Sphingolipid trafficking - Sorted out?

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van Meer, G.; Burger, K.N.J.

1992-01-01

Studies of intracellular membrane traffic have traditionally focused on the protein components of membranes, but what about lipids? Recent findings have drawn attention to the transport of one type of lipid, the sphingolipids. Their unique physical properties may allow them to aggregate into

Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations.

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Ayşe Demirkan

Full Text Available Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034 on plasma levels of 24 sphingomyelins (SPM, 9 ceramides (CER, 57 phosphatidylcholines (PC, 20 lysophosphatidylcholines (LPC, 27 phosphatidylethanolamines (PE, and 16 PE-based plasmalogens (PLPE, as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88×10(-204 and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57. After a correction for multiple comparisons (P-value<2.2×10(-9, we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1 and two with sphingolipids (PLD2 and APOE explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3 suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2 to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our

Tumor PDT-associated immune response: relevance of sphingolipids

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Korbelik, Mladen; Merchant, Soroush; Separovic, Duska M.

2010-02-01

Sphingolipids have become recognized as essential effector molecules in signal transduction with involvement in various aspects of cell function and death, immune response and cancer treatment response. Major representatives of sphingolipids family, ceramide, sphingosine and sphingosine-1-phosphate (S1P), have attracted interest in their relevance to tumor response to photodynamic therapy (PDT) because of their roles as enhancers of apoptosis, mediators of cell growth and vasculogenesis, and regulators of immune response. Our recent in vivo studies with mouse tumor models have confirmed that PDT treatment has a pronounced impact on sphingolipid profile in the targeted tumor and that significant advances in therapeutic gain with PDT can be attained by combining this modality with adjuvant treatment with ceramide analog LCL29.

Sphingolipids and Lipoproteins in Health and Metabolic Disorders.

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Iqbal, Jahangir; Walsh, Meghan T; Hammad, Samar M; Hussain, M Mahmood

2017-07-01

Sphingolipids are structurally and functionally diverse molecules with significant physiologic functions and are found associated with cellular membranes and plasma lipoproteins. The cellular and plasma concentrations of sphingolipids are altered in several metabolic disorders and may serve as prognostic and diagnostic markers. Here we discuss various sphingolipid transport mechanisms and highlight how changes in cellular and plasma sphingolipid levels contribute to cardiovascular disease, obesity, diabetes, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). Understanding of the mechanisms involved in intracellular transport, secretion, and extracellular transport may provide novel information that might be amenable to therapeutic targeting for the treatment of various metabolic disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic determinants of circulating sphingolipid concentrations in European populations.

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Andrew A Hicks

2009-10-01

Full Text Available Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI, cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS between 318,237 single-nucleotide polymorphisms (SNPs and levels of circulating sphingomyelin (SM, dihydrosphingomyelin (Dih-SM, ceramide (Cer, and glucosylceramide (GluCer single lipid species (33 traits; and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32 in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08x10(-66. The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3 associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4 or less. Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be

Sphingolipid and Ceramide Homeostasis: Potential Therapeutic Targets

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Simon A. Young

2012-01-01

Full Text Available Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has led to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer's disease, and numerous important human pathogens. In this paper we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions.

Sphingolipid and Ceramide Homeostasis: Potential Therapeutic Targets

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Young, Simon A.; Mina, John G.; Denny, Paul W.; Smith, Terry K.

2012-01-01

Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characterised many of the key enzymes involved in sphingolipid metabolism and this has led to a heightened interest in the possibility of targeting these processes for therapies against cancers, Alzheimer's disease, and numerous important human pathogens. In this paper we outline the major pathways in eukaryotic sphingolipid metabolism and discuss these in relation to disease and therapy for both chronic and infectious conditions. PMID:22400113

Preanalytical Biases in the Measurement of Human Blood Sphingolipids

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Robert Brunkhorst

2018-05-01

Full Text Available Dysregulation of blood sphingolipids is an emerging topic in clinical science. The objective of this study was to determine preanalytical biases that typically occur in clinical and translational studies and that influence measured blood sphingolipid levels. Therefore, we collected blood samples from four healthy male volunteers to investigate the effect of storage conditions (time, temperature, long-term storage, freeze–thaw cycles, blood drawing (venous or arterial sampling, prolonged venous compression, and sample preparation (centrifugation, freezing on sphingolipid levels measured by LC-MS/MS. Our data show that sphingosine 1-phosphate (S1P and sphinganine 1-phosphate (SA1P were upregulated in whole blood samples in a time- and temperature-dependent manner. Increased centrifugation at higher speeds led to lower amounts of S1P and SA1P. All other preanalytical biases did not significantly alter the amounts of S1P and SA1P. Further, in almost all settings, we did not detect differences in (dihydroceramide levels. In summary, besides time-, temperature-, and centrifugation-dependent changes in S1P and SA1P levels, sphingolipids in blood remained stable under practically relevant preanalytical conditions.

Neuronal sphingolipidoses: Membrane lipids and sphingolipid activator proteins regulate lysosomal sphingolipid catabolism.

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Sandhoff, Konrad

2016-11-01

Glycosphingolipids and sphingolipids of cellular plasma membranes (PMs) reach luminal intra-lysosomal vesicles (LVs) for degradation mainly by pathways of endocytosis. After a sorting and maturation process (e.g. degradation of sphingomyelin (SM) and secretion of cholesterol), sphingolipids of the LVs are digested by soluble enzymes with the help of activator (lipid binding and transfer) proteins. Inherited defects of lipid-cleaving enzymes and lipid binding and transfer proteins cause manifold and fatal, often neurodegenerative diseases. The review summarizes recent findings on the regulation of sphingolipid catabolism and cholesterol secretion from the endosomal compartment by lipid modifiers, an essential stimulation by anionic membrane lipids and an inhibition of crucial steps by cholesterol and SM. Reconstitution experiments in the presence of all proteins needed, hydrolase and activator proteins, reveal an up to 10-fold increase of ganglioside catabolism just by the incorporation of anionic lipids into the ganglioside carrying membranes, whereas an additional incorporation of cholesterol inhibits GM2 catabolism substantially. It is suggested that lipid and other low molecular modifiers affect the genotype-phenotype relationship observed in patients with lysosomal diseases. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study.

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Checa, A; Idborg, H; Zandian, A; Sar, D Garcia; Surowiec, I; Trygg, J; Svenungsson, E; Jakobsson, P-J; Nilsson, P; Gunnarsson, I; Wheelock, C E

2017-09-01

Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C 16:0 -ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C 16:0 -ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C 16:0 - and C 24:1 -hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated

Sphingolipid metabolism diseases.

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Kolter, Thomas; Sandhoff, Konrad

2006-12-01

Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

The GARP complex is required for cellular sphingolipid homeostasis

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Fröhlich, Florian; Petit, Constance; Kory, Nora

2015-01-01

(GARP) complex, which functions in endosome-to-Golgi retrograde vesicular transport, as a critical player in sphingolipid homeostasis. GARP deficiency leads to accumulation of sphingolipid synthesis intermediates, changes in sterol distribution, and lysosomal dysfunction. A GARP complex mutation...... analogous to a VPS53 allele causing progressive cerebello-cerebral atrophy type 2 (PCCA2) in humans exhibits similar, albeit weaker, phenotypes in yeast, providing mechanistic insights into disease pathogenesis. Inhibition of the first step of de novo sphingolipid synthesis is sufficient to mitigate many...

Altered Leukocyte Sphingolipid Pathway in Breast Cancer

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Larissa P. Maia

2017-11-01

Full Text Available Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients. To the best of our knowledge, this is the first characterization of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles favoring high SPHK1 expression toward S1P production during BC development was observed, which was reversed by chemotherapy treatment, and reached similar levels to those found in healthy donors. Such levels were also correlated with high levels of TNF-α. Our data revealed an important role of the sphingolipid pathway in immune cells in BC with skewed signaling of S1P receptors, which favored cancer development even under chemotherapy, and may probably be a trigger of cancer resistance. Thus, these molecules must be considered as a target pathway for combined BC therapeutics.

Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

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Demirkan, Ayşe; van Duijn, Cornelia M; Ugocsai, Peter

2012-01-01

, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57...

Disruption of Sphingolipid Biosynthesis Blocks Phagocytosis of Candida albicans.

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Fikadu G Tafesse

2015-10-01

Full Text Available The ability of phagocytes to clear pathogens is an essential attribute of the innate immune response. The role of signaling lipid molecules such as phosphoinositides is well established, but the role of membrane sphingolipids in phagocytosis is largely unknown. Using a genetic approach and small molecule inhibitors, we show that phagocytosis of Candida albicans requires an intact sphingolipid biosynthetic pathway. Blockade of serine-palmitoyltransferase (SPT and ceramide synthase-enzymes involved in sphingolipid biosynthesis- by myriocin and fumonisin B1, respectively, impaired phagocytosis by phagocytes. We used CRISPR/Cas9-mediated genome editing to generate Sptlc2-deficient DC2.4 dendritic cells, which lack serine palmitoyl transferase activity. Sptlc2-/- DC2.4 cells exhibited a stark defect in phagocytosis, were unable to bind fungal particles and failed to form a normal phagocytic cup to engulf C. albicans. Supplementing the growth media with GM1, the major ganglioside present at the cell surface, restored phagocytic activity of Sptlc2-/- DC2.4 cells. While overall membrane trafficking and endocytic pathways remained functional, Sptlc2-/- DC2.4 cells express reduced levels of the pattern recognition receptors Dectin-1 and TLR2 at the cell surface. Consistent with the in vitro data, compromised sphingolipid biosynthesis in mice sensitizes the animal to C. albicans infection. Sphingolipid biosynthesis is therefore critical for phagocytosis and in vivo clearance of C. albicans.

Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

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Yuichi Hirata

Full Text Available Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2 encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

Self-enhancement of hepatitis C virus replication by promotion of specific sphingolipid biosynthesis.

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Hirata, Yuichi; Ikeda, Kazutaka; Sudoh, Masayuki; Tokunaga, Yuko; Suzuki, Akemi; Weng, Leiyun; Ohta, Masatoshi; Tobita, Yoshimi; Okano, Ken; Ozeki, Kazuhisa; Kawasaki, Kenichi; Tsukuda, Takuo; Katsume, Asao; Aoki, Yuko; Umehara, Takuya; Sekiguchi, Satoshi; Toyoda, Tetsuya; Shimotohno, Kunitada; Soga, Tomoyoshi; Nishijima, Masahiro; Taguchi, Ryo; Kohara, Michinori

2012-01-01

Lipids are key components in the viral life cycle that affect host-pathogen interactions. In this study, we investigated the effect of HCV infection on sphingolipid metabolism, especially on endogenous SM levels, and the relationship between HCV replication and endogenous SM molecular species. We demonstrated that HCV induces the expression of the genes (SGMS1 and 2) encoding human SM synthases 1 and 2. We observed associated increases of both total and individual sphingolipid molecular species, as assessed in human hepatocytes and in the detergent-resistant membrane (DRM) fraction in which HCV replicates. SGMS1 expression had a correlation with HCV replication. Inhibition of sphingolipid biosynthesis with a hepatotropic serine palmitoyltransferase (SPT) inhibitor, NA808, suppressed HCV-RNA production while also interfering with sphingolipid metabolism. Further, we identified the SM molecular species that comprise the DRM fraction and demonstrated that these endogenous SM species interacted with HCV nonstructural 5B polymerase to enhance viral replication. Our results reveal that HCV alters sphingolipid metabolism to promote viral replication, providing new insights into the formation of the HCV replication complex and the involvement of host lipids in the HCV life cycle.

Synthesis of a Panel of Carbon-13-Labelled (Glyco)Sphingolipids

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Wisse, Patrick; Gold, Henrik; Mirzaian, Mina; Ferraz, Maria J.; Lutteke, Ginger; van den Berg, Richard J. B. H. N.; van den Elst, Hans; Lugtenburg, Johan; van der Marel, Gijsbert A.; Aerts, Johannes M. F. G.; Codee, Jeroen D. C.; Overkleeft, Herman S.

2015-01-01

The synthesis of a focussed library of sphingolipids differing in the number and position of C-13 labels is described. The synthesised sphingolipids differ in substitution at both the sphingosine amine (either palmitoylated or unmodified) and the sphingosine primary hydroxyl (unmodified or

Current relevance of fungal and trypanosomatid glycolipids and sphingolipids: studies defining structures conspicuously absent in mammals

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Helio K. Takahashi

2009-09-01

Full Text Available Recently, glycosphingolipids have been attracting attention due to their role on biological systems as second messengers or modulators of signal transduction, affecting several events, which range from apoptosis to regulation of the cell cycle. In pathogenic fungi, glycolipids are expressed in two classes: neutral monohexosylceramides (glucosyl-or galactosylceramide and acidic glycosylinositol phosphorylceramides (the latter class carries longer glycan chains. It is worth to mention that monohexosylceramides exhibit significant structural differences in their lipid moieties compared to their mammalian counterparts, whereas the glycosylinositol phosphorylceramides exhibit remarkable structural differences in their carbohydrate moieties in comparison to mammal glycosphingolipids counterpart. We observed that glycosylinositol phosphorylceramides are capable of promoting immune response in infected humans. In addition, inhibiting fungal glycosphingolipid biosynthetic pathways leads to an inhibition of colony formation, spore germination, cell cycle, dimorphism and hyphal growth. Other pathogens, such as trypanosomatids, also present unique glycolipids, which may have an important role for the parasite development and/or disease establishment. Regarding host-pathogen interaction, cell membrane rafts, which are enriched in sphingolipids and sterols, participate in parasite/fungal infection. In this review, it is discussed the different biological roles of (glyco (sphingolipids of pathogenic/opportunistic fungi and trypanosomatids.Recentemente, glicoesfingolipídeos têm atraído atenção devido ao seu papel na biologia celular como segundo-mensageiro ou moduladores da transdução de sinal, afetando vários eventos, desde apoptose até a regulação do ciclo celular. Em fungos patogênicos, existem duas classes de glicolipídeos: monohexosil ceramidas neutras (glucosil-ou galactosilceramida e glicosilinositol fosforilceramidas (os quais apresentam

Fiber Specific Changes in Sphingolipid Metabolism in Skeletal Muscles of Hyperthyroid Rats

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Chabowski, A.; ?endzian-Piotrowska, M.; Mik?osz, A.; ?ukaszuk, B.; Kurek, K.; G?rski, J.

2013-01-01

Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, ...

SPHINGOLIPID-DEPENDENT FUSION OF SEMLIKI FOREST VIRUS WITH CHOLESTEROL-CONTAINING LIPOSOMES REQUIRES BOTH THE 3-HYDROXYL GROUP AND THE DOUBLE-BOND OF THE SPHINGOLIPID BACKBONE

NARCIS (Netherlands)

CORVER, J; MOESBY, L; ERUKULLA, RK; REDDY, KC; BITTMAN, R; WILSCHUT, J

Low-pH-induced membrane fusion of Semliki Forest virus (SFV) in a model system is mediated by sphingolipids in the target membrane; ceramide is the sphingolipid minimally required (J. L. Nieva, R. Bron, J. Corver, and J. Wilschut, EMBO J. 13:2797-2804, 1994). Here, using various ceramide analogs, we

Sphingolipids as a new factor in the pathomechanism of preeclampsia - Mass spectrometry analysis.

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Karol Charkiewicz

Full Text Available The aim of the study was to analyse a panel of 11 sphingolipids in plasma and three blood fractions (platelet-poor plasma, platelets and red blood cells of women with mild preeclampsia.We recruited 21 women between 25-40 weeks gestation with diagnosed mild preeclampsia to the study group and 36 healthy women with uncomplicated pregnancies, who corresponded with the study group according to gestational age, to the control group. To assess the concentration of 11 sphingolipids in the blood plasma and blood fractions, we used ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS.We showed a significant increase in the concentration of eight sphingolipids in the plasma of women with preeclampsia in comparison to the control group: Sph (p = 0.0032, S1P (p = 0.0289, C20-Cer (p < 0.0001, C18-Cer (p < 0.0001, C16-Cer (p = 0.012, C18:1-Cer (p = 0.003, C22-Cer (p = 0.0071, and C24:1-Cer (p = 0.0085.We showed that selected sphingolipids, especially C20-Cer and C18-Cer, are totally new factors in the pathomechanism of PE and that these bioactive lipids may play an important role in apoptosis and autophagy.

The way we view cellular (glyco)sphingolipids.

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Hoetzl, Sandra; Sprong, Hein; van Meer, Gerrit

2007-11-01

Mammalian cells synthesize ceramide in the endoplasmic reticulum (ER) and convert this to sphingomyelin and complex glycosphingolipids on the inner, non-cytosolic surface of Golgi cisternae. From there, these lipids travel towards the outer, non-cytosolic surface of the plasma membrane and all membranes of the endocytic system, where they are eventually degraded. At the basis of the selective, anterograde traffic out of the Golgi lies the propensity of the sphingolipids to self-aggregate with cholesterol into microdomains termed 'lipid rafts'. At the plasma membrane surface these rafts are thought to function as the scaffold for various types of (glyco) signaling domains of different protein and lipid composition that can co-exist on one and the same cell. In the past decade, various unexpected findings on the sites where sphingolipid-mediated events occur have thrown a new light on the localization and transport mechanisms of sphingolipids. These findings are largely based on biochemical experiments. Further progress in the field is hampered by a lack of morphological techniques to localize lipids with nanometer resolution. In the present paper, we critically evaluate the published data and discuss techniques and potential improvements.

Sphingolipid topology and the dynamic organization and function of membrane proteins.

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van Meer, Gerrit; Hoetzl, Sandra

2010-05-03

When acquiring internal membranes and vesicular transport, eukaryotic cells started to synthesize sphingolipids and sterols. The physical differences between these and the glycerophospholipids must have enabled the cells to segregate lipids in the membrane plane. Localizing this event to the Golgi then allowed them to create membranes of different lipid composition, notably a thin, flexible ER membrane, consisting of glycerolipids, and a sturdy plasma membrane containing at least 50% sphingolipids and sterols. Besides sorting membrane proteins, in the course of evolution the simple sphingolipids obtained key positions in cellular physiology by developing specific interactions with (membrane) proteins involved in the execution and control of signaling. The few signaling sphingolipids in mammals must provide basic transmission principles that evolution has built upon for organizing the specific regulatory pathways tuned to the needs of the different cell types in the body. Copyright 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

International Nuclear Information System (INIS)

Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

2005-01-01

Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation.

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J Eduardo Rico

Full Text Available Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition. Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in

Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation

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Rico, J. Eduardo; Saed Samii, Sina; Mathews, Alice T.; Lovett, Jacqueline; Haughey, Norman J.; McFadden, Joseph W.

2017-01-01

Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition). Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in peripartal sphingolipids

Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

Science.gov (United States)

Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

2009-01-01

The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

Directory of Open Access Journals (Sweden)

Isabelle eGuillas

2013-09-01

Full Text Available Nitric oxide (NO emerged as one of the major signalling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of nitric oxide into complex signalling networks. Beside the close relationships between NO and calcium or phosphatidic acid signalling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids. This mini-review summarises our current knowledge of the influence NO and sphingolipids might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although sphingolipid-NO interplays are common features in signalling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

Autophagy in the light of sphingolipid metabolism

DEFF Research Database (Denmark)

Harvald, Eva Bang; Olsen, Anne Sofie Braun; Færgeman, Nils J.

2015-01-01

Maintenance of cellular homeostasis requires tight and coordinated control of numerous metabolic pathways, which are governed by interconnected networks of signaling pathways and energy-sensing regulators. Autophagy, a lysosomal degradation pathway by which the cell self-digests its own components......, has over the past decade been recognized as an essential part of metabolism. Autophagy not only rids the cell of excessive or damaged organelles, misfolded proteins, and invading microorganisms, it also provides nutrients to maintain crucial cellular functions. Besides serving as essential structural...... moieties of biomembranes, lipids including sphingolipids are increasingly being recognized as central regulators of a number of important cellular processes, including autophagy. In the present review we describe how sphingolipids, with special emphasis on ceramides and sphingosine-1-phosphate, can act...

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

Science.gov (United States)

Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

2017-10-01

The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

NARCIS (Netherlands)

A. Demirkan (Ayşe); C.M. van Duijn (Cornelia); P. Ugocsai (Peter); A.J. Isaacs (Aaron); P.P. Pramstaller (Peter Paul); G. Liebisch (Gerhard); J.F. Wilson (James); A. Johansson (Åsa); I. Rudan (Igor); Y.S. Aulchenko (Yurii); A.V. Kirichenko (Anatoly); A.C.J.W. Janssens (Cécile); R.C. Jansen (Ritsert); C. Gnewuch (Carsten); I. Domingues (Inês); C. Pattaro (Cristian); S.H. Wild (Sarah); I. Jonasson (Inger); O. Polasek (Ozren); I.V. Zorkoltseva (Irina); A. Hofman (Albert); L.C. Karssen (Lennart); M.V. Struchalin (Maksim); J. Floyd (Jamie); W. Igl (Wilmar); Z. Biloglav (Zrinka); L. Broer (Linda); A. Pfeufer (Arne); I. Pichler (Irene); S. Campbell (Susan); G. Zaboli (Ghazal); I. Kolcic (Ivana); F. Rivadeneira Ramirez (Fernando); J.E. Huffman (Jennifer); N. Hastie (Nick); A.G. Uitterlinden (André); L. Franke (Lude); C.S. Franklin (Christopher); V. Vitart (Veronique); C.P. Nelson (Christopher P.); M. Preuss (Michael); J.C. Bis (Joshua); C.J. O'Donnell (Christopher); N. Franceschini (Nora); J.C.M. Witteman (Jacqueline); T.I. Axenovich (Tatiana); B.A. Oostra (Ben); T. Meitinger (Thomas); A.A. Hicks (Andrew); C. Hayward (Caroline); A.F. Wright (Alan); U. Gyllensten (Ulf); H. Campbell (Harry); G. Schmitz (Gerd)

2012-01-01

textabstractPhospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological,

The sphingolipid long-chain base-Pkh1/2-Ypk1/2 signaling pathway regulates eisosome assembly and turnover

DEFF Research Database (Denmark)

Luo, Guangzuo; Gruhler, Albrecht; Liu, Ying

2008-01-01

Eisosomes are recently described fungal structures that play roles in the organization of the plasma membrane and endocytosis. Their major protein components are Pil1 and Lsp1, and previous studies showed that these proteins are phosphorylated by the sphingolipid long-chain base-activated Pkh1...... that phosphorylation is critical for eisosome organization. We also found that eisosomes are dynamic structures and disassemble when the Ypk protein kinases, which are activated by the sphingolipid-Pkh signaling pathway, are inactivated or when the sphingolipid signal is pharmacologically blocked with myriocin. We...

Low serum sphingolipids in children with attention deficit-hyperactivity disorder

Directory of Open Access Journals (Sweden)

Marcela Patricia Henríquez-Henríquez

2015-08-01

Full Text Available Background: Attention deficit-hyperactivity disorder (ADHD is the most prevalent neuropsychiatric condition in childhood. ADHD is a multifactorial trait with a strong genetic component. One neurodevelopmental hypothesis is that ADHD is associated with a lag in brain maturation. Sphingolipids are essential for brain development and neuronal functioning, but their role in ADHD pathogenesis is unexplored. We hypothesized that serum sphingolipid levels distinguish ADHD patients from unaffected subjects. Methods: We characterized serum sphingolipid profiles of ADHD patients and two control groups: non-affected relatives and non-affected subjects without a family history of ADHD. Sphingolipids were measured by LC-MS/MS in 77 participants (28 ADHD patients, 28 related controls and 21 unrelated controls. ADHD diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR. Diagnostic criteria were assessed by 2 independent observers. Groups were compared by parametrical statistics. Results: Serum sphingomyelins C16:0, C18:0, C18:1, C24:1, ceramide C24:0 and deoxy-ceramide C24:1 were significantly decreased in ADHD patients at 20-30% relative reductions. In our sample, decreased serum sphingomyelin levels distinguished ADHD patients with 79% sensitivity and 78% specificity. Conclusions: Our results showed lower levels of all major serum sphingomyelins in ADHD. These findings may reflect brain maturation and affect neuro-functional pathways characteristic for ADHD.

Fiber specific changes in sphingolipid metabolism in skeletal muscles of hyperthyroid rats.

Science.gov (United States)

Chabowski, A; Zendzian-Piotrowska, M; Mikłosz, A; Łukaszuk, B; Kurek, K; Górski, J

2013-07-01

Thyroid hormones (T3, T4) are well known modulators of different cellular signals including the sphingomyelin pathway. However, studies regarding downstream effects of T3 on sphingolipid metabolism in skeletal muscle are scarce. In the present work we sought to investigate the effects of hyperthyroidism on the activity of the key enzymes of ceramide metabolism as well as the content of fundamental sphingolipids. Based on fiber/metabolic differences, we chose three different skeletal muscles, with diverse fiber compositions: soleus (slow-twitch oxidative), red (fast-twitch oxidative-glycolytic) and white (fast-twitch glycolytic) section of gastrocnemius. We demonstrated that T3 induced accumulation of sphinganine, ceramide, sphingosine, as well as sphingomyelin, mostly in soleus and in red, but not white section of gastrocnemius. Concomitantly, the activity of serine palmitoyltransferase and acid/neutral ceramidase was increased in more oxidative muscles. In conclusion, hyperthyroidism induced fiber specific changes in the content of sphingolipids that were relatively more related to de novo synthesis of ceramide rather than to its generation via hydrolysis of sphingomyelin.

Establishment of HeLa cell mutants deficient in sphingolipid-related genes using TALENs.

Directory of Open Access Journals (Sweden)

Toshiyuki Yamaji

Full Text Available Sphingolipids are essential components in eukaryotes and have various cellular functions. Recent developments in genome-editing technologies have facilitated gene disruption in various organisms and cell lines. We here show the disruption of various sphingolipid metabolic genes in human cervical carcinoma HeLa cells by using transcription activator-like effector nucleases (TALENs. A TALEN pair targeting the human CERT gene (alternative name COL4A3BP encoding a ceramide transport protein induced a loss-of-function phenotype in more than 60% of HeLa cells even though the cell line has a pseudo-triploid karyotype. We have isolated several loss-of-function mutant clones for CERT, UGCG (encoding glucosylceramide synthase, and B4GalT5 (encoding the major lactosylceramide synthase, and also a CERT/UGCG double-deficient clone. Characterization of these clones supported previous proposals that CERT primarily contributes to the synthesis of SM but not GlcCer, and that B4GalT5 is the major LacCer synthase. These newly established sphingolipid-deficient HeLa cell mutants together with our previously established stable transfectants provide a 'sphingolipid-modified HeLa cell panel,' which will be useful to elucidate the functions of various sphingolipid species against essentially the same genomic background.

Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B1

Science.gov (United States)

Direito, Glória M.; Almeida, Adriana P.; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

2009-01-01

The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio. PMID:19333435

Membrane domains and polarized trafficking of sphingolipids

NARCIS (Netherlands)

Maier, O; Slimane, TA; Hoekstra, D

The plasma membrane of polarized cells consists of distinct domains, the apical and basolateral membrane that are characterized by a distinct lipid and protein content. Apical protein transport is largely mediated by (glyco)sphingolipid-cholesterol enriched membrane microdomains, so called rafts. In

Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

OpenAIRE

Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

2012-01-01

Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 ?M) for 24 hr induced...

Cholesterol, sphingolipids, and glycolipids: What do we know about their role in raft-like membranes?

DEFF Research Database (Denmark)

Rog, T.; Vattulainen, I.

2014-01-01

Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units with pote......Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units...... with potential specific functions. Although the understanding of the structure of rafts in living cells is quite limited, the possible functions of rafts are widely discussed in the literature, highlighting their importance in cellular functions. In this review, we discuss the understanding of rafts that has...... emerged based on recent atomistic and coarse-grained molecular dynamics simulation studies on the key lipid raft components, which include cholesterol, sphingolipids, glycolipids, and the proteins interacting with these classes of lipids. The simulation results are compared to experiments when possible...

Sphingolipid trafficking and protein sorting in epithelial cells

NARCIS (Netherlands)

Slimane, TA; Hoekstra, D

2002-01-01

Sphingolipids represent a minor, but highly dynamic subclass of lipids in all eukaryotic cells. They are involved in functions that range from structural protection to signal transduction and protein sorting, and participate in lipid raft assembly. In polarized epithelial cells, which display an

Newly identified essential amino acid residues affecting ^8-sphingolipid desaturase activity revealed by site-directed mutagenesis

Science.gov (United States)

In order to identify amino acid residues crucial for the enzymatic activity of ^8-sphingolipid desaturases, a sequence comparison was performed among ^8-sphingolipid desaturases and ^6-fatty acid desaturase from various plants. In addition to the known conserved cytb5 (cytochrome b5) HPGG motif and...

Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

OpenAIRE

Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu

2011-01-01

Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components...

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

Science.gov (United States)

Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

2016-10-01

Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

Regulation of stem-cell mediated host immunity by the sphingolipid ...

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

Regulation of stem-cell mediated host immunity by the sphingolipid pathway ... in the generation of mature immune cells and the functioning of the surrounding ... methods with human cells and genetically engineered mice to examine how the ...

Glycosylation of inositol phosphorylceramide sphingolipids is required for normal growth and reproduction in Arabidopsis

Energy Technology Data Exchange (ETDEWEB)

Tartaglio, Virginia [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Rennie, Emilie A. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Cahoon, Rebecca [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Wang, George [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Baidoo, Edward [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Mortimer, Jennifer C. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Cahoon, Edgar B. [Univ. of Nebraska, Lincoln, NE (United States). Center for Plant Science Innovation and Dept. of Biochemistry; Scheller, Henrik V. [Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States); Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology

2016-09-19

Sphingolipids are a major component of plant plasma membranes and endomembranes, and mediate a diverse range of biological processes. Study of the highly glycosylated glycosyl inositol phosphorylceramide (GIPC) sphingolipids has been slow as a result of challenges associated with the extractability of GIPCs, and their functions in the plant remain poorly characterized. We recently discovered an Arabidopsis GIPC glucuronosyltransferase, INOSITOL PHOSPHORYLCERAMIDE GLUCURONOSYLTRANSFERASE 1 (IPUT1), which is the first enzyme in the GIPC glycosylation pathway. Plants homozygous for the iput1 loss-of-function mutation were unobtainable, and so the developmental effects of reduced GIPC glucuronosylation could not be analyzed in planta. Using a pollen-specific rescue construct, we have here isolated homozygous iput1 mutants. The iput1 mutants show severe dwarfism, compromised pollen tube guidance, and constitutive activation of salicyclic acid-mediated defense pathways. The mutants also possess reduced GIPCs, increased ceramides, and an increased incorporation of short-chain fatty acids and dihydroxylated bases into inositol phosphorylceramides and GIPCs. The assignment of a direct role for GIPC glycan head groups in the impaired processes in iput1 mutants is complicated by the vast compensatory changes in the sphingolipidome; however, our results reveal that the glycosylation steps of GIPC biosynthesis are important regulated components of sphingolipid metabolism. In conclusion, this study corroborates previously suggested roles for GIPC glycans in plant growth and defense, suggests important role s for them in reproduction and demonstrates that the entire sphingolipidome is sensitive to their status.

TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

Directory of Open Access Journals (Sweden)

Brad J. Niles

2014-02-01

Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

Sphingolipid base modifying enzymes in sunflower (Helianthus annuus): cloning and characterization of a C4-hydroxylase gene and a new paralogous Δ8-desaturase gene.

Science.gov (United States)

Moreno-Pérez, Antonio J; Martínez-Force, Enrique; Garcés, Rafael; Salas, Joaquín J

2011-05-15

Sphingolipids are components of plant cell membranes that participate in the regulation of important physiological processes. Unlike their animal counterparts, plant sphingolipids are characterized by high levels of base C4-hydroxylation. Moreover, desaturation at the Δ8 position predominates over the Δ4 desaturation typically found in animal sphingolipids. These modifications are due to the action of C4-hydroxylases and Δ8-long chain base desaturases, and they are important for complex sphingolipids finally becoming functional. The long chain bases of sunflower sphingolipids have high levels of hydroxylated and unsaturated moieties. Here, a C4-long chain base hydroxylase was functionally characterized in sunflower plant, an enzyme that could complement the sur2Δ mutation when heterologously expressed in this yeast mutant deficient in hydroxylation. This hydroxylase was ubiquitously expressed in sunflower, with the highest levels found in the developing cotyledons. In addition, we identified a new Δ8-long base chain desaturase gene that displays strong homology to a previously reported desaturase gene. This desaturase was also expressed in yeast and was able to change the long chain base composition of the transformed host. We studied the expression of this desaturase and compared it with that of the other isoform described in sunflower. The desaturase form studied in this paper displayed higher expression levels in developing seeds. Copyright © 2010 Elsevier GmbH. All rights reserved.

Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

Science.gov (United States)

Lavieu, Gregory; Scarlatti, Francesca; Sala, Giusy; Levade, Thierry; Ghidoni, Riccardo; Botti, Joëlle; Codogno, Patrice

2007-01-01

Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively.

Complex modulation of peptidolytic activity of cathepsin D by sphingolipids

Czech Academy of Sciences Publication Activity Database

Žebrakovská, Iva; Máša, Martin; Srp, Jaroslav; Horn, Martin; Vávrová, K.; Mareš, Michael

2011-01-01

Roč. 1811, č. 12 (2011), s. 1097-1104 ISSN 1388-1981 R&D Projects: GA AV ČR IAA400550705 Institutional research plan: CEZ:AV0Z40550506 Keywords : sphingolipid * phospholipid * inhibition * activation * cathepsin D * enzyme regulation Subject RIV: CE - Biochemistry Impact factor: 5.269, year: 2011

Sphingolipid topology and the dynamic organization and function of membrane proteins

NARCIS (Netherlands)

van Meer, G.|info:eu-repo/dai/nl/068570368; Hoetzl, S.

2010-01-01

When acquiring internal membranes and vesicular transport, eukaryotic cells started to synthesize sphingolipids and sterols. The physical differences between these and the glycerophospholipids must have enabled the cells to segregate lipids in the membrane plane. Localizing this event to the Golgi

Two New Sphingolipids from the Leaves of Piper betle L.

OpenAIRE

Chen, Duo-Zhi; Xiong, Hua-Bin; Tian, Kai; Guo, Jun-Ming; Huang, Xiang-Zhong; Jiang, Zhi-Yong

2013-01-01

Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

Two new sphingolipids from the leaves of Piper betle L.

Science.gov (United States)

Chen, Duo-Zhi; Xiong, Hua-Bin; Tian, Kai; Guo, Jun-Ming; Huang, Xiang-Zhong; Jiang, Zhi-Yong

2013-09-12

Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs

Science.gov (United States)

Mathew, Biji; Jacobson, Jeffrey R.; Berdyshev, Evgeny; Huang, Yong; Sun, Xiaoguang; Zhao, Yutong; Gerhold, Lynnette M.; Siegler, Jessica; Evenoski, Carrie; Wang, Ting; Zhou, Tong; Zaidi, Rafe; Moreno-Vinasco, Liliana; Bittman, Robert; Chen, Chin Tu; LaRiviere, Patrick J.; Sammani, Saad; Lussier, Yves A.; Dudek, Steven M.; Natarajan, Viswanathan; Weichselbaum, Ralph R.; Garcia, Joe G. N.

2011-01-01

Clinically significant radiation-induced lung injury (RILI) is a common toxicity in patients administered thoracic radiotherapy. Although the molecular etiology is poorly understood, we previously characterized a murine model of RILI in which alterations in lung barrier integrity surfaced as a potentially important pathobiological event and genome-wide lung gene mRNA levels identified dysregulation of sphingolipid metabolic pathway genes. We hypothesized that sphingolipid signaling components serve as modulators and novel therapeutic targets of RILI. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to sphingosine 1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage fluid, and lung tissue. Mice with a targeted deletion of SphK1 (SphK1−/−) or with reduced expression of S1P receptors (S1PR1+/−, S1PR2−/−, and S1PR3−/−) exhibited marked RILI susceptibility. Finally, studies of 3 potent vascular barrier-protective S1P analogs, FTY720, (S)-FTY720-phosphonate (fTyS), and SEW-2871, identified significant RILI attenuation and radiation-induced gene dysregulation by the phosphonate analog, fTyS (0.1 and 1 mg/kg i.p., 2×/wk) and to a lesser degree by SEW-2871 (1 mg/kg i.p., 2×/wk), compared with those in controls. These results support the targeting of S1P signaling as a novel therapeutic strategy in RILI.—Mathew, B., Jacobson, J. R., Berdyshev, E., Huang, Y., Sun, X., Zhao, Y., Gerhold, L. M., Siegler, J., Evenoski, C., Wang, T., Zhou, T., Zaidi, R., Moreno-Vinasco, L., Bittman, R., Chen, C. T., LaRiviere, P. J., Sammani, S., Lussier, Y. A., Dudek, S. M., Natarajan, V., Weichselbaum, R. R., Garcia, J. G. N. Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. PMID:21712494

Transport and sorting of sphingolipids in polarized cells : the involvement of the sub-apical compartment

NARCIS (Netherlands)

IJzendoorn, Sven Christian David van

1999-01-01

The work described in this thesis has provided a novel insight into the process of sphingolipid transport and sorting in polarized cells. We have used HepG2 cells as a model system to study polarized traffic in hepatic cells. Under specific culture conditions, HepG2 cells acquire a polarized

Two New Sphingolipids from the Leaves of Piper betle L.

Directory of Open Access Journals (Sweden)

Zhi-Yong Jiang

2013-09-01

Full Text Available Two new sphingolipids, pipercerebrosides A (1 and B (2, were isolated from the leaves of Piper betle L. Their structures, including absolute configurations, were determined by spectroscopic analysis and chemical degradation. These two compounds did not show significant cytotoxic activity against the cancer cell lines K562 and HL-60 in a MTT assay.

Everybody needs sphingolipids, right! Mining for new drug targets in protozoan sphingolipid biosynthesis.

Science.gov (United States)

Mina, John G M; Denny, P W

2018-02-01

Sphingolipids (SLs) are an integral part of all eukaryotic cellular membranes. In addition, they have indispensable functions as signalling molecules controlling a myriad of cellular events. Disruption of either the de novo synthesis or the degradation pathways has been shown to have detrimental effects. The earlier identification of selective inhibitors of fungal SL biosynthesis promised potent broad-spectrum anti-fungal agents, which later encouraged testing some of those agents against protozoan parasites. In this review we focus on the key enzymes of the SL de novo biosynthetic pathway in protozoan parasites of the Apicomplexa and Kinetoplastidae, outlining the divergence and interconnection between host and pathogen metabolism. The druggability of the SL biosynthesis is considered, alongside recent technology advances that will enable the dissection and analyses of this pathway in the parasitic protozoa. The future impact of these advances for the development of new therapeutics for both globally threatening and neglected infectious diseases is potentially profound.

(Glyco)sphingolipids are sorted in sub-apical compartments in HepG2 cells : A role for non-Golgi-related intracellular sites in the polarized distribution of (glyco)sphingolipids

NARCIS (Netherlands)

van IJzendoorn, SCD; Hoekstra, D

1998-01-01

In polarized HepG2 cells, the fluorescent sphingolipid analogues of glucosylceramide (C-6-NBD-GlcCer) and sphingomyelin (C-6-NBD-SM) display a preferential localization at the apical and basolateral domain, respectively, which is expressed during apical to basolateral transcytosis of the lipids (van

Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions

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Kovacs, Erika; Harmat, Veronika; Tóth, Judit; Vértessy, Beáta G.; Módos, Károly; Kardos, József; Liliom, Károly

2010-01-01

Lipid-protein interactions are rarely characterized at a structural molecular level due to technical difficulties; however, the biological significance of understanding the mechanism of these interactions is outstanding. In this report, we provide mechanistic insight into the inhibitory complex formation of the lipid mediator sphingosylphosphorylcholine with calmodulin, the most central and ubiquitous regulator protein in calcium signaling. We applied crystallographic, thermodynamic, kinetic, and spectroscopic approaches using purified bovine calmodulin and bovine cerebral microsomal fraction to arrive at our conclusions. Here we present 1) a 1.6-Å resolution crystal structure of their complex, in which the sphingolipid occupies the conventional hydrophobic binding site on calmodulin; 2) a peculiar stoichiometry-dependent binding process: at low or high protein-to-lipid ratio calmodulin binds lipid micelles or a few lipid molecules in a compact globular conformation, respectively, and 3) evidence that the sphingolipid displaces calmodulin from its targets on cerebral microsomes. We have ascertained the specificity of the interaction using structurally related lipids as controls. Our observations reveal the structural basis of selective calmodulin inhibition by the sphingolipid. On the basis of the crystallographic and biophysical characterization of the calmodulin–sphingosylphosphorylcholine interaction, we propose a novel lipid-protein binding model, which might be applicable to other interactions as well.—Kovacs, E., Harmat, V., Tóth, J., Vértessy, B. G., Módos, K., Kardos, J., Liliom, K. Structure and mechanism of calmodulin binding to a signaling sphingolipid reveal new aspects of lipid-protein interactions. PMID:20522785

Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B1

International Nuclear Information System (INIS)

Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S.; Swanevelder, Sonja

2004-01-01

In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B 1 (FB 1 ) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB 1 containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB 1 dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB 1 treatment in the control rats was significantly (P 1 initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB 1 treatment, the initiation effected by FB 1 was less (P 1 initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P 1 treatment. Although, the FB 1 -induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

A conserved signaling network monitors delivery of sphingolipids to the plasma membrane in budding yeast.

Science.gov (United States)

Clarke, Jesse; Dephoure, Noah; Horecka, Ira; Gygi, Steven; Kellogg, Douglas

2017-10-01

In budding yeast, cell cycle progression and ribosome biogenesis are dependent on plasma membrane growth, which ensures that events of cell growth are coordinated with each other and with the cell cycle. However, the signals that link the cell cycle and ribosome biogenesis to membrane growth are poorly understood. Here we used proteome-wide mass spectrometry to systematically discover signals associated with membrane growth. The results suggest that membrane trafficking events required for membrane growth generate sphingolipid-dependent signals. A conserved signaling network appears to play an essential role in signaling by responding to delivery of sphingolipids to the plasma membrane. In addition, sphingolipid-dependent signals control phosphorylation of protein kinase C (Pkc1), which plays an essential role in the pathways that link the cell cycle and ribosome biogenesis to membrane growth. Together these discoveries provide new clues as to how growth--dependent signals control cell growth and the cell cycle. © 2017 Clarke et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Actin filaments and microtubules are involved in different membrane traffic pathways that transport sphingolipids to the apical surface of polarized HepG2 cells

NARCIS (Netherlands)

Zegers, MMP; Zaal, KJM; van Ijzendoorn, SCD; Klappe, K; Hoekstra, D

In polarized HepG2 hepatoma cells, sphingolipids are transported to the apical, bile canalicular membrane by two different transport routes, as revealed with fluorescently tagged sphingolipid analogs. One route involves direct, transcytosis-independent transport of Golgi-derived glucosylceramide and

Sphingolipids: Key Regulators of Apoptosis and Pivotal Players in Cancer Drug Resistance

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Paola Giussani

2014-03-01

Full Text Available Drug resistance elicited by cancer cells still constitutes a huge problem that frequently impairs the efficacy of both conventional and novel molecular therapies. Chemotherapy usually acts to induce apoptosis in cancer cells; therefore, the investigation of apoptosis control and of the mechanisms used by cancer cells to evade apoptosis could be translated in an improvement of therapies. Among many tools acquired by cancer cells to this end, the de-regulated synthesis and metabolism of sphingolipids have been well documented. Sphingolipids are known to play many structural and signalling roles in cells, as they are involved in the control of growth, survival, adhesion, and motility. In particular, in order to increase survival, cancer cells: (a counteract the accumulation of ceramide that is endowed with pro-apoptotic potential and is induced by many drugs; (b increase the synthesis of sphingosine-1-phosphate and glucosylceramide that are pro-survivals signals; (c modify the synthesis and the metabolism of complex glycosphingolipids, particularly increasing the levels of modified species of gangliosides such as 9-O acetylated GD3 (αNeu5Ac(2-8αNeu5Ac(2-3βGal(1-4βGlc(1-1Cer or N-glycolyl GM3 (αNeu5Ac (2-3βGal(1-4βGlc(1-1Cer and de-N-acetyl GM3 (NeuNH(2βGal(1-4βGlc(1-1Cer endowed with anti-apoptotic roles and of globoside Gb3 related to a higher expression of the multidrug resistance gene MDR1. In light of this evidence, the employment of chemical or genetic approaches specifically targeting sphingolipid dysregulations appears a promising tool for the improvement of current chemotherapy efficacy.

The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma

Czech Academy of Sciences Publication Activity Database

Paulenda, Tomáš; Dráber, Petr

2016-01-01

Roč. 71, č. 7 (2016), s. 918-930 ISSN 0105-4538 R&D Projects: GA ČR(CZ) GA14-00703S; GA ČR(CZ) GA14-09807S; GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : asthma * cellular membranes * endoplasmic * reticulum * ORMDL3 * sphingolipids Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.361, year: 2016

Sphingoid bases and the serine catabolic enzyme CHA1 define a novel feedforward/feedback mechanism in the response to serine availability.

Science.gov (United States)

Montefusco, David J; Newcomb, Benjamin; Gandy, Jason L; Brice, Sarah E; Matmati, Nabil; Cowart, L Ashley; Hannun, Yusuf A

2012-03-16

Targets of bioactive sphingolipids in Saccharomyces cerevisiae were previously identified using microarray experiments focused on sphingolipid-dependent responses to heat stress. One of these heat-induced genes is the serine deamidase/dehydratase Cha1 known to be regulated by increased serine availability. This study investigated the hypothesis that sphingolipids may mediate the induction of Cha1 in response to serine availability. The results showed that inhibition of de novo synthesis of sphingolipids, pharmacologically or genetically, prevented the induction of Cha1 in response to increased serine availability. Additional studies implicated the sphingoid bases phytosphingosine and dihydrosphingosine as the likely mediators of Cha1 up-regulation. The yeast protein kinases Pkh1 and Pkh2, known sphingoid base effectors, were found to mediate CHA1 up-regulation via the transcription factor Cha4. Because the results disclosed a role for sphingolipids in negative feedback regulation of serine metabolism, we investigated the effects of disrupting this mechanism on sphingolipid levels and on cell growth. Intriguingly, exposure of the cha1Δ strain to high serine resulted in hyperaccumulation of endogenous serine and in turn a significant accumulation of sphingoid bases and ceramides. Under these conditions, the cha1Δ strain displayed a significant growth defect that was sphingolipid-dependent. Together, this work reveals a feedforward/feedback loop whereby the sphingoid bases serve as sensors of serine availability and mediate up-regulation of Cha1 in response to serine availability, which in turn regulates sphingolipid levels by limiting serine accumulation.

Neurochemical Metabolomics Reveals Disruption to Sphingolipid Metabolism Following Chronic Haloperidol Administration.

Science.gov (United States)

McClay, Joseph L; Vunck, Sarah A; Batman, Angela M; Crowley, James J; Vann, Robert E; Beardsley, Patrick M; van den Oord, Edwin J

2015-09-01

Haloperidol is an effective antipsychotic drug for treatment of schizophrenia, but prolonged use can lead to debilitating side effects. To better understand the effects of long-term administration, we measured global metabolic changes in mouse brain following 3 mg/kg/day haloperidol for 28 days. These conditions lead to movement-related side effects in mice akin to those observed in patients after prolonged use. Brain tissue was collected following microwave tissue fixation to arrest metabolism and extracted metabolites were assessed using both liquid and gas chromatography mass spectrometry (MS). Over 300 unique compounds were identified across MS platforms. Haloperidol was found to be present in all test samples and not in controls, indicating experimental validity. Twenty-one compounds differed significantly between test and control groups at the p < 0.05 level. Top compounds were robust to analytical method, also being identified via partial least squares discriminant analysis. Four compounds (sphinganine, N-acetylornithine, leucine and adenosine diphosphate) survived correction for multiple testing in a non-parametric analysis using false discovery rate threshold < 0.1. Pathway analysis of nominally significant compounds (p < 0.05) revealed significant findings for sphingolipid metabolism (p = 0.015) and protein biosynthesis (p = 0.024). Altered sphingolipid metabolism is suggestive of disruptions to myelin. This interpretation is supported by our observation of elevated N-acetyl-aspartyl-glutamate in the haloperidol-treated mice (p = 0.004), a marker previously associated with demyelination. This study further demonstrates the utility of murine neurochemical metabolomics as a method to advance understanding of CNS drug effects.

Synthesis and processing of sphingolipid activator protein-2 (SAP-2) in cultured human fibroblasts

International Nuclear Information System (INIS)

Fujibayashi, S.; Wenger, D.A.

1986-01-01

Sphingolipid activator proteins (SAP) are relatively small molecular weight proteins that stimulate the enzymatic hydrolysis of sphingolipids in the presence of specific lysosomal hydrolases. SAP-2 has previously been demonstrated to activate the hydrolysis of glucosylceramide, galactosylceramide, and, possibly, sphingomyelin. Using monospecific rabbit antibodies against human spleen SAP-2, the synthesis and processing of SAP-2 were studied in cultured human fibroblasts. When [ 35 S]methionine was presented in the medium to control human cells for 4 h, five major areas of radiolabeling were found. These had apparent molecular weights of 73,000, 68,000, 50,000, 12,000, and 9000. Further studies indicated that the major extracellular product in normal cells given NH4Cl along with the [ 35 S]methionine and in medium from cultures from patients with I cell disease had an apparent molecular weight of 73,000. The Mr = 68,000 and 73,000 species can be converted to a species with an apparent molecular weight of 50,000 by the action of endoglycosidase F. After labeling cells for 1 h followed by a 1-h chase, the Mr = 12,000 and 9000 species appear. Treatment of the immunoprecipitated mixture with endoglycosidase F resulted in conversion of these species to one band with an apparent molecular weight of 7600. These studies indicate that this relatively low molecular weight protein is rapidly synthesized from a relatively large molecular weight highly glycosylated precursor

Methods of staining and visualization of sphingolipid enriched and non-enriched plasma membrane regions of Arabidopsis thaliana with fluorescent dyes and lipid analogues

Directory of Open Access Journals (Sweden)

Blachutzik Jörg O

2012-08-01

Full Text Available Abstract Background Sterols and Sphingolipids form lipid clusters in the plasma membranes of cell types throughout the animal and plant kingdoms. These lipid domains provide a medium for protein signaling complexes at the plasma membrane and are also observed to be principal regions of membrane contact at the inception of infection. We visualized different specific fluorescent lipophilic stains of the both sphingolipid enriched and non-sphingolipid enriched regions in the plasma membranes of live protoplasts of Arabidopsis thaliana. Results Lipid staining protocols for several fluorescent lipid analogues in plants are presented. The most emphasis was placed on successful protocols for the single and dual staining of sphingolipid enriched regions and exclusion of sphingolipid enriched regions on the plasma membrane of Arabidopsis thaliana protoplasts. A secondary focus was placed to ensure that these staining protocols presented still maintain cell viability. Furthermore, the protocols were successfully tested with the spectrally sensitive dye Laurdan. Conclusion Almost all existing staining procedures of the plasma membrane with fluorescent lipid analogues are specified for animal cells and tissues. In order to develop lipid staining protocols for plants, procedures were established with critical steps for the plasma membrane staining of Arabidopsis leaf tissue and protoplasts. The success of the plasma membrane staining protocols was additionally verified by measurements of lipid dynamics by the fluorescence recovery after photobleaching technique and by the observation of new phenomena such as time dependent lipid polarization events in living protoplasts, for which a putative physiological relevance is suggested.

A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

Science.gov (United States)

Clay, Lori; Caudron, Fabrice; Denoth-Lippuner, Annina; Boettcher, Barbara; Buvelot Frei, Stéphanie; Snapp, Erik Lee; Barral, Yves

2014-01-01

In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging. DOI: http://dx.doi.org/10.7554/eLife.01883.001 PMID:24843009

Ophiamides A-B, new potent urease inhibitory sphingolipids from Heliotropium ophioglossum.

Science.gov (United States)

Firdous, Sadiqa; Ansari, Nida Hassan; Fatima, Itrat; Malik, Abdul; Afza, Nighat; Iqbal, Lubna; Lateef, Mehreen

2012-07-01

Ophiamides A (1) and B (2), two new sphingolipids have been isolated from the n-hexane subfraction of the MeOH extract of the whole plant of Heliotropium ophioglossum along with glycerol monopalmitate (3) and β-sitosterol 3-O-β-D: -glucoside (4) reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS and 2D-NMR spectroscopy. Both the compounds 1 and 2 showed potent inhibitory activity against the enzyme urease.

19q13.12 microdeletion syndrome fibroblasts display abnormal storage of cholesterol and sphingolipids in the endo-lysosomal system.

Science.gov (United States)

Zhao, Kexin; van der Spoel, Aarnoud; Castiglioni, Claudia; Gale, Sarah; Fujiwara, Hideji; Ory, Daniel S; Ridgway, Neale D

2018-06-01

Microdeletions in 19q12q13.12 cause a rare and complex haploinsufficiency syndrome characterized by intellectual deficiency, developmental delays, and neurological movement disorders. Variability in the size and interval of the deletions makes it difficult to attribute the complex clinical phenotype of this syndrome to an underlying gene(s). As an alternate approach, we examined the biochemical and metabolic features of fibroblasts from an affected individual to derive clues as to the molecular basis for the syndrome. Immunofluorescence and electron microscopy of affected fibroblasts revealed an abnormal endo-lysosomal compartment that was characterized by rapid accumulation of lysosomotropic dyes, elevated LAMP1 and LAMP2 expression and vacuoles containing membrane whorls, common features of lysosomal lipid storage disorders. The late endosomes-lysosomes (LE/LY) of affected fibroblasts accumulated low-density lipoprotein cholesterol, and displayed reduced cholesterol esterification and increased de novo cholesterol synthesis, indicative of defective cholesterol transport to the endoplasmic reticulum. Affected fibroblasts also had increased ceramide and sphingolipid mass, altered glycosphingolipid species and accumulation of a fluorescent lactosylceramide probe in LE/LY. Autophagosomes also accumulated in affected fibroblasts because of decreased fusion with autolysosomes, a defect associated with other lysosomal storage diseases. Attempts to correct the cholesterol/sphingolipid storage defect in fibroblasts with cyclodextrin, sphingolipid synthesis inhibitors or by altering ion transport were unsuccessful. Our data show that 19q13.12 deletion fibroblasts have abnormal accumulation of cholesterol and sphingolipids in the endo-lysosomal system that compromises organelle function and could be an underlying cause of the clinical features of the syndrome. Copyright © 2018 Elsevier B.V. All rights reserved.

Fumonisin B₁ (FB₁) Induces Lamellar Separation and Alters Sphingolipid Metabolism of In Vitro Cultured Hoof Explants.

Science.gov (United States)

Reisinger, Nicole; Dohnal, Ilse; Nagl, Veronika; Schaumberger, Simone; Schatzmayr, Gerd; Mayer, Elisabeth

2016-03-24

One of the most important hoof diseases is laminitis. Yet, the pathology of laminitis is not fully understood. Different bacterial toxins, e.g. endotoxins or exotoxins, seem to play an important role. Additionally, ingestion of mycotoxins, toxic secondary metabolites of fungi, might contribute to the onset of laminitis. In this respect, fumonsins are of special interest since horses are regarded as species most susceptible to this group of mycotoxins. The aim of our study was to investigate the influence of fumonisin B₁ (FB₁) on primary isolated epidermal and dermal hoof cells, as well as on the lamellar tissue integrity and sphingolipid metabolism of hoof explants in vitro. There was no effect of FB₁ at any concentration on dermal or epidermal cells. However, FB₁ significantly reduced the separation force of explants after 24 h of incubation. The Sa/So ratio was significantly increased in supernatants of explants incubated with FB₁ (2.5-10 µg/mL) after 24 h. Observed effects on Sa/So ratio were linked to significantly increased sphinganine concentrations. Our study showed that FB₁ impairs the sphingolipid metabolism of explants and reduces lamellar integrity at non-cytotoxic concentrations. FB₁ might, therefore, affect hoof health. Further in vitro and in vivo studies are necessary to elucidate the effects of FB₁ on the equine hoof in more detail.

Occurrence of bioactive sphingolipids in meat and fish products

DEFF Research Database (Denmark)

Hellgren, Lars

2001-01-01

/neutral glycolipids varied from 1 to 2.9, while in poultry this ratio varied between 5.2 to 19.2 and in red meat it varied from 1.6 to 8.3. The fatty acid composition of sphingomyelin in fish was dominated by C24:1 (Delta (9)) or C22:1 (Delta (9)), while C16:0 and C18:0 were the dominating sphingomyelin species....... Therefore we investigated the contents of sphingomyelin and neutral glycosphingolipids in commonly consumed meat and fish products. Sphingomyelin and glycosphingolipids were found in all foodstuffs studied. The total amount varied between 118 +/- 17 nmol/g (cod) to 589 +/- 39 nmol/g (chicken leg). Generally......, lower amounts of sphingolipids were determined in fish meat than in red meat and poultry, while poultry was the richest source of this class of lipids. However, fish meat contained a relatively high content of neutral glycolipids compared with other types of meat. Thus, in fish the ratio sphingomyelin...

Membrane organization determines barrier properties of endothelial cells and short-chain sphingolipid-facilitated doxorubicin influx.

Science.gov (United States)

van Hell, A J; Klymchenko, A; Gueth, D M; van Blitterswijk, W J; Koning, G A; Verheij, M

2014-09-01

The endothelial lining and its outer lipid membrane are the first major barriers drug molecules encounter upon intravenous administration. Our previous work identified lipid analogs that counteract plasma membrane barrier function for a series of amphiphilic drugs. For example, short-chain sphingolipids (SCS), like N-octanoyl-glucosylceramide, effectively elevated doxorubicin accumulation in tumor cells, both in vitro and in vivo, and in endothelial cells, whereas other (normal) cells remained unaffected. We hypothesize here that local membrane lipid composition and the degree of lipid ordering define SCS efficacy in individual cells. To this end, we study the differential effect of SCS on bovine aortic endothelial cells (BAEC) in its confluent versus proliferative state, as a model system. While their (plasma membrane) lipidome stays remarkably unaltered when BAECs reach confluency, their lipids segregate to form apical and basolateral domains. Using probe NR12S, we reveal that lipids in the apical membrane are more condensed/liquid-ordered. SCS preferentially attenuate the barrier posed by these condensed membranes and facilitate doxorubicin influx in these particular membrane regions. We confirm these findings in MDCK cells and artificial membranes. In conclusion, SCS-facilitated drug traversal acts on condensed membrane domains, elicited by confluency in resting endothelium. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficient replacement of plasma membrane outer leaflet phospholipids and sphingolipids in cells with exogenous lipids.

Science.gov (United States)

Li, Guangtao; Kim, JiHyun; Huang, Zhen; St Clair, Johnna R; Brown, Deborah A; London, Erwin

2016-12-06

Our understanding of membranes and membrane lipid function has lagged far behind that of nucleic acids and proteins, largely because it is difficult to manipulate cellular membrane lipid composition. To help solve this problem, we show that methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange can be used to maximally replace the sphingolipids and phospholipids in the outer leaflet of the plasma membrane of living mammalian cells with exogenous lipids, including unnatural lipids. In addition, lipid exchange experiments revealed that 70-80% of cell sphingomyelin resided in the plasma membrane outer leaflet; the asymmetry of metabolically active cells was similar to that previously defined for erythrocytes, as judged by outer leaflet lipid composition; and plasma membrane outer leaflet phosphatidylcholine had a significantly lower level of unsaturation than phosphatidylcholine in the remainder of the cell. The data also provided a rough estimate for the total cellular lipids residing in the plasma membrane (about half). In addition to such lipidomics applications, the exchange method should have wide potential for investigations of lipid function and modification of cellular behavior by modification of lipids.

Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B{sub 1}

Energy Technology Data Exchange (ETDEWEB)

Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S; Swanevelder, Sonja

2004-07-15

In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B{sub 1} (FB{sub 1}) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB{sub 1} containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB{sub 1} dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB{sub 1} treatment in the control rats was significantly (P<0.05) enhanced by the 2-AAF/PH cancer promotion treatment. The nodular and surrounding Sa levels returned to baseline following FB{sub 1} initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB{sub 1} treatment, the initiation effected by FB{sub 1} was less (P<0.01) sensitive to the accumulation of Sa in the nodular and surrounding tissues than DEN initiation and the 2-AAF/PH control treatment. In contrast, the So level of FB{sub 1} initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P<0.05) higher with the secondary FB{sub 1} treatment. Although, the FB{sub 1}-induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

Vitamin E γ-Tocotrienol Inhibits Cytokine-Stimulated NF-κB Activation by Induction of Anti-Inflammatory A20 via Stress Adaptive Response Due to Modulation of Sphingolipids.

Science.gov (United States)

Wang, Yun; Park, Na-Young; Jang, Yumi; Ma, Averil; Jiang, Qing

2015-07-01

NF-κB plays a central role in pathogenesis of inflammation and cancer. Many phytochemicals, including γ-tocotrienol (γTE), a natural form of vitamin E, have been shown to inhibit NF-κB activation, but the underlying mechanism has not been identified. In this study, we show that γTE inhibited cytokine-triggered activation of NF-κB and its upstream regulator TGF-β-activated kinase-1 in murine RAW 264.7 macrophages and primary bone marrow-derived macrophages. In these cells, γTE induced upregulation of A20, an inhibitor of NF-κB. Knockout of A20 partially diminished γTE's anti-NF-κB effect, but γTE increased another NF-κB inhibitor, Cezanne, in A20(-/-) cells. In search of the reason for A20 upregulation, we found that γTE treatment increased phosphorylation of translation initiation factor 2, IκBα, and JNK, indicating induction of endoplasmic reticulum stress. Liquid chromatography-tandem mass spectrometry analyses revealed that γTE modulated sphingolipids, including enhancement of intracellular dihydroceramides, sphingoid bases in de novo synthesis of the sphingolipid pathway. Chemical inhibition of de novo sphingolipid synthesis partially reversed γTE's induction of A20 and the anti-NF-κB effect. The importance of dihydroceramide increase is further supported by the observation that C8-dihydroceramide mimicked γTE in upregulating A20, enhancing endoplasmic reticulum stress, and attenuating TNF-triggered NF-κB activation. Our study identifies a novel anti-NF-κB mechanism where A20 is induced by stress-induced adaptive response as a result of modulation of sphingolipids, and it demonstrates an immunomodulatory role of dihydrocermides. Copyright © 2015 by The American Association of Immunologists, Inc.

Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites.

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Mina, John G; Thye, Julie K; Alqaisi, Amjed Q I; Bird, Louise E; Dods, Robert H; Grøftehauge, Morten K; Mosely, Jackie A; Pratt, Steven; Shams-Eldin, Hosam; Schwarz, Ralph T; Pohl, Ehmke; Denny, Paul W

2017-07-21

Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipids are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation, and analyses of the Toxoplasma serine palmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipid biosynthesis: the condensation of serine and palmitoyl-CoA. In all eukaryotes analyzed to date, serine palmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serine palmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serine palmitoyltransferase, identified in the Sphingomonadaceae as a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

4-Hydroxynonenal Contributes to Angiogenesis through a Redox-Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

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Caroline Camaré

2017-01-01

Full Text Available The neovascularization of atherosclerotic lesions is involved in plaque development and may contribute to intraplaque hemorrhage and plaque fragilization and rupture. Among the various proangiogenic agents involved in the neovascularization process, proatherogenic oxidized LDLs (oxLDLs contribute to the formation of tubes via the generation of sphingosine 1-phosphate (S1P, a major mitogenic and proangiogenic sphingolipid mediator. In this study, we investigated whether 4-hydroxynonenal (4-HNE, an aldehydic lipid oxidation product abundantly present in oxLDLs, contributes to their proangiogenic properties. Immunofluorescence analysis of human atherosclerotic lesions from carotid endarterectomy showed the colocalization of HNE-adducts with CD31, a marker of endothelial cells, suggesting a close relationship between 4-HNE and neovessel formation. In vitro, low 4-HNE concentration (0.5–1 µM elicited the formation of tubes by human microvascular endothelial cells (HMEC-1, whereas higher concentrations were not angiogenic. The formation of tubes by 4-HNE involved the generation of reactive oxygen species and the activation of the sphingolipid pathway, namely, the neutral type 2 sphingomyelinase and sphingosine kinase-1 (nSMase2/SK-1 pathway, indicating a role for S1P in the angiogenic signaling of 4-HNE. Carbonyl scavengers hydralazine and bisvanillyl-hydralazone inhibited the nSMase2/SK1 pathway activation and the formation of tubes on Matrigel® evoked by 4-HNE. Altogether, these results emphasize the role of 4-HNE in the angiogenic effect of oxLDLs and point out the potential interest of pharmacological carbonyl scavengers to prevent the neovascularization process.

A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise.

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Saleem, Mahwesh; Herrmann, Nathan; Dinoff, Adam; Mielke, Michelle M; Oh, Paul I; Shammi, Prathiba; Cao, Xingshan; Venkata, Swarajya Lakshmi Vattem; Haughey, Norman J; Lanctôt, Krista L

2017-01-01

Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program. Patients with CAD (n = 120, mean age = 64±6 y, 84% male, years of education = 16±3) underwent CR with neuropsychological assessments and blood collected at baseline, 3-, and 6-months. Z-scores based on age, gender, and education were combined for verbal memory, visuospatial memory, processing speed, executive function, and global cognition tasks to calculate cognitive domain Z-scores. Plasma sphingolipid concentrations were measured from fasting blood samples using high performance liquid chromatography coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Mixed models were used to identify sphingolipids significantly associated with performance in verbal memory and other cognitive domains, adjusting for potential confounders. A decrease in ceramide C18:0 concentration was significantly associated with improvement in verbal memory performance (b[SE] = -0.51 [0.25], p = 0.04), visuospatial memory (b[SE] = -0.44 [0.22], p = 0.05), processing speed (b[SE] = -0.89 [0.32], p = 0.007), and global cognition (b[SE] = -1.47 [0.59], p = 0.01) over 6 months of CR. Plasma ceramide C18:0 concentrations may be a sensitive marker of cognitive response to exercise in patients with CAD.

Cutaneous water loss and sphingolipids in the stratum corneum of house sparrows, Passer domesticus L., from desert and mesic environments as determined by reversed phase high-performance liquid chromatography coupled with atmospheric pressure photospray ionization mass spectrometry.

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Muñoz-Garcia, Agustí; Ro, Jennifer; Brown, Johnie C; Williams, Joseph B

2008-02-01

Because cutaneous water loss (CWL) represents half of total water loss in birds, selection to reduce CWL may be strong in desert birds. We previously found that CWL of house sparrows from a desert population was about 25% lower than that of individuals from a mesic environment. The stratum corneum (SC), the outer layer of the epidermis, serves as the primary barrier to water vapor diffusion through the skin. The avian SC is formed by layers of corneocytes embedded in a lipid matrix consisting of cholesterol, free fatty acids and two classes of sphingolipids, ceramides and cerebrosides. The SC of birds also serves a thermoregulatory function; high rates of CWL keep body temperatures under lethal limits in episodes of heat stress. In this study, we used high-performance liquid chromatography coupled with atmospheric pressure photoionization-mass spectrometry (HPLC/APPI-MS) to identify and quantify over 200 sphingolipids in the SC of house sparrows from desert and mesic populations. Principal components analysis (PCA) led to the hypotheses that sphingolipids in the SC of desert sparrows have longer carbon chains in the fatty acid moiety and are more polar than those found in mesic sparrows. We also tested the association between principal components and CWL in both populations. Our study suggested that a reduction in CWL found in desert sparrows was, in part, the result of modifications in chain length and polarity of the sphingolipids, changes that apparently determine the interactions of the lipid molecules within the SC.

Comparative effects of fumonisins on sphingolipid metabolism and toxicity in ducks and turkeys.

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Benlasher, Emad; Geng, Xiuyu; Nguyen, Ngoc Thanh Xuan; Tardieu, Didier; Bailly, Jean-Denis; Auvergne, Alain; Guerre, Philippe

2012-03-01

Fumonisins (FBs) are mycotoxins that are found worldwide in maize and maize products. Their main toxic effects have been well characterized in poultry, but differences between species have been demonstrated. Ducks appeared very sensitive to toxicity, whereas turkeys are more resistant. At the same time, alterations of sphingolipid metabolism, with an increase of the concentration of the free sphinganine (Sa) in serum and liver, have been demonstrated in the two species, but the link between the toxicity of FBs and Sa accumulation remains difficult to interpret. The aim of the present work was to compare the effects of FBs (10 mg FB1 + FB2/kg body weight) on sphingolipid metabolism in ducks and turkeys. Growth, feed consumption, and serum biochemistry were also investigated to evaluate toxicity. The main results showed that FBs increased Sa concentrations in liver and serum in ducks and turkeys, but these accumulations were not directly correlated with toxicity. Sa accumulation was higher in the livers of turkeys than in ducks, whereas Sa levels were higher in the sera of ducks than in turkeys. Hepatic toxicity was more pronounced in ducks than in turkeys and accompanied a decrease of body weight and an increase of serum biochemistry in ducks but not in turkeys. So, although FBs increase Sa concentration in the livers of both species, this effect is not directly proportional to toxicity. The mechanisms of FB toxicity and/or the mechanisms of protection of ducks and turkeys to the Sa accumulation within the liver remain to be established.

Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?

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Guillas, Isabelle; Puyaubert, Juliette; Baudouin, Emmanuel

2013-09-12

Nitric oxide (NO) emerged as one of the major signaling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of NO into complex signaling networks. Beside the close relationships between NO and calcium or phosphatidic acid signaling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids (SLs). This mini-review summarizes our current knowledge of the influence NO and SLs might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although SL-NO interplays are common features in signaling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.

Making Sense of the Yeast Sphingolipid Pathway.

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Megyeri, Márton; Riezman, Howard; Schuldiner, Maya; Futerman, Anthony H

2016-12-04

Sphingolipids (SL) and their metabolites play key roles both as structural components of membranes and as signaling molecules. Many of the key enzymes and regulators of SL metabolism were discovered using the yeast Saccharomyces cerevisiae, and based on the high degree of conservation, a number of mammalian homologs were identified. Although yeast continues to be an important tool for SL research, the complexity of SL structure and nomenclature often hampers the ability of new researchers to grasp the subtleties of yeast SL biology and discover new modulators of this intricate pathway. Moreover, the emergence of lipidomics by mass spectrometry has enabled the rapid identification of SL species in yeast and rendered the analysis of SL composition under various physiological and pathophysiological conditions readily amenable. However, the complex nomenclature of the identified species renders much of the data inaccessible to non-specialists. In this review, we focus on parsing both the classical SL nomenclature and the nomenclature normally used during mass spectrometry analysis, which should facilitate the understanding of yeast SL data and might shed light on biological processes in which SLs are involved. Finally, we discuss a number of putative roles of various yeast SL species. Copyright © 2016 Elsevier Ltd. All rights reserved.

A combined fluorescence spectroscopy, confocal and 2-photon microscopy approach to re-evaluate the properties of sphingolipid domains.

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Pinto, Sandra N; Fernandes, Fábio; Fedorov, Alexander; Futerman, Anthony H; Silva, Liana C; Prieto, Manuel

2013-09-01

The aim of this study is to provide further insight about the interplay between important signaling lipids and to characterize the properties of the lipid domains formed by those lipids in membranes containing distinct composition. To this end, we have used a combination of fluorescence spectroscopy, confocal and two-photon microscopy and a stepwise approach to re-evaluate the biophysical properties of sphingolipid domains, particularly lipid rafts and ceramide (Cer)-platforms. By using this strategy we were able to show that, in binary mixtures, sphingolipids (Cer and sphingomyelin, SM) form more tightly packed gel domains than those formed by phospholipids with similar acyl chain length. In more complex lipid mixtures, the interaction between the different lipids is intricate and is strongly dictated by the Cer-to-Chol ratio. The results show that in quaternary phospholipid/SM/Chol/Cer mixtures, Cer forms gel domains that become less packed as Chol is increased. Moreover, the extent of gel phase formation is strongly reduced in these mixtures, even though Cer molar fraction is increased. These results suggest that in biological membranes, lipid domains such as rafts and ceramide platforms, might display distinctive biophysical properties depending on the local lipid composition at the site of the membrane where they are formed, further highlighting the potential role of membrane biophysical properties as an underlying mechanism for mediating specific biological processes. Copyright © 2013 Elsevier B.V. All rights reserved.

Extensive sphingolipid depletion does not affect lipid raft integrity or lipid raft localization and efflux function of the ABC transporter MRP1

NARCIS (Netherlands)

Klappe, Karin; Dijkhuis, Anne-Jan; Hummel, Ina; van Dam, Annie; Ivanova, Pavlina T.; Milne, Stephen B.; Myers, David S.; Brown, H. Alex; Permentier, Hjalmar; Kok, Jan W.

2010-01-01

We show that highly efficient depletion of sphingolipids in two different cell lines does not abrogate the ability to isolate Lubrol-based DRMs (detergent-resistant membranes) or detergent-free lipid rafts from these cells. Compared with control, DRM/detergent-free lipid raft fractions contain equal

Arabidopsis dynamin-related protein 1E in sphingolipid-enriched plasma membrane domains is associated with the development of freezing tolerance.

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Minami, Anzu; Tominaga, Yoko; Furuto, Akari; Kondo, Mariko; Kawamura, Yukio; Uemura, Matsuo

2015-08-01

The freezing tolerance of Arabidopsis thaliana is enhanced by cold acclimation, resulting in changes in the compositions and function of the plasma membrane. Here, we show that a dynamin-related protein 1E (DRP1E), which is thought to function in the vesicle trafficking pathway in cells, is related to an increase in freezing tolerance during cold acclimation. DRP1E accumulated in sphingolipid and sterol-enriched plasma membrane domains after cold acclimation. Analysis of drp1e mutants clearly showed that DRP1E is required for full development of freezing tolerance after cold acclimation. DRP1E fused with green fluorescent protein was visible as small foci that overlapped with fluorescent dye-labelled plasma membrane, providing evidence that DRP1E localizes non-uniformly in specific areas of the plasma membrane. These results suggest that DRP1E accumulates in sphingolipid and sterol-enriched plasma membrane domains and plays a role in freezing tolerance development during cold acclimation. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Identification of Two Suppressors of CSG2 Calcium Sensitivity, SCS7 and SUR2, as Genes Encoding Hydroxylases of the Sphingolipid Biosynthetic Pathway of Saccharomyces cerevisiae

National Research Council Canada - National Science Library

Haak, Dale A

1997-01-01

.... The biochemical significance of much of this structural variability is not well understood. The sphingolipids of the yeast Saccharomyces cerevisiae undergo the a-hydroxylation of the very long chain fatty acid (VLCFA...

Profiling of Plasma Metabolites Suggests Altered Mitochondrial Fuel Usage and Remodeling of Sphingolipid Metabolism in Individuals With Type 2 Diabetes and Kidney Disease

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Jian-Jun Liu

2017-05-01

Discussion: DKD is associated with altered fuel substrate use and remodeling of sphingolipid metabolism in T2DM with DKD. Associations of albuminuria and impaired filtration function with distinct metabolomic signatures suggest different pathophysiology underlying these 2 manifestations of DKD.

The Impact of Cholesterol, DHA, and Sphingolipids on Alzheimer’s Disease

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Marcus O. W. Grimm

2013-01-01

Full Text Available Alzheimer’s disease (AD is a devastating neurodegenerative disorder currently affecting over 35 million people worldwide. Pathological hallmarks of AD are massive amyloidosis, extracellular senile plaques, and intracellular neurofibrillary tangles accompanied by an excessive loss of synapses. Major constituents of senile plaques are 40–42 amino acid long peptides termed β-amyloid (Aβ. Aβ is produced by sequential proteolytic processing of the amyloid precursor protein (APP. APP processing and Aβ production have been one of the central scopes in AD research in the past. In the last years, lipids and lipid-related issues are more frequently discussed to contribute to the AD pathogenesis. This review summarizes lipid alterations found in AD postmortem brains, AD transgenic mouse models, and the current understanding of how lipids influence the molecular mechanisms leading to AD and Aβ generation, focusing especially on cholesterol, docosahexaenoic acid (DHA, and sphingolipids/glycosphingolipids.

The effect of the bioactive sphingolipids S1P and C1P on multipotent stromal cells--new opportunities in regenerative medicine.

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Marycz, Krzysztof; Śmieszek, Agnieszka; Jeleń, Marta; Chrząstek, Klaudia; Grzesiak, Jakub; Meissner, Justyna

2015-09-01

Sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) belong to a family of bioactive sphingolipids that act as important extracellular signaling molecules and chemoattractants. This study investigated the influence of S1P and C1P on the morphology, proliferation activity and osteogenic properties of rat multipotent stromal cells derived from bone marrow (BMSCs) and subcutaneous adipose tissue (ASCs). We show that S1P and C1P can influence mesenchymal stem cells (MSCs), each in a different manner. S1P stimulation promoted the formation of cellular aggregates of BMSCs and ASCs, while C1P had an effect on the regular growth pattern and expanded intercellular connections, thereby increasing the proliferative activity. Although osteogenic differentiation of MSCs was enhanced by the addition of S1P, the effectiveness of osteoblast differentiation was more evident in BMSCs, particularly when biochemical and molecular marker levels were considered. The results of the functional osteogenic differentiation assay, which includes an evaluation of the efficiency of extracellular matrix mineralization (SEM-EDX), revealed the formation of numerous mineral aggregates in BMSC cultures stimulated with S1P. Our data demonstrated that in an appropriate combination, the bioactive sphingolipids S1P and C1P may find wide application in regenerative medicine, particularly in bone regeneration with the use of MSCs.

Segregation of sphingolipids and sterols during formation of secretory vesicles at the trans-Golgi network

DEFF Research Database (Denmark)

Klemm, Robin W; Ejsing, Christer S.; Surma, Michal A

2009-01-01

The trans-Golgi network (TGN) is the major sorting station in the secretory pathway of all eukaryotic cells. How the TGN sorts proteins and lipids to generate the enrichment of sphingolipids and sterols at the plasma membrane is poorly understood. To address this fundamental question in membrane...... trafficking, we devised an immunoisolation procedure for specific recovery of post-Golgi secretory vesicles transporting a transmembrane raft protein from the TGN to the cell surface in the yeast Saccharomyces cerevisiae. Using a novel quantitative shotgun lipidomics approach, we could demonstrate that TGN...... than the late Golgi membrane, as measured by C-Laurdan spectrophotometry, strongly suggests that lipid rafts play a role in the TGN-sorting machinery....

A comprehensive lipidomic screen of pancreatic β-cells using mass spectroscopy defines novel features of glucose-stimulated turnover of neutral lipids, sphingolipids and plasmalogens

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Gemma L. Pearson

2016-06-01

Full Text Available Objective: Glucose promotes lipid remodelling in pancreatic β-cells, and this is thought to contribute to the regulation of insulin secretion, but the metabolic pathways and potential signalling intermediates have not been fully elaborated. Methods: Using mass spectrometry (MS we quantified changes in approximately 300 lipid metabolites in MIN6 β-cells and isolated mouse islets following 1 h stimulation with glucose. Flux through sphingolipid pathways was also assessed in 3H-sphinganine-labelled cells using TLC. Results: Glucose specifically activates the conversion of triacylglycerol (TAG to diacylglycerol (DAG. This leads indirectly to the formation of 18:1 monoacylglycerol (MAG, via degradation of saturated/monounsaturated DAG species, such as 16:0_18:1 DAG, which are the most abundant, immediate products of glucose-stimulated TAG hydrolysis. However, 16:0-containing, di-saturated DAG species are a better direct marker of TAG hydrolysis since, unlike the 18:1-containing DAGs, they are predominately formed via this route. Using multiple reaction monitoring, we confirmed that in islets under basal conditions, 18:1 MAG is the most abundant species. We further demonstrated a novel site of glucose to enhance the conversion of ceramide to sphingomyelin (SM and galactosylceramide (GalCer. Flux and product:precursor analyses suggest regulation of the enzyme SM synthase, which would constitute a separate mechanism for localized generation of DAG in response to glucose. Phosphatidylcholine (PC plasmalogen (P species, specifically those containing 20:4, 22:5 and 22:6 side chains, were also diminished in the presence of glucose, whereas the more abundant phosphatidylethanolamine plasmalogens were unchanged. Conclusion: Our results highlight 18:1 MAG, GalCer, PC(P and DAG/SM as potential contributors to metabolic stimulus-secretion coupling. Author Video: Author Video Watch what authors say about their articles Keywords: Pancreatic β-cell, Insulin

Sphingosine-1-Phosphate Lyase Deficient Cells as a Tool to Study Protein Lipid Interactions.

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Mathias J Gerl

Full Text Available Cell membranes contain hundreds to thousands of individual lipid species that are of structural importance but also specifically interact with proteins. Due to their highly controlled synthesis and role in signaling events sphingolipids are an intensely studied class of lipids. In order to investigate their metabolism and to study proteins interacting with sphingolipids, metabolic labeling based on photoactivatable sphingoid bases is the most straightforward approach. In order to monitor protein-lipid-crosslink products, sphingosine derivatives containing a reporter moiety, such as a radiolabel or a clickable group, are used. In normal cells, degradation of sphingoid bases via action of the checkpoint enzyme sphingosine-1-phosphate lyase occurs at position C2-C3 of the sphingoid base and channels the resulting hexadecenal into the glycerolipid biosynthesis pathway. In case the functionalized sphingosine looses the reporter moiety during its degradation, specificity towards sphingolipid labeling is maintained. In case degradation of a sphingosine derivative does not remove either the photoactivatable or reporter group from the resulting hexadecenal, specificity towards sphingolipid labeling can be achieved by blocking sphingosine-1-phosphate lyase activity and thus preventing sphingosine derivatives to be channeled into the sphingolipid-to-glycerolipid metabolic pathway. Here we report an approach using clustered, regularly interspaced, short palindromic repeats (CRISPR-associated nuclease Cas9 to create a sphingosine-1-phosphate lyase (SGPL1 HeLa knockout cell line to disrupt the sphingolipid-to-glycerolipid metabolic pathway. We found that the lipid and protein compositions as well as sphingolipid metabolism of SGPL1 knock-out HeLa cells only show little adaptations, which validates these cells as model systems to study transient protein-sphingolipid interactions.

Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

Science.gov (United States)

Mor, Visesato; Rella, Antonella; Farnoud, Amir M.; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B.; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J.; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B.; Wiederhold, Nathan P.; Fothergill, Annette W.; Kirkpatrick, William R.; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L.; Luberto, Chiara; Nimrichter, Leonardo

2015-01-01

ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. PMID:26106079

Defining asthma in genetic studies

NARCIS (Netherlands)

Koppelman, GH; Postma, DS; Meijer, G.

1999-01-01

Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define

Production of α-galactosylceramide by a prominent member of the human gut microbiota.

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Laura C Wieland Brown

2013-07-01

Full Text Available While the human gut microbiota are suspected to produce diffusible small molecules that modulate host signaling pathways, few of these molecules have been identified. Species of Bacteroides and their relatives, which often comprise >50% of the gut community, are unusual among bacteria in that their membrane is rich in sphingolipids, a class of signaling molecules that play a key role in inducing apoptosis and modulating the host immune response. Although known for more than three decades, the full repertoire of Bacteroides sphingolipids has not been defined. Here, we use a combination of genetics and chemistry to identify the sphingolipids produced by Bacteroides fragilis NCTC 9343. We constructed a deletion mutant of BF2461, a putative serine palmitoyltransferase whose yeast homolog catalyzes the committed step in sphingolipid biosynthesis. We show that the Δ2461 mutant is sphingolipid deficient, enabling us to purify and solve the structures of three alkaline-stable lipids present in the wild-type strain but absent from the mutant. The first compound was the known sphingolipid ceramide phosphorylethanolamine, and the second was its corresponding dihydroceramide base. Unexpectedly, the third compound was the glycosphingolipid α-galactosylceramide (α-GalCer(Bf, which is structurally related to a sponge-derived sphingolipid (α-GalCer, KRN7000 that is the prototypical agonist of CD1d-restricted natural killer T (iNKT cells. We demonstrate that α-GalCer(Bf has similar immunological properties to KRN7000: it binds to CD1d and activates both mouse and human iNKT cells both in vitro and in vivo. Thus, our study reveals BF2461 as the first known member of the Bacteroides sphingolipid pathway, and it indicates that the committed steps of the Bacteroides and eukaryotic sphingolipid pathways are identical. Moreover, our data suggest that some Bacteroides sphingolipids might influence host immune homeostasis.

Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation

Science.gov (United States)

Giorni, Paola; Dall’Asta, Chiara; Reverberi, Massimo; Scala, Valeria; Ludovici, Matteo; Cirlini, Martina; Galaverna, Gianni; Fanelli, Corrado; Battilani, Paola

2015-01-01

Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host–pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantly with maize ripening. Oxylipins and phytoceramides changed significantly within the hybrids and decreased with kernel maturation, starting from physiological maturity. Although the correlation between fumonisin accumulation and plant lipid profile is certain, the data collected so far cannot define a cause-effect relationship but open up new perspectives. Therefore, the question—“Does fumonisin alter plant lipidome or does plant lipidome modulate fumonisin accumulation?”—is still open. PMID:26378580

Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation

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Paola Giorni

2015-09-01

Full Text Available Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host–pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantly with maize ripening. Oxylipins and phytoceramides changed significantly within the hybrids and decreased with kernel maturation, starting from physiological maturity. Although the correlation between fumonisin accumulation and plant lipid profile is certain, the data collected so far cannot define a cause-effect relationship but open up new perspectives. Therefore, the question—“Does fumonisin alter plant lipidome or does plant lipidome modulate fumonisin accumulation?”—is still open.

Serum profiling of healthy aging identifies phospho- and sphingolipid species as markers of human longevity.

Science.gov (United States)

Montoliu, Ivan; Scherer, Max; Beguelin, Fiona; DaSilva, Laeticia; Mari, Daniela; Salvioli, Stefano; Martin, Francois-Pierre J; Capri, Miriam; Bucci, Laura; Ostan, Rita; Garagnani, Paolo; Monti, Daniela; Biagi, Elena; Brigidi, Patrizia; Kussmann, Martin; Rezzi, Serge; Franceschi, Claudio; Collino, Sebastiano

2014-01-01

As centenarians well represent the model of healthy aging, there are many important implications in revealing the underlying molecular mechanisms behind such successful aging. By combining NMR metabonomics and shot-gun lipidomics in serum we analyzed metabolome and lipidome composition of a group of centenarians with respect to elderly individuals. Specifically, NMR metabonomics profiling of serum revealed that centenarians are characterized by a metabolic phenotype distinct from that of elderly subjects, in particular regarding amino acids and lipid species. Shot- gun lipidomics approach displays unique changes in lipids biosynthesis in centenarians, with 41 differently abundant lipid species with respect to elderly subjects. These findings reveal phospho/sphingolipids as putative markers and biological modulators of healthy aging, in humans. Considering the particular actions of these metabolites, these data are suggestive of a better counteractive antioxidant capacity and a well-developed membrane lipid remodelling process in the healthy aging phenotype.

Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.

Science.gov (United States)

Saroha, Ashish; Pewzner-Jung, Yael; Ferreira, Natalia S; Sharma, Piyush; Jouan, Youenn; Kelly, Samuel L; Feldmesser, Ester; Merrill, Alfred H; Trottein, François; Paget, Christophe; Lang, Karl S; Futerman, Anthony H

2017-01-01

The role of sphingolipids (SLs) in the immune system has come under increasing scrutiny recently due to the emerging contributions that these important membrane components play in regulating a variety of immunological processes. The acyl chain length of SLs appears particularly critical in determining SL function. Here, we show a role for very-long acyl chain SLs (VLC-SLs) in invariant natural killer T ( i NKT) cell maturation in the thymus and homeostasis in the liver. Ceramide synthase 2-null mice, which lack VLC-SLs, were susceptible to a hepatotropic strain of lymphocytic choriomeningitis virus, which is due to a reduction in the number of i NKT cells. Bone marrow chimera experiments indicated that hematopoietic-derived VLC-SLs are essential for maturation of i NKT cells in the thymus, whereas parenchymal-derived VLC-SLs are crucial for i NKT cell survival and maintenance in the liver. Our findings suggest a critical role for VLC-SL in i NKT cell physiology.

Sphingosine basis in milk

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Slavica Ribar

2006-12-01

Full Text Available Sphingolipids are widespread membrane components that are found in all eukaryotic cells. They are defined as compounds having a long-chain sphingoid base as the backbone. The most frequent long-chain bases in most of the mammals are D-erythro-sphinganine and sphingosine. Sphingolipids can be expected in minor quantities in all food products. Milk fat contains a number of different sphingolipid classes. Originally they were presumed to contribute to the structural integrity of membranes, but there nowadays it is confirmed that they have an important physiological role. Dietary sphingolipids have gained attention because of their possibility to inhibit colon cancer. The aim of this study was to determine the concentrations of free and total sphinganine and sphingosine in milk (human, cow's, sheep’s, goat’s, soy’s Sphingolipids were extracted from milk. Free and total sphingoid bases were obtained by alkaline and acid hydrolysis respectively. Sphinganin and sphingosine were determined by means of high-performance liquid chromatography. The results of this research illustrate the differences between the concentrations of sphingoid bases in cow’s milk with various content of milk fat. The concentrations of free sphingosine and sphinganine in cow’s milk were lower than in human milk. In sheep’s and goat’s milk, the concentrations of total sphingoid bases were higher than in human and cow’s milk. Quantity of the most sphingoid bases decreased during pasteurization.

Plasma membrane proteins Slm1 and Slm2 mediate activation of the AGC kinase Ypk1 by TORC2 and sphingolipids in S. cerevisiae.

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Niles, Brad J; Powers, Ted

2012-10-15

The PH domain-containing proteins Slm1 and Slm2 were originally identified as substrates of the rapamycin-insensitive TOR complex 2 (TORC2) and as mediators of signaling by the lipid second messenger phosphatidyl-inositol-4,5-bisphosphate (PI4,5P2) in budding yeast S. cerevisiae. More recently, these proteins have been identified as critical effectors that facilitate phosphorylation and activation of the AGC kinases Ypk1 and Ypk2 by TORC2. Here, we review the molecular basis for this regulation as well as place it within the context of recent findings that have revealed Slm1/2 and TORC2-dependent phosphorylation of Ypk1 is coupled to the biosynthesis of complex sphingolipids and to their levels within the plasma membrane (PM) as well as other forms of PM stress. Together, these studies reveal the existence of an intricate homeostatic feedback mechanism, whereby the activity of these signaling components is linked to the biosynthesis of PM lipids according to cellular need.

Yeast lipids can phase separate into micrometer-scale membrane domains

DEFF Research Database (Denmark)

Klose, Christian; Ejsing, Christer S; Garcia-Saez, Ana J

2010-01-01

The lipid raft concept proposes that biological membranes have the potential to form functional domains based on a selective interaction between sphingolipids and sterols. These domains seem to be involved in signal transduction and vesicular sorting of proteins and lipids. Although there is bioc......The lipid raft concept proposes that biological membranes have the potential to form functional domains based on a selective interaction between sphingolipids and sterols. These domains seem to be involved in signal transduction and vesicular sorting of proteins and lipids. Although...... there is biochemical evidence for lipid raft-dependent protein and lipid sorting in the yeast Saccharomyces cerevisiae, direct evidence for an interaction between yeast sphingolipids and the yeast sterol ergosterol, resulting in membrane domain formation, is lacking. Here we show that model membranes formed from yeast...... total lipid extracts possess an inherent self-organization potential resulting in Ld-Lo phase coexistence at physiologically relevant temperature. Analyses of lipid extracts from mutants defective in sphingolipid metabolism as well as reconstitution of purified yeast lipids in model membranes of defined...

Definably compact groups definable in real closed fields. I

OpenAIRE

Barriga, Eliana

2017-01-01

We study definably compact definably connected groups definable in a sufficiently saturated real closed field $R$. We introduce the notion of group-generic point for $\\bigvee$-definable groups and show the existence of group-generic points for definably compact groups definable in a sufficiently saturated o-minimal expansion of a real closed field. We use this notion along with some properties of generic sets to prove that for every definably compact definably connected group $G$ definable in...

Optimization of ultra-high pressure liquid chromatography - tandem mass spectrometry determination in plasma and red blood cells of four sphingolipids and their evaluation as biomarker candidates of Gaucher's disease.

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Chipeaux, Caroline; de Person, Marine; Burguet, Nathalie; Billette de Villemeur, Thierry; Rose, Christian; Belmatoug, Nadia; Héron, Sylvie; Le Van Kim, Caroline; Franco, Mélanie; Moussa, Fathi

2017-11-24

While important advances have been recently achieved in the optimization of lipid classes' separation, information on the specific determination of medium polarity lipids such as sphingolipids (SLs) in highly complex matrices remains fragmentary. In human, disorders of SL metabolism known as sphingolipidoses are a heterogeneous group of inherited disorders affecting primarily the central nervous. Early diagnosis of these conditions is of importance notably when a corrective therapy is available. The diagnosis is generally based on the determination of specific SLs in plasma and red blood cells (RBCs). For instance, glucosylceramide (GL1), glucosylsphingosine (Lyso-GL1), sphingosine (Sph), and sphingosine-1-phosphate (S1P) are proposed as relevant biomarkers for Gaucher disease (GD). Our main objective was to evaluate these biomarker candidates in a cohort of GD patients. However, most of current methods of GL1, Lyso-GL1, Sph, and S1P determination in plasma of GD patients require at least two liquid chromatographic runs. On the other hand, except for GL1 nothing is known concerning the RBC sphingolipid content. Yet, several reversed phase LC-MS methods of SLs separation and/or determination in various media with different sample preparation approaches have been proposed since 2010. Here we focused on stationary phase selection and mobile phase composition as well as on the sample preparation step to optimize and validate an UHPLC-MS/MS method for the simultaneous quantification of the four sphingolipids in both plasma and RBCs. A comparison between seven stationary phases including two RP18, two polar embedded RP18, and three HILIC phases shows that under our conditions polar embedded RP18 phases are the most appropriate for the separation of the four SLs, in terms of efficiency, peak symmetry, and separation time. In the same way, a comparison between a single step extraction with methanol and a liquid-liquid extraction with a mixture of methanol/methyl tert

Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor

International Nuclear Information System (INIS)

Dewji, N.N.; Wenger, D.A.; O'Brien, J.S.

1987-01-01

Two cDNA clones encoding prepro-sphingolipid activator protein 1 (SAP-1) were isolated from a λ gt11 human hepatoma expression library using polyclonal antibodies. These had inserts of ≅ 2 kilobases (λ-S-1.2 and λ-S-1.3) and both were both homologous with a previously isolated clone (λ-S-1.1) for mature SAP-1. The authors report here the nucleotide sequence of the longer two EcoRI fragments of S-1.2 and S-1.3 that were not the same and the derived amino acid sequences of mature SAP-1 and its prepro form. The open reading frame encodes 19 amino acids, which are colinear with the amino-terminal sequence of mature SAP-1, and extends far beyond the predicted carboxyl terminus of mature SAP-1, indicating extensive carboxyl-terminal processing. The nucleotide sequence of cDNA encoding prepro-SAP-1 includes 1449 bases from the assigned initiation codon ATG at base-pair 472 to the stop codon TGA at base-pair 1921. The first 23 amino acids coded after the initiation ATG are characteristic of a signal peptide. The calculated molecular mass for a polypeptide encoded by 1449 bases is ≅ 53 kDa, in keeping with the reported value for pro-SAP-1. The data indicate that after removal of the signal peptide mature SAP-1 is generated by removing an additional 7 amino acids from the amino terminus and ≅ 373 amino acids from the carboxyl terminus. One potential glycosylation site was previously found in mature SAP-1. Three additional potential glycosylation sites are present in the processed carboxyl-terminal polypeptide, which they designate as P-2

Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

International Nuclear Information System (INIS)

Kamendi, Harriet; Zhou, Ying; Crosby, Meredith; Keirstead, Natalie; Snow, Debra; Bentley, Patricia; Patel, Nilaben; Barthlow, Herbert; Luo, Wenli; Dragan, Yvonne; Bialecki, Russell

2015-01-01

Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

Energy Technology Data Exchange (ETDEWEB)

Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Zhou, Ying, E-mail: yingzhou526@gmail.com [Oncology Innovative Medicines and Early Development, AstraZeneca, Waltham, MA 02451 (United States); Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Keirstead, Natalie, E-mail: Nkeirstead@alnylam.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Snow, Debra, E-mail: Debra.snow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bentley, Patricia, E-mail: patricia.bentley@abbvie.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Patel, Nilaben, E-mail: patelnilaben@yahoo.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Barthlow, Herbert, E-mail: Herbert.barthlow@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Luo, Wenli, E-mail: Wenli.luo@astrazeneca.com [Discovery Sciences, Innovative Medicines, AstraZeneca, Waltham, MA 02451 (United States); Dragan, Yvonne, E-mail: Yvonne.P.Dragan@takeda.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States); Bialecki, Russell, E-mail: russell.bialecki@astrazeneca.com [Drug Safety and Metabolism, AstraZeneca, Waltham, MA 02451 (United States)

2015-12-15

Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalized by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.

Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population

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Wilmar Igl

2013-08-01

Full Text Available Background . The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. Objective . To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. Study design . We compared a group with traditional lifestyle (TLS based on reindeer herding (TLS group with those from the same area with a non-traditional lifestyle (NTLS typical of more industrialized regions of Sweden (NTLS group. The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs and the serum blood level of a number of lipids [total cholesterol (TC, low-density lipoprotein cholesterol (LDL, high-density lipoprotein cholesterol (HDL, triglycerides (TG, glycerophospholipids and sphingolipids]. Results . The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥240 mg/dl, as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. Conclusions . The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

Women's Leadership Development: A Study of Defining Moments

Science.gov (United States)

Dahlvig, Jolyn E.; Longman, Karen A.

2010-01-01

This article reports the findings of a grounded theory study of "defining moments" that were described as pivotal in the personal and professional journeys of women who had been identified as emerging leaders within Christian higher education. Analysis of transcripts from interviews with 16 participants in a Women's Leadership Development…

Animal source food intake and association with blood cholesterol, glycerophospholipids and sphingolipids in a northern Swedish population.

Science.gov (United States)

Igl, Wilmar; Kamal-Eldin, Afaf; Johansson, Asa; Liebisch, Gerhard; Gnewuch, Carsten; Schmitz, Gerd; Gyllensten, Ulf

2013-01-01

The high intake of game meat in populations with a subsistence-based diet may affect their blood lipids and health status. To examine the association between diet and circulating levels of blood lipid levels in a northern Swedish population. We compared a group with traditional lifestyle (TLS) based on reindeer herding (TLS group) with those from the same area with a non-traditional lifestyle (NTLS) typical of more industrialized regions of Sweden (NTLS group). The analysis was based on self-reported intake of animal source food (i.e. non-game meat, game meat, fish, dairy products and eggs) and the serum blood level of a number of lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglycerides (TG), glycerophospholipids and sphingolipids]. The TLS group had higher cholesterol, LDL and HDL levels than the reference group. Of the TLS group, 65% had cholesterol levels above the threshold for increased risk of coronary heart disease (≥ 240 mg/dl), as compared to 38% of the NTLS group. Self-reported consumption of game meat was positively associated with TC and LDL. The high game meat consumption of the TLS group is associated with increased cholesterol levels. High intake of animal protein and fat and low fibre is known to increase the risk of cardiovascular disease, but other studies of the TLS in northern Sweden have shown comparable incidences of cardiovascular disease to the reference (NTLS) group from the same geographical area. This indicates that factors other than TC influence disease risk. One such possible factor is dietary phospholipids, which are also found in high amounts specifically in game meat and have been shown to inhibit cholesterol absorption.

A hybrid mathematical modeling approach of the metabolic fate of a fluorescent sphingolipid analogue to predict cancer chemosensitivity.

Science.gov (United States)

Molina-Mora, J A; Kop-Montero, M; Quirós-Fernández, I; Quiros, S; Crespo-Mariño, J L; Mora-Rodríguez, R A

2018-04-13

Sphingolipid (SL) metabolism is a complex biological system that produces and transforms ceramides and other molecules able to modulate other cellular processes, including survival or death pathways key to cell fate decisions. This signaling pathway integrates several types of stress signals, including chemotherapy, into changes in the activity of its metabolic enzymes, altering thereby the cellular composition of bioactive SLs. Therefore, the SL pathway is a promising sensor of chemosensitivity in cancer and a target hub to overcome resistance. However, there is still a gap in our understanding of how chemotherapeutic drugs can disturb the SL pathway in order to control cellular fate. We propose to bridge this gap by a systems biology approach to integrate i) a dynamic model of SL analogue (BODIPY-FL fluorescent-sphingomyelin analogue, SM-BOD) metabolism, ii) a Gaussian mixture model (GMM) of the fluorescence features to identify how the SL pathway senses the effect of chemotherapy and iii) a fuzzy logic model (FLM) to associate SL composition with cell viability by semi-quantitative rules. Altogether, this hybrid model approach was able to predict the cell viability of double experimental perturbations with chemotherapy, indicating that the SL pathway is a promising sensor to design strategies to overcome drug resistance in cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

A saposin deficiency model in Drosophila: Lysosomal storage, progressive neurodegeneration and sensory physiological decline.

Science.gov (United States)

Hindle, Samantha J; Hebbar, Sarita; Schwudke, Dominik; Elliott, Christopher J H; Sweeney, Sean T

2017-02-01

Saposin deficiency is a childhood neurodegenerative lysosomal storage disorder (LSD) that can cause premature death within three months of life. Saposins are activator proteins that promote the function of lysosomal hydrolases that mediate the degradation of sphingolipids. There are four saposin proteins in humans, which are encoded by the prosaposin gene. Mutations causing an absence or impaired function of individual saposins or the whole prosaposin gene lead to distinct LSDs due to the storage of different classes of sphingolipids. The pathological events leading to neuronal dysfunction induced by lysosomal storage of sphingolipids are as yet poorly defined. We have generated and characterised a Drosophila model of saposin deficiency that shows striking similarities to the human diseases. Drosophila saposin-related (dSap-r) mutants show a reduced longevity, progressive neurodegeneration, lysosomal storage, dramatic swelling of neuronal soma, perturbations in sphingolipid catabolism, and sensory physiological deterioration. Our data suggests a genetic interaction with a calcium exchanger (Calx) pointing to a possible calcium homeostasis deficit in dSap-r mutants. Together these findings support the use of dSap-r mutants in advancing our understanding of the cellular pathology implicated in saposin deficiency and related LSDs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis

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Giaever Guri

2009-01-01

Full Text Available Abstract Background Single genome-wide screens for the effect of altered gene dosage on drug sensitivity in the model organism Saccharomyces cerevisiae provide only a partial picture of the mechanism of action of a drug. Results Using the example of the tumor cell invasion inhibitor dihydromotuporamine C, we show that a more complete picture of drug action can be obtained by combining different chemical genomics approaches – analysis of the sensitivity of ρ0 cells lacking mitochondrial DNA, drug-induced haploinsufficiency, suppression of drug sensitivity by gene overexpression and chemical-genetic synthetic lethality screening using strains deleted of nonessential genes. Killing of yeast by this chemical requires a functional mitochondrial electron-transport chain and cytochrome c heme lyase function. However, we find that it does not require genes associated with programmed cell death in yeast. The chemical also inhibits endocytosis and intracellular vesicle trafficking and interferes with vacuolar acidification in yeast and in human cancer cells. These effects can all be ascribed to inhibition of sphingolipid biosynthesis by dihydromotuporamine C. Conclusion Despite their similar conceptual basis, namely altering drug sensitivity by modifying gene dosage, each of the screening approaches provided a distinct set of information that, when integrated, revealed a more complete picture of the mechanism of action of a drug on cells.

Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

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Anahí Capmany

2010-11-01

Full Text Available Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication.

Science.gov (United States)

Capmany, Anahí; Damiani, María Teresa

2010-11-22

Chlamydia trachomatis are obligate intracellular bacteria that survive and replicate in a bacterial-modified phagosome called inclusion. As other intracellular parasites, these bacteria subvert the phagocytic pathway to avoid degradation in phagolysosomes and exploit trafficking pathways to acquire both energy and nutrients essential for their survival. Rabs are host proteins that control intracellular vesicular trafficking. Rab14, a Golgi-related Rab, controls Golgi to endosomes transport. Since Chlamydia establish a close relationship with the Golgi apparatus, the recruitment and participation of Rab14 on inclusion development and bacteria growth were analyzed. Time course analysis revealed that Rab14 associated with inclusions by 10 h post infection and was maintained throughout the entire developmental cycle. The recruitment was bacterial protein synthesis-dependent but independent of microtubules and Golgi integrity. Overexpression of Rab14 dominant negative mutants delayed inclusion enlargement, and impaired bacteria replication as determined by IFU. Silencing of Rab14 by siRNA also decreased bacteria multiplication and infectivity. By electron microscopy, aberrant bacteria were observed in cells overexpressing the cytosolic negative Rab14 mutant. Our results showed that Rab14 facilitates the delivery of sphingolipids required for bacterial development and replication from the Golgi to chlamydial inclusions. Novel anti-chlamydial therapies could be developed based on the knowledge of how bacteria subvert host vesicular transport events through Rabs manipulation.

MRP- and BCL-2-mediated drug resistance in human SCLC: effects of apoptotic sphingolipids in vitro.

Science.gov (United States)

Khodadadian, M; Leroux, M E; Auzenne, E; Ghosh, S C; Farquhar, D; Evans, R; Spohn, W; Zou, Y; Klostergaard, J

2009-10-01

Multidrug-resistance-associated protein (MRP) and BCL-2 contribute to drug resistance expressed in SCLC. To establish whether MRP-mediated drug resistance affects sphingolipid (SL)-induced apoptosis in SCLC, we first examined the human SCLC cell line, UMCC-1, and its MRP over-expressing, drug-resistant subline, UMCC-1/VP. Despite significantly decreased sensitivity to doxorubicin (Dox) and to the etoposide, VP-16, the drug-selected line was essentially equally as sensitive to treatment with exogenous ceramide (Cer), sphingosine (Sp) or dimethyl-sphingosine (DMSP) as the parental line. Next, we observed that high BCL-2-expressing human H69 SCLC cells, that were approximately 160-fold more sensitive to Dox than their combined BCL-2 and MRP-over-expressing (H69AR) counterparts, were only approximately 5-fold more resistant to DMSP. Time-lapse fluorescence microscopy of either UMCC cell line treated with DMSP-Coumarin revealed comparable extents and kinetics of SL uptake, further ruling out MRP-mediated effects on drug uptake. DMSP potentiated the cytotoxic activity of VP-16 and Taxol, but not Dox, in drug-resistant UMCC-1/VP cells. However, this sensitization did not appear to involve DMSP-mediated effects on the function of MRP in drug export; nor did DMSP strongly shift the balance of pro-apoptotic Sps and anti-apoptotic Sp-1-Ps in these cells. We conclude that SL-induced apoptosis markedly overcomes or bypasses MRP-mediated drug resistance relevant to SCLC and may suggest a novel therapeutic approach to chemotherapy for these tumors.

Accumulation of sphingolipid activator proteins (SAPs) A and D in granular osmiophilic deposits in miniature Schnauzer dogs with ceroid-lipofuscinosis.

Science.gov (United States)

Palmer, D N; Tyynelä, J; van Mil, H C; Westlake, V J; Jolly, R D

1997-03-01

The neuronal ceroid-lipofuscinoses (NCL, Batten disease) are fatal inherited neurodegenerative diseases of children characterized by retinal and brain atrophy and the accumulation of electron-dense storage bodies in cells. Mutations in different genes underlie different major forms. The infantile disease (CLN-1, McKusick 256730) is distinguished by the storage of the sphingolipid activator proteins (SAPs) A and D in distinctive granular osmiophilic deposits (GRODs). This contrasts with the other major forms, where subunit c of mitochondrial ATP synthase is stored in various multilamellar profiles. Ceroid-lipofuscinoses also occur in dogs, including a form in miniature Schnauzers with distinctive granular osmiophilic deposit-like storage bodies. Antisera to SAPs A and D reacted to these storage bodies in situ. The presence of SAP D was confirmed by Western blotting and of SAP A by protein sequencing. Neither subunit c of mitochondrial ATP synthase nor of vacuolar ATPase is stored. This suggests that there are two families of ceroid-lipofuscinoses, the subunit c-storing forms, and those in which SAPs A and D, and perhaps other proteins, accumulate. Further work is required to determine whether other forms with granular osmiophilic deposits belong to the latter class and the genetic relationships between them and the human infantile disease.

Deficient motion-defined and texture-defined figure-ground segregation in amblyopic children.

Science.gov (United States)

Wang, Jane; Ho, Cindy S; Giaschi, Deborah E

2007-01-01

Motion-defined form deficits in the fellow eye and the amblyopic eye of children with amblyopia implicate possible direction-selective motion processing or static figure-ground segregation deficits. Deficient motion-defined form perception in the fellow eye of amblyopic children may not be fully accounted for by a general motion processing deficit. This study investigates the contribution of figure-ground segregation deficits to the motion-defined form perception deficits in amblyopia. Performances of 6 amblyopic children (5 anisometropic, 1 anisostrabismic) and 32 control children with normal vision were assessed on motion-defined form, texture-defined form, and global motion tasks. Performance on motion-defined and texture-defined form tasks was significantly worse in amblyopic children than in control children. Performance on global motion tasks was not significantly different between the 2 groups. Faulty figure-ground segregation mechanisms are likely responsible for the observed motion-defined form perception deficits in amblyopia.

DEFINING SPATIAL VIOLENCE. BUCHAREST AS A STUDY CASE

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Celia GHYKA

2015-05-01

Full Text Available The paper looks at the spatial manifestations of violence, aiming to define the category of spatial violence by focusing on the recent urban history of Bucharest; it establishes links with the longer history of natural and inflicted disasters that defined the city, and it explores the spatial, urban, social and symbolical conflicts that occured during the last 25 years, pointing at their consequences on the social and urban substance of the city.

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

phosphate, the results were mostly corroborative. The duality of biological response of sphingolipids as reported in numerous studies was comparable for the PTLF suggesting that its active component is a sphingolipid and showing its use for pigment ...

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

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Vijay R Varma

2018-01-01

Full Text Available The metabolic basis of Alzheimer disease (AD is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression.Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180 assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA (N = 44, mean age = 81.33, % female = 36.36 from AD (N = 15, control (CN; N = 14, and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15 participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63 and preclinical (BLSA (N = 207, mean age = 78.68, % female = 42.63 AD, in which we tested their associations with magnetic resonance imaging (MRI measures of AD-related brain atrophy, cerebrospinal fluid (CSF biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of

Can play be defined?

DEFF Research Database (Denmark)

Eichberg, Henning

2015-01-01

Can play be defined? There is reason to raise critical questions about the established academic demand that at phenomenon – also in humanist studies – should first of all be defined, i.e. de-lineated and by neat lines limited to a “little box” that can be handled. The following chapter develops....... Human beings can very well understand play – or whatever phenomenon in human life – without defining it....

Role of neutral ceramidase in colon cancer.

Science.gov (United States)

García-Barros, Mónica; Coant, Nicolas; Kawamori, Toshihiko; Wada, Masayuki; Snider, Ashley J; Truman, Jean-Philip; Wu, Bill X; Furuya, Hideki; Clarke, Christopher J; Bialkowska, Agnieszka B; Ghaleb, Amr; Yang, Vincent W; Obeid, Lina M; Hannun, Yusuf A

2016-12-01

Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.-García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer. © FASEB.

Changes in ceramide metabolism are essential in Madin-Darby canine kidney cell differentiation.

Science.gov (United States)

Pescio, Lucila Gisele; Santacreu, Bruno Jaime; Lopez, Vanina Gisela; Paván, Carlos Humberto; Romero, Daniela Judith; Favale, Nicolás Octavio; Sterin-Speziale, Norma Beatriz

2017-07-01

Ceramides (Cers) and complex sphingolipids with defined acyl chain lengths play important roles in numerous cell processes. Six Cer synthase (CerS) isoenzymes (CerS1-6) are the key enzymes responsible for the production of the diversity of molecular species. In this study, we investigated the changes in sphingolipid metabolism during the differentiation of Madin-Darby canine kidney (MDCK) cells. By MALDI TOF TOF MS, we analyzed the molecular species of Cer, glucosylceramide (GlcCer), lactosylceramide (LacCer), and SM in nondifferentiated and differentiated cells (cultured under hypertonicity). The molecular species detected were the same, but cells subjected to hypertonicity presented higher levels of C24:1 Cer, C24:1 GlcCer, C24:1 SM, and C16:0 LacCer. Consistently with the molecular species, MDCK cells expressed CerS2, CerS4, and CerS6, but with no differences during cell differentiation. We next evaluated the different synthesis pathways with sphingolipid inhibitors and found that cells subjected to hypertonicity in the presence of amitriptyline, an inhibitor of acid sphingomyelinase, showed decreased radiolabeled incorporation in LacCer and cells did not develop a mature apical membrane. These results suggest that hypertonicity induces the endolysosomal degradation of SM, generating the Cer used as substrate for the synthesis of specific molecular species of glycosphingolipids that are essential for MDCK cell differentiation. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Definably compact groups definable in real closed fields.II

OpenAIRE

Barriga, Eliana

2017-01-01

We continue the analysis of definably compact groups definable in a real closed field $\\mathcal{R}$. In [3], we proved that for every definably compact definably connected semialgebraic group $G$ over $\\mathcal{R}$ there are a connected $R$-algebraic group $H$, a definable injective map $\\phi$ from a generic definable neighborhood of the identity of $G$ into the group $H\\left(R\\right)$ of $R$-points of $H$ such that $\\phi$ acts as a group homomorphism inside its domain. The above result and o...

Three principles to define the success of a diagnostic study could be identified

DEFF Research Database (Denmark)

Vach, Werner; Gerke, Oke; Høilund-Carlsen, Poul Flemming

2012-01-01

of a diagnostic study on a single binary test and investigation of common statistical approaches in relation to these criteria. RESULTS: Three criteria for defining the overall success of a diagnostic study could be identified: a strong criterion, a liberal criterion, and a weak criterion. The strong criterion...... can be implemented by comparing the lower bounds of the confidence intervals for sensitivity and specificity with prespecified target values, as is typically done in many diagnostic studies. The liberal criterion allows a clinically meaningful compensation between sensitivity and specificity and can...... be implemented in different ways. If the liberal criterion is applied instead of the strong criterion, this can lead to a substantial reduction in the sample size required for a diagnostic study. The weak criterion is not very adequate for defining the success of a diagnostic study. CONCLUSION: When planning...

Defining Plagiarism: A Literature Review

Directory of Open Access Journals (Sweden)

Akbar Akbar

2018-02-01

Full Text Available Plagiarism has repeatedly occurred in Indonesia, resulting in focusing on such academic misbehavior as a “central issue” in Indonesian higher education. One of the issues of addressing plagiarism in higher education is that there is a confusion of defining plagiarism. It seems that Indonesian academics had different perception when defining plagiarism. This article aims at exploring the issue of plagiarism by helping define plagiarism to address confusion among Indonesian academics. This article applies literature review by firs finding relevant articles after identifying databases for literature searching. After the collection of required articles for review, the articles were synthesized before presenting the findings. This study has explored the definition of plagiarism in the context of higher education. This research found that plagiarism is defined in the relation of criminal acts. The huge numbers of discursive features used position plagiaristic acts as an illegal deed. This study also found that cultural backgrounds and exposure to plagiarism were influential in defining plagiarism.

Studies of isotopic defined hydrogen beams scattering from Pd single-crystal surfaces

International Nuclear Information System (INIS)

Varlam, Mihai; Steflea, Dumitru

2001-01-01

An experimental investigation of hydrogen isotopes interaction with Pd single-crystal surface has been carried out using molecular beam technique. The energy dependence of the sticking probability and its relation with the trapping probability into the precursor state is studied by integrating the scattered angular distribution of hydrogen Isotopic defined beams from Pd (111) surface in the 40-400 K surface temperature range. The dependence has been evaluated by defining hydrogen molecular beams with different isotopic concentration - from the natural one to the 5% D/(D+H) ratio - and for different incident energies. The beam was directed onto a single-crystal Pd (111) surface. In the paper, we report the experimental results and some considerations related to it. (authors)

Studies of isotopic defined hydrogen beams scattering from Pd single-crystal surfaces

International Nuclear Information System (INIS)

Varlam, Mihai; Steflea, Dumitru

1999-01-01

An experimental investigation of hydrogen isotopes interaction with Pd single-crystal surfaces has been carried out using molecular beam technique. The energy dependence of the sticking probability and its relation with the trapping probability into the precursor state is studied by integrating the scattered angular distribution of hydrogen isotopic defined beams from Pd (111) surfaces in the 40 - 400 K surface temperature range. The dependence has been evaluated by defining hydrogen molecular beams with different isotopic concentration - from the natural one until 5% D/(D + H) and different incident energies and directed onto a single - crystal Pd (111) surface. In the paper, we report the experimental results and some considerations related to them. (authors)

The equationally-defined commutator a study in equational logic and algebra

CERN Document Server

Czelakowski, Janusz

2015-01-01

This monograph introduces and explores the notions of a commutator equation and the equationally-defined commutator from the perspective of abstract algebraic logic.  An account of the commutator operation associated with equational deductive systems is presented, with an emphasis placed on logical aspects of the commutator for equational systems determined by quasivarieties of algebras.  The author discusses the general properties of the equationally-defined commutator, various centralization relations for relative congruences, the additivity and correspondence properties of the equationally-defined commutator, and its behavior in finitely generated quasivarieties. Presenting new and original research not yet considered in the mathematical literature, The Equationally-Defined Commutator will be of interest to professional algebraists and logicians, as well as graduate students and other researchers interested in problems of modern algebraic logic.

HIV-induced immunodeficiency and mortality from AIDS-defining and non-AIDS-defining malignancies

DEFF Research Database (Denmark)

Monforte, Antonella d'Arminio; Abrams, Donald; Pradier, Christian

2008-01-01

OBJECTIVE: To evaluate deaths from AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (nADM) in the D:A:D Study and to investigate the relationship between these deaths and immunodeficiency. DESIGN: Observational cohort study. METHODS: Patients (23 437) were followed prospectively......-fold higher latest CD4 cell count was associated with a halving of the risk of ADM mortality. Other predictors of an increased risk of ADM mortality were homosexual risk group, older age, a previous (non-malignancy) AIDS diagnosis and earlier calendar years. Predictors of an increased risk of nADM mortality...

Expansion of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor Function in Normal and Cancer Cells: From Membrane Restructuring to Mediation of Estrogen Signaling and Stem Cell Programming

Science.gov (United States)

2018-01-01

Sphingolipids, sphingolipid metabolizing enzymes, and their receptors network are being recognized as part of the signaling mechanisms, which govern breast cancer cell growth, migration, and survival during chemotherapy treatment. Approximately 70% of breast cancers are estrogen receptor (ER) positive and, thus, rely on estrogen signaling. Estrogen activates an intracellular network composed of many cytoplasmic and nuclear mediators. Some estrogen effects can be mediated by sphingolipids. Estrogen activates sphingosine kinase 1 (SphK1) and amplifies the intracellular concentration of sphingosine-1-phosphate (S1P) in breast cancer cells during stimulation of proliferation and survival. Specifically, Estrogen activates S1P receptors (S1PR) and induces growth factor receptor transactivation. SphK, S1P, and S1PR expression are causally associated with endocrine resistance and progression to advanced tumor stages in ER-positive breast cancers in vivo. Recently, the network of SphK/S1PR was shown to promote the development of ER-negative cancers and breast cancer stem cells, as well as stimulating angiogenesis. Novel findings confirm and broaden our knowledge about the cross-talk between sphingolipids and estrogen network in normal and malignant cells. Current S1PRs therapeutic inhibition was indicated as a promising chemotherapy approach in non-responsive and advanced malignancies. Considering that sphingolipid signaling has a prominent role in terminally differentiated cells, the impact should be considered when designing specific SphK/S1PR inhibitors. This study analyzes the dynamic of the transformation of sphingolipid axis during a transition from normal to pathological condition on the level of the whole organism. The sphingolipid-based mediation and facilitation of global effects of estrogen were critically accented as a bridging mechanism that should be explored in cancer prevention. PMID:29385066

Expansion of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor Function in Normal and Cancer Cells: From Membrane Restructuring to Mediation of Estrogen Signaling and Stem Cell Programming

Directory of Open Access Journals (Sweden)

Olga A. Sukocheva

2018-01-01

Full Text Available Sphingolipids, sphingolipid metabolizing enzymes, and their receptors network are being recognized as part of the signaling mechanisms, which govern breast cancer cell growth, migration, and survival during chemotherapy treatment. Approximately 70% of breast cancers are estrogen receptor (ER positive and, thus, rely on estrogen signaling. Estrogen activates an intracellular network composed of many cytoplasmic and nuclear mediators. Some estrogen effects can be mediated by sphingolipids. Estrogen activates sphingosine kinase 1 (SphK1 and amplifies the intracellular concentration of sphingosine-1-phosphate (S1P in breast cancer cells during stimulation of proliferation and survival. Specifically, Estrogen activates S1P receptors (S1PR and induces growth factor receptor transactivation. SphK, S1P, and S1PR expression are causally associated with endocrine resistance and progression to advanced tumor stages in ER-positive breast cancers in vivo. Recently, the network of SphK/S1PR was shown to promote the development of ER-negative cancers and breast cancer stem cells, as well as stimulating angiogenesis. Novel findings confirm and broaden our knowledge about the cross-talk between sphingolipids and estrogen network in normal and malignant cells. Current S1PRs therapeutic inhibition was indicated as a promising chemotherapy approach in non-responsive and advanced malignancies. Considering that sphingolipid signaling has a prominent role in terminally differentiated cells, the impact should be considered when designing specific SphK/S1PR inhibitors. This study analyzes the dynamic of the transformation of sphingolipid axis during a transition from normal to pathological condition on the level of the whole organism. The sphingolipid-based mediation and facilitation of global effects of estrogen were critically accented as a bridging mechanism that should be explored in cancer prevention.

How Do We Define Congenital Heart Defects for Scientific Studies?

DEFF Research Database (Denmark)

Garne, Ester; Olsen, Morten Smaerup; Johnsen, Søren Paaske

2012-01-01

of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population-based data...... practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD....

Plasma C16-Cer levels are increased in patients with preterm labor.

Science.gov (United States)

Laudanski, Piotr; Charkiewicz, Karol; Kisielewski, Rafal; Kuc, Pawel; Koc-Zorawska, Ewa; Raba, Grzegorz; Kraczkowski, Janusz; Dymicka-Piekarska, Violetta; Chabowski, Adrian; Kacerovsky, Marian; Jacobsson, Bo; Zabielski, Piotr; Blachnio-Zabielska, Agnieszka

2016-03-01

The pathogenesis of preterm labor is fragmentarily explained. The most widely accepted theory points out to infection and inflammation as possible causes, which can be mediated by potentially different factors, including sphingolipid mediators. Sphingolipids are a class of lipids that have been shown as important mediators in various cell processes such as: proliferation, growth, apoptosis, stress response, necrosis and inflammation. The aim of the study was to assess plasma concentrations of selected sphingolipids in patients with preterm labor. We used ultra-high performance liquid chromatography with triple mass spectrometry (UHPLC-ESI-MS/MS) to assess plasma concentrations of the 11 sphingolipids in patients presenting with symptoms of preterm labor (n=61) and threatened preterm labor (n=40). We observed a statistically significant increase (p-valueCer in patients with preterm labor as compared to the control group. We also found C16-Cer to be the best predictor of preterm labor in the group of patients with symptoms occurring after 32 weeks of gestation. Our findings show a possible involvement of selected sphingolipids, especially C16-Cer, in the pathogenesis of preterm labor. Their role as predictors of preterm delivery needs to be validated in the future on larger group of patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Myocardial lipid content in Fabry disease: a combined 1H-MR spectroscopy and MR imaging study at 3 Tesla.

Science.gov (United States)

Petritsch, B; Köstler, H; Weng, A M; Horn, M; Gassenmaier, T; Kunz, A S; Weidemann, F; Wanner, C; Bley, T A; Beer, M

2016-10-28

Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by 1 H magnetic resonance spectroscopy (MRS) at 3 Tesla. Myocardial lipid content was quantified in vivo by 1 H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls. The study protocol combined 1 H-MRS with cardiac cine imaging and LGE MRI in a single examination. Myocardial lipid content was not significantly elevated in Fabry disease (p = 0.225). Left ventricular (LV) mass was significantly higher in patients suffering from Fabry disease compared to controls (p = 0.019). Comparison of patients without signs of myocardial fibrosis in MRI (LGE negative; n = 12) to patients with signs of fibrosis (LGE positive; n = 18) revealed similar myocardial lipid content in both groups (p > 0.05), while the latter showed a trend towards elevated LV mass (p = 0.076). This study demonstrates the potential of lipid metabolic investigation embedded in a comprehensive examination of cardiac morphology and function in Fabry disease. There was no evidence that lysosomal storage of sphingolipids influences cardiac lipid content as measured by 1 H-MRS. Finally, the authors share the opinion that a comprehensive cardiac examination including three subsections (LGE; 1 H-MRS; T 1 mapping), could hold the highest potential for the final assessment of early and late myocardial changes in Fabry disease.

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study

Science.gov (United States)

Oommen, Anup M.; Varma, Sudhir; Casanova, Ramon; An, Yang; O’Brien, Richard; Pletnikova, Olga; Kastenmueller, Gabi; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Thambisetty, Madhav

2018-01-01

Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Methods and findings Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and “asymptomatic Alzheimer’s disease” (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes—sphingolipids and glycerophospholipids—that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer’s Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that

Lipidomic Evaluation of Feline Neurologic Disease after AAV Gene Therapy

Directory of Open Access Journals (Sweden)

Heather L. Gray-Edwards

2017-09-01

Full Text Available GM1 gangliosidosis is a fatal lysosomal disorder, for which there is no effective treatment. Adeno-associated virus (AAV gene therapy in GM1 cats has resulted in a greater than 6-fold increase in lifespan, with many cats remaining alive at >5.7 years of age, with minimal clinical signs. Glycolipids are the principal storage product in GM1 gangliosidosis whose pathogenic mechanism is not completely understood. Targeted lipidomics analysis was performed to better define disease mechanisms and identify markers of disease progression for upcoming clinical trials in humans. 36 sphingolipids and subspecies associated with ganglioside biosynthesis were tested in the cerebrospinal fluid of untreated GM1 cats at a humane endpoint (∼8 months, AAV-treated GM1 cats (∼5 years old, and normal adult controls. In untreated GM1 cats, significant alterations were noted in 16 sphingolipid species, including gangliosides (GM1 and GM3, lactosylceramides, ceramides, sphingomyelins, monohexosylceramides, and sulfatides. Variable degrees of correction in many lipid metabolites reflected the efficacy of AAV gene therapy. Sphingolipid levels were highly predictive of neurologic disease progression, with 11 metabolites having a coefficient of determination (R2 > 0.75. Also, a specific detergent additive significantly increased the recovery of certain lipid species in cerebrospinal fluid samples. This report demonstrates the methodology and utility of targeted lipidomics to examine the pathophysiology of lipid storage disorders.

Analytical methods in sphingolipidomics: Quantitative and profiling approaches in food analysis.

Science.gov (United States)

Canela, Núria; Herrero, Pol; Mariné, Sílvia; Nadal, Pedro; Ras, Maria Rosa; Rodríguez, Miguel Ángel; Arola, Lluís

2016-01-08

In recent years, sphingolipidomics has emerged as an interesting omic science that encompasses the study of the full sphingolipidome characterization, content, structure and activity in cells, tissues or organisms. Like other omics, it has the potential to impact biomarker discovery, drug development and systems biology knowledge. Concretely, dietary food sphingolipids have gained considerable importance due to their extensively reported bioactivity. Because of the complexity of this lipid family and their diversity among foods, powerful analytical methodologies are needed for their study. The analytical tools developed in the past have been improved with the enormous advances made in recent years in mass spectrometry (MS) and chromatography, which allow the convenient and sensitive identification and quantitation of sphingolipid classes and form the basis of current sphingolipidomics methodologies. In addition, novel hyphenated nuclear magnetic resonance (NMR) strategies, new ionization strategies, and MS imaging are outlined as promising technologies to shape the future of sphingolipid analyses. This review traces the analytical methods of sphingolipidomics in food analysis concerning sample extraction, chromatographic separation, the identification and quantification of sphingolipids by MS and their structural elucidation by NMR. Copyright © 2015 Elsevier B.V. All rights reserved.

Defining the Constructs of Expert Coaching: A Q-Methodological Study of Olympic Sport Coaches

Science.gov (United States)

DeWeese, Brad Heath

2012-01-01

The purpose of this study was to enhance the development of coaches for participation at International level competition through the improvement of coaching education programming. Although many studies have alluded to the benefit of various coaching education tactics, no study to date had set out to determine the constructs that define an expert…

Defining and Classifying Interest Groups

DEFF Research Database (Denmark)

Baroni, Laura; Carroll, Brendan; Chalmers, Adam

2014-01-01

The interest group concept is defined in many different ways in the existing literature and a range of different classification schemes are employed. This complicates comparisons between different studies and their findings. One of the important tasks faced by interest group scholars engaged...... in large-N studies is therefore to define the concept of an interest group and to determine which classification scheme to use for different group types. After reviewing the existing literature, this article sets out to compare different approaches to defining and classifying interest groups with a sample...... in the organizational attributes of specific interest group types. As expected, our comparison of coding schemes reveals a closer link between group attributes and group type in narrower classification schemes based on group organizational characteristics than those based on a behavioral definition of lobbying....

Development of a chemically defined medium for studying foodborne bacterial-fungal interactions

DEFF Research Database (Denmark)

Aunsbjerg, Stina Dissing; Honoré, Anders Hans; Vogensen, Finn Kvist

2015-01-01

judged by ultra-performance liquid chromatography/mass spectrometry) a chemically defined interaction medium (CDIM) was developed. The medium supported growth of antifungal cultures such as Lactobacillus paracasei and Propionibacterium freudenreichii, as well as spoilage moulds and yeasts isolated from...... fermented milk products. Both strong and weak antifungal interactions observed in milk could be reproduced in CDIM. The medium seems suitable for studying antifungal activity of bacterial cultures....

"Dermatitis" defined.

Science.gov (United States)

Smith, Suzanne M; Nedorost, Susan T

2010-01-01

The term "dermatitis" can be defined narrowly or broadly, clinically or histologically. A common and costly condition, dermatitis is underresourced compared to other chronic skin conditions. The lack of a collectively understood definition of dermatitis and its subcategories could be the primary barrier. To investigate how dermatologists define the term "dermatitis" and determine if a consensus on the definition of this term and other related terms exists. A seven-question survey of dermatologists nationwide was conducted. Of respondents (n  =  122), half consider dermatitis to be any inflammation of the skin. Nearly half (47.5%) use the term interchangeably with "eczema." Virtually all (> 96%) endorse the subcategory "atopic" under the terms "dermatitis" and "eczema," but the subcategories "contact," "drug hypersensitivity," and "occupational" are more highly endorsed under the term "dermatitis" than under the term "eczema." Over half (55.7%) personally consider "dermatitis" to have a broad meaning, and even more (62.3%) believe that dermatologists as a whole define the term broadly. There is a lack of consensus among experts in defining dermatitis, eczema, and their related subcategories.

Defining elite athletes: Issues in the study of expert performance in sport psychology

OpenAIRE

Swann, C; Moran, A; Piggott, D

2015-01-01

© 2014 Elsevier Ltd. Objectives: There has been considerable inconsistency and confusion in the definition of elite/expert athletes in sport psychology research, which has implications for studies conducted in this area and for the field as a whole. This study aimed to: (i) critically evaluate the ways in which recent research in sport psychology has defined elite/expert athletes; (ii) explore the rationale for using such athletes; and (iii) evaluate the conclusions that research in this fiel...

Studying the Ability of 7th Grade Students to Define the Circle and Its Elements in the Context of Mathematical Language

Science.gov (United States)

Akarsu, Esra; Yilmaz, Süha

2015-01-01

In this study, it was aimed to study the mathematical language skills that the 7th grade students use in defining the circle and its elements. In the study, the mathematical language skills of students that they use in defining the circle and its elements in a scenario were compared to the mathematical language skills they use in defining them…

[The importance of defining methodology for post-marketing observational studies on cardiovascular therapies].

Science.gov (United States)

Pelliccia, Francesco; Barillà, Francesco; Tanzilli, Gaetano; Viceconte, Nicola; Paravati, Vincenzo; Mangieri, Enrico; Gaudio, Carlo

2017-01-01

In recent years, a growing number of observational studies in cardiology have been carried out following the criticism that rigid design of randomized clinical trials produces information that is not applicable to the general patient. This approach is very common in several branches of medicine, first of all oncology, but has often been considered marginal in cardiology. The recent introduction of new oral anticoagulants (NOACs) on the market, however, has seen a proliferation of "real-life" studies, drawing the attention of cardiologists to the advantages and limitations of post-marketing studies. NOACs have been approved for use on the basis of large randomized clinical trials that have clearly documented their efficacy and safety. Since they have become available, the analysis of phase IV data has been considered crucial and therefore a great amount of information on the use of NOACs in daily practice has become available. It should be considered, however, that the possibility exists that results obtained from "real-world" studies, which do not apply rigid scientific criteria, may lead to incorrect conclusions. Accordingly, it is mandatory to fully define the operational standards of observational studies. All the protagonists of post-marketing analysis (physicians, epidemiologists, pharmacologists, statisticians) should handle the data strictly in order to ensure their reliability and comparability with other studies. To this end, it is crucial that researchers follow rigorous operational protocols for phase IV studies. Briefly, any "real-life" study should be prospective and adhere to what is prespecified by the research protocol - which must illustrate the background and rationale of the study, define its primary endpoint, and detail the methods, i.e. study design, population and variables.

Change in activity of serine palmitoyltransferase affects sensitivity to syringomycin E in yeast Saccharomyces cerevisiae.

Science.gov (United States)

Toume, Moeko; Tani, Motohiro

2014-09-01

Syringomycin E is a cyclic lipodepsipeptide produced by strains of the plant bacterium Pseudomonas syringae pv. syringae. Genetic studies involving the yeast Saccharomyces cerevisiae have revealed that complex sphingolipids play important roles in the action of syringomycin E. Here, we found a novel mutation that confers resistance to syringomycin E on yeast; that is, a deletion mutant of ORM1 and ORM2, which encode negative regulators of serine palmitoyltransferase catalyzing the initial step of sphingolipid biosynthesis, exhibited resistance to syringomycin E. On the contrary, overexpression of Orm2 resulted in high sensitivity to the toxin. Moreover, overexpression of Lcb1 and Lcb2, catalytic subunits of serine palmitoyltransferase, causes resistance to the toxin, whereas partial repression of expression of Lcb1 had the opposite effect. Partial reduction of complex sphingolipids by repression of expression of Aur1, an inositol phosphorylceramide synthase, also resulted in high sensitivity to the toxin. These results suggested that an increase in sphingolipid biosynthesis caused by a change in the activity of serine palmitoyltransferase causes resistance to syringomycin E. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

How do people define moderation?

Science.gov (United States)

vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

2016-06-01

Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. Copyright © 2016 Elsevier Ltd. All rights reserved.

A fluorescent glycolipid-binding peptide probe traces cholesterol dependent microdomain-derived trafficking pathways.

Directory of Open Access Journals (Sweden)

Steffen Steinert

Full Text Available BACKGROUND: The uptake and intracellular trafficking of sphingolipids, which self-associate into plasma membrane microdomains, is associated with many pathological conditions, including viral and toxin infection, lipid storage disease, and neurodegenerative disease. However, the means available to label the trafficking pathways of sphingolipids in live cells are extremely limited. In order to address this problem, we have developed an exogenous, non-toxic probe consisting of a 25-amino acid sphingolipid binding domain, the SBD, derived from the amyloid peptide Abeta, and conjugated by a neutral linker with an organic fluorophore. The current work presents the characterization of the sphingolipid binding and live cell trafficking of this novel probe, the SBD peptide. SBD was the name given to a motif originally recognized by Fantini et al in a number of glycolipid-associated proteins, and was proposed to interact with sphingolipids in membrane microdomains. METHODOLOGY/PRINCIPAL FINDINGS: In accordance with Fantini's model, optimal SBD binding to membranes depends on the presence of sphingolipids and cholesterol. In synthetic membrane binding assays, SBD interacts preferentially with raft-like lipid mixtures containing sphingomyelin, cholesterol, and complex gangliosides in a pH-dependent manner, but is less glycolipid-specific than Cholera toxin B (CtxB. Using quantitative time-course colocalization in live cells, we show that the uptake and intracellular trafficking route of SBD is unlike that of either the non-raft marker Transferrin or the raft markers CtxB and Flotillin2-GFP. However, SBD traverses an endolysosomal route that partially intersects with raft-associated pathways, with a major portion being diverted at a late time point to rab11-positive recycling endosomes. Trafficking of SBD to acidified compartments is strongly disrupted by cholesterol perturbations, consistent with the regulation of sphingolipid trafficking by cholesterol

Defining post-sternotomy mediastinitis for clinical evidence-based studies.

Science.gov (United States)

van Wingerden, Jan J; de Mol, Bas A J M; van der Horst, Chantal M A M

2016-05-01

Considerable advances have already been made in the treatment of deep thoracic wound infections following a median sternotomy for cardiac surgery. Further improvement in diagnosis, treatment, and outcome will require a targeted approach by multidisciplinary teams. Clear communication and synergy between the various clinical and supportive disciplines would assist in removing the last barriers to standardized evidence-based studies and the development of improved evidence-based guidelines. An extensive literature search without language restrictions was carried out on PubMed (Medline), EMBASE, and Web of Science, covering the period 1988 to week 16, 2014, and a manual search of the reference lists was performed regarding all possible definitions and classifications of post-sternotomy mediastinitis. Two hundred and eighteen papers describing post-sternotomy infections in a multitude of terms were identified, and the strengths and weaknesses of the most popular definitions and terms relating specifically to post-sternotomy infections were examined. This study revealed that clinicians use a multitude of terms to describe post-sternotomy infections without defining the condition under treatment. Occasionally, older epidemiological (surveillance) definitions were used. It also shows that supportive disciplines have their own definitions, or interpretations of existing definitions, to describe these infections. The outcome of this study is that clinicians have adopted no single definition, which is essential for further improvement for evidence-based studies. We suggest that it is possible to adopt a single term for thoracic infection after a sternotomy (and only sternotomy), and propose a clinical definition for this purpose. © The Author(s) 2016.

Factors defining the mentoring competencies of clinical midwives: An exploratory quantitative research study in Japan.

Science.gov (United States)

Hishinuma, Yuri; Horiuchi, Shigeko; Yanai, Haruo

2016-01-01

Clinical education is an extremely important process in cultivating healthcare professionals, and the quality of educators has a major impact on the quality of future practitioners. Although practicing clinical midwives contribute to the education of pre-registered midwives and those qualified within the past year (new midwives), the factors defining the educational competencies of clinical midwives have not been clarified. The purpose of this study was to explore the factors that define the mentoring competencies of clinical midwives involved in educating new midwives. An exploratory quantitative research study. Questionnaires were distributed to 694 midwives who had previously conducted educational activities with new midwives at the 63 facilities whose administrator or nurse manager in charge of all staff, including midwives, consented to participate. Of the 694 midwives, 464 (66.9%) returned the questionnaire and 451 (65.1%) valid responses were analyzed. Exploratory factor analyses were performed on the following three concepts: [competency as a professional], [competency as an educator], and [personal characteristics]. [Competency as a professional] consisted of two factors: and ; [competency as an educator] consisted of four factors: , , and ; and [personal characteristics consisted of three factors: exercising leadership> , and . These three concepts were defined by a total of nine sub-concepts (factors), and 41 items were extracted with a reliability coefficient (Cronbach's α) of 0.944 CONCLUSIONS: "Mentoring competencies of clinical midwives (MCCM)" are defined by three concepts and nine sub-concepts, which can be evaluated by 41 items regarding the behavior, thoughts, and characteristics that clinical midwives exhibit when they educate new midwives in clinical settings. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome-wide association studies of mri-defined brain infarcts: Meta-analysis from the charge consortium

NARCIS (Netherlands)

S. Debette (Stéphanie); J.C. Bis (Joshua); M. Fornage (Myriam); H.A. Schmid (Herbert); M.A. Ikram (Arfan); S. Sigurdsson (Stefan); G. Heiss (Gerardo); M.V. Struchalin (Maksim); A.V. Smith (Albert Vernon); A. van der Lugt (Aad); C. DeCarli (Charles); T. Lumley (Thomas); D.S. Knopman (David); C. Enzinger (Christian); G. Eiriksdottir (Gudny); P.J. Koudstaal (Peter Jan); A.L. DeStefano (Anita); B.M. Psaty (Bruce); C. Dufouil (Carole); D.J. Catellier (Diane); F. Fazekas (Franz); T. Aspelund (Thor); Y.S. Aulchenko (Yurii); A. Beiser (Alexa); J.I. Rotter (Jerome); C. Tzourio (Christophe); D.K. Shibata (Dean); M. Tscherner (Maria); T.B. Harris (Tamara); F. Rivadeneira Ramirez (Fernando); L.D. Atwood (Larry); K. Rice (Kenneth); R.F. Gottesman (Rebecca); M.A. van Buchem (Mark); A.G. Uitterlinden (André); M. Kelly-Hayes (Margaret); M. Cushman (Mary Ann); Y. Zhu (Yicheng); E.A. Boerwinkle (Eric); V. Gudnason (Vilmundur); A. Hofman (Albert); J.R. Romero (Jose Rafael); M.M.B. Breteler (Monique); R. Schmidt (Reinhold); L.J. Launer (Lenore); W.T. Longstreth Jr

2010-01-01

textabstractBackground and Purpose-Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed

Effect of immunomodulator, fingolimod, on ischemia reperfusion ...

African Journals Online (AJOL)

Marwa N. Emam

2016-07-25

Jul 25, 2016 ... Targeting the role of sphingolipid rheostat .... tunica vaginalis was opened and the left testis was delivered .... involving hypoxia, inflammatory responses and oxidative ... ROS signaling may be mediated through sphingolipid.

Podocyte Pathology and Nephropathy

Directory of Open Access Journals (Sweden)

Sandra eMerscher

2014-07-01

Full Text Available Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarily, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD, HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b is expressed in podocytes where it modulates acid sphingomyelinase (ASMase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

Definable Group Extensions and o-Minimal Group Cohomology via Spectral Sequences

OpenAIRE

BARRIGA, ELIANA

2013-01-01

We provide the theoretical foundation for the Lyndon-Hochschild-Serre spectral sequence as a tool to study the group cohomology and with this the group extensions in the category of definable groups. We also present various results on definable modules and actions, definable extensions and group cohomology of definable groups. These have applications to the study of non-definably compact groups definable in o-minimal theories (see [1]). Se presenta el fundamento teórico para las sucesiones...

Study to define NDE research for inspection of stainless steels

International Nuclear Information System (INIS)

Reinhart, E.R.

1978-08-01

After the boiling water reactor (BWR) stress corrosion cracking incidents on 4- and 10-inch stainless steel piping, the Electric Power Research Institute (EPRI) organized a round-robin ultrasonic examination of piping removed from service (TPS-75-609). Five inspection teams participated in this program, using both a standard procedure and the individual team procedure. The original intent was to section the piping after the program to evaluate the effectiveness of state-of-the-art ultrasonics in finding stress corrosion cracking. The sectioning was delayed, however, to allow research and development (R and D) groups time to perform basic measurements aimed at determining optimum search unit and instrument characteristics for the ultrasonic examination of stainless steel piping and to study the applicability of various advanced inspection methods. This additional effort was funded as part of an EPRI technical planning study (TPS-75-620), A Study to Define NDE Research for Inspection of Stainless Steels. Inspection methods evaluated in this study included (1) processing of manual scan data using a miniature programmable calculator (Aerojet Nuclear); (2) investigation into the performance characteristics of three experimental ultrasonic transducers (Battelle-Columbus Laboratories); (3) analysis of fundamental ultrasonic response data from intergranular stress corrosion cracks in stainless steels (Southwest Research Institute); and (4) a feasibility study of advanced signal processing and pattern recognition for analyzing flaws in stainless steel piping (Ultrasonics International). The results of the studies compiled in the report have indicated the direction for future research and development and have formed the basis for the recently initiated EPRI Research Project 892, Ultrasonic System Optimization

Rom2-dependent phosphorylation of Elo2 controls the abundance of very long chain fatty acids

DEFF Research Database (Denmark)

Olson, Daniel K; Fröhlich, Florian; Christiano, Romain

2015-01-01

Sphingolipids are essential components of eukaryotic membranes, where they serve to maintain membrane integrity. They are important components of membrane trafficking and function in signaling as messenger molecules. Sphingolipids are synthesized de novo from very long chain fatty acids (VLCFA...

Software Defined Cyberinfrastructure

Energy Technology Data Exchange (ETDEWEB)

Foster, Ian; Blaiszik, Ben; Chard, Kyle; Chard, Ryan

2017-07-17

Within and across thousands of science labs, researchers and students struggle to manage data produced in experiments, simulations, and analyses. Largely manual research data lifecycle management processes mean that much time is wasted, research results are often irreproducible, and data sharing and reuse remain rare. In response, we propose a new approach to data lifecycle management in which researchers are empowered to define the actions to be performed at individual storage systems when data are created or modified: actions such as analysis, transformation, copying, and publication. We term this approach software-defined cyberinfrastructure because users can implement powerful data management policies by deploying rules to local storage systems, much as software-defined networking allows users to configure networks by deploying rules to switches.We argue that this approach can enable a new class of responsive distributed storage infrastructure that will accelerate research innovation by allowing any researcher to associate data workflows with data sources, whether local or remote, for such purposes as data ingest, characterization, indexing, and sharing. We report on early experiments with this approach in the context of experimental science, in which a simple if-trigger-then-action (IFTA) notation is used to define rules.

Defining Documentary Film

DEFF Research Database (Denmark)

Juel, Henrik

2006-01-01

A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film......A discussion of various attemts at defining documentary film regarding form, content, truth, stile, genre or reception - and a propoposal of a positive list of essential, but non-exclusive characteristica of documentary film...

DEFINED CONTRIBUTION PLANS, DEFINED BENEFIT PLANS, AND THE ACCUMULATION OF RETIREMENT WEALTH

Science.gov (United States)

Poterba, James; Rauh, Joshua; Venti, Steven; Wise, David

2010-01-01

The private pension structure in the United States, once dominated by defined benefit (DB) plans, is currently divided between defined contribution (DC) and DB plans. Wealth accumulation in DC plans depends on the participant's contribution behavior and on financial market returns, while accumulation in DB plans is sensitive to a participant's labor market experience and to plan parameters. This paper simulates the distribution of retirement wealth under representative DB and DC plans. It uses data from the Health and Retirement Study (HRS) to explore how asset returns, earnings histories, and retirement plan characteristics contribute to the variation in retirement wealth outcomes. We simulate DC plan accumulation by randomly assigning individuals a share of wages that they and their employer contribute to the plan. We consider several possible asset allocation strategies, with asset returns drawn from the historical return distribution. Our DB plan simulations draw earnings histories from the HRS, and randomly assign each individual a pension plan drawn from a sample of large private and public defined benefit plans. The simulations yield distributions of both DC and DB wealth at retirement. Average retirement wealth accruals under current DC plans exceed average accruals under private sector DB plans, although DC plans are also more likely to generate very low retirement wealth outcomes. The comparison of current DC plans with more generous public sector DB plans is less definitive, because public sector DB plans are more generous on average than their private sector counterparts. PMID:21057597

Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes

OpenAIRE

Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho

2015-01-01

Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. Methods A GWAS was conducted with 945 patients with clinically defined gout and 1213 contr...

Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Vineetha Mandlik

2016-09-01

Full Text Available Inositol phosphorylceramide synthase (IPCS has emerged as an important, interesting and attractive target in the sphingolipid metabolism of Leishmania. IPCS catalyzes the conversion of ceramide to IPC which forms the most predominant sphingolipid in Leishmania. IPCS has no mammalian equivalent and also plays an important role in maintaining the infectivity and viability of the parasite. The present study explores the possibility of targeting IPCS; development of suitable inhibitors for the same would serve as a treatment strategy for the infectious disease leishmaniasis. Five coumarin derivatives were developed as inhibitors of IPCS protein. Molecular dynamics simulations of the complexes of IPCS with these inhibitors were performed which provided insights into the binding modes of the inhibitors. In vitro screening of the top three compounds has resulted in the identification of one of the compounds (compound 3 which shows little cytotoxic effects. This compound therefore represents a good starting point for further in vivo experimentation and could possibly serve as an important drug candidate for the treatment of leishmaniasis.

Generic sorting of raft lipids into secretory vesicles in yeast

DEFF Research Database (Denmark)

Surma, Michal A; Klose, Christian; Klemm, Robin W

2011-01-01

Previous work has showed that ergosterol and sphingolipids become sorted to secretory vesicles immunoisolated using a chimeric, artificial raft membrane protein as bait. In this study, we have extended this analysis to three populations of secretory vesicles isolated using natural yeast plasma...... a complete lipid overview of the yeast late secretory pathway. We could show that vesicles captured with different baits carry the same cargo and have almost identical lipid compositions; being highly enriched in ergosterol and sphingolipids. This finding indicates that lipid raft sorting is a generic...

Defining Quantum Control Flow

OpenAIRE

Ying, Mingsheng; Yu, Nengkun; Feng, Yuan

2012-01-01

A remarkable difference between quantum and classical programs is that the control flow of the former can be either classical or quantum. One of the key issues in the theory of quantum programming languages is defining and understanding quantum control flow. A functional language with quantum control flow was defined by Altenkirch and Grattage [\\textit{Proc. LICS'05}, pp. 249-258]. This paper extends their work, and we introduce a general quantum control structure by defining three new quantu...

Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-α treatment

Science.gov (United States)

Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.

2015-07-01

Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.

Dihydroceramide Desaturase Inhibition by a Cyclopropanated Dihydroceramide Analog in Cultured Keratinocytes

Directory of Open Access Journals (Sweden)

Susanne Brodesser

2011-01-01

Full Text Available Most mammalian sphingolipids contain a 4,5-(E-double bond. We report on the chemical synthesis of a dihydroceramide derivative that prevents the introduction of the double bond into sphingolipids. Minimal alteration of the parent structure by formally replacing the hydrogen atoms in the 5- and in the 6-position of the sphinganine backbone by a methylene group leads to an inhibitor of dihydroceramide desaturase in cultured cells. In the presence of 10–50 μM of compound (1, levels of biosynthetically formed dihydroceramide and—surprisingly—also of phytoceramide are elevated at the expense of ceramide. The cells respond to the lack of unsaturated sphingolipids by an elevation of mRNAs of enzymes required for sphingosine formation. At the same time, the analysis of proliferation and differentiation markers indicates that the sphingolipid double bond is required to keep the cells in a differentiated state.

Dihydroceramide desaturase inhibition by a cyclopropanated dihydroceramide analog in cultured keratinocytes.

Science.gov (United States)

Brodesser, Susanne; Kolter, Thomas

2011-01-01

Most mammalian sphingolipids contain a 4,5-(E)-double bond. We report on the chemical synthesis of a dihydroceramide derivative that prevents the introduction of the double bond into sphingolipids. Minimal alteration of the parent structure by formally replacing the hydrogen atoms in the 5- and in the 6-position of the sphinganine backbone by a methylene group leads to an inhibitor of dihydroceramide desaturase in cultured cells. In the presence of 10-50 μM of compound (1), levels of biosynthetically formed dihydroceramide and-surprisingly-also of phytoceramide are elevated at the expense of ceramide. The cells respond to the lack of unsaturated sphingolipids by an elevation of mRNAs of enzymes required for sphingosine formation. At the same time, the analysis of proliferation and differentiation markers indicates that the sphingolipid double bond is required to keep the cells in a differentiated state.

Effects of orally administered fumonisin B₁ (FB₁), partially hydrolysed FB₁, hydrolysed FB₁ and N-(1-deoxy-D-fructos-1-yl) FB₁ on the sphingolipid metabolism in rats.

Science.gov (United States)

Hahn, Irene; Nagl, Veronika; Schwartz-Zimmermann, Heidi Elisabeth; Varga, Elisabeth; Schwarz, Christiane; Slavik, Veronika; Reisinger, Nicole; Malachová, Alexandra; Cirlini, Martina; Generotti, Silvia; Dall'Asta, Chiara; Krska, Rudolf; Moll, Wulf-Dieter; Berthiller, Franz

2015-02-01

Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in maize-based food and feed. Alkaline processing like nixtamalisation of maize generates partially and fully hydrolysed FB1 (pHFB1 and HFB1) and thermal treatment in the presence of reducing sugars leads to formation of N-(1-deoxy-D-fructos-1-yl) fumonisin B1 (NDF). The toxicity of these metabolites, in particular their effect on the sphingolipid metabolism, is either unknown or discussed controversially. We produced high purity FB1, pHFB1a+b, HFB1 and NDF and fed them to male Sprague Dawley rats for three weeks. Once a week, urine and faeces samples were collected over 24 h and analysed for fumonisin metabolites as well as for the sphinganine (Sa) to sphingosine (So) ratio by validated LC-MS/MS based methods. While the latter was significantly increased in the FB1 positive control group, the Sa/So ratios of the partially and fully hydrolysed fumonisins were indifferent from the negative control group. Although NDF was partly cleaved during digestion, the liberated amounts of FB1 did not raise the Sa/So ratio. These results show that the investigated alkaline and thermal processing products of FB1 were, at the tested concentrations, non-toxic for rats, and suggest that according food processing can reduce fumonisin toxicity for humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

Science.gov (United States)

Grimm, Marcus O. W.; Grösgen, Sven; Rothhaar, Tatjana L.; Burg, Verena K.; Hundsdörfer, Benjamin; Haupenthal, Viola J.; Friess, Petra; Müller, Ulrike; Fassbender, Klaus; Riemenschneider, Matthias; Grimm, Heike S.; Hartmann, Tobias

2011-01-01

Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology. PMID:21660213

Sphingosine-1-phosphate in the lymphatic fluid determined by novel methods

Directory of Open Access Journals (Sweden)

Masayuki Nagahashi

2016-12-01

Conclusions: In agreement with the previous theory, our results confirm “S1P gradient” among blood, lymphatic fluid and peripheral lymphatic tissues. Convenient methods for collection and measurement of sphingolipids in lymphatic fluid are expected to provide new insights on functions of sphingolipids.

Defining episodes of diarrhoea: results from a three-country study in Sub Saharan Africa

CSIR Research Space (South Africa)

Wright, Jarrad A

2006-03-01

Full Text Available in the study Monday Tuesday Wednesday Thursday Friday Saturday Sunday ? ? ? ? ? ? ? Normal stool Diarrhoea With blood and/or mucus ���� ���� ���� ���� ���� ���� ���� the shape of a container... prospective study. J Trop Pediatr 1991;37:293-9. 5. Morris SS, Cousens SN, Lanata CF, Kirkwood BR. Diarrhea__defining the episode. Int J Epidemiol 1994;23:617-23. 6. Wyrsch M, Coakley K, Alexander N, Saleu G, Taime J, Kakazo M. Diarrhoea morbidity in children...

Development of a defined-sequence DNA system for use in DNA misrepair studies

International Nuclear Information System (INIS)

Sutton, S.; Tobias, C.A.

1984-01-01

The authors have developed a system that allows them to study cellular DNA repair processes at the molecular level. In particular, the authors are using this system to examine the consequences of a misrepair of radiation-induced DNA damage, as a function of dose. The cells being used are specially engineered haploid yeast cells. Maintained in the cells, at one copy per cell, is a cen plasmid, a plasmid that behaves like a functional chromosome. This plasmid carries a small defined sequence of DNA from the E. coli lac z gene. It is this lac z region (called the alpha region) that serves as the target for radiation damage. Two copies of the complimentary portion of the lac z gene are integrated into the yeast genome. Irradiated cells are screened for possible mutation in the alpha region by testing the cells' ability to hydrolyze xgal, a lactose substrate. The DNA of interest is then extracted from the cells, sequenced, and the sequence is compared to that of the control. Unlike the usual defined-sequence DNA systems, theirs is an in vivo system. A disadvantage is the relatively high background mutation rate. Results achieved with this system, as well as future applications, are discussed

Responsibility for proving and defining in abstract algebra class

Science.gov (United States)

Fukawa-Connelly, Timothy

2016-07-01

There is considerable variety in inquiry-oriented instruction, but what is common is that students assume roles in mathematical activity that in a traditional, lecture-based class are either assumed by the teacher (or text) or are not visible at all in traditional math classrooms. This paper is a case study of the teaching of an inquiry-based undergraduate abstract algebra course. In particular, gives a theoretical account of the defining and proving processes. The study examines the intellectual responsibility for the processes of defining and proving that the professor devolved to the students. While the professor wanted the students to engage in all aspects of defining and proving, he was only successful at devolving responsibility for certain aspects and much more successful at devolving responsibility for proving than conjecturing or defining. This study suggests that even a well-intentioned instructor may not be able to devolve responsibility to students for some aspects of mathematical practice without using a research-based curriculum or further professional development.

How do stakeholders from multiple hierarchical levels of a large provincial health system define engagement? A qualitative study.

Science.gov (United States)

Norris, Jill M; White, Deborah E; Nowell, Lorelli; Mrklas, Kelly; Stelfox, Henry T

2017-08-01

Engaging stakeholders from varied organizational levels is essential to successful healthcare quality improvement. However, engagement has been hard to achieve and to measure across diverse stakeholders. Further, current implementation science models provide little clarity about what engagement means, despite its importance. The aim of this study was to understand how stakeholders of healthcare improvement initiatives defined engagement. Participants (n = 86) in this qualitative thematic study were purposively sampled for individual interviews. Participants included leaders, core members, frontline clinicians, support personnel, and other stakeholders of Strategic Clinical Networks in Alberta Health Services, a Canadian provincial health system with over 108,000 employees. We used an iterative thematic approach to analyze participants' responses to the question, "How do you define engagement?" Regardless of their organizational role, participants defined engagement through three interrelated themes. First, engagement was active participation from willing and committed stakeholders, with levels that ranged from information sharing to full decision-making. Second, engagement centered on a shared decision-making process about meaningful change for everyone "around the table," those who are most impacted. Third, engagement was two-way interactions that began early in the change process, where exchanges were respectful and all stakeholders felt heard and understood. This study highlights the commonalities of how stakeholders in a large healthcare system defined engagement-a shared understanding and terminology-to guide and improve stakeholder engagement. Overall, engagement was an active and committed decision-making about a meaningful problem through respectful interactions and dialog where everyone's voice is considered. Our results may be used in conjunction with current implementation models to provide clarity about what engagement means and how to engage various

Ceramide species are elevated in human breast cancer and are associated with less aggressiveness

Science.gov (United States)

Moro, Kazuki; Kawaguchi, Tsutomu; Tsuchida, Junko; Gabriel, Emmanuel; Qi, Qianya; Yan, Li; Wakai, Toshifumi; Takabe, Kazuaki; Nagahashi, Masayuki

2018-01-01

Sphingolipids have emerged as key regulatory molecules in cancer cell survival and death. Although important roles of sphingolipids in breast cancer progression have been reported in experimental models, their roles in human patients are yet to be revealed. The aim of this study was to investigate the ceramide levels and its biosynthesis pathways in human breast cancer patients. Breast cancer, peri-tumor and normal breast tissue samples were collected from surgical specimens from a series of 44 patients with breast cancer. The amount of sphingolipid metabolites in the tissue were determined by mass spectrometry. The Cancer Genome Atlas was used to analyze gene expression related to the sphingolipid metabolism. Ceramide levels were higher in breast cancer tissue compared to both normal and peri-tumor breast tissue. Substrates and enzymes that generate ceramide were significantly increased in all three ceramide biosynthesis pathways in cancer. Further, higher levels of ceramide in breast cancer were associated with less aggressive cancer biology presented by Ki-67 index and nuclear grade of the cancer. Interestingly, patients with higher gene expressions of enzymes in the three major ceramide synthesis pathways showed significantly worse prognosis. This is the first study to reveal the clinical relevance of ceramide metabolism in breast cancer patients. We demonstrated that ceramide levels in breast cancer tissue were significantly higher than those in normal tissue, with activation of the three ceramide biosynthesis pathways. We also identified that ceramide levels have a significant association with aggressive phenotype and its enzymes have prognostic impact on breast cancer patients. PMID:29731990

Defining the public, defining sociology: hybrid science-public relations and boundary-work in early American sociology.

Science.gov (United States)

Evans, Michael S

2009-01-01

In this paper, I examine how scientific disciplines define their boundaries by defining the publics with whom they engage. The case study is an episode in the development of early American sociology. In response to the dual challenge of credibility set up by the conflict between religious Baconian science and secular positivist science, key actors engaged in specific strategies of boundary-work to create their desired "sociological public"--a hybrid form of science-public relations that appealed to hostile university scientists while excluding a supportive religious audience from participation in the production of scientific knowledge. Using this case, I offer two specific insights. First I illustrate how, in the pursuit of scientific credibility, actors engage in boundary-work to differentiate audiences, not just practitioners. Such defining of publics is constitutive of scientific disciplines in their formative stage. Second, I demonstrate how audience boundaries can be redefined through the capture of existing boundary objects. Specifically, the removal of informational content in key boundary objects creates durable boundaries that are difficult to overcome.

Languages for Software-Defined Networks

Science.gov (United States)

2013-02-01

switches, firewalls, and middleboxes) with closed and proprietary configuration inter- faces. Software - Defined Networks ( SDN ) are poised to change...how- ever, have seen growing interest in software - defined networks ( SDNs ), in which a logically-centralized controller manages the packet-processing...switches, firewalls, and middleboxes) with closed and proprietary configuration interfaces. Software - Defined Networks ( SDN ) are poised to change this

Defining a Bobath clinical framework - A modified e-Delphi study.

Science.gov (United States)

Vaughan-Graham, Julie; Cott, Cheryl

2016-11-01

To gain consensus within the expert International Bobath Instructors Training Association (IBITA) on a Bobath clinical framework on which future efficacy studies can be based. A three-round modified e-Delphi approach was used with 204 full members of the IBITA. Twenty-one initial statements were generated from the literature. Consensus was defined a priori as at least 80% of the respondents with a level of agreement on a Likert scale of 4 or 5. The Delphi questionnaire for each round was available online for two weeks. Summary reports and subsequent questionnaires were posted within four weeks. Ninety-four IBITA members responded, forming the Delphi panel, of which 68 and 66 responded to Rounds Two and Three, respectively. The 21 initial statements were revised to 17 statements and five new statements in Round Two in which eight statements were accepted and two statements were eliminated. Round Three presented 12 revised statements, all reaching consensus. The Delphi was successful in gaining consensus on a Bobath clinical framework in a geographically diverse expert association, identifying the unique components of Bobath clinical practice. Discussion throughout all three Rounds revolved primarily around the terminology of atypical and compensatory motor behavior and balance.

Exploring self-defining memories in schizophrenia.

Science.gov (United States)

Raffard, Stéphane; D'Argembeau, Arnaud; Lardi, Claudia; Bayard, Sophie; Boulenger, Jean-Philippe; Van Der Linden, Martial

2009-01-01

Previous studies have shown that patients with schizophrenia are impaired in recalling specific events from their personal past. However, the relationship between autobiographical memory impairments and disturbance of the sense of identity in schizophrenia has not been investigated in detail. In this study the authors investigated schizophrenic patients' ability to recall self-defining memories; that is, memories that play an important role in building and maintaining the self-concept. Results showed that patients recalled as many specific self-defining memories as healthy participants. However, patients with schizophrenia exhibited an abnormal reminiscence bump and reported different types of thematic content (i.e., they recalled less memories about past achievements and more memories regarding hospitalisation and stigmatisation of illness). Furthermore, the findings suggest that impairments in extracting meaning from personal memories could represent a core disturbance of autobiographical memory in patients with schizophrenia.

Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis

Directory of Open Access Journals (Sweden)

Yunpeng Qi

2013-01-01

Full Text Available Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD has been clinically used for treatment of myocardial ischemia (MI for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

Future Scenarios for Software-Defined Metro and Access Networks and Software-Defined Photonics

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Tommaso Muciaccia

2017-01-01

Full Text Available In recent years, architectures, devices, and components in telecommunication networks have been challenged by evolutionary and revolutionary factors which are drastically changing the traffic features. Most of these changes imply the need for major re-configurability and programmability not only in data-centers and core networks, but also in the metro-access segment. In a wide variety of contexts, this necessity has been addressed by the proposed introduction of the innovative paradigm of software-defined networks (SDNs. Several solutions inspired by the SDN model have been recently proposed also for metro and access networks, where the adoption of a new generation of software-defined reconfigurable integrated photonic devices is highly desirable. In this paper, we review the possible future application scenarios for software-defined metro and access networks and software-defined photonics (SDP, on the base of analytics, statistics, and surveys. This work describes the reasons underpinning the presented radical change of paradigm and summarizes the most significant solutions proposed in literature, with a specific emphasis to physical-layer reconfigurable networks and a focus on both architectures and devices.

Farm elders define health as the ability to work.

Science.gov (United States)

Reed, Deborah B; Rayens, Mary Kay; Conley, Christina K; Westneat, Susan; Adkins, Sarah M

2012-08-01

Thirty percent of America's 2.2 million farms are operated by individuals older than 65 years. This study examined how older farmers define health and determined whether demographic characteristics, farm work, and physical and mental health status predict health definition. Data were collected via telephone and mailed surveys during the baseline wave of data collection in a longitudinal study of family farmers residing in two southern states (n=1,288). Nearly 42% defined health as the "ability to work" compared to a physical health-related definition. Predictors of defining health as the ability to work included being White, performing more farm tasks in the past week, taking prescription medications daily, and having minimal health-related limitations to farm work. Health behaviors are centered on the individual's perception of health. Understanding the defining attributes of health can support better approaches to health care and health promotion, particularly among rural subcultures such as farmers, whose identity is rooted in their work. Copyright 2012, SLACK Incorporated.

A Case Study of Six Sigma Define-Measure-Analyze-Improve-Control (DMAIC Methodology in Garment Sector

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Abdur Rahman

2017-12-01

Full Text Available This paper demonstrates the empirical application of Six Sigma and Define-Measure-Analyze-Improve-Control (DMAIC methodology to reduce product defects within a garments manufacturing organization in Bangladesh which follows the DMAIC methodology to investigate defects, root causes and provide a solution to eliminate these defects. The analysis from employing Six Sigma and DMAIC indicated that the broken stitch and open seam influenced the number of defective products. Design of experiments (DOE and the analysis of variance (ANOVA techniques were combined to statistically determine the correlation of the broken stitch and open seam with defects as well as to define their optimum values needed to eliminate the defects. Thus, a reduction of about 35% in the garments defect was achieved, which helped the organization studied to reduce its defects and thus improve its Sigma level from 1.7 to 3.4.

Defining Virtual Reality: Dimensions Determining Telepresence.

Science.gov (United States)

Steuer, Jonathan

1992-01-01

Defines virtual reality as a particular type of experience (in terms of "presence" and "telepresence") rather than as a collection of hardware. Maintains that media technologies can be classified and studied in terms of vividness and interactivity, two attributes on which virtual reality ranks very high. (SR)

Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and a-linolenate

DEFF Research Database (Denmark)

Hansen, Harald S.; Jensen, B.

1985-01-01

sphingolipids. These rats showed increased evaporation which was comparable to that of essential fatty acid-deficient rats. We interpret these results as strong evidence for a very specific and essential function of linoleic acid in maintaining the integrity of the epidermal water permeability barrier......Essential fatty acid-deficient rats were supplemented with 300 mg per day of pure fatty acid esters: oleate (O), linoleate (L), arachidonate (A), and columbinate (C) for 10 days. During this period, the rats in groups L, A, and C all showed a decrease in their initially high trans-epidermal water...... loss, a classical essential fatty acid-deficiency symptom, to a level seen in non-deficient rats (group N). The trans-epidermal water loss in rats of group O was unaffected by the supplementation. Fatty acid composition of two epidermal sphingolipids, acylglucosylceramide and acylceramide, from...

How Should Energy Be Defined Throughout Schooling?

Science.gov (United States)

Bächtold, Manuel

2017-02-01

The question of how to teach energy has been renewed by recent studies focusing on the learning and teaching progressions for this concept. In this context, one question has been, for the most part, overlooked: how should energy be defined throughout schooling? This paper addresses this question in three steps. We first identify and discuss two main approaches in physics concerning the definition of energy, one claiming there is no satisfactory definition and taking conservation as a fundamental property, and the other based on Rankine's definition of energy as the capacity of a system to produce changes. We then present a study concerning how energy is actually defined throughout schooling in the case of France by analyzing national programs, physics textbooks, and the answers of teachers to a questionnaire. This study brings to light a consistency problem in the way energy is defined across school years: in primary school, an adapted version of Rankine's definition is introduced and conservation is ignored; in high school, conservation is introduced and Rankine's definition is ignored. Finally, we address this consistency problem by discussing possible teaching progressions. We argue in favor of the use of Rankine's definition throughout schooling: at primary school, it is a possible substitute to students' erroneous conceptions; at secondary school, it might help students become aware of the unifying role of energy and thereby overcome the compartmentalization problem.

Plasma cross-gestational sphingolipidomic analyses reveal potential first trimester biomarkers of preeclampsia.

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Aneta Dobierzewska

Full Text Available Preeclampsia (PE is a gestational disorder, manifested in the second half of pregnancy by maternal hypertension, proteinuria and generalized edema. PE is a major cause of maternal and fetal morbidity and mortality, accounting for nearly 40% of all premature births worldwide. Bioactive sphingolipids are emerging as key molecules involved in etiopathogenesis of PE, characterized by maternal angiogenic imbalance and symptoms of metabolic syndrome. The aim of this study was to compare the cross-gestational profile of circulating bioactive sphingolipids in maternal plasma from preeclamptic (PE versus normotensive control (CTL subjects with the goal of identifying sphingolipids as candidate first trimester biomarkers of PE for early prediction of the disease.A prospective cohort of patients was sampled at the first, second and third trimester of pregnancy for each patient (11-14, 22-24, and 32-36 weeks´ gestation. A retrospective stratified study design was used to quantify different classes of sphingolipids in maternal plasma. We used a reverse-phase high-performance liquid chromatography-tandem mass spectrometry (HPLC-ESI-MS/MS approach for determining different sphingolipid molecular species (sphingosine-1-phosphate (S1P, dihydro-sphingosine-1-phosphate (DH-S1P, sphingomyelins (SM and ceramides (Cer in cross-gestational samples of human plasma from PE (n = 7, 21 plasma samples across pregnancy and CTL (n = 7, 21 plasma samples across pregnancy patients.Plasma levels of angiogenic S1P did not change significantly in control and in preeclamptic patients´ group across gestation. DH-S1P was significantly decreased in second trimester plasma of PE patients in comparison to their first trimester, which could contribute to reduced endothelial barrier observed in PE. The major ceramide species (Cer 16:0 and Cer 24:0 tended to be up-regulated in plasma of control and PE subjects across gestation. The levels of a less abundant plasma ceramide species (Cer

Antitumor activity of a novel and orally available inhibitor of serine palmitoyltransferase

International Nuclear Information System (INIS)

Yaguchi, Masahiro; Shibata, Sachio; Satomi, Yoshinori; Hirayama, Megumi; Adachi, Ryutaro; Asano, Yasutomi; Kojima, Takuto; Hirata, Yasuhiro; Mizutani, Akio; Kiba, Atsushi; Sagiya, Yoji

2017-01-01

Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin. In the presence of compound-2, exogenously added S1P partially compensated the intracellular sphingolipid levels through the salvage pathway by partially rescuing compound-2-induced cytotoxicity. This suggested that the mechanism underlying the anti-proliferative effect of compound-2 involved the reduction of sphingolipid levels. Indeed, compound-2 promoted multinuclear formation with reduced endogenous sphingomyelin levels specifically in a compound-2-sensitive cell line, indicating that the effect was induced by sphingolipid reduction. Furthermore, compound-2 showed potent antitumor activity without causing significant body weight loss in the PL-21 acute myeloid leukemia mouse xenograft model. Therefore, SPT may be an attractive therapeutic anti-cancer drug target for which compound-2 may be a promising new drug. - Highlights: • We discovered compound-2, a novel and orally available SPT inhibitor. • Compound-2 was cytotoxic against PL-21 acute myeloid leukemia cells. • Compound-2 showed antitumor activity in the PL-21 mouse xenograft model.

Positive facial expressions during retrieval of self-defining memories.

Science.gov (United States)

Gandolphe, Marie Charlotte; Nandrino, Jean Louis; Delelis, Gérald; Ducro, Claire; Lavallee, Audrey; Saloppe, Xavier; Moustafa, Ahmed A; El Haj, Mohamad

2017-11-14

In this study, we investigated, for the first time, facial expressions during the retrieval of Self-defining memories (i.e., those vivid and emotionally intense memories of enduring concerns or unresolved conflicts). Participants self-rated the emotional valence of their Self-defining memories and autobiographical retrieval was analyzed with a facial analysis software. This software (Facereader) synthesizes the facial expression information (i.e., cheek, lips, muscles, eyebrow muscles) to describe and categorize facial expressions (i.e., neutral, happy, sad, surprised, angry, scared, and disgusted facial expressions). We found that participants showed more emotional than neutral facial expressions during the retrieval of Self-defining memories. We also found that participants showed more positive than negative facial expressions during the retrieval of Self-defining memories. Interestingly, participants attributed positive valence to the retrieved memories. These findings are the first to demonstrate the consistency between facial expressions and the emotional subjective experience of Self-defining memories. These findings provide valuable physiological information about the emotional experience of the past.

Clinical prediction in defined populations: a simulation study investigating when and how to aggregate existing models

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Glen P. Martin

2017-01-01

Full Text Available Abstract Background Clinical prediction models (CPMs are increasingly deployed to support healthcare decisions but they are derived inconsistently, in part due to limited data. An emerging alternative is to aggregate existing CPMs developed for similar settings and outcomes. This simulation study aimed to investigate the impact of between-population-heterogeneity and sample size on aggregating existing CPMs in a defined population, compared with developing a model de novo. Methods Simulations were designed to mimic a scenario in which multiple CPMs for a binary outcome had been derived in distinct, heterogeneous populations, with potentially different predictors available in each. We then generated a new ‘local’ population and compared the performance of CPMs developed for this population by aggregation, using stacked regression, principal component analysis or partial least squares, with redevelopment from scratch using backwards selection and penalised regression. Results While redevelopment approaches resulted in models that were miscalibrated for local datasets of less than 500 observations, model aggregation methods were well calibrated across all simulation scenarios. When the size of local data was less than 1000 observations and between-population-heterogeneity was small, aggregating existing CPMs gave better discrimination and had the lowest mean square error in the predicted risks compared with deriving a new model. Conversely, given greater than 1000 observations and significant between-population-heterogeneity, then redevelopment outperformed the aggregation approaches. In all other scenarios, both aggregation and de novo derivation resulted in similar predictive performance. Conclusion This study demonstrates a pragmatic approach to contextualising CPMs to defined populations. When aiming to develop models in defined populations, modellers should consider existing CPMs, with aggregation approaches being a suitable modelling

Modular Software-Defined Radio

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Rhiemeier Arnd-Ragnar

2005-01-01

Full Text Available In view of the technical and commercial boundary conditions for software-defined radio (SDR, it is suggestive to reconsider the concept anew from an unconventional point of view. The organizational principles of signal processing (rather than the signal processing algorithms themselves are the main focus of this work on modular software-defined radio. Modularity and flexibility are just two key characteristics of the SDR environment which extend smoothly into the modeling of hardware and software. In particular, the proposed model of signal processing software includes irregular, connected, directed, acyclic graphs with random node weights and random edges. Several approaches for mapping such software to a given hardware are discussed. Taking into account previous findings as well as new results from system simulations presented here, the paper finally concludes with the utility of pipelining as a general design guideline for modular software-defined radio.

Are you better? A multi-centre study of patient-defined recovery from Complex Regional Pain Syndrome

DEFF Research Database (Denmark)

Llewellyn, A; McCabe, CS; Hibberd, Y

2018-01-01

Background: Complex Regional Pain Syndrome (CRPS) symptoms can significantly differ between patients, fluctuate over time, disappear or persist. This leads to problems in defining recovery and in evaluating the efficacy of therapeutic interventions. Objectives: To define recovery from the patient...

Application-Defined Decentralized Access Control

Science.gov (United States)

Xu, Yuanzhong; Dunn, Alan M.; Hofmann, Owen S.; Lee, Michael Z.; Mehdi, Syed Akbar; Witchel, Emmett

2014-01-01

DCAC is a practical OS-level access control system that supports application-defined principals. It allows normal users to perform administrative operations within their privilege, enabling isolation and privilege separation for applications. It does not require centralized policy specification or management, giving applications freedom to manage their principals while the policies are still enforced by the OS. DCAC uses hierarchically-named attributes as a generic framework for user-defined policies such as groups defined by normal users. For both local and networked file systems, its execution time overhead is between 0%–9% on file system microbenchmarks, and under 1% on applications. This paper shows the design and implementation of DCAC, as well as several real-world use cases, including sandboxing applications, enforcing server applications’ security policies, supporting NFS, and authenticating user-defined sub-principals in SSH, all with minimal code changes. PMID:25426493

Define Project

DEFF Research Database (Denmark)

Munk-Madsen, Andreas

2005-01-01

"Project" is a key concept in IS management. The word is frequently used in textbooks and standards. Yet we seldom find a precise definition of the concept. This paper discusses how to define the concept of a project. The proposed definition covers both heavily formalized projects and informally...... organized, agile projects. Based on the proposed definition popular existing definitions are discussed....

A Diet Rich in Medium-Chain Fatty Acids Improves Systolic Function and Alters the Lipidomic Profile in Patients With Type 2 Diabetes: A Pilot Study.

Science.gov (United States)

Airhart, Sophia; Cade, W Todd; Jiang, Hui; Coggan, Andrew R; Racette, Susan B; Korenblat, Kevin; Spearie, Catherine Anderson; Waller, Suzanne; O'Connor, Robert; Bashir, Adil; Ory, Daniel S; Schaffer, Jean E; Novak, Eric; Farmer, Marsha; Waggoner, Alan D; Dávila-Román, Víctor G; Javidan-Nejad, Cylen; Peterson, Linda R

2016-02-01

Excessive cardiac long-chain fatty acid (LCFA) metabolism/storage causes cardiomyopathy in animal models of type 2 diabetes. Medium-chain fatty acids (MCFAs) are absorbed and oxidized efficiently. Data in animal models of diabetes suggest MCFAs may benefit the heart. Our objective was to test the effects of an MCFA-rich diet vs an LCFA-rich diet on plasma lipids, cardiac steatosis, and function in patients with type 2 diabetes. This was a double-blind, randomized, 2-week matched-feeding study. The study included ambulatory patients in the general community. Sixteen patients, ages 37-65 years, with type 2 diabetes, an ejection fraction greater than 45%, and no other systemic disease were included. Fourteen days of a diet rich in MCFAs or LCFAs, containing 38% as fat in total, was undertaken. Cardiac steatosis and function were the main outcome measures, with lipidomic changes considered a secondary outcome. The relatively load-independent measure of cardiac contractility, S', improved in the MCFA group (P diet decreased several plasma sphingolipids, ceramide, and acylcarnitines implicated in diabetic cardiomyopathy, and changes in several sphingolipids correlated with improved fasting insulins. Although a diet high in MCFAs does not change cardiac steatosis, our findings suggest that the MCFA-rich diet alters the plasma lipidome and may benefit or at least not harm cardiac function and fasting insulin levels in humans with type 2 diabetes. Larger, long-term studies are needed to further evaluate these effects in less-controlled settings.

Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium.

Science.gov (United States)

Lindborg, Beth A; Brekke, John H; Vegoe, Amanda L; Ulrich, Connor B; Haider, Kerri T; Subramaniam, Sandhya; Venhuizen, Scott L; Eide, Cindy R; Orchard, Paul J; Chen, Weili; Wang, Qi; Pelaez, Francisco; Scott, Carolyn M; Kokkoli, Efrosini; Keirstead, Susan A; Dutton, James R; Tolar, Jakub; O'Brien, Timothy D

2016-07-01

Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10-14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like structures and evidence of early corticogenesis. Immunostaining and quantitative reverse-transcription polymerase chain reaction demonstrated protein and gene expression representative of forebrain, midbrain, and hindbrain development. Physiologic studies showed responses to glutamate and depolarization in many cells, consistent with neural behavior. The method of cerebral organoid generation described here facilitates access to this technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. Tissue organoids are a promising technology with many potential applications, such as pharmaceutical screens and development of in vitro disease models, particularly for human polygenic conditions where animal models are insufficient. This work describes a robust and simple method for generating cerebral organoids from human induced pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. This method, by virtue of its simplicity and use of defined materials, greatly facilitates access to cerebral organoid technology, enables scalable applications, and provides a potential pathway to translational applications where defined components are desirable. ©AlphaMed Press.

Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

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Paul J Leo

2017-08-01

Full Text Available A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4% of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

Research Network of Tehran Defined Population: Methodology and Establishment

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Ali-Asghar Kolahi

2015-12-01

Full Text Available Background: We need a defined population for determining prevalence and incidence of diseases, as well as conducting interventional, cohort and longitudinal studies, calculating correct and timely public health indicators, assessing actual health needs of community, performing educational programs and interventions to promote healthy lifestyle, and enhancing quality of primary health services.The objective of this project was to determine a defined population which is representative of Tehran, the Capital of Iran. This article reports the methodology and establishment of the research network of Tehran defined population.Methods: This project started by selecting two urban health centers from each of the five district health centers affiliated to Shahid Beheshti University of Medical Sciences in 2012. Inside each selected urban health center, one defined population research station was established. Two new centers have been added during 2013 and 2014. For the time being, the number of the covered population of the network has reached 40000 individuals. The most important criterion for the defined population has been to be representative of the population of Tehran. For this, we selected two urban health centers from 12 of 22 municipality districts and from each of the five different socioeconomic of Greater Tehran. Merely 80000 individuals in neighborhoods of each defined population research station were considered as control group of the project.Findings: Totally we selected 12 defined population research stations and their under-covered population developed a defined population which is representative of Tehran population.Conclusion: a population lab is ready now in metropolitan of Tehran.

Using MFM methodology to generate and define major accident scenarios for quantitative risk assessment studies

DEFF Research Database (Denmark)

Hua, Xinsheng; Wu, Zongzhi; Lind, Morten

2017-01-01

to calculate likelihood of each MAS. Combining the likelihood of each scenario with a qualitative risk matrix, each major accident scenario is thereby ranked for consideration for detailed consequence analysis. The methodology is successfully highlighted using part of BMA-process for production of hydrogen......Generating and defining Major Accident Scenarios (MAS) are commonly agreed as the key step for quantitative risk assessment (QRA). The aim of the study is to explore the feasibility of using Multilevel Flow Modeling (MFM) methodology to formulating MAS. Traditionally this is usually done based...

Defining depth of anesthesia.

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Shafer, S L; Stanski, D R

2008-01-01

In this chapter, drawn largely from the synthesis of material that we first presented in the sixth edition of Miller's Anesthesia, Chap 31 (Stanski and Shafer 2005; used by permission of the publisher), we have defined anesthetic depth as the probability of non-response to stimulation, calibrated against the strength of the stimulus, the difficulty of suppressing the response, and the drug-induced probability of non-responsiveness at defined effect site concentrations. This definition requires measurement of multiple different stimuli and responses at well-defined drug concentrations. There is no one stimulus and response measurement that will capture depth of anesthesia in a clinically or scientifically meaningful manner. The "clinical art" of anesthesia requires calibration of these observations of stimuli and responses (verbal responses, movement, tachycardia) against the dose and concentration of anesthetic drugs used to reduce the probability of response, constantly adjusting the administered dose to achieve the desired anesthetic depth. In our definition of "depth of anesthesia" we define the need for two components to create the anesthetic state: hypnosis created with drugs such as propofol or the inhalational anesthetics and analgesia created with the opioids or nitrous oxide. We demonstrate the scientific evidence that profound degrees of hypnosis in the absence of analgesia will not prevent the hemodynamic responses to profoundly noxious stimuli. Also, profound degrees of analgesia do not guarantee unconsciousness. However, the combination of hypnosis and analgesia suppresses hemodynamic response to noxious stimuli and guarantees unconsciousness.

Defining palliative care in cystic fibrosis: A Delphi study.

Science.gov (United States)

Dellon, E P; Goggin, J; Chen, E; Sabadosa, K; Hempstead, S E; Faro, A; Homa, K

2018-05-01

The goal of palliative care is to improve quality of life for people with serious illness. We aimed to create a cystic fibrosis (CF)-specific definition of palliative care. A working group of 36 CF care providers, researchers, palliative care providers, quality improvement experts, individuals with CF, and CF caregivers completed a series of questionnaires to rate the value of each of 22 attributes of palliative care, rank top attributes to construct definitions of palliative care, and then rate proposed definitions. An average of 28 participants completed each of four questionnaires, with consistent distribution of stakeholder roles across questionnaires. Many identified overlaps in routine CF care and palliative care and highlighted the importance of a definition that feels relevant across the lifespan. Modified Delphi methodology was used to define palliative care in CF. The definition will be used as the foundation for development of CF-specific palliative care guidelines. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

All projects related to Canada | Page 2 | IDRC - International ...

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

The Bolivian public justice performance research study. Project ... A functioning immune system is critical for successful treatment of cancer. Region: ... Regulation of stem-cell mediated host immunity by the sphingolipid pathway. Project.

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

cell mediated host immunity by the sphingolipid pathway ... Of Colombia's 13 million young people, 4.5 million are neither working nor studying. ... due to the lack of accessible and affordable treatment options.

Toward defining and measuring social accountability in graduate medical education: a stakeholder study.

Science.gov (United States)

Reddy, Anjani T; Lazreg, Sonia A; Phillips, Robert L; Bazemore, Andrew W; Lucan, Sean C

2013-09-01

Since 1965, Medicare has publically financed graduate medical education (GME) in the United States. Given public financing, various advisory groups have argued that GME should be more socially accountable. Several efforts are underway to develop accountability measures for GME that could be tied to Medicare payments, but it is not clear how to measure or even define social accountability. We explored how GME stakeholders perceive, define, and measure social accountability. Through purposive and snowball sampling, we completed semistructured interviews with 18 GME stakeholders from GME training sites, government agencies, and health care organizations. We analyzed interview field notes and audiorecordings using a flexible, iterative, qualitative group process to identify themes. THREE THEMES EMERGED IN REGARDS TO DEFINING SOCIAL ACCOUNTABILITY: (1) creating a diverse physician workforce to address regional needs and primary care and specialty shortages; (2) ensuring quality in training and care to best serve patients; and (3) providing service to surrounding communities and the general public. All but 1 stakeholder believed GME institutions have a responsibility to be socially accountable. Reported barriers to achieving social accountability included training time constraints, financial limitations, and institutional resistance. Suggestions for measuring social accountability included reviewing graduates' specialties and practice locations, evaluating curricular content, and reviewing program services to surrounding communities. Most stakeholders endorsed the concept of social accountability in GME, suggesting definitions and possible measures that could inform policy makers calls for increased accountability despite recognized barriers.

Defining enthesitis in spondyloarthritis by ultrasound

DEFF Research Database (Denmark)

Terslev, Lene; Naredo, E; Iagnocco, A

2014-01-01

Objective: To standardize ultrasound (US) in enthesitis. Methods: An Initial Delphi exercise was undertaken to define US detected enthesitis and its core components. These definitions were subsequently tested on static images taken from Spondyloarthritis (SpA) patients in order to evaluate...... elementary component. On static images the intra-observer reliability showed a high degree of variability for the detection of elementary lesions with kappa coefficients ranging from 0.14 - 1. The inter-observer kappa value was variable with the lowest kappa for enthesophytes (0.24) and the best for Doppler...... activity at the enthesis (0.63). Conclusion: This is the first consensus based definition of US enthesitis and its elementary components and the first step performed to ensure a higher degree of homogeneity and comparability of results between studies and in daily clinical work. Defining Enthesitis...

Drinking Levels Defined

Science.gov (United States)

... of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol Exposure Support & Treatment Alcohol Policy Special ... Definition of Drinking at Low Risk for Developing Alcohol Use Disorder (AUD): For women, low-risk drinking is defined ...

Case study of evaluations that go beyond clinical outcomes to assess quality improvement diabetes programmes using the Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE).

Science.gov (United States)

Paquette-Warren, Jann; Harris, Stewart B; Naqshbandi Hayward, Mariam; Tompkins, Jordan W

2016-10-01

Investments in efforts to reduce the burden of diabetes on patients and health care are critical; however, more evaluation is needed to provide evidence that informs and supports future policies and programmes. The newly developed Diabetes Evaluation Framework for Innovative National Evaluations (DEFINE) incorporates the theoretical concepts needed to facilitate the capture of critical information to guide investments, policy and programmatic decision making. The aim of the study is to assess the applicability and value of DEFINE in comprehensive real-world evaluation. Using a critical and positivist approach, this intrinsic and collective case study retrospectively examines two naturalistic evaluations to demonstrate how DEFINE could be used when conducting real-world comprehensive evaluations in health care settings. The variability between the cases and the evaluation designs are described and aligned to the DEFINE goals, steps and sub-steps. The majority of the theoretical steps of DEFINE were exemplified in both cases, although limited for knowledge translation efforts. Application of DEFINE to evaluate diverse programmes that target various chronic diseases is needed to further test the inclusivity and built-in flexibility of DEFINE and its role in encouraging more comprehensive knowledge translation. This case study shows how DEFINE could be used to structure or guide comprehensive evaluations of programmes and initiatives implemented in health care settings and support scale-up of successful innovations. Future use of the framework will continue to strengthen its value in guiding programme evaluation and informing health policy to reduce the burden of diabetes and other chronic diseases. © 2016 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Developing social standards for wilderness encounters in Mount Rainier National Park: Manager-defined versus visitor-defined standards

Science.gov (United States)

Kristopher J. Lah

2000-01-01

This research compared the differences found between manager-defined and visitor-defined social standards for wilderness encounters in Mount Rainier National Park. Social standards in recreation areas of public land are defined by what is acceptable to the public, in addition to the area’s management. Social standards for the encounter indicator in Mount Rainier’s...

Stability studies needed to define the handling and transport conditions of sensitive pharmaceutical or biotechnological products.

Science.gov (United States)

Ammann, Claude

2011-12-01

Many pharmaceutical or biotechnological products require transport using temperature-controlled systems to keep their therapeutic properties. There are presently no official guidelines for testing pharmaceutical products in order to define suitable transport specifications. After reviewing the current guidance documents, this paper proposes a methodology for testing pharmaceutical products and defining appropriate transport conditions.

Small angle neutron scattering study of polyelectrolyte brushes grafted to well-defined gold nanoparticle interfaces.

Science.gov (United States)

Jia, Haidong; Grillo, Isabelle; Titmuss, Simon

2010-05-18

Small angle neutron scattering (SANS) has been used to study the conformations, and response to added salt, of a polyelectrolyte layer grafted to the interfaces of well-defined gold nanoparticles. The polyelectrolyte layer is prepared at a constant coverage by grafting thiol-functionalized polystyrene (M(w) = 53k) to gold nanoparticles of well-defined interfacial curvature (R(c) = 26.5 nm) followed by a soft-sulfonation of 38% of the segments to sodium polystyrene sulfonate (NaPSS). The SANS profiles can be fit by Fermi-Dirac distributions that are consistent with a Gaussian distribution but are better described by a parabolic distribution plus an exponential tail, particularly in the high salt regime. These distributions are consistent with the predictions and measurements for osmotic and salted brushes at interfaces of low curvature. When the concentration of added salt exceeds the concentration of counterions inside the brush, there is a salt-induced deswelling, but even at the highest salt concentration the brush remains significantly swollen due to a short-ranged excluded volume interaction. This is responsible for the observed resistance to aggregation of these comparatively high concentration polyelectrolyte stabilized gold nanoparticle dispersions even in the presence of a high concentration of added salt.

ON DEFINING S-SPACES

Directory of Open Access Journals (Sweden)

Francesco Strati

2013-05-01

Full Text Available The present work is intended to be an introduction to the Superposition Theory of David Carfì. In particular I shall depict the meaning of his brand new theory, on the one hand in an informal fashion and on the other hand by giving a formal approach of the algebraic structure of the theory: the S-linear algebra. This kind of structure underpins the notion of S-spaces (or Carfì-spaces by defining both its properties and its nature. Thus I shall define the S-triple as the fundamental principle upon which the S-linear algebra is built up.

Defining Legal Moralism

DEFF Research Database (Denmark)

Thaysen, Jens Damgaard

2015-01-01

This paper discusses how legal moralism should be defined. It is argued that legal moralism should be defined as the position that “For any X, it is always a pro tanto reason for justifiably imposing legal regulation on X that X is morally wrong (where “morally wrong” is not conceptually equivalent...... to “harmful”)”. Furthermore, a distinction between six types of legal moralism is made. The six types are grouped according to whether they are concerned with the enforcement of positive or critical morality, and whether they are concerned with criminalising, legally restricting, or refraining from legally...... protecting morally wrong behaviour. This is interesting because not all types of legal moralism are equally vulnerable to the different critiques of legal moralism that have been put forth. Indeed, I show that some interesting types of legal moralism have not been criticised at all....

Defining Tiger Parenting in Chinese Americans.

Science.gov (United States)

Kim, Su Yeong

2013-09-01

"Tiger" parenting, as described by Amy Chua [2011], has instigated scholarly discourse on this phenomenon and its possible effects on families. Our eight-year longitudinal study, published in the Asian American Journal of Psychology [Kim, Wang, Orozco-Lapray, Shen, & Murtuza, 2013b], demonstrates that tiger parenting is not a common parenting profile in a sample of 444 Chinese American families. Tiger parenting also does not relate to superior academic performance in children. In fact, the best developmental outcomes were found among children of supportive parents. We examine the complexities around defining tiger parenting by reviewing classical literature on parenting styles and scholarship on Asian American parenting, along with Amy Chua's own description of her parenting method, to develop, define, and categorize variability in parenting in a sample of Chinese American families. We also provide evidence that supportive parenting is important for the optimal development of Chinese American adolescents.

Defining the Simulation Technician Role: Results of a Survey-Based Study.

Science.gov (United States)

Bailey, Rachel; Taylor, Regina G; FitzGerald, Michael R; Kerrey, Benjamin T; LeMaster, Thomas; Geis, Gary L

2015-10-01

In health care simulation, simulation technicians perform multiple tasks to support various educational offerings. Technician responsibilities and the tasks that accompany them seem to vary between centers. The objectives were to identify the range and frequency of tasks that technicians perform and to determine if there is a correspondence between what technicians do and what they feel their responsibilities should be. We hypothesized that there is a core set of responsibilities and tasks for the technician position regardless of background, experience, and type of simulation center. We conducted a prospective, survey-based study of individuals currently functioning in a simulation technician role in a simulation center. This survey was designed internally and piloted within 3 academic simulation centers. Potential respondents were identified through a national mailing list, and the survey was distributed electronically during a 3-week period. A survey request was sent to 280 potential participants, 136 (49%) responded, and 73 met inclusion criteria. Five core tasks were identified as follows: equipment setup and breakdown, programming scenarios into software, operation of software during simulation, audiovisual support for courses, and on-site simulator maintenance. Independent of background before they were hired, technicians felt unprepared for their role once taking the position. Formal training was identified as a need; however, the majority of technicians felt experience over time was the main contributor toward developing knowledge and skills within their role. This study represents a first step in defining the technician role within simulation-based education and supports the need for the development of a formal job description to allow recruitment, development, and certification.

FINANCIAL ACCOUNTING QUALITY AND ITS DEFINING CHARACTERISTICS

Directory of Open Access Journals (Sweden)

Andra M. ACHIM

2014-11-01

Full Text Available The importance ofhigh-quality financial statements is highlighted by the main standard-setting institutions activating in the field of accounting and reporting. These have issued Conceptual Frameworks which state and describe the qualitative characteristics of accounting information. In this qualitative study, the research methodology consists of reviewing the literature related to the definition of accounting quality and striving for understanding how it can be explained. The main objective of the study is to identify the characteristics information should possess in order to be of high quality. These characteristics also contribute to the way of defining financial accounting quality. The main conclusions that arise from this research are represented by the facts that indeed financial accounting quality cannot be uniquely defined and that financial information is of good quality when it enhances the characteristics incorporated in the conceptual frameworks issued by both International Accounting Standards Board and Financial Accounting Standards Board.

Serum sphingomyelin has potential to reflect hepatic injury in chronic hepatitis B virus infection

OpenAIRE

Su-Jun Zheng; Feng Qu; Jun-Feng Li; Jing Zhao; Jing-Yun Zhang; Mei Liu; Feng Ren; Yu Chen; Jin-Lan Zhang; Zhong-Ping Duan

2015-01-01

Objective: To explore the relation between serum sphingolipids and hepatic injury in chronic HBV infection. Methods: A cohort of participants including 48 healthy persons, 103 chronic HBV-infected patients containing chronic hepatitis B (CHB) and HBV-related cirrhosis were included. High performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was performed to detect serum sphingolipids. The serological indicators were detected and quantified. The valid liver biop...

Defining Quality in Undergraduate Education

Directory of Open Access Journals (Sweden)

Alison W. Bowers

2018-01-01

Full Text Available Objectives: This research brief explores the literature addressing quality in undergraduate education to identify what previous research has said about quality and to offer future directions for research on quality in undergraduate education. Method: We conducted a scoping review to provide a broad overview of existing research. Using targeted search terms in academic databases, we identified and reviewed relevant academic literature to develop emergent themes and implications for future research. Results: The exploratory review of the literature revealed a range of thoughtful discussions and empirical studies attempting to define quality in undergraduate education. Many publications highlighted the importance of including different stakeholder perspectives and presented some of the varying perceptions of quality among different stakeholders. Conclusions: While a number of researchers have explored and written about how to define quality in undergraduate education, there is not a general consensus regarding a definition of quality in undergraduate education. Past research offers a range of insights, models, and data to inform future research. Implication for Theory and/or Practice: We provide four recommendations for future research to contribute to a high quality undergraduate educational experience. We suggest more comprehensive systematic reviews of the literature as a next step.

Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort.

Science.gov (United States)

Schmidt, Julie A; Rinaldi, Sabina; Ferrari, Pietro; Carayol, Marion; Achaintre, David; Scalbert, Augustin; Cross, Amanda J; Gunter, Marc J; Fensom, Georgina K; Appleby, Paul N; Key, Timothy J; Travis, Ruth C

2015-12-01

Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate-controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans.

On defining semantics of extended attribute grammars

DEFF Research Database (Denmark)

Madsen, Ole Lehrmann

1980-01-01

Knuth has introduced attribute grammars (AGs) as a tool to define the semanitcs of context-free languages. The use of AGs in connection with programming language definitions has mostly been to define the context-sensitive syntax of the language and to define a translation in code for a hypothetic...

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Indian Academy of Sciences (India)

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Clipboard. Ceramide trafficking: learning from the rebels ... van Meer 2004) designed a mammalian cell screen to study how the levels of sphingolipids are regu- lated. ... pathways controlling growth, response to stress and death. The rebel ...

Loss of Sphingosine Kinase Alters Life History Traits and Locomotor Function in Caenorhabditis elegans

Directory of Open Access Journals (Sweden)

Jason P. Chan

2017-09-01

Full Text Available Sphingolipid metabolism is important to balance the abundance of bioactive lipid molecules involved in cell signaling, neuronal function, and survival. Specifically, the sphingolipid sphingosine mediates cell death signaling, whereas its phosphorylated form, sphingosine-1-phosphate (S1P, mediates cell survival signaling. The enzyme sphingosine kinase produces S1P, and the activity of sphingosine kinase impacts the ability of cells to survive under stress and challenges. To examine the influence of sphingolipid metabolism, particularly enzymes regulating sphingosine and S1P, in mediating aging, neuronal function and stress response, we examined life history traits, locomotor capacities and heat stress responses of young and old animals using the model organism Caenorhabditis elegans. We found that C. elegans sphk-1 mutants, which lack sphingosine kinase, had shorter lifespans, reduced brood sizes, and smaller body sizes compared to wild type animals. By analyzing a panel of young and old animals with genetic mutations in the sphingolipid signaling pathway, we showed that aged sphk-1 mutants exhibited a greater decline in neuromuscular function and locomotor behavior. In addition, aged animals lacking sphk-1 were more susceptible to death induced by acute and prolonged heat exposure. On the other hand, older animals with loss of function mutations in ceramide synthase (hyl-1, which converts sphingosine to ceramide, showed improved neuromuscular function and stress response with age. This phenotype was dependent on sphk-1. Together, our data show that loss of sphingosine kinase contributes to poor animal health span, suggesting that sphingolipid signaling may be important for healthy neuronal function and animal stress response during aging.

Defining Modules, Modularity and Modularization

DEFF Research Database (Denmark)

Miller, Thomas Dedenroth; Pedersen, Per Erik Elgård

The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization.......The paper describes the evolution of the concept of modularity in a historical perspective. The main reasons for modularity are: create variety, utilize similarities, and reduce complexity. The paper defines the terms: Module, modularity, and modularization....

Defining Peer-to-Peer Accountability From the Nurse's Perspective.

Science.gov (United States)

Lockett, Jacqueline Jansen; Barkley, Leslie; Stichler, Jaynelle; Palomo, Jeanne; Kik, Bozena; Walker, Christopher; Donnelly, Janet; Willon, Judy; Sanborn, Julie; O'Byrne, Noeleen

2015-11-01

The aim of this study was to define and create a conceptual model for peer-to-peer accountability (P to PA). Many organizations cite the importance of peer accountability (PA) as essential in ensuring patient safety. Professionalism in nursing requires self-regulation of practice and PA. Although discussed in the literature, P to PA is not conceptually defined. A grounded theory study design with constant comparative data collection and analysis was used to explore nurses' definitions of P to PA and their perceptions of motivators and barriers to engaging in P to PA. Transcripts of digital recordings of all interviews were analyzed using line-by-line coding until identified themes emerged. P to PA was defined as the act of speaking up when one observes a peer not practicing to acceptable standards. A conceptual model illustrates the antecedents, attributes, and consequences of P to PA. P to PA is the professional responsibility of every nurse and healthcare provider and is essential for safe patient care. The conceptual definition facilitates actualization of P to PA in practice.

Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease

Directory of Open Access Journals (Sweden)

Tomasz Wollny

2017-03-01

Full Text Available Beyond their role as structural molecules, sphingolipids are involved in many important cellular processes including cell proliferation, apoptosis, inflammation, and migration. Altered sphingolipid metabolism is observed in many pathological conditions including gastrointestinal diseases. Inflammatory bowel disease (IBD represents a state of complex, unpredictable, and destructive inflammation of unknown origin within the gastrointestinal tract. The mechanisms explaining the pathophysiology of IBD involve signal transduction pathways regulating gastro-intestinal system’s immunity. Progressive intestinal tissue destruction observed in chronic inflammation may be associated with an increased risk of colon cancer. Sphingosine-1-phosphate (S1P, a sphingolipid metabolite, functions as a cofactor in inflammatory signaling and becomes a target in the treatment of IBD, which might prevent its conversion to cancer. This paper summarizes new findings indicating the impact of (S1P on IBD development and IBD-associated carcinogenesis.

Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans

DEFF Research Database (Denmark)

Mosbech, Mai-Britt; Kruse, Rikke; Harvald, Eva Bang

2013-01-01

Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2...... that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR......, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24), while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22). Here we show that functional loss of HYL-2 decreases lifespan, while loss...

Self-defining memories during exposure to music in Alzheimer's disease.

Science.gov (United States)

El Haj, Mohamad; Antoine, Pascal; Nandrino, Jean Louis; Gély-Nargeot, Marie-Christine; Raffard, Stéphane

2015-10-01

Research suggests that exposure to music may enhance autobiographical recall in Alzheimer's Disease (AD) patients. This study investigated whether exposure to music could enhance the production of self-defining memories, that is, memories that contribute to self-discovery, self-understanding, and identity in AD patients. Twenty-two mild-stage AD patients and 24 healthy controls were asked to produce autobiographical memories in silence, while listening to researcher-chosen music, and to their own-chosen music. AD patients showed better autobiographical recall when listening to their own-chosen music than to researcher-chosen music or than in silence. More precisely, they produced more self-defining memories during exposure to their own-chosen music than to researcher-chosen music or during silence. Additionally, AD patients produced more self-defining memories than autobiographical episodes or personal-semantics during exposure to their own-chosen music. This pattern contrasted with the poor production of self-defining memories during silence or during exposure to researcher-chosen music. Healthy controls did not seem to enjoy the same autobiographical benefits nor the same self-defining memory enhancement in the self-chosen music condition. Poor production of self-defining memories, as observed in AD, may somehow be alleviated by exposure to self-chosen music.

Investigation into reaction of heterogenous isotopic exchange with gaseoUs tritium in solution for preparation labelled lipid compounds

International Nuclear Information System (INIS)

Shevchenko, V.P.; Myasoedov, N.F.

1983-01-01

The applicability of the method of heterogeneous catalytic isotopic exchange with gaseous tritium in the solution for the production of labelled lipide preparations is studied. Labelled saturated and unsaturated aliphatic acids, prostaglandins, phospholipides and sphingolipides are prepared

Ten Year Study of the Stringently Defined Otitis Prone Child in Rochester, NY

Science.gov (United States)

Pichichero, Michael E.

2016-01-01

This review summarizes a prospective, longitudinal 10-year study in Rochester NY with virtually every clinically diagnosed acute otitis media (AOM) confirmed by bacterial culture of middle ear fluid. Children experiencing 3 episodes within 6 months or 4 episodes in 12 months were considered stringently-defined otitis prone (sOP). We found stringent diagnosis compared with clinical diagnosis reduced the frequency of children meeting the OP definition from 27% to 6% resulting in 14.8% and 2.4% receiving tympanostomy tubes, respectively. Significantly more often RSV infection led to AOM in sOP than non-otitis prone (NOP) children that correlated with diminished total RSV-specific serum IgG. sOP children produced low levels of antibody to Streptococcus pneumoniae and Haemophilus influenzae candidate vaccine protein antigens and to routine pediatric vaccines. sOP children generated significantly fewer memory B cells, functional and memory T cells to otopathogens following NP colonization and AOM than NOP children and they had defects in antigen presenting cells. PMID:27273691

22 CFR 92.36 - Authentication defined.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Authentication defined. 92.36 Section 92.36... Notarial Acts § 92.36 Authentication defined. An authentication is a certification of the genuineness of... recognized in another jurisdiction. Documents which may require authentication include legal instruments...

How Do Women Entrepreneurs Define Success? A Qualitative Study of Differences Among Women Entrepreneurs in Ethiopia

OpenAIRE

Atsede Tesfaye Hailemariam; Brigitte Kroon

2014-01-01

This paper describes how women entrepreneurs in Ethiopia define success in their own terms. Semi structured in-depth interviews were conducted with 24 women entrepreneurs from various sectors in Addis Ababa. The interview formats allowed the women to tell their life history and define success in their own terms. A common stereotype is that women entrepreneurs in Ethiopia operate businesses out of necessity and therefore women measure success in terms of financial rewards than personal rewards...

Defining Game Mechanics

DEFF Research Database (Denmark)

Sicart (Vila), Miguel Angel

2008-01-01

This article defins game mechanics in relation to rules and challenges. Game mechanics are methods invoked by agents for interacting with the game world. I apply this definition to a comparative analysis of the games Rez, Every Extend Extra and Shadow of the Colossus that will show the relevance...... of a formal definition of game mechanics. Udgivelsesdato: Dec 2008...

Indico CONFERENCE: Define the Call for Abstracts

CERN Multimedia

CERN. Geneva; Ferreira, Pedro

2017-01-01

In this tutorial, you will learn how to define and open a call for abstracts. When defining a call for abstracts, you will be able to define settings related to the type of questions asked during a review of an abstract, select the users who will review the abstracts, decide when to open the call for abstracts, and more.

How Should Energy Be Defined throughout Schooling?

Science.gov (United States)

Bächtold, Manuel

2018-01-01

The question of how to teach energy has been renewed by recent studies focusing on the learning and teaching progressions for this concept. In this context, one question has been, for the most part, overlooked: how should energy be defined throughout schooling? This paper addresses this question in three steps. We first identify and discuss two…

Defining and Selecting Independent Directors

Directory of Open Access Journals (Sweden)

Eric Pichet

2017-10-01

Full Text Available Drawing from the Enlightened Shareholder Theory that the author first developed in 2011, this theoretical paper with practical and normative ambitions achieves a better definition of independent director, while improving the understanding of the roles he fulfils on boards of directors. The first part defines constructs like firms, Governance system and Corporate governance, offering a clear distinction between the latter two concepts before explaining the four main missions of a board. The second part defines the ideal independent director by outlining the objective qualities that are necessary and adding those subjective aspects that have turned this into a veritable profession. The third part defines the ideal process for selecting independent directors, based on nominating committees that should themselves be independent. It also includes ways of assessing directors who are currently in function, as well as modalities for renewing their mandates. The paper’s conclusion presents the Paradox of the Independent Director.

A laboratory validation study of comfort and limit temperatures of four sleeping bags defined according to EN 13537 (2002).

Science.gov (United States)

Lin, Li-Yen; Wang, Faming; Kuklane, Kalev; Gao, Chuansi; Holmér, Ingvar; Zhao, Mengmeng

2013-03-01

In this study, we validated comfort and limit temperatures of four sleeping bags with different levels of insulation defined according to EN 13537. Six male subjects and four female subjects underwent totally 20 two-hour exposures in four sleeping bags at four intended testing temperatures: 11.2, 3.8, 2.1 and -9.0 °C. The subjective perceptions and physiological responses of these subjects were reported and analyzed. It was found that the EN 13537 defined comfort temperature and limit temperature were underestimated for sleeping bags MA3, HAG and MAM. The predictions are so conservative that further revision may be required to meet the requirements of both manufacturers and consumers. In contrast, for the sleeping bag MA0 with a low level of insulation, the limit temperature defined by EN 13537 was slightly overestimated. In addition, two individual case studies (-28.0 and -32.0 °C) demonstrated that low toe temperatures were widely observed among the male and female subjects, although the mean skin temperatures were almost within the thermoneutrality range (32.0-34.0 °C). It seems that the IREQ model (ISO 11079) overestimated both the comfort and limit temperatures of the sleeping bags. Finally, traditional sleeping bags may be required to be re-designed to provide consumers both whole body comfort as well as local thermal comfort at feet/toes or users need to be made aware of the higher need for their insulation. Copyright © 2012 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Radiologically defining horizontal gaze using EOS imaging-a prospective study of healthy subjects and a retrospective audit.

Science.gov (United States)

Hey, Hwee Weng Dennis; Tan, Kimberly-Anne; Ho, Vivienne Chien-Lin; Azhar, Syifa Bte; Lim, Joel-Louis; Liu, Gabriel Ka-Po; Wong, Hee-Kit

2018-06-01

As sagittal alignment of the cervical spine is important for maintaining horizontal gaze, it is important to determine the former for surgical correction. However, horizontal gaze remains poorly-defined from a radiological point of view. The objective of this study was to establish radiological criteria to define horizontal gaze. This study was conducted at a tertiary health-care institution over a 1-month period. A prospective cohort of healthy patients was used to determine the best radiological criteria for defining horizontal gaze. A retrospective cohort of patients without rigid spinal deformities was used to audit the incidence of horizontal gaze. Two categories of radiological parameters for determining horizontal gaze were tested: (1) the vertical offset distances of key identifiable structures from the horizontal gaze axis and (2) imaginary lines convergent with the horizontal gaze axis. Sixty-seven healthy subjects underwent whole-body EOS radiographs taken in a directed standing posture. Horizontal gaze was radiologically defined using each parameter, as represented by their means, 95% confidence intervals (CIs), and associated 2 standard deviations (SDs). Subsequently, applying the radiological criteria, we conducted a retrospective audit of such radiographs (before the implementation of a strict radioimaging standardization). The mean age of our prospective cohort was 46.8 years, whereas that of our retrospective cohort was 37.2 years. Gender was evenly distributed across both cohorts. The four parameters with the lowest 95% CI and 2 SD were the distance offsets of the midpoint of the hard palate (A) and the base of the sella turcica (B), the horizontal convergents formed by the tangential line to the hard palate (C), and the line joining the center of the orbital orifice with the internal occipital protuberance (D). In the prospective cohort, good sensitivity (>98%) was attained when two or more parameters were used. Audit using Criterion B

Self-rated driving habits among older adults with clinically-defined mild cognitive impairment, clinically-defined dementia, and normal cognition.

Science.gov (United States)

O'Connor, Melissa L; Edwards, Jerri D; Bannon, Yvonne

2013-12-01

Older adults with clinically-defined dementia may report reducing their driving more than cognitively normal controls. However, it is unclear how these groups compare to individuals with clinically-defined mild cognitive impairment (MCI) in terms of driving behaviors. The current study investigated self-reported driving habits among adults age 60 and older with clinical MCI (n=41), clinical mild dementia (n=40), and normal cognition (n=43). Participants reported their driving status, driving frequency (days per week), and how often they avoided accessing the community, making left turns, driving at night, driving in unfamiliar areas, driving on high-traffic roads, and driving in bad weather. After adjusting for education, a MANCOVA revealed that participants with MCI and dementia avoided unfamiliar areas and high-traffic roads significantly more than normal participants. Participants with dementia also avoided left turns and accessing the community more than those with normal cognition and MCI (pdriving variables did not significantly differ between groups. Thus, older adults with clinically-defined MCI, as well as those with dementia, avoided some complex driving situations more than cognitively intact adults. However, all diagnostic groups had similar rates of driving cessation and frequency. Future research should examine the safety implications of such findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Defining Cyberbullying.

Science.gov (United States)

Englander, Elizabeth; Donnerstein, Edward; Kowalski, Robin; Lin, Carolyn A; Parti, Katalin

2017-11-01

Is cyberbullying essentially the same as bullying, or is it a qualitatively different activity? The lack of a consensual, nuanced definition has limited the field's ability to examine these issues. Evidence suggests that being a perpetrator of one is related to being a perpetrator of the other; furthermore, strong relationships can also be noted between being a victim of either type of attack. It also seems that both types of social cruelty have a psychological impact, although the effects of being cyberbullied may be worse than those of being bullied in a traditional sense (evidence here is by no means definitive). A complicating factor is that the 3 characteristics that define bullying (intent, repetition, and power imbalance) do not always translate well into digital behaviors. Qualities specific to digital environments often render cyberbullying and bullying different in circumstances, motivations, and outcomes. To make significant progress in addressing cyberbullying, certain key research questions need to be addressed. These are as follows: How can we define, distinguish between, and understand the nature of cyberbullying and other forms of digital conflict and cruelty, including online harassment and sexual harassment? Once we have a functional taxonomy of the different types of digital cruelty, what are the short- and long-term effects of exposure to or participation in these social behaviors? What are the idiosyncratic characteristics of digital communication that users can be taught? Finally, how can we apply this information to develop and evaluate effective prevention programs? Copyright © 2017 by the American Academy of Pediatrics.

Defining Hardwood Veneer Log Quality Attributes

Science.gov (United States)

Jan Wiedenbeck; Michael Wiemann; Delton Alderman; John Baumgras; William Luppold

2004-01-01

This publication provides a broad spectrum of information on the hardwood veneer industry in North America. Veneer manufacturers and their customers impose guidelines in specifying wood quality attributes that are very discriminating but poorly defined (e.g., exceptional color, texture, and/or figure characteristics). To better understand and begin to define the most...

Defining Overweight and Obesity

Science.gov (United States)

... Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and Obesity Recommend on Facebook Tweet Share Compartir ... weight for a given height is described as overweight or obese. Body Mass Index, or BMI, is ...

Defining and detecting malaria epidemics in south-east Iran.

Science.gov (United States)

McKelvie, William R; Haghdoost, Ali Akbar; Raeisi, Ahmad

2012-03-23

A lack of consensus on how to define malaria epidemics has impeded the evaluation of early detection systems. This study aimed to develop local definitions of malaria epidemics in a known malarious area of Iran, and to use that definition to evaluate the validity of several epidemic alert thresholds. Epidemic definition variables generated from surveillance data were plotted against weekly malaria counts to assess which most accurately labelled aberrations. Various alert thresholds were then generated from weekly counts or log counts. Finally, the best epidemic definition was used to calculate and compare sensitivities, specificities, detection delays, and areas under ROC curves of the alert thresholds. The best epidemic definition used a minimum duration of four weeks and week-specific and overall smoothed geometric means plus 1.0 standard deviation. It defined 13 epidemics. A modified C-SUM alert of untransformed weekly counts using a threshold of mean+0.25 SD had the highest combined sensitivity and specificity. Untransformed C-SUM alerts also had the highest area under the ROC curve. Defining local malaria epidemics using objective criteria facilitated the evaluation of alert thresholds. This approach needs further study to refine epidemic definitions and prospectively evaluate epidemic alerts.

Switching industrial production processes from complex to defined media: method development and case study using the example of Penicillium chrysogenum.

Science.gov (United States)

Posch, Andreas E; Spadiut, Oliver; Herwig, Christoph

2012-06-22

Filamentous fungi are versatile cell factories and widely used for the production of antibiotics, organic acids, enzymes and other industrially relevant compounds at large scale. As a fact, industrial production processes employing filamentous fungi are commonly based on complex raw materials. However, considerable lot-to-lot variability of complex media ingredients not only demands for exhaustive incoming components inspection and quality control, but unavoidably affects process stability and performance. Thus, switching bioprocesses from complex to defined media is highly desirable. This study presents a strategy for strain characterization of filamentous fungi on partly complex media using redundant mass balancing techniques. Applying the suggested method, interdependencies between specific biomass and side-product formation rates, production of fructooligosaccharides, specific complex media component uptake rates and fungal strains were revealed. A 2-fold increase of the overall penicillin space time yield and a 3-fold increase in the maximum specific penicillin formation rate were reached in defined media compared to complex media. The newly developed methodology enabled fast characterization of two different industrial Penicillium chrysogenum candidate strains on complex media based on specific complex media component uptake kinetics and identification of the most promising strain for switching the process from complex to defined conditions. Characterization at different complex/defined media ratios using only a limited number of analytical methods allowed maximizing the overall industrial objectives of increasing both, method throughput and the generation of scientific process understanding.

A self-defining hierarchical data system

Science.gov (United States)

Bailey, J.

1992-01-01

The Self-Defining Data System (SDS) is a system which allows the creation of self-defining hierarchical data structures in a form which allows the data to be moved between different machine architectures. Because the structures are self-defining they can be used for communication between independent modules in a distributed system. Unlike disk-based hierarchical data systems such as Starlink's HDS, SDS works entirely in memory and is very fast. Data structures are created and manipulated as internal dynamic structures in memory managed by SDS itself. A structure may then be exported into a caller supplied memory buffer in a defined external format. This structure can be written as a file or sent as a message to another machine. It remains static in structure until it is reimported into SDS. SDS is written in portable C and has been run on a number of different machine architectures. Structures are portable between machines with SDS looking after conversion of byte order, floating point format, and alignment. A Fortran callable version is also available for some machines.

Haematological and serum biochemical response of growing rabbit ...

African Journals Online (AJOL)

STORAGESEVER

2008-12-03

Dec 3, 2008 ... white blood cells (WBC) of rabbits fed diet 2 and the control were similar to each other but both were ..... counts, PCV, plasma protein and glucose. In this study, .... sphingolipid biosynthesis in cultured neurons in situ. J. Biol.

Targeted electroporation of defined lateral ventricular walls: a novel and rapid method to study fate specification during postnatal forebrain neurogenesis

Directory of Open Access Journals (Sweden)

Cremer Harold

2011-04-01

Full Text Available Abstract Background Postnatal olfactory bulb (OB neurogenesis involves the generation of granule and periglomerular cells by neural stem cells (NSCs located in the walls of the lateral ventricle (LV. Recent studies show that NSCs located in different regions of the LV give rise to different types of OB neurons. However, the molecular mechanisms governing neuronal specification remain largely unknown and new methods to approach these questions are needed. Results In this study, we refine electroporation of the postnatal forebrain as a technique to perform precise and accurate delivery of transgenes to NSCs located in distinct walls of the LV in the mouse. Using this method, we confirm and expand previous studies showing that NSCs in distinct walls of the LV produce neurons that invade different layers of the OB. Fate mapping of the progeny of radial glial cells located in these distinct LV walls reveals their specification into defined subtypes of granule and periglomerular neurons. Conclusions Our results provide a baseline with which future studies aiming at investigating the role of factors in postnatal forebrain neuronal specification can be compared. Targeted electroporation of defined LV NSC populations will prove valuable to study the genetic factors involved in forebrain neuronal specification.

Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort12

Science.gov (United States)

Schmidt, Julie A; Rinaldi, Sabina; Ferrari, Pietro; Carayol, Marion; Achaintre, David; Scalbert, Augustin; Cross, Amanda J; Gunter, Marc J; Fensom, Georgina K; Appleby, Paul N; Key, Timothy J; Travis, Ruth C

2015-01-01

Background: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. Objective: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. Design: In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate–controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. Results: Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. Conclusions: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of

Defined Contribution Model: Definition, Theory and an Application for Turkey

OpenAIRE

Metin Ercen; Deniz Gokce

1998-01-01

Based on a numerical application that employs social and economic parameters of the Turkish economy, this study attempts to demonstrate that the current collapse in the Turkish social security system is not unavoidable. The present social security system in Turkey is based on the defined benefit model of pension provision. On the other hand, recent proposals for reform in the social security system are based on a multipillar system, where one of the alternatives is a defined contribution pens...

Defining childhood severe falciparum malaria for intervention studies.

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Philip Bejon

2007-08-01

Full Text Available Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for clinical purposes. However, this definition includes individuals with severe nonmalarial disease and coincident parasitaemia, so may lack specificity in vaccine trials. Although there is no "gold standard" individual test for severe malaria, malaria-attributable fractions (MAFs can be estimated among groups of children using a logistic model, which we use to test the suitability of various case definitions as trial endpoints.A total of 4,583 blood samples were taken from well children in cross-sectional surveys and from 1,361 children admitted to a Kenyan District hospital with severe disease. Among children under 2 y old with severe disease and over 2,500 parasites per microliter of blood, the MAFs were above 85% in moderate- and low-transmission areas, but only 61% in a high-transmission area. HIV and malnutrition were not associated with reduced MAFs, but gastroenteritis with severe dehydration (defined by reduced skin turgor, lower respiratory tract infection (clinician's final diagnosis, meningitis (on cerebrospinal fluid [CSF] examination, and bacteraemia were associated with reduced MAFs. The overall MAF was 85% (95% confidence interval [CI] 83.8%-86.1% without excluding these conditions, 89% (95% CI 88.4%-90.2% after exclusions, and 95% (95% CI 94.0%-95.5% when a threshold of 2,500 parasites/mul was also applied. Applying a threshold and exclusion criteria reduced sensitivity to 80% (95% CI 77%-83%.The specificity of a case definition for severe malaria is improved by applying a parasite density threshold and by excluding children with meningitis, lower respiratory tract infection (clinician's diagnosis, bacteraemia, and gastroenteritis with severe dehydration, but not by excluding children with HIV or malnutrition.

Poster: A Software-Defined Multi-Camera Network

OpenAIRE

Chen, Po-Yen; Chen, Chien; Selvaraj, Parthiban; Claesen, Luc

2016-01-01

The widespread popularity of OpenFlow leads to a significant increase in the number of applications developed in SoftwareDefined Networking (SDN). In this work, we propose the architecture of a Software-Defined Multi-Camera Network consisting of small, flexible, economic, and programmable cameras which combine the functions of the processor, switch, and camera. A Software-Defined Multi-Camera Network can effectively reduce the overall network bandwidth and reduce a large amount of the Capex a...

Cross-study analysis of genomic data defines the ciliate multigenic epiplasmin family: strategies for functional analysis in Paramecium tetraurelia

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Ravet Viviane

2009-06-01

Full Text Available Abstract Background The sub-membranous skeleton of the ciliate Paramecium, the epiplasm, is composed of hundreds of epiplasmic scales centered on basal bodies, and presents a complex set of proteins, epiplasmins, which belong to a multigenic family. The repeated duplications observed in the P. tetraurelia genome present an interesting model of the organization and evolution of a multigenic family within a single cell. Results To study this multigenic family, we used phylogenetic, structural, and analytical transcriptional approaches. The phylogenetic method defines 5 groups of epiplasmins in the multigenic family. A refined analysis by Hydrophobic Cluster Analysis (HCA identifies structural characteristics of 51 epiplasmins, defining five separate groups, and three classes. Depending on the sequential arrangement of their structural domains, the epiplasmins are defined as symmetric, asymmetric or atypical. The EST data aid in this classification, in the identification of putative regulating sequences such as TATA or CAAT boxes. When specific RNAi experiments were conducted using sequences from either symmetric or asymmetric classes, phenotypes were drastic. Local effects show either disrupted or ill-shaped epiplasmic scales. In either case, this results in aborted cell division. Using structural features, we show that 4 epiplasmins are also present in another ciliate, Tetrahymena thermophila. Their affiliation with the distinctive structural groups of Paramecium epiplasmins demonstrates an interspecific multigenic family. Conclusion The epiplasmin multigenic family illustrates the history of genomic duplication in Paramecium. This study provides a framework which can guide functional analysis of epiplasmins, the major components of the membrane skeleton in ciliates. We show that this set of proteins handles an important developmental information in Paramecium since maintenance of epiplasm organization is crucial for cell morphogenesis.

Defining chaos.

Science.gov (United States)

Hunt, Brian R; Ott, Edward

2015-09-01

In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call "expansion entropy," and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

Bilayer graphene quantum dot defined by topgates

Energy Technology Data Exchange (ETDEWEB)

Müller, André; Kaestner, Bernd; Hohls, Frank; Weimann, Thomas; Pierz, Klaus; Schumacher, Hans W., E-mail: hans.w.schumacher@ptb.de [Physikalisch-Technische Bundesanstalt, Bundesallee 100, 38116 Braunschweig (Germany)

2014-06-21

We investigate the application of nanoscale topgates on exfoliated bilayer graphene to define quantum dot devices. At temperatures below 500 mK, the conductance underneath the grounded gates is suppressed, which we attribute to nearest neighbour hopping and strain-induced piezoelectric fields. The gate-layout can thus be used to define resistive regions by tuning into the corresponding temperature range. We use this method to define a quantum dot structure in bilayer graphene showing Coulomb blockade oscillations consistent with the gate layout.

Defining the Strategy of Nuclear Activity

International Nuclear Information System (INIS)

Racana, R.

2006-01-01

This article presents nuclear activity as defined within the field of the nuclear industry, which is studied from its capacity to generate electric power to its application in industry and medicine as well as a source for weapons of mass destruction. These fields of analysis introduce some problems that the nuclear activity itself must know how to confront employing action strategies aimed at becoming an activity to be kept in mind when making use of the benefits that its peaceful use contributes to human life. (Author)

Defining the spatial relationships between eight anatomic planes in the 11+6 to 13+6 weeks fetus: a pilot study.

Science.gov (United States)

Abu-Rustum, Reem S; Ziade, M Fouad; Abu-Rustum, Sameer E

2012-09-01

Our study aims at investigating the spatial relationships between eight anatomic planes in the 11+6 to 13+6 weeks fetus. This is a retrospective pilot study where three-dimensional and four-dimensional stored data sets were manipulated to retrieve eight anatomic planes starting from the midsagittal plane of the fetus. Standardization of volumes was performed at the level of the transverse abdominal circumference plane. Parallel shift was utilized and the spatial relationships between eight anatomic planes were established. The median and the range were calculated for each of the planes, and they were evaluated as a function of the fetal crown-rump length. P planes were found to adhere to normal distribution curves, and most of the planes were in a definable relationship to each other with statistically significant correlations. To our knowledge, this is the first study to describe the possible spatial relationships between eight two-dimensional anatomic planes in the 11+6 to 13+6 weeks fetus, utilizing a standardized approach. Defining these spatial relationships may serve as the first step for the potential future development of automation software for fetal anatomic assessment at 11+6 to 13+6 weeks. © 2012 John Wiley & Sons, Ltd.

Defining and detecting malaria epidemics in south-east Iran

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McKelvie William R

2012-03-01

Full Text Available Abstract Background A lack of consensus on how to define malaria epidemics has impeded the evaluation of early detection systems. This study aimed to develop local definitions of malaria epidemics in a known malarious area of Iran, and to use that definition to evaluate the validity of several epidemic alert thresholds. Methods Epidemic definition variables generated from surveillance data were plotted against weekly malaria counts to assess which most accurately labelled aberrations. Various alert thresholds were then generated from weekly counts or log counts. Finally, the best epidemic definition was used to calculate and compare sensitivities, specificities, detection delays, and areas under ROC curves of the alert thresholds. Results The best epidemic definition used a minimum duration of four weeks and week-specific and overall smoothed geometric means plus 1.0 standard deviation. It defined 13 epidemics. A modified C-SUM alert of untransformed weekly counts using a threshold of mean + 0.25 SD had the highest combined sensitivity and specificity. Untransformed C-SUM alerts also had the highest area under the ROC curve. Conclusions Defining local malaria epidemics using objective criteria facilitated the evaluation of alert thresholds. This approach needs further study to refine epidemic definitions and prospectively evaluate epidemic alerts.

Undergraduate Performance in Solving Ill-Defined Biochemistry Problems

Science.gov (United States)

Sensibaugh, Cheryl A.; Madrid, Nathaniel J.; Choi, Hye-Jeong; Anderson, William L.; Osgood, Marcy P.

2017-01-01

With growing interest in promoting skills related to the scientific process, we studied performance in solving ill-defined problems demonstrated by graduating biochemistry majors at a public, minority-serving university. As adoption of techniques for facilitating the attainment of higher-order learning objectives broadens, so too does the need to…

Defining recovery in chronic fatigue syndrome: a critical review.

Science.gov (United States)

Adamowicz, Jenna L; Caikauskaite, Indre; Friedberg, Fred

2014-11-01

In chronic fatigue syndrome (CFS), the lack of consensus on how recovery should be defined or interpreted has generated controversy and confusion. The purpose of this paper was to systematically review, compare, and evaluate the definitions of recovery reported in the CFS literature and to make recommendations about the scope of recovery assessments. A search was done using the MEDLINE, PubMed, PsycINFO, CINAHL, and Cochrane databases for peer review papers that contained the search terms "chronic fatigue syndrome" and "recovery," "reversal," "remission," and/or "treatment response." From the 22 extracted studies, recovery was operationally defined by reference with one or more of these domains: (1) pre-morbid functioning; (2) both fatigue and function; (3) fatigue (or related symptoms) alone; (4) function alone; and/or (5) brief global assessment. Almost all of the studies measuring recovery in CFS did so differently. The brief global assessment was the most common outcome measure used to define recovery. Estimates of recovery ranged from 0 to 66 % in intervention studies and 2.6 to 62 % in naturalistic studies. Given that the term "recovery" was often based on limited assessments and less than full restoration of health, other more precise and accurate labels (e.g., clinically significant improvement) may be more appropriate and informative. In keeping with common understandings of the term recovery, we recommend a consistent definition that captures a broad-based return to health with assessments of both fatigue and function as well as the patient's perceptions of his/her recovery status.

Acid Ceramidase in Melanoma

DEFF Research Database (Denmark)

Realini, Natalia; Palese, Francesca; Pizzirani, Daniela

2016-01-01

Acid ceramidase (AC) is a lysosomal cysteine amidase that controls sphingolipid signaling by lowering the levels of ceramides and concomitantly increasing those of sphingosine and its bioactive metabolite, sphingosine 1-phosphate. In the present study, we evaluated the role of AC-regulated sphing...

The effect of dietary phytosphingosine on cholesterol levels and insulin sensitivity in subjects with the metabolic syndrome

NARCIS (Netherlands)

Snel, M.; Sleddering, M.A.; Pijl, H.; Nieuwenhuizen, W.F.; Frölich, M.; Havekes, L.M.; Romijn, J.A.; Jazet, I.M.

2010-01-01

Background: Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity.Objective:To study the effect of dietary

Defining health-related quality of life for young wheelchair users: A qualitative health economics study.

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Nathan Bray

Full Text Available Wheelchairs for children with impaired mobility provide health, developmental and psychosocial benefits, however there is limited understanding of how mobility aids affect the health-related quality of life of children with impaired mobility. Preference-based health-related quality of life outcome measures are used to calculate quality-adjusted life years; an important concept in health economics. The aim of this research was to understand how young wheelchair users and their parents define health-related quality of life in relation to mobility impairment and wheelchair use.The sampling frame was children with impaired mobility (≤18 years who use a wheelchair and their parents. Data were collected through semi-structured face-to-face interviews conducted in participants' homes. Qualitative framework analysis was used to analyse the interview transcripts. An a priori thematic coding framework was developed. Emerging codes were grouped into categories, and refined into analytical themes. The data were used to build an understanding of how children with impaired mobility define health-related quality of life in relation to mobility impairment, and to assess the applicability of two standard measures of health-related quality of life.Eleven children with impaired mobility and 24 parents were interviewed across 27 interviews. Participants defined mobility-related quality of life through three distinct but interrelated concepts: 1 participation and positive experiences; 2 self-worth and feeling fulfilled; 3 health and functioning. A good degree of consensus was found between child and parent responses, although there was some evidence to suggest a shift in perception of mobility-related quality of life with child age.Young wheelchair users define health-related quality of life in a distinct way as a result of their mobility impairment and adaptation use. Generic, preference-based measures of health-related quality of life lack sensitivity in this

Defining clogging potential for permeable concrete.

Science.gov (United States)

Kia, Alalea; Wong, Hong S; Cheeseman, Christopher R

2018-08-15

Permeable concrete is used to reduce urban flooding as it allows water to flow through normally impermeable infrastructure. It is prone to clogging by particulate matter and predicting the long-term performance of permeable concrete is challenging as there is currently no reliable means of characterising clogging potential. This paper reports on the performance of a range of laboratory-prepared and commercial permeable concretes, close packed glass spheres and aggregate particles of varying size, exposed to different clogging methods to understand this phenomena. New methods were developed to study clogging and define clogging potential. The tests involved applying flowing water containing sand and/or clay in cycles, and measuring the change in permeability. Substantial permeability reductions were observed in all samples, particularly when exposed to sand and clay simultaneously. Three methods were used to define clogging potential based on measuring the initial permeability decay, half-life cycle and number of cycles to full clogging. We show for the first time strong linear correlations between these parameters for a wide range of samples, indicating their use for service-life prediction. Copyright © 2018 Elsevier Ltd. All rights reserved.

Defining local food

DEFF Research Database (Denmark)

Eriksen, Safania Normann

2013-01-01

Despite evolving local food research, there is no consistent definition of “local food.” Various understandings are utilized, which have resulted in a diverse landscape of meaning. The main purpose of this paper is to examine how researchers within the local food systems literature define local...... food, and how these definitions can be used as a starting point to identify a new taxonomy of local food based on three domains of proximity....

Lipid Biosynthesis as an Antifungal Target

Directory of Open Access Journals (Sweden)

Jiao Pan

2018-04-01

Full Text Available Lipids, commonly including phospholipids, sphingolipids, fatty acids, sterols, and triacylglycerols (TAGs, are important biomolecules for the viability of all cells. Phospholipids, sphingolipids, and sterols are important constituents of biological membranes. Many lipids play important roles in the regulation of cell metabolism by acting as signaling molecules. Neutral lipids, including TAGs and sterol esters (STEs, are important storage lipids in cells. In view of the importance of lipid molecules, this review briefly summarizes the metabolic pathways for sterols, phospholipids, sphingolipids, fatty acids, and neutral lipids in fungi and illustrates the differences between fungal and human (or other mammalian cells, especially in relation to lipid biosynthetic pathways. These differences might provide valuable clues for us to find target proteins for novel antifungal drugs. In addition, the development of lipidomics technology in recent years has supplied us with a shortcut for finding new antifungal drug targets; this ability is important for guiding our research on pathogenic fungi.

Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice.

Directory of Open Access Journals (Sweden)

Anke Wittmann

Full Text Available Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility.

Defining and classifying syncope

NARCIS (Netherlands)

Thijs, Roland D.; Wieling, Wouter; Kaufmann, Horacio; van Dijk, Gert

2004-01-01

There is no widely adopted definition or classification of syncope and related disorders. This lack of uniformity harms patient care, research, and medical education. In this article, syncope is defined as a form of transient loss of consciousness (TLOC) due to cerebral hypoperfusion. Differences

Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

Science.gov (United States)

Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

2016-04-01

Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Five gout susceptibility loci were identified at the genome-wide significance level (pgenes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. 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/

Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival : A cohort study

NARCIS (Netherlands)

Worm, Signe W.; Bower, Mark; Reiss, Peter; Bonnet, Fabrice; Law, Matthew; Fätkenheuer, Gerd; d'Arminio Monforte, Antonella; Abrams, Donald I.; Grulich, Andrew; Fontas, Eric; Kirk, Ole; Furrer, Hansjakob; Wit, Stephane D.; Phillips, Andrew; Lundgren, Jens D.; Sabin, Caroline A.; Butcher, D.; Delforge, M.; Fanti, I.; Fontas, E.; Franquet, X.; Geffard, S.; Gras, L.; Helweg-Larsen, J.; Hillebregt, M.; Kamara, D.; Kjær, J.; Krum, E.; Lundgren, J.D.; McManus, H.; Meidahl, P.; Mocroft, A.; Nielsen, J.; Phillips, A.; Powderl, W.; Rickenbach, M.; Rode, R.; Ryom, L.; Sabin, C.A.; Salbøl Brandt, R.; Schmidt Iversen, J.; Shortman, N.; Sjøl, A.; Smith, C.; Torres, F.; Tverland, J.; Wright, S.; Zaheri, S.; de Wolf, F.; Smidt, J.; Ristola, M.; Katlama, C.; Viard, J-P.; Girard, P.-M.; Livrozet, J.M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.; Schmidt, R.; Degen, O.; van Lunzen, J.; Stellbrink, H.J.; Staszewski, S.; Bogner, J.; Fätkenheuer, G.; Gargalianos, P.; Kosmidis, J.; Perdios, J.; Xylomenos, G.; Filandras, A.; Karabatsaki, E.; Panos, G.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Burke, M.; Turner, D.; Yust, I.; Hassoun, G.; Pollack, S.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Gabbuti, A.; Mazzotta, F.; Lichtner, M.; Vullo, V.; Boer, K.; Geerlings, S.E.; Godfried, M.H.; Kuijpers, T.W.; Lange, J.M.A.; Nellen, F.J.B.; Pajkrt, D.; Prins, J.M.; Reiss, P.; Scherpbier, H.J.; Vrouenraets, S.M.E.; Wit, F.W.M.N.; van Vugt, M.; van der Meer, J.T.M.; van der Poll, T.; van der Valk, M.; Chirianni, A.; Gargiulo, M.; Montesarchio, E.; Antonucci, G.; Narciso, P.; Testa, A.; Vlassi, C.; Zaccarelli, M.; Castagna, A.; Gianotti, N.; Lazzarin, A.; Galli, M.; Ridolfo, A.; d'Arminio Monforte, A.; Rozentale, B.; Zeltina, I.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Reiss, P.; Bruun, J.; Maeland, A.; Ormaasen, V.; Lowe, S.; Oude Lashof, A.; Schreij, G.; Gasiorowski, J.; Knysz, B.; Bakowska, E.; Horban, A.; Flisiak, R.; Grzeszczuk, A.; Boron-Kaczmarska, A.; Parczewski, M.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Caldeira, L.; Doroana, M.; Mansinho, K.; Maltez, F.; Bravenboer, B.; Pronk, M.J.H.; Duiculescu, D.; Rakhmanova, A.; Zakharova, N.; Buzunova, S.; Jevtovic, D.; Mokráš, M.; Staneková, D.; Tomazic, J.; González-Lahoz, J.; Labarga, P.; Medrano, J.; Soriano, V.; Moreno, S.; Rodriguez, J.M.; Bravo, I.; Clotet, B.; Jou, A.; Paredes, R.; Puig, J.; Tural, C.; Gelinck, L.B.S.; Nouwen, J.L.; Rijnders, B.J.A.; Schurink, C.A.M.; Slobbe, L.; Verbon, A.; de Vries-Sluijs, T.E.M.S.; van der Ende, Marchina E.; van der Feltz, M.; Gatell, J.M.; Miró, J.M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M.A.; Karlsson, A.; Flamholc, L.; Ledergerber, B.; Weber, R.; Cavassini, M.; Francioli, P.; Boffi, E.; Hirschel, B.; Furrer, H.; Battegay, M.; Elzi, L.; Chentsova, N.; Kravchenko, E.; Driessen, G.J.A.; Hartwig, N.G.; Frolov, V.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A.M.; Mercey, D.; Johnson, M.A.; Mocroft, A.; Phillips, A.; Murphy, M.; Scullard, G.; Weber, J.; Fisher, M.; Leen, C.; Branger, J.; Åkerlund, B.; Morfeldt, L.; Sundström., A.; Thulin, G.; Karlsson, A.; Koppel, K.; Flamholc, L.; Ho̊kangård, C.; Angarano, G.; Antinori, A.; Armignacco, O.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Moroni, M.; Perno, C.F.; Viale, P.L.; Von Schlosser, F.; Ammassari, A.; Andreoni, M.; Antinori, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M.R.; Castagna, A.; Ceccherini-Silberstein, F.; Cinque, P.; Cozzi-Lepri, A.; De Luca, A.; Gargiulo, M.; Gervasoni, C.; Girardi, E.; Gori, A.; Guaraldi, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Murri, R.; Mussini, C.; Puoti, M.; Torti, C.; d'Arminio Monforte, A.; Cicconi, P.; Cozzi-Lepri, A.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Costantini, A.; Giacometti, A.; Riva, A.; Angarano, G.; Carrisa, C.; Monno, L.; Lazzari, G.; Maggiolo, F.; Borderi, M.; Verucchi, G.; Viale, P.L.; Kauffmann, R.H.; Schippers, E.F.; Castelli, F.; Minardi, C.; Torti, C.; Abeli, C.; Quirino, T.; Manconi, P.E.; Piano, P.; Falasca, K.; Vecchiet, J.; Segala, D.; Sighinolfi, L.; Lo Caputo, S.; Mazzotta, F.; Alessandrini, A.; Cassola, G.; Mazzarello, G.; Piscopo, R.; Viscoli, G.; Belvisi, V.; Mastroianni, C.; Bonfanti, P.; Caramma, I.; Castelli, P.; Chiodera, A.; Alleman, M.A.; Bouwhuis, J.W.; Groeneveld, P.H.P.; Bigoloni, A.; Carenzi, L.; Castagna, A.; Cicconi, P.; Formenti, T.; Galli, A.; Galli, M.; Lazzarin, A.; Moioli, M.C.; Piolini, R.; Puoti, M.; Ridolfo, A.L.; Rizzardini, G.; Rossotti, R.; Salpietro, S.; Spagnuolo, V.; Zucchi, P.; d'Arminio Monforte, A.; Bisio, L.; Mussini, C.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Gargiulo, M.; Guida, M.G.; Baldelli, F.; Belfiori, B.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M.A.; Acinapura, R.; Andreoni, M.; Antinori, A.; Capozzi, M.; Cauda, R.; De Luca, A.; Gallo, L.; Libertone, R.; Lichtner, M.; Nicastro, E.; Tebano, G.; Tozzi, V.; Vullo, V.; Zaccarelli, M.; d'Avino, A.; Madeddu, G.; Mura, M.S.; Caramello, P.; Di Perri, G.; Orofino, G.C.; Sciandra, M.; Soetekouw, R.; ten Kate, R.W.; Manfrin, V.; Pellizzer, G.; Bernard, E.; Caissotti, C.; Cua, E.; De Salvador-Guillouet, F.; Dellamonica, P.; Dollet, K.; Durant, J.; Ferrando, S.; Fontas, E.; Mondain-Miton, V.; Naqvi, A.; Perbost, I.; Pillet, S.; Pradier, C.; Prouvost-Keller, B.; Pugliese, P.; Rahelinirina, V.; Roger, P.M.; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H.C.; Burton-Jeangros, C.; Calmy, A.; Cavassini, M.; Cellerai, C.; Dubs, R.; Egger, M.; Elzi, L.; Fehr, J.; Flepp, M.; Francioli, P.; Furrer, H.; Fux, C.A.; Gorgievski, M.; Günthard, H.; Hasse, B.; Hirsch, H.H.; Hirschel, B.; Hösli, I.; Kahlert, C.; Kaiser, L.; Keiser, O.; Kind, C.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Martinetti, G.; Martinez de Tejada, B.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schöni-Affolter, F.; Schüpbach, J.; Schultze, D.; Speck, R.; Taffé, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.; von Wyl, V.; Arend, S.M.; Jolink, H.; Kroon, F.P.; de Boer, M.G.J.; van Dissel, J.T.; van Nieuwkoop, C.; van den Broek, P.J.; Pogany, K.; den Hollander, J.G.; Kortmann, W.; van Twillert, G.; Leyten, E.M.S.; Vriesendorp, R.; Kootstra, G.J.; ten Napel, C.H.H.; Blok, W.L.; Brinkman, K.; Frissen, P.H.J.; Schouten, W.E.M.; van den Berk, G.E.L.; Brouwer, A.E.; Juttmann, J.R.; van Kasteren, M.E.E.; Lettinga, K.D.; Veenstra, J.; Mulder, J.W.; Smit, P.M.; Weijer, S.; van Gorp, E.C.M.; Verhagen, D.W.M.; van Eeden, A.; Doedens, R.; Scholvinck, E.H.; Sprenger, H.G.; Stek, C.J.; van Assen, S.; Brouwer, A.M.; Dofferhoff, A.S.M.; Keuter, M.; Koopmans, P.P.; de Groot, R.; ter Hofstede, H.J.M.; van der Flier, M.; van der Ven, A.J.A.M.; Arends, J.E.; Ellerbroek, P.M.; Hoepelman, A.I.M.; Jaspers, C.A.J.J.; Maarschalk-Ellerbroek, L.J.; Mudrikova, T.; Oosterheert, J.J.; Peters, E.J.G.; Schneider, M.M.E.; Wassenberg, M.W.M.; van der Hilst, J.C.H.; Bierman, W.F.W.; Claessen, F.A.P.; Danner, S.A.; Perenboom, R.M.; bij de Vaate, E.A.; de Jong, E.V.; de Vocht, J.; van Agtmael, M.A.; Geelen, S.P.M.; Wolfs, T.F.W.; Gisolf, E.H.; Richter, J.P.; van der Berg, C.; Stegeman, A.; van den Berge, M.; Polée, M.B.; van Houte, D.P.F.; van Vonderen, M.G.A.; Duits, A.J.; Winkel, C.; Dabis, F.; Bonnet, F.; Chêne, G.; Dabis, F.; Dupon, M.; Fleury, H.; Lacoste, D.; Malvy, D.; Mercié, P.; Morlat, P.; Neau, D.; Pellegrin, I.; Pellegrin, J.L.; Thiébaut, R.; Titier, K.; Bruyand, M.; Chêne, G.; Dabis, F.; Lawson-Ayayi, S.; Thiébaut, R.; Wittkop, L.; Bernard, N.; Bonnal, F.; Bonnet, F.; Caunègre, L.; Cazanave, C.; Ceccaldi, J.; Chambon, D.; Chossat, I.; Courtaud, K.; Dauchy, F.A.; De Witte, S.; Duffau, P.; Dupon, M.; Dupont, A.; Dutronc, H.; Farbos, S.; Gaboriau, V.; Gemain, M.C.; Gerard, Y.; Greib, C.; Hessamfar, M.; Lacoste, D.; Lafarie-Castet, S.; Lataste, P.; Lazaro, E.; Longy-Boursier, M.; Malvy, D.; Meraud, J.P.; Mercié, P.; Monlun, E.; Morlat, P.; Neau, D.; Ochoa, A.; Pellegrin, J.L.; Pistone, T.; Ragnaud, J.M.; Receveur, M.C.; Roger-Schmeltz, J.; Tchamgoué, S.; Thibaut, P.; Vandenhende, M.A.; Viallard, J.F.; Moreau, J.F.; Pellegrin., I.; Fleury, H.; Lafon, M.E.; Masquelier, B.; Trimoulet, P.; Breilh, D.; Titier, K.; Haramburu, F.; Miremont-Salamé, G.; Blaizeau, M.J.; D'Ivernois, C.; Decoin, M.; Delaune, J.; Delveaux, S.; Hanappier, C.; Leleux, O.; Sicard, X.; Uwamaliya-Nziyumvira, B.; Geffard, S.; Leray, J.; Palmer, G.; Touchard, D.; Baker, D.; Bendall, C.; Bloch, M.; Carr, A.; Cooper, D.; Franic, T.; Law, M.; McManus, H.; Petoumenos, K.; Vale, R.; Wright, S.; Edwards, S.; Hoy, J.; Moore, R.; Nicholson, J.; Roth, N.; Watson, K.; Chuah, J.; Ngieng, M.; Nolan, D.; Skett, J.; Cadafalch, J.; Calvo, G.; Codina, C.; Del Cacho, E.; Domingo, P.; Fuster, M.; Gatell, J.; Mateu, S.; Sambeat, M.A.; Sirera, G.; Torres, F.; Vaqué, A.; Clumeck, N.; De Wit, S.; Delforge, M.; Gennotte, A.F.; Gerard, M.; Kabeya, K.; Konopnicki, D.; Libois, A.; Martin, C.; Necsoi, C.; Payen, M.C.; Semaille, P.; Van Laethem, Y.; Bartsch, G.; El-Sadr, W.M.; Krum, E.; Neaton, J.; Thompson, G.; Wentworth, D.; Luskin-Hawk, R.; Telzak, E.; El-Sadr, W.M.; Abrams, D.I.; Cohn, D.; Markowitz, N.; Arduino, R.; Mushatt, D.; Friedland, G.; Perez, G.; Tedaldi, E.; Fisher, E.; Gordin, F.; Crane, L.R.; Sampson, J.; Baxter, J.; Cozzi-Lepri, A.; Fischer, A.H.; Grint, D.; Kirk, O.; Kjaer, J.; Kowalska, J.; Lundgren, J.; Mocroft, A.; Nielsen, J.; Peters, L.; Podlekareva, D.; Reekie, J.; Tverland, J.; Elias, C.; Losso, M.; Vetter, N.; Zangerle, R.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V.M.; Suetnov, O.; Clumeck, N.; De Wit, S.; Delforge, M.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Jilich, D.; Machala, L.; Sedlacek, D.; Benfield, T.; Kronborg, G.; Larsen, M.; Nielsen, J.; Gerstoft, J.; Hansen, A.-B.E.; Katzenstein, T.; Skinhøj, P.; Pedersen, C.; Ostergaard, L.; Zilmer, K.

2013-01-01

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors

Defining the complement biomarker profile of c3 glomerulopathy

DEFF Research Database (Denmark)

Zhang, Yuzhou; Nester, Carla M; Martin, Bertha

2014-01-01

BACKGROUND AND OBJECTIVES: C3 glomerulopathy (C3G) applies to a group of renal diseases defined by a specific renal biopsy finding: a dominant pattern of C3 fragment deposition on immunofluorescence. The primary pathogenic mechanism involves abnormal control of the alternative complement pathway......, although a full description of the disease spectrum remains to be determined. This study sought to validate and define the association of complement dysregulation with C3G and to determine whether specific complement pathway abnormalities could inform disease definition. DESIGN, SETTING, PARTICIPANTS......, & MEASUREMENTS: This study included 34 patients with C3G (17 with C3 glomerulonephritis [C3GN] and 17 with dense deposit disease [DDD]) diagnosed between 2008 and 2013 selected from the C3G Registry. Control samples (n=100) were recruited from regional blood drives. Nineteen complement biomarkers were assayed...

Accuracy of Blood Pressure-to-Height Ratio to Define Elevated Blood Pressure in Children and Adolescents: The CASPIAN-IV Study.

Science.gov (United States)

Kelishadi, Roya; Bahreynian, Maryam; Heshmat, Ramin; Motlagh, Mohammad Esmail; Djalalinia, Shirin; Naji, Fatemeh; Ardalan, Gelayol; Asayesh, Hamid; Qorbani, Mostafa

2016-02-01

The aim of this study was to propose a simple practical diagnostic criterion for pre-hypertension (pre-HTN) and hypertension (HTN) in the pediatric age group. This study was conducted on a nationally representative sample of 14,880 students, aged 6-18 years. HTN and pre-HTN were defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ 95 and 90-95th percentile for age, gender, and height, respectively. By using the area under the curve (AUC) of the receiver operator characteristic curves, we estimated the diagnostic accuracy of two indexes of SBP-to-height ratio (SBPHR) and DBP-to-height (DBPHR) to define pre-HTN and HTN. Overall, SBPHR performed relatively well in classifying subjects to HTN (AUC 0.80-0.85) and pre-HTN (AUC 0.84-0.90). Likewise, DBPHR performed relatively well in classifying subjects to HTN (AUC 0.90-0.97) and pre-HTN (AUC 0.70-0.83). Two indexes of SBPHR and DBPHR are considered as valid, simple, inexpensive, and accurate tools to diagnose pre-HTN and HTN in pediatric age group.

Defining Abnormally Low Tenders

DEFF Research Database (Denmark)

Ølykke, Grith Skovgaard; Nyström, Johan

2017-01-01

The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

DEFINE: A Service-Oriented Dynamically Enabling Function Model

Directory of Open Access Journals (Sweden)

Tan Wei-Yi

2017-01-01

In this paper, we introduce an innovative Dynamically Enable Function In Network Equipment (DEFINE to allow tenant get the network service quickly. First, DEFINE decouples an application into different functional components, and connects these function components in a reconfigurable method. Second, DEFINE provides a programmable interface to the third party, who can develop their own processing modules according to their own needs. To verify the effectiveness of this model, we set up an evaluating network with a FPGA-based OpenFlow switch prototype, and deployed several applications on it. Our results show that DEFINE has excellent flexibility and performance.

Software Defined Coded Networking

DEFF Research Database (Denmark)

Di Paola, Carla; Roetter, Daniel Enrique Lucani; Palazzo, Sergio

2017-01-01

the quality of each link and even across neighbouring links and using simulations to show that an additional reduction of packet transmission in the order of 40% is possible. Second, to advocate for the use of network coding (NC) jointly with software defined networking (SDN) providing an implementation...

The effect of dietary phytosphingosine on cholesterol levels and insulin sensitivity in subjects with the metabolic syndrome

NARCIS (Netherlands)

Snel, M.; Sleddering, M. A.; Pijl, H.; Nieuwenhuizen, W. F.; Frölich, M.; Havekes, L. M.; Romijn, J. A.; Jazet, I. M.

2010-01-01

Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity. To study the effect of dietary supplementation with PS on

Optimum Criteria for Developing Defined Structures

Directory of Open Access Journals (Sweden)

Ion IVAN

2008-01-01

Full Text Available Basic aspects concerning distributed applications are presented: definition, particularities and importance. For distributed applications linear, arborescent, graph structures are defined with different versions and aggregation methods. Distributed applications have associated structures which through their characteristics influence the costs of the stages in the development cycle and the exploitation costs transferred to each user. The complexity of the defined structures is analyzed. The minimum and maximum criteria are enumerated for optimizing distributed application structures.

Defining collaborative business rules management solutions : framework and method

NARCIS (Netherlands)

dr. Martijn Zoet; Johan Versendaal

2014-01-01

From the publishers' website: The goal of this research is to define a method for configuring a collaborative business rules management solution from a value proposition perspective. In an earlier published study (Business rules management solutions: added value by means of business

[Ill-defined causes of death and unattended deaths, Brazil, 2003].

Science.gov (United States)

Santo, Augusto Hasiak

2008-01-01

We studied the distribution of deaths from ill-defined causes that occurred in Brazil during 2003, from which was identified the proportion of unattended deaths. Data were obtained from the Mortality Information System, coordinated by the Ministry of Health. Causes of death included in "Chapter XVIII - Symptoms, signs and abnormal clinical and laboratory findings, not classified elsewhere" of the International Statistical Classification of Diseases and Related Health Problems, tenth revision, were considered ill-defined, among which the category R98 identified "unattended deaths". In Brazil during 2003 the underlying causes of 13.3% of deaths were included in the Chapter of ill-defined causes, and the highest proportions of these deaths occurred in the Northeast and North Regions. Considering the total deaths from ill-defined causes, 53 % correspond to unattended deaths. This proportion increased to over 70% in the states of Maranhão, Piauí, Rio Grande do Norte, Pernambuco, Bahia, Paraíba and Alagoas. Due to the decentralized structure of data collection in the country, we believe that the municipalities bear the major responsibility, followed by the states, for upgrading the quality of mortality statistics.

Skew category algebras associated with partially defined dynamical systems

DEFF Research Database (Denmark)

Lundström, Patrik; Öinert, Per Johan

2012-01-01

We introduce partially defined dynamical systems defined on a topological space. To each such system we associate a functor s from a category G to Topop and show that it defines what we call a skew category algebra A ⋊σ G. We study the connection between topological freeness of s and, on the one...... hand, ideal properties of A ⋊σ G and, on the other hand, maximal commutativity of A in A ⋊σ G. In particular, we show that if G is a groupoid and for each e ∈ ob(G) the group of all morphisms e → e is countable and the topological space s(e) is Tychonoff and Baire. Then the following assertions...... are equivalent: (i) s is topologically free; (ii) A has the ideal intersection property, i.e. if I is a nonzero ideal of A ⋊σ G, then I ∩ A ≠ {0}; (iii) the ring A is a maximal abelian complex subalgebra of A ⋊σ G. Thereby, we generalize a result by Svensson, Silvestrov and de Jeu from the additive group...

Evolution of sequence-defined highly functionalized nucleic acid polymers

Science.gov (United States)

Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

2018-03-01

The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

Descriptors Used to Define Running-Related Musculoskeletal Injury: A Systematic Review

NARCIS (Netherlands)

Yamato, T.P.; Saragiotto, B.T.; Hespanhol, L.C.; Yeung, S.S.; Lopes, A.D.

2015-01-01

STUDY DESIGN: Systematic review. OBJECTIVES: To systematically review the used to define running-related musculoskeletal injury and to analyze the implications of different definitions on the results of studies. BACKGROUND: Studies have developed their own definitions of running-related

Membrane-spanning lipids for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer

Science.gov (United States)

Schwarzmann, Günter; Breiden, Bernadette; Sandhoff, Konrad

2015-01-01

A Förster resonance energy transfer-based fusion and transfer assay was developed to study, in model membranes, protein-mediated membrane fusion and intermembrane lipid transfer of fluorescent sphingolipid analogs. For this assay, it became necessary to apply labeled reporter molecules that are resistant to spontaneous as well as protein-mediated intermembrane transfer. The novelty of this assay is the use of nonextractable fluorescent membrane-spanning bipolar lipids. Starting from the tetraether lipid caldarchaeol, we synthesized fluorescent analogs with fluorophores at both polar ends. In addition, we synthesized radioactive glycosylated caldarchaeols. These labeled lipids were shown to stretch through bilayer membranes rather than to loop within a single lipid layer of liposomes. More important, the membrane-spanning lipids (MSLs) in contrast to phosphoglycerides proved to be nonextractable by proteins. We could show that the GM2 activator protein (GM2AP) is promiscuous with respect to glycero- and sphingolipid transfer. Saposin (Sap) B also transferred sphingolipids albeit with kinetics different from GM2AP. In addition, we could unambiguously show that the recombinant activator protein Sap C x His6 induced membrane fusion rather than intermembrane lipid transfer. These findings showed that these novel MSLs, in contrast with fluorescent phosphoglycerolipids, are well suited for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. PMID:26269359

Membrane-spanning lipids for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer.

Science.gov (United States)

Schwarzmann, Günter; Breiden, Bernadette; Sandhoff, Konrad

2015-10-01

A Förster resonance energy transfer-based fusion and transfer assay was developed to study, in model membranes, protein-mediated membrane fusion and intermembrane lipid transfer of fluorescent sphingolipid analogs. For this assay, it became necessary to apply labeled reporter molecules that are resistant to spontaneous as well as protein-mediated intermembrane transfer. The novelty of this assay is the use of nonextractable fluorescent membrane-spanning bipolar lipids. Starting from the tetraether lipid caldarchaeol, we synthesized fluorescent analogs with fluorophores at both polar ends. In addition, we synthesized radioactive glycosylated caldarchaeols. These labeled lipids were shown to stretch through bilayer membranes rather than to loop within a single lipid layer of liposomes. More important, the membrane-spanning lipids (MSLs) in contrast to phosphoglycerides proved to be nonextractable by proteins. We could show that the GM2 activator protein (GM2AP) is promiscuous with respect to glycero- and sphingolipid transfer. Saposin (Sap) B also transferred sphingolipids albeit with kinetics different from GM2AP. In addition, we could unambiguously show that the recombinant activator protein Sap C x His6 induced membrane fusion rather than intermembrane lipid transfer. These findings showed that these novel MSLs, in contrast with fluorescent phosphoglycerolipids, are well suited for an uncompromised monitoring of membrane fusion and intermembrane lipid transfer. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

12 CFR 914.1 - Regulatory Report defined.

Science.gov (United States)

2010-01-01

... Bank. (b) Examples. Regulatory Report includes: (1) Call reports and reports of instrument-level risk... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Regulatory Report defined. 914.1 Section 914.1... DATA AVAILABILITY AND REPORTING § 914.1 Regulatory Report defined. (a) Definition. Regulatory Report...

Pseudo-Hermitian description of PT-symmetric systems defined on a complex contour

International Nuclear Information System (INIS)

Mostafazadeh, Ali

2005-01-01

We describe a method that allows for a practical application of the theory of pseudo-Hermitian operators to PT-symmetric systems defined on a complex contour. We apply this method to study the Hamiltonians H = p 2 + x 2 (ix) ν with ν ε (-2, ∞) that are defined along the corresponding anti-Stokes lines. In particular, we reveal the intrinsic non-Hermiticity of H for the cases that ν is an even integer, so that H p 2 ± x 2+ν , and give a proof of the discreteness of the spectrum of H for all ν ε (-2, ∞). Furthermore, we study the consequences of defining a square-well Hamiltonian on a wedge-shaped complex contour. This yields a PT-symmetric system with a finite number of real eigenvalues. We present a comprehensive analysis of this system within the framework of pseudo-Hermitian quantum mechanics. We also outline a direct pseudo-Hermitian treatment of PT-symmetric systems defined on a complex contour which clarifies the underlying mathematical structure of the formulation of PT-symmetric quantum mechanics based on the charge-conjugation operator. Our results provide conclusive evidence that pseudo-Hermitian quantum mechanics provides a complete description of general PT-symmetric systems regardless of whether they are defined along the real line or a complex contour

Exposing the Myths, Defining the Future

International Nuclear Information System (INIS)

Slavov, S.

2013-01-01

With this official statement, the WEC calls for policymakers and industry leaders to ''get real'' as the World Energy Council as a global energy body exposes the myths by informing the energy debate and defines a path to a more sustainable energy future. The World Energy Council urged stakeholders to take urgent and incisive actions, to develop and transform the global energy system. Failure to do so could put aspirations on the triple challenge of WEC Energy Trilemma defined by affordability, accessibility and environmental sustainability at serious risk. Through its multi-year in-depth global studies and issue-mapping the WEC has found that challenges that energy sector is facing today are much more crucial than previously envisaged. The WEC's analysis has exposed a number of myths which influence our understanding of important aspects of the global energy landscape. If not challenged, these misconceptions will lead us down a path of complacency and missed opportunities. Much has, and still is, being done to secure energy future, but the WEC' s studies reveal that current pathways fall short of delivering on global aspirations of energy access, energy security and environmental improvements. If we are to derive the full economic and social benefits from energy resources, then we must take incisive and urgent action to modify our steps to energy solutions. The usual business approaches are not effective, the business as usual is not longer a solution. The focus has moved from large universal solutions to an appreciation of regional and national contexts and sharply differentiated consumer expectations.(author)

47 CFR 2.801 - Radiofrequency device defined.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Radiofrequency device defined. 2.801 Section 2... MATTERS; GENERAL RULES AND REGULATIONS Marketing of Radio-frequency Devices § 2.801 Radiofrequency device defined. As used in this part, a radiofrequency device is any device which in its operation is capable of...

Living Polycondensation: Synthesis of Well-Defined Aromatic Polyamide-Based Polymeric Materials

KAUST Repository

Alyami, Mram Z.

2016-11-01

Chain growth condensation polymerization is a powerful tool towards the synthesis of well-defined polyamides. This thesis focuses on one hand, on the synthesis of well-defined aromatic polyamides with different aminoalkyl pendant groups with low polydispersity and controlled molecular weights, and on the other hand, on studying their thermal properties. In the first project, well-defined poly (N-octyl-p-aminobenzoate) and poly (N-butyl-p-aminobenzoate) were synthesized, and for the first time, their thermal properties were studied. In the second project, ethyl4-aminobenzoate, ethyl 4-octyl aminobenzoate and 4-(hydroxymethyl) benzoic acid were used as novel efficient initiators of ε-caprolactone with t-BuP2 as a catalyst. Macroinitiator and Macromonomer of poly (ε-caprolactone) were synthesized with ethyl 4-octyl aminobenzoate and ethyl 4-aminobenzoate as initiators to afford polyamide-block-poly (ε-caprolactone) and polyamide-graft-poly (ε-caprolactone) by chain growth condensation polymerization (CGCP). In the third project, a new study has been done on chain growth condensation polymerization to discover the probability to synthesize new polymers and studied their thermal properties. For this purpose, poly (N-cyclohexyl-p-aminobenzoate) and poly (N-hexyl-p-aminobenzoate) were synthesized with low polydispersity and controlled molecular weights.

33 CFR 211.1 - Real estate defined.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Real estate defined. 211.1... DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.1 Real estate defined. The term real estate as used in this part includes land...

Software Defined Common Processing System (SDCPS), Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Coherent Logix, Incorporated proposes the Software Defined Common Processing System (SDCPS) program to facilitate the development of a Software Defined Radio...

S1P Signaling and De Novo Biosynthesis in Blood Pressure Homeostasis

Science.gov (United States)

Cantalupo, Anna

2016-01-01

Initially discovered as abundant components of eukaryotic cell membranes, sphingolipids are now recognized as important bioactive signaling molecules that modulate a variety of cellular functions, including those relevant to cancer and immunologic, inflammatory, and cardiovascular disorders. In this review, we discuss recent advances in our understanding of the role of sphingosine-1-phosphate (S1P) receptors in the regulation of vascular function, and focus on how de novo biosynthesized sphingolipids play a role in blood pressure homeostasis. The therapeutic potential of new drugs that target S1P signaling is also discussed. PMID:27317800

Defining fitness to practise in Australian radiation therapy: A focus group study

International Nuclear Information System (INIS)

Wright, Caroline A.; Jolly, Brian; Schneider-Kolsky, Michal E.; Baird, Marilyn A.

2011-01-01

Purpose: This paper presents the results of a study undertaken to investigate how Australian radiation therapists define fitness to practise. Method: A qualitative approach was taken to data collection with focus groups being employed to gather the data. Analysis was informed by grounded theory. Following ethics approval, three homogeneous focus groups were conducted comprising a total of 21 participants, with 5-8 participants per group. The discussions were transcribed, verified by the researcher and participants, then unitised, coded and a sample checked by a second coder. Findings: There was no consensus on the definition of fitness to practise. The terms professionalism and competence were used interchangeably in some definitions. Four themes emerged from the data, these were; fitness as a continuum (individual differences and longevity in the profession), fitness as behaviour and conduct (professionalism and competence), fitness as a state of mind (attitudes and intangible elements) and fitness as being qualified (course completion means fitness to practise). Three concepts which were not raised were illegal behaviour, impaired practice and dose errors. Conclusion: There is no consensus among radiation therapists about fitness to practise. There was confusion with how Fitness to practise relates to professionalism and competence with little mention of how impairment is interwoven into the notion of fitness to practise. Without an unambiguous definition and robust criteria, making the 'judgement call' as to whether a practitioners' fitness to practise is impaired will continue to be a challenge for educators, departmental managers and registration boards.

Body mass index bias in defining obesity of diverse young adults: The Training Intervention and Genetics of Exercise Response (TIGER) Study

Science.gov (United States)

The BMI cut-score used to define overweight and obesity was derived primarily using data from Caucasian men and women. The present study evaluated the racial/ethnic bias of BMI to estimate the adiposity of young men and women (aged 17–35 years) using dual-energy X-ray absorptiometry (DXA) determinat...

26 CFR 1.761-1 - Terms defined.

Science.gov (United States)

2010-04-01

... TAXES Definitions § 1.761-1 Terms defined. (a) Partnership. The term partnership means a partnership as... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Terms defined. 1.761-1 Section 1.761-1 Internal... means a member of a partnership. (c) Partnership agreement. For the purposes of subchapter K, a...

Theoretical approaches to elections defining

OpenAIRE

Natalya V. Lebedeva

2011-01-01

Theoretical approaches to elections defining develop the nature, essence and content of elections, help to determine their place and a role as one of the major national law institutions in democratic system.

48 CFR 311.7000 - Defining electronic information technology requirements.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Defining electronic information technology requirements. 311.7000 Section 311.7000 Federal Acquisition Regulations System HEALTH... Accessibility Standards 311.7000 Defining electronic information technology requirements. HHS staff that define...

Dilution Confusion: Conventions for Defining a Dilution

Science.gov (United States)

Fishel, Laurence A.

2010-01-01

Two conventions for preparing dilutions are used in clinical laboratories. The first convention defines an "a:b" dilution as "a" volumes of solution A plus "b" volumes of solution B. The second convention defines an "a:b" dilution as "a" volumes of solution A diluted into a final volume of "b". Use of the incorrect dilution convention could affect…

Diabetes mellitus defined by hemoglobin A1c value: Risk characterization for incidence among Japanese subjects in the JPHC Diabetes Study.

Science.gov (United States)

Kato, Masayuki; Takahashi, Yoshihiko; Matsushita, Yumi; Mizoue, Tetsuya; Inoue, Manami; Kadowaki, Takashi; Tsugane, Shoichiro; Noda, Mitsuhiko

2011-10-07

Aims/Introduction:  Although several risk factors for type 2 diabetes have been identified, most of them have been identified in studies on Western populations, and they should be evaluated in a Japanese population. In 2010, new diagnostic criteria for diabetes mellitus using hemoglobin A1c (HbA1c) were released and its use in epidemiological studies has many advantages. The aim of the present study was to evaluate risk factors for type 2 diabetes defined based on HbA1c values in a Japanese population.   A total of 9223 subjects (3076 men and 6147 women) were followed up for 5 years. Diabetes was defined based on self-report or HbA1c value. Risk factors for diabetes were evaluated as odds ratios adjusted for potential confounding factors by logistic regression.   During the 5-year follow-up period, we documented 518 incident cases of diabetes (232 men and 286 women). Of the 518 incident cases, 310 cases were diagnosed by HbA1c alone. Among the men, age, smoking (both past smoking and current smoking) and family history of diabetes significantly increased the risk of diabetes. Among the women, body mass index, family history of diabetes and hypertension significantly increased the risk of diabetes. These results did not change markedly after adjustment for the baseline HbA1c values, and the baseline HbA1c value itself was a significant risk factor for diabetes mellitus.   Known risk factors for diabetes established in Western populations also increased the risk of diabetes in a Japanese population defined on the basis of HbA1c values. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00119.x, 2011).

Theoretical approaches to elections defining

Directory of Open Access Journals (Sweden)

Natalya V. Lebedeva

2011-01-01

Full Text Available Theoretical approaches to elections defining develop the nature, essence and content of elections, help to determine their place and a role as one of the major national law institutions in democratic system.

Defining Disability: Understandings of and Attitudes Towards Ableism and Disability

Directory of Open Access Journals (Sweden)

Carli Friedman

2017-03-01

Full Text Available Disabled people, amidst political and social gains, continue to experience discrimination in multiple areas. Understanding how such discrimination, named here as ableism, operates is important and may require studying perspectives of people who do not claim a disability identity.  Ableism may be expressed in a number of ways, and examining how a particular group, in this case siblings of disabled people, understand and value disability may contribute to overall understandings about how ableism works. Thus, the purpose of this study is to explore relationships between siblings of disabled people's broad societal understandings of disability and their attitudes towards it. In order to tease out this relationship further we have also examined factors that impact how people define disability. Using both social psychological and sociological approaches, we have contextualized individual attitudes as providing additional new information about social meanings of disability, and set this study's results against the larger backdrops of debates over meanings of disability within Disability Studies. In our research, participants revealed complex understandings of disability, but most often defined disability as preventing or slowing action, as an atypical function, a lack of independence, and as a socially constructed obstacle. Participants' unconscious (implicit disability attitudes significantly related to their understandings of disability as lacking independence, impairment, and/or in relation to the norm, and their conscious (explicit disability attitudes. Moreover, longer employment in a disability-related industry was correlated with defining disability as a general difference, rather than as slowing or limiting of tasks.

Factors Defining Field Germination of Oilseed Radish Seeds

Directory of Open Access Journals (Sweden)

N.V. Dorofeev

2013-08-01

Full Text Available Influence of temperature, depth of crops and granulometric of soil structure on germination speed, laboratory and field germination of oilseed radish seeds were studied. It was established that the period of seed-germination is defined both by temperature and granulometric structure of soil. The highest field germination was marked on sandy loam at depth of crops' seeds at 3 cm and 20°С.

Modal Logics and Definability

OpenAIRE

Kuusisto, Antti

2013-01-01

In recent years, research into the mathematical foundations of modal logic has become increasingly popular. One of the main reasons for this is the fact that modal logic seems to adapt well to the requirements of a wide range of different fields of application. This paper is a summary of some of the author’s contributions to the understanding of modal definability theory.

A definability theorem for first order logic

NARCIS (Netherlands)

Butz, C.; Moerdijk, I.

1997-01-01

In this paper we will present a definability theorem for first order logic This theorem is very easy to state and its proof only uses elementary tools To explain the theorem let us first observe that if M is a model of a theory T in a language L then clearly any definable subset S M ie a subset S

Defining generic architecture for Cloud IaaS provisioning model

NARCIS (Netherlands)

Demchenko, Y.; de Laat, C.; Mavrin, A.; Leymann, F.; Ivanov, I.; van Sinderen, M.; Shishkov, B.

2011-01-01

Infrastructure as a Service (IaaS) is one of the provisioning models for Clouds as defined in the NIST Clouds definition. Although widely used, current IaaS implementations and solutions doesn’t have common and well defined architecture model. The paper attempts to define a generic architecture for

Variable Bandwidth Analog Channel Filters for Software Defined Radio

NARCIS (Netherlands)

Arkesteijn, V.J.; Klumperink, Eric A.M.; Nauta, Bram

2001-01-01

An important aspect of Software Defined Radio is the ability to define the bandwidth of the filter that selects the desired channel. This paper first explains the importance of channel filtering. Then the advantage of analog channel filtering with a variable bandwidth in a Software Defined Radio is

Defining recovery in adult bulimia nervosa.

Science.gov (United States)

Yu, Jessica; Agras, W Stewart; Bryson, Susan

2013-01-01

To examine how different definitions of recovery lead to varying rates of recovery, maintenance of recovery, and relapse in bulimia nervosa (BN), end-of-treatment (EOT) and follow-up data were obtained from 96 adults with BN. Combining behavioral, physical, and psychological criteria led to recovery rates between 15.5% and 34.4% at EOT, though relapse was approximately 50%. Combining these criteria and requiring abstinence from binge eating and purging when defining recovery may lead to lower recovery rates than those found in previous studies; however, a strength of this definition is that individuals who meet this criteria have no remaining disordered behaviors or symptoms.

Toward Edge-Defined Holey Boron Nitride Nanosheets

Science.gov (United States)

Lin, Yi; Liao, Yunlong; Chen, Zhongfan; Connell, John W.

2015-01-01

"Holey" two-dimensional (2D) nanosheets with well-defined holy morphology and edge chemistry are highly desirable for applications such as energy storage, catalysis, sensing, transistors, and molecular transport/separation. For example, holey grapheme is currently under extensive investigation for energy storage applications because of the improvement in ion transport due to through the thickness pathways provided by the holes. Without the holes, the 2D materials have significant limitations for such applications in which efficient ion transport is important. As part of an effort to apply this approach to other 2D nanomaterials, a method to etch geometrically defined pits or holes on the basal plane surface of hexagonal boron nitride (h-BN) nanosheets has been developed. The etching, conducted via heating in ambient air using metal nanoparticles as catalysts, was facile, controllable, and scalable. Starting h-BN layered crystals were etched and subsequently exfoliated into boron nitride nanosheets (BNNSs). The as-etched and exfoliated h-BN nanosheets possessed defined pit and hole shapes that were comprised of regulated nanostructures at the edges. The current finding are the first step toward the bulk preparation of holey BNNSs with defined holes and edges.

Pre-defined and optional staging for the deployment of enterprise systems: a case study and a framework

Science.gov (United States)

Lichtenstein, Yossi; Cucuy, Shy; Fink, Lior

2017-03-01

The effective deployment of enterprise systems has been a major challenge for many organisations. Customising the new system, changing business processes, and integrating multiple information sources are all difficult tasks. As such, they are typically done in carefully planned stages in a process known as phased implementation. Using ideas from Option Theory, this article critiques aspects of phased implementation. One customer relationship management (CRM) project and its phased implementation are described in detail and ten other enterprise system deployments are summarised as a basis for the observation that almost all deployment stages are pre-defined operational steps rather than decision points. However, Option Theory suggests that optional stages, to be used only when risk materialises, should be integral parts of project plans. Although such optional stages are often more valuable than pre-defined stages, the evidence presented in this article shows that they are only rarely utilised. Therefore, a simple framework is presented; it first identifies risks related to the deployment of enterprise systems, then identifies optional stages that can mitigate these risks, and finally compares the costs and benefits of both pre-defined and optional stages.

The first sight of love: Relationship-defining memories and marital satisfaction across adulthood.

Science.gov (United States)

Alea, Nicole; Vick, Stephanie C

2010-10-01

The current study begins the exploration of relationship-defining memories (i.e., the first time someone met their spouse) across adulthood. Men and women ranging from 20 to 85 years old (N=267; M age=47.19) completed a measure of marital satisfaction, wrote a relationship-defining memory, and answered questions about the quality of their memory (i.e., vividness, valence, emotional intensity, and rehearsal). Data were collected online. Results indicate that individuals over 70 and those younger than 30 rehearsed relationship-defining memories most often. Women in midlife also reported more vivid memories. The quality of relationship-defining memories also predicted marital satisfaction. Relationship-defining memories that were more vivid, positive, emotionally intense, and rehearsed related to higher marital satisfaction. Age and gender differences were minimal. Results are discussed in the context of the adaptive social function of autobiographical memories, such that these memories might have a role in influencing marital satisfaction across adulthood.

Ceramides And Stress Signalling Intersect With Autophagic Defects In Neurodegenerative Drosophila blue cheese (bchs) Mutants.

Science.gov (United States)

Hebbar, Sarita; Sahoo, Ishtapran; Matysik, Artur; Argudo Garcia, Irene; Osborne, Kathleen Amy; Papan, Cyrus; Torta, Federico; Narayanaswamy, Pradeep; Fun, Xiu Hui; Wenk, Markus R; Shevchenko, Andrej; Schwudke, Dominik; Kraut, Rachel

2015-12-07

Sphingolipid metabolites are involved in the regulation of autophagy, a degradative recycling process that is required to prevent neuronal degeneration. Drosophila blue cheese mutants neurodegenerate due to perturbations in autophagic flux, and consequent accumulation of ubiquitinated aggregates. Here, we demonstrate that blue cheese mutant brains exhibit an elevation in total ceramide levels; surprisingly, however, degeneration is ameliorated when the pool of available ceramides is further increased, and exacerbated when ceramide levels are decreased by altering sphingolipid catabolism or blocking de novo synthesis. Exogenous ceramide is seen to accumulate in autophagosomes, which are fewer in number and show less efficient clearance in blue cheese mutant neurons. Sphingolipid metabolism is also shifted away from salvage toward de novo pathways, while pro-growth Akt and MAP pathways are down-regulated, and ER stress is increased. All these defects are reversed under genetic rescue conditions that increase ceramide generation from salvage pathways. This constellation of effects suggests a possible mechanism whereby the observed deficit in a potentially ceramide-releasing autophagic pathway impedes survival signaling and exacerbates neuronal death.

Defining fitness to practise in Australian radiation therapy: A focus group study

Energy Technology Data Exchange (ETDEWEB)

Wright, Caroline A., E-mail: caroline.wright@med.monash.edu.a [Monash University, Medical Imaging and Radiation Sciences, Clayton Campus, Wellington Road Clayton, Melbourne, Victoria 3800 (Australia); Jolly, Brian [Monash University, Centre for Medical and Health Sciences Education (Australia); Schneider-Kolsky, Michal E.; Baird, Marilyn A. [Monash University, Medical Imaging and Radiation Sciences, Clayton Campus, Wellington Road Clayton, Melbourne, Victoria 3800 (Australia)

2011-02-15

Purpose: This paper presents the results of a study undertaken to investigate how Australian radiation therapists define fitness to practise. Method: A qualitative approach was taken to data collection with focus groups being employed to gather the data. Analysis was informed by grounded theory. Following ethics approval, three homogeneous focus groups were conducted comprising a total of 21 participants, with 5-8 participants per group. The discussions were transcribed, verified by the researcher and participants, then unitised, coded and a sample checked by a second coder. Findings: There was no consensus on the definition of fitness to practise. The terms professionalism and competence were used interchangeably in some definitions. Four themes emerged from the data, these were; fitness as a continuum (individual differences and longevity in the profession), fitness as behaviour and conduct (professionalism and competence), fitness as a state of mind (attitudes and intangible elements) and fitness as being qualified (course completion means fitness to practise). Three concepts which were not raised were illegal behaviour, impaired practice and dose errors. Conclusion: There is no consensus among radiation therapists about fitness to practise. There was confusion with how Fitness to practise relates to professionalism and competence with little mention of how impairment is interwoven into the notion of fitness to practise. Without an unambiguous definition and robust criteria, making the 'judgement call' as to whether a practitioners' fitness to practise is impaired will continue to be a challenge for educators, departmental managers and registration boards.

A defined medium for Leishmania culture allows definition of essential amino acids.

Science.gov (United States)

Nayak, Archana; Akpunarlieva, Snezhana; Barrett, Michael; Burchmore, Richard

2018-02-01

Axenic culture of Leishmania is generally performed in rich, serum-supplemented media which sustain robust growth over multiple passages. The use of such undefined media, however, obscures proteomic analyses and confounds the study of metabolism. We have established a simple, defined culture medium that supports the sustained growth of promastigotes over multiple passages and which yields parasites that have similar infectivity to macrophages to parasites grown in a conventional semi-defined medium. We have exploited this medium to investigate the amino acid requirements of promastigotes in culture and have found that phenylalanine, tryptophan, arginine, leucine, lysine and valine are essential for viability in culture. Most of the 20 proteogenic amino acids promote growth of Leishmania promastigotes, with the exception of alanine, asparagine, and glycine. This defined medium will be useful for further studies of promastigote substrate requirements, and will facilitate future proteomic and metabolomic analyses. Copyright © 2018 Elsevier Inc. All rights reserved.

Critical defining characteristics for nursing diagnosis about ineffective breastfeeding

Directory of Open Access Journals (Sweden)

Sandra Cristina de Alvarenga

Full Text Available ABSTRACT Objective: To investigate the Nursing diagnostic accuracy measures and to propose a model to use defining characteristics in order to judge the nursing diagnosis of ineffective breastfeeding. Method: Cross-sectional study with a sample of 73 binomials mom-child hospitalized in a maternity ward of an University Hospital, from July to August of 2014. Results: The diagnostic predominance rate was 58.9%. The characteristics that best meet the needs of logistic regression model were: discontinuance of breast sucking; infant's inability of seizing the areola-nipple region correctly; infant's crying one hour after breastfeeding and inappropriate milk supply perceived. Conclusion: Breastfeeding process is dynamic; diagnostic judgement may suffer some changes according to the time data are collected; the defining characteristics are the best predictors if associated with models and rules of use.

Mutation for nonsyndromic mental retardation in the trans-2-enoyl-CoA reductase TER gene involved in fatty acid elongation impairs the enzyme activity and stability, leading to change in sphingolipid profile.

Science.gov (United States)

Abe, Kensuke; Ohno, Yusuke; Sassa, Takayuki; Taguchi, Ryo; Çalışkan, Minal; Ober, Carole; Kihara, Akio

2013-12-20

Very long-chain fatty acids (VLCFAs, chain length >C20) exist in tissues throughout the body and are synthesized by repetition of the fatty acid (FA) elongation cycle composed of four successive enzymatic reactions. In mammals, the TER gene is the only gene encoding trans-2-enoyl-CoA reductase, which catalyzes the fourth reaction in the FA elongation cycle. The TER P182L mutation is the pathogenic mutation for nonsyndromic mental retardation. This mutation substitutes a leucine for a proline residue at amino acid 182 in the TER enzyme. Currently, the mechanism by which the TER P182L mutation causes nonsyndromic mental retardation is unknown. To understand the effect of this mutation on the TER enzyme and VLCFA synthesis, we have biochemically characterized the TER P182L mutant enzyme using yeast and mammalian cells transfected with the TER P182L mutant gene and analyzed the FA elongation cycle in the B-lymphoblastoid cell line with the homozygous TER P182L mutation (TER(P182L/P182L) B-lymphoblastoid cell line). We have found that TER P182L mutant enzyme exhibits reduced trans-2-enoyl-CoA reductase activity and protein stability, thereby impairing VLCFA synthesis and, in turn, altering the sphingolipid profile (i.e. decreased level of C24 sphingomyelin and C24 ceramide) in the TER(P182L/P182L) B-lymphoblastoid cell line. We have also found that in addition to the TER enzyme-catalyzed fourth reaction, the third reaction in the FA elongation cycle is affected by the TER P182L mutation. These findings provide new insight into the biochemical defects associated with this genetic mutation.

Defining contagion literacy: a Delphi study

Science.gov (United States)

Kilstadius, Margareta; Gericke, Niklas

2017-11-01

Against the background of climate change, which enables infectious diseases to move their frontiers and the increasing global mobility, which make people more exposed to contagion, we as citizens need to relate to this new scenario. A greater number of infectious diseases may also potentially lead to an increased need to use antibiotics and anti-parasitic substances. In view of this, the aim of this study was to identify the health literacy needed in the contemporary world and specify what should be taught in compulsory school. We present the findings of a Delphi study, performed in Sweden, regarding the opinions on contagion among experts in the field. We used Nutbeam's framework of health literacy and related it to Bloom's taxonomy of educational objectives in order to analyse and categorise the experts' responses, which were categorised into six main content themes: contagions, transmission routes, sexually transmitted diseases, hygiene, vaccinations and use of antibiotics and antibiotic resistance. These themes were then divided into the three levels of Nutbeam's framework: functional health literacy, which is about knowledge and understanding, interactive health literacy, which is about developing personal qualities and skills that promote health, and critical health literacy, which is about social and cognitive skills related to analysis and critical reflection. The implications for communication and education are then discussed and what should be taught in compulsory school is identified.

Dihydroceramide biology - Structure-specific metabolism and intracellular localization

NARCIS (Netherlands)

Kok, JW; NikolovaKarakashian, M; Klappe, K; Alexander, C; Merrill, AH

1997-01-01

This study utilized fluorescent analogs to characterize the intracellular transport and metabolism of dihydroceramide (DN-Cer), an intermediate in de novo sphingolipid biosynthesis, When 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]hexanoyl-DH-Cer (C-6-NBD-DH-Cer) was incubated with HT29, NRK, BHK,

Defining a Leader Role curriculum for radiation oncology: A global Delphi consensus study.

Science.gov (United States)

Turner, Sandra; Seel, Matthew; Trotter, Theresa; Giuliani, Meredith; Benstead, Kim; Eriksen, Jesper G; Poortmans, Philip; Verfaillie, Christine; Westerveld, Henrike; Cross, Shamira; Chan, Ming-Ka; Shaw, Timothy

2017-05-01

The need for radiation oncologists and other radiation oncology (RO) professionals to lead quality improvement activities and contribute to shaping the future of our specialty is self-evident. Leadership knowledge, skills and behaviours, like other competencies, can be learned (Blumenthal et al., 2012). The objective of this study was to define a globally applicable competency set specific to radiation oncology for the CanMEDS Leader Role (Frank et al., 2015). A modified Delphi consensus process delivering two rounds of on-line surveys was used. Participants included trainees, radiation/clinical oncologists and other RO team members (radiation therapists, physicists, and nurses), professional educators and patients. 72 of 95 (76%) invitees from nine countries completed the Round 1 (R1) survey. Of the 72 respondents to RI, 70 completed Round 2 (R2) (97%). In R1, 35 items were deemed for 'inclusion' and 21 for 'exclusion', leaving 41 'undetermined'. After review of items, informed by participant comments, 14 competencies from the 'inclusion' group went into the final curriculum; 12 from the 'undetermined' group went to R2. In R2, 6 items reached consensus for inclusion. This process resulted in 20 RO Leader Role competencies with apparent global applicability. This is the first step towards developing learning, teaching and assessment tools for this important area of training. Copyright © 2017 Elsevier B.V. All rights reserved.

An approach to define semantics for BPM systems interoperability

Science.gov (United States)

Rico, Mariela; Caliusco, María Laura; Chiotti, Omar; Rosa Galli, María

2015-04-01

This article proposes defining semantics for Business Process Management systems interoperability through the ontology of Electronic Business Documents (EBD) used to interchange the information required to perform cross-organizational processes. The semantic model generated allows aligning enterprise's business processes to support cross-organizational processes by matching the business ontology of each business partner with the EBD ontology. The result is a flexible software architecture that allows dynamically defining cross-organizational business processes by reusing the EBD ontology. For developing the semantic model, a method is presented, which is based on a strategy for discovering entity features whose interpretation depends on the context, and representing them for enriching the ontology. The proposed method complements ontology learning techniques that can not infer semantic features not represented in data sources. In order to improve the representation of these entity features, the method proposes using widely accepted ontologies, for representing time entities and relations, physical quantities, measurement units, official country names, and currencies and funds, among others. When the ontologies reuse is not possible, the method proposes identifying whether that feature is simple or complex, and defines a strategy to be followed. An empirical validation of the approach has been performed through a case study.

Using greenhouse gas fluxes to define soil functional types

Energy Technology Data Exchange (ETDEWEB)

Petrakis, Sandra; Barba, Josep; Bond-Lamberty, Ben; Vargas, Rodrigo

2017-12-04

Soils provide key ecosystem services and directly control ecosystem functions; thus, there is a need to define the reference state of soil functionality. Most common functional classifications of ecosystems are vegetation-centered and neglect soil characteristics and processes. We propose Soil Functional Types (SFTs) as a conceptual approach to represent and describe the functionality of soils based on characteristics of their greenhouse gas (GHG) flux dynamics. We used automated measurements of CO2, CH4 and N2O in a forested area to define SFTs following a simple statistical framework. This study supports the hypothesis that SFTs provide additional insights on the spatial variability of soil functionality beyond information represented by commonly measured soil parameters (e.g., soil moisture, soil temperature, litter biomass). We discuss the implications of this framework at the plot-scale and the potential of this approach at larger scales. This approach is a first step to provide a framework to define SFTs, but a community effort is necessary to harmonize any global classification for soil functionality. A global application of the proposed SFT framework will only be possible if there is a community-wide effort to share data and create a global database of GHG emissions from soils.

Desenvolupament d'un sistema de monitoratge per a Software Defined Networks (SDN)

OpenAIRE

Navarro Sánchez, Albert

2015-01-01

Les Software Defined-Networks (SDN) són una tecnologia emergent que permet als components software estendre funcionalitats sobre la xarxa. En aquest projecte s'estudia com pot encaixar Polygraph, un sistema de monitoratge per a xarxes tradicionals, dins les SDN. Software Defined-Networks (SDN) are a new tecnology that allows software components to add new functionalities on networks. This project studies how Polygraph, a monitoring system for traditional networks, can fit in a SDN scenario.

Hydroxyurea treatment inhibits proliferation of Cryptococcus neoformans in mice

Directory of Open Access Journals (Sweden)

Kaushlendra eTripathi

2012-05-01

Full Text Available The fungal pathogen Cryptococcus neoformans (Cn is a serious threat to immunocompromised individuals, especially for HIV patients who develop meningoencephalitis. For effective cryptococcal treatment, novel antifungal drugs or innovative combination therapies are needed. Recently, sphingolipids have emerged as important bioactive molecules in the regulation of microbial pathogenesis. Previously we reported that the sphingolipid pathway gene, ISC1, which is responsible for ceramide production, is a major virulence factor in Cn infection. Here we report our studies of the role of ISC1 during genotoxic stress induced by the antineoplastic hydroxyurea (HU and methylmethane sulfonate (MMS, which affect DNA replication and genome integrity. We observed that Cn cells lacking ISC1 are highly sensitive to HU and MMS in a rich culture medium. HU affected cell division of Cn cells lacking the ISC1 gene, resulting in cell clusters. Cn ISC1, when expressed in a Saccharomyces cerevisiae (Sc strain lacking its own ISC1 gene, restored HU resistance. In macrophage-like cells, although HU affected the proliferation of WT Cn cells by 50% at the concentration tested, HU completely inhibited Cn isc1-delta cell proliferation. Interestingly, our preliminary data show that mice infected with WT or Cn isc1-delta cells and subsequently treated with HU had longer lifespans than untreated, infected control mice. Our work suggests that the sphingolipid pathway gene, ISC1, is a likely target for combination therapy with traditional drugs such as HU.

Trichothecenes induce accumulation of glucosylceramide in neural cells by interfering with lactosylceramide synthase activity

International Nuclear Information System (INIS)

Kralj, Ana; Gurgui, Mihaela; Koenig, Gabriele M.; Echten-Deckert, Gerhild van

2007-01-01

Trichothecenes are sesquiterpenoid metabolites produced by several fungal strains that impair human and animal health. Since sphingolipids were connected with fungal toxicity the aim of the present study was to test the influence of fungal metabolites on sphingolipid metabolism in neural cells. The crude extract of fungal strain Spicellum roseum induced accumulation of glucosylceramide (GlcCer), and simultaneous reduction of the formation of lactosylceramide (LacCer) and complex gangliosides in primary cultured neurons. Following a bioassay-guided fractionation of the respective fungal extract we could demonstrate that the two isolated trichothecene derivatives, 8-deoxy-trichothecin (8-dT) and trichodermol (Td-ol) were responsible for this effect. Thus, incubation of primary cultured neurons as well as of neuroblastoma B104 cells for 24 h with 30 μM of either of the two fungal metabolites resulted in uncoupling of sphingolipid biosynthesis at the level of LacCer. For the observed reduction of LacCer synthase activity by about 90% cell integrity was crucial in both cell types. In neuroblastoma cells the amount of LacCer synthase mRNA was reduced in the presence of trichothecenes, whereas in primary cultured neurons this was not the case, suggesting a post-transcriptional mechanism of action in the latter cell type. The data also show that the compounds did not interfere with the translocation of GlcCer in neuroblastoma cells. Collectively, our results demonstrate that trichodermol and 8-deoxy-trichothecin inhibit LacCer synthase activity in a cell-type-specific manner

Defining Sustainable Universities Following Public Opinion Formation Process

Science.gov (United States)

Zaptcioglu Celikdemir, Deniz; Gunay, Gonca; Katrinli, Alev; Penbek Alpbaz, Sebnem

2017-01-01

Purpose: The purpose of this paper is to define the sustainable university in Turkey, by considering perspectives of various stakeholders such as experts, intellectual, public, political parties and media using public opinion formation analysis. The paper aims to re-define the "sustainable university" with all dimensions including…

Development of a chemically defined medium for the production of the antibiotic platensimycin by Streptomyces platensis.

Science.gov (United States)

Falzone, Maria; Martens, Evan; Tynan, Heather; Maggio, Christian; Golden, Samantha; Nayda, Vasyl; Crespo, Emmanuel; Inamine, Gregory; Gelber, Michael; Lemence, Ryan; Chiappini, Nicholas; Friedman, Emily; Shen, Ben; Gullo, Vincent; Demain, Arnold L

2013-11-01

The actinomycete Streptomyces platensis produces two compounds that display antibacterial activity: platensimycin and platencin. These compounds were discovered by the Merck Research Laboratories, and a complex insoluble production medium was reported. We have used this medium as our starting point in our studies. In a previous study, we developed a semi-defined production medium, i.e., PM5. In the present studies, by varying the concentration of the components of PM5, we were able to develop a superior semi-defined medium, i.e., PM6, which contains a higher concentration of lactose. Versions of PM6, containing lower concentrations of all components, were also found to be superior to PM5. The new semi-defined production media contain dextrin, lactose, MOPS buffer, and ammonium sulfate in different concentrations. We determined antibiotic production capabilities using agar diffusion assays and chemical assays via thin-layer silica chromatography and high-performance liquid chromatography. We reduced crude nutrient carryover from the seed medium by washing the cells with distilled water. Using these semi-defined media, we determined that addition of the semi-defined component soluble starch stimulated antibiotic production and that it and dextrin could both be replaced with glucose, resulting in the chemically defined medium, PM7.

User defined function for transformation of ellipsoidal coordinates

Directory of Open Access Journals (Sweden)

Ganić Aleksandar

2014-01-01

Full Text Available The topographic plane of the Earth has irregular shape, and for the purpose of mathematical defining, it is to be approximated by rotational ellipsoid. As local geodetic datum, rotational ellipsoids of various sizes are used in the world. More widely usage of the GPS while performing surveying tasks has resulted in the need to define global geodetic datum in order to obtain the best approximation the entire Earth. For this purpose, geocentric rotational ellipsoid WGS84 was defined and the results of the GPS measurements are shown in relation to it. By applying the appropriate equations, the ellipsoidal coordinates are being transformed from WGS84 into the coordinates on the local rotational ellipsoid, i.e. on the view plane. The paper shows User Defined Function created for Excel, by which the coordinates in the territory of Belgrade are being transformed from WGS84 of rotational ellipsoid into the Gauss-Krüger projection plane.

Defining the "normal" postejaculate urinalysis.

Science.gov (United States)

Mehta, Akanksha; Jarow, Jonathan P; Maples, Pat; Sigman, Mark

2012-01-01

Although sperm have been shown to be present in the postejaculate urinalysis (PEU) of both fertile and infertile men, the number of sperm present in the PEU of the general population has never been well defined. The objective of this study was to describe the semen and PEU findings in both the general and infertile population, in order to develop a better appreciation for "normal." Infertile men (n = 77) and control subjects (n = 71) were prospectively recruited. Exclusion criteria included azoospermia and medications known to affect ejaculation. All men underwent a history, physical examination, semen analysis, and PEU. The urine was split into 2 containers: PEU1, the initial voided urine, and PEU2, the remaining voided urine. Parametric statistical methods were applied for data analysis to compare sperm concentrations in each sample of semen and urine between the 2 groups of men. Controls had higher average semen volume (3.3 ± 1.6 vs 2.0 ± 1.4 mL, P sperm concentrations (112 million vs 56.2 million, P = .011), compared with infertile men. The presence of sperm in urine was common in both groups, but more prevalent among infertile men (98.7% vs 88.7%, P = .012), in whom it comprised a greater proportion of the total sperm count (46% vs 24%, P = .022). The majority of sperm present in PEU were seen in PEU1 of both controls (69%) and infertile men (88%). An association was noted between severe oligospermia (sperm counts in PEU (sperm in the urine compared with control, there is a large degree of overlap between the 2 populations, making it difficult to identify a specific threshold to define a positive test. Interpretation of a PEU should be directed by whether the number of sperm in the urine could affect subsequent management.

Are Some Attitudes More Self-Defining Than Others? Assessing Self-Related Attitude Functions and Their Consequences.

Science.gov (United States)

Zunick, Peter V; Teeny, Jacob D; Fazio, Russell H

2017-08-01

Attitudes serve multiple functions, some related to the self-concept. We call attitudes that help people define who they are "self-defining." Across four studies, we tested a brief self-report measure of the extent to which an attitude is self-defining. Studies 1 and 2 showed that self-defining attitudes tend to be extreme, positive, and unambivalent. Studies 3 and 4 produced two main findings. First, self-definition was related to, but not redundant with, a number of other characteristics of the attitude (e.g., attitude certainty). Second, self-definition predicted participants' intentions to spontaneously advocate and, in Study 4, their reactions to an opportunity to advocate behaviorally (i.e., writing about their attitude in an optional response box) following a self-threat. Overall, the results highlight the utility of this approach and, more broadly, demonstrate the value of considering the role of the self in attitudinal processes, and vice versa.

Older, wiser, and happier? Comparing older adults' and college students' self-defining memories.

Science.gov (United States)

Singer, Jefferson; Rexhaj, Blerim; Baddeley, Jenna

2007-11-01

The present study compared self-defining memories in adults 50 years of age and older to the self-defining memories of college students. Findings are largely congruent with previous memory and ageing research, but shed additional light on how personal memories are employed to achieve a sense of identity and continuity in older adults. Older adults' self-defining memories, compared to those of younger adults, were more positive in emotional tone, more summarised and less detailed, and more likely to contain integrative meaning. The implications of these findings for assessing normative personal memory in older adults are discussed along with more general observations about narrative identity in older adulthood.

Which Teachers Choose a Defined Contribution Pension Plan? Evidence from the Florida Retirement System

Science.gov (United States)

Chingos, Matthew M.; West, Martin R.

2015-01-01

Since 2002, public school teachers in Florida have been permitted to choose between a defined benefit (DB) and a defined contribution (DC) retirement plan. We exploit this unique policy environment to study new teachers' revealed preferences over pension plan structures. Roughly 30 percent of teachers hired between 2003 and 2008 selected the DC…

Defining and Differentiating the Makerspace

Science.gov (United States)

Dousay, Tonia A.

2017-01-01

Many resources now punctuate the maker movement landscape. However, some schools and communities still struggle to understand this burgeoning movement. How do we define these spaces and differentiate them from previous labs and shops? Through a multidimensional framework, stakeholders should consider how the structure, access, staffing, and tools…

Indico CONFERENCE: Define the Programme

CERN Multimedia

CERN. Geneva; Ferreira, Pedro

2017-01-01

In this tutorial you are going to learn how to define the programme of a conference in Indico. The program of your conference is divided in different “tracks”. Tracks represent the subject matter of the conference, such as “Online Computing”, “Offline Computing”, and so on.

Ethnic differences in metabolite signatures and type 2 diabetes: a nested case-control analysis among people of South Asian, African and European origin

NARCIS (Netherlands)

van Valkengoed, Irene G. M.; Argmann, Carmen; Ghauharali-van der Vlugt, Karen; Aerts, Johannes M. F. G.; Brewster, Lizzy M.; Peters, R. J. G.; Vaz, Frédéric M.; Houtkooper, Riekelt H.

2017-01-01

Accumulation of metabolites may mark or contribute to the development of type 2 diabetes mellitus (T2D), but there is a lack of data from ethnic groups at high risk. We examined sphingolipids, acylcarnitines and amino acids, and their association with T2D in a nested case-control study among 54

Ethnic differences in metabolite signatures and type 2 diabetes : a nested case-control analysis among people of South Asian, African and European origin

NARCIS (Netherlands)

Valkengoed, van I.G.M.; Argmann, C.; Ghauharali-van, der Vlugt K.; Aerts, J.M.F.G.; Brewster, L.M.; Peters, R.J.G.; Vaz, F.M.; Houtkooper, R.H.

2017-01-01

Accumulation of metabolites may mark or contribute to the development of type 2 diabetes mellitus (T2D), but there is a lack of data from ethnic groups at high risk. We examined sphingolipids, acylcarnitines and amino acids, and their association with T2D in a nested case-control study among 54

Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

Directory of Open Access Journals (Sweden)

Sandra M Eldridge

Full Text Available We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

Defining Feasibility and Pilot Studies in Preparation for Randomised Controlled Trials: Development of a Conceptual Framework.

Science.gov (United States)

Eldridge, Sandra M; Lancaster, Gillian A; Campbell, Michael J; Thabane, Lehana; Hopewell, Sally; Coleman, Claire L; Bond, Christine M

2016-01-01

We describe a framework for defining pilot and feasibility studies focusing on studies conducted in preparation for a randomised controlled trial. To develop the framework, we undertook a Delphi survey; ran an open meeting at a trial methodology conference; conducted a review of definitions outside the health research context; consulted experts at an international consensus meeting; and reviewed 27 empirical pilot or feasibility studies. We initially adopted mutually exclusive definitions of pilot and feasibility studies. However, some Delphi survey respondents and the majority of open meeting attendees disagreed with the idea of mutually exclusive definitions. Their viewpoint was supported by definitions outside the health research context, the use of the terms 'pilot' and 'feasibility' in the literature, and participants at the international consensus meeting. In our framework, pilot studies are a subset of feasibility studies, rather than the two being mutually exclusive. A feasibility study asks whether something can be done, should we proceed with it, and if so, how. A pilot study asks the same questions but also has a specific design feature: in a pilot study a future study, or part of a future study, is conducted on a smaller scale. We suggest that to facilitate their identification, these studies should be clearly identified using the terms 'feasibility' or 'pilot' as appropriate. This should include feasibility studies that are largely qualitative; we found these difficult to identify in electronic searches because researchers rarely used the term 'feasibility' in the title or abstract of such studies. Investigators should also report appropriate objectives and methods related to feasibility; and give clear confirmation that their study is in preparation for a future randomised controlled trial designed to assess the effect of an intervention.

Radiotherapy for brain metastases: defining palliative response

International Nuclear Information System (INIS)

Bezjak, Andrea; Adam, Janice; Panzarella, Tony; Levin, Wilfred; Barton, Rachael; Kirkbride, Peter; McLean, Michael; Mason, Warren; Wong, Chong Shun; Laperriere, Normand

2001-01-01

Background and purpose: Most patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT. Materials and methods: A prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose. Results: Seventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didn't change the large proportion who did not benefit (44%). Conclusions: Clinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT

16 CFR 238.0 - Bait advertising defined. 1

Science.gov (United States)

2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Bait advertising defined. 1 238.0 Section... BAIT ADVERTISING § 238.0 Bait advertising defined. 1 1 For the purpose of this part “advertising” includes any form of public notice however disseminated or utilized. Bait advertising is an alluring but...

26 CFR 1.1250-2 - Additional depreciation defined.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Additional depreciation defined. 1.1250-2... Additional depreciation defined. (a) In general—(1) Definition for purposes of section 1250(b)(1). Except as... depreciation means: (i) In the case of property which at the time of disposition has a holding period under...

Feasibility of bio-hydrogen production from sewage sludge using defined microbial consortium

Energy Technology Data Exchange (ETDEWEB)

Shireen Meher Kotay; Debabrata Das [Fermentation Technology Lab., Department of Biotechnology, Indian Institute of Technology Kharagpur, W.B., INDIA-721302 (India)

2006-07-01

Biological hydrogen production potential of a defined microbial consortium consisting of three facultative anaerobes, Enterobacter cloacae IIT-BT 08, Citrobacter freundii IIT-BT L139 and Bacillus coagulans IIT-BT S1 was studied. In this investigation their individual and combinatorial H{sub 2} production capabilities have been studied on defined media and pretreated sewage sludge. Defined medium, MYG (1% w/v Malt extract, 0.4% w/v yeast extract and 1% w/v glucose) with glucose as limiting substrate has been found to be most suitable for hydrogen production. Individually E. cloacae clearly gave higher yield (276 ml H{sub 2}/ g COD reduced) using defined medium than the other two strains. There was no considerable difference in maximal yield of hydrogen from individual and combinatorial (1:1:1 consortium) modes suggesting that E. cloacae dominated in the consortia on defined medium. Contradictorily, B. coagulans gave better bio-hydrogen yield (37.16 ml H{sub 2}/g COD consumed) than the other two strains when activated sewage sludge was used as substrate. The pretreatment of sludge included sterilization, (15% v/v) dilution and supplementation with 0.5%w/v glucose which was found to be essential to screen out the hydrogen consuming bacteria and ameliorate the hydrogenation. Considering (1:1:1) consortium as inoculum, interestingly yield of hydrogen was recorded to increase to 41.23 ml H{sub 2}/ g COD reduced inferring that in consortium, the substrate utilization was significantly higher. The hydrogen yield from pretreated sludge obtained in this study (35.54 ml H{sub 2} g sludge) has been found to be distinctively higher than the earlier reports (8.1 - 16.9 ml H{sub 2}/g sludge). However it was lower compared to the yield obtained from co-digestion of (83:17) food waste and sewage sludge (122 ml H{sub 2}/g carbohydrate COD). Employing formulated microbial consortia for bio-hydrogen production from sewage sludge was an attempt to augment the hydrogen yield from sludge

Feasibility of bio-hydrogen production from sewage sludge using defined microbial consortium

Energy Technology Data Exchange (ETDEWEB)

Shireen Meher Kotay; Debabrata Das [Fermentation Technology Lab., Department of Biotechnology, Indian Institute of Technology Kharagpur, W.B., INDIA-721302 (India)

2006-07-01

Biological hydrogen production potential of a defined microbial consortium consisting of three facultative anaerobes, Enterobacter cloacae IIT-BT 08, Citrobacter freundii IIT-BT L139 and Bacillus coagulans IIT-BT S1 was studied. In this investigation their individual and combinatorial H{sub 2} production capabilities have been studied on defined media and pretreated sewage sludge. Defined medium, MYG (1% w/v Malt extract, 0.4% w/v yeast extract and 1% w/v glucose) with glucose as limiting substrate has been found to be most suitable for hydrogen production. Individually E. cloacae clearly gave higher yield (276 ml H{sub 2}/ g COD reduced) using defined medium than the other two strains. There was no considerable difference in maximal yield of hydrogen from individual and combinatorial (1:1:1 consortium) modes suggesting that E. cloacae dominated in the consortia on defined medium. Contradictorily, B. coagulans gave better bio-hydrogen yield (37.16 ml H{sub 2}/ g COD consumed) than the other two strains when activated sewage sludge was used as substrate. The pretreatment of sludge included sterilization, (15% v/v) dilution and supplementation with 0.5% w/v glucose which was found to be essential to screen out the hydrogen consuming bacteria and ameliorate the hydrogenation. Considering (1:1:1) consortium as inoculum, interestingly yield of hydrogen was recorded to increase to 41.23 ml H{sub 2}/ g COD reduced inferring that in consortium, the substrate utilization was significantly higher. The hydrogen yield from pretreated sludge obtained in this study (35.54 ml H{sub 2}/ g sludge) has been found to be distinctively higher than the earlier reports (8.1 - 16.9 ml H{sub 2} / g sludge). However it was lower compared to the yield obtained from co-digestion of (83:17) food waste and sewage sludge (122 ml H{sub 2}/ g carbohydrate COD). Employing formulated microbial consortia for bio-hydrogen production from sewage sludge was an attempt to augment the hydrogen yield from

Feasibility of bio-hydrogen production from sewage sludge using defined microbial consortium

International Nuclear Information System (INIS)

Shireen Meher Kotay; Debabrata Das

2006-01-01

Biological hydrogen production potential of a defined microbial consortium consisting of three facultative anaerobes, Enterobacter cloacae IIT-BT 08, Citrobacter freundii IIT-BT L139 and Bacillus coagulans IIT-BT S1 was studied. In this investigation their individual and combinatorial H 2 production capabilities have been studied on defined media and pretreated sewage sludge. Defined medium, MYG (1% w/v Malt extract, 0.4% w/v yeast extract and 1% w/v glucose) with glucose as limiting substrate has been found to be most suitable for hydrogen production. Individually E. cloacae clearly gave higher yield (276 ml H 2 / g COD reduced) using defined medium than the other two strains. There was no considerable difference in maximal yield of hydrogen from individual and combinatorial (1:1:1 consortium) modes suggesting that E. cloacae dominated in the consortia on defined medium. Contradictorily, B. coagulans gave better bio-hydrogen yield (37.16 ml H 2 /g COD consumed) than the other two strains when activated sewage sludge was used as substrate. The pretreatment of sludge included sterilization, (15% v/v) dilution and supplementation with 0.5%w/v glucose which was found to be essential to screen out the hydrogen consuming bacteria and ameliorate the hydrogenation. Considering (1:1:1) consortium as inoculum, interestingly yield of hydrogen was recorded to increase to 41.23 ml H 2 / g COD reduced inferring that in consortium, the substrate utilization was significantly higher. The hydrogen yield from pretreated sludge obtained in this study (35.54 ml H 2 g sludge) has been found to be distinctively higher than the earlier reports (8.1 - 16.9 ml H 2 /g sludge). However it was lower compared to the yield obtained from co-digestion of (83:17) food waste and sewage sludge (122 ml H 2 /g carbohydrate COD). Employing formulated microbial consortia for bio-hydrogen production from sewage sludge was an attempt to augment the hydrogen yield from sludge. (authors)

Feasibility of bio-hydrogen production from sewage sludge using defined microbial consortium

International Nuclear Information System (INIS)

Shireen Meher Kotay; Debabrata Das

2006-01-01

Biological hydrogen production potential of a defined microbial consortium consisting of three facultative anaerobes, Enterobacter cloacae IIT-BT 08, Citrobacter freundii IIT-BT L139 and Bacillus coagulans IIT-BT S1 was studied. In this investigation their individual and combinatorial H 2 production capabilities have been studied on defined media and pretreated sewage sludge. Defined medium, MYG (1% w/v Malt extract, 0.4% w/v yeast extract and 1% w/v glucose) with glucose as limiting substrate has been found to be most suitable for hydrogen production. Individually E. cloacae clearly gave higher yield (276 ml H 2 / g COD reduced) using defined medium than the other two strains. There was no considerable difference in maximal yield of hydrogen from individual and combinatorial (1:1:1 consortium) modes suggesting that E. cloacae dominated in the consortia on defined medium. Contradictorily, B. coagulans gave better bio-hydrogen yield (37.16 ml H 2 / g COD consumed) than the other two strains when activated sewage sludge was used as substrate. The pretreatment of sludge included sterilization, (15% v/v) dilution and supplementation with 0.5% w/v glucose which was found to be essential to screen out the hydrogen consuming bacteria and ameliorate the hydrogenation. Considering (1:1:1) consortium as inoculum, interestingly yield of hydrogen was recorded to increase to 41.23 ml H 2 / g COD reduced inferring that in consortium, the substrate utilization was significantly higher. The hydrogen yield from pretreated sludge obtained in this study (35.54 ml H 2 / g sludge) has been found to be distinctively higher than the earlier reports (8.1 - 16.9 ml H 2 / g sludge). However it was lower compared to the yield obtained from co-digestion of (83:17) food waste and sewage sludge (122 ml H 2 / g carbohydrate COD). Employing formulated microbial consortia for bio-hydrogen production from sewage sludge was an attempt to augment the hydrogen yield from sludge. (authors)

Non-self-adjoint Hamiltonians defined by generalized Riesz bases

Energy Technology Data Exchange (ETDEWEB)

Inoue, H., E-mail: h-inoue@math.kyushu-u.ac.jp [Graduate School of Mathematics, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395 (Japan); Takakura, M., E-mail: mayumi@fukuoka-u.ac.jp [Department of Applied Mathematics, Fukuoka University, Fukuoka 814-0180 (Japan)

2016-08-15

Bagarello, Inoue, and Trapani [J. Math. Phys. 55, 033501 (2014)] investigated some operators defined by the Riesz bases. These operators connect with quasi-Hermitian quantum mechanics, and its relatives. In this paper, we introduce a notion of generalized Riesz bases which is a generalization of Riesz bases and investigate some operators defined by the generalized Riesz bases by changing the frameworks of the operators defined in the work of Bagarello, Inoue, and Trapani.

Animal bioavailability of defined xenobiotic lignin metabolites

International Nuclear Information System (INIS)

Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

1990-01-01

Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

Software defined networking applications in distributed datacenters

CERN Document Server

Qi, Heng

2016-01-01

This SpringerBrief provides essential insights on the SDN application designing and deployment in distributed datacenters. In this book, three key problems are discussed: SDN application designing, SDN deployment and SDN management. This book demonstrates how to design the SDN-based request allocation application in distributed datacenters. It also presents solutions for SDN controller placement to deploy SDN in distributed datacenters. Finally, an SDN management system is proposed to guarantee the performance of datacenter networks which are covered and controlled by many heterogeneous controllers. Researchers and practitioners alike will find this book a valuable resource for further study on Software Defined Networking. .

47 CFR 76.1904 - Encoding rules for defined business models.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Encoding rules for defined business models. 76... defined business models. (a) Commercial audiovisual content delivered as unencrypted broadcast television... the Commission pursuant to a petition with respect to a defined business model other than unencrypted...

Graphs for information security control in software defined networks

Science.gov (United States)

Grusho, Alexander A.; Abaev, Pavel O.; Shorgin, Sergey Ya.; Timonina, Elena E.

2017-07-01

Information security control in software defined networks (SDN) is connected with execution of the security policy rules regulating information accesses and protection against distribution of the malicious code and harmful influences. The paper offers a representation of a security policy in the form of hierarchical structure which in case of distribution of resources for the solution of tasks defines graphs of admissible interactions in a networks. These graphs define commutation tables of switches via the SDN controller.

Subjective but Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study.

Science.gov (United States)

Russell, Charlotte; Wearden, Alison J; Fairclough, Gillian; Emsley, Richard A; Kyle, Simon D

2016-04-01

This study aimed to (1) examine the relationship between subjective and actigraphy-defined sleep, and next-day fatigue in chronic fatigue syndrome (CFS); and (2) investigate the potential mediating role of negative mood on this relationship. We also sought to examine the effect of presleep arousal on perceptions of sleep. Twenty-seven adults meeting the Oxford criteria for CFS and self-identifying as experiencing sleep difficulties were recruited to take part in a prospective daily diary study, enabling symptom capture in real time over a 6-day period. A paper diary was used to record nightly subjective sleep and presleep arousal. Mood and fatigue symptoms were rated four times each day. Actigraphy was employed to provide objective estimations of sleep duration and continuity. Multilevel modelling revealed that subjective sleep variables, namely sleep quality, efficiency, and perceiving sleep to be unrefreshing, predicted following-day fatigue levels, with poorer subjective sleep related to increased fatigue. Lower subjective sleep efficiency and perceiving sleep as unrefreshing predicted reduced variance in fatigue across the following day. Negative mood on waking partially mediated these relationships. Increased presleep cognitive and somatic arousal predicted self-reported poor sleep. Actigraphy-defined sleep, however, was not found to predict following-day fatigue. For the first time we show that nightly subjective sleep predicts next-day fatigue in CFS and identify important factors driving this relationship. Our data suggest that sleep specific interventions, targeting presleep arousal, perceptions of sleep and negative mood on waking, may improve fatigue in CFS. © 2016 Associated Professional Sleep Societies, LLC.

Dose-dependent effects on sphingoid bases and cytokines in chickens fed diets prepared with fusarium verticillioides culture material containing fumonisins.

Science.gov (United States)

Grenier, Bertrand; Schwartz-Zimmermann, Heidi E; Caha, Sylvia; Moll, Wulf Dieter; Schatzmayr, Gerd; Applegate, Todd J

2015-04-13

In chickens, the effect of mycotoxins, especially fumonisins (FB), in the gastrointestinal tract (GIT) is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa)/sphingosine (So) ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism). Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage) from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.

Dose-Dependent Effects on Sphingoid Bases and Cytokines in Chickens Fed Diets Prepared with Fusarium Verticillioides Culture Material Containing Fumonisins

Directory of Open Access Journals (Sweden)

Bertrand Grenier

2015-04-01

Full Text Available In chickens, the effect of mycotoxins, especially fumonisins (FB, in the gastrointestinal tract (GIT is not well documented. Thus, this study in broiler chicks determined the effects of consuming diets prepared with Fusarium verticillioides culture material containing FB on intestinal gene expression and on the sphinganine (Sa/sphingosine (So ratio (Sa/So; a biomarker of FB effect due to disruption of sphingolipid metabolism. Male broilers were assigned to 6 diets (6 cages/diet; 6 birds/cage from hatch to 20 days containing 0.4, 5.6, 11.3, 17.5, 47.8, or 104.8 mg FB/kg diet. Exposure to FB altered the Sa/So ratio in all tissues analyzed, albeit to varying extents. Linear dose-responses were observed in the kidney, jejunum and cecum. The liver and the ileum were very sensitive and data fit a cubic and quadratic polynomial model, respectively. Gene expression in the small intestine revealed low but significant upregulations of cytokines involved in the pro-inflammatory, Th1/Th17 and Treg responses, especially at 10 days of age. Interestingly, the cecal tonsils exhibited a biphasic response. Unlike the sphingolipid analysis, the effects seen on gene expression were not dose dependent, even showing more effects when birds were exposed to 11.3 mg FB/kg. In conclusion, this is the first report on the disruption of the sphingolipid metabolism by FB in the GIT of poultry. Further studies are needed to reach conclusions on the biological meaning of the immunomodulation observed in the GIT, but the susceptibility of chickens to intestinal pathogens when exposed to FB, at doses lower than those that would cause overt clinical symptoms, should be addressed.

Physiological Study of Lactobacillus delbrueckii subsp. bulgaricus Strains in a Novel Chemically Defined Medium

Science.gov (United States)

Chervaux, Christian; Ehrlich, S. Dusko; Maguin, Emmanuelle

2000-01-01

We developed a chemically defined medium called milieu proche du lait (MPL), in which 22 Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) strains exhibited growth rates ranging from 0.55 to 1 h−1. MPL can also be used for cultivation of other lactobacilli and Streptococcus thermophilus. The growth characteristics of L. bulgaricus in MPL containing different carbon sources were determined, including an initial characterization of the phosphotransferase system transporters involved. For the 22 tested strains, growth on lactose was faster than on glucose, mannose, and fructose. Lactose concentrations below 0.4% were limiting for growth. We isolated 2-deoxyglucose-resistant mutants from strains CNRZ397 and ATCC 11842. CNRZ397-derived mutants were all deficient for glucose, fructose, and mannose utilization, indicating that these three sugars are probably transported via a unique mannose-specific-enzyme-II-like transporter. In contrast, mutants of ATCC 11842 exhibited diverse phenotypes, suggesting that multiple transporters may exist in that strain. We also developed a protein labeling method and verified that exopolysaccharide production and phage infection can occur in MPL. The MPL medium should thus be useful in conducting physiological studies of L. bulgaricus and other lactic acid bacteria under well controlled nutritional conditions. PMID:11097906

On functions defined by sums of products of Bessel functions

International Nuclear Information System (INIS)

Martin, P A

2008-01-01

Various functions, defined as infinite series of products of Bessel functions of the first kind, are studied. Integral representations are obtained, and then used to deduce asymptotic approximations. Although several methods have been investigated (including power series expansions and integral transforms), methods based on Fourier series emerge as the most useful

20 CFR 641.710 - How are the performance indicators defined?

Science.gov (United States)

2010-04-01

... customer satisfaction surveys administered to each of these three customer groups. The Department will... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false How are the performance indicators defined... § 641.710 How are the performance indicators defined? (a) The core indicators are defined as follows: (1...

Defining Generic Architecture for Cloud Infrastructure as a Service model

NARCIS (Netherlands)

Demchenko, Y.; de Laat, C.

2011-01-01

Infrastructure as a Service (IaaS) is one of the provisioning models for Clouds as defined in the NIST Clouds definition. Although widely used, current IaaS implementations and solutions doesn’t have common and well defined architecture model. The paper attempts to define a generic architecture for

Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

Science.gov (United States)

Beach, Adam; Leonov, Anna; Arlia-Ciommo, Anthony; Svistkova, Veronika; Lutchman, Vicky; Titorenko, Vladimir I.

2015-01-01

Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research. PMID:25768339

Mechanisms by Which Different Functional States of Mitochondria Define Yeast Longevity

Directory of Open Access Journals (Sweden)

Adam Beach

2015-03-01

Full Text Available Mitochondrial functionality is vital to organismal physiology. A body of evidence supports the notion that an age-related progressive decline in mitochondrial function is a hallmark of cellular and organismal aging in evolutionarily distant eukaryotes. Studies of the baker’s yeast Saccharomyces cerevisiae, a unicellular eukaryote, have led to discoveries of genes, signaling pathways and chemical compounds that modulate longevity-defining cellular processes in eukaryotic organisms across phyla. These studies have provided deep insights into mechanistic links that exist between different traits of mitochondrial functionality and cellular aging. The molecular mechanisms underlying the essential role of mitochondria as signaling organelles in yeast aging have begun to emerge. In this review, we discuss recent progress in understanding mechanisms by which different functional states of mitochondria define yeast longevity, outline the most important unanswered questions and suggest directions for future research.

Some properties for integro-differential operator defined by a fractional formal.

Science.gov (United States)

Abdulnaby, Zainab E; Ibrahim, Rabha W; Kılıçman, Adem

2016-01-01

Recently, the study of the fractional formal (operators, polynomials and classes of special functions) has been increased. This study not only in mathematics but extended to another topics. In this effort, we investigate a generalized integro-differential operator [Formula: see text] defined by a fractional formal (fractional differential operator) and study some its geometric properties by employing it in new subclasses of analytic univalent functions.

Defining learning goals in Honours education : what makes an excellent professional?

NARCIS (Netherlands)

Robbe, Patricia; Heijne-Penninga, Marjolein; Wijkamp, Inge; Wolfensberger, Marca

2016-01-01

Honours programs prepare talented students to become the excellent professionals of the future. However, the behavioral aspects which define an excellent professional have not been elucidated yet. We therefore performed a research study on how professionals characterize an excellent professional in

Defining the Shoah: An Opening Lesson for a Holocaust Unit

Science.gov (United States)

Lindquist, David H.

2013-01-01

Students often bring considerable prior information about the Holocaust to their study of the event, with much of that knowledge being inaccurate or incomplete. In addition, the Shoah's complexity necessitates that teachers establish a well-defined framework as they introduce the topic to their students. This article outlines an opening lesson for…

Defining the multi-dimensional aspects of household waste management: A study of reported behavior in Devon

Energy Technology Data Exchange (ETDEWEB)

Barr, Stewart; Gilg, Andrew; Ford, Nicholas [Department of Geography, School of Geography, Archaeology and Earth Resources, University of Exeter, Amory Building, Rennes Drive, Exeter, Devon EX4 4RJ (United Kingdom)

2005-10-01

This paper examines the structure of waste reduction, reuse and recycling behavior within the context of wider research on environmental action in and around the home. Using a sample of 1265 households from Devon, England, the research examined a range of environmental behaviors, focusing on energy saving, water conservation, green consumerism and waste management. Using factor analysis, the data were analysed to examine how the different behavioral variables related to each other. The research found that waste management behaviors were evident in two of the three factors identified. These related not only to recycling or reuse behaviors but also to consumption practices, such as purchasing recycled products. However, an analysis of the frequency of each of these factorially-defined behaviors revealed that recycling was still the activity most practised by individuals, with reduction behaviors least popular. This was explored further by the use of cluster analysis, which defined four distinctive behavioral types with different demographic characteristics. Accordingly, the research demonstrates that examining waste management behaviors within the context of wider environmental actions can be of use.

Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

Science.gov (United States)

Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

2017-09-01

Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

Dietary Cerebroside from Sea Cucumber (Stichopus japonicus): Absorption and Effects on Skin Barrier and Cecal Short-Chain Fatty Acids.

Science.gov (United States)

Duan, Jingjing; Ishida, Marina; Aida, Kazuhiko; Tsuduki, Tsuyoshi; Zhang, Jin; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya

2016-09-21

Sphingolipids from marine sources have attracted more attention recently because of their distinctive structures and expected functions. In this study, the content and components of cerebroside from sea cucumber Stichopus japonicus were analyzed. The absorption of cerebroside from S. japonicus was investigated with an in vivo lipid absorption assay. The result revealed that S. japonicus is a rich source of cerebroside that contained considerable amounts of odd carbon chain sphingoid bases. The cumulative recoveries of d17:1- and d19:2-containing cerebrosides were 0.31 ± 0.16 and 0.32 ± 0.10%, respectively, for 24 h after administration. To the best of the authors' knowledge, this is the first work that shows sphingolipids from a marine source could be absorbed in vivo and incorporated into ceramides. In addition, dietary supplementation with sea cucumber cerebroside to hairless mouse improved the skin barrier function and increased short-chain fatty acids in cecal contents, which have shown beneficial effects on the host.

SPHINGOSINE-1 PHOSPHATE: A NEW MODULATOR OF IMMUNE PLASTICITY IN THE TUMOR MICROENVIRONMENT

Directory of Open Access Journals (Sweden)

Yamila I Rodriguez

2016-10-01

Full Text Available In the last 15 years, increasing evidences demonstrate a strong link between sphingosine-1-phosphate (S1P in both normal physiology and progression of different diseases, including cancer and inflammation. Indeed, numerous studies show that tissue levels of this sphingolipid metabolite are augmented in many cancers, affecting survival, proliferation, angiogenesis and metastatic spread. Recent insights into the possible role of S1P as a therapeutic target has attracted enormous attention and opened new opportunities in this evolving field. In this review we will focus on the role of S1P in cancer with particular emphasis in new developments that highlight the many functions of this sphingolipid in the tumor microenvironment. We will discuss how S1P modulates phenotypic plasticity of macrophages and mast cells, tumor-induced immune evasion, differentiation and survival of immune cells in the tumor milieu, interaction between cancer and stromal cells and hypoxic response.

A Conserved Circular Network of Coregulated Lipids Modulates Innate Immune Responses.

Science.gov (United States)

Köberlin, Marielle S; Snijder, Berend; Heinz, Leonhard X; Baumann, Christoph L; Fauster, Astrid; Vladimer, Gregory I; Gavin, Anne-Claude; Superti-Furga, Giulio

2015-07-02

Lipid composition affects the biophysical properties of membranes that provide a platform for receptor-mediated cellular signaling. To study the regulatory role of membrane lipid composition, we combined genetic perturbations of sphingolipid metabolism with the quantification of diverse steps in Toll-like receptor (TLR) signaling and mass spectrometry-based lipidomics. Membrane lipid composition was broadly affected by these perturbations, revealing a circular network of coregulated sphingolipids and glycerophospholipids. This evolutionarily conserved network architecture simultaneously reflected membrane lipid metabolism, subcellular localization, and adaptation mechanisms. Integration of the diverse TLR-induced inflammatory phenotypes with changes in lipid abundance assigned distinct functional roles to individual lipid species organized across the network. This functional annotation accurately predicted the inflammatory response of cells derived from patients suffering from lipid storage disorders, based solely on their altered membrane lipid composition. The analytical strategy described here empowers the understanding of higher-level organization of membrane lipid function in diverse biological systems. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Defining nodes in complex brain networks

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Matthew Lawrence Stanley

2013-11-01

Full Text Available Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel. The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10-20 millimeter diameter spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the correct method to be used remains an open, possibly unsolvable question that

Definable group extensions and o-minimal group cohomology via spectral sequences

OpenAIRE

Barriga, Eliana

2013-01-01

Se presenta el fundamento teórico para las sucesiones espectrales de Lyndon-Hochschild-Serre como una herramienta para estudiar la cohomología de grupos y con ésta las extensiones de grupos en la categoría de los grupos definibles. También se presentan varios resultados en módulos definibles y acciones, extensiones definibles y cohomología de grupos definibles. Estos tienen aplicaciones en el estudio de los grupos definibles no definiblemente compactos en teorías o-minimales (see [1]).

Defined contribution health benefits.

Science.gov (United States)

Fronstin, P

2001-03-01

This Issue Brief discusses the emerging issue of "defined contribution" (DC) health benefits. The term "defined contribution" is used to describe a wide variety of approaches to the provision of health benefits, all of which have in common a shift in the responsibility for payment and selection of health care services from employers to employees. DC health benefits often are mentioned in the context of enabling employers to control their outlay for health benefits by avoiding increases in health care costs. DC health benefits may also shift responsibility for choosing a health plan and the associated risks of choosing a plan from employers to employees. There are three primary reasons why some employers currently are considering some sort of DC approach. First, they are once again looking for ways to keep their health care cost increases in line with overall inflation. Second, some employers are concerned that the public "backlash" against managed care will result in new legislation, regulations, and litigation that will further increase their health care costs if they do not distance themselves from health care decisions. Third, employers have modified not only most employee benefit plans, but labor market practices in general, by giving workers more choice, control, and flexibility. DC-type health benefits have existed as cafeteria plans since the 1980s. A cafeteria plan gives each employee the opportunity to determine the allocation of his or her total compensation (within employer-defined limits) among various employee benefits (primarily retirement or health). Most types of DC health benefits currently being discussed could be provided within the existing employment-based health insurance system, with or without the use of cafeteria plans. They could also allow employees to purchase health insurance directly from insurers, or they could drive new technologies and new forms of risk pooling through which health care services are provided and financed. DC health

Utilising artificial intelligence in software defined wireless sensor network

CSIR Research Space (South Africa)

Matlou, OG

2017-10-01

Full Text Available Software Defined Wireless Sensor Network (SDWSN) is realised by infusing Software Defined Network (SDN) model in Wireless Sensor Network (WSN), Reason for that is to overcome the challenges of WSN. Artificial Intelligence (AI) and machine learning...

Defining critical success factors in TOD implementation using rough set analysis

NARCIS (Netherlands)

Thomas, R.; Bertolini, L.

2017-01-01

This paper defines critical success conditions in transit-oriented development (TOD), evaluating the impact of practices, policies, and governance models on implementation. As part of a meta-analysis of 11 international case studies, 16 critical success factors were developed and validated using

A STUDY OF THE IMAGE OF TULIP SYMPHONY - A DEFINING INGREDIENT IN THE DEVELOPMENT OF THE URBAN BRAND OF PITESTI

Directory of Open Access Journals (Sweden)

Mihaela, ASANDEI

2014-11-01

Full Text Available The city is a fundamental element of the identity of contemporary society, fulfilling in each urban community complex functions that depend on the needs, interests and aspirations of the people and of the political and economic system. The urban identity of Pitesti is defined by a set of features with certain significance for each inhabitant of the city. The Tulip Symphony is a symbol that has been created, developed and promoted during the past four decades by the urban community. The present study aims to study how residents of Pitesti perceive the urban product named the Tulip Symphony is and present the conclusions of a statistical survey conducted during the 37th edition of the event.

A prospective study of the influence of a thalassaemia on morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in Gambian children

DEFF Research Database (Denmark)

Allen, S J; Rowe, P; Allsopp, C E

1993-01-01

with the sickle cell trait alone. Specific antibody responses and cell-mediated immune responses in vitro to defined Plasmodium falciparum antigens were measured in children participating in the study. In general, there was no evidence of an increased prevalence or intensity of humoral or cell-mediated immune...

Defining functional distances over Gene Ontology

Directory of Open Access Journals (Sweden)

del Pozo Angela

2008-01-01

Full Text Available Abstract Background A fundamental problem when trying to define the functional relationships between proteins is the difficulty in quantifying functional similarities, even when well-structured ontologies exist regarding the activity of proteins (i.e. 'gene ontology' -GO-. However, functional metrics can overcome the problems in the comparing and evaluating functional assignments and predictions. As a reference of proximity, previous approaches to compare GO terms considered linkage in terms of ontology weighted by a probability distribution that balances the non-uniform 'richness' of different parts of the Direct Acyclic Graph. Here, we have followed a different approach to quantify functional similarities between GO terms. Results We propose a new method to derive 'functional distances' between GO terms that is based on the simultaneous occurrence of terms in the same set of Interpro entries, instead of relying on the structure of the GO. The coincidence of GO terms reveals natural biological links between the GO functions and defines a distance model Df which fulfils the properties of a Metric Space. The distances obtained in this way can be represented as a hierarchical 'Functional Tree'. Conclusion The method proposed provides a new definition of distance that enables the similarity between GO terms to be quantified. Additionally, the 'Functional Tree' defines groups with biological meaning enhancing its utility for protein function comparison and prediction. Finally, this approach could be for function-based protein searches in databases, and for analysing the gene clusters produced by DNA array experiments.

Software Defined Networking

DEFF Research Database (Denmark)

Caba, Cosmin Marius

Network Service Providers (NSP) often choose to overprovision their networks instead of deploying proper Quality of Services (QoS) mechanisms that allow for traffic differentiation and predictable quality. This tendency of overprovisioning is not sustainable for the simple reason that network...... resources are limited. Hence, to counteract this trend, current QoS mechanisms must become simpler to deploy and operate, in order to motivate NSPs to employ QoS techniques instead of overprovisioning. Software Defined Networking (SDN) represents a paradigm shift in the way telecommunication and data...... generic perspective (e.g. service provisioning speed, resources availability). As a result, new mechanisms for providing QoS are proposed, solutions for SDN-specific QoS challenges are designed and tested, and new network management concepts are prototyped, all aiming to improve QoS for network services...

Targeting the S1P/S1PR1 axis mitigates cancer-induced bone pain and neuroinflammation.

Science.gov (United States)

Grenald, Shaness A; Doyle, Timothy M; Zhang, Hong; Slosky, Lauren M; Chen, Zhoumou; Largent-Milnes, Tally M; Spiegel, Sarah; Vanderah, Todd W; Salvemini, Daniela

2017-09-01

Metastatic bone pain is the single most common form of cancer pain and persists as a result of peripheral and central inflammatory, as well as neuropathic mechanisms. Here, we provide the first characterization of sphingolipid metabolism alterations in the spinal cord occurring during cancer-induced bone pain (CIBP). Following femoral arthrotomy and syngenic tumor implantation in mice, ceramides decreased with corresponding increases in sphingosine and the bioactive sphingolipid metabolite, sphingosine 1-phosphate (S1P). Intriguingly, de novo sphingolipid biosynthesis was increased as shown by the elevations of dihydro-ceramides and dihydro-S1P. We next identified the S1P receptor subtype 1 (S1PR1) as a novel target for therapeutic intervention. Intrathecal or systemic administration of the competitive and functional S1PR1 antagonists, TASP0277308 and FTY720/Fingolimod, respectively, attenuated cancer-induced spontaneous flinching and guarding. Inhibiting CIBP by systemic delivery of FTY720 did not result in antinociceptive tolerance over 7 days. FTY720 administration enhanced IL-10 in the lumbar ipsilateral spinal cord of CIBP animals and intrathecal injection of an IL-10 neutralizing antibody mitigated the ability of systemic FTY720 to reverse CIBP. FTY720 treatment was not associated with alterations in bone metabolism in vivo. Studies here identify a novel mechanism to inhibit bone cancer pain by blocking the actions of the bioactive metabolites S1P and dihydro-S1P in lumbar spinal cord induced by bone cancer and support potential fast-track clinical application of the FDA-approved drug, FTY720, as a therapeutic avenue for CIBP.

The role of sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P) in the trafficking of normal and malignant cells

Science.gov (United States)

Ratajczak, Mariusz Z.; Suszynska, Malwina; Borkowska, Sylwia; Ratajczak, Janina; Schneider, Gabriela

2014-01-01

Introduction A common feature of many types of cells is their responsiveness to chemotactic gradients of factors for which they express the corresponding receptors. The most studied chemoattractants so far are peptide-based growth factors and a family of cytokines endowed with strong chemotactic properties, called chemokines. However, additional evidence has accumulated that, in addition to these peptide-based chemoattractants, an important role in cell migration is played by bioactive lipids. Areas covered Solid evidence has accumulated that two bioactive phosphorylated sphingolipids that are derivatives of sphingolipid metabolism, namely sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), are potent chemoattractants for a variety of cells. In this review, we will discuss the effect of these two phosphorylated sphingolipids on the trafficking of normal and malignant cells, and, in particular, we will focus on their role in trafficking of normal hematopoietic stem/progenitor cells. Unlike other mediators, S1P under steady state conditions maintain a steep gradient between interstitial fluid and peripheral blood and lymph across the endothelial barrier, which is important in the egress of cells from bone marrow. Both S1P and C1P may be upregulated in damaged tissues, which may result in reversal of this gradient. Expert opinion S1P and C1P are important regulators of the trafficking of normal and malignant cells, and modification of their biological effects will have important applications in optimizing stem cell mobilization and homing, tissue organ/regeneration, and preventing cancer metastasis. PMID:24188167

Chronic toxicity of fumonisins in turkeys.

Science.gov (United States)

Tardieu, D; Bailly, J-D; Skiba, F; Métayer, J-P; Grosjean, F; Guerre, P

2007-09-01

Fumonisins are mycotoxins that are found worldwide. They are mainly produced by Fusarium verticillioides during its development on corn. The main toxic effects of these molecules have been well characterized in poultry in the case of acute exposure, but the subclinical and economic effects of chronic exposure are less known. Whereas the latest European recommendations suggest that maximal levels of fumonisins in corn could reach 60 mg/kg and the maximal contamination of poultry feeds could reach 20 mg/kg, no study is available at this level in turkeys. The aim of the present work was thus to characterize the effects of exposure to fumonisins (concentrations of 0, 5, 10, and 20 mg of fumonisin B1 + fumonisin B2/kg of feed) on feed consumption and growth in turkeys over a period of 9 wk. Main biochemical parameters of the liver and alteration of sphingolipid metabolism were investigated in plasma, liver, and kidney. The main results showed no effect on feed consumption and growth in exposed turkeys. Moreover, no effect was observed on the weight of tissues and markers of liver injury. By contrast, a disruption of sphingolipid metabolism was clear at a level of exposure of 10 and 20 mg of fumonisin B1 + fumonisin B2 mg/kg of feed. Both hepatic and kidney concentrations of sphinganine increased gradually throughout the exposure period. These results reveal that disruption of sphingolipid metabolism is an early and sensitive biomarker of fumonisins exposure in turkeys; the consequences on these alterations remain to be established.

Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Directory of Open Access Journals (Sweden)

Agnieszka Mikłosz

2015-01-01

Full Text Available Background: Thyroid hormones (THs are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Methods: Male Wistar rats were treated for 10 days with triiodothyronine (T3 at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. Results: We have demonstrated that prolonged, in vivo, T3 treatment increased the content of sphinganine (SFA, sphingosine (SFO, ceramide (CER and sphingomyelin (SM, but decreased the level of sphingosine-1-phosphate (S1P in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV, β-hydroxyacyl-CoA dehydrogenase (β-HAD, carnityne palmitoyltransferase I (CPT I and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α. Conclusions: We conclude that prolonged T3 treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.

Hyperthyroidism evokes myocardial ceramide accumulation.

Science.gov (United States)

Mikłosz, Agnieszka; Łukaszuk, Bartłomiej; Chabowski, Adrian; Rogowski, Filip; Kurek, Krzysztof; Żendzian-Piotrowska, Małgorzata

2015-01-01

Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Male Wistar rats were treated for 10 days with triiodothyronine (T3) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. We have demonstrated that prolonged, in vivo, T3 treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). We conclude that prolonged T3 treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content. © 2015 S. Karger AG, Basel.

Expressiveness and definability in circumscription

Directory of Open Access Journals (Sweden)

Francicleber Martins Ferreira

2011-06-01

Full Text Available We investigate expressiveness and definability issues with respect to minimal models, particularly in the scope of Circumscription. First, we give a proof of the failure of the Löwenheim-Skolem Theorem for Circumscription. Then we show that, if the class of P; Z-minimal models of a first-order sentence is Δ-elementary, then it is elementary. That is, whenever the circumscription of a first-order sentence is equivalent to a first-order theory, then it is equivalent to a finitely axiomatizable one. This means that classes of models of circumscribed theories are either elementary or not Δ-elementary. Finally, using the previous result, we prove that, whenever a relation Pi is defined in the class of P; Z-minimal models of a first-order sentence Φ and whenever such class of P; Z-minimal models is Δ-elementary, then there is an explicit definition ψ for Pi such that the class of P; Z-minimal models of Φ is the class of models of Φ ∧ ψ. In order words, the circumscription of P in Φ with Z varied can be replaced by Φ plus this explicit definition ψ for Pi.

Defining human death: an intersection of bioethics and metaphysics.

Science.gov (United States)

Manninen, Bertha Alvarez

2009-01-01

For many years now, bioethicists, physicians, and others in the medical field have disagreed concerning how to best define human death. Different theories range from the Harvard Criteria of Brain Death, which defines death as the cessation of all brain activity, to the Cognitive Criteria, which is based on the loss of almost all core mental properties, e.g., memory, self-consciousness, moral agency, and the capacity for reason. A middle ground is the Irreversibility Standard, which defines death as occurring when the capacity for consciousness is forever lost. Given all these different theories, how can we begin to approach solving the issue of how to define death? I propose that a necessary starting point is discussing an even more fundamental question that properly belongs in the philosophical field of metaphysics: we must first address the issue of diachronic identity over time, and the persistence conditions of personal identity. In this paper, I illustrate the interdependent relationship between this metaphysical question and questions concerning the definition of death. I also illustrate how it is necessary to antecedently attend to the metaphysical issue of defining death before addressing certain issues in medical ethics, e.g., whether it is morally permissible to euthanize patients in persistent vegetative states or procure organs from anencephalic infants.

Stability analysis of switched linear systems defined by graphs

OpenAIRE

Athanasopoulos, Nikolaos; Lazar, Mircea

2015-01-01

We present necessary and sufficient conditions for global exponential stability for switched discrete-time linear systems, under arbitrary switching, which is constrained within a set of admissible transitions. The class of systems studied includes the family of systems under arbitrary switching, periodic systems, and systems with minimum and maximum dwell time specifications. To reach the result, we describe the set of rules that define the admissible transitions with a weighted directed gra...

Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

International Nuclear Information System (INIS)

Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

2004-01-01

A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

The clinical nurse specialist in New Zealand: how is the role defined?

Science.gov (United States)

Roberts, Jennifer; Floyd, Sue; Thompson, Shona

2011-07-01

New Zealand, like many countries, is developing new advanced nursing practice roles to meet emerging needs. While much has been written about the Nurse Practitioner (NP), the role of Clinical Nurse Specialist (CNS) remains relatively unexplored and lacks national definition. This paper reports the findings from research designed to investigate the role of the CNS and how it is defined by New Zealand District Health Boards (DHBs). The study sought to identify the current requirements and expectations for the CNS role and how it is defined in practice. In 2008, 15 CNS job descriptions were collected from eight DHBs throughout the country generating data that were treated both quantitatively and qualitatively. Overall, few areas of consensus were found regarding the essential requirements for the CNS role and there were inconsistencies in how the roles were defined, most notably concerning requirements for postgraduate qualifications and Professional Development Recognition Programmes. Thematic analysis of the documents generated four key areas relevant to the CNS role. These described the CNS as a leader, a clinical expert, a co-ordinator and an educator. The findings indicate that the CNS role is inconsistently defined in New Zealand, particularly with respect to the postgraduate qualifications required and what is meant by 'expertise'.

Contribution of past and future self-defining event networks to personal identity.

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Demblon, Julie; D'Argembeau, Arnaud

2017-05-01

Personal identity is nourished by memories of significant past experiences and by the imagination of meaningful events that one anticipates to happen in the future. The organisation of such self-defining memories and prospective thoughts in the cognitive system has received little empirical attention, however. In the present study, our aims were to investigate to what extent self-defining memories and future projections are organised in networks of related events, and to determine the nature of the connections linking these events. Our results reveal the existence of self-defining event networks, composed of both memories and future events of similar centrality for identity and characterised by similar identity motives. These self-defining networks expressed a strong internal coherence and frequently organised events in meaningful themes and sequences (i.e., event clusters). Finally, we found that the satisfaction of identity motives in represented events and the presence of clustering across events both contributed to increase in the perceived centrality of events for the sense of identity. Overall, these findings suggest that personal identity is not only nourished by representations of significant past and future events, but also depends on the formation of coherent networks of related events that provide an overarching meaning to specific life experiences.

User constraints for reliable user-defined smart home scenarios

DEFF Research Database (Denmark)

Le Guilly, Thibaut; Nielsen, Michael Kvist; Pedersen, Thomas

2016-01-01

Defining control scenarios in a smart home is a difficult task for end users. In particular, one concern is that user-defined scenarios could lead to unsafe or undesired state of the system. To help them explore scenario specifications, we propose in this paper a system that enables specification...

7 CFR 28.950 - Terms defined.

Science.gov (United States)

2010-01-01

... Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing..., TESTING, AND STANDARDS Cotton Fiber and Processing Tests Definitions § 28.950 Terms defined. As used... Agricultural Marketing Service of the U.S. Department of Agriculture. (c) Administrator. The Administrator of...

Pointwise Extensions of GSOS-Defined Operations

NARCIS (Netherlands)

H.H. Hansen (Helle); B. Klin

2011-01-01

textabstractFinal coalgebras capture system behaviours such as streams, infinite trees and processes. Algebraic operations on a final coalgebra can be defined by distributive laws (of a syntax functor $\\FSig$ over a behaviour functor $F$). Such distributive laws correspond to abstract specification

On Defining Mass

Science.gov (United States)

Hecht, Eugene

2011-01-01

Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement surrounding the Large Hadron Collider at CERN is associated with discovering the mechanism responsible for the masses of the elementary particles. This paper will first briefly examine the leading definitions, pointing out their shortcomings. Then, utilizing relativity theory, it will propose—for consideration by the community of physicists—a conceptual definition of mass predicated on the more fundamental concept of energy, more fundamental in that everything that has mass has energy, yet not everything that has energy has mass.

Defining the mobilome.

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Siefert, Janet L

2009-01-01

This chapter defines the agents that provide for the movement of genetic material which fuels the adaptive potential of life on our planet. The chapter has been structured to be broadly comprehensive, arbitrarily categorizing the mobilome into four classes: (1) transposons, (2) plasmids, (3) bacteriophage, and (4) self-splicing molecular parasites.Our increasing understanding of the mobilome is as dynamic as the mobilome itself. With continuing discovery, it is clear that nature has not confined these genomic agents of change to neat categories, but rather the classification categories overlap and intertwine. Massive sequencing efforts and their published analyses are continuing to refine our understanding of the extent of the mobilome. This chapter provides a framework to describe our current understanding of the mobilome and a foundation on which appreciation of its impact on genome evolution can be understood.

Service-oriented Software Defined Optical Networks for Cloud Computing

Science.gov (United States)

Liu, Yuze; Li, Hui; Ji, Yuefeng

2017-10-01

With the development of big data and cloud computing technology, the traditional software-defined network is facing new challenges (e.g., ubiquitous accessibility, higher bandwidth, more flexible management and greater security). This paper proposes a new service-oriented software defined optical network architecture, including a resource layer, a service abstract layer, a control layer and an application layer. We then dwell on the corresponding service providing method. Different service ID is used to identify the service a device can offer. Finally, we experimentally evaluate that proposed service providing method can be applied to transmit different services based on the service ID in the service-oriented software defined optical network.

Defining the key roles and competencies of the clinician-educator of the 21st century: a national mixed-methods study.

Science.gov (United States)

Sherbino, Jonathan; Frank, Jason R; Snell, Linda

2014-05-01

To determine a consensus definition of a clinician-educator and the related domains of competence. During September 2010 to March 2011, the authors conducted a two-phase mixed-methods national study in Canada using (1) focus groups of deans of medicine and directors of medical education centers to define the attributes, domains of competence, and core competencies of clinician-educators using a grounded theory analysis, and (2) a survey of 1,130 deans, academic chairs, and residency program directors to validate the focus group results. The 22 focus group participants described being active in clinical practice, applying theory to practice, and engaging in education scholarship-but not holding a particular administrative position-as essential attributes of clinician-educators. Program directors accounted for 68% of the 350 survey respondents, academic chairs for 19%, and deans for 13% (response rate: 31%). Among respondents, 85% endorsed the need for physicians with advanced training in medical education to serve as educational consultants. Domains of clinician-educator competence endorsed by >85% of respondents as important or very important were assessment, communication, curriculum development, education theory, leadership, scholarship, and teaching. With regard to training requirements, 55% endorsed a master's degree in education as effective preparation, whereas 39% considered faculty development programs effective. On the basis of this study's findings, the authors defined a clinician-educator as a clinician active in health professional practice who applies theory to education practice, engages in education scholarship, and serves as a consultant to other health professionals on education issues.

Chronic kidney disease : Defining clinical cut-offs for albumin:creatinine ratio

NARCIS (Netherlands)

Bakker, Stephan J L

2013-01-01

Albuminuria is rapidly gaining recognition as a marker of the presence and of the progression of chronic kidney disease (CKD). In a new study, Naresh et al. attempt to define cut-off values for percentage change in urinary albumin:creatinine ratio that reflect changes in CKD status rather than

A Network Analysis of the American Library Association: Defining a Profession

Science.gov (United States)

Battleson, Brenda L.

2010-01-01

The term "librarianship" is a generic one, suggesting one overarching discipline despite the numerous specializations and areas of research within the profession. While many disciplines use bibliometric analysis of their literature to define subfields of study within, such methods are not appropriate to librarianship due to the nature of…

Sleep Health: Can We Define It? Does It Matter?

Science.gov (United States)

Buysse, Daniel J.

2014-01-01

Good sleep is essential to good health. Yet for most of its history, sleep medicine has focused on the definition, identification, and treatment of sleep problems. Sleep health is a term that is infrequently used and even less frequently defined. It is time for us to change this. Indeed, pressures in the research, clinical, and regulatory environments require that we do so. The health of populations is increasingly defined by positive attributes such as wellness, performance, and adaptation, and not merely by the absence of disease. Sleep health can be defined in such terms. Empirical data demonstrate several dimensions of sleep that are related to health outcomes, and that can be measured with self-report and objective methods. One suggested definition of sleep health and a description of self-report items for measuring it are provided as examples. The concept of sleep health synergizes with other health care agendas, such as empowering individuals and communities, improving population health, and reducing health care costs. Promoting sleep health also offers the field of sleep medicine new research and clinical opportunities. In this sense, defining sleep health is vital not only to the health of populations and individuals, but also to the health of sleep medicine itself. Citation: Buysse DJ. Sleep health: can we define it? Does it matter? SLEEP 2014;37(1):9-17. PMID:24470692

Spaces defined by the Paley function

Energy Technology Data Exchange (ETDEWEB)

Astashkin, S V [Samara State University, Samara (Russian Federation); Semenov, E M [Voronezh State University, Faculty of Mathematics, Voronezh (Russian Federation)

2013-07-31

The paper is concerned with Haar and Rademacher series in symmetric spaces, and also with the properties of spaces defined by the Paley function. In particular, the symmetric hull of the space of functions with uniformly bounded Paley function is found. Bibliography: 27 titles.

Pointwise extensions of GSOS-defined operations

NARCIS (Netherlands)

Hansen, H.H.; Klin, B.

2011-01-01

Final coalgebras capture system behaviours such as streams, infinite trees and processes. Algebraic operations on a final coalgebra can be defined by distributive laws (of a syntax functor S over a behaviour functor F). Such distributive laws correspond to abstract specification formats. One such

Staff and consumer perspectives on defining treatment success and failure in assertive community treatment.

Science.gov (United States)

Stull, Laura G; McGrew, John H; Salyers, Michelle P

2010-09-01

Although assertive community treatment (ACT) has been consistently recognized as effective, there has been little research as to what constitutes success in ACT. The purpose of this study was to understand how ACT consumers and staff define treatment success and failure and to examine whether definitions varied between staff and consumers. Investigators conducted semistructured interviews with 25 staff and 23 consumers from four ACT teams. Across perspectives, success and failure were most clearly related to consumer factors. Other themes included having basic needs met, being socially involved, and taking medications. Reduced hospitalizations were mentioned infrequently. Consumers were more likely than staff to identify the level or type of treatment as defining success and failure, whereas staff were more likely than consumers to discuss substance abuse when defining failure and improved symptoms when defining success. Success in ACT should be viewed more broadly than reduced hospitalizations and include domains such as social involvement.

Physical degradation of proteins in well-defined fluid flows studied within a four-roll apparatus.

Science.gov (United States)

Simon, S; Krause, H J; Weber, C; Peukert, W

2011-12-01

In most applications of biotechnology and downstream processing proteins are exposed to fluid stresses in various flow configurations which often lead to the formation of unwanted protein aggregates. In this paper we present physical degradation experiments for proteins under well-defined flow conditions in a four-roll apparatus. The flow field was characterized numerically by computational fluid dynamics (CFD) and experimentally by particle image velocimetry (PIV). The local shear strain rate as well as the local shear and elongation rate was used to characterize the hydrodynamic stress environment acting on the proteins. Lysozyme was used as a model protein and subjected to well-defined fluid stresses in high and low stress environment. By using in situ turbidity measurements during stressing the aggregate formation was monitored directly in the fluid flow. An increase in absorbance at 350 nm was attributed to a higher content of visible particles (>1 µm). In addition to lysozyme, the formation of aggregates was confirmed for two larger proteins (bovine serum albumin and alcohol dehydrogenase). Thus, the presented experimental setup is a helpful tool to monitor flow-induced protein aggregation with high reproducibility. For instance, screening experiments for formulation development of biopharmaceuticals for fill and finish operations can be performed in the lab-scale in a short time-period if the stress distributions in the application are transferred and applied in the four-roll mill. Copyright © 2011 Wiley Periodicals, Inc.

Myelination in the absence of UDP-galactose:ceramide galactosyl-transferase and fatty acid 2 -hydroxylase

Directory of Open Access Journals (Sweden)

Gieselmann Volkmar

2011-03-01

Full Text Available Abstract Background The sphingolipids galactosylceramide (GalCer and sulfatide are major myelin components and are thought to play important roles in myelin function. The importance of GalCer and sulfatide has been validated using UDP-galactose:ceramide galactosyltransferase-deficient (Cgt-/- mice, which are impaired in myelin maintenance. These mice, however, are still able to form compact myelin. Loss of GalCer and sulfatide in these mice is accompanied by up-regulation of 2-hydroxylated fatty acid containing (HFA-glucosylceramide in myelin. This was interpreted as a partial compensation of the loss of HFA-GalCer, which may prevent a more severe myelin phenotype. In order to test this hypothesis, we have generated Cgt-/- mice with an additional deletion of the fatty acid 2-hydroxylase (Fa2h gene. Results Fa2h-/-/Cgt-/- double-deficient mice lack sulfatide, GalCer, and in addition HFA-GlcCer and sphingomyelin. Interestingly, compared to Cgt-/- mice the amount of GlcCer in CNS myelin was strongly reduced in Fa2h-/-/Cgt-/- mice by more than 80%. This was accompanied by a significant increase in sphingomyelin, which was the predominant sphingolipid in Fa2h-/-/Cgt-/- mice. Despite these significant changes in myelin sphingolipids, compact myelin was formed in Fa2h-/-/Cgt-/- mice, and g-ratios of myelinated axons in the spinal cord of 4-week-old Fa2h-/-/Cgt-/- mice did not differ significantly from that of Cgt-/- mice, and there was no obvious phenotypic difference between Fa2h-/-/Cgt-/- and Cgt-/- mice Conclusions These data show that compact myelin can be formed with non-hydroxylated sphingomyelin as the predominant sphingolipid and suggest that the presence of HFA-GlcCer and HFA-sphingomyelin in Cgt-/- mice does not functionally compensate the loss of HFA-GalCer.

Defining nuclear medical file formal based on DICOM standard

International Nuclear Information System (INIS)

He Bin; Jin Yongjie; Li Yulan

2001-01-01

With the wide application of computer technology in medical area, DICOM is becoming the standard of digital imaging and communication. The author discusses how to define medical imaging file formal based on DICOM standard. It also introduces the format of ANMIS system the authors defined the validity and integrality of this format

Human papillomavirus-associated cancers as acquired immunodeficiency syndrome defining illnesses

Directory of Open Access Journals (Sweden)

Shohreh Shahabi

2013-04-01

Full Text Available The Centers for Disease Control currently report cervical, vulvar, vaginal, anal and some head and neck cancers as human papillomavirus (HPV-associated cancers. Only cervical cancer is listed amongst acquired immunodeficiency syndrome (AIDS defining illnesses. All of these cancers may represent progression of the immunocompromised state with the inability to eradicate viral infection. This study reports the case of a 27-year old HIV positive female presenting with a persistent right vulvar exophytic lesion. High-risk HPV analysis and immunostaining for P16 were both positive. A biopsy of the lesion revealed invasive squamous cell carcinoma. The patient underwent neoadjuvant radiation and chemotherapy followed by a radical vulvectomy. During treatment, her CD4 T-lymphocyte count decreased to 120 advancing her condition from HIV to AIDS. This case suggests that all HPV-associated cancers should be included as AIDS defining illnesses.

Using Procedure Codes to Define Radiation Toxicity in Administrative Data: The Devil is in the Details.

Science.gov (United States)

Meyer, Anne-Marie; Kuo, Tzy-Mey; Chang, YunKyung; Carpenter, William R; Chen, Ronald C; Sturmer, Til

2017-05-01

Systematic coding systems are used to define clinically meaningful outcomes when leveraging administrative claims data for research. How and when these codes are applied within a research study can have implications for the study validity and their specificity can vary significantly depending on treatment received. Data are from the Surveillance, Epidemiology, and End Results-Medicare linked dataset. We use propensity score methods in a retrospective cohort of prostate cancer patients first examined in a recently published radiation oncology comparative effectiveness study. With the narrowly defined outcome definition, the toxicity event outcome rate ratio was 0.88 per 100 person-years (95% confidence interval, 0.71-1.08). With the broadly defined outcome, the rate ratio was comparable, with 0.89 per 100 person-years (95% confidence interval, 0.76-1.04), although individual event rates were doubled. Some evidence of surveillance bias was suggested by a higher rate of endoscopic procedures the first year of follow-up in patients who received proton therapy compared with those receiving intensity-modulated radiation treatment (11.15 vs. 8.90, respectively). This study demonstrates the risk of introducing bias through subjective application of procedure codes. Careful consideration is required when using procedure codes to define outcomes in administrative data.

Legislative Provisions Underlying Trade Unions' Right to Define Their Organizational Structure

Science.gov (United States)

Korobchenko, Victoria V.; Penov, Yury V.; Safonov, Valery A.

2016-01-01

The article contains a comparative analysis of constitutional and other legislative provisions that ensure a trade union's right to define its own administrative structure in European states. The aim of the study is to reveal the management's problems of European trade unions, declarative and empirical mass-character legislative provisions, which…

The Lipid Raft Proteome of African Trypanosomes Contains Many Flagellar Proteins.

Science.gov (United States)

Sharma, Aabha I; Olson, Cheryl L; Engman, David M

2017-08-24

Lipid rafts are liquid-ordered membrane microdomains that form by preferential association of 3-β-hydroxysterols, sphingolipids and raft-associated proteins often having acyl modifications. We isolated lipid rafts of the protozoan parasite Trypanosoma brucei and determined the protein composition of lipid rafts in the cell. This analysis revealed a striking enrichment of flagellar proteins and several putative signaling proteins in the lipid raft proteome. Calpains and intraflagellar transport proteins, in particular, were found to be abundant in the lipid raft proteome. These findings provide additional evidence supporting the notion that the eukaryotic cilium/flagellum is a lipid raft-enriched specialized structure with high concentrations of sterols, sphingolipids and palmitoylated proteins involved in environmental sensing and cell signaling.

Structural characterization of suppressor lipids by high-resolution mass spectrometry

DEFF Research Database (Denmark)

Rovillos, Mary Joy; Pauling, Josch Konstantin; Hannibal-Bach, Hans Kristian

2016-01-01

RATIONALE: Suppressor lipids were originally identified in 1993 and reported to encompass six lipid classes that enable Saccharomyces cerevisiae to live without sphingolipids. Structural characterization, using non-mass spectrometric approaches, revealed that these suppressor lipids are very long...... chain fatty acid (VLCFA)-containing glycerophospholipids with polar head groups that are typically incorporated into sphingolipids. Here we report, for the first time, the structural characterization of the yeast suppressor lipids using high-resolution mass spectrometry. METHODS: Suppressor lipids were...... isolated by preparative chromatography and subjected to structural characterization using hybrid quadrupole time-of-flight and ion trap-orbitrap mass spectrometry. RESULTS: Our investigation recapitulates the overall structural features of the suppressor lipids and provides an in-depth characterization...

Defining cyber warfare

Directory of Open Access Journals (Sweden)

Dragan D. Mladenović

2012-04-01

Full Text Available Cyber conflicts represent a new kind of warfare that is technologically developing very rapidly. Such development results in more frequent and more intensive cyber attacks undertaken by states against adversary targets, with a wide range of diverse operations, from information operations to physical destruction of targets. Nevertheless, cyber warfare is waged through the application of the same means, techniques and methods as those used in cyber criminal, terrorism and intelligence activities. Moreover, it has a very specific nature that enables states to covertly initiate attacks against their adversaries. The starting point in defining doctrines, procedures and standards in the area of cyber warfare is determining its true nature. In this paper, a contribution to this effort was made through the analysis of the existing state doctrines and international practice in the area of cyber warfare towards the determination of its nationally acceptable definition.

AIDS defining disease: Disseminated cryptococcosis

Directory of Open Access Journals (Sweden)

Roshan Anupama

2006-01-01

Full Text Available Disseminated cryptococcosis is one of the acquired immune deficiency syndrome defining criteria and the most common cause of life threatening meningitis. Disseminated lesions in the skin manifest as papules or nodules that mimic molluscum contagiosum (MC. We report here a human immunodeficiency virus positive patient who presented with MC like lesions. Disseminated cryptococcosis was confirmed by India ink preparation and histopathology. The condition of the patient improved with amphotercin B.

46 CFR 9.5 - Night, Sunday, and holiday defined.

Science.gov (United States)

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Night, Sunday, and holiday defined. 9.5 Section 9.5... COMPENSATION FOR OVERTIME SERVICES § 9.5 Night, Sunday, and holiday defined. (a) For the purpose of this part... term holiday shall mean only national legal public holidays, viz., January 1, February 22, May 30, July...

(Re)Defining Salesperson Motivation

DEFF Research Database (Denmark)

Khusainova, Rushana; de Jong, Ad; Lee, Nick

2018-01-01

The construct of motivation is one of the central themes in selling and sales management research. Yet, to-date no review article exists that surveys the construct (both from an extrinsic and intrinsic motivation context), critically evaluates its current status, examines various key challenges...... apparent from the extant research, and suggests new research opportunities based on a thorough review of past work. The authors explore how motivation is defined, major theories underpinning motivation, how motivation has historically been measured, and key methodologies used over time. In addition......, attention is given to principal drivers and outcomes of salesperson motivation. A summarizing appendix of key articles in salesperson motivation is provided....

Sphingosine Prevents Bacterial Adherence to Endotracheal Tubes: A Novel Mechanism to Prevent Ventilator-Associated Pneumonia

Science.gov (United States)

2016-06-21

and resists the antimicrobial properties of the host defense” [9]. Bacterial adhesion is the first step in biofilm formation [10]; thus, prevention...ETTs. Future in vitro and animal studies are necessary to establish the safety of sphingolipid coatings, and future randomized clinical trials will...SUBJECT TERMS Ventilator-associated pneumonia, VAP, Gram-negative, bacteria, endotracheal tubes, sphingosine, antimicrobial coating 16. SECURITY

Software Defined Multiband EVA Radio, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — The objective of this research is to propose a reliable, lightweight, programmable, multi-band, multi-mode, miniaturized frequency-agile EVA software defined radio...

Reconfigurable, Cognitive Software Defined Radio, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — IAI is actively developing Software Defined Radio platforms that can adaptively switch between different modes of operation by modifying both transmit waveforms and...

Reconfigurable, Cognitive Software Defined Radio, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Intelligent Automation Inc, (IAI) is currently developing a software defined radio (SDR) platform that can adaptively switch between different modes of operation for...

Approach to defining de minimis, intermediate, and other classes of radioactive waste

International Nuclear Information System (INIS)

Cohen, J.J.; Smith, C.F.

1986-01-01

This study has developed a framework within which the complete spectrum of radioactive wastes can be defined. An approach has been developed that reflects both concerns in the framework of a radioactive waste classification system. In this approach, the class of any radioactive waste stream is dependent on its degree of radioactivity and its persistence. To be consistent with conventional systems, four waste classes are defined. In increasing order of concern due to radioactivity and/or duration, these are: 1. De Minimis Wastes: This waste has such a low content of radioactive material that it can be considered essentially nonradioactive and managed according to its nonradiological characteristics. 2. Low-Level Waste (LLW): Maximum concentrations for wastes considered to be in this class are prescribed in 10CFR61 as wastes that can be disposed of by shallow land burial methods. 3. Intermediate Level Waste (ILW): This category defines a class of waste whose content exceeds class C (10CFR61) levels, yet does not pose a sufficient hazard to justify management as a high-level waste (i.e., permanent isolation by deep geologic disposal). 4. High-Level Waste: HLW poses the most serious management problem and requires the most restrictive disposal methods. It is defined in NWPA as waste derived from the reprocessing of nuclear fuel and/or as highly radioactive wastes that require permanent isolation

Pyridine nucleotides in regulation of cell death and survival by redox and non-redox reactions.

Science.gov (United States)

Novak Kujundžić, Renata; Žarković, Neven; Gall Trošelj, Koraljka

2014-01-01

Changes of the level and ratios of pyridine nucleotides determine metabolism- dependent cellular redox status and the activity of poly(ADP-ribose) polymerases (PARPs) and sirtuins, thereby influencing several processes closely related to cell survival and death. Pyridine nucleotides participate in numerous metabolic reactions whereby their net cellular level remains constant, but the ratios of NAD+/NADP+ and NADH/NADPH oscillate according to metabolic changes in response to diverse stress signals. In non-redox reactions, NAD+ is degraded and quickly, afterward, resynthesized in the NAD+ salvage pathway, unless overwhelming activation of PARP-1 consumes NAD+ to the point of no return, when the cell can no longer generate enough ATP to accommodate NAD+ resynthesis. The activity of PARP-1 is mandatory for the onset of cytoprotective autophagy on sublethal stress signals. It has become increasingly clear that redox status, largely influenced by the metabolism-dependent composition of the pyridine nucleotides pool, plays an important role in the synthesis of pro-apoptotic and anti-apoptotic sphingolipids. Awareness of the involvement of the prosurvival sphingolipid, sphingosine-1-phosphate, in transition from inflammation to malignant transformation has recently emerged. Here, the participation of pyridine nucleotides in redox and non-redox reactions, sphingolipid metabolism, and their role in cell fate decisions is reviewed.

Software Defined Multiband EVA Radio, Phase II

Data.gov (United States)

National Aeronautics and Space Administration — The objective of Phase 2 is to build a reliable, lightweight, programmable, multi-mode, miniaturized EVA Software Defined Radio (SDR) that supports data telemetry,...

47 CFR 54.401 - Lifeline defined.

Science.gov (United States)

2010-10-01

... SERVICE Universal Service Support for Low-Income Consumers § 54.401 Lifeline defined. (a) As used in this subpart, Lifeline means a retail local service offering: (1) That is available only to qualifying low-income consumers; (2) For which qualifying low-income consumers pay reduced charges as a result of...

Big data and software defined networks

CERN Document Server

Taheri, Javid

2018-01-01

Big Data Analytics and Software Defined Networking (SDN) are helping to drive the management of data usage of the extraordinary increase of computer processing power provided by Cloud Data Centres (CDCs). This new book investigates areas where Big-Data and SDN can help each other in delivering more efficient services.

Software-Defined Networks as a Stage of the Network Technology Evolution

Directory of Open Access Journals (Sweden)

A. A. Krasotin

2013-01-01

Full Text Available The authors of the article focus on the concept of a software defined network. In the beginning, the brief historical account is given concerning software defined networks as a scientific concept, its formation and technological and scientific meaning. The software defined network concept is treated in the article not as the final state-of-the-art in networking, but rather as a possible step and direction in the development of a networking paradigm. The article touches on pros and cons as well of the software defined networking and gives an account of possible stages of development of this technology in the context of other technologies, considering its hybrid with MPLS, as an example. OpenFlow protocol constitutes the main part of the article. The authors further discuss various kinds of existing libraries realizing programmable management routines for a software defined network using OpenFlow. All of these libraries provide API for building modular applications for software defined network management. Touching on practical side of implementation the results of comparative tests of throughput and latency, achieved with these libraries are shown.

Evaluation of a practical expert defined approach to patient population segmentation: a case study in Singapore

Directory of Open Access Journals (Sweden)

Lian Leng Low

2017-11-01

Full Text Available Abstract Background Segmenting the population into groups that are relatively homogeneous in healthcare characteristics or needs is crucial to facilitate integrated care and resource planning. We aimed to evaluate the feasibility of segmenting the population into discrete, non-overlapping groups using a practical expert and literature driven approach. We hypothesized that this approach is feasible utilizing the electronic health record (EHR in SingHealth. Methods In addition to well-defined segments of “Mostly healthy”, “Serious acute illness but curable” and “End of life” segments that are also present in the Ministry of Health Singapore framework, patients with chronic diseases were segmented into “Stable chronic disease”, “Complex chronic diseases without frequent hospital admissions”, and “Complex chronic diseases with frequent hospital admissions”. Using the electronic health record (EHR, we applied this framework to all adult patients who had a healthcare encounter in the Singapore Health Services Regional Health System in 2012. ICD-9, 10 and polyclinic codes were used to define chronic diseases with a comprehensive look-back period of 5 years. Outcomes (hospital admissions, emergency attendances, specialist outpatient clinic attendances and mortality were analyzed for years 2012 to 2015. Results Eight hundred twenty five thousand eight hundred seventy four patients were included in this study with the majority being healthy without chronic diseases. The most common chronic disease was hypertension. Patients with “complex chronic disease” with frequent hospital admissions segment represented 0.6% of the eligible population, but accounted for the highest hospital admissions (4.33 ± 2.12 admissions; p < 0.001 and emergency attendances (ED (3.21 ± 3.16 ED visits; p < 0.001 per patient, and a high mortality rate (16%. Patients with metastatic disease accounted for the highest specialist outpatient

Defined Contribution Pension Plans: Mutual Fund Asset Allocation Changes

OpenAIRE

Clemens Sialm; Laura Starks; Hanjiang Zhang

2015-01-01

In this paper we compare changes in asset allocations between mutual funds held in defined contribution pension plans and funds held by other investors. We investigate how flows into equity and fixed income mutual funds depend on macroeconomic conditions. We find that defined contribution plans react more sensitively to these conditions, suggesting effects on mutual fund managers and other investors.

Visual memory for random block patterns defined by luminance and color contrast

NARCIS (Netherlands)

Cornelissen, FW; Greenlee, MW

2000-01-01

We studied the ability of human subjects to memorize the visual information in computer-generated random block patterns defined either by luminance contrast, by color contrast, or by both. Memory performance declines rapidly with increasing inter-stimulus interval, showing a half-life of

Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEG

Science.gov (United States)

Leibfarth, Frank A.; Johnson, Jeremiah A.; Jamison, Timothy F.

2015-01-01

We report a semiautomated synthesis of sequence and architecturally defined, unimolecular macromolecules through a marriage of multistep flow synthesis and iterative exponential growth (Flow-IEG). The Flow-IEG system performs three reactions and an in-line purification in a total residence time of under 10 min, effectively doubling the molecular weight of an oligomeric species in an uninterrupted reaction sequence. Further iterations using the Flow-IEG system enable an exponential increase in molecular weight. Incorporating a variety of monomer structures and branching units provides control over polymer sequence and architecture. The synthesis of a uniform macromolecule with a molecular weight of 4,023 g/mol is demonstrated. The user-friendly nature, scalability, and modularity of Flow-IEG provide a general strategy for the automated synthesis of sequence-defined, unimolecular macromolecules. Flow-IEG is thus an enabling tool for theory validation, structure–property studies, and advanced applications in biotechnology and materials science. PMID:26269573

Defining the key-parameters of insurance product in Islamic insurance

Directory of Open Access Journals (Sweden)

Galim Zaribzyanovich Vakhitov

2015-06-01

Full Text Available Objective to define the range of actuarial calculations in Islamic insurance to study the main differences of the traditional and Islamic insurance to define what changes in calculations entail the above differences. Methods mathematical modeling probabilistic analysis of insurance risks adaptation of methods of actuarial mathematics to the principles of Islamic insurance. Results the mathematical form of the takafulfund models is presented the distribution is analyzed of a random variable of the resulting insurance fund or the insurance company balance in a particular fixed insurance portfolio. Scientific novelty calculation are presented of the optimal tariff rate in takaful. Islamic insurance is an innovative area of insurance industry. Actuarial calculations that meet the Sharia rules are still being developed. The authors set the new tasks of actuarial calculations including the specified changes in the calculation of the optimal tariff rate imposed by the Islamic insurance principles. Practical value the results obtained can be used in the actuarial calculations of the Islamic insurance companies. nbsp

Violent crime exposure classification and adverse birth outcomes: a geographically-defined cohort study

Directory of Open Access Journals (Sweden)

Herring Amy

2006-05-01

Full Text Available Abstract Background Area-level socioeconomic disparities have long been associated with adverse pregnancy outcomes. Crime is an important element of the neighborhood environment inadequately investigated in the reproductive and public health literature. When crime has been used in research, it has been variably defined, resulting in non-comparable associations across studies. Methods Using geocoded linked birth record, crime and census data in multilevel models, this paper explored the relevance of four spatial violent crime exposures: two proximal violent crime categorizations (count of violent crime within a one-half mile radius of maternal residence and distance from maternal residence to nearest violent crime and two area-level crime categorizations (count of violent crimes within a block group and block group rate of violent crimes for adverse birth events among women in living in the city of Raleigh NC crime report area in 1999–2001. Models were adjusted for maternal age and education and area-level deprivation. Results In black and white non-Hispanic race-stratified models, crime characterized as a proximal exposure was not able to distinguish between women experiencing adverse and women experiencing normal birth outcomes. Violent crime characterized as a neighborhood attribute was positively associated with preterm birth and low birth weight among non-Hispanic white and black women. No statistically significant interaction between area-deprivation and violent crime category was observed. Conclusion Crime is variably categorized in the literature, with little rationale provided for crime type or categorization employed. This research represents the first time multiple crime categorizations have been directly compared in association with health outcomes. Finding an effect of area-level violent crime suggests crime may best be characterized as a neighborhood attribute with important implication for adverse birth outcomes.

Association between intake of less-healthy foods defined by the United Kingdom's nutrient profile model and cardiovascular disease: A population-based cohort study.

Directory of Open Access Journals (Sweden)

Oliver T Mytton

2018-01-01

Full Text Available In the United Kingdom, the Food Standards Agency-Ofcom nutrient profiling model (FSA-Ofcom model is used to define less-healthy foods that cannot be advertised to children. However, there has been limited investigation of whether less-healthy foods defined by this model are associated with prospective health outcomes. The objective of this study was to test whether consumption of less-healthy food as defined by the FSA-Ofcom model is associated with cardiovascular disease (CVD.We used data from the European Prospective Investigation of Cancer (EPIC-Norfolk cohort study in adults (n = 25,639 aged 40-79 years who completed a 7-day diet diary between 1993 and 1997. Incident CVD (primary outcome, cardiovascular mortality, and all-cause mortality (secondary outcomes were identified using record linkage to hospital admissions data and death certificates up to 31 March 2015. Each food and beverage item reported was coded and given a continuous score, using the FSA-Ofcom model, based on the consumption of energy; saturated fat; total sugar; sodium; nonsoluble fibre; protein; and fruits, vegetables, and nuts. Items were classified as less-healthy using Ofcom regulation thresholds. We used Cox proportional hazards regression to test for an association between consumption of less-healthy food and incident CVD. Sensitivity analyses explored whether the results differed based on the definition of the exposure. Analyses were adjusted for age, sex, behavioural risk factors, clinical risk factors, and socioeconomic status. Participants were followed up for a mean of 16.4 years. During follow-up, there were 4,965 incident cases of CVD (1,524 fatal within 30 days. In the unadjusted analyses, we observed an association between consumption of less-healthy food and incident CVD (test for linear trend over quintile groups, p < 0.01. After adjustment for covariates (sociodemographic, behavioural, and indices of cardiovascular risk, we found no association between

Defining decision making strategies in software ecosystem governance

DEFF Research Database (Denmark)

Manikas, Konstantinos; Wnuk, Krzysztof; Shollo, Arisa

Making the right decisions is an essential part of software ecosystem governance. Decisions related to the governance of a software ecosystem can influence the health of the ecosystem and can result in fostering the success or greatly contributing to the failure of the ecosystem. However, very few...... studies touch upon the decision making of software ecosystem governance. In this paper, we propose decomposing software ecosystem governance into three activities: input or data collection, decision making, and applying actions. We focus on the decision making activity of software ecosystem governance...... and review related literature consisted of software ecosystem governance, organizational decision making, and IT governance. Based on the identified studies, we propose a framework for defining the decision making strategies in the governance of software ecosystems. We identify five decision areas...

Recent development and prospects of neutron scattering study of biomaterials mainly on biomembrane

International Nuclear Information System (INIS)

Hirai, Mitsuhiro

2010-01-01

Due to a high-flux of pulsed neutron beam served at J-PARC, a new world of biological science will be opened in a very wide hierarchical structure and dynamics that are essential in biological phenomena. In this short review, our recent studies of 'lipid rafts' model membrane using small-angle neutron scattering and neutron spin echo are introduced. 'Lipid rafts' have been attracting great interest since they are assumed to have a function as a platform of membrane-associated events such as signal transduction, cell adhesion, lipid/protein sorting and so on. In this decade knowledge about their biological functions have been accumulated intensively. Lipid rafts are considered as a dynamic assembly of lipids (major components are sphingolipid and cholesterol) and proteins. However, their structure and dynamics in plasma membrane still remain the subject of debate. We have clarified prominent characteristics of lipid-raft model membrane composed of glycoshpingolipid (ganglioside)/cholesterol/phospholipid. (author)

Applying CSM-CERES-Maize to define a sowing window for irrigated maize crop - The Riacho´s Farm case study

Directory of Open Access Journals (Sweden)

Denise Freitas Silva

2011-08-01

Full Text Available Irrigation use constitutes an alternative to improve maize production in Central Minas Gerais State, Brazil. However, even under adequate water supply conditions, other environmental factors may influence maize crop growth and development and may, ultimately, affect grain yield. This study aimed to establish a sowing window for irrigated maize crop, based on simulation results obtained with the decision support model CSM-CERES-Maize. Simulations were made for crop management conditions of Riacho´s Farm, located in Matozinhos, Minas Gerais State, Brazil. It was employed the model´s seasonal tool, along with a data set containing 46 years of weather data records, to simulate maize yield for weekly sowing scenarios, starting on August 1st and ending on July 24th of each year. One defined an irrigated maize sowing window, taking into account the yield break risk that a farmer would be willing to take. The model proved to be an interesting tool to assist in decision making, regarding crop and irrigation management, for an irrigated maize production system. Assuming a 10% yield break in the expected average maximum maize yield, it was defined as sowing window, the period from January 23rd to March 6th, with February 20th as the best sowing date. Other sowing windows may be established according to the risk that the farmer would be willing to take.

Delta Semantics Defined By Petri Nets

DEFF Research Database (Denmark)

Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

and the possibility of using predicates to specify state changes. In this paper a formal semantics for Delta is defined and analysed using Petri nets. Petri nets was chosen because the ideas behind Petri nets and Delta concide on several points. A number of proposals for changes in Delta, which resulted from...

Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes.

Science.gov (United States)

Lindgren, David; Eriksson, Pontus; Krawczyk, Krzysztof; Nilsson, Helén; Hansson, Jennifer; Veerla, Srinivas; Sjölund, Jonas; Höglund, Mattias; Johansson, Martin E; Axelson, Håkan

2017-08-08

Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

User-Defined Meteorological (MET) Profiles from Climatological and Extreme Condition Data

Science.gov (United States)

2018-04-01

ARL-TN-0876 ● MAR 2018 US Army Research Laboratory User-Defined Meteorological (MET) Profiles from Climatological and Extreme...needed. Do not return it to the originator. ARL-TN-0876 ● MAR 2018 US Army Research Laboratory User-Defined Meteorological (MET...User-Defined Meteorological (MET) Profiles from Climatological and Extreme Condition Data 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

Contour junctions defined by dynamic image deformations enhance perceptual transparency.

Science.gov (United States)

Kawabe, Takahiro; Nishida, Shin'ya

2017-11-01

The majority of work on the perception of transparency has focused on static images with luminance-defined contour junctions, but recent work has shown that dynamic image sequences with dynamic image deformations also provide information about transparency. The present study demonstrates that when part of a static image is dynamically deformed, contour junctions at which deforming and nondeforming contours are connected facilitate the deformation-based perception of a transparent layer. We found that the impression of a transparent layer was stronger when a dynamically deforming area was adjacent to static nondeforming areas than when presented alone. When contour junctions were not formed at the dynamic-static boundaries, however, the impression of a transparent layer was not facilitated by the presence of static surrounding areas. The effect of the deformation-defined junctions was attenuated when the spatial pattern of luminance contrast at the junctions was inconsistent with the perceived transparency related to luminance contrast, while the effect did not change when the spatial luminance pattern was consistent with it. In addition, the results showed that contour completions across the junctions were required for the perception of a transparent layer. These results indicate that deformation-defined junctions that involve contour completion between deforming and nondeforming regions enhance the perception of a transparent layer, and that the deformation-based perceptual transparency can be promoted by the simultaneous presence of appropriately configured luminance and contrast-other features that can also by themselves produce the sensation of perceiving transparency.

Ultrasound-enhanced thrombolysis using Definity as a cavitation nucleation agent.

Science.gov (United States)

Datta, Saurabh; Coussios, Constantin-C; Ammi, Azzdine Y; Mast, T Douglas; de Courten-Myers, Gabrielle M; Holland, Christy K

2008-09-01

Ultrasound has been shown previously to act synergistically with a thrombolytic agent, such as recombinant tissue plasminogen activator (rt-PA) to accelerate thrombolysis. In this in vitro study, a commercial contrast agent, Definity, was used to promote and sustain the nucleation of cavitation during pulsed ultrasound exposure at 120 kHz. Ultraharmonic signals, broadband emissions and harmonics of the fundamental were measured acoustically by using a focused hydrophone as a passive cavitation detector and used to quantify the level of cavitation activity. Human whole blood clots suspended in human plasma were exposed to a combination of rt-PA, Definity and ultrasound at a range of ultrasound peak-to-peak pressure amplitudes, which were selected to expose clots to various degrees of cavitation activity. Thrombolytic efficacy was determined by measuring clot mass loss before and after the treatment and correlated with the degree of cavitation activity. The penetration depth of rt-PA and plasminogen was also evaluated in the presence of cavitating microbubbles using a dual-antibody fluorescence imaging technique. The largest mass loss (26.2%) was observed for clots treated with 120-kHz ultrasound (0.32-MPa peak-to-peak pressure amplitude), rt-PA and stable cavitation nucleated by Definity. A significant correlation was observed between mass loss and ultraharmonic signals (r = 0.85, p cavitation activity. Stable cavitation activity plays an important role in enhancement of thrombolysis and can be monitored to evaluate the efficacy of thrombolytic treatment.

Defining the end-point of mastication: A conceptual model.

Science.gov (United States)

Gray-Stuart, Eli M; Jones, Jim R; Bronlund, John E

2017-10-01

The great risks of swallowing are choking and aspiration of food into the lungs. Both are rare in normal functioning humans, which is remarkable given the diversity of foods and the estimated 10 million swallows performed in a lifetime. Nevertheless, it remains a major challenge to define the food properties that are necessary to ensure a safe swallow. Here, the mouth is viewed as a well-controlled processor where mechanical sensory assessment occurs throughout the occlusion-circulation cycle of mastication. Swallowing is a subsequent action. It is proposed here that, during mastication, temporal maps of interfacial property data are generated, which the central nervous system compares against a series of criteria in order to be sure that the bolus is safe to swallow. To determine these criteria, an engineering hazard analysis tool, alongside an understanding of fluid and particle mechanics, is used to deduce the mechanisms by which food may deposit or become stranded during swallowing. These mechanisms define the food properties that must be avoided. By inverting the thinking, from hazards to ensuring safety, six criteria arise which are necessary for a safe-to-swallow bolus. A new conceptual model is proposed to define when food is safe to swallow during mastication. This significantly advances earlier mouth models. The conceptual model proposed in this work provides a framework of decision-making to define when food is safe to swallow. This will be of interest to designers of dietary foods, foods for dysphagia sufferers and will aid the further development of mastication robots for preparation of artificial boluses for digestion research. It enables food designers to influence the swallow-point properties of their products. For example, a product may be designed to satisfy five of the criteria for a safe-to-swallow bolus, which means the sixth criterion and its attendant food properties define the swallow-point. Alongside other organoleptic factors, these

Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients.

LENUS (Irish Health Repository)

Hamilton, Hilary

2011-06-13

Previous studies have not demonstrated a consistent association between potentially inappropriate medicines (PIMs) in older patients as defined by Beers criteria and avoidable adverse drug events (ADEs). This study aimed to assess whether PIMs defined by new STOPP (Screening Tool of Older Persons\\' potentially inappropriate Prescriptions) criteria are significantly associated with ADEs in older people with acute illness.

Defining Medical Capabilities for Exploration Missions

Science.gov (United States)

Hailey, M.; Antonsen, E.; Blue, R.; Reyes, D.; Mulcahy, R.; Kerstman, E.; Bayuse, T.

2018-01-01

Exploration-class missions to the moon, Mars and beyond will require a significant change in medical capability from today's low earth orbit centric paradigm. Significant increases in autonomy will be required due to differences in duration, distance and orbital mechanics. Aerospace medicine and systems engineering teams are working together within ExMC to meet these challenges. Identifying exploration medical system needs requires accounting for planned and unplanned medical care as defined in the concept of operations. In 2017, the ExMC Clinicians group identified medical capabilities to feed into the Systems Engineering process, including: determining what and how to address planned and preventive medical care; defining an Accepted Medical Condition List (AMCL) of conditions that may occur and a subset of those that can be treated effectively within the exploration environment; and listing the medical capabilities needed to treat those conditions in the AMCL. This presentation will discuss the team's approach to addressing these issues, as well as how the outputs of the clinical process impact the systems engineering effort.

Forward and backward dynamics in implicitly defined overlapping generations models

NARCIS (Netherlands)

Gardini, L.; Hommes, C.; Tramontana, F.; de Vilder, R.

2009-01-01

In dynamic economic models derived from optimization principles, the forward equilibrium dynamics may not be uniquely defined, while the backward dynamics is well defined. We derive properties of the global forward equilibrium paths based on properties of the backward dynamics. We propose the

Forkhead Box C1 Regulates Human Primary Keratinocyte Terminal Differentiation.

Directory of Open Access Journals (Sweden)

Lianghua Bin

Full Text Available The epidermis serves as a critical protective barrier between the internal and external environment of the human body. Its remarkable barrier function is established through the keratinocyte (KC terminal differentiation program. The transcription factors specifically regulating terminal differentiation remain largely unknown. Using a RNA-sequencing (RNA-seq profiling approach, we found that forkhead box c 1 (FOXC1 was significantly up-regulated in human normal primary KC during the course of differentiation. This observation was validated in human normal primary KC from several different donors and human skin biopsies. Silencing FOXC1 in human normal primary KC undergoing differentiation led to significant down-regulation of late terminal differentiation genes markers including epidermal differentiation complex genes, keratinization genes, sphingolipid/ceramide metabolic process genes and epidermal specific cell-cell adhesion genes. We further demonstrated that FOXC1 works down-stream of ZNF750 and KLF4, and upstream of GRHL3. Thus, this study defines FOXC1 as a regulator specific for KC terminal differentiation and establishes its potential position in the genetic regulatory network.

What Happened to the IGF Binding Proteins?

Science.gov (United States)

Bach, Leon A

2018-02-01

Insulinlike growth factor (IGF) binding proteins (IGFBPs) 1 to 6 are high-affinity regulators of IGF activity. They generally inhibit IGF actions by preventing binding to the IGF-I receptor but can also enhance their actions under some conditions. Posttranslational modifications such as glycosylation and phosphorylation modulate IGFBP properties, and IGFBP proteolysis results in IGF release. IGFBPs have more recently been shown to have IGF-independent actions. A number of mechanisms are involved, including modulation of other growth factor pathways, nuclear localization and transcriptional regulation, interaction with the sphingolipid pathway, and binding to non-IGF biomolecules in the extracellular space and matrix, on the cell surface and intracellularly. IGFBPs modulate important biological processes, including cell proliferation, survival, migration, senescence, autophagy, and angiogenesis. Their actions have been implicated in growth, metabolism, cancer, stem cell maintenance and differentiation, and immune regulation. Recent studies have shown that epigenetic mechanisms are involved in the regulation of IGFBP abundance. A more complete understanding of IGFBP biology is necessary to further define their cellular roles and determine their therapeutic potential. Copyright © 2018 Endocrine Society.

Control of System with Defined Risk Level

Directory of Open Access Journals (Sweden)

Pavol Tomasov

2002-01-01

Full Text Available In the following paper the basic requirements for system control with defined risk level is presented. The paper should be an introduction to describe of theoretical apparatus, which was created during some years of research work in the Department of information and safety systems in this area. It a modification or creation of new parts of Information theory, System theory, and Control theory means. This parts are necessary for the analysis and synthesis tasks in the systems where dominant attribute of control is defined risk level. The basic problem is the creation of protect mechanism again the threats from inside and from controlled system environs. For each risk reduction mechanism is needed some redundancy which should be into control algorithm to put by exactly determined way.

Defining the Anthropocene

Science.gov (United States)

Lewis, Simon; Maslin, Mark

2016-04-01

Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Should the Anthropocene - the idea that human activity is a force acting upon the Earth system in ways that mean that Earth will be altered for millions of years - be defined as a geological time-unit at the level of an Epoch? Here we appraise the data to assess such claims, first in terms of changes to the Earth system, with particular focus on very long-lived impacts, as Epochs typically last millions of years. Can Earth really be said to be in transition from one state to another? Secondly, we then consider the formal criteria used to define geological time-units and move forward through time examining whether currently available evidence passes typical geological time-unit evidence thresholds. We suggest two time periods likely fit the criteria (1) the aftermath of the interlinking of the Old and New Worlds, which moved species across continents and ocean basins worldwide, a geologically unprecedented and permanent change, which is also the globally synchronous coolest part of the Little Ice Age (in Earth system terms), and the beginning of global trade and a new socio-economic "world system" (in historical terms), marked as a golden spike by a temporary drop in atmospheric CO2, centred on 1610 CE; and (2) the aftermath of the Second World War, when many global environmental changes accelerated and novel long-lived materials were increasingly manufactured, known as the Great Acceleration (in Earth system terms) and the beginning of the Cold War (in historical terms), marked as a golden spike by the peak in radionuclide fallout in 1964. We finish by noting that the Anthropocene debate is politically loaded, thus transparency in the presentation of evidence is essential if a formal definition of the Anthropocene is to avoid becoming a debate about bias. The

A research on the application of software defined networking in satellite network architecture

Science.gov (United States)

Song, Huan; Chen, Jinqiang; Cao, Suzhi; Cui, Dandan; Li, Tong; Su, Yuxing

2017-10-01

Software defined network is a new type of network architecture, which decouples control plane and data plane of traditional network, has the feature of flexible configurations and is a direction of the next generation terrestrial Internet development. Satellite network is an important part of the space-ground integrated information network, while the traditional satellite network has the disadvantages of difficult network topology maintenance and slow configuration. The application of SDN technology in satellite network can solve these problems that traditional satellite network faces. At present, the research on the application of SDN technology in satellite network is still in the stage of preliminary study. In this paper, we start with introducing the SDN technology and satellite network architecture. Then we mainly introduce software defined satellite network architecture, as well as the comparison of different software defined satellite network architecture and satellite network virtualization. Finally, the present research status and development trend of SDN technology in satellite network are analyzed.

Using Cognitive Control in Software Defined Networking for Port Scan Detection

Science.gov (United States)

2017-07-01

ARL-TR-8059 ● July 2017 US Army Research Laboratory Using Cognitive Control in Software -Defined Networking for Port Scan...Cognitive Control in Software -Defined Networking for Port Scan Detection by Vinod K Mishra Computational and Information Sciences Directorate, ARL...Technical Report 3. DATES COVERED (From - To) 15 June–31 July 2016 4. TITLE AND SUBTITLE Using Cognitive Control in Software -Defined Networking for

Optimal combination of illusory and luminance-defined 3-D surfaces: A role for ambiguity.

Science.gov (United States)

Hartle, Brittney; Wilcox, Laurie M; Murray, Richard F

2018-04-01

The shape of the illusory surface in stereoscopic Kanizsa figures is determined by the interpolation of depth from the luminance edges of adjacent inducing elements. Despite ambiguity in the position of illusory boundaries, observers reliably perceive a coherent three-dimensional (3-D) surface. However, this ambiguity may contribute additional uncertainty to the depth percept beyond what is expected from measurement noise alone. We evaluated the intrinsic ambiguity of illusory boundaries by using a cue-combination paradigm to measure the reliability of depth percepts elicited by stereoscopic illusory surfaces. We assessed the accuracy and precision of depth percepts using 3-D Kanizsa figures relative to luminance-defined surfaces. The location of the surface peak was defined by illusory boundaries, luminance-defined edges, or both. Accuracy and precision were assessed using a depth-discrimination paradigm. A maximum likelihood linear cue combination model was used to evaluate the relative contribution of illusory and luminance-defined signals to the perceived depth of the combined surface. Our analysis showed that the standard deviation of depth estimates was consistent with an optimal cue combination model, but the points of subjective equality indicated that observers consistently underweighted the contribution of illusory boundaries. This systematic underweighting may reflect a combination rule that attributes additional intrinsic ambiguity to the location of the illusory boundary. Although previous studies show that illusory and luminance-defined contours share many perceptual similarities, our model suggests that ambiguity plays a larger role in the perceptual representation of illusory contours than of luminance-defined contours.

Smooth Frechet subalgebras of C-algebras defined by first order ...

Indian Academy of Sciences (India)

The differential structure in a *-algebra defined by a dense Frechet subalgebra whose topology is defined by a sequence of differential seminorms of order 1 is investigated. This includes differential Arens–Michael decomposition, spectral invariance, closure under functional calculi as well as intrinsic spectral description.

Trauma-related self-defining memories and future goals in Dissociative Identity Disorder.

Science.gov (United States)

Huntjens, Rafaële J C; Wessel, Ineke; Ostafin, Brian D; Boelen, Paul A; Behrens, Friederike; van Minnen, Agnes

2016-12-01

This study examined the content of self-defining autobiographical memories in different identities in patients with Dissociative Identity Disorder (DID) and comparison groups of patients with PTSD, healthy controls, and DID simulators. Consistent with the DID trauma model, analyses of objective ratings showed that DID patients in trauma identities retrieved more negative and trauma-related self-defining memories than DID patients in avoidant identities. Inconsistent with the DID trauma model, DID patients' self-rated trauma-relatedness of self-defining memories and future life goals did not differ between trauma identities and trauma avoidant identities. That is, the DID patients did not seem to be "shut off" from their trauma while in their avoidant identity. Furthermore, DID patients in both identities reported a higher proportion of avoidance goals compared to PTSD patients, with the latter group scoring comparably to healthy controls. The simulators behaved according to the instructions to respond differently in each identity (i.e., to report memories and goals consistent with the identity tested). The discrepant task behavior by DID patients and simulators indicated that DID patients did not seem to intentionally produce the hypothesized differences in performance between identities. In conclusion, for patients with DID (i.e., in both identities) and patients with PTSD, trauma played a central role in the retrieval of self-defining memories and in the formulation of life goals. Copyright © 2016 Elsevier Ltd. All rights reserved.

29 CFR 779.247 - “Goods” defined.

Science.gov (United States)

2010-07-01

... OR SERVICES Employment to Which the Act May Apply; Enterprise Coverage Interstate Inflow Test Under... Act is defined in section 3(i) of the Act. The statutory definition is quoted in § 779.14, and is...

Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study.

Directory of Open Access Journals (Sweden)

Qi Zhao

Full Text Available Obesity is a typical metabolic disorder resulting from the imbalance between energy intake and expenditure. American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study. Using an untargeted liquid chromatography-mass spectrometry, we detected 1,364 distinct m/z features matched to known compounds in the current metabolomics databases. We conducted multivariate analysis to identify metabolic profiles for obesity, adjusting for standard obesity indicators. After adjusting for covariates and multiple testing, five metabolites were associated with body mass index and seven were associated with waist circumference. Of them, three were associated with both. Majority of the obesity-related metabolites belongs to lipids, e.g., fatty amides, sphingolipids, prenol lipids, and steroid derivatives. Other identified metabolites are amino acids or peptides. Of the nine identified metabolites, five metabolites (oleoylethanolamide, mannosyl-diinositol-phosphorylceramide, pristanic acid, glutamate, and kynurenine have been previously implicated in obesity or its related pathways. Future studies are warranted to replicate these findings in larger populations or other ethnic groups.

Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study.

Science.gov (United States)

Zhao, Qi; Zhu, Yun; Best, Lyle G; Umans, Jason G; Uppal, Karan; Tran, ViLinh T; Jones, Dean P; Lee, Elisa T; Howard, Barbara V; Zhao, Jinying

2016-01-01

Obesity is a typical metabolic disorder resulting from the imbalance between energy intake and expenditure. American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study. Using an untargeted liquid chromatography-mass spectrometry, we detected 1,364 distinct m/z features matched to known compounds in the current metabolomics databases. We conducted multivariate analysis to identify metabolic profiles for obesity, adjusting for standard obesity indicators. After adjusting for covariates and multiple testing, five metabolites were associated with body mass index and seven were associated with waist circumference. Of them, three were associated with both. Majority of the obesity-related metabolites belongs to lipids, e.g., fatty amides, sphingolipids, prenol lipids, and steroid derivatives. Other identified metabolites are amino acids or peptides. Of the nine identified metabolites, five metabolites (oleoylethanolamide, mannosyl-diinositol-phosphorylceramide, pristanic acid, glutamate, and kynurenine) have been previously implicated in obesity or its related pathways. Future studies are warranted to replicate these findings in larger populations or other ethnic groups.

Water and temperature stress define the optimal flowering period for wheat in south-eastern Australia

OpenAIRE

Evans, John; Kirkegaard, John; Hunt, James; Flohr, Bonnie

2017-01-01

Across the Australian wheat belt, the time at which wheat flowers is a critical determinant of yield. In all environments an optimal flowering period (OFP) exists which is defined by decreasing frost risk, and increasing water and heat stress. Despite their critical importance, OFPs have not been comprehensively defined across south eastern Australia′s (SEA) cropping zone using yield estimates incorporating temperature, radiation and water-stress. In this study, the widely validated cropping ...

Natural Organochlorines as Precursors of 3-Monochloropropanediol Esters in Vegetable Oils.

Science.gov (United States)

Tiong, Soon Huat; Saparin, Norliza; Teh, Huey Fang; Ng, Theresa Lee Mei; Md Zain, Mohd Zairey Bin; Neoh, Bee Keat; Md Noor, Ahmadilfitri; Tan, Chin Ping; Lai, Oi Ming; Appleton, David Ross

2018-01-31

During high-temperature refining of vegetable oils, 3-monochloropropanediol (3-MCPD) esters, possible carcinogens, are formed from acylglycerol in the presence of a chlorine source. To investigate organochlorine compounds in vegetable oils as possible precursors for 3-MCPD esters, we tested crude palm, soybean, rapeseed, sunflower, corn, coconut, and olive oils for the presence of organochlorine compounds. Having found them in all vegetable oils tested, we focused subsequent study on oil palm products. Analysis of the chlorine isotope mass pattern exhibited in high-resolution mass spectrometry enabled organochlorine compound identification in crude palm oils as constituents of wax esters, fatty acid, diacylglycerols, and sphingolipids, which are produced endogenously in oil palm mesocarp throughout ripening. Analysis of thermal decomposition and changes during refining suggested that these naturally present organochlorine compounds in palm oils and perhaps in other vegetable oils are precursors of 3-MCPD esters. Enrichment and dose-response showed a linear relationship to 3-MCPD ester formation and indicated that the sphingolipid-based organochlorine compounds are the most active precursors of 3-MCPD esters.

A Proposal for User-defined Reductions in OpenMP

Energy Technology Data Exchange (ETDEWEB)

Duran, A; Ferrer, R; Klemm, M; de Supinski, B R; Ayguade, E

2010-03-22

Reductions are commonly used in parallel programs to produce a global result from partial results computed in parallel. Currently, OpenMP only supports reductions for primitive data types and a limited set of base language operators. This is a significant limitation for those applications that employ user-defined data types (e. g., objects). Implementing manual reduction algorithms makes software development more complex and error-prone. Additionally, an OpenMP runtime system cannot optimize a manual reduction algorithm in ways typically applied to reductions on primitive types. In this paper, we propose new mechanisms to allow the use of most pre-existing binary functions on user-defined data types as User-Defined Reduction (UDR) operators. Our measurements show that our UDR prototype implementation provides consistently good performance across a range of thread counts without increasing general runtime overheads.

Employing Deceptive Dynamic Network Topology Through Software-Defined Networking

Science.gov (United States)

2014-03-01

actions. From [64] . . . . . 37 xi THIS PAGE INTENTIONALLY LEFT BLANK xii List of Acronyms and Abbreviations ACL Access Control List API Application...can be extremely useful in topology mapping through various latency-based geolocation methods [35], [36], [37]. PING 1 7 2 . 2 0 . 5 . 2 ( 1 7 2 . 2 0...defined northbound Applica- tion Programming Interfaces ( APIs ). Figure 3.1: Software-Defined Network Architecture. From [8] 29 3.3 SDN OpenFlow

Some double sequence spaces of interval numbers defined by Orlicz function

Directory of Open Access Journals (Sweden)

Ayhan Esi

2014-10-01

Full Text Available In this paper we introduce some interval valued double sequence spaces defined by Orlicz function and study different properties of these spaces like inclusion relations, solidity, etc. We establish some inclusion relations among them. Also we introduce the concept of double statistical convergence for interval number sequences and give an inclusion relation between interval valued double sequence spaces.

High-Q Variable Bandwidth Passive Filters for Software Defined Radio

NARCIS (Netherlands)

Arkesteijn, V.J.; Klumperink, Eric A.M.; Nauta, Bram

2001-01-01

An important aspect of Software Defined Radio is the ability to define the bandwidth of the filter that selects the desired channel. This paper describes a technique for channel filtering, in which two passive filters are combined to obtain a variable bandwidth. Passive filters have the advantage of

High-Q variable bandwidth passive filters for Software Defined Radio

NARCIS (Netherlands)

Arkesteijn, V.J.; Klumperink, Eric A.M.; Nauta, Bram

An important aspect of Software Defined Radio is the ability to define the bandwidth of the filter that selects the desired channel. This paper describes a technique for channel filtering, in which two passive filters are combined to obtain a variable bandwidth. Passive filters have the advantage of

75 FR 27927 - Diversification Requirements for Certain Defined Contribution Plans

Science.gov (United States)

2010-05-19

... section 414(l) with respect to any other defined benefit plan or defined contribution plan maintained by... disclosure of the fund's portfolio holdings (for example, Form N-CSR, ``Certified Shareholder Report of... securities, as well as a direct or indirect benefit that is conditioned on investment in employer securities...

Sphingosine inhibits the sarco(endo)plasmic reticulum Ca"2"+-ATPase (SERCA) activity

International Nuclear Information System (INIS)

Benaim, Gustavo; Pimentel, Adriana A.; Felibertt, Pimali; Mayora, Adriana; Colman, Laura; Sojo, Felipe; Rojas, Héctor; De Sanctis, Juan B.

2016-01-01

The increase in the intracellular Ca"2"+ concentration ([Ca"2"+]_i) is the key variable for many different processes, ranging from regulation of cell proliferation to apoptosis. In this work we demonstrated that the sphingolipid sphingosine (Sph) increases the [Ca"2"+]_i by inhibiting the sarco(endo)plasmic reticulum Ca"2"+-ATPase (SERCA), in a similar manner to thapsigargin (Tg), a specific inhibitor of this Ca"2"+ pump. The results showed that addition of sphingosine produced a release of Ca"2"+ from the endoplasmic reticulum followed by a Ca"2"+ entrance from the outside mileu. The results presented in this work support that this sphingolipid could control the activity of the SERCA, and hence sphingosine may participate in the regulation of [Ca"2"+]_I in mammalian cells.

Sporulation of Clostridium cylindrosporum on a Defined, Low-Manganese Medium

OpenAIRE

Sacks, L. E.; Smith, M. R.

1987-01-01

Clostridium cylindrosporum HC-1 grew and sporulated well on a defined medium. This is the first demonstration of sporulation of a purinolytic clostridium on a defined medium; manganese levels were below those considered essential for sporulation of most Bacillus species. Sporulation appeared to be initiated before exhaustion of the purine substrate.

Robust Hinf control of uncertain switched systems defined on polyhedral sets with Filippov solutions

DEFF Research Database (Denmark)

Ahmadi, Mohamadreza; Mojallali, Hamed; Wisniewski, Rafal

2012-01-01

This paper considers the control problem of a class of uncertain switched systems defined on polyhedral sets known as piecewise linear systems where, instead of the conventional Carathe ́odory solutions, Filippov solutions are studied. In other words, in contrast to the previous studies, solutions...

Treatment recommendations for DSM-5-defined mixed features.

Science.gov (United States)

Rosenblat, Joshua D; McIntyre, Roger S

2017-04-01

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) mixed features specifier provides a less restrictive definition of mixed mood states, compared to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), including mood episodes that manifest with subthreshold symptoms of the opposite mood state. A limited number of studies have assessed the efficacy of treatments specifically for DSM-5-defined mixed features in mood disorders. As such, there is currently an inadequate amount of data to appropriately inform evidence-based treatment guidelines of DSM-5 defined mixed features. However, given the high prevalence and morbidity of mixed features, treatment recommendations based on the currently available evidence along with expert opinion may be of benefit. This article serves to provide these interim treatment recommendations while humbly acknowledging the limited amount of evidence currently available. Second-generation antipsychotics (SGAs) appear to have the greatest promise in the treatment of bipolar disorder (BD) with mixed features. Conventional mood stabilizing agents (ie, lithium and divalproex) may also be of benefit; however, they have been inadequately studied. In the treatment of major depressive disorder (MDD) with mixed features, the comparable efficacy of antidepressants versus other treatments, such as SGAs, remains unknown. As such, antidepressants remain first-line treatment of MDD with or without mixed features; however, there are significant safety concerns associated with antidepressant monotherapy when mixed features are present, which merits increased monitoring. Lurasidone is the only SGA monotherapy that has been shown to be efficacious specifically in the treatment of MDD with mixed features. Further research is needed to accurately determine the efficacy, safety, and tolerability of treatments specifically for mood episodes with mixed features to adequately inform

Network Coded Software Defined Networking

DEFF Research Database (Denmark)

Hansen, Jonas; Roetter, Daniel Enrique Lucani; Krigslund, Jeppe

2015-01-01

Software defined networking has garnered large attention due to its potential to virtualize services in the Internet, introducing flexibility in the buffering, scheduling, processing, and routing of data in network routers. SDN breaks the deadlock that has kept Internet network protocols stagnant...... for decades, while applications and physical links have evolved. This article advocates for the use of SDN to bring about 5G network services by incorporating network coding (NC) functionalities. The latter constitutes a major leap forward compared to the state-of-the- art store and forward Internet paradigm...

Defining Usability of PN Services

DEFF Research Database (Denmark)

Nicolajsen, Hanne Westh; Ahola, Titta; Fleury, Alexandre

In this deliverable usability and user experience are defined in relation to MAGNET Beyond technologies, and it is described how the main MAGNET Beyond concepts can be evaluated through the involvement of users. The concepts include the new "Activity based communication approach" for interacting...... with the MAGNET Beyond system, as well as the core concepts: Personal Network, Personal Network-Federation, Service Discovery, User Profile Management, Personal Network Management, Privacy and Security and Context Awareness. The overall plans for the final usability evaluation are documented based on the present...

Disruption of retinoic acid receptor alpha reveals the growth promoter face of retinoic acid.

Directory of Open Access Journals (Sweden)

Giulia Somenzi

2007-09-01

Full Text Available Retinoic acid (RA, the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs, exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591. The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER, the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P, the sphingolipid with prosurvival activity.We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling.In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects

Phospholipids of Entamoeba invadens

NARCIS (Netherlands)

Vliet, H.H.D.M. van; Kamp, J.A.F. op den; Deenen, L.L.M. van

1975-01-01

The major phosphoglycerides present in Entamoeba invadens are phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. Furthermore, three different sphingolipids could be isolated from the amoeba. In addition to sphingomyelin and a phosphonolipid, ceramide

Coronary CT angiography characteristics of OCT-defined thin-cap fibroatheroma. A section-to-section comparison study

Energy Technology Data Exchange (ETDEWEB)

Yang, Dong Hyun; Koo, Hyun Jung; Kang, Joon-Won; Lim, Tae-Hwan [Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Kang, Soo-Jin; Chang, Mineok; Lee, Pil Hyung; Roh, Jae-Hyung; Ahn, Jung-Min; Park, Duk-Woo; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung; Kim, Young-Hak [Asan Medical Center, University of Ulsan College of Medicine, Department of Cardiology, Seoul (Korea, Republic of); Baek, Seunghee [Asan Medical Center, University of Ulsan College of Medicine, Department of Clinical Epidemiology and Biostatistics, Seoul (Korea, Republic of); Han, Seungbong [Gachon University, Department of Applied Statistics, Gyeonggi-do (Korea, Republic of); Mintz, Gary S. [Cardiovascular Research Foundation, New York, NY (United States)

2018-02-15

To evaluate whether plaque characteristics as assessed by coronary computed tomography angiography (CCTA) were associated with the presence of a thin-cap fibroatheroma (TCFA) - a precursor of plaque rupture - defined by optical coherence tomography (OCT) in a section-to-section-level comparison. From 28 symptomatic patients, 31 coronary lesions were evaluated on 727 cross-sections co-registered by both CCTA and OCT. CCTA plaque characteristics included low attenuation plaque (LAP, <30 HU), napkin ring sign (NRS), positive remodelling (PR, remodelling index ≥1.10), and spotty calcification and plaque area and plaque burden. By OCT, presence of TCFA, lumen area and arc of lipid were determined. OCT revealed a TCFA in 69 (9.4%) sections from 19 (61.2 %) lesions. In per-section analysis, OCT-TCFA showed higher frequency of CCTA-detected LAP (58.0% vs. 18.5%), NRS (31.9% vs. 8.8%) and PR (68.1% vs. 48.0%) and greater plaque burden (70.6% vs. 61.9%) as compared to sections without OCT-TCFA (all p < 0.05). In multivariable analysis, LAP (odds ratio [OR] 4.05, p < 0.001) and NRS (OR 2.47, p = 0.005) were associated with OCT-TCFA. CCTA-measured lumen area correlated well with OCT-measured lumen area (R = 0.859, limits of agreement -0.5 ± 3.7 mm{sup 2}). LAP and NRS in CCTA were associated with the presence of OCT-defined TCFA in a section-to-section comparison. (orig.)

Difficult cannulation as defined by a prospective study of the Scandinavian Association for Digestive Endoscopy (SADE) in 907 ERCPs

DEFF Research Database (Denmark)

Halttunen, Jorma; Meisner, Søren; Aabakken, Lars

2014-01-01

BACKGROUND: The definition of a "difficult" cannulation varies considerably in reports of endoscopic retrograde cholangiopancreatography (ERCP). AIMS: To define a difficult cannulation, which translates into higher risk of post-ERCP pancreatitis. PATIENTS AND METHODS: Prospective consecutive reco...

Psychosocial factors associated with broadly defined bulimia nervosa during early pregnancy: findings from the Norwegian Mother and Child Cohort Study.

Science.gov (United States)

Knoph Berg, Cecilie; Bulik, Cynthia M; Von Holle, Ann; Torgersen, Leila; Hamer, Robert; Sullivan, Patrick; Reichborn-Kjennerud, Ted

2008-05-01

The purpose of the present study was to investigate the relationship between psychosocial characteristics and broadly defined bulimia nervosa during early pregnancy, including factors associated with continuation, incidence and remission. A total of 41 157 women completed questionnaires at approximately gestation week 18, including items on eating disorders and psychosocial characteristics as a part of Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Incident bulimia nervosa during the first trimester was significantly associated with symptoms of anxiety and depression and low self-esteem and life satisfaction, whereas remission was significantly associated with higher self-esteem and life satisfaction. Continuation was not significantly related to any of the psychosocial variables tested. Onset of bulimia nervosa during pregnancy is associated with mood and anxiety symptoms. Remission of bulimic symptoms and new onset of bulimia nervosa are associated with opposite profiles of self-esteem, and life satisfaction measures.

Defining safety goals. 2. Basic Consideration on Defining Safety Goals

International Nuclear Information System (INIS)

Hakata, T.

2001-01-01

The purpose of this study is to develop basic safety goals that are rational and consistent for all nuclear facilities, including nuclear power plants and fuel cycle facilities. Basic safety goals (risk limits) by an index of radiation dose are discussed, which are based on health effects of detriment and fatality and risk levels presumably accepted by society. The contents of this paper are the personal opinions of the author. The desirable structure of safety goals is assumed to be 'basic safety goals plus specific safety goals (or supplemental safety goals) for each sort of facility, which reflects their characteristics'. The requisites of the basic safety goals must include (a) rational bases (scientific and social), (b) comprehensiveness (common to all sorts of nuclear facilities covering from normal to accidental conditions), and (c) applicability. To meet the requirements, the basic safety goals might have to be a risk profile expression by an index of radiation dose. The societal rationality is consideration of absolute risk levels (10 -6 or 10 -7 /yr) and/or relative risk factors (such as 0.1% of U.S. safety goals) that the general public accepts as tolerable. The following quantitative objectives are adopted in this study for protection of average individuals in the vicinity of a nuclear facility: 1. The additive annual radiation dose during normal operation must be -4 /yr (health detriment), 2x10 -6 /yr (latent cancer and severe hereditary effects), and 10 -7 /yr (acute fatality) from the statistics in Japan. The radiation effects on human beings are determined by recommendations of UNSCEAR (Ref. 1) and ICRP. The health effects considered are non-severe stochastic health detriment, i.e., detectable opacities of lens of eye (threshold 5 0.5 to 2 Sv), depression of hematopoiesis of bone marrow (0.5 Sv), and depression of reproductive capability (temporary sterility of testes ) (0.15 Sv). The LD 50/60 of acute fatality is ∼4 Sv, and fatalities by latent

User-Defined Clocks in the Real-Time Specification for Java

DEFF Research Database (Denmark)

Wellings, Andy; Schoeberl, Martin

2011-01-01

This paper analyses the new user-defined clock model that is to be supported in Version 1.1 of the Real-Time Specification for Java (RTSJ). The model is a compromise between the current position, where there is no support for user-defined clocks, and a fully integrated model. The paper investigat...

The mechanical response of lithographically defined break junctions

International Nuclear Information System (INIS)

Huisman, E. H.; Bakker, F. L.; Wees, B. J. van; Trouwborst, M. L.; Molen, S. J. van der

2011-01-01

We present an experimental study on the mechanical response of lithographically defined break junctions by measuring atomic chain formation, tunneling traces and Gundlach oscillations. The calibration factor, i.e., the ratio between the electrode movement and the bending of the substrate, is found to be 2.5 times larger than expected from a simple mechanical model. This result is consistent with previous finite-element calculations. Comparing different samples, the mechanical response is found to be similar for electrode separations >4 A. However, for smaller electrode separations significant sample-to-sample variations appear. These variations are ascribed to differences in the shape of the two electrodes on the atomic scale which cannot be controlled by the fabrication process.

Descriptors used to define running-related musculoskeletal injury: a systematic review.

Science.gov (United States)

Yamato, Tiê Parma; Saragiotto, Bruno Tirotti; Hespanhol Junior, Luiz Carlos; Yeung, Simon S; Lopes, Alexandre Dias

2015-05-01

Systematic review. To systematically review the descriptors used to define running-related musculoskeletal injury and to analyze the implications of different definitions on the results of studies. Studies have developed their own definitions of running-related musculoskeletal injuries based on different criteria. This may affect the rates of injury, which can be overestimated or underestimated due to the lack of a standard definition. Searches were conducted in the Embase, PubMed, CINAHL, SPORTDiscus, LILACS, and SciELO databases, without limits on date of publication and language. Only articles that reported a definition of running-related injury were included. The definitions were classified according to 3 domains and subcategories: (1) presence of physical complaint (symptom, body system involved, region), (2) interruption of training or competition (primary sports involved, extent of injury, extent of limitation, interruption, period of injury), and (3) need for medical assistance. Spearman rank correlation was performed to evaluate the correlation between the completeness of definitions and the rates of injury reported in the studies. A total of 48 articles were included. Most studies described more than half of the subcategories, but with no standardization between the terms used within each category, showing that there is no consensus for a definition. The injury rates ranged between 3% and 85%, and tended to increase with less specific definitions. The descriptors commonly used by researchers to define a running-related injury vary between studies and may affect the rates of injuries. The lack of a standardized definition hinders comparison between studies and rates of injuries.

Glycosylceramide modifies the flavor and metabolic characteristics of sake yeast

Directory of Open Access Journals (Sweden)

Jannatul Ferdouse

2018-05-01

Full Text Available In the manufacture of sake, Japanese traditional rice wine, sake yeast is fermented with koji, which is steamed rice fermented with the non-pathogenic fungus Aspergillus oryzae. During fermentation, sake yeast requires lipids, such as unsaturated fatty acids and sterols, in addition to substances provided by koji enzymes for fermentation. However, the role of sphingolipids on the brewing characteristics of sake yeast has not been studied. In this study, we revealed that glycosylceramide, one of the sphingolipids abundant in koji, affects yeast fermentation. The addition of soy, A. oryzae, and Grifola frondosa glycosylceramide conferred a similar effect on the flavor profiles of sake yeast. In particular, the addition of A. oryzae and G. frondosa glycosylceramide were very similar in terms of the decreases in ethyl caprylate and ethyl 9-decenoate. The addition of soy glycosylceramide induced metabolic changes to sake yeast such as a decrease in glucose, increases in ethanol and glycerol and changes in several amino acids and organic acids concentrations. Tricarboxylic acid (TCA cycle, pyruvate metabolism, starch and sucrose metabolism, and glycerolipid metabolism were overrepresented in the cultures incubated with sake yeast and soy glycosylceramide. This is the first study of the effect of glycosylceramide on the flavor and metabolic profile of sake yeast.

Glycosylceramide modifies the flavor and metabolic characteristics of sake yeast.

Science.gov (United States)

Ferdouse, Jannatul; Yamamoto, Yuki; Taguchi, Seiga; Yoshizaki, Yumiko; Takamine, Kazunori; Kitagaki, Hiroshi

2018-01-01

In the manufacture of sake, Japanese traditional rice wine, sake yeast is fermented with koji, which is steamed rice fermented with the non-pathogenic fungus Aspergillus oryzae . During fermentation, sake yeast requires lipids, such as unsaturated fatty acids and sterols, in addition to substances provided by koji enzymes for fermentation. However, the role of sphingolipids on the brewing characteristics of sake yeast has not been studied. In this study, we revealed that glycosylceramide, one of the sphingolipids abundant in koji, affects yeast fermentation. The addition of soy, A. oryzae , and Grifola frondosa glycosylceramide conferred a similar effect on the flavor profiles of sake yeast. In particular, the addition of A. oryzae and G. frondosa glycosylceramide were very similar in terms of the decreases in ethyl caprylate and ethyl 9-decenoate. The addition of soy glycosylceramide induced metabolic changes to sake yeast such as a decrease in glucose, increases in ethanol and glycerol and changes in several amino acids and organic acids concentrations. Tricarboxylic acid (TCA) cycle, pyruvate metabolism, starch and sucrose metabolism, and glycerolipid metabolism were overrepresented in the cultures incubated with sake yeast and soy glycosylceramide. This is the first study of the effect of glycosylceramide on the flavor and metabolic profile of sake yeast.

Specific membrane lipid composition is important for plasmodesmata function in Arabidopsis.

Science.gov (United States)

Grison, Magali S; Brocard, Lysiane; Fouillen, Laetitia; Nicolas, William; Wewer, Vera; Dörmann, Peter; Nacir, Houda; Benitez-Alfonso, Yoselin; Claverol, Stéphane; Germain, Véronique; Boutté, Yohann; Mongrand, Sébastien; Bayer, Emmanuelle M

2015-04-01

Plasmodesmata (PD) are nano-sized membrane-lined channels controlling intercellular communication in plants. Although progress has been made in identifying PD proteins, the role played by major membrane constituents, such as the lipids, in defining specialized membrane domains in PD remains unknown. Through a rigorous isolation of "native" PD membrane fractions and comparative mass spectrometry-based analysis, we demonstrate that lipids are laterally segregated along the plasma membrane (PM) at the PD cell-to-cell junction in Arabidopsis thaliana. Remarkably, our results show that PD membranes display enrichment in sterols and sphingolipids with very long chain saturated fatty acids when compared with the bulk of the PM. Intriguingly, this lipid profile is reminiscent of detergent-insoluble membrane microdomains, although our approach is valuably detergent-free. Modulation of the overall sterol composition of young dividing cells reversibly impaired the PD localization of the glycosylphosphatidylinositol-anchored proteins Plasmodesmata Callose Binding 1 and the β-1,3-glucanase PdBG2 and altered callose-mediated PD permeability. Altogether, this study not only provides a comprehensive analysis of the lipid constituents of PD but also identifies a role for sterols in modulating cell-to-cell connectivity, possibly by establishing and maintaining the positional specificity of callose-modifying glycosylphosphatidylinositol proteins at PD. Our work emphasizes the importance of lipids in defining PD membranes. © 2015 American Society of Plant Biologists. All rights reserved.

Defining Metabolically Healthy Obesity: Role of Dietary and Lifestyle Factors

Science.gov (United States)

Phillips, Catherine M.; Dillon, Christina; Harrington, Janas M.; McCarthy, Vera J. C.; Kearney, Patricia M.; Fitzgerald, Anthony P.; Perry, Ivan J.

2013-01-01

Background There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. Method Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥30kg/m2) and non-obese (BMI unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006). Conclusion A standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate therapeutic or intervention strategy. PMID:24146838

Microarray-based large scale detection of single feature ...

Indian Academy of Sciences (India)

Sphingolipid metabolism. Glycerolipid metabolism. Arginine and proline metabolism. Brassinosteroid biosynthesis. Protein processing in endoplasmic re culum. Cyanoamino acid metabolism. Circadian rhythm - plant. Fructose and mannose metabolism. Pyruvate metabolism. Photosynthesis beta-Alanine metabolism.

Unusual presentation of adult Gaucher′s disease: A long and difficult road to diagnosis

Directory of Open Access Journals (Sweden)

Vishakha V Jain

2011-01-01

Full Text Available Gaucher′s disease is the most frequent sphingolipid storage disease. We present a case of type 1 non-neuropathic type of adult Gaucher′s disease patient with atypical presentation.

Defined media and inert supports : their potential as solid-state fermentation production systems

NARCIS (Netherlands)

Ooijkaas, L.P.; Weber, F.J.; Buitelaar, R.M.; Tramper, J.; Rinzema, A.

2000-01-01

Solid-state fermentation (SSF) using inert supports impregnated with chemically defined liquid media has several potential applications in both scientific studies and in the industrial production of high-value products, such as metabolites, biological control agents and enzymes. As a result of its