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Sample records for mediates nephrin loss

  1. Podocytic PKC-alpha is regulated in murine and human diabetes and mediates nephrin endocytosis.

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    Irini Tossidou

    Full Text Available BACKGROUND: Microalbuminuria is an early lesion during the development of diabetic nephropathy. The loss of high molecular weight proteins in the urine is usually associated with decreased expression of slit diaphragm proteins. Nephrin, is the major component of the glomerular slit diaphragm and loss of nephrin has been well described in rodent models of experimental diabetes as well as in human diabetic nephropathy. METHODOLOGY/PRINCIPAL FINDINGS: In this manuscript we analyzed the role of PKC-alpha (PKCalpha on endocytosis of nephrin in podocytes. We found that treatment of diabetic mice with a PKCalpha-inhibitor (GO6976 leads to preserved nephrin expression and reduced proteinuria. In vitro, we found that high glucose stimulation would induce PKCalpha protein expression in murine and human podocytes. We can demonstrate that PKCalpha mediates nephrin endocytosis in podocytes and that overexpression of PKCalpha leads to an augmented endocytosis response. After PKC-activation, we demonstrate an inducible association of PKCalpha, PICK1 and nephrin in podocytes. Moreover, we can demonstrate a strong induction of PKCalpha in podocytes of patients with diabetic nephropathy. CONCLUSIONS/SIGNIFICANCE: We therefore conclude that activation of PKCalpha is a pathomechanistic key event during the development of diabetic nephropathy. PKCalpha is involved in reduction of nephrin surface expression and therefore PKCalpha inhibition might be a novel target molecule for anti-proteinuric therapy.

  2. HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

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    Doublier, Sophie; Zennaro, Cristina; Spatola, Tiziana; Lupia, Enrico; Bottelli, Antonella; Deregibus, Maria Chiara; Carraro, Michele; Conaldi, Pier Giulio; Camussi, Giovanni

    2007-02-19

    To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN). Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney. In this study, we evaluated the direct effect of Tat protein on the permeability of isolated glomeruli and on the expression of nephrin, the main slit diaphragm component, by human cultured podocytes. Permeability was studied by measuring the permeability to albumin in isolated rat glomeruli. We also evaluated the expression of nephrin in human cultured podocytes by using immunofluorescence and Western blot. We found that Tat increased albumin permeability in isolated glomeruli, and rapidly induced the redistribution and loss of nephrin in cultured podocytes. Pretreatment of glomeruli and podocytes with blocking antibodies showed that Tat reduced nephrin expression by engaging vascular endothelial growth factor receptors types 2 and 3 and the integrin alphavbeta3. Pre-incubation of podocytes with two platelet-activating factor (PAF) receptor antagonists prevented the loss and redistribution of nephrin induced by Tat, suggesting that PAF is an intracellular mediator of Tat action. Tat induced a rapid PAF synthesis by podocytes. When podocytes transfected to overexpress PAF-acetylhydrolase, the main catabolic enzyme of PAF, were stimulated with Tat, the redistribution and loss of nephrin was abrogated. The present results define a mechanism by which Tat may reduce nephrin expression in podocytes, thus increasing glomerular permeability. This provides new insights in the understanding of HIVAN pathogenesis.

  3. Shp2 Associates with and Enhances Nephrin Tyrosine Phosphorylation and Is Necessary for Foot Process Spreading in Mouse Models of Podocyte Injury

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    Verma, Rakesh; Venkatareddy, Madhusudan; Kalinowski, Anne; Patel, Sanjeevkumar R.; Salant, David J.

    2015-01-01

    In most forms of glomerular diseases, loss of size selectivity by the kidney filtration barrier is associated with changes in the morphology of podocytes. The kidney filtration barrier is comprised of the endothelial lining, the glomerular basement membrane, and the podocyte intercellular junction, or slit diaphragm. The cell adhesion proteins nephrin and neph1 localize to the slit diaphragm and transduce signals in a Src family kinase Fyn-mediated tyrosine phosphorylation-dependent manner. Studies in cell culture suggest nephrin phosphorylation-dependent signaling events are primarily involved in regulation of actin dynamics and lamellipodium formation. Nephrin phosphorylation is a proximal event that occurs both during development and following podocyte injury. We hypothesized that abrogation of nephrin phosphorylation following injury would prevent nephrin-dependent actin remodeling and foot process morphological changes. Utilizing a biased screening approach, we found nonreceptor Src homology 2 (sh2) domain-containing phosphatase Shp2 to be associated with phosphorylated nephrin. We observed an increase in nephrin tyrosine phosphorylation in the presence of Shp2 in cell culture studies. In the human glomerulopathies minimal-change nephrosis and membranous nephropathy, there is an increase in Shp2 phosphorylation, a marker of increased Shp2 activity. Mouse podocytes lacking Shp2 do not develop foot process spreading when subjected to podocyte injury in vivo using protamine sulfate or nephrotoxic serum (NTS). In the NTS model, we observed a lack of foot process spreading in mouse podocytes with Shp2 deleted and smaller amounts of proteinuria. Taken together, these results suggest that Shp2-dependent signaling events are necessary for changes in foot process structure and function following injury. PMID:26644409

  4. Inhibitory Effects of Robo2 on Nephrin: A Crosstalk between Positive and Negative Signals Regulating Podocyte Structure

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    Xueping Fan

    2012-07-01

    Full Text Available Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture.

  5. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome.

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    Doublier, S; Ruotsalainen, V; Salvidio, G; Lupia, E; Biancone, L; Conaldi, P G; Reponen, P; Tryggvason, K; Camussi, G

    2001-05-01

    We investigated the distribution of nephrin by immunofluorescence microscopy in renal biopsies of patients with nephrotic syndrome: 13 with membranous glomerulonephritis (GN), 10 with minimal change GN, and seven with focal segmental glomerulosclerosis. As control, six patients with IgA GN without nephrotic syndrome and 10 normal controls were studied. We found an extensive loss of staining for nephrin and a shift from a podocyte-staining pattern to a granular pattern in patients with nephrotic syndrome, irrespective of the primary disease. In membranous GN, nephrin was co-localized with IgG immune deposits. In the attempt to explain these results, we investigated in vitro whether stimuli acting on the cell cytoskeleton, known to be involved in the pathogenesis of GN, may induce redistribution of nephrin on the surface of human cultured podocytes. Aggregated but not disaggregated human IgG(4), plasmalemmal insertion of membrane attack complex of complement, tumor necrosis factor-alpha, and puromycin, induced the shedding of nephrin with a loss of surface expression. This phenomenon was abrogated by cytochalasin and sodium azide. These results suggest that the activation of cell cytoskeleton may modify surface expression of nephrin allowing a dislocation from plasma membrane to an extracellular site.

  6. Direct effect of plasma permeability factors from patients with idiopatic FSGS on nephrin and podocin expression in human podocytes.

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    Doublier, Sophie; Musante, Luca; Lupia, Enrico; Candiano, Giovanni; Spatola, Tiziana; Caridi, Gianluca; Zennaro, Cristina; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni

    2005-07-01

    The presence of circulating plasma factors (PF) altering renal permeability to proteins has been previously described in patients with focal segmental glomerulosclerosis (FSGS). Since these patients show reduced nephrin and podocin expression at renal biopsy, we evaluated the effect of serum and PF from patients with FSGS on nephrin and podocin expression in human podocytes. We studied 7 sera from patients with steroid-resistant FSGS, 3 from patients with nephrotic syndrome caused by non-immune disease, and 6 from healthy subjects. PF was prepared from plasmapheresis eluates of 2 patients with post-transplant recurrence of FSGS. Purification procedure was based on protein A Sepharose chromatography and differential precipitation in ammonium sulphate. Nephrin and podocin expression was semi-quantitatively evaluated by immunofluorescence. We found that serum and PF from FSGS patients rapidly induced redistribution and loss of nephrin in podocytes. This effect was associated with cytoskeleton redistribution and inhibited by cytochalasin B and sodium azide. On the contrary, podocin expression was unchanged after incubation with serum and PF from FSGS patients for short periods, but markedly reduced at 24 h. Our results demonstrate that serum and PF from FSGS patients may directly affect nephrin and podocin in human podocytes, thus providing new insights into the mechanisms causing proteinuria in FSGS.

  7. Effect of total glucosides of paeony on the expression of nephrin in the kidneys from diabetic rats.

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    Zhang, Pei; Zhang, Jing-Jing; Su, Jing; Qi, Xiang-Ming; Wu, Yong-Gui; Shen, Ji-Jia

    2009-01-01

    Total glucosides of paeony (TGP), extracted from the traditional Chinese herb root of Paeonia lactiflora pall, have been shown to have a therapeutic role in experimental diabetic nephropathy including albuminuria. Recent investigation has identified nephrin, a podocyte-specific transmembrane protein, as a key regulator in the pathogenesis of diabetic albuminuria. The aim of this study was to investigate whether TGP can attenuate albuminuria through prevention of nephrin loss in the experimental diabetic nephropathy. Fifty male Munich-Wistar rats were obtained from the Experimental Animal Center of Anhui Medical University. These rats were divided into 5 groups (n = 10); normal group, control diabetic group, and 3 TGP treated diabetic groups at different concentrations. Diabetes was induced by streptozotocin, and TGP (50, 100, 200 mg/kg) was orally administered to the 3 TGP treated diabetic groups once a day for 8 weeks, respectively. Blood glucose and 24 hour urinary albumin excretion rate (AER) were measured. The expressions of nephrin, tumor necrosis factor-alpha (TNF-alpha), NF-kappaB p65 and 3-nitrotyrosine (3-NT) protein were determined by immunoinfluorescence or Western blot analysis in the kidneys. Elevated AER was markedly attenuated by TGP treatment in diabetic rats. There was a finely dotted linear epithelial staining of nephrin in normal group glomeruli. In contrast, the staining of glomeruli from untreated diabetic rats was attenuated, more diapersed, and clustered. This diabetic-induced loss of glomerular nephrin expression was prevented in a large degree in TGP-treated diabetic rats. Western blot analysis showed that the expression of nephrin protein was reduced in the kidneys of diabetic rats, but significantly increased in the TGP treatment groups. The expressions of TNF-alpha, NF-kappaB p65 and 3-NT protein were significantly increased in the kidneys of diabetic rats, which were all significantly inhibited by TGP treatment. Our results showed that

  8. Mediation of Weight Loss and Weight Loss Maintenance through Dietary Disinhibition and Restraint.

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    JaKa, Meghan M; Sherwood, Nancy E; Flatt, Shirley W; Pacanowski, Carly R; Pakiz, Bilgé; Thomson, Cynthia A; Rock, Cheryl L

    2015-04-01

    Understanding the degree to which eating behaviors, such as disinhibition and restraint, are associated with weight loss and weight loss maintenance could contribute to further refinement of effective weight management intervention strategies. The purpose of this analysis was to examine if these factors mediate weight loss or weight loss maintenance using data from a randomized controlled trial testing a commercial weight loss program that delivered behavioral counseling and structured meal plans including prepackaged foods. Mediation analyses were used to examine whether changes in disinhibition and restraint mediated the relationship between intervention and weight change during initial weight loss (0-6 months), continued weight loss (6-12 months), or weight loss maintenance (12-24 months) phases. Only decreases in disinhibition between baseline and 6 months mediated the intervention effect on initial weight loss. Our results suggest the mediation effects of these eating behaviors are modest and other factors contribute to a larger, more complex long-term weight loss prognosis.

  9. Nephrin regulates lamellipodia formation by assembling a protein complex that includes Ship2, filamin and lamellipodin.

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    Madhusudan Venkatareddy

    Full Text Available Actin dynamics has emerged at the forefront of podocyte biology. Slit diaphragm junctional adhesion protein Nephrin is necessary for development of the podocyte morphology and transduces phosphorylation-dependent signals that regulate cytoskeletal dynamics. The present study extends our understanding of Nephrin function by showing in cultured podocytes that Nephrin activation induced actin dynamics is necessary for lamellipodia formation. Upon activation Nephrin recruits and regulates a protein complex that includes Ship2 (SH2 domain containing 5' inositol phosphatase, Filamin and Lamellipodin, proteins important in regulation of actin and focal adhesion dynamics, as well as lamellipodia formation. Using the previously described CD16-Nephrin clustering system, Nephrin ligation or activation resulted in phosphorylation of the actin crosslinking protein Filamin in a p21 activated kinase dependent manner. Nephrin activation in cell culture results in formation of lamellipodia, a process that requires specialized actin dynamics at the leading edge of the cell along with focal adhesion turnover. In the CD16-Nephrin clustering model, Nephrin ligation resulted in abnormal morphology of actin tails in human podocytes when Ship2, Filamin or Lamellipodin were individually knocked down. We also observed decreased lamellipodia formation and cell migration in these knock down cells. These data provide evidence that Nephrin not only initiates actin polymerization but also assembles a protein complex that is necessary to regulate the architecture of the generated actin filament network and focal adhesion dynamics.

  10. Inducible nitric oxide synthase mediates bone loss in ovariectomized mice.

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    Cuzzocrea, S.; Mazzon, E.; Dugo, L.; Genovese, T.; Paola, R. Di; Ruggeri, Z.; Vegeto, E.; Caputi, A.P.; Loo, F.A.J. van de; Puzzolo, D.; Maggi, A.

    2003-01-01

    Several clinical studies have shown that bone loss may be attributed to osteoclast recruitment induced by mediators of inflammation. In different experimental paradigms we have recently demonstrated that estrogen exhibits antiinflammatory activity by preventing the induction of inducible nitric

  11. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II.

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    Doublier, Sophie; Salvidio, Gennaro; Lupia, Enrico; Ruotsalainen, Vesa; Verzola, Daniela; Deferrari, Giacomo; Camussi, Giovanni

    2003-04-01

    We studied the distribution of nephrin in renal biopsies from 17 patients with diabetes and nephrotic syndrome (7 type 1 and 10 type 2 diabetes), 6 patients with diabetes and microalbuminuria (1 type 1 and 5 type 2 diabetes), and 10 normal subjects. Nephrin expression was semiquantitatively evaluated by measuring immunofluorescence intensity by digital image analysis. We found an extensive reduction of nephrin staining in both type 1 (67 +/- 9%; P < 0.001) and type 2 (65 +/- 10%; P < 0.001) diabetic patients with diabetes and nephrotic syndrome when compared with control subjects. The pattern of staining shifted from punctate/linear distribution to granular. In patients with microalbuminuria, the staining pattern of nephrin also showed granular distribution and reduction intensity of 69% in the patient with type 1 diabetes and of 62 +/- 4% (P < 0.001) in the patients with type 2 diabetes. In vitro studies on human cultured podocytes demonstrated that glycated albumin and angiotensin II reduced nephrin expression. Glycated albumin inhibited nephrin synthesis through the engagement of receptor for advanced glycation end products, whereas angiotensin II acted on cytoskeleton redistribution, inducing the shedding of nephrin. This study indicates that the alteration in nephrin expression is an early event in proteinuric patients with diabetes and suggests that glycated albumin and angiotensin II contribute to nephrin downregulation.

  12. Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.

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    Keebaugh, Erin S; Park, Jin Hong; Su, Chenchen; Yamada, Ryuichi; Ja, William W

    2017-11-01

    Plant-derived caffeine is regarded as a defensive compound produced to prevent herbivory. Caffeine is generally repellent to insects and often used to study the neurological basis for aversive responses in the model insect, Drosophila melanogaster. Caffeine is also studied for its stimulatory properties where sleep or drowsiness is suppressed across a range of species. Since limiting access to food also inhibits fly sleep-an effect known as starvation-induced sleep suppression-we tested whether aversion to caffeinated food results in reduced nutrient intake and assessed how this might influence fly studies on the stimulatory effects of caffeine. We measured sleep and total consumption during the first 24 hours of exposure to caffeinated diets containing a range of sucrose concentrations to determine the relative influence of caffeine and nutrient ingestion on sleep. Experiments were replicated using three fly strains. Caffeine reduced total consumption and nighttime sleep, but only at intermediate sucrose concentrations. Although sleep can be modeled by an exponential dose response to nutrient intake, caffeine-mediated sleep loss cannot be explained by absolute caffeine or sucrose ingestion alone. Instead, reduced sleep strongly correlates with changes in total consumption due to caffeine. Other bitter compounds phenocopy the effect of caffeine on sleep and food intake. Our results suggest that a major effect of dietary caffeine is on fly feeding behavior. Changes in feeding behavior may drive caffeine-mediated sleep loss. Future studies using psychoactive compounds should consider the potential impact of nutrition when investigating effects on sleep. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  13. Analysis of the intronic single nucleotide polymorphism rs#466452 of the nephrin gene in patients with diabetic nephropathy

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    RODRIGO GONZÁLEZ

    2009-01-01

    Full Text Available We present the analysis of an intronic polymorphism of the nephrin gene and its relationship to the development of diabetic nephropathy in a study of diabetes type 1 and type 2 patients. The frequency of the single nucleotide polymorphism rs#466452 in the nephrin gene was determined in 231 patients and control subjects. The C/T status of the polymorphism was assessed using restriction enzyme digestions and the nephrin transcript from a kidney biopsy was examined. Association between the polymorphism and clinical parameters was evaluated using multivaríate correspondence analysis. A bioinformatics analysis of the single nucleotide polymorphism rs#466452 suggested the appearance of a splicing enhancer sequence in intron 24 of the nephrin gene and a modification of proteins that bind to this sequence. However, no change in the splicing of a nephrin transcript from a renal biopsy was found. No association was found between the polymorphism and diabetes or degree of renal damage in diabetes type 1 or 2 patients. The single nucleotide polymorphism rs#466452 of the nephrin gene seems to be neutral in relation to diabetes and the development of diabetic nephropathy, and does not affect the splicing of a nephrin transcript, in spite of a splicing enhancer site.

  14. Social comparison mediates chimpanzees' responses to loss, not frustration

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    Hopper, Lydia M; Lambeth, Susan P; Schapiro, Steve

    2014-01-01

    Why do chimpanzees react when their partner gets a better deal than them? Do they note the inequity or do their responses reflect frustration in response to unattainable rewards? To tease apart inequity and contrast, we tested chimpanzees in a series of conditions that created loss through...... individual contrast, through inequity, or by both. Chimpanzees were tested in four social and two individual conditions in which they received food rewards in return for exchanging tokens with an experimenter. In conditions designed to create individual contrast, after completing an exchange, the chimpanzees...... were given a relatively less-preferred reward than the one they were previously shown. The chimpanzees' willingness to accept the less-preferred rewards was independent of previously offered foods in both the social and individual conditions. In conditions that created frustration through inequity...

  15. PODOCYTE-SPECIFIC OVEREXPRESSION OF SIRT-1 INCREASES NEPHRIN IN OBESE MICE FED A HIGH-FAT DIET

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    Han Byoung-Geun

    2012-06-01

    Taken together the results, deterioration of the kidney disease caused by obesity and hyperglycemia could be prevented by increasing the level of the nephrin expression through SIRT-1 activation. SIRT-1 may have the ability to protect the podocyte from injuries caused by obesity and hyperglycemia.

  16. Information Processing Versus Social Cognitive Mediators of Weight Loss in a Podcast-Delivered Health Intervention

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    Ko, Linda K.; Turner-McGrievy, Gabrielle M.; Campbell, Marci K.

    2014-01-01

    Podcasting is an emerging technology, and previous interventions have shown promising results using theory-based podcast for weight loss among overweight and obese individuals. This study investigated whether constructs of social cognitive theory and information processing theories (IPTs) mediate the effect of a podcast intervention on weight loss…

  17. Mediation analysis to estimate direct and indirect milk losses due to clinical mastitis in dairy cattle.

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    Detilleux, J; Kastelic, J P; Barkema, H W

    2015-03-01

    Milk losses associated with mastitis can be attributed to either effects of pathogens per se (i.e., direct losses) or effects of the immune response triggered by intramammary infection (indirect losses). The distinction is important in terms of mastitis prevention and treatment. Regardless, the number of pathogens is often unknown (particularly in field studies), making it difficult to estimate direct losses, whereas indirect losses can be approximated by measuring the association between increased somatic cell count (SCC) and milk production. An alternative is to perform a mediation analysis in which changes in milk yield are allocated into their direct and indirect components. We applied this method on data for clinical mastitis, milk and SCC test-day recordings, results of bacteriological cultures (Escherichia coli, Staphylococcus aureus, Streptococcus uberis, coagulase-negative staphylococci, Streptococcus dysgalactiae, and streptococci other than Strep. dysgalactiae and Strep. uberis), and cow characteristics. Following a diagnosis of clinical mastitis, the cow was treated and changes (increase or decrease) in milk production before and after a diagnosis were interpreted counterfactually. On a daily basis, indirect changes, mediated by SCC increase, were significantly different from zero for all bacterial species, with a milk yield decrease (ranging among species from 4 to 33g and mediated by an increase of 1000 SCC/mL/day) before and a daily milk increase (ranging among species from 2 to 12g and mediated by a decrease of 1000 SCC/mL/day) after detection. Direct changes, not mediated by SCC, were only different from zero for coagulase-negative staphylococci before diagnosis (72g per day). We concluded that mixed structural equation models were useful to estimate direct and indirect effects of the presence of clinical mastitis on milk yield. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Self-worth mediates the effects of violent loss on PTSD symptoms.

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    Mancini, Anthony D; Prati, Gabriele; Black, Sarah

    2011-02-01

    Although research has confirmed that violent losses can exacerbate grief reactions, few investigations have explored underlying mechanisms. In this study, the authors used a dataset on bereaved spouses and bereaved parents at 4- and 18-months postloss to examine the mediating effects of self-worth and worldviews (benevolence and meaningfulness beliefs). Persons bereaved by violent causes had significantly more posttraumatic stress disorder (PTSD), grief, and depression symptoms at 4- and 18-months postloss than persons bereaved by natural causes. Moreover, self-worth but not worldviews mediated the effects of violent loss on PTSD and depression symptoms cross sectionally and PTSD symptoms longitudinally. Findings underscore that self-views are a critical component of problematic reactions to violent loss, but fail to support the role of "shattered" worldviews. Copyright © 2011 International Society for Traumatic Stress Studies.

  19. Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats

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    Daniël O. Warmerdam

    2016-03-01

    Full Text Available rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5 as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability.

  20. Resveratrol Increases Nephrin and Podocin Expression and Alleviates Renal Damage in Rats Fed a High-Fat Diet

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    Qing-Rong Pan

    2014-07-01

    Full Text Available Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol. Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB and superoxide dismutase (SOD, the content of malondialdehyde (MDA, and the protein levels of tumor necrosis factor (TNF-α, monocyte chemotactic protein-1 (MCP-1, nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

  1. A pilot study on genetic variation in purine-rich elements in the nephrin gene promoter in type 2 diabetic patients

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    RODRIGO GONZÁLEZ

    2007-01-01

    Full Text Available Diabetic nephropathy (DN is one of the major complications of type 2 diabetes and is associated with coronary disease. Nephrin, a protein mainly expressed in glomeruli, is decreased in DN and other kidney diseases. Since insulin levels are misregulated in type 2 diabetes, a possible connection between DN and its decreased nephrin expression could be the presence of regulatory elements responsive to insulin in the nephrin gene (NPHS1 promoter region. In this work, using bioinformatic tools, we identified a purine-rich GAGA element in the nephrin gene promoter and conducted a genomic study in search of the presence of polymorphisms in this element and its possible association with DN in type 2 diabetic patients. We amplified and sequenced a 514 bp promoter region of 100 individuals and found no genetic variants in the purine-rich GAGA-box of the nephrin gene promoter between groups of patients with diabetes type 2 with and without renal and coronary complications, control patients without diabetes and healthy controls

  2. Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats.

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    Warmerdam, Daniël O; van den Berg, Jeroen; Medema, René H

    2016-03-22

    rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5) as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Association between Weight and Smoking Not Mediated by Weight Loss Attempts or Bullying.

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    Minaker, Leia M; Leatherdale, Scott T

    2016-01-01

    Youth smoking and obesity may both be mediated by weight control behaviors and experiences of bullying. This study examines associations between smoking and obesity among youth, and explores whether associations are mediated by weight loss attempts or bullying experiences. Data from 24,173 grade 9 to 12 students in the COMPASS study (2012-13) were used to examine the prevalence of self-reported smoking, weight status, attempting to lose weight, and being a victim of bullying. Generalized linear mixed effects models were used to examine correlates of smoking. Among youth, 11% reported currently smoking, 20% were overweight or obese, 42% reported attempting to lose weight, and 18% reported being bullied. Girls who reported attempting to lose weight had higher odds of smoking (OR = 1.42, p = .0039), and students who reported being bullied had higher odds of smoking (OR = 1.85, p weight status. For girls, weight loss attempts were associated with smoking. For both sexes, being bullied was associated with smoking, independent of weight status. Programs attempting to reduce smoking among youth should consider the effects of weight control behaviors and bullying irrespective of weight status.

  4. Mediating Effect of Body Image Distortion on Weight Loss Efforts in Normal-Weight and Underweight Korean Adolescent Girls

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    Choi, Jeong-Sil; Kim, Ji-Soo

    2017-01-01

    Background: We explored the relationship between body mass index-for-age percentile, body image distortion, and unnecessary weight loss efforts in Korean adolescent girls who are underweight and normal weight and examined the mediating effect of body image distortion on weight loss efforts. Methods: This study used data from the 2013 Korea Youth…

  5. Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro

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    Guo-Qing Wang

    2018-01-01

    Full Text Available Parkinson’s disease (PD is one of the most common neurodegenerative diseases characterized with a gradual loss of midbrain substantia nigra (SN dopamine (DA neurons. An excessive evidence demonstrated that microglia-mediated inflammation might be involved in the pathogenesis of PD. Thus, inhibition of neuroinflammation might possess a promising potential for PD treatment. Icariin (ICA, a single active component extracted from the Herba Epimedii, presents amounts of pharmacological properties, such as anti-inflammation, anti-oxidant, and anti-aging. Recent studies show ICA produced neuroprotection against brain dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are fully illuminated. In the present study, two different neurotoxins of 6-hydroxydopamine (6-OHDA and lipopolysaccharide (LPS-induced rat midbrain DA neuronal damage were applied to investigate the neuroprotective effects of ICA. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage and inhibited microglia activation and pro-inflammatory factors production via the suppression of nuclear factor-κB (NF-κB pathway activation. In animal results, ICA significantly reduced microglia activation and significantly attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior changes. Together, ICA could protect DA neurons against LPS- and 6-OHDA-induced neurotoxicity both in vivo and in vitro. These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation.

  6. Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.

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    Killinger, Bryan A; Moszczynska, Anna

    2016-02-01

    Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include

  7. Melanocortin-3 receptors in the limbic system mediate feeding-related motivational responses during weight loss

    Directory of Open Access Journals (Sweden)

    Maria Mavrikaki

    2016-07-01

    Full Text Available Objective: Appetitive responses to weight loss are mediated by a nutrient-sensing neural network comprised of melanocortin neurons. The role of neural melanocortin-3 receptors (MC3R in mediating these responses is enigmatic. Mc3r knockout mice exhibit a paradoxical phenotype of obesity and reduced feeding-related behaviors in situations of nutrient scarcity. Here we examined whether MC3Rs expressed in mesolimbic neurons regulate feeding-related motivational responses. Methods: Interactions between Mc3r genotype, cognitive function and energy balance on food self-administration were assessed using operant conditioning with fixed- and progressive ratio (FR1/PR1 settings. Inhibition of Mc3r transcription by a loxP-flanked transcriptional blocker (TB in C57BL/6JN mice (Mc3rTB/TB was reversed in mesolimbic neurons using DAT-Cre (DAT-MC3R. Results: Caloric restriction (CR caused 10–15% weight loss and increased motivation to acquire food rewards during training sessions. c-Fos-expression in the nucleus accumbens was increased 1 h following food presentation. While exhibiting weight loss, total food self-administration, enhanced motivation to self-administer food rewards in training sessions held during CR and c-Fos-activation in the nucleus accumbens following re-feeding were all markedly attenuated in Mc3rTB/TB mice. In contrast, cognitive abilities were normal in Mc3rTB/TB mice. Total food self-administration during FR1 sessions was not rescued in DAT-MC3R mice, however enhanced motivational responses to self-administer food rewards in PR1 conditions were restored. The nutrient-partitioning phenotype observed with Mc3r-deficiency was not rescued in DAT-MC3R mice. Conclusions: Mesolimbic MC3Rs mediate enhanced motivational responses during CR. However, they are insufficient to restore normal caloric loading when food is presented during CR and do not affect metabolic conditions altering nutrient partitioning. Author Video: Author Video Watch what

  8. MEL-18 loss mediates estrogen receptor-α downregulation and hormone independence.

    Science.gov (United States)

    Lee, Jeong-Yeon; Won, Hee-Young; Park, Ji-Hye; Kim, Hye-Yeon; Choi, Hee-Joo; Shin, Dong-Hui; Kang, Ju-Hee; Woo, Jong-Kyu; Oh, Seung-Hyun; Son, Taekwon; Choi, Jin-Woo; Kim, Sehwan; Kim, Hyung-Yong; Yi, Kijong; Jang, Ki-Seok; Oh, Young-Ha; Kong, Gu

    2015-05-01

    The polycomb protein MEL-18 has been proposed as a tumor suppressor in breast cancer; however, its functional relevance to the hormonal regulation of breast cancer remains unknown. Here, we demonstrated that MEL-18 loss contributes to the hormone-independent phenotype of breast cancer by modulating hormone receptor expression. In multiple breast cancer cohorts, MEL-18 was markedly downregulated in triple-negative breast cancer (TNBC). MEL-18 expression positively correlated with the expression of luminal markers, including estrogen receptor-α (ER-α, encoded by ESR1). MEL-18 loss was also associated with poor response to antihormonal therapy in ER-α-positive breast cancer. Furthermore, whereas MEL-18 loss in luminal breast cancer cells resulted in the downregulation of expression and activity of ER-α and the progesterone receptor (PR), MEL-18 overexpression restored ER-α expression in TNBC. Consistently, in vivo xenograft experiments demonstrated that MEL-18 loss induces estrogen-independent growth and tamoxifen resistance in luminal breast cancer, and that MEL-18 overexpression confers tamoxifen sensitivity in TNBC. MEL-18 suppressed SUMOylation of the ESR1 transactivators p53 and SP1, thereby driving ESR1 transcription. MEL-18 facilitated the deSUMOylation process by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SUMO1/sentrin-specific protease 1 (SENP1). These findings demonstrate that MEL-18 is a SUMO-dependent regulator of hormone receptors and suggest MEL-18 expression as a marker for determining the antihormonal therapy response in patients with breast cancer.

  9. MEL-18 loss mediates estrogen receptor–α downregulation and hormone independence

    Science.gov (United States)

    Lee, Jeong-Yeon; Won, Hee-Young; Park, Ji-Hye; Kim, Hye-Yeon; Choi, Hee-Joo; Shin, Dong-Hui; Kang, Ju-Hee; Woo, Jong-Kyu; Oh, Seung-Hyun; Son, Taekwon; Choi, Jin-Woo; Kim, Sehwan; Kim, Hyung-Yong; Yi, Kijong; Jang, Ki-Seok; Oh, Young-Ha; Kong, Gu

    2015-01-01

    The polycomb protein MEL-18 has been proposed as a tumor suppressor in breast cancer; however, its functional relevance to the hormonal regulation of breast cancer remains unknown. Here, we demonstrated that MEL-18 loss contributes to the hormone-independent phenotype of breast cancer by modulating hormone receptor expression. In multiple breast cancer cohorts, MEL-18 was markedly downregulated in triple-negative breast cancer (TNBC). MEL-18 expression positively correlated with the expression of luminal markers, including estrogen receptor–α (ER-α, encoded by ESR1). MEL-18 loss was also associated with poor response to antihormonal therapy in ER-α–positive breast cancer. Furthermore, whereas MEL-18 loss in luminal breast cancer cells resulted in the downregulation of expression and activity of ER-α and the progesterone receptor (PR), MEL-18 overexpression restored ER-α expression in TNBC. Consistently, in vivo xenograft experiments demonstrated that MEL-18 loss induces estrogen-independent growth and tamoxifen resistance in luminal breast cancer, and that MEL-18 overexpression confers tamoxifen sensitivity in TNBC. MEL-18 suppressed SUMOylation of the ESR1 transactivators p53 and SP1, thereby driving ESR1 transcription. MEL-18 facilitated the deSUMOylation process by inhibiting BMI-1/RING1B-mediated ubiquitin-proteasomal degradation of SUMO1/sentrin-specific protease 1 (SENP1). These findings demonstrate that MEL-18 is a SUMO-dependent regulator of hormone receptors and suggest MEL-18 expression as a marker for determining the antihormonal therapy response in patients with breast cancer. PMID:25822021

  10. Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss.

    Science.gov (United States)

    Mata-Castro, Nieves; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

    2018-03-01

    Current schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient. To determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse. The mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03). Azathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Retinaldehyde dehydrogenase 1 deficiency inhibits PPARγ-mediated bone loss and marrow adiposity.

    Science.gov (United States)

    Nallamshetty, Shriram; Le, Phuong T; Wang, Hong; Issacsohn, Maya J; Reeder, David J; Rhee, Eun-Jung; Kiefer, Florian W; Brown, Jonathan D; Rosen, Clifford J; Plutzky, Jorge

    2014-10-01

    PPARγ, a ligand-activated nuclear receptor, regulates fundamental aspects of bone homeostasis and skeletal remodeling. PPARγ-activating anti-diabetic thiazolidinediones in clinical use promote marrow adiposity, bone loss, and skeletal fractures. As such, delineating novel regulatory pathways that modulate the action of PPARγ, and its obligate heterodimeric partner RXR, may have important implications for our understanding and treatment of disorders of low bone mineral density. We present data here establishing retinaldehyde dehydrogenase 1 (Aldh1a1) and its substrate retinaldehyde (Rald) as novel determinants of PPARγ-RXR actions in the skeleton. When compared to wild type (WT) controls, retinaldehyde dehydrogenase-deficient (Aldh1a1(-/-)) mice were protected against bone loss and marrow adiposity induced by either the thiazolidinedione rosiglitazone or a high fat diet, both of which potently activate the PPARγ-RXR complex. Consistent with these results, Rald, which accumulates in vivo in Aldh1a1(-/-) mice, protects against rosiglitazone-mediated inhibition of osteoblastogenesis in vitro. In addition, Rald potently inhibits in vitro adipogenesis and osteoclastogenesis in WT mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) respectively. Primary Aldh1a1(-/-) HSCs also demonstrate impaired osteoclastogenesis in vitro compared to WT controls. Collectively, these findings identify Rald and retinoid metabolism through Aldh1a1 as important novel modulators of PPARγ-RXR transactivation in the marrow niche. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. C-X-C Chemokine Receptor Type 4 Plays a Crucial Role in Mediating Oxidative Stress-Induced Podocyte Injury.

    Science.gov (United States)

    Mo, Hongyan; Wu, Qinyu; Miao, Jinhua; Luo, Congwei; Hong, Xue; Wang, Yongping; Tang, Lan; Hou, Fan Fan; Liu, Youhua; Zhou, Lili

    2017-08-20

    Oxidative stress plays a role in mediating podocyte injury and proteinuria. However, the underlying mechanism remains poorly understood. In this study, we investigated the potential role of C-X-C chemokine receptor type 4 (CXCR4), the receptor for stromal cell-derived factor 1α (SDF-1α), in mediating oxidative stress-induced podocyte injury. In mouse model of adriamycin nephropathy (ADR), CXCR4 expression was significantly induced in podocytes as early as 3 days. This was accompanied by an increased upregulation of oxidative stress in podocyte, as demonstrated by malondialdehyde assay, nitrotyrosine staining and secretion of 8-hydroxy-2'-deoxyguanosine in urine, and induction of NOX2 and NOX4, major subunits of NADPH oxidase. CXCR4 was also induced in human kidney biopsies with proteinuric kidney diseases and colocalized with advanced oxidation protein products (AOPPs), an established oxidative stress trigger. Using cultured podocytes and mouse model, we found that AOPPs induced significant loss of podocyte marker Wilms tumor 1 (WT1), nephrin, and podocalyxin, accompanied by upregulation of desmin both in vitro and in vivo. Furthermore, AOPPs worsened proteinuria and aggravated glomerulosclerosis in ADR. These effects were associated with marked activation of SDF-1α/CXCR4 axis in podocytes. Administration of AMD3100, a specific inhibitor of CXCR4, reduced proteinuria and ameliorated podocyte dysfunction and renal fibrosis triggered by AOPPs in mice. In glomerular miniorgan culture, AOPPs also induced CXCR4 expression and downregulated nephrin and WT1. Innovation and Conclusion: These results suggest that chemokine receptor CXCR4 plays a crucial role in mediating oxidative stress-induced podocyte injury, proteinuria, and renal fibrosis. CXCR4 could be a new target for mitigating podocyte injury, proteinuria, and glomerular sclerosis in proteinuric chronic kidney disease. Antioxid. Redox Signal. 27, 345-362.

  13. Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

    NARCIS (Netherlands)

    Boekel, G.A.J van; Loves, S.; Sorge, A.A. van; Ruinemans-Koerts, J.; Rijnders, T.; Boer, H. de

    2008-01-01

    OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot

  14. Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK

    Science.gov (United States)

    Hill, Kayla; Yuan, Hu; Wang, Xianren

    2016-01-01

    Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKα in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL. SIGNIFICANCE STATEMENT Our results demonstrate for the first time that the activation of AMP-activated protein kinase (AMPK) α in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKα1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy. PMID:27413159

  15. Fibrin accumulation secondary to loss of plasmin-mediated fibrinolysis drives inflammatory osteoporosis in mice.

    Science.gov (United States)

    Cole, Heather A; Ohba, Tetsuro; Nyman, Jeffry S; Hirotaka, Haro; Cates, Justin M M; Flick, Matthew J; Degen, Jay L; Schoenecker, Jonathan G

    2014-08-01

    Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif. Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology. Copyright © 2014 by the American College of Rheumatology.

  16. The effects of subjective loss of control on risk-taking behavior: the mediating role of anger

    Science.gov (United States)

    Beisswingert, Birgit M.; Zhang, Keshun; Goetz, Thomas; Fang, Ping; Fischbacher, Urs

    2015-01-01

    Based on the Appraisal Tendency Framework on the antecedents and consequences of emotions two experimental studies examined the relationship between externally caused loss of control experiences and risk-taking behavior, as well as the assumed mediation of this relationship by the emotion anger. An experimental paradigm for inducing externally caused and consequently externally attributed loss of control which should lead to experiences of anger was developed and pretested in a Pilot Study. The relationship between loss of control experiences, anger, and risk-taking behavior was investigated using two separate student samples from Germany (N = 84, 54% female) and China (N = 125; 64% female). In line with our hypotheses, results showed that anger mediated the link between subjective loss of control experiences and increasing risk-taking behavior. Multiple group comparisons revealing similar patterns in both samples affirmed the results’ cross-cultural generalizability. These results implicate that anger makes people less risk averse in the process of economic decision making. PMID:26217244

  17. The Effects of Subjective Loss of Control on Risk-taking Behavior: The Mediating Role of Anger

    Directory of Open Access Journals (Sweden)

    Birgit M. Beisswingert

    2015-06-01

    Full Text Available Based on the Appraisal Tendency Framework on the antecedents and consequences of emotions two experimental studies examined the relationship between externally caused loss of control experiences and risk-taking behavior, as well as the assumed mediation of this relationship by the emotion anger. An experimental paradigm for inducing externally caused and consequently externally attributed loss of control which should lead to experiences of anger was developed and pretested in a Pilot Study. The relationship between loss of control experiences, anger and risk-taking behavior was investigated using two separate student samples from Germany (N = 84, 54% female and China (N = 125; 64% female. In line with our hypotheses, results showed that anger mediated the link between subjective loss of control experiences and increasing risk-taking behavior. Multiple group comparisons revealing similar patterns in both samples affirmed the results’ cross-cultural generalizability. These results implicate that anger makes people less risk averse in the process of economic decision making.

  18. Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK.

    Science.gov (United States)

    Hill, Kayla; Yuan, Hu; Wang, Xianren; Sha, Su-Hua

    2016-07-13

    Noise-induced hearing loss (NIHL) is a major unresolved public health problem. Here, we investigate pathomechanisms of sensory hair cell death and suggest a novel target for protective intervention. Cellular survival depends upon maintenance of energy homeostasis, largely by AMP-activated protein kinase (AMPK). In response to a noise exposure in CBA/J mice, the levels of phosphorylated AMPKα increased in hair cells in a noise intensity-dependent manner. Inhibition of AMPK via siRNA or the pharmacological inhibitor compound C attenuated noise-induced loss of outer hair cells (OHCs) and synaptic ribbons, and preserved auditory function. Additionally, noise exposure increased the activity of the upstream AMPK kinase liver kinase B1 (LKB1) in cochlear tissues. The inhibition of LKB1 by siRNA attenuated the noise-increased phosphorylation of AMPKα in OHCs, reduced the loss of inner hair cell synaptic ribbons and OHCs, and protected against NIHL. These results indicate that noise exposure induces hair cell death and synaptopathy by activating AMPK via LKB1-mediated pathways. Targeting these pathways may provide a novel route to prevent NIHL. Our results demonstrate for the first time that the activation of AMP-activated protein kinase (AMPK) α in sensory hair cells is noise intensity dependent and contributes to noise-induced hearing loss by mediating the loss of inner hair cell synaptic ribbons and outer hair cells. Noise induces the phosphorylation of AMPKα1 by liver kinase B1 (LKB1), triggered by changes in intracellular ATP levels. The inhibition of AMPK activation by silencing AMPK or LKB1, or with the pharmacological inhibitor compound C, reduced outer hair cell and synaptic ribbon loss as well as noise-induced hearing loss. This study provides new insights into mechanisms of noise-induced hearing loss and suggests novel interventions for the prevention of the loss of sensory hair cells and cochlear synaptopathy. Copyright © 2016 the authors 0270-6474/16/367497-14$15.00/0.

  19. Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors

    Directory of Open Access Journals (Sweden)

    Huiling Xu

    2014-12-01

    Full Text Available Summary: Loss of heterozygosity (LOH of the adenomatous polyposis coli (APC gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC. We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1 retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer. : Rad21 holds the cohesin complex together as part of its role in chromosome partitioning and DNA repair. Xu et al. identify Rad21 as a key mediator of Apc gene heterozygous loss, the event initiating intestinal tumorigenesis. The subsequent activation of the Wnt pathway further induces Rad21, global gene dysregulation, chromosome instability, and pervasive retrotransposon activation.

  20. Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation.

    Science.gov (United States)

    Yoshimatsu, Gumpei; Kunnathodi, Faisal; Saravanan, Prathab Balaji; Shahbazov, Rauf; Chang, Charles; Darden, Carly M; Zurawski, Sandra; Boyuk, Gulbahar; Kanak, Mazhar A; Levy, Marlon F; Naziruddin, Bashoo; Lawrence, Michael C

    2017-11-01

    Pancreatic islets produce and secrete cytokines and chemokines in response to inflammatory and metabolic stress. The physiological role of these "isletokines" in health and disease is largely unknown. We observed that islets release multiple inflammatory mediators in patients undergoing islet transplants within hours of infusion. The proinflammatory cytokine interferon-γ-induced protein 10 (IP-10/CXCL10) was among the highest released, and high levels correlated with poor islet transplant outcomes. Transgenic mouse studies confirmed that donor islet-specific expression of IP-10 contributed to islet inflammation and loss of β-cell function in islet grafts. The effects of islet-derived IP-10 could be blocked by treatment of donor islets and recipient mice with anti-IP-10 neutralizing monoclonal antibody. In vitro studies showed induction of the IP-10 gene was mediated by calcineurin-dependent NFAT signaling in pancreatic β-cells in response to oxidative or inflammatory stress. Sustained association of NFAT and p300 histone acetyltransferase with the IP-10 gene required p38 and c-Jun N-terminal kinase mitogen-activated protein kinase (MAPK) activity, which differentially regulated IP-10 expression and subsequent protein release. Overall, these findings elucidate an NFAT-MAPK signaling paradigm for induction of isletokine expression in β-cells and reveal IP-10 as a primary therapeutic target to prevent β-cell-induced inflammatory loss of graft function after islet cell transplantation. © 2017 by the American Diabetes Association.

  1. Cefoxitin resistance mediated by loss of a porin in clinical strains of Klebsiella pneumoniae and Escherichia coli

    Directory of Open Access Journals (Sweden)

    Ananthan S

    2005-01-01

    Full Text Available PURPOSE: Porins are outer membrane protein (OMP that form water filled channels that permit the diffusion of small hydrophilic solutes like -lactam antibiotics across the outer membrane. Two major porins that facilitate diffusion of antimicrobials have been described in Klebsiella spp. and Escherichia coli. The present study was carried out to examine the role of porins among Extended Spectrum -Lactamase (ESBL and AmpC -Lactamase positive strains of Klebsiella spp. and E.coli. METHODS: Preparation of OMP from phenotypically characterized clinical isolates K.pneumoniae and E.coli and the separation of the proteins by sodium dodecyl sulfate - polyacrylamide gel electrophoresis were performed as per a previously described procedure. RESULTS: OMP analysis revealed that cefoxitin and ceftazidime resistance was mediated by loss of a porin Omp K35 in the isolates of K.pneumoniae and E.coli. CONCLUSIONS: Loss of porin mediated resistance mechanism against cefoxitin was observed among the multidrug resistant K.pneumoniae and E.coli.

  2. Sex-specific weight loss mediates sexual size dimorphism in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Nicholas D Testa

    Full Text Available The selective pressures leading to the evolution of Sexual Size Dimorphism (SSD have been well studied in many organisms, yet, the underlying developmental mechanisms are poorly understood. By generating a complete growth profile by sex in Drosophila melanogaster, we describe the sex-specific pattern of growth responsible for SSD. Growth rate and critical size for pupariation significantly contributed to adult SSD, whereas duration of growth did not. Surprisingly, SSD at peak larval mass was twice that of the uneclosed adult SSD with weight loss between peak larval mass and pupariation playing an important role in generating the final SSD. Our finding that weight loss is an important regulator of SSD adds additional complexity to our understanding of how body size is regulated in different sexes. Collectively, these data allow for the elucidation of the molecular-genetic mechanisms that generate SSD, an important component of understanding how SSD evolves.

  3. Loss of Progesterone Receptor-Mediated Actions Induce Preterm Cellular and Structural Remodeling of the Cervix and Premature Birth

    Science.gov (United States)

    Yellon, Steven M.; Dobyns, Abigail E.; Beck, Hailey L.; Kurtzman, James T.; Garfield, Robert E.; Kirby, Michael A.

    2013-01-01

    A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term. PMID:24339918

  4. Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3.

    Science.gov (United States)

    Pérez-Schindler, Joaquín; Esparza, Mary C; McKendry, James; Breen, Leigh; Philp, Andrew; Schenk, Simon

    2017-09-01

    Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not change STAT3 phosphorylation in human skeletal muscle. To directly address the role of STAT3 in load-induced (i.e., adaptive) growth, we studied the anabolic effects of 14 days of synergist ablation (SA) in skeletal muscle-specific STAT3 knockout (mKO) mice and their floxed, wild-type (WT) littermates. Plantaris muscle weight and fiber area in the nonoperated leg (control; CON) was comparable between genotypes. As expected, SA significantly increased plantaris weight, muscle fiber cross-sectional area, and anabolic signaling in WT mice, although interestingly, this induction was not impaired in STAT3 mKO mice. Collectively, these data demonstrate that STAT3 is not required for overload-mediated hypertrophy in mouse skeletal muscle. Copyright © 2017 the American Physiological Society.

  5. The microbially mediated soil organic carbon loss under degenerative succession in an alpine meadow.

    Science.gov (United States)

    Zhang, Yuguang; Liu, Xiao; Cong, Jing; Lu, Hui; Sheng, Yuyu; Wang, Xiulei; Li, Diqiang; Liu, Xueduan; Yin, Huaqun; Zhou, Jizhong; Deng, Ye

    2017-07-01

    Land-cover change has long been recognized as having marked effect on the amount of soil organic carbon (SOC). However, the microbially mediated processes and mechanisms on SOC are still unclear. In this study, the soil samples in a degenerative succession from alpine meadow to alpine steppe meadow in the Qinghai-Tibetan Plateau were analysed using high-throughput technologies, including Illumina sequencing and geochip functional gene arrays. The soil microbial community structure and diversity were significantly (p carbon degradation genes (e.g., pectin and hemicellulose) was significantly higher in alpine steppe meadow than in alpine meadow, but the relative abundance of soil recalcitrant carbon degradation genes (e.g., chitin and lignin) showed the opposite tendency. The Biolog Ecoplate experiment showed that microbially mediated soil carbon utilization was more active in alpine steppe meadow than in alpine meadow. Consequently, more soil labile carbon might be decomposed in alpine steppe meadow than in alpine meadow. Therefore, the degenerative succession of alpine meadow because of climate change or anthropogenic activities would most likely decrease SOC and nutrients medicated by changing soil microbial community structure and their functional potentials for carbon decomposition. © 2017 John Wiley & Sons Ltd.

  6. Acrolein-mediated conduction loss is partially restored by K+ channel blockers

    Science.gov (United States)

    Yan, Rui; Page, Jessica C.

    2015-01-01

    Acrolein-mediated myelin damage is thought to be a critical mechanism leading to conduction failure following neurotrauma and neurodegenerative diseases. The exposure and activation of juxtaparanodal voltage-gated K+ channels due to myelin damage leads to conduction block, and K+ channel blockers have long been studied as a means for restoring axonal conduction in spinal cord injury (SCI) and multiple sclerosis (MS). In this study, we have found that 100 μM K+ channel blockers 4-aminopyridine-3-methanol (4-AP-3-MeOH), and to a lesser degree 4-aminopyridine (4-AP), can significantly restore compound action potential (CAP) conduction in spinal cord tissue following acrolein-mediated myelin damage using a well-established ex vivo SCI model. In addition, 4-AP-3-MeOH can effectively restore CAP conduction in acrolein-damaged axons with a range of concentrations from 0.1 to 100 μM. We have also shown that while both compounds at 100 μM showed no preference of small- and large-caliber axons when restoring CAP conduction, 4-AP-3-MeOH, unlike 4-AP, is able to augment CAP amplitude while causing little change in axonal responsiveness measured in refractory periods and response to repetitive stimuli. In a prior study, we show that 4-AP-3-MeOH was able to functionally rescue mechanically injured axons. In this investigation, we conclude that 4-AP-3-MeOH is an effective K+ channel blocker in restoring axonal conduction following both primary (physical) and secondary (chemical) insults. These findings also suggest that 4-AP-3-MeOH is a viable alternative of 4-AP for treating myelin damage and improving function following central nervous system trauma and neurodegenerative diseases. PMID:26581866

  7. The orally available Btk inhibitor ibrutinib (PCI-32765) protects against osteoclast-mediated bone loss.

    Science.gov (United States)

    Shinohara, Masahiro; Chang, Betty Y; Buggy, Joseph J; Nagai, Yusuke; Kodama, Tatsuhiko; Asahara, Hiroshi; Takayanagi, Hiroshi

    2014-03-01

    Bone-resorbing osteoclasts play an essential role in normal bone homeostasis, as well as in various bone disorders such as osteoporosis and rheumatoid arthritis. Previously we showed that the Tec family of tyrosine kinases is essential for the differentiation of osteoclasts and the inhibition of Btk is a promising strategy for the prevention of the bone loss in osteoclast-associated bone disorders. Here we demonstrate that an orally available Btk inhibitor, ibrutinib (PCI-32765), suppresses osteoclastic bone resorption by inhibiting both osteoclast differentiation and function. Ibrutinib downregulated the expression of NFATc1, the key transcription factor for osteoclastogenesis, and disrupted the formation of the actin ring in mature osteoclasts. In addition, genome-wide screening revealed that Btk regulates the expression of the genes involved in osteoclast differentiation and function in both an NFATc1-dependent and -independent manner. Finally, we showed that ibrutinib administration ameliorated the bone loss that developed in a RANKL-induced osteoporosis mouse model. Thus, this study suggests ibrutinib to be a promising therapeutic agent for osteoclast-associated bone diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. How Does Silicon Mediate Plant Water Uptake and Loss Under Water Deficiency?

    Directory of Open Access Journals (Sweden)

    Daoqian Chen

    2018-03-01

    Full Text Available In plants, water deficiency can result from a deficit of water from the soil, an obstacle to the uptake of water or the excess water loss; in these cases, the similar consequence is the limitation of plant growth and crop yield. Silicon (Si has been widely reported to alleviate the plant water status and water balance under variant stress conditions in both monocot and dicot plants, especially under drought and salt stresses. However, the underlying mechanism is unclear. In addition to the regulation of leaf transpiration, recently, Si application was found to be involved in the adjustment of root hydraulic conductance by up-regulating aquaporin gene expression and concentrating K in the xylem sap. Therefore, this review discusses the potential effects of Si on both leaf transpiration and root water absorption, especially focusing on how Si modulates the root hydraulic conductance. A growing number of studies support the conclusion that Si application improves plant water status by increasing root water uptake, rather than by decreasing their water loss under conditions of water deficiency. The enhancement of plant water uptake by Si is achievable through the activation of osmotic adjustment, improving aquaporin activity and increasing the root/shoot ratio. The underlying mechanisms of the Si on improving plant water uptake under water deficiency conditions are discussed.

  9. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  10. The possible critical role of T-cell help in DSA-mediated graft loss.

    Science.gov (United States)

    Süsal, Caner; Slavcev, Antonij; Pham, Lien; Zeier, Martin; Morath, Christian

    2018-06-01

    In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA-matching, and intense post-transplant monitoring, whereas exclusion of DSA-positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement-activating. © 2018 Steunstichting ESOT.

  11. Loss of Nat4 and its associated histone H4 N-terminal acetylation mediates calorie restriction-induced longevity.

    Science.gov (United States)

    Molina-Serrano, Diego; Schiza, Vassia; Demosthenous, Christis; Stavrou, Emmanouil; Oppelt, Jan; Kyriakou, Dimitris; Liu, Wei; Zisser, Gertrude; Bergler, Helmut; Dang, Weiwei; Kirmizis, Antonis

    2016-12-01

    Changes in histone modifications are an attractive model through which environmental signals, such as diet, could be integrated in the cell for regulating its lifespan. However, evidence linking dietary interventions with specific alterations in histone modifications that subsequently affect lifespan remains elusive. We show here that deletion of histone N-alpha-terminal acetyltransferase Nat4 and loss of its associated H4 N-terminal acetylation (N-acH4) extend yeast replicative lifespan. Notably, nat4Δ-induced longevity is epistatic to the effects of calorie restriction (CR). Consistent with this, (i) Nat4 expression is downregulated and the levels of N-acH4 within chromatin are reduced upon CR, (ii) constitutive expression of Nat4 and maintenance of N-acH4 levels reduces the extension of lifespan mediated by CR, and (iii) transcriptome analysis indicates that nat4Δ largely mimics the effects of CR, especially in the induction of stress-response genes. We further show that nicotinamidase Pnc1, which is typically upregulated under CR, is required for nat4Δ-mediated longevity. Collectively, these findings establish histone N-acH4 as a regulator of cellular lifespan that links CR to increased stress resistance and longevity. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  12. Nox-2-mediated phenotype loss of hippocampal parvalbumin interneurons might contribute to postoperative cognitive decline in aging mice

    Directory of Open Access Journals (Sweden)

    lili qiu

    2016-10-01

    Full Text Available Postoperative cognitive decline (POCD is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH oxidase mediated-abnormalities in parvalbumin (PV interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in sixteen-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO. Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β, markers of oxidative stress, and NADPH oxidase 2 (Nox2 in the hippocampus. In addition, lipopolysaccharide exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived ROS production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice.

  13. Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines

    International Nuclear Information System (INIS)

    Rodríguez, Teresa; Méndez, Rosa; Del Campo, Ana; Jiménez, Pilar; Aptsiauri, Natalia; Garrido, Federico; Ruiz-Cabello, Francisco

    2007-01-01

    The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines. Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan ® Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells. Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway. We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence

  14. Loss of Atrx sensitizes cells to DNA damaging agents through p53-mediated death pathways.

    Directory of Open Access Journals (Sweden)

    Damiano Conte

    Full Text Available Prevalent cell death in forebrain- and Sertoli cell-specific Atrx knockout mice suggest that Atrx is important for cell survival. However, conditional ablation in other tissues is not associated with increased death indicating that diverse cell types respond differently to the loss of this chromatin remodeling protein. Here, primary macrophages isolated from Atrx(f/f mice were infected with adenovirus expressing Cre recombinase or β-galactosidase, and assayed for cell survival under different experimental conditions. Macrophages survive without Atrx but undergo rapid apoptosis upon lipopolysaccharide (LPS activation suggesting that chromatin reorganization in response to external stimuli is compromised. Using this system we next tested the effect of different apoptotic stimuli on cell survival. We observed that survival of Atrx-null cells were similar to wild type cells in response to serum withdrawal, anti-Fas antibody, C2 ceramide or dexamethasone treatment but were more sensitive to 5-fluorouracil (5-FU. Cell survival could be rescued by re-introducing Atrx or by removal of p53 demonstrating the cell autonomous nature of the effect and its p53-dependence. Finally, we demonstrate that multiple primary cell types (myoblasts, embryonic fibroblasts and neurospheres were sensitive to 5-FU, cisplatin, and UV light treatment. Together, our results suggest that cells lacking Atrx are more sensitive to DNA damaging agents and that this may result in enhanced death during development when cells are at their proliferative peak. Moreover, it identifies potential treatment options for cancers associated with ATRX mutations, including glioblastoma and pancreatic neuroendocrine tumors.

  15. BMI-1 Mediates Estrogen-Deficiency-Induced Bone Loss by Inhibiting Reactive Oxygen Species Accumulation and T Cell Activation.

    Science.gov (United States)

    Li, Jinbo; Wang, Qian; Yang, Renlei; Zhang, Jiaqi; Li, Xing; Zhou, Xichao; Miao, Dengshun

    2017-05-01

    Previous studies have shown that estrogen regulates bone homeostasis through regulatory effects on oxidative stress. However, it is unclear how estrogen deficiency triggers reactive oxygen species (ROS) accumulation. Recent studies provide evidence that the B lymphoma Mo-MLV insertion region 1 (BMI-1) plays a critical role in protection against oxidative stress and that this gene is directly regulated by estrogen via estrogen receptor (ER) at the transcriptional level. In this study, ovariectomized mice were given drinking water with/without antioxidant N-acetyl-cysteine (NAC, 1 mg/mL) supplementation, and compared with each other and with sham mice. Results showed that ovariectomy resulted in bone loss with increased osteoclast surface, increased ROS levels, T cell activation, and increased TNF and RANKL levels in serum and in CD4 T cells; NAC supplementation largely prevented these alterations. BMI-1 expression levels were dramatically downregulated in CD4 T cells from ovariectomized mice. We supplemented drinking water to BMI-1-deficient mice with/without NAC and compared them with each other and with wild-type (WT) mice. We found that BMI-1 deficiency mimicked alterations observed in ovariectomy whereas NAC supplementation reversed all alterations induced by BMI-1 deficiency. Because T cells are critical in mediating ovariectomy-induced bone loss, we further assessed whether BMI-1 overexpression in lymphocytes can protect against estrogen deficiency-induced osteoclastogenesis and bone loss by inhibiting oxidative stress, T cell activation, and RANKL production. When WT and Eμ-BMI-1 transgenic mice with BMI-1 specifically overexpressed in lymphocytes were ovariectomized and compared with each other and with WT sham mice, we found that BMI-1 overexpression in lymphocytes clearly reversed all alterations induced by ovariectomy. Results from this study indicate that estrogen deficiency downregulates BMI-1 and subsequently increases ROS, T cell activation, and

  16. Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.

    Science.gov (United States)

    Bernard-Marissal, Nathalie; Médard, Jean-Jacques; Azzedine, Hamid; Chrast, Roman

    2015-04-01

    Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids.

    Science.gov (United States)

    Mata-Castro, Nieves; García-Chilleron, Raimon; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

    2017-10-12

    To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  18. TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Le Bras, Grégoire F.; Taylor, Chase; Koumangoye, Rainelli B. [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Revetta, Frank [Department of Pathology, Vanderbilt University, Nashville, TN (United States); Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Department of Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States)

    2015-01-01

    of esophageal keratinocytes. • Collective cell invasion is protease dependent and ADAMTS-1 is upregulated. • Inhibition of TGFβ signaling promotes EGF-mediated invasion. • Loss of TGFβ signaling promotes collagen binding and induces alterations in integrin expression. • The TGFβ target ROBO1 is downregulated in cell invasion implying mechanisms of chemorepulsion.

  19. Loss of ferulate 5-hydroxylase leads to Mediator-dependent inhibition of soluble phenylpropanoid biosynthesis in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Nickolas; Bonawitz, Nicholas D.; Nyffeler, Kayleigh E.; Chapple, Clint

    2015-06-05

    Phenylpropanoids are phenylalanine-derived specialized metabolites and include important structural components of plant cell walls, such as lignin and hydroxycinnamic acids, as well as ultraviolet and visible light-absorbing pigments, such as hydroxycinnamate esters (HCEs) and anthocyanins. Previous work has revealed a remarkable degree of plasticity in HCE biosynthesis, such that most Arabidopsis (Arabidopsis thaliana) mutants with blockages in the pathway simply redirect carbon flux to atypical HCEs. In contrast, the ferulic acid hydroxylase1 (fah1) mutant accumulates greatly reduced levels of HCEs, suggesting that phenylpropanoid biosynthesis may be repressed in response to the loss of FERULATE 5-HYDROXYLASE (F5H) activity. Here, we show that in fah1 mutant plants, the activity of HCE biosynthetic enzymes is not limiting for HCE accumulation, nor is phenylpropanoid flux diverted to the synthesis of cell wall components or flavonol glycosides. We further show that anthocyanin accumulation is also repressed in fah1 mutants and that this repression is specific to tissues in which F5H is normally expressed. Finally, we show that repression of both HCE and anthocyanin biosynthesis in fah1 mutants is dependent on the MED5a/5b subunits of the transcriptional coregulatory complex Mediator, which are similarly required for the repression of lignin biosynthesis and the stunted growth of the phenylpropanoid pathway mutant reduced epidermal fluorescence8. Taken together, these observations show that the synthesis of HCEs and anthocyanins is actively repressed in a MEDIATOR-dependent manner in Arabidopsis fah1 mutants and support an emerging model in which MED5a/5b act as central players in the homeostatic repression of phenylpropanoid metabolism.

  20. A Mediation Analysis of the ATHENA Intervention for Female Athletes: Prevention of Athletic-Enhancing Substance Use and Unhealthy Weight Loss Behaviors

    Science.gov (United States)

    Ranby, Krista W; Aiken, Leona S; Elliot, Diane L; Moe, Esther L; McGinnis, Wendy; Goldberg, Linn

    2009-01-01

    Objective To explain, through mediation analyses, the mechanisms by which ATHENA (Athletes Targeting Healthy Exercise and Nutrition Alternatives), a primary prevention and health promotion intervention designed to deter unhealthy body shaping behaviors among female high school athletes, produced immediate changes in intentions for unhealthy weight loss and steroid/creatine use, and to examine the link to long-term follow-up intentions and behaviors. Methods In a randomized trial of 1668 athletes, intervention participants completed coach-led peer-facilitated sessions during their sport season. Participants provided pre-test, immediate post-test, and 9-month follow-up assessments. Results ATHENA decreased intentions for steroid/creatine use and intentions for unhealthy weight loss behaviors at post-test. These effects were most strongly mediated by social norms and self-efficacy for healthy eating. Low post-test intentions were maintained 9 months later and predicted subsequent behavior. Conclusions ATHENA successfully modified mediators that in turn related to athletic-enhancing substance use and unhealthy weight loss practices. Mediation analyses aid in the understanding of health promotion interventions and inform program development. PMID:19386771

  1. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

    OpenAIRE

    Cheang, Kai I.; Sistrun, Sakita N.; Morel, Kelley S.; Nestler, John E.

    2016-01-01

    Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS (n = 16) and normal (n = 15) wo...

  2. Rescue of cell death and inflammation of a mouse model of complex 1-mediated vision loss by repurposed drug molecules.

    Science.gov (United States)

    Yu, Alfred K; Datta, Sandipan; McMackin, Marissa Z; Cortopassi, Gino A

    2017-12-15

    Inherited mitochondrial optic neuropathies, such as Leber's hereditary optic neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by mutant mitochondrial proteins that lead to defects in mitochondrial complex 1-driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss. Complex 1 defects also occur in patients with primary open angle glaucoma (POAG), in which there is specific RGC loss. The treatment of mitochondrial optic neuropathy in the US is only supportive. The Ndufs4 knockout (Ndufs4 KO) mouse is a mitochondrial complex 1-deficient model that leads to RGC loss and rapid vision loss and allows for streamlined testing of potential therapeutics. Preceding RGC loss in the Ndufs4 KO is the loss of starburst amacrine cells, which may be an important target in the mechanism of complex 1-deficient vision loss. Papaverine and zolpidem were recently shown to be protective of bioenergetic loss in cell models of optic neuropathy. Treatment of Ndufs4 KO mice with papaverine, zolpidem, and rapamycin-suppressed inflammation, prevented cell death, and protected from vision loss. Thus, in the Ndufs4 KO mouse model of mitochondrial optic neuropathy, papaverine and zolpidem provided significant protection from multiple pathophysiological features, and as approved drugs in wide human use could be considered for the novel indication of human optic neuropathy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

    Science.gov (United States)

    Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

    2017-12-01

    Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

  4. TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila

    Directory of Open Access Journals (Sweden)

    Lies Vanden Broeck

    2013-01-01

    Full Text Available TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43 in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up- and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up- and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function.

  5. 53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.

    Science.gov (United States)

    Fong, Chii Shyang; Mazo, Gregory; Das, Tuhin; Goodman, Joshua; Kim, Minhee; O'Rourke, Brian P; Izquierdo, Denisse; Tsou, Meng-Fu Bryan

    2016-07-02

    Mitosis occurs efficiently, but when it is disturbed or delayed, p53-dependent cell death or senescence is often triggered after mitotic exit. To characterize this process, we conducted CRISPR-mediated loss-of-function screens using a cell-based assay in which mitosis is consistently disturbed by centrosome loss. We identified 53BP1 and USP28 as essential components acting upstream of p53, evoking p21-dependent cell cycle arrest in response not only to centrosome loss, but also to other distinct defects causing prolonged mitosis. Intriguingly, 53BP1 mediates p53 activation independently of its DNA repair activity, but requiring its interacting protein USP28 that can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo. Moreover, 53BP1 can transduce prolonged mitosis to cell cycle arrest independently of the spindle assembly checkpoint (SAC), suggesting that while SAC protects mitotic accuracy by slowing down mitosis, 53BP1 and USP28 function in parallel to select against disturbed or delayed mitosis, promoting mitotic efficiency.

  6. The mediating role of social support, cognitive appraisal, and quality health care in black mothers' stress-resilience process following loss to gun violence.

    Science.gov (United States)

    Bailey, Annette; Sharma, Manoj; Jubin, Michelle

    2013-01-01

    Although much attention has been granted to the perpetrators and victims of gun violence, limitations exist in our understanding of the psychological well-being of parents grieving children lost to gun violence. The purpose of this study was to examine the mediating effects of social support, cognitive appraisal, and quality health care on the relationship between traumatic stress and resilience among Black mothers bereaving children to gun violence. A cross-sectional design and network sampling method were used to recruit 48 Black mothers living in a large Canadian city. Participants completed a survey either by phone or in person. Social support and positive appraisal were found to be protective factors of resilience for study participants. The traumatic stress experienced by the sample decreased with increased social support (beta = -.291, p = .045), leading to an increase of their resilience (beta = .297, p = .032). With positive appraisal of the loss, the stress levels of study participants decreased (beta = -.334, p = .023), leading to increased resilience (beta = .441, p = .003). Quality health care showed a significant positive relationship with the resilience of the women (beta = .313, p = .023) but did not mediate the relationship between their stress and resilience. For Black mothers who experience loss of a child to gun violence, policy and social change efforts should focus on strengthening their access to formal and informal supports and improving their abilities to find meaning in their loss.

  7. Does psychological functioning mediate the relationship between bullying involvement and weight loss preoccupation in adolescents? A two-stage cross-sectional study.

    Science.gov (United States)

    Lee, Kirsty; Guy, Alexa; Dale, Jeremy; Wolke, Dieter

    2017-03-24

    Adolescent bullying is associated with a range of adversities for those who are bullied i.e., victims and bully-victims (e.g., those who bully others and get victimised), including reduced psychological functioning and eating disorder symptoms. Bullies are generally well-adjusted psychologically, but previous research suggests that bullies may also engage in problematic diet behaviours. This study investigates a) whether adolescents involved in bullying (bullies, victims, bully-victims) are at increased risk of weight loss preoccupation, b) whether psychological functioning mediates this relationship and c) whether sex is a key moderator. A two-stage design was used. In stage 1, adolescents (n = 2782) from five UK secondary schools were screened for bullying involvement using self and peer reports. In stage 2, a sample of bullies, victims, bully-victims and uninvolved adolescents (n = 767) completed a battery of assessments. The measures included the eating behaviours component of the Child and Adolescent Psychiatric Assessment, which was reduced to one factor (weight loss preoccupation) and used as the outcome variable. Measures of self-esteem, body-esteem and emotional problems were reduced to a latent (mediator) variable of psychological functioning. Multi-group analysis examined the effects of sex and all models were adjusted for covariates (BMI, pubertal stage, age, parental education and ethnicity). Bullies, victims and bully-victims were at increased risk of weight loss preoccupation compared to adolescents uninvolved in bullying. The mechanism by which bullying involvement related to increased weight loss preoccupation varied by bullying role: in bullies the effect was direct, in victims the effect was indirect (via reduced psychological functioning) and in bully-victims the effect was both direct and indirect. Sex significantly moderated the relationship in bullies: weight loss preoccupation was only statistically significant in bullies who were

  8. DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Mahmood, Amer

    2011-01-01

    . In a number of in vitro culture systems, Dlk1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of proinflammatory bone-resorbing cytokines (eg, Il7, Tnfa, and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of Dlk1...... in the bone marrow by activated T cells. Interestingly, Dlk1(-/-) mice were significantly protected from ovx-induced bone loss compared with wild-type mice. Thus we identified Dlk1 as a novel regulator of bone mass that functions to inhibit bone formation and to stimulate bone resorption. Increasing DLK1...... production by T cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss....

  9. Loss of TET1 facilitates DLD1 colon cancer cell migration via H3K27me3-mediated down-regulation of E-cadherin.

    Science.gov (United States)

    Zhou, Zhen; Zhang, Hong-Sheng; Liu, Yang; Zhang, Zhong-Guo; Du, Guang-Yuan; Li, Hu; Yu, Xiao-Ying; Huang, Ying-Hui

    2018-02-01

    Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased EZH2 expression and reduced UTX-1 expression, thus increasing histone H3K27 tri-methylation causing repression of the target gene E-cadherin. Ectopic expression of the H3K27 demethylase UTX-1 or EZH2 depletion both impeded EZH2 binding caused a loss of H3K27 methylation at epithelial gene E-cadherin promoter, thereby suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX-1 depletion and ectopic expression of EZH2 enhanced EMT and tumor metastasis in DLD1 cells. These findings provide insight into the regulation of TET1 and E-cadherin and identify EZH2 as a critical mediator of E-cadherin repression and tumor progression. © 2017 Wiley Periodicals, Inc.

  10. Dyadic coping mediates the relationship between parents’ grief and dyadic adjustment following the loss of a child

    OpenAIRE

    Albuquerque, Sara; Narciso, Isabel; Pereira, Marco

    2018-01-01

    Background and Objectives: This study aimed to examine forms of dyadic coping (DC) as mediators of the association between parents’ grief response and dyadic adjustment and to determine whether these indirect effects were moderated by the child’s type of death, timing of death, and age. Design: The study design was cross-sectional. Method: The sample consisted of 197 bereaved parents. Participants completed the Prolonged Grief Disorder Scale, Revised Dyadic Adjustment ...

  11. Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGFβ.

    Directory of Open Access Journals (Sweden)

    Tapasi Rana

    Full Text Available Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002 and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005, both of which were rescued by anti-TGFβ antibody (1D11. Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC. Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1 expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients.

  12. Effects of a Weight Loss Program on Metabolic Syndrome, Eating Disorders and Psychological Outcomes: Mediation by Endocannabinoids.

    Science.gov (United States)

    Pataky, Zoltan; Carrard, Isabelle; Gay, Valerie; Thomas, Aurélien; Carpentier, Anne; Bobbioni-Harsch, Elisabetta; Golay, Alain

    2018-04-10

    To evaluate the effects of weight loss on endocannabinoids, cardiometabolic and psychological parameters, eating disorders (ED) as well as quality of life (QoL) and to elucidate the role of endocannabinoids in metabolic syndrome (MS). In total, 114 patients with obesity were prospectively included in a 12-month weight loss program. Plasma endocannabinoids were measured by mass spectrometry; ED, psychological and QoL-related parameters were evaluated by self-reported questionnaires; physical activity was measured by accelerometer. Nutritional assessment was done by a 3-day food diary. Among completers (n = 87), body weight decreased in 35 patients (-9.1 ± 8.6 kg), remained stable in 39 patients, and increased in 13 patients (+5.8 ± 3.4 kg). 75% of patients with MS at baseline were free of MS at follow-up, and their baseline plasma N-palmitoylethanolamide (PEA) values were significantly lower when compared to patients with persisting MS. At baseline, there was a positive relationship between PEA and waist circumference (p = 0.005, R2 = 0.08), fasting glucose (p < 0.0001, R2 = 0.12), total cholesterol (p = 0.001, R2 = 0.11), triglycerides (p = 0.001, R2 = 0.11), LDL-cholesterol (p = 0.03, R2 = 0.05) as well as depression score (p = 0.002, R2 = 0.29). Plasma PEA might play a role in metabolic improvement after weight loss. Even in subjects without weight loss, a multidisciplinary intervention improves psychological outcomes, ED, and QoL. © 2018 The Author(s) Published by S. Karger GmbH, Freiburg.

  13. Effects of a Weight Loss Program on Metabolic Syndrome, Eating Disorders and Psychological Outcomes: Mediation by Endocannabinoids?

    Directory of Open Access Journals (Sweden)

    Zoltan Pataky

    2018-04-01

    Full Text Available Objective: To evaluate the effects of weight loss on endocannabinoids, cardiometabolic and psychological parameters, eating disorders (ED as well as quality of life (QoL and to elucidate the role of endocannabinoids in metabolic syndrome (MS. Methods: In total, 114 patients with obesity were prospectively included in a 12-month weight loss program. Plasma endocannabinoids were measured by mass spectrometry; ED, psychological and QoL-related parameters were evaluated by self-reported questionnaires; physical activity was measured by accelerometer. Nutritional assessment was done by a 3-day food diary. Results: Among completers (n = 87, body weight decreased in 35 patients (-9.1 ± 8.6 kg, remained stable in 39 patients, and increased in 13 patients (+5.8 ± 3.4 kg. 75% of patients with MS at baseline were free of MS at follow-up, and their baseline plasma N-palmitoylethanolamide (PEA values were significantly lower when compared to patients with persisting MS. At baseline, there was a positive relationship between PEA and waist circumference (p = 0.005, R2 = 0.08, fasting glucose (p 2 = 0.12, total cholesterol (p = 0.001, R2 = 0.11, triglycerides (p = 0.001, R2 = 0.11, LDL-cholesterol (p = 0.03, R2 = 0.05 as well as depression score (p = 0.002, R2 = 0.29. Conclusion: Plasma PEA might play a role in metabolic improvement after weight loss. Even in subjects without weight loss, a multidisciplinary intervention improves psychological outcomes, ED, and QoL.

  14. Gefitinib, an EGFR Tyrosine Kinase inhibitor, Prevents Smoke-Mediated Ciliated Airway Epithelial Cell Loss and Promotes Their Recovery.

    Directory of Open Access Journals (Sweden)

    Monica Valencia-Gattas

    Full Text Available Cigarette smoke exposure is a major health hazard. Ciliated cells in the epithelium of the airway play a critical role in protection against the noxious effects of inhaled cigarette smoke. Ciliated cell numbers are reduced in smokers which weakens host defense and leads to disease. The mechanisms for the loss of ciliated cells are not well understood. The effects of whole cigarette smoke exposure on human airway ciliated ciliated cells were examined using in vitro cultures of normal human bronchial epithelial cells and a Vitrocell® VC 10® Smoking Robot. These experiments showed that whole cigarette smoke causes the loss of differentiated ciliated cells and inhibits differentiation of ciliated cells from undifferentiated basal cells. Furthermore, treatment with the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor, Gefitinib, during smoke exposure prevents ciliated cell loss and promotes ciliated cell differentiation from basal cells. Finally, restoration of ciliated cells was inhibited after smoke exposure was ceased but was enhanced by Gefitinib treatment. These data suggest that inhibition of EGFR activity may provide therapeutic benefit for treating smoke related diseases.

  15. The Escape of Cancer from T Cell-Mediated Immune Surveillance: HLA Class I Loss and Tumor Tissue Architecture

    Directory of Open Access Journals (Sweden)

    Federico Garrido

    2017-02-01

    Full Text Available Tumor immune escape is associated with the loss of tumor HLA class I (HLA-I expression commonly found in malignant cells. Accumulating evidence suggests that the efficacy of immunotherapy depends on the expression levels of HLA class I molecules on tumors cells. It also depends on the molecular mechanism underlying the loss of HLA expression, which could be reversible/“soft” or irreversible/“hard” due to genetic alterations in HLA, β2-microglobulin or IFN genes. Immune selection of HLA-I negative tumor cells harboring structural/irreversible alterations has been demonstrated after immunotherapy in cancer patients and in experimental cancer models. Here, we summarize recent findings indicating that tumor HLA-I loss also correlates with a reduced intra-tumor T cell infiltration and with a specific reorganization of tumor tissue. T cell immune selection of HLA-I negative tumors results in a clear separation between the stroma and the tumor parenchyma with leucocytes, macrophages and other mononuclear cells restrained outside the tumor mass. Better understanding of the structural and functional changes taking place in the tumor microenvironment may help to overcome cancer immune escape and improve the efficacy of different immunotherapeutic strategies. We also underline the urgent need for designing strategies to enhance tumor HLA class I expression that could improve tumor rejection by cytotoxic T-lymphocytes (CTL.

  16. MDMA-induced loss of parvalbumin interneurons within the dentate gyrus is mediated by 5HT2A and NMDA receptors.

    Science.gov (United States)

    Collins, Stuart A; Gudelsky, Gary A; Yamamoto, Bryan K

    2015-08-15

    MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats. Extracellular glutamate concentrations increased in the dentate gyrus during systemic and local administration of MDMA. Administration of the NMDA receptor antagonist, MK-801, during systemic injections of MDMA, prevented the loss of PV-IR interneurons seen 10 days after MDMA exposure. Local administration of MDL100907, a selective 5HT2A receptor antagonist, prevented the increases in glutamate caused by reverse dialysis of MDMA directly into the dentate gyrus and prevented the reduction of PV-IR. These findings provide evidence that MDMA causes decreases in PV within the dentate gyrus through a 5HT2A receptor-mediated increase in glutamate and subsequent NMDA receptor activation. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1(Ter/Ter) mice.

    Science.gov (United States)

    Cook, Matthew S; Coveney, Douglas; Batchvarov, Iordan; Nadeau, Joseph H; Capel, Blanche

    2009-04-15

    A homozygous nonsense mutation (Ter) in murine Dnd1 (Dnd1(Ter/Ter)) results in a significant early loss of primordial germ cells (PGCs) prior to colonization of the gonad in both sexes and all genetic backgrounds tested. The same mutation also leads to testicular teratomas only on the 129Sv/J background. Male mutants on other genetic backgrounds ultimately lose all PGCs with no incidence of teratoma formation. It is not clear how these PGCs are lost or what factors directly control the strain-specific phenotype variation. To determine the mechanism underlying early PGC loss we crossed Dnd1(Ter/Ter) embryos to a Bax-null background and found that germ cells were partially rescued. Surprisingly, on a mixed genetic background, rescued male germ cells also generated fully developed teratomas at a high rate. Double-mutant females on a mixed background did not develop teratomas, but were fertile and produced viable off-spring. However, when Dnd1(Ter/Ter) XX germ cells developed in a testicular environment they gave rise to the same neoplastic clusters as mutant XY germ cells in a testis. We conclude that BAX-mediated apoptosis plays a role in early germ cell loss and protects from testicular teratoma formation on a mixed genetic background.

  18. Catalase-dependent H2O2 consumption by cardiac mitochondria and redox-mediated loss in insulin signaling.

    Science.gov (United States)

    Rindler, Paul M; Cacciola, Angela; Kinter, Michael; Szweda, Luke I

    2016-11-01

    We have recently demonstrated that catalase content in mouse cardiac mitochondria is selectively elevated in response to high dietary fat, a nutritional state associated with oxidative stress and loss in insulin signaling. Catalase and various isoforms of glutathione peroxidase and peroxiredoxin each catalyze the consumption of H 2 O 2 Catalase, located primarily within peroxisomes and to a lesser extent mitochondria, has a low binding affinity for H 2 O 2 relative to glutathione peroxidase and peroxiredoxin. As such, the contribution of catalase to mitochondrial H 2 O 2 consumption is not well understood. In the current study, using highly purified cardiac mitochondria challenged with micromolar concentrations of H 2 O 2 , we found that catalase contributes significantly to mitochondrial H 2 O 2 consumption. In addition, catalase is solely responsible for removal of H 2 O 2 in nonrespiring or structurally disrupted mitochondria. Finally, in mice fed a high-fat diet, mitochondrial-derived H 2 O 2 is responsible for diminished insulin signaling in the heart as evidenced by reduced insulin-stimulated Akt phosphorylation. While elevated mitochondrial catalase content (∼50%) enhanced the capacity of mitochondria to consume H 2 O 2 in response to high dietary fat, the selective increase in catalase did not prevent H 2 O 2 -induced loss in cardiac insulin signaling. Taken together, our results indicate that mitochondrial catalase likely functions to preclude the formation of high levels of H 2 O 2 without perturbing redox-dependent signaling. Copyright © 2016 the American Physiological Society.

  19. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Kai I. Cheang

    2016-01-01

    Full Text Available Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG may contribute to insulin resistance in polycystic ovary syndrome (PCOS. Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS (n=16 and normal (n=15 women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUCDCI-IPG, AUCinsulin, and AUCDCI-IPG/AUCinsulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUCDCI-IPG/AUCinsulin at baseline and a significant relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p=0.0003, which was not present in controls. Weight loss was similar between PCOS (−4.08 kg and normal women (−4.29 kg, p=0.6281. Weight loss in PCOS women did not change the relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p=0.0100, and this relationship remained absent in control women. Conclusion. The association between AUCDCI-IPG/AUCinsulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

  20. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome.

    Science.gov (United States)

    Cheang, Kai I; Sistrun, Sakita N; Morel, Kelley S; Nestler, John E

    2016-01-01

    Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS ( n = 16) and normal ( n = 15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUC DCI-IPG ), AUC insulin , and AUC DCI-IPG /AUC insulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUC DCI-IPG /AUC insulin at baseline and a significant relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0003), which was not present in controls. Weight loss was similar between PCOS (-4.08 kg) and normal women (-4.29 kg, p = 0.6281). Weight loss in PCOS women did not change the relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0100), and this relationship remained absent in control women. Conclusion. The association between AUC DCI-IPG /AUC insulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

  1. DKK1 mediated inhibition of Wnt signaling in postnatal mice leads to loss of TEC progenitors and thymic degeneration.

    Directory of Open Access Journals (Sweden)

    Masako Osada

    2010-02-01

    Full Text Available Thymic epithelial cell (TEC microenvironments are essential for the recruitment of T cell precursors from the bone marrow, as well as the subsequent expansion and selection of thymocytes resulting in a mature self-tolerant T cell repertoire. The molecular mechanisms, which control both the initial development and subsequent maintenance of these critical microenvironments, are poorly defined. Wnt signaling has been shown to be important to the development of several epithelial tissues and organs. Regulation of Wnt signaling has also been shown to impact both early thymocyte and thymic epithelial development. However, early blocks in thymic organogenesis or death of the mice have prevented analysis of a role of canonical Wnt signaling in the maintenance of TECs in the postnatal thymus.Here we demonstrate that tetracycline-regulated expression of the canonical Wnt inhibitor DKK1 in TECs localized in both the cortex and medulla of adult mice, results in rapid thymic degeneration characterized by a loss of DeltaNP63(+ Foxn1(+ and Aire(+ TECs, loss of K5K8DP TECs thought to represent or contain an immature TEC progenitor, decreased TEC proliferation and the development of cystic structures, similar to an aged thymus. Removal of DKK1 from DKK1-involuted mice results in full recovery, suggesting that canonical Wnt signaling is required for the differentiation or proliferation of TEC populations needed for maintenance of properly organized adult thymic epithelial microenvironments.Taken together, the results of this study demonstrate that canonical Wnt signaling within TECs is required for the maintenance of epithelial microenvironments in the postnatal thymus, possibly through effects on TEC progenitor/stem cell populations. Downstream targets of Wnt signaling, which are responsible for maintenance of these TEC progenitors may provide useful targets for therapies aimed at counteracting age associated thymic involution or the premature thymic

  2. The transcription factor FoxB mediates temporal loss of cellular competence for notochord induction in ascidian embryos.

    Science.gov (United States)

    Hashimoto, Hidehiko; Enomoto, Takashi; Enomoto, Atsushi; Kumano, Gaku; Nishida, Hiroki

    2011-06-01

    In embryos of the ascidian Halocynthia roretzi, the competence of isolated presumptive notochord blastomeres to respond to fibroblast growth factor (FGF) for induction of the primary notochord decays by 1 hour after cleavage from the 32- to 64-cell stage. This study analyzes the molecular mechanisms responsible for this loss of competence and provides evidence for a novel mechanism. A forkhead family transcription factor, FoxB, plays a role in competence decay by preventing the induction of notochord-specific Brachyury (Bra) gene expression by the FGF/MAPK signaling pathway. Unlike the mechanisms reported previously in other animals, no component in the FGF signal transduction cascade appeared to be lost or inactivated at the time of competence loss. Knockdown of FoxB functions allowed the isolated cells to retain their competence for a longer period, and to respond to FGF with expression of Bra beyond the stage at which competence was normally lost. FoxB acts as a transcription repressor by directly binding to the cis-regulatory element of the Bra gene. Our results suggest that FoxB prevents ectopic induction of the notochord fate within the cells that assume a default nerve cord fate, after the stage when notochord induction has been completed. The merit of this system is that embryos can use the same FGF signaling cascade again for another purpose in the same cell lineage at later stages by keeping the signaling cascade itself available. Temporally and spatially regulated FoxB expression in nerve cord cells was promoted by the ZicN transcription factor and absence of FGF/MAPK signaling.

  3. Dyadic coping mediates the relationship between parents' grief and dyadic adjustment following the loss of a child.

    Science.gov (United States)

    Albuquerque, Sara; Narciso, Isabel; Pereira, Marco

    2018-01-01

    This study aimed to examine forms of dyadic coping (DC) as mediators of the association between parents' grief response and dyadic adjustment and to determine whether these indirect effects were moderated by the child's type of death, timing of death, and age. The study design was cross-sectional. The sample consisted of 197 bereaved parents. Participants completed the Prolonged Grief Disorder Scale, Revised Dyadic Adjustment Scale, and Dyadic Coping Inventory. Significant indirect effects of parents' grief response on dyadic adjustment were found through stress communication by oneself and by the partner, positive and negative DC by the partner, and joint DC. The timing of death moderated the association between grief response and dyadic adjustment and between joint DC and dyadic adjustment. Grief response was negatively associated with dyadic adjustment only when the death occurred after birth. Grief response was negatively associated with joint DC, which, in turn, was positively associated with dyadic adjustment, when the death occurred both before and after birth. However, the association was stronger in the latter. Specific forms of DC might be mechanisms through which grief response is associated with dyadic adjustment and should be promoted in clinical practice.

  4. Effects of interleukin-7/interleukin-7 receptor on RANKL-mediated osteoclast differentiation and ovariectomy-induced bone loss by regulating c-Fos/c-Jun pathway.

    Science.gov (United States)

    Zhao, Ji-Jun; Wu, Zhao-Feng; Yu, Ying-Hao; Wang, Ling; Cheng, Li

    2018-09-01

    To explore the effects of IL-7/IL-7R on the RANKL-mediated osteoclast differentiation in vitro and OVX-induced bone loss in vivo. BMMs and RAW264.7 were transfected with IL-7, IL-7R siRNA, c-Fos siRNA, and c-jun siRNA and later stimulated by RANKL. TRAP and toluidine blue staining were used to observe osteoclast formation and bone resorption, respectively. HE and TRAP staining were used to detect trabecular bone microstructure and osteoclasts of mice, respectively. qRT-PCR and Western blot analysis were used to examine expression. IL-7 unregulated the expression of CTSK, NFATc1, MMP9, and the phosphorylation of p38 and Akt by activating the c-Fos/c-Jun pathway, which increased osteoclast numbers and bone resorption in RANKL-stimulated macrophages. While IL-7R siRNA and c-Fos siRNA decreased the expression, as well as and the phosphorylation of p38 and Akt.IL-7 decreased the BMD and OPG expression in OVX-induced mice and increased the TRAP positive cells, the mRNA expression of c-fos, c-jun, and RANKL, which was contradictory to IL-7R siRNA, and c-Fos siRNA. Furthermore, IL-7R siRNA and c-Fos siRNA caused thicker trabeculae, increased trabecular number, and decreased osteolysis in OVX mice. IL-7/IL-7R can promote RANKL-mediated osteoclast formation and bone resorption by activating the c-Fos/c-Jun pathway, as well as inducing bone loss in OVX mice. © 2018 Wiley Periodicals, Inc.

  5. The Relationship Between Poor Quality of Life and Desire to Hasten Death: A Multiple Mediation Model Examining the Contributions of Depression, Demoralization, Loss of Control, and Low Self-worth.

    Science.gov (United States)

    Robinson, Sophie; Kissane, David W; Brooker, Joanne; Hempton, Courtney; Burney, Susan

    2017-02-01

    The risk of suicide is elevated in palliative care patients compared with the general population. Various psychological factors, including depression, demoralization, loss of control, and low self-worth, have been associated with a desire to hasten death. The aim of this study was to investigate whether depression, demoralization, loss of control, and low self-worth mediated the relationship between global quality of life and desire to hasten death. A sample of 162 palliative care patients completed measures of global quality of life, depression, demoralization, perceived control, self-worth, and desire to hasten death. A multiple mediation model with bootstrapping sampling tested the total (combined) indirect effect and individual indirect effects of depression, the two subscales of demoralization (Meaning and Purpose, and Distress and Coping Ability), perceived control, and self-worth. Depressive symptoms, loss of meaning and purpose, loss of control, and low self-worth mediated the direct effect of global quality of life on desire to hasten death. The Distress and Coping Ability component of demoralization was not a significant mediator. Depression, loss of meaning and purpose, loss of control, and low self-worth are strong clinical markers for desire to hasten death. Targeting these symptoms through existentially oriented therapies, such as meaning-centered therapy, may ameliorate suicidal thinking. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  6. Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry.

    Science.gov (United States)

    Sawada, Yoshikazu; Izumida, Yoshihiko; Takeuchi, Yoshinori; Aita, Yuichi; Wada, Nobuhiro; Li, EnXu; Murayama, Yuki; Piao, Xianying; Shikama, Akito; Masuda, Yukari; Nishi-Tatsumi, Makiko; Kubota, Midori; Sekiya, Motohiro; Matsuzaka, Takashi; Nakagawa, Yoshimi; Sugano, Yoko; Iwasaki, Hitoshi; Kobayashi, Kazuto; Yatoh, Shigeru; Suzuki, Hiroaki; Yagyu, Hiroaki; Kawakami, Yasushi; Kadowaki, Takashi; Shimano, Hitoshi; Yahagi, Naoya

    2017-11-04

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Prevention of inflammation-mediated bone loss in murine and canine periodontal disease via recruitment of regulatory lymphocytes.

    Science.gov (United States)

    Glowacki, Andrew J; Yoshizawa, Sayuri; Jhunjhunwala, Siddharth; Vieira, Andreia E; Garlet, Gustavo P; Sfeir, Charles; Little, Steven R

    2013-11-12

    The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu.

  8. The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent.

    Science.gov (United States)

    Bosch, Oliver J; Nair, Hemanth P; Ahern, Todd H; Neumann, Inga D; Young, Larry J

    2009-05-01

    Social relationships significantly influence physiology and behavior, including the hypothalamo-pituitary-adrenal axis, anxiety, and mental health. Disruption of social bonds through separation or death often results in profound grieving, depression, and physical illness. As the monogamous prairie vole forms enduring, selective pair bonds with the mating partner, they provide an animal model to study the physiological consequences of pair bonding and, thus, the loss of the bonded partner. Male prairie voles were paired with a novel female or male sibling. After 5 days, half of the males of each group were separated from the partner. Elevated plus-maze, forced swim, and tail suspension tests were used to assess anxiety-like and passive stress-coping behaviors indicative of depressive-like behavior. Following 4 days of separation from the female but not the male partner, experimental males displayed increased passive stress-coping. This effect was abolished by long-term intracerebroventricular infusion of a nonselective corticotropin-releasing factor (CRF) receptor antagonist without disrupting the bond itself. Both CRF type 1 and 2 receptors were involved in the emergence of passive stress-coping behavior. Furthermore, pairing with a female was associated with elevated CRF mRNA in the bed nucleus of the stria terminalis, and partner loss elicited a pronounced increase in circulating corticosteroid and adrenal weight. We speculate that the CRF system may mediate an aversive affect following separation from the female partner, which may facilitate proximity seeking between the pair-bonded individuals. Hence, the prairie vole model may provide insights into brain mechanisms involved in the psychopathological consequences of partner loss.

  9. Platelet-derived growth factor (PDGF)-signaling mediates radiation-induced apoptosis in human prostate cancer cells with loss of p53 function

    International Nuclear Information System (INIS)

    Kim, Harold E.; Han, Sue J.; Kasza, Thomas; Han, Richard; Choi, Hyeong-Seon; Palmer, Kenneth C.; Kim, Hyeong-Reh C.

    1997-01-01

    Platelet-derived growth factor (PDGF) signals a diversity of cellular responses in vitro, including cell proliferation, survival, transformation, and chemotaxis. PDGF functions as a 'competence factor' to induce a set of early response genes expressed in G 1 including p21 WAF1/CIP1 , a functional mediator of the tumor suppressor gene p53 in G 1 /S checkpoint. For PDGF-stimulated cells to progress beyond G 1 and transit the cell cycle completely, progression factors in serum such as insulin and IGF-1 are required. We have recently shown a novel role of PDGF in inducing apoptosis in growth-arrested murine fibroblasts. The PDGF-induced apoptosis is rescued by insulin, suggesting that G 1 /S checkpoint is a critical determinant for PDGF-induced apoptosis. Because recent studies suggest that radiation-induced signal transduction pathways interact with growth factor-mediated signaling pathways, we have investigated whether activation of the PDGF-signaling facilitates the radiation-induced apoptosis in the absence of functional p53. For this study we have used the 125-IL cell line, a mutant p53-containing, highly metastatic, and hormone-unresponsive human prostate carcinoma cell line. PDGF signaling is constitutively activated by transfection with a p28 v-sis expression vector, which was previously shown to activate PDGF α- and β- receptors. Although the basal level of p21 WAF1/CIP1 expression and radiation-induced apoptosis were not detectable in control 125-IL cells as would be predicted in mutant p53-containing cells, activation of PDGF-signaling induced expression of p21 WAF1/CIP1 and radiation-induced apoptosis. Our study suggests that the level of 'competence' growth factors including PDGF may be one of the critical determinants for radiation-induced apoptosis, especially in cells with loss of p53 function at the site of radiotherapy in vivo

  10. Inefficient Nef-mediated downmodulation of CD3 and MHC-I correlates with loss of CD4+T cells in natural SIV infection.

    Directory of Open Access Journals (Sweden)

    Michael Schindler

    2008-07-01

    Full Text Available Recent data suggest that Nef-mediated downmodulation of TCR-CD3 may protect SIVsmm-infected sooty mangabeys (SMs against the loss of CD4+ T cells. However, the mechanisms underlying this protective effect remain unclear. To further assess the role of Nef in nonpathogenic SIV infection, we cloned nef alleles from 11 SIVsmm-infected SMs with high (>500 and 15 animals with low (<500 CD4+ T-cells/microl in bulk into proviral HIV-1 IRES/eGFP constructs and analyzed their effects on the phenotype, activation, and apoptosis of primary T cells. We found that not only efficient Nef-mediated downmodulation of TCR-CD3 but also of MHC-I correlated with preserved CD4+ T cell counts, as well as with high numbers of Ki67+CD4+ and CD8+CD28+ T cells and reduced CD95 expression by CD4+ T cells. Moreover, effective MHC-I downregulation correlated with low proportions of effector and high percentages of naïve and memory CD8+ T cells. We found that T cells infected with viruses expressing Nef alleles from the CD4low SM group expressed significantly higher levels of the CD69, interleukin (IL-2 and programmed death (PD-1 receptors than those expressing Nefs from the CD4high group. SIVsmm Nef alleles that were less active in downmodulating TCR-CD3 were also less potent in suppressing the activation of virally infected T cells and subsequent cell death. However, only nef alleles from a single animal with very low CD4+ T cell counts rendered T cells hyper-responsive to activation, similar to those of HIV-1. Our data suggest that Nef may protect the natural hosts of SIV against the loss of CD4+ T cells by at least two mechanisms: (i downmodulation of TCR-CD3 to prevent activation-induced cell death and to suppress the induction of PD-1 that may impair T cell function and survival, and (ii downmodulation of MHC-I to reduce CTL lysis of virally infected CD4+ T cells and/or bystander CD8+ T cell activation.

  11. Loss of nitric oxide-mediated inhibition of purine neurotransmitter release in the colon in the absence of interstitial cells of Cajal.

    Science.gov (United States)

    Durnin, Leonie; Lees, Andrea; Manzoor, Sheerien; Sasse, Kent C; Sanders, Kenton M; Mutafova-Yambolieva, Violeta N

    2017-11-01

    Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα + ) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in Kit W /Kit W-v ( W/W v ) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD + )/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5'-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/W v , Nos1 -/- , and Prkg1 -/- mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/W v mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/W v mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric

  12. Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway.

    Science.gov (United States)

    Park, J H; Lee, J Y; Shin, D H; Jang, K S; Kim, H J; Kong, Gu

    2011-11-10

    Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and found that Mel-18 was a novel regulator of HIF-1α. Mel-18 negatively regulated the HIF-1α expression and its target gene VEGF transcription during both normoxia and hypoxia. We demonstrated that Mel-18 regulated the HIF-1α expression and activity via the PI3K/Akt pathway. Loss of Mel-18 downregulated Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression, consequently activating the PI3K/Akt/MDM2 pathway, and leading to an increase of HIF-1α protein level. Mel-18 modulated the HIF-1α transcriptional activity via regulating the cytoplasmic retention of FOXO3a, a downstream effector of Akt, and recruitment of HIF-1α/CBP complex to the VEGF promoter. Furthermore, our data shows that Mel-18 blocked tumor angiogenesis both in vitro and in vivo. Mel-18 overexpression inhibited in vitro tube formation in human umbilical endothelial cells (HUVECs). Xenografts in NOD/SCID mice derived from stably Mel-18 knocked down MCF7 human breast cancer cells showed increased tumor volume, microvessel density, and phospho-Akt and HIF-1α expression levels. In conclusion, our findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1α and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer.

  13. Loss of Cdk5 function in the nucleus accumbens decreases wheel running and may mediate age‐related declines in voluntary physical activity

    Science.gov (United States)

    Ruegsegger, Gregory N.; Toedebusch, Ryan G.; Childs, Thomas E.; Grigsby, Kolter B.

    2016-01-01

    Key points Physical inactivity, which drastically increases with advancing age, is associated with numerous chronic diseases.The nucleus accumbens (the pleasure and reward ‘hub’ in the brain) influences wheel running behaviour in rodents.RNA‐sequencing and subsequent bioinformatics analysis led us to hypothesize a potential relationship between the regulation of dendritic spine density, the molecules involved in synaptic transmission, and age‐related reductions in wheel running. Upon completion of follow‐up studies, we developed the working model that synaptic plasticity in the nucleus accumbens is central to age‐related changes in voluntary running.Testing this hypothesis, inhibition of Cdk5 (comprising a molecule central to the processes described above) in the nucleus accumbens reduced wheel running.The results of the present study show that reductions in synaptic transmission and Cdk5 function are related to decreases in voluntary running behaviour and provide guidance for understanding the neural mechanisms that underlie age‐dependent reductions in the motivation to be physically active. Abstract Increases in age are often associated with reduced levels of physical activity, which, in turn, associates with the development of numerous chronic diseases. We aimed to assess molecular differences in the nucleus accumbens (NAc) (a specific brain nucleus postulated to influence rewarding behaviour) with respect to wheel running and sedentary female Wistar rats at 8 and 14 weeks of age. RNA‐sequencing was used to interrogate transcriptomic changes between 8‐ and 14‐week‐old wheel running rats, and select transcripts were later analysed by quantitative RT‐PCR in age‐matched sedentary rats. Voluntary wheel running was greatest at 8 weeks and had significantly decreased by 12 weeks. From 619 differentially expressed mRNAs, bioinformatics suggested that cAMP‐mediated signalling, dopamine‐ and cAMP‐regulated neuronal phosphoprotein of 32

  14. Human tau increases amyloid β plaque size but not amyloid β-mediated synapse loss in a novel mouse model of Alzheimer's disease.

    Science.gov (United States)

    Jackson, Rosemary J; Rudinskiy, Nikita; Herrmann, Abigail G; Croft, Shaun; Kim, JeeSoo Monica; Petrova, Veselina; Ramos-Rodriguez, Juan Jose; Pitstick, Rose; Wegmann, Susanne; Garcia-Alloza, Monica; Carlson, George A; Hyman, Bradley T; Spires-Jones, Tara L

    2016-12-01

    Alzheimer's disease is characterized by the presence of aggregates of amyloid beta (Aβ) in senile plaques and tau in neurofibrillary tangles, as well as marked neuron and synapse loss. Of these pathological changes, synapse loss correlates most strongly with cognitive decline. Synapse loss occurs prominently around plaques due to accumulations of oligomeric Aβ. Recent evidence suggests that tau may also play a role in synapse loss but the interactions of Aβ and tau in synapse loss remain to be determined. In this study, we generated a novel transgenic mouse line, the APP/PS1/rTg21221 line, by crossing APP/PS1 mice, which develop Aβ-plaques and synapse loss, with rTg21221 mice, which overexpress wild-type human tau. When compared to the APP/PS1 mice without human tau, the cross-sectional area of ThioS+ dense core plaques was increased by ~50%. Along with increased plaque size, we observed an increase in plaque-associated dystrophic neurites containing misfolded tau, but there was no exacerbation of neurite curvature or local neuron loss around plaques. Array tomography analysis similarly revealed no worsening of synapse loss around plaques, and no change in the accumulation of Aβ at synapses. Together, these results indicate that adding human wild-type tau exacerbates plaque pathology and neurite deformation but does not exacerbate plaque-associated synapse loss. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Depression, anxiety and loss of resilience after multiple traumas: an illustration of a mediated moderation model of sensitization in a group of children who survived the Nazi Holocaust.

    Science.gov (United States)

    Fossion, Pierre; Leys, Christophe; Kempenaers, Chantal; Braun, Stephanie; Verbanck, Paul; Linkowski, Paul

    2013-12-01

    Depressive and anxiety disorders (DAD) have become a major public health problem. Multiple trauma is known to increase the risk of DAD through a sensitization mechanism. We investigate the hypothesis that resilience is a mediator of this mechanism. Former Hidden Children (FHC), the Jewish youths who spent World War II in various hideaway shelters across Nazi-occupied Europe, were compared with a control group. In each group, we measured the presence of multiple traumas, the resilience with the Resilience Scale for Adults, which has a six factors solution, and the DAD with the Hopkins Symptoms Checklist. We test a mediated moderation model with childhood trauma as the predictor; Later trauma as the moderator; Resilience as the mediator; and DAD as the outcome variable. Results are consistent with a sensitization model of DAD mediated by resilience: confrontation with a primary trauma during childhood followed by secondary trauma(s) after childhood damages resilience, which, in turn, results in higher level of DAD. We are unable to differentiate if the sensitization process is a consequence of the nature of the trauma endured by FHC (long-standing exposure to extreme external events) or a consequence of the fact that this first trauma occurred during childhood. Resilience construct is multi-factorial and a limited damaging of some of the factors is sufficient to lead to DAD even if other factors remain unaltered. Resilience can be altered by multiple traumas and, therefore, needs to be bolstered in therapy sessions. Copyright © 2013. Published by Elsevier B.V.

  16. Effect of Integrated Water-Nutrient Management Strategies on Soil Erosion Mediated Nutrient Loss and Crop Productivity in Cabo Verde Drylands

    Science.gov (United States)

    Baptista, Isaurinda; Ritsema, Coen; Geissen, Violette

    2015-01-01

    Soil erosion, runoff and related nutrient losses are a big risk for soil fertility in Cabo Verde drylands. In 2012, field trials were conducted in two agro-ecological zones to evaluate the effects of selected techniques of soil-water management combined with organic amendments (T1: compost/manure + soil surfactant; T2: compost/animal or green manure + pigeon-pea hedges + soil surfactant; T3: compost/animal or green manure + mulch + pigeon-pea hedges) on nitrogen (N) and phosphorus (P) losses in eroded soil and runoff and on crop yields. Three treatments and one control (traditional practice) were tested in field plots at three sites with a local maize variety and two types of beans. Runoff and eroded soil were collected after each erosive rain, quantified, and analysed for NO3-N and PO4-P concentrations. In all treatments runoff had higher concentrations of NO3-N (2.20-4.83 mg L-1) than of PO4-P (0.02-0.07 mg L-1), and the eroded soil had higher content of PO4-P (5.27-18.8 mg g-1) than of NO3-N (1.30-8.51 mg g-1). The control had significantly higher losses of both NO3-N (5.4, 4.4 and 19 kg ha-1) and PO4-P (0.2, 0.1 and 0.4 kg ha-1) than the other treatments. T3 reduced soil loss, runoff and nutrient losses to nearly a 100% while T1 and T2 reduced those losses from 43 to 88%. The losses of NO3-N and PO4-P were highly correlated with the amounts of runoff and eroded soil. Nutrient losses from the applied amendments were low (5.7% maximum), but the losses in the control could indicate long-term nutrient depletion in the soil (19 and 0.4 kg ha-1 of NO3-N and PO4-P, respectively). T1-T3 did not consistently increase crop yield or biomass in all three sites, but T1 increased both crop yield and biomass. We conclude that T3 (combining crop-residue mulch with organic amendment and runoff hedges) is the best treatment for steep slope areas but, the pigeon-pea hedges need to be managed for higher maize yield. T1 (combining organic amendment with soil surfactant) could be a

  17. Effect of Integrated Water-Nutrient Management Strategies on Soil Erosion Mediated Nutrient Loss and Crop Productivity in Cabo Verde Drylands.

    Science.gov (United States)

    Baptista, Isaurinda; Ritsema, Coen; Geissen, Violette

    2015-01-01

    Soil erosion, runoff and related nutrient losses are a big risk for soil fertility in Cabo Verde drylands. In 2012, field trials were conducted in two agro-ecological zones to evaluate the effects of selected techniques of soil-water management combined with organic amendments (T1: compost/manure + soil surfactant; T2: compost/animal or green manure + pigeon-pea hedges + soil surfactant; T3: compost/animal or green manure + mulch + pigeon-pea hedges) on nitrogen (N) and phosphorus (P) losses in eroded soil and runoff and on crop yields. Three treatments and one control (traditional practice) were tested in field plots at three sites with a local maize variety and two types of beans. Runoff and eroded soil were collected after each erosive rain, quantified, and analysed for NO3-N and PO4-P concentrations. In all treatments runoff had higher concentrations of NO3-N (2.20-4.83 mg L-1) than of PO4-P (0.02-0.07 mg L-1), and the eroded soil had higher content of PO4-P (5.27-18.8 mg g-1) than of NO3-N (1.30-8.51 mg g-1). The control had significantly higher losses of both NO3-N (5.4, 4.4 and 19 kg ha-1) and PO4-P (0.2, 0.1 and 0.4 kg ha-1) than the other treatments. T3 reduced soil loss, runoff and nutrient losses to nearly a 100% while T1 and T2 reduced those losses from 43 to 88%. The losses of NO3-N and PO4-P were highly correlated with the amounts of runoff and eroded soil. Nutrient losses from the applied amendments were low (5.7% maximum), but the losses in the control could indicate long-term nutrient depletion in the soil (19 and 0.4 kg ha-1 of NO3-N and PO4-P, respectively). T1-T3 did not consistently increase crop yield or biomass in all three sites, but T1 increased both crop yield and biomass. We conclude that T3 (combining crop-residue mulch with organic amendment and runoff hedges) is the best treatment for steep slope areas but, the pigeon-pea hedges need to be managed for higher maize yield. T1 (combining organic amendment with soil surfactant) could be a

  18. Cytokine-Mediated Loss of Blood Dendritic Cells During Epstein-Barr Virus-Associated Acute Infectious Mononucleosis: Implication for Immune Dysregulation.

    Science.gov (United States)

    Panikkar, Archana; Smith, Corey; Hislop, Andrew; Tellam, Nick; Dasari, Vijayendra; Hogquist, Kristin A; Wykes, Michelle; Moss, Denis J; Rickinson, Alan; Balfour, Henry H; Khanna, Rajiv

    2015-12-15

    Acute infectious mononucleosis (IM) is associated with altered expression of inflammatory cytokines and disturbed T-cell homeostasis, however, the precise mechanism of this immune dysregulation remains unresolved. In the current study we demonstrated a significant loss of circulating myeloid and plasmacytoid dendritic cells (DCs) during acute IM, a loss correlated with the severity of clinical symptoms. In vitro exposure of blood DCs to acute IM plasma resulted in loss of plasmacytoid DCs, and further studies with individual cytokines showed that exposure to interleukin 10 could replicate this effect. Our data provide important mechanistic insight into dysregulated immune homeostasis during acute IM. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Hearing loss

    Science.gov (United States)

    Decreased hearing; Deafness; Loss of hearing; Conductive hearing loss; Sensorineural hearing loss; Presbycusis ... Symptoms of hearing loss may include: Certain sounds seeming too loud Difficulty following conversations when two or more people are talking ...

  20. Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone.

    Directory of Open Access Journals (Sweden)

    Julieta Aisemberg

    Full Text Available Lipopolysaccharide (LPS administration to mice on day 7 of gestation led to 100% embryonic resorption after 24 h. In this model, nitric oxide is fundamental for the resorption process. Progesterone may be responsible, at least in part, for a Th2 switch in the feto-maternal interface, inducing active immune tolerance against fetal antigens. Th2 cells promote the development of T cells, producing leukemia inhibitory factor (LIF, which seems to be important due to its immunomodulatory action during early pregnancy. Our aim was to evaluate the involvement of progesterone in the mechanism of LPS-induced embryonic resorption, and whether LIF can mediate hormonal action. Using in vivo and in vitro models, we provide evidence that circulating progesterone is an important component of the process by which infection causes embryonic resorption in mice. Also, LIF seems to be a mediator of the progesterone effect under inflammatory conditions. We found that serum progesterone fell to very low levels after 24 h of LPS exposure. Moreover, progesterone supplementation prevented embryonic resorption and LPS-induced increase of uterine nitric oxide levels in vivo. Results show that LPS diminished the expression of the nuclear progesterone receptor in the uterus after 6 and 12 h of treatment. We investigated the expression of LIF in uterine tissue from pregnant mice and found that progesterone up-regulates LIF mRNA expression in vitro. We observed that LIF was able to modulate the levels of nitric oxide induced by LPS in vitro, suggesting that it could be a potential mediator of the inflammatory action of progesterone. Our observations support the view that progesterone plays a critical role in a successful pregnancy as an anti-inflammatory agent, and that it could have possible therapeutic applications in the prevention of early reproductive failure associated with inflammatory disorders.

  1. Loss of Mel-18 enhances breast cancer stem cell activity and tumorigenicity through activating Notch signaling mediated by the Wnt/TCF pathway.

    Science.gov (United States)

    Won, Hee-Young; Lee, Jeong-Yeon; Shin, Dong-Hui; Park, Ji-Hye; Nam, Jeong-Seok; Kim, Hyoung-Chin; Kong, Gu

    2012-12-01

    Mel-18 has been proposed as a negative regulator of Bmi-1, a cancer stem cell (CSC) marker, but it is still unclear whether Mel-18 is involved in CSC regulation. Here, we examined the effect of Mel-18 on the stemness of human breast CSCs. In Mel-18 small hairpin RNA (shRNA)-transduced MCF-7 cells, side population (SP) cells and breast CSC surface marker (CD44(+)/CD24(-)/ESA(+))-expressing cells, which imply a CSC population, were enriched. Moreover, the self-renewal of CSCs was enhanced by Mel-18 knockdown, as measured by the ability for tumorsphere formation in vitro and tumor-initiating capacity in vivo. Similarly, Mel-18 overexpression inhibited the number and self-renewal activity of breast CSCs in SK-BR-3 cells. Furthermore, our data showed that Mel-18 blockade up-regulated the expression of the Wnt/TCF target Jagged-1, a Notch ligand, and consequently activated the Notch pathway. Pharmacologic inhibition of the Notch and Wnt pathways abrogated Mel-18 knockdown-mediated tumorsphere formation ability. Taken together, our findings suggest that Mel-18 is a novel negative regulator of breast CSCs that inhibits the stem cell population and in vitro and in vivo self-renewal through the inactivation of Wnt-mediated Notch signaling.

  2. Basic modelling of transport in 2D wave-mechanical nanodots and billiards with balanced gain and loss mediated by complex potentials

    Science.gov (United States)

    Berggren, Karl-Fredrik; Tellander, Felix; Yakimenko, Irina

    2018-05-01

    Non-Hermitian quantum mechanics with parity-time (PT) symmetry is presently gaining great interest, especially within the fields of photonics and optics. Here, we give a brief overview of low-dimensional semiconductor nanodevices using the example of a quantum dot with input and output leads, which are mimicked by imaginary potentials for gain and loss, and how wave functions, particle flow, coalescence of levels and associated breaking of PT symmetry may be analysed within such a framework. Special attention is given to the presence of exceptional points and symmetry breaking. Related features for musical string instruments and ‘wolf-notes’ are outlined briefly with suggestions for further experiments.

  3. Loss of Intralipid®- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling.

    Directory of Open Access Journals (Sweden)

    Phing-How Lou

    Full Text Available Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury.Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1% was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-% served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained.Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3.Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection.

  4. Pregnancy Loss

    Science.gov (United States)

    ... To receive Pregnancy email updates Enter email Submit Pregnancy loss Pregnancy loss is a harsh reality faced ... have successful pregnancies. Expand all | Collapse all Why pregnancy loss happens As many as 10 to 15 ...

  5. Loss of Mitochondrial Ndufs4 in Striatal Medium Spiny Neurons Mediates Progressive Motor Impairment in a Mouse Model of Leigh Syndrome

    Directory of Open Access Journals (Sweden)

    Byron Chen

    2017-08-01

    Full Text Available Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established. Here, we used a mouse model of LS lacking Ndufs4, a mitochondrial complex I subunit, to confirm that loss of complex I, but not complex II, alters respiration in the striatum. To assess the role of striatal dysfunction in the pathology, we selectively inactivated Ndufs4 in the striatal medium spiny neurons (MSNs, which account for over 95% of striatal neurons. Our results show that lack of Ndufs4 in MSNs causes a non-fatal progressive motor impairment without affecting the cognitive function of mice. Furthermore, no inflammatory responses or neuronal loss were observed up to 6 months of age. Hence, complex I deficiency in MSNs contributes to the motor deficits observed in LS, but not to the neural degeneration, suggesting that other neuronal populations drive the plethora of clinical signs in LS.

  6. Disruption of ion-trafficking system in the cochlear spiral ligament prior to permanent hearing loss induced by exposure to intense noise: possible involvement of 4-hydroxy-2-nonenal as a mediator of oxidative stress.

    Directory of Open Access Journals (Sweden)

    Taro Yamaguchi

    Full Text Available Noise-induced hearing loss is at least in part due to disruption of endocochlear potential, which is maintained by various K(+ transport apparatuses including Na(+, K(+-ATPase and gap junction-mediated intercellular communication in the lateral wall structures. In this study, we examined the changes in the ion-trafficking-related proteins in the spiral ligament fibrocytes (SLFs following in vivo acoustic overstimulation or in vitro exposure of cultured SLFs to 4-hydroxy-2-nonenal, which is a mediator of oxidative stress. Connexin (Cx26 and Cx30 were ubiquitously expressed throughout the spiral ligament, whereas Na(+, K(+-ATPase α1 was predominantly detected in the stria vascularis and spiral prominence (type 2 SLFs. One-hour exposure of mice to 8 kHz octave band noise at a 110 dB sound pressure level produced an immediate and prolonged decrease in the Cx26 expression level and in Na+, K(+-ATPase activity, as well as a delayed decrease in Cx30 expression in the SLFs. The noise-induced hearing loss and decrease in the Cx26 protein level and Na(+, K(+-ATPase activity were abolished by a systemic treatment with a free radical-scavenging agent, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl, or with a nitric oxide synthase inhibitor, N(ω-nitro-L-arginine methyl ester hydrochloride. In vitro exposure of SLFs in primary culture to 4-hydroxy-2-nonenal produced a decrease in the protein levels of Cx26 and Na(+, K(+-ATPase α1, as well as Na(+, K(+-ATPase activity, and also resulted in dysfunction of the intercellular communication between the SLFs. Taken together, our data suggest that disruption of the ion-trafficking system in the cochlear SLFs is caused by the decrease in Cxs level and Na(+, K(+-ATPase activity, and at least in part involved in permanent hearing loss induced by intense noise. Oxidative stress-mediated products might contribute to the decrease in Cxs content and Na(+, K(+-ATPase activity in the cochlear lateral wall structures.

  7. Rac1-mediated membrane raft localization of PI3K/p110β is required for its activation by GPCRs or PTEN loss

    Science.gov (United States)

    Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen; Zhao, Jean J; Roberts, Thomas M

    2016-01-01

    We aimed to understand how spatial compartmentalization in the plasma membrane might contribute to the functions of the ubiquitous class IA phosphoinositide 3-kinase (PI3K) isoforms, p110α and p110β. We found that p110β localizes to membrane rafts in a Rac1-dependent manner. This localization potentiates Akt activation by G-protein-coupled receptors (GPCRs). Thus genetic targeting of a Rac1 binding-deficient allele of p110β to rafts alleviated the requirement for p110β-Rac1 association for GPCR signaling, cell growth and migration. In contrast, p110α, which does not play a physiological role in GPCR signaling, is found to reside in nonraft regions of the plasma membrane. Raft targeting of p110α allowed its EGFR-mediated activation by GPCRs. Notably, p110β dependent, PTEN null tumor cells critically rely upon raft-associated PI3K activity. Collectively, our findings provide a mechanistic account of how membrane raft localization regulates differential activation of distinct PI3K isoforms and offer insight into why PTEN-deficient cancers depend on p110β. DOI: http://dx.doi.org/10.7554/eLife.17635.001 PMID:27700986

  8. A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.

    Science.gov (United States)

    Wang, B; Liu, Y; Huang, L; Chen, J; Li, J J; Wang, R; Kim, E; Chen, Y; Justicia, C; Sakata, K; Chen, H; Planas, A; Ostrom, R S; Li, W; Yang, G; McDonald, M P; Chen, R; Heck, D H; Liao, F-F

    2017-07-01

    Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer's disease, without noticeable systemic toxicity. Despite a short half-life of OS47720 in mouse brain, a single intraperitoneal injection induces rapid and long-lasting (>3 days) nuclear activation of the heat-shock factor, HSF1. Mechanistic study indicates that the remedial effects of OS47720 depend upon HSF1 activation and the subsequent HSF1-mediated transcriptional events on synaptic genes. Taken together, this work reveals a novel role of HSF1 in synaptic function and memory, which likely occurs through modulation of the synaptic transcriptome.

  9. Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.

    Science.gov (United States)

    Vo, Ashley A; Sinha, Aditi; Haas, Mark; Choi, Jua; Mirocha, James; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Jordan, Stanley C

    2015-07-01

    Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern. Between July 2006 and December 2012, 226 highly sensitized patients received transplants after desensitization. Most received alemtuzumab induction and standard immunosuppression. Two groups were examined: ABMR (n = 181) and ABMR (n = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed. Significant risks for ABMR included previous transplants and pregnancies as sensitizing events, donor-specific antibody (DSA) relative intensity scores greater than 17, presence of both class I and II DSAs at transplant and time on waitlist. The ABMR showed a significant benefit for graft survival and glomerular filtration rate at 5 years (P desensitized with I+R who remain ABMR have long-term graft and patient survival. The ABMR patients have significantly reduced graft survival and glomerular filtration rate at 5 years, especially TMA. Severe ABMR episodes benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance and reduction strategies before transplantation are critical to avoiding ABMR and improving long-term outcomes.

  10. Vertical segregation among pathways mediating nitrogen loss (N2 and N2O production) across the oxygen gradient in a coastal upwelling ecosystem

    Science.gov (United States)

    Galán, Alexander; Thamdrup, Bo; Saldías, Gonzalo S.; Farías, Laura

    2017-10-01

    The upwelling system off central Chile (36.5° S) is seasonally subjected to oxygen (O2)-deficient waters, with a strong vertical gradient in O2 (from oxic to anoxic conditions) that spans a few metres (30-50 m interval) over the shelf. This condition inhibits and/or stimulates processes involved in nitrogen (N) removal (e.g. anammox, denitrification, and nitrification). During austral spring (September 2013) and summer (January 2014), the main pathways involved in N loss and its speciation, in the form of N2 and/or N2O, were studied using 15N-tracer incubations, inhibitor assays, and the natural abundance of nitrate isotopes along with hydrographic information. Incubations were developed using water retrieved from the oxycline (25 m depth) and bottom waters (85 m depth) over the continental shelf off Concepción, Chile. Results of 15N-labelled incubations revealed higher N removal activity during the austral summer, with denitrification as the dominant N2-producing pathway, which occurred together with anammox at all times. Interestingly, in both spring and summer maximum potential N removal rates were observed in the oxycline, where a greater availability of oxygen was observed (maximum O2 fluctuation between 270 and 40 µmol L-1) relative to the hypoxic bottom waters ( multiple N-cycling processes are modulating the isotopic nitrate composition over the shelf off central Chile during spring and summer. N removal processes in this coastal system appear to be related to the availability and distribution of oxygen and particles, which are a source of organic matter and the fuel for the production of other electron donors (i.e. ammonium) and acceptors (i.e. nitrate and nitrite) after its remineralization. These results highlight the links between several pathways involved in N loss. They also establish that different mechanisms supported by alternative N substrates are responsible for substantial accumulation of N2O, which are frequently observed as hotspots in the

  11. NPM-ALK mediates phosphorylation of MSH2 at tyrosine 238, creating a functional deficiency in MSH2 and the loss of mismatch repair

    International Nuclear Information System (INIS)

    Bone, K M; Wang, P; Wu, F; Wu, C; Li, L; Bacani, J T; Andrew, S E; Lai, R

    2015-01-01

    The vast majority of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ALCL) tumors express the characteristic oncogenic fusion protein NPM-ALK, which mediates tumorigenesis by exerting its constitutive tyrosine kinase activity on various substrates. We recently identified MSH2, a protein central to DNA mismatch repair (MMR), as a novel binding partner and phosphorylation substrate of NPM-ALK. Here, using liquid chromatography–mass spectrometry, we report for the first time that MSH2 is phosphorylated by NPM-ALK at a specific residue, tyrosine 238. Using GP293 cells transfected with NPM-ALK, we confirmed that the MSH2 Y238F mutant is not tyrosine phosphorylated. Furthermore, transfection of MSH2 Y238F into these cells substantially decreased the tyrosine phosphorylation of endogenous MSH2. Importantly, gene transfection of MSH2 Y238F abrogated the binding of NPM-ALK with endogenous MSH2, re-established the dimerization of MSH2:MSH6 and restored the sensitivity to DNA mismatch-inducing drugs, indicative of MMR return. Parallel findings were observed in two ALK+ALCL cell lines, Karpas 299 and SUP-M2. In addition, we found that enforced expression of MSH2 Y238F into ALK+ALCL cells alone was sufficient to induce spontaneous apoptosis. In conclusion, our findings have identified NPM-ALK-induced phosphorylation of MSH2 at Y238 as a crucial event in suppressing MMR. Our studies have provided novel insights into the mechanism by which oncogenic tyrosine kinases disrupt MMR

  12. Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis.

    Science.gov (United States)

    Azevedo, E P; Ledo, J H; Barbosa, G; Sobrinho, M; Diniz, L; Fonseca, A C C; Gomes, F; Romão, L; Lima, F R S; Palhano, F L; Ferreira, S T; Foguel, D

    2013-09-05

    Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage.

  13. CDK5-mediated phosphorylation of p19INK4d avoids DNA damage-induced neurodegeneration in mouse hippocampus and prevents loss of cognitive functions.

    Science.gov (United States)

    Ogara, María Florencia; Belluscio, Laura M; de la Fuente, Verónica; Berardino, Bruno G; Sonzogni, Silvina V; Byk, Laura; Marazita, Mariela; Cánepa, Eduardo T

    2014-07-01

    DNA damage, which perturbs genomic stability, has been linked to cognitive decline in the aging human brain, and mutations in DNA repair genes have neurological implications. Several studies have suggested that DNA damage is also increased in brain disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. However, the precise mechanisms connecting DNA damage with neurodegeneration remain poorly understood. CDK5, a critical enzyme in the development of the central nervous system, phosphorylates a number of synaptic proteins and regulates dendritic spine morphogenesis, synaptic plasticity and learning. In addition to these physiological roles, CDK5 has been involved in the neuronal death initiated by DNA damage. We hypothesized that p19INK4d, a member of the cell cycle inhibitor family INK4, is involved in a neuroprotective mechanism activated in response to DNA damage. We found that in response to genotoxic injury or increased levels of intracellular calcium, p19INK4d is transcriptionally induced and phosphorylated by CDK5 which provides it with greater stability in postmitotic neurons. p19INK4d expression improves DNA repair, decreases apoptosis and increases neuronal survival under conditions of genotoxic stress. Our in vivo experiments showed that decreased levels of p19INK4d rendered hippocampal neurons more sensitive to genotoxic insult resulting in the loss of cognitive abilities that rely on the integrity of this brain structure. We propose a feedback mechanism by which the neurotoxic effects of CDK5-p25 activated by genotoxic stress or abnormal intracellular calcium levels are counteracted by the induction and stabilization of p19INK4d protein reducing the adverse consequences on brain functions. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

    Science.gov (United States)

    Schaefer, S M; Süsal, C; Opelz, G; Döhler, B; Becker, L E; Klein, K; Sickmüller, S; Waldherr, R; Macher-Goeppinger, S; Schemmer, P; Beimler, J; Zeier, M; Morath, C

    2016-02-01

    Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Experiencing Loss

    DEFF Research Database (Denmark)

    Kristiansen, Maria; Younis, Tarek; Hassani, Amani

    2015-01-01

    In this article, we explore how Islam, minority status and refugee experiencesintersect in shaping meaning-making processes following bereavement. We do this througha phenomenological analysis of a biographical account of personal loss told by Aisha, a Muslim Palestinian refugee living in Denmark......, who narrates her experience of losing herhusband to lung cancer. By drawing on a religious framework, Aisha creates meaning fromher loss, which enables her to incorporate this loss into her life history and sustain agency.Her narrative invites wider audiences to witness her tale of overcoming loss...

  16. In Vivo Modelling of ATP1A3 G316S-Induced Ataxia in C. elegans Using CRISPR/Cas9-Mediated Homologous Recombination Reveals Dominant Loss of Function Defects.

    Directory of Open Access Journals (Sweden)

    Altar Sorkaç

    Full Text Available The NIH Undiagnosed Diseases Program admitted a male patient with unclassifiable late-onset ataxia-like symptoms. Exome sequencing revealed a heterozygous de novo mutation converting glycine 316 to serine in ATP1A3, which might cause disease. ATP1A3 encodes the Na+/K+ ATPase pump α3-subunit. Using CRISPR/Cas9-mediated homologous recombination for genome editing, we modelled this putative disease-causing allele in Caenorhabditis elegans, recreating the patient amino acid change in eat-6, the orthologue of ATP1A3. The impact of the mutation on eat-6 function at the neuromuscular junction was examined using two behavioural assays: rate of pharyngeal pumping and sensitivity to aldicarb, a drug that causes paralysis over time via the inhibition of acetylcholinesterase. The patient allele decreased pumping rates and caused hypersensitivity to aldicarb. Animals heterozygous for the allele exhibited similar defects, whereas loss of function mutations in eat-6 were recessive. These results indicate that the mutation is dominant and impairs the neuromuscular function. Thus, we conclude that the de novo G316S mutation in ATP1A3 likely causes or contributes to patient symptoms. More broadly, we conclude that, for conserved genes, it is possible to rapidly and easily model human diseases in C. elegans using CRIPSR/Cas9 genome editing.

  17. Oolong tea prevents cardiomyocyte loss against hypoxia by attenuating p-JNK mediated hypertrophy and enhancing P-IGF1R, p-akt, and p-Badser136 activity and by fortifying NRF2 antioxidation system.

    Science.gov (United States)

    Shibu, Marthandam Asokan; Kuo, Chia-Hua; Chen, Bih-Cheng; Ju, Da-Tong; Chen, Ray-Jade; Lai, Chao-Hung; Huang, Pei-Jane; Viswanadha, Vijaya Padma; Kuo, Wei-Wen; Huang, Chih-Yang

    2018-02-01

    Tea, the most widely consumed natural beverage has been associated with reduced mortality risk from cardiovascular disease. Oolong tea is a partially fermented tea containing high levels of catechins, their degree of oxidation varies between 20%-80% causing differences in their active metabolites. In this study we examined the effect of oolong tea extract (OTE) obtained by oxidation at low-temperature for short-time against hypoxic injury and found that oolong tea provides cyto-protective effects by suppressing the JNK mediated hypertrophic effects and by enhancing the innate antioxidant mechanisms in neonatal cardiomyocytes and in H9c2 cells. OTE effectively attenuates 24 h hypoxia-triggered cardiomyocyte loss by suppressing caspase-3-cleavage and apoptosis in a dose-dependent manner. OTE also enhances the IGFIR/p-Akt associated survival-mechanism involving the elevation of p-Bad ser136 in a dose-dependent manner to aid cellular adaptations against hypoxic challenge. The results show the effects and mechanism of Oolong tea to provide cardio-protective benefits during hypoxic conditions. © 2017 Wiley Periodicals, Inc.

  18. Memory loss

    Science.gov (United States)

    ... barbiturates or ( hypnotics ) ECT (electroconvulsive therapy) (most often short-term memory loss) Epilepsy that is not well controlled Illness that ... appointment. Medical history questions may include: Type of memory loss, such as short-term or long-term Time pattern, such as how ...

  19. Loss of BMI-1 dampens migration and EMT of colorectal cancer in inflammatory microenvironment through TLR4/MD-2/MyD88-mediated NF-κB signaling.

    Science.gov (United States)

    Ye, Kai; Chen, Qi-Wei; Sun, Ya-Feng; Lin, Jian-An; Xu, Jian-Hua

    2018-02-01

    Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism. We observed that the expression of BMI-1, TNF-α, and IL-1β was significantly increased in HT29 and HCT116 cells after THP-1 Conditioned-Medium (THP-1-CM) stimulation. Additionally, inhibition of BMI-1 impeded cell invasion induced by THP-1-CM-stimulation in both HT29 and HCT116 cells. BMI-1 knockdown remarkably repressed THP-1-CM-induced EMT by regulating the expression of EMT biomarkers with an increase in E-cadherin accompanied by decrease in N-cadherin and vimentin. Furthermore, downregulation of BMI-1 dramatically impeded THP-1-CM-triggered Toll-like receptor 4(TLR4)/myeloid differentiation protein 2(MD-2)/myeloid differentiation factor 88(MyD88) activity by repressing the expression of the TLR4/MD-2 complex and MyD88. Further data demonstrated that knockout of BMI-1 also dampened NF-κB THP-1-CM-triggered activity. Taken all data together, our findings established that BMI-1 modulated TLR4/MD-2/MyD88 complex-mediated NF-κB signaling involved in inflammation-induced cancer cells invasion and EMT, and therefore, could be a potential chemopreventive agent against inflammation-associated colorectal cancer. Establishment of an inflammatory microenvironment. Suppression of BMI-1 reverses THP-1-CM-induced inflammatory cytokine production in CRC. Loss of BMI-1 suppressed TLR4/MD-2/MyD88 complex-mediated NF-κB signaling. © 2017 Wiley

  20. Weight Loss

    Science.gov (United States)

    ... Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For Lawyers Food & Fitness Home Food MyFoodAdvisor ... Fit Types of Activity Weight Loss Assess Your Lifestyle Getting Started Food Choices In My Community Home ...

  1. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  2. Hidden loss

    DEFF Research Database (Denmark)

    Kieffer-Kristensen, Rikke; Johansen, Karen Lise Gaardsvig

    2013-01-01

    to participate. RESULTS: All children were affected by their parents' ABI and the altered family situation. The children's expressions led the authors to identify six themes, including fear of losing the parent, distress and estrangement, chores and responsibilities, hidden loss, coping and support. The main......PRIMARY OBJECTIVE: The purpose of this study was to listen to and learn from children showing high levels of post-traumatic stress symptoms after parental acquired brain injury (ABI), in order to achieve an in-depth understanding of the difficulties the children face in their everyday lives...... finding indicates that the children experienced numerous losses, many of which were often suppressed or neglected by the children to protect the ill parents. CONCLUSIONS: The findings indicated that the children seemed to make a special effort to hide their feelings of loss and grief in order to protect...

  3. Institutionalisation of Mediation for Dispute Resolution in the Field of Social Bankruptcy of Citizens in Russia or how to prevent losses of 300 billions rubles of Russian Federation

    Directory of Open Access Journals (Sweden)

    Avdyev Marat Aleksandrovich

    2015-12-01

    Full Text Available The important problem of modern Russia is poverty of about 22,1 billions citizens. because of illegal action or practice of lending money at unreasonably high rates of interest. About 4,2 billions citizens of Russian are social bankrupts. There are many obstacles for human right in court. Total budget for legal expenses may estimates over than 1,5-2 average annual income of household. Therefore author considers mediation as alternative procedure for dispute resolution between creditors and debtors. Some amendment of law desirable for institutionalization of mediation practice in this types conflicts such as mandatory mediation and so on.

  4. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  5. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  6. Mechanisms of HO-1 mediated attenuation of renal immune injury: a gene profiling study.

    Science.gov (United States)

    Duann, Pu; Lianos, Elias A

    2011-10-01

    Using a mouse model of immune injury directed against the renal glomerular vasculature and resembling human forms of glomerulonephritis (GN), we assessed the effect of targeted expression of the cytoprotective enzyme heme oxygenase (HO)-1. A human (h) HO-1 complementary DNAN (cDNA) sequence was targeted to glomerular epithelial cells (GECs) using a GEC-specific murine nephrin promoter. Injury by administration of antibody against the glomerular basement membrane (anti-GBM) to transgenic (TG) mice with GEC-targeted hHO-1 was attenuated compared with wild-type (WT) controls. To explore changes in the expression of genes that could mediate this salutary effect, we performed gene expression profiling using a microarray analysis of RNA isolated from the renal cortex of WT or TG mice with or without anti-GBM antibody-induced injury. Significant increases in expression were detected in 9 major histocompatibility complex (MHC)-class II genes, 2 interferon-γ (IFN-γ)-inducible guanosine triphosphate (GTP)ases, and 3 genes of the ubiquitin-proteasome system. The increase in MHC-class II and proteasome gene expression in TG mice with injury was validated by real-time polymerase chain reaction (PCR) or Western blot analysis. The observations point to novel mechanisms underlying the cytoprotective effect of HO-1 in renal immune injury. Copyright © 2011. Published by Mosby, Inc.

  7. Living with vision loss

    Science.gov (United States)

    Diabetes - vision loss; Retinopathy - vision loss; Low vision; Blindness - vision loss ... of visual aids. Some options include: Magnifiers High power reading glasses Devices that make it easier to ...

  8. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  9. Hair Loss (Alopecia)

    Science.gov (United States)

    ... care Kids’ zone Video library Find a dermatologist Hair loss Overview Hereditary hair loss: Millions of men ... of hair loss can often be successfully treated. Hair loss: Overview Also called alopecia (al-o-PEE- ...

  10. Ste20-like Kinase, SLK, a Novel Mediator of Podocyte Integrity.

    Science.gov (United States)

    Cybulsky, Andrey V; Papillon, Joan; Guillemette, Julie; Belkina, Natalya; Patino-Lopez, Genaro; Torban, Elena

    2017-11-29

    SLK is essential for embryonic development, and may play a key role in wound healing, tumor growth and metastasis. Expression and activation of SLK is increased in kidney development and during recovery from ischemic acute kidney injury. Overexpression of SLK in glomerular epithelial cells/podocytes in vivo induces injury and proteinuria. Conversely, reduced SLK expression leads to abnormalities in cell adhesion, spreading, and motility. Tight regulation of SLK expression thus may be critical for normal renal structure and function. We produced podocyte-specific SLK knockout mice to address the functional role of SLK in podocytes. Mice with podocyte-specific deletion of SLK showed reduced glomerular SLK expression and activity, compared with control. Podocyte-specific deletion of SLK resulted in albuminuria at 4-5 months of age in male mice, and 8-9 months in female mice, which persisted for up to 13 months. At 11-12 months, knockout mice showed ultrastructural changes, including focal foot process effacement and microvillous transformation of podocyte plasma membranes. Mean foot process width was ~2-fold greater in knockout, compared with control. Podocyte number was reduced by 35% in knockout mice, compared with control, and expression of nephrin, synaptopodin and podocalyxin was reduced in knockout mice by 20-30%. In summary, podocyte-specific deletion of SLK leads to albuminuria, loss of podocytes and morphologic evidence of podocyte injury. Thus, SLK is essential to the maintenance of podocyte integrity as mice age.

  11. TNFα-mediated loss of β-catenin/E-cadherin association and subsequent increase in cell migration is partially restored by NKX3.1 expression in prostate cells.

    Directory of Open Access Journals (Sweden)

    Bilge Debelec-Butuner

    Full Text Available Inflammation-induced carcinogenesis is associated with increased proliferation and migration/invasion of various types of tumor cells. In this study, altered β-catenin signaling upon TNFα exposure, and relation to loss of function of the tumor suppressor NKX3.1 was examined in prostate cancer cells. We used an in vitro prostate inflammation model to demonstrate altered sub-cellular localization of β-catenin following increased phosphorylation of Akt(S473 and GSK3β(S9. Consistently, we observed that subsequent increase in β-catenin transactivation enhanced c-myc, cyclin D1 and MMP2 expressions. Consequently, it was also observed that the β-catenin-E-cadherin association at the plasma membrane was disrupted during acute cytokine exposure. Additionally, it was demonstrated that disrupting cell-cell interactions led to increased migration of LNCaP cells in real-time migration assay. Nevertheless, ectopic expression of NKX3.1, which is degraded upon proinflammatory cytokine exposure in inflammation, was found to induce the degradation of β-catenin by inhibiting Akt(S473 phosphorylation, therefore, partially rescued the disrupted β-catenin-E-cadherin interaction as well as the cell migration in LNCaP cells upon cytokine exposure. As, the disrupted localization of β-catenin at the cell membrane as well as increased Akt(S308 priming phosphorylation was observed in human prostate tissues with prostatic inflammatory atrophy (PIA, high-grade prostatic intraepithelial neoplasia (H-PIN and carcinoma lesions correlated with loss of NKX3.1 expression. Thus, the data indicate that the β-catenin signaling; consequently sub-cellular localization is deregulated in inflammation, associates with prostatic atrophy and PIN pathology.

  12. Understanding Grief and Loss

    Science.gov (United States)

    ... the process of adapting to life after a loss. It is influenced by each person’s society, culture, and religion. Bereavement is the state of having experienced a loss. Common grief reactions Reactions to loss are called ...

  13. Nonsense-mediated mRNA decay and loss-of-function of the protein underlie the X-linked epilepsy associated with the W356× mutation in synapsin I.

    Directory of Open Access Journals (Sweden)

    Maila Giannandrea

    Full Text Available Synapsins are a family of neuronal phosphoproteins associated with the cytosolic surface of synaptic vesicles. Experimental evidence suggests a role for synapsins in synaptic vesicle clustering and recycling at the presynaptic terminal, as well as in neuronal development and synaptogenesis. Synapsin knock-out (Syn1(-/- mice display an epileptic phenotype and mutations in the SYN1 gene have been identified in individuals affected by epilepsy and/or autism spectrum disorder. We investigated the impact of the c.1067G>A nonsense transition, the first mutation described in a family affected by X-linked syndromic epilepsy, on the expression and functional properties of the synapsin I protein. We found that the presence of a premature termination codon in the human SYN1 transcript renders it susceptible to nonsense-mediated mRNA decay (NMD. Given that the NMD efficiency is highly variable among individuals and cell types, we investigated also the effects of expression of the mutant protein and found that it is expressed at lower levels compared to wild-type synapsin I, forms perinuclear aggregates and is unable to reach presynaptic terminals in mature hippocampal neurons grown in culture. Taken together, these data indicate that in patients carrying the W356× mutation the function of synapsin I is markedly impaired, due to both the strongly decreased translation and the altered function of the NMD-escaped protein, and support the value of Syn1(-/- mice as an experimental model mimicking the human pathology.

  14. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  15. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  16. Economic Loan Loss Provision and Expected Loss

    Directory of Open Access Journals (Sweden)

    Stefan Hlawatsch

    2010-10-01

    Full Text Available The intention of a loan loss provision is the anticipation of the loan's expected losses by adjusting the book value of the loan. Furthermore, this loan loss provision has to be compared to the expected loss according to Basel II and, in the case of a difference, liable equity has to be adjusted. This however assumes that the loan loss provision and the expected loss are based on a similar economic rationale, which is only valid conditionally in current loan loss provisioning methods according to IFRS. Therefore, differences between loan loss provisions and expected losses should only result from different approaches regarding the parameter estimation within each model and not due to different assumptions regarding the outcome of the model. The provisioning and accounting model developed in this paper overcomes the before-mentioned shortcomings and is consistent with an economic rationale of expected losses. Additionally, this model is based on a close-to-market valuation of the loan that is in favor of the basic idea of IFRS. Suggestions for changes in current accounting and capital requirement rules are provided.

  17. Loss of Female Sex Hormones Exacerbates Cerebrovascular and Cognitive Dysfunction in Aortic Banded Miniswine Through a Neuropeptide Y-Ca2+-Activated Potassium Channel-Nitric Oxide Mediated Mechanism.

    Science.gov (United States)

    Olver, T Dylan; Hiemstra, Jessica A; Edwards, Jenna C; Schachtman, Todd R; Heesch, Cheryl M; Fadel, Paul J; Laughlin, M Harold; Emter, Craig A

    2017-10-31

    Postmenopausal women represent the largest cohort of patients with heart failure with preserved ejection fraction, and vascular dementia represents the most common form of dementia in patients with heart failure with preserved ejection fraction. Therefore, we tested the hypotheses that the combination of cardiac pressure overload (aortic banding [AB]) and the loss of female sex hormones (ovariectomy [OVX]) impairs cerebrovascular control and spatial memory. Female Yucatan miniswine were separated into 4 groups (n=7 per group): (1) control, (2) AB, (3) OVX, and (4) AB-OVX. Pigs underwent OVX and AB at 7 and 8 months of age, respectively. At 14 months, cerebral blood flow velocity and spatial memory (spatial hole-board task) were lower in the OVX groups ( P <0.05), with significant impairments in the AB-OVX group ( P <0.05). Resting carotid artery β stiffness and vascular resistance during central hypovolemia were increased in the AB-OVX group ( P <0.05), and blood flow recovery after central hypovolemia was reduced in both OVX groups ( P <0.05). Isolated pial artery (pressure myography) vasoconstriction to neuropeptide Y was greatest in the AB-OVX group ( P <0.05), and vasodilation to the Ca 2+ -activated potassium channel α-subunit agonist NS-1619 was impaired in both AB groups ( P <0.05). The ratio of phosphorylated endothelial nitric oxide synthase:total endothelial nitric oxide synthase was depressed and Ca 2+ -activated potassium channel α-subunit protein was increased in AB groups ( P <0.05). Mechanistically, impaired cerebral blood flow control in experimental heart failure may be the result of heightened neuropeptide Y-induced vasoconstriction along with reduced vasodilation associated with decreased Ca 2+ -activated potassium channel function and impaired nitric oxide signaling, the effects of which are exacerbated in the absence of female sex hormones. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. Long-term effects of weight loss with a very-low carbohydrate, low saturated fat diet on flow mediated dilatation in patients with type 2 diabetes: A randomised controlled trial.

    Science.gov (United States)

    Wycherley, Thomas P; Thompson, Campbell H; Buckley, Jonathan D; Luscombe-Marsh, Natalie D; Noakes, Manny; Wittert, Gary A; Brinkworth, Grant D

    2016-09-01

    Very-low carbohydrate diets can improve glycaemic control in patients with type 2 diabetes (T2DM). However, compared to traditional higher carbohydrate, low fat (HighCHO) diets, they have been associated with impaired endothelial function (measured by flow mediated dilatation [FMD]) that is possibly related to saturated fat. This study aimed to examine the effects of a 12-month hypocaloric very-low carbohydrate, low saturated fat (LowCHO) diet compared to an isocaloric HighCHO diet. One hundred and fifteen obese patients with T2DM (age:58.4 ± 0.7 [SEM] yr, BMI:34.6 ± 0.4 kg/m(2), HbA1c:7.33 [56.3 mmol/mol] ± 0.10%) were randomised to consume an energy restricted LowCHO diet (Carb:Pro:Fat:Sat-Fat 14:28:58: < 10% energy; n = 58) or isocaloric HighCHO diet (53:17:30: < 10%; n = 57) whilst undertaking exercise (60 min, 3/wk). Bodyweight, HbA1c and FMD were assessed. Seventy eight participants completed the intervention (LowCHO = 41, HighCHO = 37). Both groups experienced similar reductions in weight and HbA1c (-10.6 ± 0.7 kg, -1.05 ± 0.10%; p < 0.001 time, p ≥ 0.48 time × diet). FMD did not change (p = 0.11 time, p = 0.20 time × diet). In patients with obesity and T2DM, HighCHO diet and LowCHO diet have similar effects on endothelial function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Podocyte-specific loss of cdc42 leads to congenital nephropathy

    DEFF Research Database (Denmark)

    Scott, Rizaldy P; Hawley, Steve P; Ruston, Julie

    2012-01-01

    in the absence of Cdc42, indicating a disruption of the slit diaphragm. Kidneys from Rac1- and RhoA-mutant mice, however, had normal glomerular morphology and intact foot processes. A nephrin clustering assay suggested that Cdc42 deficiency, but not Rac1 or RhoA deficiency, impairs the polymerization of actin...

  20. Hair loss in women.

    Science.gov (United States)

    Harfmann, Katya L; Bechtel, Mark A

    2015-03-01

    Hair loss is a common cause of morbidity for many women. As a key member of the woman's health care team, the obstetrician/gynecologist may be the first person to evaluate the complaint of hair loss. Common types of nonscarring hair loss, including female pattern hair loss and telogen effluvium, may be diagnosed and managed by the obstetrician/gynecologist. A systematic approach to diagnosis and management of these common forms of hair loss is presented.

  1. Unpleasant odors increase aversion to monetary losses.

    Science.gov (United States)

    Stancak, Andrej; Xie, Yuxin; Fallon, Nicholas; Bulsing, Patricia; Giesbrecht, Timo; Thomas, Anna; Pantelous, Athanasios A

    2015-04-01

    Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. PREGNANCY LOSS IN MARES

    Directory of Open Access Journals (Sweden)

    Tibary A

    2015-12-01

    Full Text Available Pregnancy loss is an important aspect of equine practice due to the economic and emotional loss that it engenders. Pregnancy loss is often divided in two categories: early pregnancy loss (EPL or embryonic death (ED (first 42 days and fetal losses (after 42 days. Diagnosis of the causes of pregnancy loss is often very challenging. Many of the causes of EPL remain poorly documented but studies on embryo development and embryo-uterine interaction have been able to shed some light on predisposing factors. Fetal losses or abortions are dominated by infectious causes and particularly bacterial placentitis. Detailed reviews of pregnancy loss were recently published by the authors (Tibary et al., 2012; Tibary and Pearson, 2012; Tibary et al., 2014. The objective of this paper is to provide an overview of the epidemiology, etiology, diagnosis and prevention of pregnancy loss in the mare.

  3. Corona helps curb losses

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, M.; Lahtinen, M.; Lustre, L.

    1996-11-01

    The greatest power losses in electricity transmission arise through a phenomenon called load losses. Corona losses caused by the surface discharge of electricity also constitute a considerable cost item. IVS, the nationwide network company, is investigating corona- induced losses, and has also commissioned similar research from IVO International, the Technical Research Centre of Finland (VTT) and from Tampere University of Technology. The research work strives to gain more in-depth knowledge on the phenomenon of frosting and its impact on corona losses. The correct prediction of frost helps reduce corona losses, while also cutting costs considerably. (orig.)

  4. Telogen Effluvium Hair Loss

    Science.gov (United States)

    ... Category: Share: Yes No, Keep Private Telogen Effluvium Hair Loss Share | It is normal to lose up to ... months after the "shock". This sudden increase in hair loss, usually described as the hair coming out in ...

  5. Recurrent pregnancy loss

    DEFF Research Database (Denmark)

    Egerup, P; Kolte, A M; Larsen, E C

    2016-01-01

    STUDY QUESTION: Is there a different prognostic impact for consecutive and non-consecutive early pregnancy losses in women with secondary recurrent pregnancy loss (RPL)? SUMMARY ANSWER: Only consecutive early pregnancy losses after the last birth have a statistically significant negative prognostic...... impact in women with secondary RPL. WHAT IS KNOWN ALREADY: The risk of a new pregnancy loss increases with the number of previous pregnancy losses in patients with RPL. Second trimester losses seem to exhibit a stronger negative impact than early losses. It is unknown whether the sequence of pregnancy...... losses plays a role for the prognosis in patients with a prior birth. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study of pregnancy outcome in patients with unexplained secondary RPL included in three previously published, Danish double-blinded placebo-controlled trials of intravenous...

  6. Genes and Hearing Loss

    Science.gov (United States)

    ... ENTCareers Marketplace Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  7. Menopause and Bone Loss

    Science.gov (United States)

    Fact Sheet & Menopause Bone Loss How are bone loss and menopause related? Throughout life your body keeps a balance between the ... lose bone faster than it can be replaced. Menopause—the time when menstrual periods end, which usually ...

  8. OI Issues: Hearing Loss

    Science.gov (United States)

    ... signals normally to the brain. In addition, hearing losses are classified according to the degree of severity: • Mild, • Moderate, • Severe, • Profound. Hearing losses are also classified according to the sound frequency ...

  9. Early Pregnancy Loss

    Science.gov (United States)

    ... go on to have successful pregnancies. Repeated pregnancy losses are rare. Testing and evaluation can be done ... find a cause if you have several pregnancy losses. Even if no cause is found, most couples ...

  10. Occupational hearing loss

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001048.htm Occupational hearing loss To use the sharing features on this page, please enable JavaScript. Occupational hearing loss is damage to the inner ear from noise ...

  11. Pregnancy Loss and Miscarriage

    Science.gov (United States)

    ... D linked to miscarriage among women with prior pregnancy loss Release: Anti-HIV drug combination does not increase preterm birth risk, study suggests Release: Elevated blood pressure before pregnancy may increase chance of pregnancy loss All related ...

  12. Coping with Memory Loss

    Science.gov (United States)

    ... Consumers Home For Consumers Consumer Updates Coping With Memory Loss Share Tweet Linkedin Pin it More sharing ... be evaluated by a health professional. What Causes Memory Loss? Anything that affects cognition—the process of ...

  13. Weight Loss Surgery

    Science.gov (United States)

    Weight loss surgery helps people with extreme obesity to lose weight. It may be an option if you cannot lose weight ... obesity. There are different types of weight loss surgery. They often limit the amount of food you ...

  14. Myopic loss aversion revisited

    OpenAIRE

    Blavatskyy, Pavlo; Pogrebna, Ganna

    2009-01-01

    In this paper we reexamine several experimental papers on myopic loss aversion by analyzing individual rather than aggregate choice patterns. We find that the behavior of the majority of subjects is inconsistent with the hypothesis of myopic loss aversion.

  15. Incidental fear cues increase monetary loss aversion.

    Science.gov (United States)

    Schulreich, Stefan; Gerhardt, Holger; Heekeren, Hauke R

    2016-04-01

    In many everyday decisions, people exhibit loss aversion-a greater sensitivity to losses relative to gains of equal size. Loss aversion is thought to be (at least partly) mediated by emotional--in particular, fear-related--processes. Decision research has shown that even incidental emotions, which are unrelated to the decision at hand, can influence decision making. The effect of incidental fear on loss aversion, however, is thus far unclear. In two studies, we experimentally investigated how incidental fear cues, presented during (Study 1) or before (Study 2) choices to accept or reject mixed gambles over real monetary stakes, influence monetary loss aversion. We find that the presentation of fearful faces, relative to the presentation of neutral faces, increased risk aversion-an effect that could be attributed to increased loss aversion. The size of this effect was moderated by psychopathic personality: Fearless dominance, in particular its interpersonal facet, but not self-centered impulsivity, attenuated the effect of incidental fear cues on loss aversion, consistent with reduced fear reactivity. Together, these results highlight the sensitivity of loss aversion to the affective context. (c) 2016 APA, all rights reserved).

  16. Help! It's Hair Loss!

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hair Loss KidsHealth / For Kids / Hair Loss What's in this ... head are in the resting phase. What Causes Hair Loss? Men, especially older men, are the ones who ...

  17. Proven Weight Loss Methods

    Science.gov (United States)

    Fact Sheet Proven Weight Loss Methods What can weight loss do for you? Losing weight can improve your health in a number of ways. It can lower ... at www.hormone.org/Spanish . Proven Weight Loss Methods Fact Sheet www.hormone.org

  18. Energy losses in switches

    International Nuclear Information System (INIS)

    Martin, T.H.; Seamen, J.F.; Jobe, D.O.

    1993-01-01

    The authors experiments show energy losses between 2 and 10 times that of the resistive time predictions. The experiments used hydrogen, helium, air, nitrogen, SF 6 polyethylene, and water for the switching dielectric. Previously underestimated switch losses have caused over predicting the accelerator outputs. Accurate estimation of these losses is now necessary for new high-efficiency pulsed power devices where the switching losses constitute the major portion of the total energy loss. They found that the switch energy losses scale as (V peak I peak ) 1.1846 . When using this scaling, the energy losses in any of the tested dielectrics are almost the same. This relationship is valid for several orders of magnitude and suggested a theoretical basis for these results. Currents up to .65 MA, with voltages to 3 MV were applied to various gaps during these experiments. The authors data and the developed theory indicates that the switch power loss continues for a much longer time than the resistive time, with peak power loss generally occurring at peak current in a ranging discharge instead of the early current time. All of the experiments were circuit code modeled after developing a new switch loss version based on the theory. The circuit code predicts switch energy loss and peak currents as a function of time. During analysis of the data they noticed slight constant offsets between the theory and data that depended on the dielectric. They modified the plasma conductivity for each tested dielectric to lessen this offset

  19. Beam Loss in Linacs

    CERN Document Server

    Plum, M.A.

    2016-01-01

    Beam loss is a critical issue in high-intensity accelerators, and much effort is expended during both the design and operation phases to minimize the loss and to keep it to manageable levels. As new accelerators become ever more powerful, beam loss becomes even more critical. Linacs for H- ion beams, such as the one at the Oak Ridge Spallation Neutron Source, have many more loss mechanisms compared to H+ (proton) linacs, such as the one being designed for the European Spallation Neutron Source. Interesting H- beam loss mechanisms include residual gas stripping, H+ capture and acceleration, field stripping, black-body radiation and the recently discovered intra-beam stripping mechanism. Beam halo formation, and ion source or RF turn on/off transients, are examples of beam loss mechanisms that are common for both H+ and H- accelerators. Machine protection systems play an important role in limiting the beam loss.

  20. [Loss of motivation in the elderly].

    Science.gov (United States)

    Thomas, Philippe; Hazif-Thomas, Cyril; Clément, Jean-Pierre

    2008-06-30

    The loss of motivation is frequent in aged person and sometimes is difficult to assess. It is associated with depression but not exclusively. It overlaps with frontal brain aging consequences. Moreover, somatic problems can interfere with a loss of motivation; loss of motivation is frequent with exhausting chronic diseases, cognitive impairment and it facilitates the social withdrawal. In elderly, loss of motivation blunts the intensity of moral pain. Depressions with conative disorders can move in a dysexecutive syndrome. Even if, owing to the treatment, the cognitive disorders disappear, several years after, an authentic dementia can be diagnosed. With aging process, elderly must cope with losses, less or more balanced: affective, physical and financial losses, triggering the reject of any personal commitment. Aging process also concerns brain amines, especially dopamine, exposing old persons to depression. It alters by a similar way others brain neuro-mediator, such acetylcholine, involved in dementia. Both loss motivation and executive disorders have to be systematically assessed. An antidepressant therapeutic is necessary in case of doubt, improving patients thymic status, quality of life of patients and their family, and sometime of frontal dysfunctions.

  1. Drugs and hair loss.

    Science.gov (United States)

    Patel, Mansi; Harrison, Shannon; Sinclair, Rodney

    2013-01-01

    Hair loss is a common complaint, both in men and women, and use of prescription medications is widespread. When there is a temporal association between the onset of hair loss and commencement of a medication, the medication is commonly thought to have caused the hair loss. However, hair loss and in particular telogen effluvium may occur in response to a number of triggers including fever, hemorrhage, severe illness, stress, and childbirth, and a thorough exclusion of these potential confounders is necessary before the hair loss can be blamed on the medication. Certain medications are known to cause hair loss by a variety of mechanisms including anagen arrest, telogen effluvium, or accentuation of androgenetic alopecia by androgens. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  2. Handbook on loss reserving

    CERN Document Server

    Schmidt, Klaus; Schnaus, Anja

    2016-01-01

    This handbook presents the basic aspects of actuarial loss reserving. Besides the traditional methods, it also includes a description of more recent ones and a discussion of certain problems occurring in actuarial practice, like inflation, scarce data, large claims, slow loss development, the use of market statistics, the need for simulation techniques and the task of calculating best estimates and ranges of future losses. In property and casualty insurance the provisions for payment obligations from losses that have occurred but have not yet been settled usually constitute the largest item on the liabilities side of an insurer's balance sheet. For this reason, the determination and evaluation of these loss reserves is of considerable economic importance for every property and casualty insurer. Actuarial students, academics as well as practicing actuaries will benefit from this overview of the most important actuarial methods of loss reserving by developing an understanding of the underlying stochastic models...

  3. Father Loss and Child Telomere Length.

    Science.gov (United States)

    Mitchell, Colter; McLanahan, Sara; Schneper, Lisa; Garfinkel, Irv; Brooks-Gunn, Jeanne; Notterman, Daniel

    2017-08-01

    Father loss during childhood has negative health and behavioral consequences, but the biological consequences are unknown. Our goal was to examine how father loss (because of separation and/or divorce, death, or incarceration) is associated with cellular function as estimated by telomere length. Data come from the 9-year follow-up of the Fragile Families and Child Wellbeing Study, a birth cohort study of children in 20 large American cities ( N = 2420). Principal measures are as follows: salivary telomere length (sTL), mother reports of father loss, and polymorphisms in genes related to serotonergic and dopaminergic signaling. At 9 years of age, children with father loss have significantly shorter telomeres (14% reduction). Paternal death has the largest association (16%), followed by incarceration (10%), and separation and/or divorce (6%). Changes in income partially mediate these associations (95% mediation for separation and/or divorce, 30% for incarceration, and 25% for death). Effects are 40% greater for boys and 90% greater for children with the most reactive alleles of the serotonin transporter genes when compared with those with the least reactive alleles. No differences were found by age at father loss or a child's race/ethnicity. Father loss has a significant association with children's sTL, with the death of a father showing the largest effect. Income loss explains most of the association between child sTL and separation and/or divorce but much less of the association with incarceration or death. This underscores the important role of fathers in the care and development of children and supplements evidence of the strong negative effects of parental incarceration. Copyright © 2017 by the American Academy of Pediatrics.

  4. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  5. Micro dynamics in mediation

    OpenAIRE

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  6. Hereditary Hearing Loss.

    Science.gov (United States)

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  7. Loss muinasjuturaamatust / Agu Veetamm

    Index Scriptorium Estoniae

    Veetamm, Agu, 1953-

    2004-01-01

    Ballindaloch on üks väheseid Shoti losse, kus omanikud aastaringselt elavad. 450 aastat on loss kuulunud Macpherson-Grantide suguvõsale. Praegu on lossi omanikuks Clare Nancy Macpherson-Grant Russell, kelle kujundatud on kiviktaimla ja rosaarium. Lossi ajaloost, omanikest, ümberehitustest, ringkäigust lossis, pargist. 14 ill

  8. Concurrent credit portfolio losses.

    Science.gov (United States)

    Sicking, Joachim; Guhr, Thomas; Schäfer, Rudi

    2018-01-01

    We consider the problem of concurrent portfolio losses in two non-overlapping credit portfolios. In order to explore the full statistical dependence structure of such portfolio losses, we estimate their empirical pairwise copulas. Instead of a Gaussian dependence, we typically find a strong asymmetry in the copulas. Concurrent large portfolio losses are much more likely than small ones. Studying the dependences of these losses as a function of portfolio size, we moreover reveal that not only large portfolios of thousands of contracts, but also medium-sized and small ones with only a few dozens of contracts exhibit notable portfolio loss correlations. Anticipated idiosyncratic effects turn out to be negligible. These are troublesome insights not only for investors in structured fixed-income products, but particularly for the stability of the financial sector. JEL codes: C32, F34, G21, G32, H81.

  9. Perceived Self-Efficacy and Financial Incentives: Factors Affecting Health Behaviors and Weight Loss in a Workplace Weight Loss Intervention.

    Science.gov (United States)

    Faghri, Pouran D; Simon, Julia; Huedo-Medina, Tania; Gorin, Amy

    2017-05-01

    To evaluate if self-efficacy (SE) and financial incentives (FI) mediate the effect of health behavior on weight loss in a group of overweight and obese nursing-home employees participating in a 16-week weight-loss intervention with 12-week follow-up. Ninety nine overweight/obese (body mass index [BMI] > 25) employees from four nursing-homes participated, with a mean age of 46.98 years and BMI of 35.33. Nursing-homes were randomized to receiving an incentive-based intervention (n = 51) and no incentive (n = 48). Participants' health behaviors and eating and exercise self-efficacy (Ex-SE) were assessed at week 1, 16, and 28 using a self-reported questionnaire. Mediation and moderated mediation analysis assessed relationships among these variables. Eating self-efficacy (Eat-SE) and Ex-SE were significant mediators between health behaviors and weight loss (P self-efficacy (P = 0.00) on weight loss. Self-efficacy and FI may affect weight loss and play a role in weight-loss interventions.

  10. Loss aversion in schizophrenia.

    Science.gov (United States)

    Trémeau, Fabien; Brady, Melissa; Saccente, Erica; Moreno, Alexis; Epstein, Henry; Citrome, Leslie; Malaspina, Dolores; Javitt, Daniel

    2008-08-01

    Loss aversion in decision-making refers to a higher sensitivity to losses than to gains. Loss aversion is conceived as an affective interference in cognitive processes such as judgment and decision-making. Loss aversion in non-risky choices has not been studied in schizophrenia. Forty-two individuals with schizophrenia and 42 non-patient control subjects, matched by gender and age, were randomized to two different scenarios (a buying scenario and a selling scenario). Subjects were asked to evaluate the price of a decorated mug. Schizophrenia subjects were re-tested four weeks later with the other scenario. Contrary to non-patient controls, schizophrenia subjects did not show loss aversion. In the schizophrenia group, absence of loss aversion was correlated with age, duration of illness, number of months in State hospitals, and poorer performance in the Wisconsin Card Sorting Test, but not with current psychopathology and two domains of emotional experience. Absence of loss aversion in schizophrenia represents a deficit in the processing of emotional information during decision-making. It can be interpreted as a lack of integration between the emotional and the cognitive systems, or to a more diffuse and de-differentiated impact of emotional information on decision-making. Future studies should bring more clarity to this question.

  11. Medicines and Bone Loss

    Science.gov (United States)

    ... The doses of thyroid hormone used to treat hypothyroidism (underactive thyroid) don’t harm bone and shouldn’t be cause for concern. Only high doses, used for thyroid cancer treatment, can cause bone loss. High doses or long- ...

  12. Hearing loss - infants

    Science.gov (United States)

    ... can allow many infants to develop normal language skills without delay. In infants born with hearing loss, ... therapy allow many children to develop normal language skills at the same age as their peers with ...

  13. Hearing Loss: Screening Newborns

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Hearing Loss Screening Newborns Past Issues / Spring 2015 Table ... deafness, which account for most cases. Screening Newborns' Hearing Now Standard In 1993, children born in the ...

  14. Main sequence mass loss

    International Nuclear Information System (INIS)

    Brunish, W.M.; Guzik, J.A.; Willson, L.A.; Bowen, G.

    1987-01-01

    It has been hypothesized that variable stars may experience mass loss, driven, at least in part, by oscillations. The class of stars we are discussing here are the δ Scuti variables. These are variable stars with masses between about 1.2 and 2.25 M/sub θ/, lying on or very near the main sequence. According to this theory, high rotation rates enhance the rate of mass loss, so main sequence stars born in this mass range would have a range of mass loss rates, depending on their initial rotation velocity and the amplitude of the oscillations. The stars would evolve rapidly down the main sequence until (at about 1.25 M/sub θ/) a surface convection zone began to form. The presence of this convective region would slow the rotation, perhaps allowing magnetic braking to occur, and thus sharply reduce the mass loss rate. 7 refs

  15. Losses in variable fields

    International Nuclear Information System (INIS)

    Bronca, G.; Fevrier, A.; Genevey, P.; Perot, J.

    1974-01-01

    After a recall of the theory of losses in type 11 superconductors and review of recent work on this topic, the characteristics of what should be an ideal conductor for a pulsed magnet are given. The requirements of pulsed magnets for high energy physics are reviewed and total losses for a 1000 GeV synchrotron estimated. Finally, recent results of prototypes are reported along with the projects of superconducting synchrotron accelerators through the world. (author)

  16. Female pattern hair loss

    Directory of Open Access Journals (Sweden)

    İdil Ünal

    2014-06-01

    Full Text Available Female androgenetic alopecia is the commonest cause of hair loss in women. It is characterized by a diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline and a characteristic pattern distribution in genetically predisposed women. Because of the uncertain relationship with the androgens Female Pattern Hair Loss (FPHL is the most preferred definition of the condition. This review has been focused on the clinical features, diagnosis and treatment alternatives of FPHL.

  17. Hair Loss Myths.

    Science.gov (United States)

    DiMarco, Gabriella; McMichael, Amy

    2017-07-01

    INTRODUCTION: Hair loss is a common complaint seen in dermatology clinics. From frustration and attempts at self-help, patients with hair loss may present to the dermatologist with false beliefs, or myths, about the causes of their condition and what treatments are effective. METHODS: We identified 12 common myths about hair loss, categorized as myths about minoxidil treatment, vitamin and mineral supplements, natural topical treatments, and hair care practices. We performed a PubMed search to find evidence to support or refute each myth. RESULTS: We found that there is little evidence to support many of these common hair loss myths. In some cases, randomized controlled trials have investigated the effects of particular therapies and point to the effectiveness of certain hair loss treatments. DISCUSSION: In many cases, there have not been sufficient randomized controlled trials to evaluate the effect of different therapies and hair care practices on hair loss. It is best to guide patients toward treatments with a long track record of efficacy and away from those where little is known scientifically. J Drugs Dermatol. 2017;16(7):690-694..

  18. Atmosphere Impact Losses

    Science.gov (United States)

    Schlichting, Hilke E.; Mukhopadhyay, Sujoy

    2018-02-01

    Determining the origin of volatiles on terrestrial planets and quantifying atmospheric loss during planet formation is crucial for understanding the history and evolution of planetary atmospheres. Using geochemical observations of noble gases and major volatiles we determine what the present day inventory of volatiles tells us about the sources, the accretion process and the early differentiation of the Earth. We further quantify the key volatile loss mechanisms and the atmospheric loss history during Earth's formation. Volatiles were accreted throughout the Earth's formation, but Earth's early accretion history was volatile poor. Although nebular Ne and possible H in the deep mantle might be a fingerprint of this early accretion, most of the mantle does not remember this signature implying that volatile loss occurred during accretion. Present day geochemistry of volatiles shows no evidence of hydrodynamic escape as the isotopic compositions of most volatiles are chondritic. This suggests that atmospheric loss generated by impacts played a major role during Earth's formation. While many of the volatiles have chondritic isotopic ratios, their relative abundances are certainly not chondritic again suggesting volatile loss tied to impacts. Geochemical evidence of atmospheric loss comes from the {}3He/{}^{22}Ne, halogen ratios (e.g., F/Cl) and low H/N ratios. In addition, the geochemical ratios indicate that most of the water could have been delivered prior to the Moon forming impact and that the Moon forming impact did not drive off the ocean. Given the importance of impacts in determining the volatile budget of the Earth we examine the contributions to atmospheric loss from both small and large impacts. We find that atmospheric mass loss due to impacts can be characterized into three different regimes: 1) Giant Impacts, that create a strong shock transversing the whole planet and that can lead to atmospheric loss globally. 2) Large enough impactors (m_{cap} ≳ √{2

  19. MANAGEMENT OF CREDIT LOSSES

    Directory of Open Access Journals (Sweden)

    Natalya P. Anoshkina

    2018-06-01

    Full Text Available The paper is devoted to the problem of credit loss management topical for modern Russian science and banking practice. The bank’s lending activity is an integral and the most profitable sphere of banking activity. Banks need to take credit risks inherent in their core business and minimize their impact through the establishment of advanced risk management systems. The study, reflected in the present paper, has been conducted in order to determine approaches to the organization of credit loss management in banking. Analysis of the system of management of credit risks and credit losses has shown that they have different scope, object and purpose. In this connection, there is an objective necessity to create a special subsystem for the management of credit losses in banks. On the basis of common bank approaches to credit risk management, the paper develops models of credit loss management: a multi-level management model in the area of ‘operational-tactical-strategic management’ and a functional management model in the area of ‘technology-execution-control’. These models are important for the modern theory and practice of banking, as they allow the bank to manage credit losses on the entire time horizon of the management process, thus opening a wide range of opportunities for the creation and implementation of large-scale programs, as well as specific techniques. This study allows drawing a conclusion about the need to consider control credit losses as a strictly regulated multi-level process, in which each division is assigned with specific objectives, tasks, functions, formally enshrined in the relevant lists, job descriptions and other legal documents.

  20. Losses in Ferroelectric Materials

    Science.gov (United States)

    Liu, Gang; Zhang, Shujun; Jiang, Wenhua; Cao, Wenwu

    2015-01-01

    Ferroelectric materials are the best dielectric and piezoelectric materials known today. Since the discovery of barium titanate in the 1940s, lead zirconate titanate ceramics in the 1950s and relaxor-PT single crystals (such as lead magnesium niobate-lead titanate and lead zinc niobate-lead titanate) in the 1980s and 1990s, perovskite ferroelectric materials have been the dominating piezoelectric materials for electromechanical devices, and are widely used in sensors, actuators and ultrasonic transducers. Energy losses (or energy dissipation) in ferroelectrics are one of the most critical issues for high power devices, such as therapeutic ultrasonic transducers, large displacement actuators, SONAR projectors, and high frequency medical imaging transducers. The losses of ferroelectric materials have three distinct types, i.e., elastic, piezoelectric and dielectric losses. People have been investigating the mechanisms of these losses and are trying hard to control and minimize them so as to reduce performance degradation in electromechanical devices. There are impressive progresses made in the past several decades on this topic, but some confusions still exist. Therefore, a systematic review to define related concepts and clear up confusions is urgently in need. With this objective in mind, we provide here a comprehensive review on the energy losses in ferroelectrics, including related mechanisms, characterization techniques and collections of published data on many ferroelectric materials to provide a useful resource for interested scientists and engineers to design electromechanical devices and to gain a global perspective on the complex physical phenomena involved. More importantly, based on the analysis of available information, we proposed a general theoretical model to describe the inherent relationships among elastic, dielectric, piezoelectric and mechanical losses. For multi-domain ferroelectric single crystals and ceramics, intrinsic and extrinsic energy

  1. Losses in Ferroelectric Materials.

    Science.gov (United States)

    Liu, Gang; Zhang, Shujun; Jiang, Wenhua; Cao, Wenwu

    2015-03-01

    Ferroelectric materials are the best dielectric and piezoelectric materials known today. Since the discovery of barium titanate in the 1940s, lead zirconate titanate ceramics in the 1950s and relaxor-PT single crystals (such as lead magnesium niobate-lead titanate and lead zinc niobate-lead titanate) in the 1980s and 1990s, perovskite ferroelectric materials have been the dominating piezoelectric materials for electromechanical devices, and are widely used in sensors, actuators and ultrasonic transducers. Energy losses (or energy dissipation) in ferroelectrics are one of the most critical issues for high power devices, such as therapeutic ultrasonic transducers, large displacement actuators, SONAR projectors, and high frequency medical imaging transducers. The losses of ferroelectric materials have three distinct types, i.e., elastic, piezoelectric and dielectric losses. People have been investigating the mechanisms of these losses and are trying hard to control and minimize them so as to reduce performance degradation in electromechanical devices. There are impressive progresses made in the past several decades on this topic, but some confusions still exist. Therefore, a systematic review to define related concepts and clear up confusions is urgently in need. With this objective in mind, we provide here a comprehensive review on the energy losses in ferroelectrics, including related mechanisms, characterization techniques and collections of published data on many ferroelectric materials to provide a useful resource for interested scientists and engineers to design electromechanical devices and to gain a global perspective on the complex physical phenomena involved. More importantly, based on the analysis of available information, we proposed a general theoretical model to describe the inherent relationships among elastic, dielectric, piezoelectric and mechanical losses. For multi-domain ferroelectric single crystals and ceramics, intrinsic and extrinsic energy

  2. Congenital sensorineural hearing loss

    International Nuclear Information System (INIS)

    Mafee, M.F.; Selis, J.E.; Yannias, D.A.; Valvassori, G.E.; Pruzansky, S.; Applebaum, E.L.; Capek, V.

    1984-01-01

    The ears of 47 selected patients with congenital sensorineural hearing loss were examined with complex-motion tomography. The patients were divided into 3 general categories: those with a recognized syndrome, those with sensorineural hearing loss unrelated to any known syndrome, and those with microtia. A great variety of inner ear anomalies was detected, but rarely were these characteristic of a particular clinical entity. The most common finding was the Mondini malformation or one of its variants. Isolated dysplasia of the internal auditory canal or the vestibular aqueduct may be responsible for sensorineural hearing loss in some patients. Patients with microtia may also have severe inner ear abnormalities despite the fact that the outer and inner ears develop embryologically from completely separate systems

  3. Congenital sensorineural hearing loss

    Energy Technology Data Exchange (ETDEWEB)

    Mafee, M.F.; Selis, J.E.; Yannias, D.A.; Valvassori, G.E.; Pruzansky, S.; Applebaum, E.L.; Capek, V.

    1984-02-01

    The ears of 47 selected patients with congenital sensorineural hearing loss were examined with complex-motion tomography. The patients were divided into 3 general categories: those with a recognized syndrome, those with sensorineural hearing loss unrelated to any known syndrome, and those with microtia. A great variety of inner ear anomalies was detected, but rarely were these characteristic of a particular clinical entity. The most common finding was the Mondini malformation or one of its variants. Isolated dysplasia of the internal auditory canal or the vestibular aqueduct may be responsible for sensorineural hearing loss in some patients. Patients with microtia may also have severe inner ear abnormalities despite the fact that the outer and inner ears develop embryologically from completely separate systems.

  4. Weight Loss Nutritional Supplements

    Science.gov (United States)

    Eckerson, Joan M.

    Obesity has reached what may be considered epidemic proportions in the United States, not only for adults but for children. Because of the medical implications and health care costs associated with obesity, as well as the negative social and psychological impacts, many individuals turn to nonprescription nutritional weight loss supplements hoping for a quick fix, and the weight loss industry has responded by offering a variety of products that generates billions of dollars each year in sales. Most nutritional weight loss supplements are purported to work by increasing energy expenditure, modulating carbohydrate or fat metabolism, increasing satiety, inducing diuresis, or blocking fat absorption. To review the literally hundreds of nutritional weight loss supplements available on the market today is well beyond the scope of this chapter. Therefore, several of the most commonly used supplements were selected for critical review, and practical recommendations are provided based on the findings of well controlled, randomized clinical trials that examined their efficacy. In most cases, the nutritional supplements reviewed either elicited no meaningful effect or resulted in changes in body weight and composition that are similar to what occurs through a restricted diet and exercise program. Although there is some evidence to suggest that herbal forms of ephedrine, such as ma huang, combined with caffeine or caffeine and aspirin (i.e., ECA stack) is effective for inducing moderate weight loss in overweight adults, because of the recent ban on ephedra manufacturers must now use ephedra-free ingredients, such as bitter orange, which do not appear to be as effective. The dietary fiber, glucomannan, also appears to hold some promise as a possible treatment for weight loss, but other related forms of dietary fiber, including guar gum and psyllium, are ineffective.

  5. ECT and memory loss.

    Science.gov (United States)

    Squire, L R

    1977-09-01

    The author reviews several studies that clarify the nature of the memory loss associated with ECT. Bilateral ECT produced greater anterograde memory loss than right unilateral ECT and more extensive retrograde amnesia than unilateral ECT. Reactivating memories just before ECT did not produce amnesia. Capacity for new learning recovered substantially by several months after ECT, but memory complaints were common in individuals who had received bilateral ECT. Other things being equal, right unilateral ECT seems preferable to bilateral ECT because the risks to memory associated with unilateral ECT are smaller.

  6. Recurrent Pregnancy Loss

    Directory of Open Access Journals (Sweden)

    Véronique Piroux

    1997-01-01

    Full Text Available Antiphospholipid antibodies (APA are associated with thrombosis, thrombocytopenia and fetal loss but they occur in a variety of diseases. Despite many efforts, a correlation between the specificity of particular subgroups of APA and particular clinical situations remains to be established. The antigens at the origin of APA remain to be identified. We discuss here the possible links between cell apoptosis or necrosis, leading to plasma membrane alterations, and the occurrence of APA in response to sustained stimulation. The pathogenic potential of APA is also considered with respect to recurrent pregnancy loss.

  7. Side Effects: Hair Loss (Alopecia)

    Science.gov (United States)

    Hair loss, also called alopecia, is a side effect of cancer treatments, such as chemotherapy and radiation therapy. Learn how to cope with and manage hair loss. Listen to tips from others who have experienced hair loss.

  8. Ionization loss in BGO

    International Nuclear Information System (INIS)

    Bakken, J.A.; Denes, P.; Piroue, P.A.; Stickland, D.P.; Sumner, R.L.; Taylor, C.; Barone, L.; Borgia, B.; Diemoz, M.; Dionisi, C.; Falciano, S.; Ferroni, F.; Gratta, G.; Longo, E.; Luminari, L.; Morganti, S.; Valente, E.; Blaising, J.J.; Boutigny, D.; Coignet, G.; Karyotakis, Y.; Sauvage, G.; Schneegans, M.; Vivargent, M.; Extermann, P.; Morand, G.; Ossmann, J.; Ruckstuhl, W.; Schaad, T.P.; Lecoq, P.; Walk, W.; Li, P.J.; Micke, M.; Micke, U.; Schmitz, D.

    1988-01-01

    We report on a precise measurement of the energy loss through ionization by pions in bismuth germanate performed at several values of the incident particles momentum with a prototype of the L3 electromagnetic calorimeter. The experimental results are in good agreement with theoretical predictions showing the relativistic rise modified by density effect. (orig.)

  9. Heat loss from Buildings

    DEFF Research Database (Denmark)

    Karlsson, Kenneth; Næraa, Rikke

    1997-01-01

    Determination of heat loss coefficients for buildings in Denmark. The coefficient are determined for 15 building groups and 3 year intervals. They are based on the BBR-registre and assumptions of U-values(W/K*m2)and computed in a simple spreed sheet model.The results are used in the REVEILLE...

  10. Independents' group posts loss

    International Nuclear Information System (INIS)

    Sanders, V.; Price, R.B.

    1992-01-01

    Low oil gas prices and special charges caused the group of 50 U.S. independent producers Oil and Gas Journal tracks to post a combined loss in first half 1992. The group logged a net loss of $53 million in the first half compared with net earnings of $354 million in first half 1991, when higher oil prices during the Persian Gulf crisis buoyed earnings in spite of crude oil and natural gas production declines. The combined loss in the first half follows a 45% drop in the group's earnings in 1991 and compares with the OGJ group of integrated oil companies whose first half 1992 income fell 47% from the prior year. Special charges, generally related to asset writedowns, accounted for most of the almost $560 million in losses posted by about the third of the group. Nerco Oil and Gas Inc., Vancouver, Wash., alone accounted for almost half that total with charges related to an asset writedown of $238 million in the first quarter. Despite the poor first half performance, the outlook is bright for sharply improved group earnings in the second half, assuming reasonably healthy oil and gas prices and increased production resulting from acquisitions and in response to those prices

  11. Deafness and Hearing Loss.

    Science.gov (United States)

    National Information Center for Children and Youth with Disabilities, Washington, DC.

    This brief overview provides information on the definition, incidence, and characteristics of children with hearing impairments and deafness. The federal definitions of hearing impairment and deafness are provided. The different types of hearing loss are noted, including: (1) conductive (caused by diseases or obstructions in the outer or middle…

  12. Pregnancy Loss and Miscarriage

    Science.gov (United States)

    ... Bulletins-Gynecology/Early-Pregnancy-Loss What are common symptoms? Causes and Risks How is it diagnosed? Is there a way to prevent? Related A-Z Topics High-Risk Pregnancy Polycystic Ovary Syndrome (PCOS) Stillbirth NICHD News Spotlights Release: Anti-HIV ...

  13. Nordic Mediation Reseach

    DEFF Research Database (Denmark)

    A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden.......A presentation of 12 studies on mediation from researchers from Denmark, Finland, Norway and Sweden....

  14. Bayesian Mediation Analysis

    OpenAIRE

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    This article proposes Bayesian analysis of mediation effects. Compared to conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian mediation analysis, inference is straightforward and exact, which makes it appealing for studies with small samples. Third, the Bayesian approach is conceptua...

  15. mediation: R Package for Causal Mediation Analysis

    Directory of Open Access Journals (Sweden)

    Dustin Tingley

    2014-09-01

    Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

  16. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  17. The role of mediation in resolving workplace relationship conflict.

    Science.gov (United States)

    McKenzie, Donna Margaret

    2015-01-01

    Stress triggered by workplace-based interpersonal conflict can result in damaged relationships, loss of productivity, diminished job satisfaction and increasingly, workers' compensation claims for psychological injury. This paper examined the literature on the role and effectiveness of mediation, as the most common method of Alternative Dispute Resolution, in resolving workplace relationship conflict. Available evidence suggests that mediation is most effective when supported by organisational commitment to ADR strategies, policies and processes, and conducted by independent, experienced and qualified mediators. The United States Postal Service program REDRESS™ is described as an illustration of the successful use of mediation to resolve conflict in the workplace. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Individual Hearing Loss

    Directory of Open Access Journals (Sweden)

    Sébastien Santurette

    2016-06-01

    Full Text Available It is well-established that hearing loss does not only lead to a reduction of hearing sensitivity. Large individual differences are typically observed among listeners with hearing impairment in a wide range of suprathreshold auditory measures. In many cases, audiometric thresholds cannot fully account for such individual differences, which make it challenging to find adequate compensation strategies in hearing devices. How to characterize, model, and compensate for individual hearing loss were the main topics of the fifth International Symposium on Auditory and Audiological Research (ISAAR, held in Nyborg, Denmark, in August 2015. The following collection of papers results from some of the work that was presented and discussed at the symposium.

  19. Decisions under unpredictable losses

    Directory of Open Access Journals (Sweden)

    Ali Ahmed

    2007-10-01

    Full Text Available An experimental test of the descriptive adequacy of the extit{restated diversification principle} is presented. The principle postulates that risk-averse utility maximizers will pool risks for their mutual benefit, even if information is missing about the probabilities of losses. It is enough for people to assume that they face equal risks when they pool risks. The results of the experiment support the principle.

  20. General gauge mediation

    International Nuclear Information System (INIS)

    Meade, Patrick; Seiberg, Nathan; Shih, David

    2009-01-01

    We give a general definition of gauge mediated supersymmetry breaking which encompasses all the known gauge mediation models. In particular, it includes both models with messengers as well as direct mediation models. A formalism for computing the soft terms in the generic model is presented. Such a formalism is necessary in strongly-coupled direct mediation models where perturbation theory cannot be used. It allows us to identify features of the entire class of gauge mediation models and to distinguish them from specific signatures of various subclasses. (author)

  1. Understanding Loss Deductions for Timber

    Science.gov (United States)

    John Greene; Michael Jacobson

    1998-01-01

    Forestland owners whose timber has been destroyed may be eligible to take a deduction for the loss on their federal income tax. The loss must be physical in nature and caused by an identifiable event or combination of events that has run its course. There are two types of losses from natural events. Casualty losses are sudden, unexpected, and unusual - as from a fire...

  2. ADT fast losses MD

    CERN Document Server

    Priebe, A; Dehning, B; Redaelli, S; Salvachua Ferrando, BM; Sapinski, M; Solfaroli Camillocci, M; Valuch, D

    2013-01-01

    The fast beam losses in the order of 1 ms are expected to be a potential major luminosity limitation for higher beam energies after the LHC long shutdown (LS1). Therefore a Quench Test is planned in the winter 2013 to estimate the quench limit in this timescale and revise the current models. This experiment was devoted to determination the LHC Transverse Damper (ADT) as a system for fast losses induction. A non-standard operation of the ADT was used to develop the beam oscillation instead of suppressing them. The sign flip method had allowed us to create the fast losses within several LHC turns at 450 GeV during the previous test (26th March 2012). Thus, the ADT could be potentially used for the studies of the UFO ("Unidentied Falling Object") impact on the cold magnets. Verification of the system capability and investigations of the disturbed beam properties were the main objectives of this MD. During the experiment, the pilot bunches of proton beam were excited independently in the horizontal and vertical ...

  3. Bayesian dynamic mediation analysis.

    Science.gov (United States)

    Huang, Jing; Yuan, Ying

    2017-12-01

    Most existing methods for mediation analysis assume that mediation is a stationary, time-invariant process, which overlooks the inherently dynamic nature of many human psychological processes and behavioral activities. In this article, we consider mediation as a dynamic process that continuously changes over time. We propose Bayesian multilevel time-varying coefficient models to describe and estimate such dynamic mediation effects. By taking the nonparametric penalized spline approach, the proposed method is flexible and able to accommodate any shape of the relationship between time and mediation effects. Simulation studies show that the proposed method works well and faithfully reflects the true nature of the mediation process. By modeling mediation effect nonparametrically as a continuous function of time, our method provides a valuable tool to help researchers obtain a more complete understanding of the dynamic nature of the mediation process underlying psychological and behavioral phenomena. We also briefly discuss an alternative approach of using dynamic autoregressive mediation model to estimate the dynamic mediation effect. The computer code is provided to implement the proposed Bayesian dynamic mediation analysis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. Loss-Aversion or Loss-Attention: The Impact of Losses on Cognitive Performance

    Science.gov (United States)

    Yechiam, Eldad; Hochman, Guy

    2013-01-01

    Losses were found to improve cognitive performance, and this has been commonly explained by increased weighting of losses compared to gains (i.e., loss aversion). We examine whether effects of losses on performance could be modulated by two alternative processes: an attentional effect leading to increased sensitivity to task incentives; and a…

  5. Female pattern hair loss

    Directory of Open Access Journals (Sweden)

    Archana Singal

    2013-01-01

    Full Text Available Female pattern hair loss (FPHL is a common cause of hair loss in women characterized by diffuse reduction in hair density over the crown and frontal scalp with retention of the frontal hairline. Its prevalence increases with advancing age and is associated with significant psychological morbidity. The pathophysiology of FPHL is still not completely understood and seems to be multifactorial. Although androgens have been implicated, the involvement of androgen-independent mechanisms is evident from frequent lack of clinical or biochemical markers of hyperandrogenism in affected women. The role of genetic polymorphisms involving the androgen and estrogen receptors is being increasingly recognized in its causation and predicting treatment response to anti-androgens. There are different clinical patterns and classifications of FPHL, knowledge of which facilitates patient management and research. Chronic telogen effluvium remains as the most important differential diagnosis. Thorough history, clinical examination, and evaluation are essential to confirm diagnosis. Patients with clinical signs of androgen excess require assessment of biochemical parameters and imaging studies. It is prudent to screen the patients for metabolic syndrome and cardiovascular risk factors. The treatment comprises medical and/or surgical modalities. Medical treatment should be initiated early as it effectively arrests hair loss progression rather than stimulating regrowth. Minoxidil continues to be the first line therapy whereas anti-androgens form the second line of treatment. The progressive nature of FPHL mandates long-term treatment for sustained effect. Medical therapy may be supplemented with cosmetic concealment in those desirous of greater hair density. Surgery may be worthwhile in some carefully selected patients.

  6. Causal mediation analysis with multiple mediators.

    Science.gov (United States)

    Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

    2015-03-01

    In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

  7. Acceptable losses: the debatable origins of loss aversion.

    Science.gov (United States)

    Yechiam, Eldad

    2018-04-16

    It is often claimed that negative events carry a larger weight than positive events. Loss aversion is the manifestation of this argument in monetary outcomes. In this review, we examine early studies of the utility function of gains and losses, and in particular the original evidence for loss aversion reported by Kahneman and Tversky (Econometrica  47:263-291, 1979). We suggest that loss aversion proponents have over-interpreted these findings. Specifically, the early studies of utility functions have shown that while very large losses are overweighted, smaller losses are often not. In addition, the findings of some of these studies have been systematically misrepresented to reflect loss aversion, though they did not find it. These findings shed light both on the inability of modern studies to reproduce loss aversion as well as a second literature arguing strongly for it.

  8. Robust loss functions for boosting.

    Science.gov (United States)

    Kanamori, Takafumi; Takenouchi, Takashi; Eguchi, Shinto; Murata, Noboru

    2007-08-01

    Boosting is known as a gradient descent algorithm over loss functions. It is often pointed out that the typical boosting algorithm, Adaboost, is highly affected by outliers. In this letter, loss functions for robust boosting are studied. Based on the concept of robust statistics, we propose a transformation of loss functions that makes boosting algorithms robust against extreme outliers. Next, the truncation of loss functions is applied to contamination models that describe the occurrence of mislabels near decision boundaries. Numerical experiments illustrate that the proposed loss functions derived from the contamination models are useful for handling highly noisy data in comparison with other loss functions.

  9. Loss Aversion and Individual Characteristics

    DEFF Research Database (Denmark)

    Hjorth, Katrine; Fosgerau, Mogens

    2011-01-01

    Many studies have shown that loss aversion affects the valuation of non-market goods. Using stated choice data, this paper presents an empirical investigation of how individual-level loss aversion varies with observable personal characteristics and with the choice context. We investigate loss...... aversion with respect to travel time and money, and find significant loss aversion in both dimensions. The degree of loss aversion in the time dimension is larger than in the money dimension, and depends on age and education. Subjects tend to be more loss averse when the reference is well established....

  10. Tragic loss at CERN

    CERN Multimedia

    CERN Ski Club

    2015-01-01

    Tragic loss at CERN The CERN community is mourning the tragic loss of two members of the CERN Ski Club. On Sunday, April 12, an avalanche buried four out of five skiers, taking part in a ski touring in the region of the Becs de Bosson in Valais (CH). The fifth skier, who had not been buried in the snow,  courageously managed to save two of the skiers, but Hervé Milcent, 49 years, federal ski instructor, and Mattieu Cattin, 33 years, were buried under two to three meters of snow, far down the avalanche slope, and did not survive, despite the fast arrival of the mountain rescue. In its 40 years of existence, the CERN Ski Club, one of the biggest in the Geneva area, has never been confronted with such a tragedy. The passing of Hervé and Matthieu has deeply shocked and saddened all volunteers of the Club as well as the entire alpine community. The ski touring section of the club would like to honour its friend Hervé, who joined the club in 1998. In 2003 he became res...

  11. Female Pattern Hair Loss

    Science.gov (United States)

    Herskovitz, Ingrid; Tosti, Antonella

    2013-01-01

    Context: Female pattern hair loss (FPHL) also known as female androgenetic alopecia is a common condition afflicting millions of women that can be cosmetically disrupting. Prompt diagnosis and treatment are essential for obtaining optimal outcome. This review addresses the clinical presentation of female pattern hair loss, its differential diagnosis and treatment modalities. Evidence Acquisition: A) Diffuse thinning of the crown region with preservation of the frontal hairline (Ludwig’s type) B) The “Christmas tree pattern” where the thinning is wider in the frontal scalp giving the alopecic area a triangular shaped figure resembling a christmas tree. C) Thinning associated with bitemporal recession (Hamilton type). Generally, FPHL is not associated with elevated androgens. Less commonly females with FPHL may have other skin or general signs of hyperandrogenism such as hirsutism, acne, irregular menses, infertility, galactorrhea and insulin resistance. The most common endocrinological abnormality associated with FPHL is polycystic ovarian syndrome (PCOS). Results: The most important diseases to consider in the differential diagnosis of FPHL include Chronic Telogen Effluvium (CTE), Permanent Alopecia after Chemotherapy (PAC), Alopecia Areata Incognito (AAI) and Frontal Fibrosing Alopecia (FFA). This review describes criteria for distinguishing these conditions from FPHL. Conclusions: The only approved treatment for FPHL, which is 2% topical Minoxidil, should be applied at the dosage of 1ml twice day for a minimum period of 12 months. This review will discuss off-label alternative modalities of treatment including 5-alfa reductase inhibitors, antiandrogens, estrogens, prostaglandin analogs, lasers, light treatments and hair transplantation. PMID:24719635

  12. Female pattern hair loss.

    Science.gov (United States)

    Herskovitz, Ingrid; Tosti, Antonella

    2013-10-01

    Female pattern hair loss (FPHL) also known as female androgenetic alopecia is a common condition afflicting millions of women that can be cosmetically disrupting. Prompt diagnosis and treatment are essential for obtaining optimal outcome. This review addresses the clinical presentation of female pattern hair loss, its differential diagnosis and treatment modalities. A) Diffuse thinning of the crown region with preservation of the frontal hairline (Ludwig's type) B) The "Christmas tree pattern" where the thinning is wider in the frontal scalp giving the alopecic area a triangular shaped figure resembling a christmas tree. C) Thinning associated with bitemporal recession (Hamilton type). Generally, FPHL is not associated with elevated androgens. Less commonly females with FPHL may have other skin or general signs of hyperandrogenism such as hirsutism, acne, irregular menses, infertility, galactorrhea and insulin resistance. The most common endocrinological abnormality associated with FPHL is polycystic ovarian syndrome (PCOS). The most important diseases to consider in the differential diagnosis of FPHL include Chronic Telogen Effluvium (CTE), Permanent Alopecia after Chemotherapy (PAC), Alopecia Areata Incognito (AAI) and Frontal Fibrosing Alopecia (FFA). This review describes criteria for distinguishing these conditions from FPHL. The only approved treatment for FPHL, which is 2% topical Minoxidil, should be applied at the dosage of 1ml twice day for a minimum period of 12 months. This review will discuss off-label alternative modalities of treatment including 5-alfa reductase inhibitors, antiandrogens, estrogens, prostaglandin analogs, lasers, light treatments and hair transplantation.

  13. Flexible Mediation Analysis With Multiple Mediators.

    Science.gov (United States)

    Steen, Johan; Loeys, Tom; Moerkerke, Beatrijs; Vansteelandt, Stijn

    2017-07-15

    The advent of counterfactual-based mediation analysis has triggered enormous progress on how, and under what assumptions, one may disentangle path-specific effects upon combining arbitrary (possibly nonlinear) models for mediator and outcome. However, current developments have largely focused on single mediators because required identification assumptions prohibit simple extensions to settings with multiple mediators that may depend on one another. In this article, we propose a procedure for obtaining fine-grained decompositions that may still be recovered from observed data in such complex settings. We first show that existing analytical approaches target specific instances of a more general set of decompositions and may therefore fail to provide a comprehensive assessment of the processes that underpin cause-effect relationships between exposure and outcome. We then outline conditions for obtaining the remaining set of decompositions. Because the number of targeted decompositions increases rapidly with the number of mediators, we introduce natural effects models along with estimation methods that allow for flexible and parsimonious modeling. Our procedure can easily be implemented using off-the-shelf software and is illustrated using a reanalysis of the World Health Organization's Large Analysis and Review of European Housing and Health Status (WHO-LARES) study on the effect of mold exposure on mental health (2002-2003). © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    This study analyzes how a group of ‘mediators’ in a large, multinational company adapted a computer-mediated communication technology (a ‘virtual workspace’) to the organizational context (and vice versa) by modifying features of the technology, providing ongoing support for users, and promoting...... appropriate conventions of use. Our findings corroborate earlier research on technology-use mediation, which suggests that such mediators can exert considerable influence on how a particular technology will be established and used in an organization. However, this study also indicates that the process...... of technology-use mediation is more complex and indeterminate than earlier literature suggests. In particular, we want to draw attention to the fact that advanced computer-mediated communication technologies are equivocal and that technology-use mediation consequently requires ongoing sensemaking (Weick 1995)....

  15. The Schizosaccharomyces pombe Mediator

    DEFF Research Database (Denmark)

    Venturi, Michela

    , Schizosaccharomyces pombe and mammalian Mediator. In our study, we have taken the S. pombe Mediator into consideration and characterized genetically and biochemically two subunits already know in S. cerevisiae, Med9 and Med11, but still not identified in the S. pombe Mediator. Genetic analysis has shown that med9......In the past several years great attention has been dedicated to the characterization of the Mediator complex in a different range of model organisms. Mediator is a conserved co-activator complex involved in transcriptional regulation and it conveys signals from regulatory transcription factors...... to the basal transcription machinery. Mediator was initially isolated from Saccharomyces cerevisiae based on its ability to render a RNA polymerase II in vitro transcription system responsive to activators. Additionally, structural studies have revealed striking structural similarities between S. cerevisiae...

  16. Applied mediation analyses

    DEFF Research Database (Denmark)

    Lange, Theis; Hansen, Kim Wadt; Sørensen, Rikke

    2017-01-01

    In recent years, mediation analysis has emerged as a powerful tool to disentangle causal pathways from an exposure/treatment to clinically relevant outcomes. Mediation analysis has been applied in scientific fields as diverse as labour market relations and randomized clinical trials of heart...... disease treatments. In parallel to these applications, the underlying mathematical theory and computer tools have been refined. This combined review and tutorial will introduce the reader to modern mediation analysis including: the mathematical framework; required assumptions; and software implementation...

  17. Immunologically mediated oral diseases

    OpenAIRE

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  18. Judged seriousness of environmental losses: reliability and cause of loss

    Science.gov (United States)

    Thomas C. Brown; Dawn Nannini; Robert B. Gorter; Paul A. Bell; George L. Peterson

    2002-01-01

    Public judgments of the seriousness of environmental losses were found to be internally consistent for most respondents, and largely unaffected by attempts to manipulate responses by altering the mix of losses being judged. Both findings enhance confidence in the feasibility of developing reliable rankings of the seriousness of environmental losses to aid resource...

  19. Implementing general gauge mediation

    International Nuclear Information System (INIS)

    Carpenter, Linda M.; Dine, Michael; Festuccia, Guido; Mason, John D.

    2009-01-01

    Recently there has been much progress in building models of gauge mediation, often with predictions different than those of minimal gauge mediation. Meade, Seiberg, and Shih have characterized the most general spectrum which can arise in gauge-mediated models. We discuss some of the challenges of building models of general gauge mediation, especially the problem of messenger parity and issues connected with R symmetry breaking and CP violation. We build a variety of viable, weakly coupled models which exhibit some or all of the possible low energy parameters.

  20. Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ao, Ying [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China); Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Li, Bin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Yang, Shuailong; Xia, Liping; Wu, Yong [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); He, Zheng [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, School of Basic Medical Science of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disorder, Wuhan 430071 (China)

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine

  1. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

    International Nuclear Information System (INIS)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-01-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT 2 R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT 1a R)/AT 2 R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT 2 R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT 2 R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits

  2. Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.

    Science.gov (United States)

    Ao, Ying; Sun, Zhaoxia; Hu, Shuangshuang; Zuo, Na; Li, Bin; Yang, Shuailong; Xia, Liping; Wu, Yong; Wang, Linlong; He, Zheng; Wang, Hui

    2015-09-01

    Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis. Copyright © 2015. Published by Elsevier Inc.

  3. Noise-Induced Hearing Loss

    Science.gov (United States)

    ... Home » Health Info » Hearing, Ear Infections, and Deafness Noise-Induced Hearing Loss On this page: What is ... I find additional information about NIHL? What is noise-induced hearing loss? Every day, we experience sound ...

  4. Noise and Hearing Loss Prevention

    Science.gov (United States)

    ... message, please visit this page: About CDC.gov . NOISE AND HEARING LOSS PREVENTION Language: English (US) Español ( ... when hazardous noise levels cannot be adequately reduced. Noise and Hearing Loss on the NIOSH Science Blog ...

  5. Age-related hearing loss

    Science.gov (United States)

    ... grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following factors contribute to age-related hearing loss: Family history (age-related hearing loss tends to run in ...

  6. Overweight, Obesity, and Weight Loss

    Science.gov (United States)

    ... Back to section menu Healthy Weight Weight and obesity Underweight Weight, fertility, and pregnancy Weight loss and ... section Home Healthy Weight Healthy Weight Weight and obesity Underweight Weight, fertility, and pregnancy Weight loss and ...

  7. Hearing Loss: Symptoms, Diagnosis & Treatment

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Hearing Loss Symptoms, Devices, Prevention & Research Past Issues / Spring ... a disease. It can accompany any type of hearing loss. It can be a side effect of ...

  8. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  9. Resource Loss and Gain, Life Satisfaction, and Health Among Retirees in Spain.

    Science.gov (United States)

    Topa, Gabriela; Jiménez, Irene; Valero, Encarna; Ovejero, Anastasio

    2017-04-01

    This article focuses on retirement transition from the Conservation of Resources (COR) perspective to better understand how aged participants' perceptions of retirement losses and gains significantly explain retirement well-being. In this article, the mediation of social support in the losses-well-being relationship is explored. The study was conducted with a two-wave longitudinal design. Participants at T1 were aged Spanish workers (>64 years) and at T2 were retirees, with a final sample of 275, who had retired during the previous 6 months. Findings supported the assertion that losses better explain well-being than gains. In addition, specific losses revealed a higher explaining power of life satisfaction and health complaints depending on their content. Social support mediated between perceived losses and well-being. This study suggests that both perceived losses and gains associated with retirement and social support during retirement should be taken into account when addressing postretirement well-being.

  10. Quantification of surgical blood loss.

    Science.gov (United States)

    Lee, Marcel H; Ingvertsen, Britt T; Kirpensteijn, Jolle; Jensen, Asger L; Kristensen, Annemarie T

    2006-06-01

    To compare gravimetric and colorimetric methods of quantifying surgical blood loss, and to determine if there is a correlation between preoperative hemostatic tests (buccal mucosa bleeding time [BMBT] and intraoperative blood loss). Prospective clinical study. Dogs (n=15) admitted for cutaneous tumor excision, orthopedic procedure, or exploratory laparotomy. Intraoperative blood loss was quantified by measuring irrigation fluid and weighing surgical sponges used for blood and fluid collection during surgery. Results of gravimetric measurements were then correlated to blood loss quantified using spectrophotometric analysis of hemoglobin (Hb) content. Hemostatic variables including BMBT were measured before surgery and compared with the calculated amount of blood loss. Blood loss quantified by gravimetric measurement showed a significant correlation with colorimetric determination of Hb content in surgical sponges and collected irrigation fluid (r=0.93, P<.0001). BMBT correlated weakly but significantly with intraoperative blood loss (r=0.56, P<.05). Quantifying intraoperative blood loss using spectrophotometric Hb analysis accurately assessed the amount of blood loss; however, it is a time-consuming procedure, primarily applicable as a research tool. Gravimetric evaluation of intraoperative blood loss was found to be an accurate method, which can be recommended for use in a clinical setting. Estimation of blood loss using a gravimetric method is accurate and applicable in the clinical setting and provides surgeons with a simple and objective tool to evaluate intraoperative blood loss.

  11. Retroactive Stop Loss Special Pay

    Science.gov (United States)

    Pay (RSLSP), providing $500 for each month/partial month served in stop loss status. Service members served under stop loss must submit a claim for the special pay. Throughout the year, the services have or extension of service, became ineligible to receive retroactive stop loss special pay. There may be

  12. Losses compensation; Compensation des pertes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    One mission of RTE (Electric Power Transportation), is to watch over the losses compensation resulting from the power transport on the electric power network. Since january 2001, RTE makes good the electric losses by the purchase of energy. To choose the marketers, a consultation has been realized by RTE. This document presents the rules concerning these losses compensation. (A.L.B.)

  13. Hypnotherapy in Weight Loss Treatment.

    Science.gov (United States)

    Cochrane, Gordon; Friesen, John

    1986-01-01

    Investigated effects of hypnosis as a treatment for weight loss among women. The primary hypothesis that hypnosis is an effective treatment for weight loss was confirmed, but seven concomitant variables and the use of audiotapes were not significant contributors to weight loss. (Author/ABB)

  14. Teaching Mediated Public Relations.

    Science.gov (United States)

    Kent, Michael L.

    2001-01-01

    Discusses approaches to teaching a mediated public relations course, emphasizing the World Wide Web. Outlines five course objectives, assignments and activities, evaluation, texts, and lecture topics. Argues that students mastering these course objectives will understand ethical issues relating to media use, using mediated technology in public…

  15. Fashion, Mediations & Method Assemblages

    DEFF Research Database (Denmark)

    Sommerlund, Julie; Jespersen, Astrid Pernille

    of handling multiple, fluid realities with multiple, fluid methods. Empirically, the paper works with mediation in fashion - that is efforts the active shaping of relations between producer and consumer through communication, marketing and PR. Fashion mediation is by no means simple, but organise complex...

  16. The Mediated Transparent Society

    DEFF Research Database (Denmark)

    Backer, Lise

    2001-01-01

    in the mediated transparent society. The paper concludes that, based on these analyses, the mediated panopticism working on the business segment is not an effective disciplinary apparatus, which can guarantee that business corporations are carrying out important ecological or ethical improvements....

  17. Laccase/Mediator Systems

    NARCIS (Netherlands)

    Hilgers, Roelant; Vincken, Jean Paul; Gruppen, Harry; Kabel, Mirjam A.

    2018-01-01

    Laccase-mediator systems (LMS) have been widely studied for their capacity to oxidize the nonphenolic subunits of lignin (70-90% of the polymer). The phenolic subunits (10-30% of the polymer), which can also be oxidized without mediators, have received considerably less attention. Consequently, it

  18. The multitalented Mediator complex.

    Science.gov (United States)

    Carlsten, Jonas O P; Zhu, Xuefeng; Gustafsson, Claes M

    2013-11-01

    The Mediator complex is needed for regulated transcription of RNA polymerase II (Pol II)-dependent genes. Initially, Mediator was only seen as a protein bridge that conveyed regulatory information from enhancers to the promoter. Later studies have added many other functions to the Mediator repertoire. Indeed, recent findings show that Mediator influences nearly all stages of transcription and coordinates these events with concomitant changes in chromatin organization. We review the multitude of activities associated with Mediator and discuss how this complex coordinates transcription with other cellular events. We also discuss the inherent difficulties associated with in vivo characterization of a coactivator complex that can indirectly affect diverse cellular processes via changes in gene transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Music, radio and mediatization

    DEFF Research Database (Denmark)

    Michelsen, Morten; Krogh, Mads

    2016-01-01

    of mediatization where media as such seem to be ascribed agency. Instead, we consider historical accounts of music–radio in order to address the complex nonlinearity of concrete processes of mediatization as they take place in the multiple meetings between a decentred notion of radio and musical life.......Mediatization has become a key concept for understanding the relations between media and other cultural and social fields. Contributing to the discussions related to the concept of mediatization, this article discusses how practices of radio and music(al life) influence each other. We follow Deacon......’s and Stanyer’s advice to supplement the concept of mediatization with ‘a series of additional concepts at lower levels of abstraction’ and suggest, in this respect, the notion of heterogeneous milieus of music–radio. Hereby, we turn away from the all-encompassing perspectives related to the concept...

  20. The Impact of Impulsivity on Weight Loss Four Years after Bariatric Surgery

    Directory of Open Access Journals (Sweden)

    Kathrin Schag

    2016-11-01

    Full Text Available Bariatric surgery has serious implications on metabolic health. The reasons for a failure of bariatric surgery, i.e., limited weight loss, are multifactorial and include psychological factors. We established a theoretical model of how impulsivity is related to weight loss outcome. We propose that depressive symptoms act as a mediator between impulsivity and pathological eating behavior, and that pathological eating behavior has a direct impact on weight loss outcome. We calculated excessive weight loss (%EWL and assessed self-reported impulsivity (using the Baratt Impulsiveness Scale (BIS-15 total score, depressive symptoms (the Patient Health Questionnaire (PHQ-9 score, and pathological eating behavior (the Eating Disorder Inventory 2 (EDI-2 total score in 65 patients four years after laparoscopic sleeve gastrectomy. Regression and mediation analyses were computed to validate the theoretical model. The BIS-15, PHQ-9, and EDI-2 have medium to high correlations between each other, and EDI-2 correlated with %EWL. The mediation analysis yielded that the PHQ-9 represents a significant mediator between BIS-15 and EDI-2. The regression model between EDI-2 and %EWL was also significant. These results support our theoretical model, i.e., suggest that impulsivity has an indirect impact on weight loss outcome after bariatric surgery, mediated by depression and transferred through pathological eating behavior. Thus, the underlying psychological factors should be addressed in post-operative care to optimize weight loss outcome.

  1. LDB1-mediated enhancer looping can be established independent of mediator and cohesin.

    Science.gov (United States)

    Krivega, Ivan; Dean, Ann

    2017-08-21

    Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected. Additional deletion of the promoter GATA1 site eliminated LDB1 complex and mediator occupancy and resulted in loss of LCR/β-globin proximity. To separate the roles of LDB1 and mediator in LCR looping, we expressed a looping-competent but transcription-activation deficient form of LDB1 in LDB1 knock down cells: LCR/β-globin proximity was restored without mediator core occupancy. Further, Cas9-directed tethering of mutant LDB1 to the β-globin promoter forced LCR loop formation in the absence of mediator or cohesin occupancy. Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

  2. Sensorineural hearing loss in children.

    LENUS (Irish Health Repository)

    Wormald, R

    2010-02-01

    The objective of the study was to examine the aetiology of sensorineural hearing loss (SNHL) in a paediatric population presenting to the National Centre of Medical Genetics. A retrospective chart review from 1998 to 2006. One hundred and twenty nine children were investigated for SNHL. The average age of diagnosis of hearing loss was 36 months. The degree of hearing loss was mild in 8 children, moderate in 33 children, severe in 31 children and profound in 57 children. Eighty-five children (66%) were diagnosed with a hereditary hearing loss, 11 (8%) children had an acquired hearing loss and no cause found in 33 (26%) children. This is the first report of the causes of hearing loss in Irish children. The mean age of diagnosis in our cohort is high and emphasises the need for a neonatal screening programme. There remains a number of children for whom the cause of hearing loss remains unknown.

  3. [Hearing loss and idoneity--the segnalation of noise-induced hearing loss hearing Loss].

    Science.gov (United States)

    Albera, Roberto; Dagna, Federico; Cassandro, Claudia; Canale, Andrea

    2011-01-01

    Work idoneity in hearing loss must be related to working ability and evolution risks. Working ability is referred to the difficulties found in speech comprehension and in signals perception. As regards hearing loss evolution it is necessary to define if the subject is affected by conductive or neurosensorial hearing loss. In conductive hearing loss it is necessary to evaluate entity and frequential distribution of the deficit. In neurosensorial hearing loss it is necessary to distinguish between noise-induced hearing loss and extraprofessional hearing loss. In noise-induced hearing loss the evolution risk is high if the noise exposure is less than 10-15 years or the actual noise exposure is louder than the former. In case of extraprofessional hearing loss the evolution risk is higher in presbycusis, endolymphatic hydrops and toxic hearing loss. The necessity to report the presence on professionale noise-induced hearing loss arises if audiometric threshold is more than 25 dB at 0.5-1-2-3-4 kHz and if it is verified the professional origine of hearing loss.

  4. General resonance mediation

    International Nuclear Information System (INIS)

    McGarrie, Moritz

    2012-07-01

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for σ(visible → hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  5. General resonance mediation

    Energy Technology Data Exchange (ETDEWEB)

    McGarrie, Moritz

    2012-07-15

    We extend the framework of general gauge mediation to cases where the mediating fields have a nontrivial spectral function, as might arise from strong dynamics. We demonstrate through examples that this setup describes a broad class of possible models of gauge mediated supersymmetry breaking. A main emphasis is to give general formulas for cross sections for {sigma}(visible {yields} hidden) in these resonance models. We will also give formulas for soft masses, A-terms and demonstrate the framework with a holographic setup.

  6. Positively deflected anomaly mediation

    International Nuclear Information System (INIS)

    Okada, Nobuchika

    2002-01-01

    We generalize the so-called 'deflected anomaly mediation' scenario to the case where threshold corrections of heavy messengers to the sparticle squared masses are positive. A concrete model realizing this scenario is also presented. The tachyonic slepton problem can be fixed with only a pair of messengers. The resultant sparticle mass spectrum is quite different from that in the conventional deflected anomaly mediation scenario, but is similar to the one in the gauge mediation scenario. The lightest sparticle is mostly B-ino

  7. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  8. Making mediation work.

    Science.gov (United States)

    Arif, Zeba

    2016-10-26

    Mediation can be an effective way of solving conflict between staff members. It signifies a willingness for people to work together to discuss their differences in a constructive way, before going down the official grievance route.

  9. Technology-Use Mediation

    DEFF Research Database (Denmark)

    Bansler, Jørgen P.; Havn, Erling C.

    2004-01-01

    Implementation of new computer-mediated communication (CMC) systems in organizations is a complex socio-technical endeavour, involving the mutual adaptation of technology and organization over time. Drawing on the analytic concept of sensemaking, this paper provides a theoretical perspective...... that deepens our understanding of how organizations appropriate new electronic communication media. The paper analyzes how a group of mediators in a large, multinational company adapted a new web-based CMC technology (a virtual workspace) to the local organizational context (and vice versa) by modifying...... features of the technology, providing ongoing support for users, and promoting appropriate conventions of use. We found that these mediators exerted considerable influence on how the technology was established and used in the organization. The mediators were not neutral facilitators of a well...

  10. My loss is your loss ... Sometimes: loss aversion and the effect of motivational biases.

    Science.gov (United States)

    Wilson, Robyn S; Arvai, Joseph L; Arkes, Hal R

    2008-08-01

    Findings from previous studies of individual decision-making behavior predict that losses will loom larger than gains. It is less clear, however, if this loss aversion applies to the way in which individuals attribute value to the gains and losses of others, or if it is robust across a broad spectrum of policy and management decision contexts. Consistent with previous work, the results from a series of experiments reported here revealed that subjects exhibited loss aversion when evaluating their own financial gains and losses. The presence of loss aversion was also confirmed for the way in which individuals attribute value to the financial gains and losses of others. However, similar evaluations within social and environmental contexts did not exhibit loss aversion. In addition, research subjects expected that individuals who were unknown to them would significantly undervalue the subjects' own losses across all contexts. The implications of these findings for risk-based policy and management are many. Specifically, they warrant caution when relying upon loss aversion to explain or predict the reaction of affected individuals to risk-based decisions that involve moral or protected values. The findings also suggest that motivational biases may lead decisionmakers to assume that their attitudes and beliefs are common among those affected by a decision, while those affected may expect unfamiliar others to be unable to identify and act in accordance with shared values.

  11. Systemic causes of hair loss.

    Science.gov (United States)

    Lin, Richard L; Garibyan, Lilit; Kimball, Alexandra B; Drake, Lynn A

    2016-09-01

    Hair loss is both a common chief complaint by patients and a clinical challenge for physicians, especially general practitioners, yet few dermatological problems yield as much patient satisfaction when resolved as hair loss. The diagnosis is often attributed to androgen-related hair loss, while other causes, some of which are life-threatening but treatable, are overlooked. We searched for relevant literature on hair loss and supported these findings with our clinical experience to identify seven major systemic etiologies of hair loss, ranging from infectious agents to consumption of unsafe supplements. Many causes are only described in the literature through case studies, though some original articles and meta-analyses are available. Careful history taking, proper examination techniques, and judicious use of laboratory tests are essential to reach at the correct diagnosis in a cost-effective manner when performing patient work-up. Such methodical evaluation of hair loss can result in the appropriate treatment plan and provide significant patient satisfaction. Key messages Hair loss is a common chief complaint and a difficult challenge for both general practitioners and dermatology consultants. We identified seven major categories of systemic hair loss etiology and present a framework for their clinical evaluation. A methodical approach to hair loss can result in the appropriate treatment plan and provide significant patient satisfaction.

  12. Drug-induced hair loss.

    Science.gov (United States)

    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  13. Soil loss prediction using universal soil loss equation (USLE ...

    African Journals Online (AJOL)

    Soil loss prediction using universal soil loss equation (USLE) simulation model in a mountainous area in Ag lasun district, Turkey. ... The need for sufficient knowledge and data for decision makers is obvious hence the present study was carried out. The study area, the Alasun district, is in the middle west of Turkey and is ...

  14. Understanding Mediation Support

    OpenAIRE

    Lanz, David; Pring, Jamie; von Burg, Corinne; Zeller, Mathias

    2017-01-01

    Recent decades have witnessed increasing institutionalization of mediation support through the establishment of mediation support structures (MSS) within foreign ministries and secretariats of multilateral organizations. This study sheds light on this trend and aims to better understand the emergence, design and development of different MSS. This study analyzes six MSS, namely those established in the United Nations (UN), the Organization for Security and Co-operation in Europe (OSCE), the Eu...

  15. ENVIRONMENTAL CONFLICT MEDIATION

    Directory of Open Access Journals (Sweden)

    GABRIELA G. MIHUT

    2011-04-01

    Full Text Available At a time of global economic crisis followed by resource crisis, a period in which the world seeks alternative resources through eco-investment, environmental conflicts are inevitable. Romania is among the few countries that do not pay enough attention to environmental conflicts and to the advantages to of solving them through mediation procedure. The present paper deals with areas in which conflicts can be applied in environmental mediation and its benefits.

  16. The metabolic burden of sleep loss.

    Science.gov (United States)

    Schmid, Sebastian M; Hallschmid, Manfred; Schultes, Bernd

    2015-01-01

    In parallel with the increasing prevalence of obesity and type 2 diabetes, sleep loss has become common in modern societies. An increasing number of epidemiological studies show an association between short sleep duration, sleep disturbances, and circadian desynchronisation of sleep with adverse metabolic traits, in particular obesity and type 2 diabetes. Furthermore, experimental studies point to distinct mechanisms by which insufficient sleep adversely affects metabolic health. Changes in the activity of neuroendocrine systems seem to be major mediators of the detrimental metabolic effects of insufficient sleep, through favouring neurobehavioural outcomes such as increased appetite, enhanced sensitivity to food stimuli, and, ultimately, a surplus in energy intake. The effect of curtailed sleep on physical activity and energy expenditure is less clear, but changes are unlikely to outweigh increases in food intake. Although long-term interventional studies proving a cause and effect association are still scarce, sleep loss seems to be an appealing target for the prevention, and probably treatment, of metabolic disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Acute Zonal Cone Photoreceptor Outer Segment Loss.

    Science.gov (United States)

    Aleman, Tomas S; Sandhu, Harpal S; Serrano, Leona W; Traband, Anastasia; Lau, Marisa K; Adamus, Grazyna; Avery, Robert A

    2017-05-01

    The diagnostic path presented narrows down the cause of acute vision loss to the cone photoreceptor outer segment and will refocus the search for the cause of similar currently idiopathic conditions. To describe the structural and functional associations found in a patient with acute zonal occult photoreceptor loss. A case report of an adolescent boy with acute visual field loss despite a normal fundus examination performed at a university teaching hospital. Results of a complete ophthalmic examination, full-field flash electroretinography (ERG) and multifocal ERG, light-adapted achromatic and 2-color dark-adapted perimetry, and microperimetry. Imaging was performed with spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) and short-wavelength (SW) fundus autofluorescence (FAF), and NIR reflectance (REF). The patient was evaluated within a week of the onset of a scotoma in the nasal field of his left eye. Visual acuity was 20/20 OU, and color vision was normal in both eyes. Results of the fundus examination and of SW-FAF and NIR-FAF imaging were normal in both eyes, whereas NIR-REF imaging showed a region of hyporeflectance temporal to the fovea that corresponded with a dense relative scotoma noted on light-adapted static perimetry in the left eye. Loss in the photoreceptor outer segment detected by SD-OCT co-localized with an area of dense cone dysfunction detected on light-adapted perimetry and multifocal ERG but with near-normal rod-mediated vision according to results of 2-color dark-adapted perimetry. Full-field flash ERG findings were normal in both eyes. The outer nuclear layer and inner retinal thicknesses were normal. Localized, isolated cone dysfunction may represent the earliest photoreceptor abnormality or a distinct entity within the acute zonal occult outer retinopathy complex. Acute zonal occult outer retinopathy should be considered in patients with acute vision loss and abnormalities on NIR-REF imaging, especially if

  18. Genes and Syndromic Hearing Loss.

    Science.gov (United States)

    Keats, Bronya J. B.

    2002-01-01

    This article provides a description of the human genome and patterns of inheritance and discusses genes that are associated with some of the syndromes for which hearing loss is a common finding, including: Waardenburg, Stickler, Jervell and Lange-Neilsen, Usher, Alport, mitochondrial encephalomyopathy, and sensorineural hearing loss. (Contains…

  19. The Stigma of Hearing Loss

    Science.gov (United States)

    Wallhagen, Margaret I.

    2010-01-01

    Purpose: To explore dimensions of stigma experienced by older adults with hearing loss and those with whom they frequently communicate to target interventions promoting engagement and positive aging. Design and Methods: This longitudinal qualitative study conducted interviews over 1 year with dyads where one partner had hearing loss. Participants…

  20. World offshore energy loss statistics

    International Nuclear Information System (INIS)

    Kaiser, Mark J.

    2007-01-01

    Offshore operations present a unique set of environmental conditions and adverse exposure not observed in a land environment taking place in a confined space in a hostile environment under the constant danger of catastrophe and loss. It is possible to engineer some risks to a very low threshold of probability, but losses and unforeseen events can never be entirely eliminated because of cost considerations, the human factor, and environmental uncertainty. Risk events occur infrequently but have the potential of generating large losses, as evident by the 2005 hurricane season in the Gulf of Mexico, which was the most destructive and costliest natural disaster in the history of offshore production. The purpose of this paper is to provide a statistical assessment of energy losses in offshore basins using the Willis Energy Loss database. A description of the loss categories and causes of property damage are provided, followed by a statistical assessment of damage and loss broken out by region, cause, and loss category for the time horizon 1970-2004. The impact of the 2004-2005 hurricane season in the Gulf of Mexico is summarized

  1. An Index of Loss Aversion

    NARCIS (Netherlands)

    Köbberling, V.; Wakker, P.P.

    2005-01-01

    To a considerable extent, risk aversion as it is commonly observed is caused by loss aversion. Several indexes of loss aversion have been proposed in the literature. The one proposed in this paper leads to a clear decomposition of risk attitude into three distinct components: basic utility,

  2. An Index of Loss Aversion

    NARCIS (Netherlands)

    V. Köbberling (Veronika); P.P. Wakker (Peter)

    2005-01-01

    textabstractTo a considerable extent, risk aversion as it is commonly observed is caused by loss aversion. Several indexes of loss aversion have been proposed in the literature. The one proposed in this paper leads to a clear decomposition of risk attitude into three distinct components: basic

  3. mma: An R Package for Mediation Analysis with Multiple Mediators

    OpenAIRE

    Qingzhao Yu; Bin Li

    2017-01-01

    Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous...

  4. [Motivation for weight loss among weight loss treatment participants].

    Science.gov (United States)

    Czeglédi, Edit

    2017-12-01

    Unrealistic expectations about weight goal and about weight loss-related benefits can hinder the effort for a successful long-term weight control. To explore weight loss-related goals and their background among overweight/obese patients. Study sample consisted of patients who participated in the inpatient weight loss treatment in the Lipidological Department of Szent Imre Hospital (n = 339, 19% men). Mean age: 50.2 years (SD = 13.47 years), mean BMI: 38.6 (SD = 7.58). self-reported anthropometric data, type and number of treated illnesses, Goals and Relative Weights Questionnaire, Motivations for Weight Loss Scale, Body Shape Questionnaire. Participants would feel disappointed with a possible 10% weight loss in a half-year time span. The acceptable weight loss percentage was higher among women, younger participants and among those who had more excess weight. Motivation regarding the increase in social desirability by weight loss is in association with body dissatisfaction, health related motivation is in association with the number of treated illnesses. Our results are contributing to the understanding of motivational factors behind weight reduction efforts, considering these can improve treatment success rates. Orv Hetil. 2017; 158(49): 1960-1967.

  5. Development and application of a loop-mediated isothermal ...

    African Journals Online (AJOL)

    Haemophilus parasuis is the causative agent of Glässer's disease that has received much attention recently, due to the increasing economic losses this disease inflicts upon the pig industry worldwide. In this study, loop-mediated isothermal amplification method (LAMP) methodology was designed for diagnosing H.

  6. Icing losses on wind turbines

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, T.; Fotsing, I.; Pearson, S. [Garrad Hassan Canada Inc., Ottawa, ON (Canada)

    2010-07-01

    This PowerPoint presentation discussed some of the energy losses that can occur as a result of icing on wind turbines. Airfoil deterioration can occur in the presence of rime and glaze ice. Anemometers are also impacted by ice, and shut-downs can occur as a result of icing events. Availability deficits that occur during the winter months can lead to annual energy losses of 0.5 percent. The impact of icing events on total wind power energy production in Quebec is estimated at between 1.3 percent to 2.7 percent. Ice loss estimates are considered during the pre-construction phases of wind power projects. However, ice loss prediction methods are often inaccurate. Studies have demonstrated that preconstruction masts show a reasonable correlation with wind turbine icing, and that icing losses are site-specific. tabs., figs.

  7. [Children in family mediation: A practice model].

    Science.gov (United States)

    Mayer, Stefan; Normann, Katrin

    2006-01-01

    The authors briefly describe the history of family mediation under the perspective of the role of the children in the process of mediation. They state that originally children were not directly included. But through empirical studies and different higher escalated families asking for help by mediation, the inclusion of children got an important issue in theory and practice. The discussion began with the question in which phases of the mediation process the children should be included - it went to the issue of the age of the children - and the authors propose to take the amount of escalation in the family as the most important point of reference to decide if and how the children should be included. They suggest to diagnose the loss of responsibility and autonomy of the parents on a nine level scale (from F. Glasl) with the parents and to decide and negotiate with them how the children will be included. They describe five different settings of inclusion of the children.

  8. Analysis of multiparty mediation processes

    NARCIS (Netherlands)

    Vuković, Siniša

    2013-01-01

    Crucial challenges for multiparty mediation processes include the achievement of adequate cooperation among the mediators and consequent coordination of their activities in the mediation process. Existing literature goes only as far as to make it clear that successful mediation requires necessary

  9. Implementation Planning and Progress on Physical Activity Goals: The Mediating Role of Life-Management Strategies

    Science.gov (United States)

    Dugas, Michelle; Gaudreau, Patrick; Carraro, Natasha

    2012-01-01

    This 4-week prospective study examined whether the use of life-management strategies mediates the relationship between implementation planning and short-term progress on physical activity goals. In particular, the strategies of elective selection, compensation, and loss-based selection were disentangled to assess their specific mediating effects.…

  10. Vasoactive mediators and splanchnic perfusion.

    Science.gov (United States)

    Reilly, P M; Bulkley, G B

    1993-02-01

    To provide an overview of the splanchnic hemodynamic response to circulatory shock. Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Pertinent data were abstracted from the cited articles. The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

  11. Nutrition and muscle loss in humans during spaceflight

    Science.gov (United States)

    Stein, T. P.

    1999-01-01

    The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.

  12. Mediation: The Wise Advocacy

    Directory of Open Access Journals (Sweden)

    Towseef Ahmad

    2016-01-01

    Full Text Available AbstractAdversarial litigation is not the only means of resolving disputes and settling of claims. There are various options. Alternative means of dispute resolution can save money and time, and can help to anchor and resolve the dispute while exploring valuable good offices, amicable approaches and facilitation. Mediation, as used in law, is a process of managing negotiation by a neutral third party in the form of Alternative Dispute Resolution (ADR, as a convenient way of resolving disputes between two or more parties with speediation processes. On the sidelines typically, a neutral third party, the mediator assists the parties to negotiate a settlement. The term “mediation” broadly refers to any instance in which a neutral third party helps others to reach an amicable and mutually acceptable agreement. More specifically, mediation has a structure, timetable and dynamic approaches that “ordinary” negotiations usually lack. The process helps the parties to flourish the healthy ideas which are different and distinct from the legal rights in a Court of law. It is well known in International Law also and disputants can submit their disputes to mediation in a variety of matters such as commercial, legal, diplomatic, workplace, community and family matters, which assumes a great significance and it is bricolaged within the framework of this article.Keywords: Adversarial, Litigation, Mediation, Negotiation and Amicable.

  13. Neurally mediated syncope in electroconvulsive therapy maintenance.

    Science.gov (United States)

    Arbaizar, Beatriz; Llorca, Javier

    2012-03-01

    Electroconvulsive therapy (ECT) is especially necessary to revert some types of depressive disease; nevertheless, it has some widely recognized adverse effects, such as short-term memory loss. Moreover, some articles have reported its potential association with falls; this literature is, however, scanty and mainly consists of case reports. We present the case of a man who has a diagnosis of neurally mediated syncope at the age of 79 years, during the maintenance ECT. The patient had a significant increase in syncope frequency in the period he was treated with ECT, followed by a dramatic decrease when ECT was discontinued.

  14. Immunologically mediated oral diseases.

    Science.gov (United States)

    Jimson, Sudha; Balachader, N; Anita, N; Babu, R

    2015-04-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  15. Immunologically mediated oral diseases

    Directory of Open Access Journals (Sweden)

    Sudha Jimson

    2015-01-01

    Full Text Available Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  16. Causal mediation analysis with multiple causally non-ordered mediators.

    Science.gov (United States)

    Taguri, Masataka; Featherstone, John; Cheng, Jing

    2018-01-01

    In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

  17. Ac losses of transposed superconductors

    International Nuclear Information System (INIS)

    Eckert, D.; Enderlein, G.; Lange, F.

    1975-01-01

    Eastham and Rhodes published results of loss measurements on transposed superconducting NbTi cables and concluded basing on an extrapolation to very large numbers of wires that transposed superconductors could be used favorably in cables for power transmission. There are some reasons to question the correctness of their extrapolation. Losses were calculated for transposed superconductors in self field and got results different from those of Eastham and Rhodes. Loss measurements were performed the results of which give evidence for the correctness of our calculations. The results lead to the conclusion that the use of transposed cables of irreversible type 2 superconductors for power transmission is not advantageous

  18. Role of vision loss, functional limitations and the supporting network in depression in a general population.

    Science.gov (United States)

    van Nispen, Ruth M A; Vreeken, Hilde L; Comijs, Hannie C; Deeg, Dorly J H; van Rens, Ger H M B

    2016-02-01

    Although the prevalence of depression in visually impaired older persons is high, the association between vision loss and depression seems to be influenced by factors other than visual impairment. In this study, the role of vision loss, functional limitations and social network characteristics in relation to depressive symptoms was investigated. Cross-sectional data (N = 1237) from the Longitudinal Aging Study Amsterdam were used to investigate the prevalence of depression (Center of Epidemiological Studies-Depression scale) within subgroups with increasing vision loss. In linear regression models, functional limitations and social network characteristics were examined as possible mediators in the association between vision loss and depression. Having a partner was considered to be a potential moderator. Although a significant linear trend was found in the presence of depressive symptoms with 14% in normally sighted, 23% in mild and 37% in severe vision loss (χ(2)(1) = 14.9; p depression. Mediators were functional limitations (p depression, a trend was found with increasing severity of vision loss, indicating the need for more attention in (mental) health care and low-vision rehabilitation. In the general older population, vision loss was not an independent determinant of depression but was mediated by functional limitations and social network size. Rather than receiving actual social support, the idea of having a social network to rely on when needed seemed to be associated with lower levels of depression. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Sleep Loss as a Factor to Induce Cellular and Molecular Inflammatory Variations

    Directory of Open Access Journals (Sweden)

    Gabriela Hurtado-Alvarado

    2013-01-01

    Full Text Available A reduction in the amount of time spent sleeping occurs chronically in modern society. Clinical and experimental studies in humans and animal models have shown that immune function is impaired when sleep loss is experienced. Sleep loss exerts a strong regulatory influence on peripheral levels of inflammatory mediators of the immune response. An increasing number of research projects support the existence of reciprocal regulation between sleep and low-intensity inflammatory response. Recent studies show that sleep deficient humans and rodents exhibit a proinflammatory component; therefore, sleep loss is considered as a risk factor for developing cardiovascular, metabolic, and neurodegenerative diseases (e.g., diabetes, Alzheimer's disease, and multiple sclerosis. Circulating levels of proinflammatory mediators depend on the intensity and duration of the method employed to induce sleep loss. Recognizing the fact that the concentration of proinflammatory mediators is different between acute and chronic sleep-loss may expand the understanding of the relationship between sleep and the immune response. The aim of this review is to integrate data from recent published reports (2002–2013 on the effects of sleep loss on the immune response. This review may allow readers to have an integrated view of the mechanisms involved in central and peripheral deficits induced by sleep loss.

  20. Thermoelastic Loss in Microscale Oscillators

    National Research Council Canada - National Science Library

    Houston, B. H; Photiadis, D. M; Marcus, M. H; Bucaro, J. A; Liu, Xiao; Vignola, J. F

    2001-01-01

    ...) and nanoelectromechanical (NEMS) oscillators. The theory defines a flexural modal participation factor, the fraction of potential energy stored in flexure, and approximates the internal friction by assuming the energy loss to occur solely via...

  1. Hires and Losses Tracking System

    Data.gov (United States)

    Social Security Administration — This database contains data about the hires and losses of employees for the Office of Systems-those who join or leave the Office of Systems and those who transfer...

  2. Mass loss from S stars

    International Nuclear Information System (INIS)

    Jura, M.

    1988-01-01

    The mass-loss process in S stars is studied using 65 S stars from the listing of Wing and Yorka (1977). The role of pulsations in the mass-loss process is examined. It is detected that stars with larger mass-loss rates have a greater amplitude of pulsations. The dust-to-gas ratio for the S stars is estimated as 0.002 and the average mass-loss rate is about 6 x 10 to the -8th solar masses/yr. Some of the properties of the S stars, such as scale height, surface density, and lifetime, are measured. It is determined that scale height is 200 pc; the total duration of the S star phase is greater than or equal to 30,000 yr; and the stars inject 3 x 10 to the -6th solar masses/sq kpc yr into the interstellar medium. 46 references

  3. Rb1 loss modifies but does not initiate alveolar rhabdomyosarcoma

    Science.gov (United States)

    2013-01-01

    Background Alveolar rhabdomyosarcoma (aRMS) is a myogenic childhood sarcoma frequently associated with a translocation-mediated fusion gene, Pax3:Foxo1a. Methods We investigated the complementary role of Rb1 loss in aRMS tumor initiation and progression using conditional mouse models. Results Rb1 loss was not a necessary and sufficient mutational event for rhabdomyosarcomagenesis, nor a strong cooperative initiating mutation. Instead, Rb1 loss was a modifier of progression and increased anaplasia and pleomorphism. Whereas Pax3:Foxo1a expression was unaltered, biomarkers of aRMS versus embryonal rhabdomyosarcoma were both increased, questioning whether these diagnostic markers are reliable in the context of Rb1 loss. Genome-wide gene expression in Pax3:Foxo1a,Rb1 tumors more closely approximated aRMS than embryonal rhabdomyosarcoma. Intrinsic loss of pRb function in aRMS was evidenced by insensitivity to a Cdk4/6 inhibitor regardless of whether Rb1 was intact or null. This loss of function could be attributed to low baseline Rb1, pRb and phospho-pRb expression in aRMS tumors for which the Rb1 locus was intact. Pax3:Foxo1a RNA interference did not increase pRb or improve Cdk inhibitor sensitivity. Human aRMS shared the feature of low and/or heterogeneous tumor cell pRb expression. Conclusions Rb1 loss from an already low pRb baseline is a significant disease modifier, raising the possibility that some cases of pleomorphic rhabdomyosarcoma may in fact be Pax3:Foxo1a-expressing aRMS with Rb1 or pRb loss of function. PMID:24274149

  4. Primary culprit for tooth loss!!

    OpenAIRE

    Nuvvula, Sailavanya; Chava, Vijay Kumar; Nuvvula, Sivakumar

    2016-01-01

    Aim: In order to facilitate planning for dental health services and to progress strategies to continue the reduction in tooth loss, it is important to identify the factors that result in such loss. therefore the aim of the study is to investigate the major cause for tooth extraction. Objective: to examine whether the major reason for tooth extraction is dental caries or periodontal disease. Materials and Methods: The study is carried out among the dental practitioners in our district. A quest...

  5. Economic Inequality Predicts Biodiversity Loss

    OpenAIRE

    Mikkelson, Gregory M.; Gonzalez, Andrew; Peterson, Garry D.

    2007-01-01

    Human activity is causing high rates of biodiversity loss. Yet, surprisingly little is known about the extent to which socioeconomic factors exacerbate or ameliorate our impacts on biological diversity. One such factor, economic inequality, has been shown to affect public health, and has been linked to environmental problems in general. We tested how strongly economic inequality is related to biodiversity loss in particular. We found that among countries, and among US states, the number of sp...

  6. Job loss and broken partnerships

    DEFF Research Database (Denmark)

    Kriegbaum, Margit; Christensen, Ulla; Lund, Rikke

    2008-01-01

    The aim of this study was to investigate the effects of the accumulated number of job losses and broken partnerships (defined as the end of cohabitation) on the risk of fatal and nonfatal events of ischemic heart disease (IHD).......The aim of this study was to investigate the effects of the accumulated number of job losses and broken partnerships (defined as the end of cohabitation) on the risk of fatal and nonfatal events of ischemic heart disease (IHD)....

  7. Water Loss in Small Settlements

    OpenAIRE

    Mindaugas Rimeika; Anželika Jurkienė

    2014-01-01

    The main performance indicators of a water supply system include the quality and safety of water, continuous work, relevant pressure and small water loss. The majority of foreign and local projects on reducing water loss have been carried out in the water supply systems of metropolitans; however, the specificity of small settlements differs from that of big cities. Differences can be observed not only in the development of infrastructure and technical indicators but also in the features of wa...

  8. Occupational hearing loss in farmers.

    OpenAIRE

    Plakke, B L; Dare, E

    1992-01-01

    Studies have shown that there is a great deal of high-frequency sensorineural hearing loss among farmers. The studies have failed, however, to differentiate farmers who have occupational noise exposure only from other potential hearing loss etiologies. This study, through extensive case history information, has isolated a farm noise-exposure group and matched its members by age with persons with no significant noise exposure. Results indicate that farmers exposed only to noise from farming ha...

  9. Loss Aversion in the Laboratory

    OpenAIRE

    Morrison, William G.; Oxoby, Robert J.

    2014-01-01

    We report the results of a laboratory experiment testing for the existence of loss aversion in a standard risk aversion protocol (Holt and Laury, 2002). In our experiment, participants earn and retain money for a week before using it in an incentivized risk preference elicitation task. We find loss aversion, distinct from risk aversion, has a significant effect on behavior resulting in participants requiring higher compensation to bear risk.

  10. Mediation analysis with time varying exposures and mediators.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

    2017-06-01

    In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

  11. Definition of fluctuant hearing loss.

    Science.gov (United States)

    Shea, J J

    1975-06-01

    In summary, fluctuant hearing loss is defined as a disorder of the inner ear characterized by fullness, roaring tinnitus, and fluctuations in hearing. It is believed to be caused by an inadequate absorption of endolymph from the endolymphatic sac, with or without one or more metabolic disorders, that interferes with the delicate balance between the production and absorption of endolymph and thus produces cochlear hydrops. This triad of fullness, roaring tinnitus, and fluctuant hearing loss resulting from cochlear hydrops is much more common than the quadrad of true turning vertigo, fullness, roaring tinnitus, and fluctuant hearing loss due to vestibular and cochlear hydrops known as Meniere's disease. Although patients with fluctuant hearing loss only may eventually develop vertigo as the chief complaint and then be said to have Meniere's disease, it is remarkable how many patients continue to suffer mainly from cochlear symptoms at all times. It would appear, because of the greater frequency of fluctuant hearing loss than in Meniere's disease, that the cochlear labyrinth is more susceptible to hydrops than the vestibular labyrinth. For the purposes of diagnosis and treatment it is very useful to separate patients into those with fluctuant hearing loss and those with Meniere's disease.

  12. When Memories are Mediated

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    that are mediated through stories: told and retold as oral stories through generations, as myths or sagas, or remediated as contemporary documentary film accounts or more fictional film accounts. In these processes of retelling acts of violence, transformations of meanings across time, cultural, social...

  13. Mediated Cultural Memories

    DEFF Research Database (Denmark)

    Frølunde, Lisbeth; Bjerregaard, Mette

    2013-01-01

    generations. Acts of mass violence also construct a sort of looking glass of culturally dominant memories that are mediated through stories: retold as oral stories through generations, as myths or sagas, or remediated in contemporary documentary or fiction films. In these processes of retelling acts...

  14. Cultural mediation in museums

    Directory of Open Access Journals (Sweden)

    Gherghina Boda

    2017-12-01

    Full Text Available If we perceive the museum not only as a place of storing and conserving the patrimony, but also of transmitting it, then we can also see it as a mediator through which cultures can become collective patrimony. Tightly connected to patrimonial appropriation, mediation appears from this perspective as a process and not an end, as it manifests itself in animation, communication and making knowledge popular in relation to a precise patrimony. That is why we can see cultural mediation as a transmission, as a transformation, as an action or social project which aims at creating social bonds, the museum thus being not only a place of meeting for the public with the objects exposed, but also as a place of meeting between different cultures. Thus, cultural mediation presents itself as the most efficient means for access to culture of all categories of the public, situated as the crossroads of culture, continuous education and entertainment and is inscribed in the field of informal education.

  15. The Bensberg Mediation Model

    Directory of Open Access Journals (Sweden)

    Raluca - Marilena Mihalcioiu

    2011-05-01

    Full Text Available The basis of the conflict through the mediation represents the objectives and procedures ofmediation, mediation of a conflict. The conflict will not be disclosed to others, but the parties will be creditedthe authority to resolve the conflict, the conflict among themselves with the help of a mediator. The disputeshould be resolved by the parties with help of a third party. The parties in conflict (it may be several personsare jointly responsible for the solution. They seek together a way that leads to long-term settlement of theconflict. The assumption of responsibility in this process strengthens the confidence and the importance oftheir decision. Important is that losers usually have no peace, because they are out for revenge. Winners don’tneed peace. If both parties lose, remains disappointing, with the understanding of which the conflict isresolved, will understand each other better developed. Reconciliation is therefore a longer-term goal.Conflicts also help to clarify roles. The paper presents Bensberg Model of Mediation, because this isdeveloped as a win win solution and his possible implementation in Romanian schools.

  16. Axionic mirage mediation

    International Nuclear Information System (INIS)

    Nakamura, Shuntaro; Okumura, Ken-ichi; Yamaguchi, Masahiro

    2008-01-01

    Although mirage mediation is one of the most plausible mediation mechanisms of supersymmetry breaking, it suffers from two crucial problems. One is the μ/Bμ problem, and the second is the cosmological one. The former stems from the fact that the B parameter tends to be comparable with the gravitino mass, which is 2 orders of magnitude larger than the other soft masses. The latter problem is caused by the decay of the modulus whose branching ratio into the gravitino pair is sizable. In this paper, we propose a model of mirage mediation, in which Peccei-Quinn symmetry is incorporated. In this axionic mirage mediation, it is shown that the Peccei-Quinn symmetry breaking scale is dynamically determined around 10 10 GeV to 10 12 GeV due to the supersymmetry breaking effects, and the μ problem can be solved naturally. Furthermore, in our model, the lightest supersymmetric particle (LSP) is the axino, that is, the superpartner of the axion. The overabundance of the LSPs due to decays of the modulus/gravitino, which is the most serious cosmological difficulty in the mirage mediation, can be avoided if the axino is sufficiently light. The next-LSPs (NLSPs) produced by the gravitino decay eventually decay into the axino LSPs, yielding the dominant component of the axinos remaining today. It is shown that the axino with a mass of O(100) MeV is naturally realized, which can constitute the dark matter of the Universe, with a free-streaming length of the order of 0.1 Mpc. The saxion, the real scalar component of the axion supermultiplet, can also be cosmologically harmless due to the dilution of the modulus decay. The lifetime of the NLSP is relatively long, but much shorter than 1 sec, when the big-bang nucleosynthesis commences. The decay of the NLSP would provide intriguing collider signatures

  17. Recurrent pregnancy loss: current perspectives

    Directory of Open Access Journals (Sweden)

    El Hachem H

    2017-05-01

    Full Text Available Hady El Hachem,1,2 Vincent Crepaux,3 Pascale May-Panloup,4 Philippe Descamps,3 Guillaume Legendre,3 Pierre-Emmanuel Bouet3 1Department of Reproductive Medicine, Ovo Clinic, Montréal, QC, Canada; 2Department of Obstetrics and Gynecology, University of Montreal, Montréal, QC, Canada; 3Department of Obstetrics and Gynecology, Angers University Hopsital, Angers, France; 4Department of Reproductive Biology, Angers University Hospital, Angers, France Abstract: Recurrent pregnancy loss is an important reproductive health issue, affecting 2%–5% of couples. Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilias, luteal phase deficiency, and high sperm DNA fragmentation levels. Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy. This article reviews the established and controversial etiologies, and the recommended therapeutic strategies, with a special focus on unexplained recurrent pregnancy losses and the empiric treatments used nowadays. It also discusses the current role of preimplantation genetic testing in the management of recurrent pregnancy

  18. Interventional Effects for Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    Vansteelandt, Stijn; Daniel, Rhian M

    2017-03-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

  19. Mediation analysis with multiple versions of the mediator.

    Science.gov (United States)

    Vanderweele, Tyler J

    2012-05-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

  20. Plasmid-mediated mineralization of 4-chlorobiphenyl

    International Nuclear Information System (INIS)

    Shields, M.S.; Hooper, S.W.; Sayler, G.S.

    1985-01-01

    Strains of Alcaligenes and Acinetobacter spp. were isolated from a mixed culture already proven to be proficient at complete mineralization of monohalogenated biphenyls. These strains were shown to harbor a 35 x 10(6)-dalton plasmid mediating a complete pathway for 4-chlorobiphenyl (4CB) oxidation. Subsequent plasmid curing of these bacteria resulted in the abolishment of the 4CB mineralization phenotype and loss of even early 4CB metabolism by Acinetobacter spp. Reestablishment of the Alcaligenes plasmid, denoted pSS50, in the cured Acinetobacter spp. via filter surface mating resulted in the restoration of 4CB mineralization abilities. 4CB mineralization, however, proved to be an unstable characteristic in some subcultured strains. Such loss was not found to coincide with any detectable alteration in plasmid size. Cultures capable of complete mineralization, as well as those limited to partial metabolism of 4CB, produced 4-chlorobenzoate as a metabolite. Demonstration of mineralization of a purified 14 C-labeled chlorobenzoate showed it to be a true intermediate in 4CB mineralization. Unlike the mineralization capability, the ability to produce a metabolite has proven to be stable on subculture. These results indicate the occurrence of a novel plasmid, or evolved catabolic plasmid, that mediates the complete mineralization of 4CB

  1. [Presbycusis - Age Related Hearing Loss].

    Science.gov (United States)

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Occupational hearing loss in Korea.

    Science.gov (United States)

    Kim, Kyoo Sang

    2010-12-01

    In this article, current status of noise exposure in workplaces, trend of workers with noise-induced hearing loss (NIHL), and prevalence of NIHL in workers by industry and job category in Korea were reviewed. In addition, trends of research on the audiological effects such as hearing loss from noise and occupational hearing loss from non-noise in Korea were addressed through reports in industrial audiology. Though noise exposure level has improved, noise still shows the highest rate of cases exceeding exposure limit among workplace hazards. NIHL is the most common occupational disease except work-related disease such as musculoskeletal disorders and cerebrovascular diseases, and NIHL prevalence is thought to be much higher than reported in official publications. Noise affecting hearing comes from various sources such as workplaces, military settings, areas with exposure to high noise, and specific noise sources. There is also occupational hearing loss by non-noise including chemicals such as organic solvents and heavy metals, barotrauma, and trauma due to welding spark. Noise affects daily life through audiological effects such as hearing loss and tinnitus, non-audiological physical effects (e.g., cardiovascular), and psychosocial and behavioral effects. Development of systematic and comprehensive hearing conservation programs for lowering the noise level in workplaces and preventing the NIHL, and preparation of technological, administrative system for its settlement at workplace are urgently needed.

  3. 27 CFR 28.110 - Losses.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Losses. 28.110 Section 28... Manufacturing Bonded Warehouse Losses § 28.110 Losses. Where there has been a loss of distilled spirits while in... of subpart O of this part, with respect to losses of spirits after withdrawal without payment of tax...

  4. Current Directions in Mediation Analysis

    Science.gov (United States)

    MacKinnon, David P.; Fairchild, Amanda J.

    2010-01-01

    Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables. PMID:20157637

  5. Current Directions in Mediation Analysis

    OpenAIRE

    MacKinnon, David P.; Fairchild, Amanda J.

    2009-01-01

    Mediating variables continue to play an important role in psychological theory and research. A mediating variable transmits the effect of an antecedent variable on to a dependent variable, thereby providing more detailed understanding of relations among variables. Methods to assess mediation have been an active area of research for the last two decades. This paper describes the current state of methods to investigate mediating variables.

  6. Economic inequality predicts biodiversity loss.

    Directory of Open Access Journals (Sweden)

    Gregory M Mikkelson

    Full Text Available Human activity is causing high rates of biodiversity loss. Yet, surprisingly little is known about the extent to which socioeconomic factors exacerbate or ameliorate our impacts on biological diversity. One such factor, economic inequality, has been shown to affect public health, and has been linked to environmental problems in general. We tested how strongly economic inequality is related to biodiversity loss in particular. We found that among countries, and among US states, the number of species that are threatened or declining increases substantially with the Gini ratio of income inequality. At both levels of analysis, the connection between income inequality and biodiversity loss persists after controlling for biophysical conditions, human population size, and per capita GDP or income. Future research should explore potential mechanisms behind this equality-biodiversity relationship. Our results suggest that economic reforms would go hand in hand with, if not serving as a prerequisite for, effective conservation.

  7. Economic inequality predicts biodiversity loss.

    Science.gov (United States)

    Mikkelson, Gregory M; Gonzalez, Andrew; Peterson, Garry D

    2007-05-16

    Human activity is causing high rates of biodiversity loss. Yet, surprisingly little is known about the extent to which socioeconomic factors exacerbate or ameliorate our impacts on biological diversity. One such factor, economic inequality, has been shown to affect public health, and has been linked to environmental problems in general. We tested how strongly economic inequality is related to biodiversity loss in particular. We found that among countries, and among US states, the number of species that are threatened or declining increases substantially with the Gini ratio of income inequality. At both levels of analysis, the connection between income inequality and biodiversity loss persists after controlling for biophysical conditions, human population size, and per capita GDP or income. Future research should explore potential mechanisms behind this equality-biodiversity relationship. Our results suggest that economic reforms would go hand in hand with, if not serving as a prerequisite for, effective conservation.

  8. Sleep loss and structural plasticity.

    Science.gov (United States)

    Areal, Cassandra C; Warby, Simon C; Mongrain, Valérie

    2017-06-01

    Wakefulness and sleep are dynamic states during which brain functioning is modified and shaped. Sleep loss is detrimental to many brain functions and results in structural changes localized at synapses in the nervous system. In this review, we present and discuss some of the latest observations of structural changes following sleep loss in some vertebrates and insects. We also emphasize that these changes are region-specific and cell type-specific and that, most importantly, these structural modifications have functional roles in sleep regulation and brain functions. Selected mechanisms driving structural modifications occurring with sleep loss are also discussed. Overall, recent research highlights that extending wakefulness impacts synapse number and shape, which in turn regulate sleep need and sleep-dependent learning/memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Lithium-mediated protection against ethanol neurotoxicity

    Directory of Open Access Journals (Sweden)

    Jia Luo

    2010-06-01

    Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

  10. Hearing loss at work? Hearing loss from leisure activities?

    CERN Multimedia

    2006-01-01

    The nurses of the Medical Service would like invite all persons working on the CERN site to take part in a: HEARING LOSS DETECTION WEEK From 28 August to 1st September 2006 At the Infirmary, Building 57 from 9 a.m. to 4 p.m. Hearing tests - advice - information - documentation - protective equipment

  11. Pathogenesis of age-related bone loss in humans.

    Science.gov (United States)

    Khosla, Sundeep

    2013-10-01

    Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD.

  12. Dissociation in mediation

    Directory of Open Access Journals (Sweden)

    Daniela Muraru

    2008-01-01

    Full Text Available This paper approaches several texts that are part of the so-called discourse of mediation, adopting a pragma-dialectical perspective of the theory of dissociation. It is an attempt to identify the uses of dissociative patterns, with special emphasis on the indicators of dissociation. The paper investigates the various uses of the concept of dissociation as a discursive technique in the argumentation on the different aspects that are involved in international conflict, such as the discussion of the notion of peace. The purpose is to identify the role of dissociation, as a device strategically used by the mediator to help the parties minimize the disagreement space, and come to a conflict resolution.

  13. [Mediation in schools].

    Science.gov (United States)

    Mickley, Angela

    2006-01-01

    In this article the guiding questions concern the objectives and effectiveness of introducing mediation into an existing school culture of dominance, competition and selection. In addition the necessity will be shown of combining conflict resolution with organisational development and the introduction of a consensual ethics and behaviour code to attain sustainable results in creating a constructive and healthy school environment. Given scarce resources and little time the decisive role of artistic methods will be looked at in providing young people with flexible methods of expressing and negotiating their interests in a changing environment of values and power structures. Some aspects of the development of nonviolent communication, conflict resolution and mediation methods in schools in Germany will be focused on with special emphasis on the type of intervention used and its long term sustainable effects.

  14. Church mediation - een vak apart

    NARCIS (Netherlands)

    Annelies Klinefelter; dr Hans A.J. Jonker

    2009-01-01

    Welke rol kan mediation in de kerk spelen in de diverse geledingen en specifieke activiteiten? In dit artikel wordt ingegaan op kerkelijke conflicten, gelaagdheid in church mediation, en specifieke dilemma's van church mediation. Daarnaast komen enkele benaderingen aan bod zoals: helende

  15. Management of hair loss diseases

    Directory of Open Access Journals (Sweden)

    Manabu Ohyama

    2010-12-01

    Full Text Available The treatment of hair loss diseases is sometimes difficult because of insufficient efficacy and limited options. However, recent advances in understanding of the pathophysiology and development of new remedies have improved the treatment of refractory hair loss conditions. In this article, an update on the management of hair loss diseases is provided, especially focusing on recently reported therapeutic approaches for alopecia areata (AA. An accurate diagnosis is indispensable to optimize treatment. Dry dermoscopy represents new diagnostic techniques, which could enable the differentiation of barely indistinguishable alopecias, e.g. AA and trichotillomania. An organized scalp biopsy adopting both vertical and transverse sectioning approaches also provides a deep insight into the pathophysiology of ongoing alopecias. Among various treatments for AA, intraregional corticosteroid and contact immunotherapy have been recognized as first-line therapies. However, some AA cases are refractory to both treatments. Recent studies have demonstrated the efficacy of pulse corticosteroid therapy or the combination of oral psoralen ultraviolet A therapy and systemic corticosteroids for severe AA. Previous clinical observations have suggested the potential role of antihistamines as supportive medications for AA. Experimental evaluation using AA model mice further supports their effectiveness in AA treatment. Finasteride opens up new possibilities for the treatment of androgenetic alopecia. For androgenetic alopecia patients refractory to finasteride, the combination of finasteride with topical minoxidil or the administration of dutasteride, another 5 alpha-reductase inhibitor, may provide better outcomes. Scarring alopecia is the most difficult form of hair loss disorder to treat. The bulge stem cell area is destroyed by unnecessary immune reactions with resultant permanent loss of hair follicle structures in scarring alopecia. Currently, treatment options for

  16. Linking loss of sodium-iodide symporter expression to DNA damage

    International Nuclear Information System (INIS)

    Lyckesvärd, Madeleine Nordén; Kapoor, Nirmal; Ingeson-Carlsson, Camilla; Carlsson, Therese; Karlsson, Jan-Olof; Postgård, Per; Himmelman, Jakob; Forssell-Aronsson, Eva; Hammarsten, Ola; Nilsson, Mikael

    2016-01-01

    Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (<1 nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. - Highlights: • DNA damage inhibits polarized iodide transport in normal thyroid cells. • Down-regulation of NIS expression is mediated by activation of the ATM kinase. • Long-term ATM inhibition also represses NIS-mediated iodide transport. • IGF-1 rescues NIS expression and iodide transport in DNA-damaged cells.

  17. Linking loss of sodium-iodide symporter expression to DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Lyckesvärd, Madeleine Nordén [Sahlgrenska Cancer Center, University of Gothenburg, Göteborg (Sweden); Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Kapoor, Nirmal [Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Ingeson-Carlsson, Camilla; Carlsson, Therese [Sahlgrenska Cancer Center, University of Gothenburg, Göteborg (Sweden); Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Karlsson, Jan-Olof [Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden); Postgård, Per; Himmelman, Jakob; Forssell-Aronsson, Eva [Department of Radiation Physics, University of Gothenburg, Göteborg (Sweden); Hammarsten, Ola [Department of Clinical Chemistry, University of Gothenburg, Göteborg (Sweden); Nilsson, Mikael, E-mail: mikael.nilsson@gu.se [Sahlgrenska Cancer Center, University of Gothenburg, Göteborg (Sweden); Department of Medical Chemistry and Cell Biology, University of Gothenburg, Göteborg (Sweden)

    2016-05-15

    Radiotherapy of thyroid cancer with I-131 is abrogated by inherent loss of radioiodine uptake due to loss of sodium iodide symporter (NIS) expression in poorly differentiated tumor cells. It is also known that ionizing radiation per se down-regulates NIS (the stunning effect), but the mechanism is unknown. Here we investigated whether loss of NIS-mediated iodide transport may be elicited by DNA damage. Calicheamicin, a fungal toxin that specifically cleaves double-stranded DNA, induced a full scale DNA damage response mediated by the ataxia-telangiectasia mutated (ATM) kinase in quiescent normal thyrocytes. At sublethal concentrations (<1 nM) calicheamicin blocked NIS mRNA expression and transepithelial iodide transport as stimulated by thyrotropin; loss of function occurred at a much faster rate than after I-131 irradiation. KU-55933, a selective ATM kinase inhibitor, partly rescued NIS expression and iodide transport in DNA-damaged cells. Prolonged ATM inhibition in healthy cells also repressed NIS-mediated iodide transport. ATM-dependent loss of iodide transport was counteracted by IGF-1. Together, these findings indicate that NIS, the major iodide transporter of the thyroid gland, is susceptible to DNA damage involving ATM-mediated mechanisms. This uncovers novel means of poor radioiodine uptake in thyroid cells subjected to extrinsic or intrinsic genotoxic stress. - Highlights: • DNA damage inhibits polarized iodide transport in normal thyroid cells. • Down-regulation of NIS expression is mediated by activation of the ATM kinase. • Long-term ATM inhibition also represses NIS-mediated iodide transport. • IGF-1 rescues NIS expression and iodide transport in DNA-damaged cells.

  18. The Mediatization of Philanthropy

    OpenAIRE

    Mitchell, Matthew

    2014-01-01

    This study seeks to better understand the motivations and mechanics of individuals contributing to nonprofits organizations today.  Through the prism of our highly mediatized (Hjarvard, 2008) social environment, this study examines the individual motivations and actions of cause-champions running in the 2013 NYC marathon and fundraising through social media and offline on behalf of the Michael J Fox Foundation (MJFF).  To gain the necessary detail and understanding of these micro-actions of a...

  19. Teachers as mediators

    DEFF Research Database (Denmark)

    Dorf, Hans; Kelly, Peter; Hohmann, Ulrike

    2012-01-01

    Within the context of lower secondary English teaching in South West England, this study identifies in broad terms the competing goals between which English teachers mediate and the explicit and hidden tensions that result. To understand the interactions of competing goals, teachers’ goal...... and cultural influences on practice. Yet the teachers observed moved smoothly between goal-oriented behaviours in a continuous and comfortable style, easily and without reflecting any tensions between them. Thus, this article elaborates an account of situated English teaching....

  20. Frequency of intron loss correlates with processed pseudogene abundance: a novel strategy to test the reverse transcriptase model of intron loss.

    Science.gov (United States)

    Zhu, Tao; Niu, Deng-Ke

    2013-03-05

    Although intron loss in evolution has been described, the mechanism involved is still unclear. Three models have been proposed, the reverse transcriptase (RT) model, genomic deletion model and double-strand-break repair model. The RT model, also termed mRNA-mediated intron loss, suggests that cDNA molecules reverse transcribed from spliced mRNA recombine with genomic DNA causing intron loss. Many studies have attempted to test this model based on its predictions, such as simultaneous loss of adjacent introns, 3'-side bias of intron loss, and germline expression of intron-lost genes. Evidence either supporting or opposing the model has been reported. The mechanism of intron loss proposed in the RT model shares the process of reverse transcription with the formation of processed pseudogenes. If the RT model is correct, genes that have produced more processed pseudogenes are more likely to undergo intron loss. In the present study, we observed that the frequency of intron loss is correlated with processed pseudogene abundance by analyzing a new dataset of intron loss obtained in mice and rats. Furthermore, we found that mRNA molecules of intron-lost genes are mostly translated on free cytoplasmic ribosomes, a feature shared by mRNA molecules of the parental genes of processed pseudogenes and long interspersed elements. This feature is likely convenient for intron-lost gene mRNA molecules to be reverse transcribed. Analyses of adjacent intron loss, 3'-side bias of intron loss, and germline expression of intron-lost genes also support the RT model. Compared with previous evidence, the correlation between the abundance of processed pseudogenes and intron loss frequency more directly supports the RT model of intron loss. Exploring such a correlation is a new strategy to test the RT model in organisms with abundant processed pseudogenes.

  1. Technologies for Decreasing Mining Losses

    Science.gov (United States)

    Valgma, Ingo; Väizene, Vivika; Kolats, Margit; Saarnak, Martin

    2013-12-01

    In case of stratified deposits like oil shale deposit in Estonia, mining losses depend on mining technologies. Current research focuses on extraction and separation possibilities of mineral resources. Selective mining, selective crushing and separation tests have been performed, showing possibilities of decreasing mining losses. Rock crushing and screening process simulations were used for optimizing rock fractions. In addition mine backfilling, fine separation, and optimized drilling and blasting have been analyzed. All tested methods show potential and depend on mineral usage. Usage in addition depends on the utilization technology. The questions like stability of the material flow and influences of the quality fluctuations to the final yield are raised.

  2. Postraumatic delayed loss of vision

    International Nuclear Information System (INIS)

    Partington, C.R.; Graves, V.B.; Ruetenacht, D.A.; Weinstein, J.M.; Strother, C.M.

    1989-01-01

    The imaging studies and clinical findings in 10 patients who suffered delayed vision loss beginning 1 day to 13 years after head trauma have been reviewed. Two different primary lesions could be identified: pseudoaneurysm of the internal carotid artery and carotid cavernous fistula. The pathologic changes associated with pseudoaneurysm included compression of the optic nerves and/or chiasm by arterial aneurysm and intracranial hematoma. Carotid cavernous fistula caused delayed vision loss by compression of the optic nerves and chiasm by saccular dilatation of the cavernous sinus and by abnormal orbital venous drainage with retinal venous stasis, retinal edema, and glaucoma

  3. Mass loss and cepheid pulsation

    International Nuclear Information System (INIS)

    Davis, C.G. Jr.

    1977-01-01

    Two purposes are served: to discuss the latest improvements in nonlinear pulsation theory indicating the ability to resolve features such as the ''Christy bump'' on the light curves and to show from the results of a bump model and recent observations that mass loss is one of the possible explanations for the mass discrepancy problem between evolutionary and pulsation theories. Recent observations by Sanford and Gow of Los Alamos and Bernat (McDonald Observatory) show that extensive mass loss has occurred in the evolution of the M supergiant α Orionis

  4. mma: An R Package for Mediation Analysis with Multiple Mediators

    Directory of Open Access Journals (Sweden)

    Qingzhao Yu

    2017-04-01

    Full Text Available Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous, exposure, or mediation variables. With these definitions, multiple mediators of different types can be considered simultaneously, and the indirect effects carried by individual mediators can be separated from the total effect. Moreover, the derived mediation analysis can be performed with general predictive models. That is, the relationships among variables can be modeled using not only generalized linear models but also nonparametric models such as the Multiple Additive Regression Trees. Therefore, more complicated variable transformations and interactions can be considered in analyzing the mediation effects. The proposed method is realized by the R package 'mma'. We illustrate in this paper the proposed method and how to use 'mma' to estimate mediation effects and make inferences.

  5. Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

    Science.gov (United States)

    Huang, Yen-Tsung; Yang, Hwai-I

    2017-05-01

    Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

  6. Immune mediated liver failure.

    Science.gov (United States)

    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  7. Lopsided Gauge Mediation

    CERN Document Server

    De Simone, Andrea; Giudice, Gian Francesco; Pappadopulo, Duccio; Rattazzi, Riccardo

    2011-01-01

    It has been recently pointed out that the unavoidable tuning among supersymmetric parameters required to raise the Higgs boson mass beyond its experimental limit opens up new avenues for dealing with the so called $\\mu$-$B_\\mu$ problem of gauge mediation. In fact, it allows for accommodating, with no further parameter tuning, large values of $B_\\mu$ and of the other Higgs-sector soft masses, as predicted in models where both $\\mu$ and $B_\\mu$ are generated at one-loop order. This class of models, called Lopsided Gauge Mediation, offers an interesting alternative to conventional gauge mediation and is characterized by a strikingly different phenomenology, with light higgsinos, very large Higgs pseudoscalar mass, and moderately light sleptons. We discuss general parametric relations involving the fine-tuning of the model and various observables such as the chargino mass and the value of $\\tan\\beta$. We build an explicit model and we study the constraints coming from LEP and Tevatron. We show that in spite of ne...

  8. Loss energy states of nonstationary quantum systems

    International Nuclear Information System (INIS)

    Dodonov, V.V.; Man'ko, V.I.

    1978-01-01

    The concept of loss energy states is introduced. The loss energy states of the quantum harmonic damping oscillator are considered in detail. The method of constructing the loss energy states for general multidimensional quadratic nonstationary quantum systems is briefly discussed

  9. Plasma losses from a magnetic well

    International Nuclear Information System (INIS)

    Kutbi, I.I.; Valfells, A.

    1981-01-01

    The particle losses from a magnetic well having an octahedral symmetry are considered. The cusp, classical diffusion, and Bohm diffusion losses are computed. Results show that: Cusp losses can be compensated for by ion beam in the Hershkowitz equation prevails. Otherwise, the losses will have to be diminished by some other means; Classical diffusion losses are relatively small; and Bohm diffusion losses are very large, should it prevail, but that is unlikely to be the case in the configuration under consideration

  10. Energy losses on tokamak startup

    International Nuclear Information System (INIS)

    Murray, J.G.; Rothe, K.E.; Bronner, G.

    1983-01-01

    During the startup of a tokamak reactor using poloidal field (PF) coils to induce plasma currents, the conducting structures carry induced currents. The associated energy losses in the circuits must be provided by the startup coils and the PF system. This paper provides quantitative and comparitive values for the energies required as a function of the thickness or resistivity of the torus shells

  11. Interface losses in multimaterial resonators

    DEFF Research Database (Denmark)

    Villanueva, L.G.; Amato, B.; Larsen, Tom

    2014-01-01

    We present an extensive study shedding light on the role of surface and bulk losses in micromechanical resonators. We fabricate thin silicon nitride membranes of different sizes and we coat them with different thicknesses of metal. We later characterize the 81 lowest out-of-plane flexural vibrati...

  12. Management of early pregnancy loss

    NARCIS (Netherlands)

    Graziosi, G. C. M.; Mol, B. W.; Ankum, W. M.; Bruinse, H. W.

    2004-01-01

    Objectives: In order to assess the available evidence on the management of early pregnancy loss, we performed a meta-analysis on the subject. Methods: MEDLINE and EMBASE were searched for randomized studies reporting on the effectiveness of expectant management, misoprostol treatment or curettage.

  13. Age-Related Hearing Loss

    Science.gov (United States)

    ... 29, 2017 Granicus - Health Topics Languages Español Download PDF version Order free publications Find organizations Syndicate content Related Topics Do You Need a Hearing Test? Hearing Loss and Older Adults News Spatial organization of cells in the inner ear enables the sense and ...

  14. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURC...

  15. When Telomerase Causes Telomere Loss.

    Science.gov (United States)

    Glousker, Galina; Lingner, Joachim

    2018-02-05

    Telomerase counteracts telomere shortening, preventing cellular senescence. Telomerase deficiency causes telomere syndromes because of premature telomere exhaustion in highly proliferative cells. Paradoxically, in a recent issue of Cell, Margalef et al. (2018) demonstrate that telomerase causes telomere loss in cells lacking the RTEL1 helicase, which is defective in Hoyeraal-Hreidarsson syndrome (HHS). Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Loss aversion is an affective forecasting error.

    Science.gov (United States)

    Kermer, Deborah A; Driver-Linn, Erin; Wilson, Timothy D; Gilbert, Daniel T

    2006-08-01

    Loss aversion occurs because people expect losses to have greater hedonic impact than gains of equal magnitude. In two studies, people predicted that losses in a gambling task would have greater hedonic impact than would gains of equal magnitude, but when people actually gambled, losses did not have as much of an emotional impact as they predicted. People overestimated the hedonic impact of losses because they underestimated their tendency to rationalize losses and overestimated their tendency to dwell on losses. The asymmetrical impact of losses and gains was thus more a property of affective forecasts than a property of affective experience.

  17. What carries a mediation process? Configural analysis of mediation.

    Science.gov (United States)

    von Eye, Alexander; Mun, Eun Young; Mair, Patrick

    2009-09-01

    Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

  18. Anxiety and Depression in Transgender Individuals: The Roles of Transition Status, Loss, Social Support, and Coping

    Science.gov (United States)

    Budge, Stephanie L.; Adelson, Jill L.; Howard, Kimberly A. S.

    2013-01-01

    Objective: The purpose of the current study was to examine facilitative and avoidant coping as mediators between distress and transition status, social support, and loss. Method: A total of 351 transgender individuals (n = 226 transgender women and n = 125 transgender men) participated in this study. Participants completed measures on transgender…

  19. The functional and structural neural basis of individual differences in loss aversion.

    Science.gov (United States)

    Canessa, Nicola; Crespi, Chiara; Motterlini, Matteo; Baud-Bovy, Gabriel; Chierchia, Gabriele; Pantaleo, Giuseppe; Tettamanti, Marco; Cappa, Stefano F

    2013-09-04

    Decision making under risk entails the anticipation of prospective outcomes, typically leading to the greater sensitivity to losses than gains known as loss aversion. Previous studies on the neural bases of choice-outcome anticipation and loss aversion provided inconsistent results, showing either bidirectional mesolimbic responses of activation for gains and deactivation for losses, or a specific amygdala involvement in processing losses. Here we focused on loss aversion with the aim to address interindividual differences in the neural bases of choice-outcome anticipation. Fifty-six healthy human participants accepted or rejected 104 mixed gambles offering equal (50%) chances of gaining or losing different amounts of money while their brain activity was measured with functional magnetic resonance imaging (fMRI). We report both bidirectional and gain/loss-specific responses while evaluating risky gambles, with amygdala and posterior insula specifically tracking the magnitude of potential losses. At the individual level, loss aversion was reflected both in limbic fMRI responses and in gray matter volume in a structural amygdala-thalamus-striatum network, in which the volume of the "output" centromedial amygdala nuclei mediating avoidance behavior was negatively correlated with monetary performance. We conclude that outcome anticipation and ensuing loss aversion involve multiple neural systems, showing functional and structural individual variability directly related to the actual financial outcomes of choices. By supporting the simultaneous involvement of both appetitive and aversive processing in economic decision making, these results contribute to the interpretation of existing inconsistencies on the neural bases of anticipating choice outcomes.

  20. Urban Songlines as Mediator

    DEFF Research Database (Denmark)

    Corlin, Anne

    2016-01-01

    The aim of this paper is to present an investigation of the method The Urban Songlines Book and how it works as a mediator for mapping the experienced space. The method contains a combination of aerial maps, photographs, and interviews as a way to understand the respondent´s use, relations...... and experiences of their neighborhood and the city. Through a presentation of the origin of the method, a description of the conducted study, and an analysis of the process in relation to theories about participatory design, social design, ANT and architectural sociology, the paper reveals how this method...

  1. Sociocultural mediators of remembering

    DEFF Research Database (Denmark)

    Wagoner, Brady; Gillespie, Alex

    2014-01-01

    , questioning and deferring contribute to the transformation and conventionalization of the material. These diverse sociocultural mediators are integrated into a partially coherent recollection by participants self-reflecting, or as Bartlett termed it, turning around upon their schemas. We demonstrate...... that this self-reflection is both a social and a psychological process, occurring because participants are responding to their own utterances in the same way that they respond to the utterances of other people. These empirical findings are used to make a case for using discursive data to look not only...

  2. DNA-Mediated Electrochemistry

    Science.gov (United States)

    Gorodetsky, Alon A.; Buzzeo, Marisa C.

    2009-01-01

    The base pair stack of DNA has been demonstrated as a medium for long range charge transport chemistry both in solution and at DNA-modified surfaces. This chemistry is exquisitely sensitive to structural perturbations in the base pair stack as occur with lesions, single base mismatches, and protein binding. We have exploited this sensitivity for the development of reliable electrochemical assays based on DNA charge transport at self-assembled DNA monolayers. Here we discuss the characteristic features, applications, and advantages of DNA-mediated electrochemistry. PMID:18980370

  3. Holographic Gauge Mediation

    Energy Technology Data Exchange (ETDEWEB)

    Benini, Francesco; /Princeton U.; Dymarsky, Anatoly; /Stanford U., ITP; Franco, Sebastian; /Santa Barbara, KITP; Kachru, Shamit; Simic, Dusan; /Stanford U., ITP /SLAC; Verlinde, Herman; /Princeton, Inst. Advanced Study

    2009-06-19

    We discuss gravitational backgrounds where supersymmetry is broken at the end of a warped throat, and the SUSY-breaking is transmitted to the Standard Model via gauginos which live in (part of) the bulk of the throat geometry. We find that the leading effect arises from splittings of certain 'messenger mesons,' which are adjoint KK-modes of the D-branes supporting the Standard Model gauge group. This picture is a gravity dual of a strongly coupled field theory where SUSY is broken in a hidden sector and transmitted to the Standard Model via a relative of semi-direct gauge mediation.

  4. 45 CFR 16.18 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 16.18 Section 16.18 Public Welfare... BOARD § 16.18 Mediation. (a) In cases pending before the Board. If the Board decides that mediation... mediation techniques and will provide or assist in selecting a mediator. The mediator may take any steps...

  5. Economic consequences of incident disease: the effect on loss of annual income

    DEFF Research Database (Denmark)

    Rayce, Signe L; Christensen, Ulla; Hougaard, Charlotte Ø

    2008-01-01

    AIMS: To estimate the effect of incident disease on loss of annual income on an individual level, to analyse whether loss of job mediates the effect on loss of annual income, to analyse whether an association is modified by socioeconomic position, and to determine whether the effect on annual inc...... on annual income. This might be interpreted as a buffering effect of the welfare policies in relation to the more discriminating demands of the labour market.......AIMS: To estimate the effect of incident disease on loss of annual income on an individual level, to analyse whether loss of job mediates the effect on loss of annual income, to analyse whether an association is modified by socioeconomic position, and to determine whether the effect on annual...... with an increased and equally strong risk for experiencing a loss of annual income corresponding to one income decile (>25,000 DKK) in the year following disease (odds ratio (OR) from 1.37 (95% confidence interval (CI) 1.09-1.72) to 1.57 (95% CI 1.21-2.04)). No significant effect of female AMI was found...

  6. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

    Science.gov (United States)

    Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni; Lupia, Enrico

    2017-01-01

    CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

  7. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

    Directory of Open Access Journals (Sweden)

    Sophie Doublier

    Full Text Available CD40/CD40 ligand (CD40L dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs. We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS, and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS, and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

  8. Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases.

    Science.gov (United States)

    Madeira, Maria H; Boia, Raquel; Santos, Paulo F; Ambrósio, António F; Santiago, Ana R

    2015-01-01

    Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microglia-mediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

  9. Interventional effects for mediation analysis with multiple mediators

    OpenAIRE

    Vansteelandt, Stijn; Daniel, Rhian M.

    2017-01-01

    The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator–outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that...

  10. Magnetic losses in composite materials

    International Nuclear Information System (INIS)

    Ramprecht, J; Sjoeberg, D

    2008-01-01

    We discuss some of the problems involved in homogenization of a composite material built from ferromagnetic inclusions in a nonmagnetic background material. The small signal permeability for a ferromagnetic spherical particle is combined with a homogenization formula to give an effective permeability for the composite material. The composite material inherits the gyrotropic structure and resonant behaviour of the single particle. The resonance frequency of the composite material is found to be independent of the volume fraction, unlike dielectric composite materials. The magnetic losses are described by a magnetic conductivity which can be made independent of frequency and proportional to the volume fraction by choosing a certain bias. Finally, some concerns regarding particles of small size, i.e. nanoparticles, are treated and the possibility of exciting exchange modes are discussed. These exchange modes may be an interesting way to increase losses in composite materials

  11. Radiation Therapy and Hearing Loss

    International Nuclear Information System (INIS)

    Bhandare, Niranjan; Jackson, Andrew; Eisbruch, Avraham; Pan, Charlie C.; Flickinger, John C.; Antonelli, Patrick; Mendenhall, William M.

    2010-01-01

    A review of literature on the development of sensorineural hearing loss after high-dose radiation therapy for head-and-neck tumors and stereotactic radiosurgery or fractionated stereotactic radiotherapy for the treatment of vestibular schwannoma is presented. Because of the small volume of the cochlea a dose-volume analysis is not feasible. Instead, the current literature on the effect of the mean dose received by the cochlea and other treatment- and patient-related factors on outcome are evaluated. Based on the data, a specific threshold dose to cochlea for sensorineural hearing loss cannot be determined; therefore, dose-prescription limits are suggested. A standard for evaluating radiation therapy-associated ototoxicity as well as a detailed approach for scoring toxicity is presented.

  12. Effects of The Coach Approach Intervention on Adherence to Exercise in Obese Women: Assessing Mediation of Social Cognitive Theory Factors

    Science.gov (United States)

    Annesi, James J.; Unruh, Jennifer L.; Marti, C. Nathan; Gorjala, Srinivasa; Tennant, Gisele

    2011-01-01

    The link between physical activity and weight loss has precipitated interest in interventions to foster adherence to exercise. It has been suggested that treatment effects, when significant, should be analyzed to determine theory-based mediators. This research assessed possible mediation of changes in Physical Self-Concept, Exercise Self-Efficacy,…

  13. Water Loss from Young Planets

    Science.gov (United States)

    Tian, Feng; Güdel, Manuel; Johnstone, Colin P.; Lammer, Helmut; Luger, Rodrigo; Odert, Petra

    2018-04-01

    Good progress has been made in the past few years to better understand the XUV evolution trend of Sun-like stars, the capture and dissipation of hydrogen dominant envelopes of planetary embryos and protoplanets, and water loss from young planets around M dwarfs. This chapter reviews these recent developments. Observations of exoplanets and theoretical works in the near future will significantly advance our understanding of one of the fundamental physical processes shaping the evolution of solar system terrestrial planets.

  14. Sangaste loss / Otto Pius Hippius

    Index Scriptorium Estoniae

    Hippius, Otto Pius, 1826-1883

    1996-01-01

    esmakordselt mainitud 13. saj. Sangaste mõisa omanik Berg, Friedrich Wilhelm (1794-1874). Lossi interjöörid, fotod 1920-ndatest aastatest, lossi välisvaade, foto 1920-ndatest aastatest, lk. 335. Loss, vaade esifassaadile, värv., lk. 336-337, Vaade lossile üle tiigi metsapargist, värv., lk. 338. Ballisaal, salong, värv.

  15. Accommodative loss after retinal cryotherapy.

    Science.gov (United States)

    Uno, Tsuyoshi; Okuyama, Michiko; Tanabe, Tatsuro; Kawamura, Ryosuke; Ideta, Hidenao

    2009-01-01

    To investigate the effects of peripheral retinal cryotherapy on accommodative amplitude in patients with retinal lattice degeneration. Prospective, observational case series. We studied 92 eyes in 69 patients (age range, 13 to 79 years) treated with cryotherapy for lattice degeneration between December 2001 and September 2004. Pretreatment and posttreatment accommodative amplitudes were measured. Acute accommodative loss was calculated from the difference between accommodative amplitudes before treatment and one week after treatment. We investigated the time course of accommodative amplitudes, acute accommodative loss in different age groups and in pretreatment accommodative amplitude groups, the influence of cryotherapy numbers on accommodative amplitude, and the influence of cryotherapy sites on accommodative amplitude. No significant difference was noted between pretreatment and posttreatment accommodative amplitudes in the overall subject cohort. Dividing subjects by age revealed significant decreases in accommodative amplitude only among patients in their 10s and 20s at one and three weeks after treatment. Accommodative amplitude was lowest among those in their 10s, followed by that among those in their 20s (P < .01). Accommodative amplitudes recovered to pretreatment level by six weeks. Acute accommodative loss was greatest in those in their 10s compared with other age groups (P < .01). A significant correlation was observed between acute accommodative loss and cryotherapy numbers (P = .03; r = 0.41). The decrease in accommodative amplitude was greatest at one week after treatment and recovered to pretreatment levels after six weeks. Accommodative amplitude showed the greatest decrease after cryotherapy among patients in their 10s and 20s. A decrease in accommodative amplitude was observed with increased numbers of cryotherapy spots administered.

  16. Sensorineural hearing loss and prematurity

    OpenAIRE

    Marlow, E.; Hunt, L.; Marlow, N.

    2000-01-01

    OBJECTIVE—To elucidate clinical antecedents of sensorineural hearing loss (SNHL) in very preterm infants.
DESIGN—Case-control study.
SUBJECTS—Fifteen children < 33 weeks' gestation with significant SNHL born between 1 January 1990 and 31 December 1994, detected within 9 months of birth, and 30 matched control children.
METHODOLOGY—Perinatal variables in the two groups were compared using non-parametric tests and conditional logistic regression (EGRET).
RESULTS—Median birth ...

  17. Prohibitions against Mourning in Childhood Sibling Loss.

    Science.gov (United States)

    Rosen, Helen

    1985-01-01

    Presents findings from a research study on sibling loss in childhood which support the idea that the loss of a sibling in childhood may be an especially significant loss for a child, in that both internal, family, and societal influences prohibit the opportunity to mourn the loss. (Author/NRB)

  18. Missing Strands? Dealing with Hair Loss

    Science.gov (United States)

    ... 2017 Print this issue Missing Strands? Dealing with Hair Loss En español Send us your comments Hair loss is often associated with men and aging, but ... or their treatments, and many other things cause hair loss. The most common type of hair loss is ...

  19. 27 CFR 28.127 - Losses.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Losses. 28.127 Section 28... to a Manufacturing Bonded Warehouse § 28.127 Losses. Where there has been a loss of wine while in..., with respect to losses of wine after withdrawal without payment of tax and to claims for remission of...

  20. 27 CFR 24.266 - Inventory losses.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Inventory losses. 24.266... OF THE TREASURY LIQUORS WINE Losses of Wine § 24.266 Inventory losses. (a) General. The proprietor... reported as required by § 24.313. (b) Bulk wine losses. The physical inventory of bulk wine will determine...

  1. 27 CFR 28.156 - Losses.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Losses. 28.156 Section 28... Exportation or Transfer to a Foreign-Trade Zone § 28.156 Losses. Where there has been a loss of specially... or a foreign-trade zone, the exporter shall file claim for allowance of the loss in accordance with...

  2. 7 CFR 1437.301 - Value loss.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Value loss. 1437.301 Section 1437.301 Agriculture... Coverage Using Value § 1437.301 Value loss. (a) Special provisions are required to assess losses and.... Assistance for these commodities is calculated based on the loss of value at the time of disaster. The agency...

  3. Interpreter-mediated dentistry.

    Science.gov (United States)

    Bridges, Susan; Drew, Paul; Zayts, Olga; McGrath, Colman; Yiu, Cynthia K Y; Wong, H M; Au, T K F

    2015-05-01

    The global movements of healthcare professionals and patient populations have increased the complexities of medical interactions at the point of service. This study examines interpreter mediated talk in cross-cultural general dentistry in Hong Kong where assisting para-professionals, in this case bilingual or multilingual Dental Surgery Assistants (DSAs), perform the dual capabilities of clinical assistant and interpreter. An initial language use survey was conducted with Polyclinic DSAs (n = 41) using a logbook approach to provide self-report data on language use in clinics. Frequencies of mean scores using a 10-point visual analogue scale (VAS) indicated that the majority of DSAs spoke mainly Cantonese in clinics and interpreted for postgraduates and professors. Conversation Analysis (CA) examined recipient design across a corpus (n = 23) of video-recorded review consultations between non-Cantonese speaking expatriate dentists and their Cantonese L1 patients. Three patterns of mediated interpreting indicated were: dentist designated expansions; dentist initiated interpretations; and assistant initiated interpretations to both the dentist and patient. The third, rather than being perceived as negative, was found to be framed either in response to patient difficulties or within the specific task routines of general dentistry. The findings illustrate trends in dentistry towards personalized care and patient empowerment as a reaction to product delivery approaches to patient management. Implications are indicated for both treatment adherence and the education of dental professionals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

    Science.gov (United States)

    Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

    2013-05-01

    Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

  5. Dysregulation of RNA Mediated Gene Expression in Motor Neuron Diseases.

    Science.gov (United States)

    Gonçalves, Inês do Carmo G; Rehorst, Wiebke A; Kye, Min Jeong

    2016-01-01

    Recent findings indicate an important role for RNA-mediated gene expression in motor neuron diseases, including ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy). ALS, also known as Lou Gehrig's disease, is an adult-onset progressive neurodegenerative disorder, whereby SMA or "children's Lou Gehrig's disease" is considered a pediatric neurodevelopmental disorder. Despite the difference in genetic causes, both ALS and SMA share common phenotypes; dysfunction/loss of motor neurons that eventually leads to muscle weakness and atrophy. With advanced techniques in molecular genetics and cell biology, current data suggest that these two distinct motor neuron diseases share more than phenotypes; ALS and SMA have similar cellular pathological mechanisms including mitochondrial dysfunction, oxidative stress and dysregulation in RNA-mediated gene expression. Here, we will discuss the current findings on these two diseases with specific focus on RNA-mediated gene regulation including miRNA expression, pre-mRNA processing and RNA binding proteins.

  6. Unresolved mourning, supernatural beliefs and dissociation: a mediation analysis.

    Science.gov (United States)

    Thomson, Paula; Jaque, S Victoria

    2014-01-01

    Unresolved mourning is marked by disorganized behavior and states of mind. In this study, we speculated that pathological dissociation would mediate the effects of unresolved mourning on supernatural beliefs. This hypothesis was determined based on findings that indicate an association between higher levels of dissociation, stronger beliefs in the supernatural and unresolved mourning. We examined two groups of participants, one classified as non-unresolved (non-U) (n = 56) and the other as unresolved (n = 26) (U) with respect to past loss/trauma as measured by the Adult Attachment Interview (AAI). Two self-report instruments were administered to measure supernatural beliefs and dissociation. As hypothesized, the multivariate analysis of variance indicated mean differences between the two groups. The unresolved group had greater belief in the supernatural and more pathological dissociative processes. The mediation analysis demonstrated that pathological dissociation fully mediated the effects of unresolved mourning on supernatural beliefs.

  7. Mediation Analysis: A Practitioner's Guide.

    Science.gov (United States)

    VanderWeele, Tyler J

    2016-01-01

    This article provides an overview of recent developments in mediation analysis, that is, analyses used to assess the relative magnitude of different pathways and mechanisms by which an exposure may affect an outcome. Traditional approaches to mediation in the biomedical and social sciences are described. Attention is given to the confounding assumptions required for a causal interpretation of direct and indirect effect estimates. Methods from the causal inference literature to conduct mediation in the presence of exposure-mediator interactions, binary outcomes, binary mediators, and case-control study designs are presented. Sensitivity analysis techniques for unmeasured confounding and measurement error are introduced. Discussion is given to extensions to time-to-event outcomes and multiple mediators. Further flexible modeling strategies arising from the precise counterfactual definitions of direct and indirect effects are also described. The focus throughout is on methodology that is easily implementable in practice across a broad range of potential applications.

  8. Losses in magnetic flux compression generators: Part 2, Radiation losses

    International Nuclear Information System (INIS)

    Fowler, C.M.

    1988-06-01

    This is the second monograph devoted to the analysis of flux losses in explosive driven magnetic flux compression generators. In the first monograph, flux losses from magnetic field penetration into conductor walls was studied by conventional diffusion theory. In the present report flux loss by radiation from the outer conductor walls is treated. Flux leakage rates through walls of finite thickness are first obtained by diffusion theory. It is shown, for normal wall thicknesses, that flux leakage is determined essentially by the wall conductance, defined as the product of wall thickness and wall conductivity. This remains true when the wall thickness is reduced to zero at unchanged conductance. In this case the wall is said to be coalesced. Solutions for a cavity bounded by a perfect conductor on one side and a coalesced wall on the other are then obtained using the complete Maxwell wave equations in both the cavity and free space beyond the coalesced wall. Several anomalies, noted earlier, that arise from diffusion analysis are resolved by the wave treatment. Conditions for the validity of the diffusion treatment are noted, and an expression is obtained within the framework of diffusion theory for energy radiated into space from the cavity walls. The free space wave equations are solved by using the method of characteristics in both the cavity and free space regions. An extension of the characteristic method to situations where the constitutive relations are non-linear is outlined in an appendix. For a special class of these relations, Riemann-like invariants are determined explicitly and used to solve a particular example

  9. Mass loss on the Asymptotic Giant Branch

    OpenAIRE

    Zijlstra, Albert

    2006-01-01

    Mass loss on the Asymptotic Giant Branch provides the origin of planetary nebulae. This paper reviews several relevant aspects of AGB evolution: pulsation properties, mass loss formalisms and time variable mass loss, evidence for asymmetries on the AGB, binarity, ISM interaction, and mass loss at low metallicity. There is growing evidence that mass loss on the AGB is already asymmetric, but with spherically symmetric velocity fields. The origin of the rings may be in pulsational instabilities...

  10. A higher form (of) mediation

    International Nuclear Information System (INIS)

    Verlinde, Herman; Wang, L-T; Yavin, Itay; Wijnholt, Martijn

    2008-01-01

    We exhibit a simple and robust mechanism for bulk mediation of supersymmetry breaking between hidden and visible sectors localized on geometrically separated D-branes in type II string theory. The mediation proceeds via RR p-forms that couple via linear Chern-Simons terms to the abelian vector bosons on the branes. From a 4-d low energy perspective, the mechanism reduces to U(1) mediation

  11. Host and Viral Factors in HIV-Mediated Bystander Apoptosis

    Science.gov (United States)

    Garg, Himanshu; Joshi, Anjali

    2017-01-01

    Human immunodeficiency virus (HIV) infections lead to a progressive loss of CD4 T cells primarily via the process of apoptosis. With a limited number of infected cells and vastly disproportionate apoptosis in HIV infected patients, it is believed that apoptosis of uninfected bystander cells plays a significant role in this process. Disease progression in HIV infected individuals is highly variable suggesting that both host and viral factors may influence HIV mediated apoptosis. Amongst the viral factors, the role of Envelope (Env) glycoprotein in bystander apoptosis is well documented. Recent evidence on the variability in apoptosis induction by primary patient derived Envs underscores the role of Env glycoprotein in HIV disease. Amongst the host factors, the role of C-C Chemokine Receptor type 5 (CCR5), a coreceptor for HIV Env, is also becoming increasingly evident. Polymorphisms in the CCR5 gene and promoter affect CCR5 cell surface expression and correlate with both apoptosis and CD4 loss. Finally, chronic immune activation in HIV infections induces multiple defects in the immune system and has recently been shown to accelerate HIV Env mediated CD4 apoptosis. Consequently, those factors that affect CCR5 expression and/or immune activation in turn indirectly regulate HIV mediated apoptosis making this phenomenon both complex and multifactorial. This review explores the complex role of various host and viral factors in determining HIV mediated bystander apoptosis. PMID:28829402

  12. Mediating Trust in Terrorism Coverage

    DEFF Research Database (Denmark)

    Mogensen, Kirsten

    crisis. While the framework is presented in the context of television coverage of a terror-related crisis situation, it can equally be used in connection with all other forms of mediated trust. Key words: National crisis, risk communication, crisis management, television coverage, mediated trust.......Mass mediated risk communication can contribute to perceptions of threats and fear of “others” and/or to perceptions of trust in fellow citizens and society to overcome problems. This paper outlines a cross-disciplinary holistic framework for research in mediated trust building during an acute...

  13. Substrate mediated enzyme prodrug therapy

    DEFF Research Database (Denmark)

    Fejerskov, Betina; Jarlstad Olesen, Morten T; Zelikin, Alexander N

    2017-01-01

    Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug administra......Substrate mediated enzyme prodrug therapy (SMEPT) is a biomedical platform developed to perform a localized synthesis of drugs mediated by implantable biomaterials. This approach combines the benefits and at the same time offers to overcome the drawbacks for traditional pill-based drug...

  14. Essential roles of mitochondrial depolarization in neuron loss through microglial activation and attraction toward neurons.

    Science.gov (United States)

    Nam, Min-Kyung; Shin, Hyun-Ah; Han, Ji-Hye; Park, Dae-Wook; Rhim, Hyangshuk

    2013-04-10

    As life spans increased, neurodegenerative disorders that affect aging populations have also increased. Progressive neuronal loss in specific brain regions is the most common cause of neurodegenerative disease; however, key determinants mediating neuron loss are not fully understood. Using a model of mitochondrial membrane potential (ΔΨm) loss, we found only 25% cell loss in SH-SY5Y (SH) neuronal mono-cultures, but interestingly, 85% neuronal loss occurred when neurons were co-cultured with BV2 microglia. SH neurons overexpressing uncoupling protein 2 exhibited an increase in neuron-microglia interactions, which represent an early step in microglial phagocytosis of neurons. This result indicates that ΔΨm loss in SH neurons is an important contributor to recruitment of BV2 microglia. Notably, we show that ΔΨm loss in BV2 microglia plays a crucial role in microglial activation and phagocytosis of damaged SH neurons. Thus, our study demonstrates that ΔΨm loss in both neurons and microglia is a critical determinant of neuron loss. These findings also offer new insights into neuroimmunological and bioenergetical aspects of neurodegenerative disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. The Strategic Mediator

    DEFF Research Database (Denmark)

    Rossignoli, Cecilia; Carugati, Andrea; Mola, Lapo

    2009-01-01

    process. Through the study of services evolving over time we show that, as marketplaces support increasingly complex business processes, the market participants begin to privilege the well connected small number to the convenience of the openness to the entire market. The participants see the marketplace......The last 10 years have witnessed the emergence of electronic marketplaces as players that leverage new technologies to facilitate B2B internet-mediated collaborative business. Nowadays these players are augmenting their services from simple intermediation to include new inter......-organizational relationships. The interest of this paper is to investigate the shift in the role and evolution of services proposed by e-marketplaces in response to the demands of the market participants. We carried out a longitudinal qualitative field study of an e-marketplace providing the outsourcing of the procurement...

  16. Mediating Potency and Fear

    DEFF Research Database (Denmark)

    Christiansen, Steen Ledet

    2018-01-01

    Action movies participate in the administration of fear [Virilio, P., 2012. The administration of fear. Translated by Ames Hodges. Los Angeles, CA: Semiotext(e)], and the networked affects of contemporary warfare [Anderson, B., 2013. Targeting affective life from above: morale and airpower. In: P......’ [Shaviro, S., 2010. Post-cinematic affect. Winchester: Zero Books]. These intensity effects mediate between the age of terror's ecology of fear [Massumi, Brian, 2002. Parables for the virtual: movement, affect, sensation. Durham: Duke University Press] and our bodies. Rather than producing fear, action...... movies work to dispel fear by producing potency and bolstering resolve. We can thus understand action movies as participating in the biopolitical effects of contemporary warfare. Affect is globalized and intensified through action movies’ aesthetics, with the aim of producing a kind of drone subject...

  17. Den sundhedsfremmende mediator

    DEFF Research Database (Denmark)

    Læssøe, Jeppe

    2009-01-01

      Mediatorer er en relativ ny aktør-type og job-funktion, som passer godt ind i det dynamiske videns- og netværkssamfund. I sundhedsfremmende arbejde med vægt på borgernes deltagelse kan mediatorer spille en nøglerolle. Det er derfor vigtigt begrebsmæssigt at kunne skelne mellem forskellige typer...... mediering samt mellem forskellige mediator-roller og tilhørsforhold. Det er også vigtigt at være bevidst om de centrale kvaliteter, risici og dilemmaer, som mediering indebærer i forhold til involvering af borgerne. Denne artikel rummer et bud på en sådan nuanceret begrebsliggørelse og refleksion, relateret...

  18. Soluble lymphocytic mediators

    Science.gov (United States)

    Pick, E.

    1974-01-01

    The effect of a number of drugs on the production of macrophage migration inhibitory factor (MIF) by antigen-stimulated sensitized guinea-pig lymph node cells was studied. The drugs were present during the entire culture period and eliminated from supernatants by dialysis. It was found that MIF secretion is inhibited by exogenous dibutyryl cyclic AMP and by theophylline and chlorphenesin, two agents raising the endogenous level of cyclic AMP. On the other hand, isoproterenol, which stimulates cyclic AMP generation in several tissues, did not block MIF production. The formation of the mediator was also suppressed by the microfilament-affecting drug, cytochalasin B. The microtubular disruptive agents, colchicine and vinblastine sulphate, did not influence MIF production. It is concluded that: (a) endogenous cyclic AMP may act as a regulator of MIF production; (b) the activity of contractile microfilaments is probably required for MIF formation; and (c) microtubules are not involved in the secretory process. PMID:4369184

  19. Protein- mediated enamel mineralization

    Science.gov (United States)

    Moradian-Oldak, Janet

    2012-01-01

    Enamel is a hard nanocomposite bioceramic with significant resilience that protects the mammalian tooth from external physical and chemical damages. The remarkable mechanical properties of enamel are associated with its hierarchical structural organization and its thorough connection with underlying dentin. This dynamic mineralizing system offers scientists a wealth of information that allows the study of basic principals of organic matrix-mediated biomineralization and can potentially be utilized in the fields of material science and engineering for development and design of biomimetic materials. This chapter will provide a brief overview of enamel hierarchical structure and properties as well as the process and stages of amelogenesis. Particular emphasis is given to current knowledge of extracellular matrix protein and proteinases, and the structural chemistry of the matrix components and their putative functions. The chapter will conclude by discussing the potential of enamel for regrowth. PMID:22652761

  20. Mediating environmental disputes

    Energy Technology Data Exchange (ETDEWEB)

    Lake, L.M.

    1977-09-01

    Environmental disputes and lawsuits are examined. Site-specific disputes focus on visible physical phenomena, such as a power plant or local river, and have an immediacy and intensity about them that make it politically hazardous for public officials to assume responsibility for resolving them. As new precedents in environmental case law become less frequent and the number of disputes increases, alternative processes for environmental conflict resolution, such as third-party intervention, become appropriate. Third-party intervention techniques of fact finding, conflict avoidance, conciliation and mediation have been applied to international, labor, prison, school, racial, and hospital disputes. Underlying concepts are described. Two case studies, the Snoqualmie Dam dispute in Washington and the West Side Highway dispute in New York City, illustrate the basic elements associated with third-party intervention. 1 map, 17 references.

  1. Mediatization and Government Communication

    DEFF Research Database (Denmark)

    Laursen, Bo; Valentini, Chiara

    2015-01-01

    do not tend to get a media coverage that matches the EU’s considerable influence on European citizens’ daily lives. This study, which is based on in-depth interviews with European Parliament press officers, concludes that these professionals are indeed attuned to a “media logic......Social actors see exposure in the news media as attractive for publicity purposes and are under pressure to adapt their press work to a “media logic” to be attractive sources for journalists and editors. This article investigates the European Parliament’s press officers’ professional practices...... in the light of mediatization and government communication theories. Without one pan-European public sphere, the European Parliament, like the other European Union (EU) institutions, competes with national actors for the news media’s attention in the EU’s twenty-eight national public spheres, where EU affairs...

  2. Primary culprit for tooth loss!!

    Directory of Open Access Journals (Sweden)

    Sailavanya Nuvvula

    2016-01-01

    Full Text Available Aim: In order to facilitate planning for dental health services and to progress strategies to continue the reduction in tooth loss, it is important to identify the factors that result in such loss. therefore the aim of the study is to investigate the major cause for tooth extraction. Objective: to examine whether the major reason for tooth extraction is dental caries or periodontal disease. Materials and Methods: The study is carried out among the dental practitioners in our district. A questionnaire containing 10 items was distributed to the dental practitioners, which included age, gender, no of teeth indicated for extraction, the reason for extraction, and the periodontal parameters that are involved with the extracted tooth and were requested to complete the form on every extraction they were to undertake. the study form was collected at the end of the study period and data was subjected to statistical analysis. Results: A total of 502 patients were enrolled during the study period, and a total of 1055 teeth were extracted for several reasons. we found that 51.14%extractions are due to dental caries in case of 20-30years age groups, which is more when compared to tooth loss due to periodontal diseases in this age group. whereas in case of >40years of age group periodontal diseases account for 54.11%, and dental caries accounts for only 29.11%. Showing more teeth were lost due to periodontal disease. Conclusion: therefore we concluded that, caries is the dominant reason for extraction in patients with 20–30 years of age while periodontal disease accounts for the majority of tooth extraction in patients older than 40 years.

  3. Tsunami Loss Assessment For Istanbul

    Science.gov (United States)

    Hancilar, Ufuk; Cakti, Eser; Zulfikar, Can; Demircioglu, Mine; Erdik, Mustafa

    2010-05-01

    Tsunami risk and loss assessment incorporating with the inundation mapping in Istanbul and the Marmara Sea region are presented in this study. The city of Istanbul is under the threat of earthquakes expected to originate from the Main Marmara branch of North Anatolian Fault System. In the Marmara region the earthquake hazard reached very high levels with 2% annual probability of occurrence of a magnitude 7+ earthquake on the Main Marmara Fault. Istanbul is the biggest city of Marmara region as well as of Turkey with its almost 12 million inhabitants. It is home to 40% of the industrial facilities in Turkey and operates as the financial and trade hub of the country. Past earthquakes have evidenced that the structural reliability of residential and industrial buildings, as well as that of lifelines including port and harbor structures in the country is questionable. These facts make the management of earthquake risks imperative for the reduction of physical and socio-economic losses. The level of expected tsunami hazard in Istanbul is low as compared to earthquake hazard. Yet the assets at risk along the shores of the city make a thorough assessment of tsunami risk imperative. Important residential and industrial centres exist along the shores of the Marmara Sea. Particularly along the northern and eastern shores we see an uninterrupted settlement pattern with industries, businesses, commercial centres and ports and harbours in between. Following the inundation maps resulting from deterministic and probabilistic tsunami hazard analyses, vulnerability and risk analyses are presented and the socio-economic losses are estimated. This study is part of EU-supported FP6 project ‘TRANSFER'.

  4. Cancer Cachexia: Beyond Weight Loss.

    Science.gov (United States)

    Bruggeman, Andrew R; Kamal, Arif H; LeBlanc, Thomas W; Ma, Joseph D; Baracos, Vickie E; Roeland, Eric J

    2016-11-01

    Cancer cachexia is a multifactorial syndrome characterized by skeletal muscle loss leading to progressive functional impairment. Despite the ubiquity of cachexia in clinical practice, prevention, early identification, and intervention remain challenging. The impact of cancer cachexia on quality of life, treatment-related toxicity, physical function, and mortality are well established; however, establishing a clinically meaningful definition has proven challenging because of the focus on weight loss alone. Attempts to more comprehensively define cachexia through body composition, physical functioning, and molecular biomarkers, while promising, are yet to be routinely incorporated into clinical practice. Pharmacologic agents that have not been approved by the US Food and Drug Administration but that are currently used in cancer cachexia (ie, megestrol, dronabinol) may improve weight but not outcomes of interest such as muscle mass, physical activity, or mortality. Their routine use is limited by adverse effects. For the practicing oncologist, early identification and management of cachexia is critical. Oncologists must recognize cachexia beyond weight loss alone, focusing instead on body composition and physical functioning. In fact, becoming emaciated is a late sign of cachexia that characterizes its refractory stage. Given that cachexia is a multifactorial syndrome, it requires early identification and polymodal intervention, including optimal cancer therapy, symptom management, nutrition, exercise, and psychosocial support. Consequently, oncologists have a role in ensuring that these resources are available to their patients. In addition, in light of the promising investigational agents, it remains imperative to refer patients with cachexia to clinical trials so that available options can be expanded to effectively treat this pervasive problem.

  5. Noise-induced hearing loss

    Directory of Open Access Journals (Sweden)

    Mariola Sliwinska-Kowalska

    2012-01-01

    Full Text Available Noise-induced hearing loss (NIHL still remains a problem in developed countries, despite reduced occupational noise exposure, strict standards for hearing protection and extensive public health awareness campaigns. Therefore NIHL continues to be the focus of noise research activities. This paper summarizes progress achieved recently in our knowledge of NIHL. It includes papers published between the years 2008-2011 (in English, which were identified by a literature search of accessible medical and other relevant databases. A substantial part of this research has been concerned with the risk of NIHL in the entertainment sector, particularly in professional, orchestral musicians. There are also constant concerns regarding noise exposure and hearing risk in "hard to control" occupations, such as farming and construction work. Although occupational noise has decreased since the early 1980s, the number of young people subject to social noise exposure has tripled. If the exposure limits from the Noise at Work Regulations are applied, discotheque music, rock concerts, as well as music from personal music players are associated with the risk of hearing loss in teenagers and young adults. Several recent research studies have increased the understanding of the pathomechanisms of acoustic trauma, the genetics of NIHL, as well as possible dietary and pharmacologic otoprotection in acoustic trauma. The results of these studies are very promising and offer grounds to expect that targeted therapies might help prevent the loss of sensory hair cells and protect the hearing of noise-exposed individuals. These studies emphasize the need to launch an improved noise exposure policy for hearing protection along with developing more efficient norms of NIHL risk assessment.

  6. Reduced reward-driven eating accounts for the impact of a mindfulness-based diet and exercise intervention on weight loss: Data from the SHINE randomized controlled trial.

    Science.gov (United States)

    Mason, Ashley E; Epel, Elissa S; Aschbacher, Kirstin; Lustig, Robert H; Acree, Michael; Kristeller, Jean; Cohn, Michael; Dallman, Mary; Moran, Patricia J; Bacchetti, Peter; Laraia, Barbara; Hecht, Frederick M; Daubenmier, Jennifer

    2016-05-01

    Many individuals with obesity report over eating despite intentions to maintain or lose weight. Two barriers to long-term weight loss are reward-driven eating, which is characterized by a lack of control over eating, a preoccupation with food, and a lack of satiety; and psychological stress. Mindfulness training may address these barriers by promoting awareness of hunger and satiety cues, self-regulatory control, and stress reduction. We examined these two barriers as potential mediators of weight loss in the Supporting Health by Integrating Nutrition and Exercise (SHINE) randomized controlled trial, which compared the effects of a 5.5-month diet and exercise intervention with or without mindfulness training on weight loss among adults with obesity. Intention-to-treat multiple mediation models tested whether post-intervention reward-driven eating and psychological stress mediated the impact of intervention arm on weight loss at 12- and 18-months post-baseline among 194 adults with obesity (BMI: 30-45). Mindfulness (relative to control) participants had significant reductions in reward-driven eating at 6 months (post-intervention), which, in turn, predicted weight loss at 12 months. Post-intervention reward-driven eating mediated 47.1% of the total intervention arm effect on weight loss at 12 months [β = -0.06, SE(β) = 0.03, p = .030, 95% CI (-0.12, -0.01)]. This mediated effect was reduced when predicting weight loss at 18 months (p = .396), accounting for 23.0% of the total intervention effect, despite similar weight loss at 12 months. Psychological stress did not mediate the effect of intervention arm on weight loss at 12 or 18 months. In conclusion, reducing reward-driven eating, which can be achieved using a diet and exercise intervention that includes mindfulness training, may promote weight loss (clinicaltrials.gov registration: NCT00960414). Published by Elsevier Ltd.

  7. Mechanical model for ductility loss

    International Nuclear Information System (INIS)

    Hu, W.L.

    1980-01-01

    A mechanical model was constructed to probe into the mechanism of ductility loss. Fracture criterion based on critical localized deformation was undertaken. Two microstructure variables were considered in the model. Namely, the strength ratio of grain boundary affected area to the matrix, Ω, and the linear fraction, x, of grain boundary affected area. A parametrical study was carried out. The study shows that the ductility is very sensitive to those microstructure parameters. The functional dependence of ductility to temperature as well as strain-rate, suggested by the model, is demonstrated to be consistent with the observation

  8. Mass loss from Eta Carinae

    International Nuclear Information System (INIS)

    Andriesse, C.D.; Viotti, R.

    1979-01-01

    This high luminosity (5x10 6 solar luminosity) star since 1840 is losing mass at the rate of 7.5x10 -2 solar masses per year. The large mass loss could be the result of vibrational instabilities produced in the CNO hydrogen burning phase of a very massive (160 solar masses) star. The presence of high excitation lines in the ultraviolet spectrum of Eta Car suggests the idea of a hot zone excited by dissipation of the supersonic turbulent flow. (Auth.)

  9. Computer loss experience and predictions

    Science.gov (United States)

    Parker, Donn B.

    1996-03-01

    The types of losses organizations must anticipate have become more difficult to predict because of the eclectic nature of computers and the data communications and the decrease in news media reporting of computer-related losses as they become commonplace. Total business crime is conjectured to be decreasing in frequency and increasing in loss per case as a result of increasing computer use. Computer crimes are probably increasing, however, as their share of the decreasing business crime rate grows. Ultimately all business crime will involve computers in some way, and we could see a decline of both together. The important information security measures in high-loss business crime generally concern controls over authorized people engaged in unauthorized activities. Such controls include authentication of users, analysis of detailed audit records, unannounced audits, segregation of development and production systems and duties, shielding the viewing of screens, and security awareness and motivation controls in high-value transaction areas. Computer crimes that involve highly publicized intriguing computer misuse methods, such as privacy violations, radio frequency emanations eavesdropping, and computer viruses, have been reported in waves that periodically have saturated the news media during the past 20 years. We must be able to anticipate such highly publicized crimes and reduce the impact and embarrassment they cause. On the basis of our most recent experience, I propose nine new types of computer crime to be aware of: computer larceny (theft and burglary of small computers), automated hacking (use of computer programs to intrude), electronic data interchange fraud (business transaction fraud), Trojan bomb extortion and sabotage (code security inserted into others' systems that can be triggered to cause damage), LANarchy (unknown equipment in use), desktop forgery (computerized forgery and counterfeiting of documents), information anarchy (indiscriminate use of

  10. electron energy-loss spectroscopy

    International Nuclear Information System (INIS)

    Egerton, R.

    1997-01-01

    As part of a commemorative series of articles to mark the hundredth anniversary of the discovery of the electron, this article describes the use of electron energy-loss spectroscopy. The physical and chemical properties of materials can be studied by considering the energy that electrons use as they travel through a solid, often in conjunction with other analytical techniques. The technique is often combined with electron diffraction and high-resolution imaging and can be used to provide elemental identification down to the atomic scale. 6 figs

  11. Electron energy-loss spectroscopy

    International Nuclear Information System (INIS)

    Egerton, R.

    1997-01-01

    As part of the commemorative series of articles to mark the hundredth anniversary of the discovery of the electron, this article discusses electron energy-loss spectroscopy. The physical and chemical properties of materials can be studied by considering the energy that electrons use as they travel through a solid, often in conjunction with other analytical techniques. The technique is often combined with electron diffraction and high-resolution imaging and can be used to provide elemental identification down to the atomic scale. (UK)

  12. The mediation procedure in Romania

    Directory of Open Access Journals (Sweden)

    Alexandrina Zaharia

    2009-06-01

    Full Text Available The mediation activity as an alternative way of solving conflicts occupies an important place in modernsociety. Currently, the mediation reached its maturity worldwide being adopted without reservations.The future of solving conflicts is undoubtedly closely related to mediation. XXth century is the century of solvingconflicts amiably outside the court room. In Romania and the mediation profession were regulated by the Law no.192/2006, on the basis of the idea that mediation is one of the major themes of the reform strategy of the judicialsystem 2005-2007. By adopting the mentioned law it was followed the idea of reducing the volume of activitycourts, and therefore, relieve them of as many cases, with the direct effect on the quality of justice. Mediation is avoluntary process in which the parties with a neutral and impartial third party, without power of decision - themediator - who is qualified to assist the parties to negotiate, facilitating the communication between them andhelping them to reach a unanimous effective and sustainable agreement. The parties may resort to mediation beforeor after triggering a trial. Mediation can be applied, in principle, on any type of conflict. However, theRomanian legislator has established special stipulations on conflict mediation in criminal, civil and familylaw. Although not expressly provided, the stipulations regarding the civil conflicts and also apply to commercialconflicts. Therefore, the mediation is applicable to most types of lawsuits, except those relating to personalrights. As a "win- win" principle, the mediation does not convert any of the parties defeated or victorious; allthose involved have gained by applying this procedure.

  13. Establishing soil loss tolerance: an overview

    Directory of Open Access Journals (Sweden)

    Costanza Di Stefano

    2016-09-01

    Full Text Available Soil loss tolerance is a criterion for establishing if a soil is potentially subjected to erosion risk, productivity loss and if a river presents downstream over-sedimentation or other off-site effects are present at basin scale. At first this paper reviews the concept of tolerable soil loss and summarises the available definitions and the knowledge on the recommended values and evaluating criteria. Then a threshold soil loss value, at the annual temporal scale, established for limiting riling was used for defining the classical soil loss tolerance. Finally, some research needs on tolerable soil loss are listed.

  14. Honeybee immunity and colony losses

    Directory of Open Access Journals (Sweden)

    F. Nazzi

    2014-10-01

    Full Text Available The decline of honeybee colonies and their eventual collapse is a widespread phenomenon in the Northern hemisphere of the globe, which severely limits the beekeeping industry. This dramatic event is associated with an enhanced impact of parasites and pathogens on honeybees, which is indicative of reduced immunocompetence. The parasitic mite Varroa destructor and the vectored viral pathogens appear to play a key-role in the induction of this complex syndrome. In particular, the Deformed Wing Virus (DWV is widespread and is now considered, along with Varroa, one of the major causes of bee colony losses. Several lines of evidence indicate that this mite/DWV association severely affects the immune system of honeybees and makes them more sensitive to the action of other stress factors. The molecular mechanisms underpinning these complex interactions are currently being investigated and the emerging information has allowed the development of a new functional model, describing how different stress factors may synergistically concur in the induction of bee immune alteration and health decline. This provides a new logical framework in which to interpret the proposed multifactorial origin of bee colony losses and sets the stage for a more comprehensive and integrated analysis of the effect that multiple stress agents may have on honeybees.

  15. Anomaly mediation deformed by axion

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Kazunori, E-mail: kazunori@hep-th.phys.s.u-tokyo.ac.jp [Department of Physics, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan); Yanagida, Tsutomu T. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwa 277-8583 (Japan)

    2013-05-13

    We show that in supersymmetric axion models the axion supermultiplet obtains a sizable F-term due to a non-supersymmetric dynamics and it generally gives the gaugino masses comparable to the anomaly mediation contribution. Thus the gaugino mass relation predicted by the anomaly mediation effect can be significantly modified in the presence of axion to solve the strong CP problem.

  16. Theorizing with/out "Mediators".

    Science.gov (United States)

    Roth, Wolff-Michael; Jornet, Alfredo

    2017-01-05

    Mediation is one of the most often cited concepts in current cultural-historical theory literature, in which cultural actions and artifacts are often characterized as mediators standing between situational stimuli and behavioral responses. Most often presented as a means to overcome Cartesian dualism between subject and object, and between individual and society, some scholars have nonetheless raised criticism suggesting that such mediators are problematic for a dialectical psychology that takes a unit analysis (monist) approach. In fact, Spinoza develops a monist theory of mind and body that goes without and even excludes every form of mediation. In this study, we follow up on the latter criticisms and explore what we consider to be problematic uses of the notion of mediation as an analytical construct in the literature. We elaborate an empirically grounded discussion on the ways the concept of mediation may lead to dualistic readings; and we offer an alternative account where the notion of mediator is not needed. We conclude discussing prospects for and implications of a cultural-historical theory where the notion of mediation no longer is invoked to account for human action and development.

  17. Comments on general gauge mediation

    International Nuclear Information System (INIS)

    Intriligator, Kenneth; Sudano, Matthew

    2008-01-01

    There has been interest in generalizing models of gauge mediation of supersymmetry breaking. As shown by Meade, Seiberg, and Shih (MSS), the soft masses of general gauge mediation can be expressed in terms of the current two-point functions of the susy-breaking sector. We here give a simple extension of their result which provides, for general gauge mediation, the full effective potential for squark pseudo-D-flat directions. The effective potential reduces to the sfermion soft masses near the origin, and the full potential, away from the origin, can be useful for cosmological applications. We also generalize the soft masses and effective potential to allow for general gauge mediation by Higgsed gauge groups. Finally, we discuss general gauge mediation in the limit of small F-terms, and how the results of MSS connect with the analytic continuation in superspace results, based on a spurion analysis.

  18. Practical Guide to Civil Mediation

    CERN Document Server

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of international organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreeme...

  19. Practical Guide to Civil Mediation

    CERN Multimedia

    2006-01-01

    The Permanent Mission of Switzerland has informed CERN that the Département des Institutions of the Republic and Canton of Geneva and the Groupement suisse des Magistrats pour la médiation (GEMME) - Swiss Association of Magistrates for Mediation have published a multilingual Practical Guide to Civil Mediation (including English). In this context, the Swiss Mission has underlined the benefits of resorting to mediation, especially for the personnel of International Organizations, and which the Secretary-General of the GEMME has summarised as follows: it is a private process not requiring the waiver of the parties' immunities; the confidentiality of the mediation process is guaranteed both by the mediator and the parties to it; the search for an amicable settlement does not need to be determined by reference to law (provided that public order is respected); the process is faster (2 to 3 sessions), less costly and more flexible than civil or arbitration procedures; in order to reinforce the agreem...

  20. Weight loss and weight loss maintenance efficacy of a novel weight loss program: The retrospective RNPC® cohort

    DEFF Research Database (Denmark)

    Thorning, Tanja Kongerslev; Fabre, Odile; Legrand, Rémy

    2018-01-01

    or obese patients treated in 54 RNPC® weight loss clinics in France. Results: A total of 10,809 (89%) patients completed the initial weight loss phase and 2996 (25%) completed the full program. Median weight loss percentage was 10.7% (Interquartile range [IQR]: 5.8; 16.5) after a median of 105 days (IQR...

  1. Novel and known nephrin gene (NPHS1) mutations in two Greek ...

    Indian Academy of Sciences (India)

    1Medical Genetics, Athens University, “Aghia Sofia” Children's Hospital, Thivon and Levadeias, Ampelokipoi 11527,. Athens, Greece ... Both probands and their parents were screened for nucleotide changes in ... ease manifesting in the first year of life. ..... influence the normal biology of the podocyte (Philippe et al. 2008).

  2. Changes in weight control behaviors and hedonic hunger during a 12-week commercial weight loss program.

    Science.gov (United States)

    O'Neil, Patrick M; Theim, Kelly R; Boeka, Abbe; Johnson, Gail; Miller-Kovach, Karen

    2012-12-01

    Greater use of key self-regulatory behaviors (e.g., self-monitoring of food intake and weight) is associated with greater weight loss within behavioral weight loss treatments, although this association is less established within widely-available commercial weight loss programs. Further, high hedonic hunger (i.e., susceptibility to environmental food cues) may present a barrier to successful behavior change and weight loss, although this has not yet been examined. Adult men and women (N=111, body mass index M±SD=31.5±2.7kg/m(2)) were assessed before and after participating in a 12-week commercial weight loss program. From pre- to post-treatment, reported usage of weight control behaviors improved and hedonic hunger decreased, and these changes were inversely associated. A decrease in hedonic hunger was associated with better weight loss. An improvement in reported weight control behaviors (e.g., self-regulatory behaviors) was associated with better weight loss, and this association was even stronger among individuals with high baseline hedonic hunger. Findings highlight the importance of specific self-regulatory behaviors within weight loss treatment, including a commercial weight loss program developed for widespread community implementation. Assessment of weight control behavioral skills usage and hedonic hunger may be useful to further identify mediators of weight loss within commercial weight loss programs. Future interventions might specifically target high hedonic hunger and prospectively examine changes in hedonic hunger during other types of weight loss treatment to inform its potential impact on sustained behavior change and weight control. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. 29 CFR 35.32 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Mediation. 35.32 Section 35.32 Labor Office of the Secretary... Mediation. (a) Referral to mediation. CRC will promptly refer to the Federal Mediation and Conciliation Service or the mediation agency designated by the Secretary of Health and Human Services under 45 CFR part...

  4. 22 CFR 143.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 143.33 Section 143.33 Foreign... Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and... participate in the mediation process to the extent necessary to reach an agreement or make an informed...

  5. 29 CFR 1203.1 - Mediation services.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation services. 1203.1 Section 1203.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD APPLICATIONS FOR SERVICE § 1203.1 Mediation services. Applications for the mediation services of the National Mediation Board under section 5, First, of the Railway...

  6. 34 CFR 81.13 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Mediation. 81.13 Section 81.13 Education Office of the... Mediation. (a) Voluntary mediation is available for proceedings that are pending before the OALJ. (b) A... mediation by filing a motion with the ALJ assigned to the case. The OALJ arranges for a mediator if the...

  7. 24 CFR 3288.35 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Mediation. 3288.35 Section 3288.35...-Administered States § 3288.35 Mediation. (a) Mediator. The dispute resolution provider will provide for the... identifies any other party that should be included in the mediation, the mediator will contact the other...

  8. 44 CFR 7.942 - Mediation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Mediation. 7.942 Section 7..., Conciliation, and Enforcement Procedures § 7.942 Mediation. (a) FEMA will promptly refer to a mediation agency... participate in the mediation process to the extent necessary to reach an agreement or for the mediator to make...

  9. 32 CFR 776.38 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Mediation. 776.38 Section 776.38 National... Professional Conduct § 776.38 Mediation. (a) Mediation: (1) A covered attorney may act as a mediator between... mediation, including the advantages and risks involved, and the effect on the attorney-client...

  10. 29 CFR 1202.1 - Mediation.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Mediation. 1202.1 Section 1202.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.1 Mediation. The mediation..., or where conferences are refused. The National Mediation Board may proffer its services in case any...

  11. Microbially mediated mineral carbonation

    Science.gov (United States)

    Power, I. M.; Wilson, S. A.; Dipple, G. M.; Southam, G.

    2010-12-01

    Mineral carbonation involves silicate dissolution and carbonate precipitation, which are both natural processes that microorganisms are able to mediate in near surface environments (Ferris et al., 1994; Eq. 1). (Ca,Mg)SiO3 + 2H2CO3 + H2O → (Ca,Mg)CO3 + H2O + H4SiO4 + O2 (1) Cyanobacteria are photoautotrophs with cell surface characteristics and metabolic processes involving inorganic carbon that can induce carbonate precipitation. This occurs partly by concentrating cations within their net-negative cell envelope and through the alkalinization of their microenvironment (Thompson & Ferris, 1990). Regions with mafic and ultramafic bedrock, such as near Atlin, British Columbia, Canada, represent the best potential sources of feedstocks for mineral carbonation. The hydromagnesite playas near Atlin are a natural biogeochemical model for the carbonation of magnesium silicate minerals (Power et al., 2009). Field-based studies at Atlin and corroborating laboratory experiments demonstrate the ability of a microbial consortium dominated by filamentous cyanobacteria to induce the precipitation of carbonate minerals. Phototrophic microbes, such as cyanobacteria, have been proposed as a means for producing biodiesel and other value added products because of their efficiency as solar collectors and low requirement for valuable, cultivable land in comparison to crops (Dismukes et al., 2008). Carbonate precipitation and biomass production could be facilitated using specifically designed ponds to collect waters rich in dissolved cations (e.g., Mg2+ and Ca2+), which would allow for evapoconcentration and provide an appropriate environment for growth of cyanobacteria. Microbially mediated carbonate precipitation does not require large quantities of energy or chemicals needed for industrial systems that have been proposed for rapid carbon capture and storage via mineral carbonation (e.g., Lackner et al., 1995). Therefore, this biogeochemical approach may represent a readily

  12. Nanoparticle mediated micromotor motion

    Science.gov (United States)

    Liu, Mei; Liu, Limei; Gao, Wenlong; Su, Miaoda; Ge, Ya; Shi, Lili; Zhang, Hui; Dong, Bin; Li, Christopher Y.

    2015-03-01

    In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric field. Both strategies lead to dramatically increased moving velocities, with the highest value reaching ~200 μm s-1. By decreasing the nanoparticles' surface wettability and increasing their catalytic activity, a maximum of a ~10-fold increase in the moving speed of the nanoparticle based micromotor can be achieved. Our results demonstrate the advantages of using nanoparticles in micromotor systems.In this paper, we report the utilization of nanoparticles to mediate the motion of a polymer single crystal catalytic micromotor. Micromotors have been fabricated by directly self-assembling functional nanoparticles (platinum and iron oxide nanoparticles) onto one or both sides of two-dimensional polymer single crystals. We show that the moving velocity of these micromotors in fluids can be readily tuned by controlling the nanoparticles' surface wettability and catalytic activity. A 3 times velocity increase has been achieved for a hydrophobic micromotor as opposed to the hydrophilic ones. Furthermore, we demonstrate that the catalytic activity of platinum nanoparticles inside the micromotor can be enhanced by their synergetic interactions with iron oxide nanoparticles and an electric

  13. The Multidimensional Loss Scale: validating a cross-cultural instrument for measuring loss.

    Science.gov (United States)

    Vromans, Lyn; Schweitzer, Robert D; Brough, Mark

    2012-04-01

    The Multidimensional Loss Scale (MLS) represents the first instrument designed specifically to index Experience of Loss Events and Loss Distress across multiple domains (cultural, social, material, and intrapersonal) relevant to refugee settlement. Recently settled Burmese adult refugees (N = 70) completed a questionnaire battery, including MLS items. Analyses explored MLS internal consistency, convergent and divergent validity, and factor structure. Cronbach alphas indicated satisfactory internal consistency for Experience of Loss Events (0.85) and Loss Distress (0.92), reflecting a unitary construct of multidimensional loss. Loss Distress did not correlate with depression or anxiety symptoms and correlated moderately with interpersonal grief and trauma symptoms, supporting divergent and convergent validity. Factor analysis provided preliminary support for a five-factor model: Loss of Symbolic Self, Loss of Interdependence, Loss of Home, Interpersonal Loss, and Loss of Intrapersonal Integrity. Received well by participants, the new scale shows promise for application in future research and practice.

  14. Outcomes of Children with Hearing Loss: Data Collection and Methods.

    Science.gov (United States)

    Tomblin, J Bruce; Walker, Elizabeth A; McCreery, Ryan W; Arenas, Richard M; Harrison, Melody; Moeller, Mary Pat

    2015-01-01

    The primary objective of this article was to describe recruitment, data collection, and methods for a longitudinal, multicenter study involving children with bilateral mild to severe hearing loss. The goals of this research program were to characterize the developmental outcomes of children with mild to severe bilateral hearing loss during infancy and the preschool years. Furthermore, the researchers examined how these outcomes were associated with the child's hearing loss and how home background and clinical interventions mediated and moderated these outcomes. The participants in this study were children who are hard of hearing (CHH) and children with normal hearing (CNH) who provided comparison data. CHH were eligible for participation if (1) their chronological age was between 6 months and 7 years of age at the time of recruitment, (2) they had a better-ear pure-tone average of 25 to 75 dB HL, (3) they had not received a cochlear implant, (4) they were from homes where English was the primary language, and (5) they did not demonstrate significant cognitive or motor delays. Across the time span of recruitment, 430 parents of potential children with hearing loss made contact with the research group. This resulted in 317 CHH who qualified for enrollment. In addition, 117 CNH qualified for enrollment. An accelerated longitudinal design was used, in which multiple age cohorts were followed long enough to provide overlap. Specifically, children were recruited and enrolled continuously across an age span of 6.5 years and were followed for at least 3 years. This design allowed for tests of time (period) versus cohort age effects that could arise by changes in services and technology over time, yet still allowed for examination of important developmental relationships. The distribution of degree of hearing loss for the CHH showed that the majority of CHH had moderate or moderate-to-severe hearing losses, indicating that the sample undersampled children with mild HL. For

  15. Loss, stress, and mental health.

    Science.gov (United States)

    Caplan, G

    1990-02-01

    1. The loss of an attachment to a loved person or of some other significant attachment leads to a prolonged period of distress and disability. 2. The upset feelings are usually associated with reduction in cognitive effectiveness and problem-solving capacity, the magnitude of which is dependent on the intensity and duration of emotional arousal. There is a reduced capacity for collecting and processing information and for access to relevant memories that associate significant meaning to perceptions. There is also a deterioration in the clarity of the person's self-concept and in his capacity to assess his ability to persevere in the face of discomfort, which weakens his will to struggle. 3. The disability following loss of an attachment is the product of three interlocking factors: (a) the pain of the rupture in the bond and the agony of coming to terms with this reality, (b) the handicapping privation of the missing assets previously derived from the lost person or resource, and (c) the cognitive erosion and reduction in problem-solving capacities and of the will to persevere. 4. These factors may lead to poor mental health in the form of an acute adjustment disorder, or else of chronic psychopathology if the individual uses maladaptive ways of trying to escape his burdens through alienation from reality or through the irrational mechanisms of psychoneurotic symptoms, or if prolonged emotional tension leads to malfunctioning of a bodily system. On the other hand, if the individual masters his problems by working out ways of effective coping, he may emerge from the experience with increased competence and resilience. 5. Eventual mastery of the burdensome experience involves reorganization of the individual's "assumptive world," namely of his intrapsychic maps of external reality and his internal system for guiding and motivating his behavior, which have been disorganized by the loss of their anchorage in the ruptured attachment. 6. This reorganization is helped by

  16. Determinants of Propranolol's Selective Effect on Loss Aversion.

    Science.gov (United States)

    Sokol-Hessner, Peter; Lackovic, Sandra F; Tobe, Russell H; Camerer, Colin F; Leventhal, Bennett L; Phelps, Elizabeth A

    2015-07-01

    Research on emotion and decision making has suggested that arousal mediates risky decisions, but several distinct and often confounded processes drive such choices. We used econometric modeling to separate and quantify the unique contributions of loss aversion, risk attitudes, and choice consistency to risky decision making. We administered the beta-blocker propranolol in a double-blind, placebo-controlled within-subjects study, targeting the neurohormonal basis of physiological arousal. Matching our intervention's pharmacological specificity with a quantitative model delineating decision-making components allowed us to identify the causal relationships between arousal and decision making that do and do not exist. Propranolol selectively reduced loss aversion in a baseline- and dose-dependent manner (i.e., as a function of initial loss aversion and body mass index), and did not affect risk attitudes or choice consistency. These findings provide evidence for a specific, modulatory, and causal relationship between precise components of emotion and risky decision making. © The Author(s) 2015.

  17. Tetrahydroxystilbene Glucoside Effectively Prevents Apoptosis Induced Hair Loss

    Directory of Open Access Journals (Sweden)

    Lulu Chen

    2018-01-01

    Full Text Available The effect of Polygonum multiflorum against hair loss has been widely recognized. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG is the main component of Polygonum multiflorum; however, its role in hair regeneration has not been established. To evaluate the hair growth-promoting activity of TSG, depilated C57BL/6J mice were topically treated with normal saline, TSG, Pifithrin-α, Minoxidil for 2 weeks. In this study, we identified that p53, Caspase-3, Active Caspase-3, and Caspase-9 were obviously upregulated in the skin of human and mice with hair loss by western blot analysis. Depilated mice treated with TSG showed markedly hair regrowth. TUNEL+ cells were also reduced in mice with TSG. These changes were accompanied with inhibition of Fas, p53, Bax, Active Caspase-3, and Procaspase-9 activities. These results demonstrated that TSG exerts great hair regrowth effect on hair loss, which was probably mediated by inhibition of p53, Fas, and Bax induced apoptosis.

  18. LOSS OF 5-HYDROXYMETHYLCYTOSINE IS AN EPIGENETIC HALLMARK OF MELANOMA

    Science.gov (United States)

    Lian, Christine Guo; Xu, Yufei; Ceol, Craig; Wu, Feizhen; Larson, Allison; Dresser, Karen; Xu, Wenji; Tan, Li; Hu, Yeguang; Zhan, Qian; Lee, Chung-wei; Hu, Di; Lian, Bill Q.; Kleffel, Sonja; Yang, Yijun; Neiswender, James; Khorasani, Abraham J.; Fang, Rui; Lezcano, Cecilia; Duncan, Lyn M.; Scolyer, Richard A.; Thompson, John F.; Kakavand, Hojabr; Houvras, Yariv; Zon, Leonard; Mihm, Martin C.; Kaiser, Ursula B.; Schatton, Tobias; Woda, Bruce A.; Murphy, George F.; Shi, Yujiang G.

    2013-01-01

    SUMMARY DNA methylation at the 5-position of cytosine (5-mC) is a key epigenetic mark critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the Ten-Eleven Translocation (TET) family of DNA hydroxylases. Here we report that “loss of 5-hmC” is an epigenetic hallmark of melanoma with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of 5-hmC landscape in the melanoma epigenome. We show that down-regulation of Isocitrate Dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy. PMID:22980977

  19. Determinants of propranolol’s selective effect on loss aversion

    Science.gov (United States)

    Sokol-Hessner, Peter; Lackovic, Sandra F.; Tobe, Russell H.; Camerer, Colin F.; Leventhal, Bennett L.; Phelps, Elizabeth A.

    2015-01-01

    Research on emotion and decision-making has suggested that arousal mediates risky decisions (e.g., Bechara et al., 1997), but several distinct and often confounded processes drive such choices. Here, we used econometric modeling to separate and quantify the unique contributions of loss aversion, risk sensitivity and choice consistency to risky decision-making. We administered the beta-blocker propranolol in a double-blind, placebo-controlled within-subjects study, targeting the neurohormonal basis of physiological arousal. Matching our intervention’s pharmacological specificity with a quantitative model delineating decision-making components allowed us to identify the causal relationships between arousal and decision-making that do and do not exist. Propranolol selectively reduced loss aversion in a baseline- and dose-dependent manner (i.e. as a function of initial loss aversion and body-mass index), and did not affect risk sensitivity or choice consistency. These findings provide evidence for a specific, modulatory, and causal relationship between precise components of both emotion and risky decision-making. PMID:26063441

  20. Global Drought Proportional Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Drought Proportional Economic Loss Risk Deciles is a 2.5 minute grid of drought hazard economic loss as proportions of Gross Domestic Product (GDP) per...

  1. Managing Chemotherapy Side Effects: Hair Loss (Alopecia)

    Science.gov (United States)

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. ... and anywhere on your body may fall out. Hair loss is called alopecia. When will my hair start ...

  2. Global Drought Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Drought Total Economic Loss Risk Deciles is a 2.5 minute grid of global drought total economic loss risks. A process of spatially allocating Gross Domestic...

  3. Loss modeling for pricing catastrophic bonds.

    Science.gov (United States)

    2008-12-01

    In the research, a loss estimation framework is presented that directly relates seismic : hazard to seismic response to damage and hence to losses. A Performance-Based Earthquake : Engineering (PBEE) approach towards assessing the seismic vulnerabili...

  4. Acoustic Trauma - Hearing Loss in Teenagers

    Science.gov (United States)

    ... I Can Hear It, It's Too Loud: Earbuds & Teen Hearing Loss Page Content ​Many parents will agree ... hearing loss." Recommended Hearing Screenings for Older Children & Teens Kids should be screened at three ages: 11- ...

  5. Herbal remedies and supplements for weight loss

    Science.gov (United States)

    Weight loss - herbal remedies and supplements; Obesity - herbal remedies; Overweight - herbal remedies ... health care provider. Nearly all over-the-counter supplements with claims of weight-loss properties contain some ...

  6. Global Landslide Total Economic Loss Risk Deciles

    Data.gov (United States)

    National Aeronautics and Space Administration — Global Landslide Total Economic Loss Risk Deciles is a 2.5 minute grid of global landslide total economic loss risks. A process of spatially allocating Gross...

  7. Wind farm array wake losses

    Energy Technology Data Exchange (ETDEWEB)

    Baker, R.W. [Impact Weather, Washougal, WA (United States); McCarthy, E.F. [Wind Economics & Technology, Inc., Martinez, CA (United States)

    1997-12-31

    A wind turbine wake study was conducted in the summer of 1987 at an Altamont Pass wind electric generating facility. The wind speed deficits, turbulence, and power deficits from an array consisting of several rows of wind turbines is discussed. A total of nine different test configurations were evaluated for a downwind spacing ranging from 7 rotor diameters (RD) to 34 RD and a cross wind spacing of 1.3 RD and 2.7 RD. Wake power deficits of 15% were measured at 16 RD and power losses of a few percent were even measurable at 27 RD for the closer cross wind spacing. For several rows of turbines separated by 7-9 RD the wake zones overlapped and formed compound wakes with higher velocity deficits. The wind speed and direction turbulence in the wake was much higher than the ambient turbulence. The results from this study are compared to the findings from other similar field measurements.

  8. Osteoarthritis, obesity and weight loss

    DEFF Research Database (Denmark)

    Bliddal, Henning; Leeds, A R; Christensen, Robin Daniel Kjersgaard

    2014-01-01

    Obesity is widely acknowledged as a risk factor for both the incidence and progression of osteoarthritis, and has a negative influence on outcomes. Loss of at least 10% of body weight, coupled with exercise, is recognized as a cornerstone in the management of obese patients with osteoarthritis......, and can lead to significant improvement in symptoms, pain relief, physical function and health-related quality of life. However, questions still remain surrounding optimal management. Given the significant health, social and economic burden of osteoarthritis, especially in obese patients, it is imperative...... to advance our knowledge of osteoarthritis and obesity, and apply this to improving care and outcomes. This paper overviews what is already known about osteoarthritis and obesity, discusses current key challenges and ongoing hypotheses arising from research in these areas, and finally, postulates what...

  9. Beam Loss Monitors at LHC

    CERN Document Server

    Dehning, B.

    2016-01-01

    One of the main functions of the LHC beam loss measurement system is the protection of equipment against damage caused by impacting particles creating secondary showers and their energy dissipation in the matter. Reliability requirements are scaled according to the acceptable consequences and the frequency of particle impact events on equipment. Increasing reliability often leads to more complex systems. The downside of complexity is a reduction of availability; therefore, an optimum has to be found for these conflicting requirements. A detailed review of selected concepts and solutions for the LHC system will be given to show approaches used in various parts of the system from the sensors, signal processing, and software implementations to the requirements for operation and documentation.

  10. New Treatments for Hair Loss.

    Science.gov (United States)

    Vañó-Galván, S; Camacho, F

    2017-04-01

    The treatment of hair loss is an important part of clinical dermatology given the prevalence of the problem and great impact on patients' quality of life. Many new treatments have been introduced in recent years. This review summarizes the main ones in 4 groups: a) For androgenetic alopecia, we discuss new excipients for oral minoxidil, dutasteride, and finasteride as well as new forms of topical application; prostaglandin agonists and antagonists; low-level laser therapy; and regenerative medicine with Wnt signaling activators and stem cell therapy. b) For alopecia areata, Janus kinase inhibitors are reviewed. c) For frontal fibrosing alopecia, we discuss the use of antiandrogens and, for some patients, pioglitazone. d) Finally, we mention new robotic devices for hair transplant procedures and techniques for optimal follicular unit extraction. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Establishing soil loss tolerance: an overview

    OpenAIRE

    Costanza Di Stefano; Vito Ferro

    2016-01-01

    Soil loss tolerance is a criterion for establishing if a soil is potentially subjected to erosion risk, productivity loss and if a river presents downstream over-sedimentation or other off-site effects are present at basin scale. At first this paper reviews the concept of tolerable soil loss and summarises the available definitions and the knowledge on the recommended values and evaluating criteria. Then a threshold soil loss value, at the annual temporal scale, established for limiting rilin...

  12. Hearing Loss due to Carbon Monoxide Poisoning

    DEFF Research Database (Denmark)

    Mehrparvar, Amir Houshang; Davari, Mohammad Hossein; Mollasadeghi, Abolfazl

    2013-01-01

    Carbon monoxide poisoning is one of the rare causes of hearing loss which may cause reversible or irreversible, unilateral or bilateral hearing loss after acute or chronic exposure. In this report, we present a case of bilateral sensorineural hearing loss in a secondary smelting workshop worker...... after an acute exposure to carbon monoxide. This complication was diagnosed by pure-tone audiometry and confirmed by transient evoked otoacoustic emissions. Hearing loss has not improved after 3 months of followup....

  13. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    OpenAIRE

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets ...

  14. Space loss following premature loss of primary second molars.

    Science.gov (United States)

    Alnahwi, Hassan H; Donly, Kevin J; Contreras, Claudia I

    2015-01-01

    This study was designed to evaluate the amount of space loss (SL) caused by premature loss of primary second molars, determine whether the eruption status of permanent first molars is an important factor in the amount of SL, and evaluate the effectiveness of space maintainers (SMs) in SL prevention. SL associated with 100 prematurely extracted primary second molars was evaluated in 87 healthy patients. Teeth were divided into groups based on the use of SMs (36 with SM and 64 without SM). Bitewing and periapical radiographs taken before extraction and 6, 12, 24, 36, and 48 months after extraction were used to determine the amount of SL. Not every patient attended every recall appointment, so the sample size varied at different evaluation times. The most significant amount of SL occurred in the first 12 months after extraction. In patients who did not use an SM, at 6 months there was a mean SL of 2.12 mm (SD, 1.65 mm) and at 12 months there was a mean of 4.02 mm (SD, 1.65), with significantly more SL in the first 6 months (P 0.05). When patients without an SM were grouped by the eruption status of the permanent first molar, there was significantly more SL in the groups with unerupted first molars than there was in the groups with erupted first molars at both 6 months (P < 0.001) and 12 months (P < 0.05). At both 6 and 12 months, the amount of SL in patients who had an SM (n = 13 and n = 14, respectively) was not significantly different from the amount of SL in those who did not have an SM (n = 33 and n = 23, respectively). SMs should be placed as soon as possible following tooth extraction to prevent undue SL. Placement of an SM a year or more after extraction has minimal benefit, since most SL takes place within the first year. SL does occur even when SMs are used.

  15. Transport AC losses in YBCO coated conductors

    Energy Technology Data Exchange (ETDEWEB)

    Majoros, M [Ohio State University, Columbus, OH 43210 (United States); Ye, L [IRC in Superconductivity, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Velichko, A V [IRC in Superconductivity, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Coombs, T A [IRC in Superconductivity, University of Cambridge, Madingley Road, Cambridge CB3 0HE (United Kingdom); Sumption, M D [Ohio State University, Columbus, OH 43210 (United States); Collings, E W [Ohio State University, Columbus, OH 43210 (United States)

    2007-09-15

    Transport AC loss measurements have been made on YBCO-coated conductors prepared on two different substrate templates-RABiTS (rolling-assisted biaxially textured substrate) and IBAD (ion-beam-assisted deposition). RABiTS samples show higher losses compared with the theoretical values obtained from the critical state model, with constant critical current density, at currents lower than the critical current. An origin of this extra AC loss was demonstrated experimentally by comparison of the AC loss of two samples with different I-V curves. Despite a difference in I-V curves and in the critical currents, their measured losses, as well as the normalized losses, were practically the same. However, the functional dependence of the losses was affected by the ferromagnetic substrate. An influence of the presence of a ferromagnetic substrate on transport AC losses in YBCO film was calculated numerically by the finite element method. The presence of a ferromagnetic substrate increases transport AC losses in YBCO films depending on its relative magnetic permeability. The two loss contributions-transport AC loss in YBCO films and ferromagnetic loss in the substrate-cannot be considered as mutually independent.

  16. Loss from variation in sawing precision

    Science.gov (United States)

    1964-01-01

    A major loss sustained by small mills results from inaccurately cut lumber. Such lumber sells only at reduced prices and encounters stiffer sales resistance than lumber from the more accurately cutting band mills. A less apparent loss is the excessive loss of material that results from inaccurate cutting.

  17. 21 CFR 1314.15 - Loss reporting.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Loss reporting. 1314.15 Section 1314.15 Food and... for the report is provided below: Regulated Person Registration number (if applicable) Name Business address City State Zip Business phone Date of loss Type of loss Description of circumstances ...

  18. Hearing Loss due to Carbon Monoxide Poisoning

    DEFF Research Database (Denmark)

    Mehrparvar, Amir Houshang; Davari, Mohammad Hossein; Mollasadeghi, Abolfazl

    2013-01-01

    Carbon monoxide poisoning is one of the rare causes of hearing loss which may cause reversible or irreversible, unilateral or bilateral hearing loss after acute or chronic exposure. In this report, we present a case of bilateral sensorineural hearing loss in a secondary smelting workshop worker a...

  19. 7 CFR 1806.5 - Losses.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Losses. 1806.5 Section 1806.5 Agriculture Regulations... INSURANCE Real Property Insurance § 1806.5 Losses. (a) Protecting property. It is the responsibility of the borrower to immediately notify the County Supervisor and insurance company or agent of any loss or damage...

  20. 26 CFR 1.165-1 - Losses.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Losses. 1.165-1 Section 1.165-1 Internal Revenue... (CONTINUED) Itemized Deductions for Individuals and Corporations § 1.165-1 Losses. (a) Allowance of deduction. Section 165(a) provides that, in computing taxable income under section 63, any loss actually sustained...

  1. 27 CFR 28.149 - Losses.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Losses. 28.149 Section 28... Exportation, Use as Supplies on Vessels and Aircraft, or Transfer to a Foreign-Trade Zone § 28.149 Losses. When there has been a loss of beer or beer concentrate while in transit from the brewery to a port for...

  2. 47 CFR 80.769 - Shadow loss.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Shadow loss. 80.769 Section 80.769... MARITIME SERVICES Standards for Computing Public Coast Station VHF Coverage § 80.769 Shadow loss. Where the transmission path is obstructed the received signal must be adjusted to include shadow loss. Attenuation due to...

  3. 36 CFR 21.10 - Losses.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Losses. 21.10 Section 21.10... NATIONAL PARK; BATHHOUSE REGULATIONS § 21.10 Losses. A bathhouse receiving deposits of jewelry, money, or... on the premises. All losses must be reported promptly to the Superintendent by the bathhouse -manager. ...

  4. 38 CFR 4.112 - Weight loss.

    Science.gov (United States)

    2010-07-01

    .... The term “inability to gain weight” means that there has been substantial weight loss with inability... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Weight loss. 4.112... DISABILITIES Disability Ratings The Digestive System § 4.112 Weight loss. For purposes of evaluating conditions...

  5. Optimal portfolio choice under loss aversion

    NARCIS (Netherlands)

    A.B. Berkelaar (Arjan); R.R.P. Kouwenberg (Roy)

    2000-01-01

    textabstractProspect theory and loss aversion play a dominant role in behavioral finance. In this paper we derive closed-form solutions for optimal portfolio choice under loss aversion. When confronted with gains a loss averse investor behaves similar to a portfolio insurer. When confronted with

  6. Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats

    NARCIS (Netherlands)

    Warmerdam, Daniel O.; van den Berg, Jeroen; Medema, Rene H.

    2016-01-01

    rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded

  7. Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats

    OpenAIRE

    Warmerdam, Daniël O.; van den Berg, Jeroen; Medema, René H.

    2016-01-01

    rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of b...

  8. Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS mediated cardiomyocyte hypertrophy

    NARCIS (Netherlands)

    Tigchelaar, Wardit; Yu, Hongjuan; De Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Sillje, Herman H W

    2015-01-01

    Recently, a genetic variant in the mitochondrial exo/endo nuclease EXOG, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and

  9. An intracellular threonine of amyloid-β precursor protein mediates synaptic plasticity deficits and memory loss.

    Directory of Open Access Journals (Sweden)

    Franco Lombino

    Full Text Available Mutations in Amyloid-ß Precursor Protein (APP and BRI2/ITM2b genes cause Familial Alzheimer and Danish Dementias (FAD/FDD, respectively. APP processing by BACE1, which is inhibited by BRI2, yields sAPPß and ß-CTF. ß-CTF is cleaved by gamma-secretase to produce Aß. A knock-in mouse model of FDD, called FDDKI, shows deficits in memory and synaptic plasticity, which can be attributed to sAPPß/ß-CTF but not Aß. We have investigated further the pathogenic function of ß-CTF focusing on Thr(668 of ß-CTF because phosphorylation of Thr(668 is increased in AD cases. We created a knock-in mouse bearing a Thr(668Ala mutation (APP(TA mice that prevents phosphorylation at this site. This mutation prevents the development of memory and synaptic plasticity deficits in FDDKI mice. These data are consistent with a role for the carboxyl-terminal APP domain in the pathogenesis of dementia and suggest that averting the noxious role of Thr(668 is a viable therapeutic strategy for human dementias.

  10. Female sex hormones are necessary for the metabolic effects mediated by loss of Interleukin 18 signaling

    DEFF Research Database (Denmark)

    Lindegaard, Birgitte; Abildgaard, Julie; Heywood, Sarah E

    2018-01-01

    OBJECTIVE: Interleukin (IL)-18 plays a crucial role in maintaining metabolic homeostasis and levels of this cytokine are influenced by gender, age, and sex hormones. The role of gender on IL-18 signaling, however, is unclear. We hypothesized that the presence of female sex hormone could preserve...

  11. Stathmin 1/2-triggered microtubule loss mediates Golgi fragmentation in mutant SOD1 motor neurons

    NARCIS (Netherlands)

    Bellouze, Sarah; Baillat, Gilbert; Buttigieg, Dorothée; de la Grange, Pierre; Rabouille, Catherine; Haase, Georg

    2016-01-01

    BACKGROUND: Pathological Golgi fragmentation represents a constant pre-clinical feature of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) but its molecular mechanisms remain hitherto unclear. RESULTS: Here, we show that the severe Golgi fragmentation in transgenic

  12. A strain-mediated corrosion model for bioabsorbable metallic stents.

    Science.gov (United States)

    Galvin, E; O'Brien, D; Cummins, C; Mac Donald, B J; Lally, C

    2017-06-01

    This paper presents a strain-mediated phenomenological corrosion model, based on the discrete finite element modelling method which was developed for use with the ANSYS Implicit finite element code. The corrosion model was calibrated from experimental data and used to simulate the corrosion performance of a WE43 magnesium alloy stent. The model was found to be capable of predicting the experimentally observed plastic strain-mediated mass loss profile. The non-linear plastic strain model, extrapolated from the experimental data, was also found to adequately capture the corrosion-induced reduction in the radial stiffness of the stent over time. The model developed will help direct future design efforts towards the minimisation of plastic strain during device manufacture, deployment and in-service, in order to reduce corrosion rates and prolong the mechanical integrity of magnesium devices. The need for corrosion models that explore the interaction of strain with corrosion damage has been recognised as one of the current challenges in degradable material modelling (Gastaldi et al., 2011). A finite element based plastic strain-mediated phenomenological corrosion model was developed in this work and was calibrated based on the results of the corrosion experiments. It was found to be capable of predicting the experimentally observed plastic strain-mediated mass loss profile and the corrosion-induced reduction in the radial stiffness of the stent over time. To the author's knowledge, the results presented here represent the first experimental calibration of a plastic strain-mediated corrosion model of a corroding magnesium stent. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Mediation of information and educational mediation: conceptual discussions

    Directory of Open Access Journals (Sweden)

    Helena Célia de Souza Sacerdote

    2016-04-01

    Full Text Available Introduction: This is systematization of theoretical and methodological contributions related to the concepts of mediation information and pedagogical mediation in the literature. Objective: To understand possible intersection of information science and Online Education with regard to these concepts to check that both can be considered as analogous in its essence and practice. Methodology: Literature review based on literature by consulting the scientific productions selected in search of SciELO.ORG databases and EBSCO Host, the portal of CAPES / MEC and Google Scholar. Results: The most cited concepts in information science and education were de Almeida Junior (2009 and Masetto (2013, respectively. Conclusion: It is observed that the concept of mediation can move interchangeably between both areas. This is because the evidence found in the productions of the last five years indicate that the concept of information of mediation seems to have found its bases in education (educational psychology.

  14. Mediator subunit18 controls flowering time and floral organ identity in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Zhengui Zheng

    Full Text Available Mediator is a conserved multi-protein complex that plays an important role in regulating transcription by mediating interactions between transcriptional activator proteins and RNA polymerase II. Much evidence exists that Mediator plays a constitutive role in the transcription of all genes transcribed by RNA polymerase II. However, evidence is mounting that specific Mediator subunits may control the developmental regulation of specific subsets of RNA polymerase II-dependent genes. Although the Mediator complex has been extensively studied in yeast and mammals, only a few reports on Mediator function in flowering time control of plants, little is known about Mediator function in floral organ identity. Here we show that in Arabidopsis thaliana, MEDIATOR SUBUNIT 18 (MED18 affects flowering time and floral organ formation through FLOWERING LOCUS C (FLC and AGAMOUS (AG. A MED18 loss-of-function mutant showed a remarkable syndrome of later flowering and altered floral organ number. We show that FLC and AG mRNA levels and AG expression patterns are altered in the mutant. Our results support parallels between the regulation of FLC and AG and demonstrate a developmental role for Mediator in plants.

  15. The mediatization of ethical consumption

    DEFF Research Database (Denmark)

    Eskjær, Mikkel Fugl

    2013-01-01

    Over the years, mediatization studies have investigated the influence of media in numerous sections of contemporary society. One area that has received limited attention is the mediatization of consumption, particularly issues concerning ethical consumption. This article presents a study of how...... mediatization is transforming modern consumption and contributing to the mainstreaming of ethical consumption. Based on a study of a Danish online eco-store, the article argues that modern ethical consumption increasingly depends on new media practices to present sustainable consumption as practical...

  16. Assay of mast cell mediators

    DEFF Research Database (Denmark)

    Rådinger, Madeleine; Jensen, Bettina M; Swindle, Emily

    2015-01-01

    Mediator release from activated mast cells is a major initiator of the symptomology associated with allergic disorders such as anaphylaxis and asthma. Thus, methods to monitor the generation and release of such mediators have widespread applicability in studies designed to understand the processes...... regulating mast cell activation and for the identification of therapeutic approaches to block mast cell-driven disease. In this chapter, we discuss approaches used for the determination of mast cell degranulation, lipid-derived inflammatory mediator production, and cytokine/chemokine gene expression as well...

  17. Doing statistical mediation and moderation

    CERN Document Server

    Jose, Paul E

    2013-01-01

    Written in a friendly, conversational style, this book offers a hands-on approach to statistical mediation and moderation for both beginning researchers and those familiar with modeling. Starting with a gentle review of regression-based analysis, Paul Jose covers basic mediation and moderation techniques before moving on to advanced topics in multilevel modeling, structural equation modeling, and hybrid combinations, such as moderated mediation. User-friendly features include numerous graphs and carefully worked-through examples; ""Helpful Suggestions"" about procedures and pitfalls; ""Knowled

  18. Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

    Science.gov (United States)

    Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

    2013-10-30

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

    Science.gov (United States)

    Nelson, Suchitra; Albert, Jeffrey M.

    2013-01-01

    Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

  20. Mediation analysis with multiple versions of the mediator

    OpenAIRE

    VanderWeele, Tyler J.

    2012-01-01

    The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well defined hypothetical interventions on the mediator. In many settings there may be multiple ways to fix the mediator to a particular value and these different hypothetical interventions may have very different implications for the outcome of interest. In this paper we cons...

  1. Detection of Equipment Faults Before Beam Loss

    CERN Document Server

    Galambos, J.

    2016-01-01

    High-power hadron accelerators have strict limits on fractional beam loss. In principle, once a high-quality beam is set up in an acceptable state, beam loss should remain steady. However, in practice, there are many trips in operational machines, owing to excessive beam loss. This paper deals with monitoring equipment health to identify precursor signals that indicate an issue with equipment that will lead to unacceptable beam loss. To this end, a variety of equipment and beam signal measurements are described. In particular, several operational examples from the Spallation Neutron Source (SNS) of deteriorating equipment functionality leading to beam loss are reported.

  2. Weight loss and bone mineral density.

    Science.gov (United States)

    Hunter, Gary R; Plaisance, Eric P; Fisher, Gordon

    2014-10-01

    Despite evidence that energy deficit produces multiple physiological and metabolic benefits, clinicians are often reluctant to prescribe weight loss in older individuals or those with low bone mineral density (BMD), fearing BMD will be decreased. Confusion exists concerning the effects that weight loss has on bone health. Bone density is more closely associated with lean mass than total body mass and fat mass. Although rapid or large weight loss is often associated with loss of bone density, slower or smaller weight loss is much less apt to adversely affect BMD, especially when it is accompanied with high intensity resistance and/or impact loading training. Maintenance of calcium and vitamin D intake seems to positively affect BMD during weight loss. Although dual energy X-ray absorptiometry is normally used to evaluate bone density, it may overestimate BMD loss following massive weight loss. Volumetric quantitative computed tomography may be more accurate for tracking bone density changes following large weight loss. Moderate weight loss does not necessarily compromise bone health, especially when exercise training is involved. Training strategies that include heavy resistance training and high impact loading that occur with jump training may be especially productive in maintaining, or even increasing bone density with weight loss.

  3. Ecological interactions drive evolutionary loss of traits.

    Science.gov (United States)

    Ellers, Jacintha; Kiers, E Toby; Currie, Cameron R; McDonald, Bradon R; Visser, Bertanne

    2012-10-01

    Loss of traits can dramatically alter the fate of species. Evidence is rapidly accumulating that the prevalence of trait loss is grossly underestimated. New findings demonstrate that traits can be lost without affecting the external phenotype, provided the lost function is compensated for by species interactions. This is important because trait loss can tighten the ecological relationship between partners, affecting the maintenance of species interactions. Here, we develop a new perspective on so-called `compensated trait loss' and how this type of trait loss may affect the evolutionary dynamics between interacting organisms. We argue that: (1) the frequency of compensated trait loss is currently underestimated because it can go unnoticed as long as ecological interactions are maintained; (2) by analysing known cases of trait loss, specific factors promoting compensated trait loss can be identified and (3) genomic sequencing is a key way forwards in detecting compensated trait loss. We present a comprehensive literature survey showing that compensated trait loss is taxonomically widespread, can involve essential traits, and often occurs as replicated evolutionary events. Despite its hidden nature, compensated trait loss is important in directing evolutionary dynamics of ecological relationships and has the potential to change facultative ecological interactions into obligatory ones. © 2012 Blackwell Publishing Ltd/CNRS.

  4. Risk factors for hearing loss in neonates

    Directory of Open Access Journals (Sweden)

    Ni Luh Putu Maharani

    2016-11-01

    Full Text Available Background An estimated 6 of 1,000 children with live births suffer from permanent hearing loss at birth or the neonatal period. At least 90% of cases occur in developing countries. Hearing loss should be diagnosed as early as possible so that intervention can be done before the age of 6 months. Objective To determine risk factors for hearing loss in neonates. Methods We performed a case-control study involving 100 neonates with and without hearing loss who were born at Sanglah Hospital, Denpasar from November 2012 to February 2013. Subjects were consisted of 2 groups, those with hearing loss (case group of 50 subjects and without hearing loss (control group of 50 subjects. The groups were matched for gender and birth weight. We assessed the following risk factors for hearing loss: severe neonatal asphyxia, hyperbilirubinemia, meningitis, history of aminoglycoside therapy, and mechanical ventilation by Chi-square analysis. The results were presented as odds ratio and its corresponding 95% confidence intervals. Results Seventy percent of neonates with hearing loss had history of aminoglycoside therapy. Multivariable analysis revealed that aminoglycoside therapy of 14 days or more was a significant risk factor for hearing loss (OR 2.7; 95%CI 1.1 to 6.8; P=0.040. There were no statistically significant associations between hearing loss and severe asphyxia, hyperbilirubinemia, meningitis, or mechanical ventilation. Conclusion Aminoglycoside therapy for >=14 days was identified as a risk factor for hearing loss in neonates.

  5. Sudden bilateral hearing loss after organophosphate inhalation

    Directory of Open Access Journals (Sweden)

    Mehmet Akif Dundar

    2016-12-01

    Full Text Available Sudden bilateral hearing loss are seen rarely and the toxic substance exposure constitutes a small part of etiology. A Fifty-eight-year-old woman admitted to our clinic with sudden bilateral hearing loss shortly after chlorpyrifos-ethyl exposure. Otolaryngologic examination findings were normal. The patient had 40 dB sensorineural hearing loss (SNHL on the right ear and 48 dB SNHL on the left ear. Additional diagnostic tests were normal. The conventional treatment for sudden hearing loss was performed. On the second week following organophosphate (OP exposure the patient's hearing loss almost completely resolved. OP's are heavily used in agriculture and should be taken into consideration as an etiologic factor in sudden hearing loss. Keywords: Organophosphates, Hearing loss, Sudden

  6. Loss Factor Characterization Methodology for Piezoelectric Ceramics

    International Nuclear Information System (INIS)

    Zhuang Yuan; Ural, Seyit O; Uchino, Kenji

    2011-01-01

    The key factor for the miniaturization of piezoelectric devices is power density, which is limited by the heat generation or loss mechanisms. There are three loss components for piezoelectric vibrators, i.e., dielectric, elastic and piezoelectric losses. The mechanical quality factor, determined by these three factors, is the figure of merit in the sense of loss or heat generation. In this paper, quality factors of resonance and antiresonance for k 31 , k 33 , and k 15 vibration modes are derived, and the methodology to determine loss factors in various directions is provided. For simplicity, we focus on materials with ∞mm (equivalent to 6mm) crystal symmetry for deriving the loss factors of polycrystalline ceramics, and 16 different loss factors among total 20 can be obtained from the admittance/ impedance measurements.

  7. Loss of ions in cavity ionization chambers

    International Nuclear Information System (INIS)

    Takata, N.; Tran, N.T.; Kim, E.; Marsoem, P.; Kurosawa, T.; Koyama, Y.

    2005-01-01

    Ion losses due to initial recombination, volume recombination, and back diffusion were each determined by measurements and calculations for different size cylindrical ionization chambers and spherical ionization chambers. By measuring signal currents from these ionization chambers irradiated with 60 Co gamma rays, two groups of ion losses were obtained. (Group 1) Ion loss due to initial recombination and diffusion, which changes proportionally to the inverse of the voltage applied to the ionization chambers; (and group 2) ion loss due to volume recombination, which changes proportionally to the inverse of the square of the applied voltage. The diffusion loss was obtained separately by computing electric field distributions in the ionization chambers. It was found that diffusion loss is larger than initial recombination loss for the cylindrical ionization chambers and vise versa for the spherical ionization chambers

  8. Hormonal therapy in female pattern hair loss

    Directory of Open Access Journals (Sweden)

    Kevin R. Brough

    2017-03-01

    Full Text Available Female pattern hair loss is the most common cause of hair loss in women and one of the most common problems seen by dermatologists. This hair loss is a nonscarring alopecia in which loss occurs on the vertex scalp, generally sparing the frontal hairline. Hair loss can have significant psychosocial effects on patients, and treatment can be long and difficult. The influence of hormones on the pathogenesis of female pattern hair loss is not entirely known. The purpose of this paper is to review physiology and potential hormonal mechanisms for the pathogenesis of female pattern hair loss. We also discuss the current hormonal and hormone-modifying therapies that are available to providers as they partner with patients to treat this frustrating issue.

  9. Proximal predictors of depressive symptomatology: perceived losses in self-worth and interpersonal domains and introjective and anaclitic mood states.

    Science.gov (United States)

    Kopala-Sibley, Daniel C; Zuroff, David C

    2010-01-01

    Although much research has demonstrated a relationship between negative life events and depressive symptoms, relatively little research has examined the mechanisms that may mediate this relationship. The theories of Blatt (1974), Bowlby (1980), and Gilbert (1992) each propose proximal predictors of depression. In accordance with these theories, this study examined the relationships among perceived losses in self-worth and interpersonal relationships, anaclitic (dependent) and introjective (self-critical) mood states, and depressive symptoms following a significant negative life event. A sample of 172 undergraduate students completed measures of depressive symptoms and depressive vulnerability factors and retrospectively described the worst period of their lives. They also rated the extent to which the events surrounding this worst period affected their self-worth and their relationships with close others. Structural equation modeling demonstrated that the effect of a perceived loss of self-worth on depressive symptoms was fully mediated by both introjective and anaclitic mood states, whereas the effect of a perceived loss of interpersonal relationships on depressive symptoms was fully mediated by an anaclitic mood state. Additionally, perceived losses of self-worth showed a stronger effect on introjective mood in highly self-critical individuals. Findings highlight the importance of perceived losses in both self-worth and interpersonal domains in response to adverse life events and suggest pathways through which perceived losses may affect depressive symptoms.

  10. Loss-free neutron polarization

    International Nuclear Information System (INIS)

    Mueller, S.; Badurek, G.

    2001-01-01

    Full text: The so-called concept of 'dynamical' neutron polarization should allow to polarize a beam of thermal or cold neutrons without loosing even one particle. It is based upon the spin-dependent energy splitting of monochromatic neutrons in a NMR-like arrangement of crossed static and oscillating magnetic fields, which causes different interaction times of the two opposite spin states with a subsequent static precession field. If this Larmor rotation is stopped at the moment when the two states are oriented parallel to a given direction, the beam will be fully polarized, on the cost of a tiny energy difference between the two states, however. At pulsed neutron sources this method should even allow loss-free polarization of polychromatic neutrons, if by a suitably chosen time dependence of either the precession or the splitting field the flight-time dispersion of the particles is adequately taken into account. However, until now this quite sophisticated method has not been realized experimentally. We have performed detailed analytical and numerical simulations of such a dynamical polarization facility for pulsed neutron beams in order to proof its feasibility. It turns out that the required space and time dependence of the magnetic fields involved are well within the scope of existing magnet technology. Ref. 1 (author)

  11. Beam Cooling with ionisation losses

    CERN Document Server

    Rubbia, Carlo; Kadi, Y; Vlachoudis, V

    2006-01-01

    A novel type of particle "cooling", called Ionization Cooling, is applicable to slow (v of the order of 0.1c) ions stored in a small ring. The many traversals through a thin foil enhance the nuclear reaction probability, in a steady configuration in which ionisation losses are recovered at each turn by a RF-cavity. For a uniform target "foil" the longitudinal momentum spread diverges exponentially since faster (slower) particles ionise less (more) than the average. In order to "cool" also longitudinally, a chromaticity has to be introduced with a wedge shaped "foil". Multiple scattering and straggling are then "cooled" in all three dimensions, with a method similar to the one of synchrotron cooling, but valid for low energy ions. Particles then stably circulate in the beam indefinitely, until they undergo for instance nuclear processes in the thin target foil. This new method is under consideration for the nuclear production of a few MeV/A ion beams. Simple reactions, for instance Li 7 + D Li 8 + p, are more ...

  12. Sleep loss produces false memories.

    Directory of Open Access Journals (Sweden)

    Susanne Diekelmann

    Full Text Available People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal",..., lacking the strongest common associate or theme word (here: "black". Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.

  13. Information Loss from Technological Progress

    International Nuclear Information System (INIS)

    Townsend, P D

    2014-01-01

    Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies

  14. Optimal compensation for neuron loss

    Science.gov (United States)

    Barrett, David GT; Denève, Sophie; Machens, Christian K

    2016-01-01

    The brain has an impressive ability to withstand neural damage. Diseases that kill neurons can go unnoticed for years, and incomplete brain lesions or silencing of neurons often fail to produce any behavioral effect. How does the brain compensate for such damage, and what are the limits of this compensation? We propose that neural circuits instantly compensate for neuron loss, thereby preserving their function as much as possible. We show that this compensation can explain changes in tuning curves induced by neuron silencing across a variety of systems, including the primary visual cortex. We find that compensatory mechanisms can be implemented through the dynamics of networks with a tight balance of excitation and inhibition, without requiring synaptic plasticity. The limits of this compensatory mechanism are reached when excitation and inhibition become unbalanced, thereby demarcating a recovery boundary, where signal representation fails and where diseases may become symptomatic. DOI: http://dx.doi.org/10.7554/eLife.12454.001 PMID:27935480

  15. Information Loss from Technological Progress

    Science.gov (United States)

    Townsend, P. D.

    2014-12-01

    Progress in electronics and optics offers faster computers, and rapid communication via the internet that is matched by ever larger and evolving storage systems. Instinctively one assumes that this must be totally beneficial. However advances in software and storage media are progressing in ways which are frequently incompatible with earlier systems and the economics and commercial pressures rarely guarantee total compatibility with earlier systems. Instead, the industries actively choose to force the users to purchase new systems and software. Thus we are moving forward with new technological variants that may have access to only the most recent systems and we will have lost earlier alternatives. The reality is that increased processing speed and storage capacity are matched by an equally rapid decline in the access and survival lifetime of older information. This pattern is not limited to modern electronic systems but is evident throughout history from writing on stone and clay tablets to papyrus and paper. It is equally evident in image systems from painting, through film, to magnetic tapes and digital cameras. In sound recording we have variously progressed from wax discs to vinyl, magnetic tape and CD formats. In each case the need for better definition and greater capacity has forced the earlier systems into oblivion. Indeed proposed interactive music systems could similarly relegate music CDs to specialist collections. The article will track some of the examples and discuss the consequences as well as noting that this information loss is further compounded by developments in language and changes in cultural views of different societies.

  16. Biodiversity losses: The downward spiral

    Science.gov (United States)

    Tomback, Diana F.; Kendall, Katherine C.; Tomback, Diana F.; Arno, Stephen F.; Keane, Robert E.

    2001-01-01

    The dramatic decline of whitebark pine (Pinus albicaulis) populations in the northwestern United States and southwestern Canada from the combined effects of fire exclusion, mountain pine beetles (Dendroctonus ponderosae), and white pine blister rust (Cronartium ribicola), and the projected decline of whitebark pine populations rangewide (Chapters 10 and 11) do not simply add up to local extirpations of a single tree species. Instead, the loss of whitebark pine has broad ecosystem-level consequences, eroding local plant and animal biodiversity, changing the time frame of succession, and altering the distribution of subalpine vegetation (Chapter 1). One potential casualty of this decline may be the midcontinental populations of the grizzly bear (Ursus arctos horribilis), which use whitebark pine seeds as a major food source (Chapter 7). Furthermore, whitebark pine is linked to other white pine ecosystems in the West through its seed-disperser, Clark's nutcracker (Nucifraga columbiana) (Chapter 5). Major declines in nutcracker populations ultimately seal the fate of several white pine ecosystems, and raise the question of whether restoration is possible once a certain threshold of decline is reached.

  17. Dimensional reduction in anomaly mediation

    International Nuclear Information System (INIS)

    Boyda, Ed; Murayama, Hitoshi; Pierce, Aaron

    2002-01-01

    We offer a guide to dimensional reduction in theories with anomaly-mediated supersymmetry breaking. Evanescent operators proportional to ε arise in the bare Lagrangian when it is reduced from d=4 to d=4-2ε dimensions. In the course of a detailed diagrammatic calculation, we show that inclusion of these operators is crucial. The evanescent operators conspire to drive the supersymmetry-breaking parameters along anomaly-mediation trajectories across heavy particle thresholds, guaranteeing the ultraviolet insensitivity

  18. Body talk among undergraduate women: why conversations about exercise and weight loss differentially predict body appreciation.

    Science.gov (United States)

    Wasylkiw, Louise; Butler, Nicole A

    2014-08-01

    Undergraduate women (N = 143) completed self-reports on exercise behavior, body orientation, body appreciation, and body-related talk. Results showed that conversations about weight loss/dieting and conversations about exercise differentially predicted body appreciation. Importantly, multiple regression analyses showed that the relationship between talk type and body appreciation was explained by the object-process dichotomy: Conversations about exercise oriented women to consider what their bodies can do which, in turn, predicted appreciation of one's body. In contrast, the relationship between conversations about weight loss/dieting and body appreciation was mediated by negative attitudes about one's body but not by an object orientation. © The Author(s) 2013.

  19. Factors affecting the loss of MED12-mutated leiomyoma cells during in vitro growth

    OpenAIRE

    Bloch, Jeannine; Holzmann, Carsten; Koczan, Dirk; Helmke, Burkhard Maria; Bullerdiek, J?rn

    2017-01-01

    Uterine leiomyomas (UL) are the most prevalent symptomatic human tumors at all and somatic mutations of the gene encoding mediator subcomplex 12 (MED12) constitute the most frequent driver mutations in UL. Recently, a rapid loss of mutated cells during in vitro growth of UL-derived cell cultures was reported, resulting in doubts about the benefits of UL-derived cell cultures. To evaluate if the rapid loss of MED12-mutated cells in UL cell cultures depends on in vitro passaging, we set up cell...

  20. Tolerance to bovine clinical mastitis: Total, direct, and indirect milk losses.

    Science.gov (United States)

    Detilleux, J

    2018-04-01

    The objectives of this paper were to estimate direct and indirect milk losses associated with mastitis. Indirect losses, linked to indirect tolerance, are mediated by the increase in milk somatic cell count (SCC) in response to bacterial infection. Direct losses, linked to weak direct tolerance, are not mediated by the increase in SCC. So far, studies have evaluated milk loss associated with clinical mastitis without considering both components, which may lead to biased estimates of their sum; that is, the total loss in milk. A total of 43,903 test-day records on milk and SCC from 3,716 cows and 5,858 lactations were analyzed with mediation mixed models and health trajectories to estimate the amount of direct, indirect, and total milk losses after adjustment for known and potentially unmeasured (sensitivity analyses) confounding factors. Estimates were formalized under the counterfactual causal theory of causation. In this study, milk losses were mostly mediated by an increase in SCC. They were highest in the first month of lactation, when SCC were highest. Milk losses were estimated at 0.5, 0.8, and 1.1 kg/d in first, second, and third and greater parity, respectively. Two phases described how changes in milk were associated with changes in SCC: on average, one occurred before and one after the day preceding the clinical diagnosis. In both phases, changes in milk were estimated at 1 mg/d per 10 3 cells/mL. After adjusting for known confounders, cow effect accounted for 20.7 and 64.2% of the variation in milk in the first and second phases, respectively. This suggests that deviations from the resilient path were highest during the second phase of inflammation and that selection for cows more tolerant to mastitis is feasible. As discussed herein, epigenetic regulation of macrophage polarization may contribute to the variation in milk observed in the second phase. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. 7 CFR 760.611 - Qualifying losses, eligible causes and types of loss.

    Science.gov (United States)

    2010-01-01

    ... final planting date; (4) The cause of loss was due to water contained or released by any governmental... containment or release of the water; (5) The cause of loss was due to conditions or events occurring outside...) Losses caused by a failure of power supply or brownout as defined in § 760.602; (2) Losses caused by the...

  2. Thinning Hair and Hair Loss: Could it be Female Pattern Hair Loss?

    Science.gov (United States)

    ... mcat1=de12", ]; for (var c = 0; c Thinning hair and hair loss: Could it be female pattern hair loss? Female pattern hair loss: Without treatment, female ... can I tell if I have female pattern hair loss? It’s best to make an appointment to ...

  3. The role of message framing in promoting MMR vaccination: evidence of a loss-frame advantage.

    Science.gov (United States)

    Abhyankar, Purva; O'Connor, Daryl B; Lawton, Rebecca

    2008-01-01

    This study examined the effects of message framing on intentions to obtain the measles, mumps and rubella (MMR) vaccine for one's child and investigated whether Theory of Planned Behaviour (TPB) and perceived outcome efficacy variables mediate and/or moderate message framing effects. One hundred and forty women read either a loss-framed or gain-framed message and then completed measures assessing their intentions to obtain the MMR vaccine for their child, and TPB and outcome efficacy variables. Exposure to the loss frame increased intentions to obtain the MMR vaccine and influenced perceptions of outcome efficacy. This suggests that outcome efficacy, but not other TPB variables may mediate framing effects within the context of MMR vaccination. Message frame, in addition to TPB variables, significantly predicted unique variance in behavioural intentions. These findings are discussed within the context of Prospect Theory, perceived risk and prevention/detection behaviours.

  4. When gains loom larger than losses: reversed loss aversion for small amounts of money.

    Science.gov (United States)

    Harinck, Fieke; Van Dijk, Eric; Van Beest, Ilja; Mersmann, Paul

    2007-12-01

    Previous research has generally shown that people are loss averse; that is, they weigh losses more heavily than gains. In a series of three experiments, we found that for small outcomes, this pattern is reversed, and gains loom larger than losses. We explain this reversal on the basis of (a) the hedonic principle, which states that individuals are motivated to maximize pleasure and to minimize pain, and (b) the assumption that small losses are more easily discounted cognitively than large losses are.

  5. Loss and modification of habitat

    Science.gov (United States)

    Lemckert, Francis; Hecnar, Stephen; Pilliod, David S.; Wilkinson, John W.; Heatwole, Harold

    2012-01-01

    Amphibians live in a wide variety of habitats around the world, many of which have been modified or destroyed by human activities. Most species have unique life history characteristics adapted to specific climates, habitats (e.g., lentic, lotic, terrestrial, arboreal, fossorial, amphibious), and local conditions that provide suitable areas for reproduction, development and growth, shelter from environmental extremes, and predation, as well as connectivity to other populations or habitats. Although some species are entirely aquatic or terrestrial, most amphibians, as their name implies, lead a dual life and require a mosaic of habitats in both aquatic and terrestrial ecosystems. With over 6 billion people on Earth, most species are now persisting in habitats that have been directly or indirectly influenced by human activities. Some species have disappeared where their habitats have been completely destroyed, reduced, or rendered unsuitable. Habitat loss and degradation are widely considered by most researchers as the most important causes of amphibian population decline globally (Barinaga 1990; Wake and Morowitz 1991; Alford and Richards 1999). In this chapter, a background on the diverse habitat requirements of amphibians is provided, followed by a discussion of the effects of urbanization, agriculture, livestock grazing, timber production and harvesting, fire and hazardous fuel management, and roads on amphibians and their habitats. Also briefly discussed is the influence on amphibian habitats of natural disturbances, such as extreme weather events and climate change, given the potential for human activities to impact climate in the longer term. For amphibians in general, microhabitats are of greater importance than for other vertebrates. As ectotherms with a skin that is permeable to water and with naked gelatinous eggs, amphibians are physiologically constrained to be active during environmental conditions that provide appropriate body temperatures and adequate

  6. Voluntary Sleep Loss in Rats

    Science.gov (United States)

    Oonk, Marcella; Krueger, James M.; Davis, Christopher J.

    2016-01-01

    Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents. Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus. Rats were allowed to self-stimulate, or underwent gentle handling-induced SDEP (GH-SDEP), during the first 6 h of the light phase, after which they were allowed to sleep. Other rats performed the 6 h ICSS and 1 w later were subjected to 6 h of noncontingent stimulation (NCS). During NCS the individual stimulation patterns recorded during ICSS were replayed. Results: After GH-SDEP, ICSS, or NCS, time in nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep increased. Further, in the 24 h after SDEP, rats recovered all of the REM sleep lost during SDEP, but only 75% to 80% of the NREM sleep lost, regardless of the SDEP method. The magnitude of EEG slow wave responses occurring during NREM sleep also increased after SDEP treatments. However, NREM sleep EEG slow wave activity (SWA) responses were attenuated following ICSS, compared to GH-SDEP and NCS. Conclusions: We conclude that ICSS and NCS can be used to sleep deprive rats. Changes in rebound NREM sleep EEG SWA occurring after ICSS, NCS, and GH-SDEP suggest that nonspecific effects of the SDEP procedure differentially affect recovery sleep phenotypes. Citation: Oonk M, Krueger JM, Davis CJ. Voluntary sleep loss in rats. SLEEP 2016;39(7):1467–1479. PMID:27166236

  7. Erosional losses of fallout plutonium

    International Nuclear Information System (INIS)

    Foster, G.R.; Hakonson, T.E.

    1987-01-01

    Plutonium from fallout after atmospheric explosion of nuclear weapons in the 1950's and 1960s is being redistributed over the landscape by soil erosion and carried on sediment by streams to oceans. Erosion rates computed with the Universal Soil Loss Equation for more than 200,000 sample points on nonfederal land across the US were used to estimate plutonium removal rates by soil erosion. On the average, only about 4% of the eroded sediment reaches the outlet of a major river. The remaining sediment is deposited en route, and because deposition is a selective process, the sediment is enriched in fine particles having the highest concentration of plutonium because of the element's strong association with clay and silt-sized sediment. Estimated enrichment ratios, sediment delivery ratios, and erosion rates were used to estimate annual delivery of fallout plutonium. These estimates ranged from 0.002% of the initial fallout plutonium inventory for the Savannah River basin to 0.01% for the Columbia River basin, to 0.02% for the Hudson and Rio Grande River basins, to 0.08% for the Mississippi River basin. If the deposition of plutonium had been uniformly 1 mCi/km 2 , the estimated plutonium activity on suspended sediment would range from about 7 fCi/g of sediment of the Savannah River basin, to 9 fCi/g for the Mississippi River basin, to 12 fCi/g for the Hudson River basin, to 14 fCi/g for the Columbia and Rio Grande River basins. 45 references, 2 figures, 17 tables

  8. Kids, candy, brain and behavior: Age differences in responses to candy gains and losses

    Directory of Open Access Journals (Sweden)

    Katherine R. Luking

    2014-07-01

    Full Text Available The development of reward-related neural systems, from adolescence through adulthood, has received much recent attention in the developmental neuroimaging literature. However, few studies have investigated behavioral and neural responses to both gains and losses in pre-pubertal child populations. To address this gap in the literature, in the present study healthy children aged 7–11 years and young-adults completed an fMRI card-guessing game using candy pieces delivered post-scan as an incentive. Age differences in behavioral and neural responses to candy gains/losses were investigated. Adults and children displayed similar responses to gains, but robust age differences were observed following candy losses within the caudate, thalamus, insula, and hippocampus. Interestingly, when task behavior was included as a factor in post hoc mediation analyses, activation following loss within the caudate/thalamus related to task behavior and relationships with age were no longer significant. Conversely, relationships between response to loss and age within the hippocampus and insula remained significant even when controlling for behavior, with children showing heightened loss responses within the dorsal/posterior insula. These results suggest that both age and task behavior influence responses within the extended reward circuitry, and that children seem to be more sensitive than adults to loss feedback particularly within the dorsal/posterior insula.

  9. Mediator Recruitment to Heat Shock Genes Requires Dual Hsf1 Activation Domains and Mediator Tail Subunits Med15 and Med16*

    Science.gov (United States)

    Kim, Sunyoung; Gross, David S.

    2013-01-01

    The evolutionarily conserved Mediator complex is central to the regulation of gene transcription in eukaryotes because it serves as a physical and functional interface between upstream regulators and the Pol II transcriptional machinery. Nonetheless, its role appears to be context-dependent, and the detailed mechanism by which it governs the expression of most genes remains unknown. Here we investigate Mediator involvement in HSP (heat shock protein) gene regulation in the yeast Saccharomyces cerevisiae. We find that in response to thermal upshift, subunits representative of each of the four Mediator modules (Head, Middle, Tail, and Kinase) are rapidly, robustly, and selectively recruited to the promoter regions of HSP genes. Their residence is transient, returning to near-background levels within 90 min. Hsf1 (heat shock factor 1) plays a central role in recruiting Mediator, as indicated by the fact that truncation of either its N- or C-terminal activation domain significantly reduces Mediator occupancy, whereas removal of both activation domains abolishes it. Likewise, ablation of either of two Mediator Tail subunits, Med15 or Med16, reduces Mediator recruitment to HSP promoters, whereas deletion of both abolishes it. Accompanying the loss of Mediator, recruitment of RNA polymerase II is substantially diminished. Interestingly, Mediator antagonizes Hsf1 occupancy of non-induced promoters yet facilitates enhanced Hsf1 association with activated ones. Collectively, our observations indicate that Hsf1, via its dual activation domains, recruits holo-Mediator to HSP promoters in response to acute heat stress through cooperative physical and/or functional interactions with the Tail module. PMID:23447536

  10. Sympathetic mediated vasomotion and skin capillary permeability in diabetic patients with peripheral neuropathy

    NARCIS (Netherlands)

    Lefrandt, JD; Hoeven, JH; Roon, AM; Smit, AJ; Hoogenberg, K

    Aims/hypothesis. A loss of sympathetic function could lead to changes in capillary fluid filtration in diabetic patients. We investigated whether a decreased sympathetically mediated vasomotion in the skin in diabetic patients with peripheral neuropathy is associated with an abnormal capillary

  11. Dietary Approaches to Protect Against Eye Blast Induced Oxidative Stress and Vision Loss

    Science.gov (United States)

    2016-11-01

    type (C57Bl/6) and Gulo-/- mice maintained on normal or low vitamin C. C, D ) MDA levels in the A) cortex and B) liver of Gulo-/- mice maintained...significantly to the progressive cell death and neuronal degeneration that we detect after ocular trauma and, thus, treating with Vitamins C and E or a...we may have identified IL-1 as an important mediator of vision loss after ocular trauma. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17

  12. Environmental cost of distribution transformer losses

    International Nuclear Information System (INIS)

    Georgilakis, Pavlos S.

    2011-01-01

    Improvements in energy efficiency of electrical equipment reduce the greenhouse gas (GHG) emissions and contribute to the protection of the environment. Moreover, as system investment and energy costs continue to increase, electric utilities are increasingly interested in installing energy-efficient transformers at their distribution networks. This paper analyzes the impact of the environmental cost of transformer losses on the economic evaluation of distribution transformers. This environmental cost is coming form the cost to buy GHG emission credits because of the GHG emissions associated with supplying transformer losses throughout the transformer lifetime. Application results on the Hellenic power system for 21 transformer offers under 9 different scenarios indicate that the environmental cost of transformer losses can reach on average 34% and 8% of transformer purchasing price for high loss and medium loss transformers, respectively. That is why it is important to incorporate the environmental cost of transformer losses into the economic evaluation of distribution transformers.

  13. Classifications of Patterned Hair Loss: A Review.

    Science.gov (United States)

    Gupta, Mrinal; Mysore, Venkataram

    2016-01-01

    Patterned hair loss is the most common cause of hair loss seen in both the sexes after puberty. Numerous classification systems have been proposed by various researchers for grading purposes. These systems vary from the simpler systems based on recession of the hairline to the more advanced multifactorial systems based on the morphological and dynamic parameters that affect the scalp and the hair itself. Most of these preexisting systems have certain limitations. Currently, the Hamilton-Norwood classification system for males and the Ludwig system for females are most commonly used to describe patterns of hair loss. In this article, we review the various classification systems for patterned hair loss in both the sexes. Relevant articles were identified through searches of MEDLINE and EMBASE. Search terms included but were not limited to androgenic alopecia classification, patterned hair loss classification, male pattern baldness classification, and female pattern hair loss classification. Further publications were identified from the reference lists of the reviewed articles.

  14. Extending Stochastic Network Calculus to Loss Analysis

    Directory of Open Access Journals (Sweden)

    Chao Luo

    2013-01-01

    Full Text Available Loss is an important parameter of Quality of Service (QoS. Though stochastic network calculus is a very useful tool for performance evaluation of computer networks, existing studies on stochastic service guarantees mainly focused on the delay and backlog. Some efforts have been made to analyse loss by deterministic network calculus, but there are few results to extend stochastic network calculus for loss analysis. In this paper, we introduce a new parameter named loss factor into stochastic network calculus and then derive the loss bound through the existing arrival curve and service curve via this parameter. We then prove that our result is suitable for the networks with multiple input flows. Simulations show the impact of buffer size, arrival traffic, and service on the loss factor.

  15. Sensorineural hearing loss in hemorrhagic dengue?

    Directory of Open Access Journals (Sweden)

    Bruna Natália Freire Ribeiro

    2015-01-01

    Discussion and conclusion: This is the first case report that brings together DHF and sudden hearing loss. In the development of this case no other cause to sudden hearing loss was found and the correlation between dengue and hearing loss was questioned. In the literature review was found that some viruses, as mumps virus, varicella-zoster virus and HSV-1 and HSV-2 are related to sudden hearing loss, all of them fit in the viral theory. Besides the viral theory of sudden hearing loss, there is the vascular theory that is the occlusion of the end artery that supplies the cochlea. DHF has a vascular commitment, and the hypothesis of a vascular cause could be elicited in this case. Many studies in this area are needed and this article has the objective of elicit the discussion about the subject. Could dengue be associated with sensorineural hearing loss?

  16. Estimation of radiation losses from sheathed thermocouples

    International Nuclear Information System (INIS)

    Roberts, I.L.; Coney, J.E.R.; Gibbs, B.M.

    2011-01-01

    Thermocouples are often used for temperature measurements in heat exchangers. However if the radiation losses from a thermocouple in a high temperature gas flow to colder surroundings are ignored significant errors can occur. Even at moderate temperature differences, these can be significant. Prediction of radiation losses from theory can be problematic, especially in situations where there are large variations in the measured temperatures as the emissivity and radiative heat transfer coefficient of the thermocouple are not constant. The following approach combines experimental results with established empirical relationships to estimate losses due to radiation in an annular heat exchanger at temperatures up to 950 o C. - Highlights: → Sheathed thermocouples are often used to measure temperatures in heat exchangers. → Errors are introduced if radiation losses are ignored. → Radiation losses are environment specific and may be significant. → Experimental and theoretical methods are used to estimate losses. → Hot side maximum temperature 950 o C.

  17. Deciding for Others Reduces Loss Aversion

    DEFF Research Database (Denmark)

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

    We study risk taking on behalf of others, both with and without potential losses. A large-scale incentivized experiment is conducted with subjects randomly drawn from the Danish population. On average, decision makers take the same risks for other people as for themselves when losses are excluded....... In contrast, when losses are possible, decisions on behalf of others are more risky. Using structural estimation, we show that this increase in risk stems from a decrease in loss aversion when others are affected by their choices.......We study risk taking on behalf of others, both with and without potential losses. A large-scale incentivized experiment is conducted with subjects randomly drawn from the Danish population. On average, decision makers take the same risks for other people as for themselves when losses are excluded...

  18. 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...

  19. 22 CFR 218.33 - Mediation.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Mediation. 218.33 Section 218.33 Foreign... § 218.33 Mediation. (a) Referral of complaints for mediation. The agency will refer to the Federal Mediation and Conciliation Service all complaints that: (1) fall within the jurisdiction of these...

  20. 15 CFR 923.54 - Mediation.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Mediation. 923.54 Section 923.54... Mediation. (a) Section 307(h) of the Act provides for mediation of serious disagreement between any Federal... cases, mediation by the Secretary, with the assistance of the Executive Office of the President, may be...