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Sample records for defining normal citrulline

  1. Normal Functions as a New Way of Defining Computable Functions

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    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert's system of recursive functions. Normal functions lack this disadvantage.

  2. Normal Functions As A New Way Of Defining Computable Functions

    Directory of Open Access Journals (Sweden)

    Leszek Dubiel

    2004-01-01

    Full Text Available Report sets new method of defining computable functions. This is formalization of traditional function descriptions, so it allows to define functions in very intuitive way. Discovery of Ackermann function proved that not all functions that can be easily computed can be so easily described with Hilbert’s system of recursive functions. Normal functions lack this disadvantage.

  3. Defining the normal turbine inflow within a wind park environment

    Energy Technology Data Exchange (ETDEWEB)

    Kelley, N.D.

    1993-06-01

    This brief paper discusses factors that must be considered when defining the [open quotes]normal[close quotes] (as opposed to [open quotes]extreme[close quotes]) loading conditions seen in wind turbines operating within a wind park environment. The author defines the [open quotes]normal[close quotes] conditions to include fatigue damage accumulation as a result of: (1) start/stop cycles, (2) emergency shutdowns, and (3) the turbulence environment associated with site and turbine location. He also interprets [open quotes]extreme[close quotes] loading conditions to include those events that can challenge the survivability of the turbine.

  4. Defining the normal turbine inflow within a wind park environment

    Energy Technology Data Exchange (ETDEWEB)

    Kelley, N.D.

    1993-06-01

    This brief paper discusses factors that must be considered when defining the {open_quotes}normal{close_quotes} (as opposed to {open_quotes}extreme{close_quotes}) loading conditions seen in wind turbines operating within a wind park environment. The author defines the {open_quotes}normal{close_quotes} conditions to include fatigue damage accumulation as a result of: (1) start/stop cycles, (2) emergency shutdowns, and (3) the turbulence environment associated with site and turbine location. He also interprets {open_quotes}extreme{close_quotes} loading conditions to include those events that can challenge the survivability of the turbine.

  5. DEFINING THE SPERMATOZOA RNA FINGERPRINT FOR THE NORMAL FERTILE MALE

    Science.gov (United States)

    Defining the spermatozoa RNA fingerprint for the normal fertile male G. Charles Ostermeier1, David Dix2, David Miller3, and Stephen A. Krawetz11Departments of Ob/Gyn, CMMG & ISC, Wayne State University, USA.2Reproductive Toxicology Division, U.S. Environmental Pr...

  6. Citrullination regulates pluripotency and histone H1 binding to chromatin

    Science.gov (United States)

    Christophorou, Maria A.; Castelo-Branco, Gonçalo; Halley-Stott, Richard P.; Oliveira, Clara Slade; Loos, Remco; Radzisheuskaya, Aliaksandra; Mowen, Kerri A.; Bertone, Paul; Silva, José C. R.; Zernicka-Goetz, Magdalena; Nielsen, Michael L.; Gurdon, John B.; Kouzarides, Tony

    2014-03-01

    Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.

  7. Citrullinated Chemokines in Rheumatoid Arthritis

    Science.gov (United States)

    2016-12-01

    analysis. Imaging was done using electrochemiluminescence (ECL) reagent after 5 minute incubation. Exposure time was 1 minute for all blots. As shown...citrullinated by peptidylarginine deiminase using 18O stable isotope labeling and mass spectrometry. Rapid Commun Mass Spectrom 2005;19:683–8. 21. Ruth JH...All human specimens were consented for use in this study by the Institutional Review Boards of the University of Michigan Medical School (IRBMED). K

  8. 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.

  9. On the derivation of an hourly local index to define the normal ionosphere

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    I. Tsagouri

    2000-06-01

    Full Text Available In this paper an hourly local ionospheric index f n F 2 is proposed to define the normal level of the undisturbed ionosphere. For the determination of this index a model is developed where the normal values of the f 0 F 2 parameter were reproduced using multiple regression analysis. For each month of the year, for a given station, a set of 48 or 72 coefficients are calculated, depending on the monthly sunspot activity. Then, the normal values of the f 0 F 2 parameter are computed as a function of the daily sunspot number. The analysis of the model results revealed the following characteristics for the f n F 2 index: first, the temporal variations that characterize the normal ionosphere, imposing some artificial effects on the monthly median values, are eliminated from the newly derived f n F 2 index. Second, the f n F 2 index does not follow the false steplike variations observed in the monthly median f 0 F 2 time series, in transition periods from one month to another. Third, during intervals of low magnetospheric activity,the f n F 2 index presents a very good degree of fit with the observed f 0 F 2 parameter, compared to the monthly median f 0 F 2 behaviour. During disturbed conditions, the f n F 2 index remains at the normal level, whereas median values are affected by ionospheric disturbances. In general, the data analysis showed that the f n F 2 index varies only with the daily sunspot number Rz and is independent of the magnetospheric activity, approaching the level of the normal ionosphere with a high degree of confidence.

  10. Phenylglyoxal-Based Visualization of Citrullinated Proteins on Western Blots

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    Sanne M. M. Hensen

    2015-04-01

    Full Text Available Citrullination is the conversion of peptidylarginine to peptidylcitrulline, which is catalyzed by peptidylarginine deiminases. This conversion is involved in different physiological processes and is associated with several diseases, including cancer and rheumatoid arthritis. A common method to detect citrullinated proteins relies on anti-modified citrulline antibodies directed to a specific chemical modification of the citrulline side chain. Here, we describe a versatile, antibody-independent method for the detection of citrullinated proteins on a membrane, based on the selective reaction of phenylglyoxal with the ureido group of citrulline under highly acidic conditions. The method makes use of 4-azidophenylglyoxal, which, after reaction with citrullinated proteins, can be visualized with alkyne-conjugated probes. The sensitivity of this procedure, using an alkyne-biotin probe, appeared to be comparable to the antibody-based detection method and independent of the sequence surrounding the citrulline.

  11. Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Garred, Peter

    2007-01-01

    To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs)....

  12. Serum metabolomics identifies citrulline as a predictor of adverse outcomes in an equine model of gut-derived sepsis.

    Science.gov (United States)

    Steelman, Samantha M; Johnson, Philip; Jackson, Amy; Schulze, James; Chowdhary, Bhanu P

    2014-05-15

    Acute laminitis is an inflammatory disease of the equine foot that often occurs secondarily to sepsis or systemic inflammation associated with gastrointestinal disease. It has been suggested that laminitis is similar to multiple organ dysfunction syndrome in humans, although in horses the weight-bearing laminar epithelium of the foot appears to be the tissue most sensitive to insult and the first "organ" to fail. Metabolomics performed on serum samples collected before (Con) and after (Lmn) experimental induction of gastrointestinal-associated sepsis in six horses detected 1,177 metabolites of both mammalian and bacterial origin in equine serum. Network and correlation analyses suggested a dysregulation of fatty acid metabolism in the Lmn group, as well as an accumulation of organic acids such as lactate. Furthermore, concentrations of the amino acid citrulline were decreased in Lmn samples from all study animals, suggesting that citrulline might be useful as a biomarker to identify critically ill animals that are at risk of developing laminitis. We therefore established normal ranges of plasma citrulline concentrations in a separate group of horses (n = 36) and tested the ability of citrulline to predict adverse outcomes (laminitis or death) in critically ill horses (n = 23). Plasma citrulline was significantly lower in critically ill horses that went on to experience adverse outcomes (n = 6). Further study is required to accurately determine a diagnostic cutoff, but the present data are suggestive of the predictive value of citrulline as a biomarker for laminar failure in equine sepsis. Copyright © 2014 the American Physiological Society.

  13. Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report

    OpenAIRE

    Alexandre-Gouabau, Marie Cécile; Pagniez, Anthony; Ouguerram, Khadija; Boquien, Clair; WINER, Norbert; Darmaun, Dominique

    2017-01-01

    A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown. LBW pups born from dams fed a low (4%) protein diet, were nursed by normally-fed dams and received isonitrogenous supplements of either l-citrulli...

  14. Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer

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    Bing Yang

    2013-04-01

    Full Text Available Prostate cancer (PCa is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA prostate to histologically indistinguishable tumor-associated (TA prostate tissues detected a distinct profile of DNA methylation alterations (0.2% using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87% occurred more frequently than hypermethylation (13%. Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1 were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm and at a distance (>1 cm from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease.

  15. Mining the human tissue proteome for protein citrullination.

    Science.gov (United States)

    Lee, Chien-Yun; Wang, Dongxue; Wilhelm, Mathias; Zolg, Daniel Paul; Schmidt, Tobias; Schnatbaum, Karsten; Reimer, Ulf; Pontén, Fredrik; Uhlén, Mathias; Hahne, Hannes; Kuster, Bernhard

    2018-04-02

    Citrullination is a post-translational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations and while the modification has been linked to several diseases including rheumatoid arthritis and cancer, its physiological or pathophysiological roles remain largely unclear. In part this is owing to limitations in available methodology able to robustly enrich, detect and localize the modification. As a result, only few citrullination sites have been identified on human proteins with high confidence. In this study, we mined data from mass spectrometry-based deep proteomic profiling of 30 human tissues to identify citrullination sites on endogenous proteins. Database searching of ~70 million tandem mass spectra yielded ~13,000 candidate spectra which were further triaged by spectrum quality metrics and the detection of the specific neutral loss of isocyanic acid from citrullinated peptides to reduce false positives. Because citrullination is easily confused with deamidation, we synthetized ~2,200 citrullinated and 1,300 deamidated peptides to build a library of reference spectra. This led to the validation of 375 citrullination sites on 209 human proteins. Further analysis showed that >80% of the identified modifications sites were new and for 56% of the proteins, citrullination was detected for the first time. Sequence motif analysis revealed a strong preference for Asp and Gly, residues around the citrullination site. Interestingly, while the modification was detected in 26 human tissues with the highest levels found in brain and lung, citrullination levels did not correlate well with protein expression of the PAD enzymes. Even though the current work represents the largest survey of protein citrullination to date, the modification was mostly detected on high abundant proteins arguing that the development of specific enrichment methods would be required in order

  16. INDUCIBLE TRANSPORT SYSTEM FOR CITRULLINE IN STREPTOCOCCUS FAECALIS.

    Science.gov (United States)

    BIBB, W R; STRAUGHN, W R

    1964-04-01

    Bibb, William R. (University of North Carolina, Chapel Hill), and W. R. Straughan. Inducible transport system for citrulline in Streptococcus faecalis. J. Bacteriol. 87:815-822. 1964.-With Streptococcus faecalis F24, it was demonstrated: that the citrulline transport mechanism, induced by growth in arginine, follows enzyme kinetics; that cell membranes from induced and noninduced cells differ considerably in their ability to adsorb citrulline; that protoplasts demonstrate a similar selectivity; and that, throughout various alterations of the growth medium and growth conditions, a consistent difference in citrulline uptake between induced and noninduced cells was present. A proposed explanation based on experimental findings is offered.

  17. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Jacobsen, Søren; Klarlund, Mette

    2006-01-01

    The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients...

  18. Quantitative assessment of thallium myocardial washout rate: Importance of peak heart rate and lung thallium uptake in defining normal values

    International Nuclear Information System (INIS)

    Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Kozuka, Takahiro; Saito, Muneyasu; Sumiyoshi, Tetsuya; National Cardiovascular Center, Suita, Osaka

    1987-01-01

    Traditionally, the results of exercise thallium scintigraphy were interpreted by transient defect analysis using initial and delayed images. Recently, washout rate analysis has been used for the relative quantification of exercise thallium scintigraphy. A diffuse slow washout from all myocardial regions has been defined as the indicator of extensive coronary artery disease. However, slow washout has occasionally been observed in normal cases and in healthy myocardial segments which are not supplied by a stenosed artery in patients with single or double vessel disease. We evaluate the factors influencing washout rate in 100 normal patients and 63 patients with angina pectoris (33 cases of single vessel disease and 30 cases of double vessel disease). The washout rates were calculated using circumferential profile analysis. In normal patients, washout rate was closely related to peak heart rate (r=0.72) and inversely related to lung thallium uptake (r=-0.56). A diffuse slow washout was observed in seven (7%) of 100 normal patients, six (18%) of 33 cases of single vessel disease and eight (24%) of 30 cases of double vessel disease. The patients with diffuse slow washout showed significantly higher lung thallium uptake values and lower peak heart rates than those without diffuse slow washout (P<0.01). Thus, this false positive slow washout should be considered in the interpretation of quantitative exercise thallium scintigraphy. (orig.)

  19. Normalization.

    Science.gov (United States)

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  20. Arginine and citrulline supplementation in sports and exercise: ergogenic nutrients?

    Science.gov (United States)

    Sureda, Antoni; Pons, Antoni

    2012-01-01

    Dietary L-citrulline malate supplements may increase levels of nitric oxide (NO) metabolites, although this response has not been related to an improvement in athletic performance. NO plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. L-Arginine is the main precursor of NO via nitric oxide synthase (NOS) activity. Additionally, L-citrulline has been indicated to be a second NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. The importance of L-citrulline as an ergogenic support derives from the fact that L-citrulline is not subject to pre-systemic elimination and, consequently, could be a more efficient way to elevate extracellular levels of L-arginine by itself. L-Citrulline malate can develop beneficial effects on the elimination of NH(3) in the course of recovery from exhaustive muscular exercise and also as an effective precursor of L-arginine and creatine. Dietary supplementation with L-citrulline alone does not improve exercise performance. The ergogenic response of L-citrulline or L-arginine supplements depends on the training status of the subjects. Studies involving untrained or moderately healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly-trained subjects were supplemented, no positive effect on performance was indicated. Copyright © 2012 S. Karger AG, Basel.

  1. Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

    Directory of Open Access Journals (Sweden)

    Bin Cai

    2016-01-01

    Full Text Available Citrulline (Cit supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1β were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

  2. Diabetic nephropathy is resistant to oral L-arginine or L-citrulline supplementation.

    Science.gov (United States)

    You, Hanning; Gao, Ting; Cooper, Timothy K; Morris, Sidney M; Awad, Alaa S

    2014-12-01

    Our recent publication showed that pharmacological blockade of arginases confers kidney protection in diabetic nephropathy via a nitric oxide (NO) synthase (NOS)3-dependent mechanism. Arginase competes with endothelial NOS (eNOS) for the common substrate L-arginine. Lack of L-arginine results in reduced NO production and eNOS uncoupling, which lead to endothelial dysfunction. Therefore, we hypothesized that L-arginine or L-citrulline supplementation would ameliorate diabetic nephropathy. DBA mice injected with multiple low doses of vehicle or streptozotocin (50 mg/kg ip for 5 days) were provided drinking water with or without L-arginine (1.5%, 6.05 g·kg(-1)·day(-1)) or L-citrulline (1.66%, 5.73 g·kg(-1)·day(-1)) for 9 wk. Nonsupplemented diabetic mice showed significant increases in albuminuria, blood urea nitrogen, glomerular histopathological changes, kidney macrophage recruitment, kidney TNF-α and fibronectin mRNA expression, kidney arginase activity, kidney arginase-2 protein expression, and urinary oxidative stress along with a significant reduction of nephrin and eNOS protein expression and kidney nitrite + nitrate compared with normal mice after 9 wk of diabetes. Surprisingly, L-arginine or L-citrulline supplementation in diabetic mice did not affect any of these parameters despite greatly increasing kidney and plasma arginine levels. These findings demonstrate that chronic L-arginine or L-citrulline supplementation does not prevent or reduce renal injury in a model of type 1 diabetes. Copyright © 2014 the American Physiological Society.

  3. Administration of L-arginine plus L-citrulline or L-citrulline alone successfully retarded endothelial senescence.

    Directory of Open Access Journals (Sweden)

    Tomoe Tsuboi

    Full Text Available L-citrulline and L-arginine supplementation has been shown to have several beneficial effects on the cardiovascular system. Nitric oxide (NO protects against the progression of atherosclerosis and is synthesized by nitric oxide synthase (NOS, which converts L-arginine (L-Arg into L-citrulline (L-Cit. Our previous study revealed that chronic administration of a combination of L-Cit and L- Arg has a better therapeutic effect on high cholesterol-induced atherosclerosis in rabbits. We investigated how L-Arg and L-Cit affect endothelial function, aging and atherosclerosis. Following a 3-day stimulation of human umbilical venous endothelial cells (HUVECs with high glucose (HG: 22 mM and L-Arg (300 μM, L-Cit (300 μM or L-Arg plus L-Cit (LALC: each 150 μM supplementation, endothelial senescence and function were evaluated. These amino acids were also administered to dyslipidemic type 2 diabetic (ZDFM rats fed a high cholesterol diet. They were fed L-Arg or L-Cit or LALC for four weeks. Aortic senescence was investigated by measuring senescence-associated ß-galactosidase (SA-ß-gal, telomerase activity, DNA damage and p16INK4a protein expression. Only L-Cit and LALC supplementation retarded the HG-induced endothelial senescence, as evaluated by SA-ß-gal activity, a widely used marker of cellular senescence, p16INK4a expression, a senescence-related protein, and DNA damage. Under HG conditions, L-Cit and LCLA restored telomerase activity to levels observed under normal glucose (NG conditions. Under HG conditions, L-Cit decreased ROS production, as measured by CM-H2DCFDA and the expression of p67phox, a major component of NADPH oxidase. Under HG conditions, L-Cit and LALC increased NO production, as measured by DAF-2AM. Endothelial NO synthase (eNOS and phosphorylated eNOS were decreased under HG conditions and L-Cit and LALC significantly increased these levels. Arginase 2 protein expression increased under the HG conditions, and L-Cit and LALC

  4. Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report.

    Science.gov (United States)

    Tran, Nhat-Thang; Alexandre-Gouabau, Marie-Cécile; Pagniez, Anthony; Ouguerram, Khadija; Boquien, Clair-Yves; Winer, Norbert; Darmaun, Dominique

    2017-04-11

    A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown. LBW pups born from dams fed a low (4%) protein diet, were nursed by normally-fed dams and received isonitrogenous supplements of either l-citrulline or l-alanine by gavage from the sixth day of life until weaning, and were subsequently exposed to 10%-fructose in drinking water from weaning to 90 days of age. The oral glucose tolerance was tested (OGTT) at 70 days of age, and rats were sacrificed at 90 days of age. Pre-weaning citrulline supplementation failed to alter the growth trajectory, OGTT, plasma triglycerides, or fat mass accretion in adulthood; yet, it was associated with increased liver triglycerides, decreased liver total cholesterol, and a distinct liver lipidomic profile that may result in a predisposition to liver disease. We conclude that pre-weaning supplementation with citrulline does not impact early growth, but might impact liver fat metabolism in adulthood upon exposure to a high fructose diet.

  5. Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

    International Nuclear Information System (INIS)

    Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

    1984-01-01

    Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

  6. Citrullination only infrequently impacts peptide binding to HLA class II MHC

    DEFF Research Database (Denmark)

    Sidney, John; Becart, Stephane; Zhou, Mimi

    2017-01-01

    It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes...... and their corresponding wild-type version for binding to 28 common HLA class II. Binding patterns were variable, and no consistent impact of citrullination was identified. Indeed, in one case citrullination significantly increased binding compared to the WT peptide, in another citrullination was associated...... with a reduction in promiscuity by 40%. For a more comprehensive analysis, we tested over 200 citrullinated peptides derived from vimentin and collagen II for their capacity to bind the RA-associated shared epitope alleles DRB1*01:01 and DRB1*04:01. The overall effect of citrullination on binding was found...

  7. Arginine and Citrulline for the Treatment of MELAS Syndrome

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    Ayman W. El-Hattab MD, FACMG

    2017-03-01

    Full Text Available Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome is a maternally inherited mitochondrial disease with a broad spectrum of manifestations. In addition to impaired energy production, nitric oxide (NO deficiency occurs in MELAS syndrome and leads to impaired blood perfusion in microvasculature that can contribute to several complications including stroke-like episodes, myopathy, and lactic acidosis. The supplementation of NO precursors, L-arginine and L-citrulline, increases NO production and hence can potentially have therapeutic utility in MELAS syndrome. L-citrulline raises NO production to a greater extent than L-arginine; therefore, L-citrulline may have a better therapeutic effect. The clinical effect of L-citrulline has not yet been studied and clinical studies on L-arginine, which are limited, only evaluated the stroke-like episodes’ aspects of the disease. Controlled studies are still needed to assess the clinical effects of L-arginine and L-citrulline on different aspects of MELAS syndrome.

  8. Defining the residual risk of adverse perinatal outcome in growth restricted fetuses with normal umbilical artery blood flow.

    LENUS (Irish Health Repository)

    O'Dwyer, Vicky

    2014-07-25

    To determine the cause of adverse perinatal outcome in fetal growth restriction(FGR) where umbilical artery Doppler(UA) was normal, as identified from the Prospective Observational Trial to Optimize Pediatric Health(PORTO). We compared cases of adverse outcome where UA Doppler was normal and abnormal.

  9. Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Hutchinson D

    2018-01-01

    Full Text Available David Hutchinson,1,2 Judith Müller,3 Joseph E McCarthy,4 Yurii K Gun’ko,4,5 Navin Kumar Verma,6 Xuezhi Bi,7 Luisana Di Cristo,8 Laura Kickham,8 Dania Movia,8 Adriele Prina-Mello,5,8 Yuri Volkov5,8,9 1Royal Cornwall Hospital NHS Trust, Treliske, 2University of Exeter Medical School Cornwall, UK; 3University of Basel, Basel, Switzerland; 4School of Chemistry, 5Advanced Materials for BioEngineering Research Centre (AMBER, Trinity College Dublin, Dublin, Ireland; 6Lee Kong Chian School of Medicine, Nanyang Technological University, 7Bioprocessing Technology Institute, A*STAR Graduate Academy, Singapore; 8Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland; 9International Laboratory of Magnetically Controlled Nanosystems for Theranostics of Oncological and Cardiovascular Diseases, ITMO University, St. Petersburg, Russia Objective: The objective of the study was to determine whether the cadmium-derived materials induce intracellular protein citrullination. Methods: Human A549 lung epithelial cells were exposed to cadmium in soluble and nanoparticulate forms represented by cadmium chloride (CdCl2 and cadmium oxide (CdO, respectively, and their combinations with ultrafine carbon black (ufCB produced by high temperature combustion, imitating cigarette burning. Protein citrullination in cell lysates was analyzed by Western immunoblotting and verified by immunofluorescent confocal microscopy. Target citrullinated proteins were identified by proteomic analysis. Results: CdO, ufCB and its combination with CdCl2 and CdO after high temperature combustion induced protein citrullination in cultured human lung epithelial cells, as detected by immunoblotting with anti-citrullinated protein antibody. Cytokeratins of type II (1, 2, 5, 6A, 6B and 77 and type I (9, 10 were identified as major intracellular citrullination targets. Immunofluorescent staining confirmed the localization of citrullinated proteins both in the

  10. Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy

    International Nuclear Information System (INIS)

    Anscher, Mitchell S.; Chen, Liguang; Rabbani, Zahid; Kang Song; Larrier, Nicole; Huang Hong; Samulski, Thaddeus V.; Dewhirst, Mark W.; Brizel, David M.; Folz, Rodney J.; Vujaskovic, Zeljko

    2005-01-01

    The ability to optimize treatments for cancer on the basis of relative risks for normal tissue injury has important implications in oncology, because higher doses of radiation might, in some diseases, improve both local control and survival. To achieve this goal, a thorough understanding of the molecular mechanisms responsible for radiation-induced toxicity will be essential. Recent research has demonstrated that ionizing radiation triggers a series of genetic and molecular events, which might lead to chronic persistent alterations in the microenvironment and an aberrant wound-healing response. Disrupted epithelial-stromal cell communication might also be important. With the application of a better understanding of fundamental biology to clinical practice, new approaches to treating and preventing normal tissue injury can focus on correcting these disturbed molecular processes

  11. Expression and diagnostic utility of anti-cyclic citrullinated peptide ...

    African Journals Online (AJOL)

    Background: Juvenile idiopathic arthritis (JIA) is a clinically heterogeneous group of arthritis occurring in children. Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been recently included in the revised diagnostic criteria for adult onset rheumatoid arthritis. Its diagnostic value in JIA is still debatable. Objective: The ...

  12. Hippocampal proteomics defines pathways associated with memory decline and resilience in normal aging and Alzheimer's disease mouse models.

    Science.gov (United States)

    Neuner, Sarah M; Wilmott, Lynda A; Hoffmann, Brian R; Mozhui, Khyobeni; Kaczorowski, Catherine C

    2017-03-30

    Alzheimer's disease (AD), the most common form of dementia in the elderly, has no cure. Thus, the identification of key molecular mediators of cognitive decline in AD remains a top priority. As aging is the most significant risk factor for AD, the goal of this study was to identify altered proteins and pathways associated with the development of normal aging and AD memory deficits, and identify unique proteins and pathways that may contribute to AD-specific symptoms. We used contextual fear conditioning to diagnose 8-month-old 5XFAD and non-transgenic (Ntg) mice as having either intact or impaired memory, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify hippocampal membrane proteins across groups. Subsequent analysis detected 113 proteins differentially expressed relative to memory status (intact vs impaired) in Ntg mice and 103 proteins in 5XFAD mice. Thirty-six proteins, including several involved in neuronal excitability and synaptic plasticity (e.g., GRIA1, GRM3, and SYN1), were altered in both normal aging and AD. Pathway analysis highlighted HDAC4 as a regulator of observed protein changes in both genotypes and identified the REST epigenetic regulatory pathway and G i intracellular signaling as AD-specific pathways involved in regulating the onset of memory deficits. Comparing the hippocampal membrane proteome of Ntg versus AD, regardless of cognitive status, identified 138 differentially expressed proteins, including confirmatory proteins APOE and CLU. Overall, we provide a novel list of putative targets and pathways with therapeutic potential, including a set of proteins associated with cognitive status in normal aging mice or gene mutations that cause AD. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance.

    Science.gov (United States)

    Figueroa, Arturo; Wong, Alexei; Jaime, Salvador J; Gonzales, Joaquin U

    2017-01-01

    L-Citrulline, either synthetic or in watermelon, may improve vascular function through increased L-arginine bioavailability and nitric oxide synthesis. This article analyses potential vascular benefits of L-citrulline and watermelon supplementation at rest and during exercise. There is clear evidence that acute L-citrulline ingestion increases plasma L-arginine, the substrate for endothelial nitric oxide synthesis. However, the subsequent acute improvement in nitric oxide production and mediated vasodilation is inconsistent, which likely explains the inability of acute L-citrulline or watermelon to improve exercise tolerance. Recent studies have shown that chronic L-citrulline supplementation increases nitric oxide synthesis, decreases blood pressure, and may increase peripheral blood flow. These changes are paralleled by improvements in skeletal muscle oxygenation and performance during endurance exercise. The antihypertensive effect of L-citrulline/watermelon supplementation is evident in adults with prehypertension or hypertension, but not in normotensives. However, L-citrulline supplementation may attenuate the blood pressure response to exercise in normotensive men. The beneficial vascular effects of L-citrulline/watermelon supplementation may stem from improvements in the L-arginine/nitric oxide pathway. Reductions in resting blood pressure with L-citrulline/watermelon supplementation may have major implications for individuals with prehypertension and hypertension. L-Citrulline supplementation, but not acute ingestion, have shown to improve exercise performance in young healthy adults.

  14. The Effects of Methylene Blue on Autophagy and Apoptosis in MRI-Defined Normal Tissue, Ischemic Penumbra and Ischemic Core.

    Directory of Open Access Journals (Sweden)

    Zhao Jiang

    Full Text Available Methylene blue (MB USP, which has energy-enhancing and antioxidant properties, is currently used to treat methemoglobinemia and cyanide poisoning in humans. We recently showed that MB administration reduces infarct volume and behavioral deficits in rat models of ischemic stroke and traumatic brain injury. This study reports the underlying molecular mechanisms of MB neuroprotection following transient ischemic stroke in rats. Rats were subjected to transient (60-mins ischemic stroke. Multimodal MRI during the acute phase and at 24 hrs were used to define three regions of interest (ROIs: i the perfusion-diffusion mismatch salvaged by reperfusion, ii the perfusion-diffusion mismatch not salvaged by reperfusion, and iii the ischemic core. The tissues from these ROIs were extracted for western blot analyses of autophagic and apoptotic markers. The major findings were: 1 MB treatment reduced infarct volume and behavioral deficits, 2 MB improved cerebral blood flow to the perfusion-diffusion mismatch tissue after reperfusion and minimized harmful hyperperfusion 24 hrs after stroke, 3 MB inhibited apoptosis and enhanced autophagy in the perfusion-diffusion mismatch, 4 MB inhibited apoptotic signaling cascades (p53-Bax-Bcl2-Caspase3, and 5 MB enhanced autophagic signaling cascades (p53-AMPK-TSC2-mTOR. MB induced neuroprotection, at least in part, by enhancing autophagy and reducing apoptosis in the perfusion-diffusion mismatch tissue following ischemic stroke.

  15. Prolonged hypoxia augments l-citrulline transport by System A in the newborn piglet pulmonary circulation

    Science.gov (United States)

    Fike, Candice D.; Sidoryk-Wegrzynowicz, Marta; Aschner, Michael; Summar, Marshall; Prince, Lawrence S.; Cunningham, Gary; Kaplowitz, Mark; Zhang, Yongmei; Aschner, Judy L.

    2012-01-01

    Aims Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can be converted to l-citrulline and nitric oxide (NO) by the enzyme NO synthase. We sought to determine whether hypoxia, a condition aetiologically linked to pulmonary hypertension, alters the transport of l-citrulline and the expression of the sodium-coupled neutral amino acid transporters (SNATs) in PAECs from newborn piglets. Methods and results PAECs isolated from newborn piglets were cultured under normoxic and hypoxic conditions and used to measure SNAT1, 2, 3, and 5 protein expression and 14C-l-citrulline uptake. SNAT1 protein expression was increased, while SNAT2, SNAT3, and SNAT5 expression was unaltered in hypoxic PAECs. 14C-l-citrulline uptake was increased in hypoxic PAECs. Studies with inhibitors of System A (SNAT1/2) and System N (SNAT3/5) revealed that the increased 14C-l-citrulline uptake was largely due to System A-mediated transport. Additional studies were performed to evaluate SNAT protein expression and l-citrulline levels in lungs of piglets with chronic hypoxia-induced pulmonary hypertension and comparable age controls. Lungs from piglets raised in chronic hypoxia exhibited greater SNAT1 expression and higher l-citrulline levels than lungs from controls. Conclusion Increased SNAT1 expression and the concomitant enhanced ability to transport l-citrulline in PAECs could represent an important regulatory mechanism to counteract NO signalling impairments known to occur during the development of chronic hypoxia-induced pulmonary hypertension in newborns. PMID:22673370

  16. Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology

    DEFF Research Database (Denmark)

    Vassiliadis, E.; Oliveira, C. P.; Alvares-da-Silva, M. R.

    2012-01-01

    Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV-citrulline ......Aim: To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes. Methods: A monoclonal antibody against the sequence RLRSSVPGV...

  17. Plasma citrulline levels predict intestinal toxicity in patients treated with pelvic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Onal, Cem; Kotek, Ayse; Arslan, Gungor; Topkan, Erkan (Dept. of Radiation Oncology, Baskent Univ. Faculty of Medicine, Adana (Turkey)), E-mail: hcemonal@hotmail.com; Unal, Birsel (Dept. of Biochemistry, Baskent Univ. Faculty of Medicine, Ankara (Turkey)); Yavuz, Aydin; Yavuz, Melek (Dept. of Radiation Oncology, Akdeniz Univ. Faculty of Medicine, Antalya (Turkey))

    2011-11-15

    Background. Radiotherapy (RT) for abdominal and pelvic malignancies often causes severe small bowel toxicity. Citrulline concentrations are known to decrease with intestinal failure. We thus evaluated the feasibility of plasma citrulline levels in predicting radiation-induced intestinal toxicity. Material and methods. Fifty-three patients (36 prostate cancer, 17 endometrial cancer) who received 45 Gy pelvic RT using conventional fractionation were prospectively evaluated. Patients with prostate cancer received an additional 25-30.6 Gy conformal boost. Plasma citrulline levels were assessed on day 0, mid- (week 3) and post-RT (week 8), and four months post-RT. Dose-volume histogram, citrulline concentration changes, and weekly intestinal toxicity scores were analyzed. Results. Mean age was 63 years (range: 43-81 years) and mean baseline citrulline concentration was 38.0 +- 10.1 mumol/l. Citrulline concentrations were significantly reduced at week 3 (27.4 +- 5.9 mumol/l; p < 0.0001), treatment end (29.9 +- 8.8 mumol/l; p < 0.0001), and four months post-treatment (34.3 +- 12.1; p 0.01). The following factor pairs were significantly positively correlated: Citrulline concentration/mean bowel dose during, end of treatment, and four months post-RT; dose-volume parameters/citrulline change groups; cumulative mean radiation dose/intestinal toxicity at end and four months post-RT; citrulline changes/intestinal toxicity during and end of RT. Citrulline concentration changes significantly differed during treatment according to RTOG intestinal toxicity grades (p < 0.0001). Although the citrulline changes differed significantly within RTOG intestinal toxicity grades (p = 0.003), the difference between Grade 0 and Grade 1 did not differ significantly at the end of the treatment. At four months after RT, no significant differences were apparent. Conclusion. Citrulline-based assessment scores are objective and should be considered in measuring radiation-induced intestinal toxicity

  18. Arginine and Citrulline and the Immune Response in Sepsis

    Science.gov (United States)

    Wijnands, Karolina A.P.; Castermans, Tessy M.R.; Hommen, Merel P.J.; Meesters, Dennis M.; Poeze, Martijn

    2015-01-01

    Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO) and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target. PMID:25699985

  19. Arginine and Citrulline and the Immune Response in Sepsis

    Directory of Open Access Journals (Sweden)

    Karolina A.P. Wijnands

    2015-02-01

    Full Text Available Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target.

  20. L-citrulline attenuates arrested alveolar growth and pulmonary hypertension in oxygen-induced lung injury in newborn rats.

    Science.gov (United States)

    Vadivel, Arul; Aschner, Judy L; Rey-Parra, Gloria J; Magarik, Jordan; Zeng, Heng; Summar, Marshall; Eaton, Farah; Thébaud, Bernard

    2010-12-01

    Bronchopulmonary dysplasia (BPD) is characterized by arrested alveolar development and complicated by pulmonary hypertension (PH). NO promotes alveolar growth. Inhaled NO (iNO) ameliorates the BPD phenotype in experimental models and in some premature infants. Arginosuccinate synthetase (ASS) and arginosuccinate lyase (ASL) convert L-citrulline to L-arginine; L-citrulline is regenerated during NO synthesis from L-arginine. Plasma levels of these NO precursors are low in PH. We hypothesized that L-citrulline prevents experimental O2-induced BPD in newborn rats. Rat pups were assigned from birth through postnatal day (P) 14 to room air (RA), RA + L-citrulline, 95% hyperoxia (BPD model), and 95%O2 + L-citrulline. Rat pups exposed to hyperoxia had fewer and enlarged air spaces and decreased capillary density, mimicking human BPD. This was associated with decreased plasma L-arginine and L-citrulline concentrations on P7. L-citrulline treatment significantly increased plasma L-arginine and L-citrulline concentrations and increased ASL protein expression in hyperoxia. L-citrulline preserved alveolar and vascular growth in O2-exposed pups and decreased pulmonary arterial medial wall thickness (MWT) and right ventricular hypertrophy (RVH). Increased lung arginase (ARG) activity in O2-exposed pups was reversed by L-citrulline treatment. L-citrulline supplementation prevents hyperoxia-induced lung injury and PH in newborn rats. L-citrulline may represent a novel therapeutic alternative to iNO for prevention of BPD.

  1. Plasma glutamine is a minor precursor for the synthesis of citrulline: A multispecies study

    Science.gov (United States)

    Glutamine is considered the main precursor for citrulline synthesis in many species, including humans. The transfer of 15N from 2[15N]-glutamine to citrulline has been used as evidence for this precursor-product relationship. However, work in mice has shown that nitrogen and carbon tracers follow di...

  2. Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in early arthritis

    NARCIS (Netherlands)

    Nielen, M. M. J.; van der Horst, A. R.; van Schaardenburg, D.; van der Horst-Bruinsma, I. E.; van de Stadt, R. J.; Aarden, L.; Dijkmans, B. A. C.; Hamann, D.

    2005-01-01

    The anti-cyclic citrullinated peptide (CCP) test has a high sensitivity and specificity for rheumatoid arthritis, although CCP is not the physiological target of the autoantibodies. Citrullinated fibrin is abundant in inflamed synovium To assess the diagnostic and prognostic value of antibodies

  3. Spatial accumulation pattern of citrulline and other nutrients in immature and mature watermelon fruits.

    Science.gov (United States)

    Akashi, Kinya; Mifune, Yuki; Morita, Kaori; Ishitsuka, Souichi; Tsujimoto, Hisashi; Ishihara, Toshiyuki

    2017-01-01

    Watermelon (Citrullus lanatus L.) originates from arid regions of southern Africa, and its fruit contains a large amount of the amino acid citrulline, an efficient hydroxyl radical scavenger. Citrulline is implicated in the production of nitric oxide in human endothelium, and potential health benefits including vasodilatation and antioxidant functions have been suggested. However, citrulline metabolism in watermelon fruits is poorly understood. This study examined the accumulation pattern of citrulline and other nutrients in immature and mature watermelon fruits. In mature fruits, highest citrulline concentration was observed in the outer peel, followed by the central portion of the flesh and inner rinds, whereas the level was lower in the peripheral portion of the flesh. Citrulline content was generally low in immature fruits. Spatial and developmental patterns of citrulline accumulation were largely different from those of the antioxidant lycopene, total proteins, and soluble sugars such as glucose, fructose, and sucrose. Principal component analysis suggested a clear distinction of the central flesh and outer peels in mature fruits from other tissues in terms of the levels of major nutrients. These observations suggested that citrulline accumulation may be regulated in a distinct manner from other nutrients during watermelon fruit maturation. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  4. Application of synthetic peptides for detection of anti-citrullinated peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole

    2016-01-01

    Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and represent an important tool for the serological diagnosis of RA. In this study, we describe ACPA reactivity to overlapping citrullinated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-derived peptides and...

  5. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis.

    Science.gov (United States)

    Wegner, Natalia; Lundberg, Karin; Kinloch, Andrew; Fisher, Benjamin; Malmström, Vivianne; Feldmann, Marc; Venables, Patrick J

    2010-01-01

    Rheumatoid arthritis (RA) is now clearly a true autoimmune disease with accumulating evidence of pathogenic disease-specific autoimmunity to citrullinated proteins. Citrullination, also termed deimination, is a modification of arginine side chains catalyzed by peptidylarginine deiminase (PAD) enzymes. This post-translational modification has the potential to alter the structure, antigenicity, and function of proteins. In RA, antibodies to cyclic citrullinated peptides are now well established for clinical diagnosis, though we argue that the identification of specific citrullinated antigens, as whole proteins, is necessary for exploring pathogenic mechanisms. Four citrullinated antigens, fibrinogen, vimentin, collagen type II, and alpha-enolase, are now well established, with others awaiting further characterization. All four proteins are expressed in the joint, and there is evidence that antibodies to citrullinated fibrinogen and collagen type II mediate inflammation by the formation of immune complexes, both in humans and animal models. Antibodies to citrullinated proteins are associated with HLA 'shared epitope' alleles, and autoimmunity to at least one antigenic sequence, the CEP-1 peptide from citrullinated alpha-enolase (KIHAcitEIFDScitGNPTVE), shows a specific association with HLA-DRB1*0401, *0404, 620W PTPN22, and smoking. Periodontitis, in which Porphyromonas gingivalis is a major pathogenic bacterium, has been linked to RA in epidemiological studies and also shares similar gene/environment associations. This is also the only bacterium identified that expresses endogenous citrullinated proteins and its own bacterial PAD enzyme, though the precise molecular mechanisms of bacterial citrullination have yet to be explored. Thus, both smoking and Porphyromonas gingivalis are attractive etiological agents for further investigation into the gene/environment/autoimmunity triad of RA.

  6. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P

    2014-01-01

    citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune...... and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel...

  7. Physical characteristics of a citrullinated pro-filaggrin epitope recognized by anti-citrullinated protein antibodies in rheumatoid arthritis sera

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole

    2016-01-01

    whether biotin labelling influence antibody recognition. The full-length cyclic pro-filaggrin peptide and a linear form with a N-terminal biotin, was recognized to the same level, whereas, a notable difference in ACPA reactivity to the linear peptides with a C-terminal biotin was found, probably due...... amino acid in position 4 C-terminal to citrulline. Collectively, peptide structure, length, the presence of charged amino acids and biotin labelling markedly influence antibody reactivity. In relation to the clinical diagnostics of ACPA, these findings may reflect the differences in diagnostic assays...

  8. [Preparation of citrulline microspheres by spray drying technique for colonic targeting].

    Science.gov (United States)

    Bahri, S; Zerrouk, N; Lassoued, M-A; Tsapis, N; Chaumeil, J-C; Sfar, S

    2014-03-01

    Citrulline is an amino acid that becomes essential in situations of intestinal insufficiency such as short bowel syndrome. It is therefore interesting to provide the patients with dosage forms for routing citrulline to the colon. The aim of this work is to formulate microspheres of citrulline for colonic targeting by the technique of spray drying. Eudragit(®) FS 30D was selected as polymer to encapsulate citrulline using the spray drying technique. Citrulline and Eudragit(®) FS 30D were dissolved in water and ethanol, respectively. The aqueous and the ethanolic solutions were then mixed in 1:2 (v/v) ratio. Microspheres were obtained by nebulizing the citrulline-Eudragit(®) FS 30D solution using a Mini spray dryer equipped with a 0.7mm nozzle. The microspheres have been formulated using citrulline and Eudragit(®) FS 30D. The size distribution of microspheres was determined by light diffraction. The morphology of the microspheres was studied by electron microscopy. Manufacturing yields, encapsulation rate and dissolution profiles were also studied. The microspheres obtained had a spherical shape with a smooth surface and a homogeneous size except for the microspheres containing the highest concentration of polymer (90 %). The formulation showed that the size and morphology of the microspheres are influenced by the polymer concentration. Manufacturing yields were about 51 % but encapsulation rate were always very high (above 90 %). The in vitro dissolution study showed that the use of the Eudragit(®) FS 30D under these conditions is not appropriate to change the dissolution profile of the citrulline. This technique has led to the formulation of microspheres with good physical properties in terms of morphology and size. The compression of the microspheres should help to control citrulline release for colonic targeting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  9. Using reference values to define disease based on the lower limit of normal biased the population attributable fraction, but not the population excess risk: the example of chronic airflow obstruction.

    Science.gov (United States)

    Burney, Peter; Minelli, Cosetta

    2018-01-01

    The impact of disease on population health is most commonly estimated by the population attributable fraction (PAF), or less commonly by the excess risk, an alternative measure that estimates the absolute risk of disease in the population that can be ascribed to the exposure. Using chronic airflow obstruction as an example, we examined the impact on these estimates of defining disease based on different "normal" values. We estimated PAF and the excess risk in scenarios in which the true rate of disease was 10% in the exposed and 5% in the unexposed, and where either 50% or 20% of the population was exposed. Disease definition was based on a "lower limit of normal", using the 5th, 1st and 0.2nd centile of values in a "normal" population as thresholds to define normality. Where normality is defined by centiles of values in a "normal" population, PAF is strongly influenced by which centile is selected to define normality. This is not true for the population excess risk. Care should be taken when interpreting estimates of PAF when disease is defined from a centile of a normal population. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Free and cued memory in relation to biomarker-defined abnormalities in clinically normal older adults and those at risk for Alzheimer's disease.

    Science.gov (United States)

    Papp, Kathryn V; Amariglio, Rebecca E; Mormino, Elizabeth C; Hedden, Trey; Dekhytar, Maria; Johnson, Keith A; Sperling, Reisa A; Rentz, Dorene M

    2015-07-01

    Furthering our understanding of the relationship between amyloidosis (Aβ), neurodegeneration (ND), and cognition is imperative for early identification and early intervention of Alzheimer's disease (AD). However, the subtle cognitive decline differentially associated with each biomarker-defined stage of preclinical AD has yet to be fully characterized. Recent work indicates that different components of memory performance (free and cued recall) may be differentially specific to memory decline in prodromal AD. We sought to examine the relationship between free and cued recall paradigms, in addition to global composites of memory, executive functioning, and processing speed in relation to stages of preclinical AD. A total of 260 clinically normal (CN) older adults (CDR=0) from the Harvard Aging Brain study were grouped according to preclinical AD stages including Stage 0 (Aβ-/ND-), Stage 1 (Aβ+/ND-), Stage 2 (Aβ+/ND+), and suspected non-Alzheimer's associated pathology (SNAP; Aβ-/ND+). General linear models controlling for age, sex, and education were used to assess for stage-based performance differences on cognitive composites of executive functioning, processing speed, and memory in addition to free and cued delayed recall on the Selective Reminding Test (SRT) and Memory Capacity Test (MCT). Global memory performance differed between preclinical stages with Stage 2 performing worse compared with Stage 0. When examining free and cued paradigms by memory test, only the MCT (and not the SRT) revealed group differences. More specifically, Stage 1 was associated with decrements in free recall compared with Stage 0 while Stage 2 was associated with decrements in both free and cued recall. There was a trend for the SNAP group to perform worse on free recall compared with Stage 0. Finally, there was no association between preclinical stage and global composites of executive functioning or processing speed. Clinically normal older adults with underlying evidence of

  11. Specific presence of intracellular citrullinated proteins in rheumatoid arthritis synovium: relevance to antifilaggrin autoantibodies

    NARCIS (Netherlands)

    Baeten, D.; Peene, I.; Union, A.; Meheus, L.; Sebbag, M.; Serre, G.; Veys, E. M.; de Keyser, F.

    2001-01-01

    OBJECTIVE: To investigate the presence of citrullinated proteins in the synovial membrane of patients with rheumatoid arthritis (RA) and controls, and to analyze a possible relationship with antifilaggrin autoantibody (AFA) reactivity. METHODS: Synovial biopsy samples were obtained from 88

  12. The effects of watermelon (Citrullus lanatus) extracts and L-citrulline on rat uterine contractility.

    Science.gov (United States)

    Munglue, Phukphon; Eumkep, Graingsak; Wray, Susan; Kupittayanant, Sajeera

    2013-04-01

    In uterine smooth muscle, the effects of watermelon and its citrulline content are unknown. The aims of this study were therefore, to determine the effects of watermelon extract and citrulline on the myometrium and to investigate their mechanisms of action. The effects of extracts of watermelon flesh and rind and L-citrulline (64 μmol/L) were evaluated on 3 types of contractile activity; spontaneous, those elicited by potassium chloride (KCl) depolarization, or oxytocin (10 nmol/L) application in isolated rat uterus. Inhibitors of nitric oxide (NO) and its mechanisms of action, N ω-Nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 μmol/L), LY83583 (1 μmol/L), and tetraethylamonium chloride (5 mmol/L), as well as Ca signaling pathways, were determined. Both flesh and rind extracts significantly decreased the force produced by all 3 mechanisms, in a dose-dependent manner. The extracts could also significantly decrease the force under conditions of sustained high Ca levels (depolarization and agonist) and when the force was produced only by sarcoplasmic reticulum (SR) Ca release. L-citrulline produced the same effects on force as watermelon extracts. With submaximal doses of extract, the additive effects of L-citrulline were found. The inhibitory effects of extracts and L-citrulline were reversed upon the addition of NO inhibitors, and pretreatment of tissues with these inhibitors prevented the actions of both extracts and L-citrulline. Thus, these data show that watermelon and citrulline are potent tocolytics, decreasing the force produced by calcium entry and SR release and arising by different pathways, including oxytocin stimulation. Their major mechanism is to stimulate the NO-cyclic guanosine monophosphate (cGMP) relaxant pathway.

  13. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity.

    Science.gov (United States)

    Wijnands, Karolina A P; Meesters, Dennis M; van Barneveld, Kevin W Y; Visschers, Ruben G J; Briedé, Jacob J; Vandendriessche, Benjamin; van Eijk, Hans M H; Bessems, Babs A F M; van den Hoven, Nadine; von Wintersdorff, Christian J H; Brouckaert, Peter; Bouvy, Nicole D; Lamers, Wouter H; Cauwels, Anje; Poeze, Martijn

    2015-06-29

    Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with L-arginine supplementation exhibited less consistent results; however, L-citrulline, the precursor of L-arginine, may be a promising alternative. In this study, we determined the effects of L-citrulline compared to L-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with L-citrulline or L-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. L-arginine and L-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that L-citrulline, and not L-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues.

  14. Peptidylarginine deiminase 2 is required for tumor necrosis factor alpha-induced citrullination and arthritis, but not neutrophil extracellular trap formation

    DEFF Research Database (Denmark)

    Bawadekar, Mandar; Shim, Daeun; Johnson, Chad J

    2017-01-01

    Citrullination, the post-translational conversion of arginines to citrullines, may contribute to rheumatoid arthritis development given the generation of anti-citrullinated protein antibodies (ACPAs). However, it is not known which peptidylarginine deiminase (PAD) catalyzes the citrullination seen...... and pathological scoring were all reduced in the absence of PAD2. Thus, PAD2 contributes to TNFα-induced citrullination and arthritis, but is not required for NETosis. In contrast, PAD4, which is critical for NETosis, is dispensable for generalized citrullination supporting the possibility that NETs may...

  15. Citrulline a More Suitable Substrate than Arginine to Restore NO Production and the Microcirculation during Endotoxemia

    Science.gov (United States)

    Wijnands, Karolina A. P.; Vink, Hans; Briedé, Jacob J.; van Faassen, Ernst E.; Lamers, Wouter H.; Buurman, Wim A.; Poeze, Martijn

    2012-01-01

    Background Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. Methodology/Principal Findings To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg•g bodyweight−1•h−1), combined with either L-Citrulline (6.25 mg•h-1), L-Arginine (6.25 mg•h−1), or L-Alanine (isonitrogenous control; 12.5 mg•h−1) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. Conclusion/Significance L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the

  16. Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia.

    Directory of Open Access Journals (Sweden)

    Karolina A P Wijnands

    Full Text Available BACKGROUND: Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. METHODOLOGY/PRINCIPAL FINDINGS: To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg • g bodyweight(-1 • h(-1, combined with either L-Citrulline (6.25 mg • h-1, L-Arginine (6.25 mg • h(-1, or L-Alanine (isonitrogenous control; 12.5 mg • h(-1 during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. CONCLUSION/SIGNIFICANCE: L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability

  17. Formation of Radioactive Citrulline During PhotosyntheticC14O2-Fixation by Blue-Green Algae

    Energy Technology Data Exchange (ETDEWEB)

    Linko, Pekka; Holm-Hansen, O; Bassham, J A; Calvin, M

    1956-08-28

    Citrilline has been isolated and identified from extracts of Nostoc muscorum. All members of the Cyanophyceae hitherto investigated show a relatively large amount of the CO fixed during photosynthesis in citrulline (ranging as high as 20% in Nostoc) when compared to the trace amounts found in the Chlorophyceae. Nostoc also has the ability to fix C{sup 14} in citrulline during dark fixation, but at a rate slower than in light. As no free urea or arginine was found in Nostoc, it is likely that citrulline is functioning in reactions other than those leading to arginine and urea synthesis. Other possible functions for citrulline are briefly discussed.

  18. Application of synthetic peptides for detection of anti-citrullinated peptide antibodies.

    Science.gov (United States)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Slot, Ole; Locht, Henning; Lindegaard, Hanne; Svendsen, Anders; Nielsen, Christoffer Tandrup; Jacobsen, Søren; Theander, Elke; Houen, Gunnar

    2016-02-01

    Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and represent an important tool for the serological diagnosis of RA. In this study, we describe ACPA reactivity to overlapping citrullinated Epstein-Barr virus nuclear antigen-1 (EBNA-1)-derived peptides and analyze their potential as substrates for ACPA detection by streptavidin capture enzyme-linked immunosorbent assay. Using systematically overlapping peptides, containing a 10 amino acid overlap, labelled with biotin C-terminally or N-terminally, sera from 160 individuals (RA sera (n=60), healthy controls (n=40), systemic lupus erythematosus (n=20), Sjögren's syndrome (n=40)) were screened for antibody reactivity. Antibodies to a panel of five citrullinated EBNA-1 peptides were found in 67% of RA sera, exclusively of the IgG isotype, while 53% of the patient sera reacted with a single peptide, ARGGSRERARGRGRG-Cit-GEKR, accounting for more than half of the ACPA reactivity alone. Moreover, these antibodies were detected in 10% of CCP2-negative RA sera. In addition, 47% of the RA sera reacted with two or three citrullinated EBNA-1 peptides from the selected peptide panel. Furthermore, a negative correlation between the biotin attachment site and the location of citrulline in the peptides was found, i.e. the closer the citrulline was located to biotin, the lower the antibody reactivity. Our data suggest that citrullinated EBNA-1 peptides may be considered a substrate for the detection of ACPAs and that the presence of Epstein-Barr virus may play a role in the induction of these autoantibodies. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. IgG reactivity against citrullinated myelin basic protein in multiple sclerosis.

    Science.gov (United States)

    de Seze, J; Dubucquoi, S; Lefranc, D; Virecoulon, F; Nuez, I; Dutoit, V; Vermersch, P; Prin, L

    2001-07-02

    An increased level of citrullinated myelin basic protein (MBP-C8) has been reported in the brains of multiple sclerosis (MS) patients. However, the involvement of the immune response to post-translational modified MBP in the pathophysiology of MS remains speculative. The aim of this study was to compare the levels of immunoglobulin G antibodies to several MBP epitopes, before and after citrullination, in the cerebrospinal fluid (CSF) and sera of MS patients using enzyme-linked immunosorbent assay (ELISA). We analyzed antibody reactivity against various MBP-peptides in the CSF and sera of 60 MS patients, and 30 patients with other neurological diseases (OND) as controls. The peptides tested were: MBP(75-98) (peptide 1), native (peptide 2) and citrullinated (peptide 3) MBP(108-126) (ARG(122)-->Cit(122)), and native (peptide 4) and citrullinated (peptide 5) MBP(151-170) (ARG(159, 170)-->Cit(159, 170)). All selected peptides could support an immune reactivity in CSF and sera of MS and OND patients. A higher reactivity against peptide 4 was found in the CSF of MS patients compared with OND patients (P<0.0001), but not against citrullinated peptides (peptides 3 and 5). However, we observed that the citrullination state of peptide 2 modified the patterns of immune reactivity more markedly in MS patients (P<0.0001) than in OND patients (P<0.02). Although some MBP epitopes could be a potential target in MS, our data did not demonstrate any difference of antibody response to MBP peptides in their citrullinated forms.

  20. The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation

    NARCIS (Netherlands)

    Nesse, Willem; Westra, Johanna; van der Wal, Jacqueline E.; Abbas, Frank; Nicholas, Anthony P.; Vissink, Arjan; Brouwer, Elisabeth; Westra J., [No Value

    Aim To determine the presence and location (stroma versus epithelium) of citrullinated proteins in periodontitis tissue as compared to non-periodontitis tissue and synovial tissue of RA patients. Materials & Methods Periodontitis, healthy periodontal and RA-affected synovial tissue samples were

  1. Anti-citrullinated protein antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell-surface binding to citrullinated heat shock protein 60.

    Science.gov (United States)

    Lu, Ming-Chi; Yu, Chia-Li; Yu, Hui-Chun; Huang, Hsien-Bin; Koo, Malcolm; Lai, Ning-Sheng

    2016-01-01

    We hypothesized that anti-citrullinated protein antibodies (ACPAs) react with osteoblast surface citrullinated proteins and affect cell function, leading to joint damage in patients with rheumatoid arthritis (RA). First, we purified ACPAs by cyclic citrullinated peptide (CCP)-conjugated affinity column chromatography. The cognate antigens of ACPAs on Saos-2 cells, a sarcoma osteogenic cell line generated from human osteoblasts, were probed by ACPAs, and the reactive bands were analyzed using proteomic analyses. We found that ACPAs bind to Saos-2 cell membrane, and several protein candidates, including HSP60, were identified. We then cloned and purified recombinant heat shock protein 60 (HSP60) and citrullinated HSP60 (citHSP60) and investigated the effect of ACPAs on Saos-2 cell. We confirmed that HSP60 obtained from Saos-2 cell membrane were citrullinated and reacted with ACPAs, which induces Saos-2 cells apoptosis via binding to surface-expressed citHSP60 through Toll-like receptor 4 signaling. ACPAs promoted interleukin (IL)-6 and IL-8 expression in Saos-2 cells. Finally, sera from patients with RA and healthy controls were examined for their titers of anti-HSP60 and anti-citHSP60 antibodies using an enzyme-linked immunosorbent assay. The radiographic change in patients with RA was evaluated using the Genant-modified Sharp scoring system. Patients with RA showed higher sera titers of anti-citHSP60, but not anti-HSP60, antibodies when compared with controls. In addition, the anti-citHSP60 level was positively associated with increased joint damage in patients with RA. In conclusion, Saos-2 cell apoptosis was mediated by ACPAs via binding to cell surface-expressed citHSP60 and the titer of anti-citHSP60 in patients with RA positively associated with joint damage. Copyright © 2015 Elsevier GmbH. All rights reserved.

  2. A combination of plasma DAO and citrulline levels as a potential marker for acute mesenteric ischemia

    Directory of Open Access Journals (Sweden)

    Rıdvan Çakmaz

    2013-03-01

    Full Text Available Introduction: There is no valid and reliable diagnostic test for early diagnosis of acute mesenteric ischemia (AMI. The aim of this study was to measure the plasma levels of diamine oxidase (DAO and citrulline in AMI to gain insight into its early diagnosis. Material and methods: A total of 21 Wistar albino rats were divided into three groups, that is, control group, short-term ischemia group, and prolonged ischemia group. The superior mesenteric artery was occluded for 15 min in the short-term ischemia group and for 12 h in the prolonged ischemia group. Twelve hours later, the experiment was terminated and plasma DAO and citrulline levels were measured. Intestinal tissue was evaluated for the histopathological changes. Results: Compared to the control group, the short-term and prolonged ischemia groups showed significant increases in the plasma levels of DAO, whereas the plasma citrulline levels decreased significantly. Prolonged ischemia caused a larger increase in the plasma DAO levels and a larger decrease in the plasma citrulline levels compared to the short-term ischemia (p=0.011 and p=0.021, respectively. Intestinal damage was shown to develop more in the prolonged ischemia group (p=0.001. Conclusion: In the early period of AMI, the plasma DAO levels increase while citrulline levels decrease, and the extent of these changes depends on the duration of ischemia.

  3. Citrullination in the periodontium--a possible link between periodontitis and rheumatoid arthritis.

    Science.gov (United States)

    Laugisch, Oliver; Wong, Alicia; Sroka, Aneta; Kantyka, Tomasz; Koziel, Joanna; Neuhaus, Klaus; Sculean, Anton; Venables, Patrick J; Potempa, Jan; Möller, Burkhard; Eick, Sigrun

    2016-05-01

    The aim of the present study was to assess human and bacterial peptidylarginine deiminase (PAD) activity in the gingival crevicular fluid (GCF) in the context of serum levels of antibodies against citrullinated epitopes in rheumatoid arthritis and periodontitis. Human PAD and Porphyromonas gingivalis-derived enzyme (PPAD) activities were measured in the GCF of 52 rheumatoid arthritis (RA) patients (48 with periodontitis and 4 without) and 44 non-RA controls (28 with periodontitis and 16 without). Serum antibodies against citrullinated epitopes were measured by ELISA. Bacteria being associated with periodontitis were determined by nucleic-acid-based methods. Citrullination was present in 26 (50%) RA patients and 23 (48%) controls. PAD and PPAD activities were detected in 36 (69%) and 30 (58%) RA patients, respectively, and in 30 (68%) and 21 (50%) controls, respectively. PPAD activity was higher in RA and non-RA patients with periodontitis than in those without (p = 0.038; p = 0.004), and was detected in 35 of 59 P. gingivalis-positive samples, and in 16 of 37 P. gingivalis-negative samples in association with high antibody levels against that species. PAD and PPAD activities within the periodontium are elevated in RA and non-RA patients with periodontitis. PPAD secreted by P. gingivalis residing in epithelial cells may exert its citrullinating activity in distant regions of the periodontium or even distant tissues. In periodontitis, the citrullination of proteins/peptides by human and bacterial peptidylarginine deiminases may generate antibodies after breaching immunotolerance in susceptible individuals.

  4. Affinity Purification and Comparative Biosensor Analysis of Citrulline-Peptide-Specific Antibodies in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Eszter Szarka

    2018-01-01

    Full Text Available Background: In rheumatoid arthritis (RA, anti-citrullinated protein/peptide antibodies (ACPAs are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide-specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement-activating peptide were used to induce selective depletion of ACPA-producing B cells. Results: KD values of affinity-purified ACPA IgGs varied between 10−6 and 10−8 M and inversely correlated with disease activity. Based on their cross-reaction with citrulline-peptides, we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two–two copies, separated with a short, neutral spacer. This peptide detected antibodies in RA sera with 66% sensitivity and 98% specificity in ELISA and was recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targeted and depleted ACPA-producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed based on ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.

  5. Heritability and genetic variance for citrulline, arginine and lycopene content in a diverse set of watermelon cultigens

    Science.gov (United States)

    Citrulline, arginine, and lycopene are naturally occurring compounds found in watermelon, Citrullus lanatus (Thumb) Matsum & Nakai, with beneficial effects on plant growth and human health. This study evaluated seven commercial cultivars and one breeding line for citrulline, arginine, and lycopene c...

  6. Shades of white : diffusion properties of T1- and FLAIR-defined white matter signal abnormalities differ in stages from cognitively normal to dementia

    NARCIS (Netherlands)

    Riphagen, Joost M.; Gronenschild, Ed HBM; Salat, David H.; Freeze, Whitney M.; Ivanov, Dimo; Clerx, Lies; Verhey, Frans R. J.; Aalten, Pauline; Jacobs, Heidi I. L.

    The underlying pathology of white matter signal abnormalities (WMSAs) is heterogeneous and may vary dependent on the magnetic resonance imaging contrast used to define them. We investigated differences in white matter diffusivity as an indicator for white matter integrity underlying WMSA based on

  7. L-citrulline supplementation reverses the impaired airway relaxation in neonatal rats exposed to hyperoxia

    Directory of Open Access Journals (Sweden)

    Sopi Ramadan B

    2012-08-01

    Full Text Available Abstract Background Hyperoxia is shown to impair airway relaxation via limiting L-arginine bioavailability to nitric oxide synthase (NOS and reducing NO production as a consequence. L-arginine can also be synthesized by L-citrulline recycling. The role of L-citrulline supplementation was investigated in the reversing of hyperoxia-induced impaired relaxation of rat tracheal smooth muscle (TSM. Methods Electrical field stimulation (EFS, 2–20 V-induced relaxation was measured under in vitro conditions in preconstricted tracheal preparations obtained from 12 day old rat pups exposed to room air or hyperoxia (>95% oxygen for 7 days supplemented with L-citrulline or saline (in vitro or in vivo. The role of the L-citrulline/L-arginine cycle under basal conditions was studied by incubation of preparations in the presence of argininosuccinate synthase (ASS inhibitor [α-methyl-D, L-aspartate, 1 mM] or argininosuccinate lyase inhibitor (ASL succinate (1 mM and/or NOS inhibitor [Nω-nitro-L-arginine methyl ester; 100 μM] with respect to the presence or absence of L-citrulline (2 mM. Results Hyperoxia impaired the EFS-induced relaxation of TSM as compared to room air control (p ; 0.5 ± 0.1% at 2 V to 50.6 ± 5.7% at 20 V in hyperoxic group: 0.7 ± 0.2 at 2 V to 80.0 ± 5.6% at 20 V in room air group. Inhibition of ASS or ASL, and L-citrulline supplementation did not affect relaxation responses under basal conditions. However, inhibition of NOS significantly reduced relaxation responses (p in vivo and in vitro also reversed the hyperoxia-impaired relaxation. The differences were significant (p ; 0.8 ± 0.3% at 2 V to 47.1 ± 4.1% at 20 V without L-citrulline; 0.9 ± 0.3% at 2 V to 68.2 ± 4.8% at 20 V with L-citrulline. Inhibition of ASS or ASL prevented this effect of L-citrulline. Conclusion The results indicate the presence of an L-citrulline/L-arginine cycle in the airways of rat pups

  8. Characterization of a Bacillus amyloliquefaciens strain for reduction of citrulline accumulation during soy sauce fermentation.

    Science.gov (United States)

    Zhang, Jiran; Du, Guocheng; Chen, Jian; Fang, Fang

    2016-10-01

    To reduce the amount of citrulline produced by arginine-consuming bacteria in the moromi mash during soy sauce production. Bacillus amyloliquefaciens JY06, a salt-tolerant strain with high arginine consumption ability and low citrulline accumulation capacity, was isolated from moromi mash. The concentration of citrulline was decreased from 26.8 to 5.1 mM and ethyl carbamate in soy sauce, after sterilization, decreased from 97 to 17 μg kg(-1) when B. amyloliquefaciens JY06 was added during fermentation. The aroma of the sauce was improved by increasing the ester content. B. amyloliquefaciens JY06 is a beneficial bacterium that can be used in soy sauce fermentation to eliminate ethyl carbonate and enhance the flavor of the sauce.

  9. l-Citrulline dilates rat retinal arterioles via nitric oxide- and prostaglandin-dependent pathways in vivo

    Directory of Open Access Journals (Sweden)

    Asami Mori

    2015-04-01

    Full Text Available l-Citrulline is an effective precursor of l-arginine produced by the l-citrulline/l-arginine cycle, and it exerts beneficial effects on the cardiovascular system by supporting enhanced nitric oxide (NO production. NO dilates retinal blood vessels via the cyclooxygenase-mediated pathway. The purpose of this study was to examine the effects of l-citrulline on retinal circulation and to investigate the potential involvement of NO and prostaglandins in l-citrulline-induced responses in rats. l-Citrulline (10–300 μg kg−1 min−1, i.v. increased the diameter of retinal arterioles without significantly changing mean blood pressure, heart rate, and fundus blood flow. The vasodilator response of retinal arterioles to l-citrulline was significantly diminished following treatment with NG-nitro-l-arginine methyl ester (30 mg/kg, i.v., an NO synthase inhibitor, or indomethacin (5 mg/kg, i.v., a cyclooxygenase inhibitor. In addition, α-methyl-dl-aspartic acid (147 mg/kg, i.v., an inhibitor of argininosuccinate synthase, the rate-limiting enzyme for the recycling of l-citrulline to l-arginine, diminished the l-citrulline-induced retinal vasodilation. These results suggest that both NO- and prostaglandin-dependent pathways contribute to the l-citrulline-induced vasodilation of rat retinal arterioles. The l-citrulline/l-arginine recycling pathway may have more importance in regulating vascular tone in retinal blood vessels than in peripheral resistance vessels.

  10. Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

    Science.gov (United States)

    Flynn, K M; Kellihan, H B; Trepanier, L A

    2017-08-01

    To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Prediction of citrullination sites by incorporating k-spaced amino acid pairs into Chou's general pseudo amino acid composition.

    Science.gov (United States)

    Ju, Zhe; Wang, Shi-Yun

    2018-04-22

    As one of the most important and common protein post-translational modifications, citrullination plays a key role in regulating various biological processes and is associated with several human diseases. The accurate identification of citrullination sites is crucial for elucidating the underlying molecular mechanisms of citrullination and designing drugs for related human diseases. In this study, a novel bioinformatics tool named CKSAAP_CitrSite is developed for the prediction of citrullination sites. With the assistance of support vector machine algorithm, the highlight of CKSAAP_CitrSite is to adopt the composition of k-spaced amino acid pairs surrounding a query site as input. As illustrated by 10-fold cross-validation, CKSAAP_CitrSite achieves a satisfactory performance with a Sensitivity of 77.59%, a Specificity of 95.26%, an Accuracy of 89.37% and a Matthew's correlation coefficient of 0.7566, which is much better than those of the existing prediction method. Feature analysis shows that the N-terminal space containing pairs may play an important role in the prediction of citrullination sites, and the arginines close to N-terminus tend to be citrullinated. The conclusions derived from this study could offer useful information for elucidating the molecular mechanisms of citrullination and related experimental validations. A user-friendly web-server for CKSAAP_CitrSite is available at 123.206.31.171/CKSAAP_CitrSite/. Copyright © 2017. Published by Elsevier B.V.

  12. Beyond citrullination: other post-translational protein modifications in rheumatoid arthritis

    NARCIS (Netherlands)

    Trouw, Leendert A.; Rispens, Theo; Toes, Rene E. M.

    2017-01-01

    The presence of autoantibodies is one of the hallmarks of rheumatoid arthritis (RA). In the past few decades, rheumatoid factors (autoantibodies that recognize the Fc-tail of immunoglobulins) as well as anti-citrullinated protein antibodies (ACPAs) have been studied intensively. ACPAs recognize

  13. Anti-cyclic citrullinated peptide (anti-CCP) antibodies in children with juvenile idiopathic arthritis

    NARCIS (Netherlands)

    van Rossum, Marion; van Soesbergen, Renée; de Kort, Sandra; ten Cate, Rebecca; Zwinderman, Aeilko H.; de Jong, Ben; Dijkmans, Ben; van Venrooij, Walther J.

    2003-01-01

    Objective. To determine if anti-cyclic citrullinated peptide antibodies (anti-CCP) can be detected in sera of patients with juvenile idiopathic arthritis (JIA) and if they can be used to identify patients with a more destructive course of disease. Methods. One hundred serum samples of 71 patients

  14. Anti-citrullinated peptide antibodies may occur in patients with psoriatic arthritis

    NARCIS (Netherlands)

    Vander Cruyssen, B.; Hoffman, I. E. A.; Zmierczak, H.; van den Berghe, M.; Kruithof, E.; de Rycke, L.; Mielants, H.; Veys, E. M.; Baeten, D.; de Keyser, F.

    2005-01-01

    BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis. OBJECTIVE: To determine the frequency of anti-CCP

  15. Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Holm, Bettina Eide; Heiden, Julie

    2018-01-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Anti-citrullinated protein antibodies (ACPA) are crucial for the serological diagnosis of RA, where Epstein-Barr virus (EBV) has been suggested to be an environmental agent in triggering the onset of the disease. This study aimed...

  16. A combination of plasma DAO and citrulline levels as a potential ...

    African Journals Online (AJOL)

    Introduction: There is no valid and reliable diagnostic test for early diagnosis of acute mesenteric ischemia (AMI). The aim of this study was to measure the plasma levels of diamine oxidase (DAO) and citrulline in. AMI to gain insight into its early diagnosis. Material and methods: A total of 21 Wistar albino rats were divided ...

  17. History and diagnostic value of antibodies to citrullinated proteins in rheumatoid arthritis

    NARCIS (Netherlands)

    Peene, I.; de Rycke, L.; Baeten, D.; Hoffman, I.; Veys, E. M.; de Keyser, F.

    2004-01-01

    Rheumatoid arthritis is a chronic inflammatory joint disease characterized by the presence of autoantibodies. The best known autoantibody is the rheumatoid factor. Another group of antibodies directed against citrullinated epitopes is proven to be more specific for rheumatoid arthritis. This review

  18. Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis

    NARCIS (Netherlands)

    van de Stadt, Lotte A.; de Koning, Margret H. M. T.; van de Stadt, Rob J.; Wolbink, Gertjan; Dijkmans, Ben A. C.; Hamann, Dörte; van Schaardenburg, Dirkjan

    2011-01-01

    To examine how anti-citrullinated protein antibody (ACPA) epitope spreading takes place prior to the onset of clinical rheumatoid arthritis (RA), and to analyze the pattern of autoantigen reactivity at the beginning of the immune response. Multiple consecutive serum samples from 79 RA patients who

  19. Analysis of variance, normal quantile-quantile correlation and effective expression support of pooled expression ratio of reference genes for defining expression stability

    Directory of Open Access Journals (Sweden)

    Himanshu Priyadarshi

    2017-01-01

    Full Text Available Identification of a reference gene unaffected by the experimental conditions is obligatory for accurate measurement of gene expression through relative quantification. Most existing methods directly analyze variability in crossing point (Cp values of reference genes and fail to account for template-independent factors that affect Cp values in their estimates. We describe the use of three simple statistical methods namely analysis of variance (ANOVA, normal quantile-quantile correlation (NQQC and effective expression support (EES, on pooled expression ratios of reference genes in a panel to overcome this issue. The pooling of expression ratios across the genes in the panel nullify the sample specific effects uniformly affecting all genes that are falsely reflected as instability. Our methods also offer the flexibility to include sample specific PCR efficiencies in estimations, when available, for improved accuracy. Additionally, we describe a correction factor from the ANOVA method to correct the relative fold change of a target gene if no truly stable reference gene could be found in the analyzed panel. The analysis is described on a synthetic data set to simplify the explanation of the statistical treatment of data.

  20. L-Citrulline Protects Skeletal Muscle Cells from Cachectic Stimuli through an iNOS-Dependent Mechanism.

    Directory of Open Access Journals (Sweden)

    Daniel J Ham

    Full Text Available Dietary L-citrulline is thought to modulate muscle protein turnover by increasing L-arginine availability. To date, the direct effects of increased L-citrulline concentrations in muscle have been completely neglected. Therefore, we determined the role of L-citrulline in regulating cell size during catabolic conditions by depriving mature C2C12 myotubes of growth factors (serum free; SF or growth factors and nutrients (HEPES buffered saline; HBS. Cells were treated with L-citrulline or equimolar concentrations of L-arginine (positive control or L-alanine (negative control and changes in cell size and protein turnover were assessed. In myotubes incubated in HBS or SF media, L-citrulline improved rates of protein synthesis (HBS: +63%, SF: +37% and myotube diameter (HBS: +18%, SF: +29%. L-citrulline treatment substantially increased iNOS mRNA expression (SF: 350%, HBS: 750%. The general NOS inhibitor L-NAME and the iNOS specific inhibitor aminoguanidine prevented these effects in both models. Depriving myotubes in SF media of L-arginine or L-leucine, exacerbated wasting which was not attenuated by L-citrulline. The increased iNOS mRNA expression was temporally associated with increases in mRNA of the endogenous antioxidants SOD1, SOD3 and catalase. Furthermore, L-citrulline prevented inflammation (LPS and oxidative stress (H2O2 induced muscle cell wasting. In conclusion, we demonstrate a novel direct protective effect of L-citrulline on skeletal muscle cell size independent of L-arginine that is mediated through induction of the inducible NOS (iNOS isoform. This discovery of a nutritional modulator of iNOS mRNA expression in skeletal muscle cells could have substantial implications for the treatment of muscle wasting conditions.

  1. Increased Plasma Citrulline in Mice Marks Diet-Induced Obesity and May Predict the Development of the Metabolic Syndrome

    Science.gov (United States)

    Sailer, Manuela; Dahlhoff, Christoph; Giesbertz, Pieter; Eidens, Mena K.; de Wit, Nicole; Rubio-Aliaga, Isabel; Boekschoten, Mark V.; Müller, Michael; Daniel, Hannelore

    2013-01-01

    In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ) to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF) feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline) is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the “diabetic fingerprint” of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic impairments. PMID

  2. Citrullination in the periodontium – a possible link between periodontitis and rheumatoid arthritis

    Science.gov (United States)

    Laugisch, Oliver; Wong, Alicia; Sroka, Aneta; Kantyka, Tomasz; Koziel, Joanna; Neuhaus, Klaus; Sculean, Anton; Venables, Patrick J.; Potempa, Jan; Möller, Burkhard; Eick, Sigrun

    2016-01-01

    Objectives The aim of the present study was to assess human and bacterial peptidylarginine deiminase (PAD) activity in the gingival crevicular fluid (GCF) in the context of serum levels of antibodies against citrullinated epitopes in rheumatoid arthritis and periodontitis. Materials and Methods Human PAD and Porphyromonas gingivalis-derived enzyme (PPAD) activities were measured in the GCF of 52 rheumatoid arthritis (RA) patients (48 with periodontitis and four without) and 44 non-RA controls (28 with periodontitis and 16 without). Serum antibodies against citrullinated epitopes were measured by ELISA. Bacteria being associated with periodontitis were determined by nucleic-acid based methods. Results Citrullination was present in 26 (50%) RA patients and 23 (48%) controls. PAD and PPAD activities were detected in 36 (69%) and 30 (58%) RA patients, respectively, and in 30 (68%) and 21 (50%) controls, respectively. PPAD activity was higher in RA and non-RA patients with periodontitis than in those without (p = 0.038; p = 0.004), and was detected in 35 of 59 P. gingivalis positive samples, and in in 16 of 37 P. gingivalis-negative samples in association with high antibody levels against that species. Conclusions PAD and PPAD activities within the periodontium are elevated in RA and non-RA patients with periodontitis. PPAD secreted by P. gingivalis residing in epithelial cells may exert its citrullinating activity in distant regions of the periodontium or even distant tissues. Clinical relevance In periodontitis, the citrullination of proteins/peptides by human and bacterial peptidylarginine deiminases may generate antibodies after breaching immunotolerance in susceptible individuals. PMID:26264638

  3. Mitochondrial citrulline synthesis from ammonia and glutamine in the liver of ureogenic air-breathing catfish, Clarias batrachus (Linnaeus).

    Science.gov (United States)

    Kharbuli, Zaiba Y; Biswas, Kuheli; Saha, Nirmalendu

    2007-12-01

    The possible synthesis of citrulline, a rate limiting step for urea synthesis via the ornithine-urea cycle (OUC) in teleosts was tested both in the presence of ammonia and glutamine as nitrogen-donating substrates by the isolated liver mitochondria of ureogenic air-breathing walking catfish, C. batrachus. Both ammonia and glutamine could be used as nitrogen-donating substrates for the synthesis of citrulline by the isolated liver mitochondria, since the rate of citrulline synthesis was almost equal in presence of both the substrates. The citrulline synthesis by the isolated liver mitochondria requires succinate at a concentration of 0.1 mM as an energy source, and also requires the involvement of intramitochondrial carbonic anhydrase activity for supplying HCO3 as another substrate for citrulline synthesis. The rate of citrulline synthesis was further stimulated significantly by the isolated liver mitochondria of the fish after pre-exposure to 25 mM NH4Cl for 7 days. Due to possessing this biochemical adaptational strategy leading to the amelioration of ammonia toxicity mainly by channeling ammonia directly and/or via the formation of glutamine to the OUC, this air-breathing catfish could succeed in surviving in high external ammonia, which it faces in its natural habitat in certain seasons of the year.

  4. RHEUMATOID FACTOR AND ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN PATIENTS WITH PSORIATIC ARTHRITIS

    Directory of Open Access Journals (Sweden)

    V. V. Badokin

    2011-01-01

    Full Text Available Objective: to define the clinical value of rheumatoid factor (RF and anti-cyclic citrullinated peptide antibodies (anti-CCP in early psori- atic arthritis (PA. Subjects and methods. Fifty-six patients (32 females and 24 males with early PA with a mean duration of 12±6.7 months were studied. The examinees' age ranged from 18 to 76 years (mean age 44±15.5 years. Mean psoriasis duration was 12.5±2.2 years. RF IgM was determined using a high-sensitive nephelometric method on a BN Pro-Spec analyzer (Siemens, Germany and serum anti-CCP concentra- tions were measured by immunochemiluminescence on a COBAS e411 analyzer (Roche, Switzerland. Group 1 included 10 patients with anti-CCP and/or RF (a study group; Group 2 comprised 46 patients without anti-CCP and RF (a control group. Results. There was anti-CCP in 7 (12.5% of the patients with early PA, RF in 8 (14.3%, both of them in 5 (9%. The study group had a severer course of PA accompanied by polyarthritis, inflamed distal interphalangeal joints, axial arthritis, dactylitis, enthesitis, and, in some cases spondylitis and sacroiliitis. In groups 1 and 2, the number of tender joints was 17.6±4 and 10±1.5, respectively (p = 0.04; that of swollen ones, 12.6±1.5 and 7.0±1.1 (p = 0.02; DAS28 index, 5.9±1.7 and 4.5±1.5 (p = 0.02; ESR, 34.5±5.9 and 22±2.3 (p = 0.04, high-sensitive C reactive protein, 70±25.3 and 24.9±5.0 (p = 0.06; and Sharp ratio, 68.7±14.3 and 21.3±3.8 (p < 0.004. Conclusion. In patients with early PA, anti-CCP and RF were encountered with an approximately equal frequency; at the same time, they were associated with polyarthritis, high disease activity, and an erosive process. 

  5. Pattern of drugs use and association with anti-mutated citrullinated vimentin antibody in rheumatoid arthritis

    OpenAIRE

    Safi, Mohammad-Ayman A.; Fathaldin, Omar A.

    2015-01-01

    Objectives: To demonstrate the pattern of disease-modifying antirheumatic drugs (DMARDs) use in Saudi and non-Saudi rheumatoid arthritis (RA) patients, and to evaluate the association of DMARDs use with anti-mutated citrullinated vimentin (anti-MCV) positivity and other factors. Methods: Retrospectively, for a period of 7 years (2007-2014), we studied 205 RA patients, at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. All patients used DMARDs. Pattern of use for all 6 DMARDs ...

  6. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    Science.gov (United States)

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  7. Streptococcus pyogenes Arginine and Citrulline Catabolism Promotes Infection and Modulates Innate Immunity

    Science.gov (United States)

    Cusumano, Zachary T.; Watson, Michael E.

    2014-01-01

    A bacterium's ability to acquire nutrients from its host during infection is an essential component of pathogenesis. For the Gram-positive pathogen Streptococcus pyogenes, catabolism of the amino acid arginine via the arginine deiminase (ADI) pathway supplements energy production and provides protection against acid stress in vitro. Its expression is enhanced in murine models of infection, suggesting an important role in vivo. To gain insight into the function of the ADI pathway in pathogenesis, the virulence of mutants defective in each of its enzymes was examined. Mutants unable to use arginine (ΔArcA) or citrulline (ΔArcB) were attenuated for carriage in a murine model of asymptomatic mucosal colonization. However, in a murine model of inflammatory infection of cutaneous tissue, the ΔArcA mutant was attenuated but the ΔArcB mutant was hyperattenuated, revealing an unexpected tissue-specific role for citrulline metabolism in pathogenesis. When mice defective for the arginine-dependent production of nitric oxide (iNOS−/−) were infected with the ΔArcA mutant, cutaneous virulence was rescued, demonstrating that the ability of S. pyogenes to utilize arginine was dispensable in the absence of nitric oxide-mediated innate immunity. This work demonstrates the importance of arginine and citrulline catabolism and suggests a novel mechanism of virulence by which S. pyogenes uses its metabolism to modulate innate immunity through depletion of an essential host nutrient. PMID:24144727

  8. Citrulline protects Streptococcus pyogenes from acid stress using the arginine deiminase pathway and the F1Fo-ATPase.

    Science.gov (United States)

    Cusumano, Zachary T; Caparon, Michael G

    2015-04-01

    A common stress encountered by both pathogenic and environmental bacteria is exposure to a low-pH environment, which can inhibit cell growth and lead to cell death. One major defense mechanism against this stress is the arginine deiminase (ADI) pathway, which catabolizes arginine to generate two ammonia molecules and one molecule of ATP. While this pathway typically relies on the utilization of arginine, citrulline has also been shown to enter into the pathway and contribute to protection against acid stress. In the pathogenic bacterium Streptococcus pyogenes, the utilization of citrulline has been demonstrated to contribute to pathogenesis in a murine model of soft tissue infection, although the mechanism underlying its role in infection is unknown. To gain insight into this question, we analyzed a panel of mutants defective in different steps in the ADI pathway to dissect how arginine and citrulline protect S. pyogenes in a low-pH environment. While protection provided by arginine utilization occurred through the buffering of the extracellular environment, citrulline catabolism protection was pH independent, requiring the generation of ATP via the ADI pathway and a functional F1Fo-ATP synthase. This work demonstrates that arginine and citrulline catabolism protect against acid stress through distinct mechanisms and have unique contributions to virulence during an infection. An important aspect of bacterial pathogenesis is the utilization of host-derived nutrients during an infection for growth and virulence. Previously published work from our lab identified a unique role for citrulline catabolism in Streptococcus pyogenes during a soft tissue infection. The present article probes the role of citrulline utilization during this infection and its contribution to protection against acid stress. This work reveals a unique and concerted action between the catabolism of citrulline and the F1Fo-ATPase that function together to provide protection for bacteria in a low

  9. Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis.

    Science.gov (United States)

    McKinley-Barnard, Sarah; Andre, Tom; Morita, Masahiko; Willoughby, Darryn S

    2015-01-01

    Nitric oxide (NO) is endogenously synthesized from L-arginine and L-citrulline. Due to its effects on nitric oxide synthase (NOS), reduced glutathione (GSH) may protect against the oxidative reduction of NO. The present study determined the effectiveness of L-citrulline and/or GSH on markers indicative of NO synthesis in in vivo conditions with rodents and humans and also in an in vitro condition. In phase one, human umbilical vein endothelial cells (HUVECs) were treated with either 0.3 mM L-citrulline, 1 mM GSH (Setria®) or a combination of each at 0.3 mM. In phase two, Sprague-Dawley rats (8 weeks old) were randomly assigned to 3 groups and received either purified water, L-citrulline (500 mg/kg/day), or a combination of L-citrulline (500 mg/kg/day) and GSH (50 mg/kg/day) by oral gavage for 3 days. Blood samples were collected and plasma NOx (nitrite + nitrate) assessed. In phase three, resistance-trained males were randomly assigned to orally ingest either cellulose placebo (2.52 g/day), L-citrulline (2 g/day), GSH (1 g/day), or L-citrulline (2 g/day) + GSH (200 mg/day) for 7 days, and then perform a resistance exercise session involving 3 sets of 10-RM involving the elbow flexors. Venous blood was obtained and used to assess plasma cGMP, nitrite, and NOx. In phase one, nitrite levels in cells treated with L-citrulline and GSH were significantly greater than control (p  0.05). However, nitrite and NOx for L-citrulline + GSH were significantly greater at 30 min post-exercise when compared to placebo (p < 0.05). Combining L-citrulline with GSH augments increases in nitrite and NOx levels during in vitro and in vivo conditions.

  10. Role of the L-citrulline/L-arginine cycle in iNANC nerve-mediated nitric oxide production and airway smooth muscle relaxation in allergic asthma

    NARCIS (Netherlands)

    Maarsingh, Ham; Leusink, John; Zaagsma, Johan; Meurs, Herman

    2006-01-01

    Nitric oxide synthase (NOS) converts L-arginine into nitric oxide (NO) and L-Citrulline. In NO-producing cells, L-citrulline can be recycled to L-arginine in a two-step reaction involving argininosuccinate synthase (ASS) and -lyase (ASL). In guinea pig trachea, L-arginine is a limiting factor in

  11. Identification of citrullination sites specific for peptidylarginine deiminase 2 (PAD2) and PAD4 in fibrinogen from synovial fluid of patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Sharma, Mandvi; Damgaard, Dan; Senolt, L.

    2017-01-01

    /4 and citrullination sites were identified by LC-MS/MS on a Q-exactive orbitrap following proteolytic digestion with Lys-C. These in vitro citrullination profiles were compared to those observed in SF fibrinogen of four RA patients with varying DAS28 scores, CRP levels and leukocyte counts. DAS28 scores >5.1 and ≤2...

  12. 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...

  13. Psychology defined.

    Science.gov (United States)

    Henriques, Gregg R

    2004-12-01

    A new form of knowledge technology is used to diagnose psychology's epistemological woes and provide a solution to the difficulties. The argument presented is that psychology has traditionally spanned two separate but intimately related problems: (a) the problem of animal behavior and (b) the problem of human behavior. Accordingly, the solution offered divides the field into two broad, logically consistent domains. The first domain is psychological formalism, which is defined as the science of mind, corresponds to animal behavior, and consists of the basic psychological sciences. The second domain is human psychology, which is defined as the science of human behavior at the individual level and is proposed as a hybrid that exists between psychological formalism and the social sciences. 2004 Wiley Periodicals, Inc.

  14. Acute Citrulline-Malate Supplementation and High-Intensity Cycling Performance.

    Science.gov (United States)

    Cunniffe, Brian; Papageorgiou, Maria; OʼBrien, Barbara; Davies, Nathan A; Grimble, George K; Cardinale, Marco

    2016-09-01

    Cunniffe, B, Papageorgiou, M, O'Brien, B, Davies, NA, Grimble, GK, and Cardinale, M. Acute citrulline-malate supplementation and high-intensity cycling performance. J Strength Cond Res 30(9): 2638-2647, 2016-Dietary L-citrulline-malate (CM) consumption has been suggested to improve skeletal muscle metabolism and contractile efficiency, which would be expected to predispose exercising individuals to greater fatigue resistance. The purpose of this study was to examine the effects of CM supplementation on acid-base balance and high-intensity exercise performance. In a double-blind, placebo-controlled, crossover study, 10 well-trained males consumed either 12 g of CM (in 400 ml) or lemon sugar-free cordial (placebo [PL]) 60 minutes before completion of 2 exercise trials. Each trial consisted of subjects performing 10 (×15 seconds) maximal cycle sprints (with 30-second rest intervals) followed by 5 minutes recovery before completing a cycle time-to-exhaustion test (TTE) at 100% of individual peak power (PP). Significant increases in plasma concentrations of citrulline (8.8-fold), ornithine (3.9-fold), and glutamine (1.3-fold) were observed 60 minutes after supplementation in the CM trial only (p ≤ 0.05) and none of the subjects experienced gastrointestinal side-effects during testing. Significantly higher exercise heart rates were observed in CM condition (vs. PL) although no between trial differences in performance related variables (TTE: [120 ± 61 seconds CM vs. 113 ± 50 seconds PL]), PP or mean power, ([power fatigue index: 36 ± 16% CM vs. 28 ± 18% PL]), subjective rating of perceived exertion or measures of acid-base balance (pH, lactate, bicarbonate, base-excess) were observed (p > 0.05). This study demonstrated that acute supplementation of 12 g CM does not provide acute ergogenic benefits using the protocol implemented in this study in well-trained males.

  15. 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.

  16. Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a useful analyte

    Directory of Open Access Journals (Sweden)

    Shane C. Quinonez

    2014-01-01

    Full Text Available Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine disease (MSUD type III, is caused by the deficiency of the E3 subunit of branched chain alpha-ketoacid dehydrogenase (BCKDH, α-ketoglutarate dehydrogenase (αKGDH, and pyruvate dehydrogenase (PDH. DLD deficiency variably presents with either a severe neonatal encephalopathic phenotype or a primarily hepatic phenotype. As a variant form of MSUD, it is considered a core condition recommended for newborn screening. The detection of variant MSUD forms has proven difficult in the past with no asymptomatic DLD deficiency patients identified by current newborn screening strategies. Citrulline has recently been identified as an elevated dried blood spot (DBS metabolite in symptomatic patients affected with DLD deficiency. Here we report the retrospective DBS analysis and second-tier allo-isoleucine testing of 2 DLD deficiency patients. We show that an elevated citrulline and an elevated allo-isoleucine on second-tier testing can be used to successfully detect DLD deficiency. We additionally recommend that DLD deficiency be included in the “citrullinemia/elevated citrulline” ACMG Act Sheet and Algorithm.

  17. Anti-cyclic Citrullinated Peptide Antibody (Anti-CCP and Diagnostic Value for Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Mehmet Agilli

    2014-02-01

    Full Text Available Rheumatoid arthritis (RA is an inflammatory multisystem disease of unknown etiology characterized by chronic destructive synovitis. It and #8217;s prevalence is about 1% all over the world. Serologic markers are also important beside some clinical situations upon RA diagnosis. Today, the most commonly used laboratory test is rheumatoid factor (RF in patients with suspected RA. RF is sensitive but not a specific biomarker for diagnosing RA. Early diagnosis of RA is essential to prevent of progressive joint damage. In recent years, anticyclic citrullinated peptide/protein antibody (anti-CCP attracts the attention as a remarkable biomarker for early diagnosis. Anti-CCP which is a family of anti-citrullinated protein antibodies (ACPA family, showed quite satisfactory specificity in the diagnosis of RA. Due to the prescence of ACPA was included to 2010 RA diagnostic criteria, in a manner of speaking, importance of anti-CCP was registered. [TAF Prev Med Bull 2014; 13(1.000: 83-88

  18. Development of a paper-based vertical flow SERS assay for citrulline detection using aptamer-conjugated gold nanoparticles

    Science.gov (United States)

    Locke, Andrea; Deutz, Nicolaas; Coté, Gerard

    2018-02-01

    Research toward development of point-of-care (POC) technologies is emerging as a means for diagnosis and monitoring of patients outside the hospital. These POC devices typically utilize assays capable of detecting low level biomarkers indicative of specific diseases. L-citrulline, an α-amino acid produced in the intestinal mucosa cells, is one such biomarker typically found circulating within the plasma at physiological concentrations of 40 μM. Researchers have found that intestinal enterocyte malfunction causes its level to be significantly lowered, establishing it as a potential diagnostic biomarker for gut function. Our research group has proposed the development of a surface enhanced Raman spectroscopy (SERS) based assay, using vertical flow paper fluidics, for citrulline detection. The assay consists of a fluorescently active, Raman reporter labeled aptamer conjugated on gold nanoparticles. The aptamer changes its confirmation on binding to its target, which in turn changes the distance between the Raman active molecule and the nanoparticle surface. These particles were embedded within a portable chip consisting of cellulose-based paper. After the chips were loaded with different concentrations of free L-citrulline in phosphate buffer, time was given for the assay to interact with the sample. A handheld Raman spectrometer (638 nm; Ocean Optics) was used to measure the SERS intensity. Results showed decrease in intensity with increasing concentration of L-citrulline (0-50μM).

  19. Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase.

    Science.gov (United States)

    Song, Wei; Sun, Xia; Chen, Xiulai; Liu, Dongxu; Liu, Liming

    2015-08-20

    In this study, a simple, efficient enzymatic production process for the environmentally friendly synthesis of l-citrulline from l-arginine was developed using arginine deiminase (ADI) from Lactococcus lactis. Following overexpression of L. lactis ADI in Escherichia. coli BL21 (DE3) and experimental evolution using error-prone PCR, mutant FMME106 was obtained with a Km for l-arginine of 3.5mM and a specific activity of 195.7U/mg. This mutant exhibited a maximal conversion of 92.6% and achieved a final l-citrulline concentration of 176.9g/L under optimal conditions (190g/L l-arginine, 15g/L whole-cell biocatalyst treated with 2% isopropanol for 30min, 50°C, pH 7.2, 8h). The average l-citrulline synthesis rate of 22.1g/L/h is considerably higher than that reported for other similar biocatalytic approaches, therefore the process developed in the present work has great potential for large-scale production of l-citrulline. Copyright © 2015. Published by Elsevier B.V.

  20. Apo AIV and Citrulline Plasma Concentrations in Short Bowel Syndrome Patients: The Influence of Short Bowel Anatomy

    Science.gov (United States)

    Targarona, Jordi; Ruiz, Jorge; García, Natalia; Oró, Denise; García-Villoria, Judit; Creus, Gloria; Pita, Ana M.

    2016-01-01

    Introduction Parenteral nutrition (PN) dependence in short bowel syndrome (SBS) patients is linked to the functionality of the remnant small bowel (RSB). Patients may wean off PN following a period of intestinal adaptation that restores this functionality. Currently, plasma citrulline is the standard biomarker for monitoring intestinal functionality and adaptation. However, available studies reveal that the relationship the biomarker with the length and function of the RSB is arguable. Thus, having additional biomarkers would improve pointing out PN weaning. Aim By measuring concomitant changes in citrulline and the novel biomarker apolipoprotein AIV (Apo AIV), as well as taking into account the anatomy of the RSB, this exploratory study aims to a better understanding of the intestinal adaptation process and characterization of the SBS patients under PN. Methods Thirty four adult SBS patients were selected and assigned to adapted (aSBS) and non-adapted (nSBS) groups after reconstructive surgeries. Remaining jejunum and ileum lengths were recorded. The aSBS patients were either on an oral diet (ORAL group), those with intestinal insufficiency, or on oral and home parenteral nutrition (HPN group), those with chronic intestinal failure. Apo AIV and citrulline were analyzed in plasma samples after overnight fasting. An exploratory ROC analysis using citrulline as gold standard was performed. Results Biomarkers, Apo AIV and citrulline showed a significant correlation with RSBL in aSBS patients. In jejuno-ileocolic patients, only Apo AIV correlated with RSBL (rb = 0.54) and with ileum length (rb = 0.84). In patients without ileum neither biomarker showed any correlation with RSBL. ROC analysis indicated the Apo AIV cut-off value to be 4.6 mg /100 mL for differentiating between the aSBS HPN and ORAL groups. Conclusions Therefore, in addition to citrulline, Apo AIV can be set as a biomarker to monitor intestinal adaptation in SBS patients. As short bowel anatomy is shown

  1. DL-7-azatryptophan and citrulline metabolism in the cyanobacterium Anabaena sp. strain 1F

    International Nuclear Information System (INIS)

    Chen, C.H.; Van Baalen, C.; Tabita, F.R.

    1987-01-01

    An alternative route for the primary assimilation of ammonia proceeds via glutamine synthetase-carbamyl phosphate synthetase and its inherent glutaminase activity in Anabaena sp. strain 1F, a marine filamentous, heterocystous cyanobacterium. Evidence for the presence of this possible alternative route to glutamate was provided by the use of amino acid analogs as specific enzyme inhibitors, enzymological studies, and radioistopic labeling experiments. The amino acid pool patterns of continuous cultures of Anabaena sp. strain 1F were markedly influenced by the nitrogen source. A relatively high concentration of glutamate was maintained in the amino acid pools of all cultures irrespective of the nitrogen source, reflecting the central role of glutamate in nitrogen metabolism. The addition of 1.0 microM azaserine increased the intracellular pools of glutamate and glutamine. All attempts to detect any enzymatic activity for glutamate synthase by measuring the formation of L-[ 14 C]glutamate from 2-keto-[1- 14 C]glutarate and glutamine failed. The addition of 10 microM DL-7-azatryptophan caused a transient accumulation of intracellular citrulline and alanine which was not affected by the presence of chloramphenicol. The in vitro activity of carbamyl phosphate synthetase and glutaminase increased severalfold in the presence of azatryptophan. Results from radioisotopic labeling experiments with [ 14 C]bicarbonate and L-[1- 14 C]ornithine also indicated that citrulline was formed via carbamyl phosphate synthetase and ornithine transcarbamylase. In addition to its effects on nitrogen metabolism, azatryptophan also affected carbon metabolism by inhibiting photosynthetic carbon assimilation and photosynthetic oxygen evolution

  2. Independence of carbohydrate-deficient isoforms of transferrin and cyclic citrullinated peptides in rheumatoid arthritis.

    Science.gov (United States)

    Gudowska, Monika; Gindzienska-Sieskiewicz, Ewa; Gruszewska, Ewa; Cylwik, Bogdan; Sierakowski, Stanislaw; Szmitkowski, Maciej; Chrostek, Lech

    The aim of this study was to assess the relationship between the two types of posttranslational modifications of proteins in RA: glycosylation on the example of carbohydrate-deficient transferrin and citrullination by means of autoantibodies to cyclic citrullinated peptides. The study was carried out in 50 RA patients. CDT was measured using N Latex CDT immunonephelometric test, the results were presented in absolute and relative units. Anti-CCP were measured using the chemiluminescent method and rheumatoid factor by immunoturbidimetric method. 80% of RA patients were positive for anti-CCP, 70% for RF and 62% for both, anti-CCP and RF. The level of %CDT was significantly elevated, but absolute CDT level was not changed. The mean absolute CDT concentration was higher in anti-CCP positive patients than that in anti-CCP negative. CDT (absolute and relative concentration) did not correlate with anti-CCP and RF. However, serum RF significantly correlated with anti-CCP. %CDT did not correlate with anti-CCP, but absolute level correlated with anti-CCP only in anti-CCP negative and RF negative patients. CDT did not correlate with RF, but solely with anti-CCP in anti-CCP negative patients. Anti-CCP correlated with DAS 28 only in anti-CCP negative RA, but CDT (absolute and relative units) correlated with DAS 28 in all patients and in anti-CCP positive RA. These results suggest that the changes in CDT and anti-CCP concentrations are not associated with oneself and indicate on the independence of these posttranslational modifications in rheumatoid arthritis. Only the alterations in transferrin glycosylation reflected the activity of RA. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  3. Sodium-coupled neutral amino acid transporter 1 (SNAT1 modulates L-citrulline transport and nitric oxide (NO signaling in piglet pulmonary arterial endothelial cells.

    Directory of Open Access Journals (Sweden)

    Anna Dikalova

    Full Text Available There is evidence that impairments in nitric oxide (NO signaling contribute to chronic hypoxia-induced pulmonary hypertension. The L-arginine-NO precursor, L-citrulline, has been shown to ameliorate pulmonary hypertension. Sodium-coupled neutral amino acid transporters (SNATs are involved in the transport of L-citrulline into pulmonary arterial endothelial cells (PAECs. The functional link between the SNATs, L-citrulline, and NO signaling has not yet been explored.We tested the hypothesis that changes in SNAT1 expression and transport function regulate NO production by modulating eNOS coupling in newborn piglet PAECs.A silencing RNA (siRNA technique was used to assess the contribution of SNAT1 to NO production and eNOS coupling (eNOS dimer-to-monomer ratios in PAECs from newborn piglets cultured under normoxic and hypoxic conditions in the presence and absence of L-citrulline. SNAT1 siRNA reduced basal NO production in normoxic PAECs and prevented L-citrulline-induced elevations in NO production in both normoxic and hypoxic PAECs. SNAT1 siRNA reduced basal eNOS dimer-to-monomer ratios in normoxic PAECs and prevented L-citrulline-induced increases in eNOS dimer-to-monomer ratios in hypoxic PAECs.SNAT1 mediated L-citrulline transport modulates eNOS coupling and thus regulates NO production in hypoxic PAECs from newborn piglets. Strategies that increase SNAT1-mediated transport and supply of L-citrulline may serve as novel therapeutic approaches to enhance NO production in patients with pulmonary vascular disease.

  4. Sodium-coupled neutral amino acid transporter 1 (SNAT1) modulates L-citrulline transport and nitric oxide (NO) signaling in piglet pulmonary arterial endothelial cells.

    Science.gov (United States)

    Dikalova, Anna; Fagiana, Angela; Aschner, Judy L; Aschner, Michael; Summar, Marshall; Fike, Candice D

    2014-01-01

    There is evidence that impairments in nitric oxide (NO) signaling contribute to chronic hypoxia-induced pulmonary hypertension. The L-arginine-NO precursor, L-citrulline, has been shown to ameliorate pulmonary hypertension. Sodium-coupled neutral amino acid transporters (SNATs) are involved in the transport of L-citrulline into pulmonary arterial endothelial cells (PAECs). The functional link between the SNATs, L-citrulline, and NO signaling has not yet been explored. We tested the hypothesis that changes in SNAT1 expression and transport function regulate NO production by modulating eNOS coupling in newborn piglet PAECs. A silencing RNA (siRNA) technique was used to assess the contribution of SNAT1 to NO production and eNOS coupling (eNOS dimer-to-monomer ratios) in PAECs from newborn piglets cultured under normoxic and hypoxic conditions in the presence and absence of L-citrulline. SNAT1 siRNA reduced basal NO production in normoxic PAECs and prevented L-citrulline-induced elevations in NO production in both normoxic and hypoxic PAECs. SNAT1 siRNA reduced basal eNOS dimer-to-monomer ratios in normoxic PAECs and prevented L-citrulline-induced increases in eNOS dimer-to-monomer ratios in hypoxic PAECs. SNAT1 mediated L-citrulline transport modulates eNOS coupling and thus regulates NO production in hypoxic PAECs from newborn piglets. Strategies that increase SNAT1-mediated transport and supply of L-citrulline may serve as novel therapeutic approaches to enhance NO production in patients with pulmonary vascular disease.

  5. Oral L-citrulline supplementation enhances cycling time trial performance in healthy trained men: Double-blind randomized placebo-controlled 2-way crossover study

    OpenAIRE

    Suzuki, Takashi; Morita, Masahiko; Kobayashi, Yoshinori; Kamimura, Ayako

    2016-01-01

    Background Many human studies report that nitric oxide (NO) improves sport performance. This is because NO is a potential modulator of blood flow, muscle energy metabolism, and mitochondrial respiration during exercise. L-Citrulline is an amino acid present in the body and is a potent endogenous precursor of L-arginine, which is a substrate for NO synthase. Here, we investigated the effect of oral L-citrulline supplementation on cycling time trial performance in humans. Methods A double-blind...

  6. Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability.

    Science.gov (United States)

    Morita, Masahiko; Hayashi, Toshio; Ochiai, Masayuki; Maeda, Morihiko; Yamaguchi, Tomoe; Ina, Koichiro; Kuzuya, Masafumi

    2014-11-07

    Chronic supplementation with L-citrulline plus L-arginine has been shown to exhibit anti-atherosclerotic effects. However, the short-term action of this combination on the nitric oxide (NO)-cGMP pathway remains to be elucidated. The objective of the present study was to investigate the acute effects of a combination of oral L-citrulline and L-arginine on plasma L-arginine and NO levels, as well as on blood circulation. Rats or New Zealand white rabbits were treated orally with L-citrulline, or L-arginine, or a combination of each at half dosage. Following supplementation, plasma levels of L-arginine, NOx, cGMP and changes in blood circulation were determined sequentially. L-Citrulline plus L-arginine supplementation caused a more rapid increase in plasma L-arginine levels and marked enhancement of NO bioavailability, including plasma cGMP concentrations, than with dosage with the single amino acids. Blood flow in the central ear artery in rabbits was also significantly increased by L-citrulline plus L-arginine administration as compared with the control. Our data show for the first time that a combination of oral L-citrulline and L-arginine effectively and rapidly augments NO-dependent responses at the acute stage. This approach may have clinical utility for the regulation of cardiovascular function in humans. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Association of levels of antibodies against citrullinated cyclic peptides and citrullinated α-enolase in chronic and aggressive periodontitis as a risk factor of Rheumatoid arthritis: a case control study.

    Science.gov (United States)

    Reichert, Stefan; Schlumberger, Wolfgang; Dähnrich, Cornelia; Hornig, Nora; Altermann, Wolfgang; Schaller, Hans-Günter; Schulz, Susanne

    2015-08-29

    Periodontal disease could be a risk factor for rheumatoid arthritis (RA). It is assumed that the bacterial strain Porphyromonas gingivalis mediates citrullination of host peptides and thereby the generation of RA-associated autoantibodies in genetically predisposed individuals. For that reason non-RA individuals who suffered from generalized aggressive (GAgP, N = 51) and generalized chronic periodontitis (GChP, N = 50) were investigated regarding the occurrence of antibodies against citrullinated cyclic peptides (anti-CCP) and citrullinated α-enolase peptide-1 (anti-CEP-1) in comparison to non-RA non-periodontitis controls (N = 89). Furthermore, putative associations between infections with five periodontopathic bacteria or expression of certain human leucocyte antigens (HLA) to these autoantibodies were investigated. The presence of anti-CCP and anti-CEP-1 in plasma samples was conducted with enzyme linked immunosorbent assay. Subgingival plaque specimens were taken from the deepest pocket of each quadrant and pooled. For detection of DNA of five periodontopathic bacteria PCR with sequence specific oligonucleotides was carried out. Low resolution HLA typing was carried out with PCR with sequence specific primers. Differences between patients and controls were assessed using Chi square test with Yates correction or Fisher`s exact test if the expected number n in one group was periodontitis and RA should be investigated in further studies.

  8. Citrullinated myelin basic protein induces experimental autoimmune encephalomyelitis in Lewis rats through a diverse T cell repertoire.

    Science.gov (United States)

    Cao, L; Sun, D; Whitaker, J N

    1998-08-01

    An increased proportion of citrullinated MBP (MBP-C8) occurs in the brains of multiple sclerosis (MS) patients. In this study, MBP-C8 from guinea pig (GP) brains was isolated and found encephalitogenic in Lewis rats upon immunization. An encephalitogenic T cell line selected with MBP-C8 preferentially reacted with MBP-C8 over unmodified MBP. This T cell line responded weakly to the dominant encephalitogenic epitope, GP-MBP peptide 70-88, and did not display restricted TCR beta-chain usage (such as Vbeta88.2). The distinctive features of MBP-C8 were also demonstrated by its ability to reinduce active EAE in 70% of rats which had recovered from unmodified MBP induced EAE. These findings raise the possibility that citrullinated MBP may elicit a different pathogenic T cell repertoire for the recurrent phases of inflammatory demyelination.

  9. Consumption of Watermelon Juice Enriched in l-Citrulline and Pomegranate Ellagitannins Enhanced Metabolism during Physical Exercise.

    Science.gov (United States)

    Martínez-Sánchez, Ascensión; Alacid, Fernando; Rubio-Arias, Jacobo A; Fernández-Lobato, Bárbara; Ramos-Campo, Domingo J; Aguayo, Encarna

    2017-06-07

    l-Citrulline is a nonessential amino acid precursor of arginine and indirectly a precursor of nitric oxide (NO), which is a vasodilator and increases mitochondrial respiration. On the other hand, the antioxidant pomegranate ellagitannins are precursors of urolithin A, which has been associated with mitophagy and increased muscle function. To elucidate if a single dose of watermelon enrichment with these compounds could have a positive effect after high-intensity exercise (eight sets of eight repetitions of half-squat exercise), a double-blind randomized crossover in vivo study was performed in healthy male subjects (n = 19). Enrichment juices maintained basal levels of blood markers of muscle damage, such as lactate dehydrogenase and myoglobin, and showed a significant maintenance of force during the exercise and a significant decrease in the rating of perceived exertion and muscle soreness after exercise. A positive effect was observed between l-citrulline and ellagitannins, improving the ergogenic effect of watermelon juice.

  10. Sperm quality in men is improved by supplementation with a combination of L-arginine, L-citrullin, roburins and Pycnogenol®.

    Science.gov (United States)

    Stanislavov, R; Rohdewald, P

    2014-12-01

    The aim of this study was to investigate the influence of Prelox®R, a combination of French maritime pine bark extract (Pycnogenol®), L-arginine, L-citrulline and roburins, on male fertility. Sperm quality of 50 subfertile men was tested in monthly intervals in a double-blind, randomized, placebo controlled, crossover study. Patients received 2 tablets Prelox®R or placebo twice daily during test periods. Following a run-in period of 1 month, patients received either Prelox®R or a placebo for 1 month. After a wash-out period of 1 month, patients received Prelox®R or a placebo in a crossover manner for 1 month. Sperm volume, concentration of spermatozoa, total count, motility, vitality and morphology were measured by standard methods of calculation of the Fertility Index (FI) in monthly intervals. Activity of e-NOS in sperm was evaluated in parallel by measuring the quantity of L-citulline produced from L-arginine. Supplementation with Prelox®R enhanced sperm volume and concentration, motility, vitality and morphology significantly versus placebo. The Fertility Index rose to normal values during treatment with Prelox®R. e-NOS activity in sperm was elevated by Prelox®R. No adverse effects were reported. Prelox®R offers a safe method to improve quality of human spermatozoa in subfertile men.

  11. Shared epitope alleles remain a risk factor for anti-citrullinated proteins antibody (ACPA--positive rheumatoid arthritis in three Asian ethnic groups.

    Directory of Open Access Journals (Sweden)

    Too Chun-Lai

    Full Text Available BACKGROUND: To investigate the associations between HLA-DRB1 shared epitope (SE alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia. METHODS: 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping. RESULTS: The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups. CONCLUSION: The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

  12. The Supplementation of Branched-Chain Amino Acids, Arginine, and Citrulline Improves Endurance Exercise Performance in Two Consecutive Days

    Directory of Open Access Journals (Sweden)

    I-Shiung Cheng, Yi-Wen Wang, I-Fan Chen, Gi-Sheng Hsu, Chun-Fang Hsueh, Chen-Kang Chang

    2016-09-01

    Full Text Available The central nervous system plays a crucial role in fatigue during endurance exercise. Branched-chain amino acids (BCAA could reduce cerebral serotonin synthesis by competing with its precursor tryptophan for crossing the blood brain barrier. Arginine and citrulline could prevent excess hyperammonemia accompanied by BCAA supplementation. This study investigated the combination of BCAA, arginine, and citrulline on endurance performance in two consecutive days. Seven male and three female endurance runners ingested 0.17 g·kg-1 BCAA, 0.05 g·kg-1 arginine and 0.05 g·kg-1 citrulline (AA trial or placebo (PL trial in a randomized cross-over design. Each trial contained a 5000 m time trial on the first day, and a 10000 m time trial on the second day. The AA trial had significantly better performance in 5000 m (AA: 1065.7 ± 33.9 s; PL: 1100.5 ± 40.4 s and 10000 m (AA: 2292.0 ± 211.3 s; PL: 2375.6 ± 244.2 s. The two trials reported similar ratings of perceived exertion. After exercise, the AA trial had significantly lower tryptophan/BCAA ratio, similar NH3, and significantly higher urea concentrations. In conclusion, the supplementation could enhance time-trial performance in two consecutive days in endurance runners, possibly through the inhibition of cerebral serotonin synthesis by BCAA and the prevention of excess hyperammonemia by increased urea genesis.

  13. Modular pathway engineering of Corynebacterium glutamicum for production of the glutamate-derived compounds ornithine, proline, putrescine, citrulline, and arginine.

    Science.gov (United States)

    Jensen, Jaide V K; Eberhardt, Dorit; Wendisch, Volker F

    2015-11-20

    The glutamate-derived bioproducts ornithine, citrulline, proline, putrescine, and arginine have applications in the food and feed, cosmetic, pharmaceutical, and chemical industries. Corynebacterium glutamicum is not only an excellent producer of glutamate but also of glutamate-derived products. Here, engineering targets beneficial for ornithine production were identified and the advantage of rationally constructing a platform strain for the production of the amino acids citrulline, proline, and arginine, and the diamine putrescine was demonstrated. Feedback alleviation of N-acetylglutamate kinase, tuning of the promoter of glutamate dehydrogenase gene gdh, lowering expression of phosphoglucoisomerase gene pgi, along with the introduction of a second copy of the arginine biosynthesis operon argCJB(A49V,M54V)D into the chromosome resulted in a C. glutamicum strain producing ornithine with a yield of 0.52 g ornithine per g glucose, an increase of 71% as compared to the parental ΔargFRG strain. Strains capable of producing 0.41 g citrulline per g glucose, 0.29 g proline per g glucose, 0.30 g arginine per g glucose, and 0.17 g putrescine per g glucose were derived from the ornithine-producing platform strain by plasmid-based overexpression of appropriate pathway modules with one to three genes. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. [Significance of antibodies to the citrullinated glucose-6-phosphate isomerase peptides in rheumatoid arthritis].

    Science.gov (United States)

    Wu, D; Sun, L; Li, C H; Yang, L; Zhao, J X; Liu, X Y

    2016-12-18

    To detect the anti-citrullinated glucose-6-phosphate isomerase (GPI) 70-88 peptide antibody (anti-C-GPI(70-88) antibody), anti-citrullinated GPI 435-453 peptide antibody (anti-C-GPI(435-453) antibody), anti-GPI 70-88 peptide antibody (anti-GPI(70-88) antibody) and anti-GPI 435-453 peptide antibody(anti-GPI(435-453) antibody) in the serum of rheumatoid arthritis (RA) patients, and examine the diagnostic values of the anti-C-GPI peptide antibodies in RA. The anti-C-GPI(70-88) antibody, anti-C-GPI(435-453) antibody, anti-GPI(70-88) antibody and anti-GPI(435-453) antibody were detected by enzyme-linked immunosorbent assay (ELISA) in 191 RA patients, 129 other rheumatic diseases and 74 healthy controls. The clinical and laboratory data of the patients with RA were collected, and the values of anti-C-GPI peptide antibodies in the diagnosis of RA and the relationships of anti-C-GPI peptide antibodies with the clinical and laboratory parameters analyzed. (1) The mean titers of the anti-C-GPI(70-88) antibody and the anti-C-GPI(435-453) antibody in the RA patients (respectively, 68.71 ± 4.20 and 51.78 ± 3.13) were significantly higher than those with other rheumatic diseases and healthy individuals (P <0.05). However, the mean titers of the anti-GPI(70-88) antibody and anti-GPI(435-453) antibody in the RA patients were similar to those with other rheumatic diseases and healthy individuals. (2) The diagnostic sensitivity and specificity of the anti-C-GPI(70-88) antibody for RA were 41.88% and 84.50% respectively; and the diagnostic sensitivity and specificity of the anti-C-GPI(435-453) antibody for RA were 46.05% and 86.05% respectively. The sensitivity of combined detection of the two anti-C-GPI peptide antibodies was 50.79%, and the specificity was 81.40%. (3) The positive rates of the anti-C-GPI(70-88) antibody and the anti-C-GPI(435-453) antibody were 35% and 45% respectively in those patients with negative anti-cyclic citrullinated peptide antibody, anti

  15. Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing

    Science.gov (United States)

    Díaz-Toscano, Miriam Lizette; Olivas-Flores, Eva Maria; Zavaleta-Muñiz, Soraya Amali; Gamez-Nava, Jorge Ivan; Cardona-Muñoz, Ernesto German; Ponce-Guarneros, Manuel; Castro-Contreras, Uriel; Nava, Arnulfo; Salazar-Paramo, Mario; Celis, Alfredo; Fajardo-Robledo, Nicte Selene; Corona-Sanchez, Esther Guadalupe; Gonzalez-Lopez, Laura

    2014-01-01

    Determination of anti-citrullinated peptide antibodies (ACPA) plays a relevant role in the diagnosis of rheumatoid arthritis (RA). To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies for the diagnosis of RA. We compared three groups: RA (n = 142), chronic inflammatory disease (CIRD, n = 86), and clinically healthy subjects (CHS, n = 56) to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR) of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2%) as compared with anti-MCV (81.0%). When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis. PMID:25025037

  16. Comparison of Two Assays to Determine Anti-Citrullinated Peptide Antibodies in Rheumatoid Arthritis in relation to Other Chronic Inflammatory Rheumatic Diseases: Assaying Anti-Modified Citrullinated Vimentin Antibodies Adds Value to Second-Generation Anti-Citrullinated Cyclic Peptides Testing

    Directory of Open Access Journals (Sweden)

    Miriam Lizette Díaz-Toscano

    2014-01-01

    Full Text Available Determination of anti-citrullinated peptide antibodies (ACPA plays a relevant role in the diagnosis of rheumatoid arthritis (RA. To date, it is still unclear if the use of several tests for these autoantibodies in the same patient offers additional value as compared to performing only one test. Therefore, we evaluated the performance of using two assays for ACPA: second-generation anti-citrullinated cyclic peptides antibodies (anti-CCP2 and anti-mutated citrullinated vimentin (anti-MCV antibodies for the diagnosis of RA. We compared three groups: RA (n=142, chronic inflammatory disease (CIRD, n=86, and clinically healthy subjects (CHS, n=56 to evaluate sensitivity, specificity, predictive values, and likelihood ratios (LR of these two assays for the presence of RA. A lower frequency of positivity for anti-CCP2 was found in RA (66.2% as compared with anti-MCV (81.0%. When comparing RA versus other CIRD, sensitivity increased when both assays were performed. This strategy of testing both assays had high specificity and LR+. We conclude that adding the assay of anti-MCV antibodies to the determination of anti-CCP2 increases the sensitivity for detecting seropositive RA. Therefore, we propose the use of both assays in the initial screening of RA in longitudinal studies, including early onset of undifferentiated arthritis.

  17. Anti-carbamylated Protein Antibody Levels Correlate with Anti-Sa (Citrullinated Vimentin) Antibody Levels in Rheumatoid Arthritis.

    Science.gov (United States)

    Challener, Gregory J; Jones, Jonathan D; Pelzek, Adam J; Hamilton, B JoNell; Boire, Gilles; de Brum-Fernandes, Artur José; Masetto, Ariel; Carrier, Nathalie; Ménard, Henri A; Silverman, Gregg J; Rigby, William F C

    2016-02-01

    The presence of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) indicates a breach in immune tolerance. Recent studies indicate that this breach extends to homocitrullination of lysines with the formation of anti-carbamylated protein (anti-CarP) antibodies. We analyzed the clinical and serologic relationships of anti-CarP in 2 RA cohorts. Circulating levels of immunoglobulin G anti-CarP antibodies were determined by ELISA in established (Dartmouth-Hitchcock Medical Center) and early (Sherbrooke University Hospital Center) cohorts and evaluated for anticyclic citrullinated peptide antibodies (anti-CCP), specific ACPA, and rheumatoid factor (RF) levels using the Student t test and correlation analysis. We identified elevated anti-CarP antibodies titers in 47.0% of seropositive patients (Dartmouth, n = 164), with relationships to anti-CCP (p < 0.0001) and IgM-RF (p = 0.001). Similarly, 38.2% of seropositive patients from the Sherbrooke cohort (n = 171) had elevated anti-CarP antibodies; titers correlated to anti-CCP (p = 0.01) but not IgM-RF (p = 0.09). A strong correlation with anti-Sa was observed: 47.9% anti-Sa+ patients were anti-CarP antibodies+ versus only 25.4% anti-Sa- in the Sherbrooke cohort (p = 0.0002), and 62.6% anti-Sa+ patients versus 26.9% anti-Sa- were anti-CarP antibodies+ in Dartmouth (p < 0.0001). We found a more variable response for reactivity to citrullinated fibrinogen or to citrullinated peptides from fibrinogen and α enolase. In 2 North American RA cohorts, we observed a high prevalence of anti-CarP antibody positivity. We also describe a surprising and unexpected association of anti-CarP with anti-Sa antibodies that could not be explained by cross-reactivity. Further, considerable heterogeneity exists between anti-CarP reactivity and other citrullinated peptide reactivity, raising the question of how the pathogenesis of antibody responses for carbamylated proteins and citrullinated proteins may be linked in vivo.

  18. Anti-citrullinated alpha enolase antibodies, interstitial lung disease and bone erosion in rheumatoid arthritis.

    Science.gov (United States)

    Alunno, Alessia; Bistoni, Onelia; Pratesi, Federico; La Paglia, Giuliana Maria Concetta; Puxeddu, Ilaria; Migliorini, Paola; Gerli, Roberto

    2018-02-14

    RA is an articular chronic inflammatory disease that in a subgroup of patients can also present with extra-articular manifestations (EAMs). Despite intense investigation on this topic, reliable biomarkers for EAMs are lacking. In recent years several ACPAs, including those targeting anti-citrullinated alpha enolase peptide-1 (anti-CEP-1), have been identified in patients with RA. Data about the ability of anti-CEP-1 to predict the development of erosive disease are confliciting and no evidence concerning their possible association with EAMs in RA is currently available. The aim of this study was to investigate the prevalence and significance of anti-CEP-1 with regard to the association with erosive disease and EAMs in a large cohort of patients with RA. Anti-CCP and anti-CEP-1 antibodies have been assessed on serum samples of RA patients, healthy donors and patients with SpA using commercially available ELISA kits. Anti-CEP-1 antibodies are detectable in over 40% of RA patients and are associated with erosive RA and with RA-associated interstitial lung disease (ILD). Anti-CEP-1 antibodies may represent a useful biomarker for RA-associated ILD and erosive disease to be employed in clinical practice. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  19. Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses.

    Science.gov (United States)

    Harlow, Lisa; Gochuico, Bernadette R; Rosas, Ivan O; Doyle, Tracy J; Osorio, Juan C; Travers, Timothy S; Camacho, Carlos C; Oddis, Chester V; Ascherman, Dana P

    2014-11-01

    Previous work has demonstrated a correlation between serum anti-citrullinated HSP90 antibodies and rheumatoid arthritis-associated interstitial lung disease (RA-ILD). To further investigate this potential pathogenic relationship, we used ELISA-based techniques to assess anti-citrullinated HSP90 antibody profiles in bronchoalveolar lavage fluid (BALF) of patients with different stages of RA-ILD. 9/21 RA-derived BALF specimens demonstrated IgG and/or IgA antibodies targeting citrullinated HSP90 proteins/peptides, highlighting disease specific responses (with a predilection for RA-ILD) that did not occur in IPF patients (0/5) or healthy control subjects (0/5). Comparison of antibody profiles between BALF and matching serum specimens revealed various recognition patterns favoring predominant production of anti-citrullinated HSP90 antibodies within the lung microenvironment-further supporting the connection between this antibody specificity and parenchymal lung disease. Equally important, qualitative as well as quantitative differences in anti-citrullinated HSP90 profiles between BALF and serum indicate that the lung plays a direct role in shaping the immune repertoire of RA/RA-ILD. Published by Elsevier Inc.

  20. Defining combined immunodeficiency.

    Science.gov (United States)

    Roifman, Chaim M; Somech, Raz; Kavadas, Fotini; Pires, Linda; Nahum, Amit; Dalal, Ilan; Grunebaum, Eyal

    2012-07-01

    responses, patients with the p.R222C mutation in the IL-2 receptor γ(IL2RG) gene as well as IL-10 receptor and CD40 ligand deficiencies had normal or near-normal mitogen responses. Finally, 51 patients had TREC levels measured. All patients with typical SCID, Omenn syndrome, and ZAP70 deficiency had low TREC levels. In contrast, patients with mutations in forkhead box protein 3 (FOXP3), CD40 ligand (CD40L), and IL-10 receptor α(IL10RA), as well as patients with the p.R222C mutation in the IL2RG gene, had normal TREC levels. Patients with typical SCID can be defined as having fewer than 500 circulating CD3(+) T cells. Most patients with autologous T cells still have profound TD, as defined by reduced in vitro function and thymus output. Some patients with conditions including TD have normal TREC levels and will therefore not be detected in a TREC-based newborn screening program. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  1. Fasting and Postprandial Plasma Citrulline and the Correlation to Intestinal Function Evaluated by 72-Hour Metabolic Balance Studies in Short Bowel Jejunostomy Patients With Intestinal Failure

    DEFF Research Database (Denmark)

    Fjermestad, Hilde; Hvistendahl, Mark; Jeppesen, Palle Bekker

    2018-01-01

    absorption parameters in short bowel syndrome patients with intestinal failure (SBS-IF). MATERIALS AND METHODS: Eight patients with SBS-IF and 8 healthy controls (HCs) were given a standardized mixed test meal, and p-citrulline was measured 15 minutes before and 60, 120, and 180 minutes after completion...... of the meal. The patients with SBS-IF had their intestinal absorption of wet weight, energy, macronutrients, and electrolytes measured in relation to 72-hour metabolic balance studies. We investigated the possible correlations between p-citrulline and short bowel length, absorptive parameters......-citrulline and bowel length, bowel absorptive function, or the dependence on PS were found. Even when excluding 2 patients in whom the intestinal absorption was adjacent to the intestinal insufficiency borderlines, these correlations were not significant. CONCLUSION: Based on findings in this small study, the optimal...

  2. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting: Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4{sup +} T cells compared

    Energy Technology Data Exchange (ETDEWEB)

    Ford, A.L.; Goodsall, A.L.; Sedgwick, J.D. [Centenary Institute of Cancer Medicine and Cell Biology, Sydney (Australia)] [and others

    1995-05-01

    Ramified microglia in the adult central nervous system (CNS) are the principal glial element up-regulating MHC class I and II expression in response to inflammatory events or neuronal damage. A proportion of these cells also express MHC class II constitutively in the normal CNS. The role of microglia as APCs for CD4{sup +} cells extravasating into the CNS remains undefined. In this study, using irradiation bone marrow chimeras in CD45-congenic rats, the phenotype CD45{sup low}CD11b/c{sup +} is shown to identify microglial cells specifically within the CNS. Highly purified populations of microglia and nonmicroglial but CNS-associated macrophages (CD45{sup high}CD11b/c{sup +}) have been obtained directly from the adult CNS, by using flow cytometric sorting. Morphologically, freshly isolated microglia vs other CNS macrophages are quite distinct. Of the two populations recovered from the normal CNS, it is the minority CD45{sup high}CD11 b/c{sup +} transitional macrophage population, and not microglia, that is the effective APC for experimental autoimmune encephalomyelitis-inducing CD4{sup +} myelin basic protein (MBP)-reactive T cells. CD45{sup high}CD11b/c{sup +} CNS macrophages also stimulate MBP-reactive T cells without addition of MBP to culture suggesting presentation of endogenous Ag. This is the first study in which microglia vs other CNS macrophages have been analyzed for APC ability directly from the CNS, with substantial cross-contamination between the two populations eliminated. The heterogeneity of these populations in terms of APC function is clearly demonstrated. Evidence is still lacking that adult CNS microglia have the capacity to interact with and stimulate CD4{sup +} T cells to proliferate or secrete IL-2. 60 refs., 6 figs., 1 tab.

  3. Use of anti-citrullinated peptide (Anti –CCP antibodies in distinguishing patients with systemic lupus erythematosus and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Harry Isbagio

    2004-12-01

    Full Text Available Diagnosis of Rheumatoid arthritis (RA and systemic lupus erythematosus (SLE can be confused in their initial stages. The joints, especially the hands, are commonly affected in both disorders, many patients with SLE are initially misdiagnosed as having RA Given that the outcome for the two diseases is diverse, it would be helpful to have serological marker to distinguish between them at onset. Anti-citrullinated peptide antibodies (anti-CCP have recently been described as highly specific for RA. The objective of this study is to confirm the specificity of anti-CCP antibodies and to determine whether they might distinguish patients with RA from those with SLE. This study is a cross sectional study on a group of patients with RA (n=27, SLE with arthritis (n=20, other autoimmune diseases (non-rheumatic diseases, n = 8, and healthy adults (n=20. Anti-CCP was determined by a commercial Elisa test and Rheumatoid factor (RF was determined by the standard slide latex test. The sensitivity and specificity of anti-CCP for the diagnosis of RA was 63.0% and 97.9% respectively, comparing with RF for RA that was 40.7 % and 85.4 %. Only 1 healthy adult was anti-CCP+, no anti-CCP was detected from SLE and other autoimmune disease. The mean of titer anti CCP in normal healthy adult, other autoimmune diseases, SLE and RA was 1.35 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 2.04, 0.63 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 0.59, 0.75 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 0.59, and 38.17 Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 ± 44.22 RU/ml, respectively. There was a highly significant difference between the mean of titer anti CCP for RA with others diseases (p <0.001. We conclude that detection of anti-CCP is very useful for the diagnosis of RA and distinguishing RA from SLE. (Med J Indones 2004; 13: 227-31Keywords

  4. Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres.

    Science.gov (United States)

    Lappin, David F; Apatzidou, Danae; Quirke, Anne-Marie; Oliver-Bell, Jessica; Butcher, John P; Kinane, Denis F; Riggio, Marcello P; Venables, Patrick; McInnes, Iain B; Culshaw, Shauna

    2013-10-01

    Anti-citrullinated protein antibody (ACPA) responses may precede clinical onset of rheumatoid arthritis. Porphyromonas gingivalis peptidylarginine deiminase can citrullinate proteins possibly inducing autoimmunity in susceptible individuals. To determine whether periodontitis, carriage of P. gingivalis, smoking and periodontal therapy influence ACPA titres. Serum and plaque samples were collected from 39 periodontitis patients before and after non-surgical periodontal treatment, and from 36 healthy subjects. Carriage of P. gingivalis was determined by PCR of plaque DNA. ACPA was determined by anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assay (ELISA). Anti-P. gingivalis titres were determined by ELISA. Untreated periodontitis patients had higher anti-CCP antibody titres than healthy controls [three patients (8%) greater than manufacturer suggested assay diagnostic threshold (5 Assay Units/AU) versus none (0%); mean ± SEM: 1.37 ± 0.23 versus 0.40 ± 0.10 AU, p Periodontitis patients who smoked demonstrated lower anti-P. gingivalis (15956 ± 4385 versus 2512 ± 1290 Units/ml, p smoking periodontitis patients (smokers: 1.31 ± 0.35; non-smokers: 1.41 ± 0.32 AU). Healthy smokers demonstrated elevated anti-CCP titres (0.75 ± 0.19 AU), at levels between healthy non-smokers (0.15 ± 0.05 AU) and non-smoker periodontitis patients. Six months after periodontal treatment, there were significant reductions in anti-CCP (non-smokers p periodontitis, P. gingivalis infection may be responsible for inducing autoimmune responses that characterize rheumatoid arthritis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies

    Science.gov (United States)

    Vignesh, Ammapati Paul Pandian; Srinivasan, Renuka

    2015-01-01

    Purpose To study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) with the ocular manifestations. Methods Three-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer’s test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests. Results Seventy-seven patients (135 eyes, 39%) out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients). The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients). Scleritis was present in 2% of the patients (four patients). Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven patients) had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001. Conclusion Ocular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a statistically significant association between the presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular manifestations. PMID:25750517

  6. Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Theodoridou Katerina

    2007-04-01

    Full Text Available Abstract Background Anti-cyclic citrullinated peptide (anti-CCP antibodies have been of diagnostic value in Northern European Caucasian patients with rheumatoid arthritis (RA. In these populations, anti-CCP antibodies are associated with the HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies in Greek patients with RA where the HLA shared epitope was reported in a minority of patients. Methods Using an enzyme-linked immunosorbent assay (ELISA (CCP2 kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also determined rheumatoid factor (RF and compared it to anti-CCP antibodies for area under the curve (AUC, sensitivity, specificity and likelihood ratios. Results Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and specificity was 95.0% and 91.2%, respectively. When considered simultaneously, the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF-negative RA patients. Anti-CCP antibodies showed a correlation with the radiographic joint damage. Anti-CCP-positive RA patients had increased the swollen joint count and serum CRP concentration compared to anti-CCP-negative RA patients (Mann-Whitney U test, p = 0.01, and p Conclusion In Greek patients with RA, anti-CCP2 antibodies exhibit a better diagnostic value than RF and a correlation with radiological joint damage and therefore are useful in everyday rheumatology practice.

  7. The clinical significance of antibody determination to cyclic citrullinated peptides in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Stamenković Bojana

    2012-01-01

    Full Text Available Introduction. Anti-citrullinated peptides antibodies (ACPA are present in 80% of sera of rheumatoid arthritis (RA patients with high specificity for diagnosis and prediction for the development of early erosive arthritis. A few studies have reported a low frequency ACPA in systemic sclerosis (SSc patients with the presence of arthritis. Objective. The aim of our study was to determine the frequency of ACPA in systemic sclerosis (SSc patients, their correlation with clinical manifestations and radiographic features. Methods. The study included 82 patients with SSc, mean age 54.4 years, 59 with the limited (lSSc and 23 with the diffuse (dSSc form of the disease. The control group included 28 healthy age and sex matched subjects. ACPA and rheumatoid factor (RF were determined in all SSc patients and healthy subjects in whom standard radiography of hands and wrists was also done. Results. The presence of ACPA was detected in 11 (13.4% of SSc patients. Their level was not increased in any of the controls. Positive RF was found in 15.9% of SSc patients. Arthritis was present in 17.1%, as well as marginal bone erosions. There was a statistically significant association between positive ACPA and arthritis (p<0.0001 and positive ACPA and marginal bone erosions (p=0.0002. Conclusion. The research confirmed the correlation between ACPA with clinical signs of arthritis and radiographic damage of hand joints. ACPA is a useful diagnostic marker in the identification of SSc patients with arthritis and anatomic bone damage enabling the use of adequate therapy in order to prevent joint damage and poor quality of life.

  8. Anti-cyclic citrullinated peptide antibodies in ulcerative colitis, and its relation with disease activity.

    Science.gov (United States)

    Shafaghi, Afshin; Mansour-Ghanaei, Fariborz; Rostamnejad, Maryam; Amir Maafi, Alireza; Haji-Abbasi, Asghar; Froutan, Hossein

    2014-01-01

    Ulcerative colitis an inflammatory bowel disease (IBD) and chronically idiopathic immune related that associates with extraintestinal manifestations such as arthritis. Despite of the highly specificity of anticyclic citrullinated peptide (CCP) antibodies for rheumatoid arthritis, their role in IBD remains unclear. There are only a few studies on the prevalence of anti-CCP antibodies in patients with IBD. This study aimed to assess the prevalence of anti- CCP antibodies in ulcerative colitis and to investigate possible associations with their clinical and laboratory characteristics Methods: In this cross-sectional study, 93 consecutive patients with ulcerative colitis referred to gastroenterology clinics in Razi referral hospital of Rasht, Iran, from September 2010 to September 2011. Rheumatologic examination, demographic data and clinical presentation of patients were recorded on specially prepared data sheets. Blood sample was collected for assessment of anti-CCP and other laboratory tests. Data were analyzed by the Chi square test, Fisher Exact test and student t test, using the SPSS 20 software for Windows, and P value less than 0.05 was considered significant. Of 93 patients, anti-CCP antibodies detected in 10.8% of cases (CI 95%: 4.5-17.1%). There were a significant relation between the prevalence of anti CCP positivity and aphthous ulcers and ocular manifestations whereas other parameters were not significantly related. Anti CCP may have a possible role in some ulcerative colitis manifestations but there was no association between the presence of these antibodies and activity or extension of inflammatory colitis. We suggest other studies especially molecular studies to investigate other aspects of these antibodies in IBD patients.

  9. Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via a chemokine-dependent mechanism.

    Science.gov (United States)

    Wigerblad, Gustaf; Bas, Duygu B; Fernades-Cerqueira, Cátia; Krishnamurthy, Akilan; Nandakumar, Kutty Selva; Rogoz, Katarzyna; Kato, Jungo; Sandor, Katalin; Su, Jie; Jimenez-Andrade, Juan Miguel; Finn, Anja; Bersellini Farinotti, Alex; Amara, Khaled; Lundberg, Karin; Holmdahl, Rikard; Jakobsson, Per-Johan; Malmström, Vivianne; Catrina, Anca I; Klareskog, Lars; Svensson, Camilla I

    2016-04-01

    An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation. 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/

  10. Study of erythrocyte sedimentation rate and anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Khalid, S.; Yousaf, J.; Rashid, A.

    2017-01-01

    Objective: To study the erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in rheumatoid arthritis patients on disease modifying anti-rheumatic drug therapy. Study Design: Cross sectional comparative study. Place and Duration of Study: Centre for Research in Experimental and Applied Medicine (CREAM-I), Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi in collaboration with Reumatology Department, Military Hospital Rawalpindi, from Jan 2016 to Jun 2016. Material and Methods: Study sample was seventy in number and was divided into two groups. Group I consisted of thirty five patients suffering from rheumatoid arthritis, while group II consisted of thirty five healthy individuals who were not suffering from any chronic illness. Non probability purposive sampling was done. ESR was measured using Westergren method, while anti-CCP was estimated by enzyme-linked immune sorbent assay (ELISA). Results: Data were analyzed using SPSS 22 version. Mean age of patients of rheumatoid arthritis was 49.69 +- 11.5 years and that of control group was 47.4 +- 10.4 years. Among the study population 30 (43%) individuals were males and 40 (57%) were females. In patient category, there were 10 (29%) males and 25 (71%) females. In control group 20 (57%) males and 15 (43%) females were present. Independent t-test was applied between the two variables i.e. ESR and anti-CCP, with showed significant p-value of less than 0.001. Conclusion: There was significant increase in both ESR and anti-CCP levels in rheumatoid arthritis patients on disease modifying anti-rheumatic drugs as compared with control group. (author)

  11. The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study.

    Science.gov (United States)

    Raikou, Vassiliki; Varvaresou, Athanasia; Panderi, Irene; Papageorgiou, Effie

    2017-06-01

    Bioactive peptides have beneficial effects on the skin. We investigated to evaluate the effect of acetyl hexapeptide-3 and tripeptide-10 citrulline and the possible synergism between these two peptides. Twenty-four healthy volunteers were randomized to receive combination of acetyl hexapeptide-3 with tripeptide-10 citrulline (Group G1), tripeptide-10 citrulline (Group, G2), acetyl hexapeptide-3 (Group G3), or neither peptide (Group G4) for 60 days. Skin properties evaluated included skin microtopography, parameters cR2 and cR3, and transepidermal water loss (TEWL) using a skin visioscan and a tewameter, respectively. After 20 days, the measurements between G1 and G2 groups (cR2 P=.045, cR3 P=.044), G2 and G3 groups (cR2 P=.017, cR3 P=.017), G3 and G4 groups (CR2 P=.022), and G2 and G4 groups (cR3 P=.028) from baseline were significant. After 60 days, measurements between groups G1 and G3 (cR2 P=.016, cR3 P=.025), groups G2 and G3 (cR2 P=.044, cR3= P=.044), and groups G1 and G4 (cR2 P=.025) were significant. After 20 days, changes in TEWL between groups G1 and G3 (P=.03), groups G2 and G3 (P=.045), and groups G3 and G4 (P=.025) were significant. After 40 days, changes between groups G2 and G3 (P=.028) and groups G3 and G4 (P=.01) from baseline were significant. Our results confirm the antiwrinkle activity of acetyl hexapeptide-3. A significant decrease in TEWL with acetyl hexapeptide-3 treatment is observed. We provided clinical evidence for the antiwrinkle efficacy of tripeptide-10 citrulline and possibly TEWL. The underlying mechanism by which these two peptides can act synergistically was not clear in this study. © 2017 Wiley Periodicals, Inc.

  12. A case of anti-cyclic citrullinated peptides antibody positive rheumatoid meningitis without arthritis at the onset of neurological symptoms.

    Science.gov (United States)

    Abe, Tetsuya; Mishima, Kazuhiko; Uchino, Akira; Sasaki, Atsushi; Tanahashi, Norio; Takao, Masaki

    2016-09-29

    We report an 84-year-old woman with rheumatoid meningitis. She developed weakness in her muscles and became cognitively impaired. However, physical examination revealed no evidence of rheumatoid arthritis. Levels of anti-cyclic citrullinated peptide antibodies were elevated. Brain magnetic resonance imaging (MRI) showed hyperintense lesions in the frontotemporoparietal subarachnoid space on fluid attenuated inversion recovery (FLAIR) images. Leptomeningeal enhancement was also evident on gadolinium-enhanced T1-weighted images. We suspected rheumatoid meningitis. A brain biopsy was performed and methylprednisolone pulse therapy was started. Subsequently, her symptoms and MRI findings rapidly improved.

  13. [Significance of anti-citrullinated human papilloma virus-47 E2(345-362) peptide antibodies in diagnosis of early-stage rheumatoid arthritis].

    Science.gov (United States)

    Li, Gui-ye; Sun, Xiao-lin; Li, Yun; Jia, Ru-lin; Jia, Yuan; Li, Zhan-guo

    2013-06-18

    To investigate the prevalence and the diagnostic values of antibodies to the citrullinated HPVP in early-stage rheumatoid arthritis. Antibodies against HPVP and citrullinated HPVP were detected by ELISA in the sera of 101 patients with early-stage RA, 149 patients with other rheumatic diseases and 40 healthy controls. The prevalence and diagnostic values of these antibodies for early-stage RA were analyzed by statistical software. (1)The prevalence of IgG, IgM antibodies to citrullinated HPVP in early-stage RA were significantly higher than that in the patients with other rheumatic diseases as well as in the healthy individuals.(2)The diagnostic sensitivity of IgG and IgM citrullinated HPVP antibodies in early-stage RA were 62.4% and 66.3% respectively and the specificity value of the two antibody isotypes were 88.7% and 89.6%,similar to that of the anti-CCP antibody. (3)The positivity rates of IgG and IgM antibodies against citrullinated HPVP were 59.4% and 71.9% in IgM-RF negative early-stage RA patients, and 39.4% and 51.5% in anti-CCP antibody negative early-stage RA patients. (4) The DAS28 score [ IgG (6.3±1.0) vs. (5.6±0.9), P=0.002; IgM (6.2±1.1) vs. (5.6±0.8), P=0.008] , X-ray stages (IgG 56.1% vs. 21.2%, P=0.001;IgM 50.9% vs. 29.4%, P=0.036),anti-CCP antibodies(IgG 96.8% vs. 55.3%, P=0.001; IgM 89.6% vs. 64.7%, P=0.023) in citrullinated HPVPP positive patients were higher than those of citrullinated HPVP negative patients. Additionally, the levels of ESR[IgG(70.3±32.4)vs.(51.9±27.8), P=0.004; IgM (67.4±31.5)vs.(53.8±27.7), P=0.035] in citrullinated HPVP positive patients were higher than those of negative patients (Pbiomarkers for early-stage RA diagnosis, and are related to disease activity and joint damage.

  14. Chronic Co-Administration of Sepiapterin and L-Citrulline Ameliorates Diabetic Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury in Obese Type 2 Diabetic Mice.

    Science.gov (United States)

    Baumgardt, Shelley L; Paterson, Mark; Leucker, Thorsten M; Fang, Juan; Zhang, David X; Bosnjak, Zeljko J; Warltier, David C; Kersten, Judy R; Ge, Zhi-Dong

    2016-01-01

    Diabetic heart disease is associated with tetrahydrobiopterin oxidation and high arginase activity, leading to endothelial nitric oxide synthase dysfunction. Sepiapterin (SEP) is a tetrahydrobiopterin precursor, and L-citrulline (L-Cit) is converted to endothelial nitric oxide synthase substrate, L-arginine. Whether SEP and L-Cit are effective at reducing diabetic heart disease is not known. The present study examined the effects of SEP and L-Cit on diabetic cardiomyopathy and ischemia/reperfusion injury in obese type 2 diabetic mice. Db/db and C57BLKS/J mice at 6 to 8 weeks of age received vehicle, SEP, or L-Cit orally alone or in combination for 8 weeks. Cardiac function was evaluated with echocardiography. Db/db mice displayed hyperglycemia, obesity, and normal blood pressure and cardiac function compared with C57BLKS/J mice at 6 to 8 weeks of age. After vehicle treatment for 8 weeks, db/db mice had reduced ejection fraction, mitral E/A ratio, endothelium-dependent relaxation of coronary arteries, tetrahydrobiopterin concentrations, ratio of endothelial nitric oxide synthase dimers/monomers, and nitric oxide levels compared with vehicle-treated C57BLKS/J mice. These detrimental effects of diabetes mellitus were abrogated by co-administration of SEP and L-Cit. Myocardial infarct size was increased, and coronary flow rate and ± dP/dt were decreased during reperfusion in vehicle-treated db/db mice subjected to ischemia/reperfusion injury compared with control mice. Co-administration of SEP and L-Cit decreased infarct size and improved coronary flow rate and cardiac function in both C57BLKS/J and db/db mice. Co-administration of SEP and L-Cit limits diabetic cardiomyopathy and ischemia/reperfusion injury in db/db mice through a tetrahydrobiopterin/endothelial nitric oxide synthase/nitric oxide pathway. © 2016 American Heart Association, Inc.

  15. Effect of the human leukocyte antigen HLA-DRB1 and anti-cyclic citrullinated peptide on the outcome of rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    H.M. Farouk

    2009-09-01

    Full Text Available Our objective was to determine whether the presence of the human leukocyte antigen HLA-DRB1 locus is associated with production of anti-cyclic citrullinated peptide antibodies (anti-CCP Abs and to what extent they are associated with increased susceptibility to and severity of rheumatoid arthritis (RA in Egyptian patients. Twenty-nine RA patients gave informed consent to participate in a case-control study that was approved by the Ain Shams University Medical Ethics Committee. RA disease activity and severity were determined using the simplified disease activity index and Larsen scores, respectively. We used a wide scale national study on the pattern of HLA typing in normal Egyptians as a control study. Anti-CCP Abs and HLA-DRB1 typing were determined for all subjects. The alleles most strongly associated with RA were HLA-DRB1 [*01 , *04 and *06] (41.4%. RA patients with serum anti-CCP Ab titers above 60 U/mL had a significantly higher frequency of HLA-DRB1*01 (58.3% and HLA-DRB1*04 alleles (83.3%. Significant positive correlations were found between serum and synovial anti-CCP Ab titer, RA disease activity, and severity (r = 0.87, 0.66 and 0.63, respectively; P < 0.05. HLA-DRB1 SE+ alleles [*01 and *04] were highly expressed among Egyptian RA patients. The presence of these alleles was associated with higher anti-CCP Ab titer, active and severe RA disease. Early determination of HLA-DRB1 SE+ alleles and serum anti-CCP Ab could facilitate the prediction of the clinical course and prognosis of RA when first evaluated leading to better disease control.

  16. Synergistic effects of citrulline supplementation and exercise on performance in male rats: evidence for implication of protein and energy metabolisms.

    Science.gov (United States)

    Goron, Arthur; Lamarche, Frédéric; Cunin, Valérie; Dubouchaud, Hervé; Hourdé, Christophe; Noirez, Philippe; Corne, Christelle; Couturier, Karine; Sève, Michel; Fontaine, Eric; Moinard, Christophe

    2017-04-25

    Background: Exercise and citrulline (CIT) are both regulators of muscle protein metabolism. However, the combination of both has been under-studied yet may have synergistic effects on muscle metabolism and performance. Methods: Three-month-old healthy male rats were randomly assigned to be fed ad libitum for 4 weeks with either a citrulline-enriched diet (1 g·kg -1 ·day -1 ) ( CIT ) or an isonitrogenous standard diet (by addition of nonessential amino acid) ( Ctrl ) and trained (running on treadmill 5 days·week -1 ) ( ex ) or not. Maximal endurance activity and body composition were assessed, and muscle protein metabolism (protein synthesis, proteomic approach) and energy metabolism [energy expenditure, mitochondrial metabolism] were explored. Results: Body composition was affected by exercise but not by CIT supplementation. Endurance training was associated with a higher maximal endurance capacity than sedentary groups ( P supplementation alone increased muscle protein synthesis (by +27% and +33%, respectively, versus Ctrl , P supplementation. However, the proteomic approach demonstrated that CIT supplementation was able to affect energy metabolism, probably due to activation of pathways generating acetyl-CoA. Conclusion: CIT supplementation and endurance training in healthy male rats modulates both muscle protein and energy metabolisms, with synergic effects on an array of parameters, including performance and protein synthesis. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  17. Early diagnostic and prognostic values of anti-cyclic citrullinated peptide antibody and cartilage oligomeric matrix protein in rheumatoid arthritis.

    Science.gov (United States)

    Algergawy, Shereen A; Abd El-Sabour, M; Osman, Ahmed S; Emam, Sherin M; Elham, N

    2013-01-01

    This study aimed to evaluate the role of Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody in comparison to Cartilage oligomeric matrix protein (COMP) in Rheumatoid Arthritis (RA) patients as predictors of the disease activity and cartilage destruction. The study included 60 patients &10 apparently healthy subjects. They were divided into 4 groups. Group 1: consisted of 20 patients with established rheumatoid arthritis( and positive rheumatoid factor). Group 2: 20 suspected (rheumatoid factor negative) patients Group 3: 20 patients with other autoimmune inflammatory diseases (15 with psoaritic arthritis, 5 with systemic lupus erthromatosis).and Group 4: 10 age and sex matched controls. For each patient medical examination and disease activity evaluation using Disease Activity Score (DAS) was performed Anti cyclic citrullinated peptide (anti CCP) level was measured by ELISA method and cartilage oligomeric matrix protein (COMP) was determined by indirect immune fluorescent method. Serum level of anti CCP antibodies and COMP were Significantly related to DAS (disease activity score) and cartilage destruction, the serum presence of COMP was highly significant in rheumatoid arthritis patients than those with other autoimmune disease, the sensitivity of anti CCP in diagnosis of RA was 77.5% and specificity was96.6%. It is concluded that anti CCP, and COMP may be a useful noninvasive markers for disease activity and cartilage destruction.

  18. Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies

    Directory of Open Access Journals (Sweden)

    Vignesh AP

    2015-02-01

    Full Text Available Ammapati Paul Pandian Vignesh, Renuka Srinivasan Department of Ophthalmology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India Purpose: To study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody with the ocular manifestations.Methods: Three-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer’s test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests.Results: Seventy-seven patients (135 eyes, 39% out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients. Of the patients, 78% was females (60 patients. The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients. Scleritis was present in 2% of the patients (four patients. Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each. Eighty-five percent (66 patients had bilateral manifestations 15% (eleven patients had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001.Conclusion: Ocular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a

  19. Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats.

    Science.gov (United States)

    Jegatheesan, Prasanthi; Beutheu, Stéphanie; Ventura, Gabrielle; Nubret, Esther; Sarfati, Gilles; Bergheim, Ina; De Bandt, Jean-Pascal

    2015-10-01

    Fructose induces nonalcoholic fatty liver disease (NAFLD). Citrulline (Cit) may exert a beneficial effect on steatosis. We compared the effects of Cit and an isonitrogenous mixture of nonessential amino acids (NEAAs) on fructose-induced NAFLD. Twenty-two male Sprague Dawley rats were randomly assigned into 4 groups (n = 4-6) to receive for 8 wk a 60% fructose diet, either alone or supplemented with Cit (1 g · kg(-1) · d(-1)), or an isonitrogenous amount of NEAAs, or the same NEAA-supplemented diet with starch and maltodextrin instead of fructose (controls). Nutritional and metabolic status, liver function, and expression of genes of hepatic lipid metabolism were determined. Compared with controls, fructose led to NAFLD with significantly higher visceral fat mass (128%), lower lean body mass (-7%), insulin resistance (135%), increased plasma triglycerides (TGs; 67%), and altered plasma amino acid concentrations with decreased Arg bioavailability (-27%). This was corrected by both NEAA and Cit supplementation. Fructose caused a 2-fold increase in the gene expression of fatty acid synthase (Fas) and 70% and 90% decreases in that of carnitine palmitoyl-transferase 1a and microsomal TG transfer protein via a nearly 10-fold higher gene expression of sterol regulatory element-binding protein-1c (Srebp1c) and carbohydrate-responsive element-binding protein (Chrebp), and a 90% lower gene expression of peroxisome proliferator-activated receptor α (Ppara). NEAA or Cit supplementation led to a Ppara gene expression similar to controls and decreased those of Srebp1c and Chrebp in the liver by 50-60%. Only Cit led to Fas gene expression and Arg bioavailability similar to controls. In our rat model, Cit and NEAAs effectively prevented fructose-induced NAFLD. On the basis of literature data and our findings, we propose that NEAAs may exert their effects specifically on the liver, whereas Cit presumably acts at both the hepatic and whole-body level, in part via improved

  20. L-citrulline protects from kidney damage in type 1 diabetic mice.

    Directory of Open Access Journals (Sweden)

    Maritza J Romero

    2013-12-01

    Full Text Available Rationale. Diabetic nephropathy is a major cause of end-stage renal disease, associated with endothelial dysfunction. Chronic supplementation of L-arginine (L-arg, the substrate for endothelial nitric oxide synthase (eNOS, failed to improve vascular function. L-citrulline (L-cit supplementation not only increases L-arg synthesis, but also inhibits cytosolic arginase I (Arg I, a competitor of eNOS for the use of L-arg, in the vasculature. Aims. To investigate whether L-cit treatment reduces diabetic nephropathy in streptozotocin (STZ-induced type 1 diabetes in mice and rats and to study its effects on arginase II (ArgII function, the main renal isoform. Methods. STZ-C57BL6 mice received L-cit or vehicle supplemented in the drinking water. For comparative analysis, diabetic ArgII knock out mice and L-cit-treated STZ-rats were evaluated. Results. L-cit exerted protective effects in kidneys of STZ-rats, and markedly reduced urinary albumin excretion, tubulo-interstitial fibrosis and kidney hypertrophy, observed in untreated diabetic mice. Intriguingly, L-cit treatment was accompanied by a sustained elevation of tubular ArgII at 16 wks and significantly enhanced plasma levels of the anti-inflammatory cytokine IL-10. Diabetic ArgII knock out mice showed greater BUN levels, hypertrophy, and dilated tubules than diabetic wild type mice. Despite a marked reduction in collagen deposition in ArgII knock out mice, their albuminuria was not significantly different from diabetic wild type animals. L-cit also restored NO/ROS balance and barrier function in high glucose-treated monolayers of human glomerular endothelial cells. Moreover, L-cit also has the ability to establish an anti-inflammatory profile, characterized by increased IL-10 and reduced IL-1beta and IL-12(p70 generation in the human proximal tubular cells. Conclusions. L-cit supplementation established an anti-inflammatory profile and significantly preserved the nephron function during type 1

  1. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis

    NARCIS (Netherlands)

    Berglin, E.; Padyukov, L.; Sundin, U.; Hallmans, G.; Stenlund, H.; Venrooij, W.J.W. van; Klareskog, L.; Dahlqvist, S.R.

    2004-01-01

    Antibodies against cyclic citrullinated peptide (CCP) and rheumatoid factors (RFs) have been demonstrated to predate the onset of rheumatoid arthritis ( RA) by years. A nested case control study was performed within the Northern Sweden Health and Disease study cohort to analyse the presence of

  2. The role of the shared epitope in arthralgia with anti-cyclic citrullinated peptide antibodies (anti-CCP), and its effect on anti-CCP levels

    NARCIS (Netherlands)

    Bos, W. H.; Ursum, J.; de Vries, N. [=Niek; Bartelds, G. M.; Wolbink, G. J.; Nurmohamed, M. T.; van der Horst-Bruinsma, I. E.; van de Stadt, R. J.; Crusius, J. B. A.; Tak, P. P.; Dijkmans, B. A. C.; van Schaardenburg, D.

    2008-01-01

    OBJECTIVES: Patients presenting with both arthralgia and antibodies to cyclic citrullinated peptide (anti-CCP) have an increased risk of developing rheumatoid arthritis (RA). To further characterise this patient group and shed more light on its relationship with clinically manifest early arthritis

  3. Responses of wild watermelon to drought stress: accumulation of an ArgE homologue and citrulline in leaves during water deficits.

    Science.gov (United States)

    Kawasaki, S; Miyake, C; Kohchi, T; Fujii, S; Uchida, M; Yokota, A

    2000-07-01

    Wild watermelon from the Botswana desert had an ability to survive under severe drought conditions by maintaining its water status (water content and water potential). In the analysis by two-dimensional electrophoresis of leaf proteins, seven spots were newly induced after watering stopped. One with the molecular mass of 40 kilodaltons of the spots was accumulated abundantly. The cDNA encoding for the protein was cloned based on its amino-terminal sequence and the amino acid sequence deduced from the determined nucleotide sequences of the cDNA exhibited homology to the enzymes belong to the ArgE/DapE/Acy1/Cpg2/YscS protein family (including acetylornithine deacetylase, carboxypeptidase and aminoacylase-1). This suggests that the protein is involved in the release of free amino acid by hydrolyzing a peptidic bond. As the drought stress progressed, citrulline became one of the major components in the total free amino acids. Eight days after withholding watering, although the lower leaves wilted significantly, the upper leaves still maintained their water status and the content of citrulline reached about 50% in the total free amino acids. The accumulation of citrulline during the drought stress in wild watermelon is an unique phenomenon in C3-plants. These results suggest that the drought tolerance of wild watermelon is related to (1) the maintenance of the water status and (2) a metabolic change to accumulate citrulline.

  4. Activation of Peptidylarginine Deiminase in the Salivary Glands of Balb/c Mice Drives the Citrullination of Ro and La Ribonucleoproteins

    Directory of Open Access Journals (Sweden)

    Mayra Rodríguez-Rodríguez

    2017-01-01

    Full Text Available The goal of the present study was to determine whether peptidylarginine deiminase PAD2 and PAD4 enzymes are present in Balb/c mouse salivary glands and whether they are able to citrullinate Ro and La ribonucleoproteins. Salivary glands from Balb/c mice were cultured in DMEM and supplemented with one of the following stimulants: ATP, LPS, TNF, IFNγ, or IL-6. A control group without stimulant was also evaluated. PAD2, PAD4, citrullinated peptides, Ro60, and La were detected by immunohistochemistry and double immunofluorescence. PAD2 and PAD4 mRNAs and protein expression were detected by qPCR and Western blot analysis. PAD activity was assessed using an antigen capture enzyme-linked immunosorbent assay. LPS, ATP, and TNF triggered PAD2 and PAD4 expression; in contrast, no expression was detected in the control group (p<0.001. PAD transcription slightly increased in response to stimulation. Additionally, PAD2/4 activity modified the arginine residues of a reporter protein (fibrinogen in vitro. PADs citrullinated Ro60 and La ribonucleoproteins in vivo. Molecular stimulants induced apoptosis in ductal cells and the externalization of Ro60 and La ribonucleoproteins onto apoptotic membranes. PAD enzymes citrullinate Ro and La ribonucleoproteins, and this experimental approach may facilitate our understanding of the role of posttranslational modifications in the pathophysiology of Sjögren’s syndrome.

  5. Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Michel Alexandre Yazbek

    2011-01-01

    Full Text Available INTRODUCTION: Epstein-Barr virus exposure appears to be an environmental trigger for rheumatoid arthritis that interacts with other risk factors. Relationships among anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status have been observed in patients with rheumatoid arthritis from different populations. OBJECTIVE: To perform an association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status in Brazilian patients with rheumatoid arthritis. METHODS: In a case-control study, 140 rheumatoid arthritis patients and 143 healthy volunteers who were matched for age, sex, and ethnicity were recruited. Anti-Epstein-Barr nuclear antigen-1 antibodies and anti-cyclic citrullinated peptide antibodies were examined using an enzyme-linked immunosorbent assay, and shared epitope alleles were identified by genotyping. Smoking information was collected from all subjects. A comparative analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope, and smoking status was performed in the patient group. Logistic regression analysis models were used to analyze the risk of rheumatoid arthritis. RESULTS: Anti-Epstein-Barr nuclear antigen-1 antibodies were not associated with anti-cyclic citrullinated peptide antibodies, shared epitope alleles, or smoking status. Anti-cyclic citrullinated peptide antibody positivity was significantly higher in smoking patients with shared epitope alleles (OR = 3.82. In a multivariate logistic regression analysis using stepwise selection, only anti-cyclic citrullinated peptide antibodies were found to be independently associated with rheumatoid arthritis (OR = 247.9. CONCLUSION: Anti-Epstein-Barr nuclear antigen-1 antibodies did not increase the risk of rheumatoid arthritis and were not associated with the rheumatoid arthritis risk factors studied. Smoking

  6. Treatment with L-citrulline in patients with post-polio syndrome: study protocol for a single-center, randomised, placebo-controlled, double-blind trial.

    Science.gov (United States)

    Schmidt, Simone; Gocheva, Vanya; Zumbrunn, Thomas; Rubino-Nacht, Daniela; Bonati, Ulrike; Fischer, Dirk; Hafner, Patricia

    2017-03-09

    Post-polio syndrome (PPS) is a condition that affects polio survivors years after recovery from an initial acute infection by the Poliomyelitis virus. Most often, patients who suffered from polio start to experience gradual new weakening in muscles, a gradual decrease in the size of muscles (muscle atrophy) and fatigue years after the acute illness. L-citrulline is known to change muscular metabolism synthesis by raising nitric oxide (NO) levels and increasing protein synthesis. This investigator-initiated, randomised, placebo-controlled, double-blind, trial aims to demonstrate that L-citrulline positively influences muscle function and increases muscular energy production in patients with PPS. Thirty ambulant PPS patients will be recruited in Switzerland. Patients will be randomly allocated to one of the two arms of the study (placebo:verum 1:1). After a 24-week run-in phase to observe natural disease history and progression, participants will be treated either with L-citrulline or placebo for 24 weeks. The primary endpoint is change in the 6-min Walking Distance Test. Secondary endpoints will include motor function measure, quantitative muscle force, quantitative muscle magnetic resonance imaging and magnetic resonance spectroscopy and serum biomarker laboratory analysis DISCUSSION: The aim of this phase IIa trial is to determine if treatment with L-citrulline shows a positive effect on clinical function and paraclinical biomarkers in PPS. If treatment with L-citrulline shows positive effects, this might represent a cost-efficient symptomatic therapy for PPS patients. ClinicalTrial.gov, ID: NCT02801071 . Registered on 6 June 2016.

  7. Validation of an enzyme-linked immunosorbent assay for the quantification of citrullinated histone H3 as a marker for neutrophil extracellular traps in human plasma.

    Science.gov (United States)

    Thålin, Charlotte; Daleskog, Maud; Göransson, Sophie Paues; Schatzberg, Daphne; Lasselin, Julie; Laska, Ann-Charlotte; Kallner, Anders; Helleday, Thomas; Wallén, Håkan; Demers, Mélanie

    2017-06-01

    There is an emerging interest in the diverse functions of neutrophil extracellular traps (NETs) in a variety of disease settings. However, data on circulating NETs rely largely upon surrogate NET markers such as cell-free DNA, nucleosomes, and NET-associated enzymes. Citrullination of histone H3 by peptidyl arginine deiminase 4 (PAD4) is central for NET formation, and citrullinated histone H3 (H3Cit) is considered a NET-specific biomarker. We therefore aimed to optimize and validate a new enzyme-linked immunosorbent assay (ELISA) to quantify the levels of H3Cit in human plasma. A standard curve made of in vitro PAD4-citrullinated histones H3 allows for the quantification of H3Cit in plasma using an anti-histone antibody as capture antibody and an anti-histone H3 citrulline antibody for detection. The assay was evaluated for linearity, stability, specificity, and precision on plasma samples obtained from a human model of inflammation before and after lipopolysaccharide injection. The results revealed linearity and high specificity demonstrated by the inability of detecting non-citrullinated histone H3. Coefficients of variation for intra- and inter-assay variability ranged from 2.1 to 5.1% and from 5.8 to 13.5%, respectively, allowing for a high precision. Furthermore, our results support an inflammatory induction of a systemic NET burden by showing, for the first time, clear intra-individual elevations of plasma H3Cit in a human model of lipopolysaccharide-induced inflammation. Taken together, our work demonstrates the development of a new method for the quantification of H3Cit by ELISA that can reliably be used for the detection of NETs in human plasma.

  8. Normalized modes at selected points without normalization

    Science.gov (United States)

    Kausel, Eduardo

    2018-04-01

    As every textbook on linear algebra demonstrates, the eigenvectors for the general eigenvalue problem | K - λM | = 0 involving two real, symmetric, positive definite matrices K , M satisfy some well-defined orthogonality conditions. Equally well-known is the fact that those eigenvectors can be normalized so that their modal mass μ =ϕT Mϕ is unity: it suffices to divide each unscaled mode by the square root of the modal mass. Thus, the normalization is the result of an explicit calculation applied to the modes after they were obtained by some means. However, we show herein that the normalized modes are not merely convenient forms of scaling, but that they are actually intrinsic properties of the pair of matrices K , M, that is, the matrices already "know" about normalization even before the modes have been obtained. This means that we can obtain individual components of the normalized modes directly from the eigenvalue problem, and without needing to obtain either all of the modes or for that matter, any one complete mode. These results are achieved by means of the residue theorem of operational calculus, a finding that is rather remarkable inasmuch as the residues themselves do not make use of any orthogonality conditions or normalization in the first place. It appears that this obscure property connecting the general eigenvalue problem of modal analysis with the residue theorem of operational calculus may have been overlooked up until now, but which has in turn interesting theoretical implications.Á

  9. The Relationship of Antibodies to Modified Citrullinated Vimentin and Markers of Bone and Cartilage Destruction in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    A. S. Avdeeva

    2014-01-01

    Full Text Available Objective. To make individualised decisions regarding treatment is one of the most important challenges in clinical practise, and identification of sensitive and specific markers of prognosis is an important research question. The main objective of this study was to evaluate relationships between the level of autoantibodies, radiographic changes and laboratory markers of bone, and cartilage destruction. Methods. A total of 114 RA patients were examined. The serum concentration of IgM RF, antibodies to cyclic citrullinated peptide (anti-CCP, modified citrullinated vimentin (anti-MCV, matrix metalloproteinase 3 (MMP-3, and cartilage oligomeric matrix protein (COMP, ng/mL were measured. The van der Heijde-modified Sharp Score was used to quantify the radiologic changes. Results. Among the patients who were high-positive for anti-MCV, the value of total modified Sharp score (mTSS (96.5; 66–120 was higher as well as the joint space narrowing (82; 60.5–105.5, and a higher level of MMP-3 was recorded more frequently (56% in comparison with negative/low-positive patients (57; 31–88, 50; 29–82, 31% resp., P<0.05. The level of COMP was also higher among patients high-positive for anti-MCV (9.7; 8.1–13.1 and 6.8; 5.4–10.7, resp., P=0.02. Conclusion. A high positive level of anti-MCV as contrasted with anti-CCP and IgM RF is associated with more pronounced destructive changes in the joints.

  10. Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

    Science.gov (United States)

    Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

    2015-01-01

    Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

  11. The use of cultured cells with defects of citrulline metabolism in diagnosis and in the study of intercellular communication

    International Nuclear Information System (INIS)

    Davidson, J.S.

    1985-02-01

    Citrullinemia and argininosuccinic aciduria are two disorders resulting from defects in two consecutive enzymes of the urea cycle, argininosuccinate synthetase and argininosuccinate lyase. Fibroblast cell lines were derived from patients with these disorders and the diagnoses, which had been made on the basis of amino acid levels in plasma and urine, were confirmed by demonstrating that the cell lines were unable to incorporate 14 C-citrulline into protein. DNA from the argininosuccinate synthetase-deficient (ASS-) cells was analysed by restriction enzyme digestion and hybridisation to a cDNA probe which had been cloned from human argininosuccinate synthetase mRNA. No defect in the patient's DNA could be demonstrated, indicating that no major deletions in the argininosuccinate synthetase genes were present in this patient. Co-cultures of the ASS- and argininosuccinate lyase-deficient (ASL-) fibroblasts were able to incorporate 14 C-citrulline into protein. Co-cultures of ASS- and ASL-cells were used as an assay system for measuring intercellular junctional communication. This allowed quantitation of the effects of pH and extra-cellular divalent cations on junctional communication. Tumor promoters such as phorbol esters and organochlorine pesticides have been reported to inhibit intercellular junctional communication in other systems, and this inhibitory activity may be related to the mechanism of tumor promotion. Retinoic acid and other retinoids also inhibited junctional communication, and the inhibitory effects of retinoic acid and TPA were additive. It is concluded that co-cultures of ASS- and ASL-cells constitute a useful system for providing quantitative measurements of intercellular junctional communication under a wide range of experimental conditions

  12. Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline levels, the precursor and co-product of nitric oxide, in rat striatum

    Directory of Open Access Journals (Sweden)

    Vallée Nicolas

    2011-07-01

    Full Text Available Abstract Previous studies performed in the laboratory have shown that nitrogen narcosis induces a decrease in striatal glutamate and dopamine levels. Although we stimulated the N-methyl-D-aspartate (NMDA receptor, an important glutamate receptor required for motor and locomotor activity managed by the striatum, and demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it was not possible to return the striatal glutamate level to its base values. We conclude that it was the striatopetal neurons of the glutamatergic pathways that were mainly affected in this hyperbaric syndrome, without understanding the principal reasons. Hence we sought to establish what happens in the vicinity of the plasma membrane, downstream the NMDA-Receptor, and we used the hypothesis that there could be neuronal nitric oxide synthase (nNOS disturbances. A microdialysis study was performed in rat striatum in order to analyse levels of citrulline, the NO co-product, and arginine, the NO precursor. Those both NO metabolites were detectable with an HPLC coupled to a fluorimetric detector. Exposure to pressurized nitrogen induced a reduction in citrulline (-18.9% and arginine (-10.4% levels. Under the control normobaric conditions, the striatal NMDA infusion enhanced the citrulline level (+85.6%, whereas under 3 MPa of nitrogen, the same NMDA infusion did not change the citrulline level which remains equivalent to that of the baseline. The level of arginine increased (+45.7% under normobaric conditions but a decrease occurred in pressurized nitrogen (-51.6%. Retrodialysis with Saclofen and KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of citrulline (+30.5% and a decrease in arginine levels (-67.4%. There was no significant difference when nitrogen at 3MPa was added. To conclude, the synthesis of citrulline/NO is reduced in nitrogen narcosis while it seems possible to activate it artificially by infusion

  13. Effect of an hyperbaric nitrogen narcotic ambience on arginine and citrulline levels, the precursor and co-product of nitric oxide, in rat striatum

    Science.gov (United States)

    2011-01-01

    Previous studies performed in the laboratory have shown that nitrogen narcosis induces a decrease in striatal glutamate and dopamine levels. Although we stimulated the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor required for motor and locomotor activity managed by the striatum, and demonstrated that the receptor was effective when exposed to nitrogen at 3MPa, it was not possible to return the striatal glutamate level to its base values. We conclude that it was the striatopetal neurons of the glutamatergic pathways that were mainly affected in this hyperbaric syndrome, without understanding the principal reasons. Hence we sought to establish what happens in the vicinity of the plasma membrane, downstream the NMDA-Receptor, and we used the hypothesis that there could be neuronal nitric oxide synthase (nNOS) disturbances. A microdialysis study was performed in rat striatum in order to analyse levels of citrulline, the NO co-product, and arginine, the NO precursor. Those both NO metabolites were detectable with an HPLC coupled to a fluorimetric detector. Exposure to pressurized nitrogen induced a reduction in citrulline (-18.9%) and arginine (-10.4%) levels. Under the control normobaric conditions, the striatal NMDA infusion enhanced the citrulline level (+85.6%), whereas under 3 MPa of nitrogen, the same NMDA infusion did not change the citrulline level which remains equivalent to that of the baseline. The level of arginine increased (+45.7%) under normobaric conditions but a decrease occurred in pressurized nitrogen (-51.6%). Retrodialysis with Saclofen and KCl in the prefrontal cortex under normobaric conditions led to an increase in striatal levels of citrulline (+30.5%) and a decrease in arginine levels (-67.4%). There was no significant difference when nitrogen at 3MPa was added. To conclude, the synthesis of citrulline/NO is reduced in nitrogen narcosis while it seems possible to activate it artificially by infusion. We have suggested

  14. Anti-citrullinated glucose-6-phosphate isomerase peptide antibodies in patients with rheumatoid arthritis are associated with HLA-DRB1 shared epitope alleles and disease activity.

    Science.gov (United States)

    Umeda, N; Matsumoto, I; Ito, I; Kawasaki, A; Tanaka, Y; Inoue, A; Tsuboi, H; Suzuki, T; Hayashi, T; Ito, S; Tsuchiya, N; Sumida, T

    2013-04-01

    To identify and characterize anti-citrullinated glucose-6-phosphate isomerase (GPI) peptide antibodies in patients with rheumatoid arthritis (RA). Nine GPI arginine-bearing peptides in human GPI protein were selected and cyclic citrullinated GPI peptides (CCG-1-9) were constructed. Samples were obtained from RA (n = 208), systemic lupus erythematosus (SLE) (n = 101), Sjögren's syndrome (SS; n = 101) and healthy controls (n = 174). Antibodies against CCG-1-9 were measured, and anti-citrullinated α-enolase-1 (CEP-1), -cyclic citrullinated peptides (CCP) and -GPI proteins antibodies were also examined. Patients with RA were genotyped for HLA-DRB1. The numbers of shared epitope (SE) alleles were counted and compared with those of the autoantibodies. Rabbit GPI was citrullinated with rabbit peptidylarginine deiminase and immunoblot analysis of RA sera performed. The levels of autoantibodies were compared before and after treatment with TNF antagonists in 58 RA patients. Anti-CCG-2, -4 and -7 antibodies were detected in 25·5, 33·2 and 37·0% patients with RA, respectively, and these antibodies were very specific for RA (specificity, 98·1-99·7%). Altogether, 44·2, 86·1 and 13·9% of RA sera were positive for anti-CEP-1, -CCP and -GPI protein antibodies, respectively. Anti-CCG-2, -4 and -7 antibodies were correlated with anti-CCP and anti-CEP-1 antibodies and with the presence of HLA-DRB1 SE alleles. Citrullinated GPI protein was detected using RA sera. Treatment with tumour necrosis factor antagonists reduced significantly the levels of anti-CCG-2 and -7 but not of anti-CEP-1 antibodies. This is the first report documenting the presence of anti-CCG antibodies in RA. Anti-CCG-2 and -7 antibodies could be considered as markers for the diagnosis of RA and its disease activity. © 2012 British Society for Immunology.

  15. Effect of ethanol and low pH on citrulline and ornithine excretion and arc gene expression by strains of Lactobacillus brevis and Pediococcus pentosaceus.

    Science.gov (United States)

    Araque, Isabel; Bordons, Albert; Reguant, Cristina

    2013-02-01

    The accumulation of citrulline and ornithine in wine or beer as a result of the arginine catabolism of some lactic acid bacteria (LAB) species increases the risk of ethyl carbamate and putrescine formation, respectively. Several LAB species, which are found as spoilage bacteria in alcoholic beverages, have been reported to be arginine degrading. This study evaluates the effect of ethanol content and low pH on the excretion of citrulline and ornithine by two strains belonging to the potential contaminant species Lactobacillus brevis and Pediococcus pentosaceus. In the conditions that most affected cell viability, arginine consumption per cell increased noticeably, indicating that arginine utilization may be a stress responsive mechanism. L. brevis showed a higher accumulation of ornithine in the media than P. pentosaceus. In the presence of ethanol, a higher expression of the arcC gene was found in P. pentosaceus, which resulted in a lower excretion of citrulline and ornithine than in L. brevis. This suggests that L. brevis is more likely to produce these amino acids, which are precursors of ethyl carbamate and putrescine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

    DEFF Research Database (Denmark)

    Damgaard, Dres; Senolt, Ladislav; Nielsen, Michael Friberg

    2014-01-01

    in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate...... for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2......) than of rhPAD4 were required for citrullination of fibrinogen. PAD activity was detected in four of five synovial fluid samples from RA patients and correlated with PAD2 concentrations in the samples (r = 0.98, P = 0.003). The calcium requirement for half-maximal activities of PAD2 and PAD4 were found...

  17. Polymorphisms and functional haplotype in PADI4: further evidence for contribution on rheumatoid arthritis susceptibility and anti-cyclic citrullinated peptide antibodies in a western Mexican population.

    Science.gov (United States)

    Guzmán-Guzmán, Iris Paola; Reyes-Castillo, Zyanya; Muñoz-Barrios, Salvador; Ruiz-Noa, Yeniley; Martínez-Bonilla, Gloria Esther; Parra-Rojas, Isela; Palafox-Sánchez, Claudia Azucena; Muñoz-Valle, José Francisco

    2015-02-01

    Peptidyl arginine deiminase IV (PADI4) enzyme catalyzes the citrullination of proteins, which are recognized by anti-cyclic citrullinated peptide antibodies (anti-CCP) in rheumatoid arthritis (RA) patients. Here, we determined the association between PADI4 gene polymorphisms and haplotypes with RA susceptibility and clinical characteristics in a western Mexican population. The relationship of PADI4 polymorphisms with anti-CCP and PADI4 mRNA expression was also evaluated. PADI4_89, PADI4_90 and PADI4_92 polymorphisms were individually associated with RA susceptibility. The GTG haplotype was significantly associated with: RA susceptibility; disease onset at ≤ 40 years and anti-CCP antibodies. PADI4 expression was three fold higher in RA patients carrying the susceptibility haplotype (GTG) than in non-susceptibility haplotype carriers (ACC). In conclusion, polymorphisms and functional haplotype (GTG) in PADI4 are associated with RA susceptibility as well as anti-CCP antibodies in a Mexican population. This supports the role of PADI4 early in RA pathogenesis by promoting the generation of citrullinated autoantigens. Copyright © 2014 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  18. Pursuing Normality

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Handberg, Charlotte

    2018-01-01

    BACKGROUND: The present study explored the reflections on cancer survivorship care of lymphoma survivors in active treatment. Lymphoma survivors have survivorship care needs, yet their participation in cancer survivorship care programs is still reported as low. OBJECTIVE: The aim of this study...... implying an influence on whether to participate in cancer survivorship care programs. Because of "pursuing normality," 8 of 9 participants opted out of cancer survivorship care programming due to prospects of "being cured" and perceptions of cancer survivorship care as "a continuation of the disease...

  19. Significance of anti-cyclic citrullinated peptide autoantibodies in immune-mediated inflammatory skin disorders with and without arthritis

    Directory of Open Access Journals (Sweden)

    Chander Grover

    2016-01-01

    Full Text Available Background: Anti-cyclic citrullinated peptides (CCPs are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF, an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP, an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. Aims and Objectives: To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. Materials and Methods: About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9] were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. Results: Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%, followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was

  20. Historically defined autobiographical periods

    DEFF Research Database (Denmark)

    Brown, Norman R.; Hansen, Tia G. B.; Lee, Peter J.

    2012-01-01

    over time and theoretical implications are discussed, notably by introducing a new approach to autobiographical memory, Transition Theory, which assumes that autobiographical memory is organized by transitional events that can be selfinitiated or externally imposed - historically defined......The chapter reviews a research programme that has demonstrated the existence of historically defined autobiographical periods and identified the conditions that bring them about. Data from four samples of World War II-generation adults show that historically defined autobiographical periods endure...... autobiographical periods are the latter....

  1. Reconstitution of T Cell Proliferation under Arginine Limitation: Activated Human T Cells Take Up Citrulline via L-Type Amino Acid Transporter 1 and Use It to Regenerate Arginine after Induction of Argininosuccinate Synthase Expression

    Directory of Open Access Journals (Sweden)

    Anke Werner

    2017-07-01

    Full Text Available In the tumor microenvironment, arginine is metabolized by arginase-expressing myeloid cells. This arginine depletion profoundly inhibits T cell functions and is crucially involved in tumor-induced immunosuppression. Reconstitution of adaptive immune functions in the context of arginase-mediated tumor immune escape is a promising therapeutic strategy to boost the immunological antitumor response. Arginine can be recycled in certain mammalian tissues from citrulline via argininosuccinate (ASA in a two-step enzymatic process involving the enzymes argininosuccinate synthase (ASS and argininosuccinate lyase (ASL. Here, we demonstrate that anti-CD3/anti-CD28-activated human primary CD4+ and CD8+ T cells upregulate ASS expression in response to low extracellular arginine concentrations, while ASL is expressed constitutively. ASS expression peaked under moderate arginine restriction (20 µM, but no relevant induction was detectable in the complete absence of extracellular arginine. The upregulated ASS correlated with a reconstitution of T cell proliferation upon supplementation of citrulline, while the suppressed production of IFN-γ was refractory to citrulline substitution. In contrast, ASA reconstituted proliferation and cytokine synthesis even in the complete absence of arginine. By direct quantification of intracellular metabolites we show that activated primary human T cells import citrulline but only metabolize it further to ASA and arginine when ASS is expressed in the context of low amounts of extracellular arginine. We then clarify that citrulline transport is largely mediated by the L-type amino acid transporter 1 (LAT1, induced upon human T cell activation. Upon siRNA-mediated knockdown of LAT1, activated T cells lost the ability to import citrulline. These data underline the potential of citrulline substitution as a promising pharmacological way to treat immunosuppression in settings of arginine deprivation.

  2. 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 ...

  3. 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 ...

  4. Defining persistent hotspots

    DEFF Research Database (Denmark)

    Kittur, Nupur; Binder, Sue; Campbell, Carl H.

    2017-01-01

    , investigators and neglected tropical disease (NTD) program managers need to define them based on changes in prevalence and/or intensity. But how should the data be analyzed to define a persistent hotspot? We have analyzed a dataset from an operational research study in western Tanzania after three annual MDAs...... and contrast the outcomes of these analyses. Our intent is to showhowthe samedataset yields different numbers of persistent hotspots depending on the approach used to define them. We suggest that investigators and NTD program managers use the approach most suited for their study or program, but whichever...... using four different approaches to define persistent hotspots. The four approaches are 1) absolute percent change in prevalence; 2) percent change in prevalence; 3) change in World Health Organization guideline categories; 4) change (absolute or percent) in both prevalence and intensity. We compare...

  5. 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...

  6. Citrulline counteracts overweight- and aging-related effects on adiponectin and leptin gene expression in rat white adipose tissue

    Directory of Open Access Journals (Sweden)

    Nolwenn Joffin

    2015-01-01

    Full Text Available We recently demonstrated that citrulline (CIT reduced the expression of inflammatory genes in cultured explants from retroperitoneal (RET white adipose tissue (WAT from young (2–4 months but not old (25 months rats. Here we show that in RET WAT from old rats and high-fat-diet-fed (HFD young rats, the basal expression of the leptin gene was increased (275–345% whereas that of the adiponectin gene was decreased (48–60%, when compared to those from control-diet-fed (CD young rats. We show also that in RET WAT from old rats, a diet supplemented with CIT for 3 months reduced macrophage (F4/80, CD68 and inflammation (interleukin-6, tumor necrosis factor-α marker genes 23–97%. CIT supplementation lowered leptin mRNA 62% and increased adiponectin mRNA 232%. In cultured explants of RET WAT from 4 month-old CD, 4 month-old HFD and 25-month-old CD rats, the exposure to 2.5 mmol/L CIT for 24 h up-regulated adiponectin gene expression 151%, 362% and 216% respectively. In contrast, leptin gene expression was down-regulated 66% selectively in CIT-treated explants from 25-month-old CD rats. These results further support the proposed beneficial effect of CIT to counteract the deleterious effects of aging and overweight on the metabolic, inflammatory and endocrine functions of WAT.

  7. The performance of anti-cyclic citrullinated peptide assays in diagnosing rheumatoid arthritis: a systematic review and meta-analysis.

    Science.gov (United States)

    Mathsson Alm, Linda; Fountain, Donna L; Cadwell, Kevin K; Madrigal, Ana Maria; Gallo, Gaia; Poorafshar, Maryam

    2018-01-01

    We assessed the ability of anti-cyclic citrullinated peptide (CCP) tests to diagnose rheumatoid arthritis (RA), comparing the effect of manufacturer assay type, study design (single- and two-gated) and duration of disease (early vs. established). We searched seven databases for relevant diagnostic studies containing data on CCP tests in known or suspected RA patients. We used a bivariate model to produce summary estimates for test sensitivity, specificity, and positive and negative likelihood ratios. Summary Receiver Operating Characteristic (sROC) curves were derived to compare early versus established RA. 83 studies were identified and included. For individual manufacturer tests there was considerable variation in both pooled sensitivity (range 67-83%) and specificity (range 90-96%) estimates. This heterogeneity was also observed when grouping studies into two-gated and single-gated designs. Study design and disease duration impacted on sensitivity, with single-gated study designs and early RA patients resulting in lower estimates than two-gated and established disease, respectively. This review highlights the large number of CCP tests that are now commercially available and the considerable variation in their diagnostic performance. This variation, although partly influenced in this analysis by the study design (single-gated vs. two-gated), seems to have different levels of impact depending on the manufacturers. The Thermo Fisher Scientific EliA and Inova Diagnostics Quanta Lite (CCP2) tests showed the least between-study variation in sensitivity and specificity suggesting they have the most consistent diagnostic performance overall.

  8. Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population - The Nagahama study.

    Science.gov (United States)

    Terao, Chikashi; Asai, Keita; Hashimoto, Motomu; Yamazaki, Toru; Ohmura, Koichiro; Yamaguchi, Akihiko; Takahashi, Katsu; Takei, Noriko; Ishii, Takanori; Kawaguchi, Takahisa; Tabara, Yasuharu; Takahashi, Meiko; Nakayama, Takeo; Kosugi, Shinji; Sekine, Akihiro; Fujii, Takao; Yamada, Ryo; Mimori, Tsuneyo; Matsuda, Fumihiko; Bessho, Kazuhisa

    2015-05-01

    Anti-citrullinated peptide antibody (ACPA) is a highly specific autoantibody to rheumatoid arthritis (RA). Recent studies have revealed that periodontal disease (PD) is closely associated with RA and production of ACPA in RA. Analyses of associations between PD and ACPA production in a healthy population may deepen our understandings. Here, we analyzed a total of 9554 adult healthy subjects. ACPA and IgM-rheumatoid factor (RF) was quantified and PD status was evaluated using the number of missing teeth (MT), the Community Periodontal Index (CPI) and Loss of Attachment (LA) for these subjects. PD status was analyzed for its association with the positivity and categorical levels of ACPA and RF conditioned for covariates which were shown to be associated with PD, ACPA or RF. As a result, all of MT, CPI and LA showed suggestive or significant associations with positivity (p = 0.024, 0.0042 and 0.037, respectively) and levels of ACPA (p ≤ 0.00031), but none of the PD parameters were associated with those of RF. These association patterns were also observed when we analyzed 6206 non-smokers of the participants. The significant associations between PD parameters and positivity and levels of ACPA in healthy population support the fundamental involvement of PD with ACPA production. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. PTPN22 -1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis.

    Science.gov (United States)

    Muñoz-Valle, José Francisco; Padilla-Gutiérrez, Jorge Ramón; Hernández-Bello, Jorge; Ruiz-Noa, Yeniley; Valle, Yeminia; Palafox-Sánchez, Claudia Azucena; Parra-Rojas, Isela; Gutiérrez-Ureña, Sergio Ramón; Rangel-Villalobos, Hector

    2017-08-10

    The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  10. Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats.

    Science.gov (United States)

    Jegatheesan, Prasanthi; Beutheu, Stéphanie; Freese, Kim; Waligora-Dupriet, Anne-Judith; Nubret, Esther; Butel, Marie-Jo; Bergheim, Ina; De Bandt, Jean-Pascal

    2016-07-01

    A Western diet induces insulin resistance, liver steatosis (non-alcoholic fatty liver disease (NAFLD)) and intestinal dysbiosis, leading to increased gut permeability and bacterial translocation, thus contributing to the progression of NAFLD to non-alcoholic steatohepatitis. In the present study, we sought, in a model of Western diet-induced NAFLD, to determine whether citrulline (Cit), an amino acid that regulates protein and energy metabolism, could decrease Western diet-induced liver injuries, as well as the mechanisms involved. Sprague-Dawley rats were fed a high-fat diet (45 %) and fructose (30 %) in drinking water or a control diet associated with water (group C) for 8 weeks. The high-fat, high-fructose diet (Western diet) was fed either alone (group WD) or with Cit (1 g/kg per d) (group WDC) or an isonitrogenous amount of non-essential amino acids (group WDA). We evaluated nutritional and metabolic status, liver function, intestinal barrier function, gut microbiota and splanchnic inflammatory status. Cit led to a lower level of hepatic TAG restricted to microvesicular lipid droplets and to a lower mRNA expression of CCAAT-enhancer-binding protein homologous protein, a marker of endoplasmic reticulum stress, of pro-inflammatory cytokines Il6 (PWestern diet alone. Cit improves Western diet-induced liver injuries via decreased lipid deposition, increased insulin sensitivity, lower inflammatory process and preserved antioxidant status. This may be related in part to its protective effects at the gut level.

  11. Defining gratuitous violence.

    African Journals Online (AJOL)

    This article engages with the question of how to define gratuitous violence. If the term gratuitous is understood to mean 'for ... definition of gratuitous violence relates to the understanding of expressive violence. It seems ... high self-esteem', related to their anger at being criticised or disrespected, is then not 'for nothing'.

  12. 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.

  13. 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…

  14. The Definability of Fields

    OpenAIRE

    BenDaniel, D. J.

    1998-01-01

    We look for a deep connection between mathematics and physics. Our approach is to propose a set theory T which leads to a concise mathematical description of physical fields and to a finite unit of action. The concept of "definability" of fields is then introduced. Definabilty of fields in T is necessary and sufficient for quantization and sufficient to avoid physical antinomies.

  15. 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...

  16. Defining depth of anesthesia.

    Science.gov (United States)

    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.

  17. 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...

  18. Hardening Software Defined Networks

    Science.gov (United States)

    2014-07-01

    the layers to act upon each other in very distinct ways. Examining the literature, we selected bipartite and tripartite network models are those...identify characteristics of multilayered networks . Bipartite and tripartite models are potentially most promising (and somewhat underutilized) in the... tripartite models are particularly well-suited to a confluence of traditional networks and software defined networks where SDN components are

  19. Defining Mathematical Giftedness

    Science.gov (United States)

    Parish, Linda

    2014-01-01

    This theoretical paper outlines the process of defining "mathematical giftedness" for a present study on how primary school teaching shapes the mindsets of children who are mathematically gifted. Mathematical giftedness is not a badge of honour or some special value attributed to a child who has achieved something exceptional.…

  20. 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

  1. Defining the fascial system.

    Science.gov (United States)

    Adstrum, Sue; Hedley, Gil; Schleip, Robert; Stecco, Carla; Yucesoy, Can A

    2017-01-01

    Fascia is a widely used yet indistinctly defined anatomical term that is concurrently applied to the description of soft collagenous connective tissue, distinct sections of membranous tissue, and a body pervading soft connective tissue system. Inconsistent use of this term is causing concern due to its potential to confuse technical communication about fascia in global, multiple discipline- and multiple profession-spanning discourse environments. The Fascia Research Society acted to address this issue by establishing a Fascia Nomenclature Committee (FNC) whose purpose was to clarify the terminology relating to fascia. This committee has since developed and defined the terms a fascia, and, more recently, the fascial system. This article reports on the FNC's proposed definition of the fascial system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 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...... the critical argument against this academic technique by going back to the history of cultural anthropology of play. This history did not develop in a linear way, but by shifts between different periods of colonial and anticolonial positions, as well as between more positivistic and more relativist approaches....... The academic imperative of definition seems to be linked to the positivistic attempts – and produces sometimes monstrous definitions. Have they any philosophical value for our knowledge of what play is? Definition is not a universal instrument of knowledge-building, but a culturally specific construction...

  3. 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....

  4. Anticorpos antiproteínas citrulinadas e a artrite reumatóide Auto-antibodies to citrullinated proteins and rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Renata Trigueirinho Alarcon

    2007-06-01

    Full Text Available Pacientes com artrite reumatóide (AR possuem uma variedade de auto-anticorpos no soro e no líquido sinovial. Entre esses auto-anticorpos, destacam-se aqueles direcionados a proteínas citrulinadas, que são específicos para AR, aparecem precocemente durante a evolução da enfermidade e são bastante úteis para auxiliar no diag-nóstico da doença. Entre os antígenos citrulinados reconhecidos por auto-anticorpos na AR, encontram-se a profilagrina, a filagrina e a vimentina. Células e tecidos ricos nessas proteínas serviram de substrato para os primeiros ensaios laboratoriais para detecção dessa classe de auto-anticorpos. A descoberta de que os epitopos reconhecidos por esses auto-anticorpos eram peptídeos contendo citrulina permitiu o desenvolvimento de uma plataforma baseada em ELISA. O formato de ELISA possibilitou maior padronização e reprodutibilidade dos ensaios, resultando em ampla aceitação mundial como os auto-anticorpos mais específicos e precoces para o diagnóstico da AR. Há controvérsia quanto à capacidade dos anticorpos contra proteínas citrulinadas predizerem a gravidade da doença. O papel dos antígenos citrulinados na fisiopatologia da artrite reumatóide é sugerido pela forte especificidade desses auto-anticorpos para a doença, pelo achado de proteínas citrulinadas na sinóvia inflamada, pela produção intra-articular desses auto-anticorpos e pela extrema afinidade de peptídeos citrulinados por moléculas de HLA-DRB1 que contêm o epitopo compartilhado. Esses achados acenam com a possibilidade de novas e fascinantes descobertas rumo à melhor compreensão da fisiopatologia da AR.Rheumatoid arthritis (RA patients have a variety of auto-antibodies in the serum and synovial fluid. Among these auto-antibodies, those directed against citrullinated proteins are distinguished because that are specific for RA, appear early during the evolution of the disease and they are important to assist in the diagnosis of

  5. Defining clinical deterioration.

    Science.gov (United States)

    Jones, Daryl; Mitchell, Imogen; Hillman, Ken; Story, David

    2013-08-01

    To review literature reporting adverse events and physiological instability in order to develop frameworks that describe and define clinical deterioration in hospitalised patients. Literature review of publications from 1960 to August 2012. Conception and refinement of models to describe clinical deterioration based on prevailing themes that developed chronologically in adverse event literature. We propose four frameworks or models that define clinical deterioration and discuss the utility of each. Early attempts used retrospective chart review and focussed on the end result of deterioration (adverse events) and iatrogenesis. Subsequent models were also retrospective, but used discrete complications (e.g. sepsis, cardiac arrest) to define deterioration, had a more clinical focus, and identified the concept of antecedent physiological instability. Current models for defining clinical deterioration are based on the presence of abnormalities in vital signs and other clinical observations and attempt to prospectively assist clinicians in predicting subsequent risk. However, use of deranged vital signs in isolation does not consider important patient-, disease-, or system-related factors that are known to adversely affect the outcome of hospitalised patients. These include pre-morbid function, frailty, extent and severity of co-morbidity, nature of presenting illness, delays in responding to deterioration and institution of treatment, and patient response to therapy. There is a need to develop multiple-variable models for deteriorating ward patients similar to those used in intensive care units. Such models may assist clinician education, prospective and real-time patient risk stratification, and guide quality improvement initiatives that prevent and improve response to clinical deterioration. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Defining Consumer Ombudsmen

    OpenAIRE

    Gill, Chris; Hirst, Carolyn

    2016-01-01

    This report seeks to describe consumer ombudsmen as they have developed in the United Kingdom. The recent European Union Directive on Consumer Alternative Dispute Resolution (2013/11/EU) defines consumer dispute resolution mechanisms in general, but does not distinguish between them individually. It does not, for instance, distinguish between consumer ombudsmen, arbitrators and adjudication schemes. Other existing approaches to definition, such as the Ombudsman Association’s criteria for ‘omb...

  7. 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....

  8. [To define internet addiction].

    Science.gov (United States)

    Tonioni, Federico

    2013-01-01

    Internet addiction is a new behavioral disorder difficult to define, especially when referring to young teenagers who make great use of web-mediated relationships. It's necessary to separate the cases of overt dependency on those in which the abuse of internet seems to have a different value, offering the only way to achieve the possible relationship. Internet is mediating a new way of communicating and thinking, this may favor the onset of clinical phenomena intended to surprise.

  9. A mode of error: Immunoglobulin binding protein (a subset of anti-citrullinated proteins can cause false positive tuberculosis test results in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Maria Greenwald

    2017-12-01

    Full Text Available Citrullinated Immunoglobulin Binding Protein (BiP is a newly described autoimmune target in rheumatoid arthritis (RA, one of many cyclic citrullinated peptides(CCP or ACPA. BiP is over-expressed in RA patients causing T cell expansion and increased interferon levels during incubation for the QuantiFERON-Gold tuberculosis test (QFT-G TB. The QFT-G TB has never been validated where interferon is increased by underlying disease, as for example RA.Of ACPA-positive RA patients (n = 126, we found a 13% false-positive TB test rate by QFT-G TB. Despite subsequent biologic therapy for 3 years of all 126 RA patients, none showed evidence of TB without INH. Most of the false-positive RA patients after treatment with biologic therapy reverted to a negative QFT-G test. False TB tests correlated with ACPA level (p < 0.02.Three healthy women without arthritis or TB exposure had negative QFT-G TB. In vitro, all three tested positive every time for TB correlating to the dose of BiP or anti-BiP added, at 2 ug/ml, 5 ug/ml, 10 ug/ml, and 20 ug/ml.BiP naturally found in the majority of ACPA-positive RA patients can result in a false positive QFT-G TB. Subsequent undertreatment of RA, if biologic therapy is withheld, and overtreatment of presumed latent TB may harm patients. Keywords: Tuberculosis, IGRA, Rheumatoid arthritis, Interferon, Anti-citrullinated peptide antibody (ACPA, Immunoglobulin binding protein (BiP

  10. Anti-Cyclic Citrullinated Peptide Antibodies and Severity of Interstitial Lung Disease in Women with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Alberto Daniel Rocha-Muñoz

    2015-01-01

    Full Text Available Objective. To evaluate whether serum titers of second-generation anticyclic citrullinated peptide antibodies (anti-CCP2 are associated with the severity and extent of interstitial lung disease in rheumatoid arthritis (RA-ILD. Methods. In across-sectional study, 39 RA-ILD patients confirmed by high-resolution computed tomography (HRCT were compared with 42 RA without lung involvement (RA only. Characteristics related to RA-ILD were assessed in all of the patients and serum anti-CCP2 titers quantified. Results. Higher anti-CCP2 titers were found in RA-ILD compared with RA only (medians 77.9 versus 30.2 U/mL, P<0.001. In the logistic regression analysis after adjustment for age, disease duration (DD, smoke exposure, disease activity, functioning, erythrocyte sedimentation rate, and methotrexate (MTX treatment duration, the characteristics associated with RA-ILD were higher anti-CCP2 titers (P=0.003 and + RF (P=0.002. In multivariate linear regression, the variables associated with severity of ground-glass score were anti-CCP2 titers (P=0.02 and with fibrosis score DD (P=0.01, anti-CCP2 titers (P<0.001, and MTX treatment duration (P<0.001. Conclusions. Anti-CCP2 antibodies are markers of severity and extent of RA-ILD in HRCT. Further longitudinal studies are required to identify if higher anti-CCP2 titers are associated with worst prognosis in RA-ILD.

  11. Anti-cyclic citrullinated peptide autoantibodies measured by an automated enzyme immunoassay: analytical performance and clinical correlations.

    Science.gov (United States)

    Tampoia, Marilina; Brescia, Vincenzo; Fontana, Antonietta; Maggiolini, Piera; Lapadula, Giovanni; Pansini, Nicola

    2005-05-01

    Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the analytical performance and clinical correlation of an automated enzyme immunoassay (DSX, DINEX Technologies), for the detection of anti-CCP autoantibodies (DIASTAT anti-CCP, Axis-Shield, DUNDEE UK). Commercial controls and serum pools were used to determine its precision, analytical sensitivity, functional sensitivity and linearity. Sera from 83 patients with established RA and from 140 controls, including patients with various autoimmune diseases, viral infections and cancer, as well as sex- and age-matched healthy subjects, were studied. The rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP findings. The total imprecision (CV%) was 4.7-7.2% for concentrations ranging between 1.98 and 71.81 U/mL. The lower detection limit was 0.038 U/mL. At a cut-off of 5 U/mL, the sensitivity and specificity for RA were 67.5% and 99.3%, respectively. The RF had a sensitivity of 66.3% and a lower specificity 82.1% than anti-CCP. When the two antibodies were used together, the specificity was 99.1%. The anti-CCP assay we examined on a fully automated system showed a good analytical performance (analytical and functional sensitivity, linearity) and good clinical correlation. We conclude that this system can provide rapid, useful data.

  12. Anti-cyclic citrullinated peptide antibodies – a role in rheumatoid arthritis and the possibility of seroconversion: A focus on abatacept

    Directory of Open Access Journals (Sweden)

    N. V. Chichasova

    2017-01-01

    Full Text Available The detection of anti-cyclic citrullinated peptide (anti-CCP antibodies plays a diagnostic and statistical predictive role in rheumatoid arthritis (RA. The decreased concentration of anti-CCP antibodies or their seroconversion is observed for not all groups of anti-inflammatory drugs. Seropositivity for anti-CCP antibodies is a predictor of the higher efficacy of abatacept (ABC. The possibility of seroconversion of anti-CCP antibodies, like rheumatoid factor, during treatment with ABC is associated with the more pronounced suppression of clinical symptoms of RA activity and progressive joint destruction, with remission achievement in a large proportion of patients.

  13. Association of Distinct Fine Specificities of Anti-Citrullinated Peptide Antibodies With Elevated Immune Responses to Prevotella intermedia in a Subgroup of Patients With Rheumatoid Arthritis and Periodontitis.

    Science.gov (United States)

    Schwenzer, Anja; Quirke, Anne-Marie; Marzeda, Anna M; Wong, Alicia; Montgomery, Anna B; Sayles, Harlan R; Eick, Sigrun; Gawron, Katarzyna; Chomyszyn-Gajewska, Maria; Łazarz-Bartyzel, Katarzyna; Davis, Simon; Potempa, Jan; Kessler, Benedikt M; Fischer, Roman; Venables, Patrick J; Payne, Jeffrey B; Mikuls, Ted R; Midwood, Kim S

    2017-12-01

    In addition to the long-established link with smoking, periodontitis (PD) is a risk factor for rheumatoid arthritis (RA). This study was undertaken to elucidate the mechanism by which PD could induce antibodies to citrullinated peptides (ACPAs), by examining the antibody response to a novel citrullinated peptide of cytokeratin 13 (CK-13) identified in gingival crevicular fluid (GCF), and comparing the response to 4 other citrullinated peptides in patients with RA who were well-characterized for PD and smoking. The citrullinomes of GCF and periodontal tissue from patients with PD were mapped by mass spectrometry. ACPAs of CK13 (cCK13), tenascin-C (cTNC5), vimentin (cVIM), α-enolase (CEP-1), and fibrinogen β (cFIBβ) were examined by enzyme-linked immunosorbent assay in patients with RA (n = 287) and patients with osteoarthritis (n = 330), and cross-reactivity was assessed by inhibition assays. A novel citrullinated peptide cCK13-1 ( 444 TSNASGR-Cit-TSDV-Cit-RP 458 ) identified in GCF exhibited elevated antibody responses in RA patients (24%). Anti-cCK13-1 antibody levels correlated with anti-cTNC5 antibody levels, and absorption experiments confirmed this was not due to cross-reactivity. Only anti-cCK13-1 and anti-cTNC5 were associated with antibodies to the periodontal pathogen Prevotella intermedia (P = 0.05 and P = 0.001, respectively), but not with antibodies to Porphyromonas gingivalis arginine gingipains. Levels of antibodies to CEP-1, cFIBβ, and cVIM correlated with each other, and with smoking and shared epitope risk factors in RA. This study identifies 2 groups of ACPA fine specificities associated with different RA risk factors. One is predominantly linked to smoking and shared epitope, and the other links anti-cTNC5 and cCK13-1 to infection with the periodontal pathogen P intermedia. © 2017 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

  14. Defining functional dyspepsia.

    Science.gov (United States)

    Mearin, Fermín; Calleja, José Luis

    2011-12-01

    Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications.During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc.The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a) food-induced dyspeptic symptoms (postprandial distress syndrome); and b) epigastric pain (epigastric pain syndrome). These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones) are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a) epigastric discomfort (as a category of severity) or pain; b) postprandial heaviness; and c) early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn). All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the other hand

  15. Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan.

    Directory of Open Access Journals (Sweden)

    Tomohiro Koga

    Full Text Available To determine prognostic factors of clinically relevant radiographic progression (CRRP in patients with rheumatoid arthritis (RA achieving remission or low disease activity (LDA in clinical practice.Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs. CRRP was defined as the yearly progression of modified total Sharp score (mTSS >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC curve to estimate the performance of relevant variables for predicting CRRP.The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA positivity at baseline (OR = 15.2, 95%CI 2.64-299, time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45, and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42.ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

  16. Defining critical thoughts.

    Science.gov (United States)

    Lovatt, Abbie

    2014-05-01

    Nursing education has long struggled to define critical thinking and explain how the process of critical thinking fits into the context of nursing. Despite this long time struggle, nurses and nurse educators continue to strive to foster critical thinking skills in nursing students as intuitively most nurses believe that critical thinking is necessary to function competently in the workplace. This article explores the most recent work of Dr. Stephen Brookfield and ties the concepts which are explored in Brookfield's work to nursing practice. Brookfield identifies that learners understand the meaning of critical thinking the best when the process is first demonstrated. Role modeling is a method educators can use to demonstrate critical thinking and is a strategy which nurses often use in the clinical area to train and mentor new nursing staff. Although it is not a new strategy in nursing education, it is a valuable strategy to engage learners in critical thinking activities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Implementing Software Defined Radio

    CERN Document Server

    Grayver, Eugene

    2013-01-01

    Software Defined Radio makes wireless communications easier, more efficient, and more reliable. This book bridges the gap between academic research and practical implementation. When beginning a project, practicing engineers, technical managers, and graduate students can save countless hours by considering the concepts presented in these pages. The author covers the myriad options and trade-offs available when selecting an appropriate hardware architecture. As demonstrated here, the choice between hardware- and software-centric architecture can mean the difference between meeting an aggressive schedule and bogging down in endless design iterations. Because of the author’s experience overseeing dozens of failed and successful developments, he is able to present many real-life examples. Some of the key concepts covered are: Choosing the right architecture for the market – laboratory, military, or commercial Hardware platforms – FPGAs, GPPs, specialized and hybrid devices Standardization efforts to ens...

  18. 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.

  19. Software Defined Networking

    DEFF Research Database (Denmark)

    Caba, Cosmin Marius

    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...... networks are designed and managed. This thesis argues that SDN can greatly simplify QoS provisioning in communication networks, and even improve QoS in various ways. To this end, the impact of SDN on QoS is assessed from both a network performance perspective (e.g. bandwidth, delay), and also from a more...... 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...

  20. Induction of bone loss in DBA/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant.

    Science.gov (United States)

    Dusad, Anand; Duryee, Michael J; Shaw, Anita T; Klassen, Lynell W; Anderson, Daniel R; Wang, Dong; Ren, Ke; Gravallese, Ellen M; O'Dell, James R; Mikuls, Ted R; Thiele, Geoffrey M

    2014-01-01

    Joint damage in rheumatoid arthritis (RA) is characterized by cartilage and bone loss resulting in pain, deformity, and loss of joint function. Anti-citrullinated protein antibody (ACPA) has been implicated in RA pathogenesis and predicts radiographical joint damage and clinical severity. Therefore, the purpose of this study was to assess bone loss by micro-CT, histological joint damage, and ACPA levels using a mouse model of RA. Arthritis was induced by immunizing DBA/1 mice with autologous citrullinated type II mouse collagen (CIT-CII) weekly for 4 weeks. Mice immunized with autologous CII served as controls. At week 5, mice were killed, ACPA levels determined, and micro-CT performed to quantitatively analyze bone damage. Micro-CT analysis revealed significant loss of bone density, volume, and surface (p bone peripheral to the inflamed joints of CIT-CII animals compared to CII controls. Histological staining demonstrated cartilage, proteoglycan, joint collagen, and bone collagen loss in the CIT-CII group compared to CII. Serum ACPA levels were increased (p = 0.03) in the CIT-CII group compared to CII, and these levels were inversely correlated with bone quantity and quality. In this study, we demonstrate that immunization with autologous CIT-CII initiates significant systemic bone and articular cartilage loss in the absence of adjuvant. Significant inverse correlations of circulating ACPA and bone quality/quantity were present. ACPA levels predict the adverse bone morphological changes in this model of early RA.

  1. 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

  2. Transforming Normal Programs by Replacement

    NARCIS (Netherlands)

    Bossi, Annalisa; Pettorossi, A.; Cocco, Nicoletta; Etalle, Sandro

    1992-01-01

    The replacement transformation operation, already defined in [28], is studied wrt normal programs. We give applicability conditions able to ensure the correctness of the operation wrt Fitting's and Kunen's semantics. We show how replacement can mimic other transformation operations such as thinning,

  3. Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females.

    Science.gov (United States)

    Glenn, Jordan M; Gray, Michelle; Wethington, Lauren N; Stone, Matthew S; Stewart, Rodger W; Moyen, Nicole E

    2017-03-01

    Citrulline malate (CM) is a nonessential amino acid that increases exercise performance in males. However, based on physiological differences between genders, these results cannot be extrapolated to females. Therefore, the purpose of this investigation was to evaluate effects of acute CM supplementation on upper- and lower-body weightlifting performance in resistance-trained females. Fifteen females (23 ± 3 years) completed two randomized, double-blind trials consuming either CM (8 g dextrose + 8 g CM) or a placebo (8 g dextrose). One hour after supplement consumption, participants performed six sets each of upper- (i.e., bench press) and lower-body (i.e., leg press) exercises to failure at 80 % of previously established one-repetition maximum. Immediately after each set, repetitions completed, heart rate and rating of perceived exertion (RPE) were recorded. Repeated-measures analysis of variance indicated that subjects completed significantly (p = .045) more repetitions throughout upper-body exercise when consuming CM versus placebo (34.1 ± 5.7 vs. 32.9 ± 6.0, respectively). When consuming CM, similar significant (p = .03) improvements in total repetitions completed were observed for lower-body exercise (66.7 ± 30.5 vs. 55.13 ± 20.64, respectively). Overall RPE score was significantly lower (p = .02) in upper-body exercise when subjects consumed CM versus placebo (7.9 ± 0.3 and 8.6 ± 0.2, respectively). The supplement consumed exhibited no significant effects on heart rate at any time point. Acute CM supplementation in females increased upper- and lower-body resistance exercise performance and decreased RPE during upper-body exercise. These data indicate that athletes competing in sports with muscular endurance-based requirements may potentially improve performance by acutely supplementing CM.

  4. Antibodies to Mutated Citrullinated Vimentin in Rheumatoid Arthritis: Diagnostic Value, Association with Radiological Damage and Axial Skeleton Affection

    Directory of Open Access Journals (Sweden)

    Howaida E. Mansour

    2010-05-01

    Full Text Available Abstract Background: Early definitive diagnosis and effective treatment are mandatory in rheumatoid arthritis (RA as it can halt the disease progression and subsequent joints destruction. Objective: To investigate the diagnostic and prognostic value of anti-mutated citrullinated vimentin (anti-MCV and its correlation with disease activity, peripheral and axial skeleton affection in RA patients. Patients and methods: A total of 123 patients with different rheumatic diseases were enrolled in a prospective-two year study at Ain Shams University hospital: 64 patients with RA and 59 patients with other rheumatic diseases as controls. RA patients were fulfilling the traditional and the new ACR/EULAR diagnostic criteria for RA. They have been followed up for two years. At baseline, all RA patients were subjected to: Clinical assessment of disease activity by taking full histories, general and local examination, measurement of 28 joint count of tender and swollen joints with calculation of disease activity score (DAS-28 for each patient. Complete blood count, erythrocytes sedimentation rate, C-reactive protein and rheumatoid factor titers were performed. Anti-MCV IgG immunoglobulins’ assay was performed at the study endpoint by ELISA. RA patients were then classified into; anti-MCV positive and anti-MCV negative groups for statistical comparison. Plain X-ray was performed on the peripheral joints and scored by the Simple Erosion Narrowing score (SEN-score. Magnetic Resonance Imaging (MRI scans were carried out to 22 RA patients on cervical and lumbosacral regions. Results: Anti-MCV antibodies were found to be of high sensitivity (79.6% and specificity (96.6% in diagnosing RA. The area under the curve was 0.893 at 95% confidence interval (CI, confers an odds ratio of 23.5. Anti-MCV positive RA patients had significantly higher DAS-28 and SEN-scores than anti-MCV negative patients; who were found to have more benign disease with lower incidence of

  5. The Diagnostic Utility of Anti-cyclic Citrullinated Peptide Antibodies, Matrix Metalloproteinase-3, Rheumatoid Factor, Erythrocyte Sedimentation Rate, and C-reactive Protein in Patients with Erosive and Non-erosive Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    O. Shovman

    2005-01-01

    Full Text Available Objective: To compare the diagnostic utility of laboratory variables, including matrix metalloproteinase-3 (MMP-3, anti-cyclic citrullinated peptide (CCP antibodies, rheumatoid factor (RF, erythrocyte sedimentation rate (ESR, and C-reactive protein (CRP in patients with erosive and non-erosive rheumatoid arthritis (RA.

  6. Defining an emerging disease.

    Science.gov (United States)

    Moutou, F; Pastoret, P-P

    2015-04-01

    Defining an emerging disease is not straightforward, as there are several different types of disease emergence. For example, there can be a 'real' emergence of a brand new disease, such as the emergence of bovine spongiform encephalopathy in the 1980s, or a geographic emergence in an area not previously affected, such as the emergence of bluetongue in northern Europe in 2006. In addition, disease can emerge in species formerly not considered affected, e.g. the emergence of bovine tuberculosis in wildlife species since 2000 in France. There can also be an unexpected increase of disease incidence in a known area and a known species, or there may simply be an increase in our knowledge or awareness of a particular disease. What all these emerging diseases have in common is that human activity frequently has a role to play in their emergence. For example, bovine spongiform encephalopathy very probably emerged as a result of changes in the manufacturing of meat-and-bone meal, bluetongue was able to spread to cooler climes as a result of uncontrolled trade in animals, and a relaxation of screening and surveillance for bovine tuberculosis enabled the disease to re-emerge in areas that had been able to drastically reduce the number of cases. Globalisation and population growth will continue to affect the epidemiology of diseases in years to come and ecosystems will continue to evolve. Furthermore, new technologies such as metagenomics and high-throughput sequencing are identifying new microorganisms all the time. Change is the one constant, and diseases will continue to emerge, and we must consider the causes and different types of emergence as we deal with these diseases in the future.

  7. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain disorder ... Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal fluid ...

  8. Normal Untreated Jurkat Cells

    Science.gov (United States)

    2004-01-01

    Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. The objective of the research was to define a way to differentiate between effects due to microgravity and those due to possible stress from non-optimal spaceflight conditions. These Jurkat cells, a human acute T-cell leukemia was obtained to evaluate three types of potential experimental stressors: a) Temperature elevation; b) Serum starvation; and c) Centrifugal force. The data from previous spaceflight experiments showed that actin filaments and cell shape are significantly different for the control. These normal cells serve as the baseline for future spaceflight experiments.

  9. Anti-mutated citrullinated vimentin (anti-MCV) and anti-65 kDa heat shock protein (anti-hsp65): new biomarkers in ankylosing spondylitis.

    Science.gov (United States)

    Bodnár, Nóra; Szekanecz, Zoltán; Prohászka, Zoltán; Kemény-Beke, Adám; Némethné-Gyurcsik, Zsuzsanna; Gulyás, Katalin; Lakos, Gabriella; Sipka, Sándor; Szántó, Sándor

    2012-01-01

    Citrullination as well as anti-citrullinated protein/peptide antibodies (ACPA) have been implicated in the pathogenesis of rheumatoid arthritis (RA). While ACPAs are specific and sensitive markers for RA, there have been hardly any reports regarding ACPAs in ankylosing spondylitis (AS). The possible role of antibodies to Mycobacterial 65 kDa heat shock protein (hsp65) has not been characterized in AS. As new laboratory biomarkers of AS are needed, we investigated the prevalence of anti-mutated citrullinated vimentin (MCV) and anti-hsp65 antibodies in AS. Altogether 43 AS and 44 healthy controls were included in the study. Anti-MCV and anti-hsp65 were determined in sera by commercial and in-house ELISA, respectively. Serum autoantibody levels were correlated with ESR, CRP, HLA-B27 status, smoking habits, pain intensity, BASDAI, BASFI and BASMI indices. Patients with AS had significantly higher serum anti-MCV levels (17.3 U/mL, range: 8.3-31.5 U/mL) in comparison to healthy subjects (8.9 U/mL, range: 5.4-13.3 U/mL) (p20 U/mL). The mean anti-hsp65 concentration in AS sera was 124.8 AU/mL (range: 27.2-1000 AU/mL), while controls exerted significantly lower anti-hsp65 levels (mean: 51.8 AU/mL; range: 22.5-88.5 AU/mL) (p<0.001). Correlation analysis revealed that both anti-MCV positivity (r=0.613; p=0.012) and absolute serum anti-MCV levels (r=0.553; p=0.021) correlated with anti-hsp65 levels. Anti-MCV positivity also correlated with ESR (r=0.437; p=0.03). Anti-MCV and anti-hsp65 may be novel biomarkers in AS. Copyright © 2011. Published by Elsevier SAS.

  10. Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis

    DEFF Research Database (Denmark)

    Mortensen, Joachim Høg; Godskesen, Line Elbjerg; Jensen, Michael Dam

    2015-01-01

    BACKGROUND AND AIMS: A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC......] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD. METHODS: Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP......-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling...

  11. Effects of maternal L-citrulline supplementation on renal function and blood pressure in offspring exposed to maternal caloric restriction: the impact of nitric oxide pathway.

    Science.gov (United States)

    Tain, You-Lin; Hsieh, Chih-Sung; Lin, I-Chun; Chen, Chih-Cheng; Sheen, Jiunn-Ming; Huang, Li-Tung

    2010-08-01

    Maternal undernutrition can cause reduced nephron number and glomerular hypertrophy, consequently leading to adult kidney disease. We intended to elucidate whether NO deficiency evolves to kidney disease vulnerability in offspring from mothers with caloric restriction diets and whether maternal L-citrulline (L-Cit) supplementation can prevent this. Using a rat model with 50% caloric restriction, four groups of 3-month-old male offspring were sacrificed to determine their renal outcome: control, caloric restriction (CR), control treated with 0.25% L-citrulline solution during the whole period of pregnancy and lactation (Cit), and CR treated in the same way (CR+Cit group). The CR group had low nephron numbers, increased glomerular diameter, and an increased plasma creatinine level compared with the control group. Maternal L-Cit supplementation prevented these effects. The CR+Cit and Cit groups developed hypertension beginning at 4 and 8weeks of age, respectively. Plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) levels were increased, but L-arginine/ADMA ratios (AAR) were decreased in the CR group vs the control group. This was prevented by maternal L-Cit supplementation. Renal cortical neuronal NOS-alpha (nNOSalpha) protein abundance was significantly decreased in the Cit and CR+Cit groups. Collectively, reduced nephron number, reduced renal nNOSalpha expression, increased ADMA, and decreased AAR contribute to the developmental programming of adult kidney disease and hypertension. Although maternal L-Cit supplementation prevents caloric restriction-induced low nephron number and renal dysfunction, it also induces hypertension. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  12. Long-Term Effects of Maternal Citrulline Supplementation on Renal Transcriptome Prevention of Nitric Oxide Depletion-Related Programmed Hypertension: The Impact of Gene-Nutrient Interactions

    Directory of Open Access Journals (Sweden)

    You-Lin Tain

    2014-12-01

    Full Text Available Maternal malnutrition can elicit gene expression leading to fetal programming. l-citrulline (CIT can be converted to l-arginine to generate nitric oxide (NO. We examined whether maternal CIT supplementation can prevent NG-nitro-l-arginine-methyl ester (l-NAME, NO synthase inhibitor-induced programmed hypertension and examined their effects on the renal transcriptome in male offspring using next generation RNA sequencing (RNA-Seq technology. Pregnant Sprague-Dawley rats received l-NAME administration at 60mg/kg/day subcutaneously via osmotic minipump during pregnancy alone or with additional 0.25% l-citrulline solution in drinking water during the whole period of pregnancy and lactation. Male offspring were assigned to three groups: control, l-NAME, and l-NAME + CIT. l-NAME exposure induced hypertension in the 12-week-old offspring, which CIT therapy prevented. Identified differentially expressed genes in l-NAME and CIT-treated offspring kidneys, including Guca2b, Hmox1, Hba2, Hba-a2, Dusp1, and Serpine1 are related to regulation of blood pressure (BP and oxidative stress. In conclusion, our data suggests that the beneficial effects of CIT supplementation are attributed to alterations in expression levels of genes related to BP control and oxidative stress. Our results suggest that early nutritional intervention by CIT has long-term impact on the renal transcriptome to prevent NO depletion-related programmed hypertension. However, our RNA-Seq results might be a secondary phenomenon. The implications of epigenetic regulation at an early stage of programming deserve further clarification.

  13. Influence of anti-cyclic citrullinated peptide on disease activity, structural severity, and bone loss in Moroccan women with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Imad Ghozlani

    2018-04-01

    Full Text Available Aim of the work: The aim of this study was to assess the influence of anti-cyclic citrullinated peptide (anti-CCP on disease activity, radiological severity, functional disability and bone loss in Moroccan women with rheumatoid arthritis (RA. Patients and methods: One hundred and thirty-six women with RA were recruited. Age, weight, height, disease duration and steroids cumulative dose were identified. Anti-CCP and Rheumatoid factor (RF were determined. Disease activity score (DAS28 was assessed and functional repercussion measured by the Health Assessment Questionnaire-disability index (HAQ-DI. Radiological status was assessed by the Sharp/van der Heijde (SvH erosion and narrowing score. Bone mineral density was determined by a Lunar Prodigy Vision Dual-energy X-ray absorptiometry and vertebral fracture assessment was classified using a combination of Genant semi-quantitative approach and morphometry. Results: Patients mean age was 49.6 ± 7.4 years and disease duration 7.7 ± 5 years. 109 (80.1% patients were anti-CCP positive. There was no significant difference in DAS28 between patients with and without anti-CCP. Nevertheless, weight, erythrocyte sedimentation rate (ESR, rheumatoid factor titer and positivity, SvH narrowing and erosion score and osteoporosis were significantly higher in patients with positive anti-CCP. Stepwise regression analysis showed that the presence of anti-CCP was independently associated with osteoporosis and SvH erosion score. Conclusions: Anti-CCP antibodies are strongly predictive for the development of osteoporosis and erosions in Moroccan RA patients. They not only have a valuable role in the disease prognosis prediction but also may be a relevant determinant of bone loss in RA. The presence of these antibodies warrants special attention. Keywords: Rheumatoid arthritis, Anti-cyclic citrullinated peptide, Disease activity, Joint damage, Bone loss

  14. Testing for normality

    CERN Document Server

    Thode, Henry C

    2002-01-01

    Describes the selection, design, theory, and application of tests for normality. Covers robust estimation, test power, and univariate and multivariate normality. Contains tests ofr multivariate normality and coordinate-dependent and invariant approaches.

  15. Denotational Aspects of Untyped Normalization by Evaluation

    DEFF Research Database (Denmark)

    Filinski, Andrzej; Rohde, Henning Korsholm

    2005-01-01

    of soundness (the output term, if any, is in normal form and ß-equivalent to the input term); identification (ß-equivalent terms are mapped to the same result); and completeness (the function is defined for all terms that do have normal forms). We also show how the semantic construction enables a simple yet...

  16. Pseudo--Normals for Signed Distance Computation

    DEFF Research Database (Denmark)

    Aanæs, Henrik; Bærentzen, Jakob Andreas

    2003-01-01

    The face normals of triangular meshes have long been used to determine whether a point is in- or outside of a given mesh. However, since normals are a differential entity they are not defined at the vertices and edges of a mesh. The latter causes problems in general algorithms for determining the...

  17. The Normal Distribution From Binomial to Normal

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 6. The Normal Distribution From Binomial to Normal. S Ramasubramanian. Series Article Volume 2 Issue 6 June 1997 pp 15-24. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/002/06/0015-0024 ...

  18. 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

  19. Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA).

    Science.gov (United States)

    Too, Chun Lai; Yahya, Abqariyah; Murad, Shahnaz; Dhaliwal, Jasbir Singh; Larsson, Per Tobias; Muhamad, Nor Asiah; Abdullah, Nor Aini; Mustafa, Amal Nasir; Klareskog, Lars; Alfredsson, Lars; Padyukov, Leonid; Bengtsson, Camilla

    2012-04-26

    Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent. A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated. In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA. The risk of developing ACPA-positive RA is

  20. A novel mass spectrometry-based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized for LC-MS-TOF and LC-MS/MS.

    Science.gov (United States)

    Wiśniewski, Jerzy; Fleszar, Mariusz G; Piechowicz, Joanna; Krzystek-Korpacka, Małgorzata; Chachaj, Angelika; Szuba, Andrzej; Lorenc-Kukula, Katarzyna; Masłowski, Leszek; Witkiewicz, Wojciech; Gamian, Andrzej

    2017-11-01

    Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of l-arginine to l-citrulline. l-Arginine methylated derivatives, asymmetric and symmetric dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric dimethylarginine, SDMA), regulate l-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of l-arginine, l-citrulline, ADMA and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse-phase column. Serum aliquots (100 μL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25°C for 10 minu using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R 2  = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67-99.91%) and precision (1.92-11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower l-arginine and l-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of l-arginine, ADMA, SDMA and l-citrulline. Copyright © 2017 John Wiley & Sons, Ltd.

  1. 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

  2. Using archetypes for defining CDA templates.

    Science.gov (United States)

    Moner, David; Moreno, Alberto; Maldonado, José A; Robles, Montserrat; Parra, Carlos

    2012-01-01

    While HL7 CDA is a widely adopted standard for the documentation of clinical information, the archetype approach proposed by CEN/ISO 13606 and openEHR is gaining recognition as a means of describing domain models and medical knowledge. This paper describes our efforts in combining both standards. Using archetypes as an alternative for defining CDA templates permit new possibilities all based on the formal nature of archetypes and their ability to merge into the same artifact medical knowledge and technical requirements for semantic interoperability of electronic health records. We describe the process followed for the normalization of existing legacy data in a hospital environment, from the importation of the HL7 CDA model into an archetype editor, the definition of CDA archetypes and the application of those archetypes to obtain normalized CDA data instances.

  3. Comorbidities in Anti-Cyclic Citrullinated Peptide Positive At-Risk Individuals Do Not Differ from Those Patients with Early Inflammatory Arthritis.

    Science.gov (United States)

    Twigg, Sarah; Nikiphorou, Elena; Nam, Jackie L; Hunt, Laura; Mankia, Kulveer; Pentony, Peta Elizabeth; Freeston, Jane E; Tan, Ai Lyn; Emery, Paul

    2018-01-01

    To compare comorbidities in a cohort of cyclic citrullinated peptide (CCP) antibody positive patients without or prior to onset of inflammatory arthritis (IA) to those in patients with early IA. Baseline data from two established cohorts were used. The first recruited people at risk of IA: CCP antibody positive cases without IA (CCP Cohort, n  = 296). The second cohort [the Inflammatory Arthritis CONtinuum study (IACON)] recruited patients with early IA ( n  = 725). Proportions of patients with given comorbidities were compared between cohorts and then logistic regression was used to determine odds ratios (OR) for the CCP cohort having specific comorbidities, compared to IACON patients. Analyses adjusted for gender, age, smoking status, and body mass index. Patients from the CCP cohort were younger (mean age 50, compared to 53 years). The proportion of patients with at least one comorbidity was higher in the IACON than the CCP cohort: (40% compared to 24%, respectively). Results of logistic regression analyses suggested the odds of hypertension, taking a lipid-lowering agent, ischemic heart disease, cerebrovascular disease, lung disease, and diabetes were not increased in either cohort. However, patients in the CCP cohort were more likely to be taking an antidepressant (OR = 1.62, 95% CI 1.03, 2.56, p  = 0.037). There was no significant difference in comorbidities among people with CCP antibodies but without IA, compared to those of patients with established IA.

  4. 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.

  5. 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.

  6. Modular Software-Defined Radio

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. Defining the Internet of Things

    OpenAIRE

    Benghozi, Pierre-Jean; Bureau, Sylvain; Massit-Folléa, Françoise

    2012-01-01

    How can a definition be given to what does not yet exist ? The Internet of Things, as it is conceptualized by researchers or imagined by science-fiction writers such as Bruce Sterling, is not yet reality and if we try to define it accurately we risk rash predictions. In order to better comprehend this notion, let us first define the main principles of the IoT as given in research papers and reports on the subject. Definitions gradually established Almost all agree that the Internet of Things...

  9. Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia

    Directory of Open Access Journals (Sweden)

    R. Walter Heinrichs

    2017-01-01

    Full Text Available This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB composite score (T=50 ± 10 and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n=39 had greater cortical thickness than both cognitively normal (n=17 and below-normal range (n=49 patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n=24 or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.

  10. Smooth Pursuit of Flicker-Defined Motion

    Science.gov (United States)

    Mulligan, Jeffrey B.; Stevenson, Scott B.

    2014-01-01

    We examined the pursuit response to stimuli defined by space-variant flicker of a dense random dot carrier pattern. On each frame, every element of the pattern could change polarity, with a probability given by a two-dimensional Gaussian distribution. A normal distribution produces a circular region of twinkle, while inverting the distribution results in a spot of static texture in a twinkling surround. In this latter case, the carrier texture could be stationary, or could move with the twinkle modulator, thereby producing first-order motion in the region of the spot. While the twinkle-defined spot produces a strong sensation of motion, the complementary stimulus defined by the absence of twinkle does not, when viewed peripherally, it appears to move in steps even when the generating distribution moves smoothly. We examined pursuit responses to these stimuli using two techniques: 1) the eye movement correlogram, obtained by cross-correlating eye velocity with the velocity of a randomly-moving stimulus; and 2) delayed visual feedback, where transient stabilization of a target can produce spontaneous oscillations of the eye, with a period empirically observed to vary linearly with the applied delay. Both techniques provide an estimate of the internal processing time, which can be as short as 100 milliseconds for a first-order target. Assessed by the correlogram method, the response to flicker-defined motion is delayed by more than 100 milliseconds, and significantly weaker (especially in the vertical dimension). When initially presented in the delayed feedback condition, purely saccadic oscillation is observed. One subject eventually developed smooth oscillations (albeit with significant saccadic intrusions), showing a period-versus-delay slope similar to that observed for first-order targets. This result is somewhat surprising, given that we interpret the slope of the period-versus-delay-function as reflecting the balance between position- and velocity

  11. Defining ‘good health’

    OpenAIRE

    Erdman, Susan E

    2016-01-01

    We all want to live a long life with ‘good health’. But what does that really mean? Clinicians often define ‘good health’ as the absence of disease. Indeed, modern biomedical research focuses on finding remedies for specific ailments, that, when absent, will yield ‘good health’.

  12. Defined medium for Moraxella bovis.

    OpenAIRE

    Juni, E; Heym, G A

    1986-01-01

    A defined medium (medium MB) for Moraxella bovis was formulated. Nineteen strains grew well on medium MB. One strain was auxotrophic for asparagine, and another was auxotrophic for methionine. Strains of M. equi and M. lacunata also grew on medium MB. All strains had an absolute requirement for thiamine and were stimulated by or actually required the other growth factors in the medium.

  13. 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…

  14. 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.

  15. Defined by Word and Space

    Science.gov (United States)

    Brisco, Nicole D.

    2010-01-01

    In the author's art class, she found that many of her students in an intro art class have some technical skill, but lack the ability to think conceptually. Her goal was to create an innovative project that combined design, painting, and sculpture into a compact unit that asked students how they define themselves. In the process of answering this…

  16. Defining poverty as distinctively human

    African Journals Online (AJOL)

    p1243322

    eradicate poverty. 117 heads of state or government attended the World. Summit for Social Development in 1995. At that event the “largest gathering yet of world ..... ostracized or marginalized for whatever reason – as poor people often are – ..... kind of poverty that causes social exclusion only be defined in terms of the.

  17. Defining fitness in evolutionary models

    Indian Academy of Sciences (India)

    2008-12-23

    Dec 23, 2008 ... The analysis of evolutionary models requires an appropriate definition for fitness. ..... of dimorphism for dormancy in plants (Cohen 1966). .... yses have assumed nonoverlapping generations (i.e. no age- structure). The solution to defining fitness when the environ- ment is spatially variable and there is a ...

  18. The Importance of Quality Specifications in Safety Assessments of Amino Acids: The Cases of l-Tryptophan and l-Citrulline.

    Science.gov (United States)

    Oketch-Rabah, Hellen A; Roe, Amy L; Gurley, Bill J; Griffiths, James C; Giancaspro, Gabriel I

    2016-12-01

    The increasing consumption of amino acids from a wide variety of sources, including dietary supplements, natural health products, medical foods, infant formulas, athletic and work-out products, herbal medicines, and other national and international categories of nutritional and functional food products, increases the exposure to amino acids to amounts far beyond those normally obtained from the diet, thereby necessitating appropriate and robust safety assessments of these ingredients. Safety assessments of amino acids, similar to all food constituents, largely rely on the establishment of an upper limit [Tolerable Upper Intake Level (UL)] considered to be a guide for avoiding high intake, above which adverse or toxic effects might occur. However, reliable ULs have been difficult or impossible to define for amino acids because of inadequate toxicity studies in animals and scarce or missing clinical data, as well as a paucity or absence of adverse event reporting data. This review examines 2 amino acids that have been associated with in-market adverse events to show how quality specifications might have helped prevent the adverse clinical outcomes. We further highlight the importance of various factors that should be incorporated into an overall safety assessment of these and other amino acids. In addition to the traditional reliance on the established UL, well-defined quality specifications, review of synthesis and production strategies, potential interactions with drugs, contraindications with certain disease states, and cautionary use within certain age groups should all be taken into consideration. © 2016 American Society for Nutrition.

  19. Corners of normal matrices

    Indian Academy of Sciences (India)

    The structure of general normal matrices is far more complicated than that of two special kinds — hermitian and unitary. There are many interesting theorems for hermitian and unitary matrices whose extensions to arbitrary normal matrices have proved to be extremely recalcitrant (see e.g., [1]). The problem whose study we ...

  20. Normalized medical information visualization.

    Science.gov (United States)

    Sánchez-de-Madariaga, Ricardo; Muñoz, Adolfo; Somolinos, Roberto; Castro, Antonio; Velázquez, Iker; Moreno, Oscar; García-Pacheco, José L; Pascual, Mario; Salvador, Carlos H

    2015-01-01

    A new mark-up programming language is introduced in order to facilitate and improve the visualization of ISO/EN 13606 dual model-based normalized medical information. This is the first time that visualization of normalized medical information is addressed and the programming language is intended to be used by medical non-IT professionals.

  1. Baby Poop: What's Normal?

    Science.gov (United States)

    ... I'm breast-feeding my newborn and her bowel movements are yellow and mushy. Is this normal for baby poop? Answers from Jay L. Hoecker, M.D. Yellow, mushy bowel movements are perfectly normal for breast-fed babies. Still, ...

  2. On normal modes and dispersive properties of plasma systems

    International Nuclear Information System (INIS)

    Weiland, J.

    1976-01-01

    The description of nonlinear wave phenomena in terms of normal modes contra that of electric fields is discussed. The possibility of defining higher order normal modes is pointed out and the field energy is expressed in terms of the normal mode and the electric field. (Auth.)

  3. Multiphoton microscopy in defining liver function

    Science.gov (United States)

    Thorling, Camilla A.; Crawford, Darrell; Burczynski, Frank J.; Liu, Xin; Liau, Ian; Roberts, Michael S.

    2014-09-01

    Multiphoton microscopy is the preferred method when in vivo deep-tissue imaging is required. This review presents the application of multiphoton microscopy in defining liver function. In particular, multiphoton microscopy is useful in imaging intracellular events, such as mitochondrial depolarization and cellular metabolism in terms of NAD(P)H changes with fluorescence lifetime imaging microscopy. The morphology of hepatocytes can be visualized without exogenously administered fluorescent dyes by utilizing their autofluorescence and second harmonic generation signal of collagen, which is useful in diagnosing liver disease. More specific imaging, such as studying drug transport in normal and diseased livers are achievable, but require exogenously administered fluorescent dyes. If these techniques can be translated into clinical use to assess liver function, it would greatly improve early diagnosis of organ viability, fibrosis, and cancer.

  4. Normal radiographic findings. 4. act. ed.; Roentgennormalbefunde

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, T.B. [Gemeinschaftspraxis fuer Radiologie und Nuklearmedizin, Dillingen (Germany)

    2003-07-01

    This book can serve the reader in three ways: First, it presents normal findings for all radiographic techniques including KM. Important data which are criteria of normal findings are indicated directly in the pictures and are also explained in full text and in summary form. Secondly, it teaches the systematics of interpreting a picture - how to look at it, what structures to regard in what order, and for what to look in particular. Checklists are presented in each case. Thirdly, findings are formulated in accordance with the image analysis procedure. All criteria of normal findings are defined in these formulations, which make them an important didactic element. (orig.)

  5. Normal radiographic findings. 4. act. ed.

    International Nuclear Information System (INIS)

    Moeller, T.B.

    2003-01-01

    This book can serve the reader in three ways: First, it presents normal findings for all radiographic techniques including KM. Important data which are criteria of normal findings are indicated directly in the pictures and are also explained in full text and in summary form. Secondly, it teaches the systematics of interpreting a picture - how to look at it, what structures to regard in what order, and for what to look in particular. Checklists are presented in each case. Thirdly, findings are formulated in accordance with the image analysis procedure. All criteria of normal findings are defined in these formulations, which make them an important didactic element. (orig.)

  6. 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.

  7. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    to citrulline-malate and faster recovery from muscle fatigue after exercise. Citrulline-malate is sufficiently characterised. The claimed effect is “maintenance of ATP levels through reduction of lactates in excess for an improved recovery from muscle fatigue”. The target population proposed by the applicant...... is healthy children above six years of age and adults. The Panel considers that faster recovery from muscle fatigue after exercise contributing to the restoration of muscle function is a beneficial physiological effect. A total of 33 references were considered as pertinent to the claim by the applicant...... to the methodological limitations of the study. A number of mechanistic, animal and in vitro studies were submitted. In the absence of evidence for an effect of consumption of citrulline-malate on a faster recovery from muscle fatigue after exercise in humans, these studies cannot be used as a source of data...

  8. How to define green adjuvants.

    Science.gov (United States)

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out. Copyright © 2012 Society of Chemical Industry.

  9. What Defines the "Kingdom" Fungi?

    Science.gov (United States)

    Richards, Thomas A; Leonard, Guy; Wideman, Jeremy G

    2017-06-01

    The application of environmental DNA techniques and increased genome sequencing of microbial diversity, combined with detailed study of cellular characters, has consistently led to the reexamination of our understanding of the tree of life. This has challenged many of the definitions of taxonomic groups, especially higher taxonomic ranks such as eukaryotic kingdoms. The Fungi is an example of a kingdom which, together with the features that define it and the taxa that are grouped within it, has been in a continual state of flux. In this article we aim to summarize multiple lines of data pertinent to understanding the early evolution and definition of the Fungi. These include ongoing cellular and genomic comparisons that, we will argue, have generally undermined all attempts to identify a synapomorphic trait that defines the Fungi. This article will also summarize ongoing work focusing on taxon discovery, combined with phylogenomic analysis, which has identified novel groups that lie proximate/adjacent to the fungal clade-wherever the boundary that defines the Fungi may be. Our hope is that, by summarizing these data in the form of a discussion, we can illustrate the ongoing efforts to understand what drove the evolutionary diversification of fungi.

  10. Normalization of Gravitational Acceleration Models

    Science.gov (United States)

    Eckman, Randy A.; Brown, Aaron J.; Adamo, Daniel R.

    2011-01-01

    Unlike the uniform density spherical shell approximations of Newton, the con- sequence of spaceflight in the real universe is that gravitational fields are sensitive to the nonsphericity of their generating central bodies. The gravitational potential of a nonspherical central body is typically resolved using spherical harmonic approximations. However, attempting to directly calculate the spherical harmonic approximations results in at least two singularities which must be removed in order to generalize the method and solve for any possible orbit, including polar orbits. Three unique algorithms have been developed to eliminate these singularities by Samuel Pines [1], Bill Lear [2], and Robert Gottlieb [3]. This paper documents the methodical normalization of two1 of the three known formulations for singularity-free gravitational acceleration (namely, the Lear [2] and Gottlieb [3] algorithms) and formulates a general method for defining normalization parameters used to generate normalized Legendre Polynomials and ALFs for any algorithm. A treatment of the conventional formulation of the gravitational potential and acceleration is also provided, in addition to a brief overview of the philosophical differences between the three known singularity-free algorithms.

  11. Making nuclear 'normal'

    International Nuclear Information System (INIS)

    Haehlen, Peter; Elmiger, Bruno

    2000-01-01

    The mechanics of the Swiss NPPs' 'come and see' programme 1995-1999 were illustrated in our contributions to all PIME workshops since 1996. Now, after four annual 'waves', all the country has been covered by the NPPs' invitation to dialogue. This makes PIME 2000 the right time to shed some light on one particular objective of this initiative: making nuclear 'normal'. The principal aim of the 'come and see' programme, namely to give the Swiss NPPs 'a voice of their own' by the end of the nuclear moratorium 1990-2000, has clearly been attained and was commented on during earlier PIMEs. It is, however, equally important that Swiss nuclear energy not only made progress in terms of public 'presence', but also in terms of being perceived as a normal part of industry, as a normal branch of the economy. The message that Swiss nuclear energy is nothing but a normal business involving normal people, was stressed by several components of the multi-prong campaign: - The speakers in the TV ads were real - 'normal' - visitors' guides and not actors; - The testimonials in the print ads were all real NPP visitors - 'normal' people - and not models; - The mailings inviting a very large number of associations to 'come and see' activated a typical channel of 'normal' Swiss social life; - Spending money on ads (a new activity for Swiss NPPs) appears to have resulted in being perceived by the media as a normal branch of the economy. Today we feel that the 'normality' message has well been received by the media. In the controversy dealing with antinuclear arguments brought forward by environmental organisations journalists nowadays as a rule give nuclear energy a voice - a normal right to be heard. As in a 'normal' controversy, the media again actively ask themselves questions about specific antinuclear claims, much more than before 1990 when the moratorium started. The result is that in many cases such arguments are discarded by journalists, because they are, e.g., found to be

  12. Supplementation with Phycocyanobilin, Citrulline, Taurine, and Supranutritional Doses of Folic Acid and Biotin—Potential for Preventing or Slowing the Progression of Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Mark F. McCarty

    2017-03-01

    Full Text Available Oxidative stress, the resulting uncoupling of endothelial nitric oxide synthase (eNOS, and loss of nitric oxide (NO bioactivity, are key mediators of the vascular and microvascular complications of diabetes. Much of this oxidative stress arises from up-regulated nicotinamide adenine dinucleotide phosphate (NADPH oxidase activity. Phycocyanobilin (PhyCB, the light-harvesting chromophore in edible cyanobacteria such as spirulina, is a biliverdin derivative that shares the ability of free bilirubin to inhibit certain isoforms of NADPH oxidase. Epidemiological studies reveal that diabetics with relatively elevated serum bilirubin are less likely to develop coronary disease or microvascular complications; this may reflect the ability of bilirubin to ward off these complications via inhibition of NADPH oxidase. Oral PhyCB may likewise have potential in this regard, and has been shown to protect diabetic mice from glomerulosclerosis. With respect to oxidant-mediated uncoupling of eNOS, high-dose folate can help to reverse this by modulating the oxidation status of the eNOS cofactor tetrahydrobiopterin (BH4. Oxidation of BH4 yields dihydrobiopterin (BH2, which competes with BH4 for binding to eNOS and promotes its uncoupling. The reduced intracellular metabolites of folate have versatile oxidant-scavenging activity that can prevent oxidation of BH4; concurrently, these metabolites promote induction of dihydrofolate reductase, which functions to reconvert BH2 to BH4, and hence alleviate the uncoupling of eNOS. The arginine metabolite asymmetric dimethylarginine (ADMA, typically elevated in diabetics, also uncouples eNOS by competitively inhibiting binding of arginine to eNOS; this effect is exacerbated by the increased expression of arginase that accompanies diabetes. These effects can be countered via supplementation with citrulline, which efficiently enhances tissue levels of arginine. With respect to the loss of NO bioactivity that contributes to

  13. Performance characteristics of rheumatoid factor and anti-cyclic citrullinated peptide antibody assays may impact ACR/EULAR classification of rheumatoid arthritis.

    Science.gov (United States)

    Van Hoovels, Lieve; Jacobs, Julie; Vander Cruyssen, Bert; Van den Bremt, Stefanie; Verschueren, Patrick; Bossuyt, Xavier

    2018-01-23

    Rheumatoid factor (RF) and anti-cyclic citrullinated protein/peptide antibodies (ACPA) are integrated in the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for rheumatoid arthritis (RA). The objectives of this study were to evaluate the technical and diagnostic performance of different RF and ACPA assays and to evaluate whether differences in performance impact RA classification. Samples from 594 consecutive patients who for the first time consulted a rheumatologist (44 of whom were diagnosed with RA) and 26 extra newly diagnosed patients with RA were analysed with six different RF assays (Menarini, Thermo Fisher, Inova, Roche, Abbott, Euroimmun) and seven different ACPA assays (Menarini, Thermo Fisher, Inova, Roche, Abbott, Euro Diagnostica, Euroimmun). We found differences in analytical performance between assays. There was poor numerical agreement between the different RF and ACPA assays. For all assays, the likelihood ratio for RA increased with increasing antibody levels. The areas under the curve of receiver operating characteristic analysis of the RF (range 0.676-0.709) and ACPA assays (range 0.672-0.769) only differed between some ACPA assays. Nevertheless, using the cut-off proposed by the manufacturer, there was a large variation in sensitivity and specificity between assays (mainly for RF). Consequently, depending on the assay used, a subgroup of patients (13% for RF, 1% for ACPA and 9% for RF/ACPA) might or might not be classified as RA according to the 2010 ACR/EULAR criteria. Due to poor harmonisation of RF and ACPA assays and of test result interpretation, RA classification according to 2010 ACR/EULAR criteria may vary when different assays are used. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Effect of Anti-Cyclic Citrullinated Peptide and HLA-DRB1 Subtypes on Clinical Disease Activity Index in Rheumatoid Arthritis Patients.

    Science.gov (United States)

    Soleimani, Akbar; Mobedi, Zahra; Al-E-Rasul, Maryam; Sharifi, Abolghasem; Vardanjani, Abdolrahim Kazemi

    2017-03-01

    Rheumatoid arthritis (RA) is a crippling disease with a global prevalence of approximately 0.5%-1% in adults. Genetic, environmental and immunologic factors contribute importantly to pathogenesis of RA. American College of Rheumatology (ACR) assists in early diagnosis of the disease. The aim of this study was to investigate the effects of HLA-DRB1 gene and anti-Cyclic Citrullinated Peptide (CCP) antibody on Clinical Disease Activity Index (CDAI) and to determine the frequency of HLA-DRB1 alleles in the patients with RA. In this descriptive-analytical study, 64 patients with RA referring rheumatology clinic of Hajar Hospital, Shahr-e-Kord, Iran were enrolled based on ACR criteria (1987) by convenience sampling. All patients were examined to assess primary CDAI and referred to laboratory for serologic tests [Rheumatoid Factor (RF) and anti-CCP]. After the patients' DNA was extracted, HLA-DRB1 was determined per single specific primer-polymerase chain reaction by inno-train kits. The patients were re-examined six months later. The most prevalent type of HLA-DRB1 in the studied patients was 04. In patients with HLA-DRB1 (04), HLA-DRB1 (01), and HLA-DRB1 (15), CDAI decreased pronouncedly after six months, but in other patients it did not (pdisease. The patients with HLA-DRB1 (04), HLA-DRB1 (01) and HLA-DRB1 (15) showed a good response to routine treatments. The patients with HLA-DRB1 (04) are likely to have no decrease in secondary CDAI. High titers of anti-CCP in patients may indicate the severity of RA in the studied region and perhaps environmental, genetic and unknown or idiopathic factors are aetiologically crucial.

  15. Identification and quantification of amino acids from psoriatic and normal epidermis by high performance liquid chromatography

    International Nuclear Information System (INIS)

    Mahesar, S.M.; Khuhawar, M.Y.

    2010-01-01

    In this study, a modified fluorescence technique high performance liquid chromatography (HPLC) was adapted to separate the amino acids from the hydrolyzed keratin samples. These samples obtained from the epidermal layer of the normal and psoriatic human subjects. The keratin extracts are quantified in gram percentage of the dried skin and the amino acids concentrations are measured in mu g/g, mean retention time (tR), slope value and the coefficient of determination (r2) of each eluted amino acid is calculated. The coefficients of variation for amino acid standards ranged from 0.12% to 0.28%, mean, standard deviation of peak area and coefficients of variation of peak area were calculated. From the normal hydrolysated keratin protein fraction, 12 amino acids were determined and identified as aspartic acid, glutamic acid, asparagines, serine, glutamine, glycine, histidine, citrulline, arganine, fi-alanine, tyrosine, and valine. These amino acids were also determined in psoriatic samples while standard deviations (SD), standard error mean (SEM) and coefficient variation (CV%) of normal and psoriatic samples were also calculated. The higher concentration of amino acids in normal samples against psoriatic samples determined as glutamic acid 92.76+- 16. 83/50. 87+-9.88, glutamine 198.05+-18.74/19.74+-3.74 while higher concentrations of amino acids determined in psoriatic samples against normal samples as asparagines 81. 06+-10+-10.62/29. 98+-3.641; arganine 164.42+-35. 11/46. 14+-46, tyrosine 214.38+-29. 61/59. 64+-8. 82, and valine 169.7+-19.35/128.06+-15.14.1 is concluded that the absolute concentration of amino acids in psoriatic skin indicated a number of variations as compared to normal skin samples. (author)

  16. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim

    2011-01-01

    . We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.......Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect...

  17. Defining and Measuring User Experience

    DEFF Research Database (Denmark)

    Stage, Jan

    2006-01-01

    User experience is being used to denote what a user goes through while using a computerized system. The concept has gained momentum as a means to distinguish new types of applications such as games and entertainment software from more traditional work-related applications. This paper focuses...... definition of usability to develop the notion of user experience....... on the intrinsic relation between definition and measurement. In the area of usability, this relation has been developed over several years. It is described how usability is defined and measured in contemporary approaches. Based on that, it is discussed to what extent we can employ experience from the conceptual...

  18. 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...

  19. (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...

  20. Normality in Analytical Psychology

    Science.gov (United States)

    Myers, Steve

    2013-01-01

    Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity. PMID:25379262

  1. Normal Female Reproductive Anatomy

    Science.gov (United States)

    ... an inner lining called the endometrium. Normal female reproductive system anatomy. Topics/Categories: Anatomy -- Gynecologic Type: Color, Medical Illustration Source: National Cancer Institute Creator: Terese Winslow (Illustrator) AV Number: CDR609921 Date Created: November 17, 2014 Date Added: ...

  2. Normal growth and development

    Science.gov (United States)

    A child's growth and development can be divided into four periods: Infancy Preschool years Middle childhood years Adolescence Soon after birth, an infant normally loses about 5% to 10% of their birth weight. By about age ...

  3. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  4. Normal Functioning Family

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  5. Normal Pressure Hydrocephalus

    Science.gov (United States)

    ... improves the chance of a good recovery. Without treatment, symptoms may worsen and cause death. What research is being done? The NINDS conducts and supports research on neurological disorders, including normal pressure hydrocephalus. Research on disorders such ...

  6. Defining Life: Synthesis and Conclusions

    Science.gov (United States)

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. §1 defends that the recognition of “life” has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. §2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. §3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about “life”. The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (§4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. §5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers to two conditions

  7. "Ser diferente é normal?"/"Being different: is it normal?"

    Directory of Open Access Journals (Sweden)

    Viviane Veras

    2007-01-01

    Full Text Available A pergunta título deste trabalho retoma o slogan “Ser diferente é normal”, que é parte da campanha criada para uma organização não-governamental que atende portadores de Síndrome de Down. O objetivo é a inclusão social da pessoa com deficiência e o primeiro passo foi propor a inclusão de um grupo de diferentes no grupo dito normal. No vídeo de lançamento da campanha, o diferente, identificado como normal, é mostrado por meio de exemplos – um negro com cabelo black-power, um skin-head, um corpo tatuado, um corpo feminino halterofílico, uma família hippie, uma garota com síndrome de Down. A visão da adolescente dançando reduz, de certo modo, o efeito imaginário que vai além da síndrome, uma vez que apenas o corpo com seus olhinhos puxados se destacam, e não se interrogam questões cognitivas. Minha proposta é refletir sobre o estatuto paradoxal do exemplo, tal como é trabalhado nesse vídeo: se, por definição, um exemplo mostra de fato seu pertencimento a uma classe, pode-se concluir que é exatamente por ser exemplar que ele se encontra fora dela, no exato momento em que a exibe e define. The question in the title of this paper refers to the slogan "ser diferente é normal" ("It´s normal to be different", which is part of a campaign created for a NGO that supports people with Down syndrome. The objective of the campaign is to promote the social inclusion of individuals with Down syndrome, and the first step was to propose the inclusion of a group of "differents" in the so-called normal group. The film launching the campaign shows the different identified as normal by means of examples: a black man exhibiting blackpower haircut, a skin-head, a tattooed body, an over-athletic female body, a hippie family and a girl with Down syndrome. The vision of the dancing teenager lessens the imaginary effect that surpasses the syndrome, since only her body and her little oriental eyes stand out and no cognitive issues are

  8. Network Coded Software Defined Networking

    DEFF Research Database (Denmark)

    Krigslund, Jeppe; Hansen, Jonas; Roetter, Daniel Enrique Lucani

    2015-01-01

    incorporate content caching and storage, all of which are key challenges of the future Internet and the upcoming 5G networks. This paper proposes some of the keys behind this intersection and supports it with use cases as well as a an implementation that integrated the Kodo library (NC) into OpenFlow (SDN......Software Defined Networking (SDN) and Network Coding (NC) are two key concepts in networking that have garnered a large attention in recent years. On the one hand, SDN's potential to virtualize services in the Internet allows a large flexibility not only for routing data, but also to manage...... buffering, scheduling, and processing over the network. On the other hand, NC has shown great potential for increasing robustness and performance when deployed on intermediate nodes in the network. This new paradigm changes the dynamics of network protocols, requiring new designs that exploit its potential...

  9. 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....... The inherent flexibility of both SDN and NC provides fertile ground to envision more efficient, robust, and secure networking designs, which may also incorporate content caching and storage, all of which are key challenges of the upcoming 5G networks. This article not only proposes the fundamentals...

  10. Defining groundwater age. Chapter 3

    International Nuclear Information System (INIS)

    Torgersen, T.; Purtschert, R.; Phillips, F.M.; Plummer, L.N.; Sanford, W.E.; Suckow, A.

    2013-01-01

    This book investigates applications of selected chemical and isotopic substances that can be used to recognize and interpret age information pertaining to ‘old’ groundwater (defined as water that was recharged on a timescale from approximately 1000 to more than 1 000 000 a). However, as discussed below, only estimates of the ‘age’ of water extracted from wells can be inferred. These groundwater age estimates are interpreted from measured concentrations of chemical and isotopic substances in the groundwater. Even then, there are many complicating factors, as discussed in this book. In spite of these limitations, much can be learned about the physics of groundwater flow and about the temporal aspects of groundwater systems from age interpretations of measured concentrations of environmental tracers in groundwater systems. This chapter puts the concept of ‘age’ into context, including its meaning and interpretation, and attempts to provide a unifying usage for the rest of the book.

  11. Miniature EVA Software Defined Radio

    Science.gov (United States)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  12. Monitoring the normal body

    DEFF Research Database (Denmark)

    Nissen, Nina Konstantin; Holm, Lotte; Baarts, Charlotte

    2015-01-01

    provides us with knowledge about how to prevent future overweight or obesity. This paper investigates body size ideals and monitoring practices among normal-weight and moderately overweight people. Methods : The study is based on in-depth interviews combined with observations. 24 participants were...... recruited by strategic sampling based on self-reported BMI 18.5-29.9 kg/m2 and socio-demographic factors. Inductive analysis was conducted. Results : Normal-weight and moderately overweight people have clear ideals for their body size. Despite being normal weight or close to this, they construct a variety...... of practices for monitoring their bodies based on different kinds of calculations of weight and body size, observations of body shape, and measurements of bodily firmness. Biometric measurements are familiar to them as are health authorities' recommendations. Despite not belonging to an extreme BMI category...

  13. NIH Human Microbiome Project defines normal bacterial makeup of the body

    Science.gov (United States)

    Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for

  14. Efecto Zeeman Normal

    OpenAIRE

    Calderón Chamochumbi, Carlos

    2015-01-01

    Se describe el Efecto Zeeman Normal y se presenta una derivación general del torque experimentado por un dipolo magnético debido a su interacción con un campo magnético externo. Los cálculos correspondientes al elemento diferencial de energía potencial magnética y de la energía potencial magnética convencional son estándares. ABSTRACT: The Normal Zeeman Effect is described and a general derivation of the torque undergone by a magnetic dipole due to its interactio...

  15. The normal holonomy group

    International Nuclear Information System (INIS)

    Olmos, C.

    1990-05-01

    The restricted holonomy group of a Riemannian manifold is a compact Lie group and its representation on the tangent space is a product of irreducible representations and a trivial one. Each one of the non-trivial factors is either an orthogonal representation of a connected compact Lie group which acts transitively on the unit sphere or it is the isotropy representation of a single Riemannian symmetric space of rank ≥ 2. We prove that, all these properties are also true for the representation on the normal space of the restricted normal holonomy group of any submanifold of a space of constant curvature. 4 refs

  16. Normal modified stable processes

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole Eiler; Shephard, N.

    2002-01-01

    This paper discusses two classes of distributions, and stochastic processes derived from them: modified stable (MS) laws and normal modified stable (NMS) laws. This extends corresponding results for the generalised inverse Gaussian (GIG) and generalised hyperbolic (GH) or normal generalised inverse...... Gaussian (NGIG) laws. The wider framework thus established provides, in particular, for added flexibility in the modelling of the dynamics of financial time series, of importance especially as regards OU based stochastic volatility models for equities. In the special case of the tempered stable OU process...

  17. Medically-enhanced normality

    DEFF Research Database (Denmark)

    Møldrup, Claus; Traulsen, Janine Morgall; Almarsdóttir, Anna Birna

    2003-01-01

    Objective: To consider public perspectives on the use of medicines for non-medical purposes, a usage called medically-enhanced normality (MEN). Method: Examples from the literature were combined with empirical data derived from two Danish research projects: a Delphi internet study and a Telebus......, to optimise economic, working and family conditions. The term "doping" does not cover or explain the use of medicines as enhancement among healthy non-athletes. Conclusion: We recommend wider use of the term medically-enhanced normality as a conceptual framework for understanding and analysing perceptions...... of what is considered rational medicine use in contemporary society....

  18. Prevalência de anticorpos contra peptídeos cíclicos citrulinados na artrite idiopática juvenil The prevalence of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis

    Directory of Open Access Journals (Sweden)

    Sandra H. Machado

    2005-12-01

    Full Text Available OBJETIVOS: Avaliar a presença de anticorpos contra peptídeos cíclicos citrulinados em uma coorte de pacientes com artrite idiopática juvenil. MÉTODOS: A presença de anticorpos contra peptídeos cíclicos citrulinados foi avaliada por ensaio imunoenzimático (ELISA no soro de pacientes com artrite idiopática juvenil com idade inferior a 18 anos, acompanhados no ambulatório de reumatologia pediátrica do Hospital de Clínicas de Porto Alegre, com tempo de diagnóstico de doença de, no mínimo, 6 meses. Também foi estudada a presença do fator reumatóide IgM e do fator antinuclear em células Hep-2 RESULTADOS: Foram analisadas amostras séricas de 45 pacientes com artrite idiopática juvenil. A presença de títulos elevados de anticorpos contra peptídeos cíclicos citrulinados foi encontrada somente no soro de uma criança (2%, a qual apresentava quadro de poliartrite com fator reumatóide reagente. CONCLUSÕES: O anticorpo contra peptídeos cíclicos citrulinados pode ser detectado em crianças com artrite idiopática juvenil, mas em freqüência muito inferior aos adultos com artrite reumatóide. Torna-se importante avaliar se anticorpos contra peptídeos cíclicos citrulinados podem identificar os pacientes com artrite idiopática juvenil com potencial de evolução para artrite reumatóide do adulto.OBJECTIVES: To assess the presence of anti-cyclic citrullinated peptide antibodies in a cohort of patients with juvenile idiopathic arthritis. METHODS: Anti-cyclic citrullinated peptide antibodies was tested for with an enzyme linked immunoabsorbent assay (ELISA in serum samples of patients from the Hospital de Clínicas de Porto Alegre, all less than 18 years old and with previous diagnosis for at least 6 months. IgMRF (rheumatoid factor and antinuclear antibodies in Hep-2 cells were also assayed. RESULTS: Serum samples were analyzed from 45 patients. The presence of high levels of anti-cyclic citrullinated peptide antibodies was found

  19. Anticorpos antipeptídeos citrulinados e fator reumatoide em pacientes sudaneses com infecção por Leishmania donovani Anti-citrullinated peptide antibodies and rheumatoid factor in Sudanese patients with Leishmania donovani infection

    Directory of Open Access Journals (Sweden)

    Erik Ahlin

    2011-12-01

    Full Text Available OBJETIVO: Este estudo avaliou a presença de anticorpos antipeptídeos citrulinados cíclicos (anti-CCP, fator reumatoide (FR e imunocomplexos circulantes (ICC em pacientes sudaneses infectados por Leishmania donovani. PACIENTES E MÉTODOS: Os soros foram coletados de pacientes infectados por Leishmania (n = 116 e de sudaneses saudáveis (n = 93. Dezenove pacientes sudaneses com artrite reumatoide (AR e anti-CCP+ foram incluídos como controles positivos. Os níveis de ICC e anti-CCP foram medidos por ELISA. Para avaliar a reatividade citrulina-específica foi usada a placa-controle com peptídeos-controle cíclicos contendo arginina em vez de citrulina. RESULTADOS: Entre os pacientes infectados por Leishmania e os pacientes com AR e anti-CCP+, a maioria (86% era positiva para FR, enquanto a frequência de positividade para ICC foi maior entre pacientes com leishmaniose visceral (LV (LV 38%; AR e anti-CCP+ 24%. Quando foi analisada a reatividade anti-CCP, 12% dos pacientes com LV foram positivos. Os níveis de anti-CCP entre os pacientes com LV correlacionaram-se bem com os níveis de ICC encontrados (r = 0,65; P OBJECTIVE: The present study evaluated the presence of anti-cyclic citrullinated peptides antibodies (anti-CCP, rheumatoid factor (RF, and circulating immune complexes (CIC in Sudanese patients infected with the Leishmania donovani parasite. PATIENTS AND METHODS: Sera were collected from Leishmania infected patients (n = 116 and healthy Sudanese (n = 93. Nineteen Sudanese anti-CCP+ RA patients were included as positive controls. Levels of CIC and anti-CCP were measured by ELISA. Control plate with cyclic control peptides containing arginine instead of citrulline was used to evaluate citrulline specifi c reactivity. RESULTS: Among Leishmania-infected patients and anti-CCP+ RA patients, most were RF positive (86%, while the frequency of CIC positivity was higher among visceral leishmaniasis (VL patients (VL 38%; anti-CCP+ RA 24%. When

  20. Defining active progressive multiple sclerosis.

    Science.gov (United States)

    Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie; Nielsen, Jørgen Erik; Vinther-Jensen, Tua; Hjermind, Lena Elisabeth; von Essen, Marina; Ratzer, Rikke Lenhard; Soelberg Sørensen, Per; Romme Christensen, Jeppe

    2017-11-01

    It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria. Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary ( n = 26) and secondary progressive MS ( n = 26) and healthy controls ( n = 24). Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations. Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.

  1. Quantitative thallium-201 myocardial exercise scintigraphy in normal subjects and patients with normal coronary arteries

    International Nuclear Information System (INIS)

    Niemeyer, M.G.; St. Antonius Hospital Nieuwegein; Laarman, G.J.; Lelbach, S.; Cramer, M.J.; Ascoop, C.A.P.L.; Verzijlbergen, J.F.; Wall, E.E. van der; Zwinderman, A.H.; Pauwels, E.K.J.

    1990-01-01

    Quantitative thallium-201 myocardial exercise scintigraphy was tested in two patient populations representing alternative standards for cardiac normality: group I comprised 18 male uncatherized patients with a low likelihood of coronary artery disease (CAD); group II contained 41 patients with normal coronary arteriograms. Group I patients were younger, they achieved a higher rate-pressure product than group II patients; all had normal findings by phisical examination and electrocardiography at rest and exercise. Group II patients comprised 21 females, 11 patients showed abnormal electrocardiography at rest, and five patients showed ischemic ST depression during exercise. Twelve patients had sign of minimal CAD. Twelve patients revealed abnormal visual and quantitative thallium findings, three of these patients had minimal CAD. Profiles of uptake and washout of thallium-201 were derived from both patient groups, and compared with normal limits developed by Maddahi et al. Furthermore, low likelihood and angiographically normal patients may differ substantially, and both sets of normal patients should be considered when establishing criteria of abnormality in exercise thallium imaging. When commercial software containing normal limits for quantitative analysis of exercise thallium-201 imaging is used in clinical practice, it is mandatory to compare these with normal limits of uptake and washout of thallium-201, derived from the less heterogeneous group of low-likelihood subjects, which should be used in selecting a normal population to define normality. (author). 37 refs.; 3 figs; 1 tab

  2. Corners of normal matrices

    Indian Academy of Sciences (India)

    ∗Department of Mathematics, University of Toronto, Toronto M5S 2E4, Canada. E-mail: rbh@isid.ac.in; choi@math.toronto.edu. To Kalyan Sinha on his sixtieth birthday. Abstract. We study various conditions on matrices B and C under which they can be the off-diagonal blocks of a partitioned normal matrix. Keywords.

  3. Normality in Analytical Psychology

    Directory of Open Access Journals (Sweden)

    Steve Myers

    2013-11-01

    Full Text Available Although C.G. Jung’s interest in normality wavered throughout his career, it was one of the areas he identified in later life as worthy of further research. He began his career using a definition of normality which would have been the target of Foucault’s criticism, had Foucault chosen to review Jung’s work. However, Jung then evolved his thinking to a standpoint that was more aligned to Foucault’s own. Thereafter, the post Jungian concept of normality has remained relatively undeveloped by comparison with psychoanalysis and mainstream psychology. Jung’s disjecta membra on the subject suggest that, in contemporary analytical psychology, too much focus is placed on the process of individuation to the neglect of applications that consider collective processes. Also, there is potential for useful research and development into the nature of conflict between individuals and societies, and how normal people typically develop in relation to the spectrum between individuation and collectivity.

  4. Normalized information distance

    NARCIS (Netherlands)

    Vitányi, P.M.B.; Balbach, F.J.; Cilibrasi, R.L.; Li, M.; Emmert-Streib, F.; Dehmer, M.

    2009-01-01

    The normalized information distance is a universal distance measure for objects of all kinds. It is based on Kolmogorov complexity and thus uncomputable, but there are ways to utilize it. First, compression algorithms can be used to approximate the Kolmogorov complexity if the objects have a string

  5. Normal weight obesity in Korean adults.

    Science.gov (United States)

    Kim, Mee Kyoung; Han, Kyungdo; Kwon, Hyuk-Sang; Song, Ki-Ho; Yim, Hyeon Woo; Lee, Won-Chul; Park, Yong-Moon

    2014-02-01

    A better way to define obesity is in terms of the percentage of body fat (BF). Subjects with normal weight, but excess BF are vulnerable to cardiovascular diseases. To evaluate the prevalence and characteristics of subjects having normal weight obesity (NWO) using optimal cut-offs of the BF percentage reflecting risk factors for cardiovascular disease (CVD) in Korean adults. The Korea National Health and Nutrition Examination Survey in the Korean population conducted in 2009-2010. We surveyed 5313 men and 6904 women aged 20 years or older. We investigated the relations between the BF percentage (measured by dual-energy X-ray absorptiometry) and obesity-related risk factors for CVD (diabetes mellitus, hypertension and dyslipidaemia) in Korean adults. NWO was defined as the combination of a normal body mass index (BMI; 18·5-22·9 kg/m(2) in Asian subjects) and BF percentages above the determined cut-off values. There were strong and graded associations of increasing BF percentages with the prevalence of CVD risk factors. The first cut-off values (defined as being overweight) in men and women were 20·6% and 33·4% BF, respectively, and the second cut-off values (defined as obesity) were 25·7% and 36·0% BF. Thirty-two per cent of normal weight adults had BF percentages greater than or equal to the overweight or obesity cut-offs (NWO). Subjects with NWO had a lower appendicular skeletal muscle mass, a more atherogenic lipid profile and greater insulin resistance. Obesity can be defined as 26% BF or greater in Korean men and 36% BF or greater in Korean women. There was a high prevalence of clustering of cardiometabolic abnormalities among subjects with NWO. © 2013 John Wiley & Sons Ltd.

  6. Comparative evaluation of treatment patterns and healthcare utilization of newly-diagnosed rheumatoid arthritis patients by anti-cyclic citrullinated peptide antibody status.

    Science.gov (United States)

    Lamerato, Lois; Price, Kwanza; Szymialis, Rick; Eaddy, Michael; Ogbonnaya, Augustina; Shih, Huai-Che; Ahmad, Harris

    2018-03-01

    Anti-cyclic citrullinated peptide (CCP) antibody positivity is an established diagnostic factor for severe disease activity and joint damage and a prognostic factor for aggressive disease in rheumatoid arthritis (RA). To compare RA-related treatment, healthcare utilization, and joint erosion between anti-CCP-positive and anti-CCP-negative RA patients. Newly-diagnosed RA patients were identified from the Henry Ford Health System database between January 1, 2009 and December 31, 2014; the date of the first RA diagnosis within the study period was the index date. Baseline anti-CCP test was used to categorize patients as anti-CCP-positive or anti-CCP-negative, and outcomes were evaluated in the 6 months post-index. There were 217 anti-CCP-positive and 191 anti-CCP-negative RA patients included in the study. A higher proportion of anti-CCP-positive patients were initiated on RA treatment than anti-CCP-negative patients (70.5% vs 23.0%; p CCP-positive patients received methotrexate (73.2% vs 56.8%; p = .0374), while more anti-CCP-negative patients received hydroxychloroquine (31.8% vs 13.1%; p = .0037) in first-line therapy. A higher proportion of anti-CCP-negative patients were tested for rheumatoid factor (RF) and erythrocyte sedimentation rate (ESR). Of those tested, there were more positive test results in the anti-CCP-positive cohort compared to the anti-CCP-negative cohort (RF: 84.4% vs 18.2%, p CCP-positive patients having any outpatient physician office visit (96.3% vs 77.5%, p CCP-negative patients. Among anti-CCP-positive (n = 113) and anti-CCP-negative (n = 58) patients with imaging results, more anti-CCP-positive patients had joint erosion compared to anti-CCP-negative patients (18.6% vs 8.6%; p = .0858); however, statistical significance was not reached. RA patients with positive anti-CCP antibodies had higher degrees of inflammation and disease activity as indicated by laboratory results, which likely contributed to their higher

  7. Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and smoking as risk factors for lymphoma in patients with rheumatoid arthritis.

    Science.gov (United States)

    Baecklund, E; Backlin, C; Rönnelid, J; Toes, R; Huizinga, Twj; Åhlin, E; Askling, J; Hochberg, F H; Klareskog, L; Kay, J; Smedby, K E

    2018-01-16

    Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is not known whether factors associated with an increased risk of RA also confer an increased risk of lymphoma. We investigated whether anti-cyclic citrullinated peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with lymphoma development in RA. From two population-based case-control studies, the Scandinavian Lymphoma Etiology (SCALE) study and the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) I study, we identified lymphoma cases with a validated RA diagnosis (n = 50), to whom we matched study participants with RA but no lymphoma (n = 261), lymphoma but no RA (n = 257), and neither RA nor lymphoma (n = 233). Lymphomas were classified according to the WHO classification. Blood samples were analysed for immunoglobulin G (IgG), IgM, and IgA isotypes and IgG 1-4 subclasses of anti-CCP antibodies and for 15 antinuclear antibody (ANA)-associated specific autoantibodies. Relative risks were estimated as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs) using logistic regression. We found no association between anti-CCP IgG ≥ 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG ≥ 500 units/mL (adjOR 1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1, 95% CI 0.5-2.2) and lymphoma risk among patients with RA. In this study, neither anti-CCP antibodies (IgG, IgG 1-4 , IgM, or IgA), nor other common autoantibodies, nor smoking predicted lymphoma risk in RA.

  8. Anti-citrullinated protein antibodies in the diagnosis of rheumatoid arthritis (RA): diagnostic performance of automated anti-CCP-2 and anti-CCP-3 antibodies assays.

    Science.gov (United States)

    Vos, Ine; Van Mol, Christof; Trouw, Leendert A; Mahler, Michael; Bakker, Jaap A; Van Offel, Jan; De Clerck, Luc; Huizinga, Tom W

    2017-07-01

    This study compares the diagnostic performance of a second generation anti-cyclic citrullinated peptide antibody (CCP2) with a third generation anti-CCP antibodies assay (CCP3), as well as the combination of both tests. Serum samples of 127 patients were analyzed. IgG anti-CCP 2 and IgM rheumatoid factor were determined by EliA™ technique on a Phadia 250 instrument (Thermo Fisher Scientific), anti-CCP3 by the Quanta Flash™ anti-CCP3 IgG kit, BIO-FLASH Rapid Response Chemiluminscence Analyzer (INOVA Diagnostics). Diagnostic performance was compared using ROC-curves, sensitivity, specificity, likelihood ratios, and predictive values. Logistic regressions were used to investigate whether using both tests (anti-CCP2 and anti-CCP3) gives a better prediction of rheumatoid arthritis. At the manufacturer's cut-offs sensitivity and specificity were 79.4 and 61.0% for CCP3 and 80.9 and 69.5% for CCP2. No significant differences could be observed regarding the areas under the curve (AUC) of both ROC-curves. The optimal cut-off point for CCP2 was 10.5 U/ml (sensitivity of 75.0% and specificity of 80.0%) and 5.6 U/ml for CCP3 (sensitivity of 86.9% and specificity of 61.0%). Binary logistic regressions indicated that the likelihood of having rheumatoid arthritis (RA) is significantly higher when testing positive on both CCP2 and CCP3 compared to CCP2 or CCP3 alone. In our cohort, comparable performance was found between the two CCP assays. Positivity for both CCP2 and CCP3 resulted in the most specific identification of RA patients. In patients with joint complaints suspected of having RA and with a weakly positive CCP 2 (≥7 and ≤16 U/ml) CCP3 testing could be of additive value for diagnosing RA.

  9. Defining Tobacco Regulatory Science Competencies.

    Science.gov (United States)

    Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

    2017-02-01

    In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Evaluating different methods of microarray data normalization

    Directory of Open Access Journals (Sweden)

    Ferreira Carlos

    2006-10-01

    Full Text Available Abstract Background With the development of DNA hybridization microarray technologies, nowadays it is possible to simultaneously assess the expression levels of thousands to tens of thousands of genes. Quantitative comparison of microarrays uncovers distinct patterns of gene expression, which define different cellular phenotypes or cellular responses to drugs. Due to technical biases, normalization of the intensity levels is a pre-requisite to performing further statistical analyses. Therefore, choosing a suitable approach for normalization can be critical, deserving judicious consideration. Results Here, we considered three commonly used normalization approaches, namely: Loess, Splines and Wavelets, and two non-parametric regression methods, which have yet to be used for normalization, namely, the Kernel smoothing and Support Vector Regression. The results obtained were compared using artificial microarray data and benchmark studies. The results indicate that the Support Vector Regression is the most robust to outliers and that Kernel is the worst normalization technique, while no practical differences were observed between Loess, Splines and Wavelets. Conclusion In face of our results, the Support Vector Regression is favored for microarray normalization due to its superiority when compared to the other methods for its robustness in estimating the normalization curve.

  11. A New Distribution-Random Limit Normal Distribution

    OpenAIRE

    Gong, Xiaolin; Yang, Shuzhen

    2013-01-01

    This paper introduces a new distribution to improve tail risk modeling. Based on the classical normal distribution, we define a new distribution by a series of heat equations. Then, we use market data to verify our model.

  12. Normal Weight Dyslipidemia

    DEFF Research Database (Denmark)

    Ipsen, David Hojland; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2016-01-01

    Objective: The liver coordinates lipid metabolism and may play a vital role in the development of dyslipidemia, even in the absence of obesity. Normal weight dyslipidemia (NWD) and patients with nonalcoholic fatty liver disease (NAFLD) who do not have obesity constitute a unique subset...... of individuals characterized by dyslipidemia and metabolic deterioration. This review examined the available literature on the role of the liver in dyslipidemia and the metabolic characteristics of patients with NAFLD who do not have obesity. Methods: PubMed was searched using the following keywords: nonobese......, dyslipidemia, NAFLD, NWD, liver, and metabolically obese/unhealthy normal weight. Additionally, article bibliographies were screened, and relevant citations were retrieved. Studies were excluded if they had not measured relevant biomarkers of dyslipidemia. Results: NWD and NAFLD without obesity share a similar...

  13. Idiopathic Normal Pressure Hydrocephalus

    Directory of Open Access Journals (Sweden)

    Basant R. Nassar BS

    2016-04-01

    Full Text Available Idiopathic normal pressure hydrocephalus (iNPH is a potentially reversible neurodegenerative disease commonly characterized by a triad of dementia, gait, and urinary disturbance. Advancements in diagnosis and treatment have aided in properly identifying and improving symptoms in patients. However, a large proportion of iNPH patients remain either undiagnosed or misdiagnosed. Using PubMed search engine of keywords “normal pressure hydrocephalus,” “diagnosis,” “shunt treatment,” “biomarkers,” “gait disturbances,” “cognitive function,” “neuropsychology,” “imaging,” and “pathogenesis,” articles were obtained for this review. The majority of the articles were retrieved from the past 10 years. The purpose of this review article is to aid general practitioners in further understanding current findings on the pathogenesis, diagnosis, and treatment of iNPH.

  14. Neuroethics beyond Normal.

    Science.gov (United States)

    Shook, John R; Giordano, James

    2016-01-01

    An integrated and principled neuroethics offers ethical guidelines able to transcend conventional and medical reliance on normality standards. Elsewhere we have proposed four principles for wise guidance on human transformations. Principles like these are already urgently needed, as bio- and cyberenhancements are rapidly emerging. Context matters. Neither "treatments" nor "enhancements" are objectively identifiable apart from performance expectations, social contexts, and civic orders. Lessons learned from disability studies about enablement and inclusion suggest a fresh way to categorize modifications to the body and its performance. The term "enhancement" should be broken apart to permit recognition of enablements and augmentations, and kinds of radical augmentation for specialized performance. Augmentations affecting the self, self-worth, and self-identity of persons require heightened ethical scrutiny. Reversibility becomes the core problem, not the easy answer, as augmented persons may not cooperate with either decommissioning or displacement into unaccommodating societies. We conclude by indicating how our four principles of self-creativity, nonobsolescence, empowerment, and citizenship establish a neuroethics beyond normal that is better prepared for a future in which humans and their societies are going so far beyond normal.

  15. Ethics and "normal birth".

    Science.gov (United States)

    Lyerly, Anne Drapkin

    2012-12-01

    The concept of "normal birth" has been promoted as ideal by several international organizations, although debate about its meaning is ongoing. In this article, I examine the concept of normalcy to explore its ethical implications and raise a trio of concerns. First, in its emphasis on nonuse of technology as a goal, the concept of normalcy may marginalize women for whom medical intervention is necessary or beneficial. Second, in its emphasis on birth as a socially meaningful event, the mantra of normalcy may unintentionally avert attention to meaning in medically complicated births. Third, the emphasis on birth as a normal and healthy event may be a contributor to the long-standing tolerance for the dearth of evidence guiding the treatment of illness during pregnancy and the failure to responsibly and productively engage pregnant women in health research. Given these concerns, it is worth debating not just what "normal birth" means, but whether the term as an ideal earns its keep. © 2012, Copyright the Authors Journal compilation © 2012, Wiley Periodicals, Inc.

  16. Topological properties of some sequences defined over 2-normed spaces.

    Science.gov (United States)

    Dutta, Hemen; Kilicman, Adem; Altun, Omer

    2016-01-01

    The paper investigates some classes of real number sequences over 2-normed spaces defined by means of Orlicz functions, a bounded sequence of strictly positive real numbers, a multiplier and a normal paranormed sequence space. Relevant properties of such classes have been investigated. Moreover, relationships among different such classes of sequences have also been studied under various parameters and conditions. Finally, the spaces are investigated for some other useful properties. The conclusion section provides many interesting facts for further research.

  17. Sonographic gallbladder wall thickness in normal adult population ...

    African Journals Online (AJOL)

    Aim. The aim of the study was to determine the ultrasonic gallbladder wall thickness in normal adult Nigerians so as to create standards for defining gallbladder abnormalities in Nigerians. Method. Four hundred adults comprising 228 (57%) women and 172 (43%) men aged 16 - 78 years, who had normal clinical history ...

  18. Normal radiological findings

    International Nuclear Information System (INIS)

    Moeller, T.B.

    1987-01-01

    This book is intended for learners in radiology, presenting a wealth of normal radiological findings together with a systematic guide for appraisal and interpretation, and for formulation of reports. The text examples and criteria given will help beginners in learning to 'read' a radiograph, and to verify their conclusions by means of checklists and standard reports. The case material covers numerous illustrations from the following sectors: Skeletal radiography, mammography, tomography, contrast radiography, organ examination by intravenous techniques, arthrography and angiography, and specialized radiography, (ECB) With 184 figs [de

  19. Citrullinated Chemokines in Rheumatoid Arthritis

    Science.gov (United States)

    2015-10-01

    Jeffrey H. Ruth, Ph.D. University of Michigan Medical School Department of Medicine , Division of Rheumatology 109 Zina Pitcher Drive, 4023...Ethical use of animals: The University of Michigan’s Unit for Laboratory Animal Medicine (ULAM) is an AAALAC (Association for Assessment and Accreditation...Michigan. ULAM is supervised by a veterinarian and operates in accordance with federal regulations. Mice were housed in sterile rodent micro-isolator

  20. Normal shoulder: MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kieft, G.J.; Bloem, J.L.; Obermann, W.R.; Verbout, A.J.; Rozing, P.M.; Doornbos, J.

    1986-06-01

    Relatively poor spatial resolution has been obtained in magnetic resonance (MR) imaging of the shoulder because the shoulder can only be placed in the periphery of the magnetic field. The authors have devised an anatomically shaped surface coil that enables MR to demonstrate normal shoulder anatomy in different planes with high spatial resolution. In the axial plane anatomy analogous to that seen on computed tomographic (CT) scans can be demonstrated. Variations in scapular position (produced by patient positioning) may make reproducibility of sagittal and coronal plane images difficult by changing the relationship of the plane to the shoulder anatomy. Oblique planes, for which the angle is chosen from the axial image, have the advantage of easy reproducibility. Obliquely oriented structures and relationships are best seen in oblique plane images and can be evaluated in detail.

  1. 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.

  2. 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 hypothetical...

  3. Constructing regular graphs with smallest defining number

    OpenAIRE

    Omoomi, Behnaz; Soltankhah, Nasrin

    2008-01-01

    In a given graph $G$, a set $S$ of vertices with an assignment of colors is a {\\sf defining set of the vertex coloring of $G$}, if there exists a unique extension of the colors of $S$ to a $\\Cchi(G)$-coloring of the vertices of $G$. A defining set with minimum cardinality is called a {\\sf smallest defining set} (of vertex coloring) and its cardinality, the {\\sf defining number}, is denoted by $d(G, \\Cchi)$. Let $ d(n, r, \\Cchi = k)$ be the smallest defining number of all $r$-regular $k$-chrom...

  4. Outcomes From Polyhydramnios With Normal Ultrasound.

    Science.gov (United States)

    Yefet, Enav; Daniel-Spiegel, Etty

    2016-02-01

    To investigate the short- and long-term outcomes of children from pregnancies complicated with polyhydramnios, defined as amniotic fluid index (AFI) >24 cm, and with a normal detailed ultrasound examination. This retrospective cohort study examined 134 children aged 4 to 9 years with polyhydramnios and normal detailed ultrasound examination during pregnancy compared with 268 controls with normal AFI and normal detailed ultrasound examination matched for maternal age, year of delivery, gestational week at delivery, and presence or absence of diabetes. The primary outcome was the rate of malformations diagnosed postnatally. Additional outcomes were obstetrics outcomes, genetic syndromes, and neurodevelopment. Polyhydramnios was associated with increased risk for cesarean delivery (CD) and birth weight >90th percentile. This elevation in CD was attributed to increased rate of elective CD due to suspected macrosomia. Polyhydramnios was associated with increased risk for congenital malformations (n = 25 [19%] compared with 27 [10%], respectively; P = .016) without a statistically significant increase in the rate of major malformations (11 [8%] vs. 10 [4%]; P = .057). Genetic syndromes were more prevalent in the polyhydramnios group (5 [3.7%] vs. 2 [0.75%]; P = .043), as were neurologic disorders and developmental delay (9.7% vs. 3%; P = .004). Despite a normal detailed ultrasound examination, polyhydramnios is associated with increased rate of fetal malformations, genetic syndromes, neurologic disorders, and developmental delay, which may be diagnosed only after birth. Copyright © 2016 by the American Academy of Pediatrics.

  5. Institutionalizing Normal: Rethinking Composition's Precedence in Normal Schools

    Science.gov (United States)

    Skinnell, Ryan

    2013-01-01

    Composition historians have recently worked to recover histories of composition in normal schools. This essay argues, however, that historians have inadvertently misconstrued the role of normal schools in American education by inaccurately comparing rhetorical education in normal schools to rhetorical education in colleges and universities.…

  6. Effect of normalization on the neutron spectrum adjustment procedure

    International Nuclear Information System (INIS)

    Zsolnay, E.M.; Zijp, W.L.; Nolthenius, H.J.

    1983-10-01

    Various computer programs currently applied for neutron spectrum adjustment based on multifoil activation data, use different ways to determine the normalization factor to be applied to an unnormalized input spectrum. The influence is shown of the various definitions of the normalization factor on the adjusted results for the case of the ORR and YAYOI spectra considered in the international REAL-80 exercise. The actual expression for defining the normalization factor is more important than previously assumed. The theory of the generalized least squares principle provides an optimal definition for the normalization factor

  7. Orientation-defined boundaries are detected with low efficiency.

    Science.gov (United States)

    Solomon, Joshua A; Morgan, Michael J

    2017-09-01

    When compared with other summary statistics (mean size, size variance, orientation variance), visual estimates of average orientation are inefficient. Observers act as if they use information from no more than two or three items. We hypothesised that observers would attain greater sampling efficiency when their task did not require an explicit representation of mean orientation. We tested this hypothesis using a texture-segmentation task. Two arrays of 32 wavelets each were presented; one left and one right of fixation. Orientations in the target array were sampled from wrapped normal distributions having two different means with the same variance. One distribution defined orientations above the horizontal meridian, the other defined orientations below the meridian. All orientations in the other array were defined by a single wrapped normal distribution having the same variance as each of the distributions in the target array. Contrary to our hypothesis, results indicate that observers effectively ignored all but one item from the top and bottom of each array. In fact, we found no change in the threshold difference between the target's two means when all but one item from the top and bottom of each array were removed. We are forced to conclude that the visual system does not compute the average of more than a few orientations, even for texture segmentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. On the Folded Normal Distribution

    Directory of Open Access Journals (Sweden)

    Michail Tsagris

    2014-02-01

    Full Text Available The characteristic function of the folded normal distribution and its moment function are derived. The entropy of the folded normal distribution and the Kullback–Leibler from the normal and half normal distributions are approximated using Taylor series. The accuracy of the results are also assessed using different criteria. The maximum likelihood estimates and confidence intervals for the parameters are obtained using the asymptotic theory and bootstrap method. The coverage of the confidence intervals is also examined.

  9. Radiation effects in normal tissues

    International Nuclear Information System (INIS)

    Trott, K.R.; Herrmann, T.; Doerr, W.

    2002-01-01

    Knowledge of radiation effects in normal tissues is fundamental for optimal planning of radiotherapy. Therefore, this book presents a review on the following aspects: General pathogenesis of acute radiation effects in normal tissues; general pathogenesis of chronic radiation effects in normal tissues; quantification of acute and chronic radiation effects in normal tissues; pathogenesis, pathology and radiation biology of various organs and organ systems. (MG) [de

  10. Phenotype of normal spirometry in an aging population.

    Science.gov (United States)

    Vaz Fragoso, Carlos A; McAvay, Gail; Van Ness, Peter H; Casaburi, Richard; Jensen, Robert L; MacIntyre, Neil; Gill, Thomas M; Yaggi, H Klar; Concato, John

    2015-10-01

    In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. Using data from COPDGene (n = 10,131; ages 45-81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0-4), health-related quality of life (St. George's Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV1 % change), computed tomography-measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George's Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the

  11. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    on the scientific substantiation of a health claim related to citrulline-malate and faster recovery from muscle fatigue after exercise. The Panel considers that citrulline-malate is sufficiently characterised. The claimed effect proposed by the applicant is “improved recovery from muscle fatigue”. Faster recovery...... from muscle fatigue by contributing to the restoration of muscle function after exercise is a beneficial physiological effect. The applicant identified, as being pertinent to the health claim, a total of 35 references, all of which, except for one human study and one animal study, were submitted...... function. The evidence provided by the applicant did not establish that a faster reduction of blood lactate concentrations through a dietary intervention leads to faster recovery from muscle fatigue by contributing to the restoration of muscle function after exercise. No conclusions could be drawn from...

  12. 7 CFR 29.12 - Terms defined.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Terms defined. 29.12 Section 29.12 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... INSPECTION Regulations Definitions § 29.12 Terms defined. As used in this subpart and in all instructions...

  13. 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

  14. Defining and measuring urban sustainability in Europe

    NARCIS (Netherlands)

    Meijering, Jurian V.; Tobi, Hilde; Kern, Kristine

    2018-01-01

    Urban sustainability rankings may be useful for urban planning. How urban sustainability is defined influences the results of urban sustainability rankings. Various efforts have been made to define the concept and to operationalize it into specific components (e.g. air quality, inequality,

  15. 50 CFR 260.6 - Terms defined.

    Science.gov (United States)

    2010-10-01

    ... Products for Human Consumption Definitions § 260.6 Terms defined. Words in the regulations in this part in... Commerce. Deviant. “Deviant” means a sample unit affected by one or more deviations or a sample unit that varies in a specifically defined manner from the requirements of a standard, specification, or other...

  16. Tableau algorithms defined naturally for pictures

    NARCIS (Netherlands)

    M.A.A. van Leeuwen

    1995-01-01

    textabstractWe consider pictures as defined by Zelevinsky. We elaborate on the generalisation of the Robinson-Schensted correspondence to pictures defined by him, and on the result of Fomin and Greene that shows that this correspondence is natural, i.e., independent of the precise ``reading'' order

  17. 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…

  18. Who defines the need for fishery reform?

    DEFF Research Database (Denmark)

    Jacobsen, Rikke Becker; Raakjær, Jesper

    2014-01-01

    of discourses and policy networks that come to define the very need for reform. A policy network is identified across state ministries, powerful officials, banks and large scale industry that defined the need for fisheries reform within a ‘grand reform’ discourse. But inertia characterised the actual decision...

  19. Hypervascular liver lesions in radiologically normal liver

    Energy Technology Data Exchange (ETDEWEB)

    Amico, Enio Campos; Alves, Jose Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; Joao, Samir Assi; Liguori, Adriano de Araujo Lima, E-mail: ecamic@uol.com.br [Hospital Universitario Onofre Lopes (HUOL/UFRN), Natal, RN (Brazil). Clinica Gastrocentro e Ambulatorios de Cirurgia do Aparelho Digestivo e de Cirurgia Hepatobiliopancreatica

    2017-09-01

    Background: The hypervascular liver lesions represent a diagnostic challenge. Aim: To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. Method: This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Results: Eighty eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p< 0.001), personal history of cancer (p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. Conclusion: It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine amino transaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. (author)

  20. Hemoglobin levels in normal Filipino pregnant women.

    Science.gov (United States)

    Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P

    1981-09-01

    The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.

  1. A normal psychology of everyday pain.

    Science.gov (United States)

    Eccleston, C

    2013-01-01

    Proposed is a psychology of pain that focusses on normal psychological reactions to pain. A normal psychology of pain seeks to explain what normal people (those who would not meet any criteria for any psychological disorder) do when faced with pain. Herein, we focus on everyday pain defined as pain that is clinically unimportant that arises from normal everyday activity. Pain functions to interrupt current concerns and promote problem solving typically in the form of escape, pain management, or request for assistance. A model of analgesic problem solving is described. Focussing on pain as an interruption leads us to think about the purpose of analgesics in repairing attention and returning function. New endpoints for analgesic performance are offered. Similarly, a focus on pain as a motivation for analgesia demands that we understand how people self-medicate its relative success, and what influences patterns of self-medication. Finally, the problem of pain in children and adolescents, including self-medication in youth, is discussed. Although there is limited small-scale research on young people and their knowledge about analgesics, very little is known about their beliefs, attitudes to analgesics and their self-medication behaviour. Adolescents in most societies are left largely unguided. There is little child-specific communication about how to manage pain. Most children rely on parental knowledge, although increasingly the internet is becoming a source of advice for young people learning about analgesics. © 2012 Blackwell Publishing Ltd.

  2. Hypervascular liver lesions in radiologically normal liver

    International Nuclear Information System (INIS)

    Amico, Enio Campos; Alves, Jose Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; Joao, Samir Assi; Liguori, Adriano de Araujo Lima

    2017-01-01

    Background: The hypervascular liver lesions represent a diagnostic challenge. Aim: To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. Method: This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Results: Eighty eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p< 0.001), personal history of cancer (p=0.020), presence of >3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. Conclusion: It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine amino transaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. (author)

  3. A Denotational Account of Untyped Normalization by Evaluation

    DEFF Research Database (Denmark)

    Filinski, Andrzej; Rohde, Henning Korsholm

    2004-01-01

    We show that the standard normalization-by-evaluation construction for the simply-typed λβγ-calculus has a natural counterpart for the untyped λβ-calculus, with the central type-indexed logical relation replaced by a recursively defined invariant relation, in the style of Pitts. In fact, the cons......We show that the standard normalization-by-evaluation construction for the simply-typed λβγ-calculus has a natural counterpart for the untyped λβ-calculus, with the central type-indexed logical relation replaced by a recursively defined invariant relation, in the style of Pitts. In fact...... of soundness (the output term, if any, is β-equivalent to the input term); standardization (β-equivalent terms are mapped to the same result); and completeness (the function is defined for all terms that do have normal forms). We also show how the semantic construction enables a simple yet formal correctness...

  4. A history of normal plates, tables and stages in vertebrate embryology

    OpenAIRE

    HOPWOOD, NICK

    2007-01-01

    Developmental biology is today unimaginable without the normal stages that define standard divisions of development. This history of normal stages, and the related normal plates and normal tables, shows how these standards have shaped and been shaped by disciplinary change in vertebrate embryology. The article highlights the Normal Plates of the Development of the Vertebrates edited by the German anatomist Franz Keibel (16 volumes, 1897–1938). These were a major response to problems in the re...

  5. Chemically defined medium and Caenorhabditis elegans

    Science.gov (United States)

    Szewczyk, Nathaniel J.; Kozak, Elena; Conley, Catharine A.

    2003-01-01

    BACKGROUND: C. elegans has been established as a powerful genetic system. Use of a chemically defined medium (C. elegans Maintenance Medium (CeMM)) now allows standardization and systematic manipulation of the nutrients that animals receive. Liquid cultivation allows automated culturing and experimentation and should be of use in large-scale growth and screening of animals. RESULTS: We find that CeMM is versatile and culturing is simple. CeMM can be used in a solid or liquid state, it can be stored unused for at least a year, unattended actively growing cultures may be maintained longer than with standard techniques, and standard C. elegans protocols work well with animals grown in defined medium. We also find that there are caveats to using defined medium. Animals in defined medium grow more slowly than on standard medium, appear to display adaptation to the defined medium, and display altered growth rates as they change the composition of the defined medium. CONCLUSIONS: As was suggested with the introduction of C. elegans as a potential genetic system, use of defined medium with C. elegans should prove a powerful tool.

  6. Bicervical normal uterus with normal vagina | Okeke | Annals of ...

    African Journals Online (AJOL)

    To the best of our knowledge, only few cases of bicervical normal uterus with normal vagina exist in the literature; one of the cases had an anterior‑posterior disposition. This form of uterine abnormality is not explicable by the existing classical theory of mullerian anomalies and suggests that a complex interplay of events ...

  7. Defining susceptibility of broiler chicks to colibacillosis

    NARCIS (Netherlands)

    Ask, B.; Waaij, van der E.H.; Eck, van J.H.H.; Arendonk, van J.A.M.; Stegeman, J.A.

    2006-01-01

    This study aimed to define the susceptibility of broilers to colibacillosis through quantification of clinical responses and to examine the relationship between susceptibility and growth retardation. A challenge experiment was carried out twice. In each trial, 192 chicks were challenged

  8. 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...

  9. 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...

  10. 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,...

  11. Learning and Action Alliances: defining and establishing

    OpenAIRE

    Lawson, Emily; Lamond, Jessica

    2015-01-01

    A factsheet describing how you define and establish a Learning and Action Alliance (LAA) using a demonstration example in Newcastle, UK, as part of the research being conducted by the Blue-Green Cities Research Project

  12. 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...

  13. Radiation Tolerant Software Defined Video Processor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — MaXentric's is proposing a radiation tolerant Software Define Video Processor, codenamed SDVP, for the problem of advanced motion imaging in the space environment....

  14. Spatial normalization of array-CGH data

    Directory of Open Access Journals (Sweden)

    Brennetot Caroline

    2006-05-01

    Full Text Available Abstract Background Array-based comparative genomic hybridization (array-CGH is a recently developed technique for analyzing changes in DNA copy number. As in all microarray analyses, normalization is required to correct for experimental artifacts while preserving the true biological signal. We investigated various sources of systematic variation in array-CGH data and identified two distinct types of spatial effect of no biological relevance as the predominant experimental artifacts: continuous spatial gradients and local spatial bias. Local spatial bias affects a large proportion of arrays, and has not previously been considered in array-CGH experiments. Results We show that existing normalization techniques do not correct these spatial effects properly. We therefore developed an automatic method for the spatial normalization of array-CGH data. This method makes it possible to delineate and to eliminate and/or correct areas affected by spatial bias. It is based on the combination of a spatial segmentation algorithm called NEM (Neighborhood Expectation Maximization and spatial trend estimation. We defined quality criteria for array-CGH data, demonstrating significant improvements in data quality with our method for three data sets coming from two different platforms (198, 175 and 26 BAC-arrays. Conclusion We have designed an automatic algorithm for the spatial normalization of BAC CGH-array data, preventing the misinterpretation of experimental artifacts as biologically relevant outliers in the genomic profile. This algorithm is implemented in the R package MANOR (Micro-Array NORmalization, which is described at http://bioinfo.curie.fr/projects/manor and available from the Bioconductor site http://www.bioconductor.org. It can also be tested on the CAPweb bioinformatics platform at http://bioinfo.curie.fr/CAPweb.

  15. Defining Translational Reprogramming in Tuberous Sclerosis Complex

    Science.gov (United States)

    2015-07-01

    misfolded or damaged proteins29 but also contributes to intracellular amino acid recycling during nutrient deprivation30. NATURE METHODS I VOL.12...independent translation. In this project, we aim to (1) Dissect the molecular l inkage between mTORC1 and protein homeostasis; (2) Define the role of...Dissect the molecular linkage between mTORC1 and protein homeostasis; (2) Define the role of mTORC1 in ribosome dynamics and translational re

  16. ENDF Cross Sections are not Uniquely Defined

    Energy Technology Data Exchange (ETDEWEB)

    Cullen, D. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2010-06-11

    Most evaluated data that is coded into the ENDF format [1] does not uniquely define cross sections, because the evaluator defined total is not equal to the sum of evaluator defined partial cross sections, i.e., the total is not equal to elastic plus capture, etc. So we have always had the question: What is the correct total cross section? This is not a new problem; it has existed since the very beginning of ENDF over forty years ago. It is a problem that is periodically discussed and apparently handled, only to have it pop up again every ten years or so, as we have the next generation of ENDF format users who are not aware of the problem. See the Appendices for a summary of the differences that exist today for the ENDF/B-VII.0 (Appendix C), JEFF- 3.1(Appendix D), JENDL-3.3 (Appendix E), and CENDL-3.1 (Appendix F) data libraries. For use in our application we need consistent, unique data. To accomplish this for decades we [2, 3] have been ignoring the evaluator defined total, and re-defining it as equal to the sum of its evaluator defined parts. This has never been completely satisfactory to us, because we have been doing this without consulting evaluators, or obtaining their approval, so that the data we actually use in our applications may or may not be what the evaluators intended.

  17. Comparison of spectrum normalization techniques for univariate ...

    Indian Academy of Sciences (India)

    Laser-induced breakdown spectroscopy; univariate study; normalization models; stainless steel; standard error of prediction. Abstract. Analytical performance of six different spectrum normalization techniques, namelyinternal normalization, normalization with total light, normalization with background along with their ...

  18. The N'ormal Distribution

    Indian Academy of Sciences (India)

    An optimal way of choosing sample size in an opinion poll is indicated using the normal distribution. Introduction. In this article, the ubiquitous normal distribution is intro- duced as a convenient approximation for computing bino- mial probabilities for large values of n. Stirling's formula. • and DeMoivre-Laplace theorem ...

  19. Normal matter storage of antiprotons

    International Nuclear Information System (INIS)

    Campbell, L.J.

    1987-01-01

    Various simple issues connected with the possible storage of anti p in relative proximity to normal matter are discussed. Although equilibrium storage looks to be impossible, condensed matter systems are sufficiently rich and controllable that nonequilibrium storage is well worth pursuing. Experiments to elucidate the anti p interactions with normal matter are suggested. 32 refs

  20. On the projective normality of Artin-Schreier curves

    Directory of Open Access Journals (Sweden)

    Alberto Ravagnani

    2013-11-01

    Full Text Available In this paper we study the projective normality of certain Artin-Schreier curves Y_f defined over a field F of characteristic p by the equations y^q+y=f(x, q being a power of p and f in F[x] being a polynomial in x of degree m, with (m,p=1. Many Y_f curves are singular and so, to be precise, here we study the projective normality of appropriate projective models of their normalization.

  1. Vertex Normals and Face Curvatures of Triangle Meshes

    KAUST Repository

    Sun, Xiang

    2016-08-12

    This study contributes to the discrete differential geometry of triangle meshes, in combination with discrete line congruences associated with such meshes. In particular we discuss when a congruence defined by linear interpolation of vertex normals deserves to be called a ʼnormal’ congruence. Our main results are a discussion of various definitions of normality, a detailed study of the geometry of such congruences, and a concept of curvatures and shape operators associated with the faces of a triangle mesh. These curvatures are compatible with both normal congruences and the Steiner formula.

  2. The diagnostic utility of matrix metalloproteinase-3 and high-sensitivity C-reactive protein for predicting rheumatoid arthritis in anti-cyclic citrullinated peptide antibody-negative patients with recent-onset undifferentiated arthritis.

    Science.gov (United States)

    Hiura, Kazuya; Iwaki-Egawa, Sachiko; Kawashima, Toshiyuki; Fujisawa, Shin-Ichi; Takeda, Tsuyoshi; Komori, Hitoshi; Watanabe, Yasuhiro

    2013-09-01

    Anti-cyclic citrullinated peptide (anti-CCP) antibodies are well-established serological markers that show high sensitivity and specificity in early rheumatoid arthritis (RA) and are associated with bone erosions of RA. However, some patients subsequently progress to RA even if there is no presence of anti-CCP antibodies in an early stage. The aim of this study is to evaluate the diagnostic utility of matrix metalloproteinase-3 (MMP-3), high-sensitivity C-reactive protein (hsCRP) and IgM rheumatoid factor for predicting RA in anti-CCP-negative patients with recent-onset undifferentiated arthritis (UA). Baseline levels of those markers were measured at the entry of the study. A total of 99 patients with UA were included, among them 44 patients (44.4 %) had been classified as having RA by a skilled rheumatologist at some point during 1-year follow-up. Of these 99 patients, 34 patients (34.3 %) had anti-CCP antibodies and 65 patients (65.7 %) had no anti-CCP antibodies. Eleven patients who were anti-CCP-negative developed RA. We compared sensitivity, specificity, positive predictive value and negative predictive value of serum markers of these anti-CCP-negative RA patients. The combined usage of MMP-3 with hsCRP is relatively superior to other markers as predictors of RA.

  3. Employer involvement in defined contribution investment education.

    Science.gov (United States)

    Blau, G; VanDerhei, J L

    2000-01-01

    In this paper the authors consider the personnel problems that may arise for defined contribution plan sponsors if major market corrections cause older employees to delay retirement beyond previous expectations. We move from that basic premise to argue that, given the continued evolution from defined benefit (DB) to defined contribution (DC) retirement plans, employers need to be more "proactive" in educating their employees about their retirement planning. A human resources perspective is used to support this argument, apart from and in addition to legal considerations such as ERISA Section 404(c). Specifics of employer involvement and its place as a component of an organization's culture are discussed. Finally, recommendations are given for employers to consider.

  4. A Technique for Defining Metamodel Translations

    Science.gov (United States)

    García-Magariño, Iván; Fuentes-Fernández, Rubén

    Model-Driven Engineering and Domain-Specific Modeling Languages are encouraging an increased used of metamodels for the definition of languages and tools. Although the Meta Object Facility language is the standard for metamodeling, there are alternative metamodeling languages that are aimed at satisfying specific requirements. In this context, sharing information throughout different domains and tools requires not only being able to translate models between modeling languages defined with the same metamodeling language, but also between different metamodeling languages. This paper addresses this latter need describing a general technique to define transformations that perform this translation. In this work, two case studies illustrate the application of this process.

  5. Normalizing cDNA libraries.

    Science.gov (United States)

    Bogdanov, Ekaterina A; Shagina, Irina; Barsova, Ekaterina V; Kelmanson, Ilya; Shagin, Dmitry A; Lukyanov, Sergey A

    2010-04-01

    The characterization of rare messages in cDNA libraries is complicated by the substantial variations that exist in the abundance levels of different transcripts in cells and tissues. The equalization (normalization) of cDNA is a helpful approach for decreasing the prevalence of abundant transcripts, thereby facilitating the assessment of rare transcripts. This unit provides a method for duplex-specific nuclease (DSN)-based normalization, which allows for the fast and reliable equalization of cDNA, thereby facilitating the generation of normalized, full-length-enriched cDNA libraries, and enabling efficient RNA analyses. (c) 2010 by John Wiley & Sons, Inc.

  6. Near-normal values of extravascular lung water in children

    NARCIS (Netherlands)

    Nusmeier, A.; Cecchetti, C.; Blohm, M.; Lehman, R.; Hoeven, J.G. van der; Lemson, J.

    2015-01-01

    OBJECTIVES: To define near-normal values of extravascular lung water indexed to body weight in children. DESIGN: Prospective multicenter observational study. SETTING: Medical/surgical PICUs of 5 multinational hospitals. PATIENTS: Fifty-eight children with a median age of 4 years (range 1 month to 17

  7. The construction of normal expectations

    DEFF Research Database (Denmark)

    Quitzau, Maj-Britt; Røpke, Inge

    2008-01-01

    The gradual upward changes of standards in normal everyday life have significant environmental implications, and it is therefore important to study how these changes come about. The intention of the article is to analyze the social construction of normal expectations through a case study. The case...... concerns the present boom in bathroom renovations in Denmark, which offers an excellent opportunity to study the interplay between a wide variety of consumption drivers and social changes pointing toward long-term changes of normal expectations regarding bathroom standards. The study is problemoriented......, and the increased focus on body care and fitness. The contours of the emerging normal expectations are outlined and discussed in an environmental perspective....

  8. Complete Normal Ordering 1: Foundations

    CERN Document Server

    Ellis, John; Skliros, Dimitri P.

    2016-01-01

    We introduce a new prescription for quantising scalar field theories perturbatively around a true minimum of the full quantum effective action, which is to `complete normal order' the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all `cephalopod' Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of `complete normal ordering' (which is an extension of the standard field theory definition of normal ordering) reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative i...

  9. THEORETICAL APPROACHES DEFINE SENSE OF INVESTMENT PROJECT

    Directory of Open Access Journals (Sweden)

    Yu. A. Burduzha

    2010-11-01

    Full Text Available The essence of terms “project”, “investment project” is defined in the article, as well as the difference between definitions of terms “project”, “plan” and “program” is determined. The main approaches to the treatment of definition of term “investment project” are considered.

  10. Precise Interval Timer for Software Defined Radio

    Science.gov (United States)

    Pozhidaev, Aleksey (Inventor)

    2014-01-01

    A precise digital fractional interval timer for software defined radios which vary their waveform on a packet-by-packet basis. The timer allows for variable length in the preamble of the RF packet and allows to adjust boundaries of the TDMA (Time Division Multiple Access) Slots of the receiver of an SDR based on the reception of the RF packet of interest.

  11. 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...

  12. 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…

  13. Software-defined anything challenges status quo

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, Wayne; Borders, Tammie

    2015-01-01

    INL successfully developed a proof of concept for "Software Defined Anything" by emulating the laboratory's business applications that run on Virtual Machines. The work INL conducted demonstrates to industry on how this methodology can be used to improve security, automate and repeat processes, and improve consistency.

  14. Towards a Southern African English Defining Vocabulary

    African Journals Online (AJOL)

    user

    of parameters, such as avoiding synonyms and antonyms, to determine which words are necessary to write definitions in a concise and simple way. It has been found that existing defining vocabularies lack certain words that would make definitions more accessible to southern African learners, and therefore there is a need ...

  15. Defining Grammatical Difficulty: A Student Teacher Perspective

    Science.gov (United States)

    Graus, Johan; Coppen, Peter-Arno

    2015-01-01

    Numerous second language acquisition (SLA) researchers have tried to define grammatical difficulty in second and foreign language acquisition--often as part of an attempt to relate the efficacy of different types of instruction to the degree of difficulty of grammatical structures. The resulting proliferation of definitions and the lack of a…

  16. 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...

  17. 9 CFR 592.2 - Terms defined.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Terms defined. 592.2 Section 592.2 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE EGG PRODUCTS... to, the state of preservation, cleanliness, soundness, wholesomeness, or fitness for human food) of...

  18. 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)

  19. Defining, constructing and assessing learning outcomes.

    Science.gov (United States)

    Taylor, R M

    2009-08-01

    Learning outcomes define the veterinary curriculum and inform students about what they must be able to demonstrate to succeed. Stakeholder consultation during their development ensures that programme learning outcomes equip graduates to contribute to the veterinary profession. Effective learning outcomes form a hierarchy linking the programme, its courses and tasks. Clear outcomes direct students towards higher quality learning by indicating the achievements intended, but leave scope for emergent learning outcomes. Defined technical competencies fit within this overarching framework, complementing higher order learning. Mapping is used to align learning outcomes horizontally and vertically so students are systematically guided towards entry-level competence and professional independence. Constructively aligned learning and assessment tasks ensure learners spend the focused time required to sequentially develop programme outcomes. Assessment by staff, peers and other stakeholders certifies achievement of intended outcomes. Effective assessment also empowers students to define and achieve their own learning outcomes, so they develop the habits of autonomous life-long learning. Evaluation of the quality and consistency of achieved outcomes informs ongoing programme improvement. If we are going to achieve the objectives of this set of papers, i.e. to improve public health education globally (Rev. sci. tech. Off. int. Epiz. 28 [2] 2009), then it is essential that they be well defined in the learning outcomes statement of all veterinary schools.

  20. Bruxism defined and graded: an international consensus

    NARCIS (Netherlands)

    Lobbezoo, F.; Ahlberg, J.; Glaros, A.G.; Kato, T.; Koyano, K.; Lavigne, G.J.; de Leeuw, R.; Manfredini, D.; Svensson, P.; Winocur, E.

    2013-01-01

    To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined

  1. nth roots of normal contractions

    International Nuclear Information System (INIS)

    Duggal, B.P.

    1992-07-01

    Given a complex separable Hilbert space H and a contraction A on H such that A n , n≥2 some integer, is normal it is shown that if the defect operator D A = (1 - A * A) 1/2 is of the Hilbert-Schmidt class, then A is similar to a normal contraction, either A or A 2 is normal, and if A 2 is normal (but A is not) then there is a normal contraction N and a positive definite contraction P of trace class such that parallel to A - N parallel to 1 = 1/2 parallel to P + P parallel to 1 (where parallel to · parallel to 1 denotes the trace norm). If T is a compact contraction such that its characteristics function admits a scalar factor, if T = A n for some integer n≥2 and contraction A with simple eigen-values, and if both T and A satisfy a ''reductive property'', then A is a compact normal contraction. (author). 16 refs

  2. HYPERVASCULAR LIVER LESIONS IN RADIOLOGICALLY NORMAL LIVER.

    Science.gov (United States)

    Amico, Enio Campos; Alves, José Roberto; Souza, Dyego Leandro Bezerra de; Salviano, Fellipe Alexandre Macena; João, Samir Assi; Liguori, Adriano de Araújo Lima

    2017-01-01

    The hypervascular liver lesions represent a diagnostic challenge. To identify risk factors for cancer in patients with non-hemangiomatous hypervascular hepatic lesions in radiologically normal liver. This prospective study included patients with hypervascular liver lesions in radiologically normal liver. The diagnosis was made by biopsy or was presumed on the basis of radiologic stability in follow-up period of one year. Cirrhosis or patients with typical imaging characteristics of haemangioma were excluded. Eighty-eight patients were included. The average age was 42.4. The lesions were unique and were between 2-5 cm in size in most cases. Liver biopsy was performed in approximately 1/3 of cases. The lesions were benign or most likely benign in 81.8%, while cancer was diagnosed in 12.5% of cases. Univariate analysis showed that age >45 years (p3 nodules (p=0.003) and elevated alkaline phosphatase (p=0.013) were significant risk factors for cancer. It is safe to observe hypervascular liver lesions in normal liver in patients up to 45 years, normal alanine aminotransaminase, up to three nodules and no personal history of cancer. Lesion biopsies are safe in patients with atypical lesions and define the treatment to be established for most of these patients. As lesões hepáticas hipervasculares representam um desafio diagnóstico. Identificar fatores de risco para câncer em pacientes portadores de lesão hepática hipervascular não-hemangiomatosa em fígado radiologicamente normal. Estudo prospectivo que incluiu pacientes com lesões hepáticas hipervasculares em que o diagnóstico final foi obtido por exame anatomopatológico ou, presumido a partir de seguimento mínimo de um ano. Diagnóstico prévio de cirrose ou radiológico de hemangioma foram considerados critérios de exclusão. Oitenta e oito pacientes foram incluídos. A relação mulher/homem foi de 5,3/1. A idade média foi de 42,4 anos. Na maior parte das vezes as lesões hepáticas foram únicas e com

  3. Mildly generalized closed sets, almost normal and mildly normal spaces

    International Nuclear Information System (INIS)

    Park, Jin Keun; Park, Jin Han

    2004-01-01

    The aim of this paper is to introduce and study the class of mildly generalized closed sets, which is properly placed between the classes of strongly generalized closed sets due to Sundaram and Pushpalatha in 2001 and weakly generalized closed sets due to Sundaram and Nagaveni in 1998. The relations with other notions directly or indirectly connected with generalized closed are investigated. Moreover we use it to obtain new characterizations and preservation theorems of almost normal spaces due to Singal and Arya and mildly normal spaces due to Singal and Singal, respectively

  4. 'Normal' markets, market imperfections and energy efficiency

    International Nuclear Information System (INIS)

    Sanstad, A.H.; Howarth, R.B.

    1994-01-01

    The conventional distinction between 'economic' and 'engineering' approaches to energy analysis obscures key methodological issues concerning the measurement of the costs and benefits of policies to promote the adoption of energy-efficient technologies. The engineering approach is in fact based upon firm economic foundations: the principle of lifecycle cost minimization that arises directly from the theory of rational investment. Thus, evidence that so-called 'market barriers' impede the adoption of cost-effective energy-efficient technologies implies the existence of market failures as defined in the context of microeconomic theory. A widely held view that the engineering view lacks economic justification, is based on the fallacy that markets are 'normally' efficient. (author)

  5. On defining the product r−k⋅∇lδ

    Directory of Open Access Journals (Sweden)

    C. K. Li

    2004-01-01

    Full Text Available Let ρ(s be a fixed infinitely differentiable function defined on R+=[0,∞ having the properties: (i ρ(s≥0, (ii ρ(s=0 for s≥1, and (iii ∫Rmδn(xdx=1 where δn(x=cmnmρ(n2r2 and cm is the constant satisfying (iii. We overcome difficulties arising from computing ∇lδn and express this regular sequence by two mutual recursions and use a Java swing program to evaluate corresponding coefficients. Hence, we are able to imply the distributional product r−k⋅∇lδ for k=1,2,… and l=0,1,2,… with the help of Pizetti's formula and the normalization.

  6. Defining Elastic Fiber Interactions by Molecular Fishing

    Science.gov (United States)

    Cain, Stuart A.; McGovern, Amanda; Small, Elaine; Ward, Lyle J.; Baldock, Clair; Shuttleworth, Adrian; Kielty, Cay M.

    2009-01-01

    Deciphering interacting networks of the extracellular matrix is a major challenge. We describe an affinity purification and mass spectrometry strategy that has provided new insights into the molecular interactions of elastic fibers, essential extracellular assemblies that provide elastic recoil in dynamic tissues. Using cell culture models, we defined primary and secondary elastic fiber interaction networks by identifying molecular interactions with the elastic fiber molecules fibrillin-1, MAGP-1, fibulin-5, and lysyl oxidase. The sensitivity and validity of our method was confirmed by identification of known interactions with the bait proteins. Our study revealed novel extracellular protein interactions with elastic fiber molecules and delineated secondary interacting networks with fibronectin and heparan sulfate-associated molecules. This strategy is a novel approach to define the macromolecular interactions that sustain complex extracellular matrix assemblies and to gain insights into how they are integrated into their surrounding matrix. PMID:19755719

  7. Defining Tiger Parenting in Chinese Americans

    Science.gov (United States)

    Kim, Su Yeong

    2016-01-01

    “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. PMID:27182075

  8. 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.

  9. 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.

  10. Normal probability plots with confidence.

    Science.gov (United States)

    Chantarangsi, Wanpen; Liu, Wei; Bretz, Frank; Kiatsupaibul, Seksan; Hayter, Anthony J; Wan, Fang

    2015-01-01

    Normal probability plots are widely used as a statistical tool for assessing whether an observed simple random sample is drawn from a normally distributed population. The users, however, have to judge subjectively, if no objective rule is provided, whether the plotted points fall close to a straight line. In this paper, we focus on how a normal probability plot can be augmented by intervals for all the points so that, if the population distribution is normal, then all the points should fall into the corresponding intervals simultaneously with probability 1-α. These simultaneous 1-α probability intervals provide therefore an objective mean to judge whether the plotted points fall close to the straight line: the plotted points fall close to the straight line if and only if all the points fall into the corresponding intervals. The powers of several normal probability plot based (graphical) tests and the most popular nongraphical Anderson-Darling and Shapiro-Wilk tests are compared by simulation. Based on this comparison, recommendations are given in Section 3 on which graphical tests should be used in what circumstances. An example is provided to illustrate the methods. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. A solution defined by fine vectors

    NARCIS (Netherlands)

    Xu, G.; Sun, H.; Sun, H.; Hoede, C.; Driessen, Theo

    Bumb and Hoede have shown that a cooperative game can be split into two games, the reward game and the fine game, by considering the sign of quantities $c_v^S$ in the c-diagram of the game. One can then define a solution $x$ for the original game as $x = x_r - x_f$ , where $x_r$ is a solution for

  12. Defining the clinical course of multiple sclerosis

    DEFF Research Database (Denmark)

    Lublin, Fred D; Reingold, Stephen C; Cohen, Jeffrey A

    2014-01-01

    of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration...... of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined....

  13. OPTIMAL PORTFOLIOS IN DEFINED CONTRIBUTION PENSION SYSTEMS

    OpenAIRE

    EDUARDO WALKER

    2006-01-01

    We study optimal portfolios for defined contribution (possibly mandatory) pension systems, which maximize expected pensions subject to a risk level. By explicitly considering the present value of future individual contributions and changing the risk-return numeraire to future pension units we obtain interesting insights, consistent with the literature, in a simpler context. Results naturally imply that the local indexed (inflation-adjusted) currency is the benchmark and that the investment ho...

  14. 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.

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

    NARCIS (Netherlands)

    Monforte, Antonella d'Arminio; Abrams, Donald; Pradier, Christian; Weber, Rainer; Reiss, Peter; Bonnet, Fabrice; Kirk, Ole; Law, Matthew; De Wit, Stephane; Friis-Møller, Nina; Phillips, Andrew N; Sabin, Caroline A; Lundgren, Jens D; Schölvinck, Elisabeth H.

    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

  16. CT and MRI normal findings

    International Nuclear Information System (INIS)

    Moeller, T.B.; Reif, E.

    1998-01-01

    This book gives answers to questions frequently heard especially from trainees and doctors not specialising in the field of radiology: Is that a normal finding? How do I decide? What are the objective criteria? The information presented is three-fold. The normal findings of the usual CT and MRI examinations are shown with high-quality pictures serving as a reference, with inscribed important additional information on measures, angles and other criteria describing the normal conditions. These criteria are further explained and evaluated in accompanying texts which also teach the systematic approach for individual picture analysis, and include a check list of major aspects, as a didactic guide for learning. The book is primarily intended for students, radiographers, radiology trainees and doctors from other medical fields, but radiology specialists will also find useful details of help in special cases. (orig./CB) [de

  17. Normalized cDNA libraries

    Science.gov (United States)

    Soares, Marcelo B.; Efstratiadis, Argiris

    1997-01-01

    This invention provides a method to normalize a directional cDNA library constructed in a vector that allows propagation in single-stranded circle form comprising: (a) propagating the directional cDNA library in single-stranded circles; (b) generating fragments complementary to the 3' noncoding sequence of the single-stranded circles in the library to produce partial duplexes; (c) purifying the partial duplexes; (d) melting and reassociating the purified partial duplexes to moderate Cot; and (e) purifying the unassociated single-stranded circles, thereby generating a normalized cDNA library.

  18. Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer.

    Science.gov (United States)

    Danforth, David N

    2016-01-01

    Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer. This review indicates that normal risk breast tissues (such as reduction mammoplasty) contain evidence of early breast carcinogenesis including loss of heterozygosity, DNA methylation of tumor suppressor and other genes, and telomere shortening. In normal tissues at high risk for breast cancer (such as normal breast tissue adjacent to breast cancer or the contralateral breast), these changes persist, and are increased and accompanied by aneuploidy, increased genomic instability, a wide range of gene expression differences, development of large cancerized fields, and increased proliferation. These changes are consistent with early and long-standing exposure to carcinogens, especially estrogens. A model for the breast carcinogenic pathway in normal risk and high-risk breast tissues is proposed. These findings should clarify our understanding of breast carcinogenesis in normal breast tissue and promote development of improved methods for risk assessment and breast cancer prevention in women.

  19. Normal mode analysis of Zika virus.

    Science.gov (United States)

    Lee, Byung Ho; Jo, Soojin; Choi, Moon-Ki; Kim, Min Hyeok; Choi, Jae Boong; Kim, Moon Ki

    2018-02-01

    In recent years, Zika virus (ZIKV) caused a new pandemic due to its rapid spread and close relationship with microcephaly. As a result, ZIKV has become an obvious global health concern. Information about the fundamental viral features or the biological process of infection remains limited, despite considerable efforts. Meanwhile, the icosahedral shell structure of the mature ZIKV was recently revealed by cryo-electron microscopy. This structural information enabled us to simulate ZIKV. In this study, we analyzed the dynamic properties of ZIKV through simulation from the mechanical viewpoint. We performed normal mode analysis (NMA) for a dimeric structure of ZIKV consisting of the envelope proteins and the membrane proteins as a unit structure. By analyzing low-frequency normal modes, we captured intrinsic vibrational motions and defined basic vibrational properties of the unit structure. Moreover, we also simulated the entire shell structure of ZIKV at the reduced computational cost, similar to the case of the unit structure, by utilizing its icosahedral symmetry. From the NMA results, we can not only comprehend the putative dynamic fluctuations of ZIKV but also verify previous inference such that highly mobile glycosylation sites would play an important role in ZIKV. Consequently, this theoretical study is expected to give us an insight on the underlying biological functions and infection mechanism of ZIKV. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Fetal liver T2* values: defining a standardized scale.

    Science.gov (United States)

    Goitein, Orly; Eshet, Yael; Hoffmann, Chen; Raviv-Zilka, Lisa; Salem, Yishay; Hamdan, Ashraf; Goitein, David; Kushnir, Tamar; Eshed, Iris; Di-Segni, Elio; Konen, Eli

    2013-12-01

    To define the normal T2* values of liver in the third trimester of pregnancy in normal fetuses. Multi-echo gradient echo T2* sequence was applied to the fetal abdomen in the axial plane in women undergoing a fetal MRI (1.5 Tesla [T], MRI system). A region of interest, best visualizing in the liver parenchyma was used for measurements. Studies were independently read by two experienced readers to assess intra- and interobserver variability. The study cohort included 46 pregnant women undergoing fetal MRI for any indication other than liver pathology evaluation. Three scans were excluded due to fetal motion. Average maternal and gestational age were 33 ± 4 years and 31.9 ± 3 weeks, respectively. Average T2* values were found to be 19.7 ± 7.4 ms. The intra- and interobserver agreement were very good: 0.93 and 0.8-0.084, respectively. T2* MRI allows noninvasive evaluation liver iron content in the third trimester fetus. Measured values at this stage of pregnancy are significantly lower compared with values cited in the literature for adults. This is of major importance in the correct diagnosis of fetal iron overload states. We propose this as the standard reference when evaluating fetal iron overload pathology. Copyright © 2013 Wiley Periodicals, Inc.

  1. Size, shape, and appearance of the normal female pituitary gland

    International Nuclear Information System (INIS)

    Wolpert, S.M.; Molitch, M.E.; Goldman, J.A.; Wood, J.B.

    1984-01-01

    One hundred seven women 18-65 years old were studied who were referred for suspected central nervous system disease not related to the pituitary gland or hypothalamus. High-resolution, direct, coronal, contrast-enhanced computed tomography (CT) was used to examine the size; shape, and density of the normal pituitary gland. There were three major conclusions: (1) the height of the normal gland can be as much as 9 mm; (2) the superior margin of the gland may bulge in normal patients; and (3) both large size and convex contour appear to be associated with younger age. It was also found that serum prolactin levels do not appear to correlate with the CT appearances. Noise artifacts inherent in high-detail, thin-section, soft-tissue scanning may be a limiting factor in defining reproducible patterns in different parts of the normal pituitary gland

  2. Progress in Defining Disease: Improved Approaches and Increased Impact.

    Science.gov (United States)

    Schwartz, Peter H

    2017-08-01

    In a series of recent papers, I have made three arguments about how to define "disease" and evaluate and apply possible definitions. First, I have argued that definitions should not be seen as traditional conceptual analyses, but instead as proposals about how to define and use the term "disease" in the future. Second, I have pointed out and attempted to address a challenge for dysfunction-requiring accounts of disease that I call the "line-drawing" problem: distinguishing between low-normal functioning and dysfunctioning. Finally, I have used a dysfunction-requiring approach to argue that some extremely prevalent conditions, such as high blood pressure, high cholesterol, and ductal carcinoma in situ, are not diseases, but instead are risk factors. Four of the papers in this issue directly engage my previous work. In this commentary, I applaud the advances these authors make, address points of disagreement, and make suggestions about where the discussion should go next. © The Author 2017. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Cartilage oligomeric matrix protein associates differentially with erosions and synovitis and has a different temporal course in cyclic citrullinated peptide antibody (anti-CCP)-positive versus anti-CCP-negative early rheumatoid arthritis.

    Science.gov (United States)

    Christensen, Anne F; Lindegaard, Hanne; Hørslev-Petersen, Kim; Hetland, Merete L; Ejbjerg, Bo; Stengaard-Pedersen, Kristian; Jacobsen, Søren; Lottenburger, Tine; Ellingsen, Torkell; Andersen, Lis S; Hansen, Ib; Skjødt, Henrik; Pedersen, Jens K; Lauridsen, Ulrik B; Svendsen, Anders; Tarp, Ulrik; Pødenphant, Jan; Østergaard, Mikkel; Junker, Peter

    2011-08-01

    Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings. A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years. Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals. Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.

  4. The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qianwen Lv

    Full Text Available OBJECTIVES: This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF and anti-cyclic citrullinated peptide (anti-CCP antibody are associated with the clinical response to anti-tumor necrosis factor (TNF alpha treatment in rheumatoid arthritis (RA. METHODS: A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot. RESULTS: A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54 and 0.88 (95% CI: 0.76-1.03, p=0.11, respectively, with I(2 values of 43% (p=0.05 and 67% (p<0.01, respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab, response criteria (DAS28 vs. ACR20 vs. EULAR response, follow-up period (≥ 6 vs. <6 months, and ethnic group did not reveal a significant association for the status of RF and anti-CCP. CONCLUSIONS: Neither the RF nor anti-CCP antibody status in RA patients is associated with a clinical response to anti-TNFα treatment.

  5. Anti-streptavidin IgG antibody interference in anti-cyclic citrullinated peptide (CCP) IgG antibody assays is a rare but important cause of false-positive anti-CCP results.

    Science.gov (United States)

    Berth, Mario; Willaert, Sofie; De Ridder, Carol

    2018-02-21

    The detection of anti-cyclic citrullinated peptide (anti-CCP) IgG antibodies in blood is mainly used for the diagnosis of rheumatoid arthritis. Falsely elevated anti-CCP IgG antibodies due to anti-streptavidin IgG antibodies were suspected in our laboratory. In this study, we evaluated, in a standardized approach, the prevalence of anti-streptavidin IgG antibodies in a primary care setting and the effect of anti-streptavidin IgG antibodies on anti-CCP IgG assays from three different important commercial manufacturers (Abbott, Roche Diagnostics, Thermo Fisher Scientific). Three different populations were consecutively and prospectively studied: serum samples from 1000 ambulatory patients, 286 serum samples from patients for which anti-CCP was requested and 89 serum samples from patients which had previously given a positive anti-CCP result on Architect® i2000. The frequency of confirmed anti-streptavidin IgG-positive samples detected in this study was 0.6% (8/1375). Anti-CCP IgG was determined on the eight samples with confirmed anti-streptavidin IgG antibodies: with the Cobas® method, seven positive anti-CCP results were observed and five positive anti-CCP results with the Architect® method. No positive anti-CCP IgG results were obtained with the EliA™ method. Rheumatoid factor was negative in these eight samples. Anti-streptavidin IgG antibodies rarely cause false-positive results in some anti-CCP assays. However, despite being an infrequent assay problem, it could possibly lead to diagnostic confusion or even an incorrect diagnosis of rheumatoid arthritis.

  6. Interpretation of Spirometry: Selection of Predicted Values and Defining Abnormality.

    Science.gov (United States)

    Chhabra, S K

    2015-01-01

    Spirometry is the most frequently performed investigation to evaluate pulmonary function. It provides clinically useful information on the mechanical properties of the lung and the thoracic cage and aids in taking management-related decisions in a wide spectrum of diseases and disorders. Few measurements in medicine are so dependent on factors related to equipment, operator and the patient. Good spirometry requires quality assured measurements and a systematic approach to interpretation. Standard guidelines on the technical aspects of equipment and their calibration as well as the test procedure have been developed and revised from time-to-time. Strict compliance with standardisation guidelines ensures quality control. Interpretation of spirometry data is based only on two basic measurements--the forced vital capacity (FVC) and the forced expiratory volume in 1 second (FEV1) and their ratio, FEV1/FVC. A meaningful and clinically useful interpretation of the measured data requires a systematic approach and consideration of several important issues. Central to interpretation is the understanding of the development and application of prediction equations. Selection of prediction equations that are appropriate for the ethnic origin of the patient is vital to avoid erroneous interpretation. Defining abnormal values is a debatable but critical aspect of spirometry. A statistically valid definition of the lower limits of normal has been advocated as the better method over the more commonly used approach of defining abnormality as a fixed percentage of the predicted value. Spirometry rarely provides a specific diagnosis. Examination of the flow-volume curve and the measured data provides information to define patterns of ventilatory impairment. Spirometry must be interpreted in conjunction with clinical information including results of other investigations.

  7. A simple method for defining malaria seasonality

    Directory of Open Access Journals (Sweden)

    Smith Lucy

    2009-12-01

    Full Text Available Abstract Background There is currently no standard way of defining malaria seasonality, resulting in a wide range of definitions reported in the literature. Malaria cases show seasonal peaks in most endemic settings, and the choice and timing for optimal malaria control may vary by seasonality. A simple approach is presented to describe the seasonality of malaria, to aid localized policymaking and targeting of interventions. Methods A series of systematic literature reviews were undertaken to identify studies reporting on monthly data for full calendar years on clinical malaria, hospital admission with malaria and entomological inoculation rates (EIR. Sites were defined as having 'marked seasonality' if 75% or more of all episodes occurred in six or less months of the year. A 'concentrated period of malaria' was defined as the six consecutive months with the highest cumulative proportion of cases. A sensitivity analysis was performed based on a variety of cut-offs. Results Monthly data for full calendar years on clinical malaria, all hospital admissions with malaria, and entomological inoculation rates were available for 13, 18, and 11 sites respectively. Most sites showed year-round transmission with seasonal peaks for both clinical malaria and hospital admissions with malaria, with a few sites fitting the definition of 'marked seasonality'. For these sites, consistent results were observed when more than one outcome or more than one calendar year was available from the same site. The use of monthly EIR data was found to be of limited value when looking at seasonal variations of malaria transmission, particularly at low and medium intensity levels. Conclusion The proposed definition discriminated well between studies with 'marked seasonality' and those with less seasonality. However, a poor fit was observed in sites with two seasonal peaks. Further work is needed to explore the applicability of this definition on a wide-scale, using routine

  8. Complete normal ordering 1: Foundations

    Directory of Open Access Journals (Sweden)

    John Ellis

    2016-08-01

    Full Text Available We introduce a new prescription for quantising scalar field theories (in generic spacetime dimension and background perturbatively around a true minimum of the full quantum effective action, which is to ‘complete normal order’ the bare action of interest. When the true vacuum of the theory is located at zero field value, the key property of this prescription is the automatic cancellation, to any finite order in perturbation theory, of all tadpole and, more generally, all ‘cephalopod’ Feynman diagrams. The latter are connected diagrams that can be disconnected into two pieces by cutting one internal vertex, with either one or both pieces free from external lines. In addition, this procedure of ‘complete normal ordering’ (which is an extension of the standard field theory definition of normal ordering reduces by a substantial factor the number of Feynman diagrams to be calculated at any given loop order. We illustrate explicitly the complete normal ordering procedure and the cancellation of cephalopod diagrams in scalar field theories with non-derivative interactions, and by using a point splitting ‘trick’ we extend this result to theories with derivative interactions, such as those appearing as non-linear σ-models in the world-sheet formulation of string theory. We focus here on theories with trivial vacua, generalising the discussion to non-trivial vacua in a follow-up paper.

  9. Normalizing Catastrophe: Sustainability and Scientism

    Science.gov (United States)

    Bonnett, Michael

    2013-01-01

    Making an adequate response to our deteriorating environmental situation is a matter of ever increasing urgency. It is argued that a central obstacle to achieving this is the way that scientism has become normalized in our thinking about environmental issues. This is taken to reflect on an underlying "metaphysics of mastery" that vitiates proper…

  10. Mixed normal inference on multicointegration

    NARCIS (Netherlands)

    Boswijk, H.P.

    2009-01-01

    Asymptotic likelihood analysis of cointegration in I(2) models, see Johansen (1997, 2006), Boswijk (2000) and Paruolo (2000), has shown that inference on most parameters is mixed normal, implying hypothesis test statistics with an asymptotic 2 null distribution. The asymptotic distribution of the

  11. 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)

  12. [Cessation of livor in defined pressure conditions].

    Science.gov (United States)

    Fechner, G; Koops, E; Henssge, C

    1984-01-01

    In 28 cases of sudden death, the corpses were tested for the effect of different storage temperatures (5 degrees C, 14 degrees-15 degrees C, 25 degrees C) regarding the reaction of livor mortis to known pressure conditions (force and duration of pressure). The reaction is dependent on the storage temperature but there is no linear relationship. At certain storage temperatures the postmortem lividity reaction is dependent on the amount and duration of the pressure. In addition, at defined storage temperature and pressure conditions, there are large interindividual differences in the estimation of time of death.

  13. 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.

  14. DEFINING THE CHEMICAL SPACE OF PUBLIC GENOMIC ...

    Science.gov (United States)

    The current project aims to chemically index the genomics content of public genomic databases to make these data accessible in relation to other publicly available, chemically-indexed toxicological information. By defining the chemical space of public genomic data, it is possible to identify classes of chemicals on which to develop methodologies for the integration of chemogenomic data into predictive toxicology. The chemical space of public genomic data will be presented as well as the methodologies and tools developed to identify this chemical space.

  15. Software-defined reconfigurable microwave photonics processor.

    Science.gov (United States)

    Pérez, Daniel; Gasulla, Ivana; Capmany, José

    2015-06-01

    We propose, for the first time to our knowledge, a software-defined reconfigurable microwave photonics signal processor architecture that can be integrated on a chip and is capable of performing all the main functionalities by suitable programming of its control signals. The basic configuration is presented and a thorough end-to-end design model derived that accounts for the performance of the overall processor taking into consideration the impact and interdependencies of both its photonic and RF parts. We demonstrate the model versatility by applying it to several relevant application examples.

  16. Defining Starch Binding by Glucan Phosphatases

    DEFF Research Database (Denmark)

    Auger, Kyle; Raththagala, Madushi; Wilkens, Casper

    2015-01-01

    Starch is a vital energy molecule in plants that has a wide variety of uses in industry, such as feedstock for biomaterial processing and biofuel production. Plants employ a three enzyme cyclic process utilizing kinases, amylases, and phosphatases to degrade starch in a diurnal manner. Starch...... is comprised of the branched glucan amylopectin and the more linear glucan amylose. Our lab has determined the first structures of these glucan phosphatases and we have defined their enzymatic action. Despite this progress, we lacked a means to quickly and efficiently quantify starch binding to glucan...

  17. Healthcare Engineering Defined: A White Paper

    Directory of Open Access Journals (Sweden)

    Ming-Chien Chyu

    2015-01-01

    Full Text Available Engineering has been playing an important role in serving and advancing healthcare. The term “Healthcare Engineering” has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of “Healthcare Engineering” remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects.

  18. Software defined networks a comprehensive approach

    CERN Document Server

    Goransson, Paul

    2014-01-01

    Software Defined Networks discusses the historical networking environment that gave rise to SDN, as well as the latest advances in SDN technology. The book gives you the state of the art knowledge needed for successful deployment of an SDN, including: How to explain to the non-technical business decision makers in your organization the potential benefits, as well as the risks, in shifting parts of a network to the SDN modelHow to make intelligent decisions about when to integrate SDN technologies in a networkHow to decide if your organization should be developing its own SDN applications or

  19. Healthcare Engineering Defined: A White Paper.

    Science.gov (United States)

    Chyu, Ming-Chien; Austin, Tony; Calisir, Fethi; Chanjaplammootil, Samuel; Davis, Mark J; Favela, Jesus; Gan, Heng; Gefen, Amit; Haddas, Ram; Hahn-Goldberg, Shoshana; Hornero, Roberto; Huang, Yu-Li; Jensen, Øystein; Jiang, Zhongwei; Katsanis, J S; Lee, Jeong-A; Lewis, Gladius; Lovell, Nigel H; Luebbers, Heinz-Theo; Morales, George G; Matis, Timothy; Matthews, Judith T; Mazur, Lukasz; Ng, Eddie Yin-Kwee; Oommen, K J; Ormand, Kevin; Rohde, Tarald; Sánchez-Morillo, Daniel; Sanz-Calcedo, Justo García; Sawan, Mohamad; Shen, Chwan-Li; Shieh, Jiann-Shing; Su, Chao-Ton; Sun, Lilly; Sun, Mingui; Sun, Yi; Tewolde, Senay N; Williams, Eric A; Yan, Chongjun; Zhang, Jiajie; Zhang, Yuan-Ting

    2015-01-01

    Engineering has been playing an important role in serving and advancing healthcare. The term "Healthcare Engineering" has been used by professional societies, universities, scientific authors, and the healthcare industry for decades. However, the definition of "Healthcare Engineering" remains ambiguous. The purpose of this position paper is to present a definition of Healthcare Engineering as an academic discipline, an area of research, a field of specialty, and a profession. Healthcare Engineering is defined in terms of what it is, who performs it, where it is performed, and how it is performed, including its purpose, scope, topics, synergy, education/training, contributions, and prospects.

  20. 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

  1. Software Defined Radio: Basic Principles and Applications

    Directory of Open Access Journals (Sweden)

    José Raúl Machado-Fernández

    2014-12-01

    Full Text Available The author makes a review of the SDR (Software Defined Radio technology, including hardware schemes and application fields. A low performance device is presented and several tests are executed with it using free software. With the acquired experience, SDR employment opportunities are identified for low-cost solutions that can solve significant problems. In addition, a list of the most important frameworks related to the technology developed in the last years is offered, recommending the use of three of them.

  2. 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. .

  3. Risk for COPD with Obstruction of Active Smokers with Normal Spirometry and Reduced Diffusion Capacity

    Science.gov (United States)

    Kaner, Robert J.; Sanders, Abraham; Vincent, Thomas L.; Mezey, Jason G.; Crystal, Ronald G.

    2016-01-01

    Background Smokers are assessed for COPD using spirometry, with COPD defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as airflow limitation not fully reversible with bronchodilators. There is a subset of smokers with normal spirometry (by GOLD criteria), who have a low diffusion capacity (DLCO), a parameter linked to emphysema and small airway disease. The natural history of these “normal spirometry/low DLCO” smokers is unknown. Methods From a cohort of 1570 smokers in the New York City metropolitian area, all of whom had normal spirometry, two groups were randomly selected for lung function follow-up: smokers with normal spirometry/normal DLCO (n=59) and smokers with normal spirometry/low DLCO (n=46). All had normal history, physical examination, CBC, urinalysis, HIV status, α1-antitrypsin level, chest X-ray, FEV1, FVC, FEV1/FVC ratio and total lung capacity (TLC). Throughout the study, all continued to be active smokers. Findings In the normal spirometry/normal DLCO group assessed over 45 ± 20 months, 3% developed GOLD-defined COPD. In contrast, in the normal spirometry/low DLCO group, followed over 41 ± 31 months, 22% developed GOLD-defined COPD. Interpretation Despite appearing “normal” by GOLD, smokers with normal spirometry but low DLCO are at significant risk for developing COPD with obstruction to airflow. PMID:26541521

  4. Fluid involvement in normal faulting

    Science.gov (United States)

    Sibson, Richard H.

    2000-04-01

    Evidence of fluid interaction with normal faults comes from their varied role as flow barriers or conduits in hydrocarbon basins and as hosting structures for hydrothermal mineralisation, and from fault-rock assemblages in exhumed footwalls of steep active normal faults and metamorphic core complexes. These last suggest involvement of predominantly aqueous fluids over a broad depth range, with implications for fault shear resistance and the mechanics of normal fault reactivation. A general downwards progression in fault rock assemblages (high-level breccia-gouge (often clay-rich) → cataclasites → phyllonites → mylonite → mylonitic gneiss with the onset of greenschist phyllonites occurring near the base of the seismogenic crust) is inferred for normal fault zones developed in quartzo-feldspathic continental crust. Fluid inclusion studies in hydrothermal veining from some footwall assemblages suggest a transition from hydrostatic to suprahydrostatic fluid pressures over the depth range 3-5 km, with some evidence for near-lithostatic to hydrostatic pressure cycling towards the base of the seismogenic zone in the phyllonitic assemblages. Development of fault-fracture meshes through mixed-mode brittle failure in rock-masses with strong competence layering is promoted by low effective stress in the absence of thoroughgoing cohesionless faults that are favourably oriented for reactivation. Meshes may develop around normal faults in the near-surface under hydrostatic fluid pressures to depths determined by rock tensile strength, and at greater depths in overpressured portions of normal fault zones and at stress heterogeneities, especially dilational jogs. Overpressures localised within developing normal fault zones also determine the extent to which they may reutilise existing discontinuities (for example, low-angle thrust faults). Brittle failure mode plots demonstrate that reactivation of existing low-angle faults under vertical σ1 trajectories is only likely if

  5. What is normal vaginal flora?

    Science.gov (United States)

    Priestley, C J; Jones, B M; Dhar, J; Goodwin, L

    1997-02-01

    To observe the composition of the vaginal flora of healthy women over time, and in relation to hormonal changes, sexual activity, and hygiene habits. A longitudinal surveillance of the vaginal flora over an eight week period. 26 female health care workers in local genitourinary medicine clinics. The participants were anonymised. They filled in diary cards daily. Blind vaginal swabs were self-taken two-seven times weekly. A smear was air-dried for later Gram staining. The swabs were also cultured for Candida spp, Gardnerella vaginalis, anaerobes, Mycoplasma hominis and Ureaplasma urealyticum. Of 26 subjects, only four had normal vaginal microbiology throughout. One woman, who was not sexually active, had bacterial vaginosis (BV) throughout and nine (35%) had intermittent BV. Candidiasis was found intermittently in eight women (31%), and eight had normal microscopy. U urealyticum was isolated intermittently in 40% of women with BV, 25% with candida, and 50% with normal microscopy. Many women were symptomatic, but symptoms correlated poorly with microbiological findings. All but two women were sexually active; however, more women with BV were exposed to semen. BV seemed to be related to frequent use of scented soap, and there appeared to be an additive effect of clothing and hygiene factors. Our study raises doubts about what should be regarded as normal vaginal flora. It calls into question the significance of finding BV or U urealyticum on a single occasion in asymptomatic women, or of finding normal flora in symptomatic women. The effect of external factors on the vaginal flora deserve further study.

  6. Sequential normal compactness versur topological normal compactness in variational analysis

    Czech Academy of Sciences Publication Activity Database

    Fabian, Marián; Mordukhovich, B. S.

    2003-01-01

    Roč. 54, č. 6 (2003), s. 1057-1067 ISSN 0362-546X R&D Projects: GA ČR GA201/01/1198 Institutional research plan: CEZ:AV0Z1019905; CEZ:AV0Z1019905 Keywords : variational analysis * sequential and topological normal compactness * Banach spaces Subject RIV: BA - General Mathematics Impact factor: 0.354, year: 2003

  7. Normal erect swallowing. Normal function and incidence of variations.

    Science.gov (United States)

    Curtis, D J; Cruess, D F; Dachman, A H

    1985-10-01

    Of 871 candidates presenting for upper gastrointestinal examinations, 16 met the rigorous criteria established for selecting asymptomatic normal volunteers. Frame-by-frame evaluation of their videorecorded pharyngeal swallow confirmed many observations made previously utilizing cine recording at much higher radiation dosages. In addition, new observations were made: the nasopharynx may not occlude until the bolus is entirely within the pharynx; air mixes with the bolus if the swallow is an "open" type; the epiglottis always inverts in normal individuals regardless of the type of swallow ("open," air filled oro-and hypopharynx into which the swallowed bolus is dropped; "closed," airless oropharynx into which the swallowed bolus is pushed by a continuous peristaltic drive of the tongue and palate, thus reconstituting the pharyngeal space); laryngeal descent may aid in stripping the bolus from the pharynx; the vestibule may not completely close during the swallow and the larynx can still be impervious to the bolus; the peristaltic wave does not begin until the bolus has breeched the cricopharyngeus; the cricopharyngeus may be seen frequently in normal individuals, but does not delay the passage of the bolus; asymmetric flow of the bolus around the larynx is common and may not be the result of epiglottic tilt or head positioning.

  8. Distributed controller clustering in software defined networks.

    Directory of Open Access Journals (Sweden)

    Ahmed Abdelaziz

    Full Text Available Software Defined Networking (SDN is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN SDN and Open Network Operating System (ONOS controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability.

  9. How Do You Define an Internship?

    Science.gov (United States)

    Wilson, C. E.; Keane, C.

    2017-12-01

    According to the American Geosciences Institute's Geoscience Student Exit Survey, internship participation rates over the past four years have been low, particularly among bachelor's and doctoral graduates. In 2016, 65% of bachelor's graduates, 44% of master's graduates, and 57% of doctoral graduates did not participate in an internship while working on their degree. When asked if they submitted applications for internship opportunities, 42% of bachelor's graduates, 23% of master's graduates, and 46% of doctoral graduates claimed to not submit any applications. These statistics have raised concern at AGI because internships provide experiences that help develop critical professional skills and industry connections that can lead to jobs after graduation. However, when internships are discussed among various representatives in geoscience industries, there are disagreements in how an internship experience is defined. For example, opinions differ on whether REUs or other research experiences count as an internship. Clear definitions of internship opportunities may help academic faculty and advisors direct students towards these opportunities and help develop a collection of resources for finding future internships. This presentation will present some of the recent statistics on internship participation among geoscience graduates and present a series of questions to ascertain defining features of internships among AGU attendees and where help is needed to increase participation in internships among current geoscience students.

  10. Defining and measuring vulnerability in young people

    Directory of Open Access Journals (Sweden)

    Shilpa Khanna Arora

    2015-01-01

    Full Text Available Adolescents and youth, together addressed as "young people", form the future building blocks of any society. They being most energetic and dynamic, tend to get involved in high-risk behaviors making themselves susceptible to criminal offences, accidents, physical injuries, emotional trauma, and medical problems - some of them extremely serious like transmission of human immunodeficiency virus (HIV. The concept of vulnerability is applicable to all the people who are more exposed to risks than their peers like the young people. In order to deal with social evils like criminal offences, domestic violence, sexual abuse, HIV, etc. we need to define vulnerability and understand the factors that influence it. This review also attempts to summarize the indicators of vulnerability and the data currently available to estimate its burden in India. Measuring the magnitude of vulnerability by means of certain indicators/variables might help us in devising tools to assess this poorly defined entity. This may also evolve a conceptual framework on which targeted remedial interventions can be devised and implemented.

  11. 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.

  12. Distributed controller clustering in software defined networks

    Science.gov (United States)

    Gani, Abdullah; Akhunzada, Adnan; Talebian, Hamid; Choo, Kim-Kwang Raymond

    2017-01-01

    Software Defined Networking (SDN) is an emerging promising paradigm for network management because of its centralized network intelligence. However, the centralized control architecture of the software-defined networks (SDNs) brings novel challenges of reliability, scalability, fault tolerance and interoperability. In this paper, we proposed a novel clustered distributed controller architecture in the real setting of SDNs. The distributed cluster implementation comprises of multiple popular SDN controllers. The proposed mechanism is evaluated using a real world network topology running on top of an emulated SDN environment. The result shows that the proposed distributed controller clustering mechanism is able to significantly reduce the average latency from 8.1% to 1.6%, the packet loss from 5.22% to 4.15%, compared to distributed controller without clustering running on HP Virtual Application Network (VAN) SDN and Open Network Operating System (ONOS) controllers respectively. Moreover, proposed method also shows reasonable CPU utilization results. Furthermore, the proposed mechanism makes possible to handle unexpected load fluctuations while maintaining a continuous network operation, even when there is a controller failure. The paper is a potential contribution stepping towards addressing the issues of reliability, scalability, fault tolerance, and inter-operability. PMID:28384312

  13. Normal zones on Zeeman manifolds with trace class heat and Feynman kernels and well defined zonal Feynman integrals

    OpenAIRE

    Szabo, Zoltan I.

    2006-01-01

    The problem of infinities (divergent integrals) appearing in quantum field theory or elementary particle physics are treated by renormalization in the current theories. By this perturbative tool the desired finite quantities are produced by differences of infinities. This paper gives a new non-perturbative approach to this problem. Namely, the Hilbert space on which the quantum Hamilton operator $H$ is acting, is decomposed into subspaces, called Zeeman zones, which are invariant under the ac...

  14. A Denotational Account of Untyped Normalization by Evaluation

    DEFF Research Database (Denmark)

    Filinski, Andrzej; Rohde, Henning Korsholm

    2004-01-01

    Abstract. We show that the standard normalization-by-evaluation construction for the simply-typed λβη-calculus has a natural counterpart for the untyped λβ-calculus, with the central type-indexed logical relation replaced by a “recursively defined” invariant relation, in the style of Pitts. In fact...... of soundness (the output term, if any, is β-equivalent to the input term); standardization (β-equivalent terms are mapped to the same result); and completeness (the function is defined for all terms that do have normal forms). We also show how the semantic construction enables a simple yet formal correctness...

  15. A Denotational Account of Untyped Normalization by Evaluation

    DEFF Research Database (Denmark)

    Filinski, Andrzej; Rohde, Henning Korsholm

    2004-01-01

    We show that the standard normalization-by-evaluation construction for the simply-typed λβγ-calculus has a natural counterpart for the untyped λβ-calculus, with the central type-indexed logical relation replaced by a recursively defined invariant relation, in the style of Pitts. In fact, the cons...... proof for the normalization algorithm, expressed as a functional program in an ML-like call-by-value language. A version of this article with detailed proofs is available as a technical report [5]....

  16. Striving for the unknown normal

    DEFF Research Database (Denmark)

    Nielsen, Mikka

    During the last decade, more and more people have received prescriptions for ADHD drug treatment, and simultaneously the legitimacy of the ADHD diagnosis has been heavily debated among both professionals and laymen. Based on an anthropological fieldwork among adults with ADHD, I illustrate how...... the ADHD diagnosis both answers and produces existential questions on what counts as normal behaviour and emotions. The diagnosis helps the diagnosed to identify, accept and handle problems by offering concrete explanations and solutions to diffuse experienced problems. But the diagnostic process......-analysing situation trying to answer: What is ADHD and what is me and my personal features? When are the drugs having the right effect? And since I have never been normal then how would I know what behavioural ideal I am striving for? Moreover, the public questioning of the diagnosis calls the individual...

  17. MRI of normal achilles tendon

    Energy Technology Data Exchange (ETDEWEB)

    Rollandi, G.A. [Institute of Radiology, Univ. of Genoa (Italy); Bertolotto, M. [Institute of Radiology, Univ. of Genoa (Italy); Perrone, R. [Institute of Radiology, Univ. of Genoa (Italy); Garlaschi, G. [Institute of Radiology, Univ. of Genoa (Italy); Derchi, L.E. [Institute of Radiology, Univ. of Genoa (Italy)

    1995-12-01

    To investigate the normal internal structure of tendons 11 volunteers without clinical evidence of tendinopathy were examined using conventional spin-echo T1-, T2- and proton-density weighted sequences. The Achilles tendon was chosen because of its high frequency of injury in athletic activity, large size, superficial position and because it is oriented nearly parallel to the static magnetic field, therefore minimizing the ``magic angle phenomenon``. The tendons exhibited areas of slighly increased signal in four T1-weighted and in all but one proton-density-weighted scans. No intratendinous signal was detected in T2-weighted images. The possible origin of these findings is discussed. We conclude that the knowledge of these normal signals may be useful to avoid incorrectly diagnosing as pathological. (orig.). With 2 figs.

  18. Spytkirtlernes normale struktur og funktion

    DEFF Research Database (Denmark)

    Dynesen, Anja Weirsøe; Jensen, Siri Beier; Pedersen, Anne Marie Lynge

    2011-01-01

    Spytkirtlernes normale struktur og funktion Makroskopisk inddeles spytkirtlerne efter deres størrelse, hvor glandulae (gll.) parotideae, gll. submandibulares og gll. sublinguales er de store parrede spytkirtler, mens de små spytkirtler er lokaliserede submukøst i kinder, læber og ganen. Mikroskop......Spytkirtlernes normale struktur og funktion Makroskopisk inddeles spytkirtlerne efter deres størrelse, hvor glandulae (gll.) parotideae, gll. submandibulares og gll. sublinguales er de store parrede spytkirtler, mens de små spytkirtler er lokaliserede submukøst i kinder, læber og ganen......, bidrager til dannelse af en beskyttende og smørende overflade på tænder og mundslimhinde, har en betydelig antimikrobiel funktion, indeholder komponenter, der forebygger demineralisering af tandoverfladen, ligesom spyt medvirker til at vedligeholde et neutralt pH i mundhulen. Endelig har spyttet betydning...

  19. Immoral, deviant, or just normal

    DEFF Research Database (Denmark)

    Fynbo, Lars

    2014-01-01

    Contemporary research often relates driving under the influence (DUI) to alcohol addiction and young drunk drivers, in particular, to social deviance. Based on qualitative interviews with 25 convicted drunk drivers, this article studies the relationship between drinking and DUI. The article focuses...... on three different categories of drunk drivers. In the first, drunk drivers consider addiction to be the main cause of DUI. In the second, they position themselves within subcultural groups often engaged in using illicit drugs, alcohol, and DUI. Both of these categories agree with conceptions of DUI...... themselves and their relationship between drinking and DUI as normal. The article thus concludes that while some drunk drivers view themselves in line with popular conceptions of DUI, others distance themselves from these associations so as to present themselves as normal....

  20. Measurement of normal auditory ossicles by high-resolusion CT with application of normal criteria to disease cases

    International Nuclear Information System (INIS)

    Hara, Jyoko

    1988-01-01

    The purposes of this study were to define criteria for the normal position of ossicles and to apply them in patients with rhinolaryngologically or pathologically confirmed diseases. Ossicles were measured on high-resolution CT images of 300 middle ears, including 241 normal ears and 59 diseased ears, in a total of 203 subjects. Angles A, B, and C to the baseline between the most lateral margins of bilateral internal auditory canals, and distance ratio b/a were defined as measurement items. Normal angles A, B, and C and distance ratio b/a ranged from 19 deg to 59 deg, 101 deg to 145 deg, 51 deg to 89 deg, and 0.49 to 0.51, respectively. Based on these criteria, all of these items were within the normal range in 30/34 (88.2 %) ears for otitis media and mastoiditis. One or more items showed far abnormal values (standard deviation; more than 3) in 5/7 (71.4 %) ears for cholesteatoma and 4/4 (100 %) ears for external ear anomaly. These normal measurements may aid in evaluating the position of auditory ossicles especially in the case of cholesteatoma and auditory ossicle abnormality. (Namekawa, K.)

  1. Measurement of normal auditory ossicles by high-resolusion CT with application of normal criteria to disease cases

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Jyoko

    1988-09-01

    The purposes of this study were to define criteria for the normal position of ossicles and to apply them in patients with rhinolaryngologically or pathologically confirmed diseases. Ossicles were measured on high-resolution CT images of 300 middle ears, including 241 normal ears and 59 diseased ears, in a total of 203 subjects. Angles A, B, and C to the baseline between the most lateral margins of bilateral internal auditory canals, and distance ratio b/a were defined as measurement items. Normal angles A, B, and C and distance ratio b/a ranged from 19 deg to 59 deg, 101 deg to 145 deg, 51 deg to 89 deg, and 0.49 to 0.51, respectively. Based on these criteria, all of these items were within the normal range in 30/34 (88.2 %) ears for otitis media and mastoiditis. One or more items showed far abnormal values (standard deviation; more than 3) in 5/7 (71.4 %) ears for cholesteatoma and 4/4 (100 %) ears for external ear anomaly. These normal measurements may aid in evaluating the position of auditory ossicles especially in the case of cholesteatoma and auditory ossicle abnormality. (Namekawa, K.).

  2. Computing platforms for software-defined radio

    CERN Document Server

    Nurmi, Jari; Isoaho, Jouni; Garzia, Fabio

    2017-01-01

    This book addresses Software-Defined Radio (SDR) baseband processing from the computer architecture point of view, providing a detailed exploration of different computing platforms by classifying different approaches, highlighting the common features related to SDR requirements and by showing pros and cons of the proposed solutions. Coverage includes architectures exploiting parallelism by extending single-processor environment (such as VLIW, SIMD, TTA approaches), multi-core platforms distributing the computation to either a homogeneous array or a set of specialized heterogeneous processors, and architectures exploiting fine-grained, coarse-grained, or hybrid reconfigurability. Describes a computer engineering approach to SDR baseband processing hardware; Discusses implementation of numerous compute-intensive signal processing algorithms on single and multicore platforms; Enables deep understanding of optimization techniques related to power and energy consumption of multicore platforms using several basic a...

  3. Quantum computing. Defining and detecting quantum speedup.

    Science.gov (United States)

    Rønnow, Troels F; Wang, Zhihui; Job, Joshua; Boixo, Sergio; Isakov, Sergei V; Wecker, David; Martinis, John M; Lidar, Daniel A; Troyer, Matthias

    2014-07-25

    The development of small-scale quantum devices raises the question of how to fairly assess and detect quantum speedup. Here, we show how to define and measure quantum speedup and how to avoid pitfalls that might mask or fake such a speedup. We illustrate our discussion with data from tests run on a D-Wave Two device with up to 503 qubits. By using random spin glass instances as a benchmark, we found no evidence of quantum speedup when the entire data set is considered and obtained inconclusive results when comparing subsets of instances on an instance-by-instance basis. Our results do not rule out the possibility of speedup for other classes of problems and illustrate the subtle nature of the quantum speedup question. Copyright © 2014, American Association for the Advancement of Science.

  4. Reconfigurable, Cognitive Software-Defined Radio

    Science.gov (United States)

    Bhat, Arvind

    2015-01-01

    Software-defined radio (SDR) technology allows radios to be reconfigured to perform different communication functions without using multiple radios to accomplish each task. Intelligent Automation, Inc., has developed SDR platforms that switch adaptively between different operation modes. The innovation works by modifying both transmit waveforms and receiver signal processing tasks. In Phase I of the project, the company developed SDR cognitive capabilities, including adaptive modulation and coding (AMC), automatic modulation recognition (AMR), and spectrum sensing. In Phase II, these capabilities were integrated into SDR platforms. The reconfigurable transceiver design employs high-speed field-programmable gate arrays, enabling multimode operation and scalable architecture. Designs are based on commercial off-the-shelf (COTS) components and are modular in nature, making it easier to upgrade individual components rather than redesigning the entire SDR platform as technology advances.

  5. Defining B cell immunodominance to viruses.

    Science.gov (United States)

    Angeletti, Davide; Gibbs, James S; Angel, Matthew; Kosik, Ivan; Hickman, Heather D; Frank, Gregory M; Das, Suman R; Wheatley, Adam K; Prabhakaran, Madhu; Leggat, David J; McDermott, Adrian B; Yewdell, Jonathan W

    2017-04-01

    Immunodominance (ID) defines the hierarchical immune response to competing antigens in complex immunogens. Little is known regarding B cell and antibody ID despite its importance in immunity to viruses and other pathogens. We show that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain. The hierarchy changed as the immune response progressed, and it was dependent on antigen formulation and delivery. Passive antibody transfer and sequential infection experiments demonstrated 'original antigenic suppression', a phenomenon in which antibodies suppress memory responses to the priming antigenic site. Our study provides a template for attaining deeper understanding of antibody ID to viruses and other complex immunogens.

  6. Defining the clinical course of multiple sclerosis

    Science.gov (United States)

    Reingold, Stephen C.; Cohen, Jeffrey A.; Cutter, Gary R.; Sørensen, Per Soelberg; Thompson, Alan J.; Wolinsky, Jerry S.; Balcer, Laura J.; Banwell, Brenda; Barkhof, Frederik; Bebo, Bruce; Calabresi, Peter A.; Clanet, Michel; Comi, Giancarlo; Fox, Robert J.; Freedman, Mark S.; Goodman, Andrew D.; Inglese, Matilde; Kappos, Ludwig; Kieseier, Bernd C.; Lincoln, John A.; Lubetzki, Catherine; Miller, Aaron E.; Montalban, Xavier; O'Connor, Paul W.; Petkau, John; Pozzilli, Carlo; Rudick, Richard A.; Sormani, Maria Pia; Stüve, Olaf; Waubant, Emmanuelle; Polman, Chris H.

    2014-01-01

    Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined. PMID:24871874

  7. Medical abortion. defining success and categorizing failures

    DEFF Research Database (Denmark)

    Rørbye, Christina; Nørgaard, Mogens; Vestermark, Vibeke

    2003-01-01

    . The difference in short- and long-term success rates increased with increasing gestational age. The majority of failures (76%) were diagnosed more than 2 weeks after initiation of the abortion. At a 2-week follow-up visit, the women who turned out to be failures had a larger endometrial width, higher beta......Medical abortion was performed in 461 consecutive women with gestational age LT /= 63 days using a regimen of mifepristone 600 mg followed 2 days later by gemeprost 1 mg vaginally. Success, defined as no surgical intervention, declined from 98.7% after 2 weeks to 94.6% after 15 weeks......-hCG values and smaller reductions of beta-hCG than those treated successfully. To optimize comparison of success rates after different medical abortion regimens, we suggest that the criteria for success are stated clearly, that the success rates are stratified according to gestational age...

  8. Defining and Supporting Narrative-driven Recommendation

    DEFF Research Database (Denmark)

    Bogers, Toine; Koolen, Marijn

    2017-01-01

    Research into recommendation algorithms has made great strides in recent years. However, these algorithms are typically applied in relatively straightforward scenarios: given information about a user's past preferences, what will they like in the future? Recommendation is often more complex......: evaluating recommended items never takes place in a vacuum, and it is often a single step in the user's more complex background task. In this paper, we define a specific type of recommendation scenario called narrative-driven recommendation, where the recommendation process is driven by both a log...... of the user's past transactions as well as a narrative description of their current interest(s). Through an analysis of a set of real-world recommendation narratives from the LibraryThing forums, we demonstrate the uniqueness and richness of this scenario and highlight common patterns and properties...

  9. 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...... their reliability. Results: High-good agreement (>80%) was obtained for including hypoechogenicity, increased thickness of the tendon insertion, calcifications, enthesophytes, erosions and Doppler activity as core elementary lesions of US detected enthesitis. US definitions were subsequently obtained for each...

  10. Software Defined Networking Demands on Software Technologies

    DEFF Research Database (Denmark)

    Galinac Grbac, T.; Caba, Cosmin Marius; Soler, José

    2015-01-01

    Software Defined Networking (SDN) is a networking approach based on a centralized control plane architecture with standardised interfaces between control and data planes. SDN enables fast configuration and reconfiguration of the network to enhance resource utilization and service performances....... This new approach enables a more dynamic and flexible network, which may adapt to user needs and application requirements. To this end, systemized solutions must be implemented in network software, aiming to provide secure network services that meet the required service performance levels. In this paper......, we review this new approach to networking from an architectural point of view, and identify and discuss some critical quality issues that require new developments in software technologies. These issues we discuss along with use case scenarios. Here in this paper we aim to identify challenges...

  11. Environmentally acceptable thread compounds: Requirements defined

    International Nuclear Information System (INIS)

    Stringfellow, W.D.; Hendriks, R.V.; Jacobs, N.L.

    1993-01-01

    New environmental regulations on thread compounds are now being enforced in several areas with strong maritime tradition and a sensitive environment. These areas include Indonesia, Alaska and portions of Norway. The industry generally recognizes the environmental concerns but, with wider enforcement of regulations imminent, has not been able to define clearly the requirements for environmental compliance. This paper, written in collaboration with The Netherlands State Supervision of Mines, is based on the National Policy on Thread Compounds of The Netherlands. This national policy is representative of policies being followed by other North Sea governments. Similar policies might well be adopted by other governments worldwide. These policies will affect the operator, drilling contractor, and supplier. This paper provides a specific and detailed definition of thread compound requirements by addressing four relevant categories. The categories of interest are regulatory approval, environmental, health, and performance

  12. Multiple Phenotypic Changes Define Neutrophil Priming

    Science.gov (United States)

    Miralda, Irina; Uriarte, Silvia M.; McLeish, Kenneth R.

    2017-01-01

    Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS) by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses. PMID:28611952

  13. "Defining Computer 'Speed': An Unsolved Challenge"

    CERN Document Server

    CERN. Geneva

    2012-01-01

    Abstract: The reason we use computers is their speed, and the reason we use parallel computers is that they're faster than single-processor computers. Yet, after 70 years of electronic digital computing, we still do not have a solid definition of what computer 'speed' means, or even what it means to be 'faster'. Unlike measures in physics, where the definition of speed is rigorous and unequivocal, in computing there is no definition of speed that is universally accepted. As a result, computer customers have made purchases misguided by dubious information, computer designers have optimized their designs for the wrong goals, and computer programmers have chosen methods that optimize the wrong things. This talk describes why some of the obvious and historical ways of defining 'speed' haven't served us well, and the things we've learned in the struggle to find a definition that works. Biography: Dr. John Gustafson is a Director ...

  14. Medical abortion. defining success and categorizing failures

    DEFF Research Database (Denmark)

    Rørbye, Christina; Nørgaard, Mogens; Vestermark, Vibeke

    2003-01-01

    Medical abortion was performed in 461 consecutive women with gestational age LT /= 63 days using a regimen of mifepristone 600 mg followed 2 days later by gemeprost 1 mg vaginally. Success, defined as no surgical intervention, declined from 98.7% after 2 weeks to 94.6% after 15 weeks....... The difference in short- and long-term success rates increased with increasing gestational age. The majority of failures (76%) were diagnosed more than 2 weeks after initiation of the abortion. At a 2-week follow-up visit, the women who turned out to be failures had a larger endometrial width, higher beta......-hCG values and smaller reductions of beta-hCG than those treated successfully. To optimize comparison of success rates after different medical abortion regimens, we suggest that the criteria for success are stated clearly, that the success rates are stratified according to gestational age...

  15. Multiple Phenotypic Changes Define Neutrophil Priming

    Directory of Open Access Journals (Sweden)

    Irina Miralda

    2017-05-01

    Full Text Available Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses.

  16. Multiple Phenotypic Changes Define Neutrophil Priming.

    Science.gov (United States)

    Miralda, Irina; Uriarte, Silvia M; McLeish, Kenneth R

    2017-01-01

    Exposure to pro-inflammatory cytokines, chemokines, mitochondrial contents, and bacterial and viral products induces neutrophils to transition from a basal state into a primed one, which is currently defined as an enhanced response to activating stimuli. Although, typically associated with enhanced generation of reactive oxygen species (ROS) by the NADPH oxidase, primed neutrophils show enhanced responsiveness of exocytosis, NET formation, and chemotaxis. Phenotypic changes associated with priming also include activation of a subset of functions, including adhesion, transcription, metabolism, and rate of apoptosis. This review summarizes the breadth of phenotypic changes associated with priming and reviews current knowledge of the molecular mechanisms behind those changes. We conclude that the current definition of priming is too restrictive. Priming represents a combination of enhanced responsiveness and activated functions that regulate both adaptive and innate immune responses.

  17. Defining Service and Education in Pediatrics.

    Science.gov (United States)

    Boyer, Debra; Gagne, Josh; Kesselheim, Jennifer C

    2017-11-01

    Program directors (PDs) and trainees are often queried regarding the balance of service and education during pediatric residency training. We aimed to use qualitative methods to learn how pediatric residents and PDs define service and education and to identify activities that exemplify these concepts. Focus groups of pediatric residents and PDs were performed and the data qualitatively analyzed. Thematic analysis revealed 4 themes from focus group data: (1) misalignment of the perceived definition of service; (2) agreement about the definition of education; (3) overlapping perceptions of the value of service to training; and (4) additional suggestions for improved integration of education and service. Pediatric residents hold positive definitions of service and believe that service adds value to their education. Importantly, the discovery of heterogeneous definitions of service between pediatric residents and PDs warrants further investigation and may have ramifications for Accreditation Council for Graduate Medical Education and those responsible for residency curricula.

  18. Chief executives define their own data needs.

    Science.gov (United States)

    Rockart, J F

    1979-01-01

    Identification of information needs of top management is discussed in this article by comparing four methods now in use with a new approach, "identification of critical success factors," developed at the Sloan School of Management. The author argues that the CSF method, implemented through a series of two to three interview sessions, helps top management define its own current information needs. Critical success factors are those performance factors which must receive the on-going attention of management if the company is to remain competitive. While not intended for strategic planning purposes, the identification of critical success factors can help top management by: (1) determining where management attention should be directed; (2) developing measures for critical success factors; and (3) determining the amount of information required and thus limiting gathering unnecessary data. The author concludes that the CSF method is both effective and efficient and should be seriously considered by top management as an important tool in assessing data needs.

  19. Engineering defined motor ensembles with DNA origami.

    Science.gov (United States)

    Goodman, Brian S; Reck-Peterson, Samara L

    2014-01-01

    Many cytoskeletal motors function in groups to coordinate the spatial and temporal positioning of cellular cargo. While methods to study the biophysical properties of single motors are well established, methods to understand how multiple motors work synergistically or antagonistically are less well developed. Here, we describe a three-dimensional synthetic cargo structure made using DNA origami, which can be used to template defined numbers and types of cytoskeletal motors with programmable geometries and spacing. We describe methods for building the DNA origami structure, covalently attaching motors to DNA, forming the motor-DNA origami structure complex, and single-molecule assays to examine the motile properties of motor ensembles. © 2014 Elsevier Inc. All rights reserved.

  20. Lithium control during normal operation

    International Nuclear Information System (INIS)

    Suryanarayan, S.; Jain, D.

    2010-01-01

    Periodic increases in lithium (Li) concentrations in the primary heat transport (PHT) system during normal operation are a generic problem at CANDU® stations. Lithiated mixed bed ion exchange resins are used at stations for pH control in the PHT system. Typically tight chemistry controls including Li concentrations are maintained in the PHT water. The reason for the Li increases during normal operation at CANDU stations such as Pickering was not fully understood. In order to address this issue a two pronged approach was employed. Firstly, PNGS-A data and information from other available sources was reviewed in an effort to identify possible factors that may contribute to the observed Li variations. Secondly, experimental studies were carried out to assess the importance of these factors in order to establish reasons for Li increases during normal operation. Based on the results of these studies, plausible mechanisms/reasons for Li increases have been identified and recommendations made for proactive control of Li concentrations in the PHT system. (author)

  1. Defining Future Directions for Endometriosis Research

    Science.gov (United States)

    D’Hooghe, Thomas M.; Fazleabas, Asgerally; Giudice, Linda C.; Montgomery, Grant W.; Petraglia, Felice; Taylor, Robert N.

    2013-01-01

    Endometriosis, defined as estrogen-dependent lesions containing endometrial glands and stroma outside the uterus, is a chronic and often painful gynecological condition that affects 6% to 10% of reproductive age women. Endometriosis has estimated annual costs of US $12 419 per woman (approximately €9579), comprising one-third of the direct health care costs with two-thirds attributed to loss of productivity. Decreased quality of life is the most important predictor of direct health care and total costs. It has been estimated that there is a mean delay of 6.7 years between onset of symptoms and a surgical diagnosis of endometriosis, and each affected woman loses on average 10.8 hours of work weekly, mainly owing to reduced effectiveness while working. To encourage and facilitate research into this debilitating disease, a consensus workshop to define future directions for endometriosis research was held as part of the 11th World Congress on Endometriosis in September 2011 in Montpellier, France. The objective of this workshop was to review and update the endometriosis research priorities consensus statement developed following the 10th World Congress on Endometriosis in 2008.1 A total of 56 recommendations for research have been developed, grouped under 6 subheadings: (1) diagnosis, (2) classification and prognosis, (3) clinical trials, treatment, and outcomes, (4) epidemiology, (5) pathophysiology, and (6) research policy. By producing this consensus international research priorities statement, it is the hope of the workshop participants that researchers will be encouraged to develop new interdisciplinary research proposals that will attract increased funding support for work on endometriosis. PMID:23427182

  2. Defining nodes in complex brain networks

    Directory of Open Access Journals (Sweden)

    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

  3. Software Defined Radios - Architectures, Systems and Functions

    Science.gov (United States)

    Sims, Herb

    2017-01-01

    Software Defined Radio is an industry term describing a method of utilizing a minimum amount of Radio Frequency (RF)/analog electronics before digitization takes place. Upon digitization all other functions are performed in software/firmware. There are as many different types of SDRs as there are data systems. Software Defined Radio (SDR) technology has been proven in the commercial sector since the early 90's. Today's rapid advancement in mobile telephone reliability and power management capabilities exemplifies the effectiveness of the SDR technology for the modern communications market. In contrast the foundations of transponder technology presently qualified for satellite applications were developed during the early space program of the 1960's. SDR technology offers potential to revolutionize satellite transponder technology by increasing science data through-put capability by at least an order of magnitude. While the SDR is adaptive in nature and is "One-size-fits-all" by design, conventional transponders are built to a specific platform and must be redesigned for every new bus. The SDR uses a minimum amount of analog/Radio Frequency components to up/down-convert the RF signal to/from a digital format. Once analog data is digitized, all processing is performed using hardware logic. Typical SDR processes include; filtering, modulation, up/down converting and demodulation. This presentation will show how the emerging SDR market has leveraged the existing commercial sector to provide a path to a radiation tolerant SDR transponder. These innovations will reduce the cost of transceivers, a decrease in power requirements and a commensurate reduction in volume. A second pay-off is the increased flexibility of the SDR by allowing the same hardware to implement multiple transponder types by altering hardware logic - no change of analog hardware is required - all of which can be ultimately accomplished in orbit. This in turn would provide high capability and low cost

  4. 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)

  5. Vaginal Discharge: What's Normal, What's Not

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Vaginal Discharge: What's Normal, What's Not KidsHealth / For Teens / Vaginal Discharge: What's Normal, What's Not Print Normal vaginal discharge ...

  6. Understanding a Normal Distribution of Data.

    Science.gov (United States)

    Maltenfort, Mitchell G

    2015-12-01

    Assuming data follow a normal distribution is essential for many common statistical tests. However, what are normal data and when can we assume that a data set follows this distribution? What can be done to analyze non-normal data?

  7. Quantiles for Finite Mixtures of Normal Distributions

    Science.gov (United States)

    Rahman, Mezbahur; Rahman, Rumanur; Pearson, Larry M.

    2006-01-01

    Quantiles for finite mixtures of normal distributions are computed. The difference between a linear combination of independent normal random variables and a linear combination of independent normal densities is emphasized. (Contains 3 tables and 1 figure.)

  8. Consumption of 125I labelled fibrinogen in normal subjects

    International Nuclear Information System (INIS)

    Langer, B.; Camargo, E.E.; Reis, J.M.M. dos; Carvalho, N.; Leao, L.E.P.

    1978-01-01

    The metabolism of iodine- 125 labeled human fibrinogen is studied by using three different sets of the radiopharmaceutical (0.9, 1.3 and 1.84 iodine atoms/fibrinogen molecule ratios) in 19 normal subjects. An aliquot of 40 μCi of fibrinogem- 125 I is injected in each subject, on normal dietary conditions and blood samples are withdrawn at 30, 60, 180, 36 and 720 minutes after the injection and, thereafter, one daily sample during 10 days. The compartmental distribution of the tracer is defined by plotting plasma and serum sample counts on a semilogarithmic graph paper. A rapid phase and 3 compartments are obtained. A 'rapid' consumption half-life and a 'real' consumption half-life are defined. The fibrinogen clottability is followed up to the last blood sample by checking the ratios of serum and plasma radioactivities [pt

  9. L-Arginine supplementation prevents allodynia and hyperalgesia in painful diabetic neuropathic rats by normalizing plasma nitric oxide concentration and increasing plasma agmatine concentration.

    Science.gov (United States)

    Rondón, Lusliany J; Farges, M C; Davin, N; Sion, B; Privat, A M; Vasson, M P; Eschalier, A; Courteix, C

    2017-07-19

    Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes. We examined whether oral L-arginine supplementation (2.58 ± 0.13 g/l in drinking water for 3 weeks) could improve the development of neuropathic pain and the clinical, biological, and metabolic complications of diabetes in streptozocin (STZ)-induced diabetic (D) rats. STZ administration induced classical symptoms of type 1 diabetes. Diabetic rats also displayed mechanical hypersensitivity, tactile, and thermal allodynia. Plasma citrulline and NO levels were increased in diabetic hyperalgesic/allodynic rats. L-Arginine supplementation failed to reduce hyperglycaemia, polyphagia, and weight loss. Moreover, it abolished hyperalgesia and allodynia by normalizing NO plasma concentration and increasing plasma agmatine concentration. L-Arginine supplementation prevented the development of mechanical hyperalgesia, tactile, and thermal allodynia in painful diabetic neuropathy with concomitant reduction of NO and increased agmatine production, offering new therapeutic opportunities for the management of diabetic neuropathic pain.

  10. Tibial bowing in children - what is normal? A radiographic study

    International Nuclear Information System (INIS)

    Zbinden, Isabella; Rutz, Erich; Jacobson, Jon A.; Magerkurth, Olaf

    2015-01-01

    To define osseous landmarks on tibia radiographs in order to establish age-related normal values characterizing physiological tibial bowing in children. Five hundred and twenty-six patients aged 0-17 years with normal radiographs of the lower legs were identified and retrospectively reviewed by two blinded radiologists. In anteroposterior (ap)/lateral (lat)-views, 3 lines defined tibial length and angulation. Line-A connecting proximal to distal corner of tibial metaphysic, lines B and C corresponding to corners of tibial metaphysis. Angle A/B defines proximal, A/C distal tibial-angulation. Tibial curvature is defined by distance of line-D parallel to A and tangential to tibial cortex. Normal values were calculated with linear-regression. Intra-/Interreader agreement were tested with a Bland-Altman-plot. Intrareader-agreement: Reader 1 showed a bias of -0.1, standard-deviation of bias was 1.9 and 95 %-limits-of-agreement -3.9- 3.7. Reader 2: -0.01, 2.4 and -4.7- 4.7. Interreader: 0.2, 1.6 and -2.9- 3.3. Angle-A/B ap was 80-100 , increasing with age (86.5-88); angle-AC ap was 82-107 (96.8-90.5), angle-AB lat was 81-107 (93.0-98.0); angle-AC lat was 76-102 (89.5-86.5); depth of curve ap was 0-11 % (8-3.5) and lat 2-13 %, (8.5-3.5). Age dependent tibial bowing can be assessed with this new measurement system and age-related normal-values characterizing physiological tibial bowing in children is established. (orig.)

  11. Normal family of meromorphic functions concerning fixed-points

    Science.gov (United States)

    Fang, Caiyun; Xu, Yan

    2017-09-01

    Let A>1 be a constant and F be a family of meromorphic functions defined in a domain D. For each f\\in F , f has only zeros of multiplicity at least 3 and satisfies the following conditions: (1) |f^' ' ' }(z)|≤ A|z| when f(z)=0 ; (2) f^' ' ' }(z)≠ z ; (3) all poles of f are multiple. In this paper, we characterize the non-normal sequences of F.

  12. Defining the acute care surgery curriculum.

    Science.gov (United States)

    Duane, Therese M; Dente, Christopher J; Fildes, John J; Davis, Kimberly A; Jurkovich, Gregory J; Meredith, J Wayne; Britt, L D

    2015-02-01

    This study was designed to define the gaps in essential and desirable (E/D) case volumes that may prompt reevaluation of the acute care surgery (ACS) curriculum or restructuring of the training provided. A review of the first 2 years of ACS case log entry (July 2011 to June 2013) was performed. Individual trainee logs were evaluated to determine how often they performed each case on the E/D list. Trainees described cases using current procedural terminology codes, which had been previously mapped to the E/D list. There were 29 trainees from 15 programs (Year 1) and 30 trainees from 13 programs (Year 2) who participated in case log entry, with some overlap between the years. There were a total of 487 fellow-months of data with an average of 14.6 current procedural terminology codes per month and 175.5 per year for cases on the E/D list versus 12 and 143.5 for cases not on the E/D list, respectively. Overall, the most common essential cases were laparotomy for trauma (1,463; 705 in Year 1, 758 in Year 2), tracheostomy (665; 372 in Year 1, 293 in Year 2) and gastrostomy tubes (566; 289 in Year 1, 277 in Year 2). There are a total of 73 types of essential operations and 45 types of desirable operations in the current curriculum. There were 16 distinct codes (13.6%) never used, of which 6 overlapped with other codes. Based on body region, the 10 E/D codes never used by any fellow were as follows: one head/face, lateral canthotomy; five neck; elective neck dissections; one thoracic, vascular trauma to chest; three pediatrics, inguinal hernia repair and small bowel obstruction treatments. The current ACS trainees lack adequate head/neck and pediatric experience as defined by the ACS curriculum. Restructuring rotations at individual institutions and a focus on novel educational modalities may be needed to augment the individual institutional exposure. Reevaluation of the curriculum may be warranted.

  13. Normal Limits of Electrocardiogram and Cut-Off Values for Left ...

    African Journals Online (AJOL)

    Gender difference exists in some cut-off values for LVH. This study defined the normal limits for electrocardiographic variables for young adult Nigerians. Racial factor should be taken into consideration in interpretation of ECG. Keywords: Normal limits, Electrocardiogram, Cut-off values, Left ventricular hypertrophy, Young ...

  14. Normal Anti-Invariant Submanifolds of Paraquaternionic Kähler Manifolds

    Directory of Open Access Journals (Sweden)

    Novac-Claudiu Chiriac

    2006-12-01

    Full Text Available We introduce normal anti-invariant submanifolds of paraquaternionic Kähler manifolds and study the geometric structures induced on them. We obtain necessary and sufficient conditions for the integrability of the distributions defined on a normal anti-invariant submanifold. Also, we present characterizations of local (global anti-invariant products.

  15. Spectrum of AIDS defining & non-AIDS defining malignancies in north India

    Directory of Open Access Journals (Sweden)

    Ravinder Kaur Sachdeva

    2016-01-01

    Full Text Available Background & objectives: There is scarcity of data on the frequency of malignancies in HIV infected individuals from India. The objective of this study was to determine the type and frequency of malignancies in HIV infected individuals attending a tertiary care hospital in north India. Methods: The study design included retrospective analysis of data of all HIV infected individuals registered in the Immunodeficiency clinic from December 2009 to December 2011 and a prospective analysis of HIV infected individuals registered from January 2012 to April 2013. The clinical details and treatment outcomes of all individuals diagnosed to have AIDS defining and non-AIDS defining malignancies were recorded. Results: Records of 2880 HIV infected individuals were reviewed. Thirty one (19 males, 12 females individuals were diagnosed to have malignancy. AIDS defining malignancy was found in the form of non-Hodgkin′s lymphoma in 12 individuals and cervical cancer in six women. Non-AIDS defining malignancies included Hodgkin′s lymphoma (n=2; and chronic myelogenous leukaemia, carcinoma base of tongue, carcinoma larynx, carcinoma bronchus, sinonasal carcinoma, ovarian carcinoma, anal carcinoma, carcinoma urinary bladder, pleomorphic sarcoma, parathyroid adenoma, and renal cell carcinoma in one individual each. Mean CD4+cell count prior to ART initiation was 250 ± 195.6 (median: 187; range, 22-805 cells/μl and at the time of diagnosis of malignancy was 272 ± 202 (median: 202; range, 15-959 cells/μl. The mean CD4+ count of individuals with AIDS defining malignancy was significantly lower when compared with non-AIDS defining malignancy (P<0.001. Fourteen individuals were alive and on regular follow up, 15 had died and two cases were lost to follow up. Interpretation & conclusions: The frequency of malignancies in HIV infected patients at our centre was 1 per cent, with non-Hodgkin′s lymphoma being the commonest. Further studies need to be done to document

  16. Normalization in human somatosensory cortex.

    Science.gov (United States)

    Brouwer, Gijs Joost; Arnedo, Vanessa; Offen, Shani; Heeger, David J; Grant, Arthur C

    2015-11-01

    Functional magnetic resonance imaging (fMRI) was used to measure activity in human somatosensory cortex and to test for cross-digit suppression. Subjects received stimulation (vibration of varying amplitudes) to the right thumb (target) with or without concurrent stimulation of the right middle finger (mask). Subjects were less sensitive to target stimulation (psychophysical detection thresholds were higher) when target and mask digits were stimulated concurrently compared with when the target was stimulated in isolation. fMRI voxels in a region of the left postcentral gyrus each responded when either digit was stimulated. A regression model (called a forward model) was used to separate the fMRI measurements from these voxels into two hypothetical channels, each of which responded selectively to only one of the two digits. For the channel tuned to the target digit, responses in the left postcentral gyrus increased with target stimulus amplitude but were suppressed by concurrent stimulation to the mask digit, evident as a shift in the gain of the response functions. For the channel tuned to the mask digit, a constant baseline response was evoked for all target amplitudes when the mask was absent and responses decreased with increasing target amplitude when the mask was concurrently presented. A computational model based on divisive normalization provided a good fit to the measurements for both mask-absent and target + mask stimulation. We conclude that the normalization model can explain cross-digit suppression in human somatosensory cortex, supporting the hypothesis that normalization is a canonical neural computation. Copyright © 2015 the American Physiological Society.

  17. Mathematical ratio in defining arch form

    Directory of Open Access Journals (Sweden)

    Johan A Budiman

    2017-01-01

    Full Text Available Introduction: The treatment of Class I malocclusion aims to arrange teeth position in a good arch form. The arch form consists of tooth size and arch dimension (intercanine width, canine depth, intermolar width, molar depth. Numerous methods have been used to describe the arch form quantitatively. The aim of this study was to develop a mathematical ratio for identifying arch form (square, oval, tapered using arch dimension variables (intercanine width, canine depth, intermolar width, molar depth. Materials and Methods: Dental cast pre and post-orthodontic treatments from 190 Indonesian patients were scanned to obtain digital data. All data were measured using “Image Tool.” The measured data (tooth size, intercanine width, intercanine depth, intermolar width, intermolar depth, and arch perimeter were analyzed statistically using ordered logistic to find out determining variables to the arch form. Results: The validity, reliability, and normality of all the data were analyzed using Stata. From analyzing the data using ordered logistic, intercanine width and intermolar depth showed a reverse relation to the arch form. The shape of the arch form (square, oval, and tapered can be described quantitatively by using ratio (CD/CW/(MD/MW; a ratio less than 45.30% indicates square, 45.30–53.37% indicates oval, and more than 53.37% indicates tapered. Conclusions: (CD/CW/(MD/MW ratio can be used to describe arch form quantitatively.

  18. Sonographic findings of normal newborn spinal cord

    International Nuclear Information System (INIS)

    Park, Chan Sup; Kim, Dong Gyu

    1988-01-01

    The authors performed spinal cord ultrasonography of 21 healthy newborn infants in Gyeongsang National University Hospital. Normal spinal cord revealed low echogenecity at that of cerebrospinal fluid and was demarcated by intense reflections from its dorsal and ventral surfaces. The central canal was routinely seen as a thin linear reflection in the center of the cord. The nerve roots making up the cauda equina formed a poorly defined collection of intense linear echoes extending from the conus. On real time image, the normal spinal cord exhibited rather slow and rhythmical anteroposterior movement within the subarachnoid fluid. A distinct and rapid vascular pulsation of the spinal cord was usually recognizable. The approximate level of vertebral bodies was determined as follows; most ventrally located vertebral body was thought to be L5 and S1 was seen slightly posterior to the L5 directed inferoposteriorly. According to the above criteria terminal portions of spinal cord were seen around the L2 body in 5 MHz and pointed termination of conus medullaris was clearly seen at L2-3 junction and in upper body of L3 by 7.5 MHz. So it would be better to examine by 5 MHz for spatial orientation and then by 7.5 MHz for more accurate examination. High-resolution, real-time ultrasonography was a safe, rapid screening technique for evaluation of the spinal cord in infants. Additional applications of spinal sonography may be possible in the evaluation of neonatal syringohydromyelia and meningocele as well as intraspinal cyst localization for possible percutaneous puncture by ultrasound guidance

  19. Diffuse brain damage in normal tension glaucoma.

    Science.gov (United States)

    Giorgio, Antonio; Zhang, Jian; Costantino, Francesco; De Stefano, Nicola; Frezzotti, Paolo

    2018-01-01

    Brain changes within and beyond the visual system have been demonstrated in primary open angle glaucoma (POAG), the most common type of glaucoma. These changes have been often interpreted as a neurodegenerative process due, at least partially, to the raised intraocular pressure (IOP). In this context, normal tension glaucoma (NTG), a form of POAG with IOP acquired multimodal brain MRI in NTG patients (n = 17) and compared them with demographically matched groups of POAG patients with raised IOP (n = 17) and normal controls (NC, n = 29). Voxelwise statistics was performed with nonparametric permutation testing. Both NTG and POAG patients showed, compared to NC, significantly more gray matter atrophy in both the visual system and in nonvisual brain regions and altered diffusion tensor imaging-derived anatomical connectivity (AC; lower fractional anisotropy and/or higher diffusivities). Compared with NTG, POAG had both more atrophic visual cortex and higher axial diffusivity in nonvisual regions. Functional connectivity (FC) with respect to NC was altered in NTG at short-range level [visual network (VN), ventral attention network] and in POAG at long-range level (between secondary VN and limbic network). FC of POAG was higher than NTG in both VN and executive network. This study provides further evidence that diffuse structural and functional abnormalities across glaucoma brain may be, at least partially, independent of raised IOP and the consequent retinal degeneration. This further defines glaucoma as a condition with neurodegeneration spreading. Hum Brain Mapp 39:532-541, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  20. Normal pediatric postmortem CT appearances

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Willemijn M.; Bosboom, Dennis G.H.; Koopmanschap, Desiree H.J.L.M. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, Nijmegen (Netherlands); Nievelstein, Rutger A.J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Nikkels, Peter G.J. [University Medical Center Utrecht, Department of Pathology, Utrecht (Netherlands); Rijn, Rick R. van [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands)

    2015-04-01

    Postmortem radiology is a rapidly developing specialty that is increasingly used as an adjunct to or substitute for conventional autopsy. The goal is to find patterns of disease and possibly the cause of death. Postmortem CT images bring to light processes of decomposition most radiologists are unfamiliar with. These postmortem changes, such as the formation of gas and edema, should not be mistaken for pathological processes that occur in living persons. In this review we discuss the normal postmortem thoraco-abdominal changes and how these appear on CT images, as well as how to differentiate these findings from those of pathological processes. (orig.)

  1. Normal modes and continuous spectra

    International Nuclear Information System (INIS)

    Balmforth, N.J.; Morrison, P.J.

    1994-12-01

    The authors consider stability problems arising in fluids, plasmas and stellar systems that contain singularities resulting from wave-mean flow or wave-particle resonances. Such resonances lead to singularities in the differential equations determining the normal modes at the so-called critical points or layers. The locations of the singularities are determined by the eigenvalue of the problem, and as a result, the spectrum of eigenvalues forms a continuum. They outline a method to construct the singular eigenfunctions comprising the continuum for a variety of problems

  2. Normal indices in Nikishin systems

    OpenAIRE

    Branquinho, A.; Bustamante, J.; Foulquié Moreno, A.; López Lagomasino, G.

    2003-01-01

    9 pages, no figures.-- MSC1991 code: Primary 42C05. MR#: MR2016675 (2004k:41025) Zbl#: Zbl 1035.41010 We improve the class of indices for which normality takes place in a Nikishin system and apply this in Hermite–Padé approximation of such systems of functions. A.B. thanks support from Grants PRAXIS XXI BCC-22201/99 and INTAS 00-272, J.B. from grant CONACYT 32181-E, A.F.M. from Grants PRAXIS XXI BPD-20396/99 and INTAS 00-272, G.L.L. from Grants PRAXIS XXI BCC-22201/99, BFM 2000-02...

  3. Defining a standard metric for electricity savings

    International Nuclear Information System (INIS)

    Koomey, Jonathan; Akbari, Hashem; Blumstein, Carl; Brown, Marilyn; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B; Greenberg, Steve

    2010-01-01

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70% capacity factor with 7% T and D losses. Displacing such a plant for one year would save 3 billion kWh/year at the meter and reduce emissions by 3 million metric tons of CO 2 per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question-Dr Arthur H Rosenfeld.

  4. Defining a standard metric for electricity savings

    Energy Technology Data Exchange (ETDEWEB)

    Koomey, Jonathan [Lawrence Berkeley National Laboratory and Stanford University, PO Box 20313, Oakland, CA 94620-0313 (United States); Akbari, Hashem; Blumstein, Carl; Brown, Marilyn; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B; Greenberg, Steve, E-mail: JGKoomey@stanford.ed

    2010-01-15

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70% capacity factor with 7% T and D losses. Displacing such a plant for one year would save 3 billion kWh/year at the meter and reduce emissions by 3 million metric tons of CO{sub 2} per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question-Dr Arthur H Rosenfeld.

  5. Radio Astronomy Software Defined Receiver Project

    Energy Technology Data Exchange (ETDEWEB)

    Vacaliuc, Bogdan [ORNL; Leech, Marcus [Shirleys Bay Radio Astronomy Consortium; Oxley, Paul [Retired; Flagg, Richard [Retired; Fields, David [ORNL

    2011-01-01

    The paper describes a Radio Astronomy Software Defined Receiver (RASDR) that is currently under development. RASDR is targeted for use by amateurs and small institutions where cost is a primary consideration. The receiver will operate from HF thru 2.8 GHz. Front-end components such as preamps, block down-converters and pre-select bandpass filters are outside the scope of this development and will be provided by the user. The receiver includes RF amplifiers and attenuators, synthesized LOs, quadrature down converters, dual 8 bit ADCs and a Signal Processor that provides firmware processing of the digital bit stream. RASDR will interface to a user s PC via a USB or higher speed Ethernet LAN connection. The PC will run software that provides processing of the bit stream, a graphical user interface, as well as data analysis and storage. Software should support MAC OS, Windows and Linux platforms and will focus on such radio astronomy applications as total power measurements, pulsar detection, and spectral line studies.

  6. Defining ecosystem assets for natural capital accounting

    Science.gov (United States)

    Hein, Lars; Bagstad, Kenneth J.; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems’ capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks.

  7. Defining Ecosystem Assets for Natural Capital Accounting.

    Science.gov (United States)

    Hein, Lars; Bagstad, Ken; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems' capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks.

  8. Defining the landscape of adaptive genetic diversity.

    Science.gov (United States)

    Eckert, Andrew J; Dyer, Rodney J

    2012-06-01

    Whether they are used to describe fitness, genome architecture or the spatial distribution of environmental variables, the concept of a landscape has figured prominently in our collective reasoning. The tradition of landscapes in evolutionary biology is one of fitness mapped onto axes defined by phenotypes or molecular sequence states. The characteristics of these landscapes depend on natural selection, which is structured across both genomic and environmental landscapes, and thus, the bridge among differing uses of the landscape concept (i.e. metaphorically or literally) is that of an adaptive phenotype and its distribution across geographical landscapes in relation to selective pressures. One of the ultimate goals of evolutionary biology should thus be to construct fitness landscapes in geographical space. Natural plant populations are ideal systems with which to explore the feasibility of attaining this goal, because much is known about the quantitative genetic architecture of complex traits for many different plant species. What is less known are the molecular components of this architecture. In this issue of Molecular Ecology, Parchman et al. (2012) pioneer one of the first truly genome-wide association studies in a tree that moves us closer to this form of mechanistic understanding for an adaptive phenotype in natural populations of lodgepole pine (Pinus contorta Dougl. ex Loud.). © 2012 Blackwell Publishing Ltd.

  9. Defining functional dyspepsia Definiendo la dispepsia funcional

    Directory of Open Access Journals (Sweden)

    Fermín Mearin

    2011-12-01

    Full Text Available Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications. During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc. The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a food-induced dyspeptic symptoms (postprandial distress syndrome; and b epigastric pain (epigastric pain syndrome. These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a epigastric discomfort (as a category of severity or pain; b postprandial heaviness; and c early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn. All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the

  10. Defining microbiota for developing new probiotics

    Directory of Open Access Journals (Sweden)

    Maria Carmen Collado

    2012-06-01

    Full Text Available The human body harbors complex communities of microbes that play a prominent role in human health. Detailed characterization of the microbiota in the target population forms the basis of probiotic use. Probiotics are defined as live bacterial preparations with clinically documented health effects in humans, and independent of their genus and species, probiotic strains are unique and their beneficial properties on human health have to be assessed in a case-by-case manner. Understanding the mechanisms by which probiotics influence microbiota would facilitate the use of probiotics for both dietary management and reduction in risk of specific diseases. The development of high throughput sequencing methods has allowed metagenomic approaches to study the human microbiome. These efforts are starting to generate an inventory of bacterial taxons and functional features bound to particular health or disease status that allow inferring aspects of the microbiome's function. In the future, this information will allow the rational design of dietary interventions aimed to improve consumer's health via modulation of the microbiota.

  11. Defining translational research: implications for training.

    Science.gov (United States)

    Rubio, Doris McGartland; Schoenbaum, Ellie E; Lee, Linda S; Schteingart, David E; Marantz, Paul R; Anderson, Karl E; Platt, Lauren Dewey; Baez, Adriana; Esposito, Karin

    2010-03-01

    Because translational research is not clearly defined, developers of translational research programs are struggling to articulate specific program objectives, delineate the knowledge and skills (competencies) that trainees are expected to develop, create an appropriate curriculum, and track outcomes to assess whether program objectives and competency requirements are being met. Members of the Evaluation Committee of the Association for Clinical Research Training (ACRT) reviewed current definitions of translational research and proposed an operational definition to use in the educational framework. In this article, the authors posit that translational research fosters the multidirectional and multidisciplinary integration of basic research, patient-oriented research, and population-based research, with the long-term aim of improving the health of the public. The authors argue that the approach to designing and evaluating the success of translational training programs must therefore be flexible enough to accommodate the needs of individual institutions and individual trainees within the institutions but that it must also be rigorous enough to document that the program is meeting its short-, intermediate-, and long-term objectives and that its trainees are meeting preestablished competency requirements. A logic model is proposed for the evaluation of translational research programs.

  12. Defining Ecosystem Assets for Natural Capital Accounting

    Science.gov (United States)

    Hein, Lars; Bagstad, Ken; Edens, Bram; Obst, Carl; de Jong, Rixt; Lesschen, Jan Peter

    2016-01-01

    In natural capital accounting, ecosystems are assets that provide ecosystem services to people. Assets can be measured using both physical and monetary units. In the international System of Environmental-Economic Accounting, ecosystem assets are generally valued on the basis of the net present value of the expected flow of ecosystem services. In this paper we argue that several additional conceptualisations of ecosystem assets are needed to understand ecosystems as assets, in support of ecosystem assessments, ecosystem accounting and ecosystem management. In particular, we define ecosystems’ capacity and capability to supply ecosystem services, as well as the potential supply of ecosystem services. Capacity relates to sustainable use levels of multiple ecosystem services, capability involves prioritising the use of one ecosystem service over a basket of services, and potential supply considers the ability of ecosystems to generate services regardless of demand for these services. We ground our definitions in the ecosystem services and accounting literature, and illustrate and compare the concepts of flow, capacity, capability, and potential supply with a range of conceptual and real-world examples drawn from case studies in Europe and North America. Our paper contributes to the development of measurement frameworks for natural capital to support environmental accounting and other assessment frameworks. PMID:27828969

  13. Methodologies for defining quality of life

    Energy Technology Data Exchange (ETDEWEB)

    Glicken, J. [Ecological Planning and Toxicology, Inc., Albuquerque, NM (United States); Engi, D. [Sandia National Labs., Albuquerque, NM (United States)

    1996-10-10

    Quality of life as a concept has been used in many ways in the public policy arena. It can be used in summative evaluations to assess the impacts of policies or programs. Alternatively, it can be applied to formative evaluations to provide input to the formation of new policies. In short, it provides the context for the understanding needed to evaluate the results of choices that have been made in the public policy arena, or the potential of choices yet to be made. In either case, the public policy question revolves around the positive or negative impact the choice will have on quality of life, and the magnitude of that impact. This discussion will develop a conceptual framework that proposes that an assessment of quality of life is based on a comparison of expectations with experience. The framework defines four basic components from which these expectations arise: natural conditions, social conditions, the body, and the mind. Each one of these components is generally described, and associated with a general policy or rhetorical category which gives it its policy vocabulary--environmental quality, economic well-being, human health, and self-fulfillment.

  14. CREATIVITY AND INNOVATION AS DEFINED BY WORKER

    Directory of Open Access Journals (Sweden)

    Sônia Maria Guedes Gondim

    2015-12-01

    Full Text Available ABSTRACT Creativity and innovation are now required given the new configurations in work processes, in organizational formats, in physical and intangible technologies, as well as in products and markets. In parallel with the growing centrality and interest in the phenomena of creativity and innovation, a broadening of its concepts is observed. The inflation and trivialization of uses tend to make them self-explanatory and not very enlightening regarding situations to which they apply and the associated effects. The lack of conceptual clarity thus contributes both to undermining policies to promote creativity and innovation in organizations, as well as to hinder the employees' adherence to such policies. The study aimed to characterize the key elements of workers' informal definitions of creativity and innovation, and identify their alignment with definitions and theoretical perspectives. The study included 231 workers from Portuguese-, Spanish-, and Basque-speaking countries, aged 22-75 years. The qualitative data analysis software ATLAS.ti 7 was used for coding and categorization. One point of convergence with the specialized literature was that creativity and innovation strongly associated with novelty in the development of an idea / product / process / service. Creativity, however, is defined more in terms of dispositional factors rather than contextual and situational factors, diverging from current theoretical perspectives. Planning as a key aspect for organizational innovation development is practically absent from the workers' definitions. It discusses some impacts of these settings for organizational management practices.

  15. Defining Astrology in Ancient and Classical History

    Science.gov (United States)

    Campion, Nicholas

    2015-05-01

    Astrology in the ancient and classical worlds can be partly defined by its role, and partly by the way in which scholars spoke about it. The problem is complicated by the fact that the word is Greek - it has no Babylonian or Egyptian cognates - and even in Greece it was interchangeable with its cousin, 'astronomy'. Yet if we are to understand the role of the sky, stars and planets in culture, debates about the nature of ancient astrology, by both classical and modern scholars, must be taken into account. This talk will consider modern scholars' typologies of ancient astrology, together with ancient debates from Cicero in the 1st century BC, to Plotinus (204/5-270 AD) and Isidore of Seville (c. 560 - 4 April 636). It will consider the implications for our understanding of astronomy's role in culture, and conclude that in the classical period astrology may be best understood through its diversity and allegiance to competing philosophies, and that its functions were therefore similarly varied.

  16. Homeostasis in defined genotypes of Matthiola incana.

    Science.gov (United States)

    Seyffert, W

    1983-02-01

    Based on 256 defined genotypes of the Brassicaceae Matthiola incana the influence of the alleles at four different loci and of their combinations on homeostasis was investigated against an isogenic background. The measured character was the anthocyanin content of the flowers. There are significant maternal and paternal influences on homeostasis. Moreover the extent of heterozygosity as well as the number of wildtype alleles, summarized over all loci, are positively correlated with the increase of homeostasis. The analysis of individual gene effects shows distinct graduations between the contributions of the particular loci. In principle, the wild-type allele proved to be more homeostatic when compared to the mutant; in some cases monogenic heterosis was indicated. Nonallelic interactions of first and second order do considerably modify the degree of expression of homeostasis; they are neither strongly correlated with the individual gene effects nor with the interactions of lower order, and hence they are not predictable. This means also that it is not possible to formulate a general hypothesis as to the causes of homeostasis. We have to assume rather that homeostasis depends on specific gene combinations which enable the organism to stabilize its phenotype by means of certain physiological conditions.

  17. Defining a learning curve for laparoscopic cardiomyotomy.

    Science.gov (United States)

    Grotenhuis, Brechtje A; Wijnhoven, Bas P L; Jamieson, Glyn G; Devitt, Peter G; Bessell, Justin R; Watson, David I

    2008-08-01

    This study was designed to determine whether there is a learning curve for laparoscopic cardiomyotomy for the treatment of achalasia. All patients who underwent a primary laparoscopic cardiomyotomy for achalasia between 1992 and 2006 in our hospitals were identified from a prospective database. The institutional and the individual surgeon's learning experiences were assessed based on operative and clinical outcome parameters. The outcomes of cardiomyotomies performed by consultant surgeons versus supervised trainees also were compared. A total of 186 patients met the inclusion criteria; 144 procedures were undertaken by consultant surgeons and 42 by a surgical trainee. The length of operation decreased after the first ten cases in both the institutional and each individual experience. The rate of conversion to open surgery also was significantly higher in the first 20 cases performed. Intraoperative complications, overall satisfaction with the outcome, reoperation rate, and postoperative dysphagia were not associated with the institutional or the surgeon's operative experience. Although the length of the operation was greater for surgical trainees (93 versus 79 minutes; p learning curve for laparoscopic cardiomyotomy for achalasia can be defined. The clinical outcome for laparoscopic cardiomyotomy does not differ between supervised surgical trainees and consultant surgeons.

  18. Defining a Standard Metric for Electricity Savings

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Marilyn; Akbari, Hashem; Blumstein, Carl; Koomey, Jonathan; Brown, Richard; Calwell, Chris; Carter, Sheryl; Cavanagh, Ralph; Chang, Audrey; Claridge, David; Craig, Paul; Diamond, Rick; Eto, Joseph H.; Fulkerson, William; Gadgil, Ashok; Geller, Howard; Goldemberg, Jose; Goldman, Chuck; Goldstein, David B.; Greenberg, Steve; Hafemeister, David; Harris, Jeff; Harvey, Hal; Heitz, Eric; Hirst, Eric; Hummel, Holmes; Kammen, Dan; Kelly, Henry; Laitner, Skip; Levine, Mark; Lovins, Amory; Masters, Gil; McMahon, James E.; Meier, Alan; Messenger, Michael; Millhone, John; Mills, Evan; Nadel, Steve; Nordman, Bruce; Price, Lynn; Romm, Joe; Ross, Marc; Rufo, Michael; Sathaye, Jayant; Schipper, Lee; Schneider, Stephen H; Sweeney, James L; Verdict, Malcolm; Vorsatz, Diana; Wang, Devra; Weinberg, Carl; Wilk, Richard; Wilson, John; Worrell, Ernst

    2009-03-01

    The growing investment by governments and electric utilities in energy efficiency programs highlights the need for simple tools to help assess and explain the size of the potential resource. One technique that is commonly used in this effort is to characterize electricity savings in terms of avoided power plants, because it is easier for people to visualize a power plant than it is to understand an abstraction such as billions of kilowatt-hours. Unfortunately, there is no standardization around the characteristics of such power plants. In this letter we define parameters for a standard avoided power plant that have physical meaning and intuitive plausibility, for use in back-of-the-envelope calculations. For the prototypical plant this article settles on a 500 MW existing coal plant operating at a 70percent capacity factor with 7percent T&D losses. Displacing such a plant for one year would save 3 billion kW h per year at the meter and reduce emissions by 3 million metric tons of CO2 per year. The proposed name for this metric is the Rosenfeld, in keeping with the tradition among scientists of naming units in honor of the person most responsible for the discovery and widespread adoption of the underlying scientific principle in question--Dr. Arthur H. Rosenfeld.

  19. Software-defined Quantum Networking Ecosystem

    Energy Technology Data Exchange (ETDEWEB)

    2017-01-01

    The software enables a user to perform modeling and simulation of software-defined quantum networks. The software addresses the problem of how to synchronize transmission of quantum and classical signals through multi-node networks and to demonstrate quantum information protocols such as quantum teleportation. The software approaches this problem by generating a graphical model of the underlying network and attributing properties to each node and link in the graph. The graphical model is then simulated using a combination of discrete-event simulators to calculate the expected state of each node and link in the graph at a future time. A user interacts with the software by providing an initial network model and instantiating methods for the nodes to transmit information with each other. This includes writing application scripts in python that make use of the software library interfaces. A user then initiates the application scripts, which invokes the software simulation. The user then uses the built-in diagnostic tools to query the state of the simulation and to collect statistics on synchronization.

  20. 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...

  1. 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...

  2. Results of radionuclide ventriculography in normal children and adolescents

    International Nuclear Information System (INIS)

    Reich, O.; Krejcir, M.; Ruth, C.

    1989-01-01

    In order to assess the range of normal values in radionuclide ventriculography, 53 normal children and adolescents were selected in retrospect. All were exdamined by radionuclide angiocardiography on account of clinical and echocardiographical suspicion of congenital heart disease with a left-to-right shunt; a significant shunt was, however, excluded. In all patients, after equilibration of the radiopharmaceutical the ventricular function was examined by radionuclide ventriculography. The usual volume, time and rate characteristics were evaluated. The normal range was defined as the mean ±2 standard deviations which is 47 to 72% for the ejection fraction of the left ventricle and 31 to 56% for the ejection fraction of the right ventricle. (author). 2 tabs., 18 refs

  3. Normal Type-2 Fuzzy Geometric Curve Modeling: A Literature Review

    Science.gov (United States)

    Adesah, R. S.; Zakaria, R.

    2017-09-01

    Type-2 Fuzzy Set Theory (T2FST) is widely used for defining uncertainty data points rather than the traditional fuzzy set theory (type-1) since 2001. Recently, T2FST is used in many fields due to its ability to handle complex uncertainty data. In this paper, a review of normal type-2 fuzzy geometric curve modeling methods and techniques is presented. In particular, there have been recent applications of Normal Type-2 Fuzzy Set Theory (NT2FST) in geometric modeling, where it has helped improving results over type-1 fuzzy sets. In this paper, a concise and representative review of the processes in normal type-2 fuzzy geometrical curve modeling such as the fuzzification is presented.

  4. Update on normal tension glaucoma

    Directory of Open Access Journals (Sweden)

    Jyotiranjan Mallick

    2016-01-01

    Full Text Available Normal tension glaucoma (NTG is labelled when typical glaucomatous disc changes, visual field defects and open anterior chamber angles are associated with intraocular pressure (IOP constantly below 21 mmHg. Chronic low vascular perfusion, Raynaud's phenomenon, migraine, nocturnal systemic hypotension and over-treated systemic hypertension are the main causes of normal tension glaucoma. Goldmann applanation tonometry, gonioscopy, slit lamp biomicroscopy, optical coherence tomography and visual field analysis are the main tools of investigation for the diagnosis of NTG. Management follows the same principles of treatment for other chronic glaucomas: To reduce IOP by a substantial amount, sufficient to prevent disabling visual loss. Treatment is generally aimed to lower IOP by 30% from pre-existing levels to 12-14 mmHg. Betaxolol, brimonidine, prostaglandin analogues, trabeculectomy (in refractory cases, systemic calcium channel blockers (such as nifedipine and 24-hour monitoring of blood pressure are considered in the management of NTG. The present review summarises risk factors, causes, pathogenesis, diagnosis and management of NTG.

  5. The KRAKEN normal mode program

    Science.gov (United States)

    Porter, M. B.

    1992-05-01

    In the late 1970's, several normal-mode models existed which were widely used for predicting acoustic transmission-loss in the ocean; however, each had its own problems. Typical difficulties included numerical instabilities for certain types of sound-speed profiles and failures to compute a complete set of ocean modes. In short, there was a need for a model that was robust, accurate, and efficient. In order to resolve these problems, a new algorithm was developed forming the basis for the KRAKEN normal mode model. Over subsequent years, KRAKEN was greatly extended, with options for modeling ocean environments that are range-independent, range-dependent, or fully 3-dimensional. The current version offers the specialist a vast number of options for treating ocean-acoustics problems (or more generally acousto-elastic waveguides). On the other hand, it is easy for a less sophisticated user to learn the small subset of tools needed for the common problem of transmission-loss modeling in range-independent ocean environments. This report addresses the need for a more complete user's guide to supplement the on-line help files. The first chapters give a fairly technical description of the mathematical and numerical basis of the model. Additional chapters give a simpler description of its use and installation in a manner that is accessible to less scientifically-oriented readers.

  6. Hearing Status Survey in Define MS Patients

    Directory of Open Access Journals (Sweden)

    Davood Rostamian

    2003-08-01

    Full Text Available Objective: This study was aimed to survey the hearing status of the patients with definite MS. The results of this study may help to confirm the diagnosis and to improve our knowledge of different aspects of this disease and to optimize the treatment and rehabilitative techniques. Material & Methods: This study is performed in audiology clinic of rehabilitation science faculty of Iran medical science university as an assesive-analytic procedure in winter of 2000 in 40 MS patients (Referred from the MS clinic of Shohada Hospital of 20 to 45 years old. All the patients have no history of otologic problems. The results of conventional audiologist tests (PTA, SRT, SDS, imittance audiometry and ABR findings of MS patients were compared to the results of control group. Results: The differences between the means of low, high and mid frequency PTAve in MS patients and control group were statistically significant (P<0.05. There was no significant difference between two groups in the speech test's results, statistically. The results of ART test show statistically significant differences between experimental and control groups. The only differences in ABR results were seen for the absolute latency of the wave V and IPLs (I-V, III-V between two groups. The amplitude ratio of V/I in MS patients 1.5 was within the normal range (0.5 to 2. There was a statistically significant relationship between mean of mid frequency PTAve and prolongation of absolute latency of the wave V. The relationship between ABR and SDS and also between ART and ABR were not statistically significant. Finally, the results of this study suggested that low, high and mid frequency PTAve, ART, absolute latency of the wave V, and IPLs III-V, I-V can be used ascomplementory method to confirm the diagnosis of MS with other conventional methods such as: MRI, CSF analysis, SEP and VEP.

  7. Defining obstructive ventilatory defect in 2015

    Directory of Open Access Journals (Sweden)

    Zied Affes

    2015-10-01

    Full Text Available Introduction: There is no clear consensus as to what constitutes an obstructive ventilatory defect (OVD: Is it FEV1/FVCnormal (LLN or<0.70 (respectively, physiological and operational definitions? Aim: To determine, according to the two definitions, the percentage of subjects having an OVD among them explored in a lung function exploration laboratory. Population and methods: This is a retrospective study including 4,730 subjects aged 17–85 years. Subjects were divided according to the presence [physio (+ or operat (+] or absence [physio (− or operat (−] of an OVD, and into younger (<45 years, n=2,076, older (≥45 years, n=2,654, smokers (n=1,208, and non-smokers (n=3,522 groups. Results: For the total sample, the younger and older groups [mean±SD of age (years, respectively, 46.7±14.1; 33.9±7.4, and 56.8±9.1], the ‘physiological definition’ detected, respectively, 13.46, 43.22, and 5.09% more OVD than the ‘operational one’ (p<0.05. In addition, the operational definition, compared with the physiological one, overdiagnosed OVD in 2.33 and 0.44% of smokers and non-smokers, respectively, and underdiagnosed it in 4.46% and 29.72% of smokers and non-smokers, respectively (p<0.05. Compared with the group ‘physio (−, operat (+’, the ‘physio (+, operat (−’ one was younger (74.2±4.7 years vs. 40.9±10.3 years and had significantly higher FEV1 (62±13% vs. 78±17% and FVC (71±15% vs. 93±19%. Conclusion: The frequency of OVD much depends on the criteria used for its definition.

  8. A pilot study of a non-invasive oral nitrate stable isotopic method suggests that arginine and citrulline supplementation increases whole-body NO production in Tanzanian children with sickle cell disease.

    Science.gov (United States)

    Marealle, Alphonce I; Siervo, Mario; Wassel, Sara; Bluck, Les; Prentice, Andrew M; Minzi, Omary; Sasi, Philip; Kamuhabwa, Appolinary; Soka, Deogratias; Makani, Julie; Cox, Sharon E

    2018-04-01

    Low bioavailability of nitric oxide (NO) is implicated in the pathophysiology of sickle cell disease (SCD). We designed a nested pilot study to be conducted within a clinical trial testing the effects of a daily ready-to-use supplementary food (RUSF) fortified with arginine (Arg) and citrulline (Citr) vs. non-fortified RUSF in children with SCD. The pilot study evaluated 1) the feasibility of a non-invasive stable isotope method to measure whole-body NO production and 2) whether Arg+Citr supplementation was associated with increased whole-body NO production. Twenty-nine children (70% male, 9-11years, weight 16.3-31.3 kg) with SCD. Sixteen children received RUSF+Arg/Citr (Arg, 0.2  g/kg/day; Citr, 0.1  g/kg/day) in combination with daily chloroquine (50 mg) and thirteen received the base RUSF in combination with weekly chloroquine (150 mg). Plasma amino acids were assessed using ion-exchange elution (Biochrom-30, Biochrom, UK) and whole-body NO production was measured using a non-invasive stable isotopic method. The RUSF+Arg/Citr intervention increased plasma arginine (P = .02) and ornithine (P = .003) and decreased the ratio of asymmetric dimethylarginine to arginine (P = .01), compared to the base RUSF. A significant increase in whole-body NO production was observed in the RUSF-Arg/Citr group compared to baseline (weight-adjusted systemic NO synthesis 3.38 ± 2.29 μmol/kg/hr vs 2.35 ± 1.13 μmol/kg/hr, P = .04). No significant changes were detected in the base RUSF group (weight-adjusted systemic NO synthesis 2.64 ± 1.14 μmol/kg/hr vs 2.53 ± 1.12 μmol/kg/hr, P = .80). The non-invasive stable isotopic method was acceptable and the results provided supporting evidence that Arg/Citr supplementation may increase systemic NO synthesis in children with SCD. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  9. A Methodology to Define Flood Resilience

    Science.gov (United States)

    Tourbier, J.

    2012-04-01

    Flood resilience has become an internationally used term with an ever-increasing number of entries on the Internet. The SMARTeST Project is looking at approaches to flood resilience through case studies at cities in various countries, including Washington D.C. in the United States. In light of U.S. experiences a methodology is being proposed by the author that is intended to meet ecologic, spatial, structural, social, disaster relief and flood risk aspects. It concludes that: "Flood resilience combines (1) spatial, (2) structural, (3) social, and (4) risk management levels of flood preparedness." Flood resilience should incorporate all four levels, but not necessarily with equal emphasis. Stakeholders can assign priorities within different flood resilience levels and the considerations they contain, dividing 100% emphasis into four levels. This evaluation would be applied to planned and completed projects, considering existing conditions, goals and concepts. We have long known that the "road to market" for the implementation of flood resilience is linked to capacity building of stakeholders. It is a multidisciplinary enterprise, involving the integration of all the above aspects into the decision-making process. Traditional flood management has largely been influenced by what in the UK has been called "Silo Thinking", involving constituent organizations that are responsible for different elements, and are interested only in their defined part of the system. This barrier to innovation also has been called the "entrapment effect". Flood resilience is being defined as (1) SPATIAL FLOOD RESILIENCE implying the management of land by floodplain zoning, urban greening and management to reduce storm runoff through depression storage and by practicing Sustainable Urban Drainage (SUD's), Best Management Practices (BMP's, or Low Impact Development (LID). Ecologic processes and cultural elements are included. (2) STRUCTURAL FLOOD RESILIENCE referring to permanent flood defense

  10. Defining food literacy: A scoping review.

    Science.gov (United States)

    Truman, Emily; Lane, Daniel; Elliott, Charlene

    2017-09-01

    The term "food literacy" describes the idea of proficiency in food related skills and knowledge. This prevalent term is broadly applied, although its core elements vary from initiative to initiative. In light of its ubiquitous use-but varying definitions-this article establishes the scope of food literacy research by identifying all articles that define 'food literacy', analysing its key conceptualizations, and reporting outcomes/measures of this concept. A scoping review was conducted to identify all articles (academic and grey literature) using the term "food literacy". Databases included Medline, Pubmed, Embase, CAB Abstracts, CINAHL, Scopus, JSTOR, and Web of Science, and Google Scholar. Of 1049 abstracts, 67 studies were included. From these, data was extracted on country of origin, study type (methodological approach), primary target population, and the primary outcomes relating to food literacy. The majority of definitions of food literacy emphasize the acquisition of critical knowledge (information and understanding) (55%) over functional knowledge (skills, abilities and choices) (8%), although some incorporate both (37%). Thematic analysis of 38 novel definitions of food literacy reveals the prevalence of six themes: skills and behaviours, food/health choices, culture, knowledge, emotions, and food systems. Study outcomes largely focus on knowledge generating measures, with very few focusing on health related outcome measures. Current definitions of food literacy incorporate components of six key themes or domains and attributes of both critical and functional knowledge. Despite this broad definition of the term, most studies aiming to improve food literacy focus on knowledge related outcomes. Few articles address health outcomes, leaving an important gap (and opportunity) for future research in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Defining the critical hurdles in cancer immunotherapy.

    Science.gov (United States)

    Fox, Bernard A; Schendel, Dolores J; Butterfield, Lisa H; Aamdal, Steinar; Allison, James P; Ascierto, Paolo Antonio; Atkins, Michael B; Bartunkova, Jirina; Bergmann, Lothar; Berinstein, Neil; Bonorino, Cristina C; Borden, Ernest; Bramson, Jonathan L; Britten, Cedrik M; Cao, Xuetao; Carson, William E; Chang, Alfred E; Characiejus, Dainius; Choudhury, A Raja; Coukos, George; de Gruijl, Tanja; Dillman, Robert O; Dolstra, Harry; Dranoff, Glenn; Durrant, Lindy G; Finke, James H; Galon, Jerome; Gollob, Jared A; Gouttefangeas, Cécile; Grizzi, Fabio; Guida, Michele; Håkansson, Leif; Hege, Kristen; Herberman, Ronald B; Hodi, F Stephen; Hoos, Axel; Huber, Christoph; Hwu, Patrick; Imai, Kohzoh; Jaffee, Elizabeth M; Janetzki, Sylvia; June, Carl H; Kalinski, Pawel; Kaufman, Howard L; Kawakami, Koji; Kawakami, Yutaka; Keilholtz, Ulrich; Khleif, Samir N; Kiessling, Rolf; Kotlan, Beatrix; Kroemer, Guido; Lapointe, Rejean; Levitsky, Hyam I; Lotze, Michael T; Maccalli, Cristina; Maio, Michele; Marschner, Jens-Peter; Mastrangelo, Michael J; Masucci, Giuseppe; Melero, Ignacio; Melief, Cornelius; Murphy, William J; Nelson, Brad; Nicolini, Andrea; Nishimura, Michael I; Odunsi, Kunle; Ohashi, Pamela S; O'Donnell-Tormey, Jill; Old, Lloyd J; Ottensmeier, Christian; Papamichail, Michael; Parmiani, Giorgio; Pawelec, Graham; Proietti, Enrico; Qin, Shukui; Rees, Robert; Ribas, Antoni; Ridolfi, Ruggero; Ritter, Gerd; Rivoltini, Licia; Romero, Pedro J; Salem, Mohamed L; Scheper, Rik J; Seliger, Barbara; Sharma, Padmanee; Shiku, Hiroshi; Singh-Jasuja, Harpreet; Song, Wenru; Straten, Per Thor; Tahara, Hideaki; Tian, Zhigang; van Der Burg, Sjoerd H; von Hoegen, Paul; Wang, Ena; Welters, Marij Jp; Winter, Hauke; Withington, Tara; Wolchok, Jedd D; Xiao, Weihua; Zitvogel, Laurence; Zwierzina, Heinz; Marincola, Francesco M; Gajewski, Thomas F; Wigginton, Jon M; Disis, Mary L

    2011-12-14

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

  12. Towards defining restlessness in individuals with dementia.

    Science.gov (United States)

    Regier, Natalie G; Gitlin, Laura N

    2017-05-01

    Most individuals with dementia develop significant behavioral problems. Restlessness is a behavioral symptom frequently endorsed by caregivers as distressing, yet is variably defined and measured. Lack of conceptual and operational clarity hinders an understanding of this common behavioral type, its prevalence, and development of effective interventions. We advance a systematic definition and understanding of restlessness from which to enhance reporting and intervention development. We reviewed the literature for existing definitions and measures of restlessness, identified common elements across existing definitions, assessed fit with relevant theoretical frameworks, and explored the relationship between restlessness and other behavioral symptoms in a data set of 272 community-dwelling persons with dementia. Twenty-five scales assessing restlessness were identified. Shared components included motor/neurological, psychiatric, and needs-based features. Exploratory analyses suggest that restlessness may co-occur primarily with argumentation, anxiety, waking the caregiver, delusions/hallucinations, and wandering. We propose that restlessness consists of three key attributes: diffuse motor activity or motion subject to limited control, non-productive or disorganized behavior, and subjective distress. Restlessness should be differentiated from and not confused with wandering or elopement, pharmacological side effects, a (non-dementia) mental or movement disorder, or behaviors occurring in the context of a delirium or at end-of-life. Restlessness appears to denote a distinct set of behaviors that have overlapping but non-equivalent features with other behavioral symptoms. We propose that it reflects a complex behavior involving three key characteristics. Understanding its specific manifestations and which components are present can enhance tailoring interventions to specific contexts of this multicomponent behavioral type.

  13. Defining the critical hurdles in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Fox Bernard A

    2011-12-01

    Full Text Available Abstract Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC, convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

  14. A hierarchical approach to defining marine heatwaves

    Science.gov (United States)

    Hobday, Alistair J.; Alexander, Lisa V.; Perkins, Sarah E.; Smale, Dan A.; Straub, Sandra C.; Oliver, Eric C. J.; Benthuysen, Jessica A.; Burrows, Michael T.; Donat, Markus G.; Feng, Ming; Holbrook, Neil J.; Moore, Pippa J.; Scannell, Hillary A.; Sen Gupta, Alex; Wernberg, Thomas

    2016-02-01

    Marine heatwaves (MHWs) have been observed around the world and are expected to increase in intensity and frequency under anthropogenic climate change. A variety of impacts have been associated with these anomalous events, including shifts in species ranges, local extinctions and economic impacts on seafood industries through declines in important fishery species and impacts on aquaculture. Extreme temperatures are increasingly seen as important influences on biological systems, yet a consistent definition of MHWs does not exist. A clear definition will facilitate retrospective comparisons between MHWs, enabling the synthesis and a mechanistic understanding of the role of MHWs in marine ecosystems. Building on research into atmospheric heatwaves, we propose both a general and specific definition for MHWs, based on a hierarchy of metrics that allow for different data sets to be used in identifying MHWs. We generally define a MHW as a prolonged discrete anomalously warm water event that can be described by its duration, intensity, rate of evolution, and spatial extent. Specifically, we consider an anomalously warm event to be a MHW if it lasts for five or more days, with temperatures warmer than the 90th percentile based on a 30-year historical baseline period. This structure provides flexibility with regard to the description of MHWs and transparency in communicating MHWs to a general audience. The use of these metrics is illustrated for three 21st century MHWs; the northern Mediterranean event in 2003, the Western Australia 'Ningaloo Niño' in 2011, and the northwest Atlantic event in 2012. We recommend a specific quantitative definition for MHWs to facilitate global comparisons and to advance our understanding of these phenomena.

  15. Defining the critical hurdles in cancer immunotherapy

    Science.gov (United States)

    2011-01-01

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer. PMID:22168571

  16. Ramifications of defining high-level waste

    International Nuclear Information System (INIS)

    Wood, D.E.; Campbell, M.H.; Shupe, M.W.

    1987-01-01

    The Nuclear Regulatory Commission (NRC) is considering rule making to provide a concentration-based definition of high-level waste (HLW) under authority derived from the Nuclear Waste Policy Act (NWPA) of 1982 and the Low Level Waste Policy Amendments Act of 1985. The Department of Energy (DOE), which has the responsibility to dispose of certain kinds of commercial waste, is supporting development of a risk-based classification system by the Oak Ridge National Laboratory to assist in developing and implementing the NRC rule. The system is two dimensional, with the axes based on the phrases highly radioactive and requires permanent isolation in the definition of HLW in the NWPA. Defining HLW will reduce the ambiguity in the present source-based definition by providing concentration limits to establish which materials are to be called HLW. The system allows the possibility of greater-confinement disposal for some wastes which do not require the degree of isolation provided by a repository. The definition of HLW will provide a firm basis for waste processing options which involve partitioning of waste into a high-activity stream for repository disposal, and a low-activity stream for disposal elsewhere. Several possible classification systems have been derived and the characteristics of each are discussed. The Defense High Level Waste Technology Lead Office at DOE - Richland Operations Office, supported by Rockwell Hanford Operations, has coordinated reviews of the ORNL work by a technical peer review group and other DOE offices. The reviews produced several recommendations and identified several issues to be addressed in the NRC rule making. 10 references, 3 figures

  17. Defining malnutrition: A plea to rethink.

    Science.gov (United States)

    Soeters, P; Bozzetti, F; Cynober, L; Forbes, A; Shenkin, A; Sobotka, L

    2017-06-01

    In a recent consensus report in Clinical Nutrition the undernourished category of malnutrition was proposed to be defined and diagnosed on the basis of a low BMI or unintentional weight loss combined with low BMI or FFMI with certain cut off points. The definition was endorsed by ESPEN despite recent endorsement of a very different definition. The approach aims to assess whether nutritional intake is sufficient but is imprecise because a low BMI does not always indicate malnutrition and individuals with increasing BMI's may have decreasing FFM's. The pathophysiology of individuals, considered to be malnourished in rich countries and in areas with endemic malnutrition, results predominantly from deficient nutrition combined with infection/inflammation. Both elements jointly determine body composition and function and consequently outcome of disease, trauma or treatment. When following the consensus statement only an imprecise estimate is acquired of nutritional intake without knowing the impact of inflammation. Most importantly, functional abilities are not assessed. Consequently it will remain uncertain how well the individual can overcome stressful events, what the causes are of dysfunction, how to set priorities for treatment and how to predict the effect of nutritional support. We therefore advise to consider the pathophysiology of malnourished individuals leading to inclusion of the following elements in the definition of malnutrition: a disordered nutritional state resulting from a combination of inflammation and a negative nutrient balance, leading to changes in body composition, function and outcome. A precise diagnosis of malnutrition should be based on assessment of these elements. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  18. Is My Penis Normal? (For Teens)

    Science.gov (United States)

    ... Videos for Educators Search English Español Is My Penis Normal? KidsHealth / For Teens / Is My Penis Normal? Print en español ¿Es normal mi pene? ... any guy who's ever worried about whether his penis is a normal size. There's a fairly wide ...

  19. Comparison of spectrum normalization techniques for univariate ...

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics; Volume 86; Issue 6 ... Abstract. Analytical performance of six different spectrum normalization techniques, namelyinternal normalization, normalization with total light, normalization with background along with their three-point smoothing methods were studied using LIBS for ...

  20. NORMAL DISTRIBUTION LAW IN MEDICAL RESEARCH

    Directory of Open Access Journals (Sweden)

    М. A. Ivanchuk

    2013-05-01

    Full Text Available The main methods for assessing normality were described. As an example, multiple samples from clinical research were tested for normality using graphical (the histogram and t he normal probability plot, and statistical methods. The majority of clinical samples were not normally distributed (60 %. The practical recommendations were provided.