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Sample records for excessive signaling leads

  1. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus

    Science.gov (United States)

    Shim, Joon W.; Sandlund, Johanna; Hameed, Mustafa Q.; Blazer-Yost, Bonnie; Zhou, Feng C.; Klagsbrun, Michael; Madsen, Joseph R.

    2016-01-01

    Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus. PMID:27243144

  2. FGF10 maintains distal lung bud epithelium and excessive signaling leads to progenitor state arrest, distalization, and goblet cell metaplasia

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    Kobberup Sune

    2008-01-01

    Full Text Available Abstract Background Interaction with the surrounding mesenchyme is necessary for development of endodermal organs, and Fibroblast growth factors have recently emerged as mesenchymal-expressed morphogens that direct endodermal morphogenesis. The fibroblast growth factor 10 (Fgf10 null mouse is characterized by the absence of lung bud development. Previous studies have shown that this requirement for Fgf10 is due in part to its role as a chemotactic factor during branching morphogenesis. In other endodermal organs Fgf10 also plays a role in regulating differentiation. Results Through gain-of-function analysis, we here find that FGF10 inhibits differentiation of the lung epithelium and promotes distalization of the embryonic lung. Ectopic expression of FGF10 in the lung epithelium caused impaired lung development and perinatal lethality in a transgenic mouse model. Lung lobes were enlarged due to increased interlobular distance and hyperplasia of the airway epithelium. Differentiation of bronchial and alveolar cell lineages was inhibited. The transgenic epithelium consisted predominantly of proliferating progenitor-like cells expressing Pro-surfactant protein C, TTF1, PEA3 and Clusterin similarly to immature distal tip cells. Strikingly, goblet cells developed within this arrested epithelium leading to goblet cell hyperplasia. Conclusion We conclude that FGF10 inhibits terminal differentiation in the embryonic lung and maintains the distal epithelium, and that excessive levels of FGF10 leads to metaplastic differentiation of goblet cells similar to that seen in chronic inflammatory diseases.

  3. Aging-associated excess formaldehyde leads to spatial memory deficits

    Science.gov (United States)

    Tong, Zhiqian; Han, Chanshuai; Luo, Wenhong; Li, Hui; Luo, Hongjun; Qiang, Min; Su, Tao; Wu, Beibei; Liu, Ying; Yang, Xu; Wan, You; Cui, Dehua; He, Rongqiao

    2013-01-01

    Recent studies show that formaldehyde participates in DNA demethylation/methylation cycle. Emerging evidence identifies that neuronal activity induces global DNA demethylation and re-methylation; and DNA methylation is a critical step for memory formation. These data suggest that endogenous formaldehyde may intrinsically link learning-responsive DNA methylation status and memory formation. Here, we report that during spatial memory formation process, spatial training induces an initial global DNA demethylation and subsequent re-methylation associated with hippocampal formaldehyde elevation then decline to baseline level in Sprague Dawley rats. Scavenging this elevated formaldehyde by formaldehyde-degrading enzyme (FDH), or enhancing DNA demethylation by a DNA demethylating agent, both led to spatial memory deficits by blocking DNA re-methylation in rats. Furthermore, we found that the normal adult rats intrahippocampally injected with excess formaldehyde can imitate the aged-related spatial memory deficits and global DNA methylation decline. These findings indicate that aging-associated excess formaldheyde contributes to cognitive decline during aging. PMID:23657727

  4. Excessive nitrite affects zebrafish valvulogenesis through yielding too much NO signaling.

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    Junbo Li

    Full Text Available Sodium nitrite, a common food additive, exists widely not only in the environment but also in our body. Excessive nitrite causes toxicological effects on human health; however, whether it affects vertebrate heart valve development remains unknown. In vertebrates, developmental defects of cardiac valves usually lead to congenital heart disease. To understand the toxic effects of nitrite on valvulogenesis, we exposed zebrafish embryos with different concentrations of sodium nitrite. Our results showed that sodium nitrite caused developmental defects of zebrafish heart dose dependently. It affected zebrafish heart development starting from 36 hpf (hour post fertilization when heart initiates looping process. Comprehensive analysis on the embryos at 24 hpf and 48 hpf showed that excessive nitrite did not affect blood circulation, vascular network, myocardium and endocardium development. But development of endocardial cells in atrioventricular canal (AVC of the embryos at 48 hpf was disrupted by too much nitrite, leading to defective formation of primitive valve leaflets at 76 hpf. Consistently, excessive nitrite diminished expressions of valve progenitor markers including bmp4, has2, vcana and notch1b at 48 hpf. Furthermore, 3', 5'-cyclic guanosine monophosphate (cGMP, downstream of nitric oxide (NO signaling, was increased its level significantly in the embryos exposed with excessive nitrite and microinjection of soluble guanylate cyclase inhibitor ODQ (1H-[1], [2], [4]Oxadiazolo[4,3-a] quinoxalin-1-one, an antagonist of NO signaling, into nitrite-exposed embryos could partly rescue the cardiac valve malformation. Taken together, our results show that excessive nitrite affects early valve leaflet formation by producing too much NO signaling.

  5. NCHS - Potentially Excess Deaths from the Five Leading Causes of Death

    Data.gov (United States)

    U.S. Department of Health & Human Services — Potentially Excess Deaths from the Five Leading Causes of Death in Nonmetropolitan and Metropolitan Areas, United States, 2005-2015. Mortality data for U.S....

  6. Necroptosis Promotes Staphylococcus aureus Clearance by Inhibiting Excessive Inflammatory Signaling

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    Kipyegon Kitur

    2016-08-01

    Full Text Available Staphylococcus aureus triggers inflammation through inflammasome activation and recruitment of neutrophils, responses that are critical for pathogen clearance but are associated with substantial tissue damage. We postulated that necroptosis, cell death mediated by the RIPK1/RIPK3/MLKL pathway, would function to limit pathological inflammation. In models of skin infection or sepsis, Mlkl−/− mice had high bacterial loads, an inability to limit interleukin-1b (IL-1b production, and excessive inflammation. Similarly, mice treated with RIPK1 or RIPK3 inhibitors had increased bacterial loads in a model of sepsis. Ripk3−/− mice exhibited increased staphylococcal clearance and decreased inflammation in skin and systemic infection, due to direct effects of RIPK3 on IL-1b activation and apoptosis. In contrast to Casp1/4−/− mice with defective S. aureus killing, the poor outcomes of Mlkl−/− mice could not be attributed to impaired phagocytic function. We conclude that necroptotic cell death limits the pathological inflammation induced by S. aureus.

  7. Tau excess impairs mitosis and kinesin-5 function, leading to aneuploidy and cell death.

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    Bougé, Anne-Laure; Parmentier, Marie-Laure

    2016-03-01

    In neurodegenerative diseases such as Alzheimer's disease (AD), cell cycle defects and associated aneuploidy have been described. However, the importance of these defects in the physiopathology of AD and the underlying mechanistic processes are largely unknown, in particular with respect to the microtubule (MT)-binding protein Tau, which is found in excess in the brain and cerebrospinal fluid of affected individuals. Although it has long been known that Tau is phosphorylated during mitosis to generate a lower affinity for MTs, there is, to our knowledge, no indication that an excess of this protein could affect mitosis. Here, we studied the effect of an excess of human Tau (hTau) protein on cell mitosis in vivo. Using the Drosophila developing wing disc epithelium as a model, we show that an excess of hTau induces a mitotic arrest, with the presence of monopolar spindles. This mitotic defect leads to aneuploidy and apoptotic cell death. We studied the mechanism of action of hTau and found that the MT-binding domain of hTau is responsible for these defects. We also demonstrate that the effects of hTau occur via the inhibition of the function of the kinesin Klp61F, the Drosophila homologue of kinesin-5 (also called Eg5 or KIF11). We finally show that this deleterious effect of hTau is also found in other Drosophila cell types (neuroblasts) and tissues (the developing eye disc), as well as in human HeLa cells. By demonstrating that MT-bound Tau inhibits the Eg5 kinesin and cell mitosis, our work provides a new framework to consider the role of Tau in neurodegenerative diseases. © 2016. Published by The Company of Biologists Ltd.

  8. Thoracic sympathectomy for peripheral vascular disease can lead to severe bronchospasm and excessive bronchial secretions

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    Vikas Deep Goyal

    2015-01-01

    Full Text Available A 57-year-old male patient suffering from Buerger′s disease presented with pre-gangrenous changes in right foot and ischemic symptoms in right hand. Computed tomographic angiography revealed diffuse distal disease not suitable for vascular bypass and angioplasty. Right lumbar sympathectomy was done using a retroperitoneal approach followed 1 year later by right thoracic sympathectomy using a transaxillary approach. Postoperatively, the patient had severe bronchospasm and excessive secretions in the respiratory tract resistant to theophylline and sympathomimetic group of drugs and without any clinical, laboratory and radiological evidence of infection. The patient was started on anticholinergics in anticipation that sympathectomy might have lead to unopposed cholinergic activity and the symptoms improved rapidly. The patient recovered well and was discharged on 10 th post-operative day.

  9. Limited Excessive Voluntary Alcohol Drinking Leads to Liver Dysfunction in Mice.

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    Wegner, Scott A; Pollard, Katherine A; Kharazia, Viktor; Darevsky, David; Perez, Luz; Roychowdhury, Sanjoy; Xu, Allison; Ron, Dorit; Nagy, Laura E; Hopf, Frederic Woodward

    2017-02-01

    Liver damage is a serious and sometimes fatal consequence of long-term alcohol intake, which progresses from early-stage fatty liver (steatosis) to later-stage steatohepatitis with inflammation and fibrosis/necrosis. However, very little is known about earlier stages of liver disruption that may occur in problem drinkers, those who drink excessively but are not dependent on alcohol. We examined how repeated binge-like alcohol drinking in C57BL/6 mice altered liver function, as compared with a single binge-intake session and with repeated moderate alcohol consumption. We measured a number of markers associated with early- and later-stage liver disruption, including liver steatosis, measures of liver cytochrome P4502E1 (CYP2E1) and alcohol dehydrogenase (ADH), alcohol metabolism, expression of cytokine mRNA, accumulation of 4-hydroxynonenal (4-HNE) as an indicator of oxidative stress, and alanine transaminase/aspartate transaminase as a measure of hepatocyte injury. Importantly, repeated binge-like alcohol drinking increased triglyceride levels in the liver and plasma, and increased lipid droplets in the liver, indicators of steatosis. In contrast, a single binge-intake session or repeated moderate alcohol consumption did not alter triglyceride levels. In addition, alcohol exposure can increase rates of alcohol metabolism through CYP2E1 and ADH, which can potentially increase oxidative stress and liver dysfunction. Intermittent, excessive alcohol intake increased liver CYP2E1 mRNA, protein, and activity, as well as ADH mRNA and activity. Furthermore, repeated, binge-like drinking, but not a single binge or moderate drinking, increased alcohol metabolism. Finally, repeated, excessive intake transiently elevated mRNA for the proinflammatory cytokine IL-1B and 4-HNE levels, but did not alter markers of later-stage liver hepatocyte injury. Together, we provide data suggesting that even relatively limited binge-like alcohol drinking can lead to disruptions in liver

  10. Dysfunction of Nrf-2 in CF epithelia leads to excess intracellular H2O2 and inflammatory cytokine production.

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    Chen, Junnan; Kinter, Michael; Shank, Samuel; Cotton, Calvin; Kelley, Thomas J; Ziady, Assem G

    2008-01-01

    Cystic fibrosis is characterized by recurring pulmonary exacerbations that lead to the deterioration of lung function and eventual lung failure. Excessive inflammatory responses by airway epithelia have been linked to the overproduction of the inflammatory cytokine IL-6 and IL-8. The mechanism by which this occurs is not fully understood, but normal IL-1beta mediated activation of the production of these cytokines occurs via H2O2 dependent signaling. Therefore, we speculated that CFTR dysfunction causes alterations in the regulation of steady state H2O2. We found significantly elevated levels of H2O2 in three cultured epithelial cell models of CF, one primary and two immortalized. Increases in H2O2 heavily contributed to the excessive IL-6 and IL-8 production in CF epithelia. Proteomic analysis of three in vitro and two in vivo models revealed a decrease in antioxidant proteins that regulate H2O2 processing, by > or =2 fold in CF vs. matched normal controls. When cells are stimulated, differential expression in CF versus normal is enhanced; corresponding to an increase in H2O2 mediated production of IL-6 and IL-8. The cause of this redox imbalance is a decrease by approximately 70% in CF cells versus normal in the expression and activity of the transcription factor Nrf-2. Inhibition of CFTR function in normal cells produced this phenotype, while N-acetyl cysteine, selenium, an activator of Nrf-2, and the overexpression of Nrf-2 all normalized H2O2 processing and decreased IL-6 and IL-8 to normal levels, in CF cells. We conclude that a paradoxical decrease in Nrf-2 driven antioxidant responses in CF epithelia results in an increase in steady state H2O2, which in turn contributes to the overproduction of the pro-inflammatory cytokines IL-6 and IL-8. Treatment with antioxidants can ameliorate exaggerated cytokine production without affecting normal responses.

  11. Probability of background to produce a signal-like excess, for all Higgs masses tested.

    CERN Multimedia

    ATLAS, collaboration

    2012-01-01

    The probability of background to produce a signal-like excess, for all the Higgs boson masses tested. At almost all masses, the probability (solid curve) is at least a few percent; however, at 126.5 GeV it dips to 3x10-7, or one chance in three million, the '5-sigma' gold-standard normally used for the discovery of a new particle. A Standard Model Higgs boson with that mass would produce a dip to 4.6 sigma.

  12. Adverse lifestyle leads to an annual excess of 2 million deaths in China.

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    G Neil Thomas

    Full Text Available BACKGROUND: Adverse lifestyle factors have been associated with increased mortality, but data are lacking on their combined effect in developing populations, which we address in the present study. METHODS: In a death registry-based, case-control study among Hong Kong Chinese aged 30+y, proxy-reported lifestyle factors 10 y ago were collected for 21,363 cases (81% of all deaths and 12,048 living controls. Risks associated with poor diet, inactivity, heavy alcohol intake, and smoking for all-cause and cause-specific mortality, adjusting for potential confounders, were determined, and excess deaths for the Chinese population were calculated. RESULTS: Adjusted odds ratios for all-cause mortality were 1.15 (95% CI 1.09, 1.23, 1.34 (1.27, 1.43, 1.36 (1.21, 1.52, and 1.58 (1.46, 1.70 for poor diet, inactivity, heavy alcohol intake and smoking, respectively. Increasing numbers of adverse lifestyle factors were associated with a dose-dependent increase in adjusted odds ratios of 1.30 (1.20, 1.40, 1.67 (1.54, 1.81, 2.32 (2.08, 2.60, and 3.85 (3.12, 4.75 for 1, 2, 3, and 4 risk factors relative to those with none. The population attributable fraction for all-cause, all-CVD and all-cancer mortality were 26.6%, 15.0%, and 32.1%, resulting in an excess of 2,017,541; 489,884; and 607,517 deaths annually, respectively. Although smoking was associated with the greatest excess loss of life (867,530, heavy drinking (680,466, and physical inactivity (678,317 were similarly important. CONCLUSION: Adverse lifestyle factors contribute to one quarter of all deaths in China. Improving lifestyle practices, particularly focussing on moderating alcohol intake and increasing activity, and smoking cessation are critical to reducing the lifestyle-associated health burden.

  13. Enhancing Resilience to Heat Extremes: Multi-model Forecasting of Excessive Heat Events at Subseasonal Lead Times

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    Vintzileos, A.; Halpert, M.; Gottschalk, J.; Allgood, A.

    2016-12-01

    Heatwaves are among the most dangerous, yet invisible, of natural hazards. According to NOAA, the distribution of 30-year based annual mean fatalities from natural hazards in the U.S. ranks as follows; those from heat (130), floods (81), tornadoes (70), lightning (48) and hurricanes (46). Early warning to excessive heat events can be improved by using multi-scale prognostic systems. We designed and developed such a system for forecasting excessive heat events at lead times beyond Week-1. This Subseasonal Excessive Heat Outlook System (SEHOS) consists of (a) a monitoring/verification component and (b) a forecasting component which in its baseline version uses NOAA's Global Ensemble Forecast System (GEFS) predictions of temperature and humidity from Day-8 to Day-14. In this presentation, we discuss the definition of heat events, sources of predictability and present the forecast skill of SEHOS for the GEFS reforecast period (1985-2014). We then use subseasonal reforecasts from several models from the S2S database and discuss the forecast value added by multi-model approaches in predicting excessive heat events.

  14. Hydrogen sulfide in plants: from dissipation of excess sulfur to signaling molecule.

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    Calderwood, Alexander; Kopriva, Stanislav

    2014-09-15

    Sulfur is essential in all organisms for the synthesis of amino acids cysteine and methionine and as an active component of numerous co-factors and prosthetic groups. However, only plants, algae, fungi, and some prokaryotes are capable of using the abundant inorganic source of sulfur, sulfate. Plants take sulfate up, reduce it, and assimilate into organic compounds with cysteine being the first product of the pathway and a donor of reduced sulfur for synthesis of other S-containing compounds. Cysteine is formed in a reaction between sulfide, derived from reduction of sulfite and an activated amino acid acceptor, O-acetylserine. Sulfide is thus an important intermediate in sulfur metabolism, but numerous other functions in plants has been revealed. Hydrogen sulfide can serve as an alternative source of sulfur for plants, which may be significant in anaerobic conditions of waterlogged soils. On the other hand, emissions of hydrogen sulfide have been detected from many plant species. Since the amount of H2S discharged correlated with sulfate supply to the plants, the emissions were considered a mechanism for dissipation of excess sulfur. Significant hydrogen sulfide emissions were also observed in plants infected with pathogens, particularly with fungi. H2S thus seems to be part of the widely discussed sulfur-induced-resistance/sulfur-enhanced-defense. Recently, however, more evidence has emerged for a role for H2S in regulation and signaling. Sulfide stabilizes the cysteine synthase complex, increasing so the synthesis of its acceptor O-acetylserine. H2S has been implicating in regulation of plant stress response, particularly draught stress. There are more and more examples of processes regulated by H2S in plants being discovered, and hydrogen sulfide is emerging as an important signaling molecule, similar to its role in the animal and human world. How similar the functions, and homeostasis of H2S are in these diverse organisms, however, remains to be elucidated

  15. Appearances of diffuse excessive high signal intensity (DEHSI) on MR imaging following preterm birth

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Anthony R. [Sheffield Teaching Hospital NHS Foundation Trust, Department of Neonatology, Jessop Wing, Sheffield (United Kingdom); University of Sheffield, Academic Unit of Radiology, Royal Hallamshire Hospital, Sheffield (United Kingdom); University of Sheffield, Department of Academic Radiology, Royal Hallamshire Hospital, Sheffield (United Kingdom); Smith, Michael F. [Sheffield Teaching Hospital NHS Foundation Trust, Department of Neonatology, Jessop Wing, Sheffield (United Kingdom); Rigby, Alan S. [University of Hull, Postgraduate Medical Centre, Castle Hill Hospital, East Yorkshire (United Kingdom); Wallis, Lauren I.; Whitby, Elspeth H. [University of Sheffield, Academic Unit of Radiology, Royal Hallamshire Hospital, Sheffield (United Kingdom)

    2010-08-15

    Diffuse damage to the periventricular white matter has recently been suggested to be a cause of the cognitive deficits seen following preterm birth. It is unclear whether this form of injury can be visualised on MR imaging, but one group has described diffuse excessive high signal intensity (DEHSI) as a possible form of diffuse white matter injury. This finding is dependant on window imaging and the subjective assessment of the reviewer, but little data have been published on the degree of subjectivity on its appearance among raters. To assess the subjectivity of DEHSI on conventional and ultrafast T2-weighted MR imaging following preterm birth. An observational study of 40 preterm infants who had MR imaging of the brain around term-equivalent age, including conventional fast spin-echo (FSE) and ultrafast single-shot fast spin-echo (SSFSE) T2-weighted sequences in the axial plane. Images were anonymised and scored twice by four observers for the presence of DEHSI. Inter- and intra-observer agreement were calculated. Sixty-five percent of conventional and 100% of the ultrafast images were of diagnostic quality. DEHSI was noted in between 0% and 69.2% of conventional images and 27.5-90% of the ultrafast images. Inter- and intra-observer agreement ranged from none to moderate. The visual appearances of DEHSI on conventional FSE and ultrafast SSFSE T2-W images are highly subjective, limiting its clinical application. (orig.)

  16. Critical loads and excess loads of cadmium, copper and lead for European forest soils

    NARCIS (Netherlands)

    Reinds, G.J.; Bril, J.; Vries, de W.; Groenenberg, J.E.; Breeuwsma, A.

    1995-01-01

    Recently, concern has arisen about the impact of the dispersion of heavy metals in Europe. Therefore, a study (ESQUAD) was initiated to assess critical loads and steady-state concentrations of cadmium, copper and lead for European forest soils. The calculation methods used strongly resemble those

  17. Gain-of-function of Stat5 leads to excessive granulopoiesis and lethal extravasation of granulocytes to the lung.

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    Wan-chi Lin

    Full Text Available The Signal Transducer and Activator of Transcription 5 (Stat5 plays a significant role in normal hematopoiesis and a variety of hematopoietic malignancies. Deficiency in Stat5 causes impaired cytokine-mediated proliferation and survival of progenitors and their differentiated descendants along major hematopoietic lineages such as erythroid, lymphoid, and myeloid cells. Overexpression and persistent activation of Stat5 are sufficient for neoplastic transformation and development of multi-lineage leukemia in a transplant model. Little is known, however, whether a continuous activation of this signal transducer is essential for the maintenance of hematopoietic malignancies. To address this issue, we developed transgenic mice that express a hyperactive mutant of Stat5 in hematopoietic progenitors and derived lineages in a ligand-controlled manner. In contrast to the transplant model, expression of mutant Stat5 did not adversely affect normal hematopoiesis in the presence of endogenous wildtype Stat5 alleles. However, the gain-of-function of this signal transducer in mice that carry Stat5a/b hypomorphic alleles resulted in abnormally high numbers of circulating granulocytes that caused severe airway obstruction. Downregulation of hyperactive Stat5 in diseased animals restored normal granulopoiesis, which also resulted in a swift clearance of granulocytes from the lung. Moreover, we demonstrate that Stat5 promotes the initiation and maintenance of severe granulophilia in a cell autonomous manner. The results of this study show that the gain-of-function of Stat5 causes excessive granulopoiesis and prolonged survival of granulocytes in circulation. Collectively, our findings underline the critical importance of Stat5 in maintaining a normal balance between myeloid and lymphoid cells during hematopoiesis, and we provide direct evidence for a function of Stat5 in granulophilia-associated pulmonary dysfunction.

  18. Gain-of-function of Stat5 leads to excessive granulopoiesis and lethal extravasation of granulocytes to the lung.

    Science.gov (United States)

    Lin, Wan-chi; Schmidt, Jeffrey W; Creamer, Bradley A; Triplett, Aleata A; Wagner, Kay-uwe

    2013-01-01

    The Signal Transducer and Activator of Transcription 5 (Stat5) plays a significant role in normal hematopoiesis and a variety of hematopoietic malignancies. Deficiency in Stat5 causes impaired cytokine-mediated proliferation and survival of progenitors and their differentiated descendants along major hematopoietic lineages such as erythroid, lymphoid, and myeloid cells. Overexpression and persistent activation of Stat5 are sufficient for neoplastic transformation and development of multi-lineage leukemia in a transplant model. Little is known, however, whether a continuous activation of this signal transducer is essential for the maintenance of hematopoietic malignancies. To address this issue, we developed transgenic mice that express a hyperactive mutant of Stat5 in hematopoietic progenitors and derived lineages in a ligand-controlled manner. In contrast to the transplant model, expression of mutant Stat5 did not adversely affect normal hematopoiesis in the presence of endogenous wildtype Stat5 alleles. However, the gain-of-function of this signal transducer in mice that carry Stat5a/b hypomorphic alleles resulted in abnormally high numbers of circulating granulocytes that caused severe airway obstruction. Downregulation of hyperactive Stat5 in diseased animals restored normal granulopoiesis, which also resulted in a swift clearance of granulocytes from the lung. Moreover, we demonstrate that Stat5 promotes the initiation and maintenance of severe granulophilia in a cell autonomous manner. The results of this study show that the gain-of-function of Stat5 causes excessive granulopoiesis and prolonged survival of granulocytes in circulation. Collectively, our findings underline the critical importance of Stat5 in maintaining a normal balance between myeloid and lymphoid cells during hematopoiesis, and we provide direct evidence for a function of Stat5 in granulophilia-associated pulmonary dysfunction.

  19. Signals from activation of B-cell receptor with anti-IgD can override the stimulatory effects of excess BAFF on mature B cells in vivo.

    Science.gov (United States)

    Nguyen, Tue G; Morris, Jonathan M

    2014-09-01

    The selection and maturation of B-cell clones are critically determined by tonic signals from activated B cell receptors (BCR) and survival signals from BAFF cytokine. These finely tuned and coordinated signals provide a net positive signal that can promote the selection, maturation, proliferation and differentiation of a developing B cell. Stimulation with an anti-IgD antibody can also activate BCR but can lead to depletion and an arrest of mature B-cell development in vivo. It is not known whether survival signals from excess BAFF can override the suppressive effects of treatment with anti-IgD on mature B cells in vivo. Herein, we examined the effects of co-treatment of BAFF and anti-IgD on the mature B-cell compartment and antibody production in vivo by treating mice with either 1mg/kg BAFF or anti-IgD alone or in combination for 3 consecutive days. We found that co-treatment with anti-IgD significantly abrogated these stimulatory effects of BAFF treatment on splenic CD19+ B cells as well as mature CD19+IgD(hi)IgM+ B cells in vivo. Anti-IgD down-regulated the expression of the BCR complex (mIgM, mIgD and CD19) and the BAFF receptor TACI without regard to the presence of BAFF. Anti-IgD treatment also significantly negated BAFF-induced IgM production in vivo. Both BAFF and anti-IgD could individually stimulate IL-10 synthesis in B cells but did not affect one another. Taken together, our data suggest that activation of BCR with an anti-IgD antibody can override the stimulatory effects from excess BAFF on B cell proliferation and antibody production by down-regulating the expression of BCR complex and BAFF receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Metabolic fate of glucose and candidate signaling and excess-fuel detoxification pathways in pancreatic β-cells.

    Science.gov (United States)

    Mugabo, Yves; Zhao, Shangang; Lamontagne, Julien; Al-Mass, Anfal; Peyot, Marie-Line; Corkey, Barbara E; Joly, Erik; Madiraju, S R Murthy; Prentki, Marc

    2017-05-05

    Glucose metabolism promotes insulin secretion in β-cells via metabolic coupling factors that are incompletely defined. Moreover, chronically elevated glucose causes β-cell dysfunction, but little is known about how cells handle excess fuels to avoid toxicity. Here we sought to determine which among the candidate pathways and coupling factors best correlates with glucose-stimulated insulin secretion (GSIS), define the fate of glucose in the β-cell, and identify pathways possibly involved in excess-fuel detoxification. We exposed isolated rat islets for 1 h to increasing glucose concentrations and measured various pathways and metabolites. Glucose oxidation, oxygen consumption, and ATP production correlated well with GSIS and saturated at 16 mm glucose. However, glucose utilization, glycerol release, triglyceride and glycogen contents, free fatty acid (FFA) content and release, and cholesterol and cholesterol esters increased linearly up to 25 mm glucose. Besides being oxidized, glucose was mainly metabolized via glycerol production and release and lipid synthesis (particularly FFA, triglycerides, and cholesterol), whereas glycogen production was comparatively low. Using targeted metabolomics in INS-1(832/13) cells, we found that several metabolites correlated well with GSIS, in particular some Krebs cycle intermediates, malonyl-CoA, and lower ADP levels. Glucose dose-dependently increased the dihydroxyacetone phosphate/glycerol 3-phosphate ratio in INS-1(832/13) cells, indicating a more oxidized state of NAD in the cytosol upon glucose stimulation. Overall, the data support a role for accelerated oxidative mitochondrial metabolism, anaplerosis, and malonyl-CoA/lipid signaling in β-cell metabolic signaling and suggest that a decrease in ADP levels is important in GSIS. The results also suggest that excess-fuel detoxification pathways in β-cells possibly comprise glycerol and FFA formation and release extracellularly and the diversion of glucose carbons to

  1. Excess Lead-210 and Plutonium-239+240: Two suitable radiogenic soil erosion tracers for mountain grassland sites.

    Science.gov (United States)

    Meusburger, K; Porto, P; Mabit, L; La Spada, C; Arata, L; Alewell, C

    2018-01-01

    The expected growing population and challenges associated with globalisation will increase local food and feed demands and enhance the pressure on local and regional upland soil resources. In light of these potential future developments it is necessary to define sustainable land use and tolerable soil loss rates with methods applicable and adapted to mountainous areas. Fallout-radionuclides (FRNs) are proven techniques to increase our knowledge about the status and resilience of agro-ecosystems. However, the use of the Caesium-137 ( 137 Cs) method is complicated in the European Alps due to its heterogeneous input and the timing of the Chernobyl fallout, which occurred during a few single rain events on partly snow covered ground. Other radioisotopic techniques have been proposed to overcome these limitations. The objective of this study is to evaluate the suitability of excess Lead-210 ( 210 Pb ex ) and Plutonium-239+240 ( 239+240 Pu) as soil erosion tracers for three different grassland management types at the steep slopes (slope angles between 35 and 38°) located in the Central Swiss Alps. All three FRNs identified pastures as having the highest mean (± standard deviation) net soil loss of -6.7 ± 1.1, -9.8 ± 6.8 and -7.0 ± 5.2 Mg ha -1 yr -1 for 137 Cs, 210 Pb ex and 239+240 Pu, respectively. A mean soil loss of -5.7 ± 1.5, -5.2 ± 1.5 and-5.6 ± 2.1 was assessed for hayfields and the lowest rates were established for pastures with dwarf-shrubs (-5.2 ± 2.5, -4.5 ± 2.5 and -3.3 ± 2.4 Mg ha -1 yr -1 for 137 Cs, 210 Pb ex and 239+240 Pu, respectively). These rates, evaluated at sites with an elevated soil erosion risk exceed the respective soil production rates. Among the three FRN methods used, 239+240 Pu appears as the most promising tracer in terms of measurement uncertainty and reduced small scale variability (CV of 13%). Despite a higher level of uncertainty, 210 Pb ex produced comparable results, with a wide range of erosion rates sensitive to changes

  2. High antipredatory efficiency of insular lizards: a warning signal of excessive specimen collection?

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    Miguel Delibes

    Full Text Available We live-captured lizards on islands in the Gulf of California and the Baja California peninsula mainland, and compared their ability to escape predation. Contrary to expectations, endemic lizard species from uninhabited islands fled from humans earlier and more efficiently than those from peninsular mainland areas. In fact, 58.2% (n=146 of the lizards we tried to capture on the various islands escaped successfully, while this percentage was only 14.4% (n=160 on the peninsular mainland. Separate evidence (e.g., proportion of regenerated tails, low human population at the collection areas, etc. challenges several potential explanations for the higher antipredatory efficiency of insular lizards (e.g., more predation pressure on islands, habituation to humans on the peninsula, etc.. Instead, we suggest that the ability of insular lizards to avoid predators may be related to harvesting by humans, perhaps due to the value of endemic species as rare taxonomic entities. If this hypothesis is correct, predation-related behavioral changes in rare species could provide early warning signals of their over-exploitation, thus encouraging the adoption of conservation measures.

  3. Can fertility signals lead to quality signals? Insights from the evolution of primate sexual swellings.

    Science.gov (United States)

    Huchard, Elise; Courtiol, Alexandre; Benavides, Julio A; Knapp, Leslie A; Raymond, Michel; Cowlishaw, Guy

    2009-05-22

    The sexual swellings of female primates have generated a great deal of interest in evolutionary biology. Two hypotheses recently proposed to elucidate their functional significance argue that maximal swelling size advertises either female fertility within a cycle or female quality across cycles. Published evidence favours the first hypothesis, and further indicates that larger swellings advertise higher fertility between cycles. If so, a male preference for large swellings might evolve, driving females to use swellings as quality indicators, as proposed by the second hypothesis. In this paper, we explore this possibility using a combination of empirical field data and mathematical modelling. We first test and find support for three key predictions of the female-quality hypothesis in wild chacma baboons (Papio ursinus): (i) inter-individual differences in swelling size are maintained across consecutive cycles, (ii) females in better condition have larger swellings and higher reproductive success, and (iii) males preferentially choose females with large swellings. We then develop an individual-based simulation model that indicates that females producing larger swellings can achieve higher mating success even when female-female competition is low and within-female variance in the trait is high. Taken together, our findings show that once sexual swellings have evolved as fertility signals, they might, in certain socio-sexual systems, be further selected to act as quality signals. These results, by reconciling two hypotheses, help to clarify the processes underlying sexual swelling evolution. More generally, our findings suggest that mate choice for direct benefits (fertility) can lead to indirect benefits (good genes).

  4. Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling

    Science.gov (United States)

    Mi, Tiejuan; Abbasi, Shahrzad; Zhang, Hong; Uray, Karen; Chunn, Janci L.; Xia, Ling Wei; Molina, Jose G.; Weisbrodt, Norman W.; Kellems, Rodney E.; Blackburn, Michael R.; Xia, Yang

    2008-01-01

    Priapism, abnormally prolonged penile erection in the absence of sexual excitation, is associated with ischemia-mediated erectile tissue damage and subsequent erectile dysfunction. It is common among males with sickle cell disease (SCD), and SCD transgenic mice are an accepted model of the disorder. Current strategies to manage priapism suffer from a poor fundamental understanding of the molecular mechanisms underlying the disorder. Here we report that mice lacking adenosine deaminase (ADA), an enzyme necessary for the breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy successfully corrected the priapic activity both in vivo and in vitro, suggesting that it was dependent on elevated adenosine levels. Further genetic and pharmacologic evidence demonstrated that A2B adenosine receptor–mediated (A2BR-mediated) cAMP and cGMP induction was required for elevated adenosine–induced prolonged penile erection. Finally, priapic activity in SCD transgenic mice was also caused by elevated adenosine levels and A2BR activation. Thus, we have shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada–/– and SCD transgenic mice. These findings provide insight regarding the molecular basis of priapism and suggest that strategies to either reduce adenosine or block A2BR activation may prove beneficial in the treatment of this disorder. PMID:18340377

  5. Excess adenosine A2B receptor signaling contributes to priapism through HIF-1α mediated reduction of PDE5 gene expression

    Science.gov (United States)

    Ning, Chen; Wen, Jiaming; Zhang, Yujin; Dai, Yingbo; Wang, Wei; Zhang, Weiru; Qi, Lin; Grenz, Almut; Eltzschig, Holger K.; Blackburn, Michael R.; Kellems, Rodney E.; Xia, Yang

    2014-01-01

    Priapism is featured with prolonged and painful penile erection and is prevalent among males with sickle cell disease (SCD). The disorder is a dangerous urological and hematological emergency since it is associated with ischemic tissue damage and erectile disability. Here we report that phosphodiesterase-5 (PDE5) gene expression and PDE activity is significantly reduced in penile tissues of two independent priapic models: SCD mice and adenosine deaminase (ADA)-deficient mice. Moreover, using ADA enzyme therapy to reduce adenosine or a specific antagonist to block A2B adenosine receptor (ADORA2B) signaling, we successfully attenuated priapism in both ADA−/− and SCD mice by restoring penile PDE5 gene expression to normal levels. This finding led us to further discover that excess adenosine signaling via ADORA2B activation directly reduces PDE5 gene expression in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. Overall, we reveal that excess adenosine-mediated ADORA2B signaling underlies reduced penile PDE activity by decreasing PDE5 gene expression in a HIF-1α-dependent manner and provide new insight for the pathogenesis of priapism and novel therapies for the disease.—Ning, C., Wen, J., Zhang, Y., Dai, Y., Wang, W., Zhang, W., Qi, L., Grenz, A., Eltzschig, H. K., Blackburn, M. R., Kellems, R. E., Xia, Y. Excess adenosine A2B receptor signaling contributes to priapism through HIF-1α mediated reduction of PDE5 gene expression. PMID:24614760

  6. Interplay between phosphoinositide lipids and calcium signals at the leading edge of chemotaxing ameboid cells☆

    Science.gov (United States)

    Falke, Joseph J.; Ziemba, Brian P.

    2014-01-01

    The chemotactic migration of eukaryotic ameboid cells up concentration gradients is among the most advanced forms of cellular behavior. Chemotaxis is controlled by a complex network of signaling proteins bound to specific lipids on the cytoplasmic surface of the plasma membrane at the front of the cell, or the leading edge. The central lipid players in this leading edge signaling pathway include the phosphoinositides PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3), both of which play multiple roles. The products of PI(4,5)P2 hydrolysis, diacylglycerol (DAG) and Ins(1,4,5)P3 (IP3), are also implicated as important players. Together, these leading edge phosphoinositides and their degradation products, in concert with a local Ca2+ signal, control the recruitment and activities of many peripheral membrane proteins that are crucial to the leading edge signaling network. The present critical review summarizes the current molecular understanding of chemotactic signaling at the leading edge, including newly discovered roles of phosphoinositide lipids and Ca2+, while highlighting key questions for future research. PMID:24451847

  7. Interplay between phosphoinositide lipids and calcium signals at the leading edge of chemotaxing ameboid cells.

    Science.gov (United States)

    Falke, Joseph J; Ziemba, Brian P

    2014-09-01

    The chemotactic migration of eukaryotic ameboid cells up concentration gradients is among the most advanced forms of cellular behavior. Chemotaxis is controlled by a complex network of signaling proteins bound to specific lipids on the cytoplasmic surface of the plasma membrane at the front of the cell, or the leading edge. The central lipid players in this leading edge signaling pathway include the phosphoinositides PI(4,5)P2 (PIP2) and PI(3,4,5)P3 (PIP3), both of which play multiple roles. The products of PI(4,5)P2 hydrolysis, diacylglycerol (DAG) and Ins(1,4,5)P3 (IP3), are also implicated as important players. Together, these leading edge phosphoinositides and their degradation products, in concert with a local Ca(2+) signal, control the recruitment and activities of many peripheral membrane proteins that are crucial to the leading edge signaling network. The present critical review summarizes the current molecular understanding of chemotactic signaling at the leading edge, including newly discovered roles of phosphoinositide lipids and Ca(2+), while highlighting key questions for future research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

  9. Transient gestational exposure to drinking water containing excess hexavalent chromium modifies insulin signaling in liver and skeletal muscle of rat progeny.

    Science.gov (United States)

    Shobana, Navaneethabalakrishnan; Aruldhas, Mariajoseph Michael; Tochhawng, Lalmuankimi; Loganathan, Ayyalu; Balaji, Sadhasivam; Kumar, Mani Kathiresh; Banu, Liaquat Alikhan Sheerin; Navin, Ajit Kumar; Mayilvanan, Chinnaiyan; Ilangovan, Ramachandran; Balasubramanian, Karundevi

    2017-11-01

    Chromium (Cr), an essential micronutrient potentiates insulin action, whereas excess hexavalent Cr (CrVI) acts as an endocrine disruptor. Pregnant mothers living in areas abutting industries using the metal and chromite ore dumps are exposed to ground water contaminated with Cr. Nevertheless, the impact of prenatal exposure to excess CrVI on insulin signaling in the progeny remains obscure. We tested the hypothesis "transient gestational exposure to drinking water containing excess CrVI may modify insulin signaling during postnatal life". Pregnant Wistar rats were given drinking water containing 50, 100 and 200 ppm CrVI (K2Cr2O7) from gestational day 9-14 encompassing the period of organogenesis; the male progenies were tested at postnatal day 60. Neither fasting blood glucose nor oral glucose tolerance was altered in CrVI treated progeny. Nevertheless, western blot detection pointed out attenuated expression level of insulin receptor (IR), its downstream signaling molecules (IRS-1, pIRS-1Tyr632, Akt and pAktSer473) and organ specific glucose transporters (GLUT2 in liver and GLUT4 in gastrocnemius muscle), along with a significant increase in serum insulin level in male progenies exposed to CrVI. While 14C-2-deoxy glucose uptake increased in the liver, the same decreased in the skeletal muscle whereas, 14C-glucose oxidation recorded a consistent decrease in both tissues of CrVI exposed rats. These findings support our hypothesis and suggest that transient gestational exposure to excess CrVI may affect insulin signaling and glucose oxidation in the progeny, predictably rendering them vulnerable to insulin resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Excessive signal transduction of gain-of-function variants of the calcium-sensing receptor (CaSR are associated with increased ER to cytosol calcium gradient.

    Directory of Open Access Journals (Sweden)

    Marianna Ranieri

    Full Text Available In humans, gain-of-function mutations of the calcium-sensing receptor (CASR gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA and reducing expression of Plasma Membrane Calcium-ATPase (PMCA. Wild-type CaSR (hCaSR-wt and its gain-of-function (hCaSR-R990G; hCaSR-N124K variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate receptor inputs to cell function.

  11. Excessive Signal Transduction of Gain-of-Function Variants of the Calcium-Sensing Receptor (CaSR) Are Associated with Increased ER to Cytosol Calcium Gradient

    Science.gov (United States)

    Di Mise, Annarita; Vezzoli, Giuseppe; Soldati, Laura; Svelto, Maria; Valenti, Giovanna

    2013-01-01

    In humans, gain-of-function mutations of the calcium-sensing receptor (CASR) gene are the cause of autosomal dominant hypocalcemia or type 5 Bartter syndrome characterized by an abnormality of calcium metabolism with low parathyroid hormone levels and excessive renal calcium excretion. Functional characterization of CaSR activating variants has been so far limited at demonstrating an increased sensitivity to external calcium leading to lower Ca-EC50. Here we combine high resolution fluorescence based techniques and provide evidence that for the efficiency of calcium signaling system, cells expressing gain-of-function variants of CaSR monitor cytosolic and ER calcium levels increasing the expression of the Sarco-Endoplasmic Reticulum Calcium-ATPase (SERCA) and reducing expression of Plasma Membrane Calcium-ATPase (PMCA). Wild-type CaSR (hCaSR-wt) and its gain-of-function (hCaSR-R990G; hCaSR-N124K) variants were transiently transfected in HEK-293 cells. Basal intracellular calcium concentration was significantly lower in cells expressing hCaSR-wt and its gain of function variants compared to mock. In line, FRET studies using the D1ER probe, which detects [Ca2+]ER directly, demonstrated significantly higher calcium accumulation in cells expressing the gain of function CaSR variants compared to hCaSR-wt. Consistently, cells expressing activating CaSR variants showed a significant increase in SERCA activity and expression and a reduced PMCA expression. This combined parallel regulation in protein expression increases the ER to cytosol calcium gradient explaining the higher sensitivity of CaSR gain-of-function variants to external calcium. This control principle provides a general explanation of how cells reliably connect (and exacerbate) receptor inputs to cell function. PMID:24244430

  12. Chronic hyperosmotic stress interferes with immune homeostasis in striped catfish (Pangasianodon hypophthalmus, S.) and leads to excessive inflammatory response during bacterial infection.

    Science.gov (United States)

    Schmitz, Mélodie; Douxfils, Jessica; Mandiki, Syaghalirwa N M; Morana, Cédric; Baekelandt, Sébastien; Kestemont, Patrick

    2016-08-01

    Hyperosmotic stress has often been investigated from osmoregulation perspectives while the effects of such stress on the immune capacity remain largely unexplored. In this study, striped catfish were submitted to three salinity profiles (freshwater, low saline water, saline water) during 20 days, followed by infection with a virulent bacteria, Edwardsiella ictaluri, responsible for the enteric septicaemia of catfish. Osmoregulatory (plasma osmolality, gill Na(+)K(+)ATPase), immune (blood cells, lysozyme activity, complement activity, respiratory burst) parameters and mortality rate were investigated. In addition, abundances of heat shock protein 70 and high mobility group box 1 were explored. With elevated salinity, plasma osmolality severely increased while gill Na(+)K(+)ATPase slightly increased. Salinity alone stimulated the number of granulocytes, lysozyme activity and respiratory burst but depleted the number of thrombocytes. Salinity in combination with infection stimulated the number of monocytes and ACH50. On the contrary, erythrocytes, hematocrit, heat shock protein 70 and high mobility group box 1 did not significantly vary with salinity profiles. Then, salinity induced earlier onset on mortalities after E. ictaluri inoculation whereas cumulative mortality reach 79.2%, 67.0% and 91.7% respectively in freshwater, low saline water and saline water. In conclusion, salinity stimulates several immune functions in striped catfish but prolonged exposure to excessive hyperosmotic condition may lead to excessive inflammatory response and death. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Lead

    Science.gov (United States)

    ... is serious about making sure companies that break the law are held accountable In the past year, EPA ... the health effects of lead in drinking water The law mandates no-lead products for drinking water after ...

  14. Excessive Reversal of Epidermal Growth Factor Receptor and Ephrin Signaling Following Tracheal Occlusion in Rabbit Model of Congenital Diaphragmatic Hernia.

    Science.gov (United States)

    Varisco, Brian M; Sbragia, Lourenco; Chen, Jing; Scorletti, Federico; Joshi, Rashika; Wong, Hector R; Lopes-Figueira, Rebecca; Oria, Marc; Peiro, Jose

    2016-07-19

    Congenital diaphragmatic hernia (CDH) causes severe pulmonary hypoplasia from herniation of abdominal contents into the thorax. Tracheal occlusion (TO) for human CDH improves survival, but morbidity and mortality remain high, and we do not fully understand the cellular pathways and processes most severely impacted by CDH and TO. We created a left diaphragmatic hernia (DH) in rabbit fetuses with subsequent TO and collected left lung sections for NextGen mRNA sequencing. DH, TO, and DHTO fetuses had comparable body and organ growth to control except for lower lung weights in DH (p<0.05). Of 13,687 expressed genes, DHTO had 687 differentially expressed genes compared to DH, but no other group-group comparison had more than 10. Considering genes in combination, many of the genes reduced in DH were more highly expressed in DHTO than in control. Benchmarking fetal rabbit lung gene expression to published lung development data, both DH and DHTO lungs were more highly correlated with the gene expression of immature lung. DNA synthesis was upregulated in DHTO compared to DH and ribosome and protein synthesis pathways were downregulated. DH reduced total and epithelial cell proliferation by half and two-thirds respectively, and DHTO increased proliferation by 2.5 and 3.4-fold respectively. Signaling pathways downregulated by DH and upregulated in DHTO were epidermal growth factor receptor signaling, ephrin signaling, and cell migration; however, levels of ephrin and EGFR signaling in DHTO exceeded that of control. Identification and inhibition of the ligands responsible for this dysregulated signaling could improve lung development in CDH.

  15. Activated Met signalling in the developing mouse heart leads to cardiac disease.

    Directory of Open Access Journals (Sweden)

    Christian Leo

    Full Text Available BACKGROUND: The Hepatocyte Growth Factor (HGF is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF or the constitutively activated Tpr-Met kinase to explore: i the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43 in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease.

  16. An application of excess lead-210 analysis for the study of fine sediment connectivity in a Mediterranean mountain basin with badlands, the Vallcebre research catchments

    Science.gov (United States)

    Moreno de las Heras, Mariano; Gallart, Francesc; Latron, Jérôme; Martínez-Carreras, Núria; Ferrer, Laura; Estrany, Joan

    2017-04-01

    Analysis of sediment dynamics in Mediterranean environments is fundamental to basin management, particularly for mountain catchments with badlands, which affect water bodies and freshwater ecosystems. Connectivity has emerged in Environmental and Earth Sciences as an evolution of the sediment delivery concept, providing a useful framework for understanding how sediments are transferred between geomorphic zones of the catchment. This study explores the feasibility of excess lead-210 (210Pbex) to analyse sediment connectivity in a 4-km2 Mediterranean mountain basin with badlands (the Vallcebre research catchments, Eastern Pyrenees) by applying simple 210Pbex mass-balance models for hypothesis generation and experimental testing in the field. Badland surfaces in the basin are weathered by freezing during the winter and are further eroded in summer by the effect of high-intensity storms. The eroded sediments may remain deposited within the catchment streams from months to years. Application of 210Pbex balance models in our basin proposes: (i) a saw-tooth seasonal pattern of badland surface 210Pbex activities (increasing from October to May, and depleted in summer) and (ii) a downstream increase in sediment activity due to fallout lead-210 accumulation in streambed sediment deposits. Both deposited and suspended sediments collected at the Vallcebre catchments showed, in general, low sediment 210Pbex concentrations, illustrating their fresh-rock origin at the badland sites, but also hampering the understanding of sediment 210Pbex patterns due to high measurement uncertainty (particularly for sediments with d50>20µm) and to strong dependence on sediment sampling methodology. Suspended sediment 210Pbex activity reproduced the simulated seasonal activity patterns for the badland surfaces. Contrary to the in-stream transit increases of sediment 210Pbex activity that were predicted by our model simulations, fallout lead-210 concentrations in the suspended sediments decreased

  17. Excessive somnolence

    Directory of Open Access Journals (Sweden)

    Stella Tavares

    Full Text Available Excessive somnolence can be quite a incapacitating manifestation, and is frequently neglected by physicians and patients. This article reviews the determinant factors, the evaluation and quantification of diurnal somnolence, and the description and treatment of the main causes of excessive somnolence.

  18. Excessive somnolence.

    Science.gov (United States)

    Tavares, S; Alóe, F; Gentil, V; Scaff, M

    1996-01-01

    Excessive somnolence can be quite a incapacitating manifestation, and is frequently neglected by physicians and patients. This article reviews the determinant factors, the evaluation and quantification of diurnal somnolence, and the description and treatment of the main causes of excessive somnolence.

  19. Secondary to excessive melatonin synthesis, the consumption of tryptophan from outside the blood-brain barrier and melatonin over-signaling in the pars tuberalis may be central to the pathophysiology of winter depression.

    Science.gov (United States)

    Pereira, José Carlos; Pradella Hallinan, Márcia; Alves, Rosana Cardoso

    2017-01-01

    Seasonal affective disorder is defined as recurrent episodes of major depression, mania, or hypomania with seasonal onset and remission. In this class of mood disturbances, a unipolar major depressive disorder known as winter depression is common in populations living in northern latitudes far from the equator. Winter depression repeatedly occurs in the autumn or winter and remits in the spring or summer, and its etiopathogenesis is currently unknown. However, one can surmise that excessive melatonin production during the reduced duration of daily sunlight in the autumn and winter plays a role in its pathophysiology. Melatonin is synthesized from tryptophan within the pineal gland, which is located outside the blood-brain barrier, and overproduction of melatonin may lead to augmented consumption of tryptophan, from which serotonin is synthesized. As tryptophan is captured from the blood and excessively utilized by the pineal gland, tryptophan blood levels may decline; as such, it is more difficult for tryptophan to pass through the blood-brain barrier and reach the serotonergic neurons as the ratio of tryptophan to the other amino acids that compete for the same transporter to enter the brain is diminished. As such, less tryptophan is available for serotonin synthesis. Moreover, melatonin is known to modulate thyrotropin expression in the thyrotrophic cells of the pars tuberalis of the pituitary gland, and overproduction of melatonin in the autumn or winter months may cause excessive signaling in the pars tuberalis, diminishing its release of thyrotropin and resulting in central hypothyroidism. Both conditions reduced serotonin production and central hypothyroidism may cause depression. Furthermore, the excessive synthesis of melatonin during the autumn and winter may negatively affect the expression of neuromedin U in the pars tuberalis, causing an increased appetite, which is common in winter depression patients. The hypersomnia common in winter depressive

  20. Lead

    Science.gov (United States)

    ... Test Safety Alert: Learn about CDC Recommendations Second Informational Call (CDC-RFA-17-1701PPHF17), April 5, 2017, ... CLPPP CAP Healthy Homes Assessment Tools Lead Health Literacy Initiative Refugee Tool Kit Resources Healthy Homes and ...

  1. Research on output signal of piezoelectric lead zirconate titanate detector using Monte Carlo method

    Energy Technology Data Exchange (ETDEWEB)

    Takechi, Seiji, E-mail: takechi@elec.eng.osaka-cu.ac.jp [Graduate School of Engineering, Osaka City University, Osaka 558-8585 (Japan); Mitsuhashi, Tomoaki; Miura, Yoshinori [Graduate School of Engineering, Osaka City University, Osaka 558-8585 (Japan); Miyachi, Takashi; Kobayashi, Masanori; Okudaira, Osamu [Planetary Exploration Research Center, Chiba Institute of Technology, Narashino, Chiba 275-0016 (Japan); Shibata, Hiromi [The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047 (Japan); Fujii, Masayuki [Famscience Co., Ltd., Tsukubamirai, Ibaraki 300-2435 (Japan); Okada, Nagaya [Honda Electronics Co., Ltd., Toyohashi, Aichi 441-3193 (Japan); Murakami, Takeshi; Uchihori, Yukio [National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2017-06-21

    The response of a radiation detector fabricated from piezoelectric lead zirconate titanate (PZT) was studied. The response signal due to a single 400 MeV/n xenon (Xe) ion was assumed to have a simple form that was composed of two variables, the amplitude and time constant. These variables were estimated by comparing two output waveforms obtained from a computer simulation and an experiment on Xe beam irradiation. Their values appeared to be dependent on the beam intensity. - Highlights: • The performance of PZT detector was studied by irradiation of a 400 MeV/n Xe beam. • Monte Carlo simulation was used to examine the formation process of the output. • The response signal due to a single Xe ion was assumed to have a simple form. • The form was composed of two variables, the amplitude and time constant. • These variables appeared to be dependent on the beam intensity.

  2. Neuro-developmental outcome at 18 months in premature infants with diffuse excessive high signal intensity on MR imaging of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Anthony [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Neonatology, Sheffield (United Kingdom); University of Sheffield, Department of Academic Radiology, Sheffield, South Yorkshire (United Kingdom); Whitby, Elspeth; Paley, Martyn [University of Sheffield, Department of Academic Radiology, Sheffield, South Yorkshire (United Kingdom); Wilkinson, Stuart; Smith, Michael [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Neonatology, Sheffield (United Kingdom); Alladi, Sathya [Sheffield Teaching Hospitals NHS Foundation Trust, Department of Child Development, Sheffield (United Kingdom)

    2011-10-15

    Diffuse excessive high signal intensity (DEHSI) may represent damage to the white matter in preterm infants, but may be best studied alongside quantitative markers. Limited published data exists on its neuro-developmental implications. The purpose of this study was to assess whether preterm children with DEHSI at term-corrected age have abnormal neuro-developmental outcome. This was a prospective observational study of 67 preterm infants with MRI of the brain around term-equivalent age, including diffusion-weighted imaging (DWI). Images were reported as being normal, overtly abnormal or to show DEHSI. A single observer placed six regions of interest in the periventricular white matter and calculated the apparent diffusion coefficients (ADC). DEHSI was defined as (1) high signal on T2-weighted images alone, (2) high signal with raised ADC values or (3) raised ADC values independent of visual appearances. The neuro-development was assessed around 18 months' corrected age using the Bayley Scales of Infant and Toddler Development (3rd Edition). Standard t tests compared outcome scores between imaging groups. No statistically significant difference in neuro-developmental outcome scores was seen between participants with normal MRI and DEHSI, regardless of which definition was used. Preterm children with DEHSI have similar neuro-developmental outcome to those with normal brain MRI, even if the definition includes objective markers alongside visual appearances. (orig.)

  3. A lightweight QRS detector for single lead ECG signals using a max-min difference algorithm.

    Science.gov (United States)

    Pandit, Diptangshu; Zhang, Li; Liu, Chengyu; Chattopadhyay, Samiran; Aslam, Nauman; Lim, Chee Peng

    2017-06-01

    Detection of the R-peak pertaining to the QRS complex of an ECG signal plays an important role for the diagnosis of a patient's heart condition. To accurately identify the QRS locations from the acquired raw ECG signals, we need to handle a number of challenges, which include noise, baseline wander, varying peak amplitudes, and signal abnormality. This research aims to address these challenges by developing an efficient lightweight algorithm for QRS (i.e., R-peak) detection from raw ECG signals. A lightweight real-time sliding window-based Max-Min Difference (MMD) algorithm for QRS detection from Lead II ECG signals is proposed. Targeting to achieve the best trade-off between computational efficiency and detection accuracy, the proposed algorithm consists of five key steps for QRS detection, namely, baseline correction, MMD curve generation, dynamic threshold computation, R-peak detection, and error correction. Five annotated databases from Physionet are used for evaluating the proposed algorithm in R-peak detection. Integrated with a feature extraction technique and a neural network classifier, the proposed ORS detection algorithm has also been extended to undertake normal and abnormal heartbeat detection from ECG signals. The proposed algorithm exhibits a high degree of robustness in QRS detection and achieves an average sensitivity of 99.62% and an average positive predictivity of 99.67%. Its performance compares favorably with those from the existing state-of-the-art models reported in the literature. In regards to normal and abnormal heartbeat detection, the proposed QRS detection algorithm in combination with the feature extraction technique and neural network classifier achieves an overall accuracy rate of 93.44% based on an empirical evaluation using the MIT-BIH Arrhythmia data set with 10-fold cross validation. In comparison with other related studies, the proposed algorithm offers a lightweight adaptive alternative for R-peak detection with good

  4. Loss of FTO antagonises Wnt signaling and leads to developmental defects associated with ciliopathies.

    Directory of Open Access Journals (Sweden)

    Daniel P S Osborn

    Full Text Available Common intronic variants in the Human fat mass and obesity-associated gene (FTO are found to be associated with an increased risk of obesity. Overexpression of FTO correlates with increased food intake and obesity, whilst loss-of-function results in lethality and severe developmental defects. Despite intense scientific discussions around the role of FTO in energy metabolism, the function of FTO during development remains undefined. Here, we show that loss of Fto leads to developmental defects such as growth retardation, craniofacial dysmorphism and aberrant neural crest cells migration in Zebrafish. We find that the important developmental pathway, Wnt, is compromised in the absence of FTO, both in vivo (zebrafish and in vitro (Fto(-/- MEFs and HEK293T. Canonical Wnt signalling is down regulated by abrogated β-Catenin translocation to the nucleus whilst non-canonical Wnt/Ca(2+ pathway is activated via its key signal mediators CaMKII and PKCδ. Moreover, we demonstrate that loss of Fto results in short, absent or disorganised cilia leading to situs inversus, renal cystogenesis, neural crest cell defects and microcephaly in Zebrafish. Congruently, Fto knockout mice display aberrant tissue specific cilia. These data identify FTO as a protein-regulator of the balanced activation between canonical and non-canonical branches of the Wnt pathway. Furthermore, we present the first evidence that FTO plays a role in development and cilia formation/function.

  5. Multiple signaling pathways leading to the activation of interferon regulatory factor 3.

    Science.gov (United States)

    Servant, Marc J; Grandvaux, Nathalie; Hiscott, John

    2002-09-01

    Virus infection of susceptible cells activates multiple signaling pathways that orchestrate the activation of genes, such as cytokines, involved in the antiviral and innate immune response. Among the kinases induced are the mitogen-activated protein (MAP) kinases, Jun-amino terminal kinases (JNK) and p38, the IkappaB kinase (IKK) and DNA-PK. In addition, virus infection also activates an uncharacterized VAK responsible for the C-terminal phosphorylation and subsequent activation of interferon regulatory factor 3 (IRF-3). Virus-mediated activation of IRF-3 through VAK is dependent on viral entry and transcription, since replication deficient virus failed to induce IRF-3 activity. The pathways leading to VAK activation are not well characterized, but IRF-3 appears to represent a novel cellular detection pathway that recognizes viral nucleocapsid (N) structure. Recently, the range of inducers responsible for IRF-3 activation has increased. In addition to virus infection, recognition of bacterial infection mediated through lipopolysaccharide by Toll-like receptor 4 has also been reported. Furthermore, MAP kinase kinase kinase (MAP KKK)-related pathways and DNA-PK induce N-terminal phosphorylation of IRF-3. This review summarizes recent observations in the identification of novel signaling pathways leading to IRF-3 activation.

  6. The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals

    Directory of Open Access Journals (Sweden)

    Libing Ye

    2015-12-01

    Full Text Available Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS; however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α, via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury.

  7. Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis

    OpenAIRE

    Tian, Lei; Wen, Qi; Dang, Xiaoqian; You, Wulin; Fan, Lihong; WANG, KUNZHENG

    2014-01-01

    Background Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. The objective of the current study was to establish a rat model to investigate the disruption of immune response in steroid-induced femoral head osteonecrosis via Toll-like receptor 4 (TLR4) signaling pathway. Methods Male SD rats were divided into the treatment group (group A) and the model group (group B) consisting of 24 rats each, and were injected intramuscularly with 20 mg/kg...

  8. Acidic environment leads to ROS-induced MAPK signaling in cancer cells.

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    Anne Riemann

    Full Text Available Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e, pH(i and mitogen-activated-protein-kinases (ERK1/2, p38 was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furthermore, p38 phosphorylation was elicited by sole intracellular lactacidosis at normal pH(e. Inhibition of ERK1/2 phosphorylation during acidosis led to necrotic cell death. No evidence for the involvement of the kinases c-SRC, PKC, PKA, PI3K or EGFR nor changes in cell volume in acidosis-induced MAPK activation was obtained. However, our data reveal that acidosis enhances the formation of reactive oxygen species (ROS, probably originating from mitochondria, which subsequently trigger MAPK phosphorylation. Scavenging of ROS prevented acidosis-induced MAPK phosphorylation whereas addition of H(2O(2 enhanced it. Finally, acidosis increased phosphorylation of the transcription factor CREB via p38, leading to increased transcriptional activity of a CRE-reporter even 24 h after switching the cells back to a normal environmental milieu. Thus, an acidic tumor microenvironment can induce a longer lasting p38-CREB-medited change in the transcriptional program, which may maintain the altered phenotype even when the cells leave the tumor environment.

  9. A Smart Shirt Made with Conductive Ink and Conductive Foam for the Measurement of Electrocardiogram Signals with Unipolar Precordial Leads

    OpenAIRE

    Yasunori Tada; Yusaku Amano; Tomonobu Sato; Shigeru Saito; Masahiro Inoue

    2015-01-01

    The Holter monitor is used to measure an electrocardiogram (ECG) signal while a subject moves. However, the Holter monitor is uncomfortable for the subject. Another method of measuring the ECG signal uses a smart shirt. We developed a smart shirt that has six electrodes on the chest and can measure a detailed ECG, obtained with unipolar precordial leads. The electrodes and wires of the shirt are made of conductive ink that is flexible and stretchable. The smart shirt is stretchable and fits t...

  10. Cardiac contractility modulation in heart failure patients: Randomized comparison of signal delivery through one vs. two ventricular leads.

    Science.gov (United States)

    Röger, Susanne; Said, Samir; Kloppe, Axel; Lawo, Thomas; Emig, Ulf; Rousso, Benny; Gutterman, David; Borggrefe, Martin; Kuschyk, Jürgen

    2017-01-01

    Cardiac contractility modulation (CCM) is an electrical stimulation treatment for symptomatic heart failure (HF) patients. The procedure involves implantation of two ventricular leads for delivery of CCM impulses. The purpose of this study is to compare the efficacy and safety of CCM when the signal is delivered through one vs. two ventricular leads. This prospective blinded randomized trial enrolled 48 patients. Eligible subjects had symptoms despite optimal HF medications, left ventricular ejection fraction leads, and were randomized to CCM active through both or just one ventricular lead; 25 patients were randomized to receive signal delivery through two leads (Group A) and 23 patients to signal delivery through one lead (Group B). The study compared the mean changes from baseline to 6 months follow-up in peakVO2, New York Heart Association (NYHA) classification, and quality of life (by MLWHFQ). Following 6 months, similar and significant (pleads. These results support the potential use of a single ventricular lead for delivery of CCM. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  11. Diffuse excessive high signal intensity in low-risk preterm infants at term-equivalent age does not predict outcome at 1 year: a prospective study

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    Leitner, Yael [Tel Aviv Sourasky Medical Centre, Child Development Centre, Dana-Dwek Children' s Hospital, Tel Aviv (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Weinstein, Maya [Tel Aviv Sourasky Medical Centre, Functional Brain Centre, The Wohl Institute for Advanced Imaging, Tel Aviv (Israel); Bar Ilan University, Department of Psychology, Gonda Multidisciplinary Brain Research Centre, Ramat-Gan (Israel); Myers, Vicki [Tel Aviv Sourasky Medical Centre, Functional Brain Centre, The Wohl Institute for Advanced Imaging, Tel Aviv (Israel); Uliel, Shimrit; Geva, Karen [Tel Aviv Sourasky Medical Centre, Child Development Centre, Dana-Dwek Children' s Hospital, Tel Aviv (Israel); Berger, Irit; Marom, Ronella [Tel Aviv Sourasky Medical Centre, Department of Neonatology, Lis Maternity Hospital, Tel Aviv (Israel); Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Bashat, Dafna Ben [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Tel Aviv University, Sagol School of Neuroscience, Tel Aviv (Israel); Ben-Sira, Liat [Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv (Israel); Tel Aviv Sourasky Medical Centre, Department of Radiology, Tel Aviv (Israel); Geva, Ronny [Bar Ilan University, Department of Psychology, Gonda Multidisciplinary Brain Research Centre, Ramat-Gan (Israel); Gross-Tsur, Varda [Shaare-Zedek Medical Centre, Neuropediatric Unit, Jerusalem (Israel)

    2014-08-15

    The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities. Fifty-eight preterm infants, gestational age 29 ± 2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation. No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI. DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants. (orig.)

  12. Neurodevelopmental outcomes in preterm infants: comparison of infants with and without diffuse excessive high signal intensity on MR images at near-term-equivalent age.

    Science.gov (United States)

    Jeon, Tae Yeon; Kim, Ji Hye; Yoo, So-Young; Eo, Hong; Kwon, Jeong-Yi; Lee, Jeehun; Lee, Munhyang; Chang, Yun Sil; Park, Won Soon

    2012-05-01

    To compare the neurodevelopmental outcomes between preterm infants with diffuse excessive high signal intensity (DEHSI) and those without DEHSI on magnetic resonance (MR) images, in association with other white matter lesions. This retrospective study was approved by the institutional review board, and requirement to obtain informed consent was waived. High-risk preterm infants (n = 126) who underwent screening brain MR imaging at near-term-equivalent age were classified into two groups according to the presence of DEHSI. Bayley Scales of Infant Development-II, presence of cerebral palsy, and neurosensory impairment between 18 and 24 months of age were compared between the two groups. The associations of MR findings of other white matter lesions (cystic encephalomalacia, punctate lesions, loss of volume, ventricular dilatation, and delayed myelination) and subsequent outcomes were also analyzed. Outcome data were evaluated by using exact logistic regression analyses and Fisher exact test. DEHSI was present in 75% (95 of 126) of infants. Subsequent neurodevelopmental outcomes did not differ significantly between the two groups. Severe motor delay and cerebral palsy were more common in infants with both DEHSI and other white matter lesions as compared with infants with normal white matter (P = .001 and P cystic encephalomalacia (odds ratio, 19.6; 95% confidence interval: 1.3, 333.3) and punctate lesions (odds ratio, 90.9; 95% confidence interval: 6.4, 1000) were significant predictors of cerebral palsy. Although the incidence of DEHSI was high (75%) in preterm infants at near-term-equivalent age MR imaging, DEHSI was not predictive of following adverse outcomes. Cystic encephalomalacia and punctate lesions were more significant predictors of cerebral palsy.

  13. Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome.

    Science.gov (United States)

    Osterweil, Emily K; Krueger, Dilja D; Reinhold, Kimberly; Bear, Mark F

    2010-11-17

    Fragile X syndrome (FXS) is caused by loss of the FMR1 gene product FMRP (fragile X mental retardation protein), a repressor of mRNA translation. According to the metabotropic glutamate receptor (mGluR) theory of FXS, excessive protein synthesis downstream of mGluR5 activation causes the synaptic pathophysiology that underlies multiple aspects of FXS. Here, we use an in vitro assay of protein synthesis in the hippocampus of male Fmr1 knock-out (KO) mice to explore the molecular mechanisms involved in this core biochemical phenotype under conditions where aberrant synaptic physiology has been observed. We find that elevated basal protein synthesis in Fmr1 KO mice is selectively reduced to wild-type levels by acute inhibition of mGluR5 or ERK1/2, but not by inhibition of mTOR (mammalian target of rapamycin). The mGluR5-ERK1/2 pathway is not constitutively overactive in the Fmr1 KO, however, suggesting that mRNA translation is hypersensitive to basal ERK1/2 activation in the absence of FMRP. We find that hypersensitivity to ERK1/2 pathway activation also contributes to audiogenic seizure susceptibility in the Fmr1 KO. These results suggest that the ERK1/2 pathway, and other neurotransmitter systems that stimulate protein synthesis via ERK1/2, represent additional therapeutic targets for FXS.

  14. High Levels of Canonical Wnt Signaling Lead to Loss of Stemness and Increased Differentiation in Hematopoietic Stem Cells

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    Farbod Famili

    2016-05-01

    Full Text Available Canonical Wnt signaling regulates the self-renewal of most if not all stem cell systems. In the blood system, the role of Wnt signaling has been the subject of much debate but there is consensus that high Wnt signals lead to loss of reconstituting capacity. To better understand this phenomenon, we have taken advantage of a series of hypomorphic mutant Apc alleles resulting in a broad range of Wnt dosages in hematopoietic stem cells (HSCs and performed whole-genome gene expression analyses. Gene expression profiling and functional studies show that HSCs with APC mutations lead to high Wnt levels, enhanced differentiation, and diminished proliferation but have no effect on apoptosis, collectively leading to loss of stemness. Thus, we provide mechanistic insight into the role of APC mutations and Wnt signaling in HSC biology. As Wnt signals are explored in various in vivo and ex vivo expansion protocols for HSCs, our findings also have clinical ramifications.

  15. Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-β Signaling

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    I. van der Pluijm, PhD

    2016-10-01

    Smad3 deficiency leads to imbalanced activation of downstream genes, no activation of MMPs in VSMCs, and immune responses resulting in rapid aortic wall dilatation and rupture. Our findings uncover new possibilities for treatment of SMAD3 patients; instead of targeting TGF-β signaling, immune suppression may be more beneficial.

  16. The contribution of leading diseases and risk factors to excess losses of healthy life in eastern Europe: burden of disease study

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    Vander Hoorn Stephen

    2005-11-01

    Full Text Available Abstract Background The East/West gradient in health across Europe has been described often, but not using metrics as comprehensive and comparable as those of the Global Burden of Disease 2000 and Comparative Risk Assessment studies. Methods Comparisons are made across 3 epidemiological subregions of the WHO region for Europe – A (very low child and adult mortality, B (low child and low adult mortality and C (low child and high adult mortality – with populations in 2000 of 412, 218 and 243 millions respectively, and using the following measures: 1. Probabilities of death by sex and causal group across 7 age intervals; 2. Loss of healthy life (DALYs to diseases and injuries per thousand population; 3. Loss of healthy life (DALYs attributable to selected risk factors across 3 age ranges. Results Absolute differences in mortality are most marked in males and in younger adults, and for deaths from vascular diseases and from injuries. Dominant contributions to east-west differences come from the nutritional/physiological group of risk factors (blood pressure, cholesterol concentration, body mass index, low fruit and vegetable consumption and inactivity contributing to vascular disease and from the legal drugs – tobacco and alcohol. Conclusion The main requirements for reducing excess health losses in the east of Europe are: 1 favorable shifts in all amenable vascular risk factors (irrespective of their current levels by population-wide and personal measures; 2 intensified tobacco control; 3 reduced alcohol consumption and injury control strategies (for example, for road traffic injuries. Cost effective strategies are broadly known but local institutional support for them needs strengthening.

  17. Transient Inhibition of FGFR2b-ligands signaling leads to irreversible loss of cellular β-catenin organization and signaling in AER during mouse limb development.

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    Soula Danopoulos

    Full Text Available The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b signaling controls the induction of the Apical Ectodermal Ridge (AER but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have investigated these roles through graded and reversible expression of soluble dominant-negative FGFR2b molecules at various times during mouse limb development, using a doxycycline/transactivator/tet(O-responsive system. Transient attenuation (≤ 24 hours of FGFR2b-ligands signaling at E8.5, prior to limb bud induction, leads mostly to the loss or truncation of proximal skeletal elements with less severe impact on distal elements. Attenuation from E9.5 onwards, however, has an irreversible effect on the stability of the AER, resulting in a progressive loss of distal limb skeletal elements. The primary consequences of FGFR2b-ligands attenuation is a transient loss of cell adhesion and down-regulation of P63, β1-integrin and E-cadherin, and a permanent loss of cellular β-catenin organization and WNT signaling within the AER. Combined, these effects lead to the progressive transformation of the AER cells from pluristratified to squamous epithelial-like cells within 24 hours of doxycycline administration. These findings show that FGFR2b-ligands signaling has critical stage-specific roles in maintaining the AER during limb development.

  18. Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis.

    Science.gov (United States)

    Tian, Lei; Wen, Qi; Dang, Xiaoqian; You, Wulin; Fan, Lihong; Wang, Kunzheng

    2014-01-15

    Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. The objective of the current study was to establish a rat model to investigate the disruption of immune response in steroid-induced femoral head osteonecrosis via Toll-like receptor 4 (TLR4) signaling pathway. Male SD rats were divided into the treatment group (group A) and the model group (group B) consisting of 24 rats each, and were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, once a week. The rats in group A were injected intravenously with 7.5 mg/kg TAK242 before each MP administration. A control group (group N) consisted of 12 rats were received saline injection. All animals were sacrificed 8, 10 and 12 weeks from the first MP injection, respectively. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in serum was tested. The signaling molecules including TLR4, MyD88, NF-κB p65 and MCP-1 were detected by immunohistochemistry, quantitative real-time PCR and Western blot. Femoral head osteonecrosis was observed in the model rats, and the concentration of TRAP and positive staining of all signaling molecules increased significantly in group B compared with that in group A and group N. Compare with the control group, the mRNA expressions and protein levels of all signaling molecules were enhanced significantly in group B, but no significant in group A. Corticosteroids can induce femoral head osteonecrosis by disturbing the immune response via TLR4 signaling pathway. These findings suggest that the disruption of immune response play a role in the pathogenesis of osteonecrosis.

  19. Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death

    Science.gov (United States)

    Graham, Nicholas A; Tahmasian, Martik; Kohli, Bitika; Komisopoulou, Evangelia; Zhu, Maggie; Vivanco, Igor; Teitell, Michael A; Wu, Hong; Ribas, Antoni; Lo, Roger S; Mellinghoff, Ingo K; Mischel, Paul S; Graeber, Thomas G

    2012-01-01

    The altered metabolism of cancer can render cells dependent on the availability of metabolic substrates for viability. Investigating the signaling mechanisms underlying cell death in cells dependent upon glucose for survival, we demonstrate that glucose withdrawal rapidly induces supra-physiological levels of phospho-tyrosine signaling, even in cells expressing constitutively active tyrosine kinases. Using unbiased mass spectrometry-based phospho-proteomics, we show that glucose withdrawal initiates a unique signature of phospho-tyrosine activation that is associated with focal adhesions. Building upon this observation, we demonstrate that glucose withdrawal activates a positive feedback loop involving generation of reactive oxygen species (ROS) by NADPH oxidase and mitochondria, inhibition of protein tyrosine phosphatases by oxidation, and increased tyrosine kinase signaling. In cells dependent on glucose for survival, glucose withdrawal-induced ROS generation and tyrosine kinase signaling synergize to amplify ROS levels, ultimately resulting in ROS-mediated cell death. Taken together, these findings illustrate the systems-level cross-talk between metabolism and signaling in the maintenance of cancer cell homeostasis. PMID:22735335

  20. Inhibition of Notch signaling during mouse incisor renewal leads to enamel defects

    Science.gov (United States)

    Jheon, Andrew H.; Prochazkova, Michaela; Meng, Bo; Wen, Timothy; Lim, Young-Jun; Naveau, Adrien; Espinoza, Ruben; Sone, Eli D.; Ganss, Bernhard; Siebel, Christian W.; Klein, Ophir D.

    2016-01-01

    Summary The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Fgf, Shh, Wnt, and Bmp pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during incisor renewal. Notch signaling components are expressed in enamel-forming ameloblasts and the underlying stratum intermedium (SI), which suggested distinct roles in incisor renewal and enamel mineralization. Here, we injected adult mice with inhibitory antibodies against several components of the Notch pathway. This blockade led to defects in the interaction between ameloblasts and the SI cells, which ultimately affected enamel formation. Furthermore, Notch signaling inhibition led to the down-regulation of desmosome-specific proteins such as PERP and desmoplakin, consistent with the importance of desmosomes in the integrity of ameloblast-SI attachment and enamel formation. Together, our data demonstrate that Notch signaling is critical for proper enamel formation during incisor renewal, in part by regulating desmosome-specific components, and that the mouse incisor provides a model system to dissect Jag-Notch signaling mechanisms in the context of mineralized tissue renewal. PMID:26179131

  1. UV-B-induced signaling events leading to enhanced-production of catharanthine in Catharanthus roseus cell suspension cultures

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    Chelliah Jayabaskaran

    2007-11-01

    Full Text Available Abstract Background Elicitations are considered to be an important strategy towards improved in vitro production of secondary metabolites. In cell cultures, biotic and abiotic elicitors have effectively stimulated the production of plant secondary metabolites. However, molecular basis of elicitor-signaling cascades leading to increased production of secondary metabolites of plant cell is largely unknown. Exposure of Catharanthus roseus cell suspension culture to low dose of UV-B irradiation was found to increase the amount of catharanthine and transcription of genes encoding tryptophan decarboxylase (Tdc and strictosidine synthase (Str. In the present study, the signaling pathway mediating UV-B-induced catharanthine accumulation in C. roseus suspension cultures were investigated. Results Here, we investigate whether cell surface receptors, medium alkalinization, Ca2+ influx, H2O2, CDPK and MAPK play required roles in UV-B signaling leading to enhanced production of catharanthine in C. roseus cell suspension cultures. C. roseus cells were pretreated with various agonists and inhibitors of known signaling components and their effects on the accumulation of Tdc and Str transcripts as well as amount of catharanthine production were investigated by various molecular biology techniques. It has been found that the catharanthine accumulation and transcription of Tdc and Str were inhibited by 3–4 fold upon pretreatment of various inhibitors like suramin, N-acetyl cysteine, inhibitors of calcium fluxes, staurosporine etc. Conclusion Our results demonstrate that cell surface receptor(s, Ca2+ influx, medium alkalinization, CDPK, H2O2 and MAPK play significant roles in UV-B signaling leading to stimulation of Tdc and Str genes and the accumulation of catharanthine in C. roseus cell suspension cultures. Based on these findings, a model for signal transduction cascade has been proposed.

  2. UV-B-induced signaling events leading to enhanced-production of catharanthine in Catharanthus roseus cell suspension cultures

    Science.gov (United States)

    Ramani, Shilpa; Chelliah, Jayabaskaran

    2007-01-01

    Background Elicitations are considered to be an important strategy towards improved in vitro production of secondary metabolites. In cell cultures, biotic and abiotic elicitors have effectively stimulated the production of plant secondary metabolites. However, molecular basis of elicitor-signaling cascades leading to increased production of secondary metabolites of plant cell is largely unknown. Exposure of Catharanthus roseus cell suspension culture to low dose of UV-B irradiation was found to increase the amount of catharanthine and transcription of genes encoding tryptophan decarboxylase (Tdc) and strictosidine synthase (Str). In the present study, the signaling pathway mediating UV-B-induced catharanthine accumulation in C. roseus suspension cultures were investigated. Results Here, we investigate whether cell surface receptors, medium alkalinization, Ca2+ influx, H2O2, CDPK and MAPK play required roles in UV-B signaling leading to enhanced production of catharanthine in C. roseus cell suspension cultures. C. roseus cells were pretreated with various agonists and inhibitors of known signaling components and their effects on the accumulation of Tdc and Str transcripts as well as amount of catharanthine production were investigated by various molecular biology techniques. It has been found that the catharanthine accumulation and transcription of Tdc and Str were inhibited by 3–4 fold upon pretreatment of various inhibitors like suramin, N-acetyl cysteine, inhibitors of calcium fluxes, staurosporine etc. Conclusion Our results demonstrate that cell surface receptor(s), Ca2+ influx, medium alkalinization, CDPK, H2O2 and MAPK play significant roles in UV-B signaling leading to stimulation of Tdc and Str genes and the accumulation of catharanthine in C. roseus cell suspension cultures. Based on these findings, a model for signal transduction cascade has been proposed. PMID:17988378

  3. Excessive crying in infants

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    Ricardo Halpern

    2016-06-01

    Full Text Available ABSTRACT Objective: Review the literature on excessive crying in young infants, also known as infantile colic, and its effects on family dynamics, its pathophysiology, and new treatment interventions. Data source: The literature review was carried out in the Medline, PsycINFO, LILACS, SciELO, and Cochrane Library databases, using the terms “excessive crying,” and “infantile colic,” as well technical books and technical reports on child development, selecting the most relevant articles on the subject, with emphasis on recent literature published in the last five years. Summary of the findings: Excessive crying is a common symptom in the first 3 months of life and leads to approximately 20% of pediatric consultations. Different prevalence rates of excessive crying have been reported, ranging from 14% to approximately 30% in infants up to 3 months of age. There is evidence linking excessive crying early in life with adaptive problems in the preschool period, as well as with early weaning, maternal anxiety and depression, attention deficit hyperactivity disorder, and other behavioral problems. Several pathophysiological mechanisms can explain these symptoms, such as circadian rhythm alterations, central nervous system immaturity, and alterations in the intestinal microbiota. Several treatment alternatives have been described, including behavioral measures, manipulation techniques, use of medication, and acupuncture, with controversial results and effectiveness. Conclusion: Excessive crying in the early months is a prevalent symptom; the pediatrician's attention is necessary to understand and adequately manage the problem and offer support to exhausted parents. The prescription of drugs of questionable action and with potential side effects is not a recommended treatment, except in extreme situations. The effectiveness of dietary treatments and use of probiotics still require confirmation. There is incomplete evidence regarding alternative

  4. Plant gravitropic signal transduction: A network analysis leads to gene discovery

    Science.gov (United States)

    Wyatt, Sarah

    Gravity plays a fundamental role in plant growth and development. Although a significant body of research has helped define the events of gravity perception, the role of the plant growth regulator auxin, and the mechanisms resulting in the gravity response, the events of signal transduction, those that link the biophysical action of perception to a biochemical signal that results in auxin redistribution, those that regulate the gravitropic effects on plant growth, remain, for the most part, a “black box.” Using a cold affect, dubbed the gravity persistent signal (GPS) response, we developed a mutant screen to specifically identify components of the signal transduction pathway. Cloning of the GPS genes have identified new proteins involved in gravitropic signaling. We have further exploited the GPS response using a multi-faceted approach including gene expression microarrays, proteomics analysis, and bioinformatics analysis and continued mutant analysis to identified additional genes, physiological and biochemical processes. Gene expression data provided the foundation of a regulatory network for gravitropic signaling. Based on these gene expression data and related data sets/information from the literature/repositories, we constructed a gravitropic signaling network for Arabidopsis inflorescence stems. To generate the network, both a dynamic Bayesian network approach and a time-lagged correlation coefficient approach were used. The dynamic Bayesian network added existing information of protein-protein interaction while the time-lagged correlation coefficient allowed incorporation of temporal regulation and thus could incorporate the time-course metric from the data set. Thus the methods complemented each other and provided us with a more comprehensive evaluation of connections. Each method generated a list of possible interactions associated with a statistical significance value. The two networks were then overlaid to generate a more rigorous, intersected

  5. The Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to excessive interleukin-1β and IL-18 production.

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    Deepti Verma

    Full Text Available The Q705K polymorphism in NLRP3 has been implicated in several chronic inflammatory diseases. In this study we determine the functional role of this commonly occurring polymorphism using an in-vitro system.NLRP3-WT and NLRP3-Q705K were retrovirally transduced into the human monocytic cell line THP-1, followed by the assessment of IL-1β and IL-18 levels in the cell culture supernatant. THP-1 cells expressing the above NLRP3 variants were sorted based upon Green Fluorescent Protein (GFP expression. Cytokine response to alum (one of the most widely used adjuvants in vaccines in the cells stably expressing NLRP3-WT and NLRP3-Q705K were determined. IL-1β and IL-18 levels were found to be elevated in THP-1 cells transduced with NLRP3-Q705K compared to the NLRP3-WT. Upon exposure to alum, THP-1 cells stably expressing NLRP3-Q705K displayed an increased release of IL-1β, IL-18 and TNF-α, in a caspase-1 and IL-1 receptor-dependent manner.Collectively, these findings show that the Q705K polymorphism in NLRP3 is a gain-of-function alteration leading to an overactive NLRP3 inflammasome. The option of IL-1β blockade may be considered in patients with chronic inflammatory disorders that are unresponsive to conventional treatments.

  6. A Smart Shirt Made with Conductive Ink and Conductive Foam for the Measurement of Electrocardiogram Signals with Unipolar Precordial Leads

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    Yasunori Tada

    2015-11-01

    Full Text Available The Holter monitor is used to measure an electrocardiogram (ECG signal while a subject moves. However, the Holter monitor is uncomfortable for the subject. Another method of measuring the ECG signal uses a smart shirt. We developed a smart shirt that has six electrodes on the chest and can measure a detailed ECG, obtained with unipolar precordial leads. The electrodes and wires of the shirt are made of conductive ink that is flexible and stretchable. The smart shirt is stretchable and fits the body well. However, because of the gap between the smart shirt and the body, electrodes V1 and V2 do not touch the body consistently. We developed a conductive foam block that fills this gap. We investigated the characteristics of the conductive foam block, and measured ECG signals using the smart shirt. The electrical resistance of the conductive foam block was reduced by pressure. This characteristic could be utilized to measure the ECG signal because the block was pressed by the body and smart shirt. We could measure the ECG signal using the smart shirt and blocks while the subject walked and could detect peaks of the ECG signal while the subject jogged slowly.

  7. Loss of guanylyl cyclase C (GCC signaling leads to dysfunctional intestinal barrier.

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    Xiaonan Han

    2011-01-01

    Full Text Available Guanylyl Cyclase C (GCC signaling via uroguanylin (UGN and guanylin activation is a critical mediator of intestinal fluid homeostasis, intestinal cell proliferation/apoptosis, and tumorigenesis. As a mechanism for some of these effects, we hypothesized that GCC signaling mediates regulation of intestinal barrier function.Paracellular permeability of intestinal segments was assessed in wild type (WT and GCC deficient (GCC-/- mice with and without lipopolysaccharide (LPS challenge, as well as in UGN deficient (UGN-/- mice. IFNγ and myosin light chain kinase (MLCK levels were determined by real time PCR. Expression of tight junction proteins (TJPs, phosphorylation of myosin II regulatory light chain (MLC, and STAT1 activation were examined in intestinal epithelial cells (IECs and intestinal mucosa. The permeability of Caco-2 and HT-29 IEC monolayers, grown on Transwell filters was determined in the absence and presence of GCC RNA interference (RNAi. We found that intestinal permeability was increased in GCC-/- and UGN-/- mice compared to WT, accompanied by increased IFNγ levels, MLCK and STAT1 activation in IECs. LPS challenge promotes greater IFNγ and STAT1 activation in IECs of GCC-/- mice compared to WT mice. Claudin-2 and JAM-A expression were reduced in GCC deficient intestine; the level of phosphorylated MLC in IECs was significantly increased in GCC-/- and UGN-/- mice compared to WT. GCC knockdown induced MLC phosphorylation, increased permeability in IEC monolayers under basal conditions, and enhanced TNFα and IFNγ-induced monolayer hyperpermeability.GCC signaling plays a protective role in the integrity of the intestinal mucosal barrier by regulating MLCK activation and TJ disassembly. GCC signaling activation may therefore represent a novel mechanism in maintaining the small bowel barrier in response to injury.

  8. Type I interferon signaling restrains IL-10R+ colonic macrophages and dendritic cells and leads to more severe Salmonella colitis.

    Directory of Open Access Journals (Sweden)

    Kailyn L Stefan

    Full Text Available Type I interferons (IFNα, IFNβ are key regulators of innate and adaptive immunity, modulating the severity of both viral and bacterial infections. While type I IFN signaling leads to improved outcomes in viral infections, its role in bacterial infections is more contextual and depends on the specific pathogen and route of infection. Given the limited evidence on whether type I IFN signaling affects enteric bacterial pathogens, we investigated the role of this signaling pathway in Salmonella enterica serovar Typhimurium (S. typhimurium-induced colitis. Comparing mice deficient in IFNAR1- the common receptor for IFNα and IFNβ- with wild-type mice, we found that type I IFN signaling leads to more rapid death, more severe colonic inflammation, higher serum levels of pro-inflammatory cytokines, and greater bacterial dissemination. Specific ablation of plasmacytoid dendritic cells (pDCs, which are prominent producers of type I IFNs in antiviral responses, did not alter survival after infection. This result established that pDCs do not play a major role in the pathogenesis of S. typhimurium colitis. Flow cytometric analysis of macrophages and conventional dendritic cells (cDCs during active colitis demonstrated an increase in CD11c- macrophages and CD103+ cDCs in the colon of Ifnar1-/- animals. Interestingly, cells expressing the anti-inflammatory cytokine receptor IL-10R are more abundant within these subsets in Ifnar1-/- than in wild-type mice. Moreover, blockade of IL-10R in Ifnar1-/- mice increased their susceptibility to S. typhimurium colitis, suggesting that altered numbers of these immunoregulatory cells may underlie the difference in disease severity. This cross-talk between type I IFN and IL-10R signaling pathways may represent a key host cellular mechanism to investigate further in order to unravel the balance between pathogenic inflammation and homeostasis of the colon. Taken together, our data clearly demonstrate that type I IFN

  9. Inhibitors of Intracellular Signaling Pathways that Lead to Stimulated Epidermal Pigmentation: Perspective of Anti-Pigmenting Agents

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    Genji Imokawa

    2014-05-01

    Full Text Available Few anti-pigmenting agents have been designed and developed according to their known hyperpigmentation mechanisms and corresponding intracellular signaling cascades. Most anti-pigmenting agents developed so far are mechanistically involved in the interruption of constitutional melanogenic mechanisms by which skin color is maintained at a normal and unstimulated level. Thus, owing to the difficulty of confining topical application to a specific hyperpigmented skin area, potent anti-pigmenting agents capable of attenuating the natural unstimulated pigmentation process have the risk of leading to hypopigmentation. Since intracellular signaling pathways within melanocytes do not function substantially in maintaining normal skin color and are activated only by environmental stimuli such as UV radiation, specifically down-regulating the activation of melanogenesis to the constitutive level would be an appropriate strategy to develop new potent anti-pigmenting agents with a low risk of hypopigmentation. In this article, we review the hyperpigmentation mechanisms and intracellular signaling pathways that lead to the stimulation of melanogenesis. We also discuss a screening and evaluation system to select candidates for new anti-melanogenic substances by focusing on inhibitors of endothelin-1 or stem cell factor-triggered intracellular signaling cascades. From this viewpoint, we show that extracts of the herbs Withania somnifera and Melia toosendan and the natural chemicals Withaferin A and Astaxanthin are new candidates for potent anti-pigmenting substances that avoid the risk of hypopigmentation.

  10. A mutation in the mouse ttc26 gene leads to impaired hedgehog signaling.

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    Ruth E Swiderski

    2014-10-01

    Full Text Available The phenotype of the spontaneous mutant mouse hop-sterile (hop is characterized by a hopping gait, polydactyly, hydrocephalus, and male sterility. Previous analyses of the hop mouse revealed a deficiency of inner dynein arms in motile cilia and a lack of sperm flagella, potentially accounting for the hydrocephalus and male sterility. The etiology of the other phenotypes and the location of the hop mutation remained unexplored. Here we show that the hop mutation is located in the Ttc26 gene and impairs Hedgehog (Hh signaling. Expression analysis showed that this mutation led to dramatically reduced levels of the Ttc26 protein, and protein-protein interaction assays demonstrated that wild-type Ttc26 binds directly to the Ift46 subunit of Intraflagellar Transport (IFT complex B. Although IFT is required for ciliogenesis, the Ttc26 defect did not result in a decrease in the number or length of primary cilia. Nevertheless, Hh signaling was reduced in the hop mouse, as revealed by impaired activation of Gli transcription factors in embryonic fibroblasts and abnormal patterning of the neural tube. Unlike the previously characterized mutations that affect IFT complex B, hop did not interfere with Hh-induced accumulation of Gli at the tip of the primary cilium, but rather with the subsequent dissociation of Gli from its negative regulator, Sufu. Our analysis of the hop mouse line provides novel insights into Hh signaling, demonstrating that Ttc26 is necessary for efficient coupling between the accumulation of Gli at the ciliary tip and its dissociation from Sufu.

  11. Embryonic Ethanol Exposure Dysregulates BMP and Notch Signaling, Leading to Persistent Atrio-Ventricular Valve Defects in Zebrafish.

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    Swapnalee Sarmah

    Full Text Available Fetal alcohol spectrum disorder (FASD, birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs, the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3-24 hours post fertilization led to defects in atrio-ventricular (AV valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC. Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/β-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish.

  12. Permutation entropy based time series analysis: Equalities in the input signal can lead to false conclusions

    Energy Technology Data Exchange (ETDEWEB)

    Zunino, Luciano, E-mail: lucianoz@ciop.unlp.edu.ar [Centro de Investigaciones Ópticas (CONICET La Plata – CIC), C.C. 3, 1897 Gonnet (Argentina); Departamento de Ciencias Básicas, Facultad de Ingeniería, Universidad Nacional de La Plata (UNLP), 1900 La Plata (Argentina); Olivares, Felipe, E-mail: olivaresfe@gmail.com [Instituto de Física, Pontificia Universidad Católica de Valparaíso (PUCV), 23-40025 Valparaíso (Chile); Scholkmann, Felix, E-mail: Felix.Scholkmann@gmail.com [Research Office for Complex Physical and Biological Systems (ROCoS), Mutschellenstr. 179, 8038 Zurich (Switzerland); Biomedical Optics Research Laboratory, Department of Neonatology, University Hospital Zurich, University of Zurich, 8091 Zurich (Switzerland); Rosso, Osvaldo A., E-mail: oarosso@gmail.com [Instituto de Física, Universidade Federal de Alagoas (UFAL), BR 104 Norte km 97, 57072-970, Maceió, Alagoas (Brazil); Instituto Tecnológico de Buenos Aires (ITBA) and CONICET, C1106ACD, Av. Eduardo Madero 399, Ciudad Autónoma de Buenos Aires (Argentina); Complex Systems Group, Facultad de Ingeniería y Ciencias Aplicadas, Universidad de los Andes, Av. Mons. Álvaro del Portillo 12.455, Las Condes, Santiago (Chile)

    2017-06-15

    A symbolic encoding scheme, based on the ordinal relation between the amplitude of neighboring values of a given data sequence, should be implemented before estimating the permutation entropy. Consequently, equalities in the analyzed signal, i.e. repeated equal values, deserve special attention and treatment. In this work, we carefully study the effect that the presence of equalities has on permutation entropy estimated values when these ties are symbolized, as it is commonly done, according to their order of appearance. On the one hand, the analysis of computer-generated time series is initially developed to understand the incidence of repeated values on permutation entropy estimations in controlled scenarios. The presence of temporal correlations is erroneously concluded when true pseudorandom time series with low amplitude resolutions are considered. On the other hand, the analysis of real-world data is included to illustrate how the presence of a significant number of equal values can give rise to false conclusions regarding the underlying temporal structures in practical contexts. - Highlights: • Impact of repeated values in a signal when estimating permutation entropy is studied. • Numerical and experimental tests are included for characterizing this limitation. • Non-negligible temporal correlations can be spuriously concluded by repeated values. • Data digitized with low amplitude resolutions could be especially affected. • Analysis with shuffled realizations can help to overcome this limitation.

  13. Loss of mesenchymal CSL signaling leads to field cancerization and multifocal epithelial tumors

    Science.gov (United States)

    Hu, Bing; Castillo, Einar; Harewood, Louise; Ostano, Paola; Reymond, Alexandre; Dummer, Reinhard; Raffoul, Wassim; Hoetzenecker, Wolfram; Hofbauer, Günther F. L.; Dotto, G. Paolo

    2012-01-01

    Summary It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-Jκ, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through up-regulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix remodeling enzymes. In human skin samples, stromal fields adjacent to cutaneous squamous cell carcinomas and multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer. PMID:22682244

  14. Improved Signal Processing Technique Leads to More Robust Self Diagnostic Accelerometer System

    Science.gov (United States)

    Tokars, Roger; Lekki, John; Jaros, Dave; Riggs, Terrence; Evans, Kenneth P.

    2010-01-01

    The self diagnostic accelerometer (SDA) is a sensor system designed to actively monitor the health of an accelerometer. In this case an accelerometer is considered healthy if it can be determined that it is operating correctly and its measurements may be relied upon. The SDA system accomplishes this by actively monitoring the accelerometer for a variety of failure conditions including accelerometer structural damage, an electrical open circuit, and most importantly accelerometer detachment. In recent testing of the SDA system in emulated engine operating conditions it has been found that a more robust signal processing technique was necessary. An improved accelerometer diagnostic technique and test results of the SDA system utilizing this technique are presented here. Furthermore, the real time, autonomous capability of the SDA system to concurrently compensate for effects from real operating conditions such as temperature changes and mechanical noise, while monitoring the condition of the accelerometer health and attachment, will be demonstrated.

  15. Hypersensitive ethylene signaling and ZMdPG1 expression lead to fruit softening and dehiscence.

    Directory of Open Access Journals (Sweden)

    Min Li

    Full Text Available 'Taishanzaoxia' fruit rapid softening and dehiscence during ripening stage and this process is very sensitive to endogenous ethylene. In this study, we cloned five ethylene signal transcription factors (ZMdEIL1, ZMdEIL2, ZMdEIL3, ZMdERF1 and ZMdERF2 and one functional gene, ZMdPG1, encoding polygalacturonase that could loose the cell connection which associated with fruit firmness decrease and fruit dehiscence to illustrate the reasons for this specific fruit phenotypic and physiological changes. Expression analysis showed that ZMdERF1 and ZMdEIL2 transcription were more abundant in 'Taishanzaoxia' softening fruit and dehiscent fruit and their expression was inhibited by an ethylene inhibitor 1-methylcyclopropene. Therefore, ZMdERF1 and ZMdEIL2 expression were responses to endogenous ethylene and associated with fruit softening and dehiscence. ZMdPG1 expression was induced when fruit softening and dehiscence but this induction can be blocked by 1-MCP, indicating that ZMdPG1 was essential for fruit softening and dehiscence and its expression was mediated by the endogenously occurred ethylene. ZMdPG1 overexpression in Arabidopsis led to silique early dehiscence while suppressing ZMdPG1 expression by antisense ZMdPG1 prevented silique naturally opening. The result also suggested that ZMdPG1 related with the connection between cells that contributed to fruit softening and dehiscence. ZMdERF1 was more closely related with ethylene signaling but it was not directly regulated the ZMdPG1, which might be regulated by the synergic pattern of ethylene transcription factors because of both the ZMdERF1 and ZMdERF2 could interact with ZMdEIL2.

  16. Testing the critical exponent in the relation between stress drop of earthquake and lead time of seismic electric signal

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    E. Dologlou

    2012-08-01

    Full Text Available The application of new data in the power law relation between the stress drop of the earthquake and the lead time of the precursory seismic electric signal led to an exponent which falls in the range of the values of critical exponents for fracture and it is in excellent agreement with a previous one found by (Dologlou, 2012. In addition, this exponent is very close to the one reported by Varotsos and Alexopoulos (1984a, which interconnects the amplitude of the precursory seismic electric signals (SES and the magnitude of the impending earthquake. Hence, the hypothesis that underlying dynamic processes evolving to criticality prevail in the pre-focal area when the SES is emitted is significantly supported.

  17. Signal transduction leading to low-temperature tolerance in Arabidopsis thaliana.

    Science.gov (United States)

    Knight, Marc R

    2002-07-29

    Calcium is used by most cells to convert external signals into biochemical events within the cytosol. To detect the effects of cold stress, a gene encoding apoaequorin has been introduced into various cell types that, in the presence of coelenterazine, allows calcium levels to be monitored by the emission of blue light. All cell types respond to the cold by elevating calcium. This event is rapid after cold stress but then shows a slower kinetic response. The magnitude is dependent on both the rate and the final temperature to which cooling occurs. It would appear that calcium is transferred both from outside the cell and from the vacuole into the cytosol. The more rapid phase involves the former and the slower phase the latter. By studying mutant plants, it has been identified that an increase in intracellular calcium can activate the expression of transcription factors that control the subsequent transcription of a whole battery of genes which must be switched on to provide cold tolerance in the plant.

  18. Permutation entropy based time series analysis: Equalities in the input signal can lead to false conclusions

    Science.gov (United States)

    Zunino, Luciano; Olivares, Felipe; Scholkmann, Felix; Rosso, Osvaldo A.

    2017-06-01

    A symbolic encoding scheme, based on the ordinal relation between the amplitude of neighboring values of a given data sequence, should be implemented before estimating the permutation entropy. Consequently, equalities in the analyzed signal, i.e. repeated equal values, deserve special attention and treatment. In this work, we carefully study the effect that the presence of equalities has on permutation entropy estimated values when these ties are symbolized, as it is commonly done, according to their order of appearance. On the one hand, the analysis of computer-generated time series is initially developed to understand the incidence of repeated values on permutation entropy estimations in controlled scenarios. The presence of temporal correlations is erroneously concluded when true pseudorandom time series with low amplitude resolutions are considered. On the other hand, the analysis of real-world data is included to illustrate how the presence of a significant number of equal values can give rise to false conclusions regarding the underlying temporal structures in practical contexts.

  19. Small molecule modulation of HH-GLI signaling: current leads, trials and tribulations.

    Science.gov (United States)

    Mas, Christophe; Ruiz i Altaba, Ariel

    2010-09-01

    Many human sporadic cancers have been recently shown to require the activity of the Hedgehog-GLI pathway for sustained growth. The survival and expansion of cancer stem cells is also HH-GLI dependent. Here we review the advances on the modulation of HH-GLI signaling by small molecules. We focus on both natural compounds and synthetic molecules that target upstream pathway components, mostly SMOOTHENED, and those that target the last steps of the pathway, the GLI transcription factors. In this review we have sought to provide some bases for useful comparisons, listing original assays used and sources to facilitate comparisons of IC50 values. This area is a rapidly expanding field where biology, medicine and chemistry intersect, both in academia and industry. We also highlight current clinical trials, with positive results in early stages. While we have tried to be exhaustive regarding the molecules, not all data is in the public domain yet. Indeed, we have opted to avoid listing chemical structures but these can be easily found in the references given. Finally, we are hopeful that the best molecules will soon reach the patients but caution about the lack of investment on compounds that lack tight IP positions. While the market in developed nations is expected to compensate the investment and risk of making HH-GLI modulators, other sources or plans must be available for developing nations and poor patient populations. The promise of curing cancer recalls the once revered dream of El Dorado, which taught us that not everything that GLI-tters is gold. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Disruption of Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the Diabetic Retina

    Directory of Open Access Journals (Sweden)

    Sandra M. Cardona

    2015-10-01

    Full Text Available Fractalkine (CX3CL1 or FKN is a membrane-bound chemokine expressed on neuronal membranes and is proteolytically cleaved to shed a soluble chemoattractant domain. FKN signals via its unique receptor CX3CR1 expressed on microglia and other peripheral leukocytes. The aim of this study is to determine the role of CX3CR1 in inflammatory-mediated damage to retinal neurons using a model of diabetic retinopathy. For this, we compared neuronal, microglial, and astroglial densities and inflammatory response in nondiabetic and diabetic (Ins2Akita CX3CR1-wild-type and CX3CR1-deficient mice at 10 and 20 weeks of age. Our results show that Ins2Akita CX3CR1-knockout mice exhibited (a decreased neuronal cell counts in the retinal ganglion cell layer, (b increased microglial cell numbers, and (c decreased astrocyte responses comparable with Ins2Akita CX3CR1-Wild-type mice at 20 weeks of age. Analyses of the inflammatory response using PCR arrays showed several inflammatory genes differentially regulated in diabetic tissues. From those, the response in Ins2Akita CX3CR1-deficient mice at 10 weeks of age revealed a significant upregulation of IL-1β at the transcript level that was confirmed by enzyme-linked immunosorbent assay in soluble retinal extracts. Overall, IL-1β, VEGF, and nitrite levels as a read out of nitric oxide production were abundant in Ins2Akita CX3CR1-deficient retina. Notably, double immunofluorescence staining shows that astrocytes act as a source of IL-1β in the Ins2Akita retina, and CX3CR1-deficient microglia potentiate the inflammatory response via IL-1β release. Collectively, these data demonstrate that dysregulated microglial responses in absence of CX3CR1 contribute to inflammatory-mediated damage of neurons in the diabetic retina.

  1. Data-driven estimation of cardiac electrical diffusivity from 12-lead ECG signals.

    Science.gov (United States)

    Zettinig, Oliver; Mansi, Tommaso; Neumann, Dominik; Georgescu, Bogdan; Rapaka, Saikiran; Seegerer, Philipp; Kayvanpour, Elham; Sedaghat-Hamedani, Farbod; Amr, Ali; Haas, Jan; Steen, Henning; Katus, Hugo; Meder, Benjamin; Navab, Nassir; Kamen, Ali; Comaniciu, Dorin

    2014-12-01

    Diagnosis and treatment of dilated cardiomyopathy (DCM) is challenging due to a large variety of causes and disease stages. Computational models of cardiac electrophysiology (EP) can be used to improve the assessment and prognosis of DCM, plan therapies and predict their outcome, but require personalization. In this work, we present a data-driven approach to estimate the electrical diffusivity parameter of an EP model from standard 12-lead electrocardiograms (ECG). An efficient forward model based on a mono-domain, phenomenological Lattice-Boltzmann model of cardiac EP, and a boundary element-based mapping of potentials to the body surface is employed. The electrical diffusivity of myocardium, left ventricle and right ventricle endocardium is then estimated using polynomial regression which takes as input the QRS duration and electrical axis. After validating the forward model, we computed 9500 EP simulations on 19 different DCM patients in just under three seconds each to learn the regression model. Using this database, we quantify the intrinsic uncertainty of electrical diffusion for given ECG features and show in a leave-one-patient-out cross-validation that the regression method is able to predict myocardium diffusion within the uncertainty range. Finally, our approach is tested on the 19 cases using their clinical ECG. 84% of them could be personalized using our method, yielding mean prediction errors of 18.7ms for the QRS duration and 6.5° for the electrical axis, both values being within clinical acceptability. By providing an estimate of diffusion parameters from readily available clinical data, our data-driven approach could therefore constitute a first calibration step toward a more complete personalization of cardiac EP. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity

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    Bodo C. Melnik

    2012-01-01

    Full Text Available Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1. Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.

  3. Understand Your Risk for Excessive Blood Clotting

    Science.gov (United States)

    ... Vascular Health Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Understand Your Risk for Excessive Blood Clotting Updated:Nov 2,2015 Many factors can lead to excessive blood clotting, leading to limited or blocked blood flow. Blood clots can travel to the arteries or ...

  4. Dysregulated estrogen receptor signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis in mice.

    Directory of Open Access Journals (Sweden)

    Mary J Laws

    2014-03-01

    Full Text Available The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E at the level of the pituitary led to increased production of luteinizing hormone (LH by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis.

  5. Dysregulated Estrogen Receptor Signaling in the Hypothalamic-Pituitary-Ovarian Axis Leads to Ovarian Epithelial Tumorigenesis in Mice

    Science.gov (United States)

    Laws, Mary J.; Kannan, Athilakshmi; Pawar, Sandeep; Haschek, Wanda M.; Bagchi, Milan K.; Bagchi, Indrani C.

    2014-01-01

    The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα) signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to increased production of luteinizing hormone (LH) by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis. PMID:24603706

  6. Amorphous lead oxide (a-PbO): suppression of signal lag via engineering of the layer structure.

    Science.gov (United States)

    Semeniuk, O; Grynko, O; Juska, G; Reznik, A

    2017-10-16

    Presence of a signal lag is a bottle neck of performance for many non-crystalline materials, considered for dynamic radiation sensing. Due to inadequate lag-related temporal performance, polycrystalline layers of CdZnTe, PbI2, HgI2 and PbO are not practically utilized, despite their superior X-ray sensitivity and low production cost (even for large area detectors). In the current manuscript, we show that a technological step to replace nonhomogeneous disorder in polycrystalline PbO with homogeneous amorphous PbO structure suppresses signal lag and improves time response to X-ray irradiation. In addition, the newly developed amorphous lead oxide (a-PbO) possesses superior X-ray sensitivity in terms of electron-hole pair creation energy [Formula: see text] in comparison with amorphous selenium - currently the only photoconductor used as an X-ray-to-charge transducer in the state-of-the-art direct conversion X-ray medical imaging systems. The proposed advances of the deposition process are low cost, easy to implement and with certain customization might potentially be applied to other materials, thus paving the way to their wide-range commercial use.

  7. Enhanced muscle nutrient content and flesh quality, resulting from tryptophan, is associated with anti-oxidative damage referred to the Nrf2 and TOR signalling factors in young grass carp (Ctenopharyngodon idella): Avoid tryptophan deficiency or excess.

    Science.gov (United States)

    Jiang, Wei-Dan; Wen, Hai-Lang; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2016-05-15

    Flesh quality, muscle antioxidant status and related signalling molecule expressions were investigated in young grass carp fed six levels of tryptophan (Trp) for 8 weeks. The results indicated that fish fed 0.7 (deficiency) and 6.1g Trp g/kg (excess) diets exhibited lower muscle water-holding capacity, tenderness, cathepsin activity, protein levels, lipids and collagen contents. Optimal Trp reversed these negative effects, which were related to enhanced glutathione (GSH) content and glutathione peroxidase (GPx) activities regulated at gene transcription levels, rather than to superoxide dismutase (SOD) or catalase (CAT). The expression of signalling molecules [Kelch-like ECH-associated protein 1, target of rapamycin (TOR) and ribosomal S6 protein kinase 1] involved in the NF-E2-related factor 2 (Nrf2) pathway revealed a potential method of Trp-enhanced antioxidant defence. Collectively, the present study indicated that appropriate Trp levels improved flesh quality partly related to the enhancement of antioxidant ability through Nrf2 and TOR signalling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. The two-component signal transduction system CopRS of Corynebacterium glutamicum is required for adaptation to copper-excess stress.

    Directory of Open Access Journals (Sweden)

    Stephanie Schelder

    Full Text Available Copper is an essential cofactor for many enzymes but at high concentrations it is toxic for the cell. Copper ion concentrations ≥50 µM inhibited growth of Corynebacterium glutamicum. The transcriptional response to 20 µM Cu(2+ was studied using DNA microarrays and revealed 20 genes that showed a ≥ 3-fold increased mRNA level, including cg3281-cg3289. Several genes in this genomic region code for proteins presumably involved in the adaption to copper-induced stress, e. g. a multicopper oxidase (CopO and a copper-transport ATPase (CopB. In addition, this region includes the copRS genes (previously named cgtRS9 which encode a two-component signal transduction system composed of the histidine kinase CopS and the response regulator CopR. Deletion of the copRS genes increased the sensitivity of C. glutamicum towards copper ions, but not to other heavy metal ions. Using comparative transcriptome analysis of the ΔcopRS mutant and the wild type in combination with electrophoretic mobility shift assays and reporter gene studies the CopR regulon and the DNA-binding motif of CopR were identified. Evidence was obtained that CopR binds only to the intergenic region between cg3285 (copR and cg3286 in the genome of C. glutamicum and activates expression of the divergently oriented gene clusters cg3285-cg3281 and cg3286-cg3289. Altogether, our data suggest that CopRS is the key regulatory system in C. glutamicum for the extracytoplasmic sensing of elevated copper ion concentrations and for induction of a set of genes capable of diminishing copper stress.

  9. Impaired Vitamin D Signaling in Endothelial Cell Leads to an Enhanced Leukocyte-Endothelium Interplay: Implications for Atherosclerosis Development.

    Directory of Open Access Journals (Sweden)

    Milica Bozic

    Full Text Available Endothelial cell activation leading to leukocyte recruitment and adhesion plays an essential role in the initiation and progression of atherosclerosis. Vitamin D has cardioprotective actions, while its deficiency is a risk factor for the progression of cardiovascular damage. Our aim was to assess the role of basal levels of vitamin D receptor (VDR on the early leukocyte recruitment and related endothelial cell-adhesion-molecule expression, as essential prerequisites for the onset of atherosclerosis. Knockdown of VDR in endothelial cells (shVDR led to endothelial cell activation, characterized by upregulation of VCAM-1, ICAM-1 and IL-6, decreased peripheral blood mononuclear cell (PBMC rolling velocity and increased PBMC rolling flux and adhesion to the endothelium. shVDR cells showed decreased IκBα levels and accumulation of p65 in the nucleus compared to shRNA controls. Inhibition of NF-κB activation with super-repressor IκBα blunted all signs of endothelial cell activation caused by downregulation of VDR in endothelial cells. In vivo, deletion of VDR led to significantly larger aortic arch and aortic root lesions in apoE-/- mice, with higher macrophage content. apoE-/-VDR-/-mice showed higher aortic expression of VCAM-1, ICAM-1 and IL-6 when compared to apoE-/-VDR+/+ mice. Our data demonstrate that lack of VDR signaling in endothelial cells leads to a state of endothelial activation with increased leukocyte-endothelial cell interactions that may contribute to the more severe plaque accumulation observed in apoE-/-VDR-/- mice. The results reveal an important role for basal levels of endothelial VDR in limiting endothelial cell inflammation and atherosclerosis.

  10. Excessive Daytime Sleepiness

    Directory of Open Access Journals (Sweden)

    Yavuz Selvi

    2016-06-01

    Full Text Available Excessive daytime sleepiness is one of the most common sleep-related patient symptoms, with preva-lence in the community estimated to be as high as 18%. Patients with excessive daytime sleepiness may exhibit life threatening road and work accidents, social maladjustment, decreased academic and occupational performance and have poorer health than comparable adults. Thus, excessive daytime sleepiness is a serious condition that requires investigation, diagnosis and treatment primarily. As with most medical condition, evaluation of excessive daytime sleepiness begins a precise history and various objective and subjective tools have been also developed to assess excessive daytime sleepiness. The most common causes of excessive daytime sleepiness are insufficient sleep hygiene, chronic sleep deprivation, medical and psychiatric conditions and sleep disorders, such as obstructive sleep apnea, medications, and narcolepsy. Treatment option should address underlying contributors and promote sleep quantity by ensuring good sleep hygiene. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 114-132

  11. Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

    Directory of Open Access Journals (Sweden)

    Jeffrey P. Perley

    2014-11-01

    Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

  12. High-fluoride acitivates the FasL signalling pathway and leads to damage of ameloblast ultrastructure.

    Science.gov (United States)

    Wang, Lin; Zhu, Yong; Wang, Danyang

    2016-11-01

    High fluoride can induce stress-mediated apoptosis and degradation of ameloblasts. Fas ligand (FasL) has been regarded as a key regulator in intracellular responses for stress-induced apoptosis in reproductive or cancerous cell lineages. The objective of this study is to explore the role of FasL in the regulation of ameloblast ultrastructure damage. Primary ameloblasts were isolated from the molar tooth germ of 4-day-old SD rats. The ameloblasts were incubated with 3.2mM NaF or nothing. After incubation for different time arranging from 12h to 72h, ELISA was used to detected the secretion levels of FasL in the medium. Then at 48h post treatment, the ameloblast ultrastructure was detected with Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM), and expression of apoptotic proteins and peroxidative enzymes/products were examined. Finally, a specific FasL inhibitor was applied to co-treat the ameloblasts with NaF, and the ameloblast ultrastructure was detected with TEM and SEM. The secretion of FasL was notably increased by 3.2mM NaF treatment, and the increase reached to the peak after incubation for 48h. High fluoride incubation damaged the ameloblast untrastructure manifesting a series of intracelluar stress responsing cell organelle destruction, and a marked increase in expression of apoptotic genes and oxidative stress. The FasL inhibitor treatment partially mitigated the untrastructure damage caused by high dose NaF. High-fluoride leads to damage of the ameloblast ultrastructure through paritially acitivating the FasL signalling pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation--divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation

    DEFF Research Database (Denmark)

    Sondergaard, B-C; Schultz, N; Madsen, S H

    2010-01-01

    Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase-mediated ......Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase......-mediated cartilage degradation....

  14. Genetics Home Reference: aromatase excess syndrome

    Science.gov (United States)

    ... Ogata T. Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression. ... 2013 Oct 18. Citation on PubMed More from Genetics Home Reference Bulletins Rare Disease Day 2018 Darwin ...

  15. Cerium Dioxide-Mediated Signal "On-Off" by Resonance Energy Transfer on a Lab-On-Paper Device for Ultrasensitive Detection of Lead Ions.

    Science.gov (United States)

    Huang, Yuzhen; Li, Li; Zhang, Yan; Zhang, Lina; Ge, Shenguang; Li, Hao; Yu, Jinghua

    2017-09-27

    In this report, a 3D microfluidic lab-on-paper device for ultrasensitive detection of lead cation was designed using phoenix tree fruit-shaped CeO2 nanoparticles (PFCeO2 NPs) as the catalyst and 50 nm silver NPs (Ag NPs) as the quencher. First, snowflake-like Ag NPs were grown on the paper working electrode through an in situ growth method and used as a matrix for DNAzymes that were specific for lead ions (Pb(2+)). After the addition of Ag NP-labeled substrate strands, the Ag NPs restrained the electrochemiluminescence (ECL) intensity of luminol greatly through the resonance energy transfer from luminol to Ag NPs. However, under the existence of Pb(2+), the substrate strands were separated, and then PFCeO2 NP-labeled signal strands were hybridized with the DNAzymes. The ECL signal was improved greatly under the fast catalytic reaction between PFCeO2 NPs and H2O2, which converted the response from signal off to signal on state, resulting in sensitive detection of Pb(2+). Under the optimal conditions, the ECL signal response exhibited a good linear relationship with the logarithm of lead cation in a wide linear range of 0.05-2000 nM and an ultralow detection limit of 0.016 nM. Meanwhile, a sensor featured with good specificity, acceptable stability, reproducibility, and low cost provides a promising portable, simple, and effective strategy for Pb(2+) detection.

  16. Prevention of excess gain.

    Science.gov (United States)

    Stevens, J; Truesdale, K P; Wang, C-H; Cai, J

    2009-11-01

    Obesity prevention trials are designed to promote healthy weight. The success of these trials is often assessed using one of three metrics--means, incidence or prevalence. In this study, we point out conceptual shortcomings of these metrics and introduce an alternative that we call 'excess gain'. A mathematical demonstration using simulated data shows a scenario in which the statistical power of excess gain compares favorably with that of incidence and prevalence. Prevention of excess gain communicates an easily understood public health message that is applicable to all individuals regardless of weight status.

  17. Signal Processing in Functional Near-Infrared Spectroscopy (fNIRS): Methodological Differences Lead to Different Statistical Results.

    Science.gov (United States)

    Pfeifer, Mischa D; Scholkmann, Felix; Labruyère, Rob

    2017-01-01

    Even though research in the field of functional near-infrared spectroscopy (fNIRS) has been performed for more than 20 years, consensus on signal processing methods is still lacking. A significant knowledge gap exists between established researchers and those entering the field. One major issue regularly observed in publications from researchers new to the field is the failure to consider possible signal contamination by hemodynamic changes unrelated to neurovascular coupling (i.e., scalp blood flow and systemic blood flow). This might be due to the fact that these researchers use the signal processing methods provided by the manufacturers of their measurement device without an advanced understanding of the performed steps. The aim of the present study was to investigate how different signal processing approaches (including and excluding approaches that partially correct for the possible signal contamination) affect the results of a typical functional neuroimaging study performed with fNIRS. In particular, we evaluated one standard signal processing method provided by a commercial company and compared it to three customized approaches. We thereby investigated the influence of the chosen method on the statistical outcome of a clinical data set (task-evoked motor cortex activity). No short-channels were used in the present study and therefore two types of multi-channel corrections based on multiple long-channels were applied. The choice of the signal processing method had a considerable influence on the outcome of the study. While methods that ignored the contamination of the fNIRS signals by task-evoked physiological noise yielded several significant hemodynamic responses over the whole head, the statistical significance of these findings disappeared when accounting for part of the contamination using a multi-channel regression. We conclude that adopting signal processing methods that correct for physiological confounding effects might yield more realistic results

  18. Characterising the 750 GeV diphoton excess

    Energy Technology Data Exchange (ETDEWEB)

    Bernon, Jérémy [Laboratoire de Physique Subatomique et de Cosmologie, Université Grenoble-Alpes, CNRS/IN2P3,53 Avenue des Martyrs, Grenoble, F-38026 (France); Goudelis, Andreas [Institute of High Energy Physics, Austrian Academy of Sciences,Nikolsdorfergasse 18, Vienna, 1050 (Austria); Kraml, Sabine [Laboratoire de Physique Subatomique et de Cosmologie, Université Grenoble-Alpes, CNRS/IN2P3,53 Avenue des Martyrs, Grenoble, F-38026 (France); Mawatari, Kentarou [Laboratoire de Physique Subatomique et de Cosmologie, Université Grenoble-Alpes, CNRS/IN2P3,53 Avenue des Martyrs, Grenoble, F-38026 (France); Theoretische Natuurkunde and IIHE/ELEM, Vrije Universiteit Brussel, and International Solvay Institutes, Pleinlaan 2, Brussels, B-1050 (Belgium); Sengupta, Dipan [Laboratoire de Physique Subatomique et de Cosmologie, Université Grenoble-Alpes, CNRS/IN2P3,53 Avenue des Martyrs, Grenoble, F-38026 (France)

    2016-05-23

    We study kinematic distributions that may help characterise the recently observed excess in diphoton events at 750 GeV at the LHC Run 2. Several scenarios are considered, including spin-0 and spin-2 750 GeV resonances that decay directly into photon pairs as well as heavier parent resonances that undergo three-body or cascade decays. We find that combinations of the distributions of the diphoton system and the leading photon can distinguish the topology and mass spectra of the different scenarios, while patterns of QCD radiation can help differentiate the production mechanisms. Moreover, missing energy is a powerful discriminator for the heavy parent scenarios if they involve (effectively) invisible particles. While our study concentrates on the current excess at 750 GeV, the analysis is general and can also be useful for characterising other potential diphoton signals in the future.

  19. S113R mutation in SLC33A1 leads to neurodegeneration and augmented BMP signaling in a mouse model

    Directory of Open Access Journals (Sweden)

    Pingting Liu

    2017-01-01

    Full Text Available The S113R mutation (c.339T>G (MIM #603690.0001 in SLC33A1 (MIM #603690, an ER membrane acetyl-CoA transporter, has been previously identified in individuals with hereditary spastic paraplegia type 42 (SPG42; MIM #612539. SLC33A1 has also been shown to inhibit the bone morphogenetic protein (BMP signaling pathway in zebrafish. To better understand the function of SLC33A1, we generated and characterized Slc33a1S113R knock-in mice. Homozygous Slc33a1S113R mutant mice were embryonic lethal, whereas heterozygous Slc33a1 mutant mice (Slc33a1wt/mut exhibited behavioral abnormalities and central neurodegeneration, which is consistent with hereditary spastic paraplegia (HSP phenotypes. Importantly, we found an upregulation of BMP signaling in the nervous system and mouse embryonic fibroblasts of Slc33a1wt/mut mice. Using a sciatic nerve crush injury model in vivo and dorsal root ganglion (DRG culture in vitro we showed that injury-induced axonal regeneration in Slc33a1wt/mut mice was accelerated and mediated by upregulated BMP signaling. Exogenous addition of BMP signaling antagonist, noggin, could efficiently alleviate the accelerated injury-induced axonal regrowth. These results indicate that SLC33A1 can negatively regulate BMP signaling in mice, further supporting the notion that upregulation of BMP signaling is a common mechanism of a subset of hereditary spastic paraplegias.

  20. OmpA signal peptide leads to heterogenous secretion of B. subtilis chitosanase enzyme from E. coli expression system.

    Science.gov (United States)

    Pechsrichuang, Phornsiri; Songsiriritthigul, Chomphunuch; Haltrich, Dietmar; Roytrakul, Sittiruk; Namvijtr, Peenida; Bonaparte, Napolean; Yamabhai, Montarop

    2016-01-01

    The production of secreted recombinant proteins from E. coli is pivotal to the biotechnological industry because it reduces the cost of downstream processing. Proteins destined for secretion contain an N-terminal signal peptide that is cleaved by secretion machinery in the plasma membrane. The resulting protein is released in an active mature form. In this study, Bacillus subtilis chitosanase (Csn) was used as a model protein to compare the effect of two signal peptides on the secretion of heterologous recombinant protein. The results showed that the E. coli secretion machinery could recognize both native bacillus and E. coli signal peptides. However, only the native bacillus signal peptide could generate the same N-terminal sequence as in the wild type bacteria. When the recombinant Csn constructs contained the E. coli OmpA signal peptide, the secreted enzymes were heterogeneous, comprising a mixed population of secreted enzymes with different N-terminal sequences. Nevertheless, the E. coli OmpA signal peptide was found to be more efficient for high expression and secretion of bacillus Csn. These findings may be used to help engineer other recombinant proteins for secretory production in E. coli.

  1. Excess wind power

    DEFF Research Database (Denmark)

    Østergaard, Poul Alberg

    2005-01-01

    analyses it is analysed how excess productions are better utilised; through conversion into hydrogen of through expansion of export connections thereby enabling sales. The results demonstrate that particularly hydrogen production is unviable under current costs but transmission expansion could...

  2. Augmented BMPRIA-mediated BMP signaling in cranial neural crest lineage leads to cleft palate formation and delayed tooth differentiation.

    Directory of Open Access Journals (Sweden)

    Lu Li

    Full Text Available The importance of BMP receptor Ia (BMPRIa mediated signaling in the development of craniofacial organs, including the tooth and palate, has been well illuminated in several mouse models of loss of function, and by its mutations associated with juvenile polyposis syndrome and facial defects in humans. In this study, we took a gain-of-function approach to further address the role of BMPR-IA-mediated signaling in the mesenchymal compartment during tooth and palate development. We generated transgenic mice expressing a constitutively active form of BmprIa (caBmprIa in cranial neural crest (CNC cells that contributes to the dental and palatal mesenchyme. Mice bearing enhanced BMPRIa-mediated signaling in CNC cells exhibit complete cleft palate and delayed odontogenic differentiation. We showed that the cleft palate defect in the transgenic animals is attributed to an altered cell proliferation rate in the anterior palatal mesenchyme and to the delayed palatal elevation in the posterior portion associated with ectopic cartilage formation. Despite enhanced activity of BMP signaling in the dental mesenchyme, tooth development and patterning in transgenic mice appeared normal except delayed odontogenic differentiation. These data support the hypothesis that a finely tuned level of BMPRIa-mediated signaling is essential for normal palate and tooth development.

  3. Loss of cytokine-STAT5 signaling in the CNS and pituitary gland alters energy balance and leads to obesity.

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Lee

    Full Text Available Signal transducers and activators of transcription (STATs are critical components of cytokine signaling pathways. STAT5A and STAT5B (STAT5, the most promiscuous members of this family, are highly expressed in specific populations of hypothalamic neurons in regions known to mediate the actions of cytokines in the regulation of energy balance. To test the hypothesis that STAT5 signaling is essential to energy homeostasis, we used Cre-mediated recombination to delete the Stat5 locus in the CNS. Mutant males and females developed severe obesity with hyperphagia, impaired thermal regulation in response to cold, hyperleptinemia and insulin resistance. Furthermore, central administration of GM-CSF mediated the nuclear accumulation of STAT5 in hypothalamic neurons and reduced food intake in control but not in mutant mice. These results demonstrate that STAT5 mediates energy homeostasis in response to endogenous cytokines such as GM-CSF.

  4. Integral Characterization of Defective BDNF/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies

    Science.gov (United States)

    Tejeda, Gonzalo S.; Díaz-Guerra, Margarita

    2017-01-01

    Enhancement of brain-derived neurotrophic factor (BDNF) signalling has great potential in therapy for neurological and psychiatric disorders. This neurotrophin not only attenuates cell death but also promotes neuronal plasticity and function. However, an important challenge to this approach is the persistence of aberrant neurotrophic signalling due to a defective function of the BDNF high-affinity receptor, tropomyosin-related kinase B (TrkB), or downstream effectors. Such changes have been already described in several disorders, but their importance as pathological mechanisms has been frequently underestimated. This review highlights the relevance of an integrative characterization of aberrant BDNF/TrkB pathways for the rational design of therapies that by combining BDNF and TrkB targets could efficiently promote neurotrophic signalling. PMID:28134845

  5. S113R mutation in SLC33A1 leads to neurodegeneration and augmented BMP signaling in a mouse model.

    Science.gov (United States)

    Liu, Pingting; Jiang, Baichun; Ma, Jian; Lin, Pengfei; Zhang, Yinshuai; Shao, Changshun; Sun, Wenjie; Gong, Yaoqin

    2017-01-01

    The S113R mutation (c.339T>G) (MIM #603690.0001) in SLC33A1 (MIM #603690), an ER membrane acetyl-CoA transporter, has been previously identified in individuals with hereditary spastic paraplegia type 42 (SPG42; MIM #612539). SLC33A1 has also been shown to inhibit the bone morphogenetic protein (BMP) signaling pathway in zebrafish. To better understand the function of SLC33A1, we generated and characterized Slc33a1(S113R) knock-in mice. Homozygous Slc33a1(S113R) mutant mice were embryonic lethal, whereas heterozygous Slc33a1 mutant mice (Slc33a1(wt/mut)) exhibited behavioral abnormalities and central neurodegeneration, which is consistent with hereditary spastic paraplegia (HSP) phenotypes. Importantly, we found an upregulation of BMP signaling in the nervous system and mouse embryonic fibroblasts of Slc33a1(wt/mut) mice. Using a sciatic nerve crush injury model in vivo and dorsal root ganglion (DRG) culture in vitro we showed that injury-induced axonal regeneration in Slc33a1(wt/mut) mice was accelerated and mediated by upregulated BMP signaling. Exogenous addition of BMP signaling antagonist, noggin, could efficiently alleviate the accelerated injury-induced axonal regrowth. These results indicate that SLC33A1 can negatively regulate BMP signaling in mice, further supporting the notion that upregulation of BMP signaling is a common mechanism of a subset of hereditary spastic paraplegias. © 2017. Published by The Company of Biologists Ltd.

  6. 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

  7. The Influence of Lead on Generation of Signalling Molecules and Accumulation of Flavonoids in Pea Seedlings in Response to Pea Aphid Infestation

    Directory of Open Access Journals (Sweden)

    Agnieszka Woźniak

    2017-08-01

    Full Text Available The aim of this study was to investigate the effect of an abiotic factor, i.e., lead at various concentrations (low causing a hormesis effect and causing high toxicity effects, on the generation of signalling molecules in pea (Pisum sativum L. cv. Cysterski seedlings and then during infestation by the pea aphid (Acyrthosiphon pisum Harris. The second objective was to verify whether the presence of lead in pea seedling organs and induction of signalling pathways dependent on the concentration of this metal trigger defense responses to A. pisum. Therefore, the profile of flavonoids and expression levels of genes encoding enzymes of the flavonoid biosynthesis pathway (phenylalanine ammonialyase and chalcone synthase were determined. A significant accumulation of total salicylic acid (TSA and abscisic acid (ABA was recorded in the roots and leaves of pea seedlings growing on lead-supplemented medium and next during infestation by aphids. Increased generation of these phytohormones strongly enhanced the biosynthesis of flavonoids, including a phytoalexin, pisatin. This research provides insights into the cross-talk between the abiotic (lead and biotic factor (aphid infestation on the level of the generation of signalling molecules and their role in the induction of flavonoid biosynthesis.

  8. The root hair assay facilitates the use of genetic and pharmacological tools in order to dissect multiple signalling pathways that lead to programmed cell death.

    Directory of Open Access Journals (Sweden)

    Joanna Kacprzyk

    Full Text Available The activation of programmed cell death (PCD is often a result of complex signalling pathways whose relationship and intersection are not well understood. We recently described a PCD root hair assay and proposed that it could be used to rapidly screen genetic or pharmacological modulators of PCD. To further assess the applicability of the root hair assay for studying multiple signalling pathways leading to PCD activation we have investigated the crosstalk between salicylic acid, autophagy and apoptosis-like PCD (AL-PCD in Arabidopsis thaliana. The root hair assay was used to determine rates of AL-PCD induced by a panel of cell death inducing treatments in wild type plants treated with chemical modulators of salicylic acid synthesis or autophagy, and in genetic lines defective in autophagy or salicylic acid signalling. The assay demonstrated that PCD induced by exogenous salicylic acid or fumonisin B1 displayed a requirement for salicylic acid signalling and was partially dependent on the salicylic acid signal transducer NPR1. Autophagy deficiency resulted in an increase in the rates of AL-PCD induced by salicylic acid and fumonisin B1, but not by gibberellic acid or abiotic stress. The phenylalanine ammonia lyase-dependent salicylic acid synthesis pathway contributed only to death induced by salicylic acid and fumonisin B1. 3-Methyladenine, which is commonly used as an inhibitor of autophagy, appeared to influence PCD induction in all treatments suggesting a possible secondary, non-autophagic, effect on a core component of the plant PCD pathway. The results suggest that salicylic acid signalling is negatively regulated by autophagy during salicylic acid and mycotoxin-induced AL-PCD. However, this crosstalk does not appear to be directly involved in PCD induced by gibberellic acid or abiotic stress. This study demonstrates that the root hair assay is an effective tool for relatively rapid investigation of complex signalling pathways leading to

  9. Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered growth factor signalling.

    Science.gov (United States)

    Hanson, D; Murray, P G; Coulson, T; Sud, A; Omokanye, A; Stratta, E; Sakhinia, F; Bonshek, C; Wilson, L C; Wakeling, E; Temtamy, S A; Aglan, M; Rosser, E M; Mansour, S; Carcavilla, A; Nampoothiri, S; Khan, W I; Banerjee, I; Chandler, K E; Black, G C M; Clayton, P E

    2012-12-01

    3-M syndrome is a primordial growth disorder caused by mutations in CUL7, OBSL1 or CCDC8. 3-M patients typically have a modest response to GH treatment, but the mechanism is unknown. Our aim was to screen 13 clinically identified 3-M families for mutations, define the status of the GH-IGF axis in 3-M children and using fibroblast cell lines assess signalling responses to GH or IGF1. Eleven CUL7, three OBSL1 and one CCDC8 mutations in nine, three and one families respectively were identified, those with CUL7 mutations being significantly shorter than those with OBSL1 or CCDC8 mutations. The majority of 3-M patients tested had normal peak serum GH and normal/low IGF1. While the generation of IGF binding proteins by 3-M cells was dysregulated, activation of STAT5b and MAPK in response to GH was normal in CUL7(-/-) cells but reduced in OBSL1(-/-) and CCDC8(-/-) cells compared with controls. Activation of AKT to IGF1 was reduced in CUL7(-/-) and OBSL1(-/-) cells at 5 min post-stimulation but normal in CCDC8(-/-) cells. The prevalence of 3-M mutations was 69% CUL7, 23% OBSL1 and 8% CCDC8. The GH-IGF axis evaluation could reflect a degree of GH resistance and/or IGF1 resistance. This is consistent with the signalling data in which the CUL7(-/-) cells showed impaired IGF1 signalling, CCDC8(-/-) cells showed impaired GH signalling and the OBSL1(-/-) cells showed impairment in both pathways. Dysregulation of the GH-IGF-IGF binding protein axis is a feature of 3-M syndrome.

  10. Genetic deletion of Rnd3 results in aqueductal stenosis leading to hydrocephalus through up-regulation of Notch signaling.

    Science.gov (United States)

    Lin, Xi; Liu, Baohui; Yang, Xiangsheng; Yue, Xiaojing; Diao, Lixia; Wang, Jing; Chang, Jiang

    2013-05-14

    Rho family guanosine triphosphatase (GTPase) 3 (Rnd3), a member of the small Rho GTPase family, is involved in the regulation of cell actin cytoskeleton dynamics, cell migration, and proliferation through the Rho kinase-dependent signaling pathway. We report a role of Rnd3 in the pathogenesis of hydrocephalus disorder. Mice with Rnd3 genetic deletion developed severe obstructive hydrocephalus with enlargement of the lateral and third ventricles, but not of the fourth ventricles. The cerebral aqueducts in Rnd3-null mice were partially or completely blocked by the overgrowth of ependymal epithelia. We examined the molecular mechanism contributing to this Rnd3-deficiency-mediated hydrocephalus and found that Rnd3 is a regulator of Notch signaling. Rnd3 deficiency, through either gene deletion or siRNA knockdown, resulted in a decrease in Notch intracellular domain (NICD) protein degradation. However, there was no correlated change in mRNA change, which in turn led to an increase in NICD protein levels. Immunoprecipitation analysis demonstrated that Rnd3 and NICD physically interacted, and that down-regulation of Rnd3 attenuated NICD protein ubiquitination. This eventually enhanced Notch signaling activity and promoted aberrant growth of aqueduct ependymal cells, resulting in aqueduct stenosis and the development of congenital hydrocephalus. Inhibition of Notch activity rescued the hydrocephalus disorder in the mutant animals.

  11. Mitogen-activated protein kinase signaling and its association with oxidative stress and apoptosis in lead-exposed hepatocytes.

    Science.gov (United States)

    Mujaibel, Latifah M; Kilarkaje, Narayana

    2015-05-01

    Lead toxicity has become a serious public health concern all over the world. Previous studies have shown that lead induces biochemical and structural changes in liver. However, although lead is known to alter liver functions, the underlying molecular mechanisms of hepatotoxicity are not yet clear. We hypothesized that a correlation exists between oxidative stress, apoptosis and mitogen-activated protein kinases (MAPKs) in lead-exposed liver. Wistar rats were treated with 0, 0.5%, and 1% lead acetate for 3d, 14d, and 35d and sacrificed the next day. On 4d, oxidative stress and apoptosis were correlated with downregulated expressions of ERK1/2 and p38-MAPKα/β, and upregulated expressions of JNK1/3 in males. In females, the correlation was with downregulated expressions of ERK1/2 and upregulated expressions of p38-MAPKα/β and JNK1/3. On 15d, the correlation was observed with upregulated expressions of p38-MAPKα/β in males and downregulated expressions of p38-MAPKα/β in females. In both sexes, a correlation was observed with upregulated expressions of ERK1/2 and JNK1/3 in 1% groups. On 36d, the correlation was observed with downregulated expressions of p38-MAPKα/β in males and their upregulated expressions in females. Time-dependent increase in lipid peroxidation on 15d and 36d correlated with upregulated expressions of p38-MAPKα/β in females and ERK1/2 in 1% groups in both sexes. The lower dose induced more apoptosis up to 15d in females and the higher dose induced in males on 36d. Generally, the female livers had more p38-MAPKα/β than the male livers. On 36d, the female livers showed more p38-MAPKα/β and JNK1/3 than the male livers. In conclusion, although not clearly defined, a correlation exists among oxidative stress, apoptosis, and the MAPKs in lead-exposed hepatocytes. The sex-dependent effects may be due to differences in hormonal or other physiological mechanisms. In lead-exposed hepatocytes, the apoptosis may be induced via oxidative stress

  12. Excessive Testing and Pupils in the Public Schools

    Science.gov (United States)

    Ediger, Marlow

    2017-01-01

    This article explores the question of excessive testing in public schools, its value in the educational process, and the impact that excessive testing may have on the student and the family unit. While assessments are valuable when used properly, excessive testing may lead to problems with unforeseen consequences.

  13. Reducing Excessive Television Viewing.

    Science.gov (United States)

    Jason, Leonard A.; Rooney-Rebeck, Patty

    1984-01-01

    A youngster who excessively watched television was placed on a modified token economy: earned tokens were used to activate the television for set periods of time. Positive effects resulted in the child's school work, in the amount of time his family spent together, and in his mother's perception of family social support. (KH)

  14. HIV Excess Cancers JNCI

    Science.gov (United States)

    In 2010, an estimated 7,760 new cancers were diagnosed among the nearly 900,000 Americans known to be living with HIV infection. According to the first comprehensive study in the United States, approximately half of these cancers were in excess of what wo

  15. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  16. Oxidative stress-induced JNK1/2 activation triggers proapoptotic signaling and apoptosis that leads to diabetic embryopathy.

    Science.gov (United States)

    Li, Xuezheng; Weng, Hongbo; Xu, Cheng; Reece, E Albert; Yang, Peixin

    2012-08-01

    Oxidative stress and apoptosis are implicated in the pathogenesis of diabetic embryopathy. The proapoptotic c-Jun NH(2)-terminal kinases (JNK)1/2 activation is associated with diabetic embryopathy. We sought to determine whether 1) hyperglycemia-induced oxidative stress is responsible for the activation of JNK1/2 signaling, 2) JNK1 contributes to the teratogenicity of hyperglycemia, and 3) both JNK1 and JNK2 activation cause activation of downstream transcription factors, caspase activation, and apoptosis, resulting in neural tube defects (NTDs). Wild-type (WT) embryos from nondiabetic WT dams and WT, superoxide dismutase (SOD)1-overexpressing, jnk1(+/-), jnk1(-/-), and jnk2(-/-) embryos exposed to maternal hyperglycemia were used to assess JNK1/2 activation, NTDs, activation of transcription factors downstream of JNK1/2, caspase cascade, and apoptosis. SOD1 overexpression abolished diabetes-induced activation of JNK1/2 and their downstream effectors: phosphorylation of c-Jun, activating transcription factor 2, and E twenty-six-like transcription factor 1 and dephosphorylation of forkhead box class O3a. jnk1(-/-) embryos had significantly lower incidences of NTDs than those of WT or jnk1(+/-) embryos. Either jnk1 or jnk2 gene deletion blocked diabetes-induced activation of JNK1/2 signaling, caspases 3 and 8, and apoptosis in Sox1(+) neural progenitors of the developing neural tube. Our results show that JNK1 and JNK2 are equally involved in diabetic embryopathy and that the oxidative stress-JNK1/2-caspase pathway mediates the proapoptotic signals and the teratogenicity of maternal diabetes.

  17. Blockade of Notch Signaling in Tumor-Bearing Mice May Lead to Tumor Regression, Progression, or Metastasis, Depending on Tumor Cell Types

    Directory of Open Access Journals (Sweden)

    Xing-Bin Hu

    2009-01-01

    Full Text Available It has been reported that blocking Notch signaling in tumor-bearing mice results in abortive angiogenesis and tumor regression. However, given that Notch signaling influences numerous cellular processes in vivo, a comprehensive evaluation of the effect of Notch inactivation on tumor growth would be favorable. In this study, we inoculated four cancer cell lines in mice with the conditional inactivation of recombination signal-binding protein-Jκ (RBP-J, which mediates signaling from all four mammalian Notch receptors. We found that whereas three tumors including hepatocarcinoma, lung cancer, and osteogenic sarcoma grew slower in the RBP-J-deficient mice, at least a melanoma, B16, grew significantly faster in the RBP-J-deficient mice than in the controls, suggesting that the RBP-J-deficient hosts could provide permissive cues for tumor growth. All these tumors showed increased microvessels and up-regulated hypoxia-inducible factor 1α, suggesting that whereas defective angiogenesis resulted in hypoxia, different tumors might grow differentially in the RBP-J-deleted mice. Similarly, increased infiltration of Gr1+/Mac1+ cells were noticed in tumors grown in the RBP-J-inactivated mice. Moreover, we found that when inoculated in the RBP-J knockout hosts, the H22 hepatoma cells had a high frequency of metastasis and lethality, suggesting that at least for H22, deficiency of environmental Notch signaling favored tumor metastasis. Our findings suggested that the general blockade of Notch signaling in tumor-bearing mice could lead to defective angiogenesis in tumors, but depending on tumor cell types, general inhibition of Notch signaling might result in tumor regression, progression, or metastasis.

  18. A Saccharomyces cerevisiae assay system to investigate ligand/AdipoR1 interactions that lead to cellular signaling.

    Directory of Open Access Journals (Sweden)

    Mustapha Aouida

    Full Text Available Adiponectin is a mammalian hormone that exerts anti-diabetic, anti-cancer and cardioprotective effects through interaction with its major ubiquitously expressed plasma membrane localized receptors, AdipoR1 and AdipoR2. Here, we report a Saccharomyces cerevisiae based method for investigating agonist-AdipoR interactions that is amenable for high-throughput scale-up and can be used to study both AdipoRs separately. Agonist-AdipoR1 interactions are detected using a split firefly luciferase assay based on reconstitution of firefly luciferase (Luc activity due to juxtaposition of its N- and C-terminal fragments, NLuc and CLuc, by ligand induced interaction of the chimeric proteins CLuc-AdipoR1 and APPL1-NLuc (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif 1-NLuc in a S. cerevisiae strain lacking the yeast homolog of AdipoRs (Izh2p. The assay monitors the earliest known step in the adiponectin-AdipoR anti-diabetic signaling cascade. We demonstrate that reconstituted Luc activity can be detected in colonies or cells using a CCD camera and quantified in cell suspensions using a microplate reader. AdipoR1-APPL1 interaction occurs in absence of ligand but can be stimulated specifically by agonists such as adiponectin and the tobacco protein osmotin that was shown to have AdipoR-dependent adiponectin-like biological activity in mammalian cells. To further validate this assay, we have modeled the three dimensional structures of receptor-ligand complexes of membrane-embedded AdipoR1 with cyclic peptides derived from osmotin or osmotin-like plant proteins. We demonstrate that the calculated AdipoR1-peptide binding energies correlate with the peptides' ability to behave as AdipoR1 agonists in the split luciferase assay. Further, we demonstrate agonist-AdipoR dependent activation of protein kinase A (PKA signaling and AMP activated protein kinase (AMPK phosphorylation in S. cerevisiae, which are

  19. A Saccharomyces cerevisiae Assay System to Investigate Ligand/AdipoR1 Interactions That Lead to Cellular Signaling

    KAUST Repository

    Aouida, Mustapha

    2013-06-07

    Adiponectin is a mammalian hormone that exerts anti-diabetic, anti-cancer and cardioprotective effects through interaction with its major ubiquitously expressed plasma membrane localized receptors, AdipoR1 and AdipoR2. Here, we report a Saccharomyces cerevisiae based method for investigating agonist-AdipoR interactions that is amenable for high-throughput scale-up and can be used to study both AdipoRs separately. Agonist-AdipoR1 interactions are detected using a split firefly luciferase assay based on reconstitution of firefly luciferase (Luc) activity due to juxtaposition of its N- and C-terminal fragments, NLuc and CLuc, by ligand induced interaction of the chimeric proteins CLuc-AdipoR1 and APPL1-NLuc (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and leucine zipper motif 1-NLuc) in a S. cerevisiae strain lacking the yeast homolog of AdipoRs (Izh2p). The assay monitors the earliest known step in the adiponectin-AdipoR anti-diabetic signaling cascade. We demonstrate that reconstituted Luc activity can be detected in colonies or cells using a CCD camera and quantified in cell suspensions using a microplate reader. AdipoR1-APPL1 interaction occurs in absence of ligand but can be stimulated specifically by agonists such as adiponectin and the tobacco protein osmotin that was shown to have AdipoR-dependent adiponectin-like biological activity in mammalian cells. To further validate this assay, we have modeled the three dimensional structures of receptor-ligand complexes of membrane-embedded AdipoR1 with cyclic peptides derived from osmotin or osmotin-like plant proteins. We demonstrate that the calculated AdipoR1-peptide binding energies correlate with the peptides\\' ability to behave as AdipoR1 agonists in the split luciferase assay. Further, we demonstrate agonist-AdipoR dependent activation of protein kinase A (PKA) signaling and AMP activated protein kinase (AMPK) phosphorylation in S. cerevisiae, which are homologous to

  20. The otherness of sexuality: excess.

    Science.gov (United States)

    Stein, Ruth

    2008-03-01

    The present essay, the second of a series of three, aims at developing an experience-near account of sexuality by rehabilitating the idea of excess and its place in sexual experience. It is suggested that various types of excess, such as excess of excitation (Freud), the excess of the other (Laplanche), excess beyond symbolization and the excess of the forbidden object of desire (Leviticus; Lacan) work synergistically to constitute the compelling power of sexuality. In addition to these notions, further notions of excess touch on its transformative potential. Such notions address excess that shatters psychic structures and that is actively sought so as to enable new ones to evolve (Bersani). Work is quoted that regards excess as a way of dealing with our lonely, discontinuous being by using the "excessive" cosmic energy circulating through us to achieve continuity against death (Bataille). Two contemporary analytic thinkers are engaged who deal with the object-relational and intersubjective vicissitudes of excess.

  1. Expression of oncogenic K-ras from its endogenous promoter leads to a partial block of erythroid differentiation and hyperactivation of cytokine-dependent signaling pathways.

    Science.gov (United States)

    Zhang, Jing; Liu, Yangang; Beard, Caroline; Tuveson, David A; Jaenisch, Rudolf; Jacks, Tyler E; Lodish, Harvey F

    2007-06-15

    When overexpressed in primary erythroid progenitors, oncogenic Ras leads to the constitutive activation of its downstream signaling pathways, severe block of terminal erythroid differentiation, and cytokine-independent growth of primary erythroid progenitors. However, whether high-level expression of oncogenic Ras is required for these phenotypes is unknown. To address this issue, we expressed oncogenic K-ras (K-ras(G12D)) from its endogenous promoter using a tetracycline-inducible system. We show that endogenous K-ras(G12D) leads to a partial block of terminal erythroid differentiation in vivo. In contrast to results obtained when oncogenic Ras was overexpressed from retroviral vectors, endogenous levels of K-ras(G12D) fail to constitutively activate but rather hyperactivate cytokine-dependent signaling pathways, including Stat5, Akt, and p44/42 MAPK, in primary erythroid progenitors. This explains previous observations that hematopoietic progenitors expressing endogenous K-ras(G12D) display hypersensitivity to cytokine stimulation in various colony assays. Our results support efforts to modulate Ras signaling for treating hematopoietic malignancies.

  2. Excessive crying in infants

    Directory of Open Access Journals (Sweden)

    Ricardo Halpern

    2016-05-01

    Conclusion: Excessive crying in the early months is a prevalent symptom; the pediatrician's attention is necessary to understand and adequately manage the problem and offer support to exhausted parents. The prescription of drugs of questionable action and with potential side effects is not a recommended treatment, except in extreme situations. The effectiveness of dietary treatments and use of probiotics still require confirmation. There is incomplete evidence regarding alternative treatments such as manipulation techniques, acupuncture, and use of the herbal supplements and behavioral interventions.

  3. Defective ALK5 signaling in the neural crest leads to increased postmigratory neural crest cell apoptosis and severe outflow tract defects

    Directory of Open Access Journals (Sweden)

    Sucov Henry M

    2006-11-01

    Full Text Available Abstract Background Congenital cardiovascular diseases are the most common form of birth defects in humans. A substantial portion of these defects has been associated with inappropriate induction, migration, differentiation and patterning of pluripotent cardiac neural crest stem cells. While TGF-β-superfamily signaling has been strongly implicated in neural crest cell development, the detailed molecular signaling mechanisms in vivo are still poorly understood. Results We deleted the TGF-β type I receptor Alk5 specifically in the mouse neural crest cell lineage. Failure in signaling via ALK5 leads to severe cardiovascular and pharyngeal defects, including inappropriate remodeling of pharyngeal arch arteries, abnormal aortic sac development, failure in pharyngeal organ migration and persistent truncus arteriosus. While ALK5 is not required for neural crest cell migration, our results demonstrate that it plays an important role in the survival of post-migratory cardiac neural crest cells. Conclusion Our results demonstrate that ALK5-mediated signaling in neural crest cells plays an essential cell-autonomous role in the pharyngeal and cardiac outflow tract development.

  4. ACTIVATION PARAMETERS AND EXCESS THERMODYANAMIC ...

    African Journals Online (AJOL)

    Applying these data, viscosity-B-coefficients, activation parameters (Δμ10≠) and (Δμ20≠) and excess thermodynamic functions, viz., excess molar volume (VE), excess viscosity, ηE and excess molar free energy of activation of flow, (GE) were calculated. The value of interaction parameter, d, of Grunberg and Nissan ...

  5. Age-Related Changes in Insulin-like Signaling Lead to Intermediate-Term Memory Impairment in Drosophila.

    Science.gov (United States)

    Tanabe, Kento; Itoh, Motoyuki; Tonoki, Ayako

    2017-02-14

    Insulin and insulin-growth-factor-like signaling (IIS) plays important roles in the regulation of development, growth, metabolic homeostasis, and aging, as well as in brain functions such as learning and memory. The temporal-spatial role of IIS in learning and memory and its effect on age-dependent memory impairment remain unclear. Here, we report that intermediate-term memory (ITM), but not short-term memory (STM), in Drosophila aversive olfactory memory requires transient IIS during adulthood. The expression of Drosophila insulin-like peptide 3 (Dilp3) in insulin-producing cells and insulin receptor function in the fat body are essential for ITM. Although the expression of dilp3 decreases with aging, which is unique among dilp genes, the transient expression of dilp3 in aged flies enhances ITM. These findings indicate that ITM is systemically regulated by communication between insulin-producing cells and fat body and that age-dependent changes in IIS contribute to age-related memory impairment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction : [Langfassung

    OpenAIRE

    Stürmer, Claudia; Langhorst, Matthias F.; Wiechers, Marianne F.; Legler, Daniel F.; Hannbeck von Hanwehr, Sylvia; Guse, Andreas H.; Plattner, Helmut

    2004-01-01

    The cellular prion protein (PrPc) resides in lipid rafts, yet the type of raft and the physiological function of PrPc are unclear. We show here that cross-linking of PrPc with specific antibodies leads to 1) PrPc capping in Jurkat and human peripheral blood T cells; 2) to cocapping with the intracellular lipid raft proteins reggie-1 and reggie-2; 3) to signal transduction as seen by MAP kinase phosphorylation and an elevation of the intracellular Ca2+ concentration; 4) to the recruitment of T...

  7. An optimized lead system for long-term esophageal electrocardiography.

    Science.gov (United States)

    Niederhauser, T; Haeberlin, A; Marisa, T; Mattle, D; Abächerli, R; Goette, J; Jacomet, M; Vogel, R

    2014-04-01

    Long-term electrocardiography (ECG) featuring adequate atrial and ventricular signal quality is highly desirable. Routinely used surface leads are limited in atrial signal sensitivity and recording capability impeding complete ECG delineation, i.e. in the presence of supraventricular arrhythmias. Long-term esophageal ECG might overcome these limitations but requires a dedicated lead system and recorder design. To this end, we analysed multiple-lead esophageal ECGs with respect to signal quality by describing the ECG waves as a function of the insertion level, interelectrode distance, electrode shape and amplifier's input range. The results derived from clinical data show that two bipolar esophageal leads, an atrial lead with short (15 mm) interelectrode distance and a ventricular lead with long (80 mm) interelectrode distance provide non-inferior ventricular signal strength and superior atrial signal strength compared to standard surface lead II. High atrial signal slope in particular is observed with the atrial esophageal lead. The proposed esophageal lead system in combination with an increased recorder input range of ±20 mV minimizes signal loss due to excessive electrode motion typically observed in esophageal ECGs. The design proposal might help to standardize long-term esophageal ECG registrations and facilitate novel ECG classification systems based on the independent detection of ventricular and atrial electrical activity.

  8. Glucocorticoids decrease the bioavailability of TGF-beta which leads to a reduced TGF-beta signaling in hepatic stellate cells.

    Science.gov (United States)

    Bolkenius, Ursula; Hahn, Daniela; Gressner, Axel M; Breitkopf, Katja; Dooley, Steven; Wickert, Lucia

    2004-12-24

    Glucocorticoids bound to their receptors transmit information, which regulates numerous physiological and pathophysiological responses, amongst others glucose metabolism, wound healing, inflammation, and stress, either directly as transcription factors by binding DNA elements of target genes or indirectly by protein-protein interactions with other transcription factors. TGF-beta, a key factor in activation of hepatic stellate cells (HSC), induces production of extracellular matrix, this being a prerequisite for the development of liver fibrosis. Glucocorticoids and their receptors may provide a crosstalk with the TGF-beta-Smad signaling pathway by antagonizing TGF-beta effects. We studied the influence of glucocorticoids on the TGF-beta isoform and Smad mRNA expression, TGF-beta secretion, and signaling in activated HSC using gene-specific real-time PCR, ELISA, and transfection techniques. Dexamethasone treatment reduces TGF-beta mRNA transcription in a time-dependent manner. Activated HSC produce TGF-beta and secrete it into the cell culture medium. After dexamethasone treatment, TGF-beta secretion into the medium is reduced dose-dependently but restorable by mifepristone. Further, we found that reduced secretion of endogenous TGF-beta is accompanied by a reduced TGF-beta signal. Additionally, reporter gene analysis after adenoviral infection with a recombinant virus encoding a Smad-binding-element showed that TGF-beta-Smad signaling is significantly down-regulated by dexamethasone in primary HSC and CFSC, a HSC related cell line. Our data suggest that glucocorticoids inhibit TGF-beta expression, prevent TGF-beta from efficient secretion, and finally lead to reduced TGF-beta signaling in primary HSC.

  9. PrPc capping in T cells promotes its association with the lipid raft proteins reggie-1 and reggie-2 and leads to signal transduction.

    Science.gov (United States)

    Stuermer, Claudia A O; Langhorst, Matthias F; Wiechers, Marianne F; Legler, Daniel F; Von Hanwehr, Sylvia Hannbeck; Guse, Andreas H; Plattner, Helmut

    2004-11-01

    The cellular prion protein (PrPc) resides in lipid rafts, yet the type of raft and the physiological function of PrPc are unclear. We show here that cross-linking of PrPc with specific antibodies leads to 1) PrPc capping in Jurkat and human peripheral blood T cells; 2) to cocapping with the intracellular lipid raft proteins reggie-1 and reggie-2; 3) to signal transduction as seen by MAP kinase phosphorylation and an elevation of the intracellular Ca2+ concentration; 4) to the recruitment of Thy-1, TCR/CD3, fyn, lck and LAT into the cap along with local tyrosine phosphorylation and F-actin polymerization, and later, internalization of PrPc together with the reggies into limp-2 positive lysosomes. Thus, PrPc association with reggie rafts triggers distinct transmembrane signal transduction events in T cells that promote the focal concentration of PrPc itself by guiding activated PrPc into preformed reggie caps and then to the recruitment of important interacting signaling molecules.

  10. Protein kinase C delta localizes to secretory lysosomes in CD8+ CTL and directly mediates TCR signals leading to granule exocytosis-mediated cytotoxicity.

    Science.gov (United States)

    Ma, Jennifer S Y; Haydar, Tarik F; Radoja, Sasa

    2008-10-01

    Lytic granule exocytosis is the major effector function used by CD8(+) CTL in response to intracellular pathogens and tumors. Despite recent progress in the field, two important aspects of this cytotoxic mechanism remain poorly understood. First, TCR-signaling pathway(s) that selectively induces granule exocytosis in CTL has not been defined to date. Second, it is unclear how Ag receptor-induced signals are converted into mobilization of lytic granules. We recently demonstrated that protein kinase C delta (PKC delta) selectively regulates TCR-induced lytic granule polarization in mouse CD8(+) CTL. To better understand how PKC delta facilitates granule movement, here we studied dynamics of intracellular localization of PKC delta in living CD8(+) CTL. Strikingly, we found that PKC delta localizes to the secretory lysosomes and polarizes toward immunological synapse during the process of target cell killing. Also, biochemical and structure-function studies demonstrated that upon TCR ligation, PKC delta becomes rapidly phosphorylated on the activation loop and regulates granule exocytosis in a kinase-dependent manner. Altogether, our current studies provide new insights concerning the regulation of TCR-induced lytic granule exocytosis by revealing novel intracellular localization of PKC delta, providing the first example of colocalization of a kinase with secretory lysosomes in CD8(+) CTL and demonstrating that PKC delta directly transduces TCR signals leading to polarized granule secretion.

  11. Excessive Positivism in Person-Centered Planning

    Science.gov (United States)

    Holburn, Steve; Cea, Christine D.

    2007-01-01

    This paper illustrates the positivistic nature of person-centered planning (PCP) that is evident in the planning methods employed, the way that individuals with disabilities are described, and in portrayal of the outcomes of PCP. However, a confluence of factors can lead to manifestation of excessive positivism that does not serve PCP…

  12. Topiramate Induced Excessive Sialorrhea

    Directory of Open Access Journals (Sweden)

    Ersel Dag

    2015-11-01

    Full Text Available It is well-known that drugs such as clozapine and lithium can cause sialorrhea. On the other hand, topiramate has not been reported to induce sialorrhea. We report a case of a patient aged 26 who was given antiepileptic and antipsychotic drugs due to severe mental retardation and intractable epilepsy and developed excessive sialorrhea complaint after the addition of topiramate for the control of seizures. His complaints continued for 1,5 years and ended after giving up topiramate. We presented this case since it was a rare sialorrhea case induced by topiramate. Clinicians should be aware of the possibility of sialorrhea development which causes serious hygiene and social problems when they want to give topiramate to the patients using multiple drugs.

  13. Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

    Science.gov (United States)

    Mauro, Claudio; Smith, Joanne; Cucchi, Danilo; Coe, David; Fu, Hongmei; Bonacina, Fabrizia; Baragetti, Andrea; Cermenati, Gaia; Caruso, Donatella; Mitro, Nico; Catapano, Alberico L; Ammirati, Enrico; Longhi, Maria P; Okkenhaug, Klaus; Norata, Giuseppe D; Marelli-Berg, Federica M

    2017-03-07

    Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4 + T cells. Memory CD4 + T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts. This was due to biased CD4 + T cell differentiation into CD44 hi -CCR7 lo -CD62L lo -CXCR3 + -LFA1 + effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observed in obese subjects in a cohort of free-living people. This developmental bias was independent of any crosstalk between CD4 + T cells and dendritic cells and was mediated via direct exposure of CD4 + T cells to palmitate, leading to increased activation of a PI3K p110δ-Akt-dependent pathway upon priming. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  14. Episodic Excessive Blinking in Children.

    Science.gov (United States)

    Mali, Yasmin Poustchi; Simon, John W; Chaudhri, Imran; Zobal-Ratner, Jitka; Barry, Gerard P

    2016-01-01

    Many children present with excessive blinking. Categorization, associated conditions, and prognosis are controversial. All children with excessive blinking were reviewed, excluding those with known uveitis, glaucoma, or obvious eyelid abnormalities. Parents were telephoned for follow-up. No ocular pathology was identified in 31 of 34 children with excessive blinking (91%). Parents were able to report a specific cause of blinking in 7 (21%). In 24 of 34 (71%), parents reported complete resolution of excessive blinking. No new ophthalmologic diagnoses were uncovered on follow-up. Episodes of excessive blinking rarely indicate neurologic disorders and frequently resolve spontaneously. Copyright 2016, SLACK Incorporated.

  15. Carrying-over effects of GVBD blocking on post-blocking meiotic progression of oocytes: species difference and the signaling pathway leading to MPF activation.

    Directory of Open Access Journals (Sweden)

    Guang-Zhong Jiao

    Full Text Available Efforts to improve the quality of in vitro matured oocytes by blocking germinal vesicle breakdown (GVBD and allowing more time for ooplasmic maturation have achieved little due to a lack of knowledge on the molecular events during GVBD blocking. Such knowledge is also important for studies aimed at regulating gene expression in maturing oocytes prior to GVBD. We studied species difference and signaling pathways leading to the carrying-over effect of GVBD blocking on post-blocking meiotic progression (PBMP. Overall, GVBD-blocking with roscovitine decelerated PBMP of mouse oocytes but accelerated that of pig oocytes. During blocking culture, whereas cyclin B of pig oocytes increased continuously, that of mouse oocytes declined first and then increased slowly. In both species, (a whereas active CDC2A showed a dynamics similar to cyclin B, inactive CDC2A decreased continuously; (b when oocytes were blocked in blocking medium containing cycloheximide, PBMP was decelerated significantly while cyclin B and active CDC2A decreasing to the lowest level; (c whereas sodium vanadate in blocking medium reduced PBMP, epidermal growth factor (EGF in blocking medium accelerated PBMP significantly with no effect on cyclin B levels. In conclusion, the EGF signaling cascade accelerated PBMP by promoting the pre-MPF (M-phase-promoting factor to MPF conversion during GVBD blocking with roscovitine. The significant difference in PBMP observed between mouse and pig oocytes was caused by species difference in cyclin B dynamics during blocking culture as no species difference was observed in either pre-MPF to MPF conversion or the EGF signaling activity.

  16. [What nosographic framework for excessive tanning?].

    Science.gov (United States)

    Petit, A; Karila, L; Lejoyeux, M

    2014-04-01

    Socially valorised tanning, like other forms of behaviour, can take on an addictive aspect. Excessive tanning, defined by the presence of impulsivity and repetition of tanning that leads to personal distress, is a psychiatric disorder that has only recently been recognized. This finding is based on the observations of many dermatologists who report an addictive relationship in their patients with tanning cabins despite announcement of the diagnosis of malignant melanoma. This article attempts to synthesize the existing literature on excessive tanning and addiction to investigate possible associations. This review focuses on the prevalence, clinical features, aetiology, and treatment of this disorder. The literature review was conducted from 1983 to 2012, using PubMed, Google Scholar, EMBASE, and PsycInfo, using the following keywords alone or combined: Tanning, Addiction, Sunbeds, Skin cancer prevention, and Treatment. We investigated different models to determine how excessive tanning met these criteria. Excessive Tanning was described in the 2000s by an American dermatologist, Carolyn Heckman. Wartham et al. were the first to have proposed a theoretical framework for addiction to sunbathing, as well as two scales (m CAGE and m DSM IV) for the diagnosis and to assess the degree of addiction. These diagnostic criteria describe the craving like-symptoms, the feeling of losing control, or the continuation of the behavior despite knowledge of negative consequences. Excessive Tanning is not present in the classifications of the DSM or ICD, but may be related to Addiction, Obsessive-Compulsive Disorder, Impulse control disorders, Anorexia, or Body Dysmorphic Disorder. Excessive tanning can be included in the spectrum of behavioural addictions due its clinical characteristics in common with classics addictive disorders. They are a variety of other models, which may offer an explanation for or insight into tanning behaviour. Further studies must be controlled, notably on

  17. Enhanced 3-epi-25-hydroxyvitamin D3 signal leads to overestimation of its concentration and amplifies interference in 25-hydroxyvitamin D LC-MS/MS assays.

    Science.gov (United States)

    Flynn, N; Lam, F; Dawnay, A

    2014-05-01

    3-epi-25-hydroxyvitamin D3 (3-epi-25OHD3) interferes in most liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for 25-hydroxyvitamin D (25OHD). The clinical significance of this is unclear, with concentrations from undetectable to 230 nmol/L reported. Many studies have quantified 3-epi-25OHD3 based on 25OHD3 calibrators or other indirect methods, and we speculated that this contributes to the observed variability in reported 3-epi-25OHD3 concentrations. We compared continuous MS/MS infusions of 3-epi-25OHD3 and 25OHD3 solutions, spiked both analytes into the same serum matrix and analysed patient samples to assess the effect of three different quantitation methods on 3-epi-25OHD3 concentration. Experiments were performed on an LC-MS/MS system using a phenyl column which does not resolve 3-epi-25OHD3, and a modified method utilizing a Zorbax SB-CN column that chromatographically resolves 3-epi-25OHD3 from 25OHD3. A greater 3-epi-25OHD3 signal, compared with 25OHD3, was observed during equimolar post-column continuous infusion of analyte solutions, and following analysis of a serum pool spiked with both analytes. 3-epi-25OHD3 signal enhancement was dependent on mobile phase composition. Compared with 3-epi-25OHD3 calibrators, indirect quantitation methods resulted in up to 10 times as many samples having 3-epi-25OHD3 concentrations ≥ 10 nmol/L, and an approximately fourfold increase in the maximum observed 3-epi-25OHD3 concentration to 95 nmol/L. Enhanced 3-epi-25OHD3 signal leads to overestimation of its concentrations in the indirect quantitation methods used in many previous studies. The enhanced signal may contribute to greater interference in some 25OHD LC-MS/MS assays than others. We highlight that equimolar responses cannot be assumed in LC-MS/MS systems, even if two molecules are structurally similar.

  18. Overnutrition, mTOR signaling, and cardiovascular diseases

    Science.gov (United States)

    Jia, Guanghong; Aroor, Annayya R.; Martinez-Lemus, Luis A.

    2014-01-01

    The prevalence of obesity and associated medical disorders has increased dramatically in the United States and throughout much of the world in the past decade. Obesity, induced by excess intake of carbohydrates and fats, is a major cause of Type 2 diabetes, hypertension, and the cardiorenal metabolic syndrome. There is emerging evidence that excessive nutrient intake promotes signaling through the mammalian target of rapamycin (mTOR), which, in turn, may lead to alterations of cellular metabolic signaling leading to insulin resistance and obesity-related diseases, such as diabetes, cardiovascular and kidney disease, as well as cancer. While the pivotal role of mTOR signaling in regulating metabolic stress, autophagy, and adaptive immune responses has received increasing attention, there remain many gaps in our knowledge regarding this important nutrient sensor. For example, the precise cellular signaling mechanisms linking excessive nutrient intake and enhanced mTOR signaling with increased cardiovascular and kidney disease, as well as cancer, are not well understood. In this review, we focus on the effects that the interaction between excess intake of nutrients and enhanced mTOR signaling have on the promotion of obesity-associated diseases and potential therapeutic strategies involving targeting mTOR signaling. PMID:25253086

  19. Resonant excess quantum noise in lasers with mixed guiding

    NARCIS (Netherlands)

    Lien, Y.; van der Togt, E.; van Exter, M.P.; Woerdman, J.P.; van Druten, N.J.

    2003-01-01

    We show experimentally that the combination of soft-edged gain and index guiding can lead to resonant excess quantum noise. Resonances with excess noise factors close to 100 are observed in end-pumped Nd 3+ YVO 4 lasers for cavity lengths in which two modes experience similar gain. An associated

  20. Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling.

    Science.gov (United States)

    Moravan, Michael J; Olschowka, John A; Williams, Jacqueline P; O'Banion, M Kerry

    2016-02-03

    Cranial radiotherapy is used to treat tumors of the central nervous system (CNS), as well as non-neoplastic conditions such as arterio-venous malformations; however, its use is limited by the tolerance of adjacent normal CNS tissue, which can lead to devastating long-term sequelae for patients. Despite decades of research, the underlying mechanisms by which radiation induces CNS tissue injury remain unclear. Neuroinflammation and immune cell infiltration are a recognized component of the CNS radiation response; however, the extent and mechanisms by which bone marrow-derived (BMD) immune cells participate in late radiation injury is unknown. Thus, we set out to better characterize the response and tested the hypothesis that C-C chemokine receptor type 2 (CCR2) signaling was required for myeloid cell recruitment following brain irradiation. We used young adult C57BL/6 male bone marrow chimeric mice created with donor mice that constitutively express enhanced green fluorescent protein (eGFP). The head was shielded to avoid brain radiation exposure during chimera construction. Radiation dose and time response studies were conducted in wild-type chimeras, and additional experiments were performed with chimeras created using donor marrow from CCR2 deficient, eGFP-expressing mice. Infiltrating eGFP+ cells were identified and quantified using immunofluorescent microscopy. Brain irradiation resulted in a dose- and time-dependent infiltration of BMD immune cells (predominately myeloid) that began at 1 month and persisted until 6 months following ≥15 Gy brain irradiation. Infiltration was limited to areas that were directly exposed to radiation. CCR2 signaling loss resulted in decreased numbers of infiltrating cells at 6 months that appeared to be restricted to cells also expressing major histocompatibility complex class II molecules. The potential roles played by infiltrating immune cells are of current importance due to increasing interest in immunotherapeutic approaches

  1. Gene Linked to Excess Male Hormones in Female Infertility Disorder

    Science.gov (United States)

    ... April 15, 2014 Gene linked to excess male hormones in female infertility disorder Discovery by NIH-supported ... may lead to the overproduction of androgens — male hormones similar to testosterone — occurring in women with polycystic ...

  2. A sensitive magnetic nanoparticle-based immunoassay of phosphorylated acetylcholinesterase using protein cage templated lead phosphate for signal amplification with graphite furnace atomic absorption spectrometry detection.

    Science.gov (United States)

    Liang, Pei; Kang, Caiyan; Yang, Enjian; Ge, Xiaoxiao; Du, Dan; Lin, Yuehe

    2016-04-07

    We developed a new magnetic nanoparticle sandwich-like immunoassay using protein cage nanoparticles (PCN) for signal amplification together with graphite furnace atomic absorption spectrometry (GFAAS) for the quantification of an organophosphorylated acetylcholinesterase adduct (OP-AChE), the biomarker of exposure to organophosphate pesticides (OPs) and nerve agents. OP-AChE adducts were firstly captured by titanium dioxide coated magnetic nanoparticles (TiO2-MNPs) from the sample matrixes through metal chelation with phospho-moieties, and then selectively recognized by anti-AChE antibody labeled on PCN which was packed with lead phosphate in its cavity (PCN-anti-AChE). The sandwich-like immunoreaction was performed among TiO2-MNPs, OP-AChE and PCN-anti-AChE to form a TiO2-MNP/OP-AChE/PCN-anti-AChE immunocomplex. The complex could be easily isolated from the sample solution with the help of magnet, and the released lead ions from PCN were detected by GFAAS for the quantification of OP-AChE. Greatly enhanced sensitivity was achieved because PCN increased the amount of metal ions in the cavity of each apoferritin. The proposed immunoassay yielded a linear response over a broad range of OP-AChE concentrations from 0.01 nM to 2 nM, with a detection limit of 2 pM, which has enough sensitivity for monitoring of low-dose exposure to OPs. This new method showed an acceptable stability and reproducibility and was validated with OP-AChE spiked human plasma.

  3. Measuring Excess Noise in SDL's

    Science.gov (United States)

    Katzberg, S. J.; Kowitz, H. R.; Rowland, C. W.; Shull, T. A.; Ruggles, S. L.; Matthews, L. F.

    1983-01-01

    New instrument gives quantitive information on "excess noise" in semiconductor-diode laser (SDL's). By proper selection of detector, instrument tests any SDL from visible wavelengths through thermal infrared. Lasers determine excess noise in SKL source by measuring photocurrent generated in photodetector exposed first to reference laser then to SKL under test.

  4. Hunger, escaping excess.

    Science.gov (United States)

    Gardner, G; Halweil, B

    2000-01-01

    According to the WHO, in spite of decades of global food surpluses, half of humanity, in both rich and poor nations, is still malnourished. Malnutrition has become a significant impediment to development in rich and poor countries, alike. At the individual level, both hunger and poor eating habits reduce a person's physical fitness, increase susceptibility to illness, and shorten lifespan. In addition, children deprived of adequate nutrients during development can suffer from permanently reduced mental capacity. At the national level, poor eating hampers educational performance, curtails economic productivity, increases the burden on health care, and reduces well-being. Confronting this epidemic of poor eating will have widespread benefits, but the myths and misconceptions permeating humanity¿s understanding of malnutrition should be addressed first. It is noted that the major cause of hunger is poverty, not scarcity of food; it is the lack of access to the goods and services essential for a healthy life. On the other hand, for those who have access to plenty of food, dietary intake includes meat, dairy products, and highly processed items loaded with fat and sugar. This leads to the problem of obesity, a condition that increases susceptibility to disease and disability, reduces worker productivity, and shortens lifespan. In view of this, efforts to improve nutrition should focus on poverty eradication, health education, agricultural change, and policy change towards promotion of good nutrition.

  5. Does Excessive Pronation Cause Pain?

    DEFF Research Database (Denmark)

    Olesen, Christian Gammelgaard; Nielsen, RG; Rathleff, M

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist...... of antipronation shoes or insoles, which latest was studied by Kulce DG., et al (2007). So far there have been no randomized controlled studies showing methods that can measure the effect of treatments with insoles. Some of the excessive pronation patients recieve antipronation training often if the patient...

  6. Does Excessive Pronation Cause Pain?

    DEFF Research Database (Denmark)

    Mølgaard, Carsten Møller; Olesen Gammelgaard, Christian; Nielsen, R. G.

    2008-01-01

    Excessive pronation could be an inborn abnormality or an acquired foot disorder caused by overuse, inadequate supported shoes or inadequate foot training. When the muscles and ligaments of the foot are insufficient it can cause an excessive pronation of the foot. The current treatment consist of ...... pronation patients recieve antipronation training often if the patient is in pain but wanted to investigate if it was possible to measure a change in foot posture after af given treatment....

  7. Personalized Recommendation via Suppressing Excessive Diffusion

    Directory of Open Access Journals (Sweden)

    Guilin Chen

    2017-01-01

    Full Text Available Efficient recommendation algorithms are fundamental to solve the problem of information overload in modern society. In physical dynamics, mass diffusion is a powerful tool to alleviate the long-standing problems of recommendation systems. However, popularity bias and redundant similarity have not been adequately studied in the literature, which are essentially caused by excessive diffusion and will lead to similarity estimation deviation and recommendation performance degradation. In this paper, we penalize the popular objects by appropriately dividing the popularity of objects and then leverage the second-order similarity to suppress excessive diffusion. Evaluation on three real benchmark datasets (MovieLens, Amazon, and RYM by 10-fold cross-validation demonstrates that our method outperforms the mainstream baselines in accuracy, diversity, and novelty.

  8. Activity-dependent alterations in the sensitivity to BDNF-TrkB signaling may promote excessive dendritic arborization and spinogenesis in fragile X syndrome in order to compensate for compromised postsynaptic activity.

    Science.gov (United States)

    Kim, Sang Woo; Cho, Kyoung Joo

    2014-10-01

    Fragile X syndrome (FXS), the most common cause of inherited human mental retardation, results from the loss of function of fragile X mental retardation protein (FMRP). To date, most researchers have thought that FXS neural pathologies are primarily caused by extreme dendritic branching and spine formation. With this rationale, several researchers attempted to prune dendritic branches and reduce the number of spines in FXS animal models. We propose that increased dendritic arborization and spinogenesis in FXS are developed rather as secondary compensatory responses to counteract the compromised postsynaptic activity during uncontrollable metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD). When postsynaptic and electrical activities become dampened in FXS, dendritic trees can increase their sensitivity to brain-derived neurotrophic factor (BDNF) by using the molecular sensor called eukaryotic elongation factor 2 (eEF2) and taking advantage of the tight coupling of mGluR and BDNF-TrkB signaling pathways. Then, this activity-dependent elevation of the BDNF signaling can strategically alter dendritic morphologies to foster branching and develop spine structures in order to improve the postsynaptic response in FXS. Our model suggests a new therapeutic rationale for FXS: correcting the postsynaptic and electrical activity first, and then repairing structural abnormalities of dendrites. Then, it may be possible to successfully fix the dendritic morphologies without affecting the survival of neurons. Our theory may also be generalized to explain aberrant dendritic structures observed in other neurobehavioral diseases, such as tuberous sclerosis, Rett syndrome, schizophrenia, and channelopathies, which accompany high postsynaptic and electrical activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Lead content of foodstuffs.

    Science.gov (United States)

    Mitchell, D G; Aldous, K M

    1974-05-01

    The lead content of a number of foodstuffs, particularly baby fruit juices and milk, is reported. Samples were analyzed in quadruplicate by using an automated Delves cup atomic absorption procedure. A large proportion of the products examined contained significant amounts of lead. Of 256 metal can examined, the contents of 62% contained a lead level of 100 mug/l. or more, 37% contained 200 mug/l. or more and 12% contained 400 mug/l. lead or more. Of products in glass and aluminum containers, only 1% had lead levels in excess of 200 mug/l. Lead levels of contents also correlate with the seam length/volume ratio of the leaded seam can. A survey of bulk milk showed a mean lead level of 40 mug/l. for 270 samples; for canned evaporated milk the mean level was 202 mug/l. These data indicate a potential health hazard.

  10. Excessive masturbation after epilepsy surgery.

    Science.gov (United States)

    Ozmen, Mine; Erdogan, Ayten; Duvenci, Sirin; Ozyurt, Emin; Ozkara, Cigdem

    2004-02-01

    Sexual behavior changes as well as depression, anxiety, and organic mood/personality disorders have been reported in temporal lobe epilepsy (TLE) patients before and after epilepsy surgery. The authors describe a 14-year-old girl with symptoms of excessive masturbation in inappropriate places, social withdrawal, irritability, aggressive behavior, and crying spells after selective amygdalohippocampectomy for medically intractable TLE with hippocampal sclerosis. Since the family members felt extremely embarrassed, they were upset and angry with the patient which, in turn, increased her depressive symptoms. Both her excessive masturbation behavior and depressive symptoms remitted within 2 months of psychoeducative intervention and treatment with citalopram 20mg/day. Excessive masturbation is proposed to be related to the psychosocial changes due to seizure-free status after surgery as well as other possible mechanisms such as Kluver-Bucy syndrome features and neurophysiologic changes associated with the cessation of epileptic discharges. This case demonstrates that psychiatric problems and sexual changes encountered after epilepsy surgery are possibly multifactorial and in adolescence hypersexuality may be manifested as excessive masturbation behavior.

  11. The tight junction protein transcript abundance changes and oxidative damage by tryptophan deficiency or excess are related to the modulation of the signalling molecules, NF-κB p65, TOR, caspase-(3,8,9) and Nrf2 mRNA levels, in the gill of young grass carp (Ctenopharyngodon idellus).

    Science.gov (United States)

    Jiang, Wei-Dan; Wen, Hai-Lang; Liu, Yang; Jiang, Jun; Kuang, Sheng-Yao; Wu, Pei; Zhao, Juan; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2015-10-01

    This study is for the first time to explore the possible effects of dietary tryptophan (Trp) on structural integrity and the related signalling factor gene expression in the gill of young grass carp (Ctenopharyngodon idella). Fish were fed with six different experimental diets containing graded levels of Trp at 0.7 (control), 1.7, 3.1, 4.0, 5.2 and 6.1 g kg(-1) diet for 8 weeks. The results firstly demonstrated that Trp deficiency or excess caused increases in reactive oxygen species (ROS) contents, and severe oxidative damage (lipid peroxidation and protein oxidation) in the gill of fish, and those negative effects could be reversed by optimal Trp levels. Secondly, compared with the optimal Trp levels, Trp deficiency could cause decreases in the mRNA levels of the barrier functional proteins (occludin, zonula occludens-1, claudin-c, and -3) and increases in the mRNA levels of the pore-formation proteins (claudin-12 and -15) mRNA levels in the gill of fish, and those were reversed by the optimal levels of Trp. The negative effects of Trp deficiency on those tight junction protein gene expression might be partly related to the increases in the mRNA levels of pro-inflammatory cytokines and related signalling factors (tumor necrosis factor α, interleukin 8, interleukin 1β and transcription factor-κB) and decreases in the mRNA levels of anti-inflammatory cytokines and related signalling factors [interleukin 10, transforming growth factor-β1, nuclear inhibitor factor κBα (iκBα), target of rapamyc and ribosome protein S6 kinase 1 (S6K1)] in the gill of fish. In addition, optimal dietary Trp protected the gill of fish against its deficiency-caused increases in the mRNA levels of the apoptosis signalling (caspase-3, caspase-8, caspase-9) and decreases in anti-superoxide radicals capacity, anti-hydroxyl radical capacity, glutathione contents and the activities of Cu/Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase

  12. Crying - excessive (0-6 months)

    Science.gov (United States)

    ... provider will check the infant's growth and development. Antibiotics may be prescribed if the baby has a bacterial infection. Alternative Names Infants - excessive crying; Well child - excessive crying ...

  13. Repeated intravenous administration of gadobutrol does not lead to increased signal intensity on unenhanced T1-weighted images - a voxel-based whole brain analysis

    Energy Technology Data Exchange (ETDEWEB)

    Langner, Soenke; Kromrey, Marie-Luise [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); University Hospital, Carl Gustav Carus University Dresden, Institute for Radiology, Dresden (Germany); Grothe, Matthias [University Medicine Greifswald, Department of Neurology, Greifswald (Germany); Domin, Martin [University Medicine Greifswald, Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany)

    2017-09-15

    To identify a possible association between repeated intravenous administration of gadobutrol and increased signal intensity in the grey and white matter using voxel-based whole-brain analysis. In this retrospective single-centre study, 217 patients with a clinically isolated syndrome underwent baseline brain magnetic resonance imaging and at least one annual follow-up examination with intravenous administration of 0.1 mmol/kg body weight of gadobutrol. Using the ''Diffeomorphic Anatomical Registration using Exponentiated Lie algebra'' (DARTEL) normalisation process, tissue templates for grey matter (GM), white matter (WM), and cerebrospinal fluid (CSF) were calculated, as were GM-CSF and WM-CSF ratios. Voxel-based whole-brain analysis was used to calculate the signal intensity for each voxel in each data set. Paired t-test was applied to test differences to baseline MRI for significance. Voxel-based whole-brain analysis demonstrated no significant changes in signal intensity of grey and white matter after up to five gadobutrol administrations. There was no significant change in GM-CSF and grey WM-CSF ratios. Voxel-based whole-brain analysis did not demonstrate increased signal intensity of GM and WM on unenhanced T1-weighted images after repeated gadobutrol administration. The molecular structure of gadolinium-based contrast agent preparations may be an essential factor causing SI increase on unenhanced T1-weighted images. (orig.)

  14. Severe rhabdomyolysis after excessive bodybuilding.

    Science.gov (United States)

    Finsterer, J; Zuntner, G; Fuchs, M; Weinberger, A

    2007-12-01

    A 46-year-old male subject performed excessive physical exertion during 4-6 h in a studio for body builders during 5 days. He was not practicing sport prior to this training and denied the use of any aiding substances. Despite muscle aching already after 1 day, he continued the exercises. After the last day, he recognized tiredness and cessation of urine production. Two days after discontinuation of the training, a Herpes simplex infection occurred. Because of acute renal failure, he required hemodialysis. There were absent tendon reflexes and creatine kinase (CK) values up to 208 274 U/L (normal: <170 U/L). After 2 weeks, CK had almost normalized and, after 4 weeks, hemodialysis was discontinued. Excessive muscle training may result in severe, hemodialysis-dependent rhabdomyolysis. Triggering factors may be prior low fitness level, viral infection, or subclinical metabolic myopathy.

  15. 10 CFR 904.9 - Excess capacity.

    Science.gov (United States)

    2010-01-01

    ... Marketing § 904.9 Excess capacity. (a) If the Uprating Program results in Excess Capacity, Western shall be entitled to such Excess Capacity to integrate the operation of the Boulder City Area Projects and other... 10 Energy 4 2010-01-01 2010-01-01 false Excess capacity. 904.9 Section 904.9 Energy DEPARTMENT OF...

  16. 12 CFR 925.23 - Excess stock.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Excess stock. 925.23 Section 925.23 Banks and... BANKS Stock Requirements § 925.23 Excess stock. (a) Sale of excess stock. Subject to the restriction in paragraph (b) of this section, a member may purchase excess stock as long as the purchase is approved by the...

  17. Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer.

    Science.gov (United States)

    So, Jae Young; Smolarek, Amanda K; Salerno, David M; Maehr, Hubert; Uskokovic, Milan; Liu, Fang; Suh, Nanjoo

    2013-01-01

    CD44, a transmembrane glycoprotein, is a major receptor for extracellular proteins involved in invasion and metastasis of human cancers. We have previously demonstrated that the novel Gemini vitamin D analog BXL0124 [1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluro-cholecalciferol] repressed CD44 expression in MCF10DCIS.com basal-like human breast cancer cells and inhibited MCF10DCIS xenograft tumor growth. In the present study, we investigated potential factors downstream of CD44 and the biological role of CD44 repression by BXL0124 in MCF10DCIS cells. The treatment with Gemini vitamin D BXL0124 decreased CD44 protein level, suppressed STAT3 signaling, and inhibited invasion and proliferation of MCF10DCIS cells. The interaction between CD44 and STAT3 was determined by co-immunoprecipitation. CD44 forms a complex with STAT3 and Janus kinase 2 (JAK2) to activate STAT3 signaling, which was inhibited by BXL0124 in MCF10DCIS cells. The role of CD44 in STAT3 signaling and invasion of MCF10DCIS cells was further determined by the knockdown of CD44 using small hairpin RNA in vitro and in vivo. MCF10DCIS cell invasion was markedly decreased by the knockdown of CD44 in vitro. The knockdown of CD44 also significantly decreased mRNA expression levels of invasion markers, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA), in MCF10DCIS cells. In MCF10DCIS xenograft tumors, CD44 knockdown decreased tumor size and weight as well as invasion markers. The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion. It also suggests that repression of CD44-STAT3 signaling is a key molecular mechanism in the inhibition of breast cancer invasion by the Gemini vitamin D analog BXL0124.

  18. Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer.

    Directory of Open Access Journals (Sweden)

    Jae Young So

    Full Text Available CD44, a transmembrane glycoprotein, is a major receptor for extracellular proteins involved in invasion and metastasis of human cancers. We have previously demonstrated that the novel Gemini vitamin D analog BXL0124 [1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl-23-yne-26,27-hexafluro-cholecalciferol] repressed CD44 expression in MCF10DCIS.com basal-like human breast cancer cells and inhibited MCF10DCIS xenograft tumor growth. In the present study, we investigated potential factors downstream of CD44 and the biological role of CD44 repression by BXL0124 in MCF10DCIS cells.The treatment with Gemini vitamin D BXL0124 decreased CD44 protein level, suppressed STAT3 signaling, and inhibited invasion and proliferation of MCF10DCIS cells. The interaction between CD44 and STAT3 was determined by co-immunoprecipitation. CD44 forms a complex with STAT3 and Janus kinase 2 (JAK2 to activate STAT3 signaling, which was inhibited by BXL0124 in MCF10DCIS cells. The role of CD44 in STAT3 signaling and invasion of MCF10DCIS cells was further determined by the knockdown of CD44 using small hairpin RNA in vitro and in vivo. MCF10DCIS cell invasion was markedly decreased by the knockdown of CD44 in vitro. The knockdown of CD44 also significantly decreased mRNA expression levels of invasion markers, matrix metalloproteinases (MMPs and urokinase plasminogen activator (uPA, in MCF10DCIS cells. In MCF10DCIS xenograft tumors, CD44 knockdown decreased tumor size and weight as well as invasion markers.The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion. It also suggests that repression of CD44-STAT3 signaling is a key molecular mechanism in the inhibition of breast cancer invasion by the Gemini vitamin D analog BXL0124.

  19. Lead Test

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Lead Send Us Your Feedback Choose Topic At a ... Related Content View Sources Also Known As Blood Lead Test Blood Lead Level BLL Formal Name Lead, ...

  20. Intravenous injection of gadobutrol in an epidemiological study group did not lead to a difference in relative signal intensities of certain brain structures after 5 years

    Energy Technology Data Exchange (ETDEWEB)

    Kromrey, Marie-Luise; Liedtke, Kim Rouven; Langner, Soenke; Kirsch, Michael; Kuehn, Jens-Peter [University Medicine Greifswald, Institute of Diagnostic Radiology and Neuroradiology, Greifswald (Germany); Ittermann, Till [University Medicine Greifswald, Institute for Community Medicine, Greifswald (Germany); Weitschies, Werner [University Greifswald, Institute of Biopharmacy and Pharmaceutical Technology, Greifswald (Germany)

    2017-02-15

    To investigate if application of macrocyclic gadolinium-based contrast agents in volunteers is associated with neuronal deposition detected by magnetic resonance imaging in a 5-year longitudinal survey. Three hundred eighty-seven volunteers who participated in a population-based study were enrolled. Subjects underwent plain T1-weighted brain MRI at baseline and 5 years later with identical sequence parameters. At baseline, 271 participants additionally received intravenous injection of the macrocyclic contrast agent gadobutrol (1.5 mmol/kg). A control group including 116 subjects received no contrast agent. Relative signal intensities of thalamus, pallidum, pons and dentate nucleus were compared at baseline and follow-up. No difference in relative signal intensities was observed between contrast group (thalamus, p = 0.865; pallidum, p = 0.263; pons, p = 0.533; dentate nucleus, p = 0.396) and control group (thalamus, p = 0.683; pallidum; p = 0.970; pons, p = 0.773; dentate nucleus, p = 0.232) at both times. Comparison between both groups revealed no significant differences in relative signal intensities (thalamus, p = 0.413; pallidum, p = 0.653; pons, p = 0.460; dentate nucleus, p = 0.751). The study showed no significant change in globus pallidus-to-thalamus or dentate nucleus-to-pons ratios. Five years after administration of a 1.5-fold dose gadobutrol to normal subjects, signal intensity of thalamus, pallidum, pons and dentate nucleus did not differ from participants who had not received gadobutrol. (orig.)

  1. Endosomal H2O2 production leads to localized cysteine sulfenic acid formation on proteins during lysophosphatidic acid-mediated cell signaling.

    Science.gov (United States)

    Klomsiri, Chananat; Rogers, LeAnn C; Soito, Laura; McCauley, Anita K; King, S Bruce; Nelson, Kimberly J; Poole, Leslie B; Daniel, Larry W

    2014-06-01

    Lysophosphatidic acid (LPA) is a growth factor for many cells including prostate and ovarian cancer-derived cell lines. LPA stimulates H2O2 production which is required for growth. However, there are significant gaps in our understanding of the spatial and temporal regulation of H2O2-dependent signaling and the way in which signals are transmitted following receptor activation. Herein, we describe the use of two reagents, DCP-Bio1 and DCP-Rho1, to evaluate the localization of active protein oxidation after LPA stimulation by detection of nascent protein sulfenic acids. We found that LPA stimulation causes internalization of LPA receptors into early endosomes that contain NADPH oxidase components and are sites of H2O2 generation. DCP-Rho1 allowed visualization of sulfenic acid formation, indicative of active protein oxidation, which was stimulated by LPA and decreased by an LPA receptor antagonist. Protein oxidation sites colocalized with LPAR1 and the endosomal marker EEA1. Concurrent with the generation of these redox signaling-active endosomes (redoxosomes) is the H2O2- and NADPH oxidase-dependent oxidation of Akt2 and PTP1B detected using DCP-Bio1. These new approaches therefore enable detection of active, H2O2-dependent protein oxidation linked to cell signaling processes. DCP-Rho1 may be a particularly useful protein oxidation imaging agent enabling spatial resolution due to the transient nature of the sulfenic acid intermediate it detects. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. A Dynamic WNT/β-CATENIN Signaling Environment Leads to WNT-Independent and WNT-Dependent Proliferation of Embryonic Intestinal Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Alana M. Chin

    2016-11-01

    Full Text Available Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13.5, E14.5 and following villus formation (E15.5 in mice. In contrast to the well-described role for WNT/β-CATENIN signaling as a regulator of stem/progenitor cells in the late fetal and adult gut, conditional epithelial deletion of β-catenin or the Frizzled co-receptors Lrp5 and Lrp6 had no effect on epithelial progenitor cell proliferation in the pseudostratified epithelium. Mutant embryos displayed obvious developmental defects, including loss of proliferation and disruptions in villus formation starting only at E15.5. Mechanistically, our data suggest that WNT signaling-mediated proliferation at the time of villus formation is driven by mesenchymal, but not epithelial, WNT ligand secretion.

  3. Mixed stops and the ATLAS on-Z excess

    Science.gov (United States)

    Collins, Jack H.; Dror, Jeff Asaf; Farina, Marco

    2015-11-01

    The ATLAS experiment has recently observed a 3 σ excess in a channel with a leptonically decaying Z , jets, and ETmiss . It is tantalizing to interpret the signal as the first sign of a natural supersymmetric spectrum. We study such a possibility in a minimal model containing light stops and a neutralino lightest supersymmetric particle. The signal is characterized by a novel topology (compared to previous attempts) where the Z is emitted from a colored particle in the first step of a decay chain, namely t˜2→t˜1Z , which is characteristic of mixed stops. We show that the excess is compatible with a compressed stop spectrum and is not excluded by any other relevant search, finding some regions of parameter space with signal strength within 1 σ of that measured by the ATLAS Collaboration. In addition, we notice that the corresponding CMS search could be prone to background contamination in unexpected topologies of this kind.

  4. Effective interpretations of a diphoton excess

    Energy Technology Data Exchange (ETDEWEB)

    Berthier, Laure [Niels Bohr International Academy & Discovery Center,Niels Bohr Institute, University of Copenhagen,Blegdamsvej 17, DK-2100, Copenhagen (Denmark); Cline, James M. [Niels Bohr International Academy & Discovery Center,Niels Bohr Institute, University of Copenhagen,Blegdamsvej 17, DK-2100, Copenhagen (Denmark); Department of Physics, McGill University,3600 Rue University, Montréal, Québec, H3A 2T8 (Canada); Shepherd, William; Trott, Michael [Niels Bohr International Academy & Discovery Center,Niels Bohr Institute, University of Copenhagen,Blegdamsvej 17, DK-2100, Copenhagen (Denmark)

    2016-04-14

    We discuss some consistency tests that must be passed for a successful explanation of a diphoton excess at larger mass scales, generated by a scalar or pseudoscalar state, possibly of a composite nature, decaying to two photons. Scalar states at mass scales above the electroweak scale decaying significantly into photon final states generically lead to modifications of Standard Model Higgs phenomenology. We characterise this effect using the formalism of Effective Field Theory (EFT) and study the modification of the effective couplings to photons and gluons of the Higgs. The modification of Higgs phenomenology comes about in a variety of ways. For scalar 0{sup +} states, a component of the Higgs and the heavy boson can mix. Lower energy phenomenology gives a limit on the mixing angle, which gets generated at one loop in any theory explaining the diphoton excess. Even if the mixing angle is set to zero, we demonstrate that a relation exists between lower energy Higgs data and a massive scalar decaying to diphoton final states. If the new boson is a pseudoscalar, we note that if it is composite, it is generic to have an excited scalar partner that can mix with a component of the Higgs, which has a stronger coupling to photons. In the case of a pseudoscalar, we also characterize how lower energy Higgs phenomenology is directly modified using EFT, even without assuming a scalar partner of the pseudoscalar state. We find that naturalness concerns can be accommodated, and that pseudoscalar models are more protected from lower energy constraints.

  5. Study of Bioreductive Anticancer Agent RH-1-Induced Signals Leading the Wild-Type p53-Bearing Lung Cancer A549 Cells to Apoptosis.

    Science.gov (United States)

    Stulpinas, Aurimas; Imbrasaitė, Aušra; Krestnikova, Natalija; Šarlauskas, Jonas; Čėnas, Narimantas; Kalvelytė, Audronė Valerija

    2016-01-19

    Aziridinylquinone RH-1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-cyclohexa-2,5-diene-1,4-dione) is a potential anticancer agent. RH-1 action is associated with quinone oxidoreductase (NQO1) which reduces this diaziridinylbenzoquinone into DNA-alkylating hydroquinone and is overexpressed in many tumors. Another suggested mechanism of RH-1 toxicity is the formation of reactive oxygen species (ROS) arising from its redox cycling. In order to improve anticancer action of this and similar antitumor quinones, we investigated the involvement of different signaling molecules in cytotoxicity induced by RH-1 by using wild-type tumor suppressor p53 bearing nonsmall cell lung carcinoma A549 cells as a model. Gradual and prolonged increase of mitogen-activated protein kinases (MAPK) ERK, P38, and JNK phosphorylation was observed during 24-h RH-1 treatment. In parallel, activation of DNA damage-sensing ATM kinase, upregulation, and phosphorylation of TP53 (human p53) took place. Inhibition studies revealed that RH-1-induced A549 apoptosis involved the NQO1-ATM-p53 signaling pathway and ROS generation. TP53 participated in ROS- and DNA damage-induced cell death differently. Moreover, MAP kinase JNK was another TP53 activator and death inducer in A549 cells. At the same time, rapid and prolonged activation of AKT kinase during RH-1 treatment was found, and it proved to be antiapoptotic kinase in our model system. Therefore, we identified that different and opposite cell death regulating signaling pathways, which may counteract one another, are induced in cancer cells during chemotherapeutic RH-1 treatment.

  6. Diphoton excess through dark mediators

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chien-Yi [Department of Physics and Astronomy, University of Victoria,Victoria, BC V8P 5C2 (Canada); Perimeter Institute for Theoretical Physics,Waterloo, ON N2J 2W9 (Canada); Lefebvre, Michel [Department of Physics and Astronomy, University of Victoria,Victoria, BC V8P 5C2 (Canada); Pospelov, Maxim [Department of Physics and Astronomy, University of Victoria,Victoria, BC V8P 5C2 (Canada); Perimeter Institute for Theoretical Physics,Waterloo, ON N2J 2W9 (Canada); Zhong, Yi-Ming [C.N. Yang Institute for Theoretical Physics, Stony Brook University,Stony Brook, New York 11794 (United States)

    2016-07-12

    Preliminary ATLAS and CMS results from the first 13 TeV LHC run have encountered an intriguing excess of events in the diphoton channel around the invariant mass of 750 GeV. We investigate a possibility that the current excess is due to a heavy resonance decaying to light metastable states, which in turn give displaced decays to very highly collimated e{sup +}e{sup −} pairs. Such decays may pass the photon selection criteria, and successfully mimic the diphoton events, especially at low counts. We investigate two classes of such models, characterized by the following underlying production and decay chains: gg→S→A{sup ′}A{sup ′}→(e{sup +}e{sup −})(e{sup +}e{sup −}) and qq̄→Z{sup ′}→sa→(e{sup +}e{sup −})(e{sup +}e{sup −}), where at the first step a heavy scalar, S, or vector, Z{sup ′}, resonances are produced that decay to light metastable vectors, A{sup ′}, or (pseudo-)scalars, s and a. Setting the parameters of the models to explain the existing excess, and taking the ATLAS detector geometry into account, we marginalize over the properties of heavy resonances in order to derive the expected lifetimes and couplings of metastable light resonances. We observe that in the case of A{sup ′}, the suggested range of masses and mixing angles ϵ is within reach of several new-generation intensity frontier experiments.

  7. Excess Early Mortality in Schizophrenia

    DEFF Research Database (Denmark)

    Laursen, Thomas Munk; Nordentoft, Merete; Mortensen, Preben Bo

    2014-01-01

    Schizophrenia is often referred to as one of the most severe mental disorders, primarily because of the very high mortality rates of those with the disorder. This article reviews the literature on excess early mortality in persons with schizophrenia and suggests reasons for the high mortality...... as well as possible ways to reduce it. Persons with schizophrenia have an exceptionally short life expectancy. High mortality is found in all age groups, resulting in a life expectancy of approximately 20 years below that of the general population. Evidence suggests that persons with schizophrenia may...

  8. Paradoxical hypomagnesemia caused by excessive ingestion of magnesium hydroxide.

    Science.gov (United States)

    Joo Suk, Oh

    2008-09-01

    Excessive ingestion of magnesium may lead to hypermagnesemia even without kidney dysfunction. Several cases of development of hypermagnesemia after overdose of magnesium hydroxide have been reported. Although magnesium hydroxide is widely used as laxative, its overdose may induce diarrhea, which is followed by excessive magnesium loss. I report a case of paradoxical hypomagnesemia developed after excessive ingestion of magnesium hydroxide. A 39-year-old woman was presented to the emergency department complaining of severe watery diarrhea and carpopedal spasm after ingesting a handful of magnesium hydroxide tablets. The laboratory tests detected hypomagnesemia, hypocalcemia, and normokalemia. Calcium gluconate was given to the patient, but her symptom did not improve shortly. The symptom disappeared spontaneously 2 days after the watery diarrhea subsided. This case shows that overdose of magnesium hydroxide, which leads to massive diarrhea, might induce hypomagnesemia unexpectedly. This case also suggests that it should be treated, as well as typical magnesium deficiency.

  9. Excessive hoarding in Parkinson's disease.

    Science.gov (United States)

    O'Sullivan, Sean S; Djamshidian, Atbin; Evans, Andrew H; Loane, Clare M; Lees, Andrew J; Lawrence, Andrew D

    2010-06-15

    Hoarding is seen in several psychiatric conditions, but has not been specifically assessed in Parkinson's disease (PD). This study investigates hoarding tendency amongst patients with PD, and its association with impulsive-compulsive spectrum behaviors (ICBs). We compare clinical features, measures of hoarding, impulse buying, self-control, obsessive-compulsive symptoms, depression, and anxiety in 39 patients with PD with ICBs (PD + ICB), 61 patients with PD without ICBs (PD - ICB), and 50 healthy controls. A much higher proportion of PD + ICB (27.8%) than PD - ICB (3.5%) were hoarders (P = 0.001). 6% of healthy controls were hoarders. Compulsive shoppers scored higher than other varieties of ICB on excessive acquisition measures. Hoarding correlated positively with impulsive buying, obsessive-compulsive symptoms, PD duration, and negatively with self-control measures. Using multivariate regression analyzes, the presence of ICBs and measures of impulsive buying were the only variables independently associated with hoarding in PD. The association of hoarding with other ICBs and low trait impulse control suggests that excessive hoarding is related to the spectrum of impulsive behaviors in PD. (c) 2010 Movement Disorder Society.

  10. Behavioral Management of Excessive Caffeine Consumption: Three Case Studies.

    Science.gov (United States)

    Johnson-Greene, Douglas; And Others

    Although caffeine is seemingly harmless in ordinary daily intake, there has been increasing concern about the possible side effects of habitual caffeine ingestion. The excessive daily ingestion of caffeine in the form of coffee, soda pop, tea, and various medications may lead to a chronic disorder known as caffeinism. This study tested the…

  11. In Vitro Palmitate Treatment of Myotubes from Postmenopausal Women Leads to Ceramide Accumulation, Inflammation and Affected Insulin Signaling

    DEFF Research Database (Denmark)

    Abildgaard, Julie; Henstridge, Darren C; Pedersen, Anette Tønnes

    2014-01-01

    treatment led to a 108% (CI 95%: 50%; 267%) increase in intramyocellular ceramide in the myotubes from the postmenopausal women (post-myotubes) compared with a 26% (CI 95%: -57%; 96%) increase in myotubes from the premenopausal women (pre-myotubes), (ppost-myotubes had a 22% (CI 95%: 4......, post-myotubes showed a blunted insulin stimulated phosphorylation of AS160 in response to chronic palmitate treatment compared with pre-myotubes (p = 0.02). The increased intramyocellular ceramide content in the post-myotubes was associated with a significantly higher mRNA expression of Serine...... Palmitoyltransferase1 (SPT1) after one day of palmitate treatment (p = 0.03) in post-myotubes compared with pre-myotubes. Our findings indicate that post-myotubes are more prone to develop lipid accumulation and defective insulin signaling following chronic saturated fatty acid exposure as compared to pre-myotubes....

  12. Walsuronoid B induces mitochondrial and lysosomal dysfunction leading to apoptotic rather than autophagic cell death via ROS/p53 signaling pathways in liver cancer.

    Science.gov (United States)

    Geng, Ya-di; Zhang, Chao; Lei, Jian-Li; Yu, Pei; Xia, Yuan-Zheng; Zhang, Hao; Yang, Lei; Kong, Ling-Yi

    2017-10-15

    Walsuronoid B is a limonoid compound extracted from Walsura robusta. Previous studies have shown that limonoid compounds possess anti-cancer potential, although the molecular mechanism of this activity remains elusive. In this study, we demonstrated for the first time that walsuronoid B inhibited cell proliferation in several human cancer lines. Liver cancer cells (HepG2 and Bel-7402) were chosen for their high sensitivity to walsuronoid B. Walsuronoid B induced cell death through G2/M phase arrest and apoptosis and induced the accumulation of autophagosomes through the suppression of mTOR signaling, which serves as a cell survival mechanism and prevents cell death. We further examined the molecular mechanisms and found that walsuronoid B-induced dysfunction of the mitochondria and lysosomes rather than the endoplasmic reticulum contributed to its cell death effect. Walsuronoid B enhanced the generation of hydrogen peroxide, nitric oxide and superoxide anion radical, resulting in elevated levels of reactive oxygen species (ROS). In addition, ROS induced by walsuronoid B upregulated p53 levels; conversely, p53 stimulated ROS. These results suggested that ROS and p53 reciprocally promoted each other's production and cooperated to induce liver cancer cell death. We found that the induction of ROS and p53 significantly triggered G2/M phase arrest and mitochondrial and lysosomal apoptosis. Finally, walsuronoid B suppressed tumor growth in vivo with few side effects. In summary, our findings demonstrated that walsuronoid B caused G2/M phase arrest and induced mitochondrial and lysosomal apoptosis through the ROS/p53 signaling pathway in human liver cancer cells in vitro and in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  14. ATLAS diboson excess from low scale supersymmetry breaking

    Energy Technology Data Exchange (ETDEWEB)

    Petersson, Christoffer [Department of Fundamental Physics, Chalmers University of Technology,412 96 Göteborg (Sweden); Physique Théorique et Mathématique, Université Libre de Bruxelles,C.P. 231, 1050 Brussels (Belgium); International Solvay Institutes,1050 Brussels (Belgium); Torre, Riccardo [Dipartimento di Fisica e Astronomia, Università di Padova and INFN Sezione di Padova,Via Marzolo 8, I-35131 Padova (Italy)

    2016-01-18

    We provide an interpretation of the recent ATLAS diboson excess in terms of a class of supersymmetric models in which the scale of supersymmetry (SUSY) breaking is in the few TeV range. The particle responsible for the excess is the scalar superpartner of the Goldstone fermion associated with SUSY breaking, the sgoldstino. This scalar couples strongly to the Standard Model vector bosons and weakly to the fermions, with all coupling strengths determined by ratios of soft SUSY breaking parameters over the SUSY breaking scale. Explaining the ATLAS excess selects particular relations and ranges for the gaugino masses, while imposing no constraints on the other superpartner masses. Moreover, this signal hypothesis predicts a rate in the Zγ final state that is expected to be observable at the LHC Run II already with a few fb{sup −1} of integrated luminosity.

  15. The effects of excessive humidity.

    Science.gov (United States)

    Williams, R B

    1998-06-01

    Humidification devices and techniques can expose the airway mucosa to a wide range of gas temperatures and humidities, some of which are excessive and may cause injury. Humidified gas is a carrier of both water and energy. The volume of water in the gas stream depends on whether the water is in a molecular form (vapor), particulate form (aerosol), or bulk form (liquid). The energy content of gas stream is the sum of the sensible heat (temperature) of the air and any water droplets in it and the heat of vaporization (latent energy) of any water vapor present. Latent heat energy is much larger than sensible heat energy, so saturated air contains much more energy than dry air. Thus every breath contains a water volume and energy (thermal) challenge to the airway mucosa. When the challenge exceeds the homeostatic mechanisms airway dysfunction begins, starting at the cellular and secretion level and progressing to whole airway function. A large challenge will result in quick progression of dysfunction. Early dysfunction is generally reversible, however, so large challenges with short exposure times may not cause irreversible injury. The mechanisms of airway injury owing to excess water are not well studied. The observation of its effects lends itself to some general conclusions, however. Alterations in the ventilation-perfusion ratio, decrease in vital capacity and compilance, and atelectasis are suggestive of partial or full occlusion of small airways. Changes in surface tension and alveolar-arterial oxygen gradient are consistent with flooding of alveoli. There also may be osmotic challenges to mucosal cell function as evidenced by the different reaction rates with hyper- and hypotonic saline. The reaction to nonisotonic saline also may partly explain increases in specific airway resistance. Aerosolized water and instilled water may be hazardous because of their demonstrated potential for delivering excessive water to the airway. Their use for airway humidification or

  16. Directional growth of Ag nanorod from polymeric silver cyanide: A potential substrate for concentration dependent SERS signal enhancement leading to melamine detection

    Science.gov (United States)

    Roy, Anindita; Sahoo, Ramkrishna; Chowdhury, Joydeep; Bhattacharya, Tara Shankar; Agarwal, Ratnesh; Pal, Tarasankar

    2017-08-01

    Attention has been directed to prepare exclusive one-dimensional silver nanostructure from the linear inorganic polymer AgCN. Successive color change from yellow to orange, to red and finally to green reflects the evolution of high yielding Ag nanorods (NRs) from well-known -[Ag-CN]- chains of polymeric AgCN at room temperature. The parental 1D morphology of AgCN is retained within the as-synthesized Ag NRs. So we could successfully exploit the Ag NR for surface-enhanced Raman scattering (SERS) studies for sensing a popular milk adulterant melamine down to picomolar level. We observed interesting concentration dependent selective SERS band enhancement of melamine. The enhanced 1327 cm- 1 SERS signal intensity at lower concentration (10- 9 and 10- 12 M) of melamine speaks for the preferential participation of -C-N of melamine molecule with Ag surface. On the other hand, '-NH2' group together with ring 'N' participation of melamine molecule onto Ag surface suggested an adsorptive stance at higher (10- 3-10- 7 M) concentration range. Thus the binding modes of the molecule at the Ag surface justify its fluxional behavior.

  17. Directional growth of Ag nanorod from polymeric silver cyanide: A potential substrate for concentration dependent SERS signal enhancement leading to melamine detection.

    Science.gov (United States)

    Roy, Anindita; Sahoo, Ramkrishna; Chowdhury, Joydeep; Bhattacharya, Tara Shankar; Agarwal, Ratnesh; Pal, Tarasankar

    2017-08-05

    Attention has been directed to prepare exclusive one-dimensional silver nanostructure from the linear inorganic polymer AgCN. Successive color change from yellow to orange, to red and finally to green reflects the evolution of high yielding Ag nanorods (NRs) from well-known -[Ag-CN]- chains of polymeric AgCN at room temperature. The parental 1D morphology of AgCN is retained within the as-synthesized Ag NRs. So we could successfully exploit the Ag NR for surface-enhanced Raman scattering (SERS) studies for sensing a popular milk adulterant melamine down to picomolar level. We observed interesting concentration dependent selective SERS band enhancement of melamine. The enhanced ~1327cm-1 SERS signal intensity at lower concentration (10-9 and 10-12M) of melamine speaks for the preferential participation of -C-N of melamine molecule with Ag surface. On the other hand, '-NH2' group together with ring 'N' participation of melamine molecule onto Ag surface suggested an adsorptive stance at higher (10-3-10-7M) concentration range. Thus the binding modes of the molecule at the Ag surface justify its fluxional behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Pitfalls using tyramide signal amplification (TSA) in the mouse gastrointestinal tract: endogenous streptavidin-binding sites lead to false positive staining.

    Science.gov (United States)

    Horling, L; Neuhuber, W L; Raab, M

    2012-02-15

    Highly sensitive immunohistochemical detection systems such as tyramide signal amplification (TSA) are widely used, since they allow using two primary antibodies raised in the same species. Most of them are based on the streptavidin-biotin-peroxidase system and include streptavidin-coupled secondary antibodies. Using TSA in cryostat-sectioned tissues of mouse esophagus, we were puzzled by negative controls with unexpected staining mostly in the ganglionic areas. This prompted us to search for the causing agent and to include also other parts of the mouse gastrointestinal tract for comparison. Streptavidin-coupled antibodies bound to endogenous binding sites yet to be characterized, which are present throughout the mouse intestines. Staining was mainly localized around neuronal cell bodies of enteric ganglia. Thus, caution is warranted when applying streptavidin-coupled antibodies in the mouse gastrointestinal tract. The use of endogenous biotin-blocking kits combined with a prolonged post-fixation time could significantly reduce unintentional staining. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Kresoxim-methyl primes Medicago truncatula plants against abiotic stress factors via altered reactive oxygen and nitrogen species signalling leading to downstream transcriptional and metabolic readjustment.

    Science.gov (United States)

    Filippou, Panagiota; Antoniou, Chrystalla; Obata, Toshihiro; Van Der Kelen, Katrien; Harokopos, Vaggelis; Kanetis, Loukas; Aidinis, Vassilis; Van Breusegem, Frank; Fernie, Alisdair R; Fotopoulos, Vasileios

    2016-03-01

    Biotic and abiotic stresses, such as fungal infection and drought, cause major yield losses in modern agriculture. Kresoxim-methyl (KM) belongs to the strobilurins, one of the most important classes of agricultural fungicides displaying a direct effect on several plant physiological and developmental processes. However, the impact of KM treatment on salt and drought stress tolerance is unknown. In this study we demonstrate that KM pre-treatment of Medicago truncatula plants results in increased protection to drought and salt stress. Foliar application with KM prior to stress imposition resulted in improvement of physiological parameters compared with stressed-only plants. This protective effect was further supported by increased proline biosynthesis, modified reactive oxygen and nitrogen species signalling, and attenuation of cellular damage. In addition, comprehensive transcriptome analysis identified a number of transcripts that are differentially accumulating in drought- and salinity-stressed plants (646 and 57, respectively) after KM pre-treatment compared with stressed plants with no KM pre-treatment. Metabolomic analysis suggests that the priming role of KM in drought- and to a lesser extent in salinity-stressed plants can be attributed to the regulation of key metabolites (including sugars and amino acids) resulting in protection against abiotic stress factors. Overall, the present study highlights the potential use of this commonly used fungicide as a priming agent against key abiotic stress conditions. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. 10 CFR 904.10 - Excess energy.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Excess energy. 904.10 Section 904.10 Energy DEPARTMENT OF ENERGY GENERAL REGULATIONS FOR THE CHARGES FOR THE SALE OF POWER FROM THE BOULDER CANYON PROJECT Power Marketing § 904.10 Excess energy. (a) If excess Energy is determined by the United States to be available...

  1. 7 CFR 985.56 - Excess oil.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Excess oil. 985.56 Section 985.56 Agriculture... HANDLING OF SPEARMINT OIL PRODUCED IN THE FAR WEST Order Regulating Handling Volume Limitations § 985.56 Excess oil. Oil of any class in excess of a producer's applicable annual allotment shall be identified as...

  2. 43 CFR 426.12 - Excess land.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Excess land. 426.12 Section 426.12 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.12 Excess land. (a) The process of designating excess and...

  3. Excess water dynamics in hydrotalcite: QENS study

    Indian Academy of Sciences (India)

    Abstract. Results of the quasi-elastic neutron scattering (QENS) measurements on the dynamics of excess water in hydrotalcite sample with varied content of excess water are reported. Translational motion of excess water can be best described by random transla- tional jump diffusion model. The observed increase in ...

  4. Acetylcholine leads to signal transducer and activator of transcription 1 (STAT-1) mediated oxidative/nitrosative stress in human bronchial epithelial cell line.

    Science.gov (United States)

    Profita, Mirella; Albano, Giusy Daniela; Montalbano, Angela Marina; Di Sano, Caterina; Anzalone, Giulia; Gagliardo, Rosalia; Riccobono, Loredana; Bonanno, Anna; Siena, Liboria; Pieper, Michael Paul; Gjomarkaj, Mark

    2013-12-01

    The induction of nitric oxide synthase (iNOS) expression via the signal transducer and activator of transcription 1 (STAT-1) is involved in the mechanism of oxidative/nitrosative stress. We investigated whether acetylcholine (ACh) generates oxidative/nitrosative stress in bronchial epithelial cells during airway inflammation of COPD and evaluated the effects of Tiotropium, a once-daily antimuscarinic drug, and Olodaterol, a long-acting β2-agonist on these mechanisms. Human bronchial epithelial cells (16-HBE) were stimulated (4h, 37°C) with induced sputum supernatants (ISSs) from healthy controls (HC) (n=10), healthy smokers (HS) (n=10) or COPD patients (n=10), as well as with ACh (from 1μM to 100μM). The activation of STAT-1 pathway (STAT-1Ser727 and STAT-1Tyr701) and iNOS was evaluated in the cell lysates by Western blot analysis as well as nitrotyrosine levels by ELISA, while reactive oxygen species (ROS) were evaluated by flow cytometry. Finally, the effect of Tiotropium (Spiriva®) (100nM), alone or in combination with Olodaterol (1nM), was tested in this model. ISSs from COPD patients significantly increased the phosphorylation of STAT-1Ser727 and STAT-1Tyr701, iNOS and ROS/Nitrotyrosine when compared with ISSs from HC or HS subjects in 16-HBE cells. Furthermore, synthetic ACh increased all these parameters in stimulated 16HBE when compared with untreated cells. Tiotropium and Olodaterol reduced the oxidative/nitrosative stress generated by ACh and ISSs. We concluded that ACh mediated the oxidative/nitrosative stress involving the STAT-1 pathway activation in human bronchial epithelial cells during COPD. β2-Long acting and antimuscarinic drugs, normally used in the treatment of COPD as bronchodilator, might be able to control these cellular events. © 2013 Elsevier B.V. All rights reserved.

  5. Neurotransmitter signalling via NMDA receptors leads to decreased T helper type 1-like and enhanced T helper type 2-like immune balance in humans.

    Science.gov (United States)

    Orihara, Kanami; Odemuyiwa, Solomon O; Stefura, William P; Ilarraza, Ramses; HayGlass, Kent T; Moqbel, Redwan

    2018-03-01

    Given the pivotal roles that CD4 + T cell imbalance plays in human immune disorders, much interest centres on better understanding influences that regulate human helper T-cell subset dominance in vivo. Here, using primary CD4 + T cells and short-term T helper type 1 (Th1) and Th2-like lines, we investigated roles and mechanisms by which neurotransmitter receptors may influence human type 1 versus type 2 immunity. We hypothesized that N-methyl-d-aspartate receptors (NMDA-R), which play key roles in memory and learning, can also regulate human CD4 + T cell function through induction of excitotoxicity. Fresh primary CD4 + T cells from healthy donors express functional NMDA-R that are strongly up-regulated upon T cell receptor (TCR) mediated activation. Synthetic and physiological NMDA-R agonists elicited Ca 2+ flux and led to marked inhibition of type 1 but not type 2 or interleukin-10 cytokine responses. Among CD4 + lines, NMDA and quinolinic acid preferentially reduced cytokine production, Ca 2+ flux, proliferation and survival of Th1-like cells through increased induction of cell death whereas Th2-like cells were largely spared. Collectively, the findings demonstrate that (i) NMDA-R is rapidly up-regulated upon CD4 + T cell activation in humans and (ii) Th1 versus Th2 cell functions such as proliferation, cytokine production and cell survival are differentially affected by NMDA-R agonists. Differential cytokine production and proliferative capacity of Th1 versus Th2 cells is attributable in part to increased physiological cell death among fully committed Th1 versus Th2 cells, leading to increased Th2-like dominance. Hence, excitotoxicity, beyond its roles in neuronal plasticity, may contribute to ongoing modulation of human T cell responses. © 2017 John Wiley & Sons Ltd.

  6. Conciliating SUSY with the Z-peaked excess

    Directory of Open Access Journals (Sweden)

    Mitsou Vasiliki A.

    2016-01-01

    Full Text Available The ATLAS experiment observed an excess at the 3σ level in the channel of Z boson, jets and high missing transverse momentum in the full 2012 dataset at 8 TeV while searching for SUSY. The question arises whether the abundance and the kinematical features of this excess are compatible with the yet unconstrained supersymmetric realm, respecting at the same time the measured Higgs boson properties and dark matter density. By trying to explain this signal with SUSY we find that only relatively light gluinos together with a heavy neutralino NLSP decaying predominantly to a Z boson plus a light gravitino could reproduce the excess. We construct an explicit general gauge mediation model able to match the observed signal. More sophisticated models could also reproduce the signal, as long as it features light gluinos, or heavy particles with a strong production cross section, producing at least one Z boson in its decay chain. The implications of our findings for the Run II at LHC with the scaling on the Z peak, as well as for the direct search of gluinos and other SUSY particles, are also discussed.

  7. Sleepiness or excessive daytime somnolence.

    Science.gov (United States)

    Edd, Ethel Mitty; Flores, Sandi

    2009-01-01

    Excessive daytime somnolence (EDS) is associated with age-related changes, environment, circadian rhythm or sleep pattern disorder, insomnia, medications, lifestyle factors, depression, pain, and illness. The notion of "sleep architecture" connotes a structure that describes the sleep cycle (i.e., stages) and wakefulness during a single sleep period-that is, rapid eye movement (REM) and non-REM sleep. Circadian rhythms perform a variety of functions including regulation of the quality and distribution of the stages of sleep. Insomnia includes delayed sleep onset as well as premature wakening; sleep is nonrestorative. Comorbidities associated with insomnia are Alzheimer's disease and other dementias, delirium, depression, congestive heart failure, chronic obstructive pulmonary disease, gastroesophageal reflux disease, pain, degenerative diseases of the neurological system, and sleep apnea. Continuous inadequate sleep affects cognitive function, physical performance, overall well-being, and quality of life. There is a greater risk of falls from insomnia than is the use of hypnotics to manage it. Sleep disruption among older adults is underrecognized and undertreated. Assessment using valid tools can be performed rapidly. There are a variety of treatment options, including sleep hygiene and pharmacological and alternative modalities.

  8. Lead poisoning

    Science.gov (United States)

    ... or dust from lead-based paint. Toys and furniture painted before 1976. Painted toys and decorations made ... by decades of car exhaust or years of house paint scrapings. Lead is more common in soil ...

  9. Lead Poisoning

    Science.gov (United States)

    ... a hard, durable surface. In 1977, federal regulations banned lead from paint for general use. But homes ... OTHERS: Lead has recently been found in some plastic mini-blinds and vertical blinds which were made ...

  10. 75 FR 27572 - Monthly Report of Excess Income and Annual Report of Uses of Excess Income

    Science.gov (United States)

    2010-05-17

    ... URBAN DEVELOPMENT Monthly Report of Excess Income and Annual Report of Uses of Excess Income AGENCY... subject proposal. Project owners are permitted to retain Excess Income for projects under terms and conditions established by HUD. Owners must request to retain some or all of their Excess Income. The request...

  11. Relational Leading

    DEFF Research Database (Denmark)

    Larsen, Mette Vinther; Rasmussen, Jørgen Gulddahl

    2015-01-01

    This first chapter presents the exploratory and curious approach to leading as relational processes – an approach that pervades the entire book. We explore leading from a perspective that emphasises the unpredictable challenges and triviality of everyday life, which we consider an interesting......, relevant and realistic way to examine leading. The chapter brings up a number of concepts and contexts as formulated by researchers within the field, and in this way seeks to construct a first understanding of relational leading....

  12. Mechanisms linking excess adiposity and carcinogenesis promotion

    Directory of Open Access Journals (Sweden)

    Ana I. Pérez-Hernández

    2014-05-01

    Full Text Available Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well-established for several tumor types, such as breast cancer in postmenopausal women, colorectal and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15-20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: i inflammatory changes leading to macrophage polarization and altered adipokine profile; ii insulin resistance development; and iii adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases.

  13. Mechanisms Linking Excess Adiposity and Carcinogenesis Promotion

    Science.gov (United States)

    Pérez-Hernández, Ana I.; Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2014-01-01

    Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well established for several tumor types, such as breast cancer in post-menopausal women, colorectal, and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15–20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: (i) inflammatory changes leading to macrophage polarization and altered adipokine profile; (ii) insulin resistance development; and (iii) adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases. PMID:24829560

  14. Fetal Programming of Obesity: Maternal Obesity and Excessive Weight Gain

    Directory of Open Access Journals (Sweden)

    Seray Kabaran

    2014-10-01

    Full Text Available The prevalence of obesity is an increasing health problem throughout the world. Maternal pre-pregnancy weight, maternal nutrition and maternal weight gain are among the factors that can cause childhood obesity. Both maternal obesity and excessive weight gain increase the risks of excessive fetal weight gain and high birth weight. Rapid weight gain during fetal period leads to changes in the newborn body composition. Specifically, the increase in body fat ratio in the early periods is associated with an increased risk of obesity in the later periods. It was reported that over-nutrition during fetal period could cause excessive food intake during postpartum period as a result of metabolic programming. By influencing the fetal metabolism and tissue development, maternal obesity and excessive weight gain change the amounts of nutrients and metabolites that pass to the fetus, thus causing excessive fetal weight gain which in turn increases the risk of obesity. Fetal over-nutrition and excessive weight gain cause permanent metabolic and physiologic changes in developing organs. While mechanisms that affect these organs are not fully understood, it is thought that the changes may occur as a result of the changes in fetal energy metabolism, appetite control, neuroendocrine functions, adipose tissue mass, epigenetic mechanisms and gene expression. In this review article, the effects of maternal body weight and weight gain on fetal development, newborn birth weight and risk of obesity were evaluated, and additionally potential mechanisms that can explain the effects of fetal over-nutrition on the risk of obesity were investigated [TAF Prev Med Bull 2014; 13(5.000: 427-434

  15. Excessive recreational computer use and food consumption behaviour among adolescents

    Directory of Open Access Journals (Sweden)

    Mao Yuping

    2010-08-01

    Full Text Available Abstract Introduction Using the 2005 California Health Interview Survey (CHIS data, we explore the association between excessive recreational computer use and specific food consumption behavior among California's adolescents aged 12-17. Method The adolescent component of CHIS 2005 measured the respondents' average number of hours spent on viewing TV on a weekday, the average number of hours spent on viewing TV on a weekend day, the average number of hours spent on playing with a computer on a weekday, and the average number of hours spent on playing with computers on a weekend day. We recode these four continuous variables into four variables of "excessive media use," and define more than three hours of using a medium per day as "excessive." These four variables are then used in logistic regressions to predict different food consumption behaviors on the previous day: having fast food, eating sugary food more than once, drinking sugary drinks more than once, and eating more than five servings of fruits and vegetables. We use the following variables as covariates in the logistic regressions: age, gender, race/ethnicity, parental education, household poverty status, whether born in the U.S., and whether living with two parents. Results Having fast food on the previous day is associated with excessive weekday TV viewing (O.R. = 1.38, p Conclusion Excessive recreational computer use independently predicts undesirable eating behaviors that could lead to overweight and obesity. Preventive measures ranging from parental/youth counseling to content regulations might be addressing the potential undesirable influence from excessive computer use on eating behaviors among children and adolescents.

  16. Excessive libido in a woman with rabies.

    OpenAIRE

    Dutta, J. K.

    1996-01-01

    Rabies is endemic in India in both wildlife and humans. Human rabies kills 25,000 to 30,000 persons every year. Several types of sexual manifestations including excessive libido may develop in cases of human rabies. A laboratory proven case of rabies in an Indian woman who manifested excessive libido is presented below. She later developed hydrophobia and died.

  17. Bladder calculus presenting as excessive masturbation.

    Science.gov (United States)

    De Alwis, A C D; Senaratne, A M R D; De Silva, S M P D; Rodrigo, V S D

    2006-09-01

    Masturbation in childhood is a normal behaviour which most commonly begins at 2 months of age, and peaks at 4 years and in adolescence. However excessive masturbation causes anxiety in parents. We describe a boy with a bladder calculus presenting as excessive masturbation.

  18. 30 CFR 57.6902 - Excessive temperatures.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Excessive temperatures. 57.6902 Section 57.6902... Requirements-Surface and Underground § 57.6902 Excessive temperatures. (a) Where heat could cause premature... shall— (1) Measure an appropriate number of blasthole temperatures in order to assess the specific mine...

  19. 30 CFR 56.6902 - Excessive temperatures.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Excessive temperatures. 56.6902 Section 56.6902... Requirements § 56.6902 Excessive temperatures. (a) Where heat could cause premature detonation, explosive... an appropriate number of blasthole temperatures in order to assess the specific mine conditions prior...

  20. Excess Based Allocation of Risk Capital

    NARCIS (Netherlands)

    van Gulick, G.; De Waegenaere, A.M.B.; Norde, H.W.

    2010-01-01

    In this paper we propose a new rule to allocate risk capital to portfolios or divisions within a firm. Specifically, we determine the capital allocation that minimizes the excesses of sets of portfolios in lexicographical sense. The excess of a set of portfolios is defined as the expected loss of

  1. The excessively crying infant : etiology and treatment

    NARCIS (Netherlands)

    Akhnikh, S.; Engelberts, A.C.; Sleuwen, B.E. van; Hoir, M.P. L’; Benninga, M.A.

    2014-01-01

    Excessive crying, often described as infantile colic, is the cause of 10% to 20% of all early pediatrician visits of infants aged 2 weeks to 3 months. Although usually benign and selflimiting, excessive crying is associated with parental exhaustion and stress. However, and underlying organic cause

  2. Triboson interpretations of the ATLAS diboson excess

    CERN Document Server

    Aguilar-Saavedra, J.A.

    2015-01-01

    The ATLAS excess in fat jet pair production is kinematically compatible with the decay of a heavy resonance into two gauge bosons plus an extra particle. This possibility would explain the absence of such a localised excess in the analogous CMS analysis of fat dijet final states, as well as the negative results of diboson resonance searches in the semi-leptonic decay modes.

  3. Lead Toxicity

    Science.gov (United States)

    ... blue-gray metal that is mined from the earth’s crust. • Lead has been used for many industrial ... including the kidneys, heart, and reproductive system, • Pregnant women should know that the developing fetus is very ...

  4. Lead Poisoning

    Science.gov (United States)

    ... has also been associated with juvenile delinquency and criminal behavior. In adults, lead can increase blood pressure ... and-forth manner, but rather from left to right (or vise-versa), or from the top of ...

  5. Lead Test

    Science.gov (United States)

    ... poison you. Most lead is present as an inorganic compound and does not move well through the ... D. R., Editors (© 2006). Contemporary Practice in Clinical Chemistry: AACC Press, Washington, DC. Pp 474. Wu, A. (© ...

  6. Can we determine what controls the spatio-temporal distribution of d-excess and 17O-excess in precipitation using the LMDZ general circulation model?

    Directory of Open Access Journals (Sweden)

    C. Risi

    2013-09-01

    Full Text Available Combined measurements of the H218O and HDO isotopic ratios in precipitation, leading to second-order parameter D-excess, have provided additional constraints on past climates compared to the H218O isotopic ratio alone. More recently, measurements of H217O have led to another second-order parameter: 17O-excess. Recent studies suggest that 17O-excess in polar ice may provide information on evaporative conditions at the moisture source. However, the processes controlling the spatio-temporal distribution of 17O-excess are still far from being fully understood. We use the isotopic general circulation model (GCM LMDZ to better understand what controls d-excess and 17O-excess in precipitation at present-day (PD and during the last glacial maximum (LGM. The simulation of D-excess and 17O-excess is evaluated against measurements in meteoric water, water vapor and polar ice cores. A set of sensitivity tests and diagnostics are used to quantify the relative effects of evaporative conditions (sea surface temperature and relative humidity, Rayleigh distillation, mixing between vapors from different origins, precipitation re-evaporation and supersaturation during condensation at low temperature. In LMDZ, simulations suggest that in the tropics convective processes and rain re-evaporation are important controls on precipitation D-excess and 17O-excess. In higher latitudes, the effect of distillation, mixing between vapors from different origins and supersaturation are the most important controls. For example, the lower d-excess and 17O-excess at LGM simulated at LGM are mainly due to the supersaturation effect. The effect of supersaturation is however very sensitive to a parameter whose tuning would require more measurements and laboratory experiments. Evaporative conditions had previously been suggested to be key controlling factors of d-excess and 17O-excess, but LMDZ underestimates their role. More generally, some shortcomings in the simulation of 17O-excess

  7. Antiaging Properties of a Grape-Derived Antioxidant Are Regulated by Mitochondrial Balance of Fusion and Fission Leading to Mitophagy Triggered by a Signaling Network of Sirt1-Sirt3-Foxo3-PINK1-PARKIN

    Directory of Open Access Journals (Sweden)

    Somak Das

    2014-01-01

    Full Text Available It was proposed that resveratrol, a polyphenolic antioxidant and a calorie restriction mimetic could promote longevity but subsequent studies could not prove this. The original proposal was based on the fact that a grape-derived antioxidant could activate the antiaging gene Sirt1. Most studies agree that indeed grape activates Sirt1, but a question remains whether Sirt1 is the cause or consequence of resveratrol treatment. Subsequently, mitochondrial Sirt3 was found to be activated. The present study on ischemic reperfusion (I/R in rat hearts demonstrates that Foxo3a is activated subsequent to Sirt3 activation, which then activates PINK1. PINK1 potentiates activation of PARKIN leading to the activation of mitochondrial fission and mitophagy. Confocal microscopy conclusively shows the coexistence of Sirt3 with Foxo3a and Foxo3a with PINK1 and PARKIN. Mitophagy was demonstrated both by confocal microscopy and transmission electron microscopy. Western blot analyses data are consistent with the results of confocal microscopy. It appears that the grape-derived antioxidant modifies the intracellular environment by changing the oxidizing milieu into a reducing milieu and upregulating intracellular glutathione, potentiates a signal transduction cascade consisting of Sirt1/Sirt3-Foxo3a-PINK1-PARKIN-mitochondrial fusion fission-mitophagy that leads to cardioprotection, and paves the way to an anti-aging environment.

  8. Excessive crying: behavioral and emotional regulation disorder in infancy

    Directory of Open Access Journals (Sweden)

    Joon Sik Kim

    2011-06-01

    Full Text Available In the pediatric literature, excessive crying has been reported solely in association with 3-month colic and is described, if at all, as unexplained crying and fussing during the first 3 months of life. The bouts of crying are generally thought to be triggered by abdominal colic (over-inflation of the still immature gastrointestinal tract, and treatment is prescribed accordingly. According to this line of reasoning, excessive crying is harmless and resolves by the end of the third month without long-term consequences. However, there is evidence that it may cause tremendous distress in the mother&#8211;infant relationship, and can lead to disorders of behavioral and emotional regulation at the toddler stage (such as sleep and feeding disorders, chronic fussiness, excessive clinginess, and temper tantrums. Early treatment of excessive crying focuses on parent&#8211;infant communication, and parent-infant interaction in the context of soothing and settling the infant to sleep is a promising approach that may prevent later behavioral and emotional disorders in infancy.

  9. 26 CFR 54.4979-1 - Excise tax on certain excess contributions and excess aggregate contributions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Excise tax on certain excess contributions and excess aggregate contributions. 54.4979-1 Section 54.4979-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4979-1 Excise tax on certain excess...

  10. Ecotoxicology: Lead

    Science.gov (United States)

    Scheuhammer, A.M.; Beyer, W.N.; Schmitt, C.J.; Jorgensen, Sven Erik; Fath, Brian D.

    2008-01-01

    Lead (Pb) is a naturally occurring metallic element; trace concentrations are found in all environmental media and in all living things. However, certain human activities, especially base metal mining and smelting; combustion of leaded gasoline; the use of Pb in hunting, target shooting, and recreational angling; the use of Pb-based paints; and the uncontrolled disposal of Pb-containing products such as old vehicle batteries and electronic devices have resulted in increased environmental levels of Pb, and have created risks for Pb exposure and toxicity in invertebrates, fish, and wildlife in some ecosystems.

  11. Predictors of excessive use of social media and excessive online gaming in Czech teenagers.

    Science.gov (United States)

    Spilková, Jana; Chomynová, Pavla; Csémy, Ladislav

    2017-12-01

    Background and aims Young people's involvement in online gaming and the use of social media are increasing rapidly, resulting in a high number of excessive Internet users in recent years. The objective of this paper is to analyze the situation of excessive Internet use among adolescents in the Czech Republic and to reveal determinants of excessive use of social media and excessive online gaming. Methods Data from secondary school students (N = 4,887) were collected within the 2015 European School Survey Project on Alcohol and Other Drugs. Logistic regression models were constructed to describe the individual and familial discriminative factors and the impact of the health risk behavior of (a) excessive users of social media and (b) excessive players of online games. Results The models confirmed important gender-specific distinctions - while girls are more prone to online communication and social media use, online gaming is far more prevalent among boys. The analysis did not indicate an influence of family composition on both the excessive use of social media and on excessive online gaming, and only marginal effects for the type of school attended. We found a connection between the excessive use of social media and binge drinking and an inverse relation between excessive online gaming and daily smoking. Discussion and conclusion The non-existence of significant associations between family environment and excessive Internet use confirmed the general, widespread of this phenomenon across the social and economic strata of the teenage population, indicating a need for further studies on the topic.

  12. Explaining CMS lepton excesses with supersymmetry

    CERN Multimedia

    CERN. Geneva; Prof. Allanach, Benjamin

    2014-01-01

    1) Kostas Theofilatos will give an introduction to CMS result 2) Ben Allanach: Several CMS analyses involving di-leptons have recently reported small 2.4-2.8 sigma local excesses: nothing to get too excited about, but worth keeping an eye on nonetheless. In particular, a search in the $lljj p_T$(miss) channel, a search for $W_R$ in the $lljj$ channel and a di-leptoquark search in the $lljj$ channel and $ljj p_T$(miss) channel have all yielded small excesses. We interpret the first excess in the MSSM, showing that the interpretation is viable in terms of other constraints, despite only having squark masses of around 1 TeV. We can explain the last three excesses with a single R-parity violating coupling that predicts a non-zero contribution to the neutrinoless double beta decay rate.

  13. Prevention of modern teenager's computer excessive gambling

    OpenAIRE

    Shamsutdinova, D.

    2011-01-01

    This article is devoted to the prevention of young people's excessive gambling. The article organized and convincingly derived the prevention strategies dependent gaming behavior among young people and teenagers.

  14. Excessive deforestation of Gishwati Mountainous forest ...

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

    sigp1. Excessive deforestation of Gishwati. Mountainous forest & biodiversity changes. Introduction. The Change in Forest cover in. Rwanda is result of the high growth of population density. The latter has doubled between 1978 and 2002. Over.

  15. Leading men

    DEFF Research Database (Denmark)

    Bekker-Nielsen, Tønnes

    2016-01-01

    Through a systematic comparison of c. 50 careers leading to the koinarchate or high priesthood of Asia, Bithynia, Galatia, Lycia, Macedonia and coastal Pontus, as described in funeral or honorary inscriptions of individual koinarchs, it is possible to identify common denominators but also disting...

  16. Purinergic signaling in kidney disease.

    Science.gov (United States)

    Menzies, Robert I; Tam, Frederick W; Unwin, Robert J; Bailey, Matthew A

    2017-02-01

    Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function. Renal cells also express ectonucleotidases that rapidly hydrolyze extracellular nucleotides. These enzymes integrate this multireceptor purinergic-signaling complex by determining the nucleotide milieu to titrate receptor activation. Purinergic signaling also regulates immune cell function by modulating the synthesis and release of various cytokines such as IL1-β and IL-18 as part of inflammasome activation. Abnormal or excessive stimulation of this intricate paracrine system can be pro- or anti-inflammatory, and is also linked to necrosis and apoptosis. Kidney tissue injury causes a localized increase in ATP concentration, and sustained activation of P2 receptors can lead to renal glomerular, tubular, and vascular cell damage. Purinergic receptors also regulate the activity and proliferation of fibroblasts, promoting both inflammation and fibrosis in chronic disease. In this short review we summarize some of the recent findings related to purinergic signaling in the kidney. We focus predominantly on the P2X7 receptor, discussing why antagonists have so far disappointed in clinical trials and how advances in our understanding of purinergic signaling might help to reposition these compounds as potential treatments for renal disease. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2017-03-01

    of SM and LPC and the amount of alcohol consumption during the past month. The proposal has both scientific and practical significance in... alcohol use (EAU). Drinking becomes excessive when it causes or elevates the risk for alcohol -related problems or complicates the management of other...the quantity of alcohol consumption during the past month. 2. KEYWORDS: Excessive alcohol use, lipidomics, timeline follow back 3. ACCOMPLISHMENTS

  18. Romanian welfare state between excess and failure

    Directory of Open Access Journals (Sweden)

    Cristina Ciuraru-Andrica

    2012-12-01

    Full Text Available Timely or not, our issue can bring back to life some prolific discussions, sometimes diametrical. We strike the social assistance, where, at this moment, is still uncertain if, once unleashed the excess, the failure will come inevitably or there is a “Salvation Ark”. However, the difference between the excess and the failure of the welfare state is almost intangible, the reason of his potential failure being actually the abuses made until the start of depression.

  19. Organizational Inertia and Excessive Product Proliferation

    OpenAIRE

    Sakuraki, Rie

    2015-01-01

    This study investigates the internal factors of excessive product proliferation. Since empirical literature on product over-proliferation focused on how to optimize existing product portfolio, the causes of excessive product proliferation have so far attracted little attention. This study employs a case study of Shiseido, a famous Japanese cosmetics company, with particular attention to product proliferation in the Shiseido chain store channel, because external factors are mostly absent from ...

  20. Avian Reovirus Protein p17 Functions as a Nucleoporin Tpr Suppressor Leading to Activation of p53, p21 and PTEN and Inactivation of PI3K/AKT/mTOR and ERK Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Wei-Ru Huang

    Full Text Available Avian reovirus (ARV protein p17 has been shown to regulate cell cycle and autophagy by activation of p53/PTEN pathway; nevertheless, it is still unclear how p53 and PTEN are activated by p17. Here, we report for the first time that p17 functions as a nucleoporin Tpr suppressor that leads to p53 nuclear accumulation and consequently activates p53, p21, and PTEN. The nuclear localization signal (119IAAKRGRQLD128 of p17 has been identified for Tpr binding. This study has shown that Tpr suppression occurs by p17 interacting with Tpr and by reducing the transcription level of Tpr, which together inhibit Tpr function. In addition to upregulation of PTEN by activation of p53 pathway, this study also suggests that ARV protein p17 acts as a positive regulator of PTEN. ARV p17 stabilizes PTEN by stimulating phosphorylation of cytoplasmic PTEN and by elevating Rak-PTEN association to prevent it from E3 ligase NEDD4-1 targeting. To activate PTEN, p17 is able to promote β-arrestin-mediated PTEN translocation from the cytoplasm to the plasma membrane via a Rock-1-dependent manner. The accumulation of p53 in the nucleus induces the PTEN- and p21-mediated downregulation of cyclin D1 and CDK4. Furthermore, Tpr and CDK4 knockdown increased virus production in contrast to depletion of p53, PTEN, and LC3 reducing virus yield. Taken together, our data suggest that p17-mediated Tpr suppression positively regulates p53, PTEN, and p21 and negatively regulates PI3K/AKT/mTOR and ERK signaling pathways, both of which are beneficial for virus replication.

  1. Effects of excessive Internet use on undergraduate students in Pakistan.

    Science.gov (United States)

    Suhail, Kausar; Bargees, Zobia

    2006-06-01

    This study was undertaken to investigate the positive and negative effects of excessive Internet use on undergraduate students. The Internet Effect Scale (IES), especially constructed by the authors to determine these effects, consisted of seven dimensions namely: behavioral problems, interpersonal problems, educational problems, psychological problems, physical problems, Internet abuse, and positive effects. The sample consisted of 200 undergraduate students studying at the GC University Lahore, Pakistan. A set of Pearson Product Moment correlations showed positive associations between time spent on the Internet and various dimensions of the IES indicating that excessive Internet use can lead to a host of problems of educational, physical, psychological and interpersonal nature. However, a greater number of students reported positive than negative effects of Internet use. Without negating the advantages of Internet, the current findings suggest that Internet use should be within reasonable limits focusing more on activities enhancing one's productivity.

  2. The Diboson Excess: Experimental Situation and Classification of Explanations; A Les Houches Pre-Proceeding

    CERN Document Server

    Brehmer, Johann; Cacciapaglia, Giacomo; Carmona, Adrian; Chivukula, R.Sekhar; Delgado, Antonio; Goertz, Florian; Hewett, JoAnne L.; Katz, Andrey; Kopp, Joachim; Lane, Kenneth; Martin, Adam; Mohan, Kirtimaan; Morse, David M.; Nardecchia, Marco; No, Jose Miguel; Oliveira, Alexandra; Pollard, Chris; Quiros, Mariano; Rizzo, Thomas G.; Santiago, Jose; Sanz, Veronica; Simmons, Elizabeth H.; Tattersall, Jamie

    2015-01-01

    We examine the `diboson' excess at $\\sim 2$ TeV seen by the LHC experiments in various channels. We provide a comparison of the excess significances as a function of the mass of the tentative resonance and give the signal cross sections needed to explain the excesses. We also present a survey of available theoretical explanations of the resonance, classified in three main approaches. Beyond that, we discuss methods to verify the anomaly, determining the major properties of the various surpluses and exploring how different models can be discriminated. Finally, we give a tabular summary of the numerous explanations, presenting their main phenomenological features.

  3. Aluminium-induced excessive ROS causes cellular damage and metabolic shifts in black gram Vigna mungo (L.) Hepper.

    Science.gov (United States)

    Chowra, Umakanta; Yanase, Emiko; Koyama, Hiroyuki; Panda, Sanjib Kumar

    2017-01-01

    Aluminium-induced oxidative damage caused by excessive ROS production was evaluated in black gram pulse crop. Black gram plants were treated with different aluminium (Al3+) concentrations (10, 50 and 100 μM with pH 4.7) and further the effects of Al3+ were characterised by means of root growth inhibition, histochemical assay, ROS content analysis, protein carbonylation quantification and 1H-NMR analysis. The results showed that aluminium induces excessive ROS production which leads to cellular damage, root injury, stunt root growth and other metabolic shifts. In black gram, Al3+ induces cellular damage at the earliest stage of stress which was characterised from histochemical analysis. From this study, it was observed that prolonged stress can activate certain aluminium detoxification defence mechanism. Probably excessive ROS triggers such defence mechanism in black gram. Al3+ can induce excessive ROS initially in the root region then transported to other parts of the plant. As much as the Al3+ concentration increases, the rate of cellular injury and ROS production also increases. But after 72 h of stress, plants showed a lowered ROS level and cellular damage which indicates the upregulation of defensive mechanisms. Metabolic shift analysis also showed that the black gram plant under stress has less metabolic content after 24 h of treatment, but gradually, it was increased after 72 h of treatment. It was assumed that ROS played the most important role as a signalling molecule for aluminium stress in black gram.

  4. Impact of Nutrient Imbalance on Wine Alcoholic Fermentations: Nitrogen Excess Enhances Yeast Cell Death in Lipid-Limited Must

    Science.gov (United States)

    Tesnière, Catherine; Delobel, Pierre; Pradal, Martine; Blondin, Bruno

    2013-01-01

    We evaluated the consequences of nutritional imbalances, particularly lipid/nitrogen imbalances, on wine yeast survival during alcoholic fermentation. We report that lipid limitation (ergosterol limitation in our model) led to a rapid loss of viability during the stationary phase of fermentation and that the cell death rate is strongly modulated by nitrogen availability and nature. Yeast survival was reduced in the presence of excess nitrogen in lipid-limited fermentations. The rapidly dying yeast cells in fermentations in high nitrogen and lipid-limited conditions displayed a lower storage of the carbohydrates trehalose and glycogen than observed in nitrogen-limited cells. We studied the cell stress response using HSP12 promoter-driven GFP expression as a marker, and found that lipid limitation triggered a weaker stress response than nitrogen limitation. We used a SCH9-deleted strain to assess the involvement of nitrogen signalling pathways in the triggering of cell death. Deletion of SCH9 increased yeast viability in the presence of excess nitrogen, indicating that a signalling pathway acting through Sch9p is involved in this nitrogen-triggered cell death. We also show that various nitrogen sources, but not histidine or proline, provoked cell death. Our various findings indicate that lipid limitation does not elicit a transcriptional programme that leads to a stress response protecting yeast cells and that nitrogen excess triggers cell death by modulating this stress response, but not through HSP12. These results reveal a possibly negative role of nitrogen in fermentation, with reported effects referring to ergosterol limitation conditions. These effects should be taken into account in the management of alcoholic fermentations. PMID:23658613

  5. Impact of nutrient imbalance on wine alcoholic fermentations: nitrogen excess enhances yeast cell death in lipid-limited must.

    Directory of Open Access Journals (Sweden)

    Catherine Tesnière

    Full Text Available We evaluated the consequences of nutritional imbalances, particularly lipid/nitrogen imbalances, on wine yeast survival during alcoholic fermentation. We report that lipid limitation (ergosterol limitation in our model led to a rapid loss of viability during the stationary phase of fermentation and that the cell death rate is strongly modulated by nitrogen availability and nature. Yeast survival was reduced in the presence of excess nitrogen in lipid-limited fermentations. The rapidly dying yeast cells in fermentations in high nitrogen and lipid-limited conditions displayed a lower storage of the carbohydrates trehalose and glycogen than observed in nitrogen-limited cells. We studied the cell stress response using HSP12 promoter-driven GFP expression as a marker, and found that lipid limitation triggered a weaker stress response than nitrogen limitation. We used a SCH9-deleted strain to assess the involvement of nitrogen signalling pathways in the triggering of cell death. Deletion of SCH9 increased yeast viability in the presence of excess nitrogen, indicating that a signalling pathway acting through Sch9p is involved in this nitrogen-triggered cell death. We also show that various nitrogen sources, but not histidine or proline, provoked cell death. Our various findings indicate that lipid limitation does not elicit a transcriptional programme that leads to a stress response protecting yeast cells and that nitrogen excess triggers cell death by modulating this stress response, but not through HSP12. These results reveal a possibly negative role of nitrogen in fermentation, with reported effects referring to ergosterol limitation conditions. These effects should be taken into account in the management of alcoholic fermentations.

  6. Who Leads China's Leading Universities?

    Science.gov (United States)

    Huang, Futao

    2017-01-01

    This study attempts to identify the major characteristics of two different groups of institutional leaders in China's leading universities. The study begins with a review of relevant literature and theory. Then, there is a brief introduction to the selection of party secretaries, deputy secretaries, presidents and vice presidents in leading…

  7. Magnesium Diboride Current Leads

    Science.gov (United States)

    Panek, John

    2010-01-01

    A recently discovered superconductor, magnesium diboride (MgB2), can be used to fabricate conducting leads used in cryogenic applications. Dis covered to be superconducting in 2001, MgB2 has the advantage of remaining superconducting at higher temperatures than the previously used material, NbTi. The purpose of these leads is to provide 2 A of electricity to motors located in a 1.3 K environment. The providing environment is a relatively warm 17 K. Requirements for these leads are to survive temperature fluctuations in the 5 K and 11 K heat sinks, and not conduct excessive heat into the 1.3 K environment. Test data showed that each lead in the assembly could conduct 5 A at 4 K, which, when scaled to 17 K, still provided more than the required 2 A. The lead assembly consists of 12 steelclad MgB2 wires, a tensioned Kevlar support, a thermal heat sink interface at 4 K, and base plates. The wires are soldered to heavy copper leads at the 17 K end, and to thin copper-clad NbTi leads at the 1.3 K end. The leads were designed, fabricated, and tested at the Forschungszentrum Karlsruhe - Institut foer Technische Physik before inclusion in Goddard's XRS (X-Ray Spectrometer) instrument onboard the Astro-E2 spacecraft. A key factor is that MgB2 remains superconducting up to 30 K, which means that it does not introduce joule heating as a resistive wire would. Because the required temperature ranges are 1.3-17 K, this provides a large margin of safety. Previous designs lost superconductivity at around 8 K. The disadvantage to MgB2 is that it is a brittle ceramic, and making thin wires from it is challenging. The solution was to encase the leads in thin steel tubes for strength. Previous designs were so brittle as to risk instrument survival. MgB2 leads can be used in any cryogenic application where small currents need to be conducted at below 30 K. Because previous designs would superconduct only at up to 8 K, this new design would be ideal for the 8-30 K range.

  8. Antidepressant induced excessive yawning and indifference

    Directory of Open Access Journals (Sweden)

    Bruno Palazzo Nazar

    2015-03-01

    Full Text Available Introduction Antidepressant induced excessive yawning has been described as a possible side effect of pharmacotherapy. A syndrome of indifference has also been described as another possible side effect. The frequency of those phenomena and their physiopathology are unknown. They are both considered benign and reversible after antidepressant discontinuation but severe cases with complications as temporomandibular lesions, have been described. Methods We report two unprecedented cases in which excessive yawning and indifference occurred simultaneously as side effects of antidepressant therapy, discussing possible physiopathological mechanisms for this co-occurrence. Case 1: A male patient presented excessive yawning (approximately 80/day and apathy after venlafaxine XR treatment. Symptoms reduced after a switch to escitalopram, with a reduction to 50 yawns/day. Case 2: A female patient presented excessive yawning (approximately 25/day and inability to react to environmental stressors with desvenlafaxine. Conclusion Induction of indifference and excessive yawning may be modulated by serotonergic and noradrenergic mechanisms. One proposal to unify these side effects would be enhancement of serotonin in midbrain, especially paraventricular and raphe nucleus.

  9. Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

    Science.gov (United States)

    Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

    2017-01-01

    Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

  10. Limiting law excess sum rule for polyelectrolytes.

    Science.gov (United States)

    Landy, Jonathan; Lee, YongJin; Jho, YongSeok

    2013-11-01

    We revisit the mean-field limiting law screening excess sum rule that holds for rodlike polyelectrolytes. We present an efficient derivation of this law that clarifies its region of applicability: The law holds in the limit of small polymer radius, measured relative to the Debye screening length. From the limiting law, we determine the individual ion excess values for single-salt electrolytes. We also consider the mean-field excess sum away from the limiting region, and we relate this quantity to the osmotic pressure of a dilute polyelectrolyte solution. Finally, we consider numerical simulations of many-body polymer-electrolyte solutions. We conclude that the limiting law often accurately describes the screening of physical charged polymers of interest, such as extended DNA.

  11. Segmental neurofibromatosis presenting with congenital excessive skin folds.

    Science.gov (United States)

    Helfand, Alexander M; Nouriel, Ariella; Zisquit, Jonah; Barzilai, Aviv; Greenberger, Shoshana

    2015-04-01

    Segmental neurofibromatosis (SNF) is a rare type of neurofibromatosis (NF-1) resulting from post-zygotic somatic mutations in the neurofibromin gene that leads to mosaicism. Reported manifestations of SNF include neurofibromas, freckling, or café-au-lait spots limited to a single body region or limb. We present a 5-month-old male referred to our clinic for evaluation of congenital excessive skin folds on the back. A mildly erythematous, poorly demarcated soft plaque was noted, consisting of excessive skin folds. A cluster of light brown hyperpigmented macules was seen overlying the plaque. A punch biopsy of the plaque confirmed a diagnosis of neurofibroma. Further investigation ruled out other manifestations of NF-1. The early onset of our patient's neurofibroma and its gross appearance with redundant skin folds are all unusual features. To our knowledge, congenital excessive skin folds found in a single tumor have not been previously described in the literature as a manifestation of SNF. Clinicians should be educated about the possibility of congenital localized skin folds in association with SNF in order to identify the disease in infancy and monitor any changes in neurofibroma pathology.

  12. Periods of Excess Energy in Extreme Weather Events

    Directory of Open Access Journals (Sweden)

    Igor G. Zurbenko

    2013-01-01

    Full Text Available The reconstruction of periodic signals that are embedded in noise is a very important task in many applications. This already difficult task is even more complex when some observations are missed or some are presented irregularly in time. Kolmogorov-Zurbenko (KZ filtration, a well-developed method, offers a solution to this problem. One section of this paper provides examples of very precise reconstructions of multiple periodic signals covered with high level noise, noise levels that make those signals invisible within the original data. The ability to reconstruct signals from noisy data is applied to the numerical reconstruction of tidal waves in atmospheric pressure. The existence of such waves was proved by well-known naturalist Chapman, but due to the high synoptic fluctuation in atmospheric pressure he was unable to numerically reproduce the waves. Reconstruction of the atmospheric tidal waves reveals a potential intensification on wind speed during hurricanes, which could increase the danger imposed by hurricanes. Due to the periodic structure of the atmospheric tidal wave, it is predictable in time and space, which is important information for the prediction of excess force in developing hurricanes.

  13. The High Price of Excessive Alcohol Consumption

    Centers for Disease Control (CDC) Podcasts

    2011-10-17

    This podcast is based on the October 2011 release of a report estimating the economic cost of excessive drinking. Excessive alcohol consumption cost the U. S. $223.5 billion in 2006, or about $1.90 per drink. Over three-quarters (76%) of these costs were due to binge drinking, defined as consuming 4 or more alcoholic beverages per occasion for women or 5 or more drinks per occasion for men.  Created: 10/17/2011 by National Center for Chronic Disease Prevention and Health Promotion.   Date Released: 10/17/2011.

  14. Contrast induced hyperthyroidism due to iodine excess

    Science.gov (United States)

    Mushtaq, Usman; Price, Timothy; Laddipeerla, Narsing; Townsend, Amanda; Broadbridge, Vy

    2009-01-01

    Iodine induced hyperthyroidism is a thyrotoxic condition caused by exposure to excessive iodine. Historically this type of hyperthyroidism has been described in areas of iodine deficiency. With advances in medicine, iodine induced hyperthyroidism has been observed following the use of drugs containing iodine—for example, amiodarone, and contrast agents used in radiological imaging. In elderly patients it is frequently difficult to diagnose and control contrast related hyperthyroidism, as most of these patients do not always present with typical signs and symptoms of hyperthyroidism. Treatment can be very challenging as drugs commonly used to treat hyperthyroidism have little effect on already formed thyroid hormone due to iodine excess. PMID:22053166

  15. Excessive users of violent video games do not show emotional desensitization: an fMRI study.

    Science.gov (United States)

    Szycik, Gregor R; Mohammadi, Bahram; Hake, Maria; Kneer, Jonas; Samii, Amir; Münte, Thomas F; Te Wildt, Bert T

    2017-06-01

    Playing violent video games have been linked to long-term emotional desensitization. We hypothesized that desensitization effects in excessive users of violent video games should lead to decreased brain activations to highly salient emotional pictures in emotional sensitivity brain regions. Twenty-eight male adult subjects showing excessive long-term use of violent video games and age and education matched control participants were examined in two experiments using standardized emotional pictures of positive, negative and neutral valence. No group differences were revealed even at reduced statistical thresholds which speaks against desensitization of emotion sensitive brain regions as a result of excessive use of violent video games.

  16. 34 CFR 300.16 - Excess costs.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Excess costs. 300.16 Section 300.16 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF CHILDREN WITH...

  17. Excessive daytime sleepiness, nocturnal sleep duration and ...

    African Journals Online (AJOL)

    Background and objectives. Short nocturnal sleep duration resulting in sleep debt may be a cause of excessive daytime sleepiness (EDS). Severity of depression (psychopathology) has been found to be directly related to EDS. There is an association between sleep duration and mental health, so there may therefore be an ...

  18. Excessive prices as abuse of dominance?

    DEFF Research Database (Denmark)

    la Cour, Lisbeth; Møllgaard, Peter

    2007-01-01

    firm abused its position by charging excessive prices. We also test whether tightening of the Danish competition act has altered the pricing behaviour on the market. We discuss our results in the light of a Danish competition case against the dominant cement producer that was abandoned by the authority...

  19. Surface temperature excess in heterogeneous catalysis

    NARCIS (Netherlands)

    Zhu, L.

    2005-01-01

    In this dissertation we study the surface temperature excess in heterogeneous catalysis. For heterogeneous reactions, such as gas-solid catalytic reactions, the reactions take place at the interfaces between the two phases: the gas and the solid catalyst. Large amount of reaction heats are released

  20. Origin of excess 176Hf in meteorites

    DEFF Research Database (Denmark)

    Thrane, Kristine; Connelly, James; Bizzarro, Martin

    2010-01-01

    with Lu/Hf elemental ratios in meteorites older than similar to 4.56 Ga meteorites unresolved. We attribute (176)Hf excess in older meteorites to an accelerated decay of (176)Lu caused by excitation of the long-lived (176)Lu ground state to a short-lived (176m)Lu isomer. The energy needed to cause...

  1. Excessive nitrogen and phosphorus in European rivers

    NARCIS (Netherlands)

    Blaas, Harry; Kroeze, Carolien

    2016-01-01

    Rivers export nutrients to coastal waters. Excess nutrient export may result in harmful algal blooms and hypoxia, affecting biodiversity, fisheries, and recreation. The purpose of this study is to quantify for European rivers (1) the extent to which N and P loads exceed levels that minimize the

  2. Excessive infant crying : definitions determine risk groups

    NARCIS (Netherlands)

    Reijneveld, SA; Brugman, E; Hirasing, RA

    We assessed risk groups for excessive infant crying using 10 published definitions, in 3179 children aged 1-6 months (response: 96.5%). Risk groups regarding parental employment, living area, lifestyle, and obstetric history varied by definition. This may explain the existence of conflicting

  3. Low excess air operations of oil boilers

    Energy Technology Data Exchange (ETDEWEB)

    Butcher, T.A.; Celebi, Y.; Litzke, Wai Lin [Brookhaven National Labs., Upton, NY (United States)

    1997-09-01

    To quantify the benefits which operation at very low excess air operation may have on heat exchanger fouling BNL has recently started a test project. The test allows simultaneous measurement of fouling rate, flue gas filterable soot, flue gas sulfuric acid content, and flue gas sulfur dioxide.

  4. Elevated Placental Adenosine Signaling Contributes to the Pathogenesis of Preeclampsia

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F.; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A.; Blackwell, Sean C.; Sibai, Baha M.; Chan, Lee-Nien L.; Chan, Teh-Sheng; Hicks, M. John; Blackburn, Michael R.; Kellems, Rodney E.; Xia, Yang

    2016-01-01

    Background Preeclampsia (PE) is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be due to placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways leading to impaired placentas and maternal disease development remain elusive. Methods and Results By using two independent animal models of PE—1) genetically-engineered pregnant mice with elevated adenosine exclusively in placentas, and 2) a pathogenic autoantibody-induced PE mouse model—we demonstrated here that chronically elevated placental adenosine was sufficient to induce hallmark features of PE including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacologic approaches revealed that elevated placental adenosine coupled with excessive A2B adenosine receptor (ADORA2B) signaling contributed to the development of these features of PE. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to PE. Conclusions We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for PE. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of PE, and, thereby highlight novel therapeutic targets. PMID:25538227

  5. Elevated placental adenosine signaling contributes to the pathogenesis of preeclampsia.

    Science.gov (United States)

    Iriyama, Takayuki; Sun, Kaiqi; Parchim, Nicholas F; Li, Jessica; Zhao, Cheng; Song, Anren; Hart, Laura A; Blackwell, Sean C; Sibai, Baha M; Chan, Lee-Nien L; Chan, Teh-Sheng; Hicks, M John; Blackburn, Michael R; Kellems, Rodney E; Xia, Yang

    2015-02-24

    Preeclampsia is a prevalent hypertensive disorder of pregnancy and a leading cause of maternal and neonatal morbidity and mortality worldwide. This pathogenic condition is speculated to be caused by placental abnormalities that contribute to the maternal syndrome. However, the specific factors and signaling pathways that lead to impaired placentas and maternal disease development remain elusive. Using 2 independent animal models of preeclampsia (genetically engineered pregnant mice with elevated adenosine exclusively in placentas and a pathogenic autoantibody-induced preeclampsia mouse model), we demonstrated that chronically elevated placental adenosine was sufficient to induce hallmark features of preeclampsia, including hypertension, proteinuria, small fetuses, and impaired placental vasculature. Genetic and pharmacological approaches revealed that elevated placental adenosine coupled with excessive A₂B adenosine receptor (ADORA2B) signaling contributed to the development of these features of preeclampsia. Mechanistically, we provided both human and mouse evidence that elevated placental CD73 is a key enzyme causing increased placental adenosine, thereby contributing to preeclampsia. We determined that elevated placental adenosine signaling is a previously unrecognized pathogenic factor for preeclampsia. Moreover, our findings revealed the molecular basis underlying the elevation of placental adenosine and the detrimental role of excess placental adenosine in the pathophysiology of preeclampsia, and thereby, we highlight novel therapeutic targets. © 2014 American Heart Association, Inc.

  6. Background model systematics for the Fermi GeV excess

    Energy Technology Data Exchange (ETDEWEB)

    Calore, Francesca; Cholis, Ilias; Weniger, Christoph

    2015-03-01

    The possible gamma-ray excess in the inner Galaxy and the Galactic center (GC) suggested by Fermi-LAT observations has triggered a large number of studies. It has been interpreted as a variety of different phenomena such as a signal from WIMP dark matter annihilation, gamma-ray emission from a population of millisecond pulsars, or emission from cosmic rays injected in a sequence of burst-like events or continuously at the GC. We present the first comprehensive study of model systematics coming from the Galactic diffuse emission in the inner part of our Galaxy and their impact on the inferred properties of the excess emission at Galactic latitudes 2° < |b| < 20° and 300 MeV to 500 GeV. We study both theoretical and empirical model systematics, which we deduce from a large range of Galactic diffuse emission models and a principal component analysis of residuals in numerous test regions along the Galactic plane. We show that the hypothesis of an extended spherical excess emission with a uniform energy spectrum is compatible with the Fermi-LAT data in our region of interest at 95% CL. Assuming that this excess is the extended counterpart of the one seen in the inner few degrees of the Galaxy, we derive a lower limit of 10.0° (95% CL) on its extension away from the GC. We show that, in light of the large correlated uncertainties that affect the subtraction of the Galactic diffuse emission in the relevant regions, the energy spectrum of the excess is equally compatible with both a simple broken power-law of break energy E(break) = 2.1 ± 0.2 GeV, and with spectra predicted by the self-annihilation of dark matter, implying in the case of bar bb final states a dark matter mass of m(χ)=49(+6.4)(-)(5.4)  GeV.

  7. Leading lead through the LHC

    CERN Multimedia

    2011-01-01

    Three of the LHC experiments - ALICE, ATLAS and CMS - will be studying the upcoming heavy-ion collisions. Given the excellent results from the short heavy-ion run last year, expectations have grown even higher in experiment control centres. Here they discuss their plans:   ALICE For the upcoming heavy-ion run, the ALICE physics programme will take advantage of a substantial increase of the LHC luminosity with respect to last year’s heavy-ion run.  The emphasis will be on the acquisition of rarely produced signals by implementing selective triggers. This is a different operation mode to that used during the first low luminosity heavy-ion run in 2010, when only minimum-bias triggered events were collected. In addition, ALICE will benefit from increased acceptance coverage by the electromagnetic calorimeter and the transition radiation detector. In order to double the amount of recorded events, ALICE will exploit the maximum available bandwidth for mass storage at 4 GB/s and t...

  8. Sublimation of amino acids with enantiomeric excess amplification

    Science.gov (United States)

    Guillemin, Jean-Claude; Guillemin, Jean-Claude; Bellec, Aurelien

    The notion of chirality was first reported in 1848 by Pasteur, when he mechanically separated the two enantiomers of tartrate salts.[1] Amino acids are considered as the most important building blocks of life with sugars. On the Earth, the living systems are only composed of L- amino acids and D-sugars. Nowadays, the origin of homochirality on Earth is still unknown, and there are many theories trying to explain this phenomenon. Recently Cooks [2] and Feringa [3] reported that the sublimation of small amounts of L and D amino acid mixtures containing an excess of one of them leads to a huge enantiomeric excess (ee) enhancement of the sublimate. We reinvestigated these experiments to determine the rules leading to this enhancement. Starting from mixtures of L- and DL leucine we observed increasing and decreasing of the ee in function of the starting ratios. By the use of 13C derivatives, the origin of the sublimed enantiomers has been precised. Various parameters (L and D, or L and DL mixtures, dissolution in water before sublimation, . . . ) were studied. We also took into consideration the recently proposed hypothesis of the role played by the eutectic ee in the sublimation. [4] The application of these results to find an explanation of the enantiomeric excess in meteorites or in the Primitive Earth scenarios will be discussed. 1 Pasteur, L. Ann. Phys., 1848, 24, 442. 2 R. H. Perry, C. Wu, M. Nefliu, R. G. Cooks, Chem. Commun., 2007, 1071-1073. 3 S. P. Fletcher, R. B. C. Jagt, B. L. Feringa, Chem. Commun., 2007, 2578-2580. 4 D. G. Blackmond, M. Klussmannb Chem. Commun., 2007, 3990-3996.

  9. Excessive social imbalances and the performance of welfare states in the EU

    NARCIS (Netherlands)

    Vandenbroucke, F.; Diris, R.; Verbist, G.

    2013-01-01

    Our paper4 starts from the premise that the disparity and lack of convergence of levels of child poverty in the Eurozone signalsexcessive imbalances’ that should be a common concern. Increasing and diverging child poverty rates warrant a common concern, first, because they contradict the

  10. Advances in cell proliferation and apoptosis signal pathway and therapies of polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Xiao-ying LIAN

    2016-12-01

    Full Text Available Polycystic kidney disease (PKD is one of the monogenic inherited diseases. In PKD, excessive cell proliferation and fluid secretion, and disruption of the mechanisms controlling tubular diameter may all lead to cyst formation. Current evidence has demonstrated that intracellular calcium ion and cAMP imbalance drive both abnormal cell proliferation and apoptosis signal pathway. The present paper summarized the evidence implicating calcium ion and cAMP as central players in the signaling pathway of cell proliferation and apoptosis in PKD, and considered the potential therapeutic approaches targeted to slow cyst growth in PKD. DOI: 10.11855/j.issn.0577-7402.2016.11.13

  11. ILLUSION OF EXCESSIVE CONSUMPTION AND ITS EFFECTS

    Directory of Open Access Journals (Sweden)

    MUNGIU-PUPĂZAN MARIANA CLAUDIA

    2015-12-01

    Full Text Available The aim is to explore, explain and describe this phenomenon to a better understanding of it and also the relationship between advertising and the consumer society members. This paper aims to present an analysis of excessive and unsustainable consumption, the evolution of a phenomenon, and the ability to find a way to combat. Unfortunately, studies show that this tendency to accumulate more than we need to consume excess means that almost all civilizations fined and placed dogmatic among the values that children learn early in life. This has been perpetuated since the time when the goods or products does not get so easy as today. Anti-consumerism has emerged in response to this economic system, not on the long term. We are witnessing the last two decades to establish a new phase of consumer capitalism: society hiperconsumtion.

  12. Conservative treatment of excessive anterior pelvic tilt

    DEFF Research Database (Denmark)

    Brekke, Anders Falk

    , DK-5000 Odense C, Denmark ABSTRACT (1795 anslag) Background: Excessive anterior pelvic tilt has been linked to pain and dysfunction of the hip and pelvic region. Conservative treatment (e.g. manual therapy and physical training) is suggested in correcting the tilt and eventually related symptoms...... demonstrated a significant reduction in anterior pelvic tilt. The two studies intervening on symptomatic subjects demonstrated a significant reduction in pain and disability, respectively. Conclusions: Very low quality of evidence suggests that further studies are needed to clarify whether conservative......Conservative treatment of excessive anterior pelvic tilt: A systematic review Anders Falk Brekke1,2,3, Søren Overgaard1,2, Asbjørn Hróbjartsson4, Anders Holsgaard-Larsen1,2 1Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, Odense University Hospital 2Department...

  13. Neurological manifestations of excessive alcohol consumption.

    Science.gov (United States)

    Planas-Ballvé, Anna; Grau-López, Laia; Morillas, Rosa María; Planas, Ramón

    2017-12-01

    This article reviews the different acute and chronic neurological manifestations of excessive alcohol consumption that affect the central or peripheral nervous system. Several mechanisms can be implicated depending on the disorder, ranging from nutritional factors, alcohol-related toxicity, metabolic changes and immune-mediated mechanisms. Recognition and early treatment of these manifestations is essential given their association with high morbidity and significantly increased mortality. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  14. Tendon rupture associated with excessive smartphone gaming.

    Science.gov (United States)

    Gilman, Luke; Cage, Dori N; Horn, Adam; Bishop, Frank; Klam, Warren P; Doan, Andrew P

    2015-06-01

    Excessive use of smartphones has been associated with injuries. A 29-year-old, right hand-dominant man presented with chronic left thumb pain and loss of active motion from playing a Match-3 puzzle video game on his smartphone all day for 6 to 8 weeks. On physical examination, the left extensor pollicis longus tendon was not palpable, and no tendon motion was noted with wrist tenodesis. The thumb metacarpophalangeal range of motion was 10° to 80°, and thumb interphalangeal range of motion was 30° to 70°. The clinical diagnosis was rupture of the left extensor pollicis longus tendon. The patient subsequently underwent an extensor indicis proprius (1 of 2 tendons that extend the index finger) to extensor pollicis longus tendon transfer. During surgery, rupture of the extensor pollicis longus tendon was seen between the metacarpophalangeal and wrist joints. The potential for video games to reduce pain perception raises clinical and social considerations about excessive use, abuse, and addiction. Future research should consider whether pain reduction is a reason some individuals play video games excessively, manifest addiction, or sustain injuries associated with video gaming.

  15. [Mortality attributable to excess weight in Spain].

    Science.gov (United States)

    Martín-Ramiro, José Javier; Álvarez-Martín, Elena; Gil-Prieto, Ruth

    2014-06-16

    Estimate the mortality attributable to higher than optimal body mass index in the Spanish population in 2006. Excess body weight prevalence data were obtained from the 2006 National Health Survey, while data on associated mortality were extracted from the National Statistic Institute. Population attributable fractions were applied and mortality attributable to higher than optimal body mass index was calculated for people between 35 and 79 years. In 2006, among the Spanish population aged 35-79 years, 25,671 lives (16,405 males and 9,266 women) were lost due to higher than optimal body mass index. Mortality attributable was 15.8% of total deaths in males and 14.8% in women, but if we refer to those causes where excess body weight is a risk factor, it is about a 30% of mortality (31.6% in men and 28% in women). The most important individual cause was cardiovascular disease (58%), followed by cancer. The individual cause with a major contribution to deaths was type 2 diabetes; nearly 70% in males and 80% in women. Overweight accounted for 54.9% deaths in men and 48.6% in women. Excess body weight is a major public health problem, with an important associated mortality. Attributable deaths are a useful tool to know the real situation and to monitor for disease control interventions. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  16. Earnings Quality Measures and Excess Returns.

    Science.gov (United States)

    Perotti, Pietro; Wagenhofer, Alfred

    2014-06-01

    This paper examines how commonly used earnings quality measures fulfill a key objective of financial reporting, i.e., improving decision usefulness for investors. We propose a stock-price-based measure for assessing the quality of earnings quality measures. We predict that firms with higher earnings quality will be less mispriced than other firms. Mispricing is measured by the difference of the mean absolute excess returns of portfolios formed on high and low values of a measure. We examine persistence, predictability, two measures of smoothness, abnormal accruals, accruals quality, earnings response coefficient and value relevance. For a large sample of US non-financial firms over the period 1988-2007, we show that all measures except for smoothness are negatively associated with absolute excess returns, suggesting that smoothness is generally a favorable attribute of earnings. Accruals measures generate the largest spread in absolute excess returns, followed by smoothness and market-based measures. These results lend support to the widespread use of accruals measures as overall measures of earnings quality in the literature.

  17. Alexithymia components in excessive internet users: a multi-factorial analysis.

    Science.gov (United States)

    Kandri, Theodora A; Bonotis, Konstantinos S; Floros, Georgios D; Zafiropoulou, Maria M

    2014-12-15

    The increasing use of computers and the internet - especially among young people - apart from its positive effects, sometimes leads to excessive and pathological use. The present study examined the relationship among the excessive use of the internet by university students, the alexithymia components and sociodemographic factors associated with internet users and their online activities. 515 university students from the University of Thessaly participated in the study. Participants anonymously completed: a) the Internet Addiction Test (IAT), b) the Toronto Alexithymia Test (TAS 20) and c) a questionnaire covering various aspects of internet use and demographic characteristics of internet users. Excessive use of the internet among Greek university students was studied within a multi-factorial context and was associated with the alexithymia and demographic factors in nonlinear correlations, forming thus a personalized emotional and demographic profile of the excessive internet users. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Light acclimation, retrograde signalling, cell death and immune defences in plants.

    Science.gov (United States)

    Karpiński, Stanisław; Szechyńska-Hebda, Magdalena; Wituszyńska, Weronika; Burdiak, Paweł

    2013-04-01

    This review confronts the classical view of plant immune defence and light acclimation with recently published data. Earlier findings have linked plant immune defences to nucleotide-binding site leucine-rich repeat (NBS-LRR)-dependent recognition of pathogen effectors and to the role of plasma membrane-localized NADPH-dependent oxidoreductase (AtRbohD), reactive oxygen species (ROS) and salicylic acid (SA). However, recent results suggest that plant immune defence also depends on the absorption of excessive light energy and photorespiration. Rapid changes in light intensity and quality often cause the absorption of energy, which is in excess of that required for photosynthesis. Such excessive light energy is considered to be a factor triggering photoinhibition and disturbance in ROS/hormonal homeostasis, which leads to cell death in foliar tissues. We highlight here the tight crosstalk between ROS- and SA-dependent pathways leading to light acclimation, and defence responses leading to pathogen resistance. We also show that LESION SIMULATING DISEASE 1 (LSD1) regulates and integrates these processes. Moreover, we discuss the role of plastid-nucleus signal transduction, photorespiration, photoelectrochemical signalling and 'light memory' in the regulation of acclimation and immune defence responses. All of these results suggest that plants have evolved a genetic system that simultaneously regulates systemic acquired resistance (SAR), cell death and systemic acquired acclimation (SAA). © 2012 Blackwell Publishing Ltd.

  19. Lead poisoning in captive wild animals

    Energy Technology Data Exchange (ETDEWEB)

    Zook, B.C.; Sauer, R.M.; Garner, F.M.

    1972-07-01

    Lead poisoning was diagnosed post-mortem in 34 simian primates, 11 parrots, and 3 Australian fruit bats at the National Zoological Park. Diagnoses were made by the finding of acid-fast intranuclear inclusion bodies in renal epithelia or hepatocytes and, in most cases, by finding excess lead in samples of liver. The estimated prevalence of lead intoxication among autopsied primates and parrots was 44% and 50% respectively. Leaded paint was found in many animal enclosures at this zoo and it was available to all the lead-poisoned animals in this study. The finding of renal intranuclear inclusion bodies in animals at several zoos, scattered reports of lead intoxication of animals dwelling in various zoos, the occurrence of leaded paint in many zoos and the high incidence of lead poisoning at this zoo, indicated that lead poisoning of zoo animals is much more common than was previously thought.

  20. The Synergistic Impact of Excessive Drinking and Smoking upon Prospective Memory.

    Directory of Open Access Journals (Sweden)

    Anna-Marie eMarshall

    2016-04-01

    Full Text Available The independent use of excessive amounts of alcohol or persistent cigarette smoking have been found to have a deleterious impact upon Prospective Memory (PM: remembering future intentions and activities, although to date, the effect of their concurrent use upon PM is yet to be explored. The present study investigated the impact of concurrent use (excessive use of alcohol and cigarette smoking in comparison to the combined effect of the single use of these substances using a single factorial independent groups design. The Cambridge Prospective Memory Test was administered to 125 adults; an excessive alcohol user group (n = 40, a group of smokers who drink very little alcohol (n = 20, a combined user group (the Polydrug group who drink excessively and smoke cigarettes (n = 40 and a non-drinker/low alcohol consumption control group (n = 25. The main findings revealed that the Polydrug users recalled significantly fewer time-based PM tasks than excessive alcohol users p<.001 and smokers p=.013. Polydrug users (mean = 11.47 also remembered significantly fewer event-based PM tasks than excessive alcohol users p<.001 and smokers p = .013. Most interestingly, Polydrug users exhibited significantly greater impaired time-based PM than the combined effect of single excessive alcohol users and smokers p=.033. However, no difference was observed between Polydrug users and the combined effect of single excessive alcohol users and smokers in event-based PM p=.757. These results provide evidence that concurrent use of these two substances has a synergistic effect in terms of deficits upon time-based PM. The observation that excessive drinking and smoking leads to greater impairments in time-based PM may be of paramount importance, given the key role PM plays in everyday independent living.

  1. Excessive sleep duration and quality of life.

    Science.gov (United States)

    Ohayon, Maurice M; Reynolds, Charles F; Dauvilliers, Yves

    2013-06-01

    Using population-based data, we document the comorbidities (medical, neurologic, and psychiatric) and consequences for daily functioning of excessive quantity of sleep (EQS), defined as a main sleep period or 24-hour sleep duration ≥ 9 hours accompanied by complaints of impaired functioning or distress due to excessive sleep, and its links to excessive sleepiness. A cross-sectional telephone study using a representative sample of 19,136 noninstitutionalized individuals living in the United States, aged ≥ 18 years (participation rate = 83.2%). The Sleep-EVAL expert system administered questions on life and sleeping habits; health; and sleep, mental, and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision; International Classification of Sleep Disorders: Diagnostic and Coding Manual II, International Classification of Diseases and Related Health Problems, 10th edition). Sleeping at least 9 hours per 24-hour period was reported by 8.4% (95% confidence interval = 8.0-8.8%) of participants; EQS (prolonged sleep episode with distress/impairment) was observed in 1.6% (1.4-1.8%) of the sample. The likelihood of EQS was 3 to 12× higher among individuals with a mood disorder. EQS individuals were 2 to 4× more likely to report poor quality of life than non-EQS individuals as well as interference with socioprofessional activities and relationships. Although between 33 and 66% of individuals with prolonged sleep perceived it as a major problem, only 6.3 to 27.5% of them reported having sought medical attention. EQS is widespread in the general population, co-occurring with a broad spectrum of sleep, medical, neurologic, and psychiatric disorders. Therefore, physicians must recognize EQS as a mixed clinical entity indicating careful assessment and specific treatment planning. © 2013 American Neurological Association.

  2. Excessive eccentric exercise-induced overtraining model leads to endoplasmic reticulum stress in mice skeletal muscles.

    Science.gov (United States)

    Pereira, Bruno C; da Rocha, Alisson L; Pinto, Ana P; Pauli, José R; de Souza, Claudio T; Cintra, Dennys E; Ropelle, Eduardo R; de Freitas, Ellen C; Zagatto, Alessandro M; da Silva, Adelino S R

    2016-01-15

    The present study verified the responses of selected endoplasmic reticulum (ER) stress proteins (i.e., BiP, ATF-6, pIRE1, pPERK, and peIF2alpha) in mice skeletal muscles after three different running overtraining (OT) protocols with same external load (i.e., intensity vs. volume), but performed in downhill, uphill and without inclination. The rodents were randomly divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR) groups. The incremental load test and exhaustive test were used as performance parameters. Forty hours after the exhaustive test performed at the end of the OT protocols (i.e., at the end of week 8) and after a 2-week total recovery period (i.e., at the end of week 10), the extensor digitorum longus (EDL) and soleus muscles were removed and used for immunoblotting. For both skeletal muscle types, the OTR/down protocol increased the pIRE-1, pPERK and peIF2alpha, which were not normalized after the total recovery period. At the end of week 8, the other two OT protocols up-regulated the BiP, pPERK and peIF2alpha levels only for the soleus muscle. These ER stress proteins were not normalized after the total recovery period for the OTR/up group. The above findings suggest that the OTR/down protocol-induced skeletal muscle ER stress may be linked to a pathological condition in EDL and soleus muscles. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. First excess levels of vector processes

    Directory of Open Access Journals (Sweden)

    Jewgeni H. Dshalalow

    1994-01-01

    Full Text Available This paper analyzes the behavior of a point process marked by a two-dimensional renewal process with dependent components about some fixed (two-dimensional level. The compound process evolves until one of its marks hits (i.e. reaches or exceeds its associated level for the first time. The author targets a joint transformation of the first excess level, first passage time, and the index of the point process which labels the first passage time. The cases when both marks are either discrete or continuous or mixed are treated. For each of them, an explicit and compact formula is derived. Various applications to stochastic models are discussed.

  4. The modulatory role of high fat feeding on gastrointestinal signals in obesity.

    Science.gov (United States)

    Duca, Frank A; Sakar, Yassine; Covasa, Mihai

    2013-10-01

    The gastrointestinal (GI) tract is a specialized sensory system that detects and responds to constant changes in nutrient- and bacterial-derived intestinal signals, thus contributing to controls of food intake. Chronic exposure to dietary fat causes morphological, physiological and metabolic changes leading to disruptions in the regulatory feeding pathways promoting more efficient fat absorption and utilization, blunted satiation signals and excess adiposity. Accumulating evidence demonstrates that impaired gastrointestinal signals following long-term high fat consumption are, at least partially, responsible for increased caloric intake. This review focuses on the role of dietary fat in modulating oral and post-oral chemosensory signaling elements responsible for lipid detection and responses, including changes in sensitivity to satiation signals, such as GLP-1, PYY and CCK and their impact on food intake and weight gain. Furthermore, the influence of the gut microbiota on mechanisms controlling energy regulation in the face of excessive fat exposure will be explored. The profound influence of dietary fats on altering complex regulatory feeding pathways can result in dysregulation of body weight and development of obesity, while restoration or manipulation of satiation signaling may prove an effective tool in prevention and treatment of obesity. © 2013.

  5. Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells

    Directory of Open Access Journals (Sweden)

    Shayda Hemmati

    2017-11-01

    Full Text Available Hematopoietic stem cells (HSCs are a rare subset of bone marrow cells that usually exist in a quiescent state, only entering the cell cycle to replenish the blood compartment, thereby limiting the potential for errors in replication. Inflammatory signals that are released in response to environmental stressors, such as infection, trigger active cycling of HSCs. These inflammatory signals can also directly induce HSCs to release cytokines into the bone marrow environment, promoting myeloid differentiation. After stress myelopoiesis is triggered, HSCs require intracellular signaling programs to deactivate this response and return to steady state. Prolonged or excessive exposure to inflammatory cytokines, such as in prolonged infection or in chronic rheumatologic conditions, can lead to continued HSC cycling and eventual HSC loss. This promotes bone marrow failure, and can precipitate preleukemic states or leukemia through the acquisition of genetic and epigenetic changes in HSCs. This can occur through the initiation of clonal hematopoiesis, followed by the emergence preleukemic stem cells (pre-LSCs. In this review, we describe the roles of multiple inflammatory signaling pathways in the generation of pre-LSCs and in progression to myelodysplastic syndrome (MDS, myeloproliferative neoplasms, and acute myeloid leukemia (AML. In AML, activation of some inflammatory signaling pathways can promote the cycling and differentiation of LSCs, and this can be exploited therapeutically. We also discuss the therapeutic potential of modulating inflammatory signaling for the treatment of myeloid malignancies.

  6. Development of ARDS after Excessive Kath Consumption: A Case Report

    Directory of Open Access Journals (Sweden)

    Marlene Wewalka

    2011-01-01

    Full Text Available Khat is a drug widely used in the Horn of Africa and the Arabian Peninsula. Khat leaves contain, among other substances, the psychoactive alkaloid cathinone, which induce central nervous system stimulation leading to euphoria, hyperactivity, restlessness, and insomnia. However, it also could cause psychological adverse effects such as lethargy, sleepiness, psychoses, and depression necessitating pharmacologic treatment. Here we report the case of a 35-year-old man from Somalia who became unconscious and developed aspiration pneumonia and subsequent ARDS after excessive consumption of khat leaves. His unconsciousness was possibly caused by the sleepiness developed after khat consumption and a benzodiazepine intake by the patient himself. Thus, khat-induced adverse effects should not primarily be treated pharmacologically, but patients should be urged to quit khat consumption in order to eliminate or, at least, reduce the severity of present psychological adverse effects.

  7. Management of bimaxillary transverse discrepancy with vertical excess

    Directory of Open Access Journals (Sweden)

    Dinesh C Chaudhary

    2015-01-01

    Full Text Available A 14-year-old boy reported with a complaint of severe irregularity of lower teeth and forwardly placed upper teeth. History revealed snoring as an occasional complaint. The case was diagnosed as mild class II skeletally with increased lower anterior face height, bimaxillary transverse discrepancy leading to severe crowding in the lower arch, V-shaped upper arch with increased overjet and deep bite. Three phase treatment was planned. In the first phase, bimaxillary expansion with mid-symphyseal distraction osteogenesis and rapid maxillary expansion was carried out. After this phase of treatment, the episodes of snoring vanished. The second phase was 1 year of orthodontics to produce symmetric well-aligned arches in good function and aesthetics. Third, the treatment concluded with reduction-advancement genioplasty for correction of vertical excess and surgical camouflage.

  8. Partial pulp necrosis caused by excessive orthodontic force

    Directory of Open Access Journals (Sweden)

    Min-Young Kim

    2011-03-01

    Full Text Available As the dental pulp is encased with a rigid, noncompliant shell, changes in pulpal blood flow or vascular tissue pressure can have serious implication for the health of pulp. Numerous studies have demonstrated that orthodontic force application may influence both blood flow and cellular metabolism, leading degenerative and/or inflammatory responses in the dental pulp. The aim of this case report is to present a case about tooth with chronic periapical abscess which showed normal vital responses. Excessive orthodontic force is thought to be the prime cause of partial pulp necrosis. Owing to remaining vital tissue, wrong dianosis can be made, and tooth falsely diagnosed as vital may be left untreated, causing the necrotic tissue to destroy the supporting tissuses. Clinician should be able to utilize various diagnostic tools for the precise diagnosis, and be aware of the endodontic-orthodontic inter-relationship.

  9. Minimal Composite Dynamics versus Axion Origin of the Diphoton excess

    DEFF Research Database (Denmark)

    Molinaro, Emiliano; Sannino, Francesco; Vignaroli, Natascia

    2016-01-01

    ATLAS and CMS observe deviations from the expected background in the diphoton invariant mass searches of new resonances around 750 GeV. We show that a simple realization in terms of a new pseudoscalar state can accommodate the observations. The model leads to further footprints that can be soon o...... that it is possible to directly test and constrain composite dynamics via processes stemming from its distinctive topological sector....... observed. The new state can be interpreted both as an axion or as a {highly natural} composite state arising from minimal models of dynamical electroweak symmetry breaking. We further show how to disentangle the two scenarios. Beyond the possible explanation of the diphoton excess the results show...

  10. Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila

    Directory of Open Access Journals (Sweden)

    Lanikea B. King

    2016-04-01

    Full Text Available Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1 exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits.

  11. Neurofibromin Loss of Function Drives Excessive Grooming in Drosophila.

    Science.gov (United States)

    King, Lanikea B; Koch, Marta; Murphy, Keith R; Velazquez, Yoheilly; Ja, William W; Tomchik, Seth M

    2016-04-07

    Neurofibromatosis I is a common genetic disorder that results in tumor formation, and predisposes individuals to a range of cognitive/behavioral symptoms, including deficits in attention, visuospatial skills, learning, language development, and sleep, and autism spectrum disorder-like traits. The nf1-encoded neurofibromin protein (Nf1) exhibits high conservation, from the common fruit fly, Drosophila melanogaster, to humans. Drosophila provides a powerful platform to investigate the signaling cascades upstream and downstream of Nf1, and the fly model exhibits similar behavioral phenotypes to mammalian models. In order to understand how loss of Nf1 affects motor behavior in flies, we combined traditional activity monitoring with video analysis of grooming behavior. In nf1 mutants, spontaneous grooming was increased up to 7x. This increase in activity was distinct from previously described dopamine-dependent hyperactivity, as dopamine transporter mutants exhibited slightly decreased grooming. Finally, we found that relative grooming frequencies can be compared in standard activity monitors that measure infrared beam breaks, enabling the use of activity monitors as an automated method to screen for grooming phenotypes. Overall, these data suggest that loss of nf1 produces excessive activity that is manifested as increased grooming, providing a platform to dissect the molecular genetics of neurofibromin signaling across neuronal circuits. Copyright © 2016 King et al.

  12. Metabolic signals and innate immune activation in obesity and exercise.

    Science.gov (United States)

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

  13. Hh signalling is essential for somatic stem cell maintenance in the Drosophila testis niche.

    Science.gov (United States)

    Michel, Marcus; Kupinski, Adam P; Raabe, Isabel; Bökel, Christian

    2012-08-01

    In the Drosophila testis, germline stem cells (GSCs) and somatic cyst stem cells (CySCs) are arranged around a group of postmitotic somatic cells, termed the hub, which produce a variety of growth factors contributing to the niche microenvironment that regulates both stem cell pools. Here we show that CySC but not GSC maintenance requires Hedgehog (Hh) signalling in addition to Jak/Stat pathway activation. CySC clones unable to transduce the Hh signal are lost by differentiation, whereas pathway overactivation leads to an increase in proliferation. However, unlike cells ectopically overexpressing Jak/Stat targets, the additional cells generated by excessive Hh signalling remain confined to the testis tip and retain the ability to differentiate. Interestingly, Hh signalling also controls somatic cell populations in the fly ovary and the mammalian testis. Our observations might therefore point towards a higher degree of organisational homology between the somatic components of gonads across the sexes and phyla than previously appreciated.

  14. BMP signaling and the maintenance of primordial germ cell identity in Drosophila embryos.

    Directory of Open Access Journals (Sweden)

    Girish Deshpande

    Full Text Available The specification of primordial germ cells (PGCs and subsequent maintenance of germ-line identity in Drosophila embryos has long been thought to occur solely under the control of cell-autonomous factors deposited in the posterior pole plasm during oogenesis. However, here we document a novel role for somatic BMP signaling in the maintenance of PGC fate during the period leading up to embryonic gonad coalescence. We find that PGCs fail to maintain their germline identity when BMP signaling is compromised. They initiate but are unable to properly assemble the germline stem cell-specific organelle, the spectrosome, and they lose expression of the germline-specific gene Vasa. BMP signaling must, however, be finely tuned as there are deleterious consequences to PGCs when the pathway is excessively active. We show that one mechanism used to calibrate the effects of BMP signals is dependent on the Ubc9 homolog Lesswright (Lwr.

  15. BMP Signaling and the Maintenance of Primordial Germ Cell Identity in Drosophila Embryos

    Science.gov (United States)

    Deshpande, Girish; Willis, Elinor; Chatterjee, Sandip; Fernandez, Robert; Dias, Kristen; Schedl, Paul

    2014-01-01

    The specification of primordial germ cells (PGCs) and subsequent maintenance of germ-line identity in Drosophila embryos has long been thought to occur solely under the control of cell-autonomous factors deposited in the posterior pole plasm during oogenesis. However, here we document a novel role for somatic BMP signaling in the maintenance of PGC fate during the period leading up to embryonic gonad coalescence. We find that PGCs fail to maintain their germline identity when BMP signaling is compromised. They initiate but are unable to properly assemble the germline stem cell-specific organelle, the spectrosome, and they lose expression of the germline-specific gene Vasa. BMP signaling must, however, be finely tuned as there are deleterious consequences to PGCs when the pathway is excessively active. We show that one mechanism used to calibrate the effects of BMP signals is dependent on the Ubc9 homolog Lesswright (Lwr). PMID:24551179

  16. [Disability attributable to excess weight in Spain].

    Science.gov (United States)

    Martín-Ramiro, José Javier; Alvarez-Martín, Elena; Gil-Prieto, Ruth

    2014-08-19

    To estimate the disability attributable to higher than optimal body mass index in the Spanish population in 2006. Excess body weight prevalence data were obtained from the 2006 National Health Survey (NHS), while the prevalence of associated morbidities was extracted from the 2006 NHS and from a national hospital data base. Population attributable fractions were applied and disability attributable was expressed as years life with disability (YLD). In 2006, in the Spanish population aged 35-79 years, 791.650 YLD were lost due to higher than optimal body mass index (46.7% in males and 53.3% in females). Overweight (body mass index 25-29.9) accounted for 45.7% of total YLD. Males YLD were higher than females under 60. The 35-39 quinquennial group showed a difference for males of 16.6% while in the 74-79 group the difference was 23.8% for women. Osteoarthritis and chronic back pain accounted for 60% of YLD while hypertensive disease and type 2 diabetes mellitus were responsible of 37%. Excess body weight is a health risk related to the development of various diseases with an important associated disability burden and social and economical cost. YLD analysis is a useful monitor tool for disease control interventions. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  17. Nonintrusive verification attributes for excess fissile materials

    Energy Technology Data Exchange (ETDEWEB)

    Nicholas, N.J.; Eccleston, G.W.; Fearey, B.L. [and others

    1997-10-01

    Under US initiatives, over two hundred metric tons of fissile materials have been declared to be excess to national defense needs. These excess materials are in both classified and unclassified forms. The US has expressed the intent to place these materials under international inspections as soon as practicable. To support these commitments, members of the US technical community are examining a variety of nonintrusive approaches (i.e., those that would not reveal classified or sensitive information) for verification of a range of potential declarations for these classified and unclassified materials. The most troublesome and potentially difficult issues involve approaches for international inspection of classified materials. The primary focus of the work to date has been on the measurement of signatures of relevant materials attributes (e.g., element, identification number, isotopic ratios, etc.), especially those related to classified materials and items. The authors are examining potential attributes and related measurement technologies in the context of possible verification approaches. The paper will discuss the current status of these activities, including their development, assessment, and benchmarking status.

  18. Planning with Open Eyes and Open Hearts: An Alternative to Excessive Positivism

    Science.gov (United States)

    O'Brien, John

    2007-01-01

    In this article, the author offers his critique on Holburn and Cea's notion on "excessive positivism" that person-centered planners are overconcerned with scientific verification and logical proof. The author believes that Holburn and Cea's notion blurs the important messages they have for person-centered planners by leading toward a debate about…

  19. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  20. Molecular simulation of excess isotherm and excess enthalpy change in gas-phase adsorption.

    Science.gov (United States)

    Do, D D; Do, H D; Nicholson, D

    2009-01-29

    We present a new approach to calculating excess isotherm and differential enthalpy of adsorption on surfaces or in confined spaces by the Monte Carlo molecular simulation method. The approach is very general and, most importantly, is unambiguous in its application to any configuration of solid structure (crystalline, graphite layer or disordered porous glass), to any type of fluid (simple or complex molecule), and to any operating conditions (subcritical or supercritical). The behavior of the adsorbed phase is studied using the partial molar energy of the simulation box. However, to characterize adsorption for comparison with experimental data, the isotherm is best described by the excess amount, and the enthalpy of adsorption is defined as the change in the total enthalpy of the simulation box with the change in the excess amount, keeping the total number (gas + adsorbed phases) constant. The excess quantities (capacity and energy) require a choice of a reference gaseous phase, which is defined as the adsorptive gas phase occupying the accessible volume and having a density equal to the bulk gas density. The accessible volume is defined as the mean volume space accessible to the center of mass of the adsorbate under consideration. With this choice, the excess isotherm passes through a maximum but always remains positive. This is in stark contrast to the literature where helium void volume is used (which is always greater than the accessible volume) and the resulting excess can be negative. Our definition of enthalpy change is equivalent to the difference between the partial molar enthalpy of the gas phase and the partial molar enthalpy of the adsorbed phase. There is no need to assume ideal gas or negligible molar volume of the adsorbed phase as is traditionally done in the literature. We illustrate this new approach with adsorption of argon, nitrogen, and carbon dioxide under subcritical and supercritical conditions.

  1. WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis.

    Science.gov (United States)

    Nalesso, Giovanna; Thomas, Bethan Lynne; Sherwood, Joanna Claire; Yu, Jing; Addimanda, Olga; Eldridge, Suzanne Elizabeth; Thorup, Anne-Sophie; Dale, Leslie; Schett, Georg; Zwerina, Jochen; Eltawil, Noha; Pitzalis, Costantino; Dell'Accio, Francesco

    2017-01-01

    Both excessive and insufficient activation of WNT signalling results in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here, we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms. Osteoarthritis was induced by destabilisation of the medial meniscus in wild-type and WNT16-deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus. WNT16-deficient mice developed more severe osteoarthritis with reduced expression of lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and lubricin expression. Increased osteoarthritis in WNT16-deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3a to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos. In osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation, thereby supporting the homeostasis of progenitor cells. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Diphoton excess from hidden U(1 gauge symmetry with large kinetic mixing

    Directory of Open Access Journals (Sweden)

    Fuminobu Takahashi

    2016-09-01

    Full Text Available We show that the 750 GeV diphoton excess can be explained by introducing vector-like quarks and hidden fermions charged under a hidden U(1 gauge symmetry, which has a relatively large coupling constant as well as a significant kinetic mixing with U(1Y. With the large kinetic mixing, the standard model gauge couplings unify around 1017 GeV, suggesting the grand unified theory without too rapid proton decay. Our scenario predicts events with a photon and missing transverse momentum, and its cross section is related to that for the diphoton excess through the kinetic mixing. We also discuss other possible collider signatures and cosmology, including various ways to evade constraints on exotic stable charged particles. In some cases where the 750 GeV diphoton excess is due to diaxion decays, our scenario also predicts triphoton and tetraphoton signals.

  3. Using the deuterium-excess to quantify lake water contributions along a pre-alpine stream

    Science.gov (United States)

    Fischer, Benjamin; Chevrolet, Alexandra; van Meerveld, Ilja; Seibert, Jan

    2017-04-01

    The stable isotopes oxygen-18 and deuterium (18O and 2H) are both often used to study runoff processes. In situations involving surface water evaporation the combination of these two isotopes into the so called deuterium-excess can be useful to trace flow contributions. In our study, we collected isotope samples in the Reppisch catchment (24 km2) in Switzerland, where a lake (0.5 km2) is located at the top of a long narrow valley. The Reppisch river runs through this valley and the different tributary streams are all smaller than 1 km2. The goal was to investigate whether it was possible (1) to observe the stable isotope signal of the lake (i.e.the deuterium-excess) in the downstream runoff and (2) to use this signal to quantify the local flow contributions along the main stem of the river. For this we collected water samples from the inflows to the lake, the lake, different sampling points along the 25 km long stream and its tributary streams. The different sampling locations were sampled weekly during the snow free period of 2010, 2011 and 2013. Precipitation was collected at two locations during the snow free period of 2013. All water samples were analyzed on the stable isotopes composition (δ18O and δ2H) from which the deuterium-excess was calculated. Results showed that the deuterium-excess from the side branches had a deuterium-excess near the Global Meteoric Waterline (GMWL, 8 to 10 permil). The deuterium-excess from the lake was near the GMWL but decreased from spring towards autumn towards 2 permil. This enriched signal from the lake was up to 12 km downstream of the lake still clearly traceable. After this point with increasing distance and catchment area the deuterium-excess approached the Global Meteoric Waterline (GMWL). However, the distance was variable due to the variability in discharge contribution of the lake and the state of the subsurface reservoirs. The results showed that the the combination of δ18O and δ2H represented by the deuterium-excess

  4. Excessive anticoagulation with warfarin or phenprocoumon may have multiple causes

    DEFF Research Database (Denmark)

    Meegaard, Peter Martin; Holck, Line H V; Pottegård, Anton

    2012-01-01

    Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation....

  5. Modeling excessive nutrient loading in the environment.

    Science.gov (United States)

    Reckhow, K H; Chapra, S C

    1999-01-01

    Models addressing excessive nutrient loading in the environment originated over 50 years ago with the simple nutrient concentration thresholds proposed by Sawyer (1947. Fertilization of lakes by agricultural and urban drainage. New Engl. Water Works Assoc. 61, 109-127). Since then, models have improved due to progress in modeling techniques and technology as well as enhancements in scientific knowledge. Several of these advances are examined here. Among the recent approaches in modeling techniques we review are error propagation, model confirmation, generalized sensitivity analysis, and Bayesian analysis. In the scientific arena and process characterization, we focus on advances in surface water modeling, discussing enhanced modeling of organic carbon, improved hydrodynamics, and refined characterization of sediment diagenesis. We conclude with some observations on future needs and anticipated developments.

  6. Managing a patient with excessive belching.

    Science.gov (United States)

    Disney, Benjamin; Trudgill, Nigel

    2014-04-01

    A 50-year-old man with end-stage renal failure was referred by his general practitioner with dyspeptic symptoms. On further questioning the patient complained of a 10-year history of frequent belching. This was noticeably worse after meals and during times of stress. He did not have nocturnal belching and episodes of belching were less frequent when the patient was talking or distracted. There was no history of gastro-oesophageal reflux, vomiting, dysphagia, loss of appetite or weight loss. He was diagnosed with excessive, probably supragastric, belching. Further investigation was not deemed necessary. His symptoms have since settled with simple reassurance and explanation of their origin provided during the clinic visit.

  7. Production of ethanol from excess ethylene

    DEFF Research Database (Denmark)

    Kadhim, Adam S.; Carlsen, Kim B.; Bisgaard, Thomas

    2012-01-01

    Ethyl alcohol is one of the most important and used chemicals. Two common routes exist for the production: synthetic route typically based on petroleum feedstock and a fermentation route. The fermentation route comprises the majority of the produced ethyl alcohol. In this work, however, we...... alcohol (azeotropic mixture) is produced from excess ethylene containing propylene and methane as impurities. The design work is based on a systematic approach consisting of 12 tasks performed in a specified hierarchy. According to this 12-tasks design procedure, information about the product and process...... is obtained in tasks 1-2. A preliminary process flowsheet is obtained in task 3 using a modified Douglas hierarchical process synthesis method. The next tasks involves making design decisions and then further refining them in tasks 4-7 related to separation factors, reactor operating conditions, product...

  8. Propylene Glycol Poisoning From Excess Whiskey Ingestion

    Directory of Open Access Journals (Sweden)

    Courtney A. Cunningham MD

    2015-09-01

    Full Text Available In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol.

  9. Excessive Fragmentary Myoclonus: What Do We Know?

    Directory of Open Access Journals (Sweden)

    Jiří Nepožitek

    2017-03-01

    Full Text Available Excessive fragmentary myoclonus (EFM is a polysomnographic finding registered by the surface electromyography (EMG and characterized as a result of the muscle activity consisting of sudden, isolated, arrhythmic, asynchronous and asymmetric brief twitches. The EMG potentials are defined by the exact criteria in The International Classification of the Sleep Disorders, 3rd edition and they appear with high intensity in all sleep stages. Clinical significance of EFM is unclear. It was observed in combination with other diseases and features such as obstructive and central sleep apnea, narcolepsy, periodic limb movements, insomnia, neurodegenerative disorders and peripheral nerve dysfunction. Relation to such wide range of diseases supports the opinion that EFM is nor a specific sleep disorder nor a specific polysomnographic sign. The option that EFM is a normal variant has also not been ruled out so far.

  10. Desaturation of excess intramyocellular triacylglycerol in obesity

    DEFF Research Database (Denmark)

    Haugaard, S B; Madsbad, S; Mu, Huiling

    2010-01-01

    OBJECTIVE: Excess intramyocellular triacylglycerol (IMTG), found especially in obese women, is slowly metabolized and, therefore, prone to longer exposure to intracellular desaturases. Accordingly, it was hypothesized that IMTG content correlates inversely with IMTG fatty acid (FA) saturation...... in sedentary subjects. In addition, it was validated if IMTG palmitic acid is associated with insulin resistance as suggested earlier. DESIGN: Cross-sectional human study. SUBJECTS: In skeletal muscle biopsies, which were obtained from sedentary subjects (34 women, age 48+/-2 years (27 obese including 7 type 2...... diabetes (T2DM), body mass index (BMI)=35.5+/-0.8 kg m(-2)) and 25 men, age 49+/-2 years (20 obese including 6 T2DM, BMI=35.8+/-0.8 kg m(-2))), IMTG FA composition was determined by gas-liquid chromatography after separation from phospholipids by thin-layer chromatography. RESULTS: Independently of gender...

  11. Excess plutonium disposition using ALWR technology

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, A. (ed.); Buckner, M.R.; Radder, J.A.; Angelos, J.G.; Inhaber, H.

    1993-02-01

    The Office of Nuclear Energy of the Department of Energy chartered the Plutonium Disposition Task Force in August 1992. The Task Force was created to assess the range of practicable means of disposition of excess weapons-grade plutonium. Within the Task Force, working groups were formed to consider: (1) storage, (2) disposal,and(3) fission options for this disposition,and a separate group to evaluate nonproliferation concerns of each of the alternatives. As a member of the Fission Working Group, the Savannah River Technology Center acted as a sponsor for light water reactor (LWR) technology. The information contained in this report details the submittal that was made to the Fission Working Group of the technical assessment of LWR technology for plutonium disposition. The following aspects were considered: (1) proliferation issues, (2) technical feasibility, (3) technical availability, (4) economics, (5) regulatory issues, and (6) political acceptance.

  12. Early Reading Proficiency. Leading Indicator Spotlight

    Science.gov (United States)

    Musen, Lindsey

    2010-01-01

    In "Beyond Test Scores: Leading Indicators for Education," Foley and colleagues (2008) define leading indicators as those that "provide early signals of progress toward academic achievement" (p. 1) and stress that educators "need leading indicators to help them see the direction their efforts are going in and to take…

  13. Invisible excess of sense in social interaction.

    Science.gov (United States)

    Koubová, Alice

    2014-01-01

    The question of visibility and invisibility in social understanding is examined here. First, the phenomenological account of expressive phenomena and key ideas of the participatory sense-making theory are presented with regard to the issue of visibility. These accounts plead for the principal visibility of agents in interaction. Although participatory sense-making does not completely rule out the existence of opacity and invisible aspects of agents in interaction, it assumes the capacity of agents to integrate disruptions, opacity and misunderstandings in mutual modulation. Invisibility is classified as the dialectical counterpart of visibility, i.e., as a lack of sense whereby the dynamics of perpetual asking, of coping with each other and of improvements in interpretation are brought into play. By means of empirical exemplification this article aims at demonstrating aspects of invisibility in social interaction which complement the enactive interpretation. Without falling back into Cartesianism, it shows through dramaturgical analysis of a practice called "(Inter)acting with the inner partner" that social interaction includes elements of opacity and invisibility whose role is performative. This means that opacity is neither an obstacle to be overcome with more precise understanding nor a lack of meaning, but rather an excess of sense, a "hiddenness" of something real that has an "active power" (Merleau-Ponty). In this way it contributes to on-going social understanding as a hidden potentiality that naturally enriches, amplifies and in part constitutes human participation in social interactions. It is also shown here that this invisible excess of sense already functions on the level of self-relationship due to the essential self-opacity and self-alterity of each agent of social interaction. The analysis consequently raises two issues: the question of the enactive ethical stance toward the alterity of the other and the question of the autonomy of the self

  14. Invisible excess of sense in social interaction.

    Directory of Open Access Journals (Sweden)

    Alice eKoubová

    2014-09-01

    Full Text Available The question of visibility and invisibility in social understanding is examined here. First, the phenomenological account of expressive phenomena and key ideas of the participatory sense-making theory are presented with regard to the issue of visibility. These accounts plead for the principal visibility of agents in interaction. Although participatory sense-making does not completely rule out the existence of opacity and invisible aspects of agents in interaction, it assumes the capacity of agents to integrate disruptions, opacity and misunderstandings in mutual modulation. Invisibility is classified as the dialectical counterpart of visibility, i.e. as a lack of sense whereby the dynamics of perpetual asking, of coping with each other and of improvements in interpretation are brought into play. By means of empirical exemplification this article aims at demonstrating aspects of invisibility in social interaction which complement the enactive interpretation. Without falling back into Cartesianism, it shows through dramaturgical analysis of a practice called ‘(Interacting with the inner partner’ that social interaction includes elements of opacity and invisibility whose role is performative. This means that opacity is neither an obstacle to be overcome with more precise understanding nor a lack of meaning, but rather an excess of sense, a hiddenness of something real that has an active power (Merleau-Ponty. In this way it contributes to on-going social understanding as a hidden potentiality that naturally enriches, amplifies and in part constitutes human participation in social interactions. It is also shown here that this invisible excess of sense already functions on the level of self-relationship due to the essential self-opacity and self-alterity of each agent of social interaction. The analysis consequently raises two issues: the question of the enactive ethical stance towards the alterity of the other and the question of the autonomy of

  15. The lifetime of excess atmospheric carbon dioxide

    Science.gov (United States)

    Moore, Berrien; Braswell, B. H.

    1994-03-01

    We explore the effects of a changing terrestrial biosphere on the atmospheric residence time of CO2 using three simple ocean carbon cycle models and a model of global terrestrial carbon cycling. We find differences in model behavior associated with the assumption of an active terrestrial biosphere (forest regrowth) and significant differences if we assume a donor-dependent flux from the atmosphere to the terrestrial component (e.g., a hypothetical terrestrial fertilization flux). To avoid numerical difficulties associated with treating the atmospheric CO2 decay (relaxation) curve as being well approximated by a weighted sum of exponential functions, we define the single half-life as the time it takes for a model atmosphere to relax from its present-day value half way to its equilibrium pCO2 value. This scenario-based approach also avoids the use of unit pulse (Dirac Delta) functions which can prove troublesome or unrealistic in the context of a terrestrial fertilization assumption. We also discuss some of the numerical problems associated with a conventional lifetime calculation which is based on an exponential model. We connect our analysis of the residence time of CO2 and the concept of single half-life to the residence time calculations which are based on using weighted sums of exponentials. We note that the single half-life concept focuses upon the early decline of CO2 under a cutoff/decay scenario. If one assumes a terrestrial biosphere with a fertilization flux, then our best estimate is that the single half-life for excess CO2 lies within the range of 19 to 49 years, with a reasonable average being 31 years. If we assume only regrowth, then the average value for the single half-life for excess CO2 increases to 72 years, and if we remove the terrestrial component completely, then it increases further to 92 years.

  16. 32 CFR 644.385 - Record of excess classification.

    Science.gov (United States)

    2010-07-01

    ... PROPERTY REAL ESTATE HANDBOOK Disposal Predisposal Action § 644.385 Record of excess classification. The DE will establish a record on ENG Form 836A, Real Property Disposal Report, of the excess classification... 32 National Defense 4 2010-07-01 2010-07-01 true Record of excess classification. 644.385 Section...

  17. 46 CFR 154.546 - Excess flow valve: Closing flow.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Excess flow valve: Closing flow. 154.546 Section 154.546... and Process Piping Systems § 154.546 Excess flow valve: Closing flow. (a) The rated closing flow of vapor or liquid cargo for an excess flow valve must be specially approved by the Commandant (CG-522). (b...

  18. Excess molar volumes, and refractive index of binary mixtures of ...

    African Journals Online (AJOL)

    Excess molar volumes (VE) viscosities and refractive index have been evaluated for binary mixtures of glycerol + water, and glycerol + methanol at 298.15 K and 303.15 K. Excess molar volumes (VE) have been calculated from density. The excess molar volume (VE) results were fitted to the Redlich and Kister type ...

  19. Diphoton excess in the 2HDM: Hastening towards instability and the nonperturbative regime

    Science.gov (United States)

    Bertuzzo, Enrico; Machado, Pedro A. N.; Taoso, Marco

    2016-12-01

    In December 2015, the ATLAS and CMS collaborations presented a possible signal in the diphoton channel. Although more data have shown that the signal was likely to be only a statistical fluctuation, it is interesting to ask what can be learned if any diphoton excess would show up in future data. Here we challenge the interpretation of any possible diphoton excess in a two-Higgs-doublet framework and find results that are valid whenever a large number of colored and charged vectorlike fermions are needed to boost the production cross section. In a broad region of parameter space, the one-loop effects of these fermions abruptly drive the scalar potential to instability even before the hypercharge gauge coupling becomes nonperturbative.

  20. Signal processing with free software practical experiments

    CERN Document Server

    Auger, François

    2014-01-01

    An ideal resource for students, industrial engineers, and researchers, Signal Processing with Free Software Practical Experiments presents practical experiments in signal processing using free software. The text introduces elementary signals through elementary waveform, signal storage files and elementary operations on signals and then presents the first tools to signal analysis such as temporal and frequency characteristics leading to Time-frequency analysis. Non-parametric spectral analysis is also discussed as well as signal processing through sampling, resampling, quantification, an

  1. Sonolência excessiva Excessive daytime sleepiness

    Directory of Open Access Journals (Sweden)

    Lia Rita Azeredo Bittencourt

    2005-05-01

    Full Text Available A sonolência é uma função biológica, definida como uma probabilidade aumentada para dormir. Já a sonolência excessiva (SE, ou hipersonia, refere-se a uma propensão aumentada ao sono com uma compulsão subjetiva para dormir, tirar cochilos involuntários e ataques de sono, quando o sono é inapropriado. As principais causas de sonolência excessiva são a privação crônica de sono (sono insuficiente, a Síndrome da Apnéia e Hipopnéia Obstrutiva do Sono (SAHOS, a narcolepsia, a Síndrome das Pernas Inquietas/Movimentos Periódicos de Membros (SPI/MPM, Distúrbios do Ritmo Circadiano, uso de drogas e medicações e a hipersonia idiopática. As principais conseqüências são prejuízo no desempenho nos estudos, no trabalho, nas relações familiares e sociais, alterações neuropsicológicas e cognitivas e risco aumentado de acidentes. O tratamento da sonolência excessiva deve estar voltado para as causas específicas. Na privação voluntária do sono, aumentar o tempo de sono e higiene do sono, o uso do CPAP (Continuous Positive Airway Pressure na Síndrome da Apnéia e Hipopnéia Obstrutiva do Sono, exercícios e agentes dopaminérgicos na Síndrome das Pernas Inquietas/Movimentos Periódicos de Membros, fototerapia e melatonina nos Distúrbios do Ritmo Circadiano, retiradas de drogas que causam sonolência excessiva e uso de estimulantes da vigília.Sleepiness is a physiological function, and can be defined as increased propension to fall asleep. However, excessive sleepiness (ES or hypersomnia refer to an abnormal increase in the probability to fall asleep, to take involuntary naps, or to have sleep atacks, when sleep is not desired. The main causes of excessive sleepiness is chronic sleep deprivation, sleep apnea syndrome, narcolepsy, movement disorders during sleep, circadian sleep disorders, use of drugs and medications, or idiopathic hypersomnia. Social, familial, work, and cognitive impairment are among the consequences of

  2. Phospholipids as Biomarkers for Excessive Alcohol Use

    Science.gov (United States)

    2015-10-01

    protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes . 2015 Apr;64(4):1211-23. doi: 10.2337/db14-0539...cardiomyopathy: review of pathophysiology and treatment. Hepatol Int. 2014 Jul;8(3):308-15. doi: 10.1007/s12072- 014-9531-y. PubMed PMID: 25221635; PubMed

  3. Insights into innate immune signalling in controlling cardiac remodelling.

    Science.gov (United States)

    Zhang, Yaxing; Huang, Zan; Li, Hongliang

    2017-11-01

    Canonical innate immune signalling involves complex cascades: multiple germline-encoded pattern recognition receptors rapidly recognize pathogen-associated or damage-associated molecular patterns to induce the production of cytokines, which bind to their corresponding receptors to orchestrate subsequent host defense phases. Inflammation is a healthy response to pathogenic signals, which are typically rapid and specific, and they terminate once the threat has passed. However, excessive activation or suppression of innate immune or inflammatory responses can lead to considerable human suffering, such as cardiac remodelling. Interestingly, recent studies have revealed that innate immune molecules in the parenchymal cells of the heart influence cardiac homeostasis not only by directly regulating innate immune responses but also through reprogrammed signalling pathways, which are independent of conventional innate immune signalling. Elucidating 'innate immune signalling reprogramming' events will help us better understand the functions of innate immune molecules and, moreover, the pathogenesis of cardiac diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  4. Signals of New Physics in the Underlying Event

    Energy Technology Data Exchange (ETDEWEB)

    Harnik, Roni; /Stanford U., ITP /SLAC; Wizansky, Tommer; /SLAC

    2010-06-11

    LHC searches for new physics focus on combinations of hard physics objects. In this work we propose a qualitatively different soft signal for new physics at the LHC - the 'anomalous underlying event'. Every hard LHC event will be accompanied by a soft underlying event due to QCD and pile-up effects. Though it is often used for QCD and monte carlo studies, here we propose the incorporation of an underlying event analysis in some searches for new physics. An excess of anomalous underlying events may be a smoking-gun signal for particular new physics scenarios such as 'quirks' or 'hidden valleys' in which large amounts of energy may be emitted by a large multiplicity of soft particles. We discuss possible search strategies for such soft diffuse signals in the tracking system and calorimetry of the LHC experiments. We present a detailed study of the calorimetric signal in a concrete example, a simple quirk model motivated by folded supersymmetry. In these models the production and radiative decay of highly excited quirk bound states leads to an 'antenna pattern' of soft unclustered energy. Using a dedicated simulation of a toy detector and a 'CMB-like' multipole analysis we compare the signal to the expected backgrounds.

  5. Energy potential of the modified excess sludge

    Directory of Open Access Journals (Sweden)

    Zawieja Iwona

    2017-01-01

    Full Text Available On the basis of the SCOD value of excess sludge it is possible to estimate an amount of energy potentially obtained during the methane fermentation process. Based on a literature review, it has been estimated that from 1 kg of SCOD it is possible to obtain 3.48 kWh of energy. Taking into account the above methane and energy ratio (i.e. 10 kWh/1Nm3 CH4, it is possible to determine the volume of methane obtained from the tested sludge. Determination of potential energy of sludge is necessary for the use of biogas as a source of power generators as cogeneration and ensure the stability of this type of system. Therefore, the aim of the study was to determine the energy potential of excess sludge subjected to the thermal and chemical disintegration. In the case of thermal disintegration, test was conducted in the low temperature 80°C. The reagent used for the chemical modification was a peracetic acid, which in an aqueous medium having strong oxidizing properties. The time of chemical modification was 6 hours. Applied dose of the reagent was 1.0 ml CH3COOOH/L of sludge. By subjecting the sludge disintegration by the test methods achieved an increase in the SCOD value of modified sludge, indicating the improvement of biodegradability along with a concomitant increase in their energy potential. The obtained experimental production of biogas from disintegrated sludge confirmed that it is possible to estimate potential intensity of its production. The SCOD value of 2576 mg O2/L, in the case of chemical disintegration, was obtained for a dose of 1.0 ml CH3COOH/L. For this dose the pH value was equal 6.85. In the case of thermal disintegration maximum SCOD value was 2246 mg O2/L obtained at 80°C and the time of preparation 6 h. It was estimated that in case of thermal disintegration as well as for the chemical disintegration for selected parameters, the potential energy for model digester of active volume of 5L was, respectively, 0.193 and 0,118 kWh.

  6. Energy potential of the modified excess sludge

    Science.gov (United States)

    Zawieja, Iwona

    2017-11-01

    On the basis of the SCOD value of excess sludge it is possible to estimate an amount of energy potentially obtained during the methane fermentation process. Based on a literature review, it has been estimated that from 1 kg of SCOD it is possible to obtain 3.48 kWh of energy. Taking into account the above methane and energy ratio (i.e. 10 kWh/1Nm3 CH4), it is possible to determine the volume of methane obtained from the tested sludge. Determination of potential energy of sludge is necessary for the use of biogas as a source of power generators as cogeneration and ensure the stability of this type of system. Therefore, the aim of the study was to determine the energy potential of excess sludge subjected to the thermal and chemical disintegration. In the case of thermal disintegration, test was conducted in the low temperature 80°C. The reagent used for the chemical modification was a peracetic acid, which in an aqueous medium having strong oxidizing properties. The time of chemical modification was 6 hours. Applied dose of the reagent was 1.0 ml CH3COOOH/L of sludge. By subjecting the sludge disintegration by the test methods achieved an increase in the SCOD value of modified sludge, indicating the improvement of biodegradability along with a concomitant increase in their energy potential. The obtained experimental production of biogas from disintegrated sludge confirmed that it is possible to estimate potential intensity of its production. The SCOD value of 2576 mg O2/L, in the case of chemical disintegration, was obtained for a dose of 1.0 ml CH3COOH/L. For this dose the pH value was equal 6.85. In the case of thermal disintegration maximum SCOD value was 2246 mg O2/L obtained at 80°C and the time of preparation 6 h. It was estimated that in case of thermal disintegration as well as for the chemical disintegration for selected parameters, the potential energy for model digester of active volume of 5L was, respectively, 0.193 and 0,118 kWh.

  7. Excessive iodine intake and thyroid dysfunction among lactating Saharawi women.

    Science.gov (United States)

    Aakre, Inger; Bjøro, Trine; Norheim, Ingrid; Strand, Tor A; Barikmo, Ingrid; Henjum, Sigrun

    2015-01-01

    Excessive iodine intake may lead to thyroid dysfunction, which may be particularly harmful during pregnancy and lactation. The main objective was to describe iodine status and the prevalence of thyroid dysfunction among lactating women in areas with high iodine (HI) and very high iodine (VHI) concentrations in drinking water. A cross-sectional survey was performed among 111 lactating women in the Saharawi refugee camps, Algeria. Breast milk iodine concentration (BMIC), urinary iodine concentration (UIC) and the iodine concentration in the most commonly consumed foods/drinks were measured. A 24-h dietary recall was used to estimate iodine intake. Thyroid hormones and antibodies were measured in serum. Median UIC, BMIC and iodine intake across both areas was 350 μg/L, 479 μg/L and 407 μg/day, respectively. In multiple regression analyses, we discovered that being from VHI area was associated with higher UIC and BMIC. BMIC was also positively associated with iodine intake. Thyroid dysfunction and/or positive thyroid antibodies were found in 33.3% of the women, of which 18.9% had hypothyroidism and 8.1% had hyperthyroidism and 6.3% had positive antibodies with normal thyroid function. Elevated thyroid antibodies were in total found in 17.1%. We found no difference in distribution of thyroid dysfunction or positive antibodies between HI and VHI areas. BMI, BMIC and elevated thyroglobulin (Tg) predicted abnormal thyroid function tests. The high prevalence of thyroid dysfunction may be caused by excessive iodine intake over several years. Copyright © 2014 Elsevier GmbH. All rights reserved.

  8. Swift recovery of Sphagnum nutrient concentrations after excess supply.

    Science.gov (United States)

    Limpens, Juul; Heijmans, Monique M P D

    2008-08-01

    Although numerous studies have addressed the effects of increased N deposition on nutrient-poor environments such as raised bogs, few studies have dealt with to what extent, and on what time-scale, reductions in atmospheric N supply would lead to recovery of the ecosystems in question. Since a considerable part of the negative effects of elevated N deposition on raised bogs can be related to an imbalance in tissue nutrient concentrations of the dominant peat-former Sphagnum, changes in Sphagnum nutrient concentration after excess N supply may be used as an early indicator of ecosystem response. This study focuses on the N and P concentrations of Sphagnum magellanicum and Sphagnum fallax before, during and after a factorial fertilization experiment with N and P in two small peatlands subject to a background bulk deposition of 2 g N m(-2) year(-1). Three years of adding N (4.0 g N m(-2) year(-1)) increased the N concentration, and adding P (0.3 g P m(-2) year(-1)) increased the P concentration in Sphagnum relative to the control treatment at both sites. Fifteen months after the nutrient additions had ceased, N concentrations were similar to the control whereas P concentrations, although strongly reduced, were still slightly elevated. The changes in the N and P concentrations were accompanied by changes in the distribution of nutrients over the capitulum and the stem and were congruent with changes in translocation. Adding N reduced the stem P concentration, whereas adding P reduced the stem N concentration in favor of the capitulum. Sphagnum nutrient concentrations quickly respond to reductions in excess nutrient supply, indicating that a management policy aimed at reducing atmospheric nutrient input to bogs can yield results within a few years.

  9. Limitations in determining enantiomeric excess of alcohols by 31P-NMR of the phosphonate derivatives

    Directory of Open Access Journals (Sweden)

    Laverde Jr. Antonio

    1999-01-01

    Full Text Available The use of diastereomeric alcohol dialkylphosphonate derivatives to determine the enantiomeric excesses via 31P-NMR signal ratios of anisochronous meso and threo isomers was successfully applied to secondary alcohols (Feringa?s method. Expansion of the methodology to primary alcohols possessing the hydroxyl groups thethered to the stereogenic centers by two or more methylene groups proved the method to be inefficent. The comparison between the coupled and decoupled spectra is important in order to identify the signals corresponding to the dialkylphosphonates. Nevertheless the methodology should be applied whenever the amount of the alcohol and its structure are not the limiting factors.

  10. Symmetrical excessive pectus excavatum in children.

    Science.gov (United States)

    Balci, Akin Eraslan; Eren, Sevval; Ozyurtkan, Mehmet Oguzhan

    2013-12-01

    The indications for repair of pectus excavatum are controversial. We present our surgical results in children with severe pectus excavatum. 27 children aged 6-15-years were included in the study. Pulmonary function tests and chest measurements were performed pre- and postoperatively. Deformed cartilages were resected subperichondrially, and a Kirchner wire was used to support the chest cage; it was removed 5 days after the operation. Fourteen children with restricted pulmonary function were considered to have excessive pectus excavatum. 3 patients had asthma-like symptoms that resolved postoperatively. None suffered chest pain postoperatively. Postoperative hospital stay was 7.1 days. Only minor complications occurred postoperatively. The mean pectus severity index was 0.27 ± 0.2 preoperatively and 0.41 ± 0.1 postoperatively (p pectus severity index pectus severity index (r = 0.8). After 6 and 13 months, a minor decrease in pulmonary function was noted. Significant increases in right and left ventricular function occurred in cases of severe deformity. Surgery is recommended not only for cosmetic reasons but also to increase cardiorespiratory functional capacity and alleviate symptoms. Kirchner wires can be used safely.

  11. [Base excess. Parameter with exceptional clinical significance].

    Science.gov (United States)

    Schaffartzik, W

    2007-05-01

    The base excess of blood (BE) plays an important role in the description of the acid-base status of a patient and is gaining in clinical interest. Apart from the Quick test, the age, the injury severity score and the Glasgow coma scale, the BE is becoming more and more important to identify, e. g. the risk of mortality for patients with multiple injuries. According to Zander the BE is calculated using the pH, pCO(2), haemoglobin concentration and the oxygen saturation of haemoglobin (sO(2)). The use of sO(2 )allows the blood gas analyser to determine only one value of BE, independent of the type of blood sample analyzed: arterial, mixed venous or venous. The BE and measurement of the lactate concentration (cLac) play an important role in diagnosing critically ill patients. In general, the change in BE corresponds to the change in cLac. If DeltaBE is smaller than DeltacLac the reason could be therapy with HCO(3)(-) but also with infusion solutions containing lactate. Physician are very familiar with the term BE, therefore, knowledge about an alkalizing or acidifying effect of an infusion solution would be very helpful in the treatment of patients, especially critically ill patients. Unfortunately, at present the description of an infusion solution with respect to BE has not yet been accepted by the manufacturers.

  12. Cool WISPs for stellar cooling excesses

    Science.gov (United States)

    Giannotti, Maurizio; Irastorza, Igor; Redondo, Javier; Ringwald, Andreas

    2016-05-01

    Several stellar systems (white dwarfs, red giants, horizontal branch stars and possibly the neutron star in the supernova remnant Cassiopeia A) show a mild preference for a non-standard cooling mechanism when compared with theoretical models. This exotic cooling could be provided by Weakly Interacting Slim Particles (WISPs), produced in the hot cores and abandoning the star unimpeded, contributing directly to the energy loss. Taken individually, these excesses do not show a strong statistical weight. However, if one mechanism could consistently explain several of them, the hint could be significant. We analyze the hints in terms of neutrino anomalous magnetic moments, minicharged particles, hidden photons and axion-like particles (ALPs). Among them, the ALP or a massless HP represent the best solution. Interestingly, the hinted ALP parameter space is accessible to the next generation proposed ALP searches, such as ALPS II and IAXO and the massless HP requires a multi TeV energy scale of new physics that might be accessible at the LHC.

  13. What controls deuterium excess in global precipitation?

    Directory of Open Access Journals (Sweden)

    S. Pfahl

    2014-04-01

    Full Text Available The deuterium excess (d of precipitation is widely used in the reconstruction of past climatic changes from ice cores. However, its most common interpretation as moisture source temperature cannot directly be inferred from present-day water isotope observations. Here, we use a new empirical relation between d and near-surface relative humidity (RH together with reanalysis data to globally predict d of surface evaporation from the ocean. The very good quantitative agreement of the predicted hemispherically averaged seasonal cycle with observed d in precipitation indicates that moisture source relative humidity, and not sea surface temperature, is the main driver of d variability on seasonal timescales. Furthermore, we review arguments for an interpretation of long-term palaeoclimatic d changes in terms of moisture source temperature, and we conclude that there remains no sufficient evidence that would justify to neglect the influence of RH on such palaeoclimatic d variations. Hence, we suggest that either the interpretation of d variations in palaeorecords should be adapted to reflect climatic influences on RH during evaporation, in particular atmospheric circulation changes, or new arguments for an interpretation in terms of moisture source temperature will have to be provided based on future research.

  14. Exposure to low level chronic radiation leads to adaptation to a subsequent acute X-ray dose and communication of modified acute X-ray induced bystander signals in medaka (Japanese rice fish, Oryzias latipes).

    Science.gov (United States)

    Smith, Richard W; Mothersill, Carmel; Hinton, Thomas; Seymour, Colin B

    2011-10-01

    To determine the effect of acute high dose X-rays on the direct and bystander response of chronically exposed medaka in vivo using the fish communication model. Medaka were obtained from the Low Dose Rate Irradiation Facility (LoDIF) located at the Savannah River Ecology Laboratory (SREL), University of Georgia, Aiken, South Carolina, USA where they had been exposed over 264 days to cumulative total doses of 0, 0.03, 0.66 and 5.88 Gy. They were exposed to the acute dose at McMaster University and then allowed to swim with unexposed medaka. All groups were sacrificed and fins were cultured as explants and assayed using an established technique and reporter assay. Directly irradiated medaka with no chronic exposure showed a classic in vivo bystander response. Chronic pre-exposure resulted in a chronic dose-dependent increase in reporter cell survival in directly exposed fish. A 'pro-survival' response was also seen in the bystander fish. The proteins bcl-2 (b cell lymphoma 2) and c-Myc (myelocytomatosis oncogene cellular) in tissue explants were good predictors of pro-life or pro-death signals. Environmentally relevant chronic exposure to medaka in vivo results in adaptive responses in fish subsequently irradiated with high acute doses and in communication of protective signals to fish swimming with exposed fish. The data have implications for interpretation of radiation effects in biota.

  15. Thermal Resonance in Signal Transmission

    OpenAIRE

    Reigada Sanz, Ramon; Sarmiento, Antonio; Lindenberg, Katja

    2001-01-01

    We use temperature tuning to control signal propagation in simple one-dimensional arrays of masses connected by hard anharmonic springs and with no local potentials. In our numerical model a sustained signal is applied at one site of a chain immersed in a thermal environment and the signal-to-noise ratio is measured at each oscillator. We show that raising the temperature can lead to enhanced signal propagation along the chain, resulting in thermal resonance effects akin to the resonance obse...

  16. OSHA issues new guidelines on lead.

    Science.gov (United States)

    1979-12-07

    The OSHA (Occupational Safety and Health Administration) issued new lead exposure standards which were effective February 1979. The policy provides that workers in childbearing years should receive protected earnings and benefits for 18 months while temporarily removed from their regular job to one with less lead exposure. Excessive lead exposure can reduce sex drive, cause impotence and sterility in men, and cause reduced fertility and menstrual disorders in women. Children of exposed parents may have birth defects, mental retardation, or die in their first year.

  17. ECG monitoring leads and special leads.

    Science.gov (United States)

    Francis, Johnson

    ECG monitoring is common place in the hospital and even pre-hospital setting. The need for different types of lead systems in different settings has been emphasised. Simple three electrode bipolar recording is ubiquitous for monitoring. This can be used to record modified bipolar chest leads as well. Using five leads gives the option of getting a chest lead in addition to bipolar limb leads, enhancing detection of ischemia during procedures. Lead stability is important when the movement of the subject is maximum as in exercise testing. Mason-Likar modification with limb leads shifted to the torso is popular for exercise testing, though the diagnostic value of the ECG is altered. Lund system with leads on proximal part of limbs have both stability and fair diagnostic value. EASI lead system permits derivation of 12 leads from just five electrodes. Lewis lead and the newly devised modified limb lead system are useful in enhancing detection of atrial activity. Fontaine lead has been designed to improve visualization of Epsilon wave in arrhythmogenic right ventricular dysplasia. Copyright © 2016 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

  18. Genital self-mutilation in a non-psychotic male to get rid of excessive sexual drive: A case report

    Directory of Open Access Journals (Sweden)

    Adarsh Tripathi

    2015-02-01

    Full Text Available Genital self-mutilation (GSM is a rare phenomenon. In the majority of cases, GSM is secondary to psychotic illness. Among the non-psychotics, the motives behind GSM are varied. We report a rare case in which a non-psychotic, non-paraphilic patient suffering from excessive sexual drive carried out GSM to curb hypersexuality. Aetiological factors behind GSM are discussed. This case report emphasises that excessive sexual drive may lead to distress and GSM. Effective management of excessive sexual drive and active inquiry into any intentions of GSM in such patients may be helpful in preventing GSM.

  19. Is excess male infant mortality from sudden infant death syndrome and other respiratory diseases X-linked?

    Science.gov (United States)

    Mage, David T; Donner, E Maria

    2014-02-01

    Male excess infant mortality is well known but unexplained. In 2004, we reported sudden infant death syndrome (SIDS) and other infant respiratory deaths showed a ~50% male excess in the United States between 1979 and 2002. This study analyses expanded US data from 1968 to 2010 to see whether infant respiratory deaths still show similar ~50% male excess and may be X-linked. The analysis compared infant mortality data from the US Centers for Disease Control and Prevention, 1968-2010, with 11 World Health Organization International Classification of Diseases (ICD) rubric groups for respiratory deaths by accidents, congenital anomalies, respiratory diseases and causes unknown. The 11 ICD groupings presented male excesses of ~50% and combining the 453,953 US cases produced a male fraction of 0.6034, a 52.1% male excess. A further 72,380 non-US respiratory cases showed a similar 0.6055 male fraction, a 53.5% male excess. The constant ~50% male excess for quite different causes of respiratory death suggests they all have a common terminal event and that is acute anoxic encephalopathy. We hypothesise that this constant male excess phenomenon must be caused by a single X-linked gene, with a recessive condition, leading to a predisposition to succumb to acute anoxic encephalopathy. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  20. In Vivo Characterization of Intracellular Signaling Pathways Activated by the Nerve Agent Sarin

    National Research Council Canada - National Science Library

    Shih, Tsung-Ming A; Snyder, Gretchen L; Hendrick, Joseph P; Fienberg, Allen A; McDonough, John H

    2004-01-01

    ..., an excessive stimulation of nicotinic and muscarinic receptors. Preliminary evidence using diverse OPs indicates that the DARPP-32/PP-1 signaling pathway is activated by nicotinic receptor stimulation...

  1. Subcellular distribution of molybdenum, ultrastructural and antioxidative responses in soybean seedlings under excess molybdenum stress.

    Science.gov (United States)

    Xu, Shoujun; Hu, Chengxiao; Tan, Qiling; Qin, Shiyu; Sun, Xuecheng

    2017-12-05

    Some studies have shown that excess molybdenum (Mo) could produce toxic effects on plants. However, little is known about the subcellular distribution of Mo and cell ultrastructure within plants under excess Mo stress. Here, we comprehensively analyzed the changes of Mo distribution in subcellular fractions, cell ultrastructure and antioxidant enzymes in leaves and roots of soybean seedlings in response to excess Mo stress. The results showed that roots exhibited higher Mo accumulation than leaves at the 100 mg L-1 Mo level, about 38.58-, 171.48- and 52.99-fold higher in cell walls, cell organelles and soluble fractions, respectively. Subcellular fractionations of Mo-containing tissues indicated that approximately 90% of Mo was accumulated in the soluble fractions and cell walls of the roots and leaves, and soluble fractions (accumulated 66.3-72.2% Mo) might serve as an effective storage site for excess Mo. Furthermore, excess Mo caused ultrastructural alterations in roots and leaves of soybean seedlings, leading to structural abnormality of chloroplast in leaf cells, plasmolysis, cellular deformity, vacuole enlargement and the swelling of cell wall and cytoplasm in root cells. Meanwhile, under excess Mo stress, the activity of POD, CAT and APX enzymes in roots was 1.43, 2.35 and 1.23 times that under standard Mo condition, while that of SOD and CAT enzymes in leaves was 1.23 and 1.94 times, respectively. This study provided novel insights into the mechanisms of excess Mo toxicity in soybean seedlings. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Learn about Lead

    Science.gov (United States)

    ... Protection Agency Search Search Lead Contact Us Share Learn about Lead General Lead Information Read more about ... water, soil, consumer products, food, and occupational settings. Learn more about sources of lead exposure: At home ...

  3. Lead Poisoning Prevention Tips

    Science.gov (United States)

    ... or removed safely. How are children exposed to lead? Lead-based paint and lead contaminated dust are ... What can be done to prevent exposure to lead? It is important to determine the construction year ...

  4. Lead levels - blood

    Science.gov (United States)

    Blood lead levels ... is used to screen people at risk for lead poisoning. This may include industrial workers and children ... also used to measure how well treatment for lead poisoning is working. Lead is common in the ...

  5. Millisecond Pulsars and the Galactic Center Excess

    Science.gov (United States)

    Gonthier, Peter L.; Koh, Yew-Meng; Kust Harding, Alice; Ferrara, Elizabeth C.

    2017-08-01

    Various groups including the Fermi team have confirmed the spectrum of the gamma- ray excess in the Galactic Center (GCE). While some authors interpret the GCE as evidence for the annihilation of dark matter (DM), others have pointed out that the GCE spectrum is nearly identical to the average spectrum of Fermi millisecond pul- sars (MSP). Assuming the Galactic Center (GC) is populated by a yet unobserved source of MSPs that has similar properties to that of MSPs in the Galactic Disk (GD), we present results of a population synthesis of MSPs from the GC. We establish parameters of various models implemented in the simulation code by matching characteristics of 54 detected Fermi MSPs in the first point source catalog and 92 detected radio MSPs in a select group of thirteen radio surveys and targeting a birth rate of 45 MSPs per mega-year. As a check of our simulation, we find excellent agreement with the estimated numbers of MSPs in eight globular clusters. In order to reproduce the gamma-ray spectrum of the GCE, we need to populate the GC with 10,000 MSPs having a Navarro-Frenk-White distribution suggested by the halo density of DM. It may be possible for Fermi to detect some of these MSPs in the near future; the simulation also predicts that many GC MSPs have radio fluxes S1400above 10 �μJy observable by future pointed radio observations. We express our gratitude for the generous support of the National Science Foundation (RUI: AST-1009731), Fermi Guest Investigator Program and the NASA Astrophysics Theory and Fundamental Program (NNX09AQ71G).

  6. Factors influencing excessive daytime sleepiness in adolescents

    Directory of Open Access Journals (Sweden)

    Thiago de Souza Vilela

    2016-04-01

    Full Text Available Abstract Objective: Sleep deprivation in adolescents has lately become a health issue that tends to increase with higher stress prevalence, extenuating routines, and new technological devices that impair adolescents' bedtime. Therefore, this study aimed to assess the excessive sleepiness frequency and the factors that might be associated to it in this population. Methods: The cross-sectional study analyzed 531 adolescents aged 10–18 years old from two private schools and one public school. Five questionnaires were applied: the Cleveland Adolescent Sleepiness Questionnaire; the Sleep Disturbance Scale for Children; the Brazilian Economic Classification Criteria; the General Health and Sexual Maturation Questionnaire; and the Physical Activity Questionnaire. The statistical analyses were based on comparisons between schools and sleepiness and non-sleepiness groups, using linear correlation and logistic regression. Results: Sleep deprivation was present in 39% of the adolescents; sleep deficit was higher in private school adolescents (p < 0.001, and there was a positive correlation between age and sleep deficit (p < 0.001; r = 0.337. Logistic regression showed that older age (p = 0.002; PR: 1.21 [CI: 1.07–1.36] and higher score level for sleep hyperhidrosis in the sleep disturbance scale (p = 0.02; PR: 1.16 [CI: 1.02–1.32] were risk factors for worse degree of sleepiness. Conclusions: Sleep deficit appears to be a reality among adolescents; the results suggest a higher prevalence in students from private schools. Sleep deprivation is associated with older age in adolescents and possible presence of sleep disorders, such as sleep hyperhidrosis.

  7. Implication of zinc excess on soil health.

    Science.gov (United States)

    Wyszkowska, Jadwiga; Boros-Lajszner, Edyta; Borowik, Agata; Baćmaga, Małgorzata; Kucharski, Jan; Tomkiel, Monika

    2016-01-01

    This study was undertaken to evaluate zinc's influence on the resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease. The experiment was conducted in a greenhouse of the University of Warmia and Mazury (UWM) in Olsztyn, Poland. Plastic pots were filled with 3 kg of sandy loam with pHKCl - 7.0 each. The experimental variables were: zinc applied to soil at six doses: 100, 300, 600, 1,200, 2,400 and 4,800 mg of Zn(2+) kg(-1) in the form of ZnCl2 (zinc chloride), and species of plant: oat (Avena sativa L.) cv. Chwat and white mustard (Sinapis alba) cv. Rota. Soil without the addition of zinc served as the control. During the growing season, soil samples were subjected to microbiological analyses on experimental days 25 and 50 to determine the abundance of organotrophic bacteria, actinomyces and fungi, and the activity of dehydrogenases, catalase and urease, which provided a basis for determining the soil resistance index (RS). The physicochemical properties of soil were determined after harvest. The results of this study indicate that excessive concentrations of zinc have an adverse impact on microbial growth and the activity of soil enzymes. The resistance of organotrophic bacteria, actinomyces, fungi, dehydrogenases, catalase and urease decreased with an increase in the degree of soil contamination with zinc. Dehydrogenases were most sensitive and urease was least sensitive to soil contamination with zinc. Zinc also exerted an adverse influence on the physicochemical properties of soil and plant development. The growth of oat and white mustard plants was almost completely inhibited in response to the highest zinc doses of 2,400 and 4,800 mg Zn(2+) kg(-1).

  8. Excess crude protein for nongravid gilts.

    Science.gov (United States)

    Fox, M C; Watkins, K L; Craig, W M; Stewart, T B; Clawson, A J; Southern, L L

    1988-04-01

    Twenty-five nongravid crossbred gilts (avg initial wt, 126 kg) were placed on either a high (38%) or a low (13%) crude protein (CP) diet and fed either at the rate of 1.82 kg/d or had ad libitum access to feed. In addition, a fifth group was pair-fed the 13% CP diet to the average intake of the gilts fed high CP ad libitum. The experimental period lasted 30 d. Corn-soybean meal diets were used and CP levels were varied by altering the corn:soybean meal ratio. Gain and gain/feed were reduced (P less than .01) in gilts fed 1.82 kg/d compared with the gilts fed ad libitum or pair-fed gilts. Gain (P less than .03) and feed intake (P less than .01) of gilts with ad libitum access to the 13% CP diet were higher than those of gilts with ad libitum access to the 38% CP diet. Gain/feed was not different (P greater than .10) between the two groups, however. Rate of gain and feed efficiency of gilts pair-fed the 13% CP diet were similar (P greater than .10) to those of gilts with ad libitum access to the 38% CP diet. Plasma total free amino acids, NH3 and total protein were not (P greater than .10) affected by treatment. Plasma urea-N and urinary total N, urea-N and orotic acid were increased (P less than .01) in gilts fed the high CP diet regardless of feed intake level. However, urinary NH3 was higher (P less than .01) in gilts fed the low-protein diet. These results indicate that excess dietary CP for nongravid gilts decreases gain and feed intake and has no effect on efficiency of feed utilization, but it increases plasma urea-N and urinary total N, urea-N and orotic acid.

  9. Iron excess in recreational marathon runners.

    Science.gov (United States)

    Mettler, S; Zimmermann, M B

    2010-05-01

    Iron deficiency and anemia may impair athletic performance, and iron supplements are commonly consumed by athletes. However, iron overload should be avoided because of the possible long-term adverse health effects. We investigated the iron status of 170 male and female recreational runners participating in the Zürich marathon. Iron deficiency was defined either as a plasma ferritin (PF) concentration or =4.5 (functional iron deficiency). After excluding subjects with elevated C-reactive protein concentrations, iron overload was defined as PF >200 microg/l. Iron depletion was found in only 2 out of 127 men (1.6% of the male study population) and in 12 out of 43 (28.0%) women. Functional iron deficiency was found in 5 (3.9%) and 11 (25.5%) male and female athletes, respectively. Body iron stores, calculated from the sTfR/PF ratio, were significantly higher (Prunners. Median PF among males was 104 microg/l, and the upper limit of the PF distribution in males was 628 microg/l. Iron overload was found in 19 out of 127 (15.0%) men but only 2 out of 43 in women (4.7%). Gender (male sex), but not age, was a predictor of higher PF (Prunners but in runners had signs of iron overload. Although iron supplements are widely used by athletes in an effort to increase performance, our findings indicate excess body iron may be common in male recreational runners and suggest supplements should only be used if tests of iron status indicate deficiency.

  10. The decreased growth performance and impaired immune function and structural integrity by dietary iron deficiency or excess are associated with TOR, NF-κB, p38MAPK, Nrf2 and MLCK signaling in head kidney, spleen and skin of grass carp (Ctenopharyngodon idella).

    Science.gov (United States)

    Guo, Yan-Lin; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Zhou, Xiao-Qiu; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Feng, Lin

    2017-06-01

    This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days. Then, a challenge test was conducted by infection of Aeromonas hydrophila for 14 days. The results firstly showed that compared with optimal iron level, iron deficiency decreased lysozyme (LZ) and acid phosphatase (ACP) activities, complement 3 (C3), C4 and immunoglobulin M (IgM) contents and down-regulated the mRNA levels of antibacterial peptides, anti-inflammatory cytokines, inhibitor of κBα (IκBα), target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1), whereas up-regulated the mRNA levels of pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) p65, IκB kinases β (IKKβ) and eIF4E-binding protein (4E-BP) in head kidney and spleen of young grass carp (P growth and impaired the immune function and structural integrity in head kidney, spleen and skin of fish. Besides, in young grass carp, based on PWG and ability against skin hemorrhage and lesion, the efficacy of ferrous fumarate relative to ferrous sulfate was 140.32% and 126.48%, respectively, and the iron requirements based on PWG, ability against skin hemorrhage and lesion, ACP activities and MDA contents in head kidney and spleen were estimated to be 75.65, 87.03, 79.74, 78.93, 83.17 and 82.14 mg/kg diet (based on ferrous fumarate), respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Inadvertent transarterial pacemaker lead placement

    Directory of Open Access Journals (Sweden)

    Ravi R. Bajaj

    2015-09-01

    Full Text Available We present a case of a 73-year-old patient with acute left-sided hemiparesis four months after right ventricular pacemaker insertion. Post-procedural electrocardiogram revealed a paced RBBB complex and an abnormal lead path on chest X-ray. Subsequent echocardiography and computed tomography showed left ventricular pacemaker malposition with retrograde passage to the punctured subclavian artery. We also discuss the utility of routine cardiac investigations post-insertion to identify signal lead malposition as well as management strategies once identified.

  12. Protein tyrosine phosphatase α in the dorsomedial striatum promotes excessive ethanol-drinking behaviors.

    Science.gov (United States)

    Ben Hamida, Sami; Darcq, Emmanuel; Wang, Jun; Wu, Su; Phamluong, Khanhky; Kharazia, Viktor; Ron, Dorit

    2013-09-04

    We previously found that excessive ethanol drinking activates Fyn in the dorsomedial striatum (DMS) (Wang et al., 2010; Gibb et al., 2011). Ethanol-mediated Fyn activation in the DMS leads to the phosphorylation of the GluN2B subunit of the NMDA receptor, to the enhancement of the channel's activity, and to the development and/or maintenance of ethanol drinking behaviors (Wang et al., 2007, 2010). Protein tyrosine phosphatase α (PTPα) is essential for Fyn kinase activation (Bhandari et al., 1998), and we showed that ethanol-mediated Fyn activation is facilitated by the recruitment of PTPα to synaptic membranes, the compartment where Fyn resides (Gibb et al., 2011). Here we tested the hypothesis that PTPα in the DMS is part of the Fyn/GluN2B pathway and is thus a major contributor to the neuroadaptations underlying excessive ethanol intake behaviors. We found that RNA interference (RNAi)-mediated PTPα knockdown in the DMS reduces excessive ethanol intake and preference in rodents. Importantly, no alterations in water, saccharine/sucrose, or quinine intake were observed. Furthermore, downregulation of PTPα in the DMS of mice significantly reduces ethanol-mediated Fyn activation, GluN2B phosphorylation, and ethanol withdrawal-induced long-term facilitation of NMDAR activity without altering the intrinsic features of DMS neurons. Together, these results position PTPα upstream of Fyn within the DMS and demonstrate the important contribution of the phosphatase to the maladaptive synaptic changes that lead to excessive ethanol intake.

  13. Excess Weapons Plutonium Immobilization in Russia

    Energy Technology Data Exchange (ETDEWEB)

    Jardine, L.; Borisov, G.B.

    2000-04-15

    The joint goal of the Russian work is to establish a full-scale plutonium immobilization facility at a Russian industrial site by 2005. To achieve this requires that the necessary engineering and technical basis be developed in these Russian projects and the needed Russian approvals be obtained to conduct industrial-scale immobilization of plutonium-containing materials at a Russian industrial site by the 2005 date. This meeting and future work will provide the basis for joint decisions. Supporting R&D projects are being carried out at Russian Institutes that directly support the technical needs of Russian industrial sites to immobilize plutonium-containing materials. Special R&D on plutonium materials is also being carried out to support excess weapons disposition in Russia and the US, including nonproliferation studies of plutonium recovery from immobilization forms and accelerated radiation damage studies of the US-specified plutonium ceramic for immobilizing plutonium. This intriguing and extraordinary cooperation on certain aspects of the weapons plutonium problem is now progressing well and much work with plutonium has been completed in the past two years. Because much excellent and unique scientific and engineering technical work has now been completed in Russia in many aspects of plutonium immobilization, this meeting in St. Petersburg was both timely and necessary to summarize, review, and discuss these efforts among those who performed the actual work. The results of this meeting will help the US and Russia jointly define the future direction of the Russian plutonium immobilization program, and make it an even stronger and more integrated Russian program. The two objectives for the meeting were to: (1) Bring together the Russian organizations, experts, and managers performing the work into one place for four days to review and discuss their work with each other; and (2) Publish a meeting summary and a proceedings to compile reports of all the excellent

  14. Excess Demand and Cost Relationships Among Kentucky Nursing Homes

    OpenAIRE

    Davis, Mark A.; Freeman, James W.

    1994-01-01

    This article examines the influence of excess demand on nursing home costs. Previous work indicates that excess demand, reflected in a pervasive shortage of nursing home beds, constrains market competition and patient care expenditures. According to this view, nursing homes located in under-bedded markets can reduce costs and quality with impunity because there is no pressure to compete for residents. Predictions based on the excess demand argument were tested using 1989 data from a sample of...

  15. ON THE NATURE OF SODIUM EXCESS OBJECTS. I. DATA AND OBSERVED TRENDS

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Hyunjin; Kyeong, Jaemann; Sung, Eon-Chang [Korea Astronomy and Space Science Institute, Daejeon 305-348 (Korea, Republic of); Yi, Sukyoung K.; Oh, Kyuseok [Department of Astronomy and Yonsei University Observatory, Yonsei University, Seoul 120-749 (Korea, Republic of); Sarzi, Marc, E-mail: hyunjin@kasi.re.kr, E-mail: yi@yonsei.ac.kr [Centre for Astrophysics Research, University of Hertfordshire, Hatfield Al10 9AB (United Kingdom)

    2013-09-15

    Several studies have reported the presence of sodium excess objects having neutral atomic absorption lines at 5895 A (Na D) and 8190 A that are deeper than expected based on stellar population models that match the stellar continuum. The origin of these lines is therefore hotly debated. van Dokkum and Conroy proposed that low-mass stars ({approx}<0.3 M{sub Sun }) are more prevalent in massive early-type galaxies, which may lead to a strong Na I 8190 line strength. It is necessary to test this prediction, however, against other prominent optical line indices such as Na D, Mg b, and Fe 5270, which can be measured with a significantly higher signal-to-noise ratio than Na I 8190. We identified a new sample of roughly 1000 Na D excess objects (NEOs; {approx}8% of galaxies in the sample) based on Na D line strength in the redshift range 0.00 {<=} z {<=} 0.08 from the Sloan Digital Sky Survey (SDSS) DR7 through detailed analysis of galaxy spectra. We explore the properties of these new objects here. The novelty of this work is that the galaxies were carefully identified through direct visual inspection of SDSS images, and we systematically compared the properties of NEOs and those of a control sample of galaxies with normal Na D line strengths. We note that the majority of galaxies with high velocity dispersions ({sigma}{sub e} > 250 km s{sup -1}) show Na D excesses. Most late-type NEOs have strong H{beta} line strengths and significant emission lines, which are indicative of the presence of young stellar populations. This result implies that the presence of the interstellar medium and/or dust contributes to the increase in Na D line strengths observed for these galaxies, which is in good agreement with the earlier study of Chen et al. who used the Na D line index to study outflow activity in star-forming disk galaxies. In contrast, the majority of early-type NEOs are predominantly luminous and massive systems, which is in agreement with the findings of van Dokkum and

  16. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia.

    Science.gov (United States)

    Fukawa, Tomoya; Yan-Jiang, Benjamin Chua; Min-Wen, Jason Chua; Jun-Hao, Elwin Tan; Huang, Dan; Qian, Chao-Nan; Ong, Pauline; Li, Zhimei; Chen, Shuwen; Mak, Shi Ya; Lim, Wan Jun; Kanayama, Hiro-Omi; Mohan, Rosmin Elsa; Wang, Ruiqi Rachel; Lai, Jiunn Herng; Chua, Clarinda; Ong, Hock Soo; Tan, Ker-Kan; Ho, Ying Swan; Tan, Iain Beehuat; Teh, Bin Tean; Shyh-Chang, Ng

    2016-06-01

    Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer. Additionally, although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid-induced oxidative stress could be targeted to prevent cancer-induced cachexia.

  17. Multi-lead heat sink

    Science.gov (United States)

    Roose, Lars D.

    1984-01-01

    The disclosure relates to a heat sink used to protect integrated circuits from the heat resulting from soldering them to circuit boards. A tubular housing contains a slidable member which engages somewhat inwardly extending connecting rods, each of which is rotatably attached at one end to the bottom of the housing. The other end of each rod is fastened to an expandable coil spring loop. As the member is pushed downward in the housing, its bottom edge engages and forces outward the connecting rods, thereby expanding the spring so that it will fit over an integrated circuit. After the device is in place, the member is slid upward and the spring contracts about the leads of the integrated circuit. Soldering is now conducted and the spring absorbs excess heat therefrom to protect the integrated circuit. The placement steps are repeated in reverse order to remove the heat sink for use again.

  18. Strong Support for the Millisecond Pulsar Origin of the Galactic Center GeV Excess.

    Science.gov (United States)

    Bartels, Richard; Krishnamurthy, Suraj; Weniger, Christoph

    2016-02-05

    Using γ-ray data from the Fermi Large Area Telescope, various groups have identified a clear excess emission in the Inner Galaxy, at energies around a few GeV. This excess resembles remarkably well a signal from dark-matter annihilation. One of the most compelling astrophysical interpretations is that the excess is caused by the combined effect of a previously undetected population of dim γ-ray sources. Because of their spectral similarity, the best candidates are millisecond pulsars. Here, we search for this hypothetical source population, using a novel approach based on wavelet decomposition of the γ-ray sky and the statistics of Gaussian random fields. Using almost seven years of Fermi-LAT data, we detect a clustering of photons as predicted for the hypothetical population of millisecond pulsar, with a statistical significance of 10.0σ. For plausible values of the luminosity function, this population explains 100% of the observed excess emission. We argue that other extragalactic or Galactic sources, a mismodeling of Galactic diffuse emission, or the thick-disk population of pulsars are unlikely to account for this observation.

  19. Lead and the Romans

    Science.gov (United States)

    Reddy, Aravind; Braun, Charles L.

    2010-01-01

    Lead poisoning has been a problem since early history and continues into modern times. An appealing characteristic of lead is that many lead salts are sweet. In the absence of cane and beet sugars, early Romans used "sugar of lead" (lead acetate) to sweeten desserts, fruits, and sour wine. People most at risk would have been those who…

  20. Hydrogen peroxide, signaling in disguise during metal phytotoxicity

    Directory of Open Access Journals (Sweden)

    Ann eCuypers

    2016-04-01

    Full Text Available Plants exposed to excess metals are challenged by an increased generation of reactive oxygen species (ROS such as superoxide (O2•-, hydrogen peroxide (H2O2 and the hydroxyl radical (•OH. The mechanisms underlying this oxidative challenge are often dependent on metal-specific properties and might play a role in stress perception, signaling and acclimation. Although ROS were initially considered as toxic compounds causing damage to various cellular structures, their role as signaling molecules became a topic of intense research over the last decade. Hydrogen peroxide in particular is important in signaling because of its relatively low toxicity, long lifespan and its ability to cross cellular membranes. The delicate balance between its production and scavenging by a plethora of enzymatic and metabolic antioxidants is crucial in the onset of diverse signaling cascades that finally lead to plant acclimation to metal stress. In this review, our current knowledge on the dual role of ROS in metal-exposed plants is presented. Evidence for a relationship between H2O2 and plant metal tolerance is provided. Furthermore, emphasis is put on recent advances in understanding cellular damage and downstream signaling responses as a result of metal-induced H2O2 production. Finally, special attention is paid to the interaction between H2O2 and other signaling components such as transcription factors, mitogen-activated protein kinases, phytohormones and regulating systems (e.g. microRNAs. These responses potentially underlie metal-induced senescence in plants. Elucidating the signaling network activated during metal stress is a pivotal step to make progress in applied technologies like phytoremediation of polluted soils.

  1. Hydrogen Peroxide, Signaling in Disguise during Metal Phytotoxicity

    Science.gov (United States)

    Cuypers, Ann; Hendrix, Sophie; Amaral dos Reis, Rafaela; De Smet, Stefanie; Deckers, Jana; Gielen, Heidi; Jozefczak, Marijke; Loix, Christophe; Vercampt, Hanne; Vangronsveld, Jaco; Keunen, Els

    2016-01-01

    Plants exposed to excess metals are challenged by an increased generation of reactive oxygen species (ROS) such as superoxide (O2•-), hydrogen peroxide (H2O2) and the hydroxyl radical (•OH). The mechanisms underlying this oxidative challenge are often dependent on metal-specific properties and might play a role in stress perception, signaling and acclimation. Although ROS were initially considered as toxic compounds causing damage to various cellular structures, their role as signaling molecules became a topic of intense research over the last decade. Hydrogen peroxide in particular is important in signaling because of its relatively low toxicity, long lifespan and its ability to cross cellular membranes. The delicate balance between its production and scavenging by a plethora of enzymatic and metabolic antioxidants is crucial in the onset of diverse signaling cascades that finally lead to plant acclimation to metal stress. In this review, our current knowledge on the dual role of ROS in metal-exposed plants is presented. Evidence for a relationship between H2O2 and plant metal tolerance is provided. Furthermore, emphasis is put on recent advances in understanding cellular damage and downstream signaling responses as a result of metal-induced H2O2 production. Finally, special attention is paid to the interaction between H2O2 and other signaling components such as transcription factors, mitogen-activated protein kinases, phytohormones and regulating systems (e.g. microRNAs). These responses potentially underlie metal-induced senescence in plants. Elucidating the signaling network activated during metal stress is a pivotal step to make progress in applied technologies like phytoremediation of polluted soils. PMID:27199999

  2. Novel lubrication system to improve the excessive wear in wind turbine yaw and pitch gears

    OpenAIRE

    Farré Lladós, Josep

    2015-01-01

    Manufacturers of wind turbines have observed a new phenomenon that appears in high power wind turbines: excessive wear in the teeth located at 0º in the pitch bearing. In order to design more efficient wind turbines, manufacturers are increasing the rotor diameter to capture more kinetic energy from the wind to generate more energy, therefore the stress in the joints/unions is increased, which leads to the elastic deformation of the system. These stresses and deformations increase in all p...

  3. New mechanisms in lead biodynamics at ultra-low levels.

    Science.gov (United States)

    Patterson, C; Settle, D

    1993-01-01

    It has been found that the mean concentration of 15 micrograms Pb/g bone ash in typical Americans today is 1000 times greater than the natural level of lead in Homo sapiens sapiens determined from analyses of ancient human bones. Since body burdens of lead only 3 to 5-fold greater than typical induce overtly poisonous effects, unrecognized dysfunctions caused by lead are probably widespread among Americans. Previous toxicological studies by others to delineate ill effects were made by comparisons of biological systems to which lead was added with systems to which no lead was added. It is now seen that such studies dealt entirely with unnatural mechanisms in lead biodynamics, and provided no knowledge of the operation of unperturbed natural mechanisms, because "non-leaded" controls were actually highly traumatized by unrecognized excessive lead exposures. New work should be carried out that would use an ultra-low lead diet to grow rats possessing "natural" lead levels which could be used as controls. Metabolisms of lead in these controls should be compared with metabolisms of lead in biological systems of rats traumatized by excessive lead exposures corresponding to typical levels within people today. Such comparisons would disclose previously unknown characteristics of intra-cellular processing of lead within osseous, neuronal, hepatic, renal and muscle tissues, and in red blood cells and sera, together with sizes and residence times of lead reservoirs in those tissues during fetal growth, maturation and adult aging in rats exposed to natural lead levels.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. New mechanisms in lead biodynamics at ultra-low levels

    Energy Technology Data Exchange (ETDEWEB)

    Patterson, C.; Settle, D. (California Institute of Technology, Pasadena (United States))

    It has been found that the mean concentration of 15 micrograms Pb/g bone ash in typical Americans today is 1000 times greater than the natural level of lead in Homo sapiens sapiens determined from analyses of ancient human bones. Since body burdens of lead only 3 to 5-fold greater than typical induce overtly poisonous effects, unrecognized dysfunctions caused by lead are probably widespread among Americans. Previous toxicological studies by others to delineate ill effects were made by comparisons of biological systems to which lead was added with systems to which no lead was added. It is now seen that such studies dealt entirely with unnatural mechanisms in lead biodynamics, and provided no knowledge of the operation of unperturbed natural mechanisms, because non-leaded controls were actually highly traumatized by unrecognized excessive lead exposures. New work should be carried out that would use an ultra-low lead diet to grow rats possessing natural lead levels which could be used as controls. Metabolisms of lead in these controls should be compared with metabolisms of lead in biological systems of rats traumatized by excessive lead exposures corresponding to typical levels within people today. Such comparisons would disclose previously unknown characteristics of intra-cellular processing of lead within osseous, neuronal, hepatic, renal and muscle tissues, and in red blood cells and sera, together with sizes and residence times of lead reservoirs in those tissues during fetal growth, maturation and adult aging in rats exposed to natural lead levels.

  5. Role of Delta-Notch signaling in cerebral cavernous malformations.

    Science.gov (United States)

    Kar, Souvik; Baisantry, Arpita; Nabavi, Arya; Bertalanffy, Helmut

    2016-10-01

    Cerebral cavernous malformations (CCM) commonly known as cavernous hemangioma are associated with abnormally enlarged thin-walled blood vessels. As a result, these dilated capillaries are prone to leakage and result in hemorrhages. Clinically, such hemorrhages lead to severe headaches, focal neurological deficits, and epileptic seizures. CCM is caused by loss of function mutations in one of the three well-known CCM genes: Krev interaction trapped 1 (KRIT1), OSM, and programmed cell death 10 (PDCD10). Loss of CCM genes have been shown to be synergistically related to decreased Notch signaling and excessive angiogenesis. Despite recent evidences indicating that Notch signaling plays a pivotal role in regulating angiogenesis, the role of Notch in CCM development and progression is still not clear. Here, we provide an update literature review on the current knowledge of the structure of Notch receptor and its ligands, its relevance to angiogenesis and more precisely to CCM pathogenesis. In addition to reviewing the current literatures, this review will also focus on the cross talk between Delta-Notch and vascular endothelial growth factor (VEGF) signaling in angiogenesis and in CCM pathogenesis. Understanding the role of Notch signaling in CCM development and progression might help provide a better insight for novel anti-angiogenic therapies.

  6. Erbin loss promotes cancer cell proliferation through feedback activation of Akt-Skp2-p27 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hao [Department of Pathophysiology, Institute of Basic Medical Sciences, Beijing 100850 (China); Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng 475004 (China); Song, Yuhua [The Affiliated Hospital of Medical College, Qingdao University, Qingdao (China); Wu, Yan; Guo, Ning [Department of Pathophysiology, Institute of Basic Medical Sciences, Beijing 100850 (China); Ma, Yuanfang [Laboratory of Cellular and Molecular Immunology, Medical School of Henan University, Kaifeng 475004 (China); Qian, Lu, E-mail: mayf@henu.edu.cn [Department of Pathophysiology, Institute of Basic Medical Sciences, Beijing 100850 (China)

    2015-07-31

    Erbin localizes at the basolateral membrane to regulate cell junctions and polarity in epithelial cells. Dysregulation of Erbin has been implicated in tumorigenesis, and yet it is still unclear if and how disrupted Erbin regulates the biological behavior of cancer cells. We report here that depletion of Erbin leads to cancer cell excessive proliferation in vitro and in vivo. Erbin deficiency accelerates S-phase entry by down-regulating CDK inhibitors p21 and p27 via two independent mechanisms. Mechanistically, Erbin loss promotes p27 degradation by enhancing E3 ligase Skp2 activity though augmenting Akt signaling. Interestingly, we also show that Erbin is an unstable protein when the Akt-Skp2 signaling is aberrantly activated, which can be specifically destructed by SCF-Skp2 ligase. Erbin loss facilitates cell proliferation and migration in Skp2-dependent manner. Thus, our finding illustrates a novel negative feedback loop between Erbin and Akt-Skp2 signaling. It suggests disrupted Erbin links polarity loss, hyperproliferation and tumorigenesis. - Highlights: • Erbin loss leads to cancer cell excessive proliferation in vitro and in vivo. • Erbin loss accelerates cell cycle though down-regulating p21 and p27 expression. • Erbin is a novel negative modulator of Akt1-Skp2-p27 signaling pathway. • Our study suggests that Erbin loss contributes to Skp2 oncogenic function.

  7. What's the Difference? Reducing the Effects of Exposure to Reality Television Shows Displaying Excessive Alcohol Use on Dutch Adolescents' Drinking Intentions

    NARCIS (Netherlands)

    Anschutz, D.J.; Berg, K. van den; Graaf, A. de; Koordeman, R.

    2014-01-01

    The present experimental study investigated the effects of strengthening or weakening adolescents' perceptions of equivalence between themselves and the leading characters of a reality show displaying excessive alcohol consumption in the Nethderlands. A randomized between-subject design was used

  8. The role of adipose tissue and excess of fatty acids in the induction of insulin resistance in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Agnieszka Błachnio-Zabielska

    2016-11-01

    Full Text Available Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes and type 2 diabetes (T2D. The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA, diacylglycerols (DAG and ceramides (Cer. It has been demonstrated that accumulation of each of the above-mentioned lipid classes negatively affects the insulin signaling pathway. It is not clear which of those lipids play the most important role in HFD-induced skeletal muscle IRes. The aim of the present work is to present the current knowledge of the role of adipose tissue and excess of fatty acids in the induction of insulin resistance.

  9. Basis for recording seismoacoustic signals

    Energy Technology Data Exchange (ETDEWEB)

    Kornowski, J.; Sokolowski, H.; Wasko, A.

    1986-06-01

    Accuracy is evaluated of the PRS-4a seismic detection system developed and manufactured by the EMAG Center for forecasting rock burst hazards in underground coal mines. The system consists of seismic detectors, preamplifiers, amplifiers, cables and receivers. The PRS-4a accurately records seismic signals within a range of 400-1000 Hz. The measuring range of the system is 200 to 1700 Hz but intensive attenuation occurs at both ends of frequency range; excessive amplification is a cause of signal distortion within the range 1200 to 1400 Hz. Test results are shown in 6 diagrams.

  10. Lead (Pb) Air Pollution

    Science.gov (United States)

    ... Environmental Protection Agency Search Search Lead (Pb) Air Pollution Contact Us Share As a result of EPA's ... protect aquatic and terrestrial ecosystems. Lead (Pb) Air Pollution Basic Information How does lead get in the ...

  11. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Hyperactivated Wnt signaling induces synthetic lethal interaction with Rb inactivation by elevating TORC1 activities.

    Directory of Open Access Journals (Sweden)

    Tianyi Zhang

    2014-05-01

    Full Text Available Inactivation of the Rb tumor suppressor can lead to increased cell proliferation or cell death depending on specific cellular context. Therefore, identification of the interacting pathways that modulate the effect of Rb loss will provide novel insights into the roles of Rb in cancer development and promote new therapeutic strategies. Here, we identify a novel synthetic lethal interaction between Rb inactivation and deregulated Wg/Wnt signaling through unbiased genetic screens. We show that a weak allele of axin, which deregulates Wg signaling and increases cell proliferation without obvious effects on cell fate specification, significantly alters metabolic gene expression, causes hypersensitivity to metabolic stress induced by fasting, and induces synergistic apoptosis with mutation of fly Rb ortholog, rbf. Furthermore, hyperactivation of Wg signaling by other components of the Wg pathway also induces synergistic apoptosis with rbf. We show that hyperactivated Wg signaling significantly increases TORC1 activity and induces excessive energy stress with rbf mutation. Inhibition of TORC1 activity significantly suppressed synergistic cell death induced by hyperactivated Wg signaling and rbf inactivation, which is correlated with decreased energy stress and decreased induction of apoptotic regulator expression. Finally the synthetic lethality between Rb and deregulated Wnt signaling is conserved in mammalian cells and that inactivation of Rb and APC induces synergistic cell death through a similar mechanism. These results suggest that elevated TORC1 activity and metabolic stress underpin the evolutionarily conserved synthetic lethal interaction between hyperactivated Wnt signaling and inactivated Rb tumor suppressor.

  13. A Practical Approach For Excess Bandwidth Distribution for EPONs

    KAUST Repository

    Elrasad, Amr

    2014-03-09

    This paper introduces a novel approach called Delayed Excess Scheduling (DES), which practically reuse the excess bandwidth in EPONs system. DES is suitable for the industrial deployment as it requires no timing constraint and achieves better performance compared to the previously reported schemes.

  14. Excess isentropic compressibility and speed of sound of the ternary ...

    Indian Academy of Sciences (India)

    These excess properties of the binary mixtures were fitted to Redlich-Kister equation, while the Cibulka's equation was used to fit the values related to the values to the ternary system. These excess properties have been used to discuss the presence of significant interactions between the component molecules in the binary ...

  15. excess molar volumes, and refractive index of binary mixtures of ...

    African Journals Online (AJOL)

    Preferred Customer

    mixtures of glycerol + water, and glycerol + methanol at 298.15 K and 303.15 K. Excess molar volumes (VE) have been calculated ... KEY WORDS: Excess molar, Density, Refractive index, Glycerol, Water, Methanol ... Biodiesel, defined as “a substitute for, or a additive to diesel fuel that is derived from the oils and fats of ...

  16. 5 CFR 530.204 - Payment of excess amounts.

    Science.gov (United States)

    2010-01-01

    ... Section 530.204 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY RATES AND SYSTEMS (GENERAL) Aggregate Limitation on Pay § 530.204 Payment of excess amounts. (a) An agency must pay the amounts that were deferred because they were in excess of the aggregate limitation...

  17. Alternative search strategies to explore ATLAS diboson excess

    Indian Academy of Sciences (India)

    2017-10-05

    Oct 5, 2017 ... We consider the s-channel resonance to fit the 2 TeV ATLAS diboson excess.We address the production mechanism of the resonance, its decay and coupling measurement. In order to explain only the hadronic channel excess, we consider the scenario where resonance decays to two new beyond ...

  18. Teachers' Knowledge of Anxiety and Identification of Excessive Anxiety in

    Science.gov (United States)

    Headley, Clea; Campbell, Marilyn A.

    2013-01-01

    This study examined primary school teachers' knowledge of anxiety and excessive anxiety symptoms in children. Three hundred and fifteen primary school teachers completed a questionnaire exploring their definitions of anxiety and the indications they associated with excessive anxiety in primary school children. Results showed that teachers had an…

  19. Management of excessive movable tissue: a modified impression technique.

    Science.gov (United States)

    Shum, Michael H C; Pow, Edmond H N

    2014-08-01

    Excessive movable tissue is a challenge in complete denture prosthetics. A modified impression technique is presented with polyvinyl siloxane impression material and a custom tray with relief areas and perforations in the area of the excessive movable tissue. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  20. 30 CFR 75.401-1 - Excessive amounts of dust.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Excessive amounts of dust. 75.401-1 Section 75.401-1 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR COAL MINE SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Combustible Materials and Rock Dusting § 75.401-1 Excessive amounts of dust. The term ...

  1. Excess Molar Volumes and Partial Molar Volumes of Binary Systems ...

    African Journals Online (AJOL)

    NJD

    Excess molar volumes have been evaluated from density measurements over the entire composition range for binary systems of an ionic liquid ... was used to fit the excess molar volume data and the partial molar volumes were determined from the Redlich-Kister coefficients. ... ture below the boiling point of water. Most of ...

  2. 43 CFR 426.13 - Excess land appraisals.

    Science.gov (United States)

    2010-10-01

    ... discretion, can initiate the appraisal. (b) Procedures Reclamation uses to determine the sale price of excess... determine the sale price of excess land and land burdened by a deed covenant, except if a landholder owns land subject to a recordable contract that was in force on October 12, 1982, or other pertinent...

  3. Excess molar volumes and isentropic compressibilities of binary ...

    Indian Academy of Sciences (India)

    Remaining five binary mixtures, n-heptane + toluene, cyclohexane + n-heptane, cyclohexane + n-hexane, toluene + nhexane and n-decane + n-hexane show negative excess molar volumes over the whole composition range. However, the large negative values of excess molar volume becomes dominant in toluene + ...

  4. Goodwill, Excess Returns, and Determinants of Value Creation and Overpayment

    NARCIS (Netherlands)

    Lycklama a Nijeholt, M.; Grift, Y.K.

    2007-01-01

    In this article we have investigated whether the determinants of excess returns (especially of target excess returns) are valid for purchased goodwill as well. Among them are acquirer’s and target’s Tobin’s q, and debt assets ratio, that explain value creation of acquisitions, and relative size,

  5. 19 CFR 10.625 - Refunds of excess customs duties.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Refunds of excess customs duties. 10.625 Section 10.625 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... and Apparel Goods § 10.625 Refunds of excess customs duties. (a) Applicability. Section 205 of the...

  6. Iodine Excess is a Risk Factor for Goiter Formation | Washington ...

    African Journals Online (AJOL)

    Iodine Excess is a Risk Factor for Goiter Formation. ... Iodine Excess is a Risk Factor for Goiter Formation. L Washington, T Makumbi, OJ Fualal, M Galukande. Abstract. Background: Goiters have been associated with iodine deficiency. Although universal salt iodization in Uganda achieved a household coverage of 95%

  7. 30 CFR 75.323 - Actions for excessive methane.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions for excessive methane. 75.323 Section... excessive methane. (a) Location of tests. Tests for methane concentrations under this section shall be made.... (1) When 1.0 percent or more methane is present in a working place or an intake air course, including...

  8. 12 CFR 740.3 - Advertising of excess insurance.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Advertising of excess insurance. 740.3 Section... ACCURACY OF ADVERTISING AND NOTICE OF INSURED STATUS § 740.3 Advertising of excess insurance. Any advertising that mentions share or savings account insurance provided by a party other than the NCUA must...

  9. Mitochondrial and cellular mechanisms for managing lipid excess

    Directory of Open Access Journals (Sweden)

    Miguel A Aon

    2014-07-01

    Full Text Available Current scientific debates center on the impact of lipids and mitochondrial function on diverse aspects of human health, nutrition and disease, among them the association of lipotoxicity with the onset of insulin resistance in skeletal muscle, and with heart dysfunction in obesity and diabetes. Mitochondria play a fundamental role in aging and in prevalent acute or chronic diseases. Lipids are main mitochondrial fuels however these molecules can also behave as uncouplers and inhibitors of oxidative phosphorylation. Knowledge about the functional composition of these contradictory effects and their impact on mitochondrial-cellular energetics/redox status is incomplete.Cells store fatty acids (FAs as triacylglycerol and package them into cytoplasmic lipid droplets (LDs. New emerging data shows the LD as a highly dynamic storage pool of FAs that can be used for energy reserve. Lipid excess packaging into LDs can be seen as an adaptive response to fulfilling energy supply without hindering mitochondrial or cellular redox status and keeping low concentration of lipotoxic intermediates.Herein we review the mechanisms of action and utilization of lipids by mitochondria reported in liver, heart and skeletal muscle under relevant physiological situations, e.g. exercise. We report on perilipins, a family of proteins that associate with LDs in response to loading of cells with lipids. Evidence showing that in addition to physical contact, mitochondria and LDs exhibit metabolic interactions is presented and discussed. A hypothetical model of channeled lipid utilization by mitochondria is proposed. Direct delivery and channeled processing of lipids in mitochondria could represent a reliable and efficient way to maintain ROS within levels compatible with signaling while ensuring robust and reliable energy supply.

  10. On Infrared Excesses Associated with Li-Rich K Giants

    Science.gov (United States)

    Rebull, Luisa M.; Carlberg, Joleen K.; Gibbs, John C.; Deeb, J. Elin; Larsen, Estefania; Black, David V.; Altepeter, Shailyn; Bucksbee, Ethan; Cashen, Sarah; Clarke, Matthew; hide

    2015-01-01

    Infrared (IR) excesses around K-type red giants (RGs) have previously been discovered using Infrared Astronomy Satellite (IRAS) data, and past studies have suggested a link between RGs with overabundant lithium and IR excesses, implying the ejection of circumstellar shells or disks. We revisit the question of IR excesses around RGs using higher spatial resolution IR data, primarily from the Wide-field Infrared Survey Explorer. Our goal was to elucidate the link between three unusual RG properties: fast rotation, enriched lithium, and IR excess. Our sample of RGs includes those with previous IR detections, a sample with well-defined rotation and lithium abundance measurements with no previous IR measurements, and a large sample of RGs asserted to be lithium-rich in the literature; we have 316 targets thought to be K giants, about 40% of which we take to be Li-rich. In 24 cases with previous detections of IR excess at low spatial resolution, we believe that source confusion is playing a role, in that either (a) the source that is bright in the optical is not responsible for the IR flux, or (b) there is more than one source responsible for the IR flux as measured in IRAS. We looked for IR excesses in the remaining sources, identifying 28 that have significant IR excesses by approximately 20 micrometers (with possible excesses for 2 additional sources). There appears to be an intriguing correlation in that the largest IR excesses are all in Li-rich K giants, though very few lithium-rich K giants have IR excesses (large or small). These largest IR excesses also tend to be found in the fastest rotators. There is no correlation of IR excess with the carbon isotopic ratio, 12C/13C. IR excesses by 20 micrometers, though relatively rare, are at least twice as common among our sample of lithium-rich K giants. If dust shell production is a common by-product of Li enrichment mechanisms, these observations suggest that the IR excess stage is very short-lived, which is supported

  11. ON INFRARED EXCESSES ASSOCIATED WITH Li-RICH K GIANTS

    Energy Technology Data Exchange (ETDEWEB)

    Rebull, Luisa M. [Spitzer Science Center (SSC) and Infrared Science Archive (IRSA), Infrared Processing and Analysis Center - IPAC, 1200 E. California Blvd., California Institute of Technology, Pasadena, CA 91125 (United States); Carlberg, Joleen K. [NASA Goddard Space Flight Center, Code 667, Greenbelt, MD 20771 (United States); Gibbs, John C.; Cashen, Sarah; Datta, Ashwin; Hodgson, Emily; Lince, Megan [Glencoe High School, 2700 NW Glencoe Rd., Hillsboro, OR 97124 (United States); Deeb, J. Elin [Bear Creek High School, 9800 W. Dartmouth Pl., Lakewood, CO 80227 (United States); Larsen, Estefania; Altepeter, Shailyn; Bucksbee, Ethan; Clarke, Matthew [Millard South High School, 14905 Q St., Omaha, NE 68137 (United States); Black, David V., E-mail: rebull@ipac.caltech.edu [Walden School of Liberal Arts, 4230 N. University Ave., Provo, UT 84604 (United States)

    2015-10-15

    Infrared (IR) excesses around K-type red giants (RGs) have previously been discovered using Infrared Astronomy Satellite (IRAS) data, and past studies have suggested a link between RGs with overabundant Li and IR excesses, implying the ejection of circumstellar shells or disks. We revisit the question of IR excesses around RGs using higher spatial resolution IR data, primarily from the Wide-field Infrared Survey Explorer. Our goal was to elucidate the link between three unusual RG properties: fast rotation, enriched Li, and IR excess. Our sample of RGs includes those with previous IR detections, a sample with well-defined rotation and Li abundance measurements with no previous IR measurements, and a large sample of RGs asserted to be Li-rich in the literature; we have 316 targets thought to be K giants, about 40% of which we take to be Li-rich. In 24 cases with previous detections of IR excess at low spatial resolution, we believe that source confusion is playing a role, in that either (a) the source that is bright in the optical is not responsible for the IR flux, or (b) there is more than one source responsible for the IR flux as measured in IRAS. We looked for IR excesses in the remaining sources, identifying 28 that have significant IR excesses by ∼20 μm (with possible excesses for 2 additional sources). There appears to be an intriguing correlation in that the largest IR excesses are all in Li-rich K giants, though very few Li-rich K giants have IR excesses (large or small). These largest IR excesses also tend to be found in the fastest rotators. There is no correlation of IR excess with the carbon isotopic ratio, {sup 12}C/{sup 13}C. IR excesses by 20 μm, though relatively rare, are at least twice as common among our sample of Li-rich K giants. If dust shell production is a common by-product of Li enrichment mechanisms, these observations suggest that the IR excess stage is very short-lived, which is supported by theoretical calculations. Conversely, the

  12. A SUSY inspired simplified model for the 750 GeV diphoton excess

    Directory of Open Access Journals (Sweden)

    E. Gabrielli

    2016-05-01

    Full Text Available The evidence for a new neutral scalar particle from the 750 GeV diphoton excess, and the absence of any other signal of new physics at the LHC so far, suggests the existence of new coloured scalars. To study this possibility, we propose a supersymmetry inspired simplified model, extending the Standard Model with a singlet scalar and with heavy scalar fields carrying both colour and electric charges – new scalar quarks. To allow the latter to decay, and to generate the dark matter of the Universe, we also add a neutral fermion to the particle content. We show that this model provides a two-parameter fit to the observed diphoton excess consistently with cosmology, while the allowed parameter space is bounded by the consistency of the model. In the context of our simplified model this implies the existence of other supersymmetric particles accessible at the LHC, rendering this scenario falsifiable.

  13. The 750 GeV diphoton excess as a first light on supersymmetry breaking

    Directory of Open Access Journals (Sweden)

    J.A. Casas

    2016-08-01

    Full Text Available One of the most exciting explanations advanced for the recent diphoton excess found by ATLAS and CMS is in terms of sgoldstino decays: a signal of low-energy supersymmetry-breaking scenarios. The sgoldstino, a scalar, couples directly to gluons and photons, with strength related to gaugino masses, that can be of the right magnitude to explain the excess. However, fitting the suggested resonance width, Γ≃45 GeV, is not so easy. In this paper we explore efficient possibilities to enhance the sgoldstino width, via the decay into two Higgses, two Higgsinos and through mixing between the sgoldstino and the Higgs boson. In addition, we present an alternative and more efficient mechanism to generate a mass splitting between the scalar and pseudoscalar components of the sgoldstino, which has been suggested as an interesting alternative explanation to the apparent width of the resonance.

  14. Galactic center GeV gamma-ray excess, from dark matter with gauged lepton numbers

    Directory of Open Access Journals (Sweden)

    Jong-Chul Park

    2016-01-01

    Full Text Available The recently observed excess in gamma-ray signal near the Galactic center suggests that dark matter particles may annihilate into charged fermions that produce gamma-ray to be observed. In this paper, we consider a leptonic dark matter, which annihilates into the standard model leptons, μ+μ− and τ+τ−, by the interaction of the gauged lepton number U(1Lμ−Lτ and fits the observed excess. Interestingly, the necessary annihilation cross section for the observed gamma-ray flux provides a good fit to the value for the relic abundance of dark matter. We identify the preferred parameter space of the model after taking the existing experimental constraints from the precision measurements including the muon (g−2, tau decay, neutrino trident production, dark matter direct detection, LHC, and LEP experiments.

  15. 26 CFR 54.4979-0 - Excise tax on certain excess contributions and excess aggregate contributions; table of contents.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Excise tax on certain excess contributions and excess aggregate contributions; table of contents. 54.4979-0 Section 54.4979-0 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.4979-0 Excise tax on...

  16. Role of Nutrient-Sensing Signals in the Pathogenesis of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Shinji Kume

    2014-01-01

    Full Text Available Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nutrient-sensing signals and their related intracellular machinery have evolved to combat prolonged periods of starvation in mammals; and these systems are conserved in the kidney. Recent studies have suggested that the activity of three nutrient-sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney. Furthermore, autophagy activity, which is regulated by the above-mentioned nutrient-sensing signals, is also altered in both podocytes and proximal tubular cells under diabetic conditions. Under diabetic conditions, an altered nutritional state owing to nutrient excess may disturb cellular homeostasis regulated by nutrient-responsible systems, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing relationships between nutrient-sensing signals, autophagy, and diabetic nephropathy and suggest the therapeutic potential of nutrient-sensing signals in diabetic nephropathy.

  17. Cryogenic current leads

    Energy Technology Data Exchange (ETDEWEB)

    Zizek, F.

    1982-01-01

    Theoretical, technical and design questions are examined of cryogenic current leads for SP of magnetic systems. Simplified mathematical models are presented for the current leads. To illustrate modeling, the calculation is made of the real current leads for 500 A and three variants of current leads for 1500 A for the enterprise ''Shkoda.''

  18. Excess iodine promotes apoptosis of thyroid follicular epithelial cells by inducing autophagy suppression and is associated with Hashimoto thyroiditis disease.

    Science.gov (United States)

    Xu, Chengcheng; Wu, Fei; Mao, Chaoming; Wang, Xuefeng; Zheng, Tingting; Bu, Ling; Mou, Xiao; Zhou, Yuepeng; Yuan, Guoyue; Wang, Shengjun; Xiao, Yichuan

    2016-12-01

    The incidence of the autoimmune thyroid disease Hashimoto thyroiditis (HT) has increased in recent years, and increasing evidence supports the contribution of excess iodine intake to thyroid disease. In this study, we examined the status of autophagy and apoptosis in thyroid tissues obtained from patients with HT, and we determined the effects of excessive iodine on the autophagy and apoptosis of thyroid follicular cells (TFCs) in an attempt to elucidate the effects of excess iodine on HT development. Our results showed decreases in the autophagy-related protein LC3B-II, and increases in caspase-3 were observed in thyroid tissues from HT patients. Interestingly, the suppression of autophagy activity in TFCs was induced by excess iodine in vitro, and this process is mediated through transforming growth factor-β1 downregulation and activation of the Akt/mTOR signaling pathway. In addition, excess iodine induced autophagy suppression and enhanced reactive oxygen species (ROS) production and apoptosis of TFCs, which could be rescued by the activation of autophagy. Taken together, our results demonstrated that excess iodine contributed to autophagy suppression and apoptosis of TFCs, which could be important factors predisposing to increased risk of HT development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1.

    Science.gov (United States)

    Shichita, Takashi; Ito, Minako; Morita, Rimpei; Komai, Kyoko; Noguchi, Yoshiko; Ooboshi, Hiroaki; Koshida, Ryusuke; Takahashi, Satoru; Kodama, Tatsuhiko; Yoshimura, Akihiko

    2017-06-01

    Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb. Combined deficiency for Msr1 and Marco, or for Mafb alone, in infiltrating myeloid cells caused impaired clearance of DAMPs, more severe inflammation, and exacerbated neuronal injury in a murine model of ischemic stroke. The retinoic acid receptor (RAR) agonist Am80 increased the expression of Mafb, thereby enhancing MSR1 expression. Am80 exhibited therapeutic efficacy when administered, even at 24 h after the onset of experimental stroke. Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury.

  20. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    NARCIS (Netherlands)

    Willuhn, Ingo; Burgeno, Lauren M; Groblewski, Peter A; Phillips, Paul E M

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

  1. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum

    NARCIS (Netherlands)

    Willuhn, Ingo; Burgeno, Lauren M.; Groblewski, Peter A.; Phillips, Paul E. M.

    2014-01-01

    Drug addiction is a neuropsychiatric disorder marked by escalating drug use. Dopamine neurotransmission in the ventromedial striatum (VMS) mediates acute reinforcing effects of abused drugs, but with protracted use the dorsolateral striatum is thought to assume control over drug seeking. We measured

  2. Postsynaptic Signaling and Plasticity Mechanisms

    Science.gov (United States)

    Sheng, Morgan; Jong Kim, Myung

    2002-10-01

    In excitatory synapses of the brain, specific receptors in the postsynaptic membrane lie ready to respond to the release of the neurotransmitter glutamate from the presynaptic terminal. Upon stimulation, these glutamate receptors activate multiple biochemical pathways that transduce signals into the postsynaptic neuron. Different kinds of synaptic activity elicit different patterns of postsynaptic signals that lead to short- or long-lasting strengthening or weakening of synaptic transmission. The complex molecular mechanisms that underlie postsynaptic signaling and plasticity are beginning to emerge.

  3. Innate Immune Signaling Activated by MDR Bacteria in the Airway

    Science.gov (United States)

    Parker, Dane; Ahn, Danielle; Cohen, Taylor; Prince, Alice

    2015-01-01

    Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation. PMID:26582515

  4. Prevalence of excessive screen time and associated factors in adolescents

    Directory of Open Access Journals (Sweden)

    Joana Marcela Sales de Lucena

    2015-12-01

    Full Text Available Objective: To determine the prevalence of excessive screen time and to analyze associated factors among adolescents. Methods: This was a cross-sectional school-based epidemiological study with 2874 high school adolescents with age 14-19 years (57.8% female from public and private schools in the city of João Pessoa, PB, Northeast Brazil. Excessive screen time was defined as watching television and playing video games or using the computer for more than 2 h/day. The associated factors analyzed were: sociodemographic (gender, age, economic class, and skin color, physical activity and nutritional status of adolescents. Results: The prevalence of excessive screen time was 79.5% (95%CI 78.1-81.1 and it was higher in males (84.3% compared to females (76.1%; p<0.001. In multivariate analysis, adolescent males, those aged 14-15 year old and the highest economic class had higher chances of exposure to excessive screen time. The level of physical activity and nutritional status of adolescents were not associated with excessive screen time. Conclusions: The prevalence of excessive screen time was high and varied according to sociodemographic characteristics of adolescents. It is necessary to develop interventions to reduce the excessive screen time among adolescents, particularly in subgroups with higher exposure.

  5. Excess zinc ions are a competitive inhibitor for carboxypeptidase A

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, J.; Ando, S.; Kidani, Y.

    1987-10-06

    The mechanism for inhibition of enzyme activity by excess zinc ions has been studied by kinetic and equilibrium dialysis methods at pH 8.2, I = 0.5 M. With carboxypeptidase A (bovine pancreas), peptide (carbobenzoxyglycyl-L-phenylalanine and hippuryl-L-phenylalanine) and ester (hippuryl-L-phenyl lactate) substrates were inhibited competitively by excess zinc ions. The K/sub i/ values for excess zinc ions with carboxypeptidase A at pH 8.2 are all similar. The apparent constant for dissociation of excess zinc ions from carboxypeptidase A was also obtained by equilibrium dialysis at pH 8.2 and was 2.4 x 10/sup -5/ M, very close to the K/sub i/ values above. With arsanilazotyrosine-248 carboxypeptidase A ((Azo-CPD)Zn)), hippuryl-L-phenylalanine, carbobenzoxyglycyl-L-phenylalanine, and hippuryl-L-phenyl lactate were also inhibited with a competitive pattern by excess zinc ions, and the K/sub i/ values were (3.0-3.5) x 10/sup -5/ M. The apparent constant for dissociation of excess zinc ions from arsanilazotyrosine-248 carboxypeptidase A, which was obtained from absorption changes at 510 nm, was 3.2 x 10/sup -5/ M and is similar to the K/sub i/ values for ((Azo-CPD)Zn). The apparent dissociation and inhibition constants, which were obtained by inhibition of enzyme activity and spectrophotometric and equilibrium dialysis methods with native carboxypeptidase A and arsanilazotyrosine-248 carboxypeptidase A, were almost the same. This agreement between the apparent dissociation and inhibition constants indicates that the zinc binding to the enzymes directly relates to the inhibition of enzyme activity by excess zinc ions. Excess zinc ions were competitive inhibitors for both peptide and ester substrates. This behavior is believed to arise by the excess zinc ions fixing the enzyme in a conformation to which the substrates cannot bind.

  6. Upper midwest climate variations: farmer responses to excess water risks.

    Science.gov (United States)

    Morton, Lois Wright; Hobbs, Jonathan; Arbuckle, J Gordon; Loy, Adam

    2015-05-01

    Persistent above average precipitation and runoff and associated increased sediment transfers from cultivated ecosystems to rivers and oceans are due to changes in climate and human action. The US Upper Midwest has experienced a 37% increase in precipitation (1958-2012), leading to increased crop damage from excess water and off-farm loss of soil and nutrients. Farmer adaptive management responses to changing weather patterns have potential to reduce crop losses and address degrading soil and water resources. This research used farmer survey ( = 4778) and climate data (1971-2011) to model influences of geophysical context, past weather, on-farm flood and saturated soils experiences, and risk and vulnerability perceptions on management practices. Seasonal precipitation varied across six Upper Midwest subregions and was significantly associated with variations in management. Increased warm-season precipitation (2007-2011) relative to the past 40 yr was positively associated with no-till, drainage, and increased planting on highly erodible land (HEL). Experience with saturated soils was significantly associated with increased use of drainage and less use of no-till, cover crops, and planting on HEL. Farmers in counties with a higher percentage of soils considered marginal for row crops were more likely to use no-till, cover crops, and plant on HEL. Respondents who sell corn through multiple markets were more likely to have planted cover crops and planted on HEL in 2011.This suggests that regional climate conditions may not well represent individual farmers' actual and perceived experiences with changing climate conditions. Accurate climate information downscaled to localized conditions has potential to influence specific adaptation strategies. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  7. Alternative search strategies to explore ATLAS diboson excess

    Science.gov (United States)

    Khosa, Charanjit K.

    2017-10-01

    We consider the s-channel resonance to fit the 2 TeV ATLAS diboson excess. We address the production mechanism of the resonance, its decay and coupling measurement. In order to explain only the hadronic channel excess, we consider the scenario where resonance decays to two new beyond Standard Model (BSM) particles (in the mass range of W / Z boson) and also explore the possibility of three-particle BSM final state mimicking diboson excess. Techniques suggested in this work are generic and could be used for heavy BSM resonance searches.

  8. Timing of Excessive Weight Gain During Pregnancy Modulates Newborn Anthropometry.

    Science.gov (United States)

    Ruchat, Stephanie-May; Allard, Catherine; Doyon, Myriam; Lacroix, Marilyn; Guillemette, Laetitia; Patenaude, Julie; Battista, Marie-Claude; Ardilouze, Jean-Luc; Perron, Patrice; Bouchard, Luigi; Hivert, Marie-France

    2016-02-01

    Excessive gestational weight gain (GWG) is associated with increased birth weight and neonatal adiposity. However, timing of excessive GWG may have a differential impact on birth outcomes. The objective of this study was to compare the effect of early and mid/late excessive GWG on newborn anthropometry in the context of the Canadian clinical recommendations that are specific for first trimester and for second/third trimesters based on maternal pre-pregnancy BMI. We included 607 glucose-tolerant women in our main analyses, after excluding women who had less than the recommended total GWG. Maternal body weight was measured in early pregnancy, mid-pregnancy, and late pregnancy. Maternal and fetal clinical outcomes were collected, including newborn anthropometry. Women were divided into four groups according to the Canadian guidelines for GWG in the first and in the second/third trimesters: (1) "overall non-excessive" (reference group); (2) "early excessive GWG"; (3) "mid/late excessive GWG"; and (4) "overall excessive GWG." Differences in newborn anthropometry were tested across GWG categories. Women had a mean (±SD) pre-pregnancy BMI of 24.7 ± 5.2 kg/m(2) and total GWG of 15.3 ± 4.4 kg. Women with mid/late excessive GWG gave birth to heavier babies (gestational age-adjusted birth weight z-score 0.33 ± 0.91) compared with women in the reference group (0.00 ± 0.77, P = 0.007), whereas women with early excessive GWG gave birth to babies of similar weight (gestational age-adjusted z-score 0.01 ± 0.86) to the reference group (0.00 ± 0.77, P = 0.84). When we stratified our analyses and investigated women who gained within the recommendations for total GWG, mid/late excessive GWG specifically was associated with greater newborn size, similar to our main analyses. Excessive GWG in mid/late pregnancy in women who did not gain weight excessively in early pregnancy is associated with increased birth size, even in those who gained within the Canadian recommendations

  9. Galactic center gamma-ray excess from dark matter annihilation: is there a black hole spike?

    Science.gov (United States)

    Fields, Brian D; Shapiro, Stuart L; Shelton, Jessie

    2014-10-10

    If the supermassive black hole Sgr A* at the center of the Milky Way grew adiabatically from an initial seed embedded in a Navarro-Frenk-White dark matter (DM) halo, then the DM profile near the hole has steepened into a spike. We calculate the dramatic enhancement to the gamma-ray flux from the Galactic center (GC) from such a spike if the 1-3 GeV excess observed in Fermi data is due to DM annihilations. We find that for the parameter values favored in recent fits, the point-source-like flux from the spike is 35 times greater than the flux from the inner 1° of the halo, far exceeding all Fermi point source detections near the GC. We consider the dependence of the spike signal on astrophysical and particle parameters and conclude that if the GC excess is due to DM, then a canonical adiabatic spike is disfavored by the data. We discuss alternative Galactic histories that predict different spike signals, including (i) the nonadiabatic growth of the black hole, possibly associated with halo and/or black hole mergers, (ii) gravitational interaction of DM with baryons in the dense core, such as heating by stars, or (iii) DM self-interactions. We emphasize that the spike signal is sensitive to a different combination of particle parameters than the halo signal and that the inclusion of a spike component to any DM signal in future analyses would provide novel information about both the history of the GC and the particle physics of DM annihilations.

  10. Hostility among adolescents in Switzerland? multivariate relations between excessive media use and forms of violence.

    Science.gov (United States)

    Kuntsche, Emmanuel N

    2004-03-01

    To determine what kind of violence-related behavior or opinion is directly related to excessive media use among adolescents in Switzerland. A national representative sample of 4222 schoolchildren (7th- and 8th-graders; mean age 13.9 years) answered questions on the frequency of television-viewing, electronic game-playing, feeling unsafe at school, bullying others, hitting others, and fighting with others, as part of the Health Behaviour in School-Aged Children (HBSC) international collaborative study protocol. The Chi-square tests and multiple logistic regression analyses were applied to high-risk groups of adolescents. For the total sample, all bivariate relationships between television-viewing/electronic game-playing and each violence-related variable are significant. In the multivariate comparison, physical violence among boys ceases to be significant. For girls, only television-viewing is linked to indirect violence. Against the hypothesis, females' electronic game-playing only had a bearing on hitting others. Experimental designs are needed that take into account gender, different forms of media, and violence to answer the question of whether excessive media use leads to violent behavior. With the exception of excessive electronic game-playing among girls, this study found that electronic media are not thought to lead directly to real-life violence but to hostility and indirect violence.

  11. Testing the Technicolor Interpretation of CDF's Dijet Excess at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Eichten, Estia; Lane, Kenneth; Martin, Adam; Pilon, Eric

    2012-01-01

    Under the assumption that the dijet excess seen by the CDF Collaboration near 150 Gev in Wjj production is due to the lightest technipion of the low-scale technicolor process $\\rho_T \\rightarrow W \\pi_T$, we study its observability in LHC detectors with 1--20 inverse femtobarns of data. We describe interesting new kinematic tests that can provide independent confirmation of this LSTC hypothesis. We find that cuts similar to those employed by CDF, and recently by ATLAS, cannot confirm the dijet signal. We propose cuts tailored to the LSTC hypothesis and its backgrounds at the LHC that may reveal $\\rho_T \\rightarrow \\ell\

  12. Reactive oxygen species and transcript analysis upon excess light treatment in wild-type Arabidopsis thaliana vs a photosensitive mutant lacking zeaxanthin and lutein

    Directory of Open Access Journals (Sweden)

    Roncaglia Enrica

    2011-04-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are unavoidable by-products of oxygenic photosynthesis, causing progressive oxidative damage and ultimately cell death. Despite their destructive activity they are also signalling molecules, priming the acclimatory response to stress stimuli. Results To investigate this role further, we exposed wild type Arabidopsis thaliana plants and the double mutant npq1lut2 to excess light. The mutant does not produce the xanthophylls lutein and zeaxanthin, whose key roles include ROS scavenging and prevention of ROS synthesis. Biochemical analysis revealed that singlet oxygen (1O2 accumulated to higher levels in the mutant while other ROS were unaffected, allowing to define the transcriptomic signature of the acclimatory response mediated by 1O2 which is enhanced by the lack of these xanthophylls species. The group of genes differentially regulated in npq1lut2 is enriched in sequences encoding chloroplast proteins involved in cell protection against the damaging effect of ROS. Among the early fine-tuned components, are proteins involved in tetrapyrrole biosynthesis, chlorophyll catabolism, protein import, folding and turnover, synthesis and membrane insertion of photosynthetic subunits. Up to now, the flu mutant was the only biological system adopted to define the regulation of gene expression by 1O2. In this work, we propose the use of mutants accumulating 1O2 by mechanisms different from those activated in flu to better identify ROS signalling. Conclusions We propose that the lack of zeaxanthin and lutein leads to 1O2 accumulation and this represents a signalling pathway in the early stages of stress acclimation, beside the response to ADP/ATP ratio and to the redox state of both plastoquinone pool. Chloroplasts respond to 1O2 accumulation by undergoing a significant change in composition and function towards a fast acclimatory response. The physiological implications of this signalling specificity are

  13. Characteristics of adolescent excessive drinkers compared with consumers and abstainers

    NARCIS (Netherlands)

    Tomcikova, Zuzana; Geckova, Andrea Madarasova; van Dijk, Jitse P.; Reijneveld, Sijmen A.

    Introduction and Aims. This study aimed at comparing adolescent abstainers, consumers and excessive drinkers in terms of family characteristics (structure of family, socioeconomic factors), perceived social support, personality characteristics (extraversion, self-esteem, aggression) and well-being.

  14. Alpha molecular epidemiological analysis of adenoviruses from excess conjunctivitis cases

    National Research Council Canada - National Science Library

    A Balasopoulou; P Κokkinos; D Pagoulatos; P Plotas; O E Makri; C D Georgakopoulos; A Vantarakis

    2017-01-01

    Background Τo perform a molecular epidemiological analysis of viral conjunctivitis among excess conjunctivitis cases recorded at the University Hospital of Patras, Greece, for the period March to June 2012...

  15. Excess Molar Volume of Binary Systems Containing Mesitylene

    Directory of Open Access Journals (Sweden)

    Morávková, L.

    2013-05-01

    Full Text Available This paper presents a review of density measurements for binary systems containing 1,3,5-trimethylbenzene (mesitylene with a variety of organic compounds at atmospheric pressure. Literature data of the binary systems were divided into nine basic groups by the type of contained organic compound with mesitylene. The excess molar volumes calculated from the experimental density values have been compared with literature data. Densities were measured by a few experimental methods, namely using a pycnometer, a dilatometer or a commercial apparatus. The overview of the experimental data and shape of the excess molar volume curve versus mole fraction is presented in this paper. The excess molar volumes were correlated by Redlich–Kister equation. The standard deviations for fitting of excess molar volume versus mole fraction are compared. Found literature data cover a huge temperature range from (288.15 to 343.15 K.

  16. Parenting Emerging Adults Who Game Excessively: Parents' Lived Experiences.

    Science.gov (United States)

    Russell, Linda L H; Johnson, Elizabeth I

    2017-01-01

    Excessive gaming among emerging adults is a growing concern, especially in cases where it interferes with key developmental milestones such as gaining an education or establishing a career. Although researchers have begun to understand the effects of excessive gaming on young people themselves, we know remarkably little about how emerging adults' gaming may affect family relationships. Utilizing phenomenological interviewing of parents of emerging adult sons who game excessively, this study presents a rich description of the experience of parenting a young adult who games excessively. In-depth interviews were conducted with two fathers and two mothers. Findings suggested that parents felt their sons were missing out on aspects of their life due to their gaming and were not meeting their full potential. They also felt their sons were different from other people their age and found it difficult to talk to them about their gaming. Finally, they believed their sons were addicted to gaming.

  17. Antigen excess in modern immunoassays: to anticipate on the unexpected.

    Science.gov (United States)

    Jacobs, Joannes F M; van der Molen, Renate G; Bossuyt, Xavier; Damoiseaux, Jan

    2015-02-01

    Immunoassays measuring sera with high analyte concentration may be prone to an artifact that causes underestimation of the analyte concentration. This phenomenon is generally described as antigen excess or the prozone effect. Characteristically, serum with high concentrations of a certain analyte can give a false negative/low result when tested at the recommended dilution, but reacts strongly positive upon further dilution. Increased insight of the antigen excess mechanisms and tools to prevent it has reduced the analytical problems caused by prozone effects in daily laboratory practice. However, misinterpretation of laboratory results caused by antigen excess does still occur, in virtually any type of immunoassay. Awareness by the laboratory specialist of the mechanisms underlying antigen excess in the different immunoassays, strategies to detect it, and adequate communication with clinicians can help to avoid reporting false negative test-results. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Modelling of excess noise attnuation by grass and forest | Onuu ...

    African Journals Online (AJOL)

    , guinea grass (panicum maximum) and forest which comprises iroko (milicia ezcelea) and white afara (terminalia superba) trees in the ratio of 2:1 approximately. Excess noise attenuation spectra have been plotted for the grass and forest for ...

  19. Iodine deficiency and iodine excess in Jiangsu Province, China

    NARCIS (Netherlands)

    Zhao, J.

    2001-01-01

    Keywords:
    iodine deficiency, iodine excess, endemic goiter, drinking water, iodine intake, thyroid function, thyroid size, iodized salt, iodized oil, IQ, physical development, hearing capacity, epidemiology, meta-analysis, IDD, randomized trial, intervention, USA, Bangladesh,

  20. Generic switching of warfarin and risk of excessive anticoagulation

    DEFF Research Database (Denmark)

    Hellfritzsch, Maja; Rathe, Jette; Stage, Tore Bjerregaard

    2015-01-01

    PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analysis......). This constituted 89.0% of all warfarin prescriptions in Denmark during the study period. We observed 19,362 switches to generic warfarin during the study period. The adjusted hazard ratio for excessive anticoagulation following a recent switch from branded to generic warfarin was 1.1 (95%CI, 0.8-1.4). The result...... was robust within subgroups and several sensitivity analyses. CONCLUSION: Switching from branded to generic warfarin is not associated with an increased risk of hospitalization with excessive anticoagulation. However, a minor excess risk of transient INR increase cannot be excluded. Pharmacoepidemiological...

  1. Internet Addiction and Excessive Social Networks Use: What About Facebook?

    National Research Council Canada - National Science Library

    Guedes, Eduardo; Sancassiani, Federica; Carta, Mauro Giovani; Campos, Carlos; Machado, Sergio; King, Anna Lucia Spear; Nardi, Antonio Egidio

    2016-01-01

    ... world. However, healthy and conscience Facebook use is contrasted by excessive use and lack of control, creating an addiction with severely impacts the everyday life of many users, mainly youths...

  2. Predictive factors for intraoperative excessive bleeding in Graves’ disease

    Directory of Open Access Journals (Sweden)

    Kosho Yamanouchi

    2015-01-01

    Conclusion: A huge goiter presented as a predictive factor for excessive bleeding during surgery for Graves’ disease, and preparation for blood transfusion should be considered in cases where thyroids weigh more than 200 g.

  3. Excess Alcohol May Speed Muscle Loss in Older Women

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_166348.html Excess Alcohol May Speed Muscle Loss in Older Women After ... risk drinking was defined as frequent and significant alcohol use, along with a lack of control over ...

  4. Study on classical and excess eddy currents losses of Terfenol-D

    Energy Technology Data Exchange (ETDEWEB)

    Talebian, Soheil; Hojjat, Yousef [Department of Mechanical Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Ghodsi, Mojtaba [Department of Mechanical and Industrial Engineering, Sultan Qaboos University, Muscat (Oman); Karafi, Mohammad Reza [Department of Mechanical Engineering, Tarbiat Modares University, Tehran (Iran, Islamic Republic of)

    2015-08-15

    In the present paper, classical and excess eddy currents losses of Terfenol-D are studied and effects of magnetic field frequency, peak of magnetic flux density and diameter of Terfenol-D on the eddy currents losses are investigated. To provide reliable data for the purpose of the paper, an experimental laboratory is fabricated and used to obtain major and minor hysteresis loops of Terfenol-D at different frequencies. In theoretical study, initially an analytical model based on uniform distribution of magnetic flux is developed which yields to calculation of classical eddy currents losses. Then, another eddy currents model based on non-uniform distribution of magnetic flux and nonlinear diffusion of electromagnetic fields is presented. The difference between output values of the two models is identified as excess eddy currents losses. Obtained results show that the values of excess losses are generally larger than classical losses and applying just classical model leads to wrong calculation of actual value of eddy currents losses. For the results obtained from two above models, empirical models with respect to the magnetic field frequency and the peak value of magnetic flux density are achieved which can predict the eddy currents losses precisely. To validate the empirical relations, experiments are repeated at a new frequency and values of power losses calculated from analytical equations are compared with the predicted values of the empirical models. The results point towards possibility to use the obtained empirical relations in order to calculate the classical and excess eddy currents losses of Terfenol-D at the frequencies below 200 Hz and different values of magnetic flux density. - Highlights: • Classical eddy currents loss of Terfenol-D is studied using Maxwell's laws. • Excess eddy currents loss of Terfenol-D is studied using Mayergoyz nonlinear model. • Effects of Terfenol-D geometry on the eddy currents losses are investigated. • Power

  5. Contributors to Excess Infant Mortality in the U.S. South

    Science.gov (United States)

    Hirai, Ashley H.; Sappenfield, William M.; Kogan, Michael D.; Barfield, Wanda D.; Goodman, David A.; Ghandour, Reem M.; Lu, Michael C.

    2015-01-01

    Background Infant mortality rates (IMRs) are disproportionally high in the U.S. South; however, the proximate contributors that could inform regional action remain unclear. Purpose To quantify the components of excess infant mortality in the U.S. South by maternal race/ethnicity, underlying cause of death, and gestational age. Methods U.S. Period Linked Birth/Infant Death Data Files 2007–2009 (analyzed in 2013) were used to compare IMRs between the South (U.S. Public Health Regions IV and VI) and all other regions combined. Results Compared to other regions, there were 1.18 excess infant deaths per 1000 live births in the South, representing about 1600 excess infant deaths annually. New Mexico and Texas did not have elevated IMRs relative to other regions; excess death rates among other states ranged from 0.62 per 1000 in Kentucky to 3.82 per 1000 in Mississippi. Racial/ethnic compositional differences, generally the greater proportion of non-Hispanic black births in the South, explained 59% of the overall regional difference; the remainder was mostly explained by higher IMRs among non-Hispanic whites. The leading causes of excess Southern infant mortality were sudden unexpected infant death (SUID; 36%, range=12% in Florida to 90% in Kentucky) and preterm-related death (22%, range=−71% in Kentucky to 51% in North Carolina). Higher rates of preterm birth, predominantly infant mortality, comprehensive strategies addressing SUID and preterm birth prevention for both non-Hispanic black and white births are needed, with state-level findings used to tailor state-specific efforts. PMID:24512860

  6. Initiation of Swarming Motility by Proteus mirabilis Occurs in Response to Specific Cues Present in Urine and Requires Excess l-Glutamine

    Science.gov (United States)

    Armbruster, Chelsie E.; Hodges, Steven A.

    2013-01-01

    Proteus mirabilis, a leading cause of catheter-associated urinary tract infection (CaUTI), differentiates into swarm cells that migrate across catheter surfaces and medium solidified with 1.5% agar. While many genes and nutrient requirements involved in the swarming process have been identified, few studies have addressed the signals that promote initiation of swarming following initial contact with a surface. In this study, we show that P. mirabilis CaUTI isolates initiate swarming in response to specific nutrients and environmental cues. Thirty-three compounds, including amino acids, polyamines, fatty acids, and tricarboxylic acid (TCA) cycle intermediates, were tested for the ability to promote swarming when added to normally nonpermissive media. l-Arginine, l-glutamine, dl-histidine, malate, and dl-ornithine promoted swarming on several types of media without enhancing swimming motility or growth rate. Testing of isogenic mutants revealed that swarming in response to the cues required putrescine biosynthesis and pathways involved in amino acid metabolism. Furthermore, excess glutamine was found to be a strict requirement for swarming on normal swarm agar in addition to being a swarming cue under normally nonpermissive conditions. We thus conclude that initiation of swarming occurs in response to specific cues and that manipulating concentrations of key nutrient cues can signal whether or not a particular environment is permissive for swarming. PMID:23316040

  7. A Portable Burn Pan for the Disposal of Excess Propellants

    Science.gov (United States)

    2016-06-01

    Measuring energetic contaminant deposition rates on snow. Water Air Soil Pollut (2012) 223:3689–3699. [25] Rasemann, W (2000) Industrial waste dumps...2013 - 06/01/2016 A Portable Burn Pan for the Disposal of Excess Propellants Michael Walsh USA CRREL USA CRREL 72 Lyme Road Hanover, NH 03755...detected in surface waters . Local regulations also require the transportation of excess charges to remote burn facilities, which results in the absence of

  8. Asymmetric Dark Matter Models and the LHC Diphoton Excess

    DEFF Research Database (Denmark)

    Frandsen, Mads T.; Shoemaker, Ian M.

    2016-01-01

    The existence of dark matter (DM) and the origin of the baryon asymmetry are persistent indications that the SM is incomplete. More recently, the ATLAS and CMS experiments have observed an excess of diphoton events with invariant mass of about 750 GeV. One interpretation of this excess is decays...... have for models of asymmetric DM that attempt to account for the similarity of the dark and visible matter abundances....

  9. Excessive computer game playing : evidence for addiction and aggression?

    OpenAIRE

    Grüsser, SM; Thalemann, R; Griffiths, MD

    2007-01-01

    Computer games have become an ever-increasing part of many adolescents’ day-to-day lives. Coupled with this phenomenon, reports of excessive gaming (computer game playing) denominated as “computer/video game addiction” have been discussed in the popular press as well as in recent scientific research. The aim of the present study was the investigation of the addictive potential of gaming as well as the relationship between excessive gaming and aggressive attitudes and behavior. A sample compri...

  10. Variables of excessive computer internet use in childhood and adolescence

    OpenAIRE

    Thalemann, Ralf

    2010-01-01

    The aim of this doctoral thesis is the characterization of excessive computer and video gaming in terms of a behavioral addiction. Therefore, the development of a diagnostic psychometric instrument was central to differentiate between normal and pathological computer gaming in adolescence. In study 1, 323 children were asked about their video game playing behavior to assess the prevalence of pathological computer gaming. Data suggest that excessive computer and video game players use thei...

  11. Searching For Infrared Excesses Around White Dwarf Stars

    Science.gov (United States)

    Deeb Wilson, Elin; Rebull, Luisa M.; Debes, John H.; Stark, Chris

    2017-01-01

    Many WDs have been found to be “polluted,” meaning they contain heavier elements in their atmospheres. Either an active process that counters gravitational settling is taking place, or an external mechanism is the cause. One proposed external mechanism for atmospheric pollution of WDs is the disintegration and accretion of rocky bodies, which would result in a circumstellar (CS) disk. As CS disks are heated, they emit excess infrared (IR) emission. WDs with IR excesses indicative of a CS disk are known as dusty WDs. Statistical studies are still needed to determine how numerous dusty, polluted WDs are, along with trends and correlations regarding rate of planetary accretion, the lifetimes of CS disks, and the structure and evolution of CS disks. These findings will allow for a better understanding of the fates of planets along with potential habitability of surviving planets.In this work, we are trying to confirm IR excesses around a sample of 69 WD stars selected as part of the WISE InfraRed Excesses around Degenerates (WIRED) Survey (Debes et al. 2011). We have archival data from WISE, Spitzer, 2MASS, DENIS, and SDSS. The targets were initially selected from the Sloan Digital Sky Survey (SDSS), and identified as containing IR excesses based on WISE data. We also have data from the Four Star Infrared Camera array, which is part of Carnegie Institution’s Magellan 6.5 meter Baade Telescope located at Las Campanas Observatory in Chile. These Four Star data are much higher spatial resolution than the WISE data that were used to determine if each WD has an IR excess. There are often not many bands delineating the IR excess portion of the SED; therefore, we are using the Four Star data to check if there is another source in the WISE beam affecting the IR excess.

  12. Excessive maps, "arrival times" and perturbation of dynamical semigroups

    Science.gov (United States)

    Holevo, A. S.

    1995-12-01

    The notion of excessive map for dynamical semigroup is introduced, and it is shown that an excessive map defines an operation-valued measure describing the measurement of an "arrival time" related to the irreversible dynamics described by the semigroup. Any such arrival time determines a positive perturbation of the dynamical semigroup describing the dynamics after "arrivals". Generators of the relevant perturbations are characterized, and several examples, both commutative and a non-commutative, are discussed, elucidating the problem of standard representation.

  13. Thyrotoxic periodic paralysis due to excessive L-thyroxine replacement in a Caucasian man.

    LENUS (Irish Health Repository)

    Hannon, M J

    2009-09-01

    Thyrotoxic periodic paralysis is a potentially fatal complication of hyperthyroidism, more common in Asian races, which is defined by a massive intracellular flux of potassium. This leads to profound hypokalaemia and muscle paralysis. Although the paralysis is temporary, it may be lethal if not diagnosed and treated rapidly, as profound hypokalaemia may induce respiratory muscle paralysis or cardiac arrest. The condition is often misdiagnosed in the west due to its comparative rarity in Caucasians; however it is now increasingly described in Caucasians and is also being seen with increasing frequency in western hospitals due to increasing immigration and population mobility. Here we describe the case of a patient with panhypopituitarism due to a craniopharyngioma, who developed thyrotoxic periodic paralysis due to excessive L-thyroxine replacement. This disorder has been described in Asian subjects but, to our knowledge, thyrotoxic periodic paralysis secondary to excessive L-thyroxine replacement has never been described in Caucasians.

  14. Excess Weapons Plutonium Disposition: Plutonium Packaging, Storage and Transportation and Waste Treatment, Storage and Disposal Activities

    Energy Technology Data Exchange (ETDEWEB)

    Jardine, L J; Borisov, G B

    2004-07-21

    A fifth annual Excess Weapons Plutonium Disposition meeting organized by Lawrence Livermore National Laboratory (LLNL) was held February 16-18, 2004, at the State Education Center (SEC), 4 Aerodromnya Drive, St. Petersburg, Russia. The meeting discussed Excess Weapons Plutonium Disposition topics for which LLNL has the US Technical Lead Organization responsibilities. The technical areas discussed included Radioactive Waste Treatment, Storage, and Disposal, Plutonium Oxide and Plutonium Metal Packaging, Storage and Transportation and Spent Fuel Packaging, Storage and Transportation. The meeting was conducted with a conference format using technical presentations of papers with simultaneous translation into English and Russian. There were 46 Russian attendees from 14 different Russian organizations and six non-Russian attendees, four from the US and two from France. Forty technical presentations were made. The meeting agenda is given in Appendix B and the attendance list is in Appendix C.

  15. Lead and tap water

    Science.gov (United States)

    Water contaminated with lead ... The Environmental Protection Agency (EPA) monitors drinking water in the United States. It requires water suppliers to produce annual water quality reports. These reports include information about lead amounts, and they ...

  16. NA49: lead-lead collision

    CERN Multimedia

    1996-01-01

    This is an image of an actual lead ion collision taken from tracking detectors on the NA49 experiment, part of the heavy ion project at CERN. These collisions produce a very complicated array of hadrons as the heavy ions break up. It is hoped that one of these collisions will eventually create a new state of matter known as quark-gluon plasma.

  17. Animal models of excessive alcohol consumption in rodents.

    Science.gov (United States)

    Becker, Howard C

    2013-01-01

    Numerous animal models have been developed to study excessive alcohol consumption in rodents. Use of such models has played a valuable role in elucidating biological underpinnings and environmental factors that mediate/promote excessive levels of alcohol drinking. A major obstacle in this work has been the need to overcome the natural tendency of rodents to either avoid alcohol or consume it in limited amounts that typically do not produce overt signs of intoxication. A variety of experimental approaches that entail modifying genetic and/or environmental factors have been employed to address this general problem and demonstrate excessive levels of alcohol consumption. Five different approaches that characterize animal models of excessive alcohol consumption are described: models that involve (a) scheduled access to alcohol; (b) scheduled periods of alcohol deprivation; (c) scheduled intermittent access to alcohol; (d) scheduled-induced polydipsia; and (e) dependence and withdrawal experience. Each of the models possesses unique experimental features that engender excessive levels of alcohol consumption. Both advantages and disadvantages for each model are described along with discussion of future challenges to be considered in developing more optimal models. Ultimately, the validity and usefulness of these models will lie in their ability to serve as a platform for studying biological underpinnings and environmental influences that drive increased motivation for alcohol seeking and consumption, as well as evaluation of treatment strategies that effectively reduce excessive levels of alcohol consumption.

  18. Lead Poisoning (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Lead Poisoning KidsHealth > For Parents > Lead Poisoning Print A ... Family en español La intoxicación por plomo About Lead Poisoning If you have young kids, it's important ...

  19. Lead Poisoning in Childhood.

    Science.gov (United States)

    Pueschel, Siegfried M., Ed.; Linakis, James G., Ed.; Anderson, Angela C., Ed.

    The magnitude of childhood lead poisoning has been inexplicably neglected by modern medicine and by legislators. However, since the 1970s, increased attention has been focused on lead poisoning, and advances have been made in several areas, including understanding of the neurodevelopmental and behavioral ramifications of lead poisoning, and…

  20. Lead poisoning: An overview

    Science.gov (United States)

    Gendel, Neil

    1993-01-01

    A problem that should be of great concern to all of us is the lead poisoning of children. First, I would like to present a short overview concerning the reasons everyone should care about lead poisoning, then discuss the history of lead poisoning, what is happening today across the country, and the future.

  1. Lead Poisoning in Children.

    Science.gov (United States)

    Drummond, A. H., Jr.

    1981-01-01

    Early symptoms of lead poisoning in children are often overlooked. Lead poisoning has its greatest effects on the brain and nervous system. The obvious long-term solution to the lead poisoning problem is removal of harmful forms of the metal from the environment. (JN)

  2. Leptin signaling, adiposity, and energy balance.

    Science.gov (United States)

    Jéquier, Eric

    2002-06-01

    A chronic minor imbalance between energy intake and energy expenditure may lead to obesity. Both lean and obese subjects eventually reach energy balance and their body weight regulation implies that the adipose tissue mass is "sensed", leading to appropriate responses of energy intake and energy expenditure. The cloning of the ob gene and the identification of its encoded protein, leptin, have provided a system signaling the amount of adipose energy stores to the brain. Leptin, a hormone secreted by fat cells, acts in rodents via hypothalamic receptors to inhibit feeding and increase thermogenesis. A feedback regulatory loop with three distinct steps has been identified: (1) a sensor (leptin production by adipose cells) monitors the size of the adipose tissue mass; (2) hypothalamic centers receive and integrate the intensity of the leptin signal through leptin receptors (LRb); (3) effector systems, including the sympathetic nervous system, control the two main determinants of energy balance-energy intake and energy expenditure. While this feedback regulatory loop is well established in rodents, there are many unsolved questions about its applicability to body weight regulation in humans. The rate of leptin production is related to adiposity, but a large portion of the interindividual variability in plasma leptin concentration is independent of body fatness. Gender is an important factor determining plasma leptin, with women having markedly higher leptin concentrations than men for any given degree of fat mass. The ob mRNA expression is also upregulated by glucocorticoids, whereas stimulation of the sympathetic nervous system results in its inhibition. Furthermore, leptin is not a satiety factor in humans because changes in food intake do not induce short-term increases in plasma leptin levels. After its binding to LRb in the hypothalamus, leptin stimulates a specific signaling cascade that results in the inhibition of several orexigenic neuropeptides, while

  3. Cardiovascular actions of lead and relationship to hypertension: a review

    Energy Technology Data Exchange (ETDEWEB)

    Kopp, S.J.; Barron, J.T.; Tow, J.P.

    1988-06-01

    Chronic and acute lead poisoning cause overt, clinical symptoms of cardiac and vascular damage with potentially lethal consequences. Morphological, biochemical, and functional derangements of the heart have all been described in patients following exposure to excessive lead levels. Disturbances in cardiac electrical and mechanical activity and postmortem evidence of morphological and biochemical derangements of the myocardium have all been reported following excessive exposure to lead in humans. In addition, signs of vascular degeneration, abnormal vascular smooth muscle function, and altered vessel compliance have been described in humans chronically and acutely exposed to toxic lead levels. Similar cardiovascular complications have been detected following excessive lead exposure in experimental animals. Myocarditis, electrocardiographic disturbances, heightened catecholamine arrhythmogenicity, altered myocardial contractile responsiveness to inotropic stimulation, degenerative structural biochemical changes affecting the musculature of the heart and vasculature, hypertension, hypercholesterolemia, atherosclerosis, and increased vascular reactivity to ..cap alpha..-adrenergic agonists have been among the reported cardiovascular disturbances linked to lead poisoning. Although controversial, chronic low-level lead exposure has been linked to hypertension and other cardiovascular disturbances in both clinical and experimental studies. In general, it can be concluded that lead over a wide range of exposure intensities can induce significant changes in the function of the cardiovascular system.

  4. Calcium signaling alterations, oxidative stress, and autophagy in aging.

    Science.gov (United States)

    Ureshino, Rodrigo Portes; Rocha, Katiucha Karolina; Lopes, Guiomar Silva; Bincoletto, Cláudia; Smaili, Soraya Soubhi

    2014-07-01

    Aging is a multi-factorial process that may be associated with several functional and structural deficits which can evolve into degenerative diseases. In this review, we present data that may depict an expanded view of molecular aging theories, beginning with the idea that reactive oxygen species (ROS) are the major effectors in this process. In addition, we have correlated the importance of autophagy as a neuroprotective mechanism and discussed a link between age-related molecules, Ca(2+) signaling, and oxidative stress. There is evidence suggesting that alterations in Ca(2+) homeostasis, including mitochondrial Ca(2+) overload and alterations in electron transport chain (ETC) complexes, which increase cell vulnerability, are linked to oxidative stress in aging. As much as Ca(2+) signaling is altered in aged cells, excess ROS can be produced due to an ineffective coupling of mitochondrial respiration. Damaged mitochondria might not be removed by the macroautophagic system, which is hampered in aging by lipofuscin accumulation, boosting ROS generation, damaging DNA, and, ultimately, leading to apoptosis. This process can lead to altered protein expression (such as p53, Sirt1, and IGF-1) and progress to cell death. This cycle can lead to increased cell vulnerability in aging and contribute to an increased susceptibility to degenerative processes. A better understanding of Ca(2+) signaling and molecular aging alterations is important for preventing apoptosis in age-related diseases. In addition, caloric restriction, resveratrol and autophagy modulation appear to be predominantly cytoprotective, and further studies of this process are promising in age-related disease therapeutics.

  5. Evidence for an excess of soft photons in hadronic decays of $Z^{0}$

    CERN Document Server

    Abdallah, J; Adam, W; Adzic, P; Albrecht, T; Alderweireld, T; Alemany-Fernandez, R; Allmendinger, T; Allport, P P; Amaldi, Ugo; Amapane, N; Amato, S; Anashkin, E; Andreazza, A; Andringa, S; Anjos, N; Antilogus, P; Apel, W D; Arnoud, Y; Ask, S; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Ballestrero, A; Bambade, P; Barbier, R; Bardin, D; Barker, G J; Baroncelli, A; Battaglia, M; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Ben-Haim, E; Benekos, N; Benvenuti, A C; Bérat, C; Berggren, M; Berntzon, L; Bertrand, D; Besançon, M; Besson, N; Bloch, D; Blom, M; Bluj, M; Bonesini, M; Boonekamp, M; Booth, P S L; Borisov, G; Botner, O; Bouquet, B; Bowcock, T J V; Boyko, I; Bracko, M; Brenner, R; Brodet, E; Brückman, P; Brunet, J M; Buschbeck, Brigitte; Buschmann, P; Calvi, M; Camporesi, T; Canale, V; Carena, F; Castro, N; Cavallo, F; Chapkin, M; Charpentier, P; Checchia, P; Chierici, R; Shlyapnikov, P; Chudoba, J; Chung, S U; Cieslik, K; Collins, P; Contri, R; Cosme, G; Cossutti, F; Costa, M J; Crennell, D J; Cuevas-Maestro, J; D'Hondt, J; Dalmau, J; Da Silva, T; Da Silva, W; Della Ricca, G; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Maria, N; De Min, A; De Paula, L; Di Ciaccio, L; Di Simone, A; Doroba, K; Drees, J; Eigen, G; Ekelöf, T J C; Ellert, M; Elsing, M; Espirito-Santo, M C; Fanourakis, G K; Fassouliotis, D; Feindt, M; Fernández, J; Ferrer, A; Ferro, F; Flagmeyer, U; Föth, H; Fokitis, E; Fulda-Quenzer, F; Fuster, J; Gandelman, M; García, C; Gavillet, P; Gazis, E; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; Graziani, E; Grosdidier, G; Grzelak, K; Guy, J; Haag, C; Hallgren, A; Hamacher, K; Hamilton, K; Haug, S; Hauler, F; Hedberg, V; Hennecke, M; Herr, H; Hoffman, J; Holmgren, S O; Holt, P J; Houlden, M A; Hultqvist, K; Jackson, J N; Jarlskog, G; Jarry, P; Jeans, D; Johansson, E K; Johansson, P D; Jonsson, P; Joram, C; Jungermann, L; Kapusta, F; Katsanevas, S; Katsoufis, E; Kernel, G; Kersevan, B P; Kerzel, U; King, B T; Kjaer, N J; Kluit, P; Kokkinias, P; Kourkoumelis, C; Kuznetsov, O; Krumshtein, Z; Kucharczyk, M; Lamsa, J; Leder, G; Ledroit, F; Leinonen, L; Leitner, R; Lemonne, J; Lepeltier, V; Lesiak, T; Liebig, W; Liko, D; Lipniacka, A; Lopes, J H; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J; Malek, A; Maltezos, S; Mandl, F; Marco, J; Marco, R; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Masik, J; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Mazzucato, F; Mazzucato, M; McNulty, R; Meroni, C; Migliore, E; Mitaroff, W A; Mjörnmark, U; Moa, T; Moch, M; Mönig, K; Monge, R; Montenegro, J; Moraes, D; Moreno, S; Morettini, P; Müller, U; Münich, K; Mulders, M; Mundim, L; Murray, W; Muryn, B; Myatt, G; Myklebust, T; Nassiakou, M; Navarria, Francesco Luigi; Nawrocki, K; Nicolaidou, R; Nikolenko, M; Oblakowska-Mucha, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, R; Österberg, K; Ouraou, A; Oyanguren, A; Paganoni, M; Paiano, S; Palacios, J P; Palka, H; Papadopoulou, T D; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Peralta, L; Perepelitsa, V F; Perrotta, A; Petrolini, A; Piedra, J; Pieri, L; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Poireau, V; Pol, M E; Polok, G; Pozdnyakov, V; Pukhaeva, N; Pullia, A; Rames, J; Read, A; Rebecchi, P; Rehn, J; Reid, D; Reinhardt, R; Renton, P B; Richard, F; Rídky, J; Rivero, M; Rodríguez, D; Romero, A; Ronchese, P; Roudeau, P; Rovelli, T; Ruhlmann-Kleider, V; Ryabtchikov, D; Sadovskii, A; Salmi, L; Salt, J; Sander, C; Savoy-Navarro, A; Schwickerath, U; Segar, A; Sekulin, R L; Siebel, M; Sisakian, A; Smadja, G; Smirnova, O; Sokolov, A; Sopczak, A; Sosnowski, R; Spassoff, Tz; Stanitzki, M; Stocchi, A; Strauss, J; Stugu, B; Szczekowski, M; Szeptycka, M; Szumlak, T; Tabarelli de Fatis, T; Taffard, A C; Tegenfeldt, F; Timmermans, J; Tkatchev, L G; Tobin, M; Todorovova, S; Tomé, B; Tonazzo, A; Tortosa, P; Travnicek, P; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Turluer, M L; Tyapkin, I A; Tyapkin, P; Tzamarias, S; Uvarov, V; Valenti, G; van Dam, P; Van Eldik, J; Van Remortel, N; Van Vulpen, I; Vegni, G; Veloso, F; Venus, W; Verdier, P; Verzi, V; Vilanova, D; Vitale, L; Vrba, V; Wahlen, H; Washbrook, A J; Weiser, C; Wicke, D; Wickens, J; Wilkinson, G; Winter, M; Witek, M; Yushchenko, O P; Zalewska-Bak, A; Zalewski, P; Zavrtanik, D; Zhuravlov, V; Zimin, N I; Zintchenko, A; Zupan, M

    2006-01-01

    Soft photons inside hadronic jets converted in front of the DELPHI main tracker (TPC) in events of qqbar disintegrations of the Z^0 were studied in the kinematic range 0.2 < E_gamma < 1 GeV and transverse momentum with respect to the closest jet direction p_T < 80 MeV/c. A clear excess of photons in the experimental data as compared to the Monte Carlo predictions is observed. This excess (uncorrected for the photon detection efficiency) is (1.17 +/- 0.06 +/- 0.27) x 10^{-3} gamma/jet in the specified kinematic region, while the expected level of the inner hadronic bremsstrahlung (which is not included in the Monte Carlo) is (0.340 +/- 0.001 +/- 0.038) x 10^{-3} gamma/jet. The ratio of the excess to the predicted bremsstrahlung rate is then (3.4 +/- 0.2 +/- 0.8), which is similar in strength to the anomalous soft photon signal observed in fixed target experiments with hadronic beams.

  6. Excess Maternal Fructose Consumption Increases Fetal Loss and Impairs Endometrial Decidualization in Mice.

    Science.gov (United States)

    Saben, Jessica L; Asghar, Zeenat; Rhee, Julie S; Drury, Andrea; Scheaffer, Suzanne; Moley, Kelle H

    2016-02-01

    The most significant increase in metabolic syndrome over the previous decade occurred in women of reproductive age, which is alarming given that metabolic syndrome is associated with reproductive problems including subfertility and early pregnancy loss. Individuals with metabolic syndrome often consume excess fructose, and several studies have concluded that excess fructose intake contributes to metabolic syndrome development. Here, we examined the effects of increased fructose consumption on pregnancy outcomes in mice. Female mice fed a high-fructose diet (HFrD) for 6 weeks developed glucose intolerance and mild fatty liver but did not develop other prominent features of metabolic syndrome such as weight gain, hyperglycemia, and hyperinsulinemia. Upon mating, HFrD-exposed mice had lower pregnancy rates and smaller litters at midgestation than chow-fed controls. To explain this phenomenon, we performed artificial decidualization experiments and found that HFrD consumption impaired decidualization. This appeared to be due to decreased circulating progesterone as exogenous progesterone administration rescued decidualization. Furthermore, HFrD intake was associated with decreased bone morphogenetic protein 2 expression and signaling, both of which were restored by exogenous progesterone. Finally, expression of forkhead box O1 and superoxide dismutase 2 [Mn] proteins were decreased in the uteri of HFrD-fed mice, suggesting that HFrD consumption promotes a prooxidative environment in the endometrium. In summary, these data suggest that excess fructose consumption impairs murine fertility by decreasing steroid hormone synthesis and promoting an adverse uterine environment.

  7. Purinergic signalling and diabetes

    DEFF Research Database (Denmark)

    Burnstock, Geoffrey; Novak, Ivana

    2013-01-01

    signalling, we will focus on the role of purinergic signalling and its changes associated with diabetes in the pancreas and selected tissues/organ systems affected by hyperglycaemia and other stress molecules of diabetes. Since this is the first review of this kind, a comprehensive historical angle is taken......The pancreas is an organ with a central role in nutrient breakdown, nutrient sensing and release of hormones regulating whole body nutrient homeostasis. In diabetes mellitus, the balance is broken-cells can be starving in the midst of plenty. There are indications that the incidence of diabetes...... type 1 and 2, and possibly pancreatogenic diabetes, is rising globally. Events leading to insulin secretion and action are complex, but there is emerging evidence that intracellular nucleotides and nucleotides are not only important as intracellular energy molecules but also as extracellular signalling...

  8. Excess Readmission vs Excess Penalties: Maximum Readmission Penalties as a Function of Socioeconomics and Geography.

    Science.gov (United States)

    Caracciolo, Chris; Parker, Devin; Marshall, Emily; Brown, Jeremiah

    2017-08-01

    The Hospital Readmission Reduction Program (HRRP) penalizes hospitals with "excess" readmissions up to 3% of Medicare reimbursement. Approximately 75% of eligible hospitals received penalties, worth an estimated $428 million, in fiscal year 2015. To identify demographic and socioeconomic disparities between matched and localized maximum-penalty and no-penalty hospitals. A case-control study in which cases included were hospitals to receive the maximum 3% penalty under the HRRP during the 2015 fiscal year. Controls were drawn from no-penalty hospitals and matched to cases by hospital characteristics (primary analysis) or geographic proximity (secondary analysis). A selectiion of 3383 US hospitals eligible for HRRP. Thirty-nine case and 39 control hospitals from the HRRP cohort. Socioeconomic status variables were collected by the American Community Survey. Hospital and health system characteristics were drawn from Centers for Medicare and Medicaid Services, American Hospital Association, and Dartmouth Atlas of Health Care. The statistical analysis was conducted using Student t tests. Thirty-nine hospitals received a maximum penalty. Relative to controls, maximum-penalty hospitals in counties with lower SES profiles are defined by increased poverty rates (19.1% vs 15.5%, = 0.015) and lower rates of high school graduation (82.2% vs 87.5%, = 0.001). County level age, sex, and ethnicity distributions were similar between cohorts. Cases were more likely than controls to be in counties with low socioeconomic status; highlighting potential unintended consequences of national benchmarks for phenomena underpinned by environmental factors; specifically, whether maximum penalties under the HRRP are a consequence of underperforming hospitals or a manifestation of underserved communities.

  9. Novel strategies in drug discovery of the calcium-sensing receptor based on biased signaling

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Smajilovic, Sanela; Bräuner-Osborne, Hans

    2012-01-01

    A hallmark of chronic kidney disease is hyperphosphatemia due to renal phosphate retention. Prolonged parathyroid gland exposure to hyperphosphatemia leads to secondary hyperparathyroidism characterized by hyperplasia of the glands and excessive secretion of parathyroid hormone (PTH), which cause...... by virtue of it not affecting calcitonin secretion. The present review will focus on recent advancements in understanding signaling and biased signaling of the CaSR, and how that may be utilized to discover new and smarter drugs targeting the CaSR....... targeting the CaSR and can be used to effectively control and reduce PTH secretion in PTH-related diseases. Cinacalcet is a positive allosteric modulator of the CaSR and affects PTH secretion from parathyroid glands by shifting the calcium-PTH concentration-response curve to the left. One major disadvantage...

  10. Lead encephalopathy in adults

    Directory of Open Access Journals (Sweden)

    Janapareddy Vijaya Bhaskara Rao

    2014-01-01

    Full Text Available Lead poisoning is a common occupational health hazard in developing countries. We report the varied clinical presentation, diagnostic and management issues in two adult patients with lead encephalopathy. Both patients worked in a battery manufacturing unit. Both patients presented with seizures and one patient also complained of abdominal colic and vomiting. Both were anemic and a lead line was present. Blood lead level in both the patients was greater than 25 µg/dl. Magnetic resonance imaging of brain revealed bilateral symmetric involvement of the thalamus, lentiform nucleus in both patients and also the external capsules, sub-cortical white matter in one patient. All these changes, seen as hyperintensities in T2-weighted images suggested demyelination. They were advised avoidance of further exposure to lead and were treated with anti-epileptics; one patient also received D-penicillamine. They improved well on follow-up. Lead encephalopathy is an uncommon but important manifestation of lead toxicity in adults.

  11. Lead in the environment

    Science.gov (United States)

    Pattee, Oliver H.; Pain, Deborah J.; Hoffman, David J.; Rattner, Barnett A.; Burton, G. Allen; Cairns, John

    2003-01-01

    Anthropogenic uses of lead have probably altered its availability and environmental distribution more than any other toxic element. Consequently, lead concentrations in many living organisms may be approaching thresholds of toxicity for the adverse effects of lead. Such thresholds are difficult to define, as they vary with the chemical and physical form of lead, exposure regime, other elements present and also vary both within and between species. The technological capability to accurately quantify low lead concentrations has increased over the last decade, and physiological and behavioral effects have been measured in wildlife with tissue lead concentrations below those previously considered safe for humans.s.236 Consequently. lead criteria for the protection of wildlife and human health are frequently under review, and 'thresholds' of lead toxicity are being reconsidered. Proposed lead criteria for the protection of natural resources have been reviewed by Eisler. Uptake of lead by plants is limited by its generally low availability in soils and sediments, and toxicity may be limited by storage mechanisms and its apparently limited translocation within most plants. Lead does not generally accumulate within the foliar parts of plants, which limits its transfer to higher trophic levels. Although lead may concentrate in plant and animal tissues, no evidence of biomagnification exists. Acid deposition onto surface waters and soils with low buffering capacity may influence the availability of lead for uptake by plants and animals, and this may merit investigation at susceptible sites. The biological significance of chronic low-level lead exposure to wildlife is sometimes difficult to quantify. Animals living in urban environments or near point sources of lead emission are inevitably subject to greater exposure to lead and enhanced risk of lead poisoning. Increasingly strict controls on lead emissions in many countries have reduced exposure to lead from some sources

  12. ALICE: Simulated lead-lead collision

    CERN Document Server

    2003-01-01

    This track is an example of simulated data modelled for the ALICE detector on the Large Hadron Collider (LHC) at CERN, which will begin taking data in 2008. ALICE will focus on the study of collisions between nuclei of lead, a heavy element that produces many different particles when collided. It is hoped that these collisions will produce a new state of matter known as the quark-gluon plasma, which existed billionths of a second after the Big Bang.

  13. Chemically prepared lead magnesium niobate dielectrics

    Energy Technology Data Exchange (ETDEWEB)

    Tuttle, B.A.; Voigt, J.A.; Sipola, D.L.; Olson, W.R.; Goy, D.M.

    1998-11-01

    A chemical solution powder synthesis technique has been developed that produces first, uniform powders of lead magnesium niobate (PMN) with 60 to 80 nm crystallite size. The synthesis technique was based on the dissolution of lead acetate and alkoxide precursors in acetic acid followed by precipitation with oxalic acid/propanol solutions. Lead magnesium niobate ceramics fabricated from these chemically derived powders had smaller, more uniform grain size and higher dielectric constants than ceramics fabricated from mixed oxide powders that were processed under similar thermal conditions. Chem-prep PMN dielectrics with peak dielectric constants greater than 22,000 and polarizations in excess of 29 {micro}C/cm{sup 2} were obtained for 1,100 C firing treatments. Substantial decreases in dielectric constant and polarization were measured for chemically prepared PMN ceramics fired at lower temperatures, consistent with previous work on mixed oxide materials.

  14. EXCESSIVE INTERNET USE AND PSYCHOPATHOLOGY: THE ROLE OF COPING

    Directory of Open Access Journals (Sweden)

    Daria J. Kuss

    2017-02-01

    Full Text Available Objective: In 2013, the American Psychiatric Association included Internet Gaming Disorder in the diagnostic manual as a condition which requires further research, indicating the scientific and clinical community are aware of potential health concerns as a consequence of excessive Internet use. From a clinical point of view, it appears that excessive/addictive Internet use is often comorbid with further psychopathologies and assessing comorbidity is relevant in clinical practice, treatment outcome and prevention as the probability to become addicted to using the Internet accelerates with additional (subclinical symptoms. Moreover, research indicates individuals play computer games excessively to cope with everyday stressors and to regulate their emotions by applying media-focused coping strategies, suggesting pathological computer game players play in order to relieve stress and to avoid daily hassles. The aims of this research were to replicate and extend previous findings and explanations of the complexities of the relationships between excessive Internet use and Internet addiction, psychopathology and dysfunctional coping strategies. Method: Participants included 681 Polish university students sampled using an online battery of validated psychometric instruments. Results: Results of structural equation models revealed dysfunctional coping strategies (i.e., distraction, denial, self-blame, substance use, venting, media use, and behavioural disengagement significantly predict excessive Internet use, and the data fit the theoretical model well. A second SEM showed media-focused coping and substance use coping significantly mediate the relationship between psychopathology (operationalised via the Global Severity Index and excessive Internet use. Conclusions: The findings lend support to the self-medication hypothesis of addictive disorders, and suggest psychopathology and dysfunctional coping have additive effects on excessive Internet use.

  15. Gibberellin signaling.

    Science.gov (United States)

    Hartweck, Lynn M

    2008-12-01

    This review covers recent advances in gibberellin (GA) signaling. GA signaling is now understood to hinge on DELLA proteins. DELLAs negatively regulate GA response by activating the promoters of several genes including Xerico, which upregulates the abscisic acid pathway which is antagonistic to GA. DELLAs also promote transcription of the GA receptor, GIBBERELLIN INSENSITIVE DWARF 1 (GID1) and indirectly regulate GA biosynthesis genes enhancing GA responsiveness and feedback control. A structural analysis of GID1 provides a model for understanding GA signaling. GA binds within a pocket of GID1, changes GID1 conformation and increases the affinity of GID1 for DELLA proteins. GA/GID1/DELLA has increased affinity for an F-Box protein and DELLAs are subsequently degraded via the proteasome. Therefore, GA induces growth through degradation of the DELLAs. The binding of DELLA proteins to three of the PHYTOCHROME INTERACTING FACTOR (PIF) proteins integrates light and GA signaling pathways. This binding prevents PIFs 3, 4, and 5 from functioning as positive transcriptional regulators of growth in the dark. Since PIFs are degraded in light, these PIFs can only function in the combined absence of light and presence of GA. New analyses suggest that GA signaling evolved at the same time or just after the plant vascular system and before plants acquired the capacity for seed reproduction. An analysis of sequences cloned from Physcomitrella suggests that GID1 and DELLAs were the first to evolve but did not initially interact. The more recently diverging spike moss Selaginella has all the genes required for GA biosynthesis and signaling, but the role of GA response in Selaginella physiology remains a mystery.

  16. Lead in new paints in Nepal.

    Science.gov (United States)

    Gottesfeld, Perry; Pokhrel, Dhiraj; Pokhrel, Amod K

    2014-07-01

    Samples from 75 paint products made by 21 domestic and foreign manufacturers were purchased from retail stores in five major cities in Nepal and tested for lead content. Information provided on product labels were noted. Samples were selected to be representative of the large number of brands and colors available in retail shops. Although a majority of the products purchased were manufactured in Nepal, paints from four additional countries were tested. Out of a total of 75 samples, 57 (76%) of the tested paints contained lead at concentrations greater than 90 ppm (ppm). Ninety-three percent of the paints that exceeded 90 ppm had levels in excess of 600 ppm. Lead concentrations in the tested paints ranged up to 200,000 ppm (20%) lead by weight and the median concentration was 5100 ppm. These results indicate that lead paint is commonly being sold for residential and other consumer applications in Nepal without any consumer warnings. Regulations are needed to specify the maximum concentration of lead allowed in paint products manufactured, imported, or distributed in the country to protect public health. Efforts must be made to get lead-containing paint products recalled from stores so that they are not used in homes, schools, and other child-occupied facilities. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Lead poisoning and brain cell function

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, G.W. (Johns Hopkins School of Medicine, Baltimore, MD (USA) Kennedy Institute, Baltimore, MD (USA))

    1990-11-01

    Exposure to excessive amounts of inorganic lead during the toddler years may produce lasting adverse effects upon brain function. Maximal ingestion of lead occurs at an age when major changes are occurring in the density of brain synaptic connections. The developmental reorganization of synapses is, in part, mediated by protein kinases, and these enzymes are particularly sensitive to stimulation by lead. By inappropriately activating specific protein kinases, lead poisoning may disrupt the development of neural networks without producing overt pathological alterations. The blood-brain barrier is another potential vulnerable site for the neurotoxic action of lead. protein kinases appear to regulate the development of brain capillaries and the expression of the blood-brain barrier properties. Stimulation of protein kinase by lead may disrupt barrier development and alter the precise regulation of the neuronal environment that is required for normal brain function. Together, these findings suggest that the sensitivity of protein kinases to lead may in part underlie the brain dysfunction observed in children poisoned by this toxicant.

  18. Organic Lead Toxicology

    Directory of Open Access Journals (Sweden)

    Jiří Patočka

    2008-01-01

    Full Text Available Lead is one of the oldest known and most widely studied occupational and environmental poison. Despite intensive study, there is still debate about the toxic effects of lead, both from low-level exposure in the general population owing to environmental pollution and historic use of lead in paint and plumbing and from exposure in the occupational setting. Significant position have organic lead compounds used more than 60 years as antiknock additives in gasoline. Chemical and toxicological characteristics of main tetraalkyl leads used as gasoline additives are discussed in this article. The majority of industries historically associated with high lead exposure have made dramatic advances in their control of occupational exposure. However, cases of unacceptably high exposure and even of frank lead poisoning are still seen, predominantly in the demolition and tank cleaning industries. Nevertheless, in most industries blood lead levels have declined below levels at which signs or symptoms are seen and the current focus of attention is on the subclinical effects of exposure. The significance of some of these effects for the overt health of the workers is often the subject of debate. Inevitably there is pressure to reduce lead exposure in the general population and in working environments, because current studies show that no level of lead exposure appears to be a ‘safe’ and even the current ‘low’ levels of exposure, especially in children, are associated with neurodevelopmental deficits.

  19. Dark matter signals in space

    Energy Technology Data Exchange (ETDEWEB)

    Salati, Pierre, E-mail: salati@lapp.in2p3.f [LAPTH, Universite de Savoie, CNRS, B.P.110, F-74941 Annecy-le-Vieux Cedex (France)

    2010-01-01

    The confirmation by the PAMELA collaboration of a positron excess above 10 GeV has triggered a lot of excitement in the field of particle astrophysics. This excess could be the first long waited hint of the presence of massive and weakly interacting species in the halo of the Milky Way. If so, the nature of the astronomical dark matter is about to be unveiled after more than seventy years of unsuccessful searches. This review summarizes the state of the art, a year of bubbling activity after the PAMELA announcement. The dark matter candidates which can potentially lead to a positron excess have quite special properties. They are severely constrained by radio and gamma observations unless they are tightly packed inside unprobable or bizarre dark matter clumps. These species could also be unstable with abnormally long lifetimes. Although the positron excess could be generated by annihilating and/or decaying dark matter particles, William of Ockham would warn us that a more natural explanation is to be found in pulsars for instance, and that entia non sunt multiplicanda praeter necessitatem.

  20. Lead-Free Piezoelectrics

    CERN Document Server

    Nahm, Sahn

    2012-01-01

    Ecological restrictions in many parts of the world are demanding the elimination of Pb from all consumer items. At this moment in the piezoelectric ceramics industry, there is no issue of more importance than the transition to lead-free materials. The goal of Lead-Free Piezoelectrics is to provide a comprehensive overview of the fundamentals and developments in the field of lead-free materials and products to leading researchers in the world. The text presents chapters on demonstrated applications of the lead-free materials, which will allow readers to conceptualize the present possibilities and will be useful for both students and professionals conducting research on ferroelectrics, piezoelectrics, smart materials, lead-free materials, and a variety of applications including sensors, actuators, ultrasonic transducers and energy harvesters.

  1. Noisy signal filtration using complex wavelet basis sets

    Science.gov (United States)

    Yaseen, A. S.; Pavlova, O. N.; Pavlov, A. N.

    2017-07-01

    Methods of noisy signal filtration using a discrete wavelet transform (DWT) with real basis sets of the Daubechies family are compared to methods employing a double-density dual-tree complex wavelet transform (DDCWT) with excess (nonorthonormalized) basis sets. Recommendations concerning the choice of filter parameters for minimization of the error of noisy signal filtration are formulated.

  2. Investigation of excess thyroid cancer incidence in Los Alamos County

    Energy Technology Data Exchange (ETDEWEB)

    Athas, W.F.

    1996-04-01

    Los Alamos County (LAC) is home to the Los Alamos National Laboratory, a U.S. Department of Energy (DOE) nuclear research and design facility. In 1991, the DOE funded the New Mexico Department of Health to conduct a review of cancer incidence rates in LAC in response to citizen concerns over what was perceived as a large excess of brain tumors and a possible relationship to radiological contaminants from the Laboratory. The study found no unusual or alarming pattern in the incidence of brain cancer, however, a fourfold excess of thyroid cancer was observed during the late-1980`s. A rapid review of the medical records for cases diagnosed between 1986 and 1990 failed to demonstrate that the thyroid cancer excess had resulted from enhanced detection. Surveillance activities subsequently undertaken to monitor the trend revealed that the excess persisted into 1993. A feasibility assessment of further studies was made, and ultimately, an investigation was conducted to document the epidemiologic characteristics of the excess in detail and to explore possible causes through a case-series records review. Findings from the investigation are the subject of this report.

  3. Excess electrons in ice: a density functional theory study.

    Science.gov (United States)

    Bhattacharya, Somesh Kr; Inam, Fakharul; Scandolo, Sandro

    2014-02-21

    We present a density functional theory study of the localization of excess electrons in the bulk and on the surface of crystalline and amorphous water ice. We analyze the initial stages of electron solvation in crystalline and amorphous ice. In the case of crystalline ice we find that excess electrons favor surface states over bulk states, even when the latter are localized at defect sites. In contrast, in amorphous ice excess electrons find it equally favorable to localize in bulk and in surface states which we attribute to the preexisting precursor states in the disordered structure. In all cases excess electrons are found to occupy the vacuum regions of the molecular network. The electron localization in the bulk of amorphous ice is assisted by its distorted hydrogen bonding network as opposed to the crystalline phase. Although qualitative, our results provide a simple interpretation of the large differences observed in the dynamics and localization of excess electrons in crystalline and amorphous ice films on metals.

  4. Twentieth century surge of excess adult male mortality

    Science.gov (United States)

    Beltrán-Sánchez, Hiram; Finch, Caleb E.; Crimmins, Eileen M.

    2015-01-01

    Using historical data from 1,763 birth cohorts from 1800 to 1935 in 13 developed countries, we show that what is now seen as normal—a large excess of female life expectancy in adulthood—is a demographic phenomenon that emerged among people born in the late 1800s. We show that excess adult male mortality is clearly rooted in specific age groups, 50–70, and that the sex asymmetry emerged in cohorts born after 1880 when male:female mortality ratios increased by as much as 50% from a baseline of about 1.1. Heart disease is the main condition associated with increased excess male mortality for those born after 1900. We further show that smoking-attributable deaths account for about 30% of excess male mortality at ages 50–70 for cohorts born in 1900–1935. However, after accounting for smoking, substantial excess male mortality at ages 50–70 remained, particularly from cardiovascular disease. The greater male vulnerability to cardiovascular conditions emerged with the reduction in infectious mortality and changes in health-related behaviors. PMID:26150507

  5. Excess healthcare costs of a large waterborne outbreak in Finland.

    Science.gov (United States)

    Huovinen, Elisa; Laine, Janne; Virtanen, Mikko J; Snellman, Marja; Hujanen, Timo; Kiiskinen, Urpo; Kujansuu, Eila; Lumio, Jukka; Ruutu, Petri; Kuusi, Markku

    2013-11-01

    The economic effects of waterborne outbreaks have rarely been reported. A large waterborne outbreak occurred in the town of Nokia in Finland in 2007 with half of the population in the contaminated area suffering from gastroenteritis. We studied the healthcare costs of this outbreak. Healthcare costs were studied using register data from the Nokia Health Care Centre, data collected in the regional university hospital, and data from laboratory register on stool samples. Total excess healthcare costs were EUR 354,496, which is approximately EUR 10 per resident of Nokia. There were 2052 excess visits because of gastroenteritis in Nokia Health Care Centre, 403 excess episodes in the university hospital, and altogether over 2000 excess stool samples due to the outbreak. Care in the Nokia Health Care Centre accounted for 44% and care in the university hospital for 42% of the excess healthcare costs while stool samples accounted for only 10%. Despite the high morbidity, the total cost was low because most patients had a relatively mild illness. The situation would have been worse if the microbes involved had been more hazardous or if the financial situation of the community had been worse. Prevention of waterborne outbreaks is important, as there is a risk of severe short- and long-term health effects and substantial health-economic costs.

  6. Assessment of lead in cosmetic products.

    Science.gov (United States)

    Al-Saleh, Iman; Al-Enazi, Sami; Shinwari, Neptune

    2009-07-01

    There have been a number of recent reports in the media and on the internet about the presence of lead in brand-names lipsticks. This has drawn our attention to assess the safety of various cheap brands of cosmetics sold at 2-riyals stores in Saudi market that are imported from countries where safety regulations are poorly enforced as well as they lack perfect conditions for manufacturing. Lead contents were determined in 26 and eight different brands of lipsticks and eye shadows using the Zeeman atomic absorption spectrophotometer coupled to graphite tube atomizer after an acid digestion procedure. Lead was detected in all the studied samples. The median (25th-75th percentile) lead content in 72 lipsticks samples was 0.73 (0.49-1.793) PPM wet wt. in the range of 0.27-3760 PPM wet wt. There were four brands of lipsticks with lead content above the FDA lead limit as impurities in color additives (20 PPM). The FDA does not set a limit for lead in lipstick. Three of them were extremely high points and considered outliers. The median (25th-75th percentile) lead contents in pressed powder eye shadow was 1.38 (0.944-1.854) PPM wet wt. (n=22) in the range of 0.42-58.7 PPM wet wt. One brand was above 20 PPM the US FDA's lead limit as impurities. The overall results indicate that lead in lipsticks and eye shadows are below the FDA lead limit as impurities and, thus, probably have no significant toxicological effects. Nevertheless, few brands had lead content above 20 PPM that might put consumers at the risk of lead poisoning. Lead is a cumulative, and applying lead-containing cosmetics several times a day or every day, can potentially add up to significant exposure levels. Pregnant and nursing mothers are vulnerable population because lead passes through placenta and human milk and affect fetus or infant's developments. Our findings call for an immediate mandatory regular testing program to check lead and other toxic metals in lipsticks and other cosmetic products imported

  7. Lead and the skin

    Energy Technology Data Exchange (ETDEWEB)

    Allen, B.R.; Moore, M.R.; Hunter, J.A.A.

    1975-01-01

    The increasing use of lead will continue to give rise to problems of toxicity. Protective measures have resulted in florid lead poisoning becoming rare. Attention has recently turned to the possibility of prolonged exposure to low doses of lead causing morbidity in the absence of the classical clinical features of poisoning. Lead is absorbed mostly through the lungs and gastrointestinal tract. Some is also absorbed through the skin but with inorganic compounds the amount is small. Shortly after the most widely used compound, tetraethyl lead, was first manufactured, cases of toxicity began to occur. Manufacture was forbidden until plant design produced greater safety. Significant absorption can occur through the skin. The hazard to those handling leaded gasoline in a normal manner is probably small, mainly because 95 percent of a dose applied to the open skin surface evaporates. Hair has been used as a biopsy material to assess lead exposure. The biological effects of lead poisoning are discussed, including the synergistic effects of lead and agents provoking porphyria.

  8. Phasor representation for the nonlinear photoacoustic signal

    Science.gov (United States)

    Santosa, I. E.; Oetama, E. J.; Harren, F. J. M.

    2017-11-01

    In CO2 laser-based photoacoustic (PA) systems, N2 takes part in the generation of the PA signal. This process causes the nonlinear relation of the photoacoustic signal to the CO2 concentration. This phenomenon can be explained simply using a phasor diagram. The model leads to the determination of the lag in the PA signal due to CO2 relaxation.

  9. Folliculin (Flcn) inactivation leads to murine cardiac hypertrophy through mTORC1 deregulation

    Science.gov (United States)

    Hasumi, Yukiko; Baba, Masaya; Hasumi, Hisashi; Huang, Ying; Lang, Martin; Reindorf, Rachel; Oh, Hyoung-bin; Sciarretta, Sebastiano; Nagashima, Kunio; Haines, Diana C.; Schneider, Michael D.; Adelstein, Robert S.; Schmidt, Laura S.; Sadoshima, Junichi; Marston Linehan, W.

    2014-01-01

    Cardiac hypertrophy, an adaptive process that responds to increased wall stress, is characterized by the enlargement of cardiomyocytes and structural remodeling. It is stimulated by various growth signals, of which the mTORC1 pathway is a well-recognized source. Here, we show that loss of Flcn, a novel AMPK–mTOR interacting molecule, causes severe cardiac hypertrophy with deregulated energy homeostasis leading to dilated cardiomyopathy in mice. We found that mTORC1 activity was upregulated in Flcn-deficient hearts, and that rapamycin treatment significantly reduced heart mass and ameliorated cardiac dysfunction. Phospho-AMP-activated protein kinase (AMPK)-alpha (T172) was reduced in Flcn-deficient hearts and nonresponsive to various stimulations including metformin and AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide). ATP levels were elevated and mitochondrial function was increased in Flcn-deficient hearts, suggesting that excess energy resulting from up-regulated mitochondrial metabolism under Flcn deficiency might attenuate AMPK activation. Expression of Ppargc1a, a central molecule for mitochondrial metabolism, was increased in Flcn-deficient hearts and indeed, inactivation of Ppargc1a in Flcn-deficient hearts significantly reduced heart mass and prolonged survival. Ppargc1a inactivation restored phospho-AMPK-alpha levels and suppressed mTORC1 activity in Flcn-deficient hearts, suggesting that up-regulated Ppargc1a confers increased mitochondrial metabolism and excess energy, leading to inactivation of AMPK and activation of mTORC1. Rapamycin treatment did not affect the heart size of Flcn/Ppargc1a doubly inactivated hearts, further supporting the idea that Ppargc1a is the critical element leading to deregulation of the AMPK–mTOR-axis and resulting in cardiac hypertrophy under Flcn deficiency. These data support an important role for Flcn in cardiac homeostasis in the murine model. PMID:24908670

  10. Disseminated blue naevus and malignant blue naevus associated with excessive aromatase syndrome.

    Science.gov (United States)

    Lobo, A Z C; Martin, R M; Belda, W; Michi, M M; Arnone, M; Festa-Neo, C; Sotto, M N; Vilela, M A C; Sanches, J A

    2008-08-01

    We report a case of a 17-year-old boy who had a giant congenital blue naevus with multiple satellite pigmented lesions. Later the patient developed melanoma arising in the pre-existing lesion. He also had gynaecomastia and was diagnosed as having aromatase excess syndrome. To our knowledge, the association of these two rare conditions has not been previously reported. Further studies should be performed to investigate this unusual combination, which may have a genetic, endocrine or local cutaneous link leading to its occurrence.

  11. Excess body weight during pregnancy and offspring obesity: potential mechanisms.

    Science.gov (United States)

    Paliy, Oleg; Piyathilake, Chandrika J; Kozyrskyj, Anita; Celep, Gulcin; Marotta, Francesco; Rastmanesh, Reza

    2014-03-01

    The rates of child and adult obesity have increased in most developed countries over the past several decades. The health consequences of obesity affect both physical and mental health, and the excess body weight can be linked to an elevated risk for developing type 2 diabetes, cardiovascular problems, and depression. Among the factors that can influence the development of obesity are higher infant weights and increased weight gain, which are associated with higher risk for excess body weight later in life. In turn, mother's excess body weight during and after pregnancy can be linked to the risk for offspring overweight and obesity through dietary habits, mode of delivery and feeding, breast milk composition, and through the influence on infant gut microbiota. This review considers current knowledge of these potential mechanisms that threaten to create an intergenerational cycle of obesity. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. The excess in the hate discourse of the haters

    Directory of Open Access Journals (Sweden)

    Rebeca Recuero Rebs

    2017-11-01

    Full Text Available The article aims to identify and comprehend the marks of the excess present in the hate discourse of the haters. By using the power of social media’s information diffusion on the internet, the haters appropriate of such spaces to disseminate ideologies related to violence, intending to generate more hate. Among the strategies utilized by this group, there is the excess. However, it is necessary to understand the subject’s social and historical contexts and the meanings of their discourse in these environments. As the corpus, we start off the analysis from the attacks towards the actress Taís Araújo occurred on Facebook. As shown by the results, the excess is perceived on authority demonstrations, on the repetition of ideals and onto the search of values such as visibility, popularity (among participants of the networks and the media, authority and reputation (inside the hater’s group of belonging.elonging.

  13. Internet Addiction and Excessive Social Networks Use: What About Facebook?

    Science.gov (United States)

    Guedes, Eduardo; Sancassiani, Federica; Carta, Mauro Giovani; Campos, Carlos; Machado, Sergio; King, Anna Lucia Spear; Nardi, Antonio Egidio

    2016-01-01

    Facebook is notably the most widely known and used social network worldwide. It has been described as a valuable tool for leisure and communication between people all over the world. However, healthy and conscience Facebook use is contrasted by excessive use and lack of control, creating an addiction with severely impacts the everyday life of many users, mainly youths. If Facebook use seems to be related to the need to belong, affiliate with others and for self-presentation, the beginning of excessive Facebook use and addiction could be associated to reward and gratification mechanisms as well as some personality traits. Studies from several countries indicate different Facebook addiction prevalence rates, mainly due to the use of a wide-range of evaluation instruments and to the lack of a clear and valid definition of this construct. Further investigations are needed to establish if excessive Facebook use can be considered as a specific online addiction disorder or an Internet addiction subtype. PMID:27418940

  14. Internet Addiction and Excessive Social Networks Use: What About Facebook?

    Science.gov (United States)

    Guedes, Eduardo; Sancassiani, Federica; Carta, Mauro Giovani; Campos, Carlos; Machado, Sergio; King, Anna Lucia Spear; Nardi, Antonio Egidio

    2016-01-01

    Facebook is notably the most widely known and used social network worldwide. It has been described as a valuable tool for leisure and communication between people all over the world. However, healthy and conscience Facebook use is contrasted by excessive use and lack of control, creating an addiction with severely impacts the everyday life of many users, mainly youths. If Facebook use seems to be related to the need to belong, affiliate with others and for self-presentation, the beginning of excessive Facebook use and addiction could be associated to reward and gratification mechanisms as well as some personality traits. Studies from several countries indicate different Facebook addiction prevalence rates, mainly due to the use of a wide-range of evaluation instruments and to the lack of a clear and valid definition of this construct. Further investigations are needed to establish if excessive Facebook use can be considered as a specific online addiction disorder or an Internet addiction subtype.

  15. Merits of excess bagasse as fuel for generating electricity. [Florida

    Energy Technology Data Exchange (ETDEWEB)

    Perea, P.

    1981-05-01

    The rising cost of fuel oil improves the economics for sugar factories of using excess bagasse to produce more electricity than they require for sale to the public utility companies. Recently, the United States Sugar Corporation, in Florida, initiated the operation of a 20 MW plant fueled with excess bagasse only, and the electricity it generates is sold to a local utility. This constitutes a saving of 10 million liters of oil per year. The operating cycle is described of a system of high-pressure boilers and automatically controlled turbogenerator for the production of energy from bagasse. This system is a pre-engineered design which is very simple to install and operate and can be fitted in with the electric-generating installations which are normally found in practically any sugar factory without making significant modifications to the factory. An economic analysis is presented of power generation using excess bagasse for a 3MW unit and a 4MW unit.

  16. Excessive computer game playing: evidence for addiction and aggression?

    Science.gov (United States)

    Grüsser, S M; Thalemann, R; Griffiths, M D

    2007-04-01

    Computer games have become an ever-increasing part of many adolescents' day-to-day lives. Coupled with this phenomenon, reports of excessive gaming (computer game playing) denominated as "computer/video game addiction" have been discussed in the popular press as well as in recent scientific research. The aim of the present study was the investigation of the addictive potential of gaming as well as the relationship between excessive gaming and aggressive attitudes and behavior. A sample comprising of 7069 gamers answered two questionnaires online. Data revealed that 11.9% of participants (840 gamers) fulfilled diagnostic criteria of addiction concerning their gaming behavior, while there is only weak evidence for the assumption that aggressive behavior is interrelated with excessive gaming in general. Results of this study contribute to the assumption that also playing games without monetary reward meets criteria of addiction. Hence, an addictive potential of gaming should be taken into consideration regarding prevention and intervention.

  17. Is nitric oxide signalling involved in the antidepressant action of ketamine?

    DEFF Research Database (Denmark)

    Liebenberg, Nico; Müller, Heidi Kaastrup; Elfving, Betina

    2012-01-01

    Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect in depre......Background and Aim: Stress-induced excessive glutamate transmission at N-methyl-D-aspartate (NMDA) receptors may underlie a major mechanism in the pathophysiology that leads to depression, while ketamine, an NMDA receptor antagonist, has been shown to induce a rapid antidepressant effect...... in depressed patients following a single intravenous administration that is sustained for ± 7 days. A number of downstream cellular mechanisms appear to mediate the antidepressant action of ketamine, and the majority of evidence point to a rapid activation of protein translation leading to increased synaptic...... receptors, while the uncoupling of the nNOS-NMDA receptor complex prevents NMDA-induced excitotoxicity. Thus, it is possible that the inhibition of nitric oxide (NO) signalling underlies a key upstream mechanism in the antidepressant action of ketamine. Methods: We used a genetic rat model of depression...

  18. Relationship among nocturnal sleep deficit, excess weight and metabolic alterations in adolescents.

    Science.gov (United States)

    Ruiz, Nelina; Rangel, Airam; Rodríguez, Carla; Rodríguez, Lisette; Rodríguez, Valeria

    2014-12-01

    Sleep modulates neuroendocrine function and metabolism; therefore, changes in sleep duration may lead to developing obesity during adolescence. To assess the possible association among nocturnal sleep duration, the presence of overweight and metabolic alterations in a group of adolescents. Cross-sectional, analytical study conducted at a school in Valencia, Venezuela, during the 2012-2013 school year. Participants were 12 to 17 year-old adolescents. A survey on nocturnal sleep duration was administered; weight, height and waist circumference were recorded; and glycemia, lipid profile and insulinemia levels were measured. Body mass index and the homeostasis model assessment of insulin resistance (HOMA-IR) index were calculated. Ninety adolescents were included. Compared to the group with normal weight, adolescents with excessive weight had, in average, fewer sleep hours Sundays through Thursdays (p sleep deficit and sleep debt (p sleep debt (p sleep debt, the risk of having excess weight was 2.70 times higher (95% CI= 1.09-6.72; p= 0.032) regardless of age, gender, sexual maturity, sleep deficit Sundays through Thursdays, and history of cardiovascular disease and diabetes in first-degree relatives. Nocturnal sleep deficit and sleep debt were significantly associated with excess weight and metabolic alterations related to a high cardiometabolic risk.

  19. The price of protein: combining evolutionary and economic analysis to understand excessive energy consumption.

    Science.gov (United States)

    Brooks, R C; Simpson, S J; Raubenheimer, D

    2010-12-01

    Excessive weight gain appears, thermodynamically at least, straightforward: growing energy intake and/or falling energy expenditure create an energetic surplus, resulting in fat accumulation. The situation is, however, far more complex, with genetic, physiological, social, psychological and economic factors all implicated. Thus the causes of excessive weight gain remain difficult to disentangle. We combine two recent developments from different areas of nutrition research: the study of food prices in relation to energy content and the hypothesis that an evolved propensity to regulate protein intake more strongly than non-protein calories exerts powerful leverage on overall energy intake. We partition the energy content of a range of common supermarket foods, and show that increasing overall energy content only modestly raises the cost of foods, largely as a result of macronutrients having very different costs. Higher food prices are associated with higher protein content and lower carbohydrate content, whereas fat content was not significantly associated with food price. We show that the differential costs of energy from protein and carbohydrates may bias consumers towards diets high in carbohydrate energy, leading them to consume excessive energy to meet their dietary protein needs. We review evidence from physiology, evolution and economics that support our suggestion. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity.

  20. On the Issue of Excess Lower Stratospheric Subtropical Transport in GEOS-DAS

    Science.gov (United States)

    Tan, Wei-Wu; Geller, Marvin; Pawson, Steven

    2002-01-01

    In recent years, data assimilation has become an indispensable tool for our understanding of the global features of meteorological variables. However, assessments of transport characteristics using trajectory related methods as well as chemical transport models (CTMs) show that results derived from assimilated (or analyzed) winds exhibit significantly larger mixing and entrainment rates compared to results derived from GCM winds, which are closer to results derived from observations (e.g., Douglass et al., 2002; Schoeberl et al., 2002). This discrepancy presents a serious challenge to our ability to understand and model global trace gas transport and distribution. We use the GEOS-DAS to explore this issue by examining how the process of data assimilation alters the dynamics of the underlying GCM and how this leads to the excess of lower stratospheric mixing and transport in the subtropics. In particular, we show that significant model biases in tropical winds necessitate large analysis increments. These increments directly force large subtropical regions of instability with negative PV gradient on the one hand, and generate excessive noise in the tropical wind fields on the other. The result is an excess of transport in the lower stratospheric subtropics.

  1. Overfat Adults and Children in Developed Countries: The Public Health Importance of Identifying Excess Body Fat

    Directory of Open Access Journals (Sweden)

    Philip B. Maffetone

    2017-07-01

    Full Text Available The global overfat pandemic is a serious public health crisis that places a substantial burden on economic resources in developed countries. The term overfat refers to the presence of excess body fat that can impair health, even for normal weight non-obese individuals. Excess body fat is associated with cardiometabolic dysfunction, a clinical situation that can progressively worsen, potentially leading to various common disease risk factors, chronic diseases, increased morbidity and mortality, and reduced quality of life. The prevalence of overfat populations in 30 of the world’s most developed countries is substantially higher than recent global estimations, with the largest growth due to a relatively recent increased number of people with excess abdominal fat. Abdominal overfat is the most unhealthful form of this condition, so it is concerning that average waist circumference measures, generally indicative of abdominal overfat, have increased. Despite a leveling off appearance of being overweight and/or obese in some developed countries, the overfat pandemic continues to grow.

  2. Information Acquisition and Excessive Risk: Impact of Policy Rate and Market Volatility

    Directory of Open Access Journals (Sweden)

    Volha Audzei

    2015-12-01

    Full Text Available Excessive risk-taking of financial agents drew a lot of attention in the aftermath of the financial crisis. Low interest rates and subdued market volatility during the Great Moderation are sometimes blamed for stimulating risk-taking and leading to the recent financial crisis. In recent years, with many central banks around the world conducting the policy of low interest rates and mitigating market risks, it has been debatable whether this policy contributes to the building up of another credit boom. This paper addresses this issue by focusing on information acquisition by the financial agents. We build a theoretical model which captures excessive risk taking in response to changes in policy rate and market volatility. This excessive risk takes the form of an increased risk appetite of the agents, but also of decreased incentives to acquire information about risky assets. As a result, with market risk being reduced, agents tend to acquire more risk in their portfolios then they would with the higher market risk. The same forces increase portfolio risk when the safe interest rate is falling. The robustness of the results is considered with different learning rules.

  3. Excess Li-Ion Storage on Reconstructed Surfaces of Nanocrystals To Boost Battery Performance

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Yandong [School; Zhang, Bingkai [School; Zheng, Jiaxin [School; Hu, Jiangtao [School; Wen, Jianguo; Miller, Dean J.; Yan, Pengfei [Environmental; Liu, Tongchao [School; Guo, Hua [School; Li, Wen [School; Song, Xiaohe [School; Zhuo, Zengqing [School; Liu, Chaokun [School; Tang, Hanting [School; Tan, Rui [School; Chen, Zonghai; Ren, Yang; Lin, Yuan [School; Yang, Wanli; Wang, Chong-Min [Environmental; Wang, Lin-Wang; Lu, Jun; Amine, Khalil; Pan, Feng [School

    2017-08-03

    Abstract. Due to the enhanced kinetic properties, nanocrystallites have received much attention as potential electrode materials for energy storage. However, because of the large specific surface areas of nanocrystallites, they usually suffer from decreased energy density, reduced cycling stability and total electrode capacity. In this work, we report a size-dependent excess capacity beyond the theoretical value of 170 mAhg-1 in a special carbon coated LiFePO4 composite cathode material, which delivers capacities of 191.2 and 213.5 mAhg-1 with the mean particle sizes of 83 nm and 42 nm, respectively. Moreover, this LiFePO4 composite also shows excellent cycling stability and high rate performance. Our further experimental tests and ab initio calculations reveal that the excess capacity comes from the charge passivation for which the C-O-Fe bonds would lead to charge redistribution on the surface of LiFePO4 and hence to enhance the bonding interaction between surface O atoms and Li-ions. The surface reconstruction for excess Li-ion storage makes full use of the large specific surface area for the nanocrystallites, which can maintain the fast Li-ion transport and enhance the capacity greatly that the nanocrystallites usually suffers.

  4. Limitations in determining enantiomeric excess of alcohols by {sup 31} P-NMR of the phosphonate derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Laverde Junior, Antonio; Conceicao, Jelson J.A. da; Pilli, Ronaldo A.; Marsaioli, Anita J. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica. E-mail: anita@unicamp.br; Miranda, Domingos S. de [Uberlandia Univ., MG (Brazil). Dept. de Quimica; Schirmer, Heiko; Meijere, Armin de [Georg-August Universitaet, Goettingen (Germany). Inst. fuer Organische Chemie

    1999-07-01

    The use of diastereomeric alcohol dialkyl-phosphonate derivatives to determine the enantiomeric excesses via {sup 31}P-NMR signal ratios of anisochronous meso and threo isomers was successfully applied to secondary alcohols (Feringa's method). Expansion of the methodology to primary alcohols processing the hydroxyl groups tethered to the stereogenic centers by two or more methylene groups proved the method to be inefficient. The comparison between the coupled and decoupled spectra is important in order to identify the signals corresponding to the dialkyl-phosphonates. Nevertheless the methodology should be applied whenever the amount of the alcohol and its structure are not the limiting factors. (author)

  5. Selenite-induced hormonal and signalling mechanisms during root growth of Arabidopsis thaliana L.

    Science.gov (United States)

    Lehotai, Nóra; Kolbert, Zsuzsanna; Peto, Andrea; Feigl, Gábor; Ördög, Attila; Kumar, Devanand; Tari, Irma; Erdei, László

    2012-09-01

    Selenium excess can cause toxicity symptoms, e.g. root growth inhibition in non-hyperaccumulator plants such as Arabidopsis. Selenite-induced hormonal and signalling mechanisms in the course of development are poorly understood; therefore this study set out to investigate the possible hormonal and signalling processes using transgenic and mutant Arabidopsis plants. Significant alterations were observed in the root architecture of the selenite-treated plants, due to the loss of cell viability in the root apex. During mild selenite excess, the plants showed symptoms of the morphogenic response: primary root (PR) shortening and increased initiation of laterals, ensuring better nutrient and water uptake and stress acclimation. As well as lower meristem cell activity, the second reason for the Se-induced growth hindrance is the hormonal imbalance, since the in situ expression of the auxin-responsive DR5::GUS, and consequently the auxin levels, significantly decreased, while that of the cytokinin-inducible ARR5::GUS and the ethylene biosynthetic ACS8::GUS increased. It is assumed that auxin and ethylene might positively regulate selenium tolerance, since reduced levels of them resulted in sensitivity. Moreover, high cytokinin levels caused notable selenite tolerance. During early seedling development, nitric oxide (NO) contents decreased but hydrogen peroxide levels increased reflecting the antagonism between the two signal molecules during Se excess. High levels of NO in gsnor1-3, lead to selenite tolerance, while low NO production in nia1nia2 resulted in selenite sensitivity. Consequently, NO derived from the root nitrate reductase activity is responsible for the large-scale selenite tolerance in Arabidopsis.

  6. Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium.

    Science.gov (United States)

    Blackburn, J; Kawasaki, K; Porntaveetus, T; Kawasaki, M; Otsuka-Tanaka, Y; Miake, Y; Ota, M S; Watanabe, M; Hishinuma, M; Nomoto, T; Oommen, S; Ghafoor, S; Harada, F; Nozawa-Inoue, K; Maeda, T; Peterková, R; Lesot, H; Inoue, J; Akiyama, T; Schmidt-Ullrich, R; Liu, B; Hu, Y; Page, A; Ramírez, Á; Sharpe, P T; Ohazama, A

    2015-01-01

    Nuclear factor kappa B (NF-κB) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. Down-regulation of NF-κB signaling during development results in hypohidrotic ectodermal dysplasia. The roles of NF-κB signaling in tooth development, however, are not fully understood. We examined mice overexpressing IKKβ, an essential component of the NF-κB pathway, under keratin 5 promoter (K5-Ikkβ). K5-Ikkβ mice showed supernumerary incisors whose formation was accompanied by up-regulation of canonical Wnt signaling. Apoptosis that is normally observed in wild-type incisor epithelium was reduced in K5-Ikkβ mice. The supernumerary incisors in K5-Ikkβ mice were found to phenocopy extra incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions. © International & American Associations for Dental Research 2014.

  7. determination of lead at nanogram level in water samples

    African Journals Online (AJOL)

    Preferred Customer

    ABSTRACT. A novel method of chemistry applicable to the determination of trace lead in water samples based on the resonance light scattering (RLS) technique has been developed. In dilute phosphoric acid medium, in the presence of a large excess of I-, Pb(II) can form [PbI4]2-, which further reacts with tetrabutyl ...

  8. Determination of lead at nanogram level in water samples by ...

    African Journals Online (AJOL)

    A novel method of chemistry applicable to the determination of trace lead in water samples based on the resonance light scattering (RLS) technique has been developed. In dilute phosphoric acid medium, in the presence of a large excess of I-, Pb(II) can form [PbI4]2-, which further reacts with tetrabutyl ammonium bromide ...

  9. The Identification and Synthesis of Lead Apatite Minerals Formed in Lead Water Pipes

    Directory of Open Access Journals (Sweden)

    Jeremy D. Hopwood

    2016-01-01

    Full Text Available Phosphate is added to drinking water in the UK to minimise the release of lead from lead water pipes. The phosphate encourages the formation of insoluble lead apatites on the walls of the pipe. Hydroxylpyromorphite Pb5(PO43OH is the lead apatite that is most often used to model lead levels in tap water; however, its presence has not been confirmed. Our aims were to identify the lead pipe apatite and synthesise it. The synthetic mineral would then be used in future solubility studies to produce better predictions of lead levels in tap water. XRD and FTIR were used to characterise the minerals on a range of lead pipes. Pyromorphite and hydroxylpyromorphite were absent and instead a range of mixed calcium lead apatites were present. For every five lead ions in the general formula Pb5(PO43X between one and two ions were replaced with calcium and there was evidence of substitution of PO43- by either CO32- or HPO42-. Calcium lead apatites with similar unit cell dimensions to those found on lead water pipes were then synthesised. The calcium : lead ratio in these reaction mixtures was in excess of 500 : 1 and the resulting crystals were shown by TEM to be nanosized rods and flakes. The synthetic apatites that most closely resembled the unit cell dimensions of the apatites on lead water pipes were shown to be Pb3.4Ca1.3(PO43Cl0.03OH0.97, Pb3.6Ca1.2(PO43Cl0.07OH0.93, and Pb3.6Ca1.2(PO43Cl0.27OH0.73.

  10. EFFECT OF LEAD ACETATE

    African Journals Online (AJOL)

    MICROSOFT

    The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

  11. Leading Acquisition Reform

    Science.gov (United States)

    2011-03-22

    Army and Undersecretary of Defense for Acquisition, for a reduction of the Excalibur and Accelerated Precision Mortar initiative rounds.25...Can’t Dance? Leading a Great Enterprise Through Dramatic Change, (New York: HarperCollins Publishers, 2003), 235. 13 John P. Kotter , Leading Change

  12. Developmental immunotoxicology of lead.

    Science.gov (United States)

    Dietert, Rodney R; Lee, Ji-Eun; Hussain, Irshad; Piepenbrink, Michael

    2004-07-15

    The heavy metal, lead, is a known developmental immunotoxicant that has been shown to produce immune alterations in humans as well as other species. Unlike many compounds that exert adverse immune effects, lead exposure at low to moderate levels does not produce widespread loss of immune cells. In contrast, changes resulting from lead exposure are subtle at the immune cell population level but, nevertheless, can be functionally dramatic. A hallmark of lead-induced immunotoxicity is a pronounced shift in the balance in T helper cell function toward T helper 2 responses at the expense of T helper 1 functions. This bias alters the nature and range of immune responses that can be produced thereby influencing host susceptibility to various diseases. Immunotoxic responses to lead appear to differ across life stages not only quantitatively with regard to dose response, but also qualitatively in terms of the spectrum of immune alterations. Experimental studies in several lab animal species suggest the latter stages of gestation are a period of considerable sensitivity for lead-induced immunotoxicity. This review describes the basic characteristics of lead-induced immunotoxicity emphasizing experimental animal results. It also provides a framework for the consideration of toxicant exposure effects across life stages. The existence of and probable basis for developmental windows of immune hyper-susceptibility are presented. Finally, the potential for lead to serve as a perinatal risk factor for childhood asthma as well as other diseases is considered.

  13. Lead - nutritional considerations

    Science.gov (United States)

    ... lead soldered cans goes into effect. If imported wine containers have a lead foil wrapper, wipe the rim and neck of the bottle with a towel moistened with lemon juice, vinegar, or wine before using. DO NOT store wine, spirits, or ...

  14. Laser absorption spectroscopy using lead salt and quantum cascade tunable lasers

    Science.gov (United States)

    Namjou-Khales, Khosrow

    A new class of analytic instruments based on the detection of chemical species through their spectroscopic absorption 'fingerprint' is emerging based on the use of tunable semiconductor lasers as the excitation source. Advantages of this approach include compact device size, in-line measurement capability, and large signal-bandwidth product. To realize these advantages will require the marriage of laser devices with broad tunability in the infrared spectral range with sophisticated signal processing techniques. Currently, commercial devices based on short wavelength telecommunications type lasers exist but there is potential for much more versatile instruments based on longer wavelength operation. This thesis is divided into two parts. In the first part I present a theoretical analysis and experimental characterization of frequency and wavelength modulation spectroscopy using long wavelength infrared tunable lasers. The experimental measurements were carried out using commercially available lead salt lasers and excellent agreement is found between theoretically predicted performance and experimental verification. The lead salt laser has several important drawbacks as a source in practical instrumentation. In the second part of the thesis I report on the use of the quantum cascade (QC) laser for use in sensitive absorption spectroscopy. The QC laser is a new type of tunable device developed at Bell Laboratories. It features broad infrared tunability, single mode distributed feedback operation, and near room temperature lasing. Using the modulation techniques developed originally for the lead salt lasers, the QC laser was used to detect Nsb2O and other small molecules with absorption features near 8 mum wavelength. The noise equivalent absorption for our measurements was 5× 10sp{-5}/sqrt{Hz} which corresponds to a detection limit of ˜0.25 ppm-m/sqrt{Hz} for Nsb2O. The QC laser sensitivity was found to be limited by excess amplitude modulation in the detection

  15. Minimal Coleman-Weinberg theory explains the diphoton excess

    DEFF Research Database (Denmark)

    Antipin, Oleg; Mojaza, Matin; Sannino, Francesco

    2016-01-01

    the introduction of an extra singlet scalar further coupled to new fermions. In this constrained setup the Higgs mass was close to the observed value and the new scalar mass was below a TeV scale. Here we first extend the previous analysis by taking into account the important difference between running mass...... and pole mass of the scalar states. We then investigate whether these theories can account for the 750 GeV excess in diphotons observed by the LHC collaborations. New QCD-colored fermions in the TeV mass range coupled to the new scalar state are needed to describe the excess. We further show, by explicit...

  16. Excess mortality in persons with severe mental disorders

    DEFF Research Database (Denmark)

    Liu, Nancy H; Daumit, Gail L; Dua, Tarun

    2017-01-01

    Excess mortality in persons with severe mental disorders (SMD) is a major public health challenge that warrants action. The number and scope of truly tested interventions in this area remain limited, and strategies for implementation and scaling up of programmes with a strong evidence base...... by that model, we describe a comprehensive framework that may be useful for designing, implementing and evaluating interventions and programmes to reduce excess mortality in persons with SMD. This framework includes individual-focused, health system-focused, and community level and policy-focused interventions...

  17. Real exchange rate persistence and the excess return puzzle

    DEFF Research Database (Denmark)

    Juselius, Katarina; Assenmacher, Katrin

    2017-01-01

    The PPP puzzle refers to the wide swings of nominal exchange rates around their long-run equilibrium values whereas the excess return puzzle represents the persistent deviation of the domestic-foreign interest rate differential from the expected change in the nominal exchange rate. Using the I(2)...... knowledge based expectations rather than so-called "rational expectations".......The PPP puzzle refers to the wide swings of nominal exchange rates around their long-run equilibrium values whereas the excess return puzzle represents the persistent deviation of the domestic-foreign interest rate differential from the expected change in the nominal exchange rate. Using the I(2...

  18. Simplified Production of Organic Compounds Containing High Enantiomer Excesses

    Science.gov (United States)

    Cooper, George W. (Inventor)

    2015-01-01

    The present invention is directed to a method for making an enantiomeric organic compound having a high amount of enantiomer excesses including the steps of a) providing an aqueous solution including an initial reactant and a catalyst; and b) subjecting said aqueous solution simultaneously to a magnetic field and photolysis radiation such that said photolysis radiation produces light rays that run substantially parallel or anti-parallel to the magnetic field passing through said aqueous solution, wherein said catalyst reacts with said initial reactant to form the enantiomeric organic compound having a high amount of enantiomer excesses.

  19. Management of excessive gingival display: Lip repositioning technique

    Directory of Open Access Journals (Sweden)

    Upasana Sthapak

    2015-01-01

    Full Text Available The lips form the frame of a smile and define the esthetic zone. Excessive gingival display during smile is often referred to as "gummy smile". A successful management of excessive gingival display with lip repositioning procedure has shown excellent results. The procedure involves removing a strip of partial thickness mucosa from maxillary vestibule, then suturing it back to the lip mucosa at the level of mucogingival junction. This technique results in restricted muscle pull and a narrow vestibule, thereby reducing the gingival display. In this case gummy smile was treated by modification of Rubinstein and Kostianovsky′s surgical lip repositioning technique which resulted in a harmonious smile.

  20. Excess europium content in Precambrian sedimentary rocks and continental evolution

    Science.gov (United States)

    Jakes, P.; Taylor, S. R.

    1974-01-01

    It is proposed that the europium excess in Precambrian sedimentary rocks, relative to those of younger age, is derived from volcanic rocks of ancient island arcs, which were the source materials for the sediments. Precambrian sedimentary rocks and present-day volcanic rocks of island arcs have similar REE patterns, total REE abundances, and excess Eu, relative to the North American shale composite. The present upper crustal REE pattern, as exemplified by that of sediments, is depleted in Eu, relative to chondrites. This depletion is considered to be a consequence of development of a granodioritic upper crust by partial melting in the lower crust, which selectively retains europium.

  1. A new approach for improving reliability of personal navigation devices under harsh GNSS signal conditions.

    Science.gov (United States)

    Dhital, Anup; Bancroft, Jared B; Lachapelle, Gérard

    2013-11-07

    In natural and urban canyon environments, Global Navigation Satellite System (GNSS) signals suffer from various challenges such as signal multipath, limited or lack of signal availability and poor geometry. Inertial sensors are often employed to improve the solution continuity under poor GNSS signal quality and availability conditions. Various fault detection schemes have been proposed in the literature to detect and remove biased GNSS measurements to obtain a more reliable navigation solution. However, many of these methods are found to be sub-optimal and often lead to unavailability of reliability measures, mostly because of the improper characterization of the measurement errors. A robust filtering architecture is thus proposed which assumes a heavy-tailed distribution for the measurement errors. Moreover, the proposed filter is capable of adapting to the changing GNSS signal conditions such as when moving from open sky conditions to deep canyons. Results obtained by processing data collected in various GNSS challenged environments show that the proposed scheme provides a robust navigation solution without having to excessively reject usable measurements. The tests reported herein show improvements of nearly 15% and 80% for position accuracy and reliability, respectively, when applying the above approach.

  2. Inflammatory milieu cultivated Sema3A signaling promotes chondrocyte apoptosis in knee osteoarthritis.

    Science.gov (United States)

    Sun, Jie; Wei, Xuelei; Wang, Zengliang; Liu, Yunjiao; Lu, Jie; Lu, Yandong; Cui, Meng; Zhang, Xi; Li, Fangguo

    2018-03-01

    Osteoarthritis (OA) is the leading degenerative joint disease and featured by articular cartilage destruction, where chondrocyte apoptosis plays a critical role. Semaphorin-3A (Sema3A) has been implicated in OA chondrocyte physiology. In this study we aimed to uncover how Sema3A signaling is regulated in chondrocytes and investigate its role in OA chondrocyte survival. Here, we report that Sema3A and its receptor neuropilin-1 (Nrp1) are synchronously upregulated in cartilage chondrocytes of knee OA patients. Their expressions in chondrocytes could be induced by the stimulation of proinflammatory cytokines IL-1β and TNF-α and subsequent transcriptional activation orchestrated by C/EBPβ. The resulting excessive Sema3A signaling promotes chondrocyte apoptosis through impairing PI3K/Akt prosurvival signaling. These findings indicate a regulatory mechanism and a proapoptotic function of aberrant Sema3A signaling in OA chondrocytes, and suggest that targeting Sema3A signaling might interfere OA pathogenesis. © 2017 Wiley Periodicals, Inc.

  3. Lead toxicity: Current concerns

    Energy Technology Data Exchange (ETDEWEB)

    Goyer, R.A. (Univ. of Western Ontario, London (Canada))

    1993-04-01

    Over the 20-year period since the first issue of Environmental Health Perspectives was published, there has been considerable progress in the understanding of the potential toxicity of exposure to lead. Many of these advances have been reviewed in published symposia, conferences, and review papers in EHP. This brief review identifies major advances as well as a number of current concerns that present opportunities for prevention and intervention strategies. The major scientific advance has been the demonstration that blood lead (PbB) levels of 10-15 micrograms/dL in newborn and very young infants result in cognitive and behavioral deficits. Further support for this observation is being obtained by prospective or longitudinal studies presently in progress. The mechanism(s) for the central nervous system effects of lead is unclear but involve lead interactions within calcium-mediated intracellular messenger systems and neurotransmission. Effects of low-level lead exposure on blood pressure, particularly in adult men, may be related to the effect of lead on calcium-mediated control of vascular smooth muscle contraction and on the renin-angiotensin system. Reproductive effects of lead have long been suspected, but low-level effects have not been well studied. Whether lead is a carcinogen or its association with renal adenocarcinoma is a consequence of cystic nephropathy is uncertain. Major risk factors for lead toxicity in children in the United States include nutrition, particularly deficiencies of essential metals, calcium, iron, and zinc, and housing and socioeconomic status. A goal for the year 2000 is to reduce prevalence of blood lead levels exceeding 15 micrograms/dL. 97 refs.

  4. Prevalence and correlates of excessive Internet use among youth in Singapore.

    Science.gov (United States)

    Mythily, Subramaniam; Qiu, Shijia; Winslow, Munidasa

    2008-01-01

    There has been an explosive growth of Internet usage worldwide and this is expected to continue with its use becoming an integral part of everyday life. The Internet provides tremendous educational benefits; however, excessive Internet use can lead to negative outcomes such as poor school performance and social isolation. The survey consisted of a 69-item, anonymous, self-administered paper-and-pencil questionnaire. Data collected included demographic data, academic performance, social support and general wellbeing as well as questions pertaining to Internet use. For the purposes of our study, we defined Internet use of more than 5 hours a day as "excessive use". Of the 2735 adolescents who took part in the study, 1349 (49.3%) were male and 1383 (50.6%) were female. The mean age of the adolescents was 13.9 years [standard deviation (SD), 1.0]. A quarter of the adolescents surveyed (25%) reported that they did not access the Internet everyday, while 17.1% of adolescents reported using it for more than 5 hours every day. Excessive Internet use was associated with (i) no rules of Internet use at home (x2 = 313.1, P Internet use (17.1%) reported in our study is not equivalent to Internet addiction as no diagnostic instruments were used. However, school counsellors and teachers need to be made aware of the prevalence of and problematic behaviours associated with excessive Internet use. Training and resources should also be made available to parents and caregivers so that they can play a greater role in setting boundaries and detecting early warning signs.

  5. The web of risk factors for excessive gestational weight gain in low income women.

    Science.gov (United States)

    Paul, Keriann H; Graham, Meredith L; Olson, Christine M

    2013-02-01

    The objective of this study is to gain an in-depth understanding of issues related to gestational weight gain (GWG) including general health, diet, and physical activity among high and low income women and to elucidate socio-ecological and psychosocial risk factors that increase risk for excessive GWG. We conducted 9 focus groups with high (n = 4 groups) and low (n = 5 groups) income pregnant women aged 18-35 years to discuss health, GWG, diet and physical activity following a discussion guide. The constant comparative method was used to code focus group notes and to identify emergent themes. Themes were categorized within the integrative model of behavioral prediction. Low income women, in contrast to high income women, had higher BMIs, had more children, and were African American. Diet and physical activity behaviors reported by low income women were more likely to promote positive energy balance than were those of high income women. The underlying behavioral, efficacy, and normative beliefs described by both groups of women explained most of these behaviors. Experiencing multiple risk factors may lead to (1) engaging in several behavior changes during pregnancy unrelated to weight and (2) holding more weight gain-promoting beliefs than weight maintaining beliefs. These factors could inhibit diet and physical activity behaviors and/or behavior changes that promote energy balance and in combination, result in excessive GWG. Low income women experience multiple risk factors for excessive GWG and successful interventions to prevent excessive GWG and pregnancy related weight gain will need to recognize the complex web of influences.

  6. Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction.

    Science.gov (United States)

    Lee, Hyo Jung; Choi, Joo Sun; Lee, Hye Ja; Kim, Won-Ho; Park, Sang Ick; Song, Jihyun

    2015-12-01

    Excessive tissue iron levels are a risk factor for insulin resistance and type 2 diabetes, which are associated with alterations in iron metabolism. However, the mechanisms underlying this association are not well understood. This study used human liver SK-HEP-1 cells to examine how excess iron induces mitochondrial dysfunction and how hepcidin controls gluconeogenesis. Excess levels of reactive oxygen species (ROS) and accumulated iron due to iron overload induced mitochondrial dysfunction, leading to a decrease in cellular adenosine triphosphate content and cytochrome c oxidase III expression, with an associated increase in gluconeogenesis. Disturbances in mitochondrial function caused excess iron deposition and unbalanced expression of iron metabolism-related proteins such as hepcidin, ferritin H and ferroportin during the activation of p38 mitogen-activated protein kinase (MAPK) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are responsible for increased phosphoenolpyruvate carboxykinase expression. Desferoxamine and n-acetylcysteine ameliorated these deteriorations by inhibiting p38 MAPK and C/EBPα activity through iron chelation and ROS scavenging activity. Based on experiments using hepcidin shRNA and hepcidin overexpression, the activation of hepcidin affects ROS generation and iron deposition, which disturbs mitochondrial function and causes an imbalance in iron metabolism and increased gluconeogenesis. Repression of hepcidin activity can reverse these changes. Our results demonstrate that iron overload is associated with mitochondrial dysfunction and that together they can cause abnormal hepatic gluconeogenesis. Hepcidin expression may modulate this disorder by regulating ROS generation and iron deposition. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Gene amplification as a cause of inherited thyroxine-binding globulin excess in two Japanese families

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Yuichi; Miura, Yoshitaka; Saito, Hidehiko [Toyota Memorial Hospital (Japan)] [and others

    1995-12-01

    T{sub 4}-binding globulin (TBG) is the major thyroid hormone transport protein in man. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency, and excess. Sequencing analysis of the TBG gene, located on Xq21-22, has uncovered the molecular defects causing partial and complete deficiency. However, the mechanism leading to inherited TBG excess remains unknown. In this study, two Japanese families, F-A and F-T, with inherited TBG excess were analyzed. Serum TBG levels in hemizygous males were 58 and 44 {mu}g/mL, 3- and 2-fold the normal value, respectively. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The sequence of the coding region and the promoter activity of the TBG gene were also indistinguishable between hemizygotes and normal subjects. The gene dosage of TBG relative to that of {beta}-globin, which is located on chromosome 11, and Duchenne muscular dystropy, which is located on Xp, was evaluated by coamplification of these target genes using polymerase chain reaction and subsequent quantitation by HPLC. The TBG/{beta}-globin ratios of the affected male and female of F-A were 3.13 and 4.13 times, respectively, that in the normal males. The TBG/Duchenne muscular dystrophy ratios were 2.92 and 2.09 times the normal value, respectively. These results are compatible with three copies of TBG gene on the affected X-chromosome. Similarly, a 2-fold increase in gene dosage was demonstrated in the affected hemizygote of F-T. A 3-fold tandem amplification of the TBG gene was shown by in situ hybridization of prometaphase and interphase chromosomes from the affected male with a biotinylated genomic TBG probe, confirming the gene dosage results. Gene amplification of TBG is the cause of inherited TBG excess in these two families. 35 refs., 3 figs., 2 tabs.

  8. Lead hepatotoxicity: Selected aspects of pathobiochemistry

    Directory of Open Access Journals (Sweden)

    Mateusz Labudda

    2013-08-01

    Full Text Available Lead (Pb that belongs to heavy metals is one of the major pollution components of the environment. Occupational and environmental exposure to lead can cause its absorption by the body and consequently exert toxic effects in the liver. In this paper biochemical determinants of hepatotoxicity caused by lead are presented. Generation of reactive oxygen species, disturbances in the cellular antioxidant system, lipid peroxidation, inhibition of enzymatic proteins and intercellular signaling are also discussed. Med Pr 2013;64(4:565–568

  9. 78 FR 73817 - Information Collection; Federal Excess Personal Property (FEPP) and Firefighter Property (FFP...

    Science.gov (United States)

    2013-12-09

    ... Forest Service Information Collection; Federal Excess Personal Property (FEPP) and Firefighter Property... currently approved information collection, Federal Excess Personal Property (FEPP) and Firefighter Property... Friday. SUPPLEMENTARY INFORMATION: Title: Federal Excess Personal Property (FEPP) and Firefighter...

  10. Extragalactic Gamma Ray Excess from Coma Supercluster Direction ...

    Indian Academy of Sciences (India)

    and the experimental data from Compton Gamma Ray Observatory (CGRO) the pre- liminary results of which are given by Osborne et al. (1994), the diffuse γ ray excess from Coma supercluster direction is calculated. 2. Methods. In this research, the model presented by Osborne et al. (1994) was used. They have used the ...

  11. Defense Innovation Unit Experimental (DIUX): Innovative or Excessive

    Science.gov (United States)

    2017-04-06

    AIR WAR COLLEGE AIR UNIVERSITY DEFENSE INNOVATION UNIT EXPERIMENTAL (DIUX): INNOVATIVE OR EXCESSIVE? by Roger Kuykendall, COL...technological superiority to near-peer competitors, Secretary of Defense Ashton Carter announced the establishment of the Defense Innovation Unit...or simply another layer of bureaucracy compensating for shortcomings in other areas. When viewed through the lens of innovation , DIUx is

  12. Densities and Excess Molar Volume for the Ternary Systems (1 ...

    African Journals Online (AJOL)

    methylimidazolium methyl sulphate ([BMIM]+[MeSO4]-) were determined. The ternary systems studied were ([BMIM]+[MeSO4]-+ nitromethane + methanol or ethanol or 1-propanol) at the temperatures (303.15 and 313.15) K. The ternary excess molar ...

  13. Excess Molar Volumes and Partial Molar Volumes of Binary Systems ...

    African Journals Online (AJOL)

    Excess molar volumes have been evaluated from density measurements over the entire composition range for binary systems of an ionic liquid (IL) and an alcohol at T = (298.15, 303.15 and 313.15) K. The IL is 1-butyl-3-methylimidazolium methylsulphate [BMIM]+[MeSO4]– and the alcohols are methanol, ethanol or ...

  14. On the excess attenuation of sound in the atmosphere

    Science.gov (United States)

    Deloach, R.

    1975-01-01

    The attenuation suffered by an acoustic plane wave propagating from an elevated source to the ground, in excess of absorption losses, was studied. Reported discrepancies between attenuation measurements made in the field and theories which only account for absorption losses are discussed. It was concluded that the scattering of sound by turbulence results in a nonnegligible contribution to the total attenuation.

  15. Financial Instability - a Result of Excess Liquidity or Credit Cycles?

    DEFF Research Database (Denmark)

    Heebøll-Christensen, Christian

    , a prolonged credit cycle starting in the mid-1990s - and possibly initiated subprime mortgage innovations - appears to have created a long-run housing bubble. Further fuelled by expansionary monetary policy and excess liquidity, the bubble accelerated in period following the dot-com crash, until it finally...

  16. Excess mortality following hip fracture: a systematic epidemiological review

    DEFF Research Database (Denmark)

    Abrahamsen, B; van Staa, T; Ariely, R

    2009-01-01

    the need for interventions to reduce this risk.Patients experiencing hip fracture after low-impact trauma are at considerable risk for subsequent osteoporotic fractures and premature death. We conducted a systematic review of the literature to identify all studies that reported unadjusted and excess...

  17. Decaying Dark Atom Constituents and Cosmic Positron Excess

    Directory of Open Access Journals (Sweden)

    K. Belotsky

    2014-01-01

    μ+μ+ and τ+τ+ produces the observed positron excess. These decays can naturally take place via GUT interactions. If it exists, such a metastable particle can be found in the next run of LHC. The model predicts also the ratio of leptons over baryons in the universe to be close to -3.

  18. High‑risk of obstructive sleep apnea and excessive daytime ...

    African Journals Online (AJOL)

    Background: The burden of obstructive sleep apnea among commercial drivers in Nigeria is not known. Aim: To assess the prevalence of high risk of obstructive sleep apnea (OSA) and excessive daytime sleepiness (EDS) among intra‑city commercial drivers. Setting and Design: A descriptive cross‑sectional study in three ...

  19. Additive effects of dietary glycotoxins and androgen excess on the ...

    African Journals Online (AJOL)

    Sotiria Palimeri

    2015-08-08

    Aug 8, 2015 ... PCOS. Abstract Background: Dietary glycotoxins and androgen excess have been independently associ- ated with a negative influence on the kidney. There are no data concerning the additive effects of these two factors on the kidney function and structure, in females. The present study aims to inves-.

  20. Searching for Excess Rotation Measures in Galaxy Clusters with the ...

    Indian Academy of Sciences (India)

    2016-01-27

    Jan 27, 2016 ... We present a statistical analysis of the rotation measure (RM) catalogue from the NVSS in search for a statistical excess of rotation measure through Abell clusters. After excluding the data known to be affected by the large-scale magnetic field of the Galaxy ( ≤ |30|), we consider RMs as a function of ...