to professional competence or conduct. (b) Among qualified... (5) The individual's academic standing, prior professional experience in a health manpower shortage...

Radical prostatectomy: evolution of surgical technique from the laparoscopic point of view

Directory of Open Access Journals (Sweden)

Xavier Cathelineau

2010-04-01

Full Text Available PURPOSE: To review the literature and present a current picture of the evolution in radical prostatectomy from the laparoscopic point of view. MATERIALS AND METHODS: We conducted an extensive Medline literature search. Articles obtained regarding laparoscopic radical prostatectomy (LRP and our experience at Institut Montsouris were used for reassessing anatomical and technical issues in radical prostatectomy. RESULTS: LRP nuances were reassessed by surgical teams in order to verify possible weaknesses in their performance. Our basic approach was to carefully study the anatomy and pioneer open surgery descriptions in order to standardized and master a technique. The learning curve is presented in terms of an objective evaluation of outcomes for cancer control and functional results. In terms of technique-outcomes, there are several key elements in radical prostatectomy, such as dorsal vein control-apex exposure and nerve sparing with particular implications in oncological and functional results. Major variations among the surgical teams' performance and follow-up prevented objective comparisons in radical prostatectomy. The remarkable evolution of LRP needs to be supported by comprehensive results. CONCLUSIONS: Radical prostatectomy is a complex surgical operation with difficult objectives. Surgical technique should be standardized in order to allow an adequate and reliable performance in all settings, keeping in mind that cancer control remains the primary objective. Reassessing anatomy and a return to basics in surgical technique is the means to improve outcomes and overcome the difficult task of the learning curve, especially in minimally access urological surgery.

Effect of serum testosterone and percent tumor volume on extra-prostatic extension and biochemical recurrence after laparoscopic radical prostatectomy

Directory of Open Access Journals (Sweden)

Eu Chang Hwang

2016-01-01

Full Text Available Several studies have revealed that the preoperative serum testosterone and percent tumor volume (PTV predict extra-prostatic extension (EPE and biochemical recurrence (BCR after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy (LRP. We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen (PSA >0.2 ng ml−1 . The threshold for serum total testosterone was 3.0 ng ml−1 . Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone (<3.0 ng ml−1 was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone (<3.0 ng ml−1 , adjusted OR, 8.52; 95% CI, 5.04-14.4, P= 0.001 predicted EPE and PTV (adjusted OR, 1.02; 95% CI, 1.01-1.05, P= 0.046 predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.

Selenoprotein P is the essential selenium transporter for bones.

Science.gov (United States)

Pietschmann, Nicole; Rijntjes, Eddy; Hoeg, Antonia; Stoedter, Mette; Schweizer, Ulrich; Seemann, Petra; Schomburg, Lutz

2014-05-01

Selenium (Se) plays an important role in bone physiology as best reflected by Kashin-Beck disease, an endemic Se-dependent osteoarthritis. Bone development is delayed in children with mutations in SECIS binding protein 2 (SBP2), a central factor for selenoprotein biosynthesis. Circulating selenoprotein P (SePP) is positively associated with bone turnover in humans, yet its function for bone homeostasis is not known. We have analysed murine models of altered Se metabolism. Most of the known selenoprotein genes and factors needed for selenoprotein biosynthesis are expressed in bones. Bone Se is not associated with the mineral but exclusively with the organic matrix. Genetic ablation of Sepp-expression causes a drastic decline in serum (25-fold) but only a mild reduction in bone (2.5-fold) Se concentrations. Cell-specific expression of a SePP transgene in hepatocytes efficiently restores bone Se levels in Sepp-knockout mice. Of the two known SePP receptors, Lrp8 was detected in bones while Lrp2 was absent. Interestingly, Lrp8 mRNA concentrations were strongly increased in bones of Sepp-knockout mice likely in order to counteract the developing Se deficiency. Our data highlight SePP as the essential Se transporter to bones, and suggest a novel feedback mechanism for preferential uptake of Se in Se-deprived bones, thereby contributing to our understanding of hepatic osteodystrophy and the consistent bone phenotype observed in subjects with inherited selenoprotein biosynthesis mutations.

Doelmatigheid van TENS-therapie bij subacute lumbosacrale radiculaire pijn (≤ 6 maanden) in vergelijking met een transforaminale epidurale injectie

NARCIS (Netherlands)

Dr. J.H. Groenewoud; E.E. Vegt; K.D. Meijers-Verhoeven

2015-01-01

Introductie Transcutane Elektrische Neuro Stimulatie (TENS) kan een bijdrage leveren aan de behandeling van lumbosacrale radiculaire pijn (LRP) maar wordt wegens onvoldoende evidence niet als standaard geadviseerd. Doel Vergelijken van het effect van TENS-behandeling met een transforaminale

On how the motor cortices resolve an inter-hemispheric response conflict: an event-related EEG potential-guided TMS study of the flankers task

DEFF Research Database (Denmark)

Verleger, Rolf; Kuniecki, Michal; Möller, Friderike

2009-01-01

in the contralateral first dorsal interosseus muscle was taken as an index of corticospinal excitability. Guided by the previous LRP measurement, magnetic stimuli were applied 0-90 ms after the individual LRP peak, to cover the epoch of conflict resolution. When flankers were incompatible with the target, excitability......An important aspect of human motor control is the ability to resolve conflicting response tendencies. Here we used single-pulse transcranial magnetic stimulation (TMS) to track the time course of excitability changes in the primary motor hand areas (M1(HAND)) while the motor system resolved...... response conflicts. Healthy volunteers had to respond fast with their right and left index fingers to right- and left-pointing arrows. These central target stimuli were preceded by flanking arrows, inducing premature response tendencies which competed with correct response activation. The time point...

Cellular uptake of lipoproteins and Persistent Organic Compounds - An update and new data

DEFF Research Database (Denmark)

Hjelmborg, Philip Sebastian; Andreassen, Thomas Kjærgaard; Bonefeld-Jørgensen, Eva Cecilie

2008-01-01

including the pesticide DDT (p,p'-dichlorodiphenyltrichloroethane), and especially its metabolite DDE (p,p'-dichlorodiphenyldichloroethene), interacts with nuclear hormone receptors causing these to malfunction, which in turn results in a range of deleterious health effects in humans. The aim of the present...... study was to determine the role of lipoprotein receptors in mouse embryonic fibroblast (MEF) cells in conjunction with uptake of DDT-lipoprotein complexes from supplemented media in vitro. Uptake of DDT by MEF cells was investigated using MEF1 cells carrying the receptors LRP (low-density lipoprotein...... receptor-related protein) and LDLR (low density lipoprotein receptor) present and MEF4 cells with no LRP and LDLR expression. Cells were incubated together with the complex of LDL and [14C]DDT. The receptor function was further evaluated by adding the 40 kDa receptor-associated protein (RAP) which blocks...

Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

NARCIS (Netherlands)

Glass, D.A.; Bialek, P.; Ahn, J.D.; Starbuck, M.; Patel, M.S.; Clevers, J.C.; Taketo, M.M.; Long, F.; McMahon, A.P.; Lang, R.A.; Karsenty, G.

2005-01-01

Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast

Can the Green Deal be fair too? Exploring new possibilities for alleviating fuel poverty

International Nuclear Information System (INIS)

Guertler, Pedro

2012-01-01

Energy efficiency and social programmes have failed to stem the dramatic increase in the number of fuel poor households in recent years. As the 2016 deadline for eradicating fuel poverty nears, energy efficiency and fuel poverty programmes are undergoing significant changes. The ambitions for Britain's Green Deal, the overhaul of supplier obligations alongside the winding down of Warm Front, and the introduction of an incentive for renewable heat combine to form a sea change in how energy efficiency and fuel poverty objectives are financed and delivered. Green Deal Finance (GDF) eliminates the up-front capital cost of energy efficiency measures to the household by linking repayments to energy savings and spreading them over many years. This paper asks whether and how GDF could be beneficial to fuel poor households. Using scenarios modelled on the English House Condition Survey, it explores the extent to which fuel poverty could be reduced, allowing for repayments incurred by GDF. It examines how much further fuel poverty could be alleviated were the capital cost subsidised or repayments supported, and concludes that a flexible design for GDF is necessary if it is to contribute to alleviating fuel poverty. - Highlights: ► The potential impact of Green Deal finance (GDF) on fuel poverty (FP) is explored. ► GDF based on actual energy use rather than notional need is better at reducing FP. ► Additional subsidy by energy companies improves the impact of GDF on FP. ► However, the resultant increases in energy bills would negate much of this effect. ► Government support for repayments could be fairer and go further.

PELAKSANAAN PEMBIAYAAN DANA TALANGAN HAJI PADA PERBANKAN SYARIAH

Directory of Open Access Journals (Sweden)

Erni Susana

2017-03-01

Full Text Available The syariah banking activity was basically the expansion of banking service for people who needed it andexpected the repayment which was not based on interest rate, but based on syariah as what determined inIslamic law. To help people to get pilgrim portion soon, syahriah banking offered agreement which was usedin financing pilgrim lending fund like al-qardh agreement and al-ijarah (ujroh system. The aim of thisresearch was to analyze financing using al-qardh agreement and al-ijarah (ujroh system agreement. Al-qardhwas giving wealth to other people that could be collected back or asked for, or in other words lending withoutexpecting repayment, while the meaning of al-ijarah agreement was an agreement of moving the use or utilizationright on goods and service, through rent payment or ujroh without being followed by transferringownership. The implementation of financing pilgrim lending fund conformed to the rule of financing pilgrimarrangement which was written in Fatwa (a binding ruling in religious matters DSN No. 29/DSN-MUI/VI/2002. The amount of al-ijarah repayment was not based on the amount of lending al-qardh given to thecustomers.

Student loan burden and its impact on career decisions in dermatology.

Science.gov (United States)

Nguyen, Jannett; Song, Eingun; Liu, Michael A; Lee, Patrick K; Truong, Sam

2017-12-01

Dermatology departments in the United States face difficulties in recruiting dermatologists to academic positions, raising concerns for the future of dermatology education and research. This preliminary study aimed to explore the impact of student loan burden on career plans in dermatology and to determine if the Public Service Loan Forgiveness (PSLF) program can be used as a recruitment tool for academic positions in dermatology. Results from this electronic survey, which was distributed to dermatology residents and attending physicians, revealed that debt burden may influence career decisions in dermatology. Dermatologists may not be fully educated on loan repayment options. With increased awareness, the PSLF can potentially be used as a recruitment tool for academic positions in dermatology.

Analysis of the binding of pro-urokinase and urokinase-plasminogen activator inhibitor-1 complex to the low density lipoprotein receptor-related protein using a Fab fragment selected from a phage-displayed Fab library

NARCIS (Netherlands)

Horn, I. R.; Moestrup, S. K.; van den Berg, B. M.; Pannekoek, H.; Nielsen, M. S.; van Zonneveld, A. J.

1995-01-01

The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) mediates endocytosis of a number of structurally unrelated ligands, including complexes of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) or urokinase plasminogen

An extrahepatic receptor-associated protein-sensitive mechanism is involved in the metabolism of triglyceride-rich lipoproteins

NARCIS (Netherlands)

Vlijmen, B.J.M. van; Rohlmann, A.; Page, S.T.; Bensadoun, A.; Bos, I.S.T.; Berkel, T.J.C. van; Havekes, L.M.; Herz, J.

1999-01-01

We have used adenovirus-mediated gene transfer in mice to investigate low density lipoprotein receptor (LDLR) and LDLR-related protein (LRP)- independent mechanisms that control the metabolism of chylomicron and very low density lipoprotein (VLDL) remnants in vivo. Overexpression of receptor-

Dissociations between motor-related EEG measures in a cued movement sequence task

NARCIS (Netherlands)

Gladwin, Thomas E.; t' Hart, Bernhard M.; de Jong, Ritske

Different aspects of preparation, especially processes related to knowing what to prepare versus applying that foreknowledge effectively, may be reflected in different types of brain activity, e.g., the lateralized readiness potential (LRP), beta-band event-related desynchronization and phase

Dynamic Incentives in Microfinance Group Lending

Directory of Open Access Journals (Sweden)

Naveen Kumar K

2012-04-01

Full Text Available One of the most essential tools of poverty reduction would be the viable expansion of institutional credit facilities to large sections of the people who neither have adequate collateral nor credit history to secure a loan. In this backdrop, social collateral is popularized through the group lending programs to address the credit market problems. Microfinance through group lending is acting as a screening device; the joint liability mechanism creates incentives for internal monitoring. Hence, it has received a lot of attention from policy makers as well as academicians. It is playing an important role in delivering financial services to the “socially and economically excluded” poor, in general, and women, in particular. The group lending works with various dynamic incentives. One such kind is principle of progressive lending and it plays a vital role in sustaining the groups for the persistent delivery of microfinance services to its members. In progressive lending, a typical borrower receives very small amounts at first, which increases with good repayment conduct or it links new, larger loans to past repayment. This article explores possible theoretical and empirical relationship between progressive lending and its determinants in group lending approach. The primary survey was conducted in 10 villages covering 106 self-help groups and 318 members in Karnataka, India. The empirical results show the progressive lending amount rising up to 698% of the initial loan of the self-help groups.

THE GENESIS OF THE FUNCTIONS OF GOVERNMENT DEBT SECURITIES

Directory of Open Access Journals (Sweden)

V. Osetskyi

2015-06-01

Full Text Available Government borrowings appear at a certain stage of development the economic system. Governments used loans many centuries ago because there are often occurred situations when borrowings were the only way to attract additional financial resources. The preconditions for government loans from the position of creditors are also important. These, in particular, include: the availability of subjects that have the temporarily available funds; investor confidence in the state, that stimulating their interest in buying government debt securities; state’s ability to repay its obligations and so on. Thus, the article deals with the basic prerequisites of the government securities market and its function at different stages of develop-ment of economic relations. So, it was found, that the main functions of local borrowing in XIV-XX centuries include the following: fiscal, public debt management, improved economic situation in some areas and repayment of previously issued loans. In modern conditions the functions of government securities have expanded and include: regulation of the money market and stock market, smoothing unevenness of funds flow to the budget, funding various pro-grams, support the liquidity of financial institutions. The author also highlights that objective necessity of using government borrowing associated with the presence of contradictions between the existing needs of society and the state’s capacity to satisfy them within existing financial re-sources. And in such situations government securities are a means of mobilizing additional financial resources to the state budget.

Skin Microbiome in Patients With Psoriasis Before and After Balneotherapy at the Thermal Care Center of La Roche-Posay.

Science.gov (United States)

Martin, Richard; Henley, Jessica B; Sarrazin, Patrick; Seité, Sophie

2015-12-01

Changes in the composition of microbial communities that colonize skin have been linked to several diseases including psoriasis. Nevertheless, the intra-individual dynamics and how these communities respond to balneotherapy remain poorly understood. This open label study was conducted between July and September 2012. Microbial communities of patients with psoriasis vulgaris were characterized prior and post a 3-week selenium-rich water balneotherapy treatment at the thermal care center La Roche-Posay (La Roche-Posay, France). Balneotherapy consisted of high-pressure filiform showers, baths, facial, and body spray treatments as well as La Roche-Posay thermal spring water (LRP-TSW) consumption. Swabs were taken from affected and proximal unaffected skin and the 16S rRNA bacterial gene was used to analyze the composition of bacterial communities. Using the same 16S rRNA gene tool, we tried to describe the LRP-TSW bacterial landscape. This study included 54 patients diagnosed with moderate to severe forms of psoriasis vulgaris. After eliminating individuals lacking paired samples from both visits, 29 individuals were analyzed for their microbiome profile. Shannon Diversity Index and global bacterial landscape indicate similar microbial communities on both unaffected and adjacent affected skin. PASI values decreased post-balneotherapy implying improvement of disease severity. No significant change in the Shannon Diversity Index was noticed at the end of the third week. The average taxonomic composition of skin microbial communities associated with unaffected and affected skin of psoriatic patients post-balneotherapy shows that treatment with LRP-TSW significantly increased the level of Xanthomonas genus and, to a lesser extent, Corynebacterium genus. The Xanthomonas genus belongs to the main Xanthomonadaceae family found in LRP-TSW and also on healthy skin. In psoriatic patients, a poor bacterial biodiversity was noticed and the bacterial communities were similar on

Renal phenotypic investigations of megalin-deficient patients

DEFF Research Database (Denmark)

Storm, Tina; Tranebjærg, Lisbeth; Frykholm, Carina

2013-01-01

analysis of proximal tubular function in megalin-deficient patients.MethodsDirect sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through...

Injection of a soluble fragment of neural agrin (NT-1654 considerably improves the muscle pathology caused by the disassembly of the neuromuscular junction.

Directory of Open Access Journals (Sweden)

Stefan Hettwer

Full Text Available Treatment of neuromuscular diseases is still an unsolved problem. Evidence over the last years strongly indicates the involvement of malformation and dysfunction of neuromuscular junctions in the development of such medical conditions. Stabilization of NMJs thus seems to be a promising approach to attenuate the disease progression of muscle wasting diseases. An important pathway for the formation and maintenance of NMJs is the agrin/Lrp4/MuSK pathway. Here we demonstrate that the agrin biologic NT-1654 is capable of activating the agrin/Lrp4/MuSK system in vivo, leading to an almost full reversal of the sarcopenia-like phenotype in neurotrypsin-overexpressing (SARCO mice. We also show that injection of NT-1654 accelerates muscle re-innervation after nerve crush. This report demonstrates that a systemically administered agrin fragment has the potential to counteract the symptoms of neuromuscular disorders.

Oligo- and polymetastatic progression in lung metastasis(es) patients is associated with specific microRNAs.

Science.gov (United States)

Lussier, Yves A; Khodarev, Nikolai N; Regan, Kelly; Corbin, Kimberly; Li, Haiquan; Ganai, Sabha; Khan, Sajid A; Gnerlich, Jennifer L; Gnerlich, Jennifer; Darga, Thomas E; Fan, Hanli; Karpenko, Oleksiy; Paty, Philip B; Posner, Mitchell C; Chmura, Steven J; Hellman, Samuel; Ferguson, Mark K; Weichselbaum, Ralph R

2012-01-01

Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy. We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤ 5 initial metastases resected with curative intent. Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset. Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.

Contextual cueing effects despite spatially cued target locations.

Science.gov (United States)

Schankin, Andrea; Schubö, Anna

2010-07-01

Reaction times (RT) to targets are faster in repeated displays relative to novel ones when the spatial arrangement of the distracting items predicts the target location (contextual cueing). It is assumed that visual-spatial attention is guided more efficiently to the target resulting in reduced RTs. In the present experiment, contextual cueing even occurred when the target location was previously peripherally cued. Electrophysiologically, repeated displays elicited an enhanced N2pc component in both conditions and resulted in an earlier onset of the stimulus-locked lateralized readiness potential (s-LRP) in the cued condition and in an enhanced P3 in the uncued condition relative to novel displays. These results indicate that attentional guidance is less important than previously assumed but that other cognitive processes, such as attentional selection (N2pc) and response-related processes (s-LRP, P3) are facilitated by context familiarity.

El Salvador - Investment Support & Financial Services

Data.gov (United States)

Millennium Challenge Corporation — Research Questions. Through an analysis of business plans, borrower files, repayment data, applicant questionnaires, as well as information from interviews with...

Improving the drug delivery characteristics of graphene oxide based polymer nanocomposites through the “one-pot” synthetic approach of single-electron-transfer living radical polymerization

Energy Technology Data Exchange (ETDEWEB)

Gao, Peng; Liu, Meiying; Tian, Jianwen; Deng, Fengjie [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wang, Ke [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China); Xu, Dazhuang [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Liu, Liangji [Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006 (China); Zhang, Xiaoyong, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: weiyen@tsinghua.edu.cn [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China)

2016-08-15

Graphical abstract: The PEGylated graphene oxides with high water dispersibility, good biocompatibility as well as high drug loading capability were fabricated via “one-pot” SET-LRP. - Highlights: • Surface modification of graphene oxide with polymers. • One-pot single-electron-transfer living radical polymerization. • Improving drug delivery characteristics. • The synthetic approach is rather simple, universal and effective. - Abstract: Graphene oxide (GO) based polymer nanocomposites have attracted extensive research interest recently for their outstanding physicochemical properties and potential applications. However, surface modification of GO with synthetic polymers has demonstrated to be trouble for most polymerization procedures are occurred under non-aqueous solution, which will in turn lead to the restacking of GO. In this work, a facile and efficient “one-pot” strategy has been developed for surface modification of GO with synthetic polymers through single-electron-transfer living radical polymerization (SET-LRP). The GO based polymer nanocomposites were obtained via SET-LRP in aqueous solution using poly(ethylene glycol) methyl ether methacrylate (PEGMA) as the monomer and 11-bromoundecanoic acid as the initiator, which could be effectively adsorbed on GO through hydrophobic interaction. The successful preparation of GO based polymer nanocomposites was confirmed by a series of characterization techniques such as {sup 1}H nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, transmission electron microscopy and X-ray photoelectron spectroscopy. The resultant products exhibit high water disperisibility, excellent biocompatibility and high efficient drug loading capability, making these PEGylated GO nanocomposites promising candidates for biomedical applications.

Microwave-assisted synthesis, molecular docking and antitubercular activity of 1,2,3,4-tetrahydropyrimidine-5-carbonitrile derivatives

Czech Academy of Sciences Publication Activity Database

Mohan, S. B.; Kumar, B. V. V. R.; Dinda, S. C.; Naik, D.; Seenivasan, S. P.; Kumar, V.; Rana, D. N.; Brahmkshatriya, Pathik

2012-01-01

Roč. 22, č. 24 (2012), s. 7539-7542 ISSN 0960-894X Institutional research plan: CEZ:AV0Z40550506 Keywords : antitubercular * binding interactions * luciferase reporter phage (LRP) assay * microwave-assisted * molecular docking Subject RIV: CC - Organic Chemistry Impact factor: 2.338, year: 2012

Early Experience with Robot-assisted Laparoscopic Radical Prostatectomy

Directory of Open Access Journals (Sweden)

Hong Gee Sim

2004-10-01

Conclusions: rLRP is feasible in a practice with a low volume of radical prostatectomies. Significant improvement in perioperative parameters occurs after the first eight cases. This technique confers the benefits of enhanced precision and dexterity for complex laparoscopic work in the pelvic cavity.

Motives for intergenerational transfers: evidence from Malaysia.

Science.gov (United States)

Lillard, L A; Willis, R J

1997-02-01

In this paper we discuss a number of hypotheses about motives for intergenerational transfers within the family. We use data on time and money transfers between generations in Malaysia, where there is neither Social Security nor Medicare, to explore these hypotheses empirically. We find evidence supporting the hypotheses that children are an important source of old age security and that old age security is, in part, children's repayment for parental investments in their education. This repayment is partly a function of the children's income and, in the case of females, a function of their spouse's income. We also find evidence supporting the hypotheses that parents and children engage in the exchange of time help for money.

Sexual Assault

Science.gov (United States)

... Professions Indian Health Careers Indian Preference Loan Repayment Military Transition Student ... Sexual Assault Sexual assault is a significant problem affecting American Indians and Alaska Natives. Sexual assault ...

Financing of gas production expansion at Taipo

International Nuclear Information System (INIS)

Chan, R.T.H.

1991-01-01

Financing strategies applied to Phase I and Phase II were quite different. In Phase I, the project was more sophisticated and involved investments in different types of assets: Site acquisition; site formation and foundations; gas-making plants and associated equipment; naptha tanks; naptha pipeline; twin submarine gas pipeline connected to the existing distribution network; and workshop and offices. For Phase II, the tenderers demanded payment in foreign currencies because of their international procurement and their concern over Hong Kong currency at the time of submitting the tender. The Phase II financing package consists of: (1) ECGD facilities with a fixed interest rate at 9.15% p.a.--8 years with repayment in 10 semiannual installments over the last 5 years. (2) Fixed rate bank borrowings at 9% p.a. with repayment at the end of 5 years (use of swaps to obtain long-term money at lower interest rate). (3) Foreign currency deposits to cover exposure in two other currencies. (4) Forward contract to cover repayment installments in Sterling in the last 5 years at much lower rates of exchange. In a nutshell, by using a combination of different financing instruments, HKCG was able to eliminate foreign exchange and interest rate risks and reduce the overall capital cost of the plant

Thermo-Responsive Starch-g-(PAM-co-PNIPAM) : Controlled Synthesis and Effect of Molecular Components on Solution Rheology

NARCIS (Netherlands)

Fan, Yifei; Boulif, Nadia; Picchioni, Francesco

2018-01-01

A series of highly branched random copolymers of acrylamide (AM) and N-isopropylacrylamide (NIPAM) have been prepared from a waxy potato starch-based macroinitiator by aqueous Cu-0-mediated living radical polymerization (Cu-0-mediated LRP). The NIPAM intake in the copolymer was varied between 0% and

Identification of megalin/gp330 as a receptor for lipoprotein(a) in vitro

DEFF Research Database (Denmark)

Niemeier, A; Willnow, T; Dieplinger, H

1999-01-01

for both LRP and megalin/gp330 were compared with regard to their ability to bind, internalize, and degrade dioctadecyltetramethylindocarbocyanine perchlorate (DiI)-fluorescence-labeled Lp(a) as well as equimolar amounts of 125I-labeled Lp(a) and LDL. Uptake and degradation of radiolabeled Lp...

Wnt signaling: Ig-norrin the dogma.

Science.gov (United States)

Clevers, Hans

2004-06-08

Secreted Wnt proteins trigger the intracellular Wnt signaling cascade upon engagement of dedicated Frizzled-Lrp receptor complexes. Unexpectedly, a non-Wnt ligand for this receptor complex has now been discovered. This novel ligand, Norrin, is mutated in the hereditary ocular Norrie syndrome. Copyright 2004 Elsevier Ltd.

75 FR 17923 - Agency Information Collection Activities: Proposed Collection: Comment Request

Science.gov (United States)

2010-04-08

... Verification and Community Site Information form, the Loan Information and Verification form, the Authorization to Release Information form, the Applicant Checklist, and the Self-Certification form. The annual... respondent responses response hours NHSC LRP Application 5,175 1 5,175 0.30 1,553 Employment Verification-- 5...

75 FR 18512 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meetings

Science.gov (United States)

2010-04-12

... Deafness and Other Communication Disorders; Notice of Closed Meetings Pursuant to section 10(d) of the... Deafness and Other Communication Disorders Special Emphasis Panel, LRP's. Date: May 3, 2010. Time: 1 p.m... Committee: National Institute on Deafness and Other Communication Disorders Special Emphasis Panel, Meniere...

Oligo- and Polymetastatic Progression in Lung Metastasis(es) Patients Is Associated with Specific MicroRNAs

Science.gov (United States)

Lussier, Yves A.; Ganai, Sabha; Khan, Sajid A.; Gnerlich, Jennifer; Darga, Thomas E.; Fan, Hanli; Karpenko, Oleksiy; Paty, Philip B.; Posner, Mitchell C.; Chmura, Steven J.; Hellman, Samuel; Ferguson, Mark K.; Weichselbaum, Ralph R.

2012-01-01

Rationale Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es) characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy. Methods We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤5 initial metastases resected with curative intent. Results Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP) and low rate of progression (LRP); the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset. Conclusion Oligo- and poly- metastasis are distinct entities at the clinical and molecular level. PMID:23251360

Compartmentalization Technologies via Self-Assembly and Cross-Linking of Amphiphilic Random Block Copolymers in Water.

Science.gov (United States)

Matsumoto, Mayuko; Terashima, Takaya; Matsumoto, Kazuma; Takenaka, Mikihito; Sawamoto, Mitsuo

2017-05-31

Orthogonal self-assembly and intramolecular cross-linking of amphiphilic random block copolymers in water afforded an approach to tailor-make well-defined compartments and domains in single polymer chains and nanoaggregates. For a double compartment single-chain polymer, an amphiphilic random block copolymer bearing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic dodecyl, benzyl, and olefin pendants was synthesized by living radical polymerization (LRP) and postfunctionalization; the dodecyl and benzyl units were incorporated into the different block segments, whereas PEG pendants were statistically attached along a chain. The copolymer self-folded via the orthogonal self-assembly of hydrophobic dodecyl and benzyl pendants in water, followed by intramolecular cross-linking, to form a single-chain polymer carrying double yet distinct hydrophobic nanocompartments. A single-chain cross-linked polymer with a chlorine terminal served as a globular macroinitiator for LRP to provide an amphiphilic tadpole macromolecule comprising a hydrophilic nanoparticle and a hydrophobic polymer tail; the tadpole thus self-assembled into multicompartment aggregates in water.

Oligo- and polymetastatic progression in lung metastasis(es patients is associated with specific microRNAs.

Directory of Open Access Journals (Sweden)

Yves A Lussier

Full Text Available RATIONALE: Strategies to stage and treat cancer rely on a presumption of either localized or widespread metastatic disease. An intermediate state of metastasis termed oligometastasis(es characterized by limited progression has been proposed. Oligometastases are amenable to treatment by surgical resection or radiotherapy. METHODS: We analyzed microRNA expression patterns from lung metastasis samples of patients with ≤ 5 initial metastases resected with curative intent. RESULTS: Patients were stratified into subgroups based on their rate of metastatic progression. We prioritized microRNAs between patients with the highest and lowest rates of recurrence. We designated these as high rate of progression (HRP and low rate of progression (LRP; the latter group included patients with no recurrences. The prioritized microRNAs distinguished HRP from LRP and were associated with rate of metastatic progression and survival in an independent validation dataset. CONCLUSION: Oligo- and poly- metastasis are distinct entities at the clinical and molecular level.

78 FR 66752 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

Science.gov (United States)

2013-11-06

... Special Emphasis Panel; Preserving Male Fertility After Cancer Therapy by Kyle E. Orwig. Date: November 14....929, Center for Medical Rehabilitation Research; 93.209, Contraception and Infertility Loan Repayment...

Researcher Story: Stuttering

Medline Plus

Full Text Available ... You Talking to Your Doctor Science Education Resources Community Resources Clear Health A–Z Publications List More ... & Compliance Grants News/Blog Contracts Loan Repayment More » ...

Talking to Your Doctor

Medline Plus

Full Text Available ... You Talking to Your Doctor Science Education Resources Community Resources Clear Health A–Z Publications List More ... & Compliance Grants News/Blog Contracts Loan Repayment More » ...

Circulating Cholesterol Levels May Link to the Factors Influencing Parkinson’s Risk

Directory of Open Access Journals (Sweden)

Lijun Zhang

2017-09-01

Full Text Available ObjectivesA growing literature suggests that circulating cholesterol levels have been associated with Parkinson’s disease (PD. In this study, we investigated a possible causal basis for the cholesterol-PD link.MethodsFasting plasma cholesterol levels were obtained from 91 PD and 70 age- and gender-matched controls from an NINDS PD Biomarkers Program cohort at the Pennsylvania State University College of Medicine. Based on the literature, genetic polymorphisms in selected cholesterol management genes (APOE, LDLR, LRP1, and LRPAP1 were chosen as confounding variables because they may influence both cholesterol levels and PD risk. First, the marginal structure model was applied, where the associations of total- and LDL-cholesterol levels with genetic polymorphisms, statin usage, and smoking history were estimated using linear regression. Then, potential causal influences of total- and LDL-cholesterol on PD occurrence were investigated using a generalized propensity score approach in the second step.ResultsBoth statins (p < 0.001 and LRP1 (p < 0.03 influenced total- and LDL-cholesterol levels. There also was a trend for APOE to affect total- and LDL-cholesterol (p = 0.08 for both, and for LRPAR1 to affect LDL-cholesterol (p = 0.05. Conversely, LDLR did not influence plasma cholesterol levels (p > 0.19. Based on propensity score methods, lower total- and LDL-cholesterol were significantly linked to PD (p < 0.001 and p = 0.04, respectively.ConclusionThe current study suggests that circulating total- and LDL-cholesterol levels potentially may be linked to the factor(s influencing PD risk. Further studies to validate these results would impact our understanding of the role of cholesterol as a risk factor in PD, and its relationship to recent public health controversies.

44 CFR 206.377 - Loan repayment.

Science.gov (United States)

2010-10-01

... interest amount due will be computed separately for each Treasury disbursement as follows: I = P X R X T, where I = the amount of simple interest, P = the principal amount disbursed; R = the interest rate of... Assistant Administrator for the Disaster Assistance Directorate. Interest will accrue on outstanding cash...

Researcher Story: Stuttering

Medline Plus

Full Text Available ... Wellness Toolkits Grants & Funding Grants Home Page Funding Forms Library Due Dates How to Apply About Grants Policy & Compliance Grants News/Blog Contracts Loan Repayment More » ...

Talking to Your Doctor

Medline Plus

Full Text Available ... Wellness Toolkits Grants & Funding Grants Home Page Funding Forms Library Due Dates How to Apply About Grants Policy & Compliance Grants News/Blog Contracts Loan Repayment More » ...

Repaying in Kind: Examination of the Reciprocity Effect in Faculty and Resident Evaluations.

Science.gov (United States)

Gardner, Aimee K; Scott, Daniel J

Although the reciprocity hypothesis (that trainees have a tendency to modify evaluations based on the grades they receive from instructors) has been documented in other fields, very little work has examined this phenomenon in the surgical residency environment. The purpose of this study was to investigate the extent to which lenient-grading faculty receive higher evaluations from surgery residents. Evaluation data from 2 consecutive academic years were collected retrospectively at a large university-based General Surgery residency program. Monthly faculty evaluations of residents (15 items) and resident evaluations of faculty (8 items; 1 = never demonstrates, 10 = always demonstrates) were included. Correlation and regression analyses were conducted with SPSS version 22 (IBM; Chicago, IL). A total of 2274 faculty assessments and 1480 resident assessments were included in this study, representing 2 years of evaluations for 32 core faculty members responsible for completing all resident evaluations and 68 PGY1-5 general surgery residents. Faculty (63% men, 13.5 ± 9.8 years out of training) represented 5 different divisions (general surgery, surgical oncology, transplant, trauma critical care, and vascular) within the general surgery department. Faculty received an average of 71.1 ± 33.9 evaluations from residents over the course of 2 years. The average rating of faculty teaching by residents was 9.5 ± 0.4. Residents received an average of 21.8 ± 0.5 evaluations with average ratings of 4.2 ± 0.4. Correlation analyses indicated a positive relationship between the average rating received from residents and the number of years since faculty completed training (r = 0.44, p = 0.01). Additionally, a significant relationship emerged between ratings received from residents and ratings given to residents (r = 0.40, p = 0.04). Regression analyses indicated that when both variables (years since training, ratings given to residents) were included in the model, only ratings

Practical solutions for staff recruitment & retention.

Science.gov (United States)

Vander Hoek, N

2001-01-01

There are three essential topics for radiology managers to consider in light of persistent staffing shortages: support of the profession and educational programs, perks as recruitment tools and incentives as retention tools. Some activities that can help support departments and educational programs for radiologic technologists are job shadowing, training for volunteer services, advanced placement for school applicants, sponsoring an educational program or clinical training site, creating a positive work environment and supporting outreach projects geared to local high schools. Traditional perks used in recruitment efforts have included relocation assistance, travel and lodging expenses during the interview process, loan repayment, scholarships and sign-on bonuses. Some common incentives for retaining employees are tuition reimbursement, cross training, availability of educational resources, continuing education opportunities, professional development and incremental increases in salary. There are many other tools that can be used, such as career ladders, creating an environment conducive to teamwork or a more personal atmosphere and showcasing talents of various staff members. There is much overlap among these suggestions in support of the profession and educational programs, recruitment and retention of qualified staff radiologic technologists. Radiology managers can and should be creative in developing different programs to build loyalty and commitment to a radiology department.

An auxin transport independent pathway is involved in phosphate stress-induced root architectural alterations in Arabidopsis. Identification of BIG as a mediator of auxin in pericycle cell activation.

Science.gov (United States)

López-Bucio, José; Hernández-Abreu, Esmeralda; Sánchez-Calderón, Lenin; Pérez-Torres, Anahí; Rampey, Rebekah A; Bartel, Bonnie; Herrera-Estrella, Luis

2005-02-01

Arabidopsis (Arabidopsis thaliana) plants display a number of root developmental responses to low phosphate availability, including primary root growth inhibition, greater formation of lateral roots, and increased root hair elongation. To gain insight into the regulatory mechanisms by which phosphorus (P) availability alters postembryonic root development, we performed a mutant screen to identify genetic determinants involved in the response to P deprivation. Three low phosphate-resistant root lines (lpr1-1 to lpr1-3) were isolated because of their reduced lateral root formation in low P conditions. Genetic and molecular analyses revealed that all lpr1 mutants were allelic to BIG, which is required for normal auxin transport in Arabidopsis. Detailed characterization of lateral root primordia (LRP) development in wild-type and lpr1 mutants revealed that BIG is required for pericycle cell activation to form LRP in both high (1 mm) and low (1 microm) P conditions, but not for the low P-induced alterations in primary root growth, lateral root emergence, and root hair elongation. Exogenously supplied auxin restored normal lateral root formation in lpr1 mutants in the two P treatments. Treatment of wild-type Arabidopsis seedlings with brefeldin A, a fungal metabolite that blocks auxin transport, phenocopies the root developmental alterations observed in lpr1 mutants in both high and low P conditions, suggesting that BIG participates in vesicular targeting of auxin transporters. Taken together, our results show that auxin transport and BIG function have fundamental roles in pericycle cell activation to form LRP and promote root hair elongation. The mechanism that activates root system architectural alterations in response to P deprivation, however, seems to be independent of auxin transport and BIG.

Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development.

Science.gov (United States)

Takeda, Haruna; Rust, Alistair G; Ward, Jerrold M; Yew, Christopher Chin Kuan; Jenkins, Nancy A; Copeland, Neal G

2016-04-05

Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC.

Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women.

Directory of Open Access Journals (Sweden)

Patricia Sarrión

Full Text Available The aims of the study were to establish the prevalence of high bone mass (HBM in a cohort of Spanish postmenopausal women (BARCOS and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600 displayed Z-scores in the HBM range (sum Z-score >4. While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F, which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM.

77 FR 26277 - Economic Impact Policy

Science.gov (United States)

2012-05-03

... transaction specific working capital guarantee to support the export of approximately $63.5 million worth of sulphur purification equipment and services to Iraq. The repayment term of the working capital guarantee...

76 FR 11499 - National Center on Minority and Health Disparities; Notice of Closed Meeting

Science.gov (United States)

2011-03-02

... and Health Disparities; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Health Disparities Special Emphasis Panel; 2011 LRP Panel 1. Date: March 18, 2011. Time: 8 a.m. to... Disparities, 6707 Democracy Boulevard, Suite 800, Bethesda, MD 20892, (301) 451-9536, [email protected

76 FR 14673 - National Center on Minority and Health Disparities; Notice of Closed Meeting

Science.gov (United States)

2011-03-17

... and Health Disparities; Notice of Closed Meeting Pursuant to section 10(d) of the Federal Advisory... and Health Disparities Special Emphasis Panel; 2011 LRP Panel 3. Date: April 13, 2011. Time: 8 a.m. to... Disparities, 6707 Democracy Boulevard, Suite 800, Bethesda, MD 20892, (301) 451-9536, [email protected

Evaluation of the agricultural extension programmes of Shell ...

African Journals Online (AJOL)

International Journal of Agriculture and Rural Development ... Agricultural Extension Services as part of her corporate social responsibilities in Rivers, ... limited by inadequate communication and transport facilities, non-repayment of soft loans ...

Federal Workforce: Attrition Rates at Ex-Im Bank and Similar Agencies

National Research Council Canada - National Science Library

Hess, James

1997-01-01

.... Financing and protection provided by Ex-Im Bank includes (1) loans to foreign buyers of U.S. exports, (2) loan guarantees to commercial lenders providing repayment protection for loans to foreign buyers...

12 CFR 250.166 - Treatment of mandatory convertible debt and subordinated notes of state member banks and bank...

Science.gov (United States)

2010-01-01

..., (B) Hold payments on the securities in trust, (C) Preserve the rights and franchises of the company... to repay the principal from the proceeds of future equity issues. (d) Previously issued subordinated...

27 CFR 6.61 - Guaranteeing loans.

Science.gov (United States)

2010-04-01

... OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Guaranteeing Loans § 6.61 Guaranteeing loans. The act by an industry member of guaranteeing any loan or the repayment of any financial...

17 CFR 210.9-03 - Balance sheets.

Science.gov (United States)

2010-04-01

... the beginning of the period, new loans, repayments, and other changes. (Other changes, if significant...; siblings; mothers and fathers-in-law; sons and daughters-in-law; and brothers and sisters-in-law. Ordinary...

7 CFR 1710.2 - Definitions and rules of construction.

Science.gov (United States)

2010-01-01

... the capability of repaying the loan in full as scheduled, in accordance with the terms of the mortgage... repair, or obsolescence of the facilities. OTIER means Operating Times Interest Earned Ratio of the...

77 FR 52337 - Eunice Kennedy Shriver National Institute of Child Health & Human Development Notice of Closed...

Science.gov (United States)

2012-08-29

... Network (Male Studies) September. Date: September 27, 2012. Time: 2 p.m. to 4 p.m. Agenda: To review and....929, Center for Medical Rehabilitation Research; 93.209, Contraception and Infertility Loan Repayment...

performance of agricultural co-operative societies in mubi zone of ...

African Journals Online (AJOL)

hp

2007-05-15

May 15, 2007 ... grassroots level farmers, an effective extension services are required by farmers on loan delivery and repayment ... traditional farming techniques of production, lack of ... socio-economic problems on banking, marketing of.

76 FR 27389 - Regulation Z; Truth in Lending

Science.gov (United States)

2011-05-11

... repay the loan. Beginning in about 2006, these concerns were heightened as mortgage delinquencies and... potential impact of such rules on rural areas and other areas where home values are lower.'' If the...

Implications of Biodiesel-Induced Land-Use Changes for CO2 Emissions: Case Studies in Tropical America, Africa, and Southeast Asia

Directory of Open Access Journals (Sweden)

Wouter M. J. Achten

2011-12-01

Full Text Available Biofuels are receiving growing negative attention. Direct and/or indirect land-use changes that result from their cultivation can cause emissions due to carbon losses in soils and biomass and could negate any eventual greenhouse gas (GHG reduction benefit. This paper evaluates the implications of land-use change emission on the climate-change mitigation potential of different biofuel production systems in 12 case studies in six countries. We calculated carbon debts created by conversion of different land-use types, ranging from annual cropland to primary forest. We evaluated case studies using three different biofuel crops: oil palm, Jatropha, and soybean. The time needed for each biofuel production system to pay back its carbon debt was calculated based on a life-cycle assessment of the GHG reduction potentials of the system. Carbon debts range from 39 to 1743.7 Mg C02 ha-1. The oil palm case studies created the largest carbon debts (472.8-1743.7 t C02 ha-1 because most of the area expansion came at the expense of dense tropical forest. The highest debt was associated with plantation on peatland. For all cases evaluated, only soybean in Guarantã do Norte and Alta Floresta, Brazil needed less than one human generation (30 years to repay the initial carbon debt. Highest repayment times were found for Jatropha (76-310 years and oil palm (59-220 years case studies. Oil palm established in peatlands had the greatest repayment times (206-220 years. High repayment times for Jatropha resulted from the combined effects of land-cover change and low CO2 emission reduction rate. These outcomes raise serious questions about the sustainability of biofuel production. The carbon implications of conversion of (semi-natural systems with medium to high biomass indicate that, in order to generate climate benefits, cultivation of biofuel feedstocks should be restricted to areas that already have low carbon content.

77 FR 71853 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Science.gov (United States)

2012-12-04

... available best-priced interest that would not lock or cross the Exchange best offer (bid). In moving the... could lock or cross the Exchange best bid or offer could be if a liquidity replenishment point (``LRP'') is reached pursuant to Rule 1000-- Equities, and automatic executions on one side of the market are...

77 FR 71658 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Science.gov (United States)

2012-12-03

... best offer (bid), but instead would peg to the next available best-priced interest that would not lock... scenario when Market Pegging Interest could lock or cross the Exchange best bid or offer could be if a liquidity replenishment point (``LRP'') is reached pursuant to NYSE Rule 1000, and automatic executions on...

Researcher Story: Stuttering

Medline Plus

Full Text Available ... Health Info NIH News in Health Wellness Toolkits Grants & Funding Grants Home Page Funding Forms Library Due Dates How to Apply About Grants Policy & Compliance Grants News/Blog Contracts Loan Repayment ...

Talking to Your Doctor

Medline Plus

Full Text Available ... Health Info NIH News in Health Wellness Toolkits Grants & Funding Grants Home Page Funding Forms Library Due Dates How to Apply About Grants Policy & Compliance Grants News/Blog Contracts Loan Repayment ...