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Sample records for endoglin haploinsufficiency reduces

  1. Endoglin haploinsufficiency attenuates radiation-induced deterioration of kidney function in mice

    International Nuclear Information System (INIS)

    Scharpfenecker, Marion; Floot, Ben; Russell, Nicola S.; Coppes, Rob P.; Stewart, Fiona A.

    2013-01-01

    Background and Purpose: Endoglin is a transforming growth receptor beta (TGF-β) co-receptor, which plays a crucial role in the development of late normal tissue damage. Mice with halved endoglin levels (Eng +/- mice) develop less inflammation, vascular damage and fibrosis after kidney irradiation compared to their wild type littermates (Eng +/+ mice). This study was aimed at investigating whether reduced tissue damage in Eng +/- mice also results in superior kidney function. Material and Methods: Kidneys of Eng +/+ and Eng +/- mice were irradiated with a single dose of 14 Gy. Functional kidney parameters and kidney histology were analysed at 20, 30 and 40 weeks after irradiation. Results: Eng +/- mice displayed improved kidney parameters (haematocrit, BUN) compared to Eng +/+ mice at 40 weeks after irradiation. Irradiation of Eng +/+ kidneys damaged the vascular network and led to an increase in PDGFR-β positive cells, indicative of fibrosis-promoting myofibroblasts. Compared to Eng +/+ kidneys, vascular perfusion and number of PDGFR-β positive cells were reduced in Eng +/- control mice; however, this did not further deteriorate after irradiation. Conclusions: Taken together, we show that not only kidney morphology, but also kidney function is improved after irradiation in Eng +/- compared to Eng +/+ mice

  2. Gad67 haploinsufficiency reduces amyloid pathology and rescues olfactory memory deficits in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Wang, Yue; Wu, Zheng; Bai, Yu-Ting; Wu, Gang-Yi; Chen, Gong

    2017-10-10

    Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder, affecting millions of people worldwide. Although dysfunction of multiple neurotransmitter systems including cholinergic, glutamatergic and GABAergic systems has been associated with AD progression the underlying mechanisms remain elusive. We and others have recently found that GABA content is elevated in AD brains and linked to cognitive deficits in AD mouse models. The glutamic acid decarboxylase 67 (GAD67) is the major enzyme converting glutamate into GABA and has been implied in a number of neurological disorders such as epilepsy and schizophrenia. However, whether Gad67 is involved in AD pathology has not been well studied. Here, we investigate the functional role of GAD67 in an AD mouse model with Gad67 haploinsufficiency that is caused by replacing one allele of Gad67 with green fluorescent protein (GFP) gene during generation of GAD67-GFP mice. To genetically reduce GAD67 in AD mouse brains, we crossed the Gad67 haploinsufficient mice (GAD67-GFP +/- ) with 5xFAD mice (harboring 5 human familial AD mutations in APP and PS1 genes) to generate a new line of bigenic mice. Immunostaining, ELISA, electrophysiology and behavior test were applied to compare the difference between groups. We found that reduction of GAD67 resulted in a significant decrease of amyloid β production in 5xFAD mice. Concurrently, the abnormal astrocytic GABA and tonic GABA currents, as well as the microglial reactivity were significantly reduced in the 5xFAD mice with Gad67 haploinsufficiency. Importantly, the olfactory memory deficit of 5xFAD mice was rescued by Gad67 haploinsufficiency. Our results demonstrate that GAD67 plays an important role in AD pathology, suggesting that GAD67 may be a potential drug target for modulating the progress of AD.

  3. Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

  4. Pathogenesis of arteriovenous malformations in the absence of endoglin.

    Science.gov (United States)

    Mahmoud, Marwa; Allinson, Kathleen R; Zhai, Zhenhua; Oakenfull, Rachael; Ghandi, Pranita; Adams, Ralf H; Fruttiger, Marcus; Arthur, Helen M

    2010-04-30

    Arteriovenous malformations (AVMs) result in anomalous direct blood flow between arteries and veins, bypassing the normal capillary bed. Depending on size and location, AVMs may lead to severe clinical effects including systemic cyanosis (pulmonary AVMs), hemorrhagic stroke (cerebral AVMs) and high output cardiac failure (hepatic AVMs). The factors leading to AVM formation are poorly understood, but patients with the familial disease hereditary hemorrhagic telangiectasia (HHT) develop AVMs at high frequency. As most HHT patients have mutations in ENG (endoglin) or ACVRL1 (activin receptor-like kinase 1), a better understanding of the role of these genes in vascular development is likely to reveal the etiology of AVM formation. Using a mouse with a conditional mutation in the Eng gene, we investigated the sequence of abnormal cellular events occurring during development of an AVM. In the absence of endoglin, subcutaneous Matrigel implants in adult mice were populated by reduced numbers of new blood vessels compared with controls, and resulted in local venous enlargement (venomegaly). To investigate abnormal vascular responses in more detail, we turned to the more readily accessible vasculature of the neonatal retina. Endoglin-deficient retinas exhibited delayed remodeling of the capillary plexus, increased proliferation of endothelial cells and localized AVMs. Muscularization of the resulting arteriovenous shunts appeared to be a secondary response to increased blood flow. AVMs develop when an angiogenic stimulus is combined with endoglin depletion. Moreover, AVM formation appears to result from the combination of delayed vascular remodeling and an inappropriate endothelial cell proliferation response in the absence of endoglin.

  5. Haploinsufficiency of the retinoblastoma protein gene reduces diet-induced obesity, insulin resistance, and hepatosteatosis in mice

    DEFF Research Database (Denmark)

    Mercader, Josep; Ribot, Joan; Murano, Incoronata

    2009-01-01

    Brown adipose tissue activity dissipates energy as heat, and there is evidence that lack of the retinoblastoma protein (pRb) may favor the development of the brown adipocyte phenotype in adipose cells. In this work we assessed the impact of germ-line haploinsufficiency of the pRb gene (Rb) on the...... first evidence that partial deficiency in the Rb gene protects against the development of obesity and associated metabolic disturbances. Key words: brown adipose tissue, white adipose tissue, energy metabolism, genetic animal model....

  6. Multiple Delivery of siRNA against Endoglin into Murine Mammary Adenocarcinoma Prevents Angiogenesis and Delays Tumor Growth

    Science.gov (United States)

    Dolinsek, Tanja; Markelc, Bostjan; Sersa, Gregor; Coer, Andrej; Stimac, Monika; Lavrencak, Jaka; Brozic, Andreja; Kranjc, Simona; Cemazar, Maja

    2013-01-01

    Endoglin is a transforming growth factor-β (TGF- β) co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA) molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11) by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches. PMID:23593103

  7. Multiple delivery of siRNA against endoglin into murine mammary adenocarcinoma prevents angiogenesis and delays tumor growth.

    Directory of Open Access Journals (Sweden)

    Tanja Dolinsek

    Full Text Available Endoglin is a transforming growth factor-β (TGF- β co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11 by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches.

  8. MMP-15 is upregulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

    Directory of Open Access Journals (Sweden)

    Tu'uhevaha J Kaitu'u-Lino

    Full Text Available Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15--phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity--also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03 up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8 compared to gestationally matched preterm controls (n = 8. However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin.

  9. Endoglin: a critical mediator of cardiovascular health

    Directory of Open Access Journals (Sweden)

    Kapur NK

    2013-05-01

    Full Text Available Navin K Kapur,1 Kevin J Morine,1 Michelle Letarte2,31Molecular Cardiology Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA; 2Molecular Structure and Function Program, Hospital for Sick Children, 3The Heart and Stroke Foundation Richard Lewar Centre of Excellence, and the Department of Immunology, University of Toronto, Toronto, Ontario, CanadaAbstract: Endoglin (CD105 is a type III auxiliary receptor for the transforming growth factor beta (TGFß superfamily. Several lines of evidence suggest that endoglin plays a critical role in maintaining cardiovascular homeostasis. Seemingly disparate disease conditions, including hereditary hemorrhagic telangiectasia, pre-eclampsia, and cardiac fibrosis, have now been associated with endoglin. Given the central role of the TGFß superfamily in multiple disease conditions, this review provides a detailed update on endoglin as an evolving therapeutic target in the management of cardiovascular disease.Keywords: endoglin, transforming growth factor beta, vascular, cardiac remodeling

  10. Anti-Human Endoglin (hCD105 Immunotoxin—Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1

    Directory of Open Access Journals (Sweden)

    Begoña Barriuso

    2016-06-01

    Full Text Available Endoglin (CD105 is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT—containing recombinant musarmin 1 (single chain ribosome-inactivating proteins linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio propionate (SPDP. The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10−10 to 10−9 M.

  11. Anti-Human Endoglin (hCD105) Immunotoxin-Containing Recombinant Single Chain Ribosome-Inactivating Protein Musarmin 1.

    Science.gov (United States)

    Barriuso, Begoña; Antolín, Pilar; Arias, F Javier; Girotti, Alessandra; Jiménez, Pilar; Cordoba-Diaz, Manuel; Cordoba-Diaz, Damián; Girbés, Tomás

    2016-06-10

    Endoglin (CD105) is an accessory component of the TGF-β receptor complex, which is expressed in a number of tissues and over-expressed in the endothelial cells of tumor neovasculature. Targeting endoglin with immunotoxins containing type 2 ribosome-inactivating proteins has proved an effective tool to reduce blood supply to B16 mice tumor xenografts. We prepared anti-endoglin immunotoxin (IT)-containing recombinant musarmin 1 (single chain ribosome-inactivating proteins) linked to the mouse anti-human CD105 44G4 mouse monoclonal antibody via N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). The immunotoxin specifically killed L929 fibroblast mouse cells transfected with the short form of human endoglin with IC50 values in the range of 5 × 10(-10) to 10(-9) M.

  12. Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome.

    Science.gov (United States)

    Han, Joan C; Thurm, Audrey; Golden Williams, Christine; Joseph, Lisa A; Zein, Wadih M; Brooks, Brian P; Butman, John A; Brady, Sheila M; Fuhr, Shannon R; Hicks, Melanie D; Huey, Amanda E; Hanish, Alyson E; Danley, Kristen M; Raygada, Margarita J; Rennert, Owen M; Martinowich, Keri; Sharp, Stephen J; Tsao, Jack W; Swedo, Susan E

    2013-01-01

    In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of variable size near the BDNF locus and can serve as a model for studying human BDNF haploinsufficiency (+/-). We hypothesized that BDNF+/- would be associated with more severe cognitive impairment in subjects with WAGR syndrome. Twenty-eight subjects with WAGR syndrome (6-28 years), 12 subjects with isolated aniridia due to PAX6 mutations/microdeletions (7-54 years), and 20 healthy controls (4-32 years) received neurocognitive assessments. Deletion boundaries for the subjects in the WAGR group were determined by high-resolution oligonucleotide array comparative genomic hybridization. Within the WAGR group, BDNF+/- subjects (n = 15), compared with BDNF intact (+/+) subjects (n = 13), had lower adaptive behaviour (p = .02), reduced cognitive functioning (p = .04), higher levels of reported historical (p = .02) and current (p = .02) social impairment, and higher percentage meeting cut-off score for autism (p = .047) on Autism Diagnostic Interview-Revised. These differences remained nominally significant after adjusting for visual acuity. Using diagnostic measures and clinical judgement, 3 subjects (2 BDNF+/- and 1 BDNF+/+) in the WAGR group (10.7%) were classified with autism spectrum disorder. A comparison group of visually impaired subjects with isolated aniridia had cognitive functioning comparable to that of healthy controls. In summary, among subjects with WAGR syndrome, BDNF+/- subjects had a mean Vineland Adaptive Behaviour Compose score that was 14-points lower and a mean intelligence quotient (IQ) that was 20-points lower than BDNF+/+ subjects. Our findings support the hypothesis that BDNF plays an important role in human neurocognitive development. Published by Elsevier Ltd.

  13. Endoglin: a critical mediator of cardiovascular health

    OpenAIRE

    Kapur, Navin K; Morine, Kevin J; Letarte, Michelle

    2013-01-01

    Navin K Kapur,1 Kevin J Morine,1 Michelle Letarte2,31Molecular Cardiology Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA; 2Molecular Structure and Function Program, Hospital for Sick Children, 3The Heart and Stroke Foundation Richard Lewar Centre of Excellence, and the Department of Immunology, University of Toronto, Toronto, Ontario, CanadaAbstract: Endoglin (CD105) is a type III auxiliary receptor for the transforming growth factor ...

  14. Endoglin concentration in peritoneal fluid of patients with endometriosis

    Directory of Open Access Journals (Sweden)

    Nusratuddin Abdullah

    2013-05-01

    Full Text Available Background: Endoglin is a specific angiogenic factor suspected to involve in the pathogenesis of endometriosis. The aim of this study was to evaluate the significance of endoglin concentration in the peritoneal fluid of patients with endometriosis.Methods: This pilot study was performed between March 2011 and July 2012 at Dr. Wahidin Sudirohusodo Hospital and another private hospital in Makassar, Indonesia. This was an observational, cross-sectional study. All patients undergoing laparoscopy for infertility and other cases with suitable inclusion criteria were asked to answer a questionnaire and had a 5 cc peritoneal fluid sample taken for measurement of peritoneal endoglin concentration using ELISA. Endometriosis stage was classified using ASRM criteria and divided into two groups, mild and severe. All data were analyed using Excel and Spearman correlation analysis.Results: In the endometriosis group peritoneal endoglin concentration ranged between 14.43- 15.65 ng/mL (median 15.04 ng/mL which is higher than control group 7.42-10.26 ng/mL (median 8.84 ng/mL. A peritoneal endoglin concentration equal to or higher than 11 ng/mL could be used to predict endometriosis.Conclusion: Endoglin concentrations increased proportionally with the severity of endometriosis, and many be used as predictive factor of endometriosis cases. (Med J Indones. 2013;22:88-91Keywords: Endoglin, endometriosis, peritoneum

  15. A Novel Stent Coated with Antibodies to Endoglin Inhibits Neointimal Formation of Porcine Coronary Arteries

    Directory of Open Access Journals (Sweden)

    Song Cui

    2014-01-01

    Full Text Available Endoglin/CD105 is an accessory protein of the transforming growth factor-β receptor system that plays a critical role in proliferation of endothelial cells and neovasculature. Here, we aimed to assess the effect of novel stents coated with antibodies to endoglin (ENDs on coronary neointima formation. Thirty ENDs, thirty sirolimus-eluting stents (SESs, and thirty bare metal stents (BMSs were randomly assigned and placed in the coronary arteries in 30 juvenile pigs. Histomorphometric analysis and scanning electron microscopy were performed after stent implantation. Our results showed that after 7 days, there was no difference in the neointimal area and percent area stenosis in ENDs compared with SMSs or BMSs. After 14 days, the neointima area and percent area stenosis in ENDs were markedly decreased than those in BMSs or SESs (P<0.05. Moreover, the percentage of reendothelialization was significantly higher in ENDs than that in SESs or BMSs (P<0.01 at 7 and 14 days. The artery injury and the inflammation scores were similar in all groups at 7 and 14 days. In conclusion, our results demonstrated for the first time to our knowledge that endoglin antibody-coated stents can markedly reduce restenosis by enhancing reendothelialization in the porcine model and potentially offer a new approach to prevent restenosis.

  16. The Role of the TGF-β Coreceptor Endoglin in Cancer

    Directory of Open Access Journals (Sweden)

    Eduardo Pérez-Gómez

    2010-01-01

    Full Text Available Endoglin (CD105 is an auxiliary membrane receptor of transforming growth factor beta (TGF-β that interacts with type I and type II TGF-β receptors and modulates TGF-β signaling. Endoglin is overexpressed in the tumor-associated vascular endothelium, where it modulates angiogenesis. This feature makes endoglin a promising target for antiangiogenic cancer therapy. In addition, recent studies on human and experimental models of carcinogenesis point to an important tumor cell–autonomous role of endoglin by regulating proliferation, migration, invasion, and metastasis. These studies suggest that endoglin behaves as a suppressor of malignancy in experimental and human epithelial carcinogenesis, although it can also promote metastasis in other types of cancer. In this review, we evaluate the implication of endoglin in tumor development underlying studies developed in our laboratories in recent years.

  17. Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction.

    Science.gov (United States)

    Brownfoot, Fiona C; Hastie, Roxanne; Hannan, Natalie J; Cannon, Ping; Tuohey, Laura; Parry, Laura J; Senadheera, Sevvandi; Illanes, Sebastian E; Kaitu'u-Lino, Tu'uhevaha J; Tong, Stephen

    2016-03-01

    Preeclampsia is associated with placental ischemia/hypoxia and secretion of soluble fms-like tyrosine kinase 1 and soluble endoglin into the maternal circulation. This causes widespread endothelial dysfunction that manifests clinically as hypertension and multisystem organ injury. Recently, small molecule inhibitors of hypoxic inducible factor 1α have been found to reduce soluble fms-like tyrosine kinase 1 and soluble endoglin secretion. However, their safety profile in pregnancy is unknown. Metformin is safe in pregnancy and is also reported to inhibit hypoxic inducible factor 1α by reducing mitochondrial electron transport chain activity. The purposes of this study were to determine (1) the effects of metformin on placental soluble fms-like tyrosine kinase 1 and soluble endoglin secretion, (2) to investigate whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion are regulated through the mitochondrial electron transport chain, and (3) to examine its effects on endothelial dysfunction, maternal blood vessel vasodilation, and angiogenesis. We performed functional (in vitro and ex vivo) experiments using primary human tissues to examine the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion from placenta, endothelial cells, and placental villous explants. We used succinate, mitochondrial complex II substrate, to examine whether the effects of metformin on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion were mediated through the mitochondria. We also isolated mitochondria from preterm preeclamptic placentas and gestationally matched control subjects and measured mitochondrial electron transport chain activity using kinetic spectrophotometric assays. Endothelial cells or whole maternal vessels were incubated with metformin to determine whether it rescued endothelial dysfunction induced by either tumor necrosis factor-α (to endothelial cells) or placenta villous

  18. Prevalence of SHOX Haploinsufficiency among Short Statured Children

    DEFF Research Database (Denmark)

    Marstrand-Joergensen, Maja Rou; Beck Jensen, Rikke; Aksglaede, Lise

    2017-01-01

    were recorded for patients with SHOX haploinsufficiency. RESULTS: Thirty-two patients were excluded due to Turner syndrome (n=28), SRY-positive 46,XX male karyotype (n=1), or lacked clinical follow-up information (n=3).The prevalence of SHOX haploinsufficiency was nine out of 542 (1.7%). The nine......=0.046, after one year of GH treatment. CONCLUSION: The prevalence of SHOX haploinsufficiency was 1.7%. The clinical findings indicating SHOX haploinsufficiency among the nine children were disproportionate short stature and forearm anomalies....

  19. An Oral DNA Vaccine Encoding Endoglin Eradicates Breast Tumors by Blocking Their Blood Supply

    National Research Council Canada - National Science Library

    Reisfeld, Ralph A

    2007-01-01

    In an effort to meet the urgent need for the development of novel and effective treatments for metastatic breast cancer, we developed and evaluated a novel, oral DNA vaccine targeting endoglin (CD105...

  20. Relationship of Liver X Receptors α and Endoglin Levels in Serum and Placenta with Preeclampsia.

    Science.gov (United States)

    Wang, Jing; Dong, Xing; Wu, Hong-Yan; Wu, Nan; Zhang, Xue-Jun; Wang, Xin; Shang, Li-Xin

    2016-01-01

    Liver X receptor alpha (LXRα) and endoglin have been postulated to play roles in trophoblast invasion and lipid metabolic disturbances. However, the relationship between LXRα and endoglin levels in serum and placenta of patients with preeclampsia remains poorly understood. The objective of this study was to identify correlations between LXRα, endoglin and preeclampsia and provide new feasible methods of clinical prediction and treatment for preeclampsia. We enrolled 45 patients with preeclampsia (24 with moderate preeclampsia and 21 with severe preeclampsia) and 15 normal pregnant women (control group) who were admitted to the Department of Obstetrics of the General Hospital of Beijing Command between October 2012 and July 2013 in this study. Serum and placental LXRα and endoglin levels were analyzed by enzyme-linked immunosorbent assay, real-time quantitative PCR, tissue microarray and immunohistochemistry. Serum and placental LXRα and endoglin levels were significantly higher in patients with preeclampsia than those in control group (Ppreeclampsia displayed significantly higher LXRα and endoglin levels than those with moderate preeclampsia (Ppreeclampsia were positively correlated (serum: r = 0.486, Ppreeclampsia pathogenesis and development and could be used as potential predictors for this disorder.

  1. Endoglin inhibits ERK-induced c-Myc and cyclin D1 expression to impede endothelial cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Christopher C.; Bloodworth, Jeffrey C. [Division of Pharmacology, Columbus, OH 43210 (United States); Mythreye, Karthikeyan [Duke University, Department of Medicine, Durham, NC 27708 (United States); Lee, Nam Y., E-mail: lee.5064@osu.edu [Division of Pharmacology, Columbus, OH 43210 (United States); Davis Heart and Lung Research Institute, Columbus, OH 43210 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Endoglin inhibits ERK activation in endothelial cells. Black-Right-Pointing-Pointer Endoglin is a regulator of c-Myc and cyclin D1 expression. Black-Right-Pointing-Pointer {beta}-arrestin2 interaction with endoglin is required for ERK/c-Myc repression. Black-Right-Pointing-Pointer Endoglin impedes cellular proliferation by targeting ERK-induced mitogenic signaling. -- Abstract: Endoglin is an endothelial-specific transforming growth factor beta (TGF-{beta}) co-receptor essential for angiogenesis and vascular remodeling. Endoglin regulates a wide range of cellular processes, including cell adhesion, migration, and proliferation, through TGF-{beta} signaling to canonical Smad and Smad-independent pathways. Despite its overall pro-angiogenic role in the vasculature, the underlying mechanism of endoglin action is poorly characterized. We previously identified {beta}-arrestin2 as a binding partner that causes endoglin internalization from the plasma membrane and inhibits ERK signaling towards endothelial migration. In the present study, we examined the mechanistic role of endoglin and {beta}-arrestin2 in endothelial cell proliferation. We show that endoglin impedes cell growth through sustained inhibition of ERK-induced c-Myc and cyclin D1 expression in a TGF-{beta}-independent manner. The down-regulation of c-Myc and cyclin D1, along with growth-inhibition, are reversed when the endoglin/{beta}-arrestin2 interaction is disrupted. Given that TGF-{beta}-induced Smad signaling potently represses c-Myc in most cell types, our findings here show a novel mechanism by which endoglin augments growth-inhibition by targeting ERK and key downstream mitogenic substrates.

  2. Hepatitis C Virus Core Protein Modulates Endoglin (CD105) Signaling Pathway for Liver Pathogenesis.

    Science.gov (United States)

    Kwon, Young-Chan; Sasaki, Reina; Meyer, Keith; Ray, Ranjit

    2017-11-01

    Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In a previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition (EMT) state and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV-associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of an HCV core-expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules. The status of phospho-SMAD1/5 and the expression of inhibitor of DNA binding protein 1 (ID1) were upregulated in HCV-infected cells or viral core gene-transfected cells. Additionally, we observed upregulation of endoglin/ID1 mRNA expression in chronic HCV patient liver biopsy samples. CSC generation by HCV core protein was dependent on the endoglin signaling pathway using activin receptor-like kinase 1 (ALK1) Fc blocking peptide and endoglin small interfering RNA (siRNA). Further, follow-up from in vitro analysis suggested that the antiapoptosis Bcl2 protein, proliferation-related cyclin D1 protein, and CSC-associated Hes1, Notch1, Nanog, and Sox2 proteins are enhanced during infection or ectopic expression of HCV core protein. IMPORTANCE Endoglin plays a crucial role in fibrogenesis and angiogenesis and is an important protein for tumor growth, survival, and cancer cell metastasis. Endoglin enhances ALK1-SMAD1/5 signaling in different cell types, leading to increased proliferation and migration responses. We have observed endoglin expression on the HCV core-expressing cell surface of human hepatocyte origin and activation of phospho-SMAD1/5 and ID1 downstream signaling molecules. ID1 protein plays a role in CSC properties, and we found that

  3. L-Endoglin Overexpression Increases Renal Fibrosis after Unilateral Ureteral Obstruction

    Science.gov (United States)

    Arévalo, Miguel; Núñez-Gómez, Elena; Pérez-Roque, Lucía; Pericacho, Miguel; González-Núñez, María; Langa, Carmen; Martínez-Salgado, Carlos; Perez-Barriocanal, Fernando; Bernabeu, Carmelo; Lopez-Novoa, José M.

    2014-01-01

    Transforming growth factor-β (TGF-β) plays a pivotal role in renal fibrosis. Endoglin, a 180 KDa membrane glycoprotein, is a TGF-β co-receptor overexpressed in several models of chronic kidney disease, but its function in renal fibrosis remains uncertain. Two membrane isoforms generated by alternative splicing have been described, L-Endoglin (long) and S-Endoglin (short) that differ from each other in their cytoplasmic tails, being L-Endoglin the most abundant isoform. The aim of this study was to assess the effect of L-Endoglin overexpression in renal tubulo-interstitial fibrosis. For this purpose, a transgenic mouse which ubiquitously overexpresses human L-Endoglin (L-ENG+) was generated and unilateral ureteral obstruction (UUO) was performed in L-ENG+ mice and their wild type (WT) littermates. Obstructed kidneys from L-ENG+ mice showed higher amounts of type I collagen and fibronectin but similar levels of α-smooth muscle actin (α-SMA) than obstructed kidneys from WT mice. Smad1 and Smad3 phosphorylation were significantly higher in obstructed kidneys from L-ENG+ than in WT mice. Our results suggest that the higher increase of renal fibrosis observed in L-ENG+ mice is not due to a major abundance of myofibroblasts, as similar levels of α-SMA were observed in both L-ENG+ and WT mice, but to the higher collagen and fibronectin synthesis by these fibroblasts. Furthermore, in vivo L-Endoglin overexpression potentiates Smad1 and Smad3 pathways and this effect is associated with higher renal fibrosis development. PMID:25313562

  4. Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet.

    Directory of Open Access Journals (Sweden)

    Daniel Beiroa

    Full Text Available Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism.

  5. SERCA2 Haploinsufficiency in a Mouse Model of Darier Disease Causes a Selective Predisposition to Heart Failure

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    Vikram Prasad

    2015-01-01

    Full Text Available Null mutations in one copy of ATP2A2, the gene encoding sarco/endoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2, cause Darier disease in humans, a skin condition involving keratinocytes. Cardiac function appears to be unimpaired in Darier disease patients, with no evidence that SERCA2 haploinsufficiency itself causes heart disease. However, SERCA2 deficiency is widely considered a contributing factor in heart failure. We therefore analyzed Atp2a2 heterozygous mice to determine whether SERCA2 haploinsufficiency can exacerbate specific heart disease conditions. Despite reduced SERCA2a levels in heart, Atp2a2 heterozygous mice resembled humans in exhibiting normal cardiac physiology. When subjected to hypothyroidism or crossed with a transgenic model of reduced myofibrillar Ca2+-sensitivity, SERCA2 deficiency caused no enhancement of the disease state. However, when combined with a transgenic model of increased myofibrillar Ca2+-sensitivity, SERCA2 haploinsufficiency caused rapid onset of hypertrophy, decompensation, and death. These effects were associated with reduced expression of the antiapoptotic Hax1, increased levels of the proapoptotic genes Chop and Casp12, and evidence of perturbations in energy metabolism. These data reveal myofibrillar Ca2+-sensitivity to be an important determinant of the cardiac effects of SERCA2 haploinsufficiency and raise the possibility that Darier disease patients are more susceptible to heart failure under certain conditions.

  6. Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

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    Monika Stimac

    Full Text Available Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET (TS plasmid, in comparison to the plasmid with constitutive promoter (CON plasmid, in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

  7. Gene Electrotransfer of Plasmid with Tissue Specific Promoter Encoding shRNA against Endoglin Exerts Antitumor Efficacy against Murine TS/A Tumors by Vascular Targeted Effects.

    Science.gov (United States)

    Stimac, Monika; Dolinsek, Tanja; Lampreht, Ursa; Cemazar, Maja; Sersa, Gregor

    2015-01-01

    Vascular targeted therapies, targeting specific endothelial cell markers, are promising approaches for the treatment of cancer. One of the targets is endoglin, transforming growth factor-β (TGF-β) co-receptor, which mediates proliferation, differentiation and migration of endothelial cells forming neovasculature. However, its specific, safe and long-lasting targeting remains the challenge. Therefore, in our study we evaluated the transfection efficacy, vascular targeted effects and therapeutic potential of the plasmid silencing endoglin with the tissue specific promoter, specific for endothelial cells marker endothelin-1 (ET) (TS plasmid), in comparison to the plasmid with constitutive promoter (CON plasmid), in vitro and in vivo. Tissue specificity of TS plasmid was demonstrated in vitro on several cell lines, and its antiangiogenic efficacy was demonstrated by reducing tube formation of 2H11 endothelial cells. In vivo, on a murine mammary TS/A tumor model, we demonstrated good antitumor effect of gene electrotransfer (GET) of either of both plasmids in treatment of smaller tumors still in avascular phase of growth, as well as on bigger tumors, already well vascularized. In support to the observations on predominantly vascular targeted effects of endoglin, histological analysis has demonstrated an increase in necrosis and a decrease in the number of blood vessels in therapeutic groups. A significant antitumor effect was observed in tumors in avascular and vascular phase of growth, possibly due to both, the antiangiogenic and the vascular disrupting effect. Furthermore, the study indicates on the potential use of TS plasmid in cancer gene therapy since the same efficacy as of CON plasmid was determined.

  8. Further confirmation of the MED13L haploinsufficiency syndrome

    NARCIS (Netherlands)

    van Haelst, M.M.; Monroe, G.R.; Duran, K.J.; van Binsbergen, E.; Breur, J.M.P.J.; Giltay, J.C.; van Haaften, G.W.

    MED13L haploinsufficiency syndrome has been described in two patients and is characterized by moderate intellectual disability (ID), conotruncal heart defects, facial abnormalities and hypotonia. Missense mutations in MED13L are linked to transposition of the great arteries and non-syndromal

  9. Lef1 haploinsufficient mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner.

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    Tommy Noh

    Full Text Available We investigated the role of Lef1, one of the four transcription factors that transmit Wnt signaling to the genome, in the regulation of bone mass. Microcomputed tomographic analysis of 13- and 17-week-old mice revealed significantly reduced trabecular bone mass in Lef1(+/- females compared to littermate wild-type females. This was attributable to decreased osteoblast activity and bone formation as indicated by histomorphometric analysis of bone remodeling. In contrast to females, bone mass was unaffected by Lef1 haploinsufficiency in males. Similarly, females were substantially more responsive than males to haploinsufficiency in Gsk3beta, a negative regulator of the Wnt pathway, displaying in this case a high bone mass phenotype. Lef1 haploinsufficiency also led to low bone mass in males lacking functional androgen receptor (AR (tfm mutants. The protective skeletal effect of AR against Wnt-related low bone mass is not necessarily a result of direct interaction between the AR and Wnt signaling pathways, because Lef1(+/- female mice had normal bone mass at the age of 34 weeks. Thus, our results indicate an age- and gender-dependent role for Lef1 in regulating bone formation and bone mass in vivo. The resistance to Lef1 haploinsufficiency in males with active AR and in old females could be due to the reduced bone turnover in these mice.

  10. Endoplasmic reticulum quality control is involved in the mechanism of endoglin-mediated hereditary haemorrhagic telangiectasia.

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    Bassam R Ali

    Full Text Available Hereditary haemorrhagic telangiectasia (HHT is an autosomal dominant genetic condition affecting the vascular system and is characterised by epistaxis, arteriovenous malformations and mucocutaneous and gastrointestinal telangiectases. This disorder affects approximately 1 in 8,000 people worldwide. Significant morbidity is associated with this condition in affected individuals, and anaemia can be a consequence of repeated haemorrhages from telangiectasia in the gut and nose. In the majority of the cases reported, the condition is caused by mutations in either ACVRL1 or endoglin genes, which encode components of the TGF-beta signalling pathway. Numerous missense mutations in endoglin have been reported as causative defects for HHT but the exact underlying cellular mechanisms caused by these mutations have not been fully established despite data supporting a role for the endoplasmic reticulum (ER quality control machinery. For this reason, we examined the subcellular trafficking of twenty-five endoglin disease-causing missense mutations. The mutant proteins were expressed in HeLa and HEK293 cell lines, and their subcellular localizations were established by confocal fluorescence microscopy alongside the analysis of their N-glycosylation profiles. ER quality control was found to be responsible in eight (L32R, V49F, C53R, V125D, A160D, P165L, I271N and A308D out of eleven mutants located on the orphan extracellular domain in addition to two (C363Y and C382W out of thirteen mutants in the Zona Pellucida (ZP domain. In addition, a single intracellular domain missense mutant was examined and found to traffic predominantly to the plasma membrane. These findings support the notion of the involvement of the ER's quality control in the mechanism of a significant number, but not all, missense endoglin mutants found in HHT type 1 patients. Other mechanisms including loss of interactions with signalling partners as well as adverse effects on functional

  11. Application of gene network analysis techniques identifies AXIN1/PDIA2 and endoglin haplotypes associated with bicuspid aortic valve.

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    Eric C Wooten

    2010-01-01

    Full Text Available Bicuspid Aortic Valve (BAV is a highly heritable congenital heart defect. The low frequency of BAV (1% of general population limits our ability to perform genome-wide association studies. We present the application of four a priori SNP selection techniques, reducing the multiple-testing penalty by restricting analysis to SNPs relevant to BAV in a genome-wide SNP dataset from a cohort of 68 BAV probands and 830 control subjects. Two knowledge-based approaches, CANDID and STRING, were used to systematically identify BAV genes, and their SNPs, from the published literature, microarray expression studies and a genome scan. We additionally tested Functionally Interpolating SNPs (fitSNPs present on the array; the fourth consisted of SNPs selected by Random Forests, a machine learning approach. These approaches reduced the multiple testing penalty by lowering the fraction of the genome probed to 0.19% of the total, while increasing the likelihood of studying SNPs within relevant BAV genes and pathways. Three loci were identified by CANDID, STRING, and fitSNPS. A haplotype within the AXIN1-PDIA2 locus (p-value of 2.926x10(-06 and a haplotype within the Endoglin gene (p-value of 5.881x10(-04 were found to be strongly associated with BAV. The Random Forests approach identified a SNP on chromosome 3 in association with BAV (p-value 5.061x10(-06. The results presented here support an important role for genetic variants in BAV and provide support for additional studies in well-powered cohorts. Further, these studies demonstrate that leveraging existing expression and genomic data in the context of GWAS studies can identify biologically relevant genes and pathways associated with a congenital heart defect.

  12. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    International Nuclear Information System (INIS)

    Boeuf, Stephane; Bovée, Judith VMG; Lehner, Burkhard; Akker, Brendy van den; Ruler, Maayke van; Cleton-Jansen, Anne-Marie; Richter, Wiltrud

    2012-01-01

    As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells

  13. BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

    Science.gov (United States)

    2012-01-01

    Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

  14. Endoglin-mediated suppression of prostate cancer invasion is regulated by activin and bone morphogenetic protein type II receptors.

    Directory of Open Access Journals (Sweden)

    Michael J Breen

    Full Text Available Mortality from prostate cancer (PCa is due to the formation of metastatic disease. Understanding how that process is regulated is therefore critical. We previously demonstrated that endoglin, a type III transforming growth factor β (TGFβ superfamily receptor, suppresses human PCa cell invasion and metastasis. Endoglin-mediated suppression of invasion was also shown by us to be dependent upon the type I TGFβ receptor, activin receptor-like kinase 2 (ALK2, and the downstream effector, Smad1. In this study we demonstrate for the first time that two type II TGFβ receptors are required for endoglin-mediated suppression of invasion: activin A receptor type IIA (ActRIIA and bone morphogenetic protein receptor type II (BMPRII. Downstream signaling through these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1 activation in a kinase-dependent manner, and this is required for suppression of invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting Smad1 signaling through its kinase domain but suppressing it through its cytoplasmic tail. BMPRII's Smad1-regulatory effects are dependent upon its expression level. Further, its ability to suppress invasion is independent of either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII physically interact, and that each also interacts with endoglin. The current findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin-mediated suppression of human PCa cell invasion, that they have differential effects on Smad1 signaling, that they make separate contributions to regulation of invasion, and that they functionally and physically interact.

  15. Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

    Science.gov (United States)

    Klar, Joakim; Blomstrand, Peter; Brunmark, Charlott; Badhai, Jitendra; Håkansson, Hanna Falk; Brange, Charlotte Sollie; Bergendal, Birgitta; Dahl, Niklas

    2011-10-01

    Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed. The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function. The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease. These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.

  16. Rai1 Haploinsufficiency Is Associated with Social Abnormalities in Mice

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    Nalini R. Rao

    2017-04-01

    Full Text Available Background: Autism is characterized by difficulties in social interaction, communication, and repetitive behaviors; with different degrees of severity in each of the core areas. Haploinsufficiency and point mutations of RAI1 are associated with Smith-Magenis syndrome (SMS, a genetic condition that scores within the autism spectrum range for social responsiveness and communication, and is characterized by neurobehavioral abnormalities, intellectual disability, developmental delay, sleep disturbance, and self-injurious behaviors. Methods: To investigate the relationship between Rai1 and social impairment, we evaluated the Rai1+/− mice with a battery of tests to address social behavior in mice. Results: We found that the mutant mice showed diminished interest in social odors, abnormal submissive tendencies, and increased repetitive behaviors when compared to wild type littermates. Conclusions: These findings suggest that Rai1 contributes to social behavior in mice, and prompt it as a candidate gene for the social behaviors observed in Smith-Magenis Syndrome patients.

  17. Tyrosine kinase receptor c-ros-oncogene 1 inhibition alleviates aberrant bone formation of TWIST-1 haploinsufficient calvarial cells from Saethre-Chotzen syndrome patients.

    Science.gov (United States)

    Camp, Esther; Anderson, Peter J; Zannettino, Andrew C W; Glackin, Carlotta A; Gronthos, Stan

    2018-09-01

    Saethre-Chotzen syndrome (SCS), associated with TWIST-1 mutations, is characterized by premature fusion of cranial sutures. TWIST-1 haploinsufficiency, leads to alterations in suture mesenchyme cellular gene expression patterns, resulting in aberrant osteogenesis and craniosynostosis. We analyzed the expression of the TWIST-1 target, Tyrosine kinase receptor c-ros-oncogene 1 (C-ROS-1) in TWIST-1 haploinsufficient calvarial cells derived from SCS patients and calvaria of Twist-1 del/+ mutant mice and found it to be highly expressed when compared to TWIST-1 wild-type controls. Knock-down of C-ROS-1 expression in TWIST-1 haploinsufficient calvarial cells derived from SCS patients was associated with decreased capacity for osteogenic differentiation in vitro. Furthermore, treatment of human SCS calvarial cells with the tyrosine kinase chemical inhibitor, Crizotinib, resulted in reduced C-ROS-1 activity and the osteogenic potential of human SCS calvarial cells with minor effects on cell viability or proliferation. Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose-dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt-related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro. Furthermore, Crizotinib treatment resulted in reduced BMP-2 mediated bone formation potential of whole Twist-1 del/+ mutant mouse calvaria organotypic cultures. Collectively, these results suggest that C-ROS-1 promotes osteogenic differentiation of TWIST-1 haploinsufficient calvarial osteogenic progenitor cells. Furthermore, the aberrant osteogenic potential of these cells is inhibited by the reduction of C-ROS-1. Therefore, targeting C-ROS-1 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST-1 function. © 2018 Wiley Periodicals, Inc.

  18. Serum Level of a Soluble Form of Endoglin (CD105 is Decreased after Goeckerman’s Therapy of Psoriasis

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    David Pohl

    2011-01-01

    Full Text Available Background. Goeckerman’s therapy (GT of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. The aim of study was to evaluate the influence of GT of psoriasis on proinflammatory and angiogenic activities expressed as changes in levels of endoglin (CD105. Methods. Serum levels of a soluble form of endoglin were measured in peripheral blood samples of 38 patients with psoriasis before and after therapy. Sixty three otherwise healthy blood donors serve as a control group. The efficacy of GT was expressed as changes in Psoriasis Area and Severity Index (PASI. Results. PASI score was significantly diminished by GT (p<0.001. Serum levels of soluble CD105 were significantly diminished after GT. The serum level of soluble CD105 dropped from 7.85 ± 2.26 ng/ml before therapy to 7.01 ± 1.71 ng/ml after therapy (p= 0.0002. Compared to serum levels of soluble CD105 in healthy blood donors, serum levels of soluble CD105 in patients before GT were significantly higher (p<0.001 and remained elevated after therapy (p<0.001. Angiogenic activity expressed as serum endoglin is diminished in patients with psoriasis treated by GT.

  19. Endoglin Expression and The Level of TGF- β are Increased in The Placental Tissue and Correlated with Low Fetal Weight in Malaria Infected Mice

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    Sujarot Dwi Sasmito

    2015-01-01

    Full Text Available Malaria infection during pregnancy can cause accumulation of infected red blood cells in placental intervillous space and induces placental tissue inflammation and hypoxia. This condition triggers endoglin expressionand release of soluble endoglin that can interfere TGF-β binding with the receptor. The aim of this study was to investigate the correlation between placental endoglin expression and TGF-β level with low fetal weight (LFW in malaria-infected mice. Nine pregnant mice infected with Plasmodium berghei on the day ninth post mating (malaria-infected group and eight normal pregnant mice (non-infected group were used in this study. The mice were sacrificed on the day 18th post mating, and all fetal body weights were measured by analytical scale. Enzyme Link Immunosorbent Assay (ELISA was done to determine the level of placental TGF-β while immunohistochemical staining was performed to examine endoglin expression in placental tissue. The mean of fetal body weights of malaria-infected group was significantly lower than non-infected group (p= 0,002, while the expression of placental endoglin in malaria- infected group was substantially higher than non-infected group (p= 0.003. The level of placental TGF-β in malaria-infected group was also considerably higher than non-infected group, but the difference was not significant (p= 0.064. Pearson correlation test showed that there were significant negative correlations between fetal body weights with the level of placental TGF-β (p= 0.017, r= -0.568 and the expression of placental endoglin (p= 0.002, r= -0.694. Malaria infection in pregnant mice will increase both TGF-β and endoglin in placenta tissue and correlate with low fetal weight.

  20. YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction

    DEFF Research Database (Denmark)

    Gabriele, Michele; Vulto-van Silfhout, Anneke T; Germain, Pierre-Luc

    2017-01-01

    that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various congenital malformations. Our combined clinical and molecular data define "YY1 syndrome" as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin...... on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators....

  1. dcc Haploinsufficiency results in blunted sensitivity to cocaine enhancement of reward seeking.

    Science.gov (United States)

    Reynolds, Lauren M; Gifuni, Anthony J; McCrea, E Tess; Shizgal, Peter; Flores, Cecilia

    2016-02-01

    Mesocortical dopamine connectivity continues to mature during adolescence. This protracted development confers increased vulnerability for environmental and genetic factors to disrupt mesocortical wiring and subsequently influence responses to drugs of abuse in adulthood. The netrin-1 receptor, DCC, orchestrates medial prefrontal cortex dopamine input during adolescence and dictates the functional organization of local circuitry. Haploinsufficiency of dcc results in increased dopamine innervation to the medial prefrontal cortex, which in turn leads to resilience against the behavioral activating effects of stimulant drugs. However, whether sensitivity to the rewarding effects of drugs of abuse is also altered in dcc haploinsufficiency remains to be resolved. Here, we used the curve-shift method to measure cocaine-induced facilitation of intracranial self-stimulation (ICSS) in adult dcc haploinsufficient mice and wild-type littermates. We found that dcc haploinsufficient mice acquire ICSS behavior at comparable stimulation parameters to wild-type controls. However, cocaine-induced potentiation of ICSS is significantly blunted in dcc haploinsufficient mice. These results are consistent with decreased sensitivity to the rewarding effects of cocaine and/or decreased proclivity to invest effort in the pursuit of reward in dcc haploinsufficient mice. Moreover, these findings suggest that DCC signaling determines adult susceptibility to drug abuse most likely by controlling prefrontal cortex development in adolescence. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A Single Sphingomyelin Species Promotes Exosomal Release of Endoglin into the Maternal Circulation in Preeclampsia.

    Science.gov (United States)

    Ermini, Leonardo; Ausman, Jonathan; Melland-Smith, Megan; Yeganeh, Behzad; Rolfo, Alessandro; Litvack, Michael L; Todros, Tullia; Letarte, Michelle; Post, Martin; Caniggia, Isabella

    2017-09-22

    Preeclampsia (PE), an hypertensive disorder of pregnancy, exhibits increased circulating levels of a short form of the auxillary TGF-beta (TGFB) receptor endoglin (sENG). Until now, its release and functionality in PE remains poorly understood. Here we show that ENG selectively interacts with sphingomyelin(SM)-18:0 which promotes its clustering with metalloproteinase 14 (MMP14) in SM-18:0 enriched lipid rafts of the apical syncytial membranes from PE placenta where ENG is cleaved by MMP14 into sENG. The SM-18:0 enriched lipid rafts also contain type 1 and 2 TGFB receptors (TGFBR1 and TGFBR2), but not soluble fms-like tyrosine kinase 1 (sFLT1), another protein secreted in excess in the circulation of women with PE. The truncated ENG is then released into the maternal circulation via SM-18:0 enriched exosomes together with TGFBR1 and 2. Such an exosomal TGFB receptor complex could be functionally active and block the vascular effects of TGFB in the circulation of PE women.

  3. OBSCN Mutations Associated with Dilated Cardiomyopathy and Haploinsufficiency.

    Directory of Open Access Journals (Sweden)

    Steven Marston

    Full Text Available Studies of the functional consequences of DCM-causing mutations have been limited to a few cases where patients with known mutations had heart transplants. To increase the number of potential tissue samples for direct investigation we performed whole exon sequencing of explanted heart muscle samples from 30 patients that had a diagnosis of familial dilated cardiomyopathy and screened for potentially disease-causing mutations in 58 HCM or DCM-related genes.We identified 5 potentially disease-causing OBSCN mutations in 4 samples; one sample had two OBSCN mutations and one mutation was judged to be not disease-related. Also identified were 6 truncating mutations in TTN, 3 mutations in MYH7, 2 in DSP and one each in TNNC1, TNNI3, MYOM1, VCL, GLA, PLB, TCAP, PKP2 and LAMA4. The mean level of obscurin mRNA was significantly greater and more variable in healthy donor samples than the DCM samples but did not correlate with OBSCN mutations. A single obscurin protein band was observed in human heart myofibrils with apparent mass 960 ± 60 kDa. The three samples with OBSCN mutations had significantly lower levels of obscurin immunoreactive material than DCM samples without OBSCN mutations (45±7, 48±3, and 72±6% of control level.Obscurin levels in DCM controls, donor heart and myectomy samples were the same.OBSCN mutations may result in the development of a DCM phenotype via haploinsufficiency. Mutations in the obscurin gene should be considered as a significant causal factor of DCM, alone or in concert with other mutations.

  4. Adiponectin haploinsufficiency promotes mammary tumor development in MMTV-PyVT mice by modulation of phosphatase and tensin homolog activities.

    Directory of Open Access Journals (Sweden)

    Janice B B Lam

    Full Text Available Adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. A negative association of adiponectin levels with breast cancer development has been demonstrated. However, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive.In the present study, MMTV-polyomavirus middle T antigen (MMTV-PyVT transgenic mice with reduced adiponectin expressions were established and the stromal effects of adiponectin haploinsufficiency on mammary tumor development evaluated. In mice from both FVB/N and C57BL/6J backgrounds, insufficient adiponectin production promoted mammary tumor onset and development. A distinctive basal-like subtype of tumors, with a more aggressive phenotype, was derived from adiponectin haplodeficient MMTV-PyVT mice. Comparing with those from control MMTV-PyVT mice, the isolated mammary tumor cells showed enhanced tumor progression in re-implanted nude mice, accelerated proliferation in primary cultures, and hyperactivated phosphatidylinositol-3-kinase (PI3K/Akt/beta-catenin signaling, which at least partly attributed to the decreased phosphatase and tensin homolog (PTEN activities. Further analysis revealed that PTEN was inactivated by a redox-regulated mechanism. Increased association of PTEN-thioredoxin complexes was detected in tumors derived from mice with reduced adiponectin levels. The activities of thioredoxin (Trx1 and thioredoxin reductase (TrxR1 were significantly elevated, whereas treatment with either curcumin, an irreversible inhibitor of TrxR1, or adiponectin largely attenuated their activities and resulted in the re-activation of PTEN in these tumor cells. Moreover, adiponectin could inhibit TrxR1 promoter-mediated transcription and restore the mRNA expressions of TrxR1.Adiponectin haploinsufficiency facilitated mammary tumorigenesis by down-regulation of PTEN activity and activation of PI3K/Akt signalling pathway through a mechanism involving Trx1/TrxR1

  5. Attenuated hypertrophic response to pressure overload in a lamin A/C haploinsufficiency mouse.

    Science.gov (United States)

    Cupesi, Mihaela; Yoshioka, Jun; Gannon, Joseph; Kudinova, Anastacia; Stewart, Colin L; Lammerding, Jan

    2010-06-01

    Inherited mutations cause approximately 30% of all dilated cardiomyopathy cases, with autosomal dominant mutations in the LMNA gene accounting for more than one third of these. The LMNA gene encodes the nuclear envelope proteins lamins A and C, which provide structural support to the nucleus and also play critical roles in transcriptional regulation. Functional deletion of a single allele is sufficient to trigger dilated cardiomyopathy in humans and mice. However, whereas Lmna(-/-) mice develop severe muscular dystrophy and dilated cardiomyopathy and die by 8 weeks of age, heterozygous Lmna(+/-) mice have a much milder phenotype, with changes in ventricular function and morphology only becoming apparent at 1 year of age. Here, we studied 8- to 20-week-old Lmna(+/-) mice and wild-type littermates in a pressure overload model to examine whether increased mechanical load can accelerate or exacerbate myocardial dysfunction in the heterozygotes. While overall survival was similar between genotypes, Lmna(+/-) animals had a significantly attenuated hypertrophic response to pressure overload as evidenced by reduced ventricular mass and myocyte size. Analysis of pressure overload-induced transcriptional changes suggested that the reduced hypertrophy in the Lmna(+/-) mice was accompanied by impaired activation of the mechanosensitive gene Egr-1. In conclusion, our findings provide further support for a critical role of lamins A and C in regulating the cellular response to mechanical stress in cardiomyocytes and demonstrate that haploinsufficiency of lamins A and C alone is sufficient to alter hypertrophic responses and cardiac function in the face of pressure overload in the heart. (c) 2009 Elsevier Ltd. All rights reserved.

  6. High-calorie diet exacerbates prostate neoplasia in mice with haploinsufficiency of Pten tumor suppressor gene

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    Jehnan Liu

    2015-03-01

    Conclusion: High-calorie diet promotes prostate cancer progression in the genetically susceptible Pten haploinsufficient mouse while preserving insulin sensitivity. This appears to be partly due to increased inflammatory response to high-caloric intake in addition to increased ability of insulin to promote lipogenesis.

  7. Dissociation of Frontotemporal Dementia–Related Deficits and Neuroinflammation in Progranulin Haploinsufficient Mice

    Science.gov (United States)

    Filiano, Anthony J.; Martens, Lauren Herl; Young, Allen H.; Warmus, Brian A.; Zhou, Ping; Diaz-Ramirez, Grisell; Jiao, Jian; Zhang, Zhijun; Huang, Eric J.; Gao, Fen-Biao; Farese, Robert V.; Roberson, Erik D.

    2013-01-01

    Frontotemporal dementia (FTD) is a neurodegenerative disease with hallmark deficits in social and emotional function. Heterozygous loss-of-function mutations in GRN, the progranulin gene, are a common genetic cause of the disorder, but the mechanisms by which progranulin haploinsufficiency causes neuronal dysfunction in FTD are unclear. Homozygous progranulin knockout (Grn−/−) mice have been studied as a model of this disorder and show behavioral deficits and a neuroinflammatory phenotype with robust microglial activation. However, homozygous GRN mutations causing complete progranulin deficiency were recently shown to cause a different neurological disorder, neuronal ceroid lipofuscinosis, suggesting that the total absence of progranulin may have effects distinct from those of haploinsufficiency. Here, we studied progranulin heterozygous (Grn+/−) mice, which model progranulin haploinsufficiency. We found that Grn+/− mice developed age-dependent social and emotional deficits potentially relevant to FTD. However, unlike Grn−/− mice, behavioral deficits in Grn+/− mice occurred in the absence of gliosis or increased expression of tumor necrosis factor–α. Instead, we found neuronal abnormalities in the amygdala, an area of selective vulnerability in FTD, in Grn+/− mice. Our findings indicate that FTD-related deficits due to progranulin haploinsufficiency can develop in the absence of detectable gliosis and neuroinflammation, thereby dissociating microglial activation from functional deficits and suggesting an important effect of progranulin deficiency on neurons. PMID:23516300

  8. Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice.

    Science.gov (United States)

    Filiano, Anthony J; Martens, Lauren Herl; Young, Allen H; Warmus, Brian A; Zhou, Ping; Diaz-Ramirez, Grisell; Jiao, Jian; Zhang, Zhijun; Huang, Eric J; Gao, Fen-Biao; Farese, Robert V; Roberson, Erik D

    2013-03-20

    Frontotemporal dementia (FTD) is a neurodegenerative disease with hallmark deficits in social and emotional function. Heterozygous loss-of-function mutations in GRN, the progranulin gene, are a common genetic cause of the disorder, but the mechanisms by which progranulin haploinsufficiency causes neuronal dysfunction in FTD are unclear. Homozygous progranulin knock-out (Grn(-/-)) mice have been studied as a model of this disorder and show behavioral deficits and a neuroinflammatory phenotype with robust microglial activation. However, homozygous GRN mutations causing complete progranulin deficiency were recently shown to cause a different neurological disorder, neuronal ceroid lipofuscinosis, suggesting that the total absence of progranulin may have effects distinct from those of haploinsufficiency. Here, we studied progranulin heterozygous (Grn(+/-)) mice, which model progranulin haploinsufficiency. We found that Grn(+/-) mice developed age-dependent social and emotional deficits potentially relevant to FTD. However, unlike Grn(-/-) mice, behavioral deficits in Grn(+/-) mice occurred in the absence of gliosis or increased expression of tumor necrosis factor-α. Instead, we found neuronal abnormalities in the amygdala, an area of selective vulnerability in FTD, in Grn(+/-) mice. Our findings indicate that FTD-related deficits resulting from progranulin haploinsufficiency can develop in the absence of detectable gliosis and neuroinflammation, thereby dissociating microglial activation from functional deficits and suggesting an important effect of progranulin deficiency on neurons.

  9. Telomere Elongation and Naive Pluripotent Stem Cells Achieved from Telomerase Haplo-Insufficient Cells by Somatic Cell Nuclear Transfer

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    Li-Ying Sung

    2014-12-01

    Full Text Available Summary: Haplo-insufficiency of telomerase genes in humans leads to telomere syndromes such as dyskeratosis congenital and idiopathic pulmonary fibrosis. Generation of pluripotent stem cells from telomerase haplo-insufficient donor cells would provide unique opportunities toward the realization of patient-specific stem cell therapies. Recently, pluripotent human embryonic stem cells (ntESCs have been efficiently achieved by somatic cell nuclear transfer (SCNT. We tested the hypothesis that SCNT could effectively elongate shortening telomeres of telomerase haplo-insufficient cells in the ntESCs with relevant mouse models. Indeed, telomeres of telomerase haplo-insufficient (Terc+/− mouse cells are elongated in ntESCs. Moreover, ntESCs derived from Terc+/− cells exhibit naive pluripotency as evidenced by generation of Terc+/− ntESC clone pups by tetraploid embryo complementation, the most stringent test of naive pluripotency. These data suggest that SCNT could offer a powerful tool to reprogram telomeres and to discover the factors for robust restoration of telomeres and pluripotency of telomerase haplo-insufficient somatic cells. : Sung et al. demonstrate in a mouse model that telomeres of telomerase haplo-insufficient cells can be elongated by somatic cell nuclear transfer. Moreover, ntESCs derived from Terc+/− cells exhibit pluripotency evidenced by generation of Terc+/−ntESC clone pups by tetraploid embryo complementation, the most stringent test of naive pluripotency.

  10. Endoglin in pregnancy complicated by fetal intrauterine growth restriction in normotensive and preeclamptic pregnant women: a comparison between preeclamptic patients with appropriate-for-gestational-age weight infants and healthy pregnant women.

    Science.gov (United States)

    Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

    2012-06-01

    The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls. The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay. Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2 ± 4.3 ng/ml in the IUGR group, 14.1 ± 3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1 ± 3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6 ± 3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight. Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and

  11. Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

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    Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

    2018-06-05

    Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

  12. Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways.

    Science.gov (United States)

    Lalli, Matthew A; Jang, Jiwon; Park, Joo-Hye C; Wang, Yidi; Guzman, Elmer; Zhou, Hongjun; Audouard, Morgane; Bridges, Daniel; Tovar, Kenneth R; Papuc, Sorina M; Tutulan-Cunita, Andreea C; Huang, Yadong; Budisteanu, Magdalena; Arghir, Aurora; Kosik, Kenneth S

    2016-04-01

    Williams syndrome (WS) is a neurodevelopmental disorder caused by a genomic deletion of ∼28 genes that results in a cognitive and behavioral profile marked by overall intellectual impairment with relative strength in expressive language and hypersocial behavior. Advancements in protocols for neuron differentiation from induced pluripotent stem cells allowed us to elucidate the molecular circuitry underpinning the ontogeny of WS. In patient-derived stem cells and neurons, we determined the expression profile of the Williams-Beuren syndrome critical region-deleted genes and the genome-wide transcriptional consequences of the hemizygous genomic microdeletion at chromosome 7q11.23. Derived neurons displayed disease-relevant hallmarks and indicated novel aberrant pathways in WS neurons including over-activated Wnt signaling accompanying an incomplete neurogenic commitment. We show that haploinsufficiency of the ATP-dependent chromatin remodeler, BAZ1B, which is deleted in WS, significantly contributes to this differentiation defect. Chromatin-immunoprecipitation (ChIP-seq) revealed BAZ1B target gene functions are enriched for neurogenesis, neuron differentiation and disease-relevant phenotypes. BAZ1B haploinsufficiency caused widespread gene expression changes in neural progenitor cells, and together with BAZ1B ChIP-seq target genes, explained 42% of the transcriptional dysregulation in WS neurons. BAZ1B contributes to regulating the balance between neural precursor self-renewal and differentiation and the differentiation defect caused by BAZ1B haploinsufficiency can be rescued by mitigating over-active Wnt signaling in neural stem cells. Altogether, these results reveal a pivotal role for BAZ1B in neurodevelopment and implicate its haploinsufficiency as a likely contributor to the neurological phenotypes in WS. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Tsc2 Haploinsufficiency Has Limited Effects on Fetal Brain Cytokine Levels during Gestational Immune Activation

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    Dan Ehninger

    2014-01-01

    Full Text Available Dysregulated TSC/mTOR signaling may play a pathogenetic role in forms of syndromic autism, such as autism associated with tuberous sclerosis, a genetic disorder caused by heterozygous TSC1 or TSC2 mutations. Environmental risk factors, such as gestational viral infections, may, in some cases, also contribute to the pathogenesis of autism and related neuropsychiatric disorders. We have recently found that a heterozygous Tsc2 mutation and the poly I:C model of maternal immune activation (MIA interactively perturb fetal development and adult social behavior in mice, suggesting that these factors converge on shared pathways. TSC/mTOR signaling plays an important role in the modulation of immune responses, raising the possibility that the damage caused by MIA was greater in Tsc2+/− than in wildtype fetuses because of an exacerbated immune response in the mutants. Here, cytokine antibody arrays were employed to measure relative cytokine abundances in the fetal brain and the placenta during MIA. Cytokines were induced by gestational poly I:C but there was no obvious modulatory effect of Tsc2 haploinsufficiency. The data indicate that cytokine exposure during MIA is comparable in Tsc2 haploinsufficient and wildtype control fetuses, suggesting that downstream molecular and cellular processes may account for the interactive effects of Tsc2 haploinsufficiency and MIA.

  14. Haploinsufficiency of KDM6A is associated with severe psychomotor retardation, global growth restriction, seizures and cleft palate.

    Science.gov (United States)

    Lindgren, Amelia M; Hoyos, Tatiana; Talkowski, Michael E; Hanscom, Carrie; Blumenthal, Ian; Chiang, Colby; Ernst, Carl; Pereira, Shahrin; Ordulu, Zehra; Clericuzio, Carol; Drautz, Joanne M; Rosenfeld, Jill A; Shaffer, Lisa G; Velsher, Lea; Pynn, Tania; Vermeesch, Joris; Harris, David J; Gusella, James F; Liao, Eric C; Morton, Cynthia C

    2013-05-01

    We describe a female subject (DGAP100) with a 46,X,t(X;5)(p11.3;q35.3)inv(5)(q35.3q35.1)dn, severe psychomotor retardation with hypotonia, global postnatal growth restriction, microcephaly, globally reduced cerebral volume, seizures, facial dysmorphia and cleft palate. Fluorescence in situ hybridization and whole-genome sequencing demonstrated that the X chromosome breakpoint disrupts KDM6A in the second intron. No genes were directly disrupted on chromosome 5. KDM6A is a histone 3 lysine 27 demethylase and a histone 3 lysine 4 methyltransferase. Expression of KDM6A is significantly reduced in DGAP100 lymphoblastoid cells compared to control samples. We identified nine additional cases with neurodevelopmental delay and various other features consistent with the DGAP100 phenotype with copy number variation encompassing KDM6A from microarray databases. We evaluated haploinsufficiency of kdm6a in a zebrafish model. kdm6a is expressed in the pharyngeal arches and ethmoid plate of the developing zebrafish, while a kdm6a morpholino knockdown exhibited craniofacial defects. We conclude KDM6A dosage regulation is associated with severe and diverse structural defects and developmental abnormalities.

  15. Key role of the endothelial TGF-β/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension.

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    Benoît Gore

    Full Text Available Mutations affecting transforming growth factor-beta (TGF-β superfamily receptors, activin receptor-like kinase (ALK-1, and endoglin (ENG occur in patients with pulmonary arterial hypertension (PAH. To determine whether the TGF-β/ALK1/ENG pathway was involved in PAH, we investigated pulmonary TGF-β, ALK1, ALK5, and ENG expressions in human lung tissue and cultured pulmonary-artery smooth-muscle-cells (PA-SMCs and pulmonary endothelial cells (PECs from 14 patients with idiopathic PAH (iPAH and 15 controls. Seeing that ENG was highly expressed in PEC, we assessed the effects of TGF-β on Smad1/5/8 and Smad2/3 activation and on growth factor production by the cells. Finally, we studied the consequence of ENG deficiency on the chronic hypoxic-PH development by measuring right ventricular (RV systolic pressure (RVSP, RV hypertrophy, and pulmonary arteriolar remodeling in ENG-deficient (Eng+/- and wild-type (Eng+/+ mice. We also evaluated the pulmonary blood vessel density, macrophage infiltration, and cytokine expression in the lungs of the animals. Compared to controls, iPAH patients had higher serum and pulmonary TGF-β levels and increased ALK1 and ENG expressions in lung tissue, predominantly in PECs. Incubation of the cells with TGF-β led to Smad1/5/8 phosphorylation and to a production of FGF2, PDGFb and endothelin-inducing PA-SMC growth. Endoglin deficiency protected mice from hypoxic PH. As compared to wild-type, Eng+/- mice had a lower pulmonary vessel density, and no change in macrophage infiltration after exposure to chronic hypoxia despite the higher pulmonary expressions of interleukin-6 and monocyte chemoattractant protein-1. The TGF-β/ALK1/ENG signaling pathway plays a key role in iPAH and experimental hypoxic PH via a direct effect on PECs leading to production of growth factors and inflammatory cytokines involved in the pathogenesis of PAH.

  16. Endoglin expression in blood and endothelium is differentially regulated by modular assembly of the Ets/Gata hemangioblast code.

    Science.gov (United States)

    Pimanda, John E; Chan, Wan Y I; Wilson, Nicola K; Smith, Aileen M; Kinston, Sarah; Knezevic, Kathy; Janes, Mary E; Landry, Josette-Renée; Kolb-Kokocinski, Anja; Frampton, Jonathan; Tannahill, David; Ottersbach, Katrin; Follows, George A; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold

    2008-12-01

    Endoglin is an accessory receptor for TGF-beta signaling and is required for normal hemangioblast, early hematopoietic, and vascular development. We have previously shown that an upstream enhancer, Eng -8, together with the promoter region, mediates robust endothelial expression yet is inactive in blood. To identify hematopoietic regulatory elements, we used array-based methods to determine chromatin accessibility across the entire locus. Subsequent transgenic analysis of candidate elements showed that an endothelial enhancer at Eng +9 when combined with an element at Eng +7 functions as a strong hemato-endothelial enhancer. Chromatin immunoprecipitation (ChIP)-chip analysis demonstrated specific binding of Ets factors to the promoter as well as to the -8, +7+9 enhancers in both blood and endothelial cells. By contrast Pu.1, an Ets factor specific to the blood lineage, and Gata2 binding was only detected in blood. Gata2 was bound only at +7 and GATA motifs were required for hematopoietic activity. This modular assembly of regulators gives blood and endothelial cells the regulatory freedom to independently fine-tune gene expression and emphasizes the role of regulatory divergence in driving functional divergence.

  17. Endoglin (CD105) expression on microvessel endothelial cells in juvenile nasopharyngeal angiofibroma: tissue microarray analysis and association with prognostic significance.

    Science.gov (United States)

    Wang, Jing-Jing; Sun, Xi-Cai; Hu, Li; Liu, Zhuo-Fu; Yu, Hua-Peng; Li, Han; Wang, Shu-Yi; Wang, De-Hui

    2013-12-01

    The purpose of this study was to examine endoglin (CD105) expression on microvessel endothelial cells (ECs) in juvenile nasopharyngeal angiofibroma (JNA) and its relationship with recurrence. Immunohistochemistry was performed to detect CD105 expression in a tissue microarray from 70 patients with JNA. Correlation between CD105 expression on microvessel ECs and clinicopathological features, as well as tumor recurrence, were analyzed. Immunohistochemistry revealed CD105 expression on ECs but not in stroma of patients with JNA. Chi-square analysis indicated CD105-based microvessel density (MVD) was correlated with JNA recurrence (p = .013). Univariate and multivariate analyses determined that MVD was a significant predictor of time to recurrence (p = .009). The CD105-based MVD was better for predicting disease recurrence (AUROC: 0.673; p = .036) than other clinicopathological features. MVD is a useful predictor for poor prognosis of patients with JNA after curative resection. Angiogenesis, which may play an important role in the occurrence and development of JNA, is therefore a potential therapeutic target for JNA. Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.

  18. Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1

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    Takako Saito

    2017-05-01

    Full Text Available Endoglin (ENG/CD105 is an essential endothelial cell co-receptor of the transforming growth factor β (TGF-β superfamily, mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1 and involved in tumor angiogenesis and preeclampsia. Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9. BMP9 interacts with a hydrophobic surface of the N-terminal orphan domain of ENG, which adopts a new duplicated fold generated by circular permutation. The interface involves residues mutated in HHT1 and overlaps with the epitope of tumor-suppressing anti-ENG monoclonal TRC105. The structure of the C-terminal zona pellucida module suggests how two copies of ENG embrace homodimeric BMP9, whose binding is compatible with ligand recognition by type I but not type II receptors. These findings shed light on the molecular basis of the BMP signaling cascade, with implications for future therapeutic interventions in this fundamental pathway.

  19. Endoglin inhibition leads to intussusceptive angiogenesis via activation of factors related to COUP-TFII signaling pathway.

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    Ruslan Hlushchuk

    Full Text Available Angiogenesis is a highly coordinated, extremely complex process orchestrated by multiple signaling molecules and blood flow conditions. While sprouting mode of angiogenesis is very well investigated, the molecular mechanisms underlying intussusception, the second mode of angiogenesis, remain largely unclear. In the current study two molecules involved in vascular growth and differentiation, namely endoglin (ENG/CD105 and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII were examined to unravel their specific roles in angiogenesis. Down- respectively up-regulation of both molecules tightly correlates with intussusceptive microvascular growth. Upon ENG inhibition in chicken embryo model, formation of irregular capillary meshwork accompanied by increased expression of COUP-TFII could be observed. This dynamic expression pattern of ENG and COUP-TFII during vascular development and remodeling correlated with formation of pillars and progression of intussusceptive angiogenesis. Similar findings could be observed in mammalian model of acute rat Thy1.1 glomerulonephritis, which was induced by intravenous injection of anti-Thy1 antibody and has shown upregulation of COUP-TFII in initial phase of intussusception, while ENG expression was not disturbed compared to the controls but decreased over the time of pillar formation. In this study, we have shown that ENG inhibition and at the same time up-regulation of COUP-TFII expression promotes intussusceptive angiogenesis.

  20. Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin

    International Nuclear Information System (INIS)

    Olsen, O E; Wader, K F; Misund, K; Våtsveen, T K; Rø, T B; Mylin, A K; Turesson, I; Størdal, B F; Moen, S H; Standal, T; Waage, A; Sundan, A; Holien, T

    2014-01-01

    Multiple myeloma is a malignancy of plasma cells predominantly located in the bone marrow. A number of bone morphogenetic proteins (BMPs) induce apoptosis in myeloma cells in vitro, and with this study we add BMP-9 to the list. BMP-9 has been found in human serum at concentrations that inhibit cancer cell growth in vitro. We here show that the level of BMP-9 in serum was elevated in myeloma patients (median 176 pg/ml, range 8–809) compared with healthy controls (median 110 pg/ml, range 8–359). BMP-9 was also present in the bone marrow and was able to induce apoptosis in 4 out of 11 primary myeloma cell samples by signaling through ALK2. BMP-9-induced apoptosis in myeloma cells was associated with c-MYC downregulation. The effects of BMP-9 were counteracted by membrane-bound (CD105) or soluble endoglin present in the bone marrow microenvironment, suggesting a mechanism for how myeloma cells can evade the tumor suppressing activity of BMP-9 in multiple myeloma

  1. Partial Tmem106b reduction does not correct abnormalities due to progranulin haploinsufficiency.

    Science.gov (United States)

    Arrant, Andrew E; Nicholson, Alexandra M; Zhou, Xiaolai; Rademakers, Rosa; Roberson, Erik D

    2018-06-22

    Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function. Heterozygous GRN mutation carriers develop FTD with TDP-43 pathology and exhibit signs of lysosomal dysfunction in the brain, with increased levels of lysosomal proteins and lipofuscin accumulation. Homozygous GRN mutation carriers develop neuronal ceroid lipofuscinosis (NCL), an earlier-onset lysosomal storage disorder caused by severe lysosomal dysfunction. Multiple genome-wide association studies have shown that risk of FTD in GRN mutation carriers is modified by polymorphisms in TMEM106B, which encodes a lysosomal membrane protein. Risk alleles of TMEM106B may increase TMEM106B levels through a variety of mechanisms. Brains from FTD patients with GRN mutations exhibit increased TMEM106B expression, and protective TMEM106B polymorphisms are associated with decreased TMEM106B expression. Together, these data raise the possibility that reduction of TMEM106B levels may protect against the pathogenic effects of progranulin haploinsufficiency. We crossed Tmem106b +/- mice with Grn +/- mice, which model the progranulin haploinsufficiency of GRN mutation carriers and develop age-dependent social deficits and lysosomal abnormalities in the brain. We tested whether partial Tmem106b reduction could normalize the social deficits and lysosomal abnormalities of Grn +/- mice. Partial reduction of Tmem106b levels did not correct the social deficits of Grn +/- mice. Tmem106b reduction also failed to normalize most lysosomal abnormalities of Grn +/- mice, except for β-glucuronidase activity, which was suppressed by Tmem106b reduction and increased by progranulin insufficiency. These data do not support the hypothesis that Tmem106b reduction protects against the pathogenic effects of progranulin haploinsufficiency, but do show that Tmem106b reduction normalizes some

  2. Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice

    Science.gov (United States)

    Hilgendorff, Anne; Parai, Kakoli; Ertsey, Robert; Navarro, Edwin; Jain, Noopur; Carandang, Francis; Peterson, Joanna; Mokres, Lucia; Milla, Carlos; Preuss, Stefanie; Alcazar, Miguel Alejandre; Khan, Suleman; Masumi, Juliet; Ferreira-Tojais, Nancy; Mujahid, Sana; Starcher, Barry; Rabinovitch, Marlene

    2014-01-01

    Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice (Eln+/−) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type (Eln+/+) and Eln+/− littermates at baseline and after MV with air for 8–24 h. Lungs of unventilated Eln+/− mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln+/+ pups. Eln+/− lungs contained fewer capillaries than Eln+/+ lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln+/+ neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln+/− mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln+/− than in Eln+/+ pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln+/− compared with Eln+/+ mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln+/+ and Eln+/− mice. Paucity of lung capillaries in Eln+/− newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln+/− mice. PMID:25539853

  3. Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence

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    Sung-Hyun Park

    2016-02-01

    Full Text Available Abstract Background Spindle assembly checkpoint components BubR1 and Sgo1 play a key role in the maintenance of chromosomal instability during cell division. These proteins function to block the anaphase entry until all condensed chromosomes have been attached by the microtubules emanating from both spindle poles. Haplo-insufficiency of either BubR1 or SGO1 results in enhanced chromosomal instability and tumor development in the intestine. Recent studies show that spindle checkpoint proteins also have a role in slowing down the ageing process. Therefore, we want to study whether haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence in mice. Methods We took advantage of the availability of BubR1 and SGO1 knockout mice and generated primary murine embryonic fibroblasts (MEFs with mutations in either BubR1, SGO1, or both and analyzed cellular senescence of the MEFs of various genetic backgrounds. Results We observed that BubR1 +/− SGO +/− MEFs had an accelerated cellular senescence characterized by morphological changes and expressed senescence-associated β-galactosidase. In addition, compared with wild-type MEFs or MEFs with a single gene deficiency, BubR1 +/− SGO1 +/− MEFs expressed enhanced levels of p21 but not p16. Conclusions Taken together, our observations suggest that combined deficiency of BubR1 and Sgo1 accelerates cellular senescence.

  4. Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible causes of growth impairment.

    Science.gov (United States)

    Celen, Cemre; Chuang, Jen-Chieh; Luo, Xin; Nijem, Nadine; Walker, Angela K; Chen, Fei; Zhang, Shuyuan; Chung, Andrew S; Nguyen, Liem H; Nassour, Ibrahim; Budhipramono, Albert; Sun, Xuxu; Bok, Levinus A; McEntagart, Meriel; Gevers, Evelien F; Birnbaum, Shari G; Eisch, Amelia J; Powell, Craig M; Ge, Woo-Ping; Santen, Gijs We; Chahrour, Maria; Zhu, Hao

    2017-07-11

    Sequencing studies have implicated haploinsufficiency of ARID1B , a SWI/SNF chromatin-remodeling subunit, in short stature (Yu et al., 2015), autism spectrum disorder (O'Roak et al., 2012), intellectual disability (Deciphering Developmental Disorders Study, 2015), and corpus callosum agenesis (Halgren et al., 2012). In addition, ARID1B is the most common cause of Coffin-Siris syndrome, a developmental delay syndrome characterized by some of the above abnormalities (Santen et al., 2012; Tsurusaki et al., 2012; Wieczorek et al., 2013). We generated Arid1b heterozygous mice, which showed social behavior impairment, altered vocalization, anxiety-like behavior, neuroanatomical abnormalities, and growth impairment. In the brain, Arid1b haploinsufficiency resulted in changes in the expression of SWI/SNF-regulated genes implicated in neuropsychiatric disorders. A focus on reversible mechanisms identified Insulin-like growth factor (IGF1) deficiency with inadequate compensation by Growth hormone-releasing hormone (GHRH) and Growth hormone (GH), underappreciated findings in ARID1B patients. Therapeutically, GH supplementation was able to correct growth retardation and muscle weakness. This model functionally validates the involvement of ARID1B in human disorders, and allows mechanistic dissection of neurodevelopmental diseases linked to chromatin-remodeling.

  5. Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.

    Directory of Open Access Journals (Sweden)

    Hanqian Mao

    2016-09-01

    Full Text Available The exon junction complex (EJC is an RNA binding complex comprised of the core components Magoh, Rbm8a, and Eif4a3. Human mutations in EJC components cause neurodevelopmental pathologies. Further, mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly. Yet despite the requirement of these genes for neurodevelopment, the pathogenic mechanisms linking EJC dysfunction to microcephaly remain poorly understood. Here we employ mouse genetics, transcriptomic and proteomic analyses to demonstrate that haploinsufficiency for each of the 3 core EJC components causes microcephaly via converging regulation of p53 signaling. Using a new conditional allele, we first show that Eif4a3 haploinsufficiency phenocopies aberrant neurogenesis and microcephaly of Magoh and Rbm8a mutant mice. Transcriptomic and proteomic analyses of embryonic brains at the onset of neurogenesis identifies common pathways altered in each of the 3 EJC mutants, including ribosome, proteasome, and p53 signaling components. We further demonstrate all 3 mutants exhibit defective splicing of RNA regulatory proteins, implying an EJC dependent RNA regulatory network that fine-tunes gene expression. Finally, we show that genetic ablation of one downstream pathway, p53, significantly rescues microcephaly of all 3 EJC mutants. This implicates p53 activation as a major node of neurodevelopmental pathogenesis following EJC impairment. Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease.

  6. Circulating soluble endoglin levels in pregnant women in Cameroon and Malawi--associations with placental malaria and fetal growth restriction.

    Science.gov (United States)

    Silver, Karlee L; Conroy, Andrea L; Leke, Rose G F; Leke, Robert J I; Gwanmesia, Philomina; Molyneux, Malcolm E; Taylor, Diane Wallace; Wallace, Diane Taylor; Rogerson, Stephen J; Kain, Kevin C

    2011-01-01

    Placental infections with Plasmodium falciparum are associated with fetal growth restriction resulting in low birth weight (LBW). The mechanisms that mediate these effects have yet to be completely described; however, they are likely to involve inflammatory processes and dysregulation of angiogenesis. Soluble endoglin (sEng), a soluble receptor of transforming growth factor (TGF)-β previously associated with preeclampsia in pregnant women and with severe malaria in children, regulates the immune system and influences angiogenesis. We hypothesized that sEng may play a role in development of LBW associated with placental malaria (PM). Plasma levels of sEng were measured in women (i) followed prospectively throughout pregnancy in Cameroon (n = 52), and (ii) in a case-control study at delivery in Malawi (n = 479). The relationships between sEng levels and gravidity, peripheral and placental parasitemia, gestational age, and adverse outcomes of PM including maternal anemia and LBW were determined. In the longitudinal cohort from Cameroon, 28 of 52 women (54%) experienced at least one malaria infection during pregnancy. In Malawi we enrolled two aparasitemic gravidity-matched controls for every case with PM. sEng levels varied over the course of gestation and were significantly higher in early and late gestation as compared to delivery (Pwomen and PM in Malawian women were each associated with elevated sEng levels following correction for gestational age and gravidity (p = 0.006 and p = 0.033, respectively). Increased sEng was also associated with the delivery of LBW infants in primigravid Malawian women (p = 0.017); the association was with fetal growth restriction (p = 0.003) but not pre-term delivery (p = 0.286). Increased circulating maternal sEng levels are associated with P. falciparum infection in pregnancy and with fetal growth restriction in primigravidae with PM.

  7. Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.

    Science.gov (United States)

    Sim, Joe C H; White, Susan M; Fitzpatrick, Elizabeth; Wilson, Gabrielle R; Gillies, Greta; Pope, Kate; Mountford, Hayley S; Torring, Pernille M; McKee, Shane; Vulto-van Silfhout, Anneke T; Jhangiani, Shalini N; Muzny, Donna M; Leventer, Richard J; Delatycki, Martin B; Amor, David J; Lockhart, Paul J

    2014-03-27

    Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified as the predominant cause of Coffin-Siris syndrome and have also been shown to be a frequent cause of nonsyndromic intellectual disability. Here, we investigate the molecular basis of a patient with an overlapping but distinctive phenotype of intellectual disability, plantar fat pads and facial dysmorphism. High density microarray analysis of the patient demonstrated a heterozygous deletion at 6q25.3, which resulted in the loss of four genes including AT Rich Interactive Domain 1B (ARID1B). Subsequent quantitative real-time PCR analysis revealed ARID1B haploinsufficiency in the patient. Analysis of both patient-derived and ARID1B knockdown fibroblasts after serum starvation demonstrated delayed cell cycle re-entry associated with reduced cell number in the S1 phase. Based on the patient's distinctive phenotype, we ascertained four additional patients and identified heterozygous de novo ARID1B frameshift or nonsense mutations in all of them. This study broadens the spectrum of ARID1B associated phenotypes by describing a distinctive phenotype including plantar fat pads but lacking the hypertrichosis or fifth nail hypoplasia associated with Coffin-Siris syndrome. We present the first direct evidence in patient-derived cells that alterations in cell cycle contribute to the underlying pathogenesis of syndromes associated with ARID1B haploinsufficiency.

  8. Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

    Science.gov (United States)

    Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

    2018-02-27

    Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

  9. Short stature caused by isolated SHOX gene haploinsufficiency: update on the diagnosis and treatment.

    Science.gov (United States)

    Jorge, Alexander A L; Funari, Mariana Fa; Nishi, Mirian Y; Mendonca, Berenice B

    2010-12-01

    Heterozygous SHOX defects are observed in about 50 to 90% of patients with Leri-Weill dyschondrosteosis (LWD), a common dominant inherited skeletal dysplasia; and in 2 to 15% of children with idiopathic short stature (ISS), indicating that SHOX defects are the most important monogenetic cause of short stature. In addition, children selected by disproportionate idiopathic short stature had a higher frequency of SHOX mutations (22%). A careful clinical evaluation of family members with short stature is recommended since it usually revealed LWD patients in families first classified as having ISS or familial short stature. SHOX-molecular analysis is indicated in families with LWD and ISS children with disproportionate short stature. Treatment with recombinant human growth hormone is considered an accepted approach to treat short stature associated with isolated SHOX defect. Here we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.

  10. IGF-1 receptor haploinsufficiency leads to age-dependent development of metabolic syndrome.

    Science.gov (United States)

    Thakur, Sachin; Garg, Neha; Zhang, Ning; Hussey, Sophie E; Musi, Nicolas; Adamo, Martin L

    2017-05-13

    Individuals born small for gestational age (SGA) are at a higher risk of developing the metabolic syndrome later in life. IGF-1 resistance has been reported in placentae from SGA births and mutations in the Igf1 receptor gene have been reported in several cohorts of SGA subjects. We have used the Igf1r heterozygous (Igf1r +/- ) male mouse as a model to investigate the mechanisms by which Igf1r haploinsufficiency leads to insulin resistance. Despite exhibiting IGF-1 resistance, insulin signaling is enhanced in young Igf1r +/- mice but is attenuated in the muscle of old Igf1r +/- mice. Although smaller than WT (wild type) mice, old-aged Igf1r +/- had increased adiposity and exhibit increased lipogenesis. We hypothesize that IGF-1 resistance initially causes a transient increase in insulin signaling thereby promoting a lipogenic phenotype, which subsequently leads to insulin resistance. Copyright © 2017. Published by Elsevier Inc.

  11. 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin.

    Science.gov (United States)

    Lund, Kaja; Olsen, Cathrine Elisabeth; Wong, Judith Jing Wen; Olsen, Petter Angell; Solberg, Nina Therese; Høgset, Anders; Krauss, Stefan; Selbo, Pål Kristian

    2017-12-19

    Development of resistance to 5-fluorouracil (5-FU) is a major problem in treatment of various cancers including pancreatic cancer. In this study, we reveal important resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma. 5-FU resistant (5-FUR), epithelial-to-mesenchymal-like sub-clones of the wild type pancreatic cancer cell line Panc03.27 were previously generated in our lab. We investigated the cytotoxic effect of the endosomal/lysosomal-localizing photosensitizer TPCS 2a (fimaporfin) combined with light (photochemical treatment, PCT) using MTS viability assay, and used fluorescence microscopy to show localization of TPCS 2a and to investigate the effect of photodamage of lysosomes. Flow cytometric analysis was performed to investigate uptake of photosensitizer and to assess intracellular ROS levels. Expression and localization of LAMP1 was assessed using RT-qPCR, western blotting, and structured illumination microscopy. MTS viability assay was used to assess the effect of combinations of 5-FU, chloroquine (CQ), and photochemical treatment. Expression of CD105 was investigated using RT-qPCR, western blotting, flow cytometry, and fluorescence microscopy, and co-localization of TPCS 2a and anti-CD105-saporin was assessed using microscopy. Lastly, the MTS assay was used to investigate cytotoxic effects of photochemical internalization (PCI) of the anti-CD105-immunotoxin. The 5-FUR cell lines display hypersensitivity to PCT, which was linked to increased uptake of TPCS 2a , altered lysosomal distribution, lysosomal photodamage and increased expression of the lysosomal marker LAMP-1 in the 5-FUR cells. We show that inhibition of autophagy induced by either chloroquine or lysosomal photodamage increases the sensitivity to 5-FU in the resistant cells. The three 5-FUR sub-clones overexpress Endoglin (CD105). Treatment with the immunotoxin anti-CD105-saporin alone significantly reduced the viability of the CD105

  12. Progranulin haploinsufficiency causes biphasic social dominance abnormalities in the tube test.

    Science.gov (United States)

    Arrant, A E; Filiano, A J; Warmus, B A; Hall, A M; Roberson, E D

    2016-07-01

    Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia (FTD), a neurodegenerative disorder in which social behavior is disrupted. Progranulin-insufficient mice, both Grn(+/-) and Grn(-/-) , are used as models of FTD due to GRN mutations, with Grn(+/-) mice mimicking the progranulin haploinsufficiency of FTD patients with GRN mutations. Grn(+/-) mice have increased social dominance in the tube test at 6 months of age, although this phenotype has not been reported in Grn(-/-) mice. In this study, we investigated how the tube test phenotype of progranulin-insufficient mice changes with age, determined its robustness under several testing conditions, and explored the associated cellular mechanisms. We observed biphasic social dominance abnormalities in Grn(+/-) mice: at 6-8 months, Grn(+/-) mice were more dominant than wild-type littermates, while after 9 months of age, Grn(+/-) mice were less dominant. In contrast, Grn(-/-) mice did not exhibit abnormal social dominance, suggesting that progranulin haploinsufficiency has distinct effects from complete progranulin deficiency. The biphasic tube test phenotype of Grn(+/-) mice was associated with abnormal cellular signaling and neuronal morphology in the amygdala and prefrontal cortex. At 6-9 months, Grn(+/-) mice exhibited increased mTORC2/Akt signaling in the amygdala and enhanced dendritic arbors in the basomedial amygdala, and at 9-16 months Grn(+/-) mice exhibited diminished basal dendritic arbors in the prelimbic cortex. These data show a progressive change in tube test dominance in Grn(+/-) mice and highlight potential underlying mechanisms by which progranulin insufficiency may disrupt social behavior. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  13. Genetic Modifiers of Cardiovascular Phenotype Caused by Elastin Haploinsufficiency Act by Extrinsic Noncomplementation*

    Science.gov (United States)

    Kozel, Beth A.; Knutsen, Russell H.; Ye, Li; Ciliberto, Christopher H.; Broekelmann, Thomas J.; Mecham, Robert P.

    2011-01-01

    Elastin haploinsufficiency causes the cardiovascular complications associated with Williams-Beuren syndrome and isolated supravalvular aortic stenosis. Significant variability exists in the vascular pathology in these individuals. Using the Eln+/− mouse, we sought to identify the source of this variability. Following outcrossing of C57Bl/6J Eln+/−, two backgrounds were identified whose cardiovascular parameters deviated significantly from the parental strain. F1 progeny of the C57Bl/6J; Eln+/−x129X1/SvJ were more hypertensive and their arteries less compliant. In contrast, Eln+/− animals crossed to DBA/2J were protected from the pathologic changes associated with elastin insufficiency. Among the crosses, aortic elastin and collagen content did not correlate with quantitative vasculopathy traits. Quantitative trait locus analysis performed on F2 C57; Eln+/−x129 intercrosses identified highly significant peaks on chromosome 1 (LOD 9.7) for systolic blood pressure and on chromosome 9 (LOD 8.7) for aortic diameter. Additional peaks were identified that affect only Eln+/−, including a region upstream of Eln on chromosome 5 (LOD 4.5). Bioinformatic analysis of the quantitative trait locus peaks revealed several interesting candidates, including Ren1, Ncf1, and Nos1; genes whose functions are unrelated to elastic fiber assembly, but whose effects may synergize with elastin insufficiency to predispose to hypertension and stiffer blood vessels. Real time RT-PCR studies show background-specific increased expression of Ncf1 (a subunit of the NOX2 NAPDH oxidase) that parallel the presence of increased oxidative stress in Eln+/− aortas. This finding raises the possibility that polymorphisms in genes affecting the generation of reactive oxygen species alter cardiovascular function in individuals with elastin haploinsufficiency through extrinsic noncomplementation. PMID:22049077

  14. Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy?

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    Valeria Barresi

    2014-04-01

    Full Text Available Despite ongoing clinical trials, the efficacy of anti-angiogenic drugs for the treatment of brain metastases (BM is still questionable. The lower response rate to anti-angiogenic therapy in the presence of BM than in metastatic disease involving other sites suggests that BM may be insensitive to these drugs, although the biological reasons underlining this phenomenon are still to be clarified. With the aim of assessing whether the targets of anti-angiogenic therapies are actually present in BM, in the present study, we analyzed the microvessel density (MVD, a measure of neo-angiogenesis, and the vascular phenotype (mature vs. immature in the tumor tissue of a series of BM derived from different primary tumors. By using immunohistochemistry against endoglin, a specific marker for newly formed vessels, we found that neo-angiogenesis widely varies in BM depending on the site of the primary tumor, as well as on its histotype. According to our results, BM from lung cancer displayed the highest MVD counts, while those from renal carcinoma had the lowest. Then, among BM from lung cancer, those from large cell and adenocarcinoma histotypes had significantly higher MVD counts than those originating from squamous cell carcinoma (p = 0.0043; p = 0.0063. Of note, MVD counts were inversely correlated with the maturation index of the endoglin-stained vessels, reflected by the coverage of smooth muscle actin (SMA positive pericytes (r = −0.693; p < 0.0001. Accordingly, all the endoglin-positive vessels in BM from pulmonary squamous cell carcinoma and renal carcinoma, displayed a mature phenotype, while vessels with an immature phenotype were found in highly vascularized BM from pulmonary large cell and adenocarcinoma. The low MVD and mature phenotype observed in BM from some primary tumors may account for their low sensitivity to anti-angiogenic therapies. Although our findings need to be validated in correlative studies with a clinical response, this should

  15. Mice haploinsufficient for Map2k7, a gene involved in neurodevelopment and risk for schizophrenia, show impaired attention, a vigilance decrement deficit and unstable cognitive processing in an attentional task: impact of minocycline.

    Science.gov (United States)

    Openshaw, R L; Thomson, D M; Penninger, J M; Pratt, J A; Morris, B J

    2017-01-01

    Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear. In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment. Attentional function in mice haploinsufficient for Map2k7 (Map2k7 +/- mice) was investigated using the five-choice serial reaction time task (5-CSRTT). Once stable performance had been achieved, Map2k7 +/- mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline-a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia-signs of improvement in attentional performance were detected. Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline.

  16. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition

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    Lesley Hart

    2014-05-01

    Full Text Available Wolf-Hirschhorn syndrome (WHS represents an archetypical example of a contiguous gene deletion disorder – a condition comprising a complex set of developmental phenotypes with a multigenic origin. Epileptic seizures, intellectual disability, growth restriction, motor delay and hypotonia are major co-morbidities in WHS. Haploinsufficiency of LETM1, which encodes a mitochondrial inner-membrane protein functioning in ion transport, has been proposed as an underlying pathomechanism, principally for seizures but also for other core features of WHS, including growth and motor delay. Growing evidence derived from several model organisms suggests that reduced LETM1 expression is associated with some element of mitochondrial dysfunction. Surprisingly, LETM1-dependent mitochondrial functional deficits have not previously been described in cells from individuals with WHS. Here, using a unique panel of WHS-patient-derived cell lines with deletions of differing sizes, incorporating LETM1 or not, we show, for the first time, that LETM1 expression is reduced in mitochondria isolated from WHS-patient cells. Furthermore, we show that this is associated with distinct mitochondrial phenotypes, including altered intracellular [Ca2+] levels, dysfunctional mitochondrial transition-pore opening, hyperpolarization and superoxide leakage from resting mitochondria. Interestingly, we find that these phenotypes segregate with seizures in our WHS cohort. Our findings identify novel cellular phenotypes in WHS attributable to a 50% reduction in LETM1 expression level; these phenotypes could underlie and/or contribute to some of the core clinical features of this condition.

  17. LETM1 haploinsufficiency causes mitochondrial defects in cells from humans with Wolf-Hirschhorn syndrome: implications for dissecting the underlying pathomechanisms in this condition.

    Science.gov (United States)

    Hart, Lesley; Rauch, Anita; Carr, Antony M; Vermeesch, Joris R; O'Driscoll, Mark

    2014-05-01

    Wolf-Hirschhorn syndrome (WHS) represents an archetypical example of a contiguous gene deletion disorder - a condition comprising a complex set of developmental phenotypes with a multigenic origin. Epileptic seizures, intellectual disability, growth restriction, motor delay and hypotonia are major co-morbidities in WHS. Haploinsufficiency of LETM1, which encodes a mitochondrial inner-membrane protein functioning in ion transport, has been proposed as an underlying pathomechanism, principally for seizures but also for other core features of WHS, including growth and motor delay. Growing evidence derived from several model organisms suggests that reduced LETM1 expression is associated with some element of mitochondrial dysfunction. Surprisingly, LETM1-dependent mitochondrial functional deficits have not previously been described in cells from individuals with WHS. Here, using a unique panel of WHS-patient-derived cell lines with deletions of differing sizes, incorporating LETM1 or not, we show, for the first time, that LETM1 expression is reduced in mitochondria isolated from WHS-patient cells. Furthermore, we show that this is associated with distinct mitochondrial phenotypes, including altered intracellular [Ca(2+)] levels, dysfunctional mitochondrial transition-pore opening, hyperpolarization and superoxide leakage from resting mitochondria. Interestingly, we find that these phenotypes segregate with seizures in our WHS cohort. Our findings identify novel cellular phenotypes in WHS attributable to a 50% reduction in LETM1 expression level; these phenotypes could underlie and/or contribute to some of the core clinical features of this condition.

  18. Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly.

    Science.gov (United States)

    Lines, Matthew A; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L; Lynch, Danielle C; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W; Lohmann, Dietmar R; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E; Wieczorek, Dagmar; Boycott, Kym M

    2012-02-10

    Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  19. Characterizing haploinsufficiency of SHELL gene to improve fruit form prediction in introgressive hybrids of oil palm.

    Science.gov (United States)

    Teh, Chee-Keng; Muaz, Siti Dalila; Tangaya, Praveena; Fong, Po-Yee; Ong, Ai-Ling; Mayes, Sean; Chew, Fook-Tim; Kulaveerasingam, Harikrishna; Appleton, David

    2017-06-08

    The fundamental trait in selective breeding of oil palm (Eleais guineensis Jacq.) is the shell thickness surrounding the kernel. The monogenic shell thickness is inversely correlated to mesocarp thickness, where the crude palm oil accumulates. Commercial thin-shelled tenera derived from thick-shelled dura × shell-less pisifera generally contain 30% higher oil per bunch. Two mutations, sh MPOB (M1) and sh AVROS (M2) in the SHELL gene - a type II MADS-box transcription factor mainly present in AVROS and Nigerian origins, were reported to be responsible for different fruit forms. In this study, we have tested 1,339 samples maintained in Sime Darby Plantation using both mutations. Five genotype-phenotype discrepancies and eight controls were then re-tested with all five reported mutations (sh AVROS , sh MPOB , sh MPOB2 , sh MPOB3 and sh MPOB4 ) within the same gene. The integration of genotypic data, pedigree records and shell formation model further explained the haploinsufficiency effect on the SHELL gene with different number of functional copies. Some rare mutations were also identified, suggesting a need to further confirm the existence of cis-compound mutations in the gene. With this, the prediction accuracy of fruit forms can be further improved, especially in introgressive hybrids of oil palm. Understanding causative variant segregation is extremely important, even for monogenic traits such as shell thickness in oil palm.

  20. Dkk1 haploinsufficiency requires expression of Bmp2 for bone anabolic activity

    Science.gov (United States)

    Intini, Giuseppe; Nyman, Jeffry S.

    2015-01-01

    Bone fractures remain a serious health burden and prevention and enhanced healing of fractures has been obtained by augmenting either BMP or Wnt signaling. However, whether BMP and Wnt signaling are both required or are self-sufficient for anabolic and fracture healing activities has never been fully elucidated. Mice haploinsufficient for Dkk1 (Dkk1+/−) exhibit a high bone mass phenotype due to an up-regulation of canonical Wnt signaling while mice lacking Bmp2 expression in the limbs (Bmp2c/c;Prx1::cre) succumb to spontaneous fracture and are unable to initiate fracture healing; combined, these mice offer an opportunity to examine the requirement for activated BMP signaling on the anabolic and fracture healing activity of Wnts. When Dkk1+/− mice were crossed with Bmp2c/c;Prx1::cre mice, the offspring bearing both genetic alterations were unable to increase bone mass and heal fractures, indicating that increased canonical Wnt signaling is unable to exploit its activity in absence of Bmp2. Thus, our data suggest that BMP signaling is required for Wnt-mediated anabolic activity and that therapies aimed at preventing fractures and fostering fracture repair may need to target both pathways for maximal efficacy. PMID:25603465

  1. Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background

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    Sara N. Koenig

    2015-03-01

    Full Text Available Thoracic aortic aneurysms (TAA are a significant cause of morbidity and mortality in humans. While the exact etiology is unknown, genetic factors play an important role. Mutations in NOTCH1 have been linked to bicuspid aortic valve (BAV and aortopathy in humans. The aim of this study was to determine if haploinsufficiency of Notch1 contributes to aortopathy using Notch1+/−; Nos3−/− mice. Echocardiographic analysis of Notch1+/−; Nos3−/− mice reveals effacement of the sinotubular junction and a trend toward dilation of the aortic sinus. Furthermore, examination of the proximal aorta of Notch1+/−; Nos3−/− mice reveals elastic fiber degradation, a trend toward increased matrix metalloproteinase 2 expression, and increased smooth muscle cell apoptosis, features characteristic of aneurysmal disease. Although at a lower penetrance, we also found features consistent with aortopathic changes in Notch1 heterozygote mice and in Nos3-null mice. Our findings implicate a novel role for Notch1 in aortopathy of the proximal aorta.

  2. Identification of Genes in Saccharomyces cerevisiae that Are Haploinsufficient for Overcoming Amino Acid Starvation

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    Nancy S. Bae

    2017-04-01

    Full Text Available The yeast Saccharomyces cerevisiae responds to amino acid deprivation by activating a pathway conserved in eukaryotes to overcome the starvation stress. We have screened the entire yeast heterozygous deletion collection to identify strains haploinsufficient for growth in the presence of sulfometuron methyl, which causes starvation for isoleucine and valine. We have discovered that cells devoid of MET15 are sensitive to sulfometuron methyl, and loss of heterozygosity at the MET15 locus can complicate screening the heterozygous deletion collection. We identified 138 cases of loss of heterozygosity in this screen. After eliminating the issues of the MET15 loss of heterozygosity, strains isolated from the collection were retested on sulfometuron methyl. To determine the general effect of the mutations for a starvation response, SMM-sensitive strains were tested for the ability to grow in the presence of canavanine, which induces arginine starvation, and strains that were MET15 were also tested for growth in the presence of ethionine, which causes methionine starvation. Many of the genes identified in our study were not previously identified as starvation-responsive genes, including a number of essential genes that are not easily screened in a systematic way. The genes identified span a broad range of biological functions, including many involved in some level of gene expression. Several unnamed proteins have also been identified, giving a clue as to possible functions of the encoded proteins.

  3. SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans.

    Science.gov (United States)

    Guan, Jing; Wang, Dayong; Cao, Wenjian; Zhao, Yali; Du, Renqian; Yuan, Hu; Liu, Qiong; Lan, Lan; Zong, Liang; Yang, Ju; Yin, Zifang; Han, Bing; Zhang, Feng; Wang, Qiuju

    2016-11-01

    The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environmental causes. However, the genetic basis for the risk of congenital ossicle malformation is poorly understood. We show here nine affected individuals in a Chinese pedigree who had bilateral conductive hearing loss with ptosis. We performed whole-genome sequencing and array comparative genomic hybridization (CGH) analysis on DNA samples from the Chinese pedigree. We confirmed the presence of a novel 60 kb heterozygous deletion in size, encompassing SIX2 in our family. Mutation screening in 169 sporadic cases with external ear and middle ear malformations identified no pathogenic variant or polymorphism. We suggest SIX2 haploinsufficiency as a potential congenital factor could be attributed to developmental malformation of the middle ear ossicles and upper eyelid. To the best of our knowledge, this is the first report to provide a description of copy number variation in the SIX2 gene resulting in syndromic conductive hearing loss.

  4. Brain size regulations by cbp haploinsufficiency evaluated by in-vivo MRI based volumetry

    Science.gov (United States)

    Ateca-Cabarga, Juan C.; Cosa, Alejandro; Pallarés, Vicente; López-Atalaya, José P.; Barco, Ángel; Canals, Santiago; Moratal, David

    2015-11-01

    The Rubinstein-Taybi Syndrome (RSTS) is a congenital disease that affects brain development causing severe cognitive deficits. In most cases the disease is associated with dominant mutations in the gene encoding the CREB binding protein (CBP). In this work, we present the first quantitative analysis of brain abnormalities in a mouse model of RSTS using magnetic resonance imaging (MRI) and two novel self-developed automated algorithms for image volumetric analysis. Our results quantitatively confirm key syndromic features observed in RSTS patients, such as reductions in brain size (-16.31%, p < 0.05), white matter volume (-16.00%, p < 0.05), and corpus callosum (-12.40%, p < 0.05). Furthermore, they provide new insight into the developmental origin of the disease. By comparing brain tissues in a region by region basis between cbp+/- and cbp+/+ littermates, we found that cbp haploinsufficiency is specifically associated with significant reductions in prosencephalic tissue, such us in the olfactory bulb and neocortex, whereas regions evolved from the embryonic rhombencephalon were spared. Despite the large volume reductions, the proportion between gray-, white-matter and cerebrospinal fluid were conserved, suggesting a role of CBP in brain size regulation. The commonalities with holoprosencephaly and arhinencephaly conditions suggest the inclusion of RSTS in the family of neuronal migration disorders.

  5. Haploinsufficiency of MeCP2-interacting transcriptional co-repressor SIN3A causes mild intellectual disability by affecting the development of cortical integrity.

    Science.gov (United States)

    Witteveen, Josefine S; Willemsen, Marjolein H; Dombroski, Thaís C D; van Bakel, Nick H M; Nillesen, Willy M; van Hulten, Josephus A; Jansen, Eric J R; Verkaik, Dave; Veenstra-Knol, Hermine E; van Ravenswaaij-Arts, Conny M A; Wassink-Ruiter, Jolien S Klein; Vincent, Marie; David, Albert; Le Caignec, Cedric; Schieving, Jolanda; Gilissen, Christian; Foulds, Nicola; Rump, Patrick; Strom, Tim; Cremer, Kirsten; Zink, Alexander M; Engels, Hartmut; de Munnik, Sonja A; Visser, Jasper E; Brunner, Han G; Martens, Gerard J M; Pfundt, Rolph; Kleefstra, Tjitske; Kolk, Sharon M

    2016-08-01

    Numerous genes are associated with neurodevelopmental disorders such as intellectual disability and autism spectrum disorder (ASD), but their dysfunction is often poorly characterized. Here we identified dominant mutations in the gene encoding the transcriptional repressor and MeCP2 interactor switch-insensitive 3 family member A (SIN3A; chromosome 15q24.2) in individuals who, in addition to mild intellectual disability and ASD, share striking features, including facial dysmorphisms, microcephaly and short stature. This phenotype is highly related to that of individuals with atypical 15q24 microdeletions, linking SIN3A to this microdeletion syndrome. Brain magnetic resonance imaging showed subtle abnormalities, including corpus callosum hypoplasia and ventriculomegaly. Intriguingly, in vivo functional knockdown of Sin3a led to reduced cortical neurogenesis, altered neuronal identity and aberrant corticocortical projections in the developing mouse brain. Together, our data establish that haploinsufficiency of SIN3A is associated with mild syndromic intellectual disability and that SIN3A can be considered to be a key transcriptional regulator of cortical brain development.

  6. Haploinsufficiency of the Sec7 guanine nucleotide exchange factor gea1 impairs septation in fission yeast.

    Directory of Open Access Journals (Sweden)

    Alan M Eckler

    Full Text Available Membrane trafficking is essential to eukaryotic life and is controlled by a complex network of proteins that regulate movement of proteins and lipids between organelles. The GBF1/GEA family of Guanine nucleotide Exchange Factors (GEFs regulates trafficking between the endoplasmic reticulum and Golgi by catalyzing the exchange of GDP for GTP on ADP Ribosylation Factors (Arfs. Activated Arfs recruit coat protein complex 1 (COP-I to form vesicles that ferry cargo between these organelles. To further explore the function of the GBF1/GEA family, we have characterized a fission yeast mutant lacking one copy of the essential gene gea1 (gea1+/-, the Schizosaccharomyces pombe ortholog of GBF1. The haploinsufficient gea1+/- strain was shown to be sensitive to the GBF1 inhibitor brefeldin A (BFA and was rescued from BFA sensitivity by gea1p overexpression. No overt defects in localization of arf1p or arf6p were observed in gea1+/- cells, but the fission yeast homolog of the COP-I cargo sac1 was mislocalized, consistent with impaired COP-I trafficking. Although Golgi morphology appeared normal, a slight increase in vacuolar size was observed in the gea1+/- mutant strain. Importantly, gea1+/- cells exhibited dramatic cytokinesis-related defects, including disorganized contractile rings, an increased septation index, and alterations in septum morphology. Septation defects appear to result from altered secretion of enzymes required for septum dynamics, as decreased secretion of eng1p, a β-glucanase required for septum breakdown, was observed in gea1+/- cells, and overexpression of eng1p suppressed the increased septation phenotype. These observations implicate gea1 in regulation of septum breakdown and establish S. pombe as a model system to explore GBF1/GEA function in cytokinesis.

  7. The contribution of CLIP2 haploinsufficiency to the clinical manifestations of the Williams-Beuren syndrome.

    Science.gov (United States)

    Vandeweyer, Geert; Van der Aa, Nathalie; Reyniers, Edwin; Kooy, R Frank

    2012-06-08

    Williams-Beuren syndrome is a rare contiguous gene syndrome, characterized by intellectual disability, facial dysmorphisms, connective-tissue abnormalities, cardiac defects, structural brain abnormalities, and transient infantile hypercalcemia. Genes lying telomeric to RFC2, including CLIP2, GTF2I and GTF2IRD1, are currently thought to be the most likely major contributors to the typical Williams syndrome cognitive profile, characterized by a better-than-expected auditory rote-memory ability, a relative sparing of language capabilities, and a severe visual-spatial constructive impairment. Atypical deletions in the region have helped to establish genotype-phenotype correlations. So far, however, hardly any deletions affecting only a single gene in the disease region have been described. We present here two healthy siblings with a pure, hemizygous deletion of CLIP2. A putative role in the cognitive and behavioral abnormalities seen in Williams-Beuren patients has been suggested for this gene on the basis of observations in a knock-out mouse model. The presented siblings did not show any of the clinical features associated with the syndrome. Cognitive testing showed an average IQ for both and no indication of the Williams syndrome cognitive profile. This shows that CLIP2 haploinsufficiency by itself does not lead to the physical or cognitive characteristics of the Williams-Beuren syndrome, nor does it lead to the Williams syndrome cognitive profile. Although contribution of CLIP2 to the phenotype cannot be excluded when it is deleted in combination with other genes, our results support the hypothesis that GTF2IRD1 and GTF2I are the main genes causing the cognitive defects associated with Williams-Beuren syndrome. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  8. 1p13.2 deletion displays clinical features overlapping Noonan syndrome, likely related to NRAS gene haploinsufficiency

    Directory of Open Access Journals (Sweden)

    Natália Duarte Linhares

    Full Text Available Abstract Deletion-induced hemizygosity may unmask deleterious autosomal recessive variants and be a cause of the phenotypic variability observed in microdeletion syndromes. We performed complete exome sequencing (WES analysis to examine this possibility in a patient with 1p13.2 microdeletion. Since the patient displayed clinical features suggestive of Noonan Syndrome (NS, we also used WES to rule out the presence of pathogenic variants in any of the genes associated with the different types of NS. We concluded that the clinical findings could be attributed solely to the 1p13.2 haploinsufficiency. Retrospective analysis of other nine reported patients with 1p13.2 microdeletions showed that six of them also presented some characteristics of NS. In all these cases, the deleted segment included the NRAS gene. Gain-of-function mutations of NRAS gene are causally related to NS type 6. Thus, it is conceivable that NRAS haploinsufficiency and gain-of-function mutations may have similar clinical consequences. The same phenomenon has been described for two other genes belonging to the Ras/MAPK pathway: MAP2K2 and SHOC2. In conclusion, we here report genotype-phenotype correlations in patients with chromosome 1p13.2 microdeletions and we propose that NRAS may be a critical gene for the NS characteristics in the patients.

  9. MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways

    Science.gov (United States)

    Paciorkowski, Alex R.; Traylor, Ryan N.; Rosenfeld, Jill A.; Hoover, Jacqueline M.; Harris, Catharine J.; Winter, Susan; Lacassie, Yves; Bialer, Martin; Lamb, Allen N.; Schultz, Roger A.; Berry-Kravis, Elizabeth; Porter, Brenda E.; Falk, Marni; Venkat, Anu; Vanzo, Rena J.; Cohen, Julie S.; Fatemi, Ali; Dobyns, William B.; Shaffer, Lisa G.; Ballif, Blake C.; Marsh, Eric D.

    2013-01-01

    MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. We report 16 new patients with MEF2C haploinsufficiency, including the oldest reported patient with MEF2C deletion at 5q14.3. We detail the neurobehavioral phenotype, epilepsy, and abnormal movements, and compare our subjects with those previously reported in the literature. We also investigate Mef2c expression in the developing mouse forebrain. A spectrum of neurofunctional deficits emerges, with hyperkinesis a consistent finding. Epilepsy varied from absent to severe, and included intractable myoclonic seizures and infantile spasms. Subjects with partial MEF2C deletion were statistically less likely to have epilepsy. Finally, we confirm that Mef2c is present both in dorsal primary neuroblasts and ventral gamma-aminobutyric acid(GABA)ergic interneurons in the forebrain of the developing mouse. Given interactions with several key neurodevelopmental genes such as ARX, FMR1, MECP2, and TBR1, it appears that MEF2C plays a role in several developmental stages of both dorsal and ventral neuronal cell types. PMID:23389741

  10. MTH1 and RGT1 demonstrate combined haploinsufficiency in regulation of the hexose transporter genes in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Dietzel Kevin L

    2012-12-01

    Full Text Available Abstract Background The SNF3 gene in the yeast Saccharomyces cerevisiae encodes a low glucose sensor that regulates expression of an important subset of the hexose transporter (HXT superfamily. Null mutations of snf3 result in a defect in growth on low glucose concentrations due to the inability to relieve repression of a subset of the HXT genes. The snf3 null mutation phenotype is suppressed by the loss of either one of the downstream co-repressor proteins Rgt1p or Mth1p. The relief of repression allows expression of HXT transporter proteins, the resumption of glucose uptake and therefore of growth in the absence of a functional Snf3 sensor. Results Strains heterozygous for both the RGT1 and MTH1 genes (RGT1/rgt1Δ MTH1/mth1Δ snf3Δ/snf3Δ but homozygous for the snf3∆ were found to grow on low glucose. Since null alleles in the heterozygous state lead to suppression, MTH1 and RGT1 display the phenomenon of combined haploinsufficiency. This observed haploinsufficiency is consistent with the finding of repressor titration as a mechanism of suppression of snf3. Mutants of the STD1 homolog of MTH1 did not display haploinsufficiency singly or in combination with mutations in RGT1. HXT gene reporter fusion assays indicated that the presence of heterozygosity at the MTH1 and RGT1 alleles leads to increased expression of the HXT2 gene. Deletion of the HXT2 gene in a heterozygous diploid, RGT1/rgt1Δ MTH1/mth1Δ snf3Δ/snf3Δ hxt2Δ/hxt2Δ, prevented the suppression of snf3Δ. Conclusions These findings support the model of relief of repression as the mechanism of restoration of growth on low glucose concentrations in the absence of functional Snf3p. Further, the observation that HXT2 is the gene responsible for restoration of growth under these conditions suggests that the numbers of repressor binding domains found in the regulatory regions of members of the HXT family may have biological relevance and enable differential regulation.

  11. Toxicology and carcinogenesis study of senna in C3B6.129F1-Trp53 tm1Brd N12 haploinsufficient mice.

    Science.gov (United States)

    Surh, Inok; Brix, Amy; French, John E; Collins, Bradley J; Sanders, J Michael; Vallant, Molly; Dunnick, June K

    2013-07-01

    Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes reduce sennosides to rhein-9-anthrone, the active form for the laxative effect. To determine the potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53 (tm1Brd) N12 haploinsufficient (p53(+/-)) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed to up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53(+/-) mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53(+/-) males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53(+/-) mouse model. There was no neoplastic change when senna was administered to p53(+/-) mouse.

  12. Transforming growth factor-β1 and its receptor soluble endoglin are altered in polycystic ovary syndrome during controlled ovarian stimulation.

    Science.gov (United States)

    Tal, Reshef; Seifer, David B; Shohat-Tal, Aya; Grazi, Richard V; Malter, Henry E

    2013-08-01

    To evaluate the relationship between transforming growth factor (TGF)-β1 and its receptor, soluble endoglin (sENG), in the serum and follicular fluid of women with polycystic ovarian syndrome (PCOS) compared with that of non-PCOS normal ovulating women during controlled ovarian stimulation (COS). Prospective case-control study. Academic-affiliated assisted reproductive technology unit. Fourteen PCOS and 14 matched non-PCOS control women undergoing COS. Serum was collected on day 3 (baseline), day of hCG, and day of retrieval. Follicular fluid (FF) was collected on day of oocyte retrieval. ELISA was performed to determine TGF-β1 and sENG protein levels. Serum and FF levels of TGF-β1 and sENG. Serum TGF-β1 did not change significantly during COS but was increased in PCOS compared with non-PCOS women on day 3 and days of hCG administration and oocyte retrieval. Serum sENG increased after hCG administration only in the non-PCOS control group. In addition, serum sENG was decreased in PCOS compared with non-PCOS control women on the days of hCG and retrieval. Accordingly, the bioavailability of TGF-β1 (TGF-β1/sENG ratio) was increased in women with PCOS compared with non-PCOS controls at all three time points. No differences in either factor were noted in FF between groups. The increased TGF-β1 bioavailability in PCOS is not only due to increased TGF-β1 levels but also to decreased levels of its receptor, sENG. These data suggest that increased TGF-β1 bioavailability may contribute to the pathogenesis of PCOS and its increased risk for ovarian hyperstimulation. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Heterozygous Lmna(delK32) mice develop dilated cardiomyopathy through a combined pathomechanism of haploinsufficiency and peptide toxicity

    DEFF Research Database (Denmark)

    Cattin, M. E.; Bertrand, A. T.; Schlossarek, S.

    2013-01-01

    itself has a clear deleterious effect on engineered heart tissues force of contraction, it also leads to the nuclear aggregation of viral-mediated expression of K32-lamin. In conclusion, Het mice are the first knock-in Lmna model with cardiac-specific phenotype at the heterozygous state. Altogether, our....... The pathomechanisms linking mutations to DCM remain to be elucidated. We investigated the phenotype and associated pathomechanisms of heterozygous Lmna(K32/) (Het) knock-in mice, which carry a human mutation. Het mice developed a cardiac-specific phenotype. Two phases, with two different pathomechanisms, could...... be observed that lead to the development of cardiac dysfunction, DCM and death between 35 and 70 weeks of age. In young Het hearts, there was a clear reduction in lamin A/C level, mainly due to the degradation of toxic K32-lamin. As a side effect, lamin A/C haploinsufficiency probably triggers the cardiac...

  14. Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia.

    Science.gov (United States)

    Holler, Christopher J; Taylor, Georgia; McEachin, Zachary T; Deng, Qiudong; Watkins, William J; Hudson, Kathryn; Easley, Charles A; Hu, William T; Hales, Chadwick M; Rossoll, Wilfried; Bassell, Gary J; Kukar, Thomas

    2016-06-24

    Progranulin (PGRN) is a secreted growth factor important for neuronal survival and may do so, in part, by regulating lysosome homeostasis. Mutations in the PGRN gene (GRN) are a common cause of frontotemporal lobar degeneration (FTLD) and lead to disease through PGRN haploinsufficiency. Additionally, complete loss of PGRN in humans leads to neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Importantly, Grn-/- mouse models recapitulate pathogenic lysosomal features of NCL. Further, GRN variants that decrease PGRN expression increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Together these findings demonstrate that insufficient PGRN predisposes neurons to degeneration. Therefore, compounds that increase PGRN levels are potential therapeutics for multiple neurodegenerative diseases. Here, we performed a cell-based screen of a library of known autophagy-lysosome modulators and identified multiple novel activators of a human GRN promoter reporter including several common mTOR inhibitors and an mTOR-independent activator of autophagy, trehalose. Secondary cellular screens identified trehalose, a natural disaccharide, as the most promising lead compound because it increased endogenous PGRN in all cell lines tested and has multiple reported neuroprotective properties. Trehalose dose-dependently increased GRN mRNA as well as intracellular and secreted PGRN in both mouse and human cell lines and this effect was independent of the transcription factor EB (TFEB). Moreover, trehalose rescued PGRN deficiency in human fibroblasts and neurons derived from induced pluripotent stem cells (iPSCs) generated from GRN mutation carriers. Finally, oral administration of trehalose to Grn haploinsufficient mice significantly increased PGRN expression in the brain. This work reports several novel autophagy-lysosome modulators that enhance PGRN expression and identifies trehalose as a promising therapeutic for raising PGRN levels to treat

  15. Haploinsufficiency of the insulin-like growth factor-1 receptor enhances endothelial repair and favorably modifies angiogenic progenitor cell phenotype.

    Science.gov (United States)

    Yuldasheva, Nadira Y; Rashid, Sheikh Tawqeer; Haywood, Natalie J; Cordell, Paul; Mughal, Romana; Viswambharan, Hema; Imrie, Helen; Sukumar, Piruthivi; Cubbon, Richard M; Aziz, Amir; Gage, Matthew; Mbonye, Kamatamu Amanda; Smith, Jessica; Galloway, Stacey; Skromna, Anna; Scott, D Julian A; Kearney, Mark T; Wheatcroft, Stephen B

    2014-09-01

    Defective endothelial regeneration predisposes to adverse arterial remodeling and is thought to contribute to cardiovascular disease in type 2 diabetes mellitus. We recently demonstrated that the type 1 insulin-like growth factor receptor (IGF1R) is a negative regulator of insulin sensitivity and nitric oxide bioavailability. In this report, we examined partial deletion of the IGF1R as a potential strategy to enhance endothelial repair. We assessed endothelial regeneration after wire injury in mice and abundance and function of angiogenic progenitor cells in mice with haploinsufficiency of the IGF1R (IGF1R(+/-)). Endothelial regeneration after arterial injury was accelerated in IGF1R(+/-) mice. Although the yield of angiogenic progenitor cells was lower in IGF1R(+/-) mice, these angiogenic progenitor cells displayed enhanced adhesion, increased secretion of insulin-like growth factor-1, and enhanced angiogenic capacity. To examine the relevance of IGF1R manipulation to cell-based therapy, we transfused IGF1R(+/-) bone marrow-derived CD117(+) cells into wild-type mice. IGF1R(+/-) cells accelerated endothelial regeneration after arterial injury compared with wild-type cells and did not alter atherosclerotic lesion formation. Haploinsufficiency of the IGF1R is associated with accelerated endothelial regeneration in vivo and enhanced tube forming and adhesive potential of angiogenic progenitor cells in vitro. Partial deletion of IGF1R in transfused bone marrow-derived CD117(+) cells enhanced their capacity to promote endothelial regeneration without altering atherosclerosis. Our data suggest that manipulation of the IGF1R could be exploited as novel therapeutic approach to enhance repair of the arterial wall after injury. © 2014 American Heart Association, Inc.

  16. Biodistribution of 125I-labeled anti-endoglin antibody using SPECT/CT imaging: Impact of in vivo deiodination on tumor accumulation in mice

    International Nuclear Information System (INIS)

    Karmani, Linda; Levêque, Philippe; Bouzin, Caroline; Bol, Anne; Dieu, Marc; Walrand, Stephan; Vander Borght, Thierry; Feron, Olivier; Grégoire, Vincent; Bonifazi, Davide

    2016-01-01

    Introduction: Radiolabeled antibodies directed against endoglin (CD105) are promising tools for imaging and antiangiogenic cancer therapy. To validate iodinated antibodies as reliable tracers, we investigated the influence of the radiolabeling method (direct or indirect) on their in vivo stability. Methods: Anti-CD105 mAbs were radioiodinated directly using chloramine-T ( 125 I-anti-CD105-mAbs) or indirectly using D-KRYRR peptide as a linker ( 125 I-KRYRR-anti-CD105-mAbs). The biodistribution was studied in B16 tumor-bearing mice via SPECT/CT imaging. Results: Radioiodinated mAbs were stable in vitro. In vivo, thyroid showed the most important increase of uptake after 24 h for 125 I-anti-CD105-mAbs (91.9 ± 4.0%ID/ml) versus 125 I-KRYRR-anti-CD105-mAbs (4.4 ± 0.6%ID/ml). Tumor uptake of 125 I-anti-CD105-mAbs (0.9 ± 0.3%ID/ml) was significantly lower than that of 125 I-KRYRR-anti-CD105-mAbs (4.7 ± 0.2%ID/ml). Conclusions: An accurate characterization of the in vivo stability of radioiodinated mAbs and the choice of an appropriate method for the radioiodination are required, especially for novel targets. The indirect radioiodination of internalizing anti-CD105 mAbs leads to more stable tracer by decreasing in vivo deiodination and improves the tumor retention of radioiodinated mAbs. Advances in knowledge and implications for patient care: To date, the only antiangiogenic antibody approved for clinical indications is bevacizumab. There is a need to develop more antibodies that have targets highly expressed on tumor endothelium. CD105 represents a promising marker of angiogenesis, but its therapeutic relevance in cancer needs to be further investigated. In this context, this study suggests the potential use of indirectly iodinated anti-CD105 mAbs for tumor imaging and for therapeutic purposes.

  17. Maternal circulating levels of activin A, inhibin A, sFlt-1 and endoglin at parturition in normal pregnancy and pre-eclampsia.

    Directory of Open Access Journals (Sweden)

    Aparna Reddy

    Full Text Available Maternal circulating levels of anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1, endoglin (sEng and placental proteins like activin A and inhibin A are increased before the onset of pre-eclampsia. There is evidence for oxidative stress in pre eclampsia. Recently it was shown that placental oxygen concentration is related to sFlt-1 and inhibin A. In addition it is reported that oxidative stress markers are increased in placental tissue delivered after labour. Therefore, the objective of this study is to investigate if these proteins are altered in maternal circulation of labouring pre-eclampsia and normal pregnancies.To assess the effects of labour, samples were taken from 10 normal pregnant (NP and 10 pre-eclamptic (PE women pre-labour, full dilation, placental delivery and 24 h. To assess the effects of placental delivery, plasma samples were taken from 10NP and 10PE women undergoing elective Caesarean section, pre-delivery, placental delivery and 10 min, 60 min and 24 h post delivery. SFlt-1 and sEng and activin A and inhibin A were measured using commercial and in house ELISA's respectively.The levels of sFlt-1 and sEng were significantly higher in PE compared to NP women in both groups. In labour, sFlt-1 levels increased significantly at full dilatation in PE women, before declining by 24 hr. However there was no significant rise in sEng levels in labour. Activin A and inhibin A levels declined rapidly with placental delivery in NP and PE pregnancies. There was a significant rise in activin A levels during labour in PE compared to pre labour, but inhibin levels did not increase.Labour in pre-eclamptic women increases the levels of sFlt-1 and activin A. This pilot data suggests that increase in the maternal levels of these factors in labour could predict and/or contribute to the maternal syndrome postpartum.

  18. Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo.

    Science.gov (United States)

    Ingram, D A; Yang, F C; Travers, J B; Wenning, M J; Hiatt, K; New, S; Hood, A; Shannon, K; Williams, D A; Clapp, D W

    2000-01-03

    Neurofibromatosis type 1 (NF1) is a common autosomal-dominant disorder characterized by cutaneous neurofibromas infiltrated with large numbers of mast cells, melanocyte hyperplasia, and a predisposition to develop malignant neoplasms. NF1 encodes a GTPase activating protein (GAP) for Ras. Consistent with Knudson's "two hit" model of tumor suppressor genes, leukemias and malignant solid tumors in NF1 patients frequently demonstrate somatic loss of the normal NF1 allele. However, the phenotypic and biochemical consequences of heterozygous inactivation of Nf1 are largely unknown. Recently neurofibromin, the protein encoded by NF1, was shown to negatively regulate Ras activity in Nf1-/- murine myeloid hematopoietic cells in vitro through the c-kit receptor tyrosine kinase (dominant white spotting, W). Since the W and Nf1 locus appear to function along a common developmental pathway, we generated mice with mutations at both loci to examine potential interactions in vivo. Here, we show that haploinsufficiency at Nf1 perturbs cell fates in mast cells in vivo, and partially rescues coat color and mast cell defects in W(41) mice. Haploinsufficiency at Nf1 also increased mast cell proliferation, survival, and colony formation in response to Steel factor, the ligand for c-kit. Furthermore, haploinsufficiency was associated with enhanced Ras-mitogen-activated protein kinase activity, a major downstream effector of Ras, via wild-type and mutant (W(41)) c-kit receptors. These observations identify a novel interaction between c-kit and neurofibromin in vivo, and offer experimental evidence that haploinsufficiency of Nf1 alters both cellular and biochemical phenotypes in two cell lineages that are affected in individuals with NF1. Collectively, these data support the emerging concept that heterozygous inactivation of tumor suppressor genes may have profound biological effects in multiple cell types.

  19. Human NF-κB1 Haploinsufficiency and Epstein-Barr Virus-Induced Disease-Molecular Mechanisms and Consequences.

    Science.gov (United States)

    Hoeger, Birgit; Serwas, Nina Kathrin; Boztug, Kaan

    2017-01-01

    Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (NF-κB1)-related human primary immune deficiencies have initially been characterized as defining a subgroup of common variable immunodeficiencies (CVIDs), representing intrinsic B-cell disorders with antibody deficiency and recurrent infections of various kind. Recent evidence indicates that NF-κB1 haploinsufficiency underlies a variable type of combined immunodeficiency (CID) affecting both B and T lymphocyte compartments, with a broadened spectrum of disease manifestations, including Epstein-Barr virus (EBV)-induced lymphoproliferative disease and immediate life-threatening consequences. As part of this review series focused on EBV-related primary immunodeficiencies, we discuss the current clinical and molecular understanding of monoallelic NFKB1 germline mutations with special focus on the emerging context of EBV-associated disease. We outline mechanistic implications of dysfunctional NF-κB1 in B and T cells and discuss the fatal relation of impaired T-cell function with the inability to clear EBV infections. Finally, we compare common and suggested treatment angles in the context of this complex disease.

  20. CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease by haploinsufficiency.

    Science.gov (United States)

    Brockmann, Sarah J; Freischmidt, Axel; Oeckl, Patrick; Müller, Kathrin; Ponna, Srinivas K; Helferich, Anika M; Paone, Christoph; Reinders, Jörg; Kojer, Kerstin; Orth, Michael; Jokela, Manu; Auranen, Mari; Udd, Bjarne; Hermann, Andreas; Danzer, Karin M; Lichtner, Peter; Walther, Paul; Ludolph, Albert C; Andersen, Peter M; Otto, Markus; Kursula, Petri; Just, Steffen; Weishaupt, Jochen H

    2018-02-15

    Mutations in the mitochondrially located protein CHCHD10 cause motoneuron disease by an unknown mechanism. In this study, we investigate the mutations p.R15L and p.G66V in comparison to wild-type CHCHD10 and the non-pathogenic variant p.P34S in vitro, in patient cells as well as in the vertebrate in vivo model zebrafish. We demonstrate a reduction of CHCHD10 protein levels in p.R15L and p.G66V mutant patient cells to approximately 50%. Quantitative real-time PCR revealed that expression of CHCHD10 p.R15L, but not of CHCHD10 p.G66V, is already abrogated at the mRNA level. Altered secondary structure and rapid protein degradation are observed with regard to the CHCHD10 p.G66V mutant. In contrast, no significant differences in expression, degradation rate or secondary structure of non-pathogenic CHCHD10 p.P34S are detected when compared with wild-type protein. Knockdown of CHCHD10 expression in zebrafish to about 50% causes motoneuron pathology, abnormal myofibrillar structure and motility deficits in vivo. Thus, our data show that the CHCHD10 mutations p.R15L and p.G66V cause motoneuron disease primarily based on haploinsufficiency of CHCHD10. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Impaired associative fear learning in mice with complete loss or haploinsufficiency of AMPA GluR1 receptors

    Directory of Open Access Journals (Sweden)

    Michael Feyder

    2007-12-01

    Full Text Available There is compelling evidence that L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA glutamate receptors containing the GluR1 subunit contribute to the molecular mechanisms associated with learning. AMPA GluR1 glutamate receptor knockout mice (KO exhibit abnormal hippocampal and amygdala plasticity, and deficits on various assays for cognition including Pavlovian fear conditioning. Here we examined associative fear learning in mice with complete absence (KO or partial loss (heterozygous mutant, HET of GluR1 on multiple fear conditioning paradigms. After multi-trial delay or trace conditioning, KO displayed impaired tone and context fear recall relative to WT, whereas HET were normal. After one-trial delay conditioning, both KO and HET showed impaired tone and context recall. HET and KO showed normal nociceptive sensitivity in the hot plate and tail flick tests. These data demonstrate that the complete absence of GluR1 subunit-containing receptors prevents the formation of associative fear memories, while GluR1 haploinsufficiency is sufficient to impair one-trial fear learning. These findings support growing evidence of a major role for GluR1-containing AMPA receptors in amygdalamediated forms of learning and memory.

  2. Congenital Hyperinsulinism in Infants with Turner Syndrome: Possible Association with Monosomy X and KDM6A Haploinsufficiency.

    Science.gov (United States)

    Gibson, Christopher E; Boodhansingh, Kara E; Li, Changhong; Conlin, Laura; Chen, Pan; Becker, Susan A; Bhatti, Tricia; Bamba, Vaneeta; Adzick, N Scott; De Leon, Diva D; Ganguly, Arupa; Stanley, Charles A

    2018-06-14

    Previous case reports have suggested a possible association of congenital hyperinsulinism with Turner syndrome. We examined the clinical and molecular features in girls with both congenital hyperinsulinism and Turner syndrome seen at The Children's Hospital of Philadelphia (CHOP) between 1974 and 2017. Records of girls with hyperinsulinism and Turner syndrome were reviewed. Insulin secretion was studied in pancreatic islets and in mouse islets treated with an inhibitor of KDM6A, an X chromosome gene associated with hyperinsulinism in Kabuki syndrome. Hyperinsulinism was diagnosed in 12 girls with Turner syndrome. Six were diazoxide-unresponsive; 3 had pancreatectomies. The incidence of Turner syndrome among CHOP patients with hyperinsulinism (10 of 1,050 from 1997 to 2017) was 48 times more frequent than expected. The only consistent chromosomal anomaly in these girls was the presence of a 45,X cell line. Studies of isolated islets from 1 case showed abnormal elevated cytosolic calcium and heightened sensitivity to amino acid-stimulated insulin release; similar alterations were demonstrated in mouse islets treated with a KDM6A inhibitor. These results demonstrate a higher than expected frequency of Turner syndrome among children with hyperinsulinism. Our data suggest that haploinsufficiency for KDM6A due to mosaic X chromosome monosomy may be responsible for hyperinsulinism in Turner syndrome. © 2018 S. Karger AG, Basel.

  3. Autosomal dominant inheritance of Williams-Beuren syndrome in a father and son with haploinsufficiency for FKBP6.

    Science.gov (United States)

    Metcalfe, Kay; Simeonov, Emil; Beckett, William; Donnai, Dian; Tassabehji, May

    2005-04-01

    Williams-Beuren syndrome (WBS) is a neurodevelopmental microdeletion disorder that usually occurs sporadically due to its location within a highly repetitive genomic region that is unstable and prone to unequal cross-over during meiosis. The consequential loss of chromosomal material includes approximately 1.5 Mb of DNA at 7q11.23. Whilst cases of dominant inheritance have been described in the literature, there have been few reports of molecular confirmation and none have carried out detailed genotyping. We describe a Bulgarian father and son with WBS detected by fluorescent in situ hybridisation (with an elastin gene probe) and loss of heterozygosity mapping using microsatellite markers located in the critical region. These individuals appear to have a common WBS heterozygous deletion, confirming the expected dominant transmission and adding to the few familial cases reported. The deletion includes the gene FKBP6 which has recently been shown to play a role in homologous chromosome pairing in meiosis and male fertility in mouse models. Homozygous Fkbp6 -/- male mice are infertile and our data suggests that haploinsufficiency for FKBP6 does not appear to preclude male fertility in WBS, although male infertility involving this gene has the potential to follow the mouse model as a human autosomal recessive condition.

  4. Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A.

    Directory of Open Access Journals (Sweden)

    Glòria Arqué

    Full Text Available BACKGROUND: Pathogenic aneuploidies involve the concept of dosage-sensitive genes leading to over- and underexpression phenotypes. Monosomy 21 in human leads to mental retardation and skeletal, immune and respiratory function disturbances. Most of the human condition corresponds to partial monosomies suggesting that critical haploinsufficient genes may be responsible for the phenotypes. The DYRK1A gene is localized on the human chromosome 21q22.2 region, and has been proposed to participate in monosomy 21 phenotypes. It encodes a dual-specificity kinase involved in neuronal development and in adult brain physiology, but its possible role as critical haploinsufficient gene in cognitive function has not been explored. METHODOLOGY/PRINCIPAL FINDINGS: We used mice heterozygous for a Dyrk1A targeted mutation (Dyrk1A+/- to investigate the implication of this gene in the cognitive phenotypes of monosomy 21. Performance of Dyrk1A+/- mice was assayed 1/ in a navigational task using the standard hippocampally related version of the Morris water maze, 2/ in a swimming test designed to reveal potential kinesthetic and stress-related behavioral differences between control and heterozygous mice under two levels of aversiveness (25 degrees C and 17 degrees C and 3/ in a long-term novel object recognition task, sensitive to hippocampal damage. Dyrk1A+/- mice showed impairment in the development of spatial learning strategies in a hippocampally-dependent memory task, they were impaired in their novel object recognition ability and were more sensitive to aversive conditions in the swimming test than euploid control animals. CONCLUSIONS/SIGNIFICANCE: The present results are clear examples where removal of a single gene has a profound effect on phenotype and indicate that haploinsufficiency of DYRK1A might contribute to an impairment of cognitive functions and stress coping behavior in human monosomy 21.

  5. Human Pluripotent Stem Cell-derived Cortical Neurons for High Throughput Medication Screening in Autism: A Proof of Concept Study in SHANK3 Haploinsufficiency Syndrome

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    Hélène Darville

    2016-07-01

    Full Text Available Autism spectrum disorders affect millions of individuals worldwide, but their heterogeneity complicates therapeutic intervention that is essentially symptomatic. A versatile yet relevant model to rationally screen among hundreds of therapeutic options would help improving clinical practice. Here we investigated whether neurons differentiated from pluripotent stem cells can provide such a tool using SHANK3 haploinsufficiency as a proof of principle. A library of compounds was screened for potential to increase SHANK3 mRNA content in neurons differentiated from control human embryonic stem cells. Using induced pluripotent stem cell technology, active compounds were then evaluated for efficacy in correcting dysfunctional networks of neurons differentiated from individuals with deleterious point mutations of SHANK3. Among 202 compounds tested, lithium and valproic acid showed the best efficacy at corrected SHANK3 haploinsufficiency associated phenotypes in cellulo. Lithium pharmacotherapy was subsequently provided to one patient and, after one year, an encouraging decrease in autism severity was observed. This demonstrated that pluripotent stem cell-derived neurons provide a novel cellular paradigm exploitable in the search for specific disease-modifying treatments.

  6. Haploinsufficiency of the 22q11.2 microdeletion gene Mrpl40 disrupts short-term synaptic plasticity and working memory through dysregulation of mitochondrial calcium.

    Science.gov (United States)

    Devaraju, P; Yu, J; Eddins, D; Mellado-Lagarde, M M; Earls, L R; Westmoreland, J J; Quarato, G; Green, D R; Zakharenko, S S

    2017-09-01

    Hemizygous deletion of a 1.5- to 3-megabase region on chromosome 22 causes 22q11.2 deletion syndrome (22q11DS), which constitutes one of the strongest genetic risks for schizophrenia. Mouse models of 22q11DS have abnormal short-term synaptic plasticity that contributes to working-memory deficiencies similar to those in schizophrenia. We screened mutant mice carrying hemizygous deletions of 22q11DS genes and identified haploinsufficiency of Mrpl40 (mitochondrial large ribosomal subunit protein 40) as a contributor to abnormal short-term potentiation (STP), a major form of short-term synaptic plasticity. Two-photon imaging of the genetically encoded fluorescent calcium indicator GCaMP6, expressed in presynaptic cytosol or mitochondria, showed that Mrpl40 haploinsufficiency deregulates STP via impaired calcium extrusion from the mitochondrial matrix through the mitochondrial permeability transition pore. This led to abnormally high cytosolic calcium transients in presynaptic terminals and deficient working memory but did not affect long-term spatial memory. Thus, we propose that mitochondrial calcium deregulation is a novel pathogenic mechanism of cognitive deficiencies in schizophrenia.

  7. EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome.

    Science.gov (United States)

    Li, Chuan; Chen, Rongyu; Fan, Xin; Luo, Jingsi; Qian, Jiale; Wang, Jin; Xie, Bobo; Shen, Yiping; Chen, Shaoke

    2015-04-11

    Waardenburg syndrome type I (WS1), an auditory-pigmentary genetic disorder, is caused by heterozygous loss-of-function mutations in PAX3. Abnormal physical signs such as dystopia canthorum, patchy hypopigmentation and sensorineural hearing loss are common, but short stature is not associated with WS1. We reported a 4-year and 6 month-old boy with a rare combination of WS1 and severe short stature (83.5 cm (-5.8SD)). His facial features include dystopia canthorum, mild synophrys, slightly up-slanted palpebral fissure, posteriorly rotated ears, alae nasi hypoplasia and micrognathia. No heterochromia was noticed. He had a normal intelligence quotient and hearing. Insulin-like growth factor-1 (IGF-1) was 52.7 ng/ml, lower than the normal range (55 ~ 452 ng/ml) and the peak growth hormone level was 7.57 ng/ml at 90 minutes after taking moderate levodopa and pyridostigmine bromide. The patient exhibited a good response to human growth hormone (rhGH) replacement therapy, showing a 9.2 cm/year growth rate and an improvement of 1 standard deviation (SD) of height after one year treatment. CMA test of patient's DNA revealed a 4.46 Mb de novo deletion at 2q35-q36.2 (hg19; chr2:221,234,146-225,697,363). PAX3 haploinsufficiency is known to cause Waardenburg syndrome. Examining overlapping deletions in patients led to the conclusion that EPHA4 is a novel short stature gene. The finding is supported by the splotch-retarded and epha4 knockout mouse models which both showed growth retardation. We believe this rare condition is caused by the haploinsufficiency of both PAX3 and EPH4 genes. We further reported a growth response to recombinant human growth hormone treatment in this patient.

  8. A Transition Zone Showing Highly Discontinuous or Alternating Levels of Stem Cell and Proliferation Markers Characterizes the Development of PTEN-Haploinsufficient Colorectal Cancer.

    Science.gov (United States)

    Arvai, Kevin J; Hsu, Ya-Hsuan; Lee, Lobin A; Jones, Dan

    2015-01-01

    Stepwise acquisition of oncogene mutations and deletion/inactivation of tumor suppressor genes characterize the development of colorectal cancer (CRC). These genetic events interact with discrete morphologic transitions from hyperplastic mucosa to adenomatous areas, followed by in situ malignant transformation and finally invasive carcinoma. The goal of this study was to identify tissue markers of the adenoma-carcinoma morphogenetic transitions in CRC. We analyzed the patterns of expression of growth regulatory and stem cell markers across these distinct morphologic transition zones in 735 primary CRC tumors. In 202 cases with preserved adenoma-adenocarcinoma transition, we identified, in 37.1% of cases, a zone of adenomatous epithelium, located immediately adjacent to the invasive component, that showed rapidly alternating intraglandular stretches of PTEN+ and PTEN- epithelium. This zone exactly overlapped with similar alternating expression of Ki-67 and inversely with the transforming growth factor-beta (TGF-β) growth regulator SMAD4. These zones also show parallel alternating levels and/or subcellular localization of multiple cancer stem/progenitor cell (CSC) markers, including β-catenin/CTNNB1, ALDH1, and CD44. PTEN was always re-expressed in the invasive tumor in these cases, unlike those with complete loss of PTEN expression. Genomic microarray analysis of CRC with prominent CSC-like expansions demonstrated a high frequency of PTEN genomic deletion/haploinsufficiency in tumors with CSC-like transition zones (62.5%) but not in tumors with downregulated but non-alternating PTEN expression (14.3%). There were no significant differences in the levels of KRAS mutation or CTNNB1 mutation in CSC-like tumors as compared to unselected CRC cases. In conclusion, we have identified a distinctive CSC-like pre-invasive transition zone in PTEN-haploinsufficient CRC that shows convergent on-off regulation of the PTEN/AKT, TGF-β/SMAD and Wnt/β-catenin pathways. This

  9. A Transition Zone Showing Highly Discontinuous or Alternating Levels of Stem Cell and Proliferation Markers Characterizes the Development of PTEN-Haploinsufficient Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Kevin J Arvai

    Full Text Available Stepwise acquisition of oncogene mutations and deletion/inactivation of tumor suppressor genes characterize the development of colorectal cancer (CRC. These genetic events interact with discrete morphologic transitions from hyperplastic mucosa to adenomatous areas, followed by in situ malignant transformation and finally invasive carcinoma. The goal of this study was to identify tissue markers of the adenoma-carcinoma morphogenetic transitions in CRC.We analyzed the patterns of expression of growth regulatory and stem cell markers across these distinct morphologic transition zones in 735 primary CRC tumors. In 202 cases with preserved adenoma-adenocarcinoma transition, we identified, in 37.1% of cases, a zone of adenomatous epithelium, located immediately adjacent to the invasive component, that showed rapidly alternating intraglandular stretches of PTEN+ and PTEN- epithelium. This zone exactly overlapped with similar alternating expression of Ki-67 and inversely with the transforming growth factor-beta (TGF-β growth regulator SMAD4. These zones also show parallel alternating levels and/or subcellular localization of multiple cancer stem/progenitor cell (CSC markers, including β-catenin/CTNNB1, ALDH1, and CD44. PTEN was always re-expressed in the invasive tumor in these cases, unlike those with complete loss of PTEN expression. Genomic microarray analysis of CRC with prominent CSC-like expansions demonstrated a high frequency of PTEN genomic deletion/haploinsufficiency in tumors with CSC-like transition zones (62.5% but not in tumors with downregulated but non-alternating PTEN expression (14.3%. There were no significant differences in the levels of KRAS mutation or CTNNB1 mutation in CSC-like tumors as compared to unselected CRC cases.In conclusion, we have identified a distinctive CSC-like pre-invasive transition zone in PTEN-haploinsufficient CRC that shows convergent on-off regulation of the PTEN/AKT, TGF-β/SMAD and Wnt

  10. Toxicology and Carcinogenesis Study of Senna in the C3B6.129F1-Trp53tm1Brd N12 haploinsufficient mice

    Science.gov (United States)

    Surh, Inok; Brix, Amy; French, John E.; Collins, Bradley J.; Sanders, J. Michael; Vallant, Molly; Dunnick, June K.

    2013-01-01

    Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes break sennosides and release rhein-9-anthrone, the active form for the laxative effect. To determine potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53tm1Brd N12 haploinsufficient (p53+/−) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53+/− mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53(+/−) males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53+/− mouse model. There was no neoplastic change, when senna was administered to p53 +/− mouse. PMID:23125117

  11. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

    KAUST Repository

    Chatel, Benjamin; Bendahan, David; Hourdé , Christophe; Pellerin, Luc; Lengacher, Sylvain; Magistretti, Pierre J.; Le Fur, Yann; Vilmen, Christophe; Bernard, Monique; Messonnier, Laurent A.

    2017-01-01

    The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1(+/-) mice). Twenty-four MCT1(+/-) and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1(+/-) mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1(+/-) mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1(+/-) mice had higher specific peak (P < 0.05) and maximum tetanic (P < 0.01) forces and lower fatigability (P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1(+/-) mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

  12. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

    KAUST Repository

    Chatel, Benjamin

    2017-03-03

    The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1(+/-) mice). Twenty-four MCT1(+/-) and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1(+/-) mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1(+/-) mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1(+/-) mice had higher specific peak (P < 0.05) and maximum tetanic (P < 0.01) forces and lower fatigability (P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1(+/-) mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

  13. Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors: Implications for low bone mass phenotype

    International Nuclear Information System (INIS)

    Yang Jieping; Murthy, Sreemala; Winata, Therry; Werner, Sean; Abe, Masumi; Prahalad, Agasanur K.; Hock, Janet M.

    2006-01-01

    The cellular and molecular mechanisms that underlie skeletal abnormalities in defective Recql4-related syndromes are poorly understood. Our objective in this study was to explore the function of Recql4 in osteoblast biology both in vitro and in vivo. Immunohistochemistry on adult mouse bone showed Recql4 protein localization in active osteoblasts around growth plate, but not in fully differentiated osteocytes. Consistent with this finding, Recql4 gene expression was high in proliferating mouse osteoblastic MC3T3.E1 cells and decreased as cells progressively lost their proliferation activity during differentiation. Recql4 overexpression in osteoblastic cells exhibited higher proliferation activity, while its depletion impeded cell growth. In addition, bone marrow stromal cells from male Recql4+/- mice had fewer progenitor cells, including osteoprogenitors, indicated by reduced total fibroblast colony forming units (CFU-f) and alkaline phosphatase-positive CFU-f colonies concomitant with reduced bone mass. These findings provide evidence that Recql4 functions as a regulatory protein during osteoprogenitor proliferation, a critical cellular event during skeleton development

  14. Cortical Development Requires Mesodermal Expression of Tbx1, a Gene Haploinsufficient in 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Flore, Gemma; Cioffi, Sara; Bilio, Marchesa; Illingworth, Elizabeth

    2017-03-01

    In mammals, proper temporal control of neurogenesis and neural migration during embryonic development ensures correct formation of the cerebral cortex. Changes in the distribution of cortical projection neurons and interneurons are associated with behavioral disorders and psychiatric diseases, including schizophrenia and autism, suggesting that disrupted cortical connectivity contributes to the brain pathology. TBX1 is the major candidate gene for 22q11.2 deletion syndrome (22q11.2DS), a chromosomal deletion disorder characterized by a greatly increased risk for schizophrenia. We have previously shown that Tbx1 heterozygous mice have reduced prepulse inhibition, a behavioral abnormality that is associated with 22q11.2DS and nonsyndromic schizophrenia. Here, we show that loss of Tbx1 disrupts corticogenesis in mice by promoting premature neuronal differentiation in the medio-lateral embryonic cortex, which gives rise to the somatosensory cortex (S1). In addition, we found altered polarity in both radially migrating excitatory neurons and tangentially migrating inhibitory interneurons. Together, these abnormalities lead to altered lamination in the S1 at the terminal stages of corticogenesis in Tbx1 null mice and similar anomalies in Tbx1 heterozygous adult mice. Finally, we show that mesoderm-specific inactivation of Tbx1 is sufficient to recapitulate the brain phenotype indicating that Tbx1 exerts a cell nonautonomous role in cortical development from the mesoderm. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Azamat Aslanukov

    2006-10-01

    Full Text Available The Ran-binding protein 2 (RanBP2 is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/- are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/- mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

  16. RanBP2 modulates Cox11 and hexokinase I activities and haploinsufficiency of RanBP2 causes deficits in glucose metabolism.

    Science.gov (United States)

    Aslanukov, Azamat; Bhowmick, Reshma; Guruju, Mallikarjuna; Oswald, John; Raz, Dorit; Bush, Ronald A; Sieving, Paul A; Lu, Xinrong; Bock, Cheryl B; Ferreira, Paulo A

    2006-10-01

    The Ran-binding protein 2 (RanBP2) is a large multimodular and pleiotropic protein. Several molecular partners with distinct functions interacting specifically with selective modules of RanBP2 have been identified. Yet, the significance of these interactions with RanBP2 and the genetic and physiological role(s) of RanBP2 in a whole-animal model remain elusive. Here, we report the identification of two novel partners of RanBP2 and a novel physiological role of RanBP2 in a mouse model. RanBP2 associates in vitro and in vivo and colocalizes with the mitochondrial metallochaperone, Cox11, and the pacemaker of glycolysis, hexokinase type I (HKI) via its leucine-rich domain. The leucine-rich domain of RanBP2 also exhibits strong chaperone activity toward intermediate and mature folding species of Cox11 supporting a chaperone role of RanBP2 in the cytosol during Cox11 biogenesis. Cox11 partially colocalizes with HKI, thus supporting additional and distinct roles in cell function. Cox11 is a strong inhibitor of HKI, and RanBP2 suppresses the inhibitory activity of Cox11 over HKI. To probe the physiological role of RanBP2 and its role in HKI function, a mouse model harboring a genetically disrupted RanBP2 locus was generated. RanBP2(-/-) are embryonically lethal, and haploinsufficiency of RanBP2 in an inbred strain causes a pronounced decrease of HKI and ATP levels selectively in the central nervous system. Inbred RanBP2(+/-) mice also exhibit deficits in growth rates and glucose catabolism without impairment of glucose uptake and gluconeogenesis. These phenotypes are accompanied by a decrease in the electrophysiological responses of photosensory and postreceptoral neurons. Hence, RanBP2 and its partners emerge as critical modulators of neuronal HKI, glucose catabolism, energy homeostasis, and targets for metabolic, aging disorders and allied neuropathies.

  17. Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia.

    Science.gov (United States)

    Newton, Timothy; Allison, Rachel; Edgar, James R; Lumb, Jennifer H; Rodger, Catherine E; Manna, Paul T; Rizo, Tania; Kohl, Zacharias; Nygren, Anders O H; Arning, Larissa; Schüle, Rebecca; Depienne, Christel; Goldberg, Lisa; Frahm, Christiane; Stevanin, Giovanni; Durr, Alexandra; Schöls, Ludger; Winner, Beate; Beetz, Christian; Reid, Evan

    2018-05-01

    Many genetic neurological disorders exhibit variable expression within affected families, often exemplified by variations in disease age at onset. Epistatic effects (i.e. effects of modifier genes on the disease gene) may underlie this variation, but the mechanistic basis for such epistatic interactions is rarely understood. Here we report a novel epistatic interaction between SPAST and the contiguous gene DPY30, which modifies age at onset in hereditary spastic paraplegia, a genetic axonopathy. We found that patients with hereditary spastic paraplegia caused by genomic deletions of SPAST that extended into DPY30 had a significantly younger age at onset. We show that, like spastin, the protein encoded by SPAST, the DPY30 protein controls endosomal tubule fission, traffic of mannose 6-phosphate receptors from endosomes to the Golgi, and lysosomal ultrastructural morphology. We propose that additive effects on this pathway explain the reduced age at onset of hereditary spastic paraplegia in patients who are haploinsufficient for both genes.

  18. Hematopoietic defects in response to reduced Arhgap21

    Directory of Open Access Journals (Sweden)

    Juliana Xavier-Ferrucio

    2018-01-01

    Full Text Available Arhgap21 is a member of the Rho GTPase activating protein (RhoGAP family, which function as negative regulators of Rho GTPases. Arhgap21 has been implicated in adhesion and migration of cancer cells. However, the role of Arhgap21 has never been investigated in hematopoietic cells. Herein, we evaluated functional aspects of hematopoietic stem and progenitor cells (HSPC using a haploinsufficient (Arhgap21+/− mouse. Our results show that Arhgap21+/− mice have an increased frequency of phenotypic HSC, impaired ability to form progenitor colonies in vitro and decreased hematopoietic engraftment in vivo, along with a decrease in LSK cell frequency during serial bone marrow transplantation. Arhgap21+/− hematopoietic progenitor cells have impaired adhesion and enhanced mobilization of immature LSK and myeloid progenitors. Arhgap21+/− mice also exhibit reduced erythroid commitment and differentiation, which was recapitulated in human primary cells, in which knockdown of ARHGAP21 in CMP and MEP resulted in decreased erythroid commitment. Finally, we observed enhanced RhoC activity in the bone marrow cells of Arhgap21+/− mice, indicating that Arhgap21 functions in hematopoiesis may be at least partially mediated by RhoC inactivation. Keywords: Arhgap21, Hematopoiesis, Erythroid cells, Hematopoietic stem and progenitor cells, Fate decision

  19. An analysis on the roles of angiogenesis-related factors including serum vitamin D, soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt1), and vascular endothelial growth factor (VEGF) in the diagnosis and severity of late-onset preeclampsia.

    Science.gov (United States)

    Cim, Numan; Kurdoglu, Mertihan; Ege, Serhat; Yoruk, Ibrahim; Yaman, Gorkem; Yildizhan, Recep

    2017-07-01

    The aim of this study was to evaluate the roles of proangiogenic factors including serum vitamin D and vascular endothelial growth factor (VEGF) and anti-angiogenic factors including soluble endoglin (sEng) and soluble fms-like tyrosine kinase 1 (sFlt1) in the diagnosis and severity of late-onset preeclampsia. The study was conducted at Yuzuncu Yil University Research and Education Hospital Department of Gynecology and Obstetrics. The study included a patient group of 40 women with late-onset preeclampsia who were pregnant at ≥32 weeks of gestation according to the last menstrual period (LMP) or ultrasonographic fetal biometric measurement and a control group of 40 healthy pregnant women who presented to our clinic for routine pregnancy examination and were at the same age and gestational period with those in the patient group. The two groups were compared in terms of maternal age, gravida, parity, week of gestation, systolic/diastolic blood pressure, total protein in spot urine sample, 24-h urine protein, white blood cell (WBC), hemoglobin (Hgb), platelet count, urea, creatinine, liver function tests (AST, ALT, LDH), vitamin D 3 , 25(OH) vitamin D 3 , 1,25(OH) vitamin D 3 , sEng, sFlt1, and VEGF levels, mode of delivery, the infant APGAR score at 1 and 5 min after delivery, and infant weight at delivery. The groups were similar in terms of age, gravida, parity, week of gestation, serum vitamin D 3 , 25(OH) vitamin D 3 , 1,25(OH) 2 vitamin D 3 and VEGF levels, and infant weight at delivery (p > 0.05). Systolic/diastolic blood pressure, total protein in spot urine sample, 24-h urine protein, WBC, Hgb, serum urea, creatine, AST, ALT, and LDH were significantly higher in the preeclamptic group compared to the healthy group (p preeclampsia compared to the women with mild preeclampsia (p preeclampsia (p > 0.05). Both sEng and sFlt1 levels are remarkably high in patients with late-onset preeclampsia; however, only sEng may be a useful tool in the

  20. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Science.gov (United States)

    Nuytens, Kim; Tuand, Krizia; Fu, Quili; Stijnen, Pieter; Pruniau, Vincent; Meulemans, Sandra; Vankelecom, Hugo; Creemers, John W M

    2014-01-01

    Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea) have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH) genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH) signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  1. The dwarf phenotype in GH240B mice, haploinsufficient for the autism candidate gene Neurobeachin, is caused by ectopic expression of recombinant human growth hormone.

    Directory of Open Access Journals (Sweden)

    Kim Nuytens

    Full Text Available Two knockout mouse models for the autism candidate gene Neurobeachin (Nbea have been generated independently. Although both models have similar phenotypes, one striking difference is the dwarf phenotype observed in the heterozygous configuration of the GH240B model that is generated by the serendipitous insertion of a promoterless human growth hormone (hGH genomic fragment in the Nbea gene. In order to elucidate this discrepancy, the dwarfism present in this Nbea mouse model was investigated in detail. The growth deficiency in Nbea+/- mice coincided with an increased percentage of fat mass and a decrease in bone mineral density. Low but detectable levels of hGH were detected in the pituitary and hypothalamus of Nbea+/- mice but not in liver, hippocampus nor in serum. As a consequence, several members of the mouse growth hormone (mGH signaling cascade showed altered mRNA levels, including a reduction in growth hormone-releasing hormone mRNA in the hypothalamus. Moreover, somatotrope cells were less numerous in the pituitary of Nbea+/- mice and both contained and secreted significantly less mGH resulting in reduced levels of circulating insulin-like growth factor 1. These findings demonstrate that the random integration of the hGH transgene in this mouse model has not only inactivated Nbea but has also resulted in the tissue-specific expression of hGH causing a negative feedback loop, mGH hyposecretion and dwarfism.

  2. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  3. Reducing costs by reducing size

    International Nuclear Information System (INIS)

    Hayns, M.R.; Shepherd, J.

    1991-01-01

    The present paper discusses briefly the many factors, including capital cost, which have to be taken into account in determining whether a series of power stations based on a small nuclear plant can be competitive with a series based on traditional large unit sizes giving the guaranteed level of supply. The 320 MWe UK/US Safe Integral Reactor is described as a good example of how the factors discussed can be beneficially incorporated into a design using proven technology. Finally it goes on to illustrate how the overall costs of a generating system can indeed by reduced by use of the 320 MWe Safe Integral Reactor rather than conventional units of around 1200 MWe. (author). 9 figs

  4. Toxicology study of senna (CAS No. 8013-11-4) in C57BL/6NTAC Mice and toxicology and carcinogenesis study of senna in genetically modified C3B6.129F1/Tac-Trp53tm1Brd haploinsufficient mice (Feed Studies).

    Science.gov (United States)

    2012-04-01

    Senna is used as a stimulant laxative in the management of constipation resulting from opioid use or when treatment with bulking or osmotic agents has failed. Increased use of senna was expected due to the removal of the stimulant laxatives danthron and phenolphthalein from the market. Senna was nominated for study by the Center for Drug Evaluation and Research, United States Food and Drug Administration (FDA) due to the wide use of laxative preparations, positive genotoxicity in vitro for some senna components or metabolites, and unknown carcinogenic potential. Because a 2-year rat study was ongoing by the manufacturer, the FDA requested that the NTP conduct a senna study in the p53(+/-) mouse. In this study, the potential for carcinogenic effects of senna was studied in the C3B6.129F1/Tac-Trp53tm1Brd N12 haploinsufficient (heterozygous F1 p53(+/-)) mouse model as an ongoing goal of the NTP to develop and test model systems for toxicology and carcinogenesis studies, especially those that can provide mechanistic information relative to understanding an agents mode of action. C57BL/6NTac mice were exposed to senna in feed for 5 weeks; heterozygous F1 p53(+/-) mice were exposed to senna in feed for 40 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes.

  5. Reduced Rank Regression

    DEFF Research Database (Denmark)

    Johansen, Søren

    2008-01-01

    The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating...

  6. Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients

    Directory of Open Access Journals (Sweden)

    Camargo Anamaria A

    2009-12-01

    Full Text Available Abstract Background Treacher Collins syndrome (TCS is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in the TCOF1 gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD. Haploinsufficiency of the gene product (treacle during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown if TCOF1 expression levels are decreased in post-embryonic human cells. Methods We have estimated TCOF1 transcript levels through real time PCR in mRNA obtained from leucocytes and mesenchymal cells of TCS patients (n = 23 and controls (n = 18. Mutational screening and analysis of NMD were performed by direct sequencing of gDNA and cDNA, respectively. Results All the 23 patients had typical clinical features of the syndrome and pathogenic mutations were detected in 19 of them. We demonstrated that the expression level of TCOF1 is 18-31% lower in patients than in controls (p , even if we exclude the patients in whom we did not detect the pathogenic mutation. We also observed that the mutant allele is usually less abundant than the wild type one in mesenchymal cells. Conclusions This is the first study to report decreased expression levels of TCOF1 in TCS adult human cells, but it is still unknown if this finding is associated to any phenotype in adulthood. In addition, as we demonstrated that alleles harboring the pathogenic mutations have lower expression, we herein corroborate the current hypothesis of NMD of the mutant transcript as the explanation for diminished levels of TCOF1 expression. Further, considering that TCOF1 deficiency in adult cells could be associated to pathologic clinical findings, it will be important to verify if TCS patients have an impairment in adult stem cell properties, as this can reduce the efficiency of plastic surgery results during rehabilitation of these

  7. Reduced abrasion drilling fluid

    NARCIS (Netherlands)

    2010-01-01

    A reduced abrasion drilling fluid system and method of drilling a borehole by circulating the reduced abrasion drilling fluid through the borehole is disclosed. The reduced abrasion drilling fluid comprises a drilling fluid, a first additive and a weighting agent, wherein the weighting agent has a

  8. Reduced abrasion drilling fluid

    NARCIS (Netherlands)

    2012-01-01

    A reduced abrasion drilling fluid system and method of drilling a borehole by circulating the reduced abrasion drilling fluid through the borehole is disclosed. The reduced abrasion drilling fluid comprises a drilling fluid, a first additive and a weighting agent, wherein the weighting agent has a

  9. Reducible oxide based catalysts

    Science.gov (United States)

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

  10. Direct oxide reducing method

    International Nuclear Information System (INIS)

    Tokiwai, Moriyasu.

    1995-01-01

    Calcium oxides and magnetic oxides as wastes generated upon direct reduction are subjected to molten salt electrolysis, and reduced metallic calcium and magnesium are separated and recovered. Then calcium and magnesium are used recyclically as the reducing agent upon conducting direct oxide reduction. Even calcium oxides and magnesium oxides, which have high melting points and difficult to be melted usually, can be melted in molten salts of mixed fluorides or chlorides by molten-salt electrolysis. Oxides are decomposed by electrolysis, and oxygen is removed in the form of carbon monoxide, while the reduced metallic calcium and magnesium rise above the molten salts on the side of a cathode, and then separated. Since only carbon monoxide is generated as radioactive wastes upon molten salt electrolysis, the amount of radioactive wastes can be greatly reduced, and the amount of the reducing agent used can also be decreased remarkably. (N.H.)

  11. Pipeline Drag Reducers

    International Nuclear Information System (INIS)

    Marawan, H.

    2004-01-01

    Pipeline drag reducers have proven to be an extremely powerful tool in fluid transportation. High molecular weight polymers are used to reduce the frictional pressure loss ratio in crude oil pipelines, refined fuel and aqueous pipelines. Chemical structure of the main used pipeline drag reducers is one of the following polymers and copolymers classified according to the type of fluid to ; low density polyethylene, copolymer of I-hexane cross linked with divinyl benzene, polyacrylamide, polyalkylene oxide polymers and their copolymers, fluorocarbons, polyalkyl methacrylates and terpolymer of styrene, alkyl acrylate and acrylic acid. Drag reduction is the increase in pump ability of a fluid caused by the addition of small amounts of an additive to the fluid. The effectiveness of a drag reducer is normally expressed in terms of percent drag reduction. Frictional pressure loss in a pipeline system is a waste of energy and it costly. The drag reducing additive minimizes the flow turbulence, increases throughput and reduces the energy costs. The Flow can be increased by more than 80 % with existing assets. The effectiveness of the injected drag reducer in Mostorod to Tanta crude oil pipeline achieved 35.4 % drag reduction and 23.2 % flow increase of the actual performance The experimental application of DRA on Arab Petroleum Pipeline Company (Summed) achieved a flow increase ranging from 9-32 %

  12. Reducing Pesticide Drift

    Science.gov (United States)

    Provides information about pesticide spray drift, including problems associated with drift, managing risks from drift and the voluntary Drift Reduction Technology program that seeks to reduce spray drift through improved spray equipment design.

  13. Reducing Childhood Obesity

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  14. Reducing The Nuclear Danger

    Science.gov (United States)

    1995-10-01

    off convention • Eliminate the civil use of HEU (includes RERTR ) • Reduce stockpiles of civil HEU and plutonium • Promote alternatives to the...these countries. ANL supports the Department’s Reduced Enrichment for Research and Test Reactor ( RERTR ) Program by providing the technical means to...scientists and engineers at 60 institutes in Russia, Ukraine, Kazakhstan and Belarus. The United States and Russia have agreed to pursue a joint RERTR

  15. Using reduce in supersymmetry

    International Nuclear Information System (INIS)

    Santos, R.P. dos.

    1987-01-01

    A procedure which allows one to do Supersymmetry calculus in REDUCE is described. Using the concept of an eight-dimensional 'superspace' (spanned by four space-time and four anticommuting coordinates) and of 'superfields' (which represent an entire supermultiplet of particles that transform among themselves), covariant derivatives with respect to supersymmetry are defined. Then, combining the vector facility and LET statement in REDUCE, spinors are simulated in a way to control the algebraic manipulation. (G.D.F.) [pt

  16. Impact of MCT1 Haploinsufficiency on the Mouse Retina

    KAUST Repository

    Peachey, Neal S.

    2018-05-02

    The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

  17. Impact of MCT1 Haploinsufficiency on the Mouse Retina

    KAUST Repository

    Peachey, Neal S.; Yu, Minzhong; Han, John Y. S.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Philp, Nancy J.

    2018-01-01

    The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

  18. Haploinsufficiency of TAB2 causes congenital heart defects in humans

    DEFF Research Database (Denmark)

    Thienpont, Bernard; Zhang, Litu; Postma, Alex V

    2010-01-01

    . To definitively confirm the role of this candidate gene in CHDs, we performed mutation analysis of TAB2 in 402 patients with a CHD, which revealed two evolutionarily conserved missense mutations. Finally, a balanced translocation was identified, cosegregating with familial CHD. Mapping of the breakpoints...... demonstrated that this translocation disrupts TAB2. Taken together, these data clearly demonstrate a role for TAB2 in human cardiac development....

  19. Tank closure reducing grout

    International Nuclear Information System (INIS)

    Caldwell, T.B.

    1997-01-01

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr 90 , the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel

  20. Reduced Braginskii equations

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, M. [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment; Horton, W. [Texas Univ., Austin, TX (United States). Inst. for Fusion Studies

    1993-11-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite {beta} that we solve the perpendicular component of Ohm`s law to conserve the physical energy while ensuring the relation {del} {center_dot} j = 0.

  1. Reduced Braginskii equations

    International Nuclear Information System (INIS)

    Yagi, M.; Horton, W.

    1993-11-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite β that we solve the perpendicular component of Ohm's law to conserve the physical energy while ensuring the relation ∇ · j = 0

  2. Reuse, Reduce, Recycle.

    Science.gov (United States)

    Briscoe, Georgia

    1991-01-01

    Discussion of recycling paper in law libraries is also applicable to other types of libraries. Results of surveys of law libraries that investigated recycling practices in 1987 and again in 1990 are reported, and suggestions for reducing the amount of paper used and reusing as much as possible are offered. (LRW)

  3. Reduced multiplication modules

    Indian Academy of Sciences (India)

    if M is a von Neumann regular module (VNM); i.e., every principal submodule of M is a summand submodule. Also if M is an injective R-module, then M is a VNM. Keywords. Multiplication module; reduced module; minimal prime submodule;. Zariski topology; extremally disconnected. 1. Introduction. In this paper all rings are ...

  4. Reduced Braginskii equations

    International Nuclear Information System (INIS)

    Yagi, M.; Horton, W.

    1994-01-01

    A set of reduced Braginskii equations is derived without assuming flute ordering and the Boussinesq approximation. These model equations conserve the physical energy. It is crucial at finite β that the perpendicular component of Ohm's law be solved to ensure ∇·j=0 for energy conservation

  5. Reducing infant mortality.

    Science.gov (United States)

    Johnson, T R

    1994-01-01

    Public health and social policies at the population level (e.g., oral rehydration therapy and immunization) are responsible for the major reduction in infant mortality worldwide. The gap in infant mortality rates between developing and developed regions is much less than that in maternal mortality rates. This indicates that maternal and child health (MCH) programs and women's health care should be combined. Since 1950, 66% of infant deaths occur in the 1st 28 days, indicating adverse prenatal and intrapartum events (e.g., congenital malformation and birth injuries). Infection, especially pneumonia and diarrhea, and low birth weight are the major causes of infant mortality worldwide. An estimated US$25 billion are needed to secure the resources to control major childhood diseases, reduce malnutrition 50%, reduce child deaths by 4 million/year, provide potable water and sanitation to all communities, provide basic education, and make family planning available to all. This cost for saving children's lives is lower than current expenditures for cigarettes (US$50 billion in Europe/year). Vitamin A supplementation, breast feeding, and prenatal diagnosis of congenital malformations are low-cost strategies that can significantly affect infant well-being and reduce child mortality in many developing countries. The US has a higher infant mortality rate than have other developed countries. The American College of Obstetricians and Gynecologists and the US National Institutes of Health are focusing on prematurity, low birth weight, multiple pregnancy, violence, alcohol abuse, and poverty to reduce infant mortality. Obstetricians should be important members of MCH teams, which also include traditional birth attendants, community health workers, nurses, midwives, and medical officers. We have the financial resources to allocate resources to improve MCH care and to reduce infant mortality.

  6. Why reduce health inequalities?

    Science.gov (United States)

    Woodward, A; Kawachi, I

    2000-12-01

    It is well known that social, cultural and economic factors cause substantial inequalities in health. Should we strive to achieve a more even share of good health, beyond improving the average health status of the population? We examine four arguments for the reduction of health inequalities.1 Inequalities are unfair. Inequalities in health are undesirable to the extent that they are unfair, or unjust. Distinguishing between health inequalities and health inequities can be contentious. Our view is that inequalities become "unfair" when poor health is itself the consequence of an unjust distribution of the underlying social determinants of health (for example, unequal opportunities in education or employment).2 Inequalities affect everyone. Conditions that lead to marked health disparities are detrimental to all members of society. Some types of health inequalities have obvious spillover effects on the rest of society, for example, the spread of infectious diseases, the consequences of alcohol and drug misuse, or the occurrence of violence and crime.3 Inequalities are avoidable. Disparities in health are avoidable to the extent that they stem from identifiable policy options exercised by governments, such as tax policy, regulation of business and labour, welfare benefits and health care funding. It follows that health inequalities are, in principle, amenable to policy interventions. A government that cares about improving the health of the population ought therefore to incorporate considerations of the health impact of alternative options in its policy setting process.3 Interventions to reduce health inequalities are cost effective. Public health programmes that reduce health inequalities can also be cost effective. The case can be made to give priority to such programmes (for example, improving access to cervical cancer screening in low income women) on efficiency grounds. On the other hand, few programmes designed to reduce health inequalities have been formally

  7. Crif1 Deficiency Reduces Adipose OXPHOS Capacity and Triggers Inflammation and Insulin Resistance in Mice

    Science.gov (United States)

    Ryu, Min Jeong; Kim, Soung Jung; Kim, Yong Kyung; Choi, Min Jeong; Tadi, Surendar; Lee, Min Hee; Lee, Seong Eun; Chung, Hyo Kyun; Jung, Saet Byel; Kim, Hyun-Jin; Jo, Young Suk; Kim, Koon Soon; Lee, Sang-Hee; Kim, Jin Man; Kweon, Gi Ryang; Park, Ki Cheol; Lee, Jung Uee; Kong, Young Yun; Lee, Chul-Ho; Chung, Jongkyeong; Shong, Minho

    2013-01-01

    Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance. PMID:23516375

  8. Reducing rotor weight

    Energy Technology Data Exchange (ETDEWEB)

    Cheney, M.C. [PS Enterprises, Inc., Glastonbury, CT (United States)

    1997-12-31

    The cost of energy for renewables has gained greater significance in recent years due to the drop in price in some competing energy sources, particularly natural gas. In pursuit of lower manufacturing costs for wind turbine systems, work was conducted to explore an innovative rotor designed to reduce weight and cost over conventional rotor systems. Trade-off studies were conducted to measure the influence of number of blades, stiffness, and manufacturing method on COE. The study showed that increasing number of blades at constant solidity significantly reduced rotor weight and that manufacturing the blades using pultrusion technology produced the lowest cost per pound. Under contracts with the National Renewable Energy Laboratory and the California Energy Commission, a 400 kW (33m diameter) turbine was designed employing this technology. The project included tests of an 80 kW (15.5m diameter) dynamically scaled rotor which demonstrated the viability of the design.

  9. Reducing Employment Insecurity

    Directory of Open Access Journals (Sweden)

    Florence Lebert

    2016-10-01

    Full Text Available The perception of job insecurity is known to be a stressful condition for employees. Less is known about employment insecurity and the ways employees and their families deal with it. This study investigates whether participation in further training is a strategy that employees adopt to reduce perceived employment insecurity. As participation in further training is often costly and time-consuming, we assume that the family context is of importance for the decision to take part in further training. To take account of possible self-selection, we apply a propensity score matching procedure on longitudinal data from the Swiss Household Panel (2004-2013. Three main findings can be emphasized: first, participation in further training is not a strategy adopted particularly by employees who perceive high employment insecurity as they are less likely to train than their secure counterparts. Second, even though further training is not a strategy that is actively adopted, employees who train subsequently report lower levels of perceived employment insecurity. Third, the family context indeed influences the likelihood to train: partnered employees are more likely to train and preschool-aged children act as a constraint on women’s but enhance men’s participation in further training. Yet, in the context of high perceived employment insecurity, children generally reduce their parents’ likelihood to train as the parents may turn to other strategies that reduce perceived employment insecurity.

  10. Reduced cost of ownership

    International Nuclear Information System (INIS)

    Wyse, W.H.; Newton, J.C.

    1995-01-01

    There is common drive throughout industry towards reduced costs of ownership of plant and equipment. Rolls-Royce and Associates Ltd. has developed the systems and expertise necessary to achieve these objectives. This Paper outlines the methods being used on existing facilities, and describes a new all embracing process called Planned Lifetime Management. This process, based on the military standard Integrated Logistic Support, ensures that all aspects of support are clearly identified at the design stage and that support is monitored to allow through-life support costs to be optimized. (author)

  11. Reducing Outdoor Advertising

    Directory of Open Access Journals (Sweden)

    Patrice de Rendinger

    2006-05-01

    Full Text Available The fundamental concept is that public space is not a private property. So, a facade (the outer skin, the last millimeter belongs to the town, not to the owner of the building. Changing the rendering, a window, adding or removing anything from a facade requires a permission delivered by the town's authority.In places like Paris, Bordeaux, Marseilles, Lyon, Strasbourg… everywhere one can find a registrated building such as a cathedral, a castle, or a group of ancient buildings, a national administration is controlling this permission. This administration is called «historical monuments administration» and is locally lead by a specialized architect.In the late seventies, French government decided to reduce advertising on the roads and on the city walls. Advertising on the road was leading to a confusion reducing the efficacy of the roadsigns and direction signs, which is dangerous. The reduction was under control of a national administration: the ministry of equipment in charge of the roads design. Advertising on the walls with publicity boards was under control of the cities. Every city has a townplanning regulation. Many cities included forbidding advertisement boards on the walls in this regulation.A couple of firms, but mainly once (Decaux found clever to give a hand to the cities to control advertising. Decaux developed a line of bus stop shelters including advertisements and advertising panels and paid the cities the right to put rather smaller publicities on the public domain.Now Decaux is no more alone on this market and the cities are comparing offers.Marseille turned to a foreign advertising firm who pays three times the price Decaux paid… for half of the advertising surface. Freiburg erased totally the public domain advertisements, selling the tramways and bus coachwork as advertising spaces. Paris is reopening the advertising market before the end of Deacaux's contract and will pay Deacaux a huge amount

  12. Reduced NOX combustion method

    International Nuclear Information System (INIS)

    Delano, M.A.

    1991-01-01

    This patent describes a method for combusting fuel and oxidant to achieve reduced formation of nitrogen oxides. It comprises: It comprises: heating a combustion zone to a temperature at least equal to 1500 degrees F.; injecting into the heated combustion zone a stream of oxidant at a velocity within the range of from 200 to 1070 feet per second; injecting into the combustion zone, spaced from the oxidant stream, a fuel stream at a velocity such that the ratio of oxidant stream velocity to fuel stream velocity does not exceed 20; aspirating combustion gases into the oxidant stream and thereafter intermixing the aspirated oxidant stream and fuel stream to form a combustible mixture; combusting the combustible mixture to produce combustion gases for the aspiration; and maintaining the fuel stream substantially free from contact with oxidant prior to the intermixture with aspirated oxidant

  13. Method of reducing zirconium

    International Nuclear Information System (INIS)

    Megy, J.A.

    1980-01-01

    A method was developed for making nuclear-grade zirconium from a zirconium compound, which ismore economical than previous methods since it uses aluminum as the reductant metal rather than the more expensive magnesium. A fused salt phase containing the zirconium compound to be reduced is first prepared. The fused salt phase is then contacted with a molten metal phase which contains aluminum and zinc. The reduction is effected by mutual displacment. Aluminum is transported from the molten metal phase to the fused salt phase, replacing zirconium in the salt. Zirconium is transported from the fused salt phase to the molten metal phase. The fused salt phase and the molten metal phase are then separated, and the solvent metal and zirconium are separated by distillation or other means. (DN)

  14. Generalized reduced magnetohydrodynamic equations

    International Nuclear Information System (INIS)

    Kruger, S.E.

    1999-01-01

    A new derivation of reduced magnetohydrodynamic (MHD) equations is presented. A multiple-time-scale expansion is employed. It has the advantage of clearly separating the three time scales of the problem associated with (1) MHD equilibrium, (2) fluctuations whose wave vector is aligned perpendicular to the magnetic field, and (3) those aligned parallel to the magnetic field. The derivation is carried out without relying on a large aspect ratio assumption; therefore this model can be applied to any general configuration. By accounting for the MHD equilibrium and constraints to eliminate the fast perpendicular waves, equations are derived to evolve scalar potential quantities on a time scale associated with the parallel wave vector (shear-Alfven wave time scale), which is the time scale of interest for MHD instability studies. Careful attention is given in the derivation to satisfy energy conservation and to have manifestly divergence-free magnetic fields to all orders in the expansion parameter. Additionally, neoclassical closures and equilibrium shear flow effects are easily accounted for in this model. Equations for the inner resistive layer are derived which reproduce the linear ideal and resistive stability criterion of Glasser, Greene, and Johnson. The equations have been programmed into a spectral initial value code and run with shear flow that is consistent with the equilibrium input into the code. Linear results of tearing modes with shear flow are presented which differentiate the effects of shear flow gradients in the layer with the effects of the shear flow decoupling multiple harmonics

  15. Reducing maintenance costs

    International Nuclear Information System (INIS)

    Zaiss, W.; Reuschle, K.; Baier, B.

    2002-01-01

    The increasingly more expensive maintenance measures, cuts in the cost budget, and the loss of know-how on the part of vendors all require a change of policy with respect to maintenance concepts of the part of operators. This also applies to the existing valve concepts, the drives included. Under these aspects, the current drive, which is self-actuated and actuated by outside media, for a parallel-plate valve of a nomial width of 700 was reconsidered. The effort served to reduce maintenance costs and, at the same time, simplify the drive concept as well as cut back on the number of in-service inspections. Moreover, the number of active components were to be minimized and installation conditions in the plant were to be improved. When the boundary conditions to be observed with respect to process technology had been laid down, the competent technical department developed a concept of modification of the drive. A major constituent part was the demonstration of the functioning capability of the new drive under accident conditions. It was achieved mainly by an analytical approach. In the resultant drive concept, the same control valves are employed to actuate a driving cylinder by means of self-actuation or by an outside medium as a function of pressure. (orig.) [de

  16. Generalized reduced MHD equations

    International Nuclear Information System (INIS)

    Kruger, S.E.; Hegna, C.C.; Callen, J.D.

    1998-07-01

    A new derivation of reduced magnetohydrodynamic (MHD) equations is presented. A multiple-time-scale expansion is employed. It has the advantage of clearly separating the three time scales of the problem associated with (1) MHD equilibrium, (2) fluctuations whose wave vector is aligned perpendicular to the magnetic field, and (3) those aligned parallel to the magnetic field. The derivation is carried out without relying on a large aspect ratio assumption; therefore this model can be applied to any general toroidal configuration. By accounting for the MHD equilibrium and constraints to eliminate the fast perpendicular waves, equations are derived to evolve scalar potential quantities on a time scale associated with the parallel wave vector (shear-alfven wave time scale), which is the time scale of interest for MHD instability studies. Careful attention is given in the derivation to satisfy energy conservation and to have manifestly divergence-free magnetic fields to all orders in the expansion parameter. Additionally, neoclassical closures and equilibrium shear flow effects are easily accounted for in this model. Equations for the inner resistive layer are derived which reproduce the linear ideal and resistive stability criterion of Glasser, Greene, and Johnson

  17. Soluble Endoglin as a new marker for prediction of pre-eclampsia in early pregnancy

    Directory of Open Access Journals (Sweden)

    Khaled Gaber

    2010-01-01

    Conclusion: Pregnant women who are at risk of developing pre-eclampsia can be offered measuring these markers as a screening method to point out those who are more likely to develop pre-eclampsia and warrant close observation and intervention.

  18. Serum Endoglin Levels in Patients Suffering from Systemic Sclerosis and Elevated Systolic Pulmonary Arterial Pressure

    Directory of Open Access Journals (Sweden)

    Paola Ximena Coral-Alvarado

    2010-01-01

    Full Text Available Background. Pulmonary arterial hypertension (PAH is the main cause of morbimortality in systemic sclerosis (SSc. Increased Eng expression has been demonstrated in SSc patients. Objective. Ascertaining serum levels of Eng in SSc patients with and without elevated systolic pulmonary arterial pressure (sPAP and comparing them with that of healthy volunteers. Methods. A cross-sectional study was carried out. A commercial ELISA kit was used for measuring serum concentrations of Eng in 60 subjects: 40 patients with SSc with and without elevated sPAP, compared to 20 healthy control subjects. Elevated sPAP was detected by echocardiogram. Results. No association between positive Eng and elevated sPAP was found when compared to the SSc without elevated sPAP group (OR=2.85; 0.65–12.88 95% CI; P=.11; however, an association was found between positive Eng and elevated sPAP compared to healthy controls (OR=23.22; 2.46–1050.33 95% CI; P=.001, and weak association was found between the positive Eng with SSc without elevated sPAP group compared to healthy controls (OR=8.14, 0.8–393.74 95% CI; P=.046. Conclusion. Raised serum levels of Eng in SSc patients compared to healthy controls were found, suggesting a role for Eng in SSc vasculopathy and not just in elevated sPAP. However, prospective studies are needed to verify such observations.

  19. Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

    NARCIS (Netherlands)

    Pardali, E.; Schaft, van der D.W.J.; Wiercinska, E.; Gorter, A.; Hogendoorn, P.C.W.; Griffioen, A.W.; Dijke, ten P.

    2011-01-01

    Tumor cell plasticity enables certain types of highly malignant tumor cells to dedifferentiate and engage a plastic multipotent embryonic-like phenotype, which enables them to ‘adapt’ during tumor progression and escape conventional therapeutic strategies. This plastic phenotype of aggressive cancer

  20. Reducing the impact.

    Science.gov (United States)

    Mahathir, M

    1997-01-01

    In Asia, attempts to control HIV/AIDS through education have not achieved the necessary behavior changes. This is especially true for young women who are unable to apply their knowledge to their sex behavior because of inequalities in gender relations. Thus, the impact of AIDS on women is significantly greater in settings where the status of women is low. Women in developing countries are at greatest risk because the epidemic is fueled by poverty, lack of information, and lack of autonomy. Prosperity in a developing country, such as Malaysia, entails its own risks because it creates new social norms and values that exist in tandem with debilitating old norms, such as the patriarchy that disempowers women and a resurgence in polygamy and wife abandonment. Subservient gender roles not only increase women's chances of infection, they also target women as the primary caregivers for infected individuals. Young girls may have to abandon school to care for infected parents, and female health care providers are assigned to the lowest ranks of the profession. While most women have been infected by their husbands, they must also bear the stigma of being considered immoral infectors of their husbands. The futures of AIDS widows and orphans is jeopardized by the discrimination that attends the disease, and if the mother dies, her young children face a higher death rate. In settings new to the epidemic, it is difficult to convince men of the importance of addressing women's needs and of seeking the input of women in policy and program development. Only by empowering both sexes to work together to protect society will there be a reasonable chance of reducing the impact of HIV/AIDS.

  1. Review of pump suction reducer selection: Eccentric or concentric reducers

    OpenAIRE

    Mahaffey, R M; van Vuuren, S J

    2014-01-01

    Eccentric reducers are traditionally recommended for the pump suction reducer fitting to allow for transportation of air through the fitting to the pump. The ability of a concentric reducer to provide an improved approach flow to the pump while still allowing air to be transported through the fitting is investigated. Computational fluid dynamics (CFD) were utilised to analyse six concentric and six eccentric reducer geometries at four different inlet velocities to determine the flow velocity ...

  2. Shrinkage Reducing Admixture for Concrete

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    Concrete shrinkage cracking is a common problem in all types of concrete structures, especially for structures and environments where the cracks are prevalent and the repercussions are most severe. A liquid shrinkage reducing admixture for concrete, developed by GRACE Construction Products and ARCO Chemical Company, that reduces significantly the shrinkage during concrete drying and potentially reduces overall cracking over time.

  3. Oxygen-reducing catalyst layer

    Science.gov (United States)

    O'Brien, Dennis P [Maplewood, MN; Schmoeckel, Alison K [Stillwater, MN; Vernstrom, George D [Cottage Grove, MN; Atanasoski, Radoslav [Edina, MN; Wood, Thomas E [Stillwater, MN; Yang, Ruizhi [Halifax, CA; Easton, E Bradley [Halifax, CA; Dahn, Jeffrey R [Hubley, CA; O'Neill, David G [Lake Elmo, MN

    2011-03-22

    An oxygen-reducing catalyst layer, and a method of making the oxygen-reducing catalyst layer, where the oxygen-reducing catalyst layer includes a catalytic material film disposed on a substrate with the use of physical vapor deposition and thermal treatment. The catalytic material film includes a transition metal that is substantially free of platinum. At least one of the physical vapor deposition and the thermal treatment is performed in a processing environment comprising a nitrogen-containing gas.

  4. Endogenous mobility-reducing norms

    NARCIS (Netherlands)

    Haagsma, R.; Koning, N.B.J.

    2002-01-01

    We present a model where a mobility-reducing norm arises in response to adverse economic conditions. Our example is the classical farm problem of low returns. A temporary transition barrier induces cognitive dissonance in farm youths, which they try to reduce by developing a belief that revalues

  5. Reducing Lookups for Invariant Checking

    DEFF Research Database (Denmark)

    Thomsen, Jakob Grauenkjær; Clausen, Christian; Andersen, Kristoffer Just

    2013-01-01

    This paper helps reduce the cost of invariant checking in cases where access to data is expensive. Assume that a set of variables satisfy a given invariant and a request is received to update a subset of them. We reduce the set of variables to inspect, in order to verify that the invariant is still...

  6. System for actively reducing sound

    NARCIS (Netherlands)

    Berkhoff, Arthur P.

    2005-01-01

    A system for actively reducing sound from a primary noise source, such as traffic noise, comprising: a loudspeaker connector for connecting to at least one loudspeaker for generating anti-sound for reducing said noisy sound; a microphone connector for connecting to at least a first microphone placed

  7. Reducing the Burden of Price.

    Science.gov (United States)

    Hansen, Janet S.

    1984-01-01

    Setting prices for undergraduate education and assessing their effects on consumers and institutions is complicated by widespread price discounting. Student aid programs, credit, subsidized employment, and tax policy can reduce the actual costs paid by students and their families. (MSE)

  8. Filtering reducer of flushing fluid

    Energy Technology Data Exchange (ETDEWEB)

    Secu, P; Apostu, M; Basarabescu, T; Popescu, F

    1981-02-28

    This is a patent of a filtering reducer of flushing fluid on a water base with low content of solid particles used at temperatures of roughly 200/sup 0/C. With the use of the proposed filtering reducer, there is no excessive increase in viscosity and gelatinization of the flushing fluids without restriction in the quantity of reducer needed to guarantee the required filtering. There is a possibility of recovering the polyalkylphenol vat residues obtained in the production of nonyl phenol. It is possible to reduce the time of treatment and dissolving of the product; there is no danger of plugging of the productive oil beds. The process of hydration of clay is excluded.

  9. Interference, reduced action, and trajectories

    OpenAIRE

    Floyd, Edward R.

    2006-01-01

    Instead of investigating the interference between two stationary, rectilinear wave functions in a trajectory representation by examining the two rectilinear wave functions individually, we examine a dichromatic wave function that is synthesized from the two interfering wave functions. The physics of interference is contained in the reduced action for the dichromatic wave function. As this reduced action is a generator of the motion for the dichromatic wave function, it determines the dichroma...

  10. Learning to REDUCE: A Reduced Electricity Consumption Prediction Ensemble

    Energy Technology Data Exchange (ETDEWEB)

    Aman, Saima; Chelmis, Charalampos; Prasanna, Viktor

    2016-02-12

    Utilities use Demand Response (DR) to balance supply and demand in the electric grid by involving customers in efforts to reduce electricity consumption during peak periods. To implement and adapt DR under dynamically changing conditions of the grid, reliable prediction of reduced consumption is critical. However, despite the wealth of research on electricity consumption prediction and DR being long in practice, the problem of reduced consumption prediction remains largely un-addressed. In this paper, we identify unique computational challenges associated with the prediction of reduced consumption and contrast this to that of normal consumption and DR baseline prediction.We propose a novel ensemble model that leverages different sequences of daily electricity consumption on DR event days as well as contextual attributes for reduced consumption prediction. We demonstrate the success of our model on a large, real-world, high resolution dataset from a university microgrid comprising of over 950 DR events across a diverse set of 32 buildings. Our model achieves an average error of 13.5%, an 8.8% improvement over the baseline. Our work is particularly relevant for buildings where electricity consumption is not tied to strict schedules. Our results and insights should prove useful to the researchers and practitioners working in the sustainable energy domain.

  11. Sleep can reduce proactive interference.

    Science.gov (United States)

    Abel, Magdalena; Bäuml, Karl-Heinz T

    2014-01-01

    Sleep has repeatedly been connected to processes of memory consolidation. While extensive research indeed documents beneficial effects of sleep on memory, little is yet known about the role of sleep for interference effects in episodic memory. Although two prior studies reported sleep to reduce retroactive interference, no sleep effect has previously been found for proactive interference. Here we applied a study format differing from that employed by the prior studies to induce a high degree of proactive interference, and asked participants to encode a single list or two interfering lists of paired associates via pure study cycles. Testing occurred after 12 hours of diurnal wakefulness or nocturnal sleep. Consistent with the prior work, we found sleep in comparison to wake did not affect memory for the single list, but reduced retroactive interference. In addition we found sleep reduced proactive interference, and reduced retroactive and proactive interference to the same extent. The finding is consistent with the view that arising benefits of sleep are caused by the reactivation of memory contents during sleep, which has been suggested to strengthen and stabilise memories. Such stabilisation may make memories less susceptible to competition from interfering memories at test and thus reduce interference effects.

  12. Six ways to reduce inventory.

    Science.gov (United States)

    Lunn, T

    1996-05-01

    The purpose of this presentation is to help you reduce the inventory in your operation. We will accomplish that task by discussing six specific methods that companies have used successfully to reduce their inventory. One common attribute of these successes is that they also build teamwork among the people. Every business operation today is concerned with methods to improve customer service. The real trick is to accomplish that task without increasing inventory. We are all concerned with improving our skills at keeping inventory low.

  13. The Gambling Reducing Slot Machine

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Thomsen, Kristine Rømer; Linnet, Jakob

    2007-01-01

      The Gambling Reducing Slot Machine - Preliminary results Mette Buhl Callesen, Kristine Rømer Thomsen, Jakob Linnet and Arne Møller The PET Centre, Aarhus University Hospital and Centre of Functionally Integrative Neuroscience, Aarhus, Denmark   Slot machines are among the most addictive forms...... and willingness to continue gambling. The results may have important implications for understanding how to reduce gambling behavior in pathological gamblers.   [1] Griffiths, M. 1999. Gambling Technologies: Prospects for Problem Gambling. Journal of Gambling Studies, vol. 15(3), pp. 265-283.    ...

  14. DOES FINANCIAL DEVELOPMENT REDUCE CORRUPTION?

    OpenAIRE

    John Thornton

    2009-01-01

    I estimate the impact of bank cred it to the private sector on corruption using indicators of a country's legal origin as instrumental variables to assess causality. I find that bank credit reduces corruption, with the result robust to instrumenting for bank credit and for different controls.

  15. Reduced False Memory after Sleep

    Science.gov (United States)

    Fenn, Kimberly M.; Gallo, David A.; Margoliash, Daniel; Roediger, Henry L., III; Nusbaum, Howard C.

    2009-01-01

    Several studies have shown that sleep contributes to the successful maintenance of previously encoded information. This research has focused exclusively on memory for studied events, as opposed to false memories. Here we report three experiments showing that sleep reduces false memories in the Deese-Roediger-McDermott (DRM) memory illusion. False…

  16. Reducing cement's CO2 footprint

    Science.gov (United States)

    van Oss, Hendrik G.

    2011-01-01

    The manufacturing process for Portland cement causes high levels of greenhouse gas emissions. However, environmental impacts can be reduced by using more energy-efficient kilns and replacing fossil energy with alternative fuels. Although carbon capture and new cements with less CO2 emission are still in the experimental phase, all these innovations can help develop a cleaner cement industry.

  17. Reducing ammonia emissions in Europe

    DEFF Research Database (Denmark)

    Jacobsen, Brian H.

    2011-01-01

    The NEC directive has set targets for the 2010 ammonia emissions from a number of European countries. The target will be reached by most EU-countries and the total emission for EU-27 has been reduced by 22% from 1990 to 2007. Denmark is one of the countries with the largest reductions since 1990...

  18. Does Microfinance Reduce Income Inequality?

    NARCIS (Netherlands)

    Hermes, Niels

    2014-01-01

    This study addresses the question whether participation of the poor in microfinance contributes to reducing a country’s level of income inequality. Using data from 70 developing countries, we show that higher levels of microfinance participation are indeed associated with a reduction of the income

  19. Ways to reduce miner absenteeism

    Energy Technology Data Exchange (ETDEWEB)

    1989-11-01

    Discussion is presented of the use of attendance programs at mines, to reduce interruptions to production, decrease labour costs, and to improve safety. Techniques described include use of absentee charts, frequency of attendance charts, and rewards for good attendance. 3 figs.

  20. SURFACE PROPERTIES OF ELECTROCHEMICALLY REDUCED ...

    African Journals Online (AJOL)

    DJFLEX

    A viscose rayon based activated carbon cloth (ACC) was electrochemically reduced ..... bath of liquid nitrogen at a temperature of 77 K. ... that above 59,400 c/g extent of oxidation, the ..... ACC react with aldehyde groups to produce ether.

  1. Distinguishing iron-reducing from sulfate-reducing conditions

    Science.gov (United States)

    Chapelle, F.H.; Bradley, P.M.; Thomas, M.A.; McMahon, P.B.

    2009-01-01

    Ground water systems dominated by iron- or sulfate-reducing conditions may be distinguished by observing concentrations of dissolved iron (Fe2+) and sulfide (sum of H2S, HS-, and S= species and denoted here as "H2S"). This approach is based on the observation that concentrations of Fe2+ and H2S in ground water systems tend to be inversely related according to a hyperbolic function. That is, when Fe2+ concentrations are high, H2S concentrations tend to be low and vice versa. This relation partly reflects the rapid reaction kinetics of Fe2+ with H2S to produce relatively insoluble ferrous sulfides (FeS). This relation also reflects competition for organic substrates between the iron- and the sulfate-reducing microorganisms that catalyze the production of Fe2+ and H 2S. These solubility and microbial constraints operate in tandem, resulting in the observed hyperbolic relation between Fe2+ and H 2S concentrations. Concentrations of redox indicators, including dissolved hydrogen (H2) measured in a shallow aquifer in Hanahan, South Carolina, suggest that if the Fe2+/H2S mass ratio (units of mg/L) exceeded 10, the screened interval being tapped was consistently iron reducing (H2 ???0.2 to 0.8 nM). Conversely, if the Fe 2+/H2S ratio was less than 0.30, consistent sulfate-reducing (H2 ???1 to 5 nM) conditions were observed over time. Concomitantly high Fe2+ and H2S concentrations were associated with H2 concentrations that varied between 0.2 and 5.0 nM over time, suggesting mixing of water from adjacent iron- and sulfate-reducing zones or concomitant iron and sulfate reduction under nonelectron donor-limited conditions. These observations suggest that Fe2+/H2S mass ratios may provide useful information concerning the occurrence and distribution of iron and sulfate reduction in ground water systems. ?? 2009 National Ground Water Association.

  2. Ferroelectric capacitor with reduced imprint

    Science.gov (United States)

    Evans, Jr., Joseph T.; Warren, William L.; Tuttle, Bruce A.; Dimos, Duane B.; Pike, Gordon E.

    1997-01-01

    An improved ferroelectric capacitor exhibiting reduced imprint effects in comparison to prior art capacitors. A capacitor according to the present invention includes top and bottom electrodes and a ferroelectric layer sandwiched between the top and bottom electrodes, the ferroelectric layer comprising a perovskite structure of the chemical composition ABO.sub.3 wherein the B-site comprises first and second elements and a dopant element that has an oxidation state greater than +4. The concentration of the dopant is sufficient to reduce shifts in the coercive voltage of the capacitor with time. In the preferred embodiment of the present invention, the ferroelectric element comprises Pb in the A-site, and the first and second elements are Zr and Ti, respectively. The preferred dopant is chosen from the group consisting of Niobium, Tantalum, and Tungsten. In the preferred embodiment of the present invention, the dopant occupies between 1 and 8% of the B-sites.

  3. Alcohol reduces aversion to ambiguity

    Directory of Open Access Journals (Sweden)

    Tadeusz eTyszka

    2015-01-01

    Full Text Available Several years ago, Cohen, Dearnaley, and Hansel [1] demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly [2]. The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar, where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women.

  4. Alcohol reduces aversion to ambiguity.

    Science.gov (United States)

    Tyszka, Tadeusz; Macko, Anna; Stańczak, Maciej

    2014-01-01

    Several years ago, Cohen et al. (1958) demonstrated that under the influence of alcohol drivers became more risk prone, although their risk perception remained unchanged. Research shows that ambiguity aversion is to some extent positively correlated with risk aversion, though not very highly (Camerer and Weber, 1992). The question addressed by the present research is whether alcohol reduces ambiguity aversion. Our research was conducted in a natural setting (a restaurant bar), where customers with differing levels of alcohol intoxication were offered a choice between a risky and an ambiguous lottery. We found that alcohol reduced ambiguity aversion and that the effect occurred in men but not women. We interpret these findings in terms of the risk-as-value hypothesis, according to which, people in Western culture tend to value risk, and suggest that alcohol consumption triggers adherence to socially and culturally valued patterns of conduct different for men and women.

  5. Breastfeeding reduces postpartum weight retention

    DEFF Research Database (Denmark)

    Baker, Jennifer Lyn; Gamborg, Michael; Heitmann, Berit L

    2008-01-01

    BACKGROUND: Weight gained during pregnancy and not lost postpartum may contribute to obesity in women of childbearing age. OBJECTIVE: We aimed to determine whether breastfeeding reduces postpartum weight retention (PPWR) in a population among which full breastfeeding is common and breastfeeding...... duration is long. DESIGN: We selected women from the Danish National Birth Cohort who ever breastfed (>98%), and we conducted the interviews at 6 (n = 36 030) and 18 (n = 26 846) mo postpartum. We used regression analyses to investigate whether breastfeeding (scored to account for duration and intensity......) reduced PPWR at 6 and 18 mo after adjustment for maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG). RESULTS: GWG was positively (P postpartum. Breastfeeding was negatively associated with PPWR in all women but those...

  6. Rheological measurements in reduced gravity

    Science.gov (United States)

    Bakhtiyarov, Sayavur I.; Overfelt, Ruel A.

    1999-01-01

    Rheology of fluidized beds and settling suspensions were studied experimentally in a series of reduced gravity parabolic flights aboard NASA's KC-135 aircraft. Silica sands of two different size distributions were fluidized by air. The slurries were made using silica sand and Glycerol solution. The experimental set up incorporated instrumentation to measure the air flow rate, the pressure drop and the apparent viscosity of the fluidized sand and sand suspensions at a wide range of the shear rates. The fluidization chamber and container had transparent walls to allow visualization of the structure changes involved in fluidization and in Couette flow in reduced gravity. Experiments were performed over a broad range of gravitational accelerations including microgravity and double gravity conditions. The results of the flight and ground experiments reveal significant differences in overall void fraction and hence in the apparent viscosity of fluidized sand and sand suspensions under microgravity as compared to one-g conditions.

  7. Reducing carbon dioxide to products

    Science.gov (United States)

    Cole, Emily Barton; Sivasankar, Narayanappa; Parajuli, Rishi; Keets, Kate A

    2014-09-30

    A method reducing carbon dioxide to one or more products may include steps (A) to (C). Step (A) may bubble said carbon dioxide into a solution of an electrolyte and a catalyst in a divided electrochemical cell. The divided electrochemical cell may include an anode in a first cell compartment and a cathode in a second cell compartment. The cathode may reduce said carbon dioxide into said products. Step (B) may adjust one or more of (a) a cathode material, (b) a surface morphology of said cathode, (c) said electrolyte, (d) a manner in which said carbon dioxide is bubbled, (e), a pH level of said solution, and (f) an electrical potential of said divided electrochemical cell, to vary at least one of (i) which of said products is produced and (ii) a faradaic yield of said products. Step (C) may separate said products from said solution.

  8. BCJ numerators from reduced Pfaffian

    Energy Technology Data Exchange (ETDEWEB)

    Du, Yi-Jian [Center for Theoretical Physics, School of Physics and Technology, Wuhan University,No. 299 Bayi Road, Wuhan 430072 (China); Teng, Fei [Department of Physics and Astronomy, University of Utah,115 South 1400 East, Salt Lake City, UT 84112 (United States)

    2017-04-07

    By expanding the reduced Pfaffian in the tree level Cachazo-He-Yuan (CHY) integrands for Yang-Mills (YM) and nonlinear sigma model (NLSM), we can get the Bern-Carrasco-Johansson (BCJ) numerators in Del Duca-Dixon-Maltoni (DDM) form for arbitrary number of particles in any spacetime dimensions. In this work, we give a set of very straightforward graphic rules based on spanning trees for a direct evaluation of the BCJ numerators for YM and NLSM. Such rules can be derived from the Laplace expansion of the corresponding reduced Pfaffian. For YM, the each one of the (n−2)! DDM form BCJ numerators contains exactly (n−1)! terms, corresponding to the increasing trees with respect to the color order. For NLSM, the number of nonzero numerators is at most (n−2)!−(n−3)!, less than those of several previous constructions.

  9. Correlated Electrons in Reduced Dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Bonesteel, Nicholas E [Florida State Univ., Tallahassee, FL (United States)

    2015-01-31

    This report summarizes the work accomplished under the support of US DOE grant # DE-FG02-97ER45639, "Correlated Electrons in Reduced Dimensions." The underlying hypothesis of the research supported by this grant has been that studying the unique behavior of correlated electrons in reduced dimensions can lead to new ways of understanding how matter can order and how it can potentially be used. The systems under study have included i) fractional quantum Hall matter, which is realized when electrons are confined to two-dimensions and placed in a strong magnetic field at low temperature, ii) one-dimensional chains of spins and exotic quasiparticle excitations of topologically ordered matter, and iii) electrons confined in effectively ``zero-dimensional" semiconductor quantum dots.

  10. Numbers for reducible cubic scrolls

    Directory of Open Access Journals (Sweden)

    Israel Vainsencher

    2004-12-01

    Full Text Available We show how to compute the number of reducible cubic scrolls of codimension 2 in (math blackboard symbol Pn incident to the appropriate number of linear spaces.Mostramos como calcular o número de rolos cúbicos redutíveis de codimensão 2 em (math blackboard symbol Pn incidentes a espaços lineares apropriados.

  11. Increasing sales by reducing procrastination

    OpenAIRE

    Gjedrem, William Gilje

    2012-01-01

    Master's thesis in Finance In this paper I analyze whether an intervention program increases productivity and sales, by reducing potential procrastination problems that employees face at work. The intervention was introduced to stores in a large retail chain in Norway, and contained different tools that could lead to lower perceived costs of higher effort. In a difference-in-differences analysis I find that the intervention increases sales after a 14 weeks long implementation period. Fu...

  12. Reduced Deforestation and Economic Growth

    OpenAIRE

    Patrick Doupe

    2014-01-01

    The clearing of forests for agricultural land and other marketable purposes is a well-trodden path of economic development. With these private benefits from deforestation come external costs: emissions from deforestation currently account for 12 per cent of global carbon emissions. A widespread intervention in reducing emissions from deforestation will affect the paths of agricultural expansion and economic growth of lower income nations. To investigate these processes, this paper presents a ...

  13. Relativistic mechanics with reduced fields

    International Nuclear Information System (INIS)

    Sokolov, S.N.

    1996-01-01

    A new relativistic classical mechanics of interacting particles using a concept of a reduced field (RF) os proposed. RF is a mediator of interactions, the state of which is described by a finite number of two-argument functions. Ten of these functions correspond to the generators of the Poincare group. Equations of motion contain the retardation of interactions required by the causality principle and have form of a finite system of ordinary hereditary differential equations [ru

  14. Reduced embodied simulation in psychopathy.

    Science.gov (United States)

    Mier, Daniela; Haddad, Leila; Diers, Kersten; Dressing, Harald; Meyer-Lindenberg, Andreas; Kirsch, Peter

    2014-08-01

    Psychopathy is characterized by severe deficits in emotion processing and empathy. These emotional deficits might not only affect the feeling of own emotions, but also the understanding of others' emotional and mental states. The present study aims on identifying the neurobiological correlates of social-cognitive related alterations in psychopathy. We applied a social-cognitive paradigm for the investigation of face processing, emotion recognition, and affective Theory of Mind (ToM) to 11 imprisoned psychopaths and 18 healthy controls. Functional magnetic resonance imaging was used to measure task-related brain activation. While showing no overall behavioural deficit, psychopathy was associated with altered brain activation. Psychopaths had reduced fusiform activation related to face processing. Related to affective ToM, psychopaths had hypoactivation in amygdala, inferior prefrontal gyrus and superior temporal sulcus, areas associated with embodied simulation of emotions and intentions. Furthermore, psychopaths lacked connectivity between superior temporal sulcus and amygdala during affective ToM. These results replicate findings of alterations in basal face processing in psychopathy. In addition, they provide evidence for reduced embodied simulation in psychopathy in concert with a lack of communication between motor areas and amygdala which might provide the neural substrate of reduced feeling with others during social cognition.

  15. Reducing consumption through communal living

    Energy Technology Data Exchange (ETDEWEB)

    Herring, Horace [The Open Univ., Milton Keynes (United Kingdom). Energy and Environment Research Unit

    2003-07-01

    This paper examines ways consumers and communities can voluntarily adopt a low consumption (or low carbon) lifestyle, often termed 'voluntary simplicity' or a policy of 'sufficiency'. There is an increasing academic literature within Europe in the last five years on the whole question of 'sustainable consumption', and the relationship between income levels and consumption particularly at the household. This debate has moved beyond 'green consumerism' to look at building 'new concepts of prosperity' through local community actions, or reducing working time to allow more time for the creation of social capital. The paper will concentrate on one aspect of the quest for sustainable communities, the relevance of communal living to reducing consumption through examining energy consumption (both direct and indirect) in one such community in the UK. The results from this preliminary study reveal that it is not the sharing of resources that reduces consumption but the mutual reinforcement of attitudes towards a low consumption lifestyle. Thus it is the creation of social capital in a community that is its key to its ecological lifestyle.

  16. Reduced Vlasov-Maxwell simulations

    International Nuclear Information System (INIS)

    Helluy, P.; Navoret, L.; Pham, N.; Crestetto, A.

    2014-01-01

    The Maxwell-Vlasov system is a fundamental model in physics. It can be applied to plasma simulations, charged particles beam, astrophysics, etc. The unknowns are the electromagnetic field, solution to the Maxwell equations and the distribution function, solution to the Vlasov equation. In this paper we review two different numerical methods for Vlasov-Maxwell simulations. The first method is based on a coupling between a Discontinuous Galerkin (DG) Maxwell solver and a Particle-In-Cell (PIC) Vlasov solver. The second method only uses a DG approach for the Vlasov and Maxwell equations. The Vlasov equation is first reduced to a space-only hyperbolic system thanks to the finite-element method. The two numerical methods are implemented using OpenCL in order to achieve high performance on recent Graphic Processing Units (GPU). We obtained interesting speedups, but we also observe that the PIC method is the most expensive part of the computation. Therefore we propose another fully Eulerian approach. Thanks to a decomposition of the distribution function on velocity basis functions, we obtain a reduced Vlasov model, which appears to be a hyperbolic system of conservation laws written only in the (x,t) space. We can thus adapt very easily our DG solver to the reduced model

  17. On nonlinear reduced order modeling

    International Nuclear Information System (INIS)

    Abdel-Khalik, Hany S.

    2011-01-01

    When applied to a model that receives n input parameters and predicts m output responses, a reduced order model estimates the variations in the m outputs of the original model resulting from variations in its n inputs. While direct execution of the forward model could provide these variations, reduced order modeling plays an indispensable role for most real-world complex models. This follows because the solutions of complex models are expensive in terms of required computational overhead, thus rendering their repeated execution computationally infeasible. To overcome this problem, reduced order modeling determines a relationship (often referred to as a surrogate model) between the input and output variations that is much cheaper to evaluate than the original model. While it is desirable to seek highly accurate surrogates, the computational overhead becomes quickly intractable especially for high dimensional model, n ≫ 10. In this manuscript, we demonstrate a novel reduced order modeling method for building a surrogate model that employs only 'local first-order' derivatives and a new tensor-free expansion to efficiently identify all the important features of the original model to reach a predetermined level of accuracy. This is achieved via a hybrid approach in which local first-order derivatives (i.e., gradient) of a pseudo response (a pseudo response represents a random linear combination of original model’s responses) are randomly sampled utilizing a tensor-free expansion around some reference point, with the resulting gradient information aggregated in a subspace (denoted by the active subspace) of dimension much less than the dimension of the input parameters space. The active subspace is then sampled employing the state-of-the-art techniques for global sampling methods. The proposed method hybridizes the use of global sampling methods for uncertainty quantification and local variational methods for sensitivity analysis. In a similar manner to

  18. Welfare-Reducing Trade Liberalization

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Jørgensen, Jan G.

    Recent literature on the workhorse model of intra-industry trade has explored heterogeneous cost structures at the firm level. These approaches have proven to add realism and predictive power. This note shows, however, that this added realism also implies that there may exist a positive bilateral...... tariff that maximizes national and world welfare. Applying one of the simplest specifications possible, namely a symmetric two-country intra-industry trade model with fixed export costs that are heterogeneous across firms, we find that the reciprocal reduction of small tariffs reduces welfare. We explore...

  19. Welfare-Reducing Trade Liberalization

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Jørgensen, Jan G.

    Recent literature on the workhorse model of intra-industry trade has explored heterogeneous cost structures at the firm level. These approaches have proven to add realism and predictive power. This paper shows, however, that this added realism also implies that there may exist a positive bilateral...... tariff that maximizes national and world welfare. Applying one of the simplest specifications possible, namely a symmetric two-country intra-industry trade model with fixed export costs that are heterogeneous across firms, we find that the reciprocal reduction of small tariffs reduces welfare....

  20. Reducing emissions from diesel combustion

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper contains information dealing with engine design to reduce emissions and improve or maintain fuel economy. Topics include: Observation of High Pressure Fuel Spray with Laser Light Sheet Method; Determination of Engine Cylinder Pressures from Crankshaft Speed Fluctuations; Combustion Similarity for Different Size Diesel Engines: Theoretical Prediction and Experimental Results; Prediction of Diesel Engine Particulate Emission During Transient Cycles; Characteristics and Combustibility of Particulate Matter; Dual-Fuel Diesel Engine Using Butane; Measurement of Flame Temperature Distribution in D.I. Diesel Engine with High Pressure Fuel Injection: and Combustion in a Small DI Diesel Engine at Starting

  1. Will sex selection reduce fertility?

    Science.gov (United States)

    Leung, S F

    1994-01-01

    Population control is one of the primary policies applied against poverty in many low income countries. The widespread prevalence of son preference in some countries such as China and India, however, works against any reduction of fertility. This is so because parents often continue to have children until they obtain the number of sons which they desire. The bias against girls has also led to higher abortion and mortality rates of female children. It is frequently argued that if sex selection methods are made available to parents so that they can control the gender of their children, population growth would be lowered and women's welfare improved. The author investigates both theoretically and numerically the impact of sex selection on fertility. A static quantity-quality model of fertility is used to compare fertility choices when parents cannot choose the gender of children versus a situation in which parents can choose gender. Empirical data are drawn from the 1976 Malaysian Family Life Survey. Analysis found that whether sex selection reduces fertility depends upon the second and third derivatives of the utility function and the child expenditure function. A numerical dynamic analysis is also presented. The simulation shows, using empirical dynamic models of fertility and the Monte Carlo integration technique, that sex selection on the firstborn child among the Chinese in Malaysia could reduce fertility by about 3%.

  2. Reduced prefrontal connectivity in psychopathy.

    Science.gov (United States)

    Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Koenigs, Michael

    2011-11-30

    Linking psychopathy to a specific brain abnormality could have significant clinical, legal, and scientific implications. Theories on the neurobiological basis of the disorder typically propose dysfunction in a circuit involving ventromedial prefrontal cortex (vmPFC). However, to date there is limited brain imaging data to directly test whether psychopathy may indeed be associated with any structural or functional abnormality within this brain area. In this study, we employ two complementary imaging techniques to assess the structural and functional connectivity of vmPFC in psychopathic and non-psychopathic criminals. Using diffusion tensor imaging, we show that psychopathy is associated with reduced structural integrity in the right uncinate fasciculus, the primary white matter connection between vmPFC and anterior temporal lobe. Using functional magnetic resonance imaging, we show that psychopathy is associated with reduced functional connectivity between vmPFC and amygdala as well as between vmPFC and medial parietal cortex. Together, these data converge to implicate diminished vmPFC connectivity as a characteristic neurobiological feature of psychopathy.

  3. Reduced Mastication Impairs Memory Function.

    Science.gov (United States)

    Fukushima-Nakayama, Y; Ono, Takehito; Hayashi, M; Inoue, M; Wake, H; Ono, Takashi; Nakashima, T

    2017-08-01

    Mastication is an indispensable oral function related to physical, mental, and social health throughout life. The elderly tend to have a masticatory dysfunction due to tooth loss and fragility in the masticatory muscles with aging, potentially resulting in impaired cognitive function. Masticatory stimulation has influence on the development of the central nervous system (CNS) as well as the growth of maxillofacial tissue in children. Although the relationship between mastication and cognitive function is potentially important in the growth period, the cellular and molecular mechanisms have not been sufficiently elucidated. Here, we show that the reduced mastication resulted in impaired spatial memory and learning function owing to the morphological change and decreased activity in the hippocampus. We used an in vivo model for reduced masticatory stimuli, in which juvenile mice were fed with powder diet and found that masticatory stimulation during the growth period positively regulated long-term spatial memory to promote cognitive function. The functional linkage between mastication and brain was validated by the decrease in neurons, neurogenesis, neuronal activity, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These findings taken together provide in vivo evidence for a functional linkage between mastication and cognitive function in the growth period, suggesting a need for novel therapeutic strategies in masticatory function-related cognitive dysfunction.

  4. Hypothermia reduces sulphur mustard toxicity

    International Nuclear Information System (INIS)

    Mi Lei; Gong Wenrong; Nelson, Peggy; Martin, Leanne; Sawyer, Thomas W.

    2003-01-01

    The effect of temperature on the development of sulphur mustard (HD)-induced toxicity was investigated in first passage cultures of human skin keratinocytes and on hairless guinea pig skin. When cells exposed to HD were incubated at 37 deg. C, a concentration-dependent decline in viability was observed that was maximal by 2 days. In contrast, no significant HD-induced toxicity was evident up to 4 days posttreatment when the cells were incubated at 25 deg. C. However, these protective effects were lost by 24 h when the cells were switched back to 37 deg. C. The protective effects of hypothermia were also demonstrated when apoptotic endpoints were examined. The HD concentration-dependent induction of fragmented DNA (as quantitated using soluble DNA and the TUNEL reaction), morphology, and p53 expression were all significantly depressed when cell cultures were incubated at 25 deg. C compared to 37 deg. C. When animals were exposed to HD vapour for 2, 4, and 6 min and left at room temperature, lesions were produced whose severity was dependent on exposure time and that were maximal by 72 h posttreatment. Moderate cooling (5-10 deg. C) of HD exposure sites posttreatment (4-6 h) significantly reduced the severity of the resultant lesions. However, in contrast to the in vitro results, these effects were permanent. It appears that the early and noninvasive act of cooling HD-exposed skin may provide a facile means of reducing the severity of HD-induced cutaneous lesions

  5. The HCM-linked W792R mutation in cardiac myosin-binding protein C reduces C6 FnIII domain stability.

    Science.gov (United States)

    Smelter, Dan F; de Lange, Willem J; Cai, Wenxuan; Ge, Ying; Ralphe, J Carter

    2018-06-01

    haploinsufficiency. NEW & NOTEWORTHY This study is one of the first to describe a disease mechanism for a missense mutation in cardiac myosin-binding protein C linked to hypertrophic cardiomyopathy. The mutation decreases stability of the fibronectin type III domain and results in substantially reduced mutant protein expression dissonant to transcript abundance.

  6. Reducing noise in uranium exploration

    International Nuclear Information System (INIS)

    Ward, W.J. III.

    1977-01-01

    A method and apparatus are described for reducing or removing the background noise caused by thoron gas ( 220 Rn) in uranium exploration conducted by the detection of radon gas ( 222 Rn) emanating from the ground. This is accomplished by the use of a number of alpha particle detectors, each of which is disposed in a protective enclosure. A permselective membrane, which permits, but selectively retards, the passage therethrough of gases is disposed in the path to be traversed before such gases can reach the alpha particle detector. The retarding influence of the membrane should be sufficient to make the concentration of thoron inside the enclosure small relative to the concentration of thoron outside the enclosure. The influence of the membrane of radon should be negligible, i.e., the radon concentration inside and outside the enclosure should be substantially equal

  7. Reducing Susceptibility to Courtesy Stigma.

    Science.gov (United States)

    Bachleda, Catherine L; El Menzhi, Leila

    2018-06-01

    In light of the chronic shortage of health professionals willing to care for HIV/AIDS patients, and rising epidemics in many Muslim countries, this qualitative study examined susceptibility and resistance to courtesy stigma as experienced by nurses, doctors, and social workers in Morocco. Forty-nine in-depth interviews provided rich insights into the process of courtesy stigma and how it is managed, within the context of interactions with Islam, interactions within the workplace (patients, other health professionals), and interactions outside the workplace (the general public, friends, and family). Theoretically, the findings extend understanding of courtesy stigma and the dirty work literature. The findings also offer practical suggestions for the development of culturally appropriate strategies to reduce susceptibility to courtesy stigmatization. This study represents the first to explore courtesy stigma as a process experienced by health professionals providing HIV/AIDS care in an Islamic country.

  8. Moral Violations Reduce Oral Consumption

    Science.gov (United States)

    Chan, Cindy; Van Boven, Leaf; Andrade, Eduardo B.; Ariely, Dan

    2014-01-01

    Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that “moral disgust” influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior. PMID:25125931

  9. Moral Violations Reduce Oral Consumption.

    Science.gov (United States)

    Chan, Cindy; Van Boven, Leaf; Andrade, Eduardo B; Ariely, Dan

    2014-07-01

    Consumers frequently encounter moral violations in everyday life. They watch movies and television shows about crime and deception, hear news reports of corporate fraud and tax evasion, and hear gossip about cheaters and thieves. How does exposure to moral violations influence consumption? Because moral violations arouse disgust and because disgust is an evolutionarily important signal of contamination that should provoke a multi-modal response, we hypothesize that moral violations affect a key behavioral response to disgust: reduced oral consumption. In three experiments, compared with those in control conditions, people drank less water and chocolate milk while (a) watching a film portraying the moral violations of incest, (b) writing about moral violations of cheating or theft, and (c) listening to a report about fraud and manipulation. These findings imply that "moral disgust" influences consumption in ways similar to core disgust, and thus provide evidence for the associations between moral violations, emotions, and consumer behavior.

  10. The ITER reduced cost design

    International Nuclear Information System (INIS)

    Aymar, R.

    2000-01-01

    Six years of joint work under the international thermonuclear experimental reactor (ITER) EDA agreement yielded a mature design for ITER which met the objectives set for it (ITER final design report (FDR)), together with a corpus of scientific and technological data, large/full scale models or prototypes of key components/systems and progress in understanding which both validated the specific design and are generally applicable to a next step, reactor-oriented tokamak on the road to the development of fusion as an energy source. In response to requests from the parties to explore the scope for addressing ITER's programmatic objective at reduced cost, the study of options for cost reduction has been the main feature of ITER work since summer 1998, using the advances in physics and technology databases, understandings, and tools arising out of the ITER collaboration to date. A joint concept improvement task force drawn from the joint central team and home teams has overseen and co-ordinated studies of the key issues in physics and technology which control the possibility of reducing the overall investment and simultaneously achieving the required objectives. The aim of this task force is to achieve common understandings of these issues and their consequences so as to inform and to influence the best cost-benefit choice, which will attract consensus between the ITER partners. A report to be submitted to the parties by the end of 1999 will present key elements of a specific design of minimum capital investment, with a target cost saving of about 50% the cost of the ITER FDR design, and a restricted number of design variants. Outline conclusions from the work of the task force are presented in terms of physics, operations, and design of the main tokamak systems. Possible implications for the way forward are discussed

  11. Breastfeeding Reduces Childhood Obesity Risks.

    Science.gov (United States)

    Wang, Liang; Collins, Candice; Ratliff, Melanie; Xie, Bin; Wang, Youfa

    2017-06-01

    The present study examined the effects of breastfeeding and its duration on the development of childhood obesity from 24 months through grade 6. U.S. longitudinal data collected from 1234 children were analyzed using logistic regression models and generalized estimating equation (GEE). Child height and weight were measured six times at ages of 24 months, 36 months, 54 months, grade 1, grade 3, and grade 6. During the early 1990s, prevalence of breastfeeding was low in the United States, 60% and 48% at 1 and 6 months, respectively. Nonsmoking, white, married mothers with both parents in the household, and with income above the poverty line, were more likely to breastfeed at 1 month of age of their babies. Obesity rate of the children increased with age from 24 months to grade 6. Logistic regression showed that breastfeeding at month 1 was associated with 53% (odds ratio [OR]: 0.47, 95% confidence interval [CI]: 0.30-0.73) and 47% (OR: 0.53, 95% CI: 0.36-0.78) decreased risks for childhood obesity at grades 1 and 6, respectively. GEE analysis showed that breastfeeding at 1 month reduced risk for childhood obesity by 36% (95% CI: 0.47-0.88) from ages 24 months through grade 6. Regarding breastfeeding duration, more than 6 months (vs. never) was associated with a decreased risk for childhood obesity by 42% (OR: 0.58, 95% CI: 0.36-0.94). Breastfeeding at 1 month and more than 6 months reduced the risk of childhood obesity. Rate of breastfeeding was low in the United States in the 1990s, which may have had long-term implications on children.

  12. SIR (Safe Integral Reactor) - reducing size can reduce cost

    International Nuclear Information System (INIS)

    Hayns, M.R.

    1991-01-01

    Traditional engineering economics have favoured the advantages of larger size as a means of reducing specific capital costs and hence unit generating costs. For large and small plants utilising the same concept, e.g. a small four-loop PWR vs a large four-loop PWR with the same number of components, economies of scale are well established. If, however, a smaller plant is sized to take advantage of features which are only feasible at smaller outputs, is of simpler design, with the advantage taken of the simplified design to produce the most cost-effective layout, and incorporates fewer, more easily replaceable components with minimal assembly on site, it is possible to produce a plant which is competitive with larger plant of more traditional design. When 'system' effects, such as better matching of installed capacity to the growth in demand and the fact that a smaller total capacity will be needed to meet a given demand with a specified level of confidence, are taken into account, it can be shown that a utility's overall cash-flow position can be improved with lower associated absolute financial risks. The UK/US Safe Integral Reactor (SIR) is an integral pressurized water reactor in the 300-400 MW(e) range which utilises conventional water reactor technology in a way not feasible at the very large, sizes of recent years. The SIR concept is briefly explained and its technical and economic advantages in terms of simplicity, construction, maintenance, availability, decommissioning, safety and siting described. The results of system analyses which demonstrate the overall financial advantages to a utility are presented. (author)

  13. Reducing stillbirths: interventions during labour

    Science.gov (United States)

    Darmstadt, Gary L; Yakoob, Mohammad Yawar; Haws, Rachel A; Menezes, Esme V; Soomro, Tanya; Bhutta, Zulfiqar A

    2009-01-01

    Background Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined. Methods We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies. Results We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact

  14. The benefits of reduced morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Krupnick, A; Hood, C; Harrison, K

    1994-07-01

    Morbidity benefits refer to increases in utility arising from reductions in incidents of acute health impairments and from increases in the probability of developing chronic diseases. The impairments would run the gamut from a cough-day to a bed-disability-day, while the chronic diseases include classic pollution-related diseases, such as cancer, to in utero effects and learning disabilities. As with mortality benefits, there could be benefits to oneself and family and friends as well as benefits based on altruism. A major difference between the mortality and morbidity valuation literatures is that while estimates of the former are always based on risk (one is never trying to obtain values for avoiding certain death), estimates of the latter generally are not. That is, most of the theory and empirical estimates are based on models where the effect to be avoided is certain. This assumption holds reasonably well for estimating common acute effects, for example, the willingness to pay (WTP) for one less cough-day. It works less well, if at all, for chronic illness endpoints, where benefits seem to be appropriately expressed in terms of reduced risk of developing a disease or impairment.

  15. Incorrect predictions reduce switch costs.

    Science.gov (United States)

    Kleinsorge, Thomas; Scheil, Juliane

    2015-07-01

    In three experiments, we combined two sources of conflict within a modified task-switching procedure. The first source of conflict was the one inherent in any task switching situation, namely the conflict between a task set activated by the recent performance of another task and the task set needed to perform the actually relevant task. The second source of conflict was induced by requiring participants to guess aspects of the upcoming task (Exps. 1 & 2: task identity; Exp. 3: position of task precue). In case of an incorrect guess, a conflict accrues between the representation of the guessed task and the actually relevant task. In Experiments 1 and 2, incorrect guesses led to an overall increase of reaction times and error rates, but they reduced task switch costs compared to conditions in which participants predicted the correct task. In Experiment 3, incorrect guesses resulted in faster performance overall and to a selective decrease of reaction times in task switch trials when the cue-target interval was long. We interpret these findings in terms of an enhanced level of controlled processing induced by a combination of two sources of conflict converging upon the same target of cognitive control. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. The benefits of reduced morbidity

    International Nuclear Information System (INIS)

    Krupnick, A.; Hood, C.; Harrison, K.

    1994-01-01

    Morbidity benefits refer to increases in utility arising from reductions in incidents of acute health impairments and from increases in the probability of developing chronic diseases. The impairments would run the gamut from a cough-day to a bed-disability-day, while the chronic diseases include classic pollution-related diseases, such as cancer, to in utero effects and learning disabilities. As with mortality benefits, there could be benefits to oneself and family and friends as well as benefits based on altruism. A major difference between the mortality and morbidity valuation literatures is that while estimates of the former are always based on risk (one is never trying to obtain values for avoiding certain death), estimates of the latter generally are not. That is, most of the theory and empirical estimates are based on models where the effect to be avoided is certain. This assumption holds reasonably well for estimating common acute effects, for example, the willingness to pay (WTP) for one less cough-day. It works less well, if at all, for chronic illness endpoints, where benefits seem to be appropriately expressed in terms of reduced risk of developing a disease or impairment

  17. Quantifying and Reducing Light Pollution

    Science.gov (United States)

    Gokhale, Vayujeet; Caples, David; Goins, Jordan; Herdman, Ashley; Pankey, Steven; Wren, Emily

    2018-06-01

    We describe the current level of light pollution in and around Kirksville, Missouri and around Anderson Mesa near Flagstaff, Arizona. We quantify the amount of light that is projected up towards the sky, instead of the ground, using Unihedron sky quality meters installed at various locations. We also present results from DSLR photometry of several standard stars, and compare the photometric quality of the data collected at locations with varying levels of light pollution. Presently, light fixture shields and ‘warm-colored’ lights are being installed on Truman State University’s campus in order to reduce light pollution. We discuss the experimental procedure we use to test the effectiveness of the different light fixtures shields in a controlled setting inside the Del and Norma Robison Planetarium.Apart from negatively affecting the quality of the night sky for astronomers, light pollution adversely affects migratory patterns of some animals and sleep-patterns in humans, increases our carbon footprint, and wastes resources and money. This problem threatens to get particularly acute with the increasing use of outdoor LED lamps. We conclude with a call to action to all professional and amateur astronomers to act against the growing nuisance of light pollution.

  18. Variational integrators for reduced magnetohydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, Michael, E-mail: michael.kraus@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Boltzmannstraße 2, 85748 Garching (Germany); Technische Universität München, Zentrum Mathematik, Boltzmannstraße 3, 85748 Garching (Germany); Tassi, Emanuele, E-mail: tassi@cpt.univ-mrs.fr [Aix-Marseille Université, Université de Toulon, CNRS, CPT, UMR 7332, 163 avenue de Luminy, case 907, 13288 cedex 9 Marseille (France); Grasso, Daniela, E-mail: daniela.grasso@infm.polito.it [ISC-CNR and Politecnico di Torino, Dipartimento Energia, C.so Duca degli Abruzzi 24, 10129 Torino (Italy)

    2016-09-15

    Reduced magnetohydrodynamics is a simplified set of magnetohydrodynamics equations with applications to both fusion and astrophysical plasmas, possessing a noncanonical Hamiltonian structure and consequently a number of conserved functionals. We propose a new discretisation strategy for these equations based on a discrete variational principle applied to a formal Lagrangian. The resulting integrator preserves important quantities like the total energy, magnetic helicity and cross helicity exactly (up to machine precision). As the integrator is free of numerical resistivity, spurious reconnection along current sheets is absent in the ideal case. If effects of electron inertia are added, reconnection of magnetic field lines is allowed, although the resulting model still possesses a noncanonical Hamiltonian structure. After reviewing the conservation laws of the model equations, the adopted variational principle with the related conservation laws is described both at the continuous and discrete level. We verify the favourable properties of the variational integrator in particular with respect to the preservation of the invariants of the models under consideration and compare with results from the literature and those of a pseudo-spectral code.

  19. Reducing power usage on demand

    Science.gov (United States)

    Corbett, G.; Dewhurst, A.

    2016-10-01

    The Science and Technology Facilities Council (STFC) datacentre provides large- scale High Performance Computing facilities for the scientific community. It currently consumes approximately 1.5MW and this has risen by 25% in the past two years. STFC has been investigating leveraging preemption in the Tier 1 batch farm to save power. HEP experiments are increasing using jobs that can be killed to take advantage of opportunistic CPU resources or novel cost models such as Amazon's spot pricing. Additionally, schemes from energy providers are available that offer financial incentives to reduce power consumption at peak times. Under normal operating conditions, 3% of the batch farm capacity is wasted due to draining machines. By using preempt-able jobs, nodes can be rapidly made available to run multicore jobs without this wasted resource. The use of preempt-able jobs has been extended so that at peak times machines can be hibernated quickly to save energy. This paper describes the implementation of the above and demonstrates that STFC could in future take advantage of such energy saving schemes.

  20. Hamiltonian formulation of reduced magnetohydrodynamics

    International Nuclear Information System (INIS)

    Morrison, P.J.; Hazeltine, R.D.

    1983-07-01

    Reduced magnetohydrodynamics (RMHD) has become a principal tool for understanding nonlinear processes, including disruptions, in tokamak plasmas. Although analytical studies of RMHD turbulence have been useful, the model's impressive ability to simulate tokamak fluid behavior has been revealed primarily by numerical solution. The present work describes a new analytical approach, not restricted to turbulent regimes, based on Hamiltonian field theory. It is shown that the nonlinear (ideal) RMHD system, in both its high-beta and low-beta versions, can be expressed in Hanmiltonian form. Thus a Poisson bracket, [ , ], is constructed such that each RMHD field quantitity, xi/sub i/, evolves according to xi/sub i/ = [xi/sub i/,H], where H is the total field energy. The new formulation makes RMHD accessible to the methodology of Hamiltonian mechanics; it has lead, in particular, to the recognition of new RMHD invariants and even exact, nonlinear RMHD solutions. A canonical version of the Poisson bracket, which requires the introduction of additional fields, leads to a nonlinear variational principle for time-dependent RMHD

  1. Generalized Reduced Order Model Generation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — M4 Engineering proposes to develop a generalized reduced order model generation method. This method will allow for creation of reduced order aeroservoelastic state...

  2. Process for reducing the pertechnetate anion

    International Nuclear Information System (INIS)

    Ruddock, C.F.

    1980-01-01

    Process for reducing the 'pertechnetate' ion TcO 4 - , whereby an aqueous solution of 'pertechnetate' is mixed with tin metal or a tin alloy as 'pertechnetate' reducing agent, and a soluble salt of a metal below tin in the electro-chemical tension scale, as activator for the reducing tin. This reduced 'pertechnetate' is used for forming usable complexes in medical diagnosis exploration [fr

  3. Reducing Sugar in Children's Diets: Why? How?

    Science.gov (United States)

    Rogers, Cosby S.; Morris, Sandra S.

    1986-01-01

    Maintains that sugar intake should be reduced in young children's diets because of its link to dental cavities, poor nutrition, and obesity. Reducing the focus on sweetness, limiting sugar consumption, and using natural sources of sweetness and other treats are ways to help reduce sugar intake. (BB)

  4. Servo Reduces Friction In Flexure Bearing

    Science.gov (United States)

    Clingman, W. Dean

    1991-01-01

    Proposed servocontrol device reduces such resistive torques as stiction, friction, ripple, and cogging in flexure bearing described in LAR-14348, "Flexure Bearing Reduces Startup Friction". Reduces frictional "bump" torque encountered when bearing ball runs into buildup of grease on bearing race. Also used as cable follower to reduce torque caused by cable and hoses when they bend because of motion of bearing. New device includes torquer across ball race. Torquer controlled by servo striving to keep flexure at null, removing torque to outer ring. In effect, device is inner control loop reducing friction, but does not control platforms or any outer-control-loop functions.

  5. Microprocessor Protection of Power Reducing Transformers

    Directory of Open Access Journals (Sweden)

    F. A. Romanuk

    2011-01-01

    Full Text Available The paper contains analysis of advantages and disadvantages of existing differential protection terminals of power reducing transformers. The paper shows that there are good reasons to develop microprocessor protection of power reducing transformer which contains required functions and settings and which is based on Belarusian principles of relay protection system construction. The paper presents functional structure of microprocessor terminal of power reducing transformer which is developed. 

  6. Microprocessor Protection of Power Reducing Transformers

    OpenAIRE

    F. A. Romanuk; S. P. Korolev; M. S. Loman

    2011-01-01

    The paper contains analysis of advantages and disadvantages of existing differential protection terminals of power reducing transformers. The paper shows that there are good reasons to develop microprocessor protection of power reducing transformer which contains required functions and settings and which is based on Belarusian principles of relay protection system construction. The paper presents functional structure of microprocessor terminal of power reducing transformer which is developed. 

  7. 40 CFR 141.623 - Reduced monitoring.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Reduced monitoring. 141.623 Section....623 Reduced monitoring. (a) You may reduce monitoring to the level specified in the table in this paragraph (a) any time the LRAA is ≤0.040 mg/L for TTHM and ≤0.030 mg/L for HAA5 at all monitoring locations...

  8. Reduced kinetic equations: An influence functional approach

    International Nuclear Information System (INIS)

    Wio, H.S.

    1985-01-01

    The author discusses a scheme for obtaining reduced descriptions of multivariate kinetic equations based on the 'influence functional' method of Feynmann. It is applied to the case of Fokker-Planck equations showing the form that results for the reduced equation. The possibility of Markovian or non-Markovian reduced description is discussed. As a particular example, the reduction of the Kramers equation to the Smoluchwski equation in the limit of high friction is also discussed

  9. Bactericide for sulfate-reducing bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Shklyar, T F; Anoshina, G M; Blokhin, V Ye; Kisarrev, Ye L; Novikovsa, G M

    1981-01-01

    The aim of the invention is to find a bactericide for sulfate-reducing bacteria of oil fields in Western Siberia in order to suppress the biocorrosive activity on oil industry equipment. This goal is achieved by using M-nitroacetanylide as the bactericide of sulfate-reducing bacteria. This agent suppresses the activity of a stored culture of sulfate-reducing bacteria that comes from industrial waste waters injection wells of the Smotlor oil field.

  10. Rescue of TET2 Haploinsufficiency in Myelodysplastic Syndrome Patients Using Turbo Cosubstrate

    Science.gov (United States)

    2017-07-01

    prevalent in a number of myeloid malignancies such as MDS-myeloproliferative neoplasms (MDS-MPN) and acute myeloid leukemia derived from MDS and MDS...Myelodysplastic syndromes (MDS), MDS-myeloproliferative neoplasms (MDS-MPN), Acute myeloid leukemia (AML), 5-methylcytosine (5mC), Mutation...normal initially, with age, develop diverse myeloid malignancies similar to humans. The objective in this project is to develop effective strategies

  11. Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice.

    OpenAIRE

    Lengacher Sylvain; Nehiri-Sitayeb Touria; Steiner Nadia; Carneiro Lionel; Favrod Céline; Preitner Frédéric; Thorens Bernard; Stehle Jean-Christophe; Dix Laure; Pralong François; Magistretti Pierre J; Pellerin Luc

    2013-01-01

    The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1(+/-) mice developed normally. However, when fed high fat diet (HFD), MCT1(+/-) mice displayed resistance to development of diet-induced obesity ...

  12. Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure

    Directory of Open Access Journals (Sweden)

    Nusinowitz Steven

    2001-11-01

    Full Text Available Abstract Background Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP. In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma. Results Bmp4+/- mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities, over 80% or more of their angle's extent, have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve. Conclusions We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp4+/- mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.

  13. Characterizing haploinsufficiency of SHELL gene to improve fruit form prediction in introgressive hybrids of oil palm

    OpenAIRE

    Teh, Chee Keng; Muaz, Siti Dalila; Tangaya, Praveena; Fong, Po-Yee; Ong, Ai Ling; Mayes, Sean; Chew, Fook Tim; Kulaveerasingam, Harikrishna; Appleton, David Ross

    2017-01-01

    The fundamental trait in selective breeding of oil palm (Eleais guineensis Jacq.) is the shell thickness surrounding the kernel. The monogenic shell thickness is inversely correlated to mesocarp thickness, where the crude palm oil accumulates. Commercial thin-shelled tenera derived from thick-shelled dura???shell-less pisifera generally contain 30% higher oil per bunch. Two mutations, sh MPOB (M1) and sh AVROS (M2) in the SHELL gene ? a type II MADS-box transcription factor mainly present in ...

  14. Deletion mutagenesis identifies a haploinsufficient role for gamma-zein in opaque-2 endosperm modification

    Science.gov (United States)

    Quality Protein Maize (QPM) is a hard kernel variant of the high-lysine mutant, opaque-2. Using gamma irradiation, we created opaque QPM variants to identify opaque-2 modifier genes and to investigate deletion mutagenesis combined with Illumina sequencing as a maize functional genomics tool. A K0326...

  15. Exercise does not protect against MPTP-induced neurotoxicity in BDNF haploinsufficient mice.

    Directory of Open Access Journals (Sweden)

    Kim M Gerecke

    Full Text Available Exercise has been demonstrated to potently protect substantia nigra pars compacta (SN dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicity. One mechanism proposed to account for this neuroprotection is the upregulation of neurotrophic factors. Several neurotrophic factors, including Brain Derived Neurotrophic Factor (BDNF, have been shown to upregulate in response to exercise. In order to determine if exercise-induced neuroprotection is dependent upon BDNF, we compared the neuroprotective effects of voluntary exercise in mice heterozygous for the BDNF gene (BDNF+/- with strain-matched wild-type (WT mice. Stereological estimates of SNpc DA neurons from WT mice allowed 90 days exercise via unrestricted running demonstrated complete protection against the MPTP-induced neurotoxicity. However, BDNF+/- mice allowed 90 days of unrestricted exercise were not protected from MPTP-induced SNpc DA neuron loss. Proteomic analysis comparing SN and striatum from 90 day exercised WT and BDNF+/- mice showed differential expression of proteins related to energy regulation, intracellular signaling and trafficking. These results suggest that a full genetic complement of BDNF is critical for the exercise-induced neuroprotection of SNpc DA neurons.

  16. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    Directory of Open Access Journals (Sweden)

    Ullrich Stephen E

    2011-01-01

    Full Text Available Abstract Background The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. Methods UVB-irradiated p53+/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. Results UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19+, CD5+, B220+, IgM+ and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19 translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. Conclusion UV-irradiated p53+/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal tumors after chronic exposure to UV light. The induction of B cell lymphoma in UV-irradiated p53 heterozygous mice may provide a useful model for lymphoma development in humans.

  17. VDR haploinsufficiency impacts body composition and skeletal acquisition in a gender-specific manner.

    Science.gov (United States)

    de Paula, Francisco J A; Dick-de-Paula, Ingrid; Bornstein, Sheila; Rostama, Bahman; Le, Phuong; Lotinun, Sutada; Baron, Roland; Rosen, Clifford J

    2011-09-01

    The vitamin D receptor (VDR) is crucial for virtually all of vitamin D's actions and is thought to be ubiquitously expressed. We hypothesized that disruption of one allele of the VDR gene would impact bone development and would have metabolic consequences. Body composition and bone mass (BMD) in VDR heterozygous (VDR HET) mice were compared to those obtained in male and female VDR KO and WT mice at 8 weeks of age. Male mice were also evaluated at 16 weeks, and bone marrow mesenchymal stem cell (MSC) differentiation was evaluated in VDR female mice. Additionally, female VDR HET and WT mice received intermittent PTH treatment or vehicle (VH) for 4 weeks. BMD was determined at baseline and after treatment. MRI was done in vivo at the end of treatment; μCT and bone histomorphometry were performed after killing the animals. VDR HET male mice had normal skeletal development until 16 weeks of age but showed significantly less gain in fat mass than WT mice. In contrast, female VDR HET mice showed decreased total-body BMD at age 8 weeks but had a normal skeletal response to PTH. MSC differentiation was also impaired in VDR HET female mice. Thus, female VDR HET mice show early impairment in bone acquisition, while male VDR HET mice exhibit a lean phenotype. Our results indicate that the VDR HET mouse is a useful model for studying the metabolic and skeletal impact of decreased vitamin D sensitivity.

  18. Induction of B-cell lymphoma by UVB Radiation in p53 Haploinsufficient Mice

    International Nuclear Information System (INIS)

    Puebla-Osorio, Nahum; Miyahara, Yasuko; Coimbatore, Sreevidya; Limón-Flores, Alberto Y; Kazimi, Nasser; Ullrich, Stephen E; Zhu, Chengming

    2011-01-01

    The incidence of non-Hodgkin's lymphoma has increased over recent years. The exact etiology of lymphoma remains unknown. Ultraviolet light exposure has been associated with the development of internal lymphoid malignancies and some reports suggest that it may play a role in the development of lymphoma in humans. Here we describe the characterization and progression of lymphoma in p53 heterozygous mice exposed to UVB irradiation. UVB-irradiated p53 +/- mice developed enlargement of the spleen. Isolated spleen cells were transplanted into Rag deficient hosts. The UV-induced tumor cells were analyzed by flow cytometry. The tumor cells were tagged with GFP to study their metastatic potential. SKY and karyotypic analysis were carried out for the detection of chromosomal abnormalities. Functional assays included in vitro class switch recombination assay, immunoglobulin rearrangement assay, as well as cytokine profiling. UVB-exposed mice showed enlargement of the spleen and lymph nodes. Cells transplanted into Rag deficient mice developed aggressive tumors that infiltrated the lymph nodes, the spleen and the bone marrow. The tumor cells did not grow in immune competent syngeneic C57Bl/6 mice yet showed a modest growth in UV-irradiated B6 mice. Phenotypic analysis of these tumor cells revealed these cells are positive for B cell markers CD19 + , CD5 + , B220 + , IgM + and negative for T cell, NK or dendritic cell markers. The UV-induced tumor cells underwent robust in vitro immunoglobulin class switch recombination in response to lipopolysaccharide. Cytogenetic analysis revealed a t(14;19) translocation and trisomy of chromosome 6. These tumor cells secret IL-10, which can promote tumor growth and cause systemic immunosuppression. UV-irradiated p53 +/- mice developed lymphoid tumors that corresponded to a mature B cell lymphoma. Our results suggest that an indirect mechanism is involved in the development of internal tumors after chronic exposure to UV light. The induction of B cell lymphoma in UV-irradiated p53 heterozygous mice may provide a useful model for lymphoma development in humans

  19. Attenuated hypertrophic response to pressure overload in a lamin A/C haploinsufficiency mouse

    OpenAIRE

    Cupesi, Mihaela; Yoshioka, Jun; Gannon, Joseph; Kudinova, Anastacia; Stewart, Colin L.; Lammerding, Jan

    2009-01-01

    Inherited mutations cause approximately 30% of all dilated cardiomyopathy cases, with autosomal dominant mutations in the LMNA gene accounting for more than one third of these. The LMNA gene encodes the nuclear envelope proteins lamins A and C, which provide structural support to the nucleus and also play critical roles in transcriptional regulation. Functional deletion of a single allele is sufficient to trigger dilated cardiomyopathy in humans and mice. However, whereas Lmna−/− mice develop...

  20. A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency

    DEFF Research Database (Denmark)

    Jansen, Sandra; Hoischen, Alexander; Coe, Bradley P

    2018-01-01

    Genotype-first combined with reverse phenotyping has shown to be a powerful tool in human genetics, especially in the era of next generation sequencing. This combines the identification of individuals with mutations in the same gene and linking these to consistent (endo)phenotypes to establish di...

  1. Cornelia de Lange Syndrome: NIPBL haploinsufficiency downregulates canonical Wnt pathway in zebrafish embryos and patients fibroblasts.

    Science.gov (United States)

    Pistocchi, A; Fazio, G; Cereda, A; Ferrari, L; Bettini, L R; Messina, G; Cotelli, F; Biondi, A; Selicorni, A; Massa, V

    2013-10-17

    Cornelia de Lange Syndrome is a severe genetic disorder characterized by malformations affecting multiple systems, with a common feature of severe mental retardation. Genetic variants within four genes (NIPBL (Nipped-B-like), SMC1A, SMC3, and HDAC8) are believed to be responsible for the majority of cases; all these genes encode proteins that are part of the 'cohesin complex'. Cohesins exhibit two temporally separated major roles in cells: one controlling the cell cycle and the other involved in regulating the gene expression. The present study focuses on the role of the zebrafish nipblb paralog during neural development, examining its expression in the central nervous system, and analyzing the consequences of nipblb loss of function. Neural development was impaired by the knockdown of nipblb in zebrafish. nipblb-loss-of-function embryos presented with increased apoptosis in the developing neural tissues, downregulation of canonical Wnt pathway genes, and subsequent decreased Cyclin D1 (Ccnd1) levels. Importantly, the same pattern of canonical WNT pathway and CCND1 downregulation was observed in NIPBL-mutated patient-specific fibroblasts. Finally, chemical activation of the pathway in nipblb-loss-of-function embryos rescued the adverse phenotype and restored the physiological levels of cell death.

  2. Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

    NARCIS (Netherlands)

    Gostynska, Katarzyna B.; Yuen, Wing Yan; Pasmooij, Anna Maria Gerdina; Stellingsma, Cornelius; Pas, Hendri H.; Lemmink, Henny; Jonkman, Marcel F.

    2017-01-01

    The hereditary blistering disease junctional epidermolysis bullosa (JEB) is always accompanied by structural enamel abnormalities of primary and secondary dentition, characterized as amelogenesis imperfecta. Autosomal recessive mutations in LAMA3, LAMB3 and LAMC2 encoding the heterotrimer laminin

  3. Why the CDM can reduce carbon leakage

    International Nuclear Information System (INIS)

    Kallbekken, S.

    2006-04-01

    Carbon leakage is an important concern because it can reduce the environmental effectiveness of the Kyoto Protocol. The Clean Development Mechanism, one of the flexibility mechanisms allowed under the protocol, has the potential to reduce carbon leakage significantly because it reduces the relative competitive disadvantage to Annex B countries of restricting greenhouse gas emissions. The economic intuition behind this mechanism is explored in a theoretical analysis. It is then analyzed numerically using a CGE model. The results indicate that, assuming appropriate accounting for leakage and under realistic assumptions on CDM activity, the CDM has the potential to reduce the magnitude of carbon leakage by around three fifths

  4. Solar Cels With Reduced Contact Areas

    Science.gov (United States)

    Daud, T.; Crotty, G. T.; Kachare, A. H.; Lewis, J. T.

    1987-01-01

    Efficiency of silicon solar cells increased about 20 percent using smaller metal-contact area on silicon at front and back of each cell. Reduction in contact area reduces surface recombination velocity under contact and thus reduces reverse saturation current and increases opencircuit voltage..

  5. Filter apparatus for actively reducing noise

    NARCIS (Netherlands)

    Berkhoff, Arthur P.; Nijsse, G.

    2010-01-01

    A filter apparatus for reducing noise from a primary noise source, comprising a secondary source signal connector for generating secondary noise to reduce said primary noise and a sensor connector for connecting to a sensor for measuring said primary and secondary noise as an error signal. A first

  6. A filter apparatus for actively reducing noise

    NARCIS (Netherlands)

    Berkhoff, Arthur P.; Nijsse, G.

    2006-01-01

    A filter apparatus for reducing noise from a primary noise source, comprising a secondary source signal connector for generating secondary noise to reduce said primary noise and a sensor connector for connecting to a sensor for measuring said primary and secondary noise as an error signal. A first

  7. Extending OFDM Symbols to Reduce Power Consumption

    NARCIS (Netherlands)

    Kokkeler, Andre B.J.; Smit, Gerardus Johannes Maria

    2012-01-01

    Existing communication standards have limited capabilities to adapt to low SNR environments or to exploit low data rate requirements in a power efficient way. Existing techniques like e.g. control coding do not reduce the computational load when reducing data rates. In this paper, we introduce

  8. Nonperturbative treatment of reduced model with fermions

    International Nuclear Information System (INIS)

    Gutierrez, W.R.

    1983-01-01

    A nonperturbative method is presented to show that the reduced model produces the correct leading large-N contribution to the fermion Green's functions. A new form of the reduced model is introduced, which avoids the quenching procedure. Also the equation for the meson bound states is discussed. The method is illustrated in the case of two-dimensional QCD

  9. Reduced Worktime: Tool to Fight Umemployment

    Science.gov (United States)

    Levitan, Sar A.; Belous, Richard S.

    1978-01-01

    Discusses the use of reduced worktime, including work sharing, as a strategy in combating unemployment. Covers the experiences of Western European countries in using this strategy to reduce unemployment. It also covers the negative aspects of work sharing, Americans' desires for increased leisure time, and, finally, some issues and answers. (EM)

  10. Sludge displacement verification for reducing grout report

    International Nuclear Information System (INIS)

    Caldwell, T.B.; Langton, C.A.

    1997-01-01

    To support the closure of HLW tanks at SRS, a reducing grout was developed that is formulated to reduce the mobility of radionuclides left in each tank. During non-radioactive flow tests of the grout, it was discovered that, in addition to its desired properties, the grout has the ability to move residual waste a considerable distance across the tank floor

  11. Holonomy-reduced dynamics of triatomic molecules

    International Nuclear Information System (INIS)

    Ciftci, Uenver; Waalkens, Holger

    2011-01-01

    Whereas it is easy to reduce the translational symmetry of a molecular system using, e.g., Jacobi coordinates, the situation is much more involved for rotational symmetry. In this paper, we address the latter problem using holonomy reduction. We suggest that the configuration space may be considered as the reduced holonomy bundle with a connection induced by the mechanical connection. Using the fact that for the special case of the three-body problem the holonomy group is SO(2) (as opposed to SO(3) like in systems with more than three bodies), we obtain a holonomy-reduced configuration space of topology R + 3 xS 1 . The dynamics then takes place on the cotangent bundle over the holonomy-reduced configuration space. On this phase space, there is an S 1 symmetry action coming from the conserved reduced angular momentum which can be reduced using the standard symplectic reduction method. Using a theorem by Arnold it follows that the resulting symmetry-reduced phase space is again a natural mechanical phase space, i.e. a cotangent bundle. This is different from what is obtained from the usual approach where symplectic reduction is used from the outset. This difference is discussed in some detail, and a connection between the reduced dynamics of a triatomic molecule and the motion of a charged particle in a magnetic field is established.

  12. Holonomy-reduced dynamics of triatomic molecules

    Energy Technology Data Exchange (ETDEWEB)

    Ciftci, Uenver [Department of Mathematics, Namik Kemal University, 59030 Tekirdag (Turkey); Waalkens, Holger, E-mail: uciftci@nku.edu.tr, E-mail: h.waalkens@rug.nl [Johann Bernoulli Institute for Mathematics and Computer Science, University of Groningen, PO Box 407, 9700 AK Groningen (Netherlands)

    2011-04-22

    Whereas it is easy to reduce the translational symmetry of a molecular system using, e.g., Jacobi coordinates, the situation is much more involved for rotational symmetry. In this paper, we address the latter problem using holonomy reduction. We suggest that the configuration space may be considered as the reduced holonomy bundle with a connection induced by the mechanical connection. Using the fact that for the special case of the three-body problem the holonomy group is SO(2) (as opposed to SO(3) like in systems with more than three bodies), we obtain a holonomy-reduced configuration space of topology R{sub +}{sup 3}xS{sup 1}. The dynamics then takes place on the cotangent bundle over the holonomy-reduced configuration space. On this phase space, there is an S{sup 1} symmetry action coming from the conserved reduced angular momentum which can be reduced using the standard symplectic reduction method. Using a theorem by Arnold it follows that the resulting symmetry-reduced phase space is again a natural mechanical phase space, i.e. a cotangent bundle. This is different from what is obtained from the usual approach where symplectic reduction is used from the outset. This difference is discussed in some detail, and a connection between the reduced dynamics of a triatomic molecule and the motion of a charged particle in a magnetic field is established.

  13. REDUCE system in elementary particle physics

    International Nuclear Information System (INIS)

    Grozin, A.G.

    1990-01-01

    This preprint is the first part of the problem book on using REDUCE for calculations of cross sections and decay probabilities in elementary particle physics. It contains the review of the necessary formulae and examples of using REDUCE for calculations with vectors and Dirac matrices. 5 refs.; 11 figs

  14. Method and container for reducing pertechnetate

    International Nuclear Information System (INIS)

    Ruddock, C.F.

    1980-01-01

    A method of reducing the pertechnetate in TcO 4 - comprises mixing together an aqueous solution of pertechnetate, e.g. the eluant from a technetium generator, metallic tin or an alloy thereof as a reducing agent for the pertechnetate, and a soluble salt of a metal below tin in the electrochemical series, e.g. copper, as an activator for the tin metal reducing agent. A complexing agent for the reduced technetium or a colloid stabiliser may also be included. The pH is preferably 3 to 12. Also claimed is a closed container containing the tin reducing agent, the activator, and the complexant or colloid stabiliser if used, preferably in a freeze-dried sterile state, to which the pertechnetate solution may be added. (author)

  15. Using REDUCE in high energy physics

    International Nuclear Information System (INIS)

    Grozin, A.G.

    1997-01-01

    This book describes the use of the symbolic manipulation language REDUCE in particle physics. There are several general purpose mathematics packages available to physicists, including Mathematica, Maple, and REDUCE. Each has advantages and disadvantages, but REDUCE has been found to be both powerful and convenient in solving a wide range of problems. This book introduces the reader to REDUCE and demonstrates its utility as a mathematical tool in physics. The first chapter of the book describes the REDUCE system, including some library packages. The following chapters show the use of REDUCE in examples from classical mechanics, hydrodynamics, general relativity, and quantum mechanics. The rest of the book systematically presents the Standard Model of particle physics (QED, weak interactions, QCD). A large number of scattering and decay processes are calculated with REDUCE. All example programs from the book can be downloaded via Internet. The emphasis throughout is on learning through worked examples. This will be an essential introduction and reference for high energy and theoretical physicists. (author)

  16. Sucralfate significantly reduces ciprofloxacin concentrations in serum.

    OpenAIRE

    Garrelts, J C; Godley, P J; Peterie, J D; Gerlach, E H; Yakshe, C C

    1990-01-01

    The effect of sucralfate on the bioavailability of ciprofloxacin was evaluated in eight healthy subjects utilizing a randomized, crossover design. The area under the concentration-time curve from 0 to 12 h was reduced from 8.8 to 1.1 micrograms.h/ml by sucralfate (P less than 0.005). Similarly, the maximum concentration of ciprofloxacin in serum was reduced from 2.0 to 0.2 micrograms/ml (P less than 0.005). We conclude that concurrent ingestion of sucralfate significantly reduces the concentr...

  17. Biased lineups: sequential presentation reduces the problem.

    Science.gov (United States)

    Lindsay, R C; Lea, J A; Nosworthy, G J; Fulford, J A; Hector, J; LeVan, V; Seabrook, C

    1991-12-01

    Biased lineups have been shown to increase significantly false, but not correct, identification rates (Lindsay, Wallbridge, & Drennan, 1987; Lindsay & Wells, 1980; Malpass & Devine, 1981). Lindsay and Wells (1985) found that sequential lineup presentation reduced false identification rates, presumably by reducing reliance on relative judgment processes. Five staged-crime experiments were conducted to examine the effect of lineup biases and sequential presentation on eyewitness recognition accuracy. Sequential lineup presentation significantly reduced false identification rates from fair lineups as well as from lineups biased with regard to foil similarity, instructions, or witness attire, and from lineups biased in all of these ways. The results support recommendations that police present lineups sequentially.

  18. Reducing health inequalities for older LGBTQ+ people.

    Science.gov (United States)

    Thomas, Ben

    2016-10-26

    The recent LGBTQ+ history exhibition Speak Out London, Diversity City presented a fantastic collection of stories, documents and photographs from LGBTQ+ Londoners. It also provided a reminder of how far we have come in reducing stigma, prejudice and discrimination.

  19. Focus Cities : Reducing the Vulnerability, Poverty and ...

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

    Focus Cities : Reducing the Vulnerability, Poverty and Environmental Load in ... 000 lives in closely constructed houses built right up to the edge of the Rimac River. ... and the Lima Metropolitan Urban Plan will be updated in light of the results.

  20. Cogeneration, renewables and reducing greenhouse gas emissions

    International Nuclear Information System (INIS)

    Naughten, B.; Dlugosz, J.

    1996-01-01

    The MENSA model is used to assess the potential role of cogeneration and selected new renewable energy technologies in cost-effectively reducing Greenhouse gas emissions. The model framework for analyzing these issues is introduced, together with an account of relevant aspects of its application. In the discussion of selected new renewable energy technologies, it is shown how microeconomic reform may encourage these technologies and fuels, and thereby reduce sector wide carbon dioxide emissions. Policy scenarios modelled are described and the simulation results are presented. Certain interventions in microeconomic reform may result in economic benefits while also reducing emissions: no regrets' opportunities. Some renewable energy technologies are also shown to be cost-effective in the event that targets and timetables for reducing Greenhouse gas emissions are imposed. However, ad hoc interventions in support of particular renewables options are unlikely to be consistent with a least cost approach to achieving environmental objectives. (author). 5 tabs., 5 figs., 21 refs

  1. Does ethamsylate reduce haemorrhage in transurethral prostatectomy?

    Science.gov (United States)

    Lyth, D R; Booth, C M

    1990-12-01

    A double-blind, randomised trial of 44 consecutive patients undergoing transurethral prostatectomy demonstrated that ethamsylate (Dicynene) did not reduce blood loss during either the operative or the post- operative periods.

  2. Quilting after mastectomy significantly reduces seroma formation

    African Journals Online (AJOL)

    reduce or prevent seroma formation among mastectomy patients ... of this prospective study is to evaluate the effect of surgical quilting ... Seroma was more common in smokers (p=0.003) and was not decreased by the .... explain its aetiology.

  3. REDUCE in elementary particle physics. Quantum electrodynamics

    International Nuclear Information System (INIS)

    Grozin, A.G.

    1990-01-01

    This preprint is the second part of the problem book on using REDUCE for calculations of cross sections and decay probabilities in elementary particle physics. It contains examples of calculations in quantum electrodynamics. 5 refs

  4. Increased backcrossing has reduced the usefulness of ...

    African Journals Online (AJOL)

    Increased backcrossing has reduced the usefulness of morphological and allozyme data for identifying Oreochromis niloticus , O. mossambicus (Teleostei: Cichlidae) and their hybrids in the Pafuri reach of the Luvuvhu River in the Kruger National Park, South Africa.

  5. Synthesis of battery grade reduced silver powder

    International Nuclear Information System (INIS)

    Qadeer, R.; Hameed, M.; Ikram, S.; Munir, A.

    2002-01-01

    Process for production of battery grade reduced silver powder, an active positive material for zinc-silver oxide batteries, having specific characteristics has been optimized and the synthesized reduced silver powder was characterized. Results reveal that the values of bulk density (1.25 0.1 g/cm3) and activity (73.27 %) of synthesized reduced silver powder lies within the recommended range for use as battery material. It has purity ≥ 98% and contains Fe and Cu as traces in the concentration range of 30 5 ppm and 15 7 ppm respectively. Others determined values of surface and pores parameters are: surface area 2.6 .4 m2/g: pore volume 3.10 cm3/g: pore diameter 0.043 mu m and porosity 20%. XRD studies reveal that reduced silver powder has a cubic structure. (author)

  6. Reduced Disparities in Birth Rates Among Teens

    Science.gov (United States)

    ... Teens Winnable Battles Social Media at CDC Reduced Disparities in Birth Rates among Teens Aged 15–19 ... Pregnancy Prevention Community-Wide Initiative. National Rates and Disparities Nationally, the teen birth rate (number of births ...

  7. Boundaries, injective envelopes, and reduced crossed products

    DEFF Research Database (Denmark)

    Bryder, Rasmus Sylvester

    In this dissertation, we study boundary actions, equivariant injective envelopes, as well as theideal structure of reduced crossed products. These topics have recently been linked to thestudy of C-simple groups, that is, groups with simple reduced group C-algebras.In joint work with Matthew Kennedy......, we consider reduced twisted crossed products overC-simple groups. For any twisted C-dynamical system over a C-simple group, we provethat there is a one-to-one correspondence between maximal invariant ideals in the underlyingC-algebra and maximal ideals in the reduced crossed product. When......*-algebras, and relate the intersection property for group actions on unital C*-algebras to the intersection property for theequivariant injective envelope. Moreover, we also prove that the equivariant injective envelopeof the centre of the injective envelope of a unital C*-algebra can be regarded as a C...

  8. Electronic states in systems of reduced dimensionality

    International Nuclear Information System (INIS)

    Ulloa, S.E.

    1992-01-01

    This report briefly discusses the following research: magnetically modulated systems, inelastic magnetotunneling, ballistic transport review, screening in reduced dimensions, raman and electron energy loss spectroscopy; and ballistic quantum interference effects. (LSP)

  9. Do conditional benefits reduce equilibrium unemployment?

    NARCIS (Netherlands)

    van der Ploeg, F.

    2006-01-01

    Although unconditional unemployment benefits destroy jobs in competitive and noncompetitive labor markets, conditional benefits can spur job growth in noncompetitive labor markets. Unconditional benefits reduce the penalty of shirking and misconduct, while conditional benefits increase this penalty.

  10. Roadside management strategies to reduce greenhouse gases.

    Science.gov (United States)

    2010-06-01

    Californias Global Warming Solutions Act of 2006 (AB 32), Sustainable Communities and Climate Protection Act : (SB 375), and Executive Order S-14-08 direct Caltrans to develop actions to reduce greenhouse gases (GHGs). Air : pollution reduction is...

  11. Boiler burden reduced at Bedford site.

    Science.gov (United States)

    Horsley, Chris

    2011-10-01

    With the NHS aiming to reduce its 2007 carbon footprint by 10% by 2015, Chris Horsley, managing director of Babcock Wanson UK, a provider of industrial boilers and burners, thermal oxidisers, air treatment, water treatment, and associated services, looks at how one NHS Trust has approached the challenge, and considerably reduced its carbon emissions, by refurbishing its boiler house and moving from oil to gas-fired steam generation.

  12. Programming MapReduce with Scalding

    CERN Document Server

    Chalkiopoulos, Antonios

    2014-01-01

    This book is an easy-to-understand, practical guide to designing, testing, and implementing complex MapReduce applications in Scala using the Scalding framework. It is packed with examples featuring log-processing, ad-targeting, and machine learning. This book is for developers who are willing to discover how to effectively develop MapReduce applications. Prior knowledge of Hadoop or Scala is not required; however, investing some time on those topics would certainly be beneficial.

  13. IHadoop: Asynchronous iterations for MapReduce

    KAUST Repository

    Elnikety, Eslam Mohamed Ibrahim

    2011-11-01

    MapReduce is a distributed programming frame-work designed to ease the development of scalable data-intensive applications for large clusters of commodity machines. Most machine learning and data mining applications involve iterative computations over large datasets, such as the Web hyperlink structures and social network graphs. Yet, the MapReduce model does not efficiently support this important class of applications. The architecture of MapReduce, most critically its dataflow techniques and task scheduling, is completely unaware of the nature of iterative applications; tasks are scheduled according to a policy that optimizes the execution for a single iteration which wastes bandwidth, I/O, and CPU cycles when compared with an optimal execution for a consecutive set of iterations. This work presents iHadoop, a modified MapReduce model, and an associated implementation, optimized for iterative computations. The iHadoop model schedules iterations asynchronously. It connects the output of one iteration to the next, allowing both to process their data concurrently. iHadoop\\'s task scheduler exploits inter-iteration data locality by scheduling tasks that exhibit a producer/consumer relation on the same physical machine allowing a fast local data transfer. For those iterative applications that require satisfying certain criteria before termination, iHadoop runs the check concurrently during the execution of the subsequent iteration to further reduce the application\\'s latency. This paper also describes our implementation of the iHadoop model, and evaluates its performance against Hadoop, the widely used open source implementation of MapReduce. Experiments using different data analysis applications over real-world and synthetic datasets show that iHadoop performs better than Hadoop for iterative algorithms, reducing execution time of iterative applications by 25% on average. Furthermore, integrating iHadoop with HaLoop, a variant Hadoop implementation that caches

  14. The role of preschool in reducing inequality

    OpenAIRE

    Waldfogel, Jane

    2015-01-01

    Children from disadvantaged families have lower levels of school readiness when they enter school than do children from more advantaged families. Many countries have tried to reduce this inequality through publicly provided preschool. Evidence on the potential of these programs to reduce inequality in child development is now quite strong. Long-term studies of large publicly funded programs in Europe and Latin America, and newer studies on state and local prekindergarten programs implemented ...

  15. Do Workplace Smoking Bans Reduce Smoking?

    OpenAIRE

    Matthew C. Farrelly; William N. Evans; Edward Montgomery

    1999-01-01

    In recent years there has been a heightened public concern over the potentially harmful effects of environmental tobacco smoke (ETS). In response, smoking has been banned on many jobs. Using data from the 1991 and 1993 National Health Interview Survey and smoking supplements to the September 1992 and May 1993 Current Population Survey, we investigate whether these workplace policies reduce smoking prevalence and smoking intensity among workers. Our estimates suggest that workplace bans reduce...

  16. IHadoop: Asynchronous iterations for MapReduce

    KAUST Repository

    Elnikety, Eslam Mohamed Ibrahim; El Sayed, Tamer S.; Ramadan, Hany E.

    2011-01-01

    MapReduce is a distributed programming frame-work designed to ease the development of scalable data-intensive applications for large clusters of commodity machines. Most machine learning and data mining applications involve iterative computations over large datasets, such as the Web hyperlink structures and social network graphs. Yet, the MapReduce model does not efficiently support this important class of applications. The architecture of MapReduce, most critically its dataflow techniques and task scheduling, is completely unaware of the nature of iterative applications; tasks are scheduled according to a policy that optimizes the execution for a single iteration which wastes bandwidth, I/O, and CPU cycles when compared with an optimal execution for a consecutive set of iterations. This work presents iHadoop, a modified MapReduce model, and an associated implementation, optimized for iterative computations. The iHadoop model schedules iterations asynchronously. It connects the output of one iteration to the next, allowing both to process their data concurrently. iHadoop's task scheduler exploits inter-iteration data locality by scheduling tasks that exhibit a producer/consumer relation on the same physical machine allowing a fast local data transfer. For those iterative applications that require satisfying certain criteria before termination, iHadoop runs the check concurrently during the execution of the subsequent iteration to further reduce the application's latency. This paper also describes our implementation of the iHadoop model, and evaluates its performance against Hadoop, the widely used open source implementation of MapReduce. Experiments using different data analysis applications over real-world and synthetic datasets show that iHadoop performs better than Hadoop for iterative algorithms, reducing execution time of iterative applications by 25% on average. Furthermore, integrating iHadoop with HaLoop, a variant Hadoop implementation that caches

  17. Evaluating Active Interventions to Reduce Student Procrastination

    OpenAIRE

    Martin, Joshua Deckert

    2015-01-01

    Procrastination is a pervasive problem in education. In computer science, procrastination and lack of necessary time management skills to complete programming projects are viewed as primary causes of student attrition. The most effective techniques known to reduce procrastination are resource-intensive and do not scale well to large classrooms. In this thesis, we examine three course interventions designed to both reduce procrastination and be scalable for large classrooms. Reflective writ...

  18. Reduced chemical kinetic mechanisms for hydrocarbon fuels

    International Nuclear Information System (INIS)

    Montgomery, C.J.; Cremer, M.A.; Heap, M.P.; Chen, J-Y.; Westbrook, C.K.; Maurice, L.Q.

    1999-01-01

    Using CARM (Computer Aided Reduction Method), a computer program that automates the mechanism reduction process, a variety of different reduced chemical kinetic mechanisms for ethylene and n-heptane have been generated. The reduced mechanisms have been compared to detailed chemistry calculations in simple homogeneous reactors and experiments. Reduced mechanisms for combustion of ethylene having as few as 10 species were found to give reasonable agreement with detailed chemistry over a range of stoichiometries and showed significant improvement over currently used global mechanisms. The performance of reduced mechanisms derived from a large detailed mechanism for n-heptane was compared to results from a reduced mechanism derived from a smaller semi-empirical mechanism. The semi-empirical mechanism was advantageous as a starting point for reduction for ignition delay, but not for PSR calculations. Reduced mechanisms with as few as 12 species gave excellent results for n-heptane/air PSR calculations but 16-25 or more species are needed to simulate n-heptane ignition delay

  19. Reduced waste generation technical work plan

    International Nuclear Information System (INIS)

    1987-05-01

    The United States Department of Energy has established policies for avoiding plutonium losses to the waste streams and minimizing the generation of wastes produced at its nuclear facilities. This policy is evidenced in DOE Order 5820.2, which states ''Technical and administrative controls shall be directed towards reducing the gross volume of TRU waste generated and the amount of radioactivity in such waste.'' To comply with the DOE directive, the Defense Transuranic Waste Program (DTWP) supports and provides funding for specific research and development tasks at the various DOE sites to reduce the generation of waste. This document has been prepared to give an overview of current and past Reduced Waste Generation task activities which are to be based on technical and cost/benefit factors. The document is updated annually, or as needed, to reflect the status of program direction. Reduced Waste Generation (RWG) tasks encompass a wide range of goals which are basically oriented toward (1) avoiding the generation of waste, (2) changing processes or operations to reduce waste, (3) converting TRU waste into LLW by sorting or decontamination, and (4) reducing volumes through operations such as incineration or compaction

  20. Evolution of technetium speciation in reducing grout

    Energy Technology Data Exchange (ETDEWEB)

    Lukens, Wayne W.; Bucher, Jerome J.; Shuh, David K.; Edelstein,Norman M.

    2003-11-24

    Cementitious waste forms (CWFs) are an important component of the strategy to immobilize high-level nuclear waste resulting from plutonium production by the U.S. Department of Energy (DOE). Technetium (99Tc) is an abundant fission product of particular concern in CWFs due to the high solubility and mobility of pertechnetate, TcO4-, the stable form of technetium in aerobic environments. CWFs can more effectively immobilize 99Tc if they contain additives that reduce mobile TcO4- to immobile Tc(IV) species. Leaching of 99Tc from reducing CWFs that contain Tc(IV) is much slower than for CWFs containing TcO4-. Previous X-ray absorption fine structure (XAFS) studies showed that the Tc(IV) species were oxidized to TcO4- in reducing grout samples prepared on a laboratory scale. Whether the oxidizer was atmospheric O2 or NO3- in the waste simulant was not determined. In actual CWFs, rapid oxidation of Tc(IV) by NO3- would be a concern, whereas oxidation by atmospheric O2 would be of less concern due to the slow diffusion and reaction of O2 with the reducing CWF. To address this uncertainty, two series of reducing grouts were prepared using TcO4- containing waste simulants with and without NO3-. In the first series of samples, the TcO4- was completely reduced using Na2S, and the samples were placed in containers that permitted O2 diffusion. In these samples, all of the technetium was initially present as aTc(IV) sulfide compound, TcSx, which was characterized using extended X-ray absorption fine structure (EXAFS) spectroscopy, and is likely Tc2S7. The TcSx initially present in the grout samples was steadily oxidized over 4 years. In the second series of samples, all of the TcO4- was not initially reduced, and the grout samples were placed in airtight containers. In these samples, the remaining TcO4- continued to be reduced as the samples aged, presumably due to the presence of reducing blast furnace slag. When samples in the second series were exposed to atmosphere, the

  1. Understanding Uranium Behavior in a Reduced Aquifer

    Science.gov (United States)

    Janot, N.; Lezama-Pacheco, J. S.; Williams, K. H.; Bernier-Latmani, R.; Long, P. E.; Davis, J. A.; Fox, P. M.; Yang, L.; Giammar, D.; Cerrato, J. M.; Bargar, J.

    2012-12-01

    Uranium contamination of groundwater is a concern at several US Department of Energy sites, such Old Rifle, CO. Uranium transport in the environment is mainly controlled by its oxidation state, since oxidized U(VI) is relatively mobile, whereas U(IV) is relatively insoluble. Bio-remediation of contaminated aquifers aims at immobilizing uranium in a reduced form. Previous laboratory and field studies have shown that adding electron donor (lactate, acetate, ethanol) to groundwater stimulates the activity of metal- and sulfate-reducing bacteria, which promotes U(VI) reduction in contaminated aquifers. However, obtaining information on chemical and physical forms of U, Fe and S species for sediments biostimulated in the field, as well as kinetic parameters such as U(VI) reduction rate, is challenging due to the low concentration of uranium in the aquifers (typically bio-remediation experiment at the Old Rifle site, CO, from early iron-reducing conditions to the transition to sulfate-reducing conditions. Several in-well chromatographic columns packed with sediment were deployed and were sampled at different days after the start of bio-reduction. X-ray absorption spectroscopy and X-ray microscopy were used to obtain information on Fe, S and U speciation and distribution. Chemical extractions of the reduced sediments have also been performed, to determine the rate of Fe(II) and U(IV) accumulation.

  2. Bioremediation: Effectiveness in reducing the ecological impact

    International Nuclear Information System (INIS)

    Scholten, M.C.T.

    1992-01-01

    Bioremediation becomes an important technique in oil spill combat programmes. The purpose is to shorten the exposure time of biota to oil compounds, in order to reduce long term environmental effects. Although bioremediation products have the advantage of stimulating the natural capacity to degrade oil, there are some limitations to be considered. Application as a technique for first emergency actions following an oil spill is not effective, and can therefore be no alternative for dispersion or mechanical removal of floating or freshly stranded oil slicks. Acute toxic effects are related to the short term exposure to unweathered oils. An immediate removal of oil is necessary to reduce the extent of the environmental impact of an oil spill. Physical processes (transport, dilution and evaporation) are determining the initial fate of environmentally released oil. Biodegradation only becomes important as a process of removing oil in the next phase. It is the only effective way to further reduce the concentration of oil that is left in (intertidal) coastal areas. Bioremediation thus reduces the duration of the environmental impact of an oil spill. This is especially important in ecosystems with a low recovery potential (e.g., salt marshes, rocky shores). The experimental evaluation of bioremediation products is mainly based on the capacity to reduce fresh oil and the acute toxicity of the product itself, rather than on the capacity to enhance the further reduction of weathered oil and the toxicological consequences of higher release rates of intermediate metabolites produced during the biotransformation processes

  3. Local stressors reduce coral resilience to bleaching.

    Science.gov (United States)

    Carilli, Jessica E; Norris, Richard D; Black, Bryan A; Walsh, Sheila M; McField, Melanie

    2009-07-22

    Coral bleaching, during which corals lose their symbiotic dinoflagellates, typically corresponds with periods of intense heat stress, and appears to be increasing in frequency and geographic extent as the climate warms. A fundamental question in coral reef ecology is whether chronic local stress reduces coral resistance and resilience from episodic stress such as bleaching, or alternatively promotes acclimatization, potentially increasing resistance and resilience. Here we show that following a major bleaching event, Montastraea faveolata coral growth rates at sites with higher local anthropogenic stressors remained suppressed for at least 8 years, while coral growth rates at sites with lower stress recovered in 2-3 years. Instead of promoting acclimatization, our data indicate that background stress reduces coral fitness and resilience to episodic events. We also suggest that reducing chronic stress through local coral reef management efforts may increase coral resilience to global climate change.

  4. Targets set to reduce Lake Erie algae

    Science.gov (United States)

    Evans, Mary

    2016-01-01

    In February 2016, the Great Lakes Executive Committee, which oversees the implementation of the Great Lakes Water Quality Agreement (GLWQA) between the U.S. and Canada, approved phosphorus loading targets for Lake Erie to reduce the size of harmful algal blooms (HABs), reduce the presence of the low oxygen zone in the central basin, and protect nearshore water quality. The targets are set with respect to the nutrient loads calculated for 2008. To reduce the impacts of HABs on Lake Erie a target was set of a 40 percent reduction in total and soluble reactive phosphorus loads in the spring from two Canadian rivers and several Michigan and Ohio rivers, especially the Maumee River (https://binational.net/2016/02/22/ finalptargets-ciblesfinalesdep/). States and the province of Ontario are already developing Domestic Action Plans to accomplish the reductions and scientists are developing research and monitoring plans to assess progress.

  5. Reducing longitudinal emittance growth in RFQ accelerators

    International Nuclear Information System (INIS)

    Koscielniak, S.

    1994-08-01

    Bunching and capture of a monochromatic beam into an rf bucket inevitably lead to substantial emittance growth through the mechanisms of filamentation and non-adiabatic variation of parameters. We describe a three step strategy for minimizing this growth, based on a clear understanding of the non-linear beam dynamics, and apply to acceleration of heavy ions with Z/A = 1/60 (and initial kinetic energy 60 keV/u) in a radio frequency quadrupole (RFQ) operating at 25 MHz. We also describe a scheme, to further reduce the emittance, based upon the use of an external RFQ-type prebuncher before the main accelerator. The external unit permits the bunching voltage to be reduced, to inject into a moving bucket, and to reduce the structure length. (author). 7 refs., 6 figs

  6. Corn Cultivation to Reduce the Mycotoxin Contamination

    Directory of Open Access Journals (Sweden)

    Yangseon Kim

    2017-09-01

    Full Text Available The effects of insecticide and fungicide treatment were investigated to reduce mycotoxin contamination of corn (Zea mays L. seeds. Deoxynivalenol and zearalenone contents were reduced in the treated seeds, but aflatoxin, ochratoxin A, fumonisin, and T-2 toxin were not effective by chemical treatments. The chemical treatment did not affect the growth of saprophyte, but inhibited the pathogenic fungi such as Fusarium verticillioides, F. graminearum and F. equiseti. Myotoxin contents at different harvesting time were compared. As the harvest time was delayed, both levels of deoxynivalenol and zearalenone and frequency of Fusarium spp. increased. However, the major nutrient contents of corn seeds were not affected by harvesting period. These results show that chemical treatments are necessary to reduce the fungal contamination of corn and harvest without delay is important as well.

  7. Reducing online identity disclosure using warnings.

    Science.gov (United States)

    Carpenter, Sandra; Zhu, Feng; Kolimi, Swapna

    2014-09-01

    In an experimental design, we tested whether written warnings can reduce the amount of identity information exposure online. A psychological attack on information privacy that has been shown to be effective in previous research was launched. This attack took advantage of the fact that people respond to certain types of requests in a relatively automatic, or mindless, fashion. The experiment manipulated the word that was used in the alert header: "warning", "caution", or "hazard". All warnings proved to be effective in reducing disclosure, but "hazard" proved to be most effective. Also warnings were more effective in reducing disclosure of driver's license numbers than email addresses. The discussion (a) provides tentative conclusions why these patterns were obtained, (b) suggests how to design warnings in cyber-environments, and (c) addresses future possibilities for research on this topic. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  8. Quantum Entanglement and Reduced Density Matrices

    Science.gov (United States)

    Purwanto, Agus; Sukamto, Heru; Yuwana, Lila

    2018-05-01

    We investigate entanglement and separability criteria of multipartite (n-partite) state by examining ranks of its reduced density matrices. Firstly, we construct the general formula to determine the criterion. A rank of origin density matrix always equals one, meanwhile ranks of reduced matrices have various ranks. Next, separability and entanglement criterion of multipartite is determined by calculating ranks of reduced density matrices. In this article we diversify multipartite state criteria into completely entangled state, completely separable state, and compound state, i.e. sub-entangled state and sub-entangledseparable state. Furthermore, we also shorten the calculation proposed by the previous research to determine separability of multipartite state and expand the methods to be able to differ multipartite state based on criteria above.

  9. Moral elevation reduces prejudice against gay men.

    Science.gov (United States)

    Lai, Calvin K; Haidt, Jonathan; Nosek, Brian A

    2014-01-01

    Disgust is linked to social evaluation. People with higher disgust sensitivity exhibit more sexual prejudice, and inducing disgust increases sexual prejudice. We tested whether inducing moral elevation, the theoretical opposite of disgust, would reduce sexual prejudice. In four studies (N = 3622), we induced elevation with inspiring videos and then measured sexual prejudice with implicit and explicit measures. Compared to control videos that elicited no particular affective state, we found that elevation reduced implicit and explicit sexual prejudice, albeit very slightly. No effect was observed when the target of social evaluation was changed to race (Black-White). Inducing amusement, another positive emotion, did not significantly affect sexual prejudice. We conclude that elevation weakly but reliably reduces prejudice towards gay men.

  10. Experimental knee pain reduces muscle strength

    DEFF Research Database (Denmark)

    Henriksen, Marius; Mortensen, Sara Rosager; Aaboe, Jens

    2011-01-01

    Pain is the principal symptom in knee pathologies and reduced muscle strength is a common observation among knee patients. However, the relationship between knee joint pain and muscle strength remains to be clarified. This study aimed at investigating the changes in knee muscle strength following...... experimental knee pain in healthy volunteers, and if these changes were associated with the pain intensities. In a crossover study, 18 healthy subjects were tested on 2 different days. Using an isokinetic dynamometer, maximal muscle strength in knee extension and flexion was measured at angular velocities 0....... Knee pain reduced the muscle strength by 5 to 15% compared to the control conditions (P knee extension and flexion at all angular velocities. The reduction in muscle strength was positively correlated to the pain intensity. Experimental knee pain significantly reduced knee extension...

  11. Hierarchical Traces for Reduced NSM Memory Requirements

    Science.gov (United States)

    Dahl, Torbjørn S.

    This paper presents work on using hierarchical long term memory to reduce the memory requirements of nearest sequence memory (NSM) learning, a previously published, instance-based reinforcement learning algorithm. A hierarchical memory representation reduces the memory requirements by allowing traces to share common sub-sequences. We present moderated mechanisms for estimating discounted future rewards and for dealing with hidden state using hierarchical memory. We also present an experimental analysis of how the sub-sequence length affects the memory compression achieved and show that the reduced memory requirements do not effect the speed of learning. Finally, we analyse and discuss the persistence of the sub-sequences independent of specific trace instances.

  12. Nature of Reduced Carbon in Martian Meteorites

    Science.gov (United States)

    Gibson, Everett K., Jr.; McKay, D. S.; Thomas-Keprta, K. L.; Clemett, S. J.; White, L. M.

    2012-01-01

    Martian meteorites provide important information on the nature of reduced carbon components present on Mars throughout its history. The first in situ analyses for carbon on the surface of Mars by the Viking landers yielded disappointing results. With the recognition of Martian meteorites on Earth, investigations have shown carbon-bearing phases exist on Mars. Studies have yielded presence of reduced carbon, carbonates and inferred graphitic carbon phases. Samples ranging in age from the first approximately 4 Ga of Mars history [e.g. ALH84001] to nakhlites with a crystallization age of 1.3 Ga [e.g. Nakhla] with aqueous alteration processes occurring 0.5-0.7 Ga after crystallizaton. Shergottites demonstrate formation ages around 165-500 Ma with younger aqueous alterations events. Only a limited number of the Martian meteorites do not show evidence of significance terrestrial alterations. Selected areas within ALH84001, Nakhla, Yamato 000593 and possibly Tissint are suitable for study of their indigenous reduced carbon bearing phases. Nakhla possesses discrete, well-defined carbonaceous phases present within iddingsite alteration zones. Based upon both isotopic measurements and analysis of Nakhla's organic phases the presence of pre-terrestrial organics is now recognized. The reduced carbon-bearing phases appear to have been deposited during preterrestrial aqueous alteration events that produced clays. In addition, the microcrystalline layers of Nakhla's iddingsite have discrete units of salt crystals suggestive of evaporation processes. While we can only speculate on the origin of these unique carbonaceous structures, we note that the significance of such observations is that it may allow us to understand the role of Martian carbon as seen in the Martian meteorites with obvious implications for astrobiology and the pre-biotic evolution of Mars. In any case, our observations strongly suggest that reduced organic carbon exists as micrometer- size, discrete structures

  13. Reducing dust and allergen exposure in bakeries

    Directory of Open Access Journals (Sweden)

    Howard J Mason

    2017-12-01

    Full Text Available Bakers have a continuing high incidence of occupational allergic asthma. In factory bakeries they are exposed not only to flour dust containing allergens, but also improvers whose ingredients enhance the strength and workability of the dough and its speed of rising. Improvers are flour-based but can contain added soya, fungal or bacterial enzymes that are also allergenic, as well as vegetable oil, calcium sulphate/silicate and organic esters. This study investigated the dustiness of the components used in factory bakeries and whether altering improver ingredients could reduce dust and allergen exposure. A standardised rotating drum test was employed on the individual components, as well as a representative improver and three practicable improver modifications by decreasing calcium sulphate, calcium silicate or increasing oil content. Levels of dust, the allergens wheat flour amylase inhibitor (WAAI and soya trypsin inhibitor (STI were measured in the generated inhalable, thoracic and respirable sized fractions. A “scooping and pouring” workplace simulation was also performed. Initial tests showed that dustiness of several wheat flours was relatively low, and even lower for soya flour, but increased in combination with some other improver components. All three improver modifications generally reduced levels of dust, STI and WAAI, but increasing oil content significantly decreased dust and STI in comparison to the standard improver and those improvers with reduced calcium silicate or sulphate. The simulation demonstrated that increased oil content reduced inhalable levels of gravimetric dust, STI and WAAI. Changing improver formulation, such as increasing oil content of flour by a small amount, may represent a simple, practical method of reducing bakery workers’ exposure to dust and allergens where improvers are used. It may be a useful adjunct to engineering control, changes to work practices and appropriate training in reducing the risk to

  14. Detecting reduced renal function in children

    DEFF Research Database (Denmark)

    Andersen, Trine Borup; Jødal, Lars; Erlandsen, Erland J

    2013-01-01

    Background The aim of this study was to compare the ability of renal indicators [serum creatinine (SCr), cystatin C (SCysC)] and glomerular filtration rate (GFR)-models to discriminate normal and reduced renal function. As a single cut-off level will always lead to false classifications, we propose...... function was defined as a GFR ofcreatinine (SCr-ratio), and eight published GFR-models were compared for their ability to correctly classify renal function as normal or reduced. Cut-off levels were determined so as to give 99 % certainty outside the gray zone...

  15. Reducing the capacitance of piezoelectric film sensors

    Energy Technology Data Exchange (ETDEWEB)

    González, Martín G., E-mail: mggonza@fi.uba.ar [Grupo de Láser, Óptica de Materiales y Aplicaciones Electromagnéticas (GLOMAE), Departamento de Física, Facultad de Ingeniería, Universidad de Buenos Aires, Paseo Colón 850, C1063ACV Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1425FQB Buenos Aires (Argentina); Sorichetti, Patricio A.; Santiago, Guillermo D. [Grupo de Láser, Óptica de Materiales y Aplicaciones Electromagnéticas (GLOMAE), Departamento de Física, Facultad de Ingeniería, Universidad de Buenos Aires, Paseo Colón 850, C1063ACV Buenos Aires (Argentina)

    2016-04-15

    We present a novel design for large area, wideband, polymer piezoelectric sensor with low capacitance. The large area allows better spatial resolution in applications such as photoacoustic tomography and the reduced capacitance eases the design of fast transimpedance amplifiers. The metalized piezoelectric polymer thin film is segmented into N sections, electrically connected in series. In this way, the total capacitance is reduced by a factor 1/N{sup 2}, whereas the mechanical response and the active area of the sensor are not modified. We show the construction details for a two-section sensor, together with the impedance spectroscopy and impulse response experimental results that validate the design.

  16. Electron microscopy at reduced levels of irradiation

    International Nuclear Information System (INIS)

    Kuo, I.A.M.

    1975-05-01

    Specimen damage by electron radiation is one of the factors that limits high resolution electron microscopy of biological specimens. A method was developed to record images of periodic objects at a reduced electron exposure in order to preserve high resolution structural detail. The resulting image would tend to be a statistically noisy one, as the electron exposure is reduced to lower and lower values. Reconstruction of a statistically defined image from such data is possible by spatial averaging of the electron signals from a large number of identical unit cells. (U.S.)

  17. Reduced central blood volume in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Sørensen, T I

    1989-01-01

    than 0.0001). The lowest values (18 ml/kg) were found in patients with gross ascites and a reduced systemic vascular resistance. In patients with cirrhosis central blood volume was inversely correlated to the hepatic venous pressure gradient (r = -0.41, p less than 0.01), and the total blood volume...... was inversely correlated to the systemic vascular resistance (r = -0.49, p less than 0.001), the latter being significantly reduced in the patient group. Patients with cirrhosis apparently are unable to maintain a normal central blood volume. This may be due to arteriolar vasodilation, portosystemic collateral...

  18. Reduced TCA Flux in Diabetic Myotubes

    DEFF Research Database (Denmark)

    Gaster, Michael

    2012-01-01

    The diabetic phenotype is complex, requiring elucidation of key initiating defects. Diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux but at present it is unclear in which part of the TCA cycle the defect is localised. In order to localise the defect we studied ATP p...... production of investigated substrate combinations was significantly reduced in mitochondria isolated from type 2 diabetic subjects compared to lean. However, when ATP synthesis rates at different substrate combinations were normalized to the corresponding individual pyruvate-malate rate...

  19. Reducing hypothetical bias in choice experiments

    DEFF Research Database (Denmark)

    Ladenburg, Jacob; Olsen, Søren Bøye; Nielsen, Rasmus Christian Fejer

    eliminate some of the hypothetical bias. The present paper tests an addition to Cheap Talk, an Opt-Out Reminder. The Opt-Out Reminder is an objective short script presented prior to the choice sets, prompting the respondent to choose the opt-out alternative, if he/she finds the proposed policy generated...... alternatives in a choice set too expensive. The results suggest that adding an Opt-Out Reminder to Cheap Talk can in fact reduce hypothetical bias even further and reduces some of the ineffectiveness of CT in relation to the survey bid range and experienced respondents....

  20. The reduced enrichment program for JRR-4

    International Nuclear Information System (INIS)

    Takayanagi, M.

    1992-01-01

    Japan Research Reactor No. 4(JRR-4) with the rated power of 3.5 MW, swimming pool type research reactor, 93 % enriched uranium ETR-type fuel used, light water moderated and cooled. The first criticality reached on 28th January, 1965. The reactor has operated for about 26 years. However, it was planed to the reduced enrichment of the fuels to low enrichment according to the International Reduced Enrichment for Research and Test Reactors (RERTR) program. This paper describes the program for conversion of the enrichment of fuel from 93 % to less than 20 %. (author)

  1. Preparation of potassium-reduced tantalum powders

    International Nuclear Information System (INIS)

    Kolosov, V.N.; Miroshnichenko, M.N.; Orlov, V.M.; Prokhorova, T.Yu.

    2005-01-01

    Characteristics of tantalum powders prepared by reduction of molten potassium heptafluorotantalate with liquid potassium are studied in a temperature range of 750 - 850 deg C using potassium chloride as a flux at a ratio of K 2 TaF 7 : KCl = 1, 2, and 3. The use of potassium as a reducing agent facilitates washing of tantalum powders for impurity salt removal, reduces sodium content and leakage currents in the anodes. As compared to sodium process, the potassium reduction results in a high yield of sponge material, a decrease in the specific surface area and yield of tantalum powder suitable for manufacture of capacitor anodes [ru

  2. Reducing the capacitance of piezoelectric film sensors

    International Nuclear Information System (INIS)

    González, Martín G.; Sorichetti, Patricio A.; Santiago, Guillermo D.

    2016-01-01

    We present a novel design for large area, wideband, polymer piezoelectric sensor with low capacitance. The large area allows better spatial resolution in applications such as photoacoustic tomography and the reduced capacitance eases the design of fast transimpedance amplifiers. The metalized piezoelectric polymer thin film is segmented into N sections, electrically connected in series. In this way, the total capacitance is reduced by a factor 1/N"2, whereas the mechanical response and the active area of the sensor are not modified. We show the construction details for a two-section sensor, together with the impedance spectroscopy and impulse response experimental results that validate the design.

  3. Novel Reduced-Feedback Wireless Communication Systems

    KAUST Repository

    Shaqfeh, Mohammad Obaidah; Alnuweiri, Hussein; Alouini, Mohamed-Slim

    2011-01-01

    We have recently contributed to this field and published several journal and conference papers. We are the pioneers to propose a novel reduced-feedback opportunistic scheduling scheme that combines many desired features including fairness in resources distribution across the active terminals and distributed processing at the MAC layer level. In addition our scheme operates close to the upper capacity limits of achievable transmission rates over wireless links. We have also proposed another hybrid scheme that enables adjusting the feedback load flexibly based on rates requirements. We are currently investigating other novel ideas to design reduced-feedback communication systems.

  4. Does Formal Employment Reduce Informal Caregiving?

    Science.gov (United States)

    He, Daifeng; McHenry, Peter

    2016-07-01

    Using the Survey of Income and Program Participation, we examine the impact of formal employment on informal caregiving. We instrument for individual work hours with state unemployment rates. We find that, among women of prime caregiving ages (40-64 years), working 10% more hours per week reduces the probability of providing informal care by about 2 percentage points. The effects are stronger for more time-intensive caregiving and if care recipients are household members. Our results imply that work-promoting policies have the unintended consequence of reducing informal caregiving in an aging society. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus.

    Directory of Open Access Journals (Sweden)

    Jarod Swant

    2010-06-01

    Full Text Available Methamphetamine (METH is an addictive psychostimulant whose societal impact is on the rise. Emerging evidence suggests that psychostimulants alter synaptic plasticity in the brain--which may partly account for their adverse effects. While it is known that METH increases the extracellular concentration of monoamines dopamine, serotonin, and norepinephrine, it is not clear how METH alters glutamatergic transmission. Within this context, the aim of the present study was to investigate the effects of acute and systemic METH on basal synaptic transmission and long-term potentiation (LTP; an activity-induced increase in synaptic efficacy in CA1 sub-field in the hippocampus. Both the acute ex vivo application of METH to hippocampal slices and systemic administration of METH decreased LTP. Interestingly, the acute ex vivo application of METH at a concentration of 30 or 60 microM increased baseline synaptic transmission as well as decreased LTP. Pretreatment with eticlopride (D2-like receptor antagonist did not alter the effects of METH on synaptic transmission or LTP. In contrast, pretreatment with D1/D5 dopamine receptor antagonist SCH23390 or 5-HT1A receptor antagonist NAN-190 abrogated the effect of METH on synaptic transmission. Furthermore, METH did not increase baseline synaptic transmission in D1 dopamine receptor haploinsufficient mice. Our findings suggest that METH affects excitatory synaptic transmission via activation of dopamine and serotonin receptor systems in the hippocampus. This modulation may contribute to synaptic maladaption induced by METH addiction and/or METH-mediated cognitive dysfunction.

  6. Hybrid reduced order modeling for assembly calculations

    International Nuclear Information System (INIS)

    Bang, Youngsuk; Abdel-Khalik, Hany S.; Jessee, Matthew A.; Mertyurek, Ugur

    2015-01-01

    Highlights: • Reducing computational cost in engineering calculations. • Reduced order modeling algorithm for multi-physics problem like assembly calculation. • Non-intrusive algorithm with random sampling. • Pattern recognition in the components with high sensitive and large variation. - Abstract: While the accuracy of assembly calculations has considerably improved due to the increase in computer power enabling more refined description of the phase space and use of more sophisticated numerical algorithms, the computational cost continues to increase which limits the full utilization of their effectiveness for routine engineering analysis. Reduced order modeling is a mathematical vehicle that scales down the dimensionality of large-scale numerical problems to enable their repeated executions on small computing environment, often available to end users. This is done by capturing the most dominant underlying relationships between the model's inputs and outputs. Previous works demonstrated the use of the reduced order modeling for a single physics code, such as a radiation transport calculation. This manuscript extends those works to coupled code systems as currently employed in assembly calculations. Numerical tests are conducted using realistic SCALE assembly models with resonance self-shielding, neutron transport, and nuclides transmutation/depletion models representing the components of the coupled code system.

  7. Cost reducing investments and spatial competition

    OpenAIRE

    Domenico Scalera; Alberto Zazzaro

    2005-01-01

    In this paper we analyze the relationship between competition and cost reducing investments in the context of a location model. In particular, we derive the symmetric subgame-perfect equilibrium of a three-stage circular city model with closed-loop strategies, and study the effects of changes in competition fundamentals under both a given number of firms and free entry

  8. Reducing Research Anxiety among MSW Students

    Science.gov (United States)

    Einbinder, Susan Dana

    2014-01-01

    Research anxiety significantly declined in a diverse sample of 59 MSW students in their first-year hybrid online research course in which the instructor used an array of innovative educational techniques empirically proven to reduce this phenomenon. The pretest/posttest study, the standardized survey instruments used, and a summary of these…

  9. Characterization of (per)chlorate-reducing bacteria

    NARCIS (Netherlands)

    Wolterink, A.F.W.M.

    2004-01-01

    Some bacteria can use (per)chlorateas terminal electron acceptor for growth. These bacteria convert perchlorate via chlorate and chlorite into chloride and molecular oxygen. Oxygen formation in microbial respiration is unique. In this study two chlorate-reducing strains

  10. Hybrid reduced order modeling for assembly calculations

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Youngsuk, E-mail: ysbang00@fnctech.com [FNC Technology, Co. Ltd., Yongin-si (Korea, Republic of); Abdel-Khalik, Hany S., E-mail: abdelkhalik@purdue.edu [Purdue University, West Lafayette, IN (United States); Jessee, Matthew A., E-mail: jesseema@ornl.gov [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Mertyurek, Ugur, E-mail: mertyurek@ornl.gov [Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    2015-12-15

    Highlights: • Reducing computational cost in engineering calculations. • Reduced order modeling algorithm for multi-physics problem like assembly calculation. • Non-intrusive algorithm with random sampling. • Pattern recognition in the components with high sensitive and large variation. - Abstract: While the accuracy of assembly calculations has considerably improved due to the increase in computer power enabling more refined description of the phase space and use of more sophisticated numerical algorithms, the computational cost continues to increase which limits the full utilization of their effectiveness for routine engineering analysis. Reduced order modeling is a mathematical vehicle that scales down the dimensionality of large-scale numerical problems to enable their repeated executions on small computing environment, often available to end users. This is done by capturing the most dominant underlying relationships between the model's inputs and outputs. Previous works demonstrated the use of the reduced order modeling for a single physics code, such as a radiation transport calculation. This manuscript extends those works to coupled code systems as currently employed in assembly calculations. Numerical tests are conducted using realistic SCALE assembly models with resonance self-shielding, neutron transport, and nuclides transmutation/depletion models representing the components of the coupled code system.

  11. Reducing the risk of nuclear terrorism

    International Nuclear Information System (INIS)

    Hibbs, R.

    2005-01-01

    Full text: The March 2005 'International conference on nuclear security, global directions for the future' noted that nuclear terrorism is one of the greatest threats to society. Eminent members of a multi-national panel stated that there is no one principal activity to reduce the risk of nuclear terrorism and that a combination of activities is required. This paper seeks to identify those activities by analyzing the elements that comprise the risk of nuclear terrorism. For the purpose of the analysis, risk is the product of the probability of a terrorist attack (A p ), the success of a terrorist act (S p ) and the consequence (C) of the attack: R=A p * S p * C. The paper examines each of these three elements of risk with the objective of identifying what we are doing and what else we could be doing to reduce risk. It takes into consideration some historic catastrophes, examines how they might have been prevented or their consequences reduced, and if there are lessons that are applicable to reducing the risk of nuclear terrorism. The paper demonstrates that we have concentrated on only one of the three elements of risk and offer suggestions for diminishing the risk of nuclear terrorism by addressing all the elements. (author)

  12. How to reduce your fire insurance rates

    Science.gov (United States)

    Dubain, M.

    1971-01-01

    Construction procedures and utilization of materials to reduce the cost of insuring large buildings against losses from fire are discussed. Examples of good and bad techniques in building construction and fire safety management are provided. The inadequacies of building codes and the hazards resulting from improper construction are examined.

  13. Strategies for Reducing Criminal Violence among Athletes.

    Science.gov (United States)

    Staffo, Donald F.

    2001-01-01

    Discusses the serious problem of criminal violence in the personal lives of athletes, suggesting strategies that physical educators, coaches, and school systems can implement with young athletes which could reduce the incidence and severity of violence later in life (e.g., teaching unconditional respect for others, continually reinforcing social…

  14. Estimating Reduced Consumption for Dynamic Demand Response

    Energy Technology Data Exchange (ETDEWEB)

    Chelmis, Charalampos [Univ. of Southern California, Los Angeles, CA (United States); Aman, Saima [Univ. of Southern California, Los Angeles, CA (United States); Saeed, Muhammad Rizwan [Univ. of Southern California, Los Angeles, CA (United States); Frincu, Marc [Univ. of Southern California, Los Angeles, CA (United States); Prasanna, Viktor K. [Univ. of Southern California, Los Angeles, CA (United States)

    2015-01-30

    Growing demand is straining our existing electricity generation facilities and requires active participation of the utility and the consumers to achieve energy sustainability. One of the most effective and widely used ways to achieve this goal in the smart grid is demand response (DR), whereby consumers reduce their electricity consumption in response to a request sent from the utility whenever it anticipates a peak in demand. To successfully plan and implement demand response, the utility requires reliable estimate of reduced consumption during DR. This also helps in optimal selection of consumers and curtailment strategies during DR. While much work has been done on predicting normal consumption, reduced consumption prediction is an open problem that is under-studied. In this paper, we introduce and formalize the problem of reduced consumption prediction, and discuss the challenges associated with it. We also describe computational methods that use historical DR data as well as pre-DR conditions to make such predictions. Our experiments are conducted in the real-world setting of a university campus microgrid, and our preliminary results set the foundation for more detailed modeling.

  15. Targeting incentives to reduce habitat fragmentation

    Science.gov (United States)

    David Lewis; Andrew Plantinga; Junjie Wu

    2009-01-01

    This article develops a theoretical model to analyze the spatial targeting of incentives for the restoration of forested landscapes when wildlife habitat can be enhanced by reducing fragmentation. The key theoretical result is that the marginal net benefits of increasing forest can be convex, in which case corner solutions--converting either none or all of the...

  16. The Three Rs: Reduce, Reuse, Recycle.

    Science.gov (United States)

    Science Activities, 1991

    1991-01-01

    A student hand-out for a recycling unit defines the terms reduce, recycle, and reuse as they relate to solid waste management. Presents the characteristics of recyclable items such as yard wastes, metals, glass, and paper. Lists organizations through which more information about recycling can be obtained. (MCO)

  17. Engaging to reduce emissions and solidarity

    International Nuclear Information System (INIS)

    Colombier, M.; Dessus, B.; Laponche, B.

    1997-01-01

    The different negotiations about the reduction of greenhouse gases emissions is studied in this article. The problem of developing countries or fast developing countries such asian countries is evoked. The rate of carbon dioxide emission could be calculated in function of GDP (gross domestic product) to allow to reduce the gaps between the different countries. (N.C.)

  18. Sodium Valproate Withdrawal Correlates with Reduced Aggression

    Science.gov (United States)

    Pritchard, Duncan; Hoerger, Marguerite; Dyer, Tim; Graham, Nicola; Penney, Heather; Mace, F. Charles

    2014-01-01

    People with learning disabilities are sometimes prescribed psychotropic medication to help manage their challenging behaviour. This case study describes how a multicomponent behavioural intervention in conjunction with the systematic withdrawal of sodium valproate was strongly correlated with reduced aggression. No symptoms of bipolar disorder or…

  19. QUIESST Guidebook to Noise Reducing Devices optimisation

    NARCIS (Netherlands)

    Clairbois, J.P.; Roo, F. de; Garai, M.; Conter, M.; Defrance, J.; Oltean-Dumbrava, C.A.; Durso, C.

    2012-01-01

    The aim of this guidebook is to become a reference tool for noise mitigation through a better use of Noise Reducing Devices (NRD) (e.g.: Noise Barriers or sound Absorptive Claddings). It targets all the stakeholders involved in NRD projects (designers, manufacturers, authorities, construction

  20. Reducing Depression in Pregnancy: Designing Multimodel Interventions.

    Science.gov (United States)

    Cunningham, Maddy; Zayas, Luis H.

    2002-01-01

    High levels of stress on low-income, inner-city women from ethnic minority groups often causes both poor maternal functioning and infant development outcomes. This article reviews literature that proposes using several social work treatment options instead a single approach to reduce maternal depression, expand mothers' social networks, and…

  1. Reducing methane emissions from ruminant animals

    Energy Technology Data Exchange (ETDEWEB)

    Mathison, G.W.; Okine, E.K.; McAllister, T.A.; Dong, Y.; Galbraith, J.; Dmytruk, O.I.N. [University of Alberta, Edmonton, AB (Canada). Dept. of Agriculture, Food and Nutrition Science

    1998-09-01

    In 1992 it was estimated that 30 x 10{sup 12}g more methane was emitted into the atmosphere than was removed, with animals being considered the largest single anthropogenic source. Ruminants produce 97% of the methane generated in enteric fermentation by animals. Estimates for methane emissions from animal wastes vary between 6 and 31% of that produced directly by the animal, with the most likely value being between 5 and 10% globally. Methane inhibitors can reduce methane emissions to zero in the short term but due to microbial adaptation the effects of these compounds are quickly neutralized and feed intake is often depressed. Methane emissions per unit of feed consumed from sheep and cattle fed hay diets appear to be quite similar but differences between other ruminants have been measured. The most practical way of influencing methane emissions per unit product is to increase productivity level since the proportion of feed energy required to just maintain the animal will be reduced, methane production falls with increased intake level, and the animal may go to market sooner. The most promising avenues for future research for reducing methanogenesis are the development of new products for reducing protozoal numbers in the rumen and the use of bacterocins or other compounds which specifically target methanogenic bacteria.

  2. Reducing cardiovascular risk : protecting the kidney

    NARCIS (Netherlands)

    Dobre, Daniela; Lambers Heerspink, Hiddo J.; de Zeeuw, Dick

    2009-01-01

    Progressive decline of renal function in chronic kidney disease (CKD), measured by a reduced glomerular filtration rate or albuminuria, is linked to an increased risk of cardiovascular (CV) disease. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), most

  3. Prehydrolyzed dietary protein reduces gastrocnemial DNA without ...

    African Journals Online (AJOL)

    Prehydrolyzed dietary protein reduces gastrocnemial DNA without impairing physical capacity in the rat. Viviane Costa Silva Zaffani, Carolina Cauduro Bensabath Carneiro-Leão, Giovana Ermetice de Almeida Costa, Pablo Christiano Barboza Lollo, Emilianne Miguel Salomão, Maria Cristina Cintra Gomes-Marcondes, ...

  4. Sulfate reducing potential in an estuarine beach

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.; Chandramohan, D.

    Sulfate reducing bacteria (SRB) and their activity (SRA) together with total anaerobic and aerobic bacterial flora were estimated during July 1982-April 1983 and July-August 1984 from 1, 3 and 5 cm depths using core samples. The average number (no...

  5. Managing Risk, Reducing Vulnerability and Enhancing Productivity ...

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

    Managing Risk, Reducing Vulnerability and Enhancing Productivity under a Changing Climate. The countries of the Greater Horn of Africa are particularly vulnerable to drought, exacerbated by widespread poverty and dependence on rainfed agriculture. Even with normal rainfall, the region does not produce enough food to ...

  6. Reducing the Risk of Methadone Overdose

    Centers for Disease Control (CDC) Podcasts

    2012-07-03

    This podcast is based on the July 2012 CDC Vital Signs report. Approximately 14 people die every day of overdoses related to methadone. Listen to learn how to reduce your risk of an overdose.  Created: 7/3/2012 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/3/2012.

  7. Sexual Harassment at Camp: Reducing Liability.

    Science.gov (United States)

    Oakleaf, Linda; Grube, Angela Johnson

    2003-01-01

    Employers are responsible for sexual harassment perpetrated by a supervisor. Camps may be responsible for sexual harassment between campers. Steps to reduce liability include providing multiple channels for reporting sexual harassment; having written policies prohibiting sexual harassment and procedures for reporting it; posting these policies and…

  8. Factorial and reduced K-means reconsidered

    NARCIS (Netherlands)

    Timmerman, Marieke E.; Ceulemans, Eva; Kiers, Henk A. L.; Vichi, Maurizio

    2010-01-01

    Factorial K-means analysis (FKM) and Reduced K-means analysis (RKM) are clustering methods that aim at simultaneously achieving a clustering of the objects and a dimension reduction of the variables. Because a comprehensive comparison between FKM and RKM is lacking in the literature so far, a

  9. Reducing operational costs through MIPS management

    NARCIS (Netherlands)

    Kwiatkowski, L.M.; Verhoef, C.

    2015-01-01

    We focus on an approach to reducing the costs of running applications. MIPS, which is a traditional acronym for millions of instructions per second, have evolved to become a measurement of processing power and CPU resource consumption. The need for controlling MIPS attributed costs is indispensable

  10. The 'polypill' to reduce cardiovascular risk

    DEFF Research Database (Denmark)

    Patel, Vinod; Pedersen, Oluf; Morrissey, John

    2004-01-01

    This article considers data from the Steno-2 multifactorial intervention study in type 2 diabetes to which are applied the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Mathematical analyses support the use of a 'polypill' to reduce cardiovascular risk in type 2 diabetes. It is s...

  11. General Reducibility and Solvability of Polynomial Equations ...

    African Journals Online (AJOL)

    General Reducibility and Solvability of Polynomial Equations. ... Unlike quadratic, cubic, and quartic polynomials, the general quintic and higher degree polynomials cannot be solved algebraically in terms of finite number of additions, ... Galois Theory, Solving Polynomial Systems, Polynomial factorization, Polynomial Ring ...

  12. Reducing nitrogen oxides from power stations

    International Nuclear Information System (INIS)

    Scheller, W.

    1986-12-01

    The report contains 17 individual lectures of the seminar included in databanks. The lectures concern combustion and waste gas measures for reducing the sulfur dioxide and nitrogen oxide emission from coal-fired and gas-fired power stations. (PW) [de

  13. Reduced Voltage Scaling in Clock Distribution Networks

    Directory of Open Access Journals (Sweden)

    Khader Mohammad

    2009-01-01

    Full Text Available We propose a novel circuit technique to generate a reduced voltage swing (RVS signals for active power reduction on main buses and clocks. This is achieved without performance degradation, without extra power supply requirement, and with minimum area overhead. The technique stops the discharge path on the net that is swinging low at a certain voltage value. It reduces active power on the target net by as much as 33% compared to traditional full swing signaling. The logic 0 voltage value is programmable through control bits. If desired, the reduced-swing mode can also be disabled. The approach assumes that the logic 0 voltage value is always less than the threshold voltage of the nMOS receivers, which eliminate the need of the low to high voltage translation. The reduced noise margin and the increased leakage on the receiver transistors using this approach have been addressed through the selective usage of multithreshold voltage (MTV devices and the programmability of the low voltage value.

  14. Method for reducing snap in magnetic amplifiers

    Science.gov (United States)

    Fischer, R. L. E.; Word, J. L.

    1968-01-01

    Method of reducing snap in magnetic amplifiers uses a degenerative feedback circuit consisting of a resistor and a separate winding on a magnetic core. The feedback circuit extends amplifier range by allowing it to be used at lower values of output current.

  15. Software system for reducing PAM-2 data

    Science.gov (United States)

    Pepin, T. J.

    1982-01-01

    A software system for reducing PAM-II data was constructed. The data reduction process concatenates data tapes; determines ephemeris; and inverts full sun extinction data. Tests of this data reduction process show that PAM-II data can be compared with data from other, similar satellites.

  16. Quasi-equilibria in reduced Liouville spaces.

    Science.gov (United States)

    Halse, Meghan E; Dumez, Jean-Nicolas; Emsley, Lyndon

    2012-06-14

    The quasi-equilibrium behaviour of isolated nuclear spin systems in full and reduced Liouville spaces is discussed. We focus in particular on the reduced Liouville spaces used in the low-order correlations in Liouville space (LCL) simulation method, a restricted-spin-space approach to efficiently modelling the dynamics of large networks of strongly coupled spins. General numerical methods for the calculation of quasi-equilibrium expectation values of observables in Liouville space are presented. In particular, we treat the cases of a time-independent Hamiltonian, a time-periodic Hamiltonian (with and without stroboscopic sampling) and powder averaging. These quasi-equilibrium calculation methods are applied to the example case of spin diffusion in solid-state nuclear magnetic resonance. We show that there are marked differences between the quasi-equilibrium behaviour of spin systems in the full and reduced spaces. These differences are particularly interesting in the time-periodic-Hamiltonian case, where simulations carried out in the reduced space demonstrate ergodic behaviour even for small spins systems (as few as five homonuclei). The implications of this ergodic property on the success of the LCL method in modelling the dynamics of spin diffusion in magic-angle spinning experiments of powders is discussed.

  17. Costs of emission-reducing manure application

    NARCIS (Netherlands)

    Huijsmans, J.F.M.; Verwijs, B.; Rodhe, L.; Smith, K.

    2004-01-01

    Favourable economics of handling and application of manure are of fundamental importance to encourage the implementation of emission-reducing application techniques. The economics of manure application depend on the costs of the equipment and the time to carry out the field operation. In this study

  18. Interventions: Employees’ Perceptions of What Reduces Stress

    Directory of Open Access Journals (Sweden)

    Silvia Pignata

    2017-01-01

    Full Text Available Objective. To build upon research evaluating stress interventions, this qualitative study tests the framework of the extended Job Demands-Resources model to investigate employees’ perceptions of the stress-reduction measures implemented at 13 Australian universities. Methods. In a cross-sectional survey design, tenured and contract staff indicated whether their overall level of stress had changed during the previous three-four years, and, if so, they described the major causes. A total of 462 staff reported that their level of stress had decreased; the study examines commentary from 115 academic and 304 nonacademic staff who provided details of what they perceived to be effective in reducing stress. Results. Thematic analyses show that the key perceived causes were changes in job or work role, new heads of departments or supervisors, and the use of organizational strategies to reduce or manage stress. A higher percentage of academic staff reported reduced stress due to using protective coping strategies or their increased recognition and/or success, whereas a higher percentage of nonacademic staff reported reduced stress due to increases in staffing resources and/or systems. Conclusion. These results identify the importance of implementing multilevel strategies to enhance employees’ well-being. Nonacademic staff, in particular, specified a variety of organizational stress-reduction interventions.

  19. Reducible cationic lipids for gene transfer.

    Science.gov (United States)

    Wetzer, B; Byk, G; Frederic, M; Airiau, M; Blanche, F; Pitard, B; Scherman, D

    2001-01-01

    One of the main challenges of gene therapy remains the increase of gene delivery into eukaryotic cells. We tested whether intracellular DNA release, an essential step for gene transfer, could be facilitated by using reducible cationic DNA-delivery vectors. For this purpose, plasmid DNA was complexed with cationic lipids bearing a disulphide bond. This reduction-sensitive linker is expected to be reduced and cleaved in the reducing milieu of the cytoplasm, thus potentially improving DNA release and consequently transfection. The DNA--disulphide-lipid complexation was monitored by ethidium bromide exclusion, and the size of complexes was determined by dynamic light scattering. It was found that the reduction kinetics of disulphide groups in DNA--lipid complexes depended on the position of the disulphide linker within the lipid molecule. Furthermore, the internal structure of DNA--lipid particles was examined by small-angle X-ray scattering before and after lipid reduction. DNA release from lipid complexes was observed after the reduction of disulphide bonds of several lipids. Cell-transfection experiments suggested that complexes formed with selected reducible lipids resulted in up to 1000-fold higher reporter-gene activity, when compared with their analogues without disulphide bonds. In conclusion, reduction-sensitive groups introduced into cationic lipid backbones potentially allow enhanced DNA release from DNA--lipid complexes after intracellular reduction and represent a tool for improved vectorization. PMID:11389682

  20. Holonomy-reduced dynamics of triatomic molecules

    NARCIS (Netherlands)

    Çiftçi, Ünver; Waalkens, Holger

    2011-01-01

    Whereas it is easy to reduce the translational symmetry of a molecular system using, e.g., Jacobi coordinates, the situation is much more involved for rotational symmetry. In this paper, we address the latter problem using holonomy reduction. We suggest that the configuration space may be considered

  1. Heat Pipes Reduce Engine-Exhaust Emissions

    Science.gov (United States)

    Schultz, D. F.

    1986-01-01

    Increased fuel vaporization raises engine efficiency. Heat-pipe technology increased efficiency of heat transfer beyond that obtained by metallic conduction. Resulted in both improved engine operation and reduction in fuel consumption. Raw material conservation through reduced dependence on strategic materials also benefit from this type of heat-pipe technology. Applications result in improved engine performance and cleaner environment.

  2. Reducing Heating In High-Speed Cinematography

    Science.gov (United States)

    Slater, Howard A.

    1989-01-01

    Infrared-absorbing and infrared-reflecting glass filters simple and effective means for reducing rise in temperature during high-speed motion-picture photography. "Hot-mirror" and "cold-mirror" configurations, employed in projection of images, helps prevent excessive heating of scenes by powerful lamps used in high-speed photography.

  3. Approaches to reduce bullying in schools

    DEFF Research Database (Denmark)

    Kousholt, Kristine; Fisker, Tine Basse

    2015-01-01

    processes) to embrace the different understandings of bullying and to discuss these critically. The purpose is to present important knowledge to reduce bullying and to engage in a discussion of different perspectives on bullying. This article contributes to the existing knowledge of the field by discussing...

  4. Reducing Ripple In A Switching Voltage Regulator

    Science.gov (United States)

    Paulkovich, John; Rodriguez, G. Ernest

    1994-01-01

    Ripple voltage in output of switching voltage regulator reduced substantially by simple additional circuitry adding little to overall weight and size of regulator. Heretofore, additional filtering circuitry needed to obtain comparable reductions in ripple typically as large and heavy as original regulator. Current opposing ripple current injected into filter capacitor.

  5. Thermal properties of graphite oxide, thermally reduced graphene and chemically reduced graphene

    Science.gov (United States)

    Jankovský, Ondřej; Sedmidubský, David; Lojka, Michal; Sofer, Zdeněk

    2017-07-01

    We compared thermal behavior and other properties of graphite oxide, thermally reduced graphene and chemically reduced graphene. Graphite was oxidized according to the Hofmann method using potassium chlorate as oxidizing agent in strongly acidic environment. In the next step, the formed graphite oxide was chemically or thermally reduced yielding graphene. The mechanism of thermal reduction was studied using STA-MS. Graphite oxide and both thermally and chemically reduced graphenes were analysed by SEM, EDS, elemental combustion analysis, XPS, Raman spectroscopy, XRD and BET. These findings will help for the large scale production of graphene with appropriate chemical composition.

  6. Human Performance in Simulated Reduced Gravity Environments

    Science.gov (United States)

    Cowley, Matthew; Harvill, Lauren; Rajulu, Sudhakar

    2014-01-01

    NASA is currently designing a new space suit capable of working in deep space and on Mars. Designing a suit is very difficult and often requires trade-offs between performance, cost, mass, and system complexity. Our current understanding of human performance in reduced gravity in a planetary environment (the moon or Mars) is limited to lunar observations, studies from the Apollo program, and recent suit tests conducted at JSC using reduced gravity simulators. This study will look at our most recent reduced gravity simulations performed on the new Active Response Gravity Offload System (ARGOS) compared to the C-9 reduced gravity plane. Methods: Subjects ambulated in reduced gravity analogs to obtain a baseline for human performance. Subjects were tested in lunar gravity (1.6 m/sq s) and Earth gravity (9.8 m/sq s) in shirt-sleeves. Subjects ambulated over ground at prescribed speeds on the ARGOS, but ambulated at a self-selected speed on the C-9 due to time limitations. Subjects on the ARGOS were given over 3 minutes to acclimate to the different conditions before data was collected. Nine healthy subjects were tested in the ARGOS (6 males, 3 females, 79.5 +/- 15.7 kg), while six subjects were tested on the C-9 (6 males, 78.8 +/- 11.2 kg). Data was collected with an optical motion capture system (Vicon, Oxford, UK) and was analyzed using customized analysis scripts in BodyBuilder (Vicon, Oxford, UK) and MATLAB (MathWorks, Natick, MA, USA). Results: In all offloaded conditions, variation between subjects increased compared to 1-g. Kinematics in the ARGOS at lunar gravity resembled earth gravity ambulation more closely than the C-9 ambulation. Toe-off occurred 10% earlier in both reduced gravity environments compared to earth gravity, shortening the stance phase. Likewise, ankle, knee, and hip angles remained consistently flexed and had reduced peaks compared to earth gravity. Ground reaction forces in lunar gravity (normalized to Earth body weight) were 0.4 +/- 0.2 on

  7. Simulation of sediment settling in reduced gravity

    Science.gov (United States)

    Kuhn, Nikolaus; Kuhn, Brigitte; Rüegg, Hans-Rudolf; Gartmann, Andres

    2015-04-01

    Gravity has a non-linear effect on the settling velocity of sediment particles in liquids and gases due to the interdependence of settling velocity, drag and friction. However, Stokes' Law or similar empirical models, the common way of estimating the terminal velocity of a particle settling in a gas or liquid, carry the notion of a drag as a property of a particle, rather than a force generated by the flow around the particle. For terrestrial applications, this simplifying assumption is not relevant, but it may strongly influence the terminal velocity achieved by settling particles on other planetary bodies. False estimates of these settling velocities will, in turn, affect the interpretation of particle sizes observed in sedimentary rocks, e.g. on Mars and the search for traces of life. Simulating sediment settling velocities on other planets based on a numeric simulation using Navier-Stokes equations and Computational Fluid Dynamics requires a prohibitive amount of time and lacks measurements to test the quality of the results. The aim of the experiments presented in this study was therefore to quantify the error incurred by using settling velocity models calibrated on Earth at reduced gravities, such as those on the Moon and Mars. In principle, the effect of lower gravity on settling velocity can be achieved by reducing the difference in density between particle and liquid. However, the use of such analogues creates other problems because the properties (i.e. viscosity) and interaction of the liquids and sediment (i.e. flow around the boundary layer between liquid and particle) differ from those of water and mineral particles. An alternative for measuring the actual settling velocities of particles under reduced gravity, on Earth, is offered by placing a settling tube on a reduced gravity flight and conduct settling velocity measurements within the 20 to 25 seconds of Martian gravity that can be simulated during such a flight. In this presentation, the results

  8. Primaquine for reducing Plasmodium falciparum transmission.

    Science.gov (United States)

    Graves, Patricia M; Gelband, Hellen; Garner, Paul

    2012-09-12

    Mosquitoes become infected with malaria when they ingest gametocyte stages of the parasite from the blood of a human host. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ). The World Health Organization (WHO) recommends giving a single dose or short course of PQ alongside primary treatment for people ill with P. falciparum infection to reduce malaria transmission. Gametocytes themselves cause no symptoms, so this intervention does not directly benefit individuals. PQ causes haemolysis in some people with glucose-6-phosphate dehydrogenase (G6PD) deficiency so may not be safe.   To assess whether a single dose or short course of PQ added to treatments for malaria caused by P. falciparum infection reduces malaria transmission and is safe. We searched the following databases up to 10 April 2012 for studies: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT) and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and we contacted likely researchers and organizations for relevant trials. Trials of mass treatment of whole populations (or actively detected fever or malaria cases within such populations) with antimalarial drugs, compared to treatment with the same drug plus PQ; or patients with clinical malaria being treated for malaria at health facilities randomized to short course/single dose PQ versus no PQ. Two authors (PMG and HG) independently screened all abstracts, applied inclusion criteria, and abstracted data. We sought data on the effect of PQ on malaria transmission intensity, participant infectiousness, the number of participants with gametocytes, and gametocyte density over time. We stratified results by primary treatment drug as

  9. Advanced technology development reducing CO2 emissions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sup

    2010-09-15

    Responding to Korean government policies on green growth and global energy/ environmental challenges, SK energy has been developing new technologies to reduce CO2 emissions by 1) CO2 capture and utilization, 2) efficiency improvement, and 3) Li-ion batteries. The paper introduces three advanced technologies developed by SK energy; GreenPol, ACO, and Li-ion battery. Contributing to company vision, a more energy and less CO2, the three technologies are characterized as follows. GreenPol utilizes CO2 as a feedstock for making polymer. Advanced Catalytic Olefin (ACO) reduces CO2 emission by 20% and increase olefin production by 17%. Li-ion Batteries for automotive industries improves CO2 emission.

  10. Restricted fish feeding reduces cod otolith opacity

    DEFF Research Database (Denmark)

    Høie, H.; Folkvord, A.; Mosegaard, Henrik

    2008-01-01

    The purpose of this work was to examine the effect of reduced feeding and constant temperature on cod otolith opacity. Three groups of juvenile cod were given restricted food rations at different times for 4 months, resulting in depressed somatic growth. Otolith opacity was measured on pictures...... in otolith opacity were found between individual fish both within groups and between groups. In two of the three groups significantly more translucent otolith material was deposited in response to reduced feeding. Our results show that variations in feeding and hence fish growth resulted in variation...... in otolith opacity, but the effect was minor compared to that of variations in ambient temperature. The combined influence of these effects, which both act on fish metabolism, are most likely controlling the seasonal opacity changes observed in wild fish. Our results help explain the variations seen in fish...

  11. Producing Knowledge to Reduce Rhetorical Distance

    DEFF Research Database (Denmark)

    Kampf, Constance

    writers a larger public forum into which they can extend their identity. When the identity being extended represents a minority group, the web offers an opportunity for members of that group to engage mainstream ideology and work at reducing the rhetorical distance between their identity and mainstream......Producing Knowledge to Reduce Rhetorical Distance: Extending Identity and Engaging Mainstream Ideology via the Web Constance Kampf, Department of Research Knowledge Communication, Aarhus School of Business, Denmark McLuhan describes technologies as extensions -the wheel being an extension...... perceptions. This paper theorizes about ways in which the Internet can change the act of producing knowledge through the characteristics of speed and reach, allowing minorities to access a widespread audience much more easily than before the Internet. Access to a widespread audience, in turn, offers...

  12. Costs of reducing nutrient losses in Denmark

    DEFF Research Database (Denmark)

    Jacobsen, Brian H.; Abildtrup, Jens; Jensen, Jørgen Dejgård

    to the eastern part of Denmark. The final plan for the Aquatic Environment III from 2004 included a 13% reduction of N-leaching until 2015 based on cost effective administrative measures like wetlands and catch crops. Also a tax on mineral phosphorus in feedstuffs was included in order to half the phosphorus......The economic calculations carried out prior to the Plan for the Aquatic Environment III included a comparison of regulation systems aimed at reducing nitrogen leaching, analyses of measures for reducing phosphorus losses and estimation of administrative costs. The conclusions were that taxation...... surplus. The measures in the Plan will have to be supplemented by more measures to meet the targets in the EU's Water Framework Directive....

  13. Evaluating State Options for Reducing Medicaid Churning

    Science.gov (United States)

    Swartz, Katherine; Short, Pamela Farley; Graefe, Deborah R.; Uberoi, Namrata

    2015-01-01

    Medicaid churning - the constant exit and re-entry of beneficiaries as their eligibility changes - has long been a problem for both Medicaid administrators and recipients. Churning will continue under the Affordable Care Act, because despite new federal rules, Medicaid eligibility will continue to be based on current monthly income. We developed a longitudinal simulation model to evaluate four policy options for modifying or extending Medicaid eligibility to reduce churning. The simulations suggest that two options, extending Medicaid eligibility either to the end of a calendar year or for twelve months after enrollment, would be far more effective in reducing churning than the other options of a three-month extension or eligibility based on projected annual income. States should consider implementation of the option that best balances costs, including both administration and services, with improved health of Medicaid enrollees. PMID:26153313

  14. Handgun waiting periods reduce gun deaths.

    Science.gov (United States)

    Luca, Michael; Malhotra, Deepak; Poliquin, Christopher

    2017-11-14

    Handgun waiting periods are laws that impose a delay between the initiation of a purchase and final acquisition of a firearm. We show that waiting periods, which create a "cooling off" period among buyers, significantly reduce the incidence of gun violence. We estimate the impact of waiting periods on gun deaths, exploiting all changes to state-level policies in the Unites States since 1970. We find that waiting periods reduce gun homicides by roughly 17%. We provide further support for the causal impact of waiting periods on homicides by exploiting a natural experiment resulting from a federal law in 1994 that imposed a temporary waiting period on a subset of states. Copyright © 2017 the Author(s). Published by PNAS.

  15. Reduced graphite oxide in supercapacitor electrodes.

    Science.gov (United States)

    Lobato, Belén; Vretenár, Viliam; Kotrusz, Peter; Hulman, Martin; Centeno, Teresa A

    2015-05-15

    The current energy needs have put the focus on highly efficient energy storage systems such as supercapacitors. At present, much attention focuses on graphene-like materials as promising supercapacitor electrodes. Here we show that reduced graphite oxide offers a very interesting potential. Materials obtained by oxidation of natural graphite and subsequent sonication and reduction by hydrazine achieve specific capacitances as high as 170 F/g in H2SO4 and 84F/g in (C2H5)4NBF4/acetonitrile. Although the particle size of the raw graphite has no significant effect on the physico-chemical characteristics of the reduced materials, that exfoliated from smaller particles (materials may suffer from a drop in their specific surface area upon fabrication of electrodes with features of the existing commercial devices. This should be taken into account for a reliable interpretation of their performance in supercapacitors. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Reducing Psychological Resistance to Digital Repositories

    Directory of Open Access Journals (Sweden)

    Brian Quinn

    2010-06-01

    Full Text Available The potential value of digital repositories is dependent on the cooperation of scholars to deposit their work. Although many researchers have been resistant to submitting their work, the literature on digital repositories contains very little research on the psychology of resistance. This article looks at the psychological literature on resistance and explores what its implications might be for reducing the resistance of scholars to submitting their work to digital repositories. Psychologists have devised many potentially useful strategies for reducing resistance that might be used to address the problem; this article examines these strategies and how they might be applied.

  17. Activating Attachments Reduces Memories of Traumatic Images.

    Directory of Open Access Journals (Sweden)

    Richard A Bryant

    Full Text Available Emotional memories, and especially intrusive memories, are a common feature of many psychological disorders, and are overconsolidated by stress. Attachment theory posits that activation of mental representations of attachment figures can reduce stress and boost coping. This study tested the proposition that attachment activation would reduce consolidation of emotional and intrusive memories. Sixty-seven undergraduate students viewed subliminal presentations of traumatic and neutral images, which were preceded by subliminal presentations of either attachment-related images or non-attachment-related images; free recall and intrusive memories were assessed two days later. Participants with low avoidant attachment tendencies who received the attachment primes recalled fewer memories and reported fewer intrusions than those who received the non-attachment primes. Unexpectedly, those with high anxious attachment tendencies reported fewer memories. These findings generally accord with attachment theory, and suggest that consolidation of emotional memories can be moderated by activation of attachment representations.

  18. FETC Programs for Reducing Greenhouse Gas Emissions

    International Nuclear Information System (INIS)

    Ruether, J.A.

    1998-02-01

    Mark Twain once quipped that everyone talks about the weather but no one does anything about it. With interest in global climate change on the rise, researchers in the fossil-energy sector are feeling the heat to provide new technology to permit continued use of fossil fuels but with reduced emissions of so-called 'greenhouse gases.' Three important greenhouse gases, carbon dioxide, methane, and nitrous oxide, are released to the atmosphere in the course of recovering and combusting fossil fuels. Their importance for trapping radiation, called forcing, is in the order given. In this report, we briefly review how greenhouse gases cause forcing and why this has a warming effect on the Earth's atmosphere. Then we discuss programs underway at FETC that are aimed at reducing emissions of methane and carbon dioxide

  19. Vitamin D with calcium reduces mortality

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Avenell, Alison; Masud, Tahir

    2012-01-01

    Introduction: Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either...... vitamin D alone or vitamin D with calcium. Subjects and Methods: Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each......,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62-77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88-0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin...

  20. Method of reducing radioactivity in nuclear reactors

    International Nuclear Information System (INIS)

    Koshino, Yasuo

    1987-01-01

    Purpose: To prevent increase of radiation dose ratio in primary coolant circuit pipeways of nuclear reactor and reduce operators' exposure dose upon periodical inspection, etc. Method: β-diketone such as acetylacetone is added in a predetermined amount to reactor cooling water. β-diketone dissolves to catch metal ions and iron oxides as the main ingredient of cruds. The resultant β-diketone complex of metals is slightly water soluble neutron molecule, and the total metal amount in the reactor coolant is at a concentration of less than 10 ppb and completely dissolved in water. Accordingly, deposition of clads in the coolant to pipeways can be prevented thereby enabling to prevent the increase in the radiation dose ratio in the pipeways and thus reduce the operators' exposure dose. (Takahashi, M.)

  1. Preoperative antiseptic skin preparations and reducing SSI.

    Science.gov (United States)

    Al Maqbali, Mohammed Abdullah

    Surgical site infection (SSI) can affect the quality of care and increase the morbidity and mortality rate in after-surgical procedure. The use of an antiseptic skin preparation agent before the procedure can reduce the pathogens in the skin surface around the incision. Indicating the type of skin antiseptic preparation could prevent the infection and contamination of the wound. The most commonly used types of skin preparations are chlorhexidine and povidone iodine. However, the antiseptic solutions of both agents are strengthened with alcohol to prevent postoperative wound infection. The aim of this paper is to identify the best antiseptic agent in terms of skin preparation by evaluating the evidence in the literature. The factors associated with choosing the antiseptic skin agent, such as patients' allergies, skin condition and environmental risk, are also taken into account. This review suggests that cholorhexdine with alcohol may be the most effective in terms of reducing SSI.

  2. Deciding for Others Reduces Loss Aversion

    DEFF Research Database (Denmark)

    Andersson, Ola; Holm, Håkan J.; Tyran, Jean-Robert Karl

    2016-01-01

    We study risk taking on behalf of others, both when choices involve losses and when they do not. A large-scale incentivized experiment with subjects randomly drawn from the Danish population is conducted. We find that deciding for others reduces loss aversion. When choosing between risky prospects...... when losses loom. This finding is consistent with an interpretation of loss aversion as a bias in decision making driven by emotions and that these emotions are reduced when making decisions for others....... for which losses are ruled out by design, subjects make the same choices for themselves as for others. In contrast, when losses are possible, we find that the two types of choices differ. In particular, we find that subjects who make choices for themselves take less risk than those who decide for others...

  3. ECONOMIC GROWTH AND EQUALITY IN REDUCING POVERTY

    Directory of Open Access Journals (Sweden)

    Zaenal Muttaqin

    2016-02-01

    Full Text Available In some developing countries, the instrument to alleviate the poverty is by using the economic growth. So, the increasing in investment, infrastructure development, and macroeconomics stability always be priority from developing countries. In this article explain that economic growth is not the important factor to alleviate the poverty, because equality sometimes is more important rather than the economic growth. In this context, its measure by inequality growth trade off index (IGTI. This method is to measure the influence of economic growth to reducing the inequality, with this method every country can measure which one is better to reducing the poverty whether the economic growth or equality. With this method, Laos in 2000 show that economic growth is more important than equality, but in the same year in Thailand show that equality is more important than economic growth.DOI: 10.15408/sjie.v1i1.2592

  4. Advanced technology for reducing aircraft engine pollution

    Science.gov (United States)

    Jones, R. E.

    1973-01-01

    The proposed EPA regulations covering emissions of gas turbine engines will require extensive combustor development. The NASA is working to develop technology to meet these goals through a wide variety of combustor research programs conducted in-house, by contract, and by university grant. In-house efforts using the swirl-can modular combustor have demonstrated sizable reduction in NO emission levels. Testing to reduce idle pollutants has included the modification of duplex fuel nozzles to air-assisted nozzles and an exploration of the potential improvements possible with combustors using fuel staging and variable geometry. The Experimental Clean Combustor Program, a large contracted effort, is devoted to the testing and development of combustor concepts designed to achieve a large reduction in the levels of all emissions. This effort is planned to be conducted in three phases with the final phase to be an engine demonstration of the best reduced emission concepts.

  5. Analysis of reduced widths and size

    International Nuclear Information System (INIS)

    Sharma, H.C.; Ram Raj; Nath, N.

    1977-01-01

    Recent data on S-wave neutron reduced widths for a large number of nuclei have been analysed nucleus-wise and the calculations for the degree of freedom of the associated (chi) 2 -distribution have been made using the Porter and Thomas procedure. It is noted that a number of nuclei can be fitted by a (chi) 2 -distribution with degree of freedom one, while there are few which are identified to follow a (chi) 2 -distribution with degree of freedom two and even more than two. The present analysis thus contradicts the usual presumption according to which the degree of freedom is taken to be always unity. An analytical attempt has also been made to ascertain the suitability of the data on reduced widths to be used for the analysis. These considerations are likely to modify the neutron cross-section evaluations. (author)

  6. Reducing CQI Signalling Overhead in HSPA

    Directory of Open Access Journals (Sweden)

    Saied M. Abd El-atty

    2008-01-01

    Full Text Available The efficiency of adaptive modulation and coding (AMC procedure in high speed Downlink packet access (HSDPA depends on the frequency of the channel quality information (CQI reports transmitted by the UE to Node B. The more frequent the reports are the more accurate the link adaptation procedure is. On the other hand, the frequent CQI reports increase uplink interference, reducing thus the signal reception quality at the uplink. In this study, we propose an improved CQI reporting scheme which aims to reduce the required CQI signaling by exploiting a CQI prediction method based on a finite-state Markov chain (FSMC model of the wireless channel. The simulation results show that under a high downlink traffic load, the proposed scheme has a near-to-optimum performance while produces less interference compared to the respective periodic CQI scheme.

  7. Female employment reduces fertility in rural Senegal.

    Science.gov (United States)

    Van den Broeck, Goedele; Maertens, Miet

    2015-01-01

    Economic growth and modernization of society are generally associated with fertility rate decreases but which forces trigger this is unclear. In this paper we assess how fertility changes with increased labor market participation of women in rural Senegal. Evidence from high-income countries suggests that higher female employment rates lead to reduced fertility rates but evidence from developing countries at an early stage of demographic transition is largely absent. We concentrate on a rural area in northern Senegal where a recent boom in horticultural exports has been associated with a sudden increase in female off-farm employment. Using survey data we show that employed women have a significantly higher age at marriage and at first childbirth, and significantly fewer children. As causal identification strategy we use instrumental variable and difference-in-differences estimations, combined with propensity score matching. We find that female employment reduces the number of children per woman by 25%, and that this fertility-reducing effect is as large for poor as for non-poor women and larger for illiterate than for literate women. Results imply that female employment is a strong instrument for empowering rural women, reducing fertility rates and accelerating the demographic transition in poor countries. The effectiveness of family planning programs can increase if targeted to areas where female employment is increasing or to female employees directly because of a higher likelihood to reach women with low-fertility preferences. Our results show that changes in fertility preferences not necessarily result from a cultural evolution but can also be driven by sudden and individual changes in economic opportunities.

  8. Improving food preservation to reduce food waste

    OpenAIRE

    Gronert, Alicja; Bikova, Borislava; Salce, Luca; Nogués, Marc; Batistelli, Patryk; Farid, Yomna

    2014-01-01

    The theme and issue of ‘Improving food preservation to reduce food waste’ is associated with all group members participating in this research project. This topic covers multiple processes including purchasing, preserving, preparing and storing food. The industry of fresh fruits and vegetables is an enormous market, which will not disappear any time soon. Food waste is mostly disregarded as fresh fruits and vegetables are mostly inexpensive. All group members believe that this mindset needs to...

  9. Does Auditor Tenure Reduce Audit Quality?

    OpenAIRE

    Junaidi, -; Miharjo, Setiyono; Hartadi, Bambang

    2012-01-01

    Reduced auditor independence and the rise of corporate accounting manipulations have caused trust of the users in audited financial statements to begin to decline, so users of financial statements are questioning whether public accountants are independent parties. This research issue is related to the Decree of the Minister of Finance No. 17 in 2008 about public accountant services. Giving attestation services, in the form of financial statements about an entity, are conducted by the audit fi...

  10. Clinker mineral hydration at reduced relative humidities

    DEFF Research Database (Denmark)

    Jensen, Ole Mejlhede

    1998-01-01

    This report deals with gas phase hydration of pure cement clinker minerals at reduced relative humidities. This is an important subject in relation to modern high performance concrete which may self-desiccate during hydration. In addition the subject has relevance to storage stability where...... prehydration may occur. In the report both theoretical considerations and experimental data are presented. It is suggested that the initiation of hydration during water vapour exposure is nucleation controlled....

  11. Phytosterol glycosides reduce cholesterol absorption in humans

    OpenAIRE

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series ...

  12. Leveraging Technology to Reduce Patient Transaction Costs.

    Science.gov (United States)

    Edlow, Richard C

    2015-01-01

    Medical practices are under significant pressure to provide superior customer service in an environment of declining or flat reimbursement. The solution for many practices involves the integration of a variety of third-party technologies that conveniently interface with one's electronic practice management and medical records systems. Typically, the applications allow the practice to reduce the cost of each patient interaction. Drilling down to quantify the cost of each individual patient interaction helps to determine the practicality of implementation.

  13. ''Reduced'' magnetohydrodynamics and minimum dissipation rates

    International Nuclear Information System (INIS)

    Montgomery, D.

    1992-01-01

    It is demonstrated that all solutions of the equations of ''reduced'' magnetohydrodynamics approach a uniform-current, zero-flow state for long times, given a constant wall electric field, uniform scalar viscosity and resistivity, and uniform mass density. This state is the state of minimum energy dissipation rate for these boundary conditions. No steady-state turbulence is possible. The result contrasts sharply with results for full three-dimensional magnetohydrodynamics before the reduction occurs

  14. Reduced energy conservation law for magnetized plasma

    International Nuclear Information System (INIS)

    Sosenko, P.P.; Decyk, V.K.

    1994-01-01

    A global energy conservation law for a magnetized plasma is studied within the context of a quasiparticle description. A reduced energy conservation law is derived for low-frequency, as compared to the gyromagnetic frequency, plasma motions with regard to both non-uniform mean flows and fluctuations in the plasma. The mean value of plasma energy is calculated and sufficient stability conditions for non-equilibrium plasmas are derived. (orig.)

  15. Female employment reduces fertility in rural Senegal.

    Directory of Open Access Journals (Sweden)

    Goedele Van den Broeck

    Full Text Available Economic growth and modernization of society are generally associated with fertility rate decreases but which forces trigger this is unclear. In this paper we assess how fertility changes with increased labor market participation of women in rural Senegal. Evidence from high-income countries suggests that higher female employment rates lead to reduced fertility rates but evidence from developing countries at an early stage of demographic transition is largely absent. We concentrate on a rural area in northern Senegal where a recent boom in horticultural exports has been associated with a sudden increase in female off-farm employment. Using survey data we show that employed women have a significantly higher age at marriage and at first childbirth, and significantly fewer children. As causal identification strategy we use instrumental variable and difference-in-differences estimations, combined with propensity score matching. We find that female employment reduces the number of children per woman by 25%, and that this fertility-reducing effect is as large for poor as for non-poor women and larger for illiterate than for literate women. Results imply that female employment is a strong instrument for empowering rural women, reducing fertility rates and accelerating the demographic transition in poor countries. The effectiveness of family planning programs can increase if targeted to areas where female employment is increasing or to female employees directly because of a higher likelihood to reach women with low-fertility preferences. Our results show that changes in fertility preferences not necessarily result from a cultural evolution but can also be driven by sudden and individual changes in economic opportunities.

  16. Apparatus for reducing solvent luminescence background emissions

    Energy Technology Data Exchange (ETDEWEB)

    Affleck, Rhett L. (Los Alamos, NM); Ambrose, W. Patrick (Los Alamos, NM); Demas, James N. (Charlottesville, VA); Goodwin, Peter M. (Jemez Springs, NM); Johnson, Mitchell E. (Pittsburgh, PA); Keller, Richard A. (Los Alamos, NM); Petty, Jeffrey T. (Los Alamos, NM); Schecker, Jay A. (Sante Fe, NM); Wu, Ming (Los Alamos, NM)

    1998-01-01

    The detectability of luminescent molecules in solution is enhanced by reducing the background luminescence due to impurity species also present in the solution. A light source that illuminates the solution acts to photolyze the impurities so that the impurities do not luminesce in the fluorescence band of the molecule of interest. Molecules of interest may be carried through the photolysis region in the solution or may be introduced into the solution after the photolysis region.

  17. Incentives for reducing emissions in Krakow

    International Nuclear Information System (INIS)

    Uberman, R.; Pierce, B.; Lazecki, A.

    1994-01-01

    This effort is identifying, specific incentives that may be used by Krakow city officials to encourage, residents to change the way they heat their homes and businesses in order to reduce pollution. This paper describes the incentives study for converting small coal or coke-fired boilers to gas in the Old Town area. A similar study looked at incentives for expanding the district heating system and future analyses will be performed for home stove options

  18. On Nakhleh's metric for reduced phylogenetic networks

    OpenAIRE

    Cardona, Gabriel; Llabrés, Mercè; Rosselló, Francesc; Valiente Feruglio, Gabriel Alejandro

    2009-01-01

    We prove that Nakhleh’s metric for reduced phylogenetic networks is also a metric on the classes of tree-child phylogenetic networks, semibinary tree-sibling time consistent phylogenetic networks, and multilabeled phylogenetic trees. We also prove that it separates distinguishable phylogenetic networks. In this way, it becomes the strongest dissimilarity measure for phylogenetic networks available so far. Furthermore, we propose a generalization of that metric that separates arbitrary phyl...

  19. Reducing stigma and discrimination: Candidate interventions

    OpenAIRE

    Thornicroft, Graham; Brohan, Elaine; Kassam, Aliya; Lewis-Holmes, Elanor

    2008-01-01

    Abstract This paper proposes that stigma in relation to people with mental illness can be understood as a combination of problems of knowledge (ignorance), attitudes (prejudice) and behaviour (discrimination). From a literature review, a series of candidate interventions are identified which may be effective in reducing stigmatisation and discrimination at the following levels: individuals with mental illness and their family members; the workplace; and local, national and international. The ...

  20. Oxytocin reduces alcohol consumption in prairie voles.

    Science.gov (United States)

    Stevenson, J R; Wenner, S M; Freestone, D M; Romaine, C C; Parian, M C; Christian, S M; Bohidar, A E; Ndem, J R; Vogel, I R; O'Kane, C M

    2017-10-01

    Alcohol use disorder (AUD) negatively affects millions of people every year in the United States, and effective treatments for AUD are still needed. The neuropeptide oxytocin has shown promise for reducing alcohol drinking in mice and rats. Because oxytocin also plays a key role in complex prosocial behaviors like bonding and attachment, we tested the effect of oxytocin on alcohol drinking in prairie voles, a species that both consumes high amounts of alcohol and forms oxytocin dependent social bonds in a manner similar to humans. Oxytocin treatment (1.0, 3.0, and 10.0mg/kg, i.p.) reduced alcohol consumption in male and female prairie voles in animals that had access to 15% ethanol vs water every other day for 12 alcohol drinking sessions. In animals with continuous access to 15% alcohol and water, oxytocin (3.0mg/kg) reduced alcohol consumption only in the first hour of access after treatment, with no significant effects on consumption over the 24-hr period. In an open field locomotor test, oxytocin (1.0, 3.0, and 10.0mg/kg, i.p.) did not affect overall locomotor activity; however, ethanol (2g/kg, i.p.) increased locomotor activity in males and females, and produced anxiolytic effects (increased time in the center of an open field) in females only. Because prairie voles have been shown to match the alcohol consumption of their cage mate, we evaluated the relationship between cage mates' alcohol drinking. There was an overall pattern of social facilitation (consumption by one cage mate predicted consumption by the other cage mate); however, we found significant individual differences across cages in which many cages did not show significant matching, and, in some cases one cage mate's consumption negatively predicted the other cage mate's consumption. Overall, our data provide support for the potential of oxytocin as a treatment to reduce alcohol consumption. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Thermosyphon Flooding in Reduced Gravity Environments

    Science.gov (United States)

    Gibson, Marc Andrew

    2013-01-01

    An innovative experiment to study the thermosyphon flooding limits was designed and flown on aparabolic flight campaign to achieve the Reduced Gravity Environments (RGE) needed to obtainempirical data for analysis. Current correlation models of Faghri and Tien and Chung do not agreewith the data. A new model is presented that predicts the flooding limits for thermosyphons inearths gravity and lunar gravity with a 95 confidence level of +- 5W.

  2. Reducing leakage current in semiconductor devices

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Bin; Matioli, Elison de Nazareth; Palacios, Tomas Apostol

    2018-03-06

    A semiconductor device includes a first region having a first semiconductor material and a second region having a second semiconductor material. The second region is formed over the first region. The semiconductor device also includes a current blocking structure formed in the first region between first and second terminals of the semiconductor device. The current blocking structure is configured to reduce current flow in the first region between the first and second terminals.

  3. Biochemical characterization of cholesterol-reducing Eubacterium.

    OpenAIRE

    Mott, G E; Brinkley, A W; Mersinger, C L

    1980-01-01

    We characterized two isolates of cholesterol-reducing Eubacterium by conducting conventional biochemical tests and by testing various sterols and glycerolipids as potential growth factors. In media containing cholesterol and plasmenylethanolamine, the tests for nitrate reduction, indole production, and gelatin and starch hydrolyses were negative, and no acid was produced from any of 22 carbohydrates. Both isolates hydrolyzed esculin to esculetin, indicating beta-glycosidase activity. In addit...

  4. Process for reducing radioactive contamination in phosphogypsum

    International Nuclear Information System (INIS)

    Palmer, J.W.; Gaynor, J.C.

    1983-01-01

    In a process for reducing radioactive contamination of phosphogypsum, anhydrite crystals are obtained through dehydration of the phosphogypsum in strong sulfuric acid: a portion of the anhydrite crystals is converted to subtantially radiation free gypsum by crystallizing out on radiation free gypsum seed crystals. These coarse radiation free gypsum crystals are then separated from the small anhydrite crystal relics containing substantially all of the radioactive contamination

  5. Reduced Cortisol Metabolism during Critical Illness

    Science.gov (United States)

    Boonen, Eva; Vervenne, Hilke; Meersseman, Philippe; Andrew, Ruth; Mortier, Leen; Declercq, Peter E.; Vanwijngaerden, Yoo-Mee; Spriet, Isabel; Wouters, Pieter J.; Perre, Sarah Vander; Langouche, Lies; Vanhorebeek, Ilse; Walker, Brian R.; Van den Berghe, Greet

    2015-01-01

    BACKGROUND Critical illness is often accompanied by hypercortisolemia, which has been attributed to stress-induced activation of the hypothalamic–pituitary–adrenal axis. However, low corticotropin levels have also been reported in critically ill patients, which may be due to reduced cortisol metabolism. METHODS In a total of 158 patients in the intensive care unit and 64 matched controls, we tested five aspects of cortisol metabolism: daily levels of corticotropin and cortisol; plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; plasma clearance of 100 mg of hydrocortisone; levels of urinary cortisol metabolites; and levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. RESULTS Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (PCortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (Pcortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). CONCLUSIONS During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression. The diagnostic and therapeutic implications for critically ill patients are unknown. (Funded by the Belgian

  6. Pyruvate reduces 4-aminophenol in vitro toxicity

    International Nuclear Information System (INIS)

    Harmon, R. Christopher; Kiningham, Kinsley K.; Valentovic, Monica A.

    2006-01-01

    Pyruvate has been observed to reduce the nephrotoxicity of some agents by maintaining glutathione status and preventing lipid peroxidation. This study examined the mechanism for pyruvate protection of p-aminophenol (PAP) nephrotoxicity. Renal cortical slices from male Fischer 344 rats were incubated for 30-120 min with 0, 0.1, 0.25 or 0.5 mM PAP in oxygenated Krebs buffer containing 0 or 10 mM pyruvate or glucose (1.28 or 5.5 mM). LDH leakage was increased above control by 0.25 and 0.5 mM PAP beginning at 60 min and by 0.1 mM PAP at 120 min. Pyruvate prevented an increase in LDH leakage at 60- and 120-min exposure to 0.1 and 0.25 mM PAP. Pyruvate also prevented a decline in ATP levels. Glucose (1.28 and 5.5 mM) provided less protection than pyruvate from PAP toxicity. Total glutathione levels were diminished by 0.1 and 0.25 mM PAP within 60 and 30 min, respectively. Pyruvate prevented the decline in glutathione by 0.1 mM PAP at both time periods and at 30 min for 0.25 mM PAP. Pyruvate reduced the magnitude of glutathione depletion by 0.25 mM PAP following a 60-min incubation. Glutathione disulfide (GSSG) levels in renal slices were increased at 60 min by exposure to 0.25 mM PAP, while pyruvate prevented increased GSSG levels by PAP. Pyruvate also reduced the extent of 4-hydroxynonenal (4-HNE)-adducted proteins present after a 90-min incubation with PAP. These results indicate that pyruvate provided protection for PAP toxicity by providing an energy substrate and reducing oxidative stress

  7. A statewide partnership for reducing readmissions.

    Science.gov (United States)

    Landman, James H

    2013-06-01

    Three core programs have heped reduce reedrmissions in Illinois hospitals: Projct BOOST (better Outcomem by Optimizing Safe Transitions), whih focuses on redesigning hospital discharge processes and improving transitions of care. HP3: Hospitalist Program Peak Performance which provides ducational resources, motivation, and a process improvement structure for hospitalist programs. Communications and Palliative Care, which teaches physicians and dclinicians how to work with paients to define their goal of care and identify options to improve their quality of life.

  8. Can we reduce workplace fatalities by half?

    Science.gov (United States)

    Koh, David Soo Quee

    2012-06-01

    Singapore, an island republic of over 5 million inhabitants, has 3.1 million workers. Most are employed in the service, finance and tourist/transport industry. Significant numbers work in manufacturing, construction and heavy industry. Following a series of construction and shipyard accidents with multiple deaths in 2004, the government announced its intention to reduce workplace fatalities from 4.9 to 2.5 per 100,000 by 2015. There was strong political will to achieve this target. The strategic approaches were to build workplace safety and health (WSH) capabilities; implement legislative changes with enforcement; promote benefits of WSH and recognize best practices, and enhance partnership with stakeholders. The anticipated outcomes were to reduce workplace fatality and injury rates; have WSH as an integral part of business; and establish a progressive and pervasive WSH culture. With these measures, the workplace fatality rate declined from 4.9/100,000 in 2004, to 2.2/100,000 in 2010. However, other confounding factors could also account for this decline, and have to be considered. The next target, announced by Singapore's Prime Minister in 2008, is to further reduce the workplace fatality rate to 1.8/100,000 by 2018, and to have "one of the best workplace safety records in the world".

  9. DOUBLE SHEAR DESIGN TO REDUCED STAMPING FORCE

    Directory of Open Access Journals (Sweden)

    Rudi Kurniawan Arief

    2017-12-01

    Full Text Available Ideally processing of part using stamping machine using only 70-80 % of available force to keep machine in good shape for a long periods. But in some certain case the force may equal to or exceed the available maximum force so the company must sent the process to another outsource company. A case found in a metal stamping company where a final product consist of 3 parts to assembly with one part exceeded the force of available machine. This part can only process in a 1000 tons machine while this company only have 2 of this machine with full workload. Sending this parts outsource will induce delivery problems because other parts are processed, assembled and paint inhouse, this also need additional transportation cost and extra supervision to ensure the quality and delivery schedule. The only exit action of this problem is by reducing the force tonnage. This paper using punch inclining method to reduce the force. The incline punch will distributed the force along the inclined surface that reduce stamping force as well. Inclined surface of punch also cause another major problems that the product becoming curved after process. This problems solved with additional flattening process that add more process cost but better than to outsource the process. Chisel type of inclining punch tip was choosen to avoid worst deformation of product. This paper will give the scientific recomendation to the company.

  10. Refractory of Furnaces to Reduce Environmental Impact

    Science.gov (United States)

    Hanzawa, Shigeru

    2011-10-01

    The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO2 produced from this high energy load. To improve this situation, R&D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

  11. Some mechanisms which may reduce radiolysis

    Energy Technology Data Exchange (ETDEWEB)

    Neretnieks, I; Faghihi, M. [Royal Inst. of Tech., Stockholm (Sweden). Dept. of Chemical Engineering

    1991-08-01

    In this report two mechanisms which may considerably decrease the rate of radiolysis are studied. The first main effect is that capillary forces in the very fine pores of the bentonite which surround the canisters do not permit the release of water if there is a gas over pressure inside the canister. As long as there is gas inside the canister the gap will partly be gas filled and the alpha-particles will have less water to radiolyze. Because some hydrogen will be dissolved and will escape by diffusion, a rate of radiolysis will be maintained which balances the rate of diffusion. This in turn will be influenced by the geometry of the diffusion path. The size of the hole in the copper canister seems to be one of the critical items which determine the escape of the hydrogen and thus the rate of radiolysis. The other main effect which will reduce the radiolysis is the accumulation of the corrosion products in the gap. This reduces the water content in the gap. Consequently there will be less water which can be radiolyzed. The presence of corrosion products which have a higher density than water will also consume the energy of the alpha-particles faster. Both effects seem to, independently, have a potential of reducing the rate of radiolysis by a few order of magnitude.

  12. Reducing enrichment of fuel for research reactors

    International Nuclear Information System (INIS)

    Kanda, Keiji; Matsuura, Shojiro.

    1980-01-01

    In research reactors, highly enriched uranium (HEU) is used as fuel for their purposes of operation. However, the United States strongly required in 1977 that these HEU should be replaced by low enrichment uranium (LEU) of 20% or less, or even in unavoidable cases, it should be replaced by medium enrichment uranium (MEU). INFCE (International Nuclear Fuel Cycle Evaluation) which started its activity just at that time decided to discuss this problem in the research reactor group of No. 8 sectional committee. Japan has been able to forward the work, taking a leading part in the international opinion because she has taken the countermeasures quickly. INFCE investigated the problem along the lines of policy that the possibility of reducing the degree of enrichment should be limited to the degree in which the core structures and equipments of research reactors will be modified as little as possible, and the change of fuel element geometry will be done within the permissible thermohydrodynamic capacity, and concluded that it might be possible in near future to reduce the degree of enrichment to about 45% MEU, while the reduction to 20% LEU might require considerable research, development and verification. On the other hand, the joint researches by Kyoto University and ANL (Argonne National Laboratory) and by Japan Atomic Energy Research Institute and ANL are being continued. IAEA has edited the guidebook (IAEA-TECDOC-233) for reducing the degree of enrichment for developing countries. (Wakatsuki, Y.)

  13. Reoxidation of Bioreduced Uranium Under Reducing Conditions

    International Nuclear Information System (INIS)

    Wan, Jiamin; Tokunaga, Tetsu K.; Brodie, Eoin; Wang, Zheming; Zheng, Zuoping; Herman, Don; Hazen, Terry C.; Firestone, Mary K.; Sutton, Steven R.

    2005-01-01

    Uranium mining and processing for nuclear weapons and fuel have left thousands of sites with toxic levels of this actinide in soil and ground water. An emerging strategy for remediating such environments involves using organic carbon to promote microbially-mediated reduction and precipitation of insoluble U(IV) minerals. Although previous U bioreduction studies have shown promising results, they were of short duration (up to a few months). Our longer-term (20 months) laboratory study using historically contaminated sediment has alarmingly shown that microbial reduction of U was transient even under reducing (methanogenic) conditions. Uranium was reductively immobilized during the first 100 days, but later (150 to 600 days) reoxidized and mobilized, although a microbial community capable of reducing U(VI) remained through the end of the experiment. The formation of Ca2UO2(CO3)3 complexes (caused by the elevated carbonate concentration from microbial respiration and presence of calcium) drove the U(IV)/U(VI) reduction potential to much more reducing conditions. Fe(III) and Mn(IV) were found to be likely terminal electron acceptors (TEAs) for U reoxidation. Thus, U remediation by organic carbon based reductive precipitation is not sustainable in calcareous, neutral to alkaline soils and ground waters

  14. Some mechanisms which may reduce radiolysis

    International Nuclear Information System (INIS)

    Neretnieks, I; Faghihi, M.

    1991-08-01

    In this report two mechanisms which may considerably decrease the rate of radiolysis are studied. The first main effect is that capillary forces in the very fine pores of the bentonite which surround the canisters do not permit the release of water if there is a gas over pressure inside the canister. As long as there is gas inside the canister the gap will partly be gas filled and the alpha-particles will have less water to radiolyze. Because some hydrogen will be dissolved and will escape by diffusion, a rate of radiolysis will be maintained which balances the rate of diffusion. This in turn will be influenced by the geometry of the diffusion path. The size of the hole in the copper canister seems to be one of the critical items which determine the escape of the hydrogen and thus the rate of radiolysis. The other main effect which will reduce the radiolysis is the accumulation of the corrosion products in the gap. This reduces the water content in the gap. Consequently there will be less water which can be radiolyzed. The presence of corrosion products which have a higher density than water will also consume the energy of the alpha-particles faster. Both effects seem to, independently, have a potential of reducing the rate of radiolysis by a few order of magnitude

  15. Refractory of Furnaces to Reduce Environmental Impact

    International Nuclear Information System (INIS)

    Hanzawa, Shigeru

    2011-01-01

    The energy load of furnaces used in the manufacturing process of ceramics is quite large. Most of the environmental impact of ceramics manufacturing is due to the CO 2 produced from this high energy load. To improve this situation, R and D has focused on furnace systems and techniques of control in order to reduce energy load. Since furnaces are comprised of refractory, consideration of their mechanical and thermal characteristics is important. Herein are described several refractory types which were chosen through comparison of the characteristics which contribute to heat capacity reduction, heat insulating reinforcement and high emissivity, thereby improving thermal radiation heat transfer efficiency to the ceramic articles. One selected refractory material which will reduce the environmental impact of a furnace, chosen considering low heat capacity and high emissivity characteristics, is SiC. In this study, thermal radiation heat transfer efficiency improvement and its effect on ceramic articles in the furnace and oxidation behaviour were investigated at 1700K. A high density SiC refractory, built into the furnace at construction, has relatively high oxidation durability and has the ability to reduce environmental impact-CO 2 by 10 percent by decreasing the furnace's energy load. However, new oxidation prevention techniques for SiC will be necessary for long-term use in industrial furnaces, because passive to active oxidation transition behaviour of commercial SiC refractory is coming to close ideal.

  16. Analytic thinking reduces belief in conspiracy theories.

    Science.gov (United States)

    Swami, Viren; Voracek, Martin; Stieger, Stefan; Tran, Ulrich S; Furnham, Adrian

    2014-12-01

    Belief in conspiracy theories has been associated with a range of negative health, civic, and social outcomes, requiring reliable methods of reducing such belief. Thinking dispositions have been highlighted as one possible factor associated with belief in conspiracy theories, but actual relationships have only been infrequently studied. In Study 1, we examined associations between belief in conspiracy theories and a range of measures of thinking dispositions in a British sample (N=990). Results indicated that a stronger belief in conspiracy theories was significantly associated with lower analytic thinking and open-mindedness and greater intuitive thinking. In Studies 2-4, we examined the causational role played by analytic thinking in relation to conspiracist ideation. In Study 2 (N=112), we showed that a verbal fluency task that elicited analytic thinking reduced belief in conspiracy theories. In Study 3 (N=189), we found that an alternative method of eliciting analytic thinking, which related to cognitive disfluency, was effective at reducing conspiracist ideation in a student sample. In Study 4, we replicated the results of Study 3 among a general population sample (N=140) in relation to generic conspiracist ideation and belief in conspiracy theories about the July 7, 2005, bombings in London. Our results highlight the potential utility of supporting attempts to promote analytic thinking as a means of countering the widespread acceptance of conspiracy theories. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Breast Cancer Detection with Reduced Feature Set

    Directory of Open Access Journals (Sweden)

    Ahmet Mert

    2015-01-01

    Full Text Available This paper explores feature reduction properties of independent component analysis (ICA on breast cancer decision support system. Wisconsin diagnostic breast cancer (WDBC dataset is reduced to one-dimensional feature vector computing an independent component (IC. The original data with 30 features and reduced one feature (IC are used to evaluate diagnostic accuracy of the classifiers such as k-nearest neighbor (k-NN, artificial neural network (ANN, radial basis function neural network (RBFNN, and support vector machine (SVM. The comparison of the proposed classification using the IC with original feature set is also tested on different validation (5/10-fold cross-validations and partitioning (20%–40% methods. These classifiers are evaluated how to effectively categorize tumors as benign and malignant in terms of specificity, sensitivity, accuracy, F-score, Youden’s index, discriminant power, and the receiver operating characteristic (ROC curve with its criterion values including area under curve (AUC and 95% confidential interval (CI. This represents an improvement in diagnostic decision support system, while reducing computational complexity.

  18. Method of reducing radon levels in buildings

    International Nuclear Information System (INIS)

    Khajdarov, R.A.; Gapurova, O.U.; Khajdarov, R.R.

    2004-01-01

    Radon concentration can be reduced by using polymeric compositions which fill pores inside building materials and decrease the coefficient of permeation of radon atoms and water molecules in building materials (concrete, gypsum, etc.). Polymeric silico-organic compounds were investigated and selected as the chemicals to prevent radon seeping indoors. Gas (air, Ar, 222 Rn, H 2 O) permeability of concrete and gypsum after treatment with chemicals was examined. The effect of the cement and sand types, preliminary treatment with various chemicals, type of the polymeric silico-organic compounds, time between treatments, moisture of concrete, time between the preparation of chemicals and the treatment of concrete (ageing of chemicals), time between the treatment of concrete and testing (ageing of treated concrete) were examined. Surfaces of the samples were treated by spraying. The experiments gave evidence that the chosen method of treatment of the construction materials allows reducing the coefficient of gas permeability in 200 - 400 times. Treatment of the floor, walls and ceiling of the basement of 5 buildings reduced the radon concentration in the premises of the first floor from 400-600 Bq/m 3 to the background value of 17-20 Bq/m 3

  19. Can We Reduce Workplace Fatalities by Half?

    Directory of Open Access Journals (Sweden)

    David Soo Quee Koh

    2012-06-01

    Full Text Available Singapore, an island republic of over 5 million inhabitants, has 3.1 million workers. Most are employed in the service, finance and tourist/transport industry. Significant numbers work in manufacturing, construction and heavy industry. Following a series of construction and shipyard accidents with multiple deaths in 2004, the government announced its intention to reduce workplace fatalities from 4.9 to 2.5 per 100,000 by 2015. There was strong political will to achieve this target. The strategic approaches were to build workplace safety and health (WSH capabilities; implement legislative changes with enforcement; promote benefits of WSH and recognize best practices, and enhance partnership with stakeholders. The anticipated outcomes were to reduce workplace fatality and injury rates; have WSH as an integral part of business; and establish a progressive and pervasive WSH culture. With these measures, the workplace fatality rate declined from 4.9/100,000 in 2004, to 2.2/100,000 in 2010. However, other confounding factors could also account for this decline, and have to be considered. The next target, announced by Singapore’s Prime Minister in 2008, is to further reduce the workplace fatality rate to 1.8/100,000 by 2018, and to have “one of the best workplace safety records in the world”.

  20. Reducing the likelihood of long tennis matches.

    Science.gov (United States)

    Barnett, Tristan; Alan, Brown; Pollard, Graham

    2006-01-01

    Long matches can cause problems for tournaments. For example, the starting times of subsequent matches can be substantially delayed causing inconvenience to players, spectators, officials and television scheduling. They can even be seen as unfair in the tournament setting when the winner of a very long match, who may have negative aftereffects from such a match, plays the winner of an average or shorter length match in the next round. Long matches can also lead to injuries to the participating players. One factor that can lead to long matches is the use of the advantage set as the fifth set, as in the Australian Open, the French Open and Wimbledon. Another factor is long rallies and a greater than average number of points per game. This tends to occur more frequently on the slower surfaces such as at the French Open. The mathematical method of generating functions is used to show that the likelihood of long matches can be substantially reduced by using the tiebreak game in the fifth set, or more effectively by using a new type of game, the 50-40 game, throughout the match. Key PointsThe cumulant generating function has nice properties for calculating the parameters of distributions in a tennis matchA final tiebreaker set reduces the length of matches as currently being used in the US OpenA new 50-40 game reduces the length of matches whilst maintaining comparable probabilities for the better player to win the match.

  1. Biochemical characterization of cholesterol-reducing Eubacterium.

    Science.gov (United States)

    Mott, G E; Brinkley, A W; Mersinger, C L

    1980-12-01

    We characterized two isolates of cholesterol-reducing Eubacterium by conducting conventional biochemical tests and by testing various sterols and glycerolipids as potential growth factors. In media containing cholesterol and plasmenylethanolamine, the tests for nitrate reduction, indole production, and gelatin and starch hydrolyses were negative, and no acid was produced from any of 22 carbohydrates. Both isolates hydrolyzed esculin to esculetin, indicating beta-glycosidase activity. In addition to plasmenylethanolamine, five other lipids which contain an alkenyl ether residue supported growth of Eubacterium strain 403 in a lecithin-cholesterol base medium. Of six steroids tested, cholesterol, cholest-4-en-3-one, cholest-4-en-3 beta-ol (allocholesterol), and androst-5-en-3 beta-ol-17-one supported growth of Eubacterium strain 403. All four steroids were reduced to the 3 beta-ol, 5 beta-H products. The delta 5 steroids cholest-5-en-3 alpha-ol (epicholesterol) and 22,23-bisnor-5-cholenic acid-3-beta-ol were not reduced and did not support growth of the Eubacterium strain.

  2. Monitoring sulfide and sulfate-reducing bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Tanner, R.S.

    1995-12-31

    Simple yet precise and accurate methods for monitoring sulfate-reducing bacteria (SRB) and sulfide remain useful for the study of bacterial souring and corrosion. Test kits are available to measure sulfide in field samples. A more precise methylene blue sulfide assay for both field and laboratory studies is described here. Improved media, compared to that in API RP-38, for enumeration of SRB have been formulated. One of these, API-RST, contained cysteine (1.1 mM) as a reducing agent, which may be a confounding source of sulfide. While cysteine was required for rapid enumeration of SRB from environmental samples, the concentration of cysteine in medium could be reduced to 0.4 mM. It was also determined that elevated levels of yeast extract (>1 g/liter) could interfere with enumeration of SRB from environmental samples. The API-RST medium was modified to a RST-11 medium. Other changes in medium composition, in addition to reduction of cysteine, included reduction of the concentration of phosphate from 3.4 mM to 2.2 mM, reduction of the concentration of ferrous iron from 0.8 mM to 0.5 mM and preparation of a stock mineral solution to ease medium preparation. SRB from environmental samples could be enumerated in a week in this medium.

  3. Does Metformin Reduce Cancer Risks? Methodologic Considerations.

    Science.gov (United States)

    Golozar, Asieh; Liu, Shuiqing; Lin, Joeseph A; Peairs, Kimberly; Yeh, Hsin-Chieh

    2016-01-01

    The substantial burden of cancer and diabetes and the association between the two conditions has been a motivation for researchers to look for targeted strategies that can simultaneously affect both diseases and reduce their overlapping burden. In the absence of randomized clinical trials, researchers have taken advantage of the availability and richness of administrative databases and electronic medical records to investigate the effects of drugs on cancer risk among diabetic individuals. The majority of these studies suggest that metformin could potentially reduce cancer risk. However, the validity of this purported reduction in cancer risk is limited by several methodological flaws either in the study design or in the analysis. Whether metformin use decreases cancer risk relies heavily on the availability of valid data sources with complete information on confounders, accurate assessment of drug use, appropriate study design, and robust analytical techniques. The majority of the observational studies assessing the association between metformin and cancer risk suffer from methodological shortcomings and efforts to address these issues have been incomplete. Future investigations on the association between metformin and cancer risk should clearly address the methodological issues due to confounding by indication, prevalent user bias, and time-related biases. Although the proposed strategies do not guarantee a bias-free estimate for the association between metformin and cancer, they will reduce synthesis of and reporting of erroneous results.

  4. Reducing transfusion requirements in liver transplantation.

    Science.gov (United States)

    Donohue, Ciara I; Mallett, Susan V

    2015-12-24

    Liver transplantation (LT) was historically associated with massive blood loss and transfusion. Over the past two decades transfusion requirements have reduced dramatically and increasingly transfusion-free transplantation is a reality. Both bleeding and transfusion are associated with adverse outcomes in LT. Minimising bleeding and reducing unnecessary transfusions are therefore key goals in the perioperative period. As the understanding of the causes of bleeding has evolved so too have techniques to minimize or reduce the impact of blood loss. Surgical "piggyback" techniques, anaesthetic low central venous pressure and haemodilution strategies and the use of autologous cell salvage, point of care monitoring and targeted correction of coagulopathy, particularly through use of factor concentrates, have all contributed to declining reliance on allogenic blood products. Pre-emptive management of preoperative anaemia and adoption of more restrictive transfusion thresholds is increasingly common as patient blood management (PBM) gains momentum. Despite progress, increasing use of marginal grafts and transplantation of sicker recipients will continue to present new challenges in bleeding and transfusion management. Variation in practice across different centres and within the literature demonstrates the current lack of clear transfusion guidance. In this article we summarise the causes and predictors of bleeding and present the evidence for a variety of PBM strategies in LT.

  5. Symmetry of semi-reduced lattices.

    Science.gov (United States)

    Stróż, Kazimierz

    2015-05-01

    The main result of this work is extension of the famous characterization of Bravais lattices according to their metrical, algebraic and geometric properties onto a wide class of primitive lattices (including Buerger-reduced, nearly Buerger-reduced and a substantial part of Delaunay-reduced) related to low-restricted semi-reduced descriptions (s.r.d.'s). While the `geometric' operations in Bravais lattices map the basis vectors into themselves, the `arithmetic' operators in s.r.d. transform the basis vectors into cell vectors (basis vectors, face or space diagonals) and are represented by matrices from the set {\\bb V} of all 960 matrices with the determinant ±1 and elements {0, ±1} of the matrix powers. A lattice is in s.r.d. if the moduli of off-diagonal elements in both the metric tensors M and M(-1) are smaller than corresponding diagonal elements sharing the same column or row. Such lattices are split into 379 s.r.d. types relative to the arithmetic holohedries. Metrical criteria for each type do not need to be explicitly given but may be modelled as linear derivatives {\\bb M}(p,q,r), where {\\bb M} denotes the set of 39 highest-symmetry metric tensors, and p,q,r describe changes of appropriate interplanar distances. A sole filtering of {\\bb V} according to an experimental s.r.d. metric and subsequent geometric interpretation of the filtered matrices lead to mathematically stable and rich information on the Bravais-lattice symmetry and deviations from the exact symmetry. The emphasis on the crystallographic features of lattices was obtained by shifting the focus (i) from analysis of a lattice metric to analysis of symmetry matrices [Himes & Mighell (1987). Acta Cryst. A43, 375-384], (ii) from the isometric approach and invariant subspaces to the orthogonality concept {some ideas in Le Page [J. Appl. Cryst. (1982), 15, 255-259]} and splitting indices [Stróż (2011). Acta Cryst. A67, 421-429] and (iii) from fixed cell transformations to transformations

  6. Reducing Spatial Data Complexity for Classification Models

    International Nuclear Information System (INIS)

    Ruta, Dymitr; Gabrys, Bogdan

    2007-01-01

    Intelligent data analytics gradually becomes a day-to-day reality of today's businesses. However, despite rapidly increasing storage and computational power current state-of-the-art predictive models still can not handle massive and noisy corporate data warehouses. What is more adaptive and real-time operational environment requires multiple models to be frequently retrained which further hinders their use. Various data reduction techniques ranging from data sampling up to density retention models attempt to address this challenge by capturing a summarised data structure, yet they either do not account for labelled data or degrade the classification performance of the model trained on the condensed dataset. Our response is a proposition of a new general framework for reducing the complexity of labelled data by means of controlled spatial redistribution of class densities in the input space. On the example of Parzen Labelled Data Compressor (PLDC) we demonstrate a simulatory data condensation process directly inspired by the electrostatic field interaction where the data are moved and merged following the attracting and repelling interactions with the other labelled data. The process is controlled by the class density function built on the original data that acts as a class-sensitive potential field ensuring preservation of the original class density distributions, yet allowing data to rearrange and merge joining together their soft class partitions. As a result we achieved a model that reduces the labelled datasets much further than any competitive approaches yet with the maximum retention of the original class densities and hence the classification performance. PLDC leaves the reduced dataset with the soft accumulative class weights allowing for efficient online updates and as shown in a series of experiments if coupled with Parzen Density Classifier (PDC) significantly outperforms competitive data condensation methods in terms of classification performance at the

  7. Intensive agriculture reduces soil biodiversity across Europe.

    Science.gov (United States)

    Tsiafouli, Maria A; Thébault, Elisa; Sgardelis, Stefanos P; de Ruiter, Peter C; van der Putten, Wim H; Birkhofer, Klaus; Hemerik, Lia; de Vries, Franciska T; Bardgett, Richard D; Brady, Mark Vincent; Bjornlund, Lisa; Jørgensen, Helene Bracht; Christensen, Sören; Hertefeldt, Tina D'; Hotes, Stefan; Gera Hol, W H; Frouz, Jan; Liiri, Mira; Mortimer, Simon R; Setälä, Heikki; Tzanopoulos, Joseph; Uteseny, Karoline; Pižl, Václav; Stary, Josef; Wolters, Volkmar; Hedlund, Katarina

    2015-02-01

    Soil biodiversity plays a key role in regulating the processes that underpin the delivery of ecosystem goods and services in terrestrial ecosystems. Agricultural intensification is known to change the diversity of individual groups of soil biota, but less is known about how intensification affects biodiversity of the soil food web as a whole, and whether or not these effects may be generalized across regions. We examined biodiversity in soil food webs from grasslands, extensive, and intensive rotations in four agricultural regions across Europe: in Sweden, the UK, the Czech Republic and Greece. Effects of land-use intensity were quantified based on structure and diversity among functional groups in the soil food web, as well as on community-weighted mean body mass of soil fauna. We also elucidate land-use intensity effects on diversity of taxonomic units within taxonomic groups of soil fauna. We found that between regions soil food web diversity measures were variable, but that increasing land-use intensity caused highly consistent responses. In particular, land-use intensification reduced the complexity in the soil food webs, as well as the community-weighted mean body mass of soil fauna. In all regions across Europe, species richness of earthworms, Collembolans, and oribatid mites was negatively affected by increased land-use intensity. The taxonomic distinctness, which is a measure of taxonomic relatedness of species in a community that is independent of species richness, was also reduced by land-use intensification. We conclude that intensive agriculture reduces soil biodiversity, making soil food webs less diverse and composed of smaller bodied organisms. Land-use intensification results in fewer functional groups of soil biota with fewer and taxonomically more closely related species. We discuss how these changes in soil biodiversity due to land-use intensification may threaten the functioning of soil in agricultural production systems. © 2014 John Wiley

  8. Reducing Delay in Diagnosis: Multistage Recommendation Tracking.

    Science.gov (United States)

    Wandtke, Ben; Gallagher, Sarah

    2017-11-01

    The purpose of this study was to determine whether a multistage tracking system could improve communication between health care providers, reducing the risk of delay in diagnosis related to inconsistent communication and tracking of radiology follow-up recommendations. Unconditional recommendations for imaging follow-up of all diagnostic imaging modalities excluding mammography (n = 589) were entered into a database and tracked through a multistage tracking system for 13 months. Tracking interventions were performed for patients for whom completion of recommended follow-up imaging could not be identified 1 month after the recommendation due date. Postintervention compliance with the follow-up recommendation required examination completion or clinical closure (i.e., biopsy, limited life expectancy or death, or subspecialist referral). Baseline radiology information system checks performed 1 month after the recommendation due date revealed timely completion of 43.1% of recommended imaging studies at our institution before intervention. Three separate tracking interventions were studied, showing effectiveness between 29.0% and 57.8%. The multistage tracking system increased the examination completion rate to 70.5% (a 52% increase) and reduced the rate of unknown follow-up compliance and the associated risk of delay in diagnosis to 13.9% (a 74% decrease). Examinations completed after tracking intervention generated revenue of 4.1 times greater than the labor cost. Performing sequential radiology recommendation tracking interventions can substantially reduce the rate of unknown follow-up compliance and add value to the health system. Unknown follow-up compliance is a risk factor for delay in diagnosis, a form of preventable medical error commonly identified in malpractice claims involving radiologists and office-based practitioners.

  9. Employing innovative techniques to reduce inspection times

    International Nuclear Information System (INIS)

    Heumueller, R.; Guse, G.; Dirauf, F.; Fischer, E.

    1997-01-01

    Shorter inspection periods mean lower revision costs and less tight revision schedules, but must not detract from the quality of inspection findings. This requirement imposes upon the company performing the inspection the need for top achievements both in quality management and in the use of innovative techniques. Flexible equipment systems and inspection techniques adapted to specific purposes are able to reduce inspection times in many inspection jobs. As part of a complete system designed to reduce inspection times, the new Saphir (Siemens Alok Phased Array Integrated Reliable UT-System) inspection equipment system is the core of most of the recent innovations. Being an integrated inspection equipment system, it is able to handle conventional US probes as well as arrays and phased arrays. It is open for further matching to specific inspection and administrative requirements and developments, and it may be incorporated in the network of an integrated system with a database. A technological leap in probe design in the past few years has allowed controllable wave fields to be generated which are in no way inferior to those of conventional probes with fixed angles of incidence. In this way, a number of inspection techniques can be implemented with a single probe. This reduces inspection times, setup and retooling times, and doses. Typical examples already used in practice are the LLT (longitudinal-longitudinal-transverse waves) technique and the integration of inspections for longitudinal and transverse defects in a single run. In the near future, surfaces with complicated curvatures will be inspected by novel modular robot systems consisting of individual modules of linear axes and rotational axes. (orig.) [de

  10. Reducing Spatial Data Complexity for Classification Models

    Science.gov (United States)

    Ruta, Dymitr; Gabrys, Bogdan

    2007-11-01

    Intelligent data analytics gradually becomes a day-to-day reality of today's businesses. However, despite rapidly increasing storage and computational power current state-of-the-art predictive models still can not handle massive and noisy corporate data warehouses. What is more adaptive and real-time operational environment requires multiple models to be frequently retrained which further hinders their use. Various data reduction techniques ranging from data sampling up to density retention models attempt to address this challenge by capturing a summarised data structure, yet they either do not account for labelled data or degrade the classification performance of the model trained on the condensed dataset. Our response is a proposition of a new general framework for reducing the complexity of labelled data by means of controlled spatial redistribution of class densities in the input space. On the example of Parzen Labelled Data Compressor (PLDC) we demonstrate a simulatory data condensation process directly inspired by the electrostatic field interaction where the data are moved and merged following the attracting and repelling interactions with the other labelled data. The process is controlled by the class density function built on the original data that acts as a class-sensitive potential field ensuring preservation of the original class density distributions, yet allowing data to rearrange and merge joining together their soft class partitions. As a result we achieved a model that reduces the labelled datasets much further than any competitive approaches yet with the maximum retention of the original class densities and hence the classification performance. PLDC leaves the reduced dataset with the soft accumulative class weights allowing for efficient online updates and as shown in a series of experiments if coupled with Parzen Density Classifier (PDC) significantly outperforms competitive data condensation methods in terms of classification performance at the

  11. Slow brushing reduces heat pain in humans.

    Science.gov (United States)

    Liljencrantz, J; Strigo, I; Ellingsen, D M; Krämer, H H; Lundblad, L C; Nagi, S S; Leknes, S; Olausson, H

    2017-08-01

    C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT sub-optimal (fast brushing or vibration) stimuli. Three different experimental paradigms were used: Concurrent application of heat pain and tactile (slow brushing or vibration) stimulation; Slow brushing, applied for variable duration and intervals, preceding heat pain; Slow versus fast brushing preceding heat pain. Slow brushing was effective in reducing pain, whereas fast brushing or vibration was not. The reduction in pain was significant not only when the CT optimal touch was applied simultaneously with the painful stimulus but also when the two stimuli were separated in time. For subsequent stimulation, the pain reduction was more pronounced for a shorter time interval between brushing and pain. Likewise, the effect was more robust when pain was preceded by a longer duration of brush stimulation. Strong CT-related pain reduction was associated with low anxiety and high calmness scores obtained by a state anxiety questionnaire. Slow brushing - optimal for CT activation - is effective in reducing pain from cutaneous heating. The precise mechanisms for the pain relief are as yet unknown but possible mechanisms include inhibition of nociceptive projection neurons at the level of the dorsal horn as well as analgesia through cortical mechanisms. Slow brushing stimuli - optimal for activation of C-tactile fibres - can reduce pain from cutaneous heating. No such effect was seen with fast brushing or vibration. These observations indicate the role of C-tactile fibres in pain modulation. © 2017 European Pain Federation - EFIC®.

  12. Reducing stigma and discrimination: Candidate interventions

    Directory of Open Access Journals (Sweden)

    Kassam Aliya

    2008-04-01

    Full Text Available Abstract This paper proposes that stigma in relation to people with mental illness can be understood as a combination of problems of knowledge (ignorance, attitudes (prejudice and behaviour (discrimination. From a literature review, a series of candidate interventions are identified which may be effective in reducing stigmatisation and discrimination at the following levels: individuals with mental illness and their family members; the workplace; and local, national and international. The strongest evidence for effective interventions at present is for (i direct social contact with people with mental illness at the individual level, and (ii social marketing at the population level.

  13. Urban warming reduces aboveground carbon storage

    DEFF Research Database (Denmark)

    Meineke, Emily; Youngsteadt, Elsa; Dunn, Robert Roberdeau

    2016-01-01

    sequestration (carbon stored per year) of mature trees. Urban warming increased herbivorous arthropod abundance on trees, but these herbivores had negligible effects on tree carbon sequestration. Instead, urban warming was associated with an estimated 12% loss of carbon sequestration, in part because...... photosynthesis was reduced at hotter sites. Ecosystem service assessments that do not consider urban conditions may overestimate urban tree carbon storage. Because urban and global warming are becoming more intense, our results suggest that urban trees will sequester even less carbon in the future....

  14. Electroactive biofilms of sulphate reducing bacteria

    International Nuclear Information System (INIS)

    Cordas, Cristina M.; Guerra, L. Tiago; Xavier, Catarina; Moura, Jose J.G.

    2008-01-01

    Biofilms formed from a pure strain of Desulfovibrio desulfuricans 27774 on stainless steel and graphite polarised surfaces were studied. The polarisation conditions applied were -0.4 V vs. SCE for different times. A cathodic current related with the biofilms growth was observed with a maximum intensity of -270 mA m -2 that remained stable for several days using graphite electrodes. These sulphate reducing bacteria biofilms present electrocatalytic activity towards hydrogen and oxygen reduction reactions. Electrode polarisation has a selective effect on the catalytic activity. The biofilms were also observed by scanning electronic microscopy revealing the formation of homogeneous films on the surfaces

  15. Apparatus for reducing shock and overpressure

    Science.gov (United States)

    Walter, C.E.

    1975-01-28

    An apparatus for reducing shock and overpressure is particularly useful in connection with the sequential detonation of a series of nuclear explosives under ground. A coupling and decoupling arrangement between adjacent nuclear explosives in the tubing string utilized to emplace the explosives is able to support lower elements on the string but yields in a manner which absorbs energy when subjected to the shock wave produced upon detonation of one of the explosives. Overpressure is accomodated by an arrangement in the string which provides an additional space into which the pressurized material can expand at a predetermined overpressure. (10 claims)

  16. Clinker mineral hydration at reduced relative humidities

    DEFF Research Database (Denmark)

    Jensen, Ole Mejlhede; Hansen, Per Freiesleben; Lachowski, Eric E.

    1999-01-01

    and experimental data are presented showing that C(3)A can hydrate at lower humidities than either C3S or C2S. It is suggested that the initiation of hydration during exposure to water vapour is nucleation controlled. When C(3)A hydrates at low humidity, the characteristic hydration product is C(3)AH(6......Vapour phase hydration of purl cement clinker minerals at reduced relative humidities is described. This is relevant to modern high performance concrete that may self-desiccate during hydration and is also relevant to the quality of the cement during storage. Both the oretical considerations...

  17. Reducing occupational radiation exposures at LWRs

    International Nuclear Information System (INIS)

    Lattanzi, D.; Neri, C.; Papa, C.; Paribelli, S.

    1980-01-01

    The occupational radiation doses received by nuclear power plant personnel during a period of several years of operation are briefly reviewed. Comparisons are made between the data for BWRs and PWRs in order to identify the more ''critical'' reactor type, from a radiological poin; of view. Attention is also devoted to GCRs. Furthermore the areas which contribute most to personnel doses are considered and briefly reviewed. The main steps to be taken in order to reduce occupational radiation exposures at LWRs are discussed. (H.K.)

  18. Suspensions with reduced violin string modes

    International Nuclear Information System (INIS)

    Lee, B H; Ju, L; Blair, D G

    2006-01-01

    We discuss the possibility of significantly reducing the number and Q-factor of violin string modes in the mirror suspension. Simulations of a bar-flexure suspension and an orthogonal ribbon have shown a reduction in the number of violin string modes when compared to a normal ribbon suspension. By calculating the expected suspension thermal noise, we find that the orthogonal ribbon provides a promising suspension alternative. A lower number of violin modes oscillating in the direction of the laser and a reduction in violin mode peak values of at least 23dB can be achieved with a slight increase in thermal noise above 40Hz

  19. Suspensions with reduced violin string modes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, B H; Ju, L; Blair, D G [School of Physics, University of Western Australia, Crawley 6009, WA (Australia)

    2006-03-02

    We discuss the possibility of significantly reducing the number and Q-factor of violin string modes in the mirror suspension. Simulations of a bar-flexure suspension and an orthogonal ribbon have shown a reduction in the number of violin string modes when compared to a normal ribbon suspension. By calculating the expected suspension thermal noise, we find that the orthogonal ribbon provides a promising suspension alternative. A lower number of violin modes oscillating in the direction of the laser and a reduction in violin mode peak values of at least 23dB can be achieved with a slight increase in thermal noise above 40Hz.

  20. Hadoop MapReduce v2 cookbook

    CERN Document Server

    Gunarathne, Thilina

    2015-01-01

    If you are a Big Data enthusiast and wish to use Hadoop v2 to solve your problems, then this book is for you. This book is for Java programmers with little to moderate knowledge of Hadoop MapReduce. This is also a one-stop reference for developers and system admins who want to quickly get up to speed with using Hadoop v2. It would be helpful to have a basic knowledge of software development using Java and a basic working knowledge of Linux.

  1. Meteorological Data Analysis Using MapReduce

    Directory of Open Access Journals (Sweden)

    Wei Fang

    2014-01-01

    Full Text Available In the atmospheric science, the scale of meteorological data is massive and growing rapidly. K-means is a fast and available cluster algorithm which has been used in many fields. However, for the large-scale meteorological data, the traditional K-means algorithm is not capable enough to satisfy the actual application needs efficiently. This paper proposes an improved MK-means algorithm (MK-means based on MapReduce according to characteristics of large meteorological datasets. The experimental results show that MK-means has more computing ability and scalability.

  2. Reducing status quo bias in choice experiments

    DEFF Research Database (Denmark)

    Bonnichsen, Ole; Ladenburg, Jacob

    In stated preference literature, the tendency to choose the alternative representing the status quo situation seems to exceed real life status quo effects. Accordingly, status quo bias can be a problem. In Choice Experiments, status quo bias is found to be strongly correlated with protest attitudes...... toward the cost attribute. If economic values are to be elicited, this problem is difficult to remedy. In a split sample framework we test a novel ex-ante entreaty aimed specifically at the cost attribute and find that it effectively reduces status quo bias and improves the internal validity...

  3. Reducing the spectral index in supernatural inflation

    International Nuclear Information System (INIS)

    Lin, C.-M.; Cheung, Kingman

    2009-01-01

    Supernatural inflation is an attractive model based on just a flat direction with soft supersymmetry breaking mass terms in the framework of supersymmetry. The beauty of the model is that it needs no fine-tuning. However, the prediction of the spectral index is n s > or approx. 1, in contrast to experimental data. In this paper, we discuss supernatural inflation with the spectral index reduced to n s =0.96 without any fine-tuning, considering the general feature that a flat direction is lifted by a nonrenormalizable term with an A-term.

  4. Reducing the spectral index in supernatural inflation

    Science.gov (United States)

    Lin, Chia-Min; Cheung, Kingman

    2009-04-01

    Supernatural inflation is an attractive model based on just a flat direction with soft supersymmetry breaking mass terms in the framework of supersymmetry. The beauty of the model is that it needs no fine-tuning. However, the prediction of the spectral index is ns≳1, in contrast to experimental data. In this paper, we discuss supernatural inflation with the spectral index reduced to ns=0.96 without any fine-tuning, considering the general feature that a flat direction is lifted by a nonrenormalizable term with an A-term.

  5. Reducing stigma and discrimination: Candidate interventions.

    Science.gov (United States)

    Thornicroft, Graham; Brohan, Elaine; Kassam, Aliya; Lewis-Holmes, Elanor

    2008-04-13

    This paper proposes that stigma in relation to people with mental illness can be understood as a combination of problems of knowledge (ignorance), attitudes (prejudice) and behaviour (discrimination). From a literature review, a series of candidate interventions are identified which may be effective in reducing stigmatisation and discrimination at the following levels: individuals with mental illness and their family members; the workplace; and local, national and international. The strongest evidence for effective interventions at present is for (i) direct social contact with people with mental illness at the individual level, and (ii) social marketing at the population level.

  6. Autonomous Droop Scheme With Reduced Generation Cost

    DEFF Research Database (Denmark)

    Nutkani, Inam Ullah; Loh, Poh Chiang; Wang, Peng

    2014-01-01

    ) of the microgrid. To reduce this TGC without relying on fast communication links, an autonomous droop scheme is proposed here, whose resulting power sharing is decided by the individual DG generation costs. Comparing it with the traditional scheme, the proposed scheme retains its simplicity and it is hence more....... This objective might, however, not suit microgrids well since DGs are usually of different types, unlike synchronous generators. Other factors like cost, efficiency, and emission penalty of each DG at different loading must be considered since they contribute directly to the total generation cost (TGC...

  7. Reducing hazards for animals from humans

    Directory of Open Access Journals (Sweden)

    Paul-Pierre Pastoret

    2012-06-01

    Full Text Available If animals may be a source of hazards for humans, the reverse is equally true. The main sources of hazards from humans to animals, are the impact of human introduction of transboundary animal diseases, climate change, globalisation, introduction of invasive species and reduction of biodiversity.There is also a trend toward reducing genetic diversity in domestic animals, such as cattle; there are presently around 700 different breeds of cattle many of which at the verge of extinction (less than 100 reproductive females. The impact of humans is also indirect through detrimental effects on the environment. It is therefore urgent to implement the new concept of “one health"....

  8. Active compressor engine silencer reduces exhaust noise

    International Nuclear Information System (INIS)

    Denenberg, J.N.; Miller, S.K.; Jay, M.A.

    1994-01-01

    An active industrial silencer on a compressor engine at a Tenneco Gas station has reduced low-frequency 'rumbling' noise by 8 dB during trials while lowering backpressure about 90$. This 8 dB reduction of the piston firing frequency corresponds to a more than 80% decrease in emitted acoustic power. The silencing unit, installed on one of six engines at the station near Eden, N.Y., continues in operation. Based on the results, the manufacturer is identifying additional compressor sites for further tests. This paper reviews this project

  9. Statistical analysis of partial reduced width distributions

    International Nuclear Information System (INIS)

    Tran Quoc Thuong.

    1973-01-01

    The aim of this study was to develop rigorous methods for analysing experimental event distributions according to a law in chi 2 and to check if the number of degrees of freedom ν is compatible with the value 1 for the reduced neutron width distribution. Two statistical methods were used (the maximum-likelihood method and the method of moments); it was shown, in a few particular cases, that ν is compatible with 1. The difference between ν and 1, if it exists, should not exceed 3%. These results confirm the validity of the compound nucleus model [fr

  10. RHIC ABORT KICKER WITH REDUCED COUPLING IMPEDANCE

    International Nuclear Information System (INIS)

    HAHN, H.; DAVINO, D.

    2002-01-01

    Kicker magnets typically represent the most important contributors to the transverse impedance budget of accelerators and storage rings. Methods of reducing the impedance value of the SNS extraction kicker presently under construction and, in view of a future performance upgrade, that of the RHIC abort kicker have been thoroughly studied at this laboratory. In this paper, the investigation of a potential improvement from using ferrite different from the BNL standard CMD5005 is reported. Permeability measurements of several ferrite types have been performed. Measurements on two kicker magnets using CMD5005 and C2050 suggest that the impedance of a magnet without external resistive damping, such as the RHIC abort kicker, would benefit

  11. Rotational Rebound Attacks on Reduced Skein

    DEFF Research Database (Denmark)

    Khovratovich, Dmitry; Nikolić, Ivica; Rechberger, Christian

    2014-01-01

    ciphers, including the new standard SHA-3 (Keccak). The rebound attack is a start-from-the-middle approach for finding differential paths and conforming pairs in byte-oriented designs like Substitution-Permutation networks and AES. We apply our new compositional attack to the reduced version of the hash...... number of rounds. We also use neutral bits and message modification methods from the practice of collision search in MD5 and SHA-1 hash functions. These methods push the rotational property through more rounds than previous analysis suggested, and eventually establish a distinguishing property...

  12. Electroactive biofilms of sulphate reducing bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Cordas, Cristina M.; Guerra, L. Tiago; Xavier, Catarina [Requimte-CQFB, Departamento de Quimica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Moura, Jose J.G. [Requimte-CQFB, Departamento de Quimica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal)], E-mail: jose.moura@dq.fct.unl.pt

    2008-12-01

    Biofilms formed from a pure strain of Desulfovibrio desulfuricans 27774 on stainless steel and graphite polarised surfaces were studied. The polarisation conditions applied were -0.4 V vs. SCE for different times. A cathodic current related with the biofilms growth was observed with a maximum intensity of -270 mA m{sup -2} that remained stable for several days using graphite electrodes. These sulphate reducing bacteria biofilms present electrocatalytic activity towards hydrogen and oxygen reduction reactions. Electrode polarisation has a selective effect on the catalytic activity. The biofilms were also observed by scanning electronic microscopy revealing the formation of homogeneous films on the surfaces.

  13. Deciding for Future Selves Reduces Loss Aversion

    Directory of Open Access Journals (Sweden)

    Qiqi Cheng

    2017-09-01

    Full Text Available In this paper, we present an incentivized experiment to investigate the degree of loss aversion when people make decisions for their current selves and future selves under risk. We find that when participants make decisions for their future selves, they are less loss averse compared to when they make decisions for their current selves. This finding is consistent with the interpretation of loss aversion as a bias in decision-making driven by emotions, which are reduced when making decisions for future selves. Our findings endorsed the external validity of previous studies on the impact of emotion on loss aversion in a real world decision-making environment.

  14. Cosmic anisotropy with reduced relativistic gas

    Energy Technology Data Exchange (ETDEWEB)

    Castardelli dos Reis, Simpliciano [Universidade Federal de Juiz de Fora, Departamento de Fisica, ICE, Juiz de Fora, MG (Brazil); Shapiro, Ilya L. [Universidade Federal de Juiz de Fora, Departamento de Fisica, ICE, Juiz de Fora, MG (Brazil); Tomsk State Pedagogical University, Tomsk (Russian Federation); Tomsk State University, Tomsk (Russian Federation)

    2018-02-15

    The dynamics of cosmological anisotropies is investigated for Bianchi type I universe filled by a relativistic matter represented by the reduced relativistic gas model (RRG), with equation of state interpolating between radiation and matter. Previously it was shown that the interpolation is observed in the background cosmological solutions for homogeneous and isotropic universe and also for the linear cosmological perturbations. We extend the application of RRG to the Bianchi type I anisotropic model and find that the solutions evolve to the isotropic universe with the pressureless matter contents. (orig.)

  15. Environment, Renewable Energy and Reduced Carbon Emissions

    Science.gov (United States)

    Sen, S.; Khazanov, G.; Kishimoto, Y.

    2011-01-01

    Increased energy security and reduced carbon emissions pose significant challenges for science and technology. However, they also create substantial opportunities for innovative research and development. In this review paper, we highlight some of the key opportunities and mention public policies that are needed to enable the efforts and to maximize the probability of their success. Climate is among the uttermost nonlinear behaviors found around us. As recent studies showed the possible effect of cosmic rays on the Earth's climate, we investigate how complex interactions between the planet and its environment can be responsible for climate anomalies.

  16. Novel Reduced-Feedback Wireless Communication Systems

    KAUST Repository

    Shaqfeh, Mohammad Obaidah

    2011-11-20

    Modern communication systems apply channel-aware adaptive transmission techniques and dynamic resource allocation in order to exploit the peak conditions of the fading wireless links and to enable significant performance gains. However, conveying the channel state information among the users’ mobile terminals into the access points of the network consumes a significant portion of the scarce air-link resources and depletes the battery resources of the mobile terminals rapidly. Despite its evident drawbacks, the channel information feedback cannot be eliminated in modern wireless networks because blind communication technologies cannot support the ever-increasing transmission rates and high quality of experience demands of current ubiquitous services. Developing new transmission technologies with reduced-feedback requirements is sought. Network operators will benefit from releasing the bandwidth resources reserved for the feedback communications and the clients will enjoy the extended battery life of their mobile devices. The main technical challenge is to preserve the prospected transmission rates over the network despite decreasing the channel information feedback significantly. This is a noteworthy research theme especially that there is no mature theory for feedback communication in the existing literature despite the growing number of publications about the topic in the last few years. More research efforts are needed to characterize the trade-off between the achievable rate and the required channel information and to design new reduced-feedback schemes that can be flexibly controlled based on the operator preferences. Such schemes can be then introduced into the standardization bodies for consideration in next generation broadband systems. We have recently contributed to this field and published several journal and conference papers. We are the pioneers to propose a novel reduced-feedback opportunistic scheduling scheme that combines many desired features

  17. Polymer Coatings Reduce Electro-osmosis

    Science.gov (United States)

    Herren, Blair J.; Snyder, Robert; Shafer, Steven G.; Harris, J. Milton; Van Alstine, James M.

    1989-01-01

    Poly(ethylene glycol) film controls electrostatic potential. Electro-osmosis in quartz or glass chambers reduced or reversed by coating inside surface of chambers with monomacromolecular layers of poly(ethylene glycol). Stable over long times. Electrostatic potential across surface of untreated glass or plastic chamber used in electro-phoresis is negative and attracts cations in aqueous electrolyte. Cations solvated, entrains flow of electrolyte migrating toward cathode. Electro-osmotic flow interferes with desired electrophoresis of particles suspended in electrolyte. Polymer coats nontoxic, transparent, and neutral, advantageous for use in electrophoresis.

  18. Reducing Future International Chemical and Biological Dangers.

    Energy Technology Data Exchange (ETDEWEB)

    Haddal, Chad [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bull, Diana L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hernandez, Patricia Marie [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Foley, John T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2017-12-01

    The International Biological and Chemical Threat Reduction Program at Sandia National Laboratories is developing a 15 - year technology road map in support the United States Government efforts to reduce international chemical and biological dangers . In 2017, the program leadership chartered an analysis team to explore dangers in the future international chemical and biological landscape through engagements with national security experts within and beyond Sandia to gain a multidisciplinary perspective on the future . This report offers a hi gh level landscape of future chemical and biological dangers based upon analysis of those engagements and provides support for further technology road map development.

  19. How writing records reduces clinical knowledge

    DEFF Research Database (Denmark)

    Buus, Niels

    2009-01-01

    drew on data from an extended fieldwork on two Danish "special observation" wards. The results indicated that the nurses' recording produced "stereotyping" representations of the patients and reduced the nurses' clinical knowledge but that this particular way of recording made good sense in relation......Through the practices of recording, psychiatric nurses produce clinical knowledge about the patients in their care. The objective of this study was to examine the conventionalized practices of recording among psychiatric nurses and the typical linguistic organization of their records. The study...

  20. Reduced multiple empirical kernel learning machine.

    Science.gov (United States)

    Wang, Zhe; Lu, MingZhe; Gao, Daqi

    2015-02-01

    Multiple kernel learning (MKL) is demonstrated to be flexible and effective in depicting heterogeneous data sources since MKL can introduce multiple kernels rather than a single fixed kernel into applications. However, MKL would get a high time and space complexity in contrast to single kernel learning, which is not expected in real-world applications. Meanwhile, it is known that the kernel mapping ways of MKL generally have two forms including implicit kernel mapping and empirical kernel mapping (EKM), where the latter is less attracted. In this paper, we focus on the MKL with the EKM, and propose a reduced multiple empirical kernel learning machine named RMEKLM for short. To the best of our knowledge, it is the first to reduce both time and space complexity of the MKL with EKM. Different from the existing MKL, the proposed RMEKLM adopts the Gauss Elimination technique to extract a set of feature vectors, which is validated that doing so does not lose much information of the original feature space. Then RMEKLM adopts the extracted feature vectors to span a reduced orthonormal subspace of the feature space, which is visualized in terms of the geometry structure. It can be demonstrated that the spanned subspace is isomorphic to the original feature space, which means that the dot product of two vectors in the original feature space is equal to that of the two corresponding vectors in the generated orthonormal subspace. More importantly, the proposed RMEKLM brings a simpler computation and meanwhile needs a less storage space, especially in the processing of testing. Finally, the experimental results show that RMEKLM owns a much efficient and effective performance in terms of both complexity and classification. The contributions of this paper can be given as follows: (1) by mapping the input space into an orthonormal subspace, the geometry of the generated subspace is visualized; (2) this paper first reduces both the time and space complexity of the EKM-based MKL; (3

  1. Reducing risk where tectonic plates collide

    Science.gov (United States)

    Gomberg, Joan S.; Ludwig, Kristin A.

    2017-06-19

    Most of the world’s earthquakes, tsunamis, landslides, and volcanic eruptions are caused by the continuous motions of the many tectonic plates that make up the Earth’s outer shell. The most powerful of these natural hazards occur in subduction zones, where two plates collide and one is thrust beneath another. The U.S. Geological Survey’s (USGS) “Reducing Risk Where Tectonic Plates Collide—A USGS Plan to Advance Subduction Zone Science” is a blueprint for building the crucial scientific foundation needed to inform the policies and practices that can make our Nation more resilient to subduction zone-related hazards.

  2. Improving Realism in Reduced Gravity Simulators

    Science.gov (United States)

    Cowley, Matthew; Harvil, Lauren; Clowers, Kurt; Clark, Timothy; Rajulu, Sudhakar

    2010-01-01

    Since man was first determined to walk on the moon, simulating the lunar environment became a priority. Providing an accurate reduced gravity environment is crucial for astronaut training and hardware testing. This presentation will follow the development of reduced gravity simulators to a final comparison of environments between the currently used systems. During the Apollo program era, multiple systems were built and tested, with several NASA centers having their own unique device. These systems ranged from marionette-like suspension devices where the subject laid on his side, to pneumatically driven offloading harnesses, to parabolic flights. However, only token comparisons, if any, were made between systems. Parabolic flight allows the entire body to fall at the same rate, giving an excellent simulation of reduced gravity as far as the biomechanics and physical perceptions are concerned. While the effects are accurate, there is limited workspace, limited time, and high cost associated with these tests. With all mechanical offload systems only the parts of the body that are actively offloaded feel any reduced gravity effects. The rest of the body still feels the full effect of gravity. The Partial Gravity System (Pogo) is the current ground-based offload system used to training and testing at the NASA Johnson Space Center. The Pogo is a pneumatic type system that allows for offloaded motion in the z-axis and free movement in the x-axis, but has limited motion in the y-axis. The pneumatic system itself is limited by cylinder stroke length and response time. The Active Response Gravity Offload System (ARGOS) is a next generation groundbased offload system, currently in development, that is based on modern robotic manufacturing lines. This system is projected to provide more z-axis travel and full freedom in both the x and y-axes. Current characterization tests are underway to determine how the ground-based offloading systems perform, how they compare to parabolic

  3. Deciding for Future Selves Reduces Loss Aversion.

    Science.gov (United States)

    Cheng, Qiqi; He, Guibing

    2017-01-01

    In this paper, we present an incentivized experiment to investigate the degree of loss aversion when people make decisions for their current selves and future selves under risk. We find that when participants make decisions for their future selves, they are less loss averse compared to when they make decisions for their current selves. This finding is consistent with the interpretation of loss aversion as a bias in decision-making driven by emotions, which are reduced when making decisions for future selves. Our findings endorsed the external validity of previous studies on the impact of emotion on loss aversion in a real world decision-making environment.

  4. Rationale for reduced tornado design bases

    International Nuclear Information System (INIS)

    Rutherford, P.D.; Ho, H.W.; Hartung, J.A.; Kastenberg, W.E.

    1985-01-01

    This paper provides a rationale for relaxing the present NRC tornado design requirements, which are based on a design basis tornado (DBT) whose frequency of exceedance is 10 -7 per year. It is proposed that a reduced DBT frequency of 10 -5 to 10 -6 per year is acceptable. This change in the tornado design bases for LMFBRs (and possibly all types of nuclear plants) is justified based on (1) existing NRC regulations and guidelines, (2) probabilistic arguments, (3) consistency with NRC trial safety goals, and (4) cost-benefit analysis

  5. Activin receptor-like kinase 5 inhibition reverses impairment of endothelial cell viability by endogenous islet mesenchymal stromal cells.

    Science.gov (United States)

    Clarkin, Claire E; King, Aileen J; Dhadda, Paramjeet; Chagastelles, Pedro; Nardi, Nance; Wheeler-Jones, Caroline P; Jones, Peter M

    2013-03-01

    Following islet transplantation, islet graft revascularization is compromised due to loss of endothelial cells (ECs) during islet culture. TGF-β signaling pathways are essential for vascular homeostasis but their importance for islet EC function is unclear. We have identified a population of multipotent mesenchymal stromal cells (MSCs) within islets and investigated how modulation of TGF-β signaling by these cells influences islet EC viability. Cultured islets exhibited reduced expression of EC markers (VEGFR2, VE-cadherin and CD31), which was associated with diminished but sustained expression of endoglin a marker of both ECs and MSCs. Double fluorescent labeling of islets in situ with the EC marker CD31 disclosed a population of CD31-negative cells which were positive for endoglin. In vitro coculture of microvascular ECs with endoglin-positive, CD31-negative islet MSCs reduced VEGFR2 protein expression, disrupted EC angiogenic behavior, and increased EC detachment. Medium conditioned by islet MSCs significantly decreased EC viability and increased EC caspase 3/7 activity. EC:MSC cocultures showed enhanced Smad2 phosphorylation consistent with altered ALK5 signaling. Pharmacological inhibition of ALK5 activity with SB431542 (SB) improved EC survival upon contact with MSCs, and SB-treated cultured islets retained EC marker expression and sensitivity to exogenous VEGF164 . Thus, endoglin-expressing islet MSCs influence EC ALK5 signaling in vitro, which decreases EC viability, and changes in ALK5 activity in whole cultured islets contribute to islet EC loss. Modifying TGF-β signaling may enable maintenance of islet ECs during islet isolation and thus improve islet graft revascularization post-transplantation. Copyright © 2013 AlphaMed Press.

  6. Internet treatment for social phobia reduces comorbidity.

    Science.gov (United States)

    Titov, Nickolai; Gibson, Matthew; Andrews, Gavin; McEvoy, Peter

    2009-08-01

    Social phobia can be treated by brief Internet-based cognitive behaviour therapy (CBT). Most people with social phobia, however, meet criteria for another mental disorder; this comorbidity is associated with significant disability, and cases of comorbidity may be more difficult to treat. The present study examined the impact of the Shyness programme, an Internet-based treatment programme for social phobia, on comorbid symptoms of depression and generalized anxiety disorder. Data from three randomized controlled trials using the Shyness programme to treat social phobia were reanalysed. The 211 subjects, all of whom met DSM-IV criteria for social phobia, were divided into four groups: (i) social phobia only; (ii) social phobia with elevated symptoms of depression; (iii) social phobia with elevated symptoms of generalized anxiety; and (iv) social phobia with elevated symptoms of both generalized anxiety and depression. The improvement in social phobia, depression and anxiety following Internet-based treatment for social phobia was measured. Improvement in social phobia was seen in all groups, whether comorbid or not. Significant improvements in comorbid symptoms of depression and generalized anxiety occurred even though the treatment was focused on the social phobia. Brief Internet-based CBT can reduce both the target disorder as well as comorbid symptoms. These findings are consistent with evidence that unified or transdiagnostic programmes may reduce the severity of comorbid disorders and symptoms, indicating an important direction for future research.

  7. Polaron interaction energies in reduced tungsten trioxide

    International Nuclear Information System (INIS)

    Iguchi, E.; Salje, E.; Tilley, R.J.D.

    1981-01-01

    Consideration of the properties of reduced tungsten trioxide suggest that the mobile charge carriers are polarons. As it is uncertain how the presence of polarons will influence the microstructures of the crystallographic shear (CS) planes present in reduced tungsten trioxide we have calculated both the polaron-CS plane and polaron-polaron interaction energy for a variety of circumstances. Three CS plane geometries were considered, (102), (103), and (001) CS plane arrays, and the nominal compositions of the crystals ranged from WO 2 70 to WO 3 0 . The polarons were assumed to have radii from 0.6 to 1.0 nm and the polaron-CS plane electrostatic interaction was assumed to be screened. The results suggest that for the most part the total interaction energy is small and is unlikely to be of major importance in controlling the microstructures found in CS planes. However, at very high polaron densities the interaction energy could be appreciable and may have some influence on the existence range of CS phases

  8. Quantifying data worth toward reducing predictive uncertainty

    Science.gov (United States)

    Dausman, A.M.; Doherty, J.; Langevin, C.D.; Sukop, M.C.

    2010-01-01

    The present study demonstrates a methodology for optimization of environmental data acquisition. Based on the premise that the worth of data increases in proportion to its ability to reduce the uncertainty of key model predictions, the methodology can be used to compare the worth of different data types, gathered at different locations within study areas of arbitrary complexity. The method is applied to a hypothetical nonlinear, variable density numerical model of salt and heat transport. The relative utilities of temperature and concentration measurements at different locations within the model domain are assessed in terms of their ability to reduce the uncertainty associated with predictions of movement of the salt water interface in response to a decrease in fresh water recharge. In order to test the sensitivity of the method to nonlinear model behavior, analyses were repeated for multiple realizations of system properties. Rankings of observation worth were similar for all realizations, indicating robust performance of the methodology when employed in conjunction with a highly nonlinear model. The analysis showed that while concentration and temperature measurements can both aid in the prediction of interface movement, concentration measurements, especially when taken in proximity to the interface at locations where the interface is expected to move, are of greater worth than temperature measurements. Nevertheless, it was also demonstrated that pairs of temperature measurements, taken in strategic locations with respect to the interface, can also lead to more precise predictions of interface movement. Journal compilation ?? 2010 National Ground Water Association.

  9. Remifentanil Reduces Blood Loss During Orthognathic Surgery.

    Science.gov (United States)

    Matsuura, Nobuyuki; Okamura, Taiki; Ide, Satoko; Ichinohe, Tatsuya

    2017-01-01

    Remifentanil is reported to reduce oral tissue blood flow. We performed a retrospective investigation using logistic regression analysis of anesthesia records to investigate whether the use of remifentanil infusion in a balanced anesthesia technique was useful as a primary technique to reduce blood loss during orthognathic surgery. Subjects were 80 patients who underwent Le Fort I osteotomy and sagittal split ramus osteotomy of the mandible. The variables included gender, age, weight, type of maintenance anesthetic, type and dose or infusion rate of opioid, mean systolic blood pressure (SBP-mean), coefficient of variation of systolic blood pressure (CVSBP) during surgery, mean heart rate (HR-mean), duration of surgery, total blood loss, volume of infusion used, amount of local anesthetic used, body temperature, and urine output. Gender, type of maintenance anesthetic, type of opioid, SBP-mean, CVSBP, HR-mean, and duration of surgery were used as candidates for independent variables. Logistic regression analysis was performed for the selected independent variables with the total blood loss as the dependent variable. The factors associated with the reduction of blood loss were the use of remifentanil (odds ratio, 3.112; 95% CI, 1.166-8.307; P = .023) and smaller CVSBP (odds ratio, 2.747; 95% CI, 1.07-7.053; P = .036). Use of remifentanil and smaller CVSBP were associated with a reduction of blood loss during orthognathic surgery.

  10. Phytosterol glycosides reduce cholesterol absorption in humans

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received ∼300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4–5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6 ± 4.8% (P lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content. PMID:19246636

  11. Reducing violent injuries: priorities for pediatrician advocacy.

    Science.gov (United States)

    Dolins, J C; Christoffel, K K

    1994-10-01

    A basic framework for developing an advocacy plan must systematically break down the large task of policy development implementation into manageable components. The basic framework described in detail in this paper includes three steps: Setting policy objectives by narrowing the scope of policy, by reviewing policy options, and by examining options against selected criteria. Developing strategies for educating the public and for approaching legislative/regulatory bodies. Evaluating the effectiveness of the advocacy action plan as a process and as an agent for change. To illustrate the variety of ways in which pediatricians can be involved in the policy process to reduce violent injuries among children and adolescents, we apply this systematic approach to three priority areas. Prohibiting the use of corporal punishment in schools is intended to curb the institutionalized legitimacy of violence that has been associated with future use of violence. Efforts to remove handguns from the environments of children and adolescents are aimed at reducing the numbers of firearm injuries inflicted upon and by minors. Comprehensive treatment of adolescent victims of assault is intended to decrease the reoccurrence of violent injuries.

  12. Phytosterol glycosides reduce cholesterol absorption in humans.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Anderson Spearie, Catherine L; Ostlund, Richard E

    2009-04-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (Pphytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

  13. Ice load reducer for dams : laboratory tests

    Energy Technology Data Exchange (ETDEWEB)

    Lupien, R.; Cote, A.; Robert, A. [Institut de Recherche d' Hydro-Quebec, Varennes, PQ (Canada)

    2009-07-01

    Many studies have focused on measuring static ice loads on various hydraulic structures in Canada. This paper discussed a Hydro-Quebec research project whose main purpose was to harmonize the ice thrust value in load combinations for use in general hydraulic works or for specific cases. The objectives of the project were to obtain a better understanding of existing data and to characterize sites and their influence on ice thrust; study the structural mechanisms involved in the generation of ice thrust, their consequences on the structural behaviour of ice and the natural mitigating circumstances that may be offered by ice properties or site operating procedures; and examine the relevance of developing an ice load reducer for works that might not fit the harmonized design value. The paper presented the main research goals and ice load reducer goals, with particular focus on the four pipe samples that were planned, built and tested. The experimental program involved checking the pipe shape behaviour in terms of flexibility-stiffness; maximum deformations; maximum load reduction; permanent deformations; and, ability to shape recovering. The testing also involved examining the strength versus strain rate; creep versus strain rate; and creep capacity under biaxial state of tension and compression. It was concluded that the two phenomena involved in generation of ice thrust, notably thermal expansion and water level changes, had very low strain rates. 8 refs., 2 tabs., 16 figs.

  14. Hybrid reduced order modeling for assembly calculations

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Y.; Abdel-Khalik, H. S. [North Carolina State University, Raleigh, NC (United States); Jessee, M. A.; Mertyurek, U. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    2013-07-01

    While the accuracy of assembly calculations has considerably improved due to the increase in computer power enabling more refined description of the phase space and use of more sophisticated numerical algorithms, the computational cost continues to increase which limits the full utilization of their effectiveness for routine engineering analysis. Reduced order modeling is a mathematical vehicle that scales down the dimensionality of large-scale numerical problems to enable their repeated executions on small computing environment, often available to end users. This is done by capturing the most dominant underlying relationships between the model's inputs and outputs. Previous works demonstrated the use of the reduced order modeling for a single physics code, such as a radiation transport calculation. This manuscript extends those works to coupled code systems as currently employed in assembly calculations. Numerical tests are conducted using realistic SCALE assembly models with resonance self-shielding, neutron transport, and nuclides transmutation/depletion models representing the components of the coupled code system. (authors)

  15. Reduced cooling following future volcanic eruptions

    Science.gov (United States)

    Hopcroft, Peter O.; Kandlbauer, Jessy; Valdes, Paul J.; Sparks, R. Stephen J.

    2017-11-01

    Volcanic eruptions are an important influence on decadal to centennial climate variability. Large eruptions lead to the formation of a stratospheric sulphate aerosol layer which can cause short-term global cooling. This response is modulated by feedback processes in the earth system, but the influence from future warming has not been assessed before. Using earth system model simulations we find that the eruption-induced cooling is significantly weaker in the future state. This is predominantly due to an increase in planetary albedo caused by increased tropospheric aerosol loading with a contribution from associated changes in cloud properties. The increased albedo of the troposphere reduces the effective volcanic aerosol radiative forcing. Reduced sea-ice coverage and hence feedbacks also contribute over high-latitudes, and an enhanced winter warming signal emerges in the future eruption ensemble. These findings show that the eruption response is a complex function of the environmental conditions, which has implications for the role of eruptions in climate variability in the future and potentially in the past.

  16. Energy conservation by reducing process variability

    Energy Technology Data Exchange (ETDEWEB)

    Wising, Ulrika; Lafourcade, Sebastien [Pepite S.A., Liege (Belgium); Mack, Philippe [Pepite Technologies Inc., Montreal (Canada)

    2011-12-21

    Energy conservation is becoming an increasingly important instrument to stay competitive in today is increasingly global market. Important investments have been made in infrastructure and personnel in order to improve the management of energy such as increased metering, energy dashboards, energy managers, etc. Despite these investments, the results have not materialized and there is still a significant potential to further reduce energy consumption. In this paper a new methodology will be presented that helps industry better operate existing assets in order to reduce energy consumption, without having to make capital investments. The methodology uses a combination of advanced data analysis tools and a specific implementation scheme that has lead to significant savings in industry. The advanced data analysis tools are used to analyze the variability of the process in order to assess when the plant has been operated well or not so well in the past. By finding the root causes of these variations and the key variables that can explain them, improved operating guidelines and models can be developed and implemented. The specific implementation scheme is an important part of the methodology as it involves the people operating the plant. Several user cases will be presented showing an energy conservation of between 10%-20% without capital investments necessary. (author)

  17. Positive autobiographical memory retrieval reduces temporal discounting

    Science.gov (United States)

    Lempert, Karolina M; Speer, Megan E; Delgado, Mauricio R

    2017-01-01

    Abstract People generally prefer rewards sooner rather than later. This phenomenon, temporal discounting, underlies many societal problems, including addiction and obesity. One way to reduce temporal discounting is to imagine positive future experiences. Since there is overlap in the neural circuitry associated with imagining future experiences and remembering past events, here we investigate whether recalling positive memories can also promote more patient choice. We found that participants were more patient after retrieving positive autobiographical memories, but not when they recalled negative memories. Moreover, individuals were more impulsive after imagining novel positive scenes that were not related to their memories, showing that positive imagery alone does not drive this effect. Activity in the striatum and temporo parietal junction during memory retrieval predicted more patient choice, suggesting that to the extent that memory recall is rewarding and involves perspective-taking, it influences decision-making. Furthermore, representational similarity in the ventromedial prefrontal cortex between memory recall and decision phases correlated with the behavioral effect across participants. Thus, we have identified a novel manipulation for reducing temporal discounting—remembering the positive past—and have begun to characterize the psychological and neural mechanisms behind it. PMID:28655195

  18. CHROMagar Orientation Medium Reduces Urine Culture Workload

    Science.gov (United States)

    Manickam, Kanchana; Karlowsky, James A.; Adam, Heather; Lagacé-Wiens, Philippe R. S.; Rendina, Assunta; Pang, Paulette; Murray, Brenda-Lee

    2013-01-01

    Microbiology laboratories continually strive to streamline and improve their urine culture algorithms because of the high volumes of urine specimens they receive and the modest numbers of those specimens that are ultimately considered clinically significant. In the current study, we quantitatively measured the impact of the introduction of CHROMagar Orientation (CO) medium into routine use in two hospital laboratories and compared it to conventional culture on blood and MacConkey agars. Based on data extracted from our Laboratory Information System from 2006 to 2011, the use of CO medium resulted in a 28% reduction in workload for additional procedures such as Gram stains, subcultures, identification panels, agglutination tests, and biochemical tests. The average number of workload units (one workload unit equals 1 min of hands-on labor) per urine specimen was significantly reduced (P < 0.0001; 95% confidence interval [CI], 0.5326 to 1.047) from 2.67 in 2006 (preimplementation of CO medium) to 1.88 in 2011 (postimplementation of CO medium). We conclude that the use of CO medium streamlined the urine culture process and increased bench throughput by reducing both workload and turnaround time in our laboratories. PMID:23363839

  19. Measures of reducing obstetric emergencies hysterectomy incidence.

    Science.gov (United States)

    Ren, Guo-ping; Wang, Bao-lian; Wang, Yan-hong

    2016-03-01

    To study the obstetric emergency hysterectomy which can reduce the incidence of measures. In maternity of Xinxiang Central Hospital, the total number of deliveries cases has been up to 50,526 in 20 years, of which 48 cases were retrospectively analyzed for the clinical data of Emergency uterine surgery cases. Cases underwent obstetric emergency hysterectomy accounted for 0.095% of total deliveries (48/50 526), in which 11 cases of vaginal delivery, 37 cases of cesarean section. The indications for surgery: 27 cases were cased by placental factors accounted for 56.25%; 14 cases of uterine inertia, accounting for 29.17%; uterine rupture in 4 cases, accounting for 8.33%; 3 cases of coagulopathy, accounting for 6.25%. Where the maternal placental factors hysterectomy is the most common (69.70%, 23/33) and the predominant factor is early maternal uterine inertia (60.00%, 9/15). There are 74.09% (20/27) of patients with placental abnormalities history of previous cesarean section or uterine surgery. The major risk factors leading to obstetric emergency hysterectomy is placental factors. Preventing the occurrence of placental abnormalities planting actively can effectively reduce the rate of obstetric hysterectomy.

  20. Reducing Environmental Allergic Triggers: Policy Issues.

    Science.gov (United States)

    Abramson, Stuart L

    The implementation of policies to reduce environmental allergic triggers can be an important adjunct to optimal patient care for allergic rhinitis and allergic asthma. Policies at the local level in schools and other public as well as private buildings can make an impact on disease morbidity. Occupational exposures for allergens have not yet been met with the same rigorous policy standards applied for exposures to toxicants by Occupational Safety and Health Administration. Further benefit may be obtained through policies by local, county, state, and national governments, and possibly through international cooperative agreements. The reduction of allergenic exposures can and should be affected by policies with strong scientific, evidence-based derivation. However, a judicious application of the precautionary principle may be needed in circumstances where the health effect of inaction could lead to more serious threats to vulnerable populations with allergic disease. This commentary covers the scientific basis, current implementation, knowledge gaps, and pro/con views on policy issues in reducing environmental allergic triggers. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Recommendations for reducing ambiguity in written procedures.

    Energy Technology Data Exchange (ETDEWEB)

    Matzen, Laura E.

    2009-11-01

    Previous studies in the nuclear weapons complex have shown that ambiguous work instructions (WIs) and operating procedures (OPs) can lead to human error, which is a major cause for concern. This report outlines some of the sources of ambiguity in written English and describes three recommendations for reducing ambiguity in WIs and OPs. The recommendations are based on commonly used research techniques in the fields of linguistics and cognitive psychology. The first recommendation is to gather empirical data that can be used to improve the recommended word lists that are provided to technical writers. The second recommendation is to have a review in which new WIs and OPs and checked for ambiguities and clarity. The third recommendation is to use self-paced reading time studies to identify any remaining ambiguities before the new WIs and OPs are put into use. If these three steps are followed for new WIs and OPs, the likelihood of human errors related to ambiguity could be greatly reduced.

  2. Online Hemodiafiltration Reduces Bisphenol A Levels.

    Science.gov (United States)

    Quiroga, Borja; Bosch, Ricardo J; Fiallos, Ruth A; Sánchez-Heras, Marta; Olea-Herrero, Nuria; López-Aparicio, Pilar; Muñóz-Moreno, Carmen; Pérez-Alvarsan, Miguel Angel; De Arriba, Gabriel

    2017-02-01

    Several uremic toxins have been identified and related to higher rates of morbidity and mortality in dialysis patients. Bisphenol A (BPA) accumulates in patients with chronic kidney disease. The aim of this study is to demonstrate the usefulness of online hemodiafiltration (OL-HDF) in reducing BPA levels. Thirty stable hemodialysis patients were selected to participate in this paired study. During three periods of 3 weeks each, patients were switched from high-flux hemodialysis (HF-HD) to OL-HDF, and back to HF-HD. BPA levels were measured in the last session of each period (pre- and post-dialysis) using ELISA and HPLC. Twenty-two patients (mean age 73 ± 14 years; 86.4% males) were included. Measurements of BPA levels by HPLC and ELISA assays showed a weak but significant correlation (r = 0.218, P = 0.012). BPA levels decreased in the OL-HDF period of hemodialysis, in contrast to the HF-HD period when they remained stable (P = 0.002). In conclusion, OL-HDF reduced BPA levels in dialysis patients. © 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  3. Explicit information reduces discounting behavior in monkeys

    Directory of Open Access Journals (Sweden)

    John ePearson

    2010-12-01

    Full Text Available Animals are notoriously impulsive in common laboratory experiments, preferring smaller, sooner rewards to larger, delayed rewards even when this reduces average reward rates. By contrast, the same animals often engage in natural behaviors that require extreme patience, such as food caching, stalking prey, and traveling long distances to high quality food sites. One possible explanation for this discrepancy is that standard laboratory delay discounting tasks artificially inflate impulsivity by subverting animals’ common learning strategies. To test this idea, we examined choices made by rhesus macaques in two variants of a standard delay discounting task. In the conventional variant, post-reward delays were uncued and adjusted to render total trial length constant; in the second, all delays were cued explicitly. We found that measured discounting was significantly reduced in the cued task, with discount rates well below those reported in studies using the standard uncued design. When monkeys had complete information, their decisions were more consistent with a strategy of reward rate maximization. These results indicate that monkeys, and perhaps other animals, are more patient than is normally assumed, and that laboratory measures of delay discounting may overstate impulsivity.

  4. REDUCING GONAD IRRADIATION IN PEDIATRIC DIAGNOSIS

    Science.gov (United States)

    Bishop, Harry A.; Webber, Milo; O'Loughlin, Bernard J.

    1959-01-01

    The greatest danger of carcinogenesis and of genetic damage through diagnostic radiologic procedures is in children, whose smaller bodies are more vulnerable and who have a longer life span in which this damage can be realized. Film badges placed on the gonad area during radiologic studies indicated widely varying degrees of gonad irradiation from similar procedures. These results emphasize the importance of technique in protecting children from unnecessary exposure. Such exposure can be reduced by greater beam filtration, use of higher tube potentials, careful beam collimation and centering, closer coning and shielding of the gonads. A new film tested reduced exposure time by 50 per cent. Further reduction was obtained by high-speed screens. A most important measure is avoidance of unnecessary, repetitious and undiagnostic studies. Fluoroscopy should be avoided if possible. If not, the operator must dark-adapt his eyes, use the smallest possible current, the narrowest beam, and the shortest exposure time. Image intensification promotes these aims. Modern equipment, properly shielded, assures against unsuspected exposure. PMID:13618739

  5. Mechanisms and Effectivity of Sulfate Reducing Bioreactors ...

    Science.gov (United States)

    Mining-influenced water (MIW) is the main environmental challenges associated with the mining industry. Passive MIW remediation can be achieved through microbial activity in sulfate-reducing bioreactors (SRBRs), but their actual removal rates depend on different factors, one of which is the substrate composition. Chitinous materials have demonstrated high metal removal rates, particularly for the two recalcitrant MIW contaminants Zn and Mn, but their removal mechanisms need further study. We studied Cd, Fe, Zn, and Mn removal in bioactive and abiotic SRBRs to elucidate the metal removal mechanisms and the differences in metal and sulfate removal rates using a chitinous material as substrate. We found that sulfate-reducing bacteria are effective in increasing metal and sulfate removal rates and duration of operation in SRBRs, and that the main mechanism involved was metal precipitation as sulfides. The solid residues provided evidence of the presence of sulfides in the bioactive column, more specifically ZnS, according to XPS analysis. The feasibility of passive treatments with a chitinous substrate could be an important option for MIW remediation. Mining influenced water (MIW) remediation is still one of the top priorities for the agency because it addresses the most important environmental problem associated with the mining industry and that affects thousands of communities in the U.S. and worldwide. In this paper, the MIW bioremediation mechanisms are studied

  6. Carbonate stability in the reduced lower mantle

    Science.gov (United States)

    Dorfman, Susannah M.; Badro, James; Nabiei, Farhang; Prakapenka, Vitali B.; Cantoni, Marco; Gillet, Philippe

    2018-05-01

    Carbonate minerals are important hosts of carbon in the crust and mantle with a key role in the transport and storage of carbon in Earth's deep interior over the history of the planet. Whether subducted carbonates efficiently melt and break down due to interactions with reduced phases or are preserved to great depths and ultimately reach the core-mantle boundary remains controversial. In this study, experiments in the laser-heated diamond anvil cell (LHDAC) on layered samples of dolomite (Mg, Ca)CO3 and iron at pressure and temperature conditions reaching those of the deep lower mantle show that carbon-iron redox interactions destabilize the MgCO3 component, producing a mixture of diamond, Fe7C3, and (Mg, Fe)O. However, CaCO3 is preserved, supporting its relative stability in carbonate-rich lithologies under reducing lower mantle conditions. These results constrain the thermodynamic stability of redox-driven breakdown of carbonates and demonstrate progress towards multiphase mantle petrology in the LHDAC at conditions of the lowermost mantle.

  7. Treating Fibrous Insulation to Reduce Thermal Conductivity

    Science.gov (United States)

    Zinn, Alfred; Tarkanian, Ryan

    2009-01-01

    A chemical treatment reduces the convective and radiative contributions to the effective thermal conductivity of porous fibrous thermal-insulation tile. The net effect of the treatment is to coat the surfaces of fibers with a mixture of transition-metal oxides (TMOs) without filling the pores. The TMO coats reduce the cross-sectional areas available for convection while absorbing and scattering thermal radiation in the pores, thereby rendering the tile largely opaque to thermal radiation. The treatment involves a sol-gel process: A solution containing a mixture of transition-metal-oxide-precursor salts plus a gelling agent (e.g., tetraethylorthosilicate) is partially cured, then, before it visibly gels, is used to impregnate the tile. The solution in the tile is gelled, then dried, and then the tile is fired to convert the precursor salts to the desired mixed TMO phases. The amounts of the various TMOs ultimately incorporated into the tile can be tailored via the concentrations of salts in the solution, and the impregnation depth can be tailored via the viscosity of the solution and/or the volume of the solution relative to that of the tile. The amounts of the TMOs determine the absorption and scattering spectra.

  8. Listening to music reduces eye movements.

    Science.gov (United States)

    Schäfer, Thomas; Fachner, Jörg

    2015-02-01

    Listening to music can change the way that people visually experience the environment, probably as a result of an inwardly directed shift of attention. We investigated whether this attentional shift can be demonstrated by reduced eye movement activity, and if so, whether that reduction depends on absorption. Participants listened to their preferred music, to unknown neutral music, or to no music while viewing a visual stimulus (a picture or a film clip). Preference and absorption were significantly higher for the preferred music than for the unknown music. Participants exhibited longer fixations, fewer saccades, and more blinks when they listened to music than when they sat in silence. However, no differences emerged between the preferred music condition and the neutral music condition. Thus, music significantly reduces eye movement activity, but an attentional shift from the outer to the inner world (i.e., to the emotions and memories evoked by the music) emerged as only one potential explanation. Other explanations, such as a shift of attention from visual to auditory input, are discussed.

  9. Positive autobiographical memory retrieval reduces temporal discounting.

    Science.gov (United States)

    Lempert, Karolina M; Speer, Megan E; Delgado, Mauricio R; Phelps, Elizabeth A

    2017-10-01

    People generally prefer rewards sooner rather than later. This phenomenon, temporal discounting, underlies many societal problems, including addiction and obesity. One way to reduce temporal discounting is to imagine positive future experiences. Since there is overlap in the neural circuitry associated with imagining future experiences and remembering past events, here we investigate whether recalling positive memories can also promote more patient choice. We found that participants were more patient after retrieving positive autobiographical memories, but not when they recalled negative memories. Moreover, individuals were more impulsive after imagining novel positive scenes that were not related to their memories, showing that positive imagery alone does not drive this effect. Activity in the striatum and temporo parietal junction during memory retrieval predicted more patient choice, suggesting that to the extent that memory recall is rewarding and involves perspective-taking, it influences decision-making. Furthermore, representational similarity in the ventromedial prefrontal cortex between memory recall and decision phases correlated with the behavioral effect across participants. Thus, we have identified a novel manipulation for reducing temporal discounting-remembering the positive past-and have begun to characterize the psychological and neural mechanisms behind it. © The Author (2017). Published by Oxford University Press.

  10. REDUCING GREENHOUSE EMISSIONS AND FUEL CONSUMPTION

    Directory of Open Access Journals (Sweden)

    Susan A. SHAHEEN, Ph.D.

    2007-01-01

    Fortunately, transportation technologies and strategies are emerging that can help to meet the climate challenge. These include automotive and fuel technologies, intelligent transportation systems (ITS, and mobility management strategies that can reduce the demand for private vehicles. While the climate change benefits of innovative engine and vehicle technologies are relatively well understood, there are fewer studies available on the energy and emission impacts of ITS and mobility management strategies. In the future, ITS and mobility management will likely play a greater role in reducing fuel consumption. Studies are often based on simulation models, scenario analysis, and limited deployment experience. Thus, more research is needed to quantify potential impacts. Of the nine ITS technologies examined, traffic signal control, electronic toll collection, bus rapid transit, and traveler information have been deployed more widely and demonstrated positive impacts (but often on a limited basis. Mobility management approaches that have established the greatest CO2 reduction potential, to date, include road pricing policies (congestion and cordon and carsharing (short-term auto access. Other approaches have also indicated CO2 reduction potential including: low-speed modes, integrated regional smart cards, park-and-ride facilities, parking cash out, smart growth, telecommuting, and carpooling.

  11. Reducing human nitrogen use for food production.

    Science.gov (United States)

    Liu, Junguo; Ma, Kun; Ciais, Philippe; Polasky, Stephen

    2016-07-22

    Reactive nitrogen (N) is created in order to sustain food production, but only a small fraction of this N ends up being consumed as food, the rest being lost to the environment. We calculated that the total N input (TN) of global food production was 171 Tg N yr(-1) in 2000. The production of animal products accounted for over 50% of the TN, against 17% for global calories production. Under current TN per unit of food production and assuming no change in agricultural practices and waste-to-food ratios, we estimate that an additional TN of 100 Tg N yr(-1) will be needed by 2030 for a baseline scenario that would meet hunger alleviation targets for over 9 billion people. Increased animal production will have the largest impact on increasing TN, which calls for new food production systems with better N-recycling, such as cooperation between crop and livestock producing farms. Increased N-use efficiency, healthier diet and decreased food waste could mitigate this increase and even reduce TN in 2030 by 8% relative to the 2000 level. Achieving a worldwide reduction of TN is a major challenge that requires sustained actions to improve nitrogen management practices and reduce nitrogen losses into the environment.

  12. Action plan to reduce perinatal mortality.

    Science.gov (United States)

    Bhakoo, O N; Kumar, R

    1990-01-01

    The government of India has set a goal of reducing perinatal mortality from its current rate of 48/1000 to 30-35/1000 by the year 2000. Perinatal deaths result from maternal malnutrition, inadequate prenatal care, complications of delivery, and infections in the postpartum period. Since reductions in perinatal mortality require attention to social, economic, and behavioral factors, as well as improvements in the health care delivery system, a comprehensive strategy is required. Social measures, such as raising the age at marriage to 18 years for females, improving the nutritional status of adolescent girls, reducing the strenuousness of work during pregnancy, improving female literacy, raising women's status in the society and thus in the family, and poverty alleviation programs, would all help eliminate the extent of complications of pregnancy. Measures required to enhance infant survival include improved prenatal care, prenatal tetanus toxoid immunization, use of sterile disposable cord care kits, the provision of mucus extractors and resuscitation materials to birth attendants, the creation of neonatal care units in health facilities, and more efficient referral of high-risk newborns and mothers. Since 90% of births in rural India take place at home priority must be given to training traditional birth attendants in the identification of high risk factors during pregnancy, delivery, and the newborn period.

  13. Optimizing substrate for sulfate-reducing bacteria

    International Nuclear Information System (INIS)

    Chang, L.K.; Updegraff, D.M.; Wildeman, T.R.

    1991-01-01

    Microbial sulfate reduction followed by sulfide precipitation effectively removes heavy metals from wastewaters. The substrate in the anaerobic zone in a constructed wetland can be designed to emphasize this removal process. This group of bacteria requires CH 2 O, P, N, and SO 4 =, reducing conditions, and pH range of 5-9 (pH=7 is optimum). The objective of this study was to find an inexpensive source of nutrients that would give the best initial production of sulfide and make a good wetland substrate. All tested materials contain sufficient P and N; mine drainage provides sulfate. Thus, tests focused on finding organic material that provides the proper nutrients and does not cause the culture to fall below pH of 5. Among chemical nutrients, sodium lactate combined with (NH 4 ) 2 HPO 4 were the only compounds that produced sulfide after 11 days. Among complex nutrients, only cow manure produced sulfide after 26 days. Among complex carbohydrates, cracked corn and raw rice produced sulfide after 10 days. Most substrates failed to produce sulfide because anaerobic fermentation reduced the pH below 5. Presently, cracked corn is the best candidate for a substrate. Five grams of cow manure produced 0.14 millimole of sulfide whereas 0.1 g of cracked corn produced 0.22 millimole

  14. Iterative reconstruction reduces abdominal CT dose

    International Nuclear Information System (INIS)

    Martinsen, Anne Catrine Trægde; Sæther, Hilde Kjernlie; Hol, Per Kristian; Olsen, Dag Rune; Skaane, Per

    2012-01-01

    Objective: In medical imaging, lowering radiation dose from computed tomography scanning, without reducing diagnostic performance is a desired achievement. Iterative image reconstruction may be one tool to achieve dose reduction. This study reports the diagnostic performance using a blending of 50% statistical iterative reconstruction (ASIR) and filtered back projection reconstruction (FBP) compared to standard FBP image reconstruction at different dose levels for liver phantom examinations. Methods: An anthropomorphic liver phantom was scanned at 250, 185, 155, 140, 120 and 100 mA s, on a 64-slice GE Lightspeed VCT scanner. All scans were reconstructed with ASIR and FBP. Four readers evaluated independently on a 5-point scale 21 images, each containing 32 test sectors. In total 672 areas were assessed. ROC analysis was used to evaluate the differences. Results: There was a difference in AUC between the 250 mA s FBP images and the 120 and 100 mA s FBP images. ASIR reconstruction gave a significantly higher diagnostic performance compared to standard reconstruction at 100 mA s. Conclusion: A blending of 50–90% ASIR and FBP may improve image quality of low dose CT examinations of the liver, and thus give a potential for reducing radiation dose.

  15. [Cholesterol reducing food certainly is useful].

    Science.gov (United States)

    Stalenhoef, A F

    1997-12-27

    The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease.

  16. Endotoxemia reduces cerebral perfusion but enhances dynamic cerebrovascular autoregulation at reduced arterial carbon dioxide tension*

    DEFF Research Database (Denmark)

    Brassard, Patrice; Kim, Yu-Sok; van Lieshout, Johannes

    2012-01-01

    OBJECTIVE:: The administration of endotoxin to healthy humans reduces cerebral blood flow but its influence on dynamic cerebral autoregulation remains unknown. We considered that a reduction in arterial carbon dioxide tension would attenuate cerebral perfusion and improve dynamic cerebral autoreg...

  17. Workplace interventions for reducing sitting at work.

    Science.gov (United States)

    Shrestha, Nipun; Kukkonen-Harjula, Katriina T; Verbeek, Jos H; Ijaz, Sharea; Hermans, Veerle; Bhaumik, Soumyadeep

    2016-03-17

    Office work has changed considerably over the previous couple of decades and has become sedentary in nature. Physical inactivity at workplaces and particularly increased sitting has been linked to increase in cardiovascular disease, obesity and overall mortality. To evaluate the effects of workplace interventions to reduce sitting at work compared to no intervention or alternative interventions. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, OSH UPDATE, PsycINFO, Clinical trials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal up to 2 June, 2015. We also screened reference lists of articles and contacted authors to find more studies to include. We included randomised controlled trials (RCTs), cluster-randomised controlled trials (cRCTs), and quasi-randomised controlled trials of interventions to reduce sitting at work. For changes of workplace arrangements, we also included controlled before-and-after studies (CBAs) with a concurrent control group. The primary outcome was time spent sitting at work per day, either self-reported or objectively measured by means of an accelerometer-inclinometer. We considered energy expenditure, duration and number of sitting episodes lasting 30 minutes or more, work productivity and adverse events as secondary outcomes. Two review authors independently screened titles, abstracts and full-text articles for study eligibility. Two review authors independently extracted data and assessed risk of bias. We contacted authors for additional data where required. We included 20 studies, two cross-over RCTs, 11 RCTs, three cRCTs and four CBAs, with a total of 2180 participants from high income nations. The studies evaluated physical workplace changes (nine studies), policy changes (two studies), information and counselling (seven studies) and interventions from multiple categories (two studies). One study had both physical

  18. The European Procedure on Reduced Value Claims

    Directory of Open Access Journals (Sweden)

    Alexandrina Zaharia

    2009-06-01

    Full Text Available Maintaining and developing the area of freedom, security and justice is a major objective of theEuropean Community, which guarantees the free movement of persons. As a result of litigations regardingthe applications with a reduced value arising among physical or legal persons, it was felt the need for acommunity legislation that would guarantee identical conditions, both for creditors and debtors throughoutthe entire European Union territory. The European procedure regarding the debts recovery of reducedvalue facilitates the access to justice and it is characterized by simplifying and expediting the settling of thetransboundary litigations, reducing costs, the recognition and execution of the court order in a MemberState given in another Member State. This procedure is available to litigants as an alternative to theprocedures provided by the laws of Member States. The Regulation (EC no. 861/2007 establishing aEuropean procedure regarding the applications with reduced value applies in civil and commercial matters inthe transboundary cases, regardless the nature of the court when the application value, without taking intoaccount the interest, expenditures and other costs, does not exceed 2000 Euro at the time of receiving theapplication form by the competent court. This procedure does not apply to revenue, customs oradministrative matters or in regard to state responsibility for acts or omissions in exercising the publicauthority, and other matters specifically referred to in the Regulation. A cause is transboundary in naturewhen one of the parties has its habitual residence in a Member State, other than the one where the courtreceives such application. The proper procedure of application resolution for the recovery of debts withreduced value is governed by the rules of procedural law of the Member State in which the proceedings areconducted, and the execution of court of law is made by state legislation in which it takes place. The

  19. Understanding and potentially reducing second breast cancer

    International Nuclear Information System (INIS)

    Brenner, D.

    2011-01-01

    Full text: Long term survival after breast cancer diagnosis has increased markedly in the last decade: 15-year relative survival after breast cancer diagnosis is now 75% in the US. Associated with these excellent survival prospects, however, long term studies suggest that contralateral second breast cancer rates are in the range from 10 to 15% at 15 years post treatment, and are still higher for BRCA1/2 carriers, as well as for still longer term survivors. These second cancer risks are much higher than those for a comparable healthy woman to develop a first breast cancer. It follows that women with breast cancer are highly prone to develop a second breast cancer. We propose here a new option for reducing the disturbingly high risk of a contralateral second breast cancer. in patients with both estrogen positive and negative primary breast cancer: prophylactic mammary irradiation (PMI) of the contralateral breast. The rationale behind PMI is evidence that standard post-Iumpectomy radiotherapy of the affected (ipsilateral) breast substantially reduces the long-term genetically-based second cancer risk in the ipsilateral breast, by killing the existing premalignant cells in that breast. This suggests that there are relatively few premalignant cells in the breast (hundreds or thousands, not millions), so even a fairly modest radiation cell-kill level across the whole breast would be expected to kill essentially all of them. If this is so, then a modest radiation dose-much lower than that to the affected breast--delivered uniformly to the whole contralateral breast, and typically delivered at the same time as the radiotherapy of the ipsilateral breast, would have the potential to markedly reduce second-cancer risks in the contralateral breast by killing essentially all the pre-malignant cells in that breast while causing only a very low level of radiation-induced sequelae. Therefore we hypothesize that low-dose prophylactic mammary irradiation of the contralateral breast

  20. Octanol reduces end-plate channel lifetime

    Science.gov (United States)

    Gage, Peter W.; McBurney, Robert N.; Van Helden, Dirk

    1978-01-01

    1. Post-synaptic effects of n-octanol at concentrations of 0·1-1 mM were examined in toad sartorius muscles by use of extracellular and voltage-clamp techniques. 2. Octanol depressed the amplitude and duration of miniature end-plate currents and hence depressed neuromuscular transmission. 3. The decay of miniature end-plate currents remained exponential in octanol solutions even when the time constant of decay (τD) was decreased by 80-90%. 4. The lifetime of end-plate channels, obtained by analysis of acetylcholine noise, was also decreased by octanol. The average lifetime measured from noise spectra agreed reasonably well with the time constant of decay of miniature end-plate currents, both in control solution and in octanol solutions. 5. Octanol caused a reduction in the conductance of end-plate channels. Single channel conductance was on average about 25 pS in control solution and 20 pS in octanol. 6. In most cells the normal voltage sensitivity of the decay of miniature end-plate currents was retained in octanol solutions. The lifetime of end-plate channels measured from acetylcholine noise also remained voltage-sensitive in octanol solutions. In some experiments in which channel lifetime was exceptionally reduced the voltage sensitivity was less than normal. 7. In octanol solutions, τD was still very sensitive to temperature changes in most cells although in some the temperature sensitivity of τD was clearly reduced. Changes in τD with temperature could generally be fitted by the Arrhenius equation suggesting that a single step reaction controlled the decay of currents both in control and in octanol solutions. In some cells in which τD became less than 0·3 ms, the relationship between τD and temperature became inconsistent with the Arrhenius equation. 8. As the decay of end-plate currents in octanol solutions remains exponential, and the voltage and temperature sensitivity can be unchanged even when τD is significantly reduced, it seems likely that

  1. Urban trees reduce nutrient leaching to groundwater.

    Science.gov (United States)

    Nidzgorski, Daniel A; Hobbie, Sarah E

    2016-07-01

    Many urban waterways suffer from excess nitrogen (N) and phosphorus (P), feeding algal blooms, which cause lower water clarity and oxygen levels, bad odor and taste, and the loss of desirable species. Nutrient movement from land to water is likely to be influenced by urban vegetation, but there are few empirical studies addressing this. In this study, we examined whether or not urban trees can reduce nutrient leaching to groundwater, an important nutrient export pathway that has received less attention than stormwater. We characterized leaching beneath 33 trees of 14 species, and seven open turfgrass areas, across three city parks in Saint Paul, Minnesota, USA. We installed lysimeters at 60 cm depth to collect soil water approximately biweekly from July 2011 through October 2013, except during winter and drought periods, measured dissolved organic carbon (C), N, and P in soil water, and modeled water fluxes using the BROOK90 hydrologic model. We also measured soil nutrient pools (bulk C and N, KCl-extractable inorganic N, Brays-P), tree tissue nutrient concentrations (C, N, and P of green leaves, leaf litter, and roots), and canopy size parameters (leaf biomass, leaf area index) to explore correlations with nutrient leaching. Trees had similar or lower N leaching than turfgrass in 2012 but higher N leaching in 2013; trees reduced P leaching compared with turfgrass in both 2012 and 2013, with lower leaching under deciduous than evergreen trees. Scaling up our measurements to an urban subwatershed of the Mississippi River (~17 400 ha, containing ~1.5 million trees), we estimated that trees reduced P leaching to groundwater by 533 kg in 2012 (0.031 kg/ha or 3.1 kg/km 2 ) and 1201 kg in 2013 (0.069 kg/ha or 6.9 kg/km 2 ). Removing these same amounts of P using stormwater infrastructure would cost $2.2 million and $5.0 million per year (2012 and 2013 removal amounts, respectively). © 2016 by the Ecological Society of America.

  2. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  3. Reducing multiple births in assisted reproduction technology.

    Science.gov (United States)

    Bhattacharya, Siladitya; Kamath, Mohan S

    2014-02-01

    Multiple pregnancy, a complication of assisted reproduction technology, is associated with poorer maternal and perinatal outcomes. The primary reason behind this is the strategy of replacing more than one embryo during an assisted reproduction technology cycle to maximise pregnancy rates. The solution to this problem is to reduce the number of embryos transferred during in-vitro fertilisation. The transition from triple- to double-embryo transfer, which decreased the risk of triplets without compromising pregnancy rates, was easily implemented. The adoption of a single embryo transfer policy has been slow because of concerns about impaired pregnancy rates in a fresh assisted reproduction technology cycle. Widespread availability of effective cryopreservation programmes means that elective single embryo transfer, along with subsequent frozen embryo transfers, could provide a way forward. Any such strategy will need to consider couples' preferences and existing funding policies, both of which have a profound influence on decision making around embryo transfer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Motivational Counseling to Reduce Sitting Time

    DEFF Research Database (Denmark)

    Aadahl, Mette; Linneberg, Allan; Møller, Trine C

    2014-01-01

    counseling intervention aimed at reducing sitting time. DESIGN: A randomized, controlled, observer-blinded, community-based trial with two parallel groups using open-end randomization with 1:1 allocation. SETTING/PARTICIPANTS: A total of 166 sedentary adults were consecutively recruited from the population......-based Health2010 Study. INTERVENTION: Participants were randomized to a control (usual lifestyle) or intervention group with four individual theory-based counseling sessions. MAIN OUTCOME MEASURES: Objectively measured overall sitting time (ActivPAL 3TM, 7 days); secondary measures were breaks in sitting time......, anthropometric measures, and cardiometabolic biomarkers, assessed at baseline and after 6 months. Data were collected in 2010-2012 and analyzed in 2013-2014 using repeated measures multiple regression analyses. RESULTS: Ninety-three participants were randomized to the intervention group and 73 to the control...

  5. Reduced Dietary Sodium Intake Increases Heart Rate

    DEFF Research Database (Denmark)

    Graudal, Niels A; Hubeck-Graudal, Thorbjørn; Jürgens, Gesche

    2016-01-01

    Reduced dietary sodium intake (sodium reduction) increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side......-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs) published in the period 1973-2014. Sixty-three of the RCTs including 72 study...... populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction...

  6. Ligand-Stabilized Reduced-Dimensionality Perovskites

    KAUST Repository

    Quan, Li Na; Yuan, Mingjian; Comin, Riccardo; Voznyy, Oleksandr; Beauregard, Eric M.; Hoogland, Sjoerd; Buin, Andrei; Kirmani, Ahmad R.; Zhao, Kui; Amassian, Aram; Kim, Dong Ha; Sargent, Edward H.

    2016-01-01

    Metal halide perovskites have rapidly advanced thin film photovoltaic performance; as a result, the materials’ observed instabilities urgently require a solution. Using density functional theory (DFT), we show that a low energy of formation, exacerbated in the presence of humidity, explains the propensity of perovskites to decompose back into their precursors. We find, also using DFT, that intercalation of phenylethylammonium between perovskite layers introduces quantitatively appreciable van der Waals interactions; and these drive an increased formation energy and should therefore improve material stability. Here we report the reduced-dimensionality (quasi-2D) perovskite films that exhibit improved stability while retaining the high performance of conventional three-dimensional perovskites. Continuous tuning of the dimensionality, as assessed using photophysical studies, is achieved by the choice of stoichiometry in materials synthesis. We achieved the first certified hysteresis-free solar power conversion in a planar perovskite solar cell, obtaining a 15.3% certified PCE, and observe greatly improved performance longevity.

  7. Power module assembly with reduced inductance

    Energy Technology Data Exchange (ETDEWEB)

    Ward, Terence G.; Stancu, Constantin C.; Jaksic, Marko; Mann, Brooks S.

    2018-03-13

    A power module assembly has a plurality of electrically conducting layers, including a first layer and a third layer. One or more electrically insulating layers are operatively connected to each of the plurality of electrically conducting layers. The electrically insulating layers include a second layer positioned between and configured to electrically isolate the first and the third layers. The first layer is configured to carry a first current flowing in a first direction. The third layer is configured to carry a second current flowing in a second direction opposite to the first direction, thereby reducing an inductance of the assembly. The electrically insulating layers may include a fourth layer positioned between and configured to electrically isolate the third layer and a fifth layer. The assembly results in a combined substrate and heat sink structure. The assembly eliminates the requirements for connections between separate substrate and heat sink structures.

  8. The value of reducing HIV stigma.

    Science.gov (United States)

    Brent, Robert J

    2016-02-01

    HIV-stigma is a major reason why HIV continues to be a global epidemic. Interventions targeting HIV-stigma are therefore necessary. To find an intervention that is worthwhile, a Cost-Benefit Analysis is needed which compares costs and benefits. There are many documented costs of HIV-stigma. What is missing is a valuation of the benefits of reducing HIV-stigma. The purpose of this paper is to present a general method that can be used to value the benefits of stigma reduction programs. The method involves estimating the marginal rate of substitution (MRS) between stigma and income in the utility function of older people with HIV. To illustrate how our framework can be used, we applied it to a sample of just over 900 people coming from the 2005-06 ROAH study (Research on Older Adults with HIV) in New York City. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Composite binders for concrete with reduced permeability

    International Nuclear Information System (INIS)

    Fediuk, R; Yushin, A

    2016-01-01

    Composite binder consisting of cement (55%), acid fly ash (40%) and limestone (5%) has been designed. It is obtained by co-milling to a specific surface of 550 kg/m 2 , it has an activity of 77.3 MPa and can produce a more dense cement stone structure. Integrated study revealed that the concrete on the composite binder basis provides an effective diffusion coefficient D. So we can conclude that the concrete layer protects buildings from toxic effects of expanded polystyrene. Low water absorption of the material (2.5% by weight) is due to the structure of its cement stone pore space. Besides lime powder prevents the penetration of moisture, reduces water saturation of the coverage that has a positive effect on useful life period. It also explains rather low water vapor permeability of the material - 0.021 mg/(m- hour-Pa). (paper)

  10. Reduced attentional scope in cocaine polydrug users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption. We asked whether recreational use of cocaine impacts early attentional selection processes. Cocaine-free polydrug controls (n = 18 and cocaine polydrug users (n = 18 were matched on sex, age, alcohol consumption, and IQ (using the Raven's progressive matrices, and were tested by using the Global-Local task to measure the scope of attention. Cocaine polydrug users attended significantly more to local aspects of attended events, which fits with the idea that a reduced scope of attention may be associated with the perpetuation of the use of the drug.

  11. Sensorless magnetically levitated system with reduced observer

    Energy Technology Data Exchange (ETDEWEB)

    Friedrich, T [Inst. fuer Elektrische Maschinen, RWTH Aachen (Germany); Henneberger, G [Inst. fuer Elektrische Maschinen, RWTH Aachen (Germany); Ress, C [Inst. fuer Elektrische Maschinen, RWTH Aachen (Germany)

    1996-12-31

    The present paper describes the use of a reduced observer for a hybrid excited magnetic levitation system. The latter is part of a contactless and energy saving driven conveyance system. Thereby one has to select the working point of the system in such a way, that the force due to the weight of the vehicle including its load will be compensated only by the permanent magnets. The linearized model is observable even if only the current in the coils is measured. Therefore it seems reasonable to evaluate the other variables of the state vector by an observer. Thus the sensors for the airgap can be omitted. Using an observer has another advantage as well. It will tune the airgap automatically to the value which is necessary in order to operate the system in the most energy saving way. The whole design was simulated. (orig.)

  12. Multiple hearth furnace for reducing iron oxide

    Science.gov (United States)

    Brandon, Mark M [Charlotte, NC; True, Bradford G [Charlotte, NC

    2012-03-13

    A multiple moving hearth furnace (10) having a furnace housing (11) with at least two moving hearths (20) positioned laterally within the furnace housing, the hearths moving in opposite directions and each moving hearth (20) capable of being charged with at least one layer of iron oxide and carbon bearing material at one end, and being capable of discharging reduced material at the other end. A heat insulating partition (92) is positioned between adjacent moving hearths of at least portions of the conversion zones (13), and is capable of communicating gases between the atmospheres of the conversion zones of adjacent moving hearths. A drying/preheat zone (12), a conversion zone (13), and optionally a cooling zone (15) are sequentially positioned along each moving hearth (30) in the furnace housing (11).

  13. A relatively reduced Hadean continental crust

    Science.gov (United States)

    Yang, Xiaozhi; Gaillard, Fabrice; Scaillet, Bruno

    2014-05-01

    Among the physical and chemical parameters used to characterize the Earth, oxidation state, as reflected by its prevailing oxygen fugacity (fO2), is a particularly important one. It controls many physicochemical properties and geological processes of the Earth's different reservoirs, and affects the partitioning of elements between coexisting phases and the speciation of degassed volatiles in melts. In the past decades, numerous studies have been conducted to document the evolution of mantle and atmospheric oxidation state with time and in particular the possible transition from an early reduced state to the present oxidized conditions. So far, it has been established that the oxidation state of the uppermost mantle is within ±2 log units of the quartz-fayalite-magnetite (QFM) buffer, probably back to ~4.4 billion years ago (Ga) based on trace-elements studies of mantle-derived komatiites, kimberlites, basalts, volcanics and zircons, and that the O2 levels of atmosphere were initially low and rose markedly ~2.3 Ga known as the Great Oxidation Event (GOE), progressively reaching its present oxidation state of ~10 log units above QFM. In contrast, the secular evolution of oxidation state of the continental crust, an important boundary separating the underlying upper mantle from the surrounding atmosphere and buffering the exchanges and interactions between the Earth's interior and exterior, has rarely been addressed, although the presence of evolved crustal materials on the Earth can be traced back to ~4.4 Ga, e.g. by detrital zircons. Zircon is a common accessory mineral in nature, occurring in a wide variety of igneous, sedimentary and metamorphic rocks, and is almost ubiquitous in crustal rocks. The physical and chemical durability of zircons makes them widely used in geochemical studies in terms of trace-elements, isotopes, ages and melt/mineral inclusions; in particular, zircons are persistent under most crustal conditions and can survive many secondary

  14. Reducing the harms associated with risk assessments

    International Nuclear Information System (INIS)

    Montague, Peter

    2004-01-01

    Risk assessments are the intellectual products of dedicated public health and environmental professionals. Like many other products, risk assessments carry with them the potential for both good and harm. This paper briefly examines some of the harms to which risk assessments have contributed, and then suggests that the legal 'duty to warn' doctrine offers a logical and practical way to reduce some of these harms. The paper suggests concepts that could be incorporated into warnings accompanying every formal risk assessment as routine 'boiler plate' addenda, just as other potentially harmful products, such as lawn mowers and cook stoves, are accompanied by warnings. Finally, the paper briefly examines the 'Code of Ethics and Standards of Practice for Environmental Professionals' (promulgated by the National Association of Environmental Professionals) and shows that the suggested warnings are consistent with recommended practices for environmental professionals

  15. Reducing US Oil Dependence Using Simulation

    Science.gov (United States)

    Ayoub, Fadi; Arnaout, Georges M.

    2011-01-01

    People across the world are addicted to oil; as a result, the instability of oil prices and the shortage of oil reserves have influenced human behaviors and global businesses. Today, the United States makes up only 5% of the global population but consumes 25% of the. world total energy. Most of this energy is generated from fossil fuels in the form of electricity. The contribution of this paper is to examine the possibilities of replacing fossil fuel with renewable energies to generate electricity as well as to examine other methods to reduce oil and gas consumption. We propose a system dynamics model in an attempt to predict the future US dependence on fossil fuels by using renewable energy resources such as, nuclear, wind, solar, and hydro powers. Based on the findings of our model, the study expects to provide insights towards promising solutions of the oil dependency problem.

  16. Spot Spraying Reduces Herbicide Concentrations in Runoff.

    Science.gov (United States)

    Melland, Alice R; Silburn, D Mark; McHugh, Allen D; Fillols, Emilie; Rojas-Ponce, Samuel; Baillie, Craig; Lewis, Stephen

    2016-05-25

    Rainfall simulator trials were conducted on sugar cane paddocks across dry-tropical and subtropical Queensland, Australia, to examine the potential for spot spraying to reduce herbicide losses in runoff. Recommended rates of the herbicides glyphosate, 2,4-D, fluoroxypyr, atrazine, and diuron were sprayed onto 0, 20, 40, 50, 70, or 100% of the area of runoff plots. Simulated rainfall was applied 2 days after spraying to induce runoff at one plant cane and three ratoon crop sites. Over 50% of all herbicides were transported in the dissolved phase of runoff, regardless of the herbicide's sediment-water partition coefficient. For most sites and herbicides, runoff herbicide concentrations decreased with decreasing spray coverage and with decreasing herbicide load in the soil and cane residues. Importantly, sites with higher infiltration prior to runoff and lower total runoff had lower runoff herbicide concentrations.

  17. Plasma gelsolin is reduced in trauma patients

    DEFF Research Database (Denmark)

    Dahl, B; Schiødt, F V; Ott, P

    1999-01-01

    in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase...... after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20......-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P

  18. Reducing SMEs informal economy through institutionalization.

    Directory of Open Access Journals (Sweden)

    Alfonso Lopez Lira Arjona

    2014-01-01

    Full Text Available The informal sector has been growing throughout the last century in emerging economies. Particularly in Latin America, both a long-term instability in economic and political environments, and a continuous migration from rural to urban areas; have triggered the appearance of unregulated businesses and employments. Small and Medium-sized Enterprises (SMEs operate informally in one or more business processes, in order to reduce costs and maximize profits. Leaving aside tax evasion and illegal labor, such SMEs often have low technology and an unskilled work force; which threatens its survival in highly competitive environments. The purpose of this paper is to highlight the impact of the Multi National Corporation (MNC and the Academia in the formalization of SMEs. This is aimed through a collaborative model for the institutionalization of operational and managerial knowledge within SMEs. Qualitative results indicate that improvements are triggered by a self-conscious awareness of the value derived from institutionalizing best business practices.

  19. Communication in reducing facility siting risk

    International Nuclear Information System (INIS)

    Bisconti, A.S.

    1992-01-01

    Today, social considerations are as important as technical ones in siting new nuclear facilities. Siting any industrial facility has become extremely difficult in this era of not in my backyard (NIMBY). Even if NIMBY does not arise locally, well-organized national opposition groups can be counted on to step in to fan the flames, especially when the industrial facility has to do with anything nuclear. It is now generally recognized that the greatest risk of failure for new nuclear facilities is not technical but social. Applying lessons gained from past experience and social science research can help reduce that risk. From these lessons, six principles for public interaction and communication stand out: (1) create goodwill now; (2) involve the community early; (3) establish the need; (4) communicate controls, not risk; (5) avoid jargon; (6) understand your public

  20. Design features to reduce occupational exposure

    International Nuclear Information System (INIS)

    Adam, J.A.; DiSabatino, A.A. Jr.; Vanasse, R.E.

    1975-01-01

    Some of the design principles which are important considerations in the evolution of a nuclear power plant design to ensure that occupational radiation exposures can be minimized are discussed. Emphasis is placed on the design features affecting the basic layout and equipment locations within the plant. Examples are provided showing how these design objectives are realized in the Stone and Webster Reference Nuclear Power Plant Design, with particular emphasis on the Annulus Building portion of the reference plant. Design features which are useful in reducing occupational exposure during normal operation are discussed initially, followed by those that chiefly affect exposures during maintenance activity. Finally, those provisions in the design which assist in preventing the spread of radioactive contamination are presented