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Sample records for alpha 1-antitrypsin

  1. Alpha-1 Antitrypsin Deficiency

    Science.gov (United States)

    ... by blood tests showing the low levels of alpha-1 antitrypsin and abnormal liver tests. Other tests such as ultrasound imaging or tests using specialized X-ray techniques may be necessary. A liver biopsy may ...

  2. Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Dahl, Morten; Nordestgaard, B G; Lange, P;

    2001-01-01

    We tested whether intermediate (MZ, SZ) and severe (ZZ) alpha(1)-antitrypsin deficiency affects lung function in the population at large.......We tested whether intermediate (MZ, SZ) and severe (ZZ) alpha(1)-antitrypsin deficiency affects lung function in the population at large....

  3. Fibrinogen and alpha(1)-antitrypsin in COPD exacerbations

    DEFF Research Database (Denmark)

    Sylvan Ingebrigtsen, Truls; Marott, J. L.; Rode, L.

    2015-01-01

    Background We tested the hypotheses that fibrinogen and alpha(1)-antitrypsin are observationally and genetically associated with exacerbations in COPD. Methods We studied 13 591 individuals with COPD from the Copenhagen General Population Study (2003-2013), of whom 6857 were genotyped for FGB -455...... and exacerbations in instrumental variable analyses. Results Elevated fibrinogen and alpha(1)-antitrypsin levels were associated with increased risk of exacerbations in COPD, HR=1.14 (1.07 to 1.22, p...

  4. Hereditary fructose intolerance and alpha(1) antitrypsin deficiency.

    Science.gov (United States)

    Hillebrand, G; Schneppenheim, R; Oldigs, H D; Santer, R

    2000-07-01

    A patient with coexisting hereditary fructose intolerance (HFI) and alpha(1) antitrypsin deficiency (alpha(1)ATD) is described. Protease inhibitor typing was not conclusive, presumably because of impaired N-glycosylation secondary to HFI. The case underlines the diagnostic role of molecular genetic techniques in inborn errors of metabolism.

  5. Deficiency of a alpha-1-antitrypsin influences systemic iron homeostasis

    Science.gov (United States)

    Abstract Background: There is evidence that proteases and anti-proteases participate in the iron homeostasis of cells and living systems. We tested the postulate that alpha-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this anti-protease in humans are asso...

  6. alpha 1-Antitrypsin and coeliac disease in spain.

    Science.gov (United States)

    Klasen, E C; Polanco, I; Biemond, I; Vazquez, C; Peña, A S

    1980-01-01

    Ninety-three Spanish children suffering from coeliac disease and 103 control subjects from the same area were screened for the amount of alpha 1-antitrypsin (alpha 1AT) and for any electrophoretic variations in it. In this case-control study no significant differences were detected either in phenotype distribution or amount. The present results indicate that no genetic association exists between alpha 1AT and coeliac disease. PMID:6969683

  7. Alpha1-antitrypsin deficiency: a clinical-genetic overview

    Directory of Open Access Journals (Sweden)

    Abboud RT

    2011-03-01

    in patients with chronic irreversible airflow obstruction, especially in those with early onset of disease or positive family history. Testing is also recommended for immediate family members of those with AATD, asthmatics with persistent airflow obstruction, and infants and older subjects with unexplained liver disease. There are over 100 different AAT gene variants; most are rare and only some are associated with clinical disease.Keywords: AAT, AATD, ZZ, early onset emphysema, panacinar emphysema, neonatal jaundice and hepatitis, childhood liver disease, genetics of alpha1-antitrypsin, alpha1-antitrypsin laboratory testing and phenotyping

  8. Safety and efficacy of alpha-1-antitrypsin augmentation therapy in the treatment of patients with alpha-1-antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Irina Petrache

    2009-05-01

    Full Text Available Irina Petrache1, Joud Hajjar1, Michael Campos21Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; 2Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Miller School of Medicine, University of Miami, Florida, USA Abstract: Alpha-1-antitrypsin deficiency (AATD, also known as alpha1-proteinase inhibitor deficiency, is an autosomal co-dominant condition. The genotypes associated with AATD include null, deficient, and dysfunctional alpha-1-antitrypsin (A1AT variants, which result in low levels of circulating functional A1AT, unbalanced protease activity, and an increased risk of developing lung emphysema, the leading cause of morbidity in these patients. Furthermore, the most common abnormal genotype, Pi*ZZ may also cause trapping of abnormally folded protein polymers in hepatocytes causing liver dysfunction. A major focus of therapy for patients with lung disease due to AATD is to correct the A1AT deficiency state by augmenting serum levels with intravenous infusions of human plasma-derived A1AT. This strategy has been associated with effective elevations of A1AT levels and function in serum and lung epithelial fluid and observational studies suggest that it may lead to attenuation in lung function decline, particularly in patients with moderate impairment of lung function. In addition, an observational study suggests that augmentation therapy is associated with a reduction of mortality in subjects with AATD and moderate to severe lung impairment. More recent randomized placebo-controlled studies utilizing computer scan densitometry suggest that this therapy attenuates lung tissue loss. Augmentation therapy has a relative paucity of side effects, but it is highly expensive. Therefore, this therapy is recommended for patients with AATD who have a high-risk A1AT genotype with plasma A1AT below protective levels (11 µM and evidence of obstructive lung disease. In this article, we

  9. An ECLIPSE View of Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Lomas, David A

    2016-08-01

    Chronic obstructive pulmonary disease (COPD) is a multicomponent condition that is estimated to become the third leading cause of death in 2020. The ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study, funded by GlaxoSmithKline, is an observational study designed to define outcomes that can be used as endpoints in clinical trials in individuals with COPD. It allowed us to describe the heterogeneity of COPD, the stability of the exacerbation phenotype, and the factors associated with a progressive decline in lung function and the progression of emphysema on computed tomography scans. The cohort was also used to define genetic factors and biomarkers associated with COPD and disease progression. This review considers how the results from ECLIPSE can inform our understanding of the lung disease associated with alpha-1 antitrypsin deficiency.

  10. Diagnosis of alpha-1-antitrypsin deficiency by DNA analysis of children with liver disease

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    De TOMMASO Adriana Maria Alves

    2001-01-01

    Full Text Available Background - Alpha-1-antitrypsin deficiency is a genetic disorder which is transmitted in a co-dominant, autosomal form. Alpha-1-antitrypsin deficiency affects mainly the lungs and the liver leading, in the latter case, to neonatal cholestasis, chronic hepatitis or cirrhosis. A precise diagnosis of Alpha-1-antitrypsin deficiency may be obtained by biochemical or molecular analysis. Objective - The purpose of this study was to use DNA analysis to examine the presence of an alpha-1-antitrypsin deficiency in 12 children suspected of having this deficiency and who showed laboratory and clinical characteristics of the disease. Patients and Methods - Twelve patients, aged 3 months to 19 years, who had serum alpha-1-antitrypsin levels lower than normal and/or had hepatic disease of undefined etiology were studied. The mutant alleles S and Z of the alpha-1-antitrypsin gene were investigated in the 12 children. Alpha-1-antitrypsin gene organization was analyzed by amplification of genoma through the polymerase chain reaction and digestion with the restriction enzymes Xmnl (S allele and Taq 1 (Z allele. Results - Seven of the 12 patients had chronic liver disease of undefined etiology and the other five patients had low serum levels of alpha-1-antitrypsin as well as a diagnosis of neonatal cholestasis and/or chronic liver disease of undefined etiology. Five of the 12 patients were homozygous for the Z allele (ZZ and two had the S allele with another allele (*S different from Z. Conclusion - These results show that alpha-1-antitrypsin deficiency is relatively frequent in children with chronic hepatic disease of undefined etiology and/or low alpha-1-antitrypsin levels (41.6%. A correct diagnosis is important for effective clinical follow-up and for genetic counseling.

  11. Blood pressure, risk of ischemic cerebrovascular and ischemic heart disease, and longevity in alpha(1)-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Sillesen, Henrik

    2003-01-01

    Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity.......Because elastase in alpha(1)-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether alpha(1)-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity....

  12. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences

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    Stolk Jan

    2008-06-01

    Full Text Available Abstract Alpha-1-antitrypsin deficiency (AATD is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing, early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness

  13. Alpha-1-antitrypsin deficiency: An overview of recent advances

    Directory of Open Access Journals (Sweden)

    El Hazmi Mohsen

    1996-01-01

    Full Text Available Alpha 1-antitrypsin (αl AT, a serpine, is one of the most important proteinase inhibitor in the serum and plays an essential role in protection of the lung tissues against the proteolytic attach of elastase. The gene for a1AT is located on chromosome 14 q 32 and is highly susceptible to mutations. A large number of variants of α 1 AT are known and some including PiZ and PiS result in a1AT deficiency. In patients with PiZ, the most severe and common α1AT deficient variant, the α1AT protein accumulates in the liver and results in severe hepatic diseases. Other clinical consequences of α1AT deficiency include emphysema in majority of the patients. This state is further aggravated in patients who smoke. Several treatment strategies have been suggested, including replacement therapy by purified α1AT or recombinant α1AT given intravenously or as aerosol. Synthetic peptides. lung transplantation and volume reduction surgery are under investigation and evaluation. This paper updates the information on α1 AT and its deficiency state.

  14. Role of alpha-1 antitrypsin in human health and disease.

    Science.gov (United States)

    de Serres, F; Blanco, I

    2014-10-01

    Alpha-1 antitrypsin (AAT) deficiency is an under-recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals and has its highest prevalence (1 : 2000-1 : 5000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000-10 000. Prevalence is five times lower in Latin American countries and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counselling and, in selected cases, the application of augmentation therapy. Over the past decade, it has been demonstrated that AAT is a broad-spectrum anti-inflammatory, immunomodulatory, anti-infective and tissue-repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency.

  15. Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin

    DEFF Research Database (Denmark)

    Burgess, Jefferey L; Kurzius-Spencer, Margaret; Poplin, Gerald S;

    2014-01-01

    Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether...... this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic...... arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium...

  16. Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes

    DEFF Research Database (Denmark)

    Hersh, C P; Dahl, Morten; Ly, N P;

    2004-01-01

    Severe alpha(1)-antitrypsin deficiency, usually related to homozygosity for the protease inhibitor (PI) Z allele, is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD). The risk of COPD in PI MZ heterozygous individuals is controversial....

  17. Disposition of Alpha-1-Antitrypsin in the Isolate Perfused Rabbit Lung

    Directory of Open Access Journals (Sweden)

    MOHAMMAD K. HASSANZADEH PHILIP R. MAYER

    1999-08-01

    Full Text Available The potential for delivering large molecular weight proteins into the lungs to reach local or systemic sites of action was investigated by examining the disposition of alpha-1-antitrypsin in the isolated rabbit lung. Alpha-1-antitrypsin, a model protein, was measured in the periusion medium following intravascular administration and was found to remain constant, indicating limited uptake or metabolism by lung tissue. Intrabronchial instillation of 10 mg of alpha-1-antitrypsin in water resulted in no measurable concentration in the recirculating perfusate during the two hours experiment. These data suggest that transport of large proteins may be limited across lung-blood membrane barriers in either direction. Though this would limit the ability of inhaled drugs with large molecular weights to reach the general circulation, proteins which are used to treat respiratory diseases, such as alpha-1-antitrypsin, might be delivered locally by inhalation with only negligible systemic exposure.

  18. The prevalence of alpha-1 antitrypsin deficiency in Ireland.

    LENUS (Irish Health Repository)

    Carroll, Tomas P

    2012-02-01

    BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. METHODS: We present data from the first 3,000 individuals screened following ATS\\/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. RESULTS: The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes. CONCLUSION: Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.

  19. Alpha 1-antitrypsin does not inhibit human monocyte caspase-1.

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    Mohd Akhlakur Rahman

    Full Text Available Alpha 1-antitrypsin (A1AT is a 52 kDa serine protease inhibitor produced largely by hepatocytes but also by mononuclear phagocytes. A1AT chiefly inhibits neutrophil elastase and proteinase-3 but has also been reported to have immune modulatory functions including the ability to inhibit caspases. Its clinical availability for infusion suggests that A1AT therapy might modulate caspase related inflammation. Here we tested the ability of A1AT to modulate caspase-1 function in human mononuclear phagocytes.Purified plasma derived A1AT was added to active caspase-1 in a cell-free system (THP-1 lysates as well as added exogenously to cell-culture models and human whole blood models of caspase-1 activation. Functional caspase-1 activity was quantified by the cleavage of the caspase-1 specific fluorogenic tetrapeptide substrate (WEHD-afc and the release of processed IL-18 and IL-1β.THP-1 cell lysates generated spontaneous activation of caspase-1 both by WEHD-afc cleavage and the generation of p20 caspase-1. A1AT added to this cell free system was unable to inhibit caspase-1 activity. Release of processed IL-18 by THP-1 cells was also unaffected by the addition of exogenous A1AT prior to stimulation with LPS/ATP, a standard caspase-1 activating signal. Importantly, the A1AT exhibited potent neutrophil elastase inhibitory capacity. Furthermore, A1AT complexed to NE (and hence conformationally modified also did not affect THP-1 cell caspase-1 activation. Finally, exogenous A1AT did not inhibit the ability of human whole blood samples to process and release IL-1β.A1AT does not inhibit human monocyte caspase-1.

  20. The prevalence of alpha-1 antitrypsin deficiency in Ireland

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    Morris Valerie B

    2011-07-01

    Full Text Available Abstract Background Alpha-1 antitrypsin deficiency (AATD results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD, non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. Methods We present data from the first 3,000 individuals screened following ATS/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP. We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. Results The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes. Conclusion Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.

  1. The prevalence of alpha-1 antitrypsin deficiency in Ireland.

    LENUS (Irish Health Repository)

    Carroll, Tomas P

    2011-07-13

    Abstract Background Alpha-1 antitrypsin deficiency (AATD) results from mutations in the SERPINA1 gene and classically presents with early-onset emphysema and liver disease. The most common mutation presenting with clinical evidence is the Z mutation, while the S mutation is associated with a milder plasma deficiency. AATD is an under-diagnosed condition and the World Health Organisation recommends targeted detection programmes for AATD in patients with chronic obstructive pulmonary disease (COPD), non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients. Methods We present data from the first 3,000 individuals screened following ATS\\/ERS guidelines as part of the Irish National Targeted Detection Programme (INTDP). We also investigated a DNA collection of 1,100 individuals randomly sampled from the general population. Serum and DNA was collected from both groups and mutations in the SERPINA1 gene detected by phenotyping or genotyping. Results The Irish National Targeted Detection Programme identified 42 ZZ, 44 SZ, 14 SS, 430 MZ, 263 MS, 20 IX and 2 rare mutations. Analysis of 1,100 randomly selected individuals identified 113 MS, 46 MZ, 2 SS and 2 SZ genotypes. Conclusion Our findings demonstrate that AATD in Ireland is more prevalent than previously estimated with Z and S allele frequencies among the highest in the world. Furthermore, our targeted detection programme enriched the population of those carrying the Z but not the S allele, suggesting the Z allele is more important in the pathogenesis of those conditions targeted by the detection programme.

  2. Alpha1-antitrypsin deficiency with fatal intracranial hemorrhage in a newborn.

    Science.gov (United States)

    Israels, S J; Gilfix, B M

    1999-01-01

    A 4-week-old boy had a fatal intracranial hemorrhage resulting from vitamin K deficiency. The infant had received no vitamin K prophylaxis and was exclusively breastfed. At autopsy, examination of the liver showed cholestasis and fibrosis. DNA was isolated from a blood spot on a Gutherie sample card obtained from the infant for routine metabolic screening. This DNA was used for alpha1-antitrypsin genotyping studies. Genotyping studies identified homozygosity for the point mutation 9989G-->A, confirming a diagnosis of alpha1-antitrypsin deficiency (ZZ phenotype), and resulted in appropriate screening of siblings born after this child's death. Alpha1-antitrypsin deficiency should be considered in the differential diagnosis of infants with late hemorrhagic disease of the newborn. Use of blood from the metabolic screening card as a source of DNA allowed confirmation of this diagnosis after the infant's death.

  3. ALPHA1 ANTITRYPSIN IN SMOKERS AND NON SMOKERS CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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    Panchal Mittal A, Shaikh Sahema M, Sadariya Bhavesh R, Bhoi Bharat K, Sharma Hariom M

    2015-01-01

    Full Text Available Aim: The aim of the present study is to correlate and compare alpha-1 antitrypsin level in smoker and non smoker chronic obstructive pulmonary disease patients. Material and Methods: A comparative study was carried out in 200 subjects, more than 40 years of age and having chronic obstructive pulmonary disease for more than 1 year with a history of smoking at least 20 cigarettes per day (Group A and without a history of smoking (Group B. Pulmonary function tests were used to diagnose the disease as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD classification. Alpha-1 antitrypsin level was done by turbidimetry method on fully auto analyzer I-Lab 650 (Instrumentation Laboratory, USA at Clinical Biochemistry Section, Laboratory Services Sir Takhtsinhji Hospital, Bhavnagar. Statistical analysis was done by using unpaired t-test and Pearson’s correlation coefficient. Results: Results of present study shows that alpha-1 antitrypsin level was decreased in smoker chronic obstructive pulmonary disease patients (150.83±18.853 when compared to non smokers (183.97±29.383. There was statistically significant difference in alpha-1 antitrypsin level between the two groups with ‘p’ value of <0.0001. Pearson’s correlation test show negative correlation between smoker and non-smoker chronic obstructive pulmonary disease patients. Conclusion: The values of serum alpha-1 antitrypsin levels were more significantly decreased in smokers indicating an important role of smoking in pathogenesis of chronic obstructive pulmonary disease. Alpha-1 antitrypsin can act as a predictor for future development of chronic obstructive pulmonary disease in smokers and in nonsmokers.

  4. Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Lange, Peter

    2002-01-01

    A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain.......A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain....

  5. alpha 1-Antitrypsin-levels and phenotypes in Crohn's disease in the Netherlands.

    Science.gov (United States)

    Klasen, E C; Biemond, I; Weterman, I T

    1980-01-01

    A group of 310 unrelated patients suffering from Crohn's disease has been screened for quantitative and electrophoretic variations of alpha 1-antitrypsin (alpha 1AT). A comparison was made betweeen patients and healthy controls. The distribution of electrophoretic alpha 1AT variants in the patients showed no significant deviation from the controls. The alpha 1AT quantities are significantly higher in the Crohn's disease population than in the controls. PMID:6969207

  6. Alpha-1 antitrypsin reduces ovariectomy-induced bone loss in mice

    Science.gov (United States)

    Alpha-1antitrypsin (AAT) is a multifunctional protein with proteinase inhibitor and anti-inflammatory activities. Recent studies showed that AAT has therapeutic effect for diseases associated with inflammation, such as type 1 diabetes and arthritis. Proinflammatory cytokines are primary mediators of...

  7. Vitamin K deficiency bleeding in cholestatic infants with alpha-1-antitrypsin deficiency.

    NARCIS (Netherlands)

    Hasselt, P.M. van; Kok, K.F.; Vorselaars, A.D.; Vlerken, L. van; Nieuwenhuys, E.; Koning, T.J. de; Vries, R.A. de; Houwen, R.H.J.

    2009-01-01

    OBJECTIVE: Exclusively breastfed infants with unrecognised cholestatic jaundice are at high risk of a vitamin K deficiency (VKD) bleeding. It is presently unknown whether (the size of) this risk depends on the degree of cholestasis. Since alpha-1-antitrypsin deficiency (A1AD) induces a variable degr

  8. Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema

    Directory of Open Access Journals (Sweden)

    de Serres Frederick

    2011-04-01

    Full Text Available Abstract Up to now alpha 1-antitrypsin (AAT augmentation therapy has been approved only for commercial use in selected adults with severe AAT deficiency-related pulmonary emphysema (i.e. PI*ZZ genotypes as well as combinations of Z, rare and null alleles expressing AAT serum concentrations

  9. Sequestration of mutated alpha1-antitrypsin into inclusion bodies is a cell-protective mechanism to maintain endoplasmic reticulum function.

    Science.gov (United States)

    Granell, Susana; Baldini, Giovanna; Mohammad, Sameer; Nicolin, Vanessa; Narducci, Paola; Storrie, Brian; Baldini, Giulia

    2008-02-01

    A variant alpha1-antitrypsin with E342K mutation has a high tendency to form intracellular polymers, and it is associated with liver disease. In the hepatocytes of individuals carrying the mutation, alpha1-antitrypsin localizes both to the endoplasmic reticulum (ER) and to membrane-surrounded inclusion bodies (IBs). It is unclear whether the IBs contribute to cell toxicity or whether they are protective to the cell. We found that in hepatoma cells, mutated alpha1-antitrypsin exited the ER and accumulated in IBs that were negative for autophagosomal and lysosomal markers, and contained several ER components, but not calnexin. Mutated alpha1-antitrypsin induced IBs also in neuroendocrine cells, showing that formation of these organelles is not cell type specific. In the presence of IBs, ER function was largely maintained. Increased levels of calnexin, but not of protein disulfide isomerase, inhibited formation of IBs and lead to retention of mutated alpha1-antitrypsin in the ER. In hepatoma cells, shift of mutated alpha1-antitrypsin localization to the ER by calnexin overexpression lead to cell shrinkage, ER stress, and impairment of the secretory pathway at the ER level. We conclude that segregation of mutated alpha1-antitrypsin from the ER to the IBs is a protective cell response to maintain a functional secretory pathway.

  10. Alpha-1-antitrypsin deficiency resulting in a hitherto unseen presentation of hepatocellular carcinoma: Polycythemia but with normal alpha fetoprotein

    Institute of Scientific and Technical Information of China (English)

    David Ryan Owen; Ramachandran Sivakumar; Eui-Sik Suh; Murugiah Seevaratnam

    2006-01-01

    Polycythemia is a known paraneopastic manifestation of hepatoma, but only in the presence of alpha-fetopro (AFP). We present a case of polycythemia in the absence of AFP, and suggest concurrent alpha-1-antitrypsin deficiency as the cause for breaking this rule. We also suggest a reason for the apparent constant conjunction between polycythemia and AFP in hepatoma.

  11. In silico analysis of alpha1-antitrypsin variants: the effects of a novel mutation

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    Sabri Denden

    2010-01-01

    Full Text Available Alpha1-antitrypsin (AAT is a highly polymorphic protein with more than 120 variants that are classified as normal (normal protein secretion, deficient (reduced circulating AAT level caused by defective secretion or null (no protein secretion. Alpha1-antitrypsin deficiency, one of the most common genetic disorders, predisposes adults to pulmonary emphysema and, to a lesser extent, chronic liver disease and cirrhosis. In this report, we provide additional sequence data for alpha1-antitrypsin based on the characterization of a novel variant detected in a 53-year-old heterozygous patient with chronic obstructive pulmonary disease. The mutation occurred on a PI*M2 base allele and was characterized by a T → C transition at nt 97 in exon II that led to the replacement of phenylalanine by leucine (F33L. Since the mutation was found in the heterozygous state with the expression of a normally secreted variant (PI*M1 it was not possible to assess the pattern of F33L secretion. However, computational analyses based on evolutionary, structural and functional information indicated a reduction of 23 ų in the side chain volume and the creation of a cavity in the protein hydrophobic core that likely disturbed the tridimensional structure and folding of AAT. The accuracy of the in silico prediction was confirmed by testing known mutations.

  12. alpha-1-antitrypsin in breast milk of healthy Nigerian mothers.

    Science.gov (United States)

    Omeme, J A; Lantos, J D; Ihongbe, J C

    1981-01-01

    Alpha-1-antitryspin (x-1-AT) may play a possible role as effector of immunological stasis. This study examines the levels of this glycoprotein in 73 breast milk samples from 60 healthy Nigerian mothers. Levels of x-1-AT were measured by single radial immunodiffusion according to the method of Mancini. Serum protein was measured by Lowry's method, albumin by Doumas' method. Highest mean levels of x-1-AT were found in colostrum (25 mg/dl). The level was significantly higher compared to transitional milk (14.2 mg/dl) or mature milk (165 mg/dl) (p0.001). Breast milk contains substantial amounts of x-1-AT which is not destroyed by pasturization at 56 degrees Centigrade. The immunological protective properties of breast milk are ideal for newborn babies, particularly those who are low birthweight and are thus most susceptible to neonatal necrotizing enterocolitis.

  13. Alpha-1-antitrypsin phenotypes in Saudi Arabia: A study in the central province.

    Science.gov (United States)

    Warsy, A S; El-Hazmi, M A; Sedrani, S H; Kinhal, M

    1991-03-01

    This study was conducted on 204 plasma samples obtained from Saudis living in the central province of Saudi Arabia, to determine the prevalence of alpha-1-antitrypsin (alpha1AT) phenotypes. The alpha1AT phenotypes were separated by isoelectric focusing on ampholine gels (pH 4-5). The prevalences of PiMM, MS, MZ, SZ, and ZZ were 0.8676, 0.0931, 0.0245, 0.0098, and 0.0049, respectively. The gene frequencies of the alpha1AT variants, i.e.., PiM, PiS, and PiZ, were 0.9265, 0.0515, 0.022, respectively. We describe and compare our results in a Saudi population with those reported for other populations.

  14. Indications for active case searches and intravenous alpha-1 antitrypsin treatment for patients with alpha-1 antitrypsin deficiency chronic pulmonary obstructive disease: an update.

    Science.gov (United States)

    Casas, Francisco; Blanco, Ignacio; Martínez, María Teresa; Bustamante, Ana; Miravitlles, Marc; Cadenas, Sergio; Hernández, José M; Lázaro, Lourdes; Rodríguez, Esther; Rodríguez-Frías, Francisco; Torres, María; Lara, Beatriz

    2015-04-01

    The effect of hereditary alpha-1 antitrypsin (AAT) deficiency can manifest clinically in the form of chronic obstructive pulmonary disease (COPD). AAT deficiency (AATD) is defined as a serum concentration lower than 35% of the expected mean value or 50 mg/dl (determined by nephelometry). It is associated in over 95% of cases with Pi*ZZ genotypes, and much less frequently with other genotypes resulting from combinations of Z, S, rare and null alleles. A systematic qualitative review was made of 107 articles, focusing mainly on an active search for AATD in COPD patients and intravenous (iv) treatment with AAT. On the basis of this review, the consultant committee of the Spanish Registry of Patients with AATD recommends that all COPD patients be screened for AATD with the determination of AAT serum concentrations, and when these are low, the evaluation must be completed with phenotyping and, on occasions, genotyping. Patients with severe AATD COPD should receive the pharmacological and non-pharmacological treatment recommended in the COPD guidelines. There is enough evidence from large observational studies and randomized placebo-controlled clinical trials to show that the administration of iv AAT reduces mortality and slows the progression of emphysema, hence its indication in selected cases that meet the inclusion criteria stipulated in international guidelines. The administration of periodic infusions of AAT is the only specific treatment for delaying the progression of emphysema associated with AATD.

  15. Increased outer arm and core fucose residues on the N-glycans of mutated alpha-1 antitrypsin protein from alpha-1 antitrypsin deficient individuals.

    Science.gov (United States)

    McCarthy, Cormac; Saldova, Radka; O'Brien, M Emmet; Bergin, David A; Carroll, Tomás P; Keenan, Joanne; Meleady, Paula; Henry, Michael; Clynes, Martin; Rudd, Pauline M; Reeves, Emer P; McElvaney, Noel G

    2014-02-01

    Alpha-1 antitrypsin (AAT) is the major physiological inhibitor of a range of serine proteases, and in the lung, it maintains a protease-antiprotease balance. AAT deficiency (AATD) is an autosomal co-dominant condition with the Z mutation being the most common cause. Individuals homozygous for Z (PiZZ) have low levels of circulating mutant Z-AAT protein leading to premature emphysematous lung disease. Extensive glycoanalysis has been performed on normal AAT (M-AAT) from healthy individuals and the importance of glycosylation in affecting the immune modulatory roles of AAT is documented. However, no glycoanalysis has been carried out on Z-AAT from deficient individuals to date. In this study, we investigate whether the glycans present on Z-AAT differ to those found on M-AAT from healthy controls. Plasma AAT was purified from 10 individuals: 5 AATD donors with the PiZZ phenotype and 5 PiMM healthy controls. Glycoanalysis was performed employing N-glycan release, exoglycosidase digestion and UPLC analysis. No difference in branched glycans was identified between AATD and healthy controls. However, a significant increase in both outer arm (α1-3) (p = 0.04) and core (α1-6) fucosylated glycans (p < 0.0001) was found on Z-AAT compared to M-AAT. This study has identified increased fucosylation on N-glycans of Z-AAT indicative of ongoing inflammation in AATD individuals with implications for early therapeutic intervention.

  16. Production of human alpha-1-antitrypsin from transgenic rice cell culture in a membrane bioreactor.

    Science.gov (United States)

    McDonald, Karen A; Hong, Lo Ming; Trombly, David M; Xie, Qing; Jackman, Alan P

    2005-01-01

    Transgenic plant cell cultures offer a number of advantages over alternative host expression systems, but so far relatively low product concentrations have been achieved. In this study, transgenic rice cells are used in a two-compartment membrane bioreactor (CELLine 350, Integra Biosciences) for the production of recombinant alpha-1-antitrypsin (rAAT). Expression of rAAT is controlled by the rice alpha-amylase (RAmy3D) promoter, which is induced in the absence of sugar. The extracellular product is retained in the bioreactor's relatively small cell compartment, thereby increasing product concentration. Due to the packed nature of the cell aggregates in the cell compartment, a clarified product solution can be withdrawn from the bioreactor. Active rAAT reached levels of 100-247 mg/L (4-10% of the total extracellular protein) in the cell compartment at 5-6 days postinduction, and multiple inductions of the RAmy3D promoter were demonstrated.

  17. Alpha-1 antitrypsin: a potent anti-inflammatory and potential novel therapeutic agent.

    LENUS (Irish Health Repository)

    Bergin, David A

    2012-04-01

    Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

  18. Alpha-1 antitrypsin is markedly decreased following pulmonary F. tularensis challenge

    Directory of Open Access Journals (Sweden)

    James Patrick Chambers

    2011-12-01

    Full Text Available Alpha-1 antitrypsin, a small glycoprotein clade A serpine serine protease inhibitor of neutrophil elastase has been shown to increase in humans following bacterial and viral infection. However, we report here significant reduction of this major inhibitor of elastase in plasma of F. tularensis LVS and SCHU S4 (Type A strain following pulmonary challenge. Consistent with an imbalance of protease-antiprotease function at the alveolar level in lungs of infected animals, increased elastase activity was observed in lung lavage fluids accompanied by decrease lung function, i.e., loss of lung elastance with concomitant increase of pulmonary hysteresistivity. These data are suggestive of targeted tissue destruction via unchecked neutrophhil elastase activity in infected animals.

  19. Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Caitriona McLean

    2009-01-01

    Full Text Available Caitriona McLean*, Catherine M Greene*, Noel G McElvaneyRespiratory Research Division, Dept. Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland; *Each of these authors contributed equally to this workAbstract: Alpha-1 antitrypsin (A1AT is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to <35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys. ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs and RNA interference (RNAi, which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.Keywords: alpha-1 antitrypsin deficiency, siRNA, peptide nucleic acid, ribozymes

  20. Inhibition of Lassa virus glycoprotein cleavage and multicycle replication by site 1 protease-adapted alpha(1-antitrypsin variants.

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    Anna Maisa

    Full Text Available BACKGROUND: Proteolytic processing of the Lassa virus envelope glycoprotein precursor GP-C by the host proprotein convertase site 1 protease (S1P is a prerequisite for the incorporation of the subunits GP-1 and GP-2 into viral particles and, hence, essential for infectivity and virus spread. Therefore, we tested in this study the concept of using S1P as a target to block efficient virus replication. METHODOLOGY/PRINCIPAL FINDING: We demonstrate that stable cell lines inducibly expressing S1P-adapted alpha(1-antitrypsin variants inhibit the proteolytic maturation of GP-C. Introduction of the S1P recognition motifs RRIL and RRLL into the reactive center loop of alpha(1-antitrypsin resulted in abrogation of GP-C processing by endogenous S1P to a similar level observed in S1P-deficient cells. Moreover, S1P-specific alpha(1-antitrypsins significantly inhibited replication and spread of a replication-competent recombinant vesicular stomatitis virus expressing the Lassa virus glycoprotein GP as well as authentic Lassa virus. Inhibition of viral replication correlated with the ability of the different alpha(1-antitrypsin variants to inhibit the processing of the Lassa virus glycoprotein precursor. CONCLUSIONS/SIGNIFICANCE: Our data suggest that glycoprotein cleavage by S1P is a promising target for the development of novel anti-arenaviral strategies.

  1. Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.

    LENUS (Irish Health Repository)

    Greene, C M

    2010-05-01

    alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival.

  2. How Can We Improve the Detection of Alpha1-Antitrypsin Deficiency?

    Directory of Open Access Journals (Sweden)

    Ilaria Ferrarotti

    Full Text Available The Z deficiency in α1-antitrypsin (A1ATD is an under-recognized condition. Alpha1-antitrypsin (A1AT is the main protein in the α1-globulin fraction of serum protein electrophoresis (SPE; however, evaluation of the α1-globulin protein fraction has received very little attention. Serum Z-type A1AT manifests in polymeric forms, but their interference with quantitative immunoassays has not been reported. Here, 214 894 samples were evaluated by SPE at the G. Fracastoro Hospital of Verona, Italy. Patients with an A1AT level ≤ 0.92 g/L were recalled to complete A1ATD diagnosis. In parallel, to qualitatively and quantitatively characterize A1AT, sera samples from 10 PiZZ and 10 PiMM subjects obtained at the National Institute of Tuberculosis and Lung Diseases in Warsaw, Poland, were subjected to non-denaturing 7.5% PAGE and 7.5% SDS-PAGE followed by Western blot. Moreover, purified A1AT was heated at 60°C and analyzed by a non-denaturing PAGE and 4-15% gradient SDS-PAGE followed by Western blot as well as by isolelectrofocusing and nephelometry. A total of 966 samples manifested percentages ≤ 2.8 or a double band in the alpha1-zone. According to the nephelometry data, 23 samples were classified as severe (A1AT ≤ 0.49 g/L and 462 as intermediate (A1AT >0.49≤ 1.0 g/L A1ATD. Twenty subjects agreed to complete the diagnosis and an additional 21 subjects agreed to family screening. We detected 9 cases with severe and 26 with intermediate A1ATD. Parallel experiments revealed that polymerization of M-type A1AT, when measured by nephelometry or isolelectrofocusing, yields inaccurate results, leading to the erroneous impression that it was Z type and not M-type A1AT. We illustrate the need for confirmation of Z A1AT values by "state of the art" method. Clinicians should consider a more in-depth investigation of A1ATD in patients when they exhibit serum polymers and low α1-globulin protein levels by SPE.

  3. How Can We Improve the Detection of Alpha1-Antitrypsin Deficiency?

    Science.gov (United States)

    Trevisan, Maria Teresa; Dresel, Marc; Koczulla, Rembert; Ottaviani, Stefania; Baldo, Raffaele; Gorrini, Marina; Sala, Giorgia; Cavallon, Luana; Welte, Tobias; Chorostowska-Wynimko, Joanna; Luisetti, Maurizio; Janciauskiene, Sabina

    2015-01-01

    The Z deficiency in α1-antitrypsin (A1ATD) is an under-recognized condition. Alpha1-antitrypsin (A1AT) is the main protein in the α1-globulin fraction of serum protein electrophoresis (SPE); however, evaluation of the α1-globulin protein fraction has received very little attention. Serum Z-type A1AT manifests in polymeric forms, but their interference with quantitative immunoassays has not been reported. Here, 214 894 samples were evaluated by SPE at the G. Fracastoro Hospital of Verona, Italy. Patients with an A1AT level ≤ 0.92 g/L were recalled to complete A1ATD diagnosis. In parallel, to qualitatively and quantitatively characterize A1AT, sera samples from 10 PiZZ and 10 PiMM subjects obtained at the National Institute of Tuberculosis and Lung Diseases in Warsaw, Poland, were subjected to non-denaturing 7.5% PAGE and 7.5% SDS-PAGE followed by Western blot. Moreover, purified A1AT was heated at 60°C and analyzed by a non-denaturing PAGE and 4–15% gradient SDS-PAGE followed by Western blot as well as by isolelectrofocusing and nephelometry. A total of 966 samples manifested percentages ≤ 2.8 or a double band in the alpha1-zone. According to the nephelometry data, 23 samples were classified as severe (A1AT ≤ 0.49 g/L) and 462 as intermediate (A1AT >0.49≤ 1.0 g/L) A1ATD. Twenty subjects agreed to complete the diagnosis and an additional 21 subjects agreed to family screening. We detected 9 cases with severe and 26 with intermediate A1ATD. Parallel experiments revealed that polymerization of M-type A1AT, when measured by nephelometry or isolelectrofocusing, yields inaccurate results, leading to the erroneous impression that it was Z type and not M-type A1AT. We illustrate the need for confirmation of Z A1AT values by “state of the art” method. Clinicians should consider a more in-depth investigation of A1ATD in patients when they exhibit serum polymers and low α1-globulin protein levels by SPE. PMID:26270547

  4. [Relationship between serum levels of C-reactive protein and alpha1-antitrypsin and insulin resistance in obese women].

    Science.gov (United States)

    Ramírez Alvarado, María Matilde; Sánchez Roitz, César

    2014-09-01

    Adipose tissue produces cytokines involved in insulin resistance (IR) such as IL-6, IL-8, TNF-alpha and proinflammatory molecules such as C reactive protein (CRP). alpha1-antitrypsin is an inflammation-sensitive plasma protein. The objective of this study is to determine the correlation between serum CRP high-sensitivity (CRPhs) and alpha1-antitrypsin levels with IR indices in obese Venezuelan women. The study population consisted of 15 normal weight women (BMI 21.8 +/- 1.9 kg/m2) and 15 obese women (BMI 35.3 +/- 5.3 kg/m2). Obese and lean women underwent a 2 h-75 g oral glucose tolerance test and the following indices were calculated: homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta cell function (HOMA-beta), Matsuda Index and Insulinogenic Index. The relationship between serum CRPhs and alpha1-antitrypsin levels and these indices were determined. Obese women had higher CRPhs levels (p = 0.001) compared with normal weight women. In obese women, serum CRPhs levels were positively correlated with HOMA-IR (r = 0.73, p = 0.0021), HOMA-beta (r = 0.53, p = 0.031) and negatively correlated with the Matsuda Index (r = -0.60, p = 0.017). No correlation between serum levels of alpha1-antitrypsin and IR indices in the obese group and the lean group was observed. There was a relation between serum CRPhs levels and insulin resistance, suggesting a role of subclinical inflammation in IR.

  5. Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD

    Directory of Open Access Journals (Sweden)

    Sabri Denden

    2010-01-01

    Full Text Available Alpha-1-antitrypsin (AAT plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD. In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val, PiM2 (Arg101His, PiM3 (Glu376Asp, PiS (Glu264Val and PiZ (Glu342Lys SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3 and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms.

  6. Gene targeted therapeutics for liver disease in alpha-1 antitrypsin deficiency.

    LENUS (Irish Health Repository)

    McLean, Caitriona

    2009-01-01

    Alpha-1 antitrypsin (A1AT) is a 52 kDa serine protease inhibitor that is synthesized in and secreted from the liver. Although it is present in all tissues in the body the present consensus is that its main role is to inhibit neutrophil elastase in the lung. A1AT deficiency occurs due to mutations of the A1AT gene that reduce serum A1AT levels to <35% of normal. The most clinically significant form of A1AT deficiency is caused by the Z mutation (Glu342Lys). ZA1AT polymerizes in the endoplasmic reticulum of liver cells and the resulting accumulation of the mutant protein can lead to liver disease, while the reduction in circulating A1AT can result in lung disease including early onset emphysema. There is currently no available treatment for the liver disease other than transplantation and therapies for the lung manifestations of the disease remain limited. Gene therapy is an evolving field which may be of use as a treatment for A1AT deficiency. As the liver disease associated with A1AT deficiency may represent a gain of function possible gene therapies for this condition include the use of ribozymes, peptide nucleic acids (PNAs) and RNA interference (RNAi), which by decreasing the amount of aberrant protein in cells may impact on the pathogenesis of the condition.

  7. Alpha-1 Antitrypsin Deficiency Targeted Testing and Augmentation Therapy: A Canadian Thoracic Society Clinical Practice Guideline

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    DD Marciniuk

    2012-01-01

    Full Text Available Alpha-1 antitrypsin (A1AT functions primarily to inhibit neutrophil elastase, and deficiency predisposes individuals to the development of chronic obstructive pulmonary disease (COPD. Severe A1AT deficiency occurs in one in 5000 to one in 5500 of the North American population. While the exact prevalence of A1AT deficiency in patients with diagnosed COPD is not known, results from small studies provide estimates of 1% to 5%. The present document updates a previous Canadian Thoracic Society position statement from 2001, and was initiated because of lack of consensus and understanding of appropriate patients suitable for targeted testing for A1AT deficiency, and for the use of A1AT augmentation therapy. Using revised guideline development methodology, the present clinical practice guideline document systematically reviews the published literature and provides an evidence-based update. The evidence supports the practice that targeted testing for A1AT deficiency be considered in individuals with COPD diagnosed before 65 years of age or with a smoking history of <20 pack years. The evidence also supports consideration of A1AT augmentation therapy in nonsmoking or exsmoking patients with COPD (forced expiratory volume in 1 s of 25% to 80% predicted attributable to emphysema and documented A1AT deficiency (level ≤11 μmol/L who are receiving optimal pharmacological and nonpharmacological therapies (including comprehensive case management and pulmonary rehabilitation because of benefits in computed tomography scan lung density and mortality.

  8. Evidence for unfolded protein response activation in monocytes from individuals with alpha-1 antitrypsin deficiency.

    LENUS (Irish Health Repository)

    Carroll, Tomás P

    2010-04-15

    The hereditary disorder alpha-1 antitrypsin (AAT) deficiency results from mutations in the SERPINA1 gene and presents with emphysema in young adults and liver disease in childhood. The most common form of AAT deficiency occurs because of the Z mutation, causing the protein to fold aberrantly and accumulate in the endoplasmic reticulum (ER). This leads to ER stress and contributes significantly to the liver disease associated with the condition. In addition to hepatocytes, AAT is also synthesized by monocytes, neutrophils, and epithelial cells. In this study we show for the first time that the unfolded protein response (UPR) is activated in quiescent monocytes from ZZ individuals. Activating transcription factor 4, X-box binding protein 1, and a subset of genes involved in the UPR are increased in monocytes from ZZ compared with MM individuals. This contributes to an inflammatory phenotype with ZZ monocytes exhibiting enhanced cytokine production and activation of the NF-kappaB pathway when compared with MM monocytes. In addition, we demonstrate intracellular accumulation of AAT within the ER of ZZ monocytes. These are the first data showing that Z AAT protein accumulation induces UPR activation in peripheral blood monocytes. These findings change the current paradigm regarding lung inflammation in AAT deficiency, which up until now was derived from the protease-anti-protease hypothesis, but which now must include the exaggerated inflammatory response generated by accumulated aberrantly folded AAT in circulating blood cells.

  9. Lung clearance index for monitoring early lung disease in alpha-1-antitrypsin deficiency.

    Science.gov (United States)

    Fuchs, Susanne I; Schwerk, Nicolaus; Pittschieler, Klaus; Ahrens, Frank; Baden, Winfried; Bals, Robert; Fähndrich, Sebastian; Gleiber, Wolfgang; Griese, Matthias; Hülskamp, Georg; Köhnlein, Thomas; Reckling, Ludmilla; Rietschel, Ernst; Staab, Doris; Gappa, Monika

    2016-07-01

    Patients with alpha-1-antitrypsin deficiency (AATD) and a PI-ZZ genotype are at high risk to develop severe emphysema during adulthood. However, little is known about early stages of emphysema and disease manifestation in other PI-types. Spirometry is commonly used for monitoring although early manifestation of emphysema is suspected within the peripheral airways that are not accessible by forced expiratory manoeuvres. We hypothesized that the Lung Clearance Index (LCI) derived from multiple breath nitrogen-washout (N2-washout) is useful to bridge this diagnostic gap. Patients from age 4 years onward and different PI-types performed N2-washout and spirometry. Results were compared to controls. 193 patients (4-79 years, 75% PI-ZZ) and 33 controls (8-60 years) were included. Mean (SD) LCI in patients was 9.1 (3.1) and 6.3 (0.6) in controls (p ≤ 0.001). 47% of adult patients with other than PI-ZZ genotypes and 39% of all patients with normal spirometry had abnormal LCIs. The LCI measured by N2-washout discriminates between patients with AATD and controls, reflects AATD related lung disease in all stages and appears to identify early peripheral lung changes in younger age than spirometry. We conclude that a normal spirometry does not exclude presence of AATD related lung disease even in genotypes other than PI-ZZ.

  10. Selenoprotein S/SEPS1 modifies endoplasmic reticulum stress in Z variant alpha1-antitrypsin deficiency.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2009-06-19

    Z alpha(1)-antitrypsin (ZAAT) deficiency is a disease associated with emphysematous lung disease and also with liver disease. The liver disease of AAT deficiency is associated with endoplasmic reticulum (ER) stress. SEPS1 is a selenoprotein that, through a chaperone activity, decreases ER stress. To determine the effect of SEPS1 on ER stress in ZAAT deficiency, we measured activity of the grp78 promoter and levels of active ATF6 as markers of the unfolded protein response in HepG2 cells transfected with the mutant form of AAT, a ZAAT transgene. We evaluated levels of NFkappaB activity as a marker of the ER overload response. To determine the effect of selenium supplementation on the function of SEPS1, we investigated glutathione peroxidase activity, grp78 promoter activity, and NFkappaB activity in the presence or absence of selenium. SEPS1 reduced levels of active ATF6. Overexpression of SEPS1 also inhibited grp78 promoter and NFkappaB activity, and this effect was enhanced in the presence of selenium supplementation. This finding demonstrates a role for SEPS1 in ZAAT deficiency and suggests a possible therapeutic potential for selenium supplementation.

  11. Is PiSS Alpha-1 Antitrypsin Deficiency Associated with Disease?

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    Dawn McGee

    2010-01-01

    Full Text Available Background. Alpha-1 antitrypsin deficiency (AAT is an inherited condition that predisposes to lung and/or liver disease. Objective. The current study examined the clinical features of the PiSS genotype. Methods. Nineteen study participants (PiSS and 29 matched control participants (PiMM were telephone interviewed using a standardized questionnaire. Demographic features, cigarette smoking, vocation, medication history, and clinical diagnoses were compared. Statistical analysis was performed. Finally, a comprehensive literature review was performed by two investigators. Results. 12/19 (63.2% study participants reported the presence of lung and/or liver disease compared to 12/29 (41.4% control participants. There trended toward having a higher frequency of medication allergies in the study population (42.11% versus 20.69%. Conclusions. The PiSS genotype was associated with a similar incidence of obstructive lung disease to controls. Selective bias intrinsic in testing for AAT deficiency and the rarity of the PiSS genotype will make future study of this association dependent on population-based tests.

  12. Conductivity in Exhaled Breath Condensate from Subjects with Emphysema and Type ZZ alpha-1-Antitrypsin Deficiency.

    Science.gov (United States)

    Stolk, Jan; Fumagalli, Marco; Viglio, Simona; Iadarola, Paolo

    2015-05-01

    The assessment of biomarkers in biological samples from the lung has long been employed. Upon cooling water vapor present in exhaled breath, variable amounts of droplets of condensate (EBC) containing volatile and non-volatile compounds may be easily and non-invasively obtained from patients of any age.Objective of the present study was to compare the level of EBC conductivity determined for cohorts of individuals with different inflammatory lung disorders with that of healthy never-smoking individuals.The conductivity in EBC of PiZZ-Alpha-1-antitrypsin deficiency patients with a diagnosis of emphysema (PiZZ-AATD) was 3 fold lower than in spouse controls (54.5 ± 11.6 vs 165.3 ± 10.7 μS/cm). Non-PiZZ emphysema patients had conductivity in EBC of 59.6 ± 5.8 μS/cm and patients with sarcoidosis without airflow obstruction had EBC conductivity of 178,8 ± 6,2 μS/cm, 
not significantly different (p = 0.5) from healthy controls. Conductivity in serial EBC samples from patients with PiZZ-AATD emphysema and healthy controls was stable in 6 different samples collected over a period of 14 months. We conclude that conductivity values in EBC can be used as a correction factor for dilution of non-volatile components in EBC.

  13. C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function

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    Nancy Blaurock

    2016-01-01

    Full Text Available Systemic inflammatory response syndrome (SIRS is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim of this study was to elucidate the pathophysiological role of CAAP48, a C-terminal alpha-1 antitrypsin fragment, that we found to be elevated in septic patients and to apply this peptide as diagnostic marker for infectious and noninfectious etiologies of SIRS. Incubation of human polymorphonuclear neutrophils with synthetic CAAP48, the SNP-variant CAAP47, and several control peptides revealed intense neutrophil activation, induction of neutrophil chemotaxis, reduction of neutrophil viability, and release of cytokines. We determined the abundance of CAAP48 in patients with severe sepsis, severe SIRS of noninfectious origin, and viral infection. CAAP48 levels were 3-4-fold higher in patients with sepsis compared to SIRS of noninfectious origin and allowed discrimination of those patients with high sensitivity and specificity. Our results suggest that CAAP48 is a promising discriminatory sepsis biomarker with immunomodulatory functions, particularly on human neutrophils, supporting its important role in the host response and pathophysiology of sepsis.

  14. Aberrant disulphide bonding contributes to the ER retention of alpha1-antitrypsin deficiency variants.

    Science.gov (United States)

    Ronzoni, Riccardo; Berardelli, Romina; Medicina, Daniela; Sitia, Roberto; Gooptu, Bibek; Fra, Anna Maria

    2016-02-15

    Mutations in alpha1-antitrypsin (AAT) can cause the protein to polymerise and be retained in the endoplasmic reticulum (ER) of hepatocytes. The ensuing systemic AAT deficiency leads to pulmonary emphysema, while intracellular polymers are toxic and cause chronic liver disease. The severity of this process varies considerably between individuals, suggesting the involvement of mechanistic co-factors and potential for therapeutically beneficial interventions. We show in Hepa1.6 cells that the mildly polymerogenic I (Arg39Cys) AAT mutant forms aberrant inter- and intra-molecular disulphide bonds involving the acquired Cys39 and the only cysteine residue in the wild-type (M) sequence (Cys232). Substitution of Cys39 to serine partially restores secretion, showing that disulphide bonding contributes to the intracellular retention of I AAT. Covalent homodimers mediated by inter-Cys232 bonding alone are also observed in cells expressing the common Z and other polymerising AAT variants where conformational behaviour is abnormal, but not in those expressing M AAT. Prevention of such disulphide linkage through the introduction of the Cys232Ser mutation or by treatment of cells with reducing agents increases Z AAT secretion. Our results reveal that disulphide interactions enhance intracellular accumulation of AAT mutants and implicate the oxidative ER state as a pathogenic co-factor. Redox modulation, e.g. by anti-oxidant strategies, may therefore be beneficial in AAT deficiency-associated liver disease.

  15. The Influence of Cigarette Smoking on Gingival Bleeding and Serum Concentrations of Haptoglobin and Alpha 1-Antitrypsin

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    Fouad H. Al-Bayaty

    2013-01-01

    Full Text Available The objectives of this study were to evaluate the influence of cigarette smoking on gingival bleeding and serum concentrations of cotinine, haptoglobin, and alpha 1-antitrypsin in Malaysian smokers. A total of 197 male smokers and nonsmokers were recruited for this study. Plaque index, bleeding on probing (BOP, and levels of serum cotinine, haptoglobin, and alpha 1-antitrypsin were evaluated. The data were analyzed using SPSS version 20.0, with the significance level set at α≤0.05. Linear regression analyses were performed. The mean cigarette consumption per day was 13.39±5.75 cigarettes; the mean duration was 16.03±8.78 years. Relatively low BOP values (26.05±1.48 and moderate plaque indexes (51.35±11.27 were found. The levels of serum cotinine (106.9±30.71 ng/dL, haptoglobin (76.04±52.48 mg/dL, and alpha 1-antitrypsin (141.90±18.40 mg/dL were significantly higher in smokers compared to non-smokers. Multiple logistic regression models for all variables and smokers demonstrated observed differences between BOP, the number of cigarettes per day, and duration of smoking, while serum cotinine, haptoglobin and alpha-1 antitrypsin levels showed no significant differences. Duration of smoking (years and the cotinine level in serum showed a significant correlation with plaque index. The present analysis demonstrated that the duration of smoking in years, but not the number of cigarettes smoked per day, was associated with reduced gingival bleeding in smokers.

  16. Individualized lung function trends in alpha-1-antitrypsin deficiency: a need for patience in order to provide patient centered management?

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    Stockley RA

    2016-08-01

    Full Text Available Robert A Stockley,1 Ross G Edgar,1 Anilkumar Pillai,1 Alice M Turner2 1Department of Lung Function and Sleep, University Hospitals Birmingham NHS Foundation Trust, 2Department of Inflammation and Ageing, University of Birmingham, Edgbaston, Birmingham, UK Background: Chronic obstructive pulmonary disease (COPD is characterized by fixed airflow obstruction and accelerated decline of forced expired volume in 1 second (FEV1. Alpha-1-antitrypsin deficiency is a genetic cause of COPD and associated with more rapid decline in lung function, even in some never smokers (NS but the potential for individualized assessment to reveal differences when compared to group analyses has rarely been considered. Methods: We analyzed decline in post-bronchodilator FEV1 and gas transfer (% predicted over at least 3 years (mean= 6.11, 95% CI 5.80–6.41 in our unique data set of 482 patients with alpha-1-antitrypsin deficiency (PiZ to determine individual rates of decline, implications for prognosis, and potential clinical management. Findings: There was a marked variation in individual rates of FEV1 decline from levels consistent with normal aging (observed in 23.5% of patients with established COPD, 57.5% of those without to those of rapidly declining COPD. Gas transfer did not decline in 12.8% of NS and 20.7% of ex-smokers with established COPD (33.3% and 25.0%, respectively, for those without COPD. There was no correlation between decline in gas transfer and FEV1 for those with COPD, although a weak relationship existed for those without (r=0.218; P<0.025. Conclusion: These data confirm differing individual rates of lung function decline in alpha-1-antitrypsin deficiency, indicating the importance of comprehensive physiological assessment and a personalized approach to patient management. Keywords: alpha-1-antitrypsin deficiency, COPD, emphysema, lung function

  17. Alpha-1 antitrypsin protein and gene therapies decrease autoimmunity and delay arthritis development in mouse model

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    Atkinson Mark A

    2011-02-01

    Full Text Available Abstract Background Alpha-1 antitrypsin (AAT is a multi-functional protein that has anti-inflammatory and tissue protective properties. We previously reported that human AAT (hAAT gene therapy prevented autoimmune diabetes in non-obese diabetic (NOD mice and suppressed arthritis development in combination with doxycycline in mice. In the present study we investigated the feasibility of hAAT monotherapy for the treatment of chronic arthritis in collagen-induced arthritis (CIA, a mouse model of rheumatoid arthritis (RA. Methods DBA/1 mice were immunized with bovine type II collagen (bCII to induce arthritis. These mice were pretreated either with hAAT protein or with recombinant adeno-associated virus vector expressing hAAT (rAAV-hAAT. Control groups received saline injections. Arthritis development was evaluated by prevalence of arthritis and arthritic index. Serum levels of B-cell activating factor of the TNF-α family (BAFF, antibodies against both bovine (bCII and mouse collagen II (mCII were tested by ELISA. Results Human AAT protein therapy as well as recombinant adeno-associated virus (rAAV8-mediated hAAT gene therapy significantly delayed onset and ameliorated disease development of arthritis in CIA mouse model. Importantly, hAAT therapies significantly reduced serum levels of BAFF and autoantibodies against bCII and mCII, suggesting that the effects are mediated via B-cells, at least partially. Conclusion These results present a new drug for arthritis therapy. Human AAT protein and gene therapies are able to ameliorate and delay arthritis development and reduce autoimmunity, indicating promising potential of these therapies as a new treatment strategy for RA.

  18. Chitosan-genipin nanohydrogel as a vehicle for sustained delivery of alpha-1 antitrypsin.

    Science.gov (United States)

    Ghasemi, Ahmad; Mohtashami, Mahnaz; Sheijani, Samaneh Sotoudeh; Aliakbari, Kamelya

    2015-01-01

    Alpha-1antitrypsin (A1AT) deficiency, an inherited disorder, has been shown to be the cause of lung diseases such as emphysema and chronic obstructive pulmonary disease. One of the treatment strategies to provide appropriate and adequate concentrations of A1AT in the lungsis the application of nanoparticles (NPs) in pulmonary drug delivery. In the current study, biocompatible nanohydrogels were prepared using chemically cross-linked chitosan with ginepin, a natural cross linker reagent, and used as a carrier to deposit A1AT into the lung tissue. Colloidal and monodispersed NPs were synthesized through reverse microemulsion. Nanohydrogels were characterized with TEM, LLS, FTIR, ZTEA potential, UV spectrum, and swelling test. Encapsulation efficacy was determined at different concentrations of A1AT using Bradford assay. Effect of processing variables such as pH, loading efficiency, and release media components on drug release profile was determined in simulated lung fluids. To evaluate the inhibitory activity of the A1AT after release from NPs, trypsin inhibitory capacity assay was carried out. Results from FTIR and UV spectrum confirmed the development of chitosan cross linkage. Spherical chitosan-genipin NPs were sized from 30-100 nm. NPs exhibited the ability to release 49% of the drug within 12-dayperiodatpH 7. However, there were variations with the drug release profile due to pH variations and loading efficacy. Drug release was higher in pseudo alveolar fluid in comparison with saline solution. These data indicate that application of chitosan nanohydrogels can be a useful tool for sustained release of A1AT in the lung tissue.

  19. Alpha-1 antitrypsin deficiency and the risk of hepatocellularcarcinoma in end-stage liver disease

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To evaluate the association between alpha-1antitrypsin deficiency (A1ATD) and hepatocellularcarcinoma (HCC) in patients with end-stage liver disease(ESLD).METHODS: Patients with cirrhosis and ESLD referred tothe Cleveland Clinic Foundation for liver transplantationbetween 2003 and 2014 were included in the study (N =675). ESLD was defined as having histological features ofcirrhosis and/or radiological evidence of cirrhosis in thecontext of portal hypertension (ascites, variceal bleeding,thrombocytopenia, or hepatic encephalopathy). A1ATDwas diagnosed using phenotype characterization (MZor ZZ), liver biopsy detection of PAS-positive diastaseresistant(PAS+) globules, or both. Patients with othercauses of liver diseases such as hepatitis C virus (HCV),alcoholic liver disease and non-alcoholic steatohepatitis(NASH) or NASH were also included in the study. HCCwas diagnosed by using imaging modalities, biopsyfindings, or explanted liver inspection. Follow-up timewas defined as the number of years from the diagnosisof cirrhosis to the diagnosis of hepatocellular carcinoma,or from the diagnosis of cirrhosis to the last follow upvisit. The rate of HCC was assessed using time-tointervalanalysis for interval censored data.RESULTS: This study included 675 patients. 7% ofsubjects had A1ATD (n = 47). Out of all subjects whodid not have A1ATD, 46% had HCV, 17% had alcoholicliver disease, 19% had NASH and 18% had anotherprimary diagnosis. Of the 47 subjects with A1ATD, 15had a primary diagnosis of A1ATD (PI*ZZ phenotypeand PAS+ globules), 8 had a PI*MZ phenotype alone,14 had PAS+ alone, and 10 had both the PI*MZphenotype and PAS+. Median follow-up time was 3.4(25th, 75th percentiles: 1, 5.2) years. The overall rate ofhepatocellular carcinoma in all subjects was 29% (n =199). In the A1ATD group, the incidence rate of HCCwas 8.5% compared to 31% in the group of patientswith other causes of cirrhosis (P = 0

  20. Alpha-1 proteinase inhibitors for the treatment of alpha-1 antitrypsin deficiency: safety, tolerability, and patient outcomes

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    Chotirmall SH

    2015-01-01

    Full Text Available Sanjay H Chotirmall,1 Mazen Al-Alawi,2 Thomas McEnery,2 Noel G McElvaney2 1Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 2Department of Respiratory Medicine, Beaumont Hospital, Dublin, Republic of Ireland Abstract: Alpha-1 antitrypsin (AAT deficiency remains an underrecognized genetic disease with predominantly pulmonary and hepatic manifestations. AAT is derived primarily from hepatocytes; however, macrophages and neutrophils are secondary sources. As the natural physiological inhibitor of several proteases, most importantly neutrophil elastase (NE, it plays a key role in maintaining pulmonary protease–antiprotease balance. In deficient states, unrestrained NE activity promotes damage to the lung matrix, causing structural defects and impairing host defenses. The commonest form of AAT deficiency results in a mutated Z AAT that is abnormally folded, polymerized, and aggregated in the liver. Consequently, systemic levels are lower, resulting in diminished pulmonary concentrations. Hepatic disease occurs due to liver aggregation of the protein, while lung destruction ensues from unopposed protease-mediated damage. In this review, we will discuss AAT deficiency, its clinical manifestations, and augmentation therapy. We will address the safety and tolerability profiles of AAT replacement in the context of patient outcomes and cost-effectiveness and outline future directions for work in this field. Keywords: alpha-1, augmentation, deficiency, replacement, emphysema

  1. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Dirksen, A; Piitulainen, E; Parr, D G;

    2009-01-01

    for the assessment of the therapeutic effect of augmentation therapy in subjects with alpha(1)-antitrypsin (alpha(1)-AT) deficiency. In total, 77 subjects (protease inhibitor type Z) were randomised to weekly infusions of 60 mg x kg(-1) human alpha(1)-AT (Prolastin) or placebo for 2-2.5 yrs. The primary end......-point was change in CT lung density, and an exploratory approach was adopted to identify optimal methodology, including two methods of adjustment for lung volume variability and two statistical approaches. Other end-points were exacerbations, health status and physiological indices. CT was more sensitive than...... other measures of emphysema progression, and the changes in CT and forced expiratory volume in 1 s were correlated. All methods of densitometric analysis concordantly showed a trend suggestive of treatment benefit (p-values for Prolastin versus placebo ranged 0.049-0.084). Exacerbation frequency...

  2. Art, alpha-1-antitrypsin polymorphisms and intense creative energy: blessing or curse?

    Science.gov (United States)

    Schmechel, Donald Everett

    2007-09-01

    Persons heterozygous for Z, S and rare alpha-1-antitrypsin (AAT, SERPIN1A) polymorphisms (ca. 9% of population) are often considered 'silent' carriers with increased vulnerability to environmentally modulated liver and lung disease. They may have significantly more anxiety and bipolar spectrum disorders, nutritional compromise, and white matter disease [Schmechel DE, Browndyke J, Ghio A. Strategies for the dissection of genetic-environmental interactions in neurodegenerative disorders. Neurotoxicology 2006;27:637-57]. Given association of art and mood disorders, we examined occupation and artistic vocation from this same series. One thousand five hundred and thirty-seven consecutive persons aged 16-90 years old received comprehensive work-up including testing for AAT 'phenotype' and level, nutritional factors, and inflammatory, iron and copper indices. Occupations were grouped by Bureau of Labor Standards classification and information gathered on artistic activities. Proportion of reactive airway disease, obstructive pulmonary disease, and pre-existing anxiety disorder or bipolar disorder were significantly increased in persons carrying AAT non-M polymorphisms compared to normal MM genotype (respectively, 10, 20, 21, and 33% compared to 8, 12, 11, and 9%; contingency table, pulmonary: chi2 37, p=0.0001; affective disorder: chi2=171, p=0.0001). In persons with artistic avocation (n=189) or occupation (n=57), AAT non-M polymorphisms are significantly increased (respectively, proportions of 44 and 40% compared to background rate of 9%; contingency table, avocation: chi2=172, p=0.0001; occupation: chi2=57, p=0.0007). Artistic ability and 'anxiety/bipolar spectrum' mood disorders may represent phenotypic attributes that had selective advantage during recent human evolution, an 'intensive creative energy' (ICE) behavioral phenotype. Background proportion of ICE of 7% consists of 49 of 1312 persons with AAT MM genotype (4%), and 58 of 225 persons with non-MM genotypes

  3. Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update

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    Blanco I

    2017-02-01

    Full Text Available Ignacio Blanco,1 Patricia Bueno,2 Isidro Diego,3 Sergio Pérez-Holanda,4 Francisco Casas-Maldonado,5 Cristina Esquinas,6 Marc Miravitlles6,7 1Alpha1-Antitrypsin Deficiency Spanish Registry (REDAAT, Fundación Respira, Spanish Society of Pneumology and Thoracic Surgery (SEPAR, Barcelona, 2Internal Medicine Department, County Hospital of Jarrio, 3Materials and Energy Department, School of Mining Engineering, Oviedo University, 4Surgical Department, University Central Hospital of Asturias (HUCA, Oviedo, Principality of Asturias, 5Pneumology Department, Complejo Hospitalario Universitario de Granada, Granada, 6Pneumology Department, Hospital Universitari Vall d’Hebron, 7CIBER de Enfermedades Respiratorias (CIBERES, Barcelona, Spain Abstract: In alpha-1 antitrypsin deficiency (AATD, the Z allele is present in 98% of cases with severe disease, and knowledge of the frequency of this allele is essential from a public health perspective. However, there is a remarkable lack of epidemiological data on AATD worldwide, and many of the data currently used are outdated. Therefore, the objective of this study was to update the knowledge of the frequency of the Z allele to achieve accurate estimates of the prevalence and number of Pi*ZZ genotypes worldwide based on studies performed according to the following criteria: 1 samples representative of the general population, 2 AAT phenotyping characterized by adequate methods, and 3 measurements performed using a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop maps with an inverse distance weighted (IDW-interpolation method, providing numerical and graphical information of Pi*Z distribution worldwide. A total of 224 cohorts from 65 countries were included in the study. With the data provided by these cohorts, a total of 253,404 Pi*ZZ were estimated worldwide: 119,594 in Europe, 91,490 in America and Caribbean, 3,824 in

  4. A comparative ultrastructural and molecular biological study on Chlamydia psittaci infection in alpha-1 antitrypsin deficiency and non-alpha-1 antitrypsin deficiency emphysema versus lung tissue of patients with hamartochondroma

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    Mogilevski Grigori

    2004-09-01

    Full Text Available Abstract Background Chlamydiales are familiar causes of acute and chronic infections in humans and animals. Human pulmonary emphysema is a component of chronic obstructive pulmonary disease (COPD and a condition in which chronic inflammation manifested as bronchiolitis and intra-alveolar accumulation of macrophages is common. It is generally presumed to be of infectious origin. Previous investigations based on serology and immunohistochemistry indicated Chlamydophila pneumoniae infection in cases of COPD. Furthermore, immunofluorescence with genus-specific antibodies and electron microscopy suggested involvement of chlamydial infection in most cases of pulmonary emphysema, but these findings could not be verified by PCR. Therefore, we examined the possibility of other chlamydial species being present in these patients. Methods Tissue samples from patients having undergone lung volume reduction surgery for advanced alpha-1 antitrypsin deficiency (AATD, n = 6 or non-alpha-1 antitrypsin deficiency emphysema (n = 34 or wedge resection for hamartochondroma (n = 14 were examined by transmission electron microscopy and PCR. Results In all cases of AATD and 79.4% of non-AATD, persistent chlamydial infection was detected by ultrastructural examination. Intra-alveolar accumulation of macrophages and acute as well as chronic bronchiolitis were seen in all positive cases. The presence of Chlamydia psittaci was demonstrated by PCR in lung tissue of 66.7% AATD vs. 29.0% non-AATD emphysema patients. Partial DNA sequencing of four positive samples confirmed the identity of the agent as Chlamydophila psittaci. In contrast, Chlamydophila pneumoniae was detected only in one AATD patient. Lung tissue of the control group of non-smokers with hamartochondroma was completely negative for chlamydial bodies by TEM or chlamydial DNA by PCR. Conclusions These data indicate a role of Chlamydophila psittaci in pulmonary emphysema by linking this chronic inflammatory process

  5. A novel SERPINA1 mutation causing serum alpha(1-antitrypsin deficiency.

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    Darren N Saunders

    Full Text Available Mutations in the SERPINA1 gene can cause deficiency in the circulating serine protease inhibitor α(1-Antitrypsin (α(1AT. α(1AT deficiency is the major contributor to pulmonary emphysema and liver disease in persons of European ancestry, with a prevalence of 1 in 2500 in the USA. We present the discovery and characterization of a novel SERPINA1 mutant from an asymptomatic Middle Eastern male with circulating α(1AT deficiency. This 49 base pair deletion mutation (T379Δ, originally mistyped by IEF, causes a frame-shift replacement of the last sixteen α(1AT residues and adds an extra twenty-four residues. Functional analysis showed that the mutant protein is not secreted and prone to intracellular aggregation.

  6. Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis

    DEFF Research Database (Denmark)

    Clemmensen, Stine N; Jacobsen, Lars C; Rørvig, Sara;

    2011-01-01

    . Neutrophils from patients with A1AT-deficiency carrying the (PI)ZZ mutation in the A1AT gene appeared structurally and functionally normal, but A1AT produced in leukocytes of these patients lacked the ability to bind proteases efficiently. We conclude that A1AT generation and release from neutrophils add......Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT is expressed by human neutrophil granulocytes during all developmental stages. A1AT has hitherto only been found associated......1AT is produced at all stages of myeloid maturation in the bone marrow. The production increases as neutrophils enter circulation and increases further upon migration to tissues as observed in skin windows and when blood neutrophils are incubated with granulocyte colony-stimulating factor...

  7. A challenging diagnosis of alpha-1-antitrypsin deficiency: identification of a patient with a novel F/Null phenotype

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    Ringenbach Michael R

    2011-11-01

    Full Text Available Abstract Alpha-1-antitrypsin (A1AT deficiency is a genetic disease characterized by low levels and/or function of A1AT protein. A1AT deficiency can result in the development of COPD, liver disease, and certain skin conditions. The disease can be diagnosed by demonstrating a low level of A1AT protein and genotype screening for S and Z mutations, which are the most common. However, there are many genetic variants in A1AT deficiency, and this screening may miss rarer cases, such as those caused by dysfunctional protein. We identified a patient with a previously unreported F/null phenotype that was missed by routine screening. This case highlights the wide variation in possible mutations, limitations in diagnostics, and the importance of combining clinical suspicion with measurement of protein levels, phenotypic analysis, and in appropriate cases expanded genetic analysis.

  8. Alpha-1 antitrypsin and granulocyte colony-stimulating factor as serum biomarkers of disease severity in ulcerative colitis

    DEFF Research Database (Denmark)

    Soendergaard, Christoffer; Nielsen, Ole Haagen; Seidelin, Jakob Benedict

    2015-01-01

    biomarkers are currently needed for identification of patients with mild or moderate disease activity. Using a commercially available platform, we aimed at identifying serum biomarkers that are able to grade the disease severity. METHODS: Serum samples from 65 patients with UC with varying disease activity......-stimulating factor produced a predictive model with an AUC of 0.72 when differentiating mild and moderate UC, and an AUC of 0.96 when differentiating moderate and severe UC, the latter being as reliable as CRP. CONCLUSIONS: Alpha-1 antitrypsin is identified as a potential serum biomarker of mild-to-moderate disease......BACKGROUND: Initial assessment of patients with ulcerative colitis (UC) is challenging and relies on apparent clinical symptoms and measurements of surrogate markers (e.g., C-reactive protein [CRP] or similar acute phase proteins). As CRP only reliably identifies patients with severe disease, novel...

  9. Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma

    Science.gov (United States)

    Lin, Shih-Yi; Chang, Chao-Hsiang; Wu, His-Chin; Lin, Ching-Chan; Chang, Kai-Po; Yang, Chi-Rei; Huang, Chi-Ping; Hsu, Wu-Huei; Chang, Chiz-Tzung; Chen, Chao-Jung

    2016-01-01

    MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1-antitrypsin (p = 0.038) and H2B1K (p = 0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p exosome proteins alpha 1-antitrypsin and histone H2B1K, which are identified through MALDI-TOF analysis, could facilitate rapid diagnosis and prognosis of UC. PMID:27686150

  10. RELEVANCE OF CLASSIC ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY (C-ANCA)-MEDIATED INHIBITION OF PROTEINASE 3-ALPHA-1-ANTITRYPSIN COMPLEXATION TO DISEASE-ACTIVITY IN WEGENER-GRANULOMATOSIS

    NARCIS (Netherlands)

    DOLMAN, KM; STEGEMAN, CA; VANDEWIEL, BA; HACK, CE; BORNE, AEGKV; KALLENBERG, CGM; GOLDSCHMEDING, R

    1993-01-01

    In the sera of patients with Wegener's granulomatosis (WG), C-ANCA can be detected that are directed against proteinase 3 (PR3). We have previously observed that C-ANCA interfere with PR3 proteolytic activity and with complexation of PR3 with its major physiologic inhibitor, alpha1-antitrypsin (alph

  11. Effect of Recombinant alpha1-Antitrypsin Fc-Fused (AAT-Fc)Protein on the Inhibition of Inflammatory Cytokine Production and Streptozotocin-Induced Diabetes

    NARCIS (Netherlands)

    Lee, S.; Lee, Y.; Hong, K.; Hong, J.; Bae, S.; Choi, J.; Jhun, H.; Kwak, A.; Kim, E.; Jo, S.; Dinarello, C.A.; Kim, S.

    2013-01-01

    alpha1-Antitrypsin (AAT) is a member of the serine proteinase inhibitor family that impedes the enzymatic activity of serine proteinases, including human neutrophil elastase, cathepsin G and neutrophil proteinase 3. Here, we expressed recombinant AAT by fusing the intact AAT gene to the constant reg

  12. Deficiência de alfa-1 antitripsina: diagnóstico e tratamento Alpha-1 antitrypsin deficiency: diagnosis and treatment

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    Aquiles A Camelier

    2008-07-01

    Full Text Available A deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que determina polimerização e acúmulo dentro dos hepatócitos. O acúmulo e a conseqüente redução dos níveis séricos de alfa-1 antitripsina determinam, respectivamente, doença hepática e pulmonar, sendo que esta se manifesta principalmente sob a forma de enfisema de aparecimento precoce, habitualmente com predomínio basal. O diagnóstico envolve a detecção de níveis séricos reduzidos de alfa-1 antitripsina e a confirmação fenotípica. Além do tratamento usual para doença pulmonar obstrutiva crônica, existe atualmente uma terapia específica com infusão de concentrados de alfa-1 antitripsina. Essa terapia de reposição, aparentemente segura, ainda não teve a eficácia clínica definitivamente comprovada, e o custo-efetividade também é um tema controverso e ainda pouco abordado. Apesar da sua importância, não existem dados epidemiológicos brasileiros a respeito da prevalência da doença ou da freqüência de ocorrência dos alelos deficientes. O subdiagnóstico também tem sido uma importante limitação tanto para o estudo da doença quanto para o tratamento adequado dos pacientes. Espera-se que a criação do Registro Internacional de Alfa-1 venha a resolver essas e outras importantes questões.Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical

  13. Polymorphism of alpha 1 antitrypsin in North American species of Canis

    Science.gov (United States)

    Federoff, N.E.; Kueppers, F.

    2000-01-01

    a1-Antitrypsin (A1AT) is a major protease inhibitor present in all mammalian sera that have thus far been investigated. A1AT is also highly polymorphic and is therefore a useful genetic marker. Previously reported A1AT polymorphism in domestic dogs consisted of two alleles designated as PiM and PiS which exhibited frequencies of 0.72 and 0.28, respectively, in a group of randomly collected mongrel dogs. North American species of Canis, which included gray wolves (n=29), Mexican wolves (n=20), coyotes (n=24), wolfdog crosses (n=9), and red wolves (n=27) were tested for A1AT polymorphism. A1AT phenotypes were determined by isoelectric focusing, followed by direct immunoblotting using a specific antiserum. A1AT concentrations were determined by radial immunodiffusion. Concentrations of A1AT were similar to those found in domestic dogs (2.26 + 0.3 mg/ml SD) and tended to be higher in females than in males, possibly indicating that A1AT may be hormonally influenced in females. Three phenotypic band patterns were observed (M, MS, S). The allele frequencies for domestic dogs and gray wolves were very similar, 0.72 and 0.69 for PiM and 0.28 and 0.31 for PiS, respectively. The Mexican wolves had a significantly lower frequency of PiS= 0.10. Coyotes and red wolves were all found to be monomorphic for the PiS allele and were indistinguishable from each other in that respect.

  14. Refractory Classical Hodgkin Lymphoma Presenting with Atypical Cutaneous Involvement and Diagnosis of ZZ Phenotype Alpha-1 Antitrypsin Deficiency

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    Mohamad Khawandanah

    2014-01-01

    Full Text Available Cutaneous Hodgkin lymphoma is a rare condition. Specific neoplastic involvement can be primary (confined to the skin or secondary to systemic involvement (metastatic. Cutaneous involvement by HL usually occurs late in the course and is associated with poor prognosis; however in some cases it can exhibit indolent behavior. Skin involvement with nonspecific cutaneous findings may represent a paraneoplastic syndrome. We describe a case of 46-year-old white male patient presented with rash and lymphadenopathy which led to the diagnosis of stage IVE mixed cellularity classical Hodgkin lymphoma with skin involvement. His disease was refractory to multiple lines of chemotherapy including (1 AVD (doxorubicin/bleomycin/dacarbazine, (2 brentuximab, and (3 bendamustine, he later achieved complete remission with (4 GCD (gemcitabine/carboplatin/dexamethasone salvage regimen. Bleomycin was not given secondary to poor pulmonary function tests. His treatment was complicated after AVD with multiple pneumothoraces which unmasked the diagnosis of ZZ phenotype alpha-1 antitrypsin (ATT deficiency. Simultaneous existence of Hodgkin lymphoma and ATT is rarely reported.

  15. Prevalence of S and Z alpha 1-antitrypsin mutations in patients with pancreatic diseases in Serbian population

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    Nikolić Aleksandra

    2010-01-01

    Full Text Available One of the key points in research of pancreatic disease pathology is further elucidation of the role of proteases and antiproteases, since their imbalance can lead to pancreatic injury. Alpha 1-antitrypsin (AAT is one of the most important serum inhibitors of proteolytic enzymes, including pancreatic enzymes trypsin, chymotrypsin and elastase. It is speculated that mutations in the AAT gene may influence the onset and the development of pancreatic disease. The presence of the most common AAT mutations Z and S was analyzed in 160 patients with pancreatic diseases (50 patients with pancreatic cancer, 50 patients with chronic pancreatitis and 60 patients with type 2 diabetes mellitus and 129 healthy individuals by PCR-mediated site-directed mutagenesis (PSM method. One patient with pancreatic cancer was found to be a carrier of Z mutation, as well as one patient with type 2 diabetes mellitus. One patient with chronic pancreatitis was found to be a carrier of S mutation. The common AAT mutations were statistically significantly over-represented in patients with pancreatic diseases (3 of 160 patients, allelic frequency 0.9% than in the control group (1 of 129 individuals, allelic frequency 0.4%. The results of this study, requiring confirmation, suggest that common AAT mutations Z and S may be associated with a modest increase in susceptibility to the development of pancreatic disease.

  16. Vitamin K deficiency bleeding in cholestatic infants with alpha-1-antitrypsin deficiency

    NARCIS (Netherlands)

    van Hasselt, P. M.; Kok, K.; Vorselaars, A. D. M.; van Vlerken, L.; Nieuwenhuys, E.; de Koning, T. J.; de Vries, Rindert; Houwen, R. H. J.

    2009-01-01

    Objective: Exclusively breastfed infants with unrecognised cholestatic jaundice are at high risk of a vitamin K deficiency (VKD) bleeding. It is presently unknown whether (the size of) this risk depends on the degree of cholestasis. Since alpha-l-antitrypsin deficiency (A1AD) induces a variable degr

  17. Association of IREB2 and CHRNA3 polymorphisms with airflow obstruction in severe alpha-1 antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Kim Woo Jin

    2012-02-01

    Full Text Available Abstract Background The development of COPD in subjects with alpha-1 antitrypsin (AAT deficiency is likely to be influenced by modifier genes. Genome-wide association studies and integrative genomics approaches in COPD have demonstrated significant associations with SNPs in the chromosome 15q region that includes CHRNA3 (cholinergic nicotine receptor alpha3 and IREB2 (iron regulatory binding protein 2. We investigated whether SNPs in the chromosome 15q region would be modifiers for lung function and COPD in AAT deficiency. Methods The current analysis included 378 PIZZ subjects in the AAT Genetic Modifiers Study and a replication cohort of 458 subjects from the UK AAT Deficiency National Registry. Nine SNPs in LOC123688, CHRNA3 and IREB2 were selected for genotyping. FEV1 percent of predicted and FEV1/FVC ratio were analyzed as quantitative phenotypes. Family-based association analysis was performed in the AAT Genetic Modifiers Study. In the replication set, general linear models were used for quantitative phenotypes and logistic regression models were used for the presence/absence of emphysema or COPD. Results Three SNPs (rs2568494 in IREB2, rs8034191 in LOC123688, and rs1051730 in CHRNA3 were associated with pre-bronchodilator FEV1 percent of predicted in the AAT Genetic Modifiers Study. Two SNPs (rs2568494 and rs1051730 were associated with the post-bronchodilator FEV1 percent of predicted and pre-bronchodilator FEV1/FVC ratio; SNP-by-gender interactions were observed. In the UK National Registry dataset, rs2568494 was significantly associated with emphysema in the male subgroup; significant SNP-by-smoking interactions were observed. Conclusions IREB2 and CHRNA3 are potential genetic modifiers of COPD phenotypes in individuals with severe AAT deficiency and may be sex-specific in their impact.

  18. Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update

    Science.gov (United States)

    Blanco, Ignacio; Bueno, Patricia; Diego, Isidro; Pérez-Holanda, Sergio; Casas-Maldonado, Francisco; Esquinas, Cristina; Miravitlles, Marc

    2017-01-01

    In alpha-1 antitrypsin deficiency (AATD), the Z allele is present in 98% of cases with severe disease, and knowledge of the frequency of this allele is essential from a public health perspective. However, there is a remarkable lack of epidemiological data on AATD worldwide, and many of the data currently used are outdated. Therefore, the objective of this study was to update the knowledge of the frequency of the Z allele to achieve accurate estimates of the prevalence and number of Pi*ZZ genotypes worldwide based on studies performed according to the following criteria: 1) samples representative of the general population, 2) AAT phenotyping characterized by adequate methods, and 3) measurements performed using a coefficient of variation calculated from the sample size and 95% confidence intervals. Studies fulfilling these criteria were used to develop maps with an inverse distance weighted (IDW)-interpolation method, providing numerical and graphical information of Pi*Z distribution worldwide. A total of 224 cohorts from 65 countries were included in the study. With the data provided by these cohorts, a total of 253,404 Pi*ZZ were estimated worldwide: 119,594 in Europe, 91,490 in America and Caribbean, 3,824 in Africa, 32,154 in Asia, 4,126 in Australia, and 2,216 in New Zealand. In addition, the IDW-interpolation maps predicted Pi*Z frequencies throughout the world even in some areas that lack real data. In conclusion, the inclusion of new well-designed studies and the exclusion of the low-quality ones have significantly improved the reliability of results, which may be useful to plan strategies for future research and diagnosis and to rationalize the therapeutic resources available. PMID:28243076

  19. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol.

    Science.gov (United States)

    Moller, David R; Koth, Laura L; Maier, Lisa A; Morris, Alison; Drake, Wonder; Rossman, Milton; Leader, Joseph K; Collman, Ronald G; Hamzeh, Nabeel; Sweiss, Nadera J; Zhang, Yingze; O'Neal, Scott; Senior, Robert M; Becich, Michael; Hochheiser, Harry S; Kaminski, Naftali; Wisniewski, Stephen R; Gibson, Kevin F

    2015-10-01

    Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

  20. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

    biennially to exchange views and research findings. The fourth biennial meeting was held in Copenhagen, Denmark, on 2-3 June 2005. This review covers the wide range of AAT deficiency-related topics that were addressed encompassing advances in genetic characterization, risk factor identification, clinical...... epidemiology, inflammatory and signalling processes, therapeutic advances, and lung imaging techniques....

  1. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

    Directory of Open Access Journals (Sweden)

    Pirooznia Nazanin

    2012-05-01

    Full Text Available Abstract Background Alpha 1- antitrypsin (α1AT belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide (PLGA is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD, encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC. To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release

  2. Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels.

    Directory of Open Access Journals (Sweden)

    Gian Andri Thun

    Full Text Available Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD. The role of more common SERPINA1 single nucleotide polymorphisms (SNPs in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of β = -0.068 g/L per minor allele (P = 1.20*10(-12. But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410, suggested that AAT serum level is causally determined at this locus by rare (MAF<1% and low-frequent (MAF 1-5% variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273 was successful (P<0.0001, as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57. Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397, associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene

  3. Causal and Synthetic Associations of Variants in the SERPINA Gene Cluster with Alpha1-antitrypsin Serum Levels

    Science.gov (United States)

    Thun, Gian Andri; Kumar, Ashish; Obeidat, Ma'en; Zorzetto, Michele; Haun, Margot; Curjuric, Ivan; Couto Alves, Alexessander; Jackson, Victoria E.; Albrecht, Eva; Ried, Janina S.; Teumer, Alexander; Lopez, Lorna M.; Huffman, Jennifer E.; Enroth, Stefan; Bossé, Yohan; Hao, Ke; Timens, Wim; Gyllensten, Ulf; Polasek, Ozren; Wilson, James F.; Rudan, Igor; Hayward, Caroline; Sandford, Andrew J.; Deary, Ian J.; Koch, Beate; Reischl, Eva; Schulz, Holger; Hui, Jennie; James, Alan L.; Rochat, Thierry; Russi, Erich W.; Jarvelin, Marjo-Riitta; Strachan, David P.; Hall, Ian P.; Tobin, Martin D.; Dahl, Morten; Fallgaard Nielsen, Sune; Nordestgaard, Børge G.; Kronenberg, Florian; Luisetti, Maurizio; Probst-Hensch, Nicole M.

    2013-01-01

    Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of β = −0.068 g/L per minor allele (P = 1.20*10−12). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1–5%) variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z) variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001), as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57). Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397), associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in

  4. Exploring the optimum approach to the use of CT densitometry in a randomised placebo-controlled study of augmentation therapy in alpha 1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Parr, David G; Dirksen, Asger; Piitulainen, Eeva;

    2009-01-01

    lung assessment. The EXAcerbations and CT scan as Lung Endpoints (EXACTLE) trial aimed to clarify the optimum approach to the use of CT densitometry data for the assessment of alpha 1-antitrypsin (AAT) augmentation therapy on the progression of emphysema in AAT deficiency (AATD). METHODS: Patients...... [MLD] and voxel index at a threshold of -910 [VI-910] and -950 [VI-950] Hounsfield Units) obtained from whole lung scans at baseline and at 24 to 30 months. Targeted regional sampling was compared with whole lung assessment. RESULTS: Whole lung analysis of the total change (baseline to last CT scan...

  5. Features of the milk whey protein partitioning in polyethyleneglycol-sodium citrate aqueous two-phase systems with the goal of isolating human alpha-1 antitrypsin expressed in bovine milk.

    Science.gov (United States)

    Boaglio, Andrea; Bassani, Georgina; Picó, Guillermo; Nerli, Bibiana

    2006-06-06

    Partitioning behaviour of the bovine whey proteins (bovine serum albumin, alpha-lactoalbumin and beta-lactoglobulin) and human alpha-1 antitrypsin in aqueous two-phase systems prepared with polyethyleneglycol (molecular masses: 1000, 1450 and 3350)-sodium citrate was analysed at pH 5.2, 6.2 and 8.2. Alpha lactoalbumin concentrated in the polyethyleneglycol rich-phase, while beta-lactoglobulin, bovine serum albumin and alpha-1 antitrypsin showed affinity for the citrate rich-phase. In aqueous two-phase systems of high medium pH and high polyethyleneglycol molecular mass the protein partitioning equilibrium is displaced to the citrate rich-phase. The polyethyleneglycol 1450-pH 5.2 system with a top/bottom phase-volume ratio of 3 showed to have the best capability of recovering the alpha-1 antitrypsin from a mixture prepared with natural milk whey and human alpha-1 antitrypsin. The recovery of this protein in the bottom phase was of 90% and the purity of the obtained product was of 98%. The method appears to be suitable as a starting point to isolate other human proteins expressed in transgenic bovine milk.

  6. Relationship between frequency, length, and treatment outcome of exacerbations to baseline lung function and lung density in alpha-1 antitrypsin-deficient COPD

    Directory of Open Access Journals (Sweden)

    Vijayasaratha K

    2012-11-01

    Full Text Available Kesavaperumal Vijayasaratha,1 Robert A Stockley21Lung Investigation Unit, 2Research and Development, University Hospital Birmingham NHS Trust, Birmingham, UKBackground: Diary cards are useful for analyzing exacerbations in chronic obstructive pulmonary disease (COPD, although factors influencing the length and frequency of each episode are poorly understood. This study investigated factors that influence the features of exacerbations in patients with alpha-1 antitrypsin (AAT deficiency (PiZ phenotype and COPD.Methods: Daily diary cards were collected over 2 years. Patients had emphysema visualized and quantified by computed tomography scan, and had at least one documented exacerbation in the previous year.Results: The patients (n = 23 had a mean age of 52.5 years, forced expiratory volume in one second (FEV1 of 1.2 L (38.4% predicted, corrected gas transfer (KCO of 0.90 mmol/min/kPa/L (59.7% predicted, and 15th percentile lung density of 44.55 g/L. Two hundred and sixty-three exacerbations (164 treated were identified. The frequency of treated exacerbations correlated negatively with KCO% predicted (r = −0.432; P = 0.022. Exacerbation length (determined for 17 of the patients for whom diary card data through the episode were available correlated negatively with baseline 15th percentile lung density (r = −0.361; P = 0.003, and increased the longer treatment was delayed (r = 0.503; P < 0.001. Treatment delay was shorter with higher day 1 symptom score, lower baseline FEV1, FEV1/forced vital capacity, and lower 15th percentile lung density (r = −0.368, 0.272, 0.461, and 0.786; P = 0.004, 0.036, <0.001, and <0.001, respectively. Time to resolution of exacerbation after treatment initiation was not affected by treatment delay, but correlated negatively with KCO% predicted (r = −0.647; P = 0.007.Conclusion: In alpha-1 antitrypsin deficiency, the frequency and length of resolution of exacerbation were related to baseline gas transfer. Treatment

  7. Identification of a novel SERPINA-1 mutation causing alpha-1 antitrypsin deficiency in a patient with severe bronchiectasis and pulmonary embolism

    Directory of Open Access Journals (Sweden)

    Milger K

    2015-05-01

    Full Text Available Katrin Milger,1 Lesca Miriam Holdt,2 Daniel Teupser,2 Rudolf Maria Huber,1 Jürgen Behr,1 Nikolaus Kneidinger1 1Department of Internal Medicine V, University of Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research, 2Institute of Laboratory Medicine, University of Munich, Munich, Germany Abstract: Deficiency in the serine protease inhibitor, alpha-1 antitrypsin (AAT, is known to cause emphysema and liver disease. Other manifestations, including airway disease or skin disorders, have also been described. A 44-year-old woman presented to our emergency department with dyspnea and respiratory insufficiency. She had never smoked, and had been diagnosed with COPD 9 years earlier. Three months previously, she had suffered a pulmonary embolism. Chest computed tomography scan revealed severe cystic bronchiectasis with destruction of the lung parenchyma. The sweat test was normal and there was no evidence of the cystic fibrosis transmembrane conductance regulator (CFTR mutation. Capillary zone electrophoresis showed a decrease of alpha-1 globin band and AAT levels were below the quantification limit (<25 mg/dL. No S or Z mutation was identified, but sequencing analysis found a homozygous cytosine and adenine (CA insertion in exon 2 of the SERPINA-1 gene, probably leading to a dysfunctional protein (PI Null/Null. This mutation has not been previously identified. The atypical presentation of the patient, with severe cystic bronchiectasis, highlights AAT deficiency as a differential diagnosis in bronchiectasis. Further, awareness should be raised regarding a possible increased risk of thromboembolism associated with AAT deficiency. Keywords: alpha-1 antitrypsin deficiency, bronchiectasis, SERPINA-1 mutation, pulmonary embolism

  8. Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response.

    Science.gov (United States)

    Hidvegi, Tunda; Schmidt, Bela Z; Hale, Pamela; Perlmutter, David H

    2005-11-25

    In alpha(1)-antitrypsin (alpha1AT) deficiency, a polymerogenic mutant form of the secretory glycoprotein alpha1AT, alpha1ATZ, is retained in the endoplasmic reticulum (ER) of liver cells. It is not yet known how this results in liver injury in a subgroup of deficient individuals and how the remainder of deficient individuals escapes liver disease. One possible explanation is that the "susceptible" subgroup is unable to mount the appropriate protective cellular responses. Here we examined the effect of mutant alpha1ATZ on several potential protective signaling pathways by using cell lines with inducible expression of mutant alpha1AT as well as liver from transgenic mice with liver-specific inducible expression of mutant alpha1AT. The results show that ER retention of polymerogenic mutant alpha1ATZ does not result in an unfolded protein response (UPR). The UPR can be induced in the presence of alpha1ATZ by tunicamycin excluding the possibility that the pathway has been disabled. In striking contrast, ER retention of nonpolymerogenic alpha1AT mutants does induce the UPR. These results indicate that the machinery responsible for activation of the UPR can distinguish the physical characteristics of proteins that accumulate in the ER in such a way that it can respond to misfolded but not relatively ordered polymeric structures. Accumulation of mutant alpha1ATZ does activate specific signaling pathways, including caspase-12 in mouse, caspase-4 in human, NFkappaB, and BAP31, a profile that was distinct from that activated by nonpolymerogenic alpha1AT mutants.

  9. Two novel nonradioactive polymerase chain reaction-based assays of dried blood spots, genomic DNA, or whole cells for fast, reliable detection of Z and S mutations in the alpha 1-antitrypsin gene

    DEFF Research Database (Denmark)

    Andresen, B S; Knudsen, I; Jensen, P K;

    1992-01-01

    Two new nonradioactive polymerase chain reaction (PCR)-based assays for the Z and S mutations in the alpha 1-antitrypsin gene are presented. The assays take advantage of PCR-mediated mutagenesis, creating new diagnostic restriction enzyme sites for unambiguous discrimination between test samples...

  10. Progression of emphysema evaluated by MRI using hyperpolarized (3)He (HP (3)He) measurements in patients with alpha-1-antitrypsin (A1AT) deficiency compared with CT and lung function tests

    DEFF Research Database (Denmark)

    Stavngaard, T; Søgaard, L Vejby; Batz, M

    2009-01-01

    as compared to yearly decline. PURPOSE: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) (3)He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. MATERIAL AND METHODS: Nine patients with severe A1AT...

  11. Evaluation of alpha 1-antitrypsin and the levels of mRNA expression of matrix metalloproteinase 7, urokinase type plasminogen activator receptor and COX-2 for the diagnosis of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Luis Bujanda

    Full Text Available BACKGROUND: Colorectal cancer (CRC is the second most common cause of death from cancer in both men and women in the majority of developed countries. Molecular tests of blood could potentially provide this ideal screening tool. AIM: Our objective was to assess the usefulness of serum markers and mRNA expression levels in the diagnosis of CRC. METHODS: In a prospective study, we measured mRNA expression levels of 13 markers (carbonic anhydrase, guanylyl cyclase C, plasminogen activator inhibitor, matrix metalloproteinase 7 (MMP7, urokinase-type plasminogen activator receptor (uPAR, urokinase-type plasminogen activator, survivin, tetranectin, vascular endothelial growth factor (VEGF, cytokeratin 20, thymidylate synthase, cyclooxygenase 2 (COX-2, and CD44 and three proteins in serum (alpha 1 antitrypsin, carcinoembryonic antigen (CEA and activated C3 in 42 patients with CRC and 33 with normal colonoscopy results. RESULTS: Alpha 1-antitrypsin was the serum marker that was most useful for CRC diagnosis (1.79 ± 0.25 in the CRC group vs 1.27 ± 0.25 in the control group, P<0.0005. The area under the ROC curve for alpha 1-antitrypsin was 0.88 (0.79-0.96. The mRNA expression levels of five markers were statistically different between CRC cases and controls: those for which the ROC area was over 75% were MMP7 (0.81 and tetranectin (0.80, COX-2 (0.78, uPAR (0.78 and carbonic anhydrase (0.77. The markers which identified early stage CRC (Stages I and II were alpha 1-antitrypsin, uPAR, COX-2 and MMP7. CONCLUSIONS: Serum alpha 1-antitrypsin and the levels of mRNA expression of MMP7, COX-2 and uPAR have good diagnostic accuracy for CRC, even in the early stages.

  12. Understanding Lung Deposition of Alpha-1 Antitrypsin in Acute Experimental Mouse Lung Injury Model Using Fluorescence Microscopy

    Directory of Open Access Journals (Sweden)

    Mengmeng Wang

    2016-01-01

    Full Text Available Human plasma-derived α1-antitrypsin (AAT delivered by intravenous infusion is used as augmentation therapy in patients with emphysema who have a genetic mutation resulting in deficiency of AAT. Inhalation is an alternative route of administration that can potentially increase the efficacy and convenience of treatment. This study was conducted to determine whether delivery to the lungs, initially via the intratracheal (IT route of administration, would deliver efficacious levels of a recombinant AAT (rAAT to the site of action in the lungs in mice. 125I-radiolabeled rAAT, fluorophore-conjugated rAAT (rAAT-Alexa488, and NE680 (neutrophil elastase 680, a silent fluorescent substrate of neutrophil elastase which fluoresces in the near-infrared range upon activation by neutrophil elastase were used to characterize the pharmacokinetics and tissue distribution profile, distribution of rAAT within the lung, and efficacy of rAAT to inhibit neutrophil elastase at the site of action, respectively. The study has demonstrated that rAAT was able to gain access to locations where neutrophil elastase was localized. The histochemical quantification of rAAT activity relative to dose at the site of action provided here will improve confidence in predicting the human dose via the inhalation route.

  13. Rapid DNA extraction protocol for detection of alpha-1 antitrypsin deficiency from dried blood spots by real-time PCR.

    Science.gov (United States)

    Struniawski, R; Szpechcinski, A; Poplawska, B; Skronski, M; Chorostowska-Wynimko, J

    2013-01-01

    The dried blood spot (DBS) specimens have been successfully employed for the large-scale diagnostics of α1-antitrypsin (AAT) deficiency as an easy to collect and transport alternative to plasma/serum. In the present study we propose a fast, efficient, and cost effective protocol of DNA extraction from dried blood spot (DBS) samples that provides sufficient quantity and quality of DNA and effectively eliminates any natural PCR inhibitors, allowing for successful AAT genotyping by real-time PCR and direct sequencing. DNA extracted from 84 DBS samples from chronic obstructive pulmonary disease patients was genotyped for AAT deficiency variants by real-time PCR. The results of DBS AAT genotyping were validated by serum IEF phenotyping and AAT concentration measurement. The proposed protocol allowed successful DNA extraction from all analyzed DBS samples. Both quantity and quality of DNA were sufficient for further real-time PCR and, if necessary, for genetic sequence analysis. A 100% concordance between AAT DBS genotypes and serum phenotypes in positive detection of two major deficiency S- and Z- alleles was achieved. Both assays, DBS AAT genotyping by real-time PCR and serum AAT phenotyping by IEF, positively identified PI*S and PI*Z allele in 8 out of the 84 (9.5%) and 16 out of 84 (19.0%) patients, respectively. In conclusion, the proposed protocol noticeably reduces the costs and the hand-on-time of DBS samples preparation providing genomic DNA of sufficient quantity and quality for further real-time PCR or genetic sequence analysis. Consequently, it is ideally suited for large-scale AAT deficiency screening programs and should be method of choice.

  14. Congruence-Incongruence Patterns in Alpha-1 Antitrypsin Deficiency Couples' Genetic Determinist Beliefs and Perceived Control over Genes: Implications for Clinical and Public Health Genomic Communication.

    Science.gov (United States)

    Parrott, Roxanne L; Smith, Rachel A; Hong, Soo Jung; Worthington, Amber

    2015-06-01

    Genomics makes possible the isolation of multiple genes as co-factors that increase, but do not determine, risk for many adult-onset medical conditions, including alpha-1 antitrypsin deficiency (AATD). Those diagnosed with an adult-onset medical condition, such as AATD, are often married and make decisions about testing and care as a couple. We examined genetic essentialist and threat beliefs, focusing on beliefs about the genetic contribution to disease susceptibility and severity, as well as perceptions of control related to genes and health for married couples (N =59), in which one spouse has been tested for genetic mutations associated with AATD. The intraclass correlation for spouses' beliefs about genetic essentialism was strong and statistically significant, but the associations for their other beliefs were not. Incongruence between AATD participants and their spouses regarding genes' influence on disease severity directly related to incongruent perceptions of control and genetic contribution to disease susceptibility. Results revealed an inverse relationship to AATD participants' perceptions of behavioral control and a direct relationship to their beliefs about genes' influence on disease severity. This suggests a pattern of incongruence in which AATD participants have low levels of perceived control over genes' influence on health and high levels of perceived genetic influence on disease severity compared to spouses. With public health communication efforts lagging behind the science of genomics, insights regarding the congruence or incongruence associated with married couples' beliefs about genes' influence on disease afford pathways to guide clinical and public health communication about genomics.

  15. Validation and development of an immunonephelometric assay for the determination of alpha-1 antitrypsin levels in dried blood spots from patients with COPD

    Directory of Open Access Journals (Sweden)

    Laura Russo Zillmer

    2013-09-01

    Full Text Available OBJECTIVE: To validate and develop an immunonephelometric assay for the determination of alpha-1 antitrypsin (AAT levels in dried blood spots from COPD patients in Brazil. METHODS: We determined AAT levels in serum samples and dried blood spots from 192 COPD patients. For the preparation of dried blood spots, a disk (diameter, 6 mm was placed into a tube, eluted with 200 µL of PBS, and stored overnight at 4ºC. All of the samples were analyzed by immunonephelometry in duplicate. We used the bootstrap resampling method in order to determine a cut-off point for AAT levels in dried blood spots. RESULTS: The correlation coefficient between the AAT levels in serum samples and those in dried blood spots was r = 0.45. For dried blood spots, the cut-off value was 2.02 mg/dL (97% CI: 1.45-2.64 mg/dL, with a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 95.7%, 27.2%, and 100%, respectively. CONCLUSIONS: This method for the determination of AAT levels in dried blood spots appears to be a reliable screening tool for patients with AAT deficiency.

  16. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  17. The role and importance of glycosylation of acute phase proteins with focus on alpha-1 antitrypsin in acute and chronic inflammatory conditions.

    Science.gov (United States)

    McCarthy, Cormac; Saldova, Radka; Wormald, Mark R; Rudd, Pauline M; McElvaney, Noel G; Reeves, Emer P

    2014-07-03

    Acute phase proteins (APPs) are a group of circulating plasma proteins which undergo changes quantitatively or qualitatively at the time of inflammation. Many of these APPs are glycosylated, and it has been shown that alterations in glycosylation may occur in inflammatory and malignant conditions. Changes in glycosylation have been studied as potential biomarkers in cancer and also in chronic inflammatory conditions and have been shown to correlate with disease severity in certain conditions. Serine protease inhibitors (serpins), many of which are also APPs, are proteins involved in the control of proteases in numerous pathways. Alpha-1 Antitrypsin (AAT) is the most abundant serpin within the circulation and is an APP which has been shown to increase in response to inflammation. The primary role of AAT is maintaining the protease/antiprotease balance in the lung, but it also possesses important anti-inflammatory and immune-modulating properties. Several glycoforms of AAT exist, and they possess differing properties in regard to plasma half-life and stability. Glycosylation may also be important in determining the immune modulatory properties of AAT. The review will focus on the role and importance of glycosylation in acute phase proteins with particular attention to AAT and its use as a biomarker of disease. The review describes the processes involved in glycosylation, how glycosylation changes in differing disease states, and the alterations that occur to glycans of APPs with disease and inflammation. Finally, the review explores the importance of changes in glycosylation of AAT at times of inflammation and in malignant conditions and how this may impact upon the functions of AAT.

  18. A1ATVar: a relational database of human SERPINA1 gene variants leading to alpha1-antitrypsin deficiency and application of the VariVis software.

    Science.gov (United States)

    Zaimidou, Sophia; van Baal, Sjozef; Smith, Timothy D; Mitropoulos, Konstantinos; Ljujic, Mila; Radojkovic, Dragica; Cotton, Richard G; Patrinos, George P

    2009-03-01

    We have developed a relational database of human SERPINA1 gene mutations, leading to alpha(1)-antitrypsin (AAT) deficiency, called A(1)ATVar, which can be accessed over the World Wide Web at www.goldenhelix.org/A1ATVar. Extensive information has been extracted from the literature and converted into a searchable database, including genotype information, clinical phenotype, allelic frequencies for the commonest AAT variant alleles, methods of detection, and references. Mutation summaries are automatically displayed and user-generated queries can be formulated based on fields in the database. A separate module, linked to the FINDbase database for frequencies of inherited disorders allows the user to access allele frequency information for the three most frequent AAT alleles, namely PiM, PiS, and PiZ. The available experimental protocols to detect AAT variant alleles at the protein and DNA levels have been archived in a searchable format. A visualization tool, called VariVis, has been implemented to combine A(1)ATVar variant information with SERPINA1 sequence and annotation data. A direct data submission tool allows registered users to submit data on novel AAT variant alleles as well as experimental protocols to explore SERPINA1 genetic heterogeneity, via a password-protected interface. Database access is free of charge and there are no registration requirements for querying the data. The A(1)ATVar database is the only integrated database on the Internet offering summarized information on AAT allelic variants and could be useful not only for clinical diagnosis and research on AAT deficiency and the SERPINA1 gene, but could also serve as an example for an all-in-one solution for locus-specific database (LSDB) development and curation.

  19. Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: a multicenter, randomized, double-blind, crossover study (SPARK).

    Science.gov (United States)

    Campos, Michael A; Kueppers, Friedrich; Stocks, James M; Strange, Charlie; Chen, Junliang; Griffin, Rhonda; Wang-Smith, Laurene; Brantly, Mark L

    2013-12-01

    Augmentation therapy with the approved dose of 60 mg/kg weekly intravenous (IV) alpha-1 proteinase inhibitor (alpha1-PI), achieves a trough serum level of 11 μM in individuals with alpha-1 antitrypsin deficiency (AATD), yet this is still below the level observed in healthy individuals. This study assessed the safety and pharmacokinetic profile of weekly infusions of a 120 mg/kg dose of alpha1-PI in 30 adults with AATD. Subjects with symptomatic, genetically determined (genotypes PI*ZZ, PI*Z(null), PI*(null)(null) or PI*(Z)Mmalton) AATD were randomly assigned to weekly infusions of 60 or 120 mg/kg alpha1-PI (Prolastin-C®) for 8 weeks before crossing over to the alternate dose for 8 weeks. Adverse events (AEs) (including exacerbations), vital signs, pulmonary function tests, and laboratory assessments were recorded. Pharmacokinetic measurements included AUC0-7days, Cmax, trough, tmax, and t1/2, based on serum alpha1-PI concentrations. In total for both treatments, 112 AEs were reported, with exacerbation of COPD being the most frequent, consistent with the subjects' diagnoses. Mean steady-state serum alpha1-PI concentrations following 120 mg/kg weekly IV alpha1-PI were higher than with the 60 mg/kg dose and mean trough concentrations were 27.7 versus 17.3 μM, respectively. Dose proportionality was demonstrated for AUC0-7days and Cmax, with low inter-subject variability. The 120 mg/kg alpha1-PI weekly dose was considered to be safe and well tolerated, and provided more favorable physiologic alpha1-PI serum levels than the currently recommended 60 mg/kg dose. The effect of this dosing regimen on slowing and/or preventing emphysema progression in subjects with AATD warrants further investigation.

  20. Plasma levels of alpha1-antichymotrypsin and secretory leukocyte proteinase inhibitor in healthy and chronic obstructive pulmonary disease (COPD subjects with and without severe α1-antitrypsin deficiency

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    Sveger Tomas

    2007-01-01

    Full Text Available Abstract Background Individuals with severe Z α1-antitrypsin (AAT deficiency have a considerably increased risk of developing chronic obstructive lung disease (COPD. It has been hypothesized that compensatory increases in levels of other protease inhibitors mitigate the effects of this AAT deficiency. We analysed plasma levels of AAT, α1-antichymotrypsin (ACT and secretory leukocyte protease inhibitor (SLPI in healthy (asymptomatic and COPD subjects with and without AAT deficiency. Methods Studied groups included: 71 asymptomatic AAT-deficient subjects (ZZ, n = 48 and SZ, n = 23, age 31 ± 0.5 identified during Swedish neonatal screening for AAT deficiency between 1972 and 1974; age-matched controls (MM, n = 57, age 30.7 ± 0.6; older asymptomatic ZZ (n = 10; healthy MM (n = 20, age 53 ± 9.6; and COPD patients (ZZ, n = 10, age 47.4 ± 11 and MM, n = 10, age 59.4 ± 6.7. Plasma levels of SLPI, AAT and ACT were analysed using ELISA and immunoelectrophoresis. Results No significant difference was found in plasma ACT and SLPI levels between the healthy MM and the ZZ or SZ subjects in the studied groups. Independent of the genetic variant, subjects with COPD (n = 19 had elevated plasma levels of SLPI and ACT relative to controls (n = 153 (49.5 ± 7.2 vs 40.7 ± 9.1 ng/ml, p Conclusion Our findings show that plasma levels of ACT and SLPI are not elevated in subjects with genetic AAT deficiency compared MM controls and do not appear to compensate for the deficiency of plasma AAT.

  1. Significance of correlation between levels of carcinoembryonic antigen and carbohydrate antigen 19-9, carcinoembryonic antigen and C-reactive protein, carcinoembryonic antigen and alpha-1 antitrypsin in gastric and colon cancer patients

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    Bhawna Bagaria

    2014-01-01

    Full Text Available Aim: Recent progress in proteomics studies profiled that serum proteins of cancer patients and those of normal individuals have altered cancer antigen and acute phase protein expression for distinct types and stages of cancer. In our study, correlation between carcinoembryonic antigen (CEA and carbohydrate antigen (CA 19-9, CEA and C-reactive protein (CRP, CEA and alpha-1 antitrypsin (A1AT were evaluated in gastric and colon cancer patients. Materials and Methods: CEA was estimated by solid phase, two-site sequential chemiluminescent immunometric assay, CA19-9 by solid phase enzyme-linked immunosorbent assay, CRP by latex turbidimetry method and A1AT by turbidimetry method. Results: A significant correlation was seen in levels of CEA and CA19-9 in gastric (r = 0.457, P < 0.001 and colon cancer (r = 0.451, P < 0.001 patients. Correlation between CEA and CRP was significant in gastric (r = 0.462, P < 0.001 and colon cancer (r = 0.759, P < 0.001 patients and between CEA and A1AT also, correlation was found to be significant in gastric (r = 0.631, P < 0.001 and colon cancer patients (r = 0.516, P ≤ 0.001. Conclusion: Serum acute-phase protein concentrations, when combined with CEA increases the sensitivity of CEA and provide substantial information concerning the diagnosis of gastrointestinal cancers. They have a definite role as a significant prognostic indicator which undoubtedly correlates with progression of cancer. Combined CEA and CA19-9 positivity reflected more biologic malignant properties and were significantly correlated with lymph node metastasis, hepatic metastasis and lower rates of curative resection. Surgical outcomes of patients who were CEA and CA19-9 positive were poorer than those of patients with normal CEA and CA19-9 levels.

  2. Prevalence of the serpin peptidase inhibitor (alpha-1-antitrypsin PI*S and PI*Z alleles in Brazilian children with liver disease

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    Guilherme Baldo

    2008-01-01

    Full Text Available Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin, member 1 (SERPINA1 deficiency is one of the main genetic causes related to liver disease in children. In SERPINA1 deficiency the most frequent SERPINA1 alleles found are the PI*S and PI*Z alleles. We used the polymerase chain reaction and the amplification created restriction site (ACRS technique to investigate the prevalence of the PI*S and PI*Z alleles in a group of Brazilian children (n = 200 with liver disease and established the general frequency of the PI*S allele in our population. We found a significant association of the PI*Z allele and liver disease, but no such relationship was found for the PI*S allele. Our results show that SERPINA1 deficiency due to the PI*Z allele, even when heterozygous, is a frequent cause of liver disease in our group of Brazilian children but that the PI*S allele does not confer an increased risk of hepatic disorders in our group of Brazilian children.

  3. Alpha-1 antitrypsin deficiency: diagnosis and treatment

    OpenAIRE

    2008-01-01

    A deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que de...

  4. How Is Alpha-1 Antitrypsin Deficiency Treated?

    Science.gov (United States)

    ... How the Lungs Work Lung Transplant Oxygen Therapy Pulmonary Function Tests Send a link to NHLBI to someone by E-MAIL | PRINT | SHARE this page from the ... a lung disease called COPD (chronic obstructive pulmonary disease). If you have symptoms related to AAT ...

  5. Learning about Alpha-1 Antitrypsin Deficiency (AATD)

    Science.gov (United States)

    ... of Genetic Tests Genomics and Health Disparities Genetic Discrimination Human Subjects Research Informed Consent for Genomics Research ... Smoking or exposure to tobacco smoke increases the appearance of symptoms and damage to the lungs. Other ...

  6. Living with Alpha-1 Antitrypsin Deficiency

    Science.gov (United States)

    ... secondhand smoke and other lung irritants, such as dust, fumes, or toxins. Check your living and working spaces for things that may irritate your lungs. Examples include flower and tree pollen, ash, allergens, air pollution, wood burning stoves, paint fumes, and fumes from cleaning ...

  7. 1H, 15N and 13C backbone resonance assignments of the archetypal serpin α1-antitrypsin.

    Science.gov (United States)

    Nyon, Mun Peak; Kirkpatrick, John; Cabrita, Lisa D; Christodoulou, John; Gooptu, Bibek

    2012-10-01

    Alpha(1)-antitrypsin is a 45-kDa (394-residue) serine protease inhibitor synthesized by hepatocytes, which is released into the circulatory system and protects the lung from the actions of neutrophil elastase via a conformational transition within a dynamic inhibitory mechanism. Relatively common point mutations subvert this transition, causing polymerisation of α(1)-antitrypsin and deficiency of the circulating protein, predisposing carriers to severe lung and liver disease. We have assigned the backbone resonances of α(1)-antitrypsin using multidimensional heteronuclear NMR spectroscopy. These assignments provide the starting point for a detailed solution state characterization of the structural properties of this highly dynamic protein via NMR methods.

  8. Deficiency of α-1-antitrypsin influences systemic iron homeostasis

    Directory of Open Access Journals (Sweden)

    Ghio AJ

    2013-01-01

    Full Text Available Andrew J Ghio,1 Joleen M Soukup,1 Judy H Richards,1 Bernard M Fischer,2 Judith A Voynow,2 Donald E Schmechel31US Environmental Protection Agency, Chapel Hill, NC, USA; 2Division of Pediatric Pulmonary Medicine, Department of Pediatrics,3Joseph and Kathleen Bryan Alzheimer Disease Research Center, Department of Medicine (Neurology, Duke University Medical Center, Durham, NC, USAAbstract: There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP. Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES. Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Keywords: α-1

  9. Targeted screening programmes in COPD: how to identify individuals with α1-antitrypsin deficiency.

    Science.gov (United States)

    Chorostowska-Wynimko, Joanna

    2015-03-01

    α1-antitrypsin deficiency (AATD) is a significantly under-recognised autosomal genetic disorder with individuals being clinically diagnosed. Moreover, rigorous genetic epidemiological data regarding AATD are lacking. The majority of findings come from the USA and Western Europe, and no information is available for many countries. To address this concern, an α1-antitrypsin (AAT) laboratory was set up in 2009 at the National Institute of Tuberculosis and Lung Diseases (Warsaw, Poland). In 2010, an AATD screening programme targeting patients with respiratory disorders was initiated in Poland. This targeted survey has provided valuable information regarding AAT-deficient genotypes, clinical disease and levels of expertise at the physician level. After 4 years, almost 2500 patients with chronic obstructive pulmonary disorders have been screened and, in this cohort, ∼13% had AATD alleles. In these patients, the detection frequency for S and Z alleles was four times greater, and the frequency of homozygous PI*ZZ was 16 times greater than that of the general population. These results highlight the need to build awareness in the medical community, and the project is currently being extended to cover central Eastern Europe, with the creation of the Central Eastern European Alpha-1 Antitrypsin Network.

  10. Evaluación del efecto de la ingesta de una alta carga de ácidos grasos saturados sobre los niveles séricos de la proteína C reactiva, alfa1-antitripsina, fibrinógeno y alfa1-glicoproteína ácida en mujeres obesas Effect of a high saturated fatty acids load on serum concentrations of C-reactive protein, alpha1-antitrypsin, fibrinogen and alpha1-acid glycoprotein in obese women

    Directory of Open Access Journals (Sweden)

    M.ª M. Ramírez Alvarado

    2010-02-01

    en mujeres obesas. Los niveles séricos de PCR y fibrinógeno están incrementados en mujeres obesas y se correlacionan positivamente con el IMC.Obesity is associated with increased inflammation. Creactive protein (CRP and inflammation-sensitive plasma protein (ISPs are inflammatory markers. Proinflammatory process may be influenced by high saturated fatty acid intake. Objective: The aim of the present study was to evaluate the role of saturated fatty acids load on postprandial circulating levels of PCR and ISPs (alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen in obese women. Design: A total of 15 obese women (age = 31,7 ± 4,5 years, BMI = 37,9 ± 7,3 kg/m² and 15 lean controls women (age = 30,6 ± 4,6 years, BMI = 20,6 ± 2,6 kg/m² were recruited for this study. After and overnight fast subjects ate the fat load consisted of 75 g of fat (100% saturated fatty acid, 0% cholesterol, 5 g of carbohydrates, and 6 g of protein per m2 body surface area. Postprandial serum levels of CRP, alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen were measured. Anthropometry and blood biochemical parameters were measured in both groups. Results: The obese women had fasting serum PCR levels higher (p = 0,013 and fibrinogen (p = 0,04 than those of control women. Serum CRP and fibrinogen levels was positively related to body mass index (BMI in obese group. There weren't differences in fasting serum alpha1- antitrypsin levels (p = 0,40, and alpha1-acid glucoprotein (p = 0,28 levels in obese group in comparison to lean control group. Serum CRP, alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen did not change postprandially (p = > 0,05 difference to fasting levels. Conclusion: A high-saturated fatty acids load is not associated with serum CRP, alpha1-antitrypsin, alpha1-acid glucoprotein, and fibrinogen levels increase. Serum alpha1-antitripsin and alpha1-acid glucoprotein levels are not increased in obese women. Serum PCR and fibrinogen levels are

  11. Intravenous alpha-1 antitrypsin augmentation therapy: systematic review

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    2010-01-01

    trials were included with a total of 140 patients. The trials ran for two to three years. Mortality data were not reported. There was no information on harms in the first trial; in the second trial, serious adverse events were reported in ten of 38 patients in the drug group and in 18 of 39 patients...

  12. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID)

    DEFF Research Database (Denmark)

    Chapman, Kenneth R; Burdon, Jonathan G W; Piitulainen, Eeva;

    2015-01-01

    BACKGROUND: The efficacy of α1 proteinase inhibitor (A1PI) augmentation treatment for α1 antitrypsin deficiency has not been substantiated by a randomised, placebo-controlled trial. CT-measured lung density is a more sensitive measure of disease progression in α1 antitrypsin deficiency emphysema ...

  13. Characterising the association of latency with α1-antitrypsin polymerisation using a novel monoclonal antibody

    Science.gov (United States)

    Tan, Lu; Perez, Juan; Mela, Marianna; Miranda, Elena; Burling, Keith A; Rouhani, Farshid N; DeMeo, Dawn L; Haq, Imran; Irving, James A; Ordóñez, Adriana; Dickens, Jennifer A; Brantly, Mark; Marciniak, Stefan J; Alexander, Graeme J M; Gooptu, Bibek; Lomas, David A

    2015-01-01

    α1-Antitrypsin is primarily synthesised in the liver, circulates to the lung and protects pulmonary tissues from proteolytic damage. The Z mutant (Glu342Lys) undergoes inactivating conformational change and polymerises. Polymers are retained within the hepatocyte endoplasmic reticulum (ER) in homozygous (PiZZ) individuals, predisposing the individuals to hepatic cirrhosis and emphysema. Latency is an analogous process of inactivating, intra-molecular conformational change and may co-occur with polymerisation. However, the relationship between latency and polymerisation remained unexplored in the absence of a suitable probe. We have developed a novel monoclonal antibody specific for latent α1-antitrypsin and used it in combination with a polymer-specific antibody, to assess the association of both conformers in vitro, in disease and during augmentation therapy. In vitro kinetics analysis showed polymerisation dominated the pathway but latency could be promoted by stabilising monomeric α1-antitrypsin. Polymers were extensively produced in hepatocytes and a cell line expressing Z α1-antitrypsin but the latent protein was not detected despite manipulation of the secretory pathway. However, α1-antitrypsin augmentation therapy contains latent α1-antitrypsin, as did the plasma of 63/274 PiZZ individuals treated with augmentation therapy but 0/264 who were not receiving this medication (p < 10−14). We conclude that latent α1-antitrypsin is a by-product of the polymerisation pathway, that the intracellular folding environment is resistant to formation of the latent conformer but that augmentation therapy introduces latent α1-antitrypsin into the circulation. A suite of monoclonal antibodies and methodologies developed in this study can characterise α1-antitrypsin folding and conformational transitions, and screen methods to improve augmentation therapy. PMID:25462157

  14. Longer telomere length in COPD patients with α1-antitrypsin deficiency independent of lung function.

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    Aabida Saferali

    Full Text Available Oxidative stress is involved in the pathogenesis of airway obstruction in α1-antitrypsin deficient patients. This may result in a shortening of telomere length, resulting in cellular senescence. To test whether telomere length differs in α1-antitrypsin deficient patients compared with controls, we measured telomere length in DNA from peripheral blood cells of 217 α1-antitrypsin deficient patients and 217 control COPD patients. We also tested for differences in telomere length between DNA from blood and DNA from lung tissue in a subset of 51 controls. We found that telomere length in the blood was significantly longer in α1-antitrypsin deficient COPD patients compared with control COPD patients (p = 1×10(-29. Telomere length was not related to lung function in α1-antitrypsin deficient patients (p = 0.3122 or in COPD controls (p = 0.1430. Although mean telomere length was significantly shorter in the blood when compared with the lungs (p = 0.0078, telomere length was correlated between the two tissue types (p = 0.0122. Our results indicate that telomere length is better preserved in α1-antitrypsin deficient COPD patients than in non-deficient patients. In addition, measurement of telomere length in the blood may be a suitable surrogate for measurement in the lung.

  15. Longer telomere length in COPD patients with α1-antitrypsin deficiency independent of lung function.

    Science.gov (United States)

    Saferali, Aabida; Lee, Jee; Sin, Don D; Rouhani, Farshid N; Brantly, Mark L; Sandford, Andrew J

    2014-01-01

    Oxidative stress is involved in the pathogenesis of airway obstruction in α1-antitrypsin deficient patients. This may result in a shortening of telomere length, resulting in cellular senescence. To test whether telomere length differs in α1-antitrypsin deficient patients compared with controls, we measured telomere length in DNA from peripheral blood cells of 217 α1-antitrypsin deficient patients and 217 control COPD patients. We also tested for differences in telomere length between DNA from blood and DNA from lung tissue in a subset of 51 controls. We found that telomere length in the blood was significantly longer in α1-antitrypsin deficient COPD patients compared with control COPD patients (p = 1×10(-29)). Telomere length was not related to lung function in α1-antitrypsin deficient patients (p = 0.3122) or in COPD controls (p = 0.1430). Although mean telomere length was significantly shorter in the blood when compared with the lungs (p = 0.0078), telomere length was correlated between the two tissue types (p = 0.0122). Our results indicate that telomere length is better preserved in α1-antitrypsin deficient COPD patients than in non-deficient patients. In addition, measurement of telomere length in the blood may be a suitable surrogate for measurement in the lung.

  16. Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency

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    Rames Alexis

    2011-03-01

    Full Text Available Abstract Background Matrix metalloproteinase-9 (MMP-9 may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes. Methods We utilized data from the placebo arm (n = 126 of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT, and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models. Results At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p = 0.03, FVC (p Conclusions Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.

  17. [Place of genotyping in addition to the phenotype and the assay of serum α-1 antitrypsin].

    Science.gov (United States)

    Joly, Philippe; Francina, Alain; Lacan, Philippe; Heraut, Jessica; Chapuis-Cellier, Colette

    2011-01-01

    The diagnosis of deficiency of alpha-1 antitrypsin (A1AT) is based on isoelectric focusing of serum proteins and the extent of serum. However, the focusing is technically difficult and a greatly reduced concentration in abnormal A1AT tapeless does not differentiate an unstable variant of a variant called 'null' (that is to say without any phenotypic expression) to 'heterozygous' state. In this study, we compared the results of the assay, the phenotype and genotype of A1AT in 50 patients. Normal A1AT alleles (Pi*M1 to Pi*M4) or loss of the most common (Pi*S and Pi*Z) were clearly identified in phenotyping. However, genotyping was necessary to characterize: (i) certain alleles rarer A1AT (S-Munich, X-Christchurch); (ii) a null allele and; (iii) two new alleles A1AT not yet described in the literature. In conclusion, although the A1AT genotyping is generally not necessary, it is necessary to resolve complex cases and to obtain witnesses validated for isoelectric focusing.

  18. Molecular Mechanism of Z α1-Antitrypsin Deficiency.

    Science.gov (United States)

    Huang, Xin; Zheng, Ying; Zhang, Fei; Wei, Zhenquan; Wang, Yugang; Carrell, Robin W; Read, Randy J; Chen, Guo-Qiang; Zhou, Aiwu

    2016-07-22

    The Z mutation (E342K) of α1-antitrypsin (α1-AT), carried by 4% of Northern Europeans, predisposes to early onset of emphysema due to decreased functional α1-AT in the lung and to liver cirrhosis due to accumulation of polymers in hepatocytes. However, it remains unclear why the Z mutation causes intracellular polymerization of nascent Z α1-AT and why 15% of the expressed Z α1-AT is secreted into circulation as functional, but polymerogenic, monomers. Here, we solve the crystal structure of the Z-monomer and have engineered replacements to assess the conformational role of residue Glu-342 in α1-AT. The results reveal that Z α1-AT has a labile strand 5 of the central β-sheet A (s5A) with a consequent equilibrium between a native inhibitory conformation, as in its crystal structure here, and an aberrant conformation with s5A only partially incorporated into the central β-sheet. This aberrant conformation, induced by the loss of interactions from the Glu-342 side chain, explains why Z α1-AT is prone to polymerization and readily binds to a 6-mer peptide, and it supports that annealing of s5A into the central β-sheet is a crucial step in the serpins' metastable conformational formation. The demonstration that the aberrant conformation can be rectified through stabilization of the labile s5A by binding of a small molecule opens a potential therapeutic approach for Z α1-AT deficiency.

  19. Lower-zone emphysema in young patients without α1-antitrypsin deficiency

    Science.gov (United States)

    Martelli, Nestor A.; Goldman, Ernesto; Roncoroni, Aquiles J.

    1974-01-01

    Martelli, N. A., Goldman, E., and Roncoroni, A. J. (1974).Thorax, 29, 237-244. Lowerzone emphysema in young patients without α1-antitrypsin deficiency. Three young patients with radiographic pulmonary emphysema predominantly in the lower zones are reported. The clinical and physiological features were those observed in severe pulmonary emphysema. Predominance of the main lesions in the lower zones was confirmed in two cases by selective pulmonary angiography. One of the patients died and extensive panlobular emphysema was found at necropsy. Although the similarities between our patients and those with emphysema and α1-antitrypsin deficiency were remarkable, the latter condition was ruled out. Images PMID:4545502

  20. α1-Antitrypsin Activates Protein Phosphatase 2A to Counter Lung Inflammatory Responses

    OpenAIRE

    Geraghty, Patrick; Eden, Edward; Pillai, Manju; Campos, Michael; McElvaney, Noel G; Foronjy, Robert F.

    2014-01-01

    Rationale: α1-Antitrypsin (A1AT) was identified as a plasma protease inhibitor; however, it is now recognized as a multifunctional protein that modulates immunity, inflammation, proteostasis, apoptosis, and cellular senescence. Like A1AT, protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, regulates similar biologic processes and plays a key role in chronic obstructive pulmonary disease.

  1. Exploration of α1-Antitrypsin Treatment Protocol for Islet Transplantation: Dosing Plan and Route of Administration

    OpenAIRE

    Baranovski, Boris M.; Ozeri, Eyal; Shahaf, Galit; Ochayon, David E.; Schuster, Ronen; Bahar, Nofar; Kalay, Noa; Cal, Pablo; Mizrahi, Mark I.; Nisim, Omer; Strauss, Pnina; Schenker, Eran; Eli C Lewis

    2016-01-01

    Lifelong weekly infusions of human α1-antitrypsin (hAAT) are currently administered as augmentation therapy for patients with genetic AAT deficiency (AATD). Several recent clinical trials attempt to extend hAAT therapy to conditions outside AATD, including type 1 diabetes. Because the endpoint for AATD is primarily the reduction of risk for pulmonary emphysema, the present study explores hAAT dose protocols and routes of administration in attempt to optimize hAAT therapy for islet-related inj...

  2. Avaliação da concentração de alfa 1-antitripsina e da presença dos alelos S e Z em uma população de indivíduos sintomáticos respiratórios crônicos Determination of alpha 1-antitrypsin levels and of the presence of S and Z alleles in a population of patients with chronic respiratory symptoms

    Directory of Open Access Journals (Sweden)

    Heliane Guerra Serra

    2008-12-01

    Full Text Available OBJETIVO: Determinar a concentração de alfa 1-antitripsina (AAT e a prevalência dos alelos S e Z em indivíduos sintomáticos respiratórios crônicos. MÉTODOS: Pacientes com tosse crônica e dispnéia foram submetidos à avaliação clínica, espirometria, tomografia computadorizada de tórax, dosagem de AAT por nefelometria e pesquisa das mutações S e Z por reação em cadeia da polimerase. Foram consideradas como variáveis dependentes a concentração de AAT e o tabagismo. RESULTADOS: Dos 89 pacientes incluídos no estudo (44 mulheres; idade média, 51,3 ± 18,2 anos, os alelos S e Z foram detectados em 33,3% e 5,7%, respectivamente, com freqüência gênica dos alelos S e Z de 0,16 e 0,028. Dois pacientes tinham genótipo SZ (AAT 141 mg/dL (normal, Grupo 2, n = 57. A freqüência de fumantes foi igual nos dois grupos, com carga tabágica maior no Grupo 2. O alelo S estava presente em 13 e 14 pacientes dos Grupos 1 e 2, respectivamente, enquanto que o alelo Z estava presente em 2 e 1 paciente dos mesmos grupos. Não houve diferença nos testes de função pulmonar, nem na freqüência de bronquiectasias ou enfisema entre os dois grupos. Os valores espirométricos e as concentrações de AAT foram similares entre fumantes e não-fumantes. Bronquiectasias foram mais freqüentes entre os não fumantes, e enfisema foi mais freqüente entre os fumantes. CONCLUSÕES: Trinta pacientes apresentaram níveis de AAT abaixo da média esperada para os genótipos MM e MS, e este fato não pode ser explicado por uma freqüência maior dos alelos S e Z.OBJECTIVE: To determine the levels of alpha-1 antitrypsin (AAT and the presence of S and Z alleles in patients with chronic respiratory symptoms. METHODS: Patients with chronic cough and dyspnea were submitted to clinical evaluation, pulmonary function tests, high-resolution computed tomography, nephelometric determination of AAT and determination of S and Z alleles by polymerase chain reaction. Smoking

  3. A single-chain variable fragment intrabody prevents intracellular polymerization of Z α1-antitrypsin while allowing its antiproteinase activity.

    Science.gov (United States)

    Ordóñez, Adriana; Pérez, Juan; Tan, Lu; Dickens, Jennifer A; Motamedi-Shad, Neda; Irving, James A; Haq, Imran; Ekeowa, Ugo; Marciniak, Stefan J; Miranda, Elena; Lomas, David A

    2015-06-01

    Mutant Z α1-antitrypsin (E342K) accumulates as polymers within the endoplasmic reticulum (ER) of hepatocytes predisposing to liver disease, whereas low levels of circulating Z α1-antitrypsin lead to emphysema by loss of inhibition of neutrophil elastase. The ideal therapy should prevent polymer formation while preserving inhibitory activity. Here we used mAb technology to identify interactors with Z α1-antitrypsin that comply with both requirements. We report the generation of an mAb (4B12) that blocked α1-antitrypsin polymerization in vitro at a 1:1 molar ratio, causing a small increase of the stoichiometry of inhibition for neutrophil elastase. A single-chain variable fragment (scFv) intrabody was generated based on the sequence of mAb4B12. The expression of scFv4B12 within the ER (scFv4B12KDEL) and along the secretory pathway (scFv4B12) reduced the intracellular polymerization of Z α1-antitrypsin by 60%. The scFv4B12 intrabody also increased the secretion of Z α1-antitrypsin that retained inhibitory activity against neutrophil elastase. MAb4B12 recognized a discontinuous epitope probably located in the region of helices A/C/G/H/I and seems to act by altering protein dynamics rather than binding preferentially to the native state. This novel approach could reveal new target sites for small-molecule intervention that may block the transition to aberrant polymers without compromising the inhibitory activity of Z α1-antitrypsin.

  4. Diagnosing α1-antitrypsin deficiency: how to improve the current algorithm

    Directory of Open Access Journals (Sweden)

    Noel G. McElvaney

    2015-03-01

    Full Text Available Over the past 10–15 years, the diagnosis of α1-antitrypsin deficiency (AATD has markedly improved as a result of increasing awareness and the publication of diagnostic recommendations by the American Thoracic Society (ATS/European Respiratory Society (ERS. Nevertheless, the condition remains substantially underdiagnosed. Furthermore, when AATD is diagnosed there is a delay before treatment is introduced. This may help explain why AATD is the fourth most common cause of lung transplantation. Clearly we need to do better. The ATS/ERS recommend testing high-risk groups, such as: all chronic obstructive pulmonary disease patients; all nonresponsive asthmatic adults/adolescents; all cases of cryptogenic cirrhosis/liver disease; subjects with granulomatosis with polyangitis; bronchiectasis of unknown aetiology; panniculitis and first-degree relatives of patients with AATD. In terms of laboratory diagnosis, measurement of α1-antitrypsin levels will identify patients with protein deficiency, but cannot differentiate between the various genetic subtypes of AATD. Phenotyping is the current gold standard for detecting rare variants of AATD (except null variants, while advances in molecular diagnostics are making genotyping more effective. An accurate diagnosis facilitates the physician's ability to actively intervene with measures such as smoking cessation and perhaps augmentation therapy, and it will also help provide a better understanding of the natural history of the disease.

  5. Screening for Alpha 1 antitrypsin deficiency in Tunisian subjects with obstructive lung disease: a feasibility report

    Directory of Open Access Journals (Sweden)

    Chibani Jemni

    2009-04-01

    Full Text Available Abstract Background AATD is one of the most common inherited disorders in the World. However, it is generally accepted that AATD in North African populations is not a risk factor for lung and/or liver disease, based on a number of small studies. We therefore planned a screening study for detection of AATD in patients with OLD in a cohort of patients from Kairouan in central Tunisia. Methods: One hundred twenty patients with OLD (asthma, emphysema, COPD were enrolled in the screening programme. Laboratory diagnosis for AATD was performed according to current diagnostic standards. Results We found that 6/120 OLD patients carried an AAT deficient allele, 1 PI*MZ, 1 PI*MPlowel, 3 PI*MMmalton, 1 PI*MMwurzburg. Conclusion this pilot study demonstrated that alleles related to deficiency of AAT are not absent in the Tunisian population, and that rare AATD variants prevailed over commonest PI*Z variant. These results would support a larger scale screening for AATD in Tunisia.

  6. Alpha-1 antitrypsin gene therapy prevented bone loss in ovariectomy induced osteoporosis mouse model

    Science.gov (United States)

    Osteoporosis is a major healthcare burden affecting mostly postmenopausal women characterized by compromised bone strength and increased risk of fragility fracture. Although pathogenesis of this disease is complex, elevated proinflammatory cytokine production is clearly involved in bone loss at meno...

  7. The roles of helix I and strand 5A in the folding, function and misfolding of α1-antitrypsin.

    Directory of Open Access Journals (Sweden)

    Anja S Knaupp

    Full Text Available α(1-Antitrypsin, the archetypal member of the serpin superfamily, is a metastable protein prone to polymerization when exposed to stressors such as elevated temperature, low denaturant concentrations or through the presence of deleterious mutations which, in a physiological context, are often associated with disease. Experimental evidence suggests that α(1-Antitrypsin can polymerize via several alternative mechanisms in vitro. In these polymerization mechanisms different parts of the molecule are proposed to undergo conformational change. Both strand 5 and helix I are proposed to adopt different conformations when forming the various polymers, and possess a number of highly conserved residues however their role in the folding and misfolding of α(1-Antitrypsin has never been examined. We have therefore created a range of α(1Antitypsin variants in order to explore the role of these conserved residues in serpin folding, misfolding, stability and function. Our data suggest that key residues in helix I mediate efficient folding from the folding intermediate and residues in strand 5A ensure native state stability in order to prevent misfolding. Additionally, our data indicate that helix I is involved in the inhibitory process and that both structural elements undergo differing conformational rearrangements during unfolding and misfolding. These findings suggest that the ability of α(1-Antitrypsin to adopt different types of polymers under different denaturing conditions may be due to subtle conformational differences in the transiently populated structures adopted prior to the I and M* states.

  8. α1-Antitrypsin reduces rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Berman R

    2016-06-01

    Full Text Available Reena Berman, Di Jiang, Qun Wu, Hong Wei Chu Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: Human rhinovirus (HRV infections target airway epithelium and are the leading cause of acute exacerbations of COPD. Cigarette smoke (CS increases the severity of viral infections, but there is no effective therapy for HRV infection. We determined whether α1-antitrypsin (A1AT reduces HRV-16 infection in CS-exposed primary human airway epithelial cells. Brushed bronchial epithelial cells from normal subjects and patients diagnosed with COPD were cultured at air–liquid interface to induce mucociliary differentiation. These cells were treated with A1AT or bovine serum albumin for 2 hours and then exposed to air or whole cigarette smoke (WCS with or without HRV-16 (5×104 50% Tissue Culture Infective Dose [TCID50]/transwell infection for 24 hours. WCS exposure significantly increased viral load by an average of fivefold and decreased the expression of antiviral genes interferon-λ1, OAS1, and MX1. When A1AT was added to WCS-exposed cells, viral load significantly decreased by an average of 29-fold. HRV-16 infection significantly increased HRV-16 receptor intercellular adhesion molecule-1 messenger RNA expression in air-exposed cells, which was decreased by A1AT. A1AT-mediated reduction of viral load was not accompanied by increased epithelial antiviral gene expression or by inhibiting the activity of 3C protease involved in viral replication or maturation. Our findings demonstrate that A1AT treatment prevents a WCS-induced increase in viral load and for the first time suggest a therapeutic effect of A1AT on HRV infection. Keywords: α1-antitrypsin, rhinovirus, COPD, cigarette smoke, ICAM-1

  9. Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-10-06

    The serine proteinase inhibitor α-1 antitrypsin (AAT) is produced principally by the liver at the rate of 2 g\\/d. It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung, where it can neutralise the activity of the serine protease neutrophil elastase. Mutations leading to deficiency in AAT are associated with liver and lung disease. The most notable is the Z AAT mutation, which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine. More than 95% of all individuals with AAT deficiency carry at least one Z allele. ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum (ER) of hepatocytes and other AAT-producing cells. This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT. However, the misfolded protein acquires a toxic gain of function that impacts on the ER. A major function of the ER is to ensure correct protein folding. ZAAT interferes with this function and promotes ER stress responses and inflammation. Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.

  10. Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response

    Institute of Scientific and Technical Information of China (English)

    Catherine; M; Greene; Noel; G; McElvaney

    2010-01-01

    The serine proteinase inhibitor α-1 antitrypsin(AAT) is produced principally by the liver at the rate of 2 g/d.It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung,where it can neutralise the activity of the serine protease neutrophil elastase.Mutations leading to def iciency in AAT are associated with liver and lung disease.The most notable is the Z AAT mutation,which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine.More than 95% of all individuals with AAT def iciency carry at least one Z allele.ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum(ER) of hepatocytes and other AAT-producing cells.This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT.However,the misfolded protein acquires a toxic gain of function that impacts on the ER.A major function of the ER is to ensure correct protein folding.ZAAT interferes with this function and promotes ER stress responses and inflammation.Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.

  11. Fecal calprotectin and α1-antitrypsin dynamics in gastrointestinal GvHD.

    Science.gov (United States)

    O'Meara, A; Kapel, N; Xhaard, A; Sicre de Fontbrune, F; Manéné, D; Dhedin, N; de Latour, R P; Socié, G; Robin, M

    2015-08-01

    In a previous study, the fecal biomarkers calprotectin and α1-antitrypsin (α1-AT) at symptom onset were reported to be significantly associated with the response to steroids in gastrointestinal GvHD (GI-GvHD). The purpose of this trial was to evaluate the dynamics of the fecal biomarkers calprotectin and α1-AT throughout the course of GvHD. Patients who were refractory to steroids had initially higher biomarker levels and in the course of GvHD demonstrated a continuous increase in fecal biomarkers. In contrast, the dynamics of calprotectin and α1-AT demonstrated low and decreasing levels in cortico-sensitive GvHD. In steroid-refractory patients who received a second line of treatment, the biomarker levels at the beginning of second-line treatment did not predict the subsequent response. Nevertheless, calprotectin levels progressively decreased in subsequent responders, whereas non-responders demonstrated continuously high levels of calprotectin. α1-AT values correlated to a lesser extent with the response to second-line treatment and remained elevated in both non-responders and responders. In conclusion, calprotectin monitoring can be of use in the management of immunosuppressive treatment in GI-GvHD.

  12. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

    LENUS (Irish Health Repository)

    Bergin, David A

    2010-12-01

    Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.

  13. α1-Antitrypsin Activates Protein Phosphatase 2A to Counter Lung Inflammatory Responses

    Science.gov (United States)

    Geraghty, Patrick; Eden, Edward; Pillai, Manju; Campos, Michael; McElvaney, Noel G.

    2014-01-01

    Rationale: α1-Antitrypsin (A1AT) was identified as a plasma protease inhibitor; however, it is now recognized as a multifunctional protein that modulates immunity, inflammation, proteostasis, apoptosis, and cellular senescence. Like A1AT, protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, regulates similar biologic processes and plays a key role in chronic obstructive pulmonary disease. Objectives: Given their common effects, this study investigated whether A1AT acts via PP2A to alter tumor necrosis factor (TNF) signaling, inflammation, and proteolytic responses in this disease. Methods: PP2A activity was measured in peripheral blood neutrophils from A1AT-deficient (PiZZ) and healthy (PiMM) individuals and in alveolar macrophages from normal (60 mg/kg) and high-dose (120 mg/kg) A1AT-treated PiZZ subjects. PP2A activation was assessed in human neutrophils, airway epithelial cells, and peripheral blood monocytes treated with plasma purified A1AT protein. Similarly, lung PP2A activity was measured in mice administered intranasal A1AT. PP2A was silenced in lung epithelial cells treated with A1AT and matrix metalloproteinase and cytokine production was then measured following TNF-α stimulation. Measurements and Main Results: PP2A was significantly lower in neutrophils isolated from PiZZ compared with PiMM subjects. A1AT protein activated PP2A in human alveolar macrophages, monocytes, neutrophils, airway epithelial cells, and in mouse lungs. This activation required functionally active A1AT protein and protein tyrosine phosphatase 1B expression. A1AT treatment acted via PP2A to prevent p38 and IκBα phosphorylation and matrix metalloproteinase and cytokine induction in TNF-α–stimulated epithelial cells. Conclusions: Together, these data indicate that A1AT modulates PP2A to counter inflammatory and proteolytic responses induced by TNF signaling in the lung. PMID:25341065

  14. Prolastin, a pharmaceutical preparation of purified human α1-antitrypsin, blocks endotoxin-mediated cytokine release

    Directory of Open Access Journals (Sweden)

    Westin Ulla

    2005-01-01

    Full Text Available Abstract Background α1-antitrypsin (AAT serves primarily as an inhibitor of the elastin degrading proteases, neutrophil elastase and proteinase 3. There is ample clinical evidence that inherited severe AAT deficiency predisposes to chronic obstructive pulmonary disease. Augmentation therapy for AAT deficiency has been available for many years, but to date no sufficient data exist to demonstrate its efficacy. There is increasing evidence that AAT is able to exert effects other than protease inhibition. We investigated whether Prolastin, a preparation of purified pooled human AAT used for augmentation therapy, exhibits anti-bacterial effects. Methods Human monocytes and neutrophils were isolated from buffy coats or whole peripheral blood by the Ficoll-Hypaque procedure. Cells were stimulated with lipopolysaccharide (LPS or zymosan, either alone or in combination with Prolastin, native AAT or polymerised AAT for 18 h, and analysed to determine the release of TNFα, IL-1β and IL-8. At 2-week intervals, seven subjects were submitted to a nasal challenge with sterile saline, LPS (25 μg and LPS-Prolastin combination. The concentration of IL-8 was analysed in nasal lavages performed before, and 2, 6 and 24 h after the challenge. Results In vitro, Prolastin showed a concentration-dependent (0.5 to 16 mg/ml inhibition of endotoxin-stimulated TNFα and IL-1β release from monocytes and IL-8 release from neutrophils. At 8 and 16 mg/ml the inhibitory effects of Prolastin appeared to be maximal for neutrophil IL-8 release (5.3-fold, p Conclusion Our data demonstrate for the first time that Prolastin inhibits bacterial endotoxin-induced pro-inflammatory responses in vitro and in vivo, and provide scientific bases to explore new Prolastin-based therapies for individuals with inherited AAT deficiency, but also for other clinical conditions.

  15. The Z Mutation Alters the Global Structural Dynamics of α1-Antitrypsin

    Science.gov (United States)

    Hughes, Victoria A.; Meklemburg, Robert; Bottomley, Stephen P.; Wintrode, Patrick L.

    2014-01-01

    α1-Antitrypsin (α1AT) deficiency, the most common serpinopathy, results in both emphysema and liver disease. Over 90% of all clinical cases of α1AT deficiency are caused by the Z variant in which Glu342, located at the top of s5A, is replaced by a Lys which results in polymerization both in vivo and in vitro. The Glu342Lys mutation removes a salt bridge and a hydrogen bond but does not effect the thermodynamic stability of Z α1AT compared to the wild type protein, M α1AT, and so it is unclear why Z α1AT has an increased polymerization propensity. We speculated that the loss of these interactions would make the native state of Z α1AT more dynamic than M α1AT and that this change renders the protein more polymerization prone. We have used hydrogen/deuterium exchange combined with mass spectrometry (HXMS) to determine the structural and dynamic differences between native Z and M α1AT to reveal the molecular basis of Z α1AT polymerization. Our HXMS data shows that the Z mutation significantly perturbs the region around the site of mutation. Strikingly the Z mutation also alters the dynamics of regions distant to the mutation such as the B, D and I helices and specific regions of each β-sheet. These changes in global dynamics may lead to an increase in the likelihood of Z α1AT sampling a polymerogenic structure thereby causing disease. PMID:25181470

  16. The Z mutation alters the global structural dynamics of α1-antitrypsin.

    Directory of Open Access Journals (Sweden)

    Victoria A Hughes

    Full Text Available α1-Antitrypsin (α1AT deficiency, the most common serpinopathy, results in both emphysema and liver disease. Over 90% of all clinical cases of α1AT deficiency are caused by the Z variant in which Glu342, located at the top of s5A, is replaced by a Lys which results in polymerization both in vivo and in vitro. The Glu342Lys mutation removes a salt bridge and a hydrogen bond but does not effect the thermodynamic stability of Z α1AT compared to the wild type protein, M α1AT, and so it is unclear why Z α1AT has an increased polymerization propensity. We speculated that the loss of these interactions would make the native state of Z α1AT more dynamic than M α1AT and that this change renders the protein more polymerization prone. We have used hydrogen/deuterium exchange combined with mass spectrometry (HXMS to determine the structural and dynamic differences between native Z and M α1AT to reveal the molecular basis of Z α1AT polymerization. Our HXMS data shows that the Z mutation significantly perturbs the region around the site of mutation. Strikingly the Z mutation also alters the dynamics of regions distant to the mutation such as the B, D and I helices and specific regions of each β-sheet. These changes in global dynamics may lead to an increase in the likelihood of Z α1AT sampling a polymerogenic structure thereby causing disease.

  17. Exploration of α1-antitrypsin treatment protocol for islet transplantation: dosing plan and route of administration.

    Science.gov (United States)

    Baranovski, Boris M; Ozeri, Eyal; Shahaf, Galit; Ochayon, David E; Schuster, Ronen; Bahar, Nofar; Kalay, Noa; Cal, Pablo; Mizrahi, Mark I; Nisim, Omer; Strauss, Pnina; Schenker, Eran; Lewis, Eli C

    2016-11-07

    Life-long weekly infusions of human α1-antitrypsin (hAAT) are currently administered as augmentation therapy for patients with genetic AAT deficiency (AATD). Several recent clinical trials attempt to extend hAAT therapy to conditions outside AATD, including type 1 diabetes. Since the endpoint for AATD is primarily the reduction of risk for pulmonary emphysema, the present study explores hAAT dose protocols and routes of administration in attempt to optimize hAAT therapy for islet-related injury. Islet-grafted mice were treated with hAAT (Glassia™; i.p. or s.c.) under an array of clinically relevant dosing plans. Serum hAAT and immunocyte cell membrane association were examined, as well as parameters of islet survival. Results indicate that dividing the commonly prescribed 60 mg/kg i.p. dose to three 20 mg/kg injections is superior in affording islet graft survival; in addition, a short dynamic descending dose protocol (240→120→60→60 mg/kg i.p.) is comparable in outcomes to indefinite 60 mg/kg injections. While hAAT pharmacokinetics after i.p. administration in mice resembles exogenous hAAT treatment in humans, s.c. administration better imitated the physiological progressive rise of hAAT during acute phase responses; nonetheless, only the 60 mg/kg dose depicted an advantage using the s.c. route. Taken together, this study provides a platform for extrapolating an islet-relevant clinical protocol from animal models that use hAAT to protect islets. In addition, the study places emphasis on outcome-oriented analyses of drug efficacy, particularly important when considering that hAAT is presently at an era of drug-repurposing towards an extended list of clinical indications outside genetic AATD.

  18. Plasma α1-antitrypsin: A Neglected Predictor of Angiographic Severity in Patients with Stable Angina Pectoris

    Institute of Scientific and Technical Information of China (English)

    Hui Zhao; Hong Liu; Lin Chai; Ping Xu; Lu Hua; Xiao-Yuan Guan; Bing Duan

    2015-01-01

    Background:As an acute phase protein,α1-antitrypsin (AAT) has been extensively studied in acute coronary syndrome,but it is unclear whether a relationship exists between AAT and stable angina pectoris (SAP).The purpose of the present study was to investigate the association between AAT plasma levels and SAP.Methods:Overall,103 SAP patients diagnosed by coronary angiography and clinical manifestations and 118 control subjects matched for age and gender were enrolled in this case-control study.Plasma levels of AAT,high-sensitivity C-reactive protein (hsCRP),lipid profiles and other clinical parameters were assayed for all participants.The severity of coronary lesions was evaluated based on the Gensini score (GS) assessed by coronary angiography.Results:Positively correlated with the GS (r =0.564,P < 0.001),the plasma AAT level in the SAP group was significantly higher than that in the control group (142.08 ± 19.61 mg/dl vs.125.50 ± 19.67 mg/dl,P < 0.001).The plasma AAT level was an independent predictor for both SAP (odds ratio [OR] =1.037,95% confidence interval [CO:1.020-1.054,P < 0.001) and a high GS (OR =1.087,95% CI:1.051-1.124,P < 0.001) in a multivariate logistic regression model.In the receiver operating characteristic curve analysis,plasma AAT level was found to have a larger area under the curve (AUC) for predicting a high GS (AUC =0.858,95% CI:0.788-0.929,P < 0.001) than that of hsCRP (AUC =0.665,95% CI:0.557-0.773,P =0.006; Z =2.9363,P < 0.001),with an optimal cut-off value of 137.85 mg/dl (sensitivity:94.3%,specificity:68.2%).Conclusions:Plasma AAT levels correlate with both the presence and severity of coronary stenosis in patients with SAP,suggesting that it could be a potential predictive marker of severe stenosis in SAP patients.

  19. The effects of weekly augmentation therapy in patients with PiZZ α1-antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Schmid ST

    2012-09-01

    Full Text Available ST Schmid,1 J Koepke,1 M Dresel,1 A Hattesohl,1 E Frenzel,2 J Perez,3 DA Lomas,4 E Miranda,5 T Greulich,1 S Noeske,1 M Wencker,6 H Teschler,6 C Vogelmeier,1 S Janciauskiene,2,* AR Koczulla1,*1Department of Internal Medicine, Division for Pulmonary Diseases, University Hospital Marburg, Marburg, Germany; 2Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany; 3Department of Cellular Biology, University of Malaga, Malaga, Spain; 4Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; 5Department of Biology and Biotechnology, Istituto Pasteur – Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy; 6Department of Pneumology, West German Lung Clinic, Essen University Hospital, Essen, Germany*These authors contributed equally to this workBackground: The major concept behind augmentation therapy with human α1-antitrypsin (AAT is to raise the levels of AAT in patients with protease inhibitor phenotype ZZ (Glu342Lys-inherited AAT deficiency and to protect lung tissues from proteolysis and progression of emphysema.Objective: To evaluate the short-term effects of augmentation therapy (Prolastin® on plasma levels of AAT, C-reactive protein, and chemokines/cytokines.Materials and methods: Serum and exhaled breath condensate were collected from individuals with protease inhibitor phenotype ZZ AAT deficiency-related emphysema (n = 12 on the first, third, and seventh day after the infusion of intravenous Prolastin. Concentrations of total and polymeric AAT, interleukin-8 (IL-8, monocyte chemotactic protein-1, IL-6, tumor necrosis factor-α, vascular endothelial growth factor, and C-reactive protein were determined. Blood neutrophils and primary epithelial cells were also exposed to Prolastin (1 mg/mL.Results: There were significant fluctuations in serum (but not in exhaled breath condensate levels of AAT polymers, IL-8, monocyte chemotactic protein-1, IL

  20. Plasma α1-antitrypsin: A Neglected Predictor of Angiographic Severity in Patients with Stable Angina Pectoris

    Directory of Open Access Journals (Sweden)

    Hui Zhao

    2015-01-01

    Full Text Available Background: As an acute phase protein, α1-antitrypsin (AAT has been extensively studied in acute coronary syndrome, but it is unclear whether a relationship exists between AAT and stable angina pectoris (SAP. The purpose of the present study was to investigate the association between AAT plasma levels and SAP. Methods: Overall, 103 SAP patients diagnosed by coronary angiography and clinical manifestations and 118 control subjects matched for age and gender were enrolled in this case-control study. Plasma levels of AAT, high-sensitivity C-reactive protein (hsCRP, lipid profiles and other clinical parameters were assayed for all participants. The severity of coronary lesions was evaluated based on the Gensini score (GS assessed by coronary angiography. Results: Positively correlated with the GS (r = 0.564, P < 0.001, the plasma AAT level in the SAP group was significantly higher than that in the control group (142.08 ± 19.61 mg/dl vs. 125.50 ± 19.67 mg/dl, P < 0.001. The plasma AAT level was an independent predictor for both SAP (odds ratio [OR] = 1.037, 95% confidence interval [CI]: 1.020-1.054, P < 0.001 and a high GS (OR = 1.087, 95% CI: 1.051-1.124, P < 0.001 in a multivariate logistic regression model. In the receiver operating characteristic curve analysis, plasma AAT level was found to have a larger area under the curve (AUC for predicting a high GS (AUC = 0.858, 95% CI: 0.788-0.929, P < 0.001 than that of hsCRP (AUC = 0.665, 95% CI: 0.557-0.773, P = 0.006; Z = 2.9363, P < 0.001, with an optimal cut-off value of 137.85 mg/dl (sensitivity: 94.3%, specificity: 68.2%. Conclusions: Plasma AAT levels correlate with both the presence and severity of coronary stenosis in patients with SAP, suggesting that it could be a potential predictive marker of severe stenosis in SAP patients.

  1. Quantitation of residual trypsin in cell-based therapeutics using immobilized α-1-antitrypsin or SBTI in an ELISA format.

    Science.gov (United States)

    Braatz, James A; Elias, Christopher; Finny, Joseph G; Tran, Huan; McCaman, Michael

    2015-02-01

    An Enzyme-Linked Immunosorbent Assay (ELISA) has been developed for the quantitation of porcine trypsin as a process residual in cell therapy products based on its capture by either of two immobilized anti-trypsins, α-1-antitrypsin (α1AT) or soybean trypsin inhibitor (SBTI) followed by detection with a polyclonal goat anti-porcine trypsin-IgG conjugated with peroxidase. It was demonstrated that an extended range of antigen quantitation could be achieved that covered nearly three orders of magnitude of trypsin concentration. The utility of the assay was demonstrated by its application to samples generated in a cell-based therapeutic manufacturing setting.

  2. α-1-Antitrypsin detected by MALDI imaging in the study of glomerulonephritis: Its relevance in chronic kidney disease progression.

    Science.gov (United States)

    Smith, Andrew; L'Imperio, Vincenzo; De Sio, Gabriele; Ferrario, Franco; Scalia, Carla; Dell'Antonio, Giacomo; Pieruzzi, Federico; Pontillo, Claudia; Filip, Szymon; Markoska, Katerina; Granata, Antonio; Spasovski, Goce; Jankowski, Joachim; Capasso, Giovambattista; Pagni, Fabio; Magni, Fulvio

    2016-06-01

    Idiopathic glomerulonephritis (GN), such as membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS), and IgA nephropathy (IgAN), represent the most frequent primary glomerular kidney diseases (GKDs) worldwide. Although the renal biopsy currently remains the gold standard for the routine diagnosis of idiopathic GN, the invasiveness and diagnostic difficulty related with this procedure highlight the strong need for new diagnostic and prognostic biomarkers to be translated into less invasive diagnostic tools. MALDI-MS imaging MALDI-MSI was applied to fresh-frozen bioptic renal tissue from patients with a histological diagnosis of FSGS (n = 6), IgAN, (n = 6) and membranous glomerulonephritis (n = 7), and from controls (n = 4) in order to detect specific molecular signatures of primary glomerulonephritis. MALDI-MSI was able to generate molecular signatures capable to distinguish between normal kidney and pathological GN, with specific signals (m/z 4025, 4048, and 4963) representing potential indicators of chronic kidney disease development. Moreover, specific disease-related signatures (m/z 4025 and 4048 for FSGS, m/z 4963 and 5072 for IgAN) were detected. Of these signals, m/z 4048 was identified as α-1-antitrypsin and was shown to be localized to the podocytes within sclerotic glomeruli by immunohistochemistry. α-1-Antitrypsin could be one of the markers of podocyte stress that is correlated with the development of FSGS due to both an excessive loss and a hypertrophy of podocytes.

  3. Mixture-Based Combinatorial Libraries from Small Individual Peptide Libraries: A Case Study on α1-Antitrypsin Deficiency

    Directory of Open Access Journals (Sweden)

    Yi-Pin Chang

    2014-05-01

    Full Text Available The design, synthesis and screening of diversity-oriented peptide libraries using a “libraries from libraries” strategy for the development of inhibitors of α1-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods.

  4. Mixture-based combinatorial libraries from small individual peptide libraries: a case study on α1-antitrypsin deficiency.

    Science.gov (United States)

    Chang, Yi-Pin; Chu, Yen-Ho

    2014-05-16

    The design, synthesis and screening of diversity-oriented peptide libraries using a "libraries from libraries" strategy for the development of inhibitors of α1-antitrypsin deficiency are described. The major buttress of the biochemical approach presented here is the use of well-established solid-phase split-and-mix method for the generation of mixture-based libraries. The combinatorial technique iterative deconvolution was employed for library screening. While molecular diversity is the general consideration of combinatorial libraries, exquisite design through systematic screening of small individual libraries is a prerequisite for effective library screening and can avoid potential problems in some cases. This review will also illustrate how large peptide libraries were designed, as well as how a conformation-sensitive assay was developed based on the mechanism of the conformational disease. Finally, the combinatorially selected peptide inhibitor capable of blocking abnormal protein aggregation will be characterized by biophysical, cellular and computational methods.

  5. The effects of weight gain after smoking cessation on atherogenic α1-antitrypsin-low-density lipoprotein.

    Science.gov (United States)

    Komiyama, Maki; Wada, Hiromichi; Ura, Shuichi; Yamakage, Hajime; Satoh-Asahara, Noriko; Shimada, Sayaka; Akao, Masaharu; Koyama, Hiroshi; Kono, Koichi; Shimatsu, Akira; Takahashi, Yuko; Hasegawa, Koji

    2015-11-01

    Although cardiovascular risks decrease after quitting smoking, body weight often increases in the early period after smoking cessation. We have previously reported that the serum level of the α1-antitrypsin-low-density lipoprotein complex (AT-LDL)-an oxidatively modified low-density lipoprotein that accelerates atherosclerosis-is high in current smokers, and that the level rapidly decreases after smoking cessation. However, the effects of weight gain after smoking cessation on this cardiovascular marker are unknown. In 183 outpatients (134 males, 49 females) who had successfully quit smoking, serum AT-LDL levels were measured using an enzyme-linked immunosorbent assay. For all persons who had successfully quit smoking, body mass index (BMI) significantly increased 12 weeks after the first examination (p smoking is influenced by weight gain after smoking cessation.

  6. The Shapes of Z-α1-Antitrypsin Polymers in Solution Support the C-Terminal Domain-Swap Mechanism of Polymerization

    DEFF Research Database (Denmark)

    Behrens, Manja Annette; Sendall, Timothy J.; Pedersen, Jan Skov;

    2014-01-01

    Emphysema and liver cirrhosis can be caused by the Z mutation (Glu342Lys) in the serine protease inhibitor α1-antitrypsin (α1AT), which is found in more than 4% of the Northern European population. Homozygotes experience deficiency in the lung concomitantly with a massive accumulation of polymers...

  7. Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin α1-antitrypsin Z.

    Directory of Open Access Journals (Sweden)

    Sager J Gosai

    Full Text Available The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms.

  8. Causal and Synthetic Associations of Variants in the SERPINA Gene Cluster with Alpha1-antitrypsin Serum Levels

    DEFF Research Database (Denmark)

    Thun, Gian Andri; Imboden, Medea; Ferrarotti, Ilaria

    2013-01-01

    a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated...

  9. Hypersensitivity Vasculitis with Leukocytoclastic Vasculitis Associated with Alpha-1-Proteinase Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicola W. Mwirigi

    2009-01-01

    Full Text Available Prolastin is a commercially available form of alpha-1-antitrypsin (AAT that is derived from pooled human plasma and used for treatment of severe alpha-1-antitrypsin deficiency (AATD. We describe a patient with AATD who developed presumed hypersensitivity vasculitis (HV following a Prolastin infusion. Hypersensitivity vasculitis (HV, or cutaneous vasculitis, is characterized by inflammation of the small vessels of the skin with resultant ischemia to the distally supplied areas. To our knowledge, this is the first reported case of presumed hypersensitivity vasculitis following Prolastin infusion.

  10. Conformational properties of the disease-causing Z variant of α1-antitrypsin revealed by theory and experiment.

    Science.gov (United States)

    Kass, Itamar; Knaupp, Anja S; Bottomley, Stephen P; Buckle, Ashley M

    2012-06-20

    The human serine protease inhibitor (serpin) α-1 antitrypsin (α1-AT) protects tissues from proteases of inflammatory cells. The most common disease-causing mutation in α1-AT is the Z-mutation (E342K) that results in an increased propensity of α1-AT to polymerize in the ER of hepatocytes, leading to a lack of secretion into the circulation. The structural consequences of this mutation, however, remain elusive. We report a comparative molecular dynamics investigation of the native states of wild-type and Z α1-AT, revealing a striking contrast between their structures and dynamics in the breach region at the top of β-sheet A, which is closed in the wild-type simulations but open in the Z form. Our findings are consistent with experimental observations, notably the increased solvent exposure of buried residues in the breach region in Z, as well as polymerization via domain swapping, whereby the reactive center loop is rapidly inserted into an open A-sheet before proper folding of the C-terminal β-strands, allowing C-terminal domain swapping with a neighboring molecule. Taken together, our experimental and simulation data imply that mutations at residue 342 that either stabilize an open form of the top of β-sheet A or increase the local flexibility in this region, may favor polymerization and hence aggregation.

  11. Correlation Between Arteriosclerosis and Periodontal Condition Assessed by Lactoferrin and α1-Antitrypsin Levels in Gingival Crevicular Fluid.

    Science.gov (United States)

    Hayashi, Shuji; Yamada, Hirotsugu; Fukui, Makoto; Ito, Hiro-o; Sata, Masataka

    2015-01-01

    Patients with periodontal disease exhibit exacerbated atherosclerosis, aortic stiffness, or vascular endothelial dysfunction. However, in a recent scientific statement, the American Heart Association noted that neither has periodontal disease been proven to cause atherosclerotic vascular disease nor has the treatment of periodontal disease been proven to prevent atherosclerotic vascular disease. Therefore, the aim of the present study was to examine the correlation between periodontal condition and arteriosclerosis in patients with coronary artery disease (CAD), which is usually accompanied by systemic arteriosclerosis.We measured levels of gingival crevicular fluid lactoferrin (GCF-Lf) and α1-antitrypsin (GCF-AT) in 72 patients (67 ± 8 years, 56 men) with CAD. Furthermore, we evaluated the maximum intima-media thickness (max IMT) and plaque score of the carotid arteries as well as brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) of the brachial artery, each of which is a parameter for determining arteriosclerosis status. The average level of GCF-Lf was 0.29 ± 0.36 µg/mL and that of GCF-AT was 0.31 ± 0.66 µg/mL, with significant correlation between the two (r = 0.701, P arteriosclerosis parameters (ie, max IMT, plaque score, baPWV, and FMD) and GCF-Lf or GCF-AT.No correlation between the GCF biomarkers and the severity of arteriosclerosis was detected. This result may suggest that worsening of the periodontal condition assessed by GCF biomarkers is not a major potential risk factor for arteriosclerosis.

  12. Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.

    Science.gov (United States)

    Cummings, Erin E; O'Reilly, Linda P; King, Dale E; Silverman, Richard M; Miedel, Mark T; Luke, Cliff J; Perlmutter, David H; Silverman, Gary A; Pak, Stephen C

    2015-01-01

    α1-antitrypsin deficiency (ATD) predisposes patients to both loss-of-function (emphysema) and gain-of-function (liver cirrhosis) phenotypes depending on the type of mutation. Although the Z mutation (ATZ) is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (null (Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype) induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS), showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of different AT variants using a transgenic approach.

  13. Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.

    Directory of Open Access Journals (Sweden)

    Erin E Cummings

    Full Text Available α1-antitrypsin deficiency (ATD predisposes patients to both loss-of-function (emphysema and gain-of-function (liver cirrhosis phenotypes depending on the type of mutation. Although the Z mutation (ATZ is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels or null (<1% normal levels alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS, showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of

  14. Possible Role of α1-Antitrypsin in Endometriosis-Like Grafts From a Mouse Model of Endometriosis.

    Science.gov (United States)

    Tamura, Kazuhiro; Takashima, Haruka; Fumoto, Keiko; Kajihara, Takeshi; Uchino, Satomi; Ishihara, Osamu; Yoshie, Mikihiro; Kusama, Kazuya; Tachikawa, Eiichi

    2015-09-01

    Previous study indicated that bleeding into the peritoneum may accelerate inflammatory response in endometriosis-like grafts in mice. To identify changes in protein levels in the grafts from mice that underwent unilateral ovariectomy (uOVX), which causes bleeding from ovarian arteries and vein, the grafts were generated by injecting a suspension of human endometrial cells in BALB/c nude female mice, and protein profile changes were compared with non-uOVX control mice. The level of α1-antitrypsin (α1-AT) decreased in grafts from nude mice that underwent uOVX. The levels of phosphorylated Akt, mammalian target of rapamycin, S6K, regulatory factors for cell survival, and of phosphorylated nuclear factor κB, an inflammatory mediator, were higher in endometriosis-like grafts from the uOVX group than from the control. The grafts were mostly comprised of stromal cells. The bioactivity of α1-AT was assessed by investigating cytokine expression in protease-activated receptor (PAR) 1/2 agonists-stimulated stromal cells. The PARs promoted the expression of interleukin 8 (IL-8), but treatment with α1-AT blocked IL-8 expression dose dependently. Knocking down α1-AT expression increased the constitutive IL-6, IL-8, and cyclooxygenase 2 expression as well as PAR1 agonist-stimulated IL-6 expression. These findings support the notion that decreased α1-AT protein in the grafts constituted with human endometrial cells in mice may have exacerbated inflammation in endometriosis-like grafts, suggesting the possible involvement of α1-AT in the pathophysiology of endometriosis.

  15. Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results.

    LENUS (Irish Health Repository)

    Flotte, Terence R

    2011-10-01

    Recombinant adeno-associated virus (rAAV) vectors offer promise for the gene therapy of α(1)-antitrypsin (AAT) deficiency. In our prior trial, an rAAV vector expressing human AAT (rAAV1-CB-hAAT) provided sustained, vector-derived AAT expression for >1 year. In the current phase 2 clinical trial, this same vector, produced by a herpes simplex virus complementation method, was administered to nine AAT-deficient individuals by intramuscular injection at doses of 6.0×10(11), 1.9×10(12), and 6.0×10(12) vector genomes\\/kg (n=3 subjects\\/dose). Vector-derived expression of normal (M-type) AAT in serum was dose dependent, peaked on day 30, and persisted for at least 90 days. Vector administration was well tolerated, with only mild injection site reactions and no serious adverse events. Serum creatine kinase was transiently elevated on day 30 in five of six subjects in the two higher dose groups and normalized by day 45. As expected, all subjects developed anti-AAV antibodies and interferon-γ enzyme-linked immunospot responses to AAV peptides, and no subjects developed antibodies to AAT. One subject in the mid-dose group developed T cell responses to a single AAT peptide unassociated with any clinical effects. Muscle biopsies obtained on day 90 showed strong immunostaining for AAT and moderate to marked inflammatory cell infiltrates composed primarily of CD3-reactive T lymphocytes that were primarily of the CD8(+) subtype. These results support the feasibility and safety of AAV gene therapy for AAT deficiency, and indicate that serum levels of vector-derived normal human AAT >20 μg\\/ml can be achieved. However, further improvements in the design or delivery of rAAV-AAT vectors will be required to achieve therapeutic target serum AAT concentrations.

  16. Acute-phase protein α1-antitrypsin--a novel regulator of angiopoietin-like protein 4 transcription and secretion.

    Science.gov (United States)

    Frenzel, Eileen; Wrenger, Sabine; Immenschuh, Stephan; Koczulla, Rembert; Mahadeva, Ravi; Deeg, H Joachim; Dinarello, Charles A; Welte, Tobias; Marcondes, A Mario Q; Janciauskiene, Sabina

    2014-06-01

    The angiopoietin-like protein 4 (angptl4, also known as peroxisome proliferator-activated receptor [PPAR]γ-induced angiopoietin-related protein) is a multifunctional protein associated with acute-phase response. The mechanisms accounting for the increase in angptl4 expression are largely unknown. This study shows that human α1-antitrypsin (A1AT) upregulates expression and release of angplt4 in human blood adherent mononuclear cells and in primary human lung microvascular endothelial cells in a concentration- and time-dependent manner. Mononuclear cells treated for 1 h with A1AT (from 0.1 to 4 mg/ml) increased mRNA of angptl4 from 2- to 174-fold, respectively, relative to controls. In endothelial cells, the maximal effect on angptl4 expression was achieved at 8 h with 2 mg/ml A1AT (11-fold induction versus controls). In 10 emphysema patients receiving A1AT therapy (Prolastin), plasma angptl4 levels were higher relative to patients without therapy (nanograms per milliliter, mean [95% confidence interval] 127.1 [99.5-154.6] versus 76.8 [54.8-98.8], respectively, p = 0.045) and correlated with A1AT levels. The effect of A1AT on angptl4 expression was significantly diminished in cells pretreated with a specific inhibitor of ERK1/2 activation (UO126), irreversible and selective PPARγ antagonist (GW9662), or genistein, a ligand for PPARγ. GW9662 did not alter the ability of A1AT to induce ERK1/2 phosphorylation, suggesting that PPARγ is a critical mediator in the A1AT-driven angptl4 expression. In contrast, the forced accumulation of HIF-1α, an upregulator of angptl4 expression, enhanced the effect of A1AT. Thus, acute-phase protein A1AT is a physiological regulator of angptl4, another acute-phase protein.

  17. α1-antitrypsin and its C-terminal fragment attenuate effects of degranulated neutrophil-conditioned medium on lung cancer HCC cells, in vitro

    Directory of Open Access Journals (Sweden)

    Westin Ulla

    2004-11-01

    Full Text Available Abstract Background Tumor microenvironment, which is largely affected by inflammatory cells, is a crucial participant in the neoplastic process through promotion of cell proliferation, survival and migration. We measured the effects of polymorphonuclear neutrophil (PMN conditioned medium alone, and supplemented with serine proteinase inhibitor α-1 antitrypsin (AAT or its C-terminal fragment (C-36 peptide, on cultured lung cancer cells. Methods Lung cancer HCC cells were grown in a regular medium or in a PMN-conditioned medium in the presence or absence of AAT (0.5 mg/ml or its C-36 peptide (0.06 mg/ml for 24 h. Cell proliferation, invasiveness and release of IL-8 and VEGF were analyzed by [3H]-thymidine incorporation, Matrigel invasion and ELISA methods, respectively. Results Cells exposed to PMN-conditioned medium show decreased proliferation and IL-8 release by 3.9-fold, p Conclusions Our data provide evidence that neutrophil derived factors decrease lung cancer HCC cell proliferation and IL-8 release, but increase cell invasiveness. These effects were found to be modulated by exogenously present serine proteinase inhibitor, AAT, and its C-terminal fragment, which points to a complexity of the relationships between tumor cell biological activities and local microenvironment.

  18. Metabolic flux rearrangement in the amino acid metabolism reduces ammonia stress in the α1-antitrypsin producing human AGE1.HN cell line.

    Science.gov (United States)

    Priesnitz, Christian; Niklas, Jens; Rose, Thomas; Sandig, Volker; Heinzle, Elmar

    2012-03-01

    This study focused on metabolic changes in the neuronal human cell line AGE1.HN upon increased ammonia stress. Batch cultivations of α(1)-antitrypsin (A1AT) producing AGE1.HN cells were carried out in media with initial ammonia concentrations ranging from 0mM to 5mM. Growth, A1AT production, metabolite dynamics and finally metabolic fluxes calculated by metabolite balancing were compared. Growth and A1AT production decreased with increasing ammonia concentration. The maximum A1AT concentration decreased from 0.63g/l to 0.51g/l. Central energy metabolism remained relatively unaffected exhibiting only slightly increased glycolytic flux at high initial ammonia concentration in the medium. However, the amino acid metabolism was significantly changed. Fluxes through transaminases involved in amino acid degradation were reduced concurrently with a reduced uptake of amino acids. On the other hand fluxes through transaminases working in the direction of amino acid synthesis, i.e., alanine and phosphoserine, were increased leading to increased storage of excess nitrogen in extracellular alanine and serine. Glutamate dehydrogenase flux was reversed increasingly fixing free ammonia with increasing ammonia concentration. Urea production additionally observed was associated with arginine uptake by the cells and did not increase at high ammonia stress. It was therefore not used as nitrogen sink to remove excess ammonia. The results indicate that the AGE1.HN cell line can adapt to ammonia concentrations usually present during the cultivation process to a large extent by changing metabolism but with slightly reduced A1AT production and growth.

  19. α1-Antitrypsin modifies general NK cell interactions with dendritic cells and specific interactions with islet β-cells in favor of protection from autoimmune diabetes.

    Science.gov (United States)

    Guttman, Ofer; Yossef, Rami; Freixo-Lima, Gabriella; Rider, Peleg; Porgador, Angel; Lewis, Eli C

    2014-10-13

    The autoimmune destruction of pancreatic β-cells is the hallmark of type 1 diabetes (T1D). Failure of anti-CD3 antibodies to provide long-lasting reversal of T1D and the expression of an NK cell ligand on β-cells suggest that NK cells play a role in disease pathogenesis. Indeed, killing of β-cells by NK cells has been shown to occur, mediated by activation of the NK cell activating receptor, NKp46. α1-antitrypsin (AAT), an anti-inflammatory and immunomodulatory glycoprotein, protects β-cells from injurious immune responses and is currently evaluated as a therapeutic for recent onset T1D. While isolated T lymphocytes are not inhibited by AAT, dendritic cells (DCs) become tolerogenic in its presence and other innate immune cells become less inflammatory. Yet a comprehensive profile of NK cell responses in the presence of AAT has yet to be described. In the present study, we demonstrate that AAT significantly reduces NK cell degranulation against β-cells, albeit in the whole animal and not in isolated NK cell cultures. AAT-treated mice, and not isolated cultured β-cells, exhibited a marked reduction in NKp46 ligand levels on β-cells. In related experiments, AAT-treated DCs exhibited reduced inducible DC-expressed IL-15 levels and evoked a weaker NK cell response. NK cell depletion in a T1D mouse model resulted in improved β-cell function and survival, similar to the effects observed by AAT treatment alone; nonetheless, the two approaches were non-synergistic. Our data suggest that AAT is a selective immunomodulator that retains pivotal NK cell responses, while diverting their activities away from islet β-cells. This article is protected by copyright. All rights reserved.

  20. Associação entre deficiência de alfa-1-antitripsina e a gravidade da fibrose cística Association between alpha 1 antitrypsin deficiency and cystic fibrosis severity

    OpenAIRE

    2005-01-01

    OBJETIVO: Verificar a distribuição dos genótipos da alfa-1-antitripsina e correlacionar com a gravidade da doença pulmonar em pacientes fibrocísticos. MÉTODO: Estudo clínico-laboratorial de corte transversal, com 70 pacientes fibrocísticos do Hospital Universitário da UNICAMP. Os fibrocísticos tiveram diagnóstico confirmado clínica e laboratorialmente. A gravidade da fibrose cística foi avaliada pelo escore de Shwachman. Todos os pacientes foram analisados para os alelos S e Z de alfa-1-antit...

  1. Evaluación del efecto de la ingesta de una sobrecarga de glucosa sobre los niveles séricos de la proteína C reactiva y de la α1-antitripsina en mujeres obesas Effect of a high glucose load on serum concentrations of C-reactive protein and α1-antitrypsin in obese women

    Directory of Open Access Journals (Sweden)

    M.ª M. Ramírez A.

    2008-08-01

    Full Text Available La obesidad está asociada con un estado inflamatorio. La proteína C reactiva (PCR es una molécula proinflamatoria y la α1-antitripsina es una proteína plasmática sensible a inflamación. El proceso proinflamatorio puede ser influenciado por la hiperglicemia postprandial. Objetivo: Evaluar el efecto de la ingesta de una sobrecarga de glucosa sobre los niveles séricos de PCR y de α1-antitripsina en mujeres obesas con tolerancia normal a la glucosa. Metodología: La población estuvo conformada por 15 mujeres obesas (edad = 34,4 ± 4,3 años, IMC = 35,3 ± 5,3 kg/m² y 15 mujeres normopeso (edad = 33,9 ± 2,9 años, IMC = 21,8 ± 1,9 kg/m². Los sujetos en ayuno se sometieron a una prueba de tolerancia oral a la glucosa (75 g y 2 h. Se midió los niveles pre y postprandiales de PCR y de α1-antitripsina. Los parámetros antropométricos y bioquímicos se midieron en ambos grupos. Resultados: Las mujeres obesas presentaron mayores niveles de PCR en ayuno (P = 0,05 diferencia con el nivel preprandial. Los niveles séricos de PCR se correlacionaron positivamente con el índice de masa corporal (IMC en el grupo obeso. Los niveles séricos de α1-antitripsina no se correlacionaron con el IMC en ninguno de los dos grupos estudio. Conclusión: La ingesta de una sobrecarga de glucosa no tiene ningún efecto sobre los niveles séricos de PCR y α1-antitripsina. Los niveles séricos de α1-antitripsina no están incrementados en mujeres obesas. Los niveles séricos de PCR están incrementados en mujeres obesas y se correlacionan positivamente con el IMC.Obesity is associated with increased inflammation. C-reactive protein (CRP is a proinflammatory molecule, and α1-antitrypsin is an inflammation-sensitive plasma protein. Proinflammatory process may be influenced by postprandial hyperglycemia. Objective: The aim of the present study was to evaluate the role of high-glucose load on postprandial circulating levels of PCR and α1-antitrypsin in obese

  2. Alpha Thalassemia

    Science.gov (United States)

    Alpha Thalassemia Physicians often mistake alpha thalassemia trait for iron deficiency anemia and incorrectly prescribe iron supplements that have no effect 1 on the anemia. αα αα Normal alpha ...

  3. Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome: implications.

    Science.gov (United States)

    Tsiouris, J A; Mehta, P D; Patti, P J; Madrid, R E; Raguthu, S; Barshatzky, M R; Cohen, I L; Sersen, E

    2000-12-01

    Studies of immune function during depression in persons without intellectual disability (ID) have revealed elevated levels of alpha2 macroglobulin (alpha2M) and an acute phase protein (APP) response. Clinical observation suggests that people with Down's syndrome (DS) may have associated genetic abnormalities in their immune systems. The APP response and alpha2M changes in depressed versus non-depressed adults with DS was the subject of the present study. The serum pan-proteinase inhibitor alpha2M, and the AP proteins c-reactive protein (CRP), alpha1 antitrypsin (alpha1AT), ceruloplasmin (Cp), beta2 Macroglobulin (beta2M), transthyretin (Trans), serum amyloid protein (SAP), and albumin (Alb) were measured in 38 adults with DS, 19 of whom were diagnosed with and 19 without depression using a sandwich enzyme-linked immunosorbent assay (ELISA). The DSM-IV criteria were used for diagnoses. Medical and neurological examinations excluded medical disorders associated with APP response. Only alpha2M and CRP were significantly different in the depressed versus non-depressed groups. The alpha2M was higher, a response similar to one observed in depressed people without ID, but the CRP was lower in the depressed group, especially in those subjects not on psychotropic medications, contrary to the expected APP response to depression. The results suggest that alpha2M elevation in depressed adults with DS is independent of the APP response. An alternative explanation for its elevation is proposed linking the core symptom of depression with the mammalian dormancy/hibernation process. Further studies are needed to confirm that alpha2M elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID.

  4. Alpha fetoprotein

    Science.gov (United States)

    Fetal alpha globulin; AFP ... Greater than normal levels of AFP may be due to: Cancer in testes , ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer ...

  5. $\\alpha_s$ review (2016)

    CERN Document Server

    d'Enterria, David

    2016-01-01

    The current world-average of the strong coupling at the Z pole mass, $\\alpha_s(m^2_{Z}) = 0.1181 \\pm 0.0013$, is obtained from a comparison of perturbative QCD calculations computed, at least, at next-to-next-to-leading-order accuracy, to a set of 6 groups of experimental observables: (i) lattice QCD "data", (ii) $\\tau$ hadronic decays, (iii) proton structure functions, (iv) event shapes and jet rates in $e^+e^-$ collisions, (v) Z boson hadronic decays, and (vi) top-quark cross sections in p-p collisions. In addition, at least 8 other $\\alpha_s$ extractions, usually with a lower level of theoretical and/or experimental precision today, have been proposed: pion, $\\Upsilon$, W hadronic decays; soft and hard fragmentation functions; jets cross sections in pp, e-p and $\\gamma$-p collisions; and photon F$_2$ structure function in $\\gamma\\,\\gamma$ collisions. These 14 $\\alpha_s$ determinations are reviewed, and the perspectives of reduction of their present uncertainties are discussed.

  6. 发色底物法在酶促反应初速度内测定α1抗胰蛋白酶的活性%Detection ofα1 antitrypsin activity by chromogenic substrate assay with initial veloci-ty of enzymatic reaction

    Institute of Scientific and Technical Information of China (English)

    张晋超; 赵雄; 吕茂民; 尹惠琼; 王延琳; 章金刚

    2015-01-01

    Objective To detect the activity of α1 antitrypsin(AAT) with initial velocity of enzymatic reaction in order to detect the activity of samples in the process of separating and purifying plasma protein ,chromogenic substrate assay was optimized.Methods The effect of trypsin concentration and reaction time on enzymatic reaction was acquired by the kinetic monitoring mode of the microplate reader .Initial velocity was calculated to confirm the largest concentration of trypsin which was saturated by substrate .AAT was incubated with trypsin and absorbance produced by enzymatic reaction of remaining trypsin and substrate could reflect the activity of AAT .A standard curve was established with △D fitting with the activity of AAT standard.The activity of related samples was detected and the precision and accuracy of the method were evaluated . Results Trypsin concentration was 0.0625 mg/ml.Within 20 minutes, enzymatic reaction was with initial velocity .The range of the standard curve was 200-1200 IU/ml.Correlation coefficient was more than 0.99.The activity of Cohn Ⅳ, samples of pre-processing and elution were (720.59 ±18.63), (601.84 ±19.18),and (568.09 ±24.83)IU/ml, respec-tively.The relative standard deviation was less than 10%. Sample recovery rate was 90%-110%.Conclusion The optimized chromogenic substrate assay greatly improves accuracy and precision .The method can be used for the detec-tion of AAT activity of samples in laboratories and workshops .%目的:优化发色底物法,使其在酶促反应初速度内测定α1抗胰蛋白酶( AAT)的活性并用于血浆蛋白纯化过程中各样品活性的检测。方法采用酶标仪动态监测模式观察酶浓度和反应时间对酶促反应的影响;计算初速度并确定被底物饱和的最大酶浓度。将AAT与胰蛋白酶孵育,剩余靶酶和底物作用产生的光密度可反映AAT的活性。通过△D与AAT标准品活性进行拟合建立标准曲线,测定相关样品的活

  7. Ab initio alpha-alpha scattering

    CERN Document Server

    Elhatisari, Serdar; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-01-01

    Processes involving alpha particles and alpha-like nuclei comprise a major part of stellar nucleosynthesis and hypothesized mechanisms for thermonuclear supernovae. In an effort towards understanding alpha processes from first principles, we describe in this letter the first ab initio calculation of alpha-alpha scattering. We use lattice effective field theory to describe the low-energy interactions of nucleons and apply a technique called the adiabatic projection method to reduce the eight-body system to an effective two-cluster system. We find good agreement between lattice results and experimental phase shifts for S-wave and D-wave scattering. The computational scaling with particle number suggests that alpha processes involving heavier nuclei are also within reach in the near future.

  8. Faddeev calculation of 3 alpha and alpha alpha Lambda systems using alpha alpha resonating-group method kernel

    CERN Document Server

    Fujiwara, Y; Kohno, M; Suzuki, Y; Baye, D; Sparenberg, J M

    2004-01-01

    We carry out Faddeev calculations of three-alpha (3 alpha) and two-alpha plus Lambda (alpha alpha Lambda) systems, using two-cluster resonating-group method kernels. The input includes an effective two-nucleon force for the alpha alpha resonating-group method and a new effective Lambda N force for the Lambda alpha interaction. The latter force is a simple two-range Gaussian potential for each spin-singlet and triplet state, generated from the phase-shift behavior of the quark-model hyperon-nucleon interaction, fss2, by using an inversion method based on supersymmetric quantum mechanics. Owing to the exact treatment of the Pauli-forbidden states between the clusters, the present three-cluster Faddeev formalism can describe the mutually related, alpha alpha, 3 alpha and alpha alpha Lambda systems, in terms of a unique set of the baryon-baryon interactions. For the three-range Minnesota force which describes the alpha alpha phase shifts quite accurately, the ground-state and excitation energies of 9Be Lambda are...

  9. The determination of $\\alpha_s$ by the ALPHA collaboration

    CERN Document Server

    Bruno, Mattia; Fritzsch, Patrick; Korzec, Tomasz; Ramos, Alberto; Schaefer, Stefan; Simma, Hubert; Sint, Stefan; Sommer, Rainer

    2016-01-01

    We review the ALPHA collaboration strategy for obtaining the QCD coupling at high scale. In the three-flavor effective theory it avoids the use of perturbation theory at $\\alpha > 0.2$ and at the same time has the physical scales small compared to the cutoff $1/a$ in all stages of the computation. The result $\\Lambda_\\overline{MS}^{(3)}=332(14)$~MeV is translated to $\\alpha_\\overline{MS}(m_Z)=0.1179(10)(2)$ by use of (high order) perturbative relations between the effective theory couplings at the charm and beauty quark "thresholds". The error of this perturbative step is discussed and estimated as $0.0002$.

  10. New ALPHA-2 magnet

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

  11. Lyman Alpha Control

    CERN Document Server

    Nielsen, Daniel Stefaniak

    2015-01-01

    This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

  12. Interpreting EEG alpha activity.

    Science.gov (United States)

    Bazanova, O M; Vernon, D

    2014-07-01

    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  13. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    2009-01-01

    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  14. Alpha-1-antitripsin deficiency: the need of a new diagnostic algorithm for improving the diagnostic ability of perinatologists and pediatricians

    Directory of Open Access Journals (Sweden)

    Gavino Faa

    2015-02-01

    Full Text Available Caution should be taken in considering immunoelectrofocusing (IEF as the best method for the diagnosis of alpha-1-antitrypsin (A1AT deficiency, particularly in some population, including Sardinians, in which a M-like variant represents the most frequent pathological A1AT variant. Regarding the future, my opinion is that the algorithm generally suggested for reaching a proper diagnosis of this disease should be completely changed. The cut-off of the A1AT serum values should be reconsidered, not to avoid the diagnosis of a number of heterozygous subjects who may be affected by liver and/or lung disease. Given that the two A1AT alleles are co-dominant, and since A1AT is a phase acute protein, in all heterozygous PiMZ or PiM/M-Cagliari subjects carrying an inflammation, the M allele is induced to produce high quantities of A1AT, whose serum levels may reach normal values. In these cases, PCR serum levels should be evaluated and, when increased, the diagnosis of A1AT deficiency should not be excluded even in the presence of serum A1AT levels within the normal range. Gene sequencing should be included, on the basis of our experience, in all neonates and pediatric patients with liver or lung disease of unknown origin, including asthma, avoiding IEF. Finally, for a screening in the perinatal period, I suggest the accurate examination of the electrophoresis of serum proteins. With a similar new approach, I think that we will transform A1AT deficiency from a rare disease into a previously rarely diagnosed disease, changing completely the epidemiology of this complex and fascinating metabolic disease.

  15. Buffett’s Alpha

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

    Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

  16. Laser assisted {alpha} decay

    Energy Technology Data Exchange (ETDEWEB)

    Castaneda Cortes, Hector Mauricio

    2012-02-01

    Excited or short-lived nuclei often decay by emitting alpha particles that are assumed to be preformed inside the nucleus and confined in the nuclear potential well. In this picture, {alpha} decay refers to the tunneling of the alpha particle through the potential barrier. In this thesis we investigate for the first time how strong laser fields can assist the tunneling of the alpha particle and thus influence the nuclear decay. Generally speaking, laser-assisted {alpha} decay can be described as laser-assisted tunneling of a quasistationary state, i.e, a slowly decaying state. Our theoretical treatment is developed starting from the complex trajectory formulation of the well-known strong-field approximation used to describe laser-induced ionization. We extend this formulation and develop a method to treat the decay of quasistationary states. The effect of both static and optical and X-ray monochromatic fields on the lifetimes and {alpha}-particle emission spectra are investigated for a number of {alpha}-emitting nuclei. We find that even at strong intensities, the laser-induced acceleration of the {alpha} decay is negligible, ranging from a relative modification in the decay rate of 10{sup -3} for static fields of electric field strengths of 10{sup 15} V/m, to 10{sup -8} for strong optical fields with intensities of 10{sup 22} W/cm{sup 2}, and to 10{sup -6} for strong X-ray fields with laser intensities around 10{sup 24} W/cm{sup 2}. However, the effect of the external field is visible in the spectrum of emitted alpha particles, leading in the case of optical fields even to rescattering phenomena for intensities approaching 6 x 10{sup 22} W/cm{sup 2}. The dynamics of the alpha particle in laser fields of intensities below the rescattering limit is investigated.

  17. Genetics Home Reference: alpha thalassemia

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions alpha thalassemia alpha thalassemia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Alpha thalassemia is a blood disorder that reduces the production ...

  18. ATZ11 recognizes not only Z-α1-antitrypsin-polymers and complexed forms of non-Z-α1-antitrypsin but also the von Willebrand factor.

    Directory of Open Access Journals (Sweden)

    Diane Goltz

    Full Text Available AIMS: The ATZ11 antibody has been well established for the identification of α1-anti-trypsin (AAT molecule type PiZ (Z-AAT in blood samples and liver tissue. In this study, we systematically analyzed the antibody for additional binding sites in human tissue. METHODS AND RESULTS: Ultrastructural ATZ11 binding was investigated immunoelectron microscopically in human umbilical vein endothelial cells (HUVECs and in platelets of a healthy individual. Human embryonic kidney (HEK293 cells were transiently transfected with Von Willebrand factor (VWF and analyzed immunocytochemically using confocal microscopy and SDS-PAGE electrophoresis followed by western blotting (WB. Platelets and serum samples of VWF-competent and VWF-deficient patients were investigated using native PAGE and SDS-PAGE electrophoresis followed by WB. The specificity of the ATZ11 reaction was tested immunohistochemically by extensive antibody-mediated blocking of AAT- and VWF-antigens. ATZ11-positive epitopes could be detected in Weibel-Palade bodies (WPBs of HUVECs and α-granules of platelets. ATZ11 stains pseudo-WBP containing recombinant wild-type VWF (rVWF-WT in HEK293 cells. In SDS-PAGE electrophoresis followed by WB, anti-VWF and ATZ11 both identified rVWF-WT. However, neither rVWF-WT-multimers, human VWF-multimers, nor serum proteins of VWF-deficient patients were detected using ATZ11 by WB, whereas anti-VWF antibody (anti-VWF detected rVWF-WT-multimers as well as human VWF-multimers. In human tissue specimens, AAT-antigen blockade using anti-AAT antibody abolished ATZ11 staining of Z-AAT in a heterozygous AAT-deficient patient, whereas VWF-antigen blockade using anti-VWF abolished ATZ11 staining of endothelial cells and megakaryocytes. CONCLUSIONS: ATZ11 reacts with cellular bound and denatured rVWF-WT and human VWF as shown using immunocytochemistry and subsequent confocal imaging, immunoelectron microscopy, SDS-PAGE and WB, and immunohistology. These immunoreactions are

  19. alpha_s from tau decays revisited

    CERN Document Server

    Boito, D; Golterman, M; Jamin, M; Maltman, K; Osborne, J; Peris, S

    2011-01-01

    Being a determination at low energies, the analysis of hadronic tau decay data provides a rather precise determination of the strong coupling alpha_s after evolving the result to M_Z. At such a level of precision, even small non-perturbative effects become relevant for the central value and error. While those effects had been taken into account in the framework of the operator product expansion, contributions going beyond it, so-called duality violations, have previously been neglected. The following investigation fills this gap through a finite-energy sum rule analysis of tau decay spectra from the OPAL experiment, including duality violations and performing a consistent fit of all appearing QCD parameters. The resulting values for alpha_s(M_tau) are 0.307(19) in fixed-order perturbation theory and 0.322(26) in contour-improved perturbation theory, which translates to the n_f=5 values 0.1169(25) and 0.1187(32) at M_Z, respectively.

  20. AlphaACT

    Science.gov (United States)

    2014-07-20

    CBR can be found in the world around us (e.g., a doctor’s diagnosis based on a prior patient case, a lawyer preparing arguments based on legal ... metaphors in decision research. Judgment & Decision Making, 3(3), 195-204. Payne, J., Bettman, J., & Johnson, E. (1993). The Adaptive Decision Maker...alphaact. com 64 AlphaACT HAZMAT User Guide 8.3 Changing Measurement Units AlphaACT HAZMAT lets you show distances in either metric or English

  1. ALPHA-2: the sequel

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.   The ALPHA team lower the new superconducting solenoid magnet into place. The ALPHA collaboration is working at full speed to complete the ALPHA-2 set-up for mid-November – this will give them a few weeks of running before the AD shutdown on 17 December. “We really want to get some experience with this device this year so that, if we need to make any changes, we will have time during the long shutdown in which to make them,” says Jeffrey Hangst, ALPHA spokesperson. “Rather than starting the 2014 run in the commissioning stage, we will be up and running from the get go.&...

  2. ALPHA MIS: Reference manual

    Energy Technology Data Exchange (ETDEWEB)

    Lovin, J.K.; Haese, R.L.; Heatherly, R.D.; Hughes, S.E.; Ishee, J.S.; Pratt, S.M.; Smith, D.W.

    1992-02-01

    ALPHA is a powerful and versatile management information system (MIS) initiated and sponsored and by the Finance and Business Management Division of Oak Ridge National Laboratory, who maintain and develop it in concert with the Business Systems Division for its Information Center. A general-purpose MIS, ALPHA allows users to access System 1022 and System 1032 databases to obtain and manage information. From a personal computer or a data terminal, Energy Systems employees can use ALPHA to control their own report reprocessing. Using four general commands (Database, Select, Sort, and Report) they can (1) choose a mainframe database, (2) define subsets within it, (3) sequentially order a subset by one or more variables, and (4) generate a report with their own or a canned format.

  3. AlphaSphere

    OpenAIRE

    Place, A.; Lacey, L.; Mitchell, T.

    2013-01-01

    The AlphaSphere is an electronic musical instrument featuring a series of tactile, pressure sensitive touch pads arranged in a spherical form. It is designed to offer a new playing style, while allowing for the expressive real-time modulation of sound available in electronic-based music. It is also designed to be programmable, enabling the flexibility to map a series of different notational arrangements to the pad-based interface.\\ud \\ud The AlphaSphere functions as an HID, MIDI and OSC devic...

  4. Alpha Antihydrogen Experiment

    CERN Document Server

    Fujiwara, M C; Ashkezari, M D; Baquero-Ruiz, M; Bertsche, W; Bray, C C; Butler, E; Cesar, C L; Chapman, S; Charlton, M; Cesar, C L; Fajans, J; Friesen, T; Gill, D R; Hangst, J S; Hardy, W N; Hayano, R S; Hayden, M E; Humphries, A J; Hydomako, R; Jonsell, S; Kurchaninov, L; Lambo, R; Madsen, N; Menary, S; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Pusa, P; Robicheaux, F; Sarid, E; Silveira, D M; So, C; Storey, J W; Thompson, R I; van der Werf, D P; Wilding, D; Wurtele, J S; Yamazaki, Y

    2011-01-01

    ALPHA is an experiment at CERN, whose ultimate goal is to perform a precise test of CPT symmetry with trapped antihydrogen atoms. After reviewing the motivations, we discuss our recent progress toward the initial goal of stable trapping of antihydrogen, with some emphasis on particle detection techniques.

  5. Case Study - Alpha

    Directory of Open Access Journals (Sweden)

    Stephen Leybourne

    2016-11-01

    Full Text Available This case study was developed from an actual scenario by Dr. Steve Leybourne of Boston University.  The case documents the historical evolution of an organization, and has been used successfully in courses dealing with organizational and cultural change, and the utilization of ‘soft skills’ in project-based management. This is a short case, ideal for classroom use and discussion.  The issues are easily accessible to students, and there is a single wide ranging question that allows for the inclusion of many issues surrounding strategic decision-making, and behavioural and cultural change. Alpha was one of the earlier companies in the USA to invest in large, edge-of-town superstores, with plentiful free vehicle parking, selling food and related household products. Alpha was created in the 1950s as a subsidiary of a major publicly quoted retail group.  It started business by opening a string of very large discount stores in converted industrial and warehouse premises in the south of the United States. In the early days shoppers were offered a limited range of very competitively priced products. When Alpha went public in 1981 it was the fourth largest food retailer in the US, selling an ever-widening range of food and non-food products.  Its success continued to be based on high volume, low margins and good value for money, under the slogan of ‘Alpha Price.’

  6. Alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line; Stensland, Hilde Monica Frostad Riise; Olsen, Klaus Juul;

    2015-01-01

    of the three subgroups of genotype/subcellular localisation and the clinical and biochemical data were done to investigate the potential relationship between genotype and phenotype in alpha-mannosidosis. Statistical analyses were performed using the SPSS software. Analyses of covariance were performed...

  7. HB Hillingdon [alpha46(CE4)Phe-->Val (alpha1 Or alpha2)]: a new alpha chain hemoglobin variant.

    Science.gov (United States)

    Babb, Anna; Solaiman, Susannah; Green, Brian N; Mantio, Debbie; Patel, Ketan

    2009-01-01

    Routine antenatal hemoglobinopathy screening detected a new alpha chain variant that eluted with Hb A(2) on cation exchange high performance liquid chromatography (HPLC) in a lady of Sri Lankan origin who had normal hematological indices. The mutation was identified by electrospray ionization mass spectrometry (ESI-MS) as alpha46(CE4)Phe-->Val, inferring that the variant was due to a single base change at codon 46 (TTC>GTC) of the alpha1- or alpha2-globin genes.

  8. $\\alpha$-Representation for QCD

    OpenAIRE

    Tuan, Richard Hong

    1998-01-01

    An $\\alpha$-parameter representation is derived for gauge field theories.It involves, relative to a scalar field theory, only constants and derivatives with respect to the $\\alpha$-parameters. Simple rules are given to obtain the $\\alpha$-representation for a Feynman graph with an arbitrary number of loops in gauge theories in the Feynman gauge.

  9. α1-ANTITRYPSIN ATTENUATES ENDOTOXIN-INDUCED ACUTE LUNG INJURY IN RABBITS

    Institute of Scientific and Technical Information of China (English)

    揭志军; 蔡映云; 杨文兰; 金美玲; 朱威; 祝慈芳

    2003-01-01

    Objective To investigate whether pretreatment with α1-AT can attenuate acute lung injury (ALI) in rabbits induced with endotoxin. Methods Thirty-two New Zealand rabbits were randomly assigned to four groups(n=8):1.Infusion of endotoxin(Lipopolysaccharide,LPS 500μg/kg)without α1-AT (group LPS).2.Infusion α1-AT 120mg/kg at 15min before challenge with LPS(group LAV).3.Infusion of α1-AT 120mg/kg(group AAT).4 Infusion of saline 4ml/kg as control (group NS).Arterial blood gases,peripheral leukocyte counts and airway pressure were recorded every 1h.Physiologic intrapulmonary shunting (Qs/Qt) was measured every 4h.After 8h the bloods were collected for measurement of plasma concentration and activity of α1-AT.Then bronchoalveolar lavage fluid (BALF)was collected for measurement of concentrations of total protein (TP),interleukin-8(IL-8),tumor necrosis factor(TNF-α),the activities of elastase-like and α1-AT,total phospholipids(TPL) and disaturated phosphatidylcholine (DSPC).In addition,the wet-to-dry lung weight ratio(W/D) was measured. Results After infusion of endotoxin,it was observed that PaO2,peripheral luekocyte counts,total respiratory compliance progressively decreased and Ppeak and Qs/Qt increased comparing with the baseline values.In contrast to group NS,the increased plasma concentration but reduced activity of α1-AT was found in group LPS.In the BALF,the activity of α1-AT,TPL,DSPC/TPL were lower,but the concentrations of albumin,IL-8,TNF-α,and the activity of NE were higher.The ratio of W/D also increased.The pretreatment of α1-AT attenuated the deterioration of oxygenation,the reduction of compliance and the deterioration of other physiological,biochemical parameters mentioned above. Conclusion Pretreatment with α1-AT could attenuate endotoxin-induced lung injury in rabbits.Those beneficial effects of α1-AT might be due in part to the inhibitory effect on neutrophil elastase.

  10. Alpha and Beta Determinations

    CERN Document Server

    Dunietz, Isard

    1999-01-01

    Because the Bd -> J/psi Ks asymmetry determines only sin(2 beta), a discrete ambiguity in the true value of beta remains. This note reviews how the ambiguity can be removed. Extractions of the CKM angle alpha are discussed next. Some of the methods require very large data samples and will not be feasible in the near future. In the near future, semi-inclusive CP-violating searches could be undertaken, which are reviewed last.

  11. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze

    2015-11-01

    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  12. Orthopositronium lifetime. Analytic results in O ({alpha}) and O ({alpha}{sup 3} ln {alpha})

    Energy Technology Data Exchange (ETDEWEB)

    Kniehl, B.A.; Kotikov, A.V.; Veretin, O.L. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2008-06-15

    We present the O({alpha}) and O({alpha}{sup 3}ln {alpha}) corrections to the total decay width of orthopositronium in closed analytic form, in terms of basic transcendental numbers, which can be evaluated numerically to arbitrary precision. (orig.)

  13. [Comparative studies on the value of acute phase proteins and CA-125 for monitoring patients with ovarian cancer].

    Science.gov (United States)

    Kölbl, H; Tatra, G; Schieder, K; Bieglmayer, C

    1988-12-01

    In a study of 71 patients with malignant ovarian tumors serum levels of CA-125, C-reactive protein (CRP), alpha-1-antitrypsin and coeruloplasmin were analysed. In contrast to the tumor-free group significantly higher values of CA-125, CRP and alpha-1-antitrypsin were found in the group with recurrent disease. However, the serum-concentrations of coeruloplasmin remained unchanged in both groups. In the group with progressive disease the median values of CA-125 were greater than 65 U/ml and of CRP greater than 12 micron/ml, respectively. The median serum concentrations of alpha-1-antitrypsin (2 to 4 mg/ml) and coeruloplasmin (150 to 600 ng/ml) did not reach their cut-off levels. Beside CA-125 the analysis of CRP and alpha-1-antitrypsin is an additional helpful procedure for the monitoring of patients with malignant ovarian tumors.

  14. Alpha-mannosidosis

    Directory of Open Access Journals (Sweden)

    Nilssen Øivind

    2008-07-01

    Full Text Available Abstract Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual disability. It occurs in approximately 1 of 500,000 live births. The children are often born apparently normal, and their condition worsens progressively. Some children are born with ankle equinus or develop hydrocephalus in the first year of life. Main features are immune deficiency (manifested by recurrent infections, especially in the first decade of life, skeletal abnormalities (mild-to-moderate dysostosis multiplex, scoliosis and deformation of the sternum, hearing impairment (moderate-to-severe sensorineural hearing loss, gradual impairment of mental functions and speech, and often, periods of psychosis. Associated motor function disturbances include muscular weakness, joint abnormalities and ataxia. The facial trait include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, and prognathism. Slight strabismus is common. The clinical variability is significant, representing a continuum in severity. The disorder is caused by lysosomal alpha-mannosidase deficiency. Alpha-mannosidosis is inherited in an autosomal recessive fashion and is caused by mutations in the MAN2B1 gene located on chromosome 19 (19 p13.2-q12. Diagnosis is made by measuring acid alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed by genetic testing. Elevated urinary secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic. Differential diagnoses are mainly the other lysosomal storage diseases like the mucopolysaccharidoses. Genetic counseling should be given to explain the nature of the disease and to detect carriers. Antenatal diagnosis is possible, based on both biochemical and genetic methods. The management should be pro-active, preventing complications and treating

  15. Alpha phoenix公司

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    德国Alpha phoenix公司成立于2009年.专注于制药领域清洗机器的研发和生产,产品符合cGMP的要求。公司的人员是制药领域清洗机器研发和生产的专家,他们具有20多年的全自动清洗机器的设计和生产经验。

  16. Are alpha-gliadins glycosylated?

    Science.gov (United States)

    Turner, J B; Garner, G V; Gordon, D B; Brookes, S J; Smith, C A

    2002-02-01

    Alpha-gliadins isolated by carboxymethylcellulose chromatography contain noncovalently bound glucose probably due to contaminating proteoglycans and to material shed from the column. Traces of carbohydrate remain strongly bound to alpha-gliadins even after harsh denaturation, but our results indicate alpha-gliadins are not glycoproteins. Suggestions that gliadins are glycoproteins are probably due to contamination with this glucose and the presence of these proteoglycans.

  17. Robust estimation of Cronbach's alpha

    OpenAIRE

    2002-01-01

    Cronbach’s alpha is a popular method to measure reliability, e.g. in quantifying the reliability of a score to summarize the information of several items in questionnaires. The alpha coefficient is known to be non-robust. We study the behavior of this coefficient in different settings to identify situations, which can easily occur in practice, but under which the Cronbach’s alpha coefficient is extremely sensitive to violations of the classical model assumptions. Furthermore, we construct a r...

  18. PDFs, $\\alpha_s$, and quark masses from global fits

    CERN Document Server

    Alekhin, S; Moch, S; Placakyte, R

    2016-01-01

    The strong coupling constant $\\alpha_s$ and the heavy-quark masses, $m_c$, $m_b$, $m_t$ are extracted simultaneosly with the parton distribution functions (PDFs) in the updated ABM12 fit including recent data from CERN-SPS, HERA, Tevatron, and the LHC. The values of \\begin{eqnarray} \

  19. Molecular characterization of alpha 1- and alpha 2-adrenoceptors.

    Science.gov (United States)

    Harrison, J K; Pearson, W R; Lynch, K R

    1991-02-01

    Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin Lynch and his colleagues discuss these questions in this review.

  20. Alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Danielsen, E R; Thomsen, Carsten;

    2016-01-01

    Alpha-mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty......-protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated...... concentrations of CSF-biomarkers and CSF-oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment....

  1. DFT CONFORMATIONAL STUDIES OF ALPHA-MALTOTRIOSE

    Science.gov (United States)

    Recent DFT optimization studies on alpha-maltose improved our understanding of the preferred conformations of alpha-maltose and the present study extends these studies to alpha-maltotriose with three alpha-D-glucopyranose residues linked by two alpha-[1-4] bridges, denoted herein as DP-3's. Combina...

  2. The ALPHA antihydrogen trapping apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Amole, C. [Department of Physics and Astronomy, York University, Toronto ON Canada, M3J 1P3 (Canada); Andresen, G.B. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Ashkezari, M.D. [Department of Physics, Simon Fraser University, Burnaby, BC Canada, V5A 1S6 (Canada); Baquero-Ruiz, M. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Bertsche, W. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); School of Physics and Astronomy, University of Manchester, Manchester M13 9PL (United Kingdom); The Cockcroft Institute, Warrington WA4 4AD (United Kingdom); Bowe, P.D. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Butler, E. [Physics Department, CERN, CH-1211 Geneva 23 (Switzerland); Capra, A. [Department of Physics and Astronomy, York University, Toronto ON Canada, M3J 1P3 (Canada); Carpenter, P.T. [Department of Physics, Auburn University, Auburn, AL 36849-5311 (United States); Cesar, C.L. [Instituto de Física, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-972 (Brazil); Chapman, S. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Charlton, M.; Deller, A.; Eriksson, S. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); Escallier, J. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Fajans, J. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Friesen, T. [Department of Physics and Astronomy, University of Calgary, Calgary AB, Canada, T2N 1N4 (Canada); Fujiwara, M.C.; Gill, D.R. [TRIUMF, 4004 Wesbrook Mall, Vancouver BC, Canada V6T 2A3 (Canada); Gutierrez, A. [Department of Physics and Astronomy, University of British Columbia, Vancouver BC, Canada V6T 1Z4 (Canada); and others

    2014-01-21

    The ALPHA collaboration, based at CERN, has recently succeeded in confining cold antihydrogen atoms in a magnetic minimum neutral atom trap and has performed the first study of a resonant transition of the anti-atoms. The ALPHA apparatus will be described herein, with emphasis on the structural aspects, diagnostic methods and techniques that have enabled antihydrogen trapping and experimentation to be achieved.

  3. Alpha particle emitters in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.

    1989-09-01

    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ({sup 211}At) and natural bismuth-212 ({sup 212}Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ({sup 223}Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs.

  4. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

    Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.;

    2004-01-01

    Proteins that inhibit alpha-amylases have been isolated from plants and microorganisms. These inhibitors can have natural roles in the control of endogenous a-amylase activity or in defence against pathogens and pests; certain inhibitors are reported to be antinutritional factors. The alpha-amylase...... inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha-amylases...... in complex with inhibitors from five families. These structures indicate major diversity but also some similarity in the structural basis of alpha-amylase inhibition. Mutational analysis of the mechanism of inhibition was performed in a few cases and various protein engineering and biotechnological...

  5. Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum.

    Science.gov (United States)

    Porcu, Patrizia; O'Buckley, Todd K; Alward, Sarah E; Marx, Christine E; Shampine, Lawrence J; Girdler, Susan S; Morrow, A Leslie

    2009-01-01

    The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, psteroid was detected only in 3/16 control subjects. Levels of 3alpha,5alpha-A, 3alpha,5beta-A and pregnenolone were not altered. This method can be used to investigate the physiological and pathological role of neuroactive steroids and to develop biomarkers and new therapeutics for neurological and psychiatric disorders.

  6. Radiative Corrections to the Muonium Hyperfine Structure; 2, The $\\alpha (Z\\alpha)^2$ Correction

    CERN Document Server

    Nio, M

    1997-01-01

    This is the second of a series of papers on the radiative corrections of order $\\alpha^2 (Z\\alpha)$, $\\alpha (Z\\alpha )^2$, and various logarithmic terms of order $\\alpha^4$, to the hyperfine structure of the muonium ground state. This paper deals with the $\\alpha (Z\\alpha)^2$ correction. Based on the NRQED bound state theory, we isolated the term of order $\\alpha(Z\\alpha)^2$ exactly. Our result $+16.904~2~(11) \\alpha(Z\\alpha)^2 E_F / \\pi$ for the non-logarithmic part is consistent with the $\\alpha (Z\\alpha)^2$ part of Sapirstein's calculation and the recent result of Pachucki, and reduces the numerical uncertainty in the $\\alpha (Z\\alpha)^2$ term by two orders of magnitude.

  7. ALPHA freezes antiprotons

    CERN Multimedia

    CERN Bulletin

    2010-01-01

    Laboratories like CERN can routinely produce many different types of antiparticles. In 1995, the PS210 experiment formed the first antihydrogen atoms and a few years later, in 2002, ATRAP and ATHENA were already able to produce several thousand of them. However, no experiment in the world has succeeded in ‘trapping’ these anti-atoms in order to study them. This is the goal of the ALPHA experiment, which has recently managed to cool down the antiprotons to just a few Kelvin. This represents a major step towards trapping the anti-atom, thus opening a new avenue into the investigation of antimatter properties.   Members of the ALPHA collaboration working on the apparatus in the Antiproton Decelerator experimental hall at CERN. Just like the atom, the anti-atom is neutral. Unlike the atom, the anti-atom is made up of antiprotons (as opposed to protons in the atom) and positrons (as opposed to electrons). In order to thoroughly study the properties of the anti-atoms, scien...

  8. Venus - Alpha Regio

    Science.gov (United States)

    1990-01-01

    The eastern edge of Alpha Regio is shown in this image centered at 30 degrees south latitude and 11.8 degrees east longitude (longitude on Venus is measured from 0 degrees to 360 degrees east). Seven circular, dome-like hills, averaging 25 kilometers (15 miles) in diameter with maximum heights of 750 meters (2,475 feet) dominate the scene. These features are interpreted as very thick lava flows that came from an opening on the relatively level ground, which allowed the lava to flow in an even pattern outward from the opening. The complex fractures on top of the domes suggest that if the domes were created by lava flows, a cooled outer layer formed and then further lava flowing in the interior stretched the surface. The domes may be similar to volcanic domes on Earth. Another interpretation is that the domes are the result of molten rock or magma in the interior that pushed the surface layer upward. The near-surface magma then withdrew to deeper levels, causing the collapse and fracturing of the dome surface. The bright margins possibly indicate the presence of rock debris on the slopes of the domes. Some of the fractures on the plains cut through the domes, while others appear to be covered by the domes. This indicates that active processes pre date and post date the dome-like hills. The prominent black area in the northeast corner of the image is a data gap. North is at the top of the image.

  9. Partitioning $\\alpha$-large sets for $\\alpha<\\varepsilon_{\\omega}$

    CERN Document Server

    De Smet, Michiel

    2010-01-01

    We generalise the results by Bigorajska and Kotlarski about partitioning $\\alpha$-large sets, by extending the domain up to ordinals below $\\varepsilon_{\\omega}$. These results will be very useful to give a miniaturisation of the infinite Ramsey Theorem.

  10. Two alpha, three alpha and multiple heavy-ion radioactivities

    Energy Technology Data Exchange (ETDEWEB)

    Poenaru, D.N.; Ivascu, M. (Institute for Physics and Nuclear Engineering, Bucharest (Romania))

    1985-07-01

    New decay modes by spontaneous emission of two and three ..cap alpha.. particles and two identical or different heavy ions, are predicted. The analytical variant of the superasymmetric fission model is used to estimate the half lives.

  11. Alpha heating in toroidal devices

    Energy Technology Data Exchange (ETDEWEB)

    Miley, G.H.

    1978-01-01

    Ignition (or near-ignition) by alpha heating is a key objective for the achievement of economic fusion reactors. While good confinement of high-energy alphas appears possible in larger reactors, near-term tokamak-type ignition experiments as well as some concepts for small reactors (e.g., the Field-Reversed Mirror or FRM) potentially face marginal situations. Consequently, there is a strong motivation to develop methods to evaluate alpha losses and heating profiles in some detail. Such studies for a TFTR-size tokamak and for a small FRM are described here.

  12. The Lyman alpha reference sample

    DEFF Research Database (Denmark)

    Hayes, M.; Östlin, G.; Schaerer, D.

    2013-01-01

    We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 ... with quantities that scale with dust content, in the sense that a low dust abundance is a necessary requirement (although not the only one) in order to spread Lyα photons throughout the interstellar medium and drive a large extended Lyα halo. © 2013. The American Astronomical Society. All rights reserved....

  13. Almost Redundant Components in the 3 alpha Faddeev Equation for the Buck, Friedlich and Wheatly alpha alpha Potential

    CERN Document Server

    Fujiwara, Y; Kohno, M

    2004-01-01

    The 3 alpha orthogonality condition model using the Pauli-forbidden bound states of the Buck, Friedlich and Wheatly alpha alpha potential can yield a compact 3 alpha ground state with a large binding energy, in which a small admixture of the redundant components can never be eliminated.

  14. Changes in blood levels of proteinase inhibitors, pregnancy zone protein, steroid carriers and complement factors induced by oral contraceptives

    DEFF Research Database (Denmark)

    Nielsen, C H; Poulsen, H K; Teisner, B

    1993-01-01

    levels of antithrombin III (AT III), alpha 2-macroglobulin (alpha 2M) alpha 1-antitrypsin (alpha 1at), complement factors (factor B, C3, C4), pregnancy zone protein (PZP), corticosteroid binding globulin (CBG), sex hormone binding globulin (SHBG) and albumin were measured before treatment and during...

  15. Investigation of the Pygmy Dipole Resonance in (alpha, alpha 'gamma) coincidence experiments

    NARCIS (Netherlands)

    Savran, D.; Babilon, M.; van den Berg, A. M.; Harakeh, M. N.; Hasper, J.; Wortche, H. J.; Zilges, A.

    2007-01-01

    We report on first results from experiments using the (alpha, alpha'gamma) reaction at E alpha = 136 MeV to investigate bound electric dipole (El) excitations building the so-called Pygmy Dipole Resonance (PDR) in the semi-magic nucleus Ce-140. The method of (alpha, alpha'gamma) allows the separatio

  16. Workshop on Precision Measurements of $\\alpha_s$

    Energy Technology Data Exchange (ETDEWEB)

    Bethke, Siegfried; /Munich, Max Planck Inst.; Hoang, Andre H.; /Vienna U.; Kluth, Stefan; /Munich, Max Planck Inst.; Schieck, Jochen; /Munich U.; Stewart, Iain W.; Aoki, S.; Beneke, M.; Bethke, S.; Blumlein, J.; Brambilla, N.; Brodsky, S.; /MIT, LNS

    2011-10-01

    These are the proceedings of the Workshop on Precision Measurements of {alpha}{sub s} held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of {alpha}{sub s}(m{sub Z}) in the {ovr MS} scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, {tau}-decays, electro-weak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

  17. Scale Setting for $\\alpha_{s}$ Beyond Leading Order

    CERN Document Server

    Hornbostel, K; Morningstar, C J

    2001-01-01

    We present a general procedure for applying the scale-setting prescription of Brodsky, Lepage and Mackenzie to higher orders in the strong coupling constant $\\alphas$. In particular, we show how to apply this prescription when the leading coefficient or coefficients in a series in $\\alphas$ are anomalously small. We give a general method for computing an optimum scale numerically, within dimensional regularization, and in cases when the coefficients of a series are known. We find significant corrections to the scales for $R_{e^+ e^-}$, $\\Gamma(B \\to X_u e \\bar{\

  18. Proxima's orbit around Alpha Centauri

    CERN Document Server

    Kervella, P

    2016-01-01

    Proxima and Alpha Centauri AB have almost identical distances and proper motions with respect to the Sun. Although the probability of such similar parameters is in principle very low, the question whether they actually form a single gravitationally bound triple system has been open since the discovery of Proxima one century ago. Owing to recent high precision radial velocity measurements and the revision of the parameters of the Alpha Cen pair, we show that Proxima and Alpha Cen are gravitationally bound with a high degree of confidence. The orbital period of Proxima is approximately 600 000 years, with a moderate excentricity of 0.42 +0.07 -0.08. Proxima comes within 5.3 -0.9 +1.2 kAU of Alpha Cen at periastron, and the apastron occurs at 12.9 +0.3 -0.1 kAU. This orbital motion may have influenced the formation or evolution of the recently discovered planet orbiting Proxima as well as circumbinary planet formation around Alpha Cen.

  19. Bioisosteric phentolamine analogs as selective human alpha(2)- versus alpha(1)-adrenoceptor ligands.

    Science.gov (United States)

    Bavadekar, Supriya A; Hong, Seoung-Soo; Lee, Sang-Ii; Miller, Duane D; Feller, Dennis R

    2008-08-20

    Phentolamine is known to act as a competitive, non-subtype-selective alpha-adrenoceptor antagonist. In an attempt to improve alpha(2)- versus alpha(1)-adrenoceptor selectivity and alpha(2)-adrenoceptor subtype-selectivity, two new chemical series of bioisosteric phentolamine analogs were prepared and evaluated. These compounds were evaluated for binding affinities on alpha(1)- (alpha(1A)-, alpha(1B)-, alpha(1D)-) and alpha(2)- (alpha(2A)-, alpha(2B)-, alpha(2C)-) adrenoceptor subtypes that had been stably expressed in human embryonic kidney and Chinese hamster ovary cell lines, respectively. Methylation of the phenolic hydroxy group and replacement of the 4-methyl group of phentolamine with varying lipophilic substituents yielded bioisosteric analogs selective for the alpha(2)- versus alpha(1)-adrenoceptors. Within the alpha(2)-adrenoceptors, these analogs bound with higher affinity at the alpha(2A)- and alpha(2C)-subtypes as compared to the alpha(2B)-subtype. In particular, the t-butyl analog was found to be the most selective, its binding at the alpha(2C)-adrenoceptor (Ki=3.6 nM) being 37- to 173-fold higher than that at the alpha(1)-adrenoceptors, and around 2- and 19-fold higher than at the alpha(2A)- and alpha(2B)-adrenoceptors, respectively. Data from luciferase reporter gene assays confirmed the functional antagonist activities of selected compounds from the bioisosteric series on human alpha(1A)- and alpha(2C)-adrenoceptors. Thus, the results with these bioisosteric analogs of phentolamine provide a lead to the rational design of potent and selective alpha(2)-adrenoceptor ligands that may be useful in improving the therapeutic profile of this drug class for human disorders.

  20. NACA Physicist Studying Alpha Rays

    Science.gov (United States)

    1957-01-01

    NACA Physicits studying Alpha Rays in a continuous cloud chamber. A cloud chamber is used by Lewis scientists to obtain information aimed at minimizing undesirable effects of radiation on nuclear-powered aircraft components. Here, alpha particles from a polonium source emit in a flower-like pattern at the cloud chamber's center. The particles are made visible by means of alcohol vapor diffusing from an area at room temperature to an area at minus -78 deg. Centigrade. Nuclear-powered aircraft were never developed and aircraft nuclear propulsion systems were canceled in the early 1960s.

  1. Simulating the Lyman Alpha Forest

    CERN Document Server

    Machacek, M E; Anninos, P; Meiksin, A; Norman, M L; Machacek, Marie E.; Bryan, Greg L.; Anninos, Peter; Meiksin, Avery; Norman, Michael L.

    1998-01-01

    In this paper we review the importance of the Lyman alpha forest as a probe of structure formation in the universe. We first discuss the statistics used to describe the Lyman alpha forest and the numerical techniques used to produce simulated spectra of the forest from a given cosmological model. We then discuss the physical picture of the absorbing structures that emerges from these numerical simulations. Finally, we comment on how two of the statistics, the slope of the column density distribution and the b parameter distribution, may be used to constrain competing cosmologies.

  2. Safety and tolerability of an intravenously administered alpha1-proteinase inhibitor at an increased infusion rate: a novel, randomized, placebo-masked, infusion rate-controlled, crossover study in healthy adults

    Directory of Open Access Journals (Sweden)

    Ngo LY

    2014-06-01

    Full Text Available Leock Y Ngo,1 Adam Haeberle,1 Jacqueline Dyck-Jones,1 David Gelmont,1 Leman Yel11Baxter Healthcare Corporation, Westlake Village, CA, USAPurpose: Alpha1-proteinase inhibitor (A1PI is indicated for chronic augmentation therapy in adults with emphysema due to congenital deficiency of A1PI. An intravenous infusion rate of 0.04 mL/kg/minute is currently recommended for the A1PI product, Glassia®. This randomized, placebo-masked, rate-controlled, crossover study was designed to evaluate the safety and tolerability of A1PI administration at an increased infusion rate.Patients and methods: A total of 30 healthy male and female subjects aged 19–61 years were enrolled. Each subject received simultaneous intravenous infusions of A1PI (Glassia® and placebo (human albumin 2.5% administered through a single infusion site on two separate treatment periods. Subjects were randomized in a 1:1 ratio to receive either test treatment (A1PI 0.2 mL/kg/minute + placebo 0.04 mL/kg/minute, or reference treatment (A1PI 0.04 mL/kg/minute + placebo 0.2 mL/kg/minute on Day 1. On Day 15, subjects received the other treatment regimen in a crossover sequence.Results: A total of 36 adverse events (AEs, regardless of causality, were reported; all were non-serious and of mild intensity, with headaches and dizziness occurring most frequently (12 [33.3%] and three [8.3%] of 36 AEs, respectively. Only seven AEs in six subjects were assessed as related to study treatment: with two AEs reported in two subjects treated with the 0.2 mL/kg/minute rate compared with five AEs in four subjects treated with the 0.04 mL/kg/minute rate.Conclusions: This study demonstrated the safety and tolerability of an A1PI product at an increased infusion rate (0.2 mL/kg/minute resulting in a shorter infusion duration in healthy subjects.Keywords: A1PI, Glassia, administration rate, Alpha-1 antitrypsin, ATT

  3. Alpha-nucleus potential for alpha-decay and sub-barrier fusion

    CERN Document Server

    Denisov, V Y

    2005-01-01

    The set of parameters for alpha-nucleus potential is derived by using the data for both the alpha-decay half-lives and the fusion cross-sections around the barrier for reactions alpha+40Ca, alpha+59Co, alpha+208Pb. The alpha-decay half-lives are obtained in the framework of a cluster model using the WKB approximation. The evaluated alpha-decay half-lives and the fusion cross-sections agreed well with the data. Fusion reactions between alpha-particle and heavy nuclei can be used for both the formation of very heavy nuclei and spectroscopic studies of the formed compound nuclei.

  4. Alpha-nucleus potential for alpha-decay and sub-barrier fusion

    OpenAIRE

    Denisov, V. Yu.; Ikezoe, H.

    2005-01-01

    The set of parameters for alpha-nucleus potential is derived by using the data for both the alpha-decay half-lives and the fusion cross-sections around the barrier for reactions alpha+40Ca, alpha+59Co, alpha+208Pb. The alpha-decay half-lives are obtained in the framework of a cluster model using the WKB approximation. The evaluated alpha-decay half-lives and the fusion cross-sections agreed well with the data. Fusion reactions between alpha-particle and heavy nuclei can be used for both the f...

  5. Inflaton Decay in an Alpha Vacuum

    CERN Document Server

    Naidu, S; Naidu, Siddartha; Holman, Richard

    2004-01-01

    We study the alpha vacua of de Sitter space by considering the decay rate of the inflaton field coupled to a scalar field placed in an alpha vacuum. We find an {\\em alpha dependent} Bose enhancement relative to the Bunch-Davies vacuum and, surprisingly, no non-renormalizable divergences. We also consider a modified alpha dependent time ordering prescription for the Feynman propagator and show that it leads to an alpha independent result. This result suggests that it may be possible to calculate in any alpha vacuum if we employ the appropriate causality preserving prescription.

  6. What Powers Lyman alpha Blobs?

    CERN Document Server

    Ao, Y; Beelen, A; Henkel, C; Cen, R; De Breuck, C; Francis, P; Kovacs, A; Lagache, G; Lehnert, M; Mao, M; Menten, K M; Norris, R; Omont, A; Tatemastu, K; Weiss, A; Zheng, Z

    2015-01-01

    Lyman alpha blobs (LABs) are spatially extended lyman alpha nebulae seen at high redshift. The origin of Lyman alpha emission in the LABs is still unclear and under debate. To study their heating mechanism(s), we present Australia Telescope Compact Array (ATCA) observations of the 20 cm radio emission and Herschel PACS and SPIRE measurements of the far-infrared (FIR) emission towards the four LABs in the protocluster J2143-4423 at z=2.38. Among the four LABs, B6 and B7 are detected in the radio with fluxes of 67+/-17 microJy and 77+/-16 microJy, respectively, and B5 is marginally detected at 3 sigma (51+/-16 microJy). For all detected sources, their radio positions are consistent with the central positions of the LABs. B6 and B7 are obviously also detected in the FIR. By fitting the data with different templates, we obtained redshifts of 2.20$^{+0.30}_{-0.35}$ for B6 and 2.20$^{+0.45}_{-0.30}$ for B7 which are consistent with the redshift of the lyman alpha emission within uncertainties, indicating that both ...

  7. Alpha proton x ray spectrometer

    Science.gov (United States)

    Rieder, Rudi; Waeke, H.; Economou, T.

    1994-01-01

    Mars Pathfinder will carry an alpha-proton x ray spectrometer (APX) for the determination of the elemental chemical composition of Martian rocks and soils. The instrument will measure the concentration of all major and some minor elements, including C, N, and O at levels above typically 1 percent.

  8. Sparse Coding for Alpha Matting.

    Science.gov (United States)

    Johnson, Jubin; Varnousfaderani, Ehsan; Cholakkal, Hisham; Rajan, Deepu

    2016-04-21

    Existing color sampling based alpha matting methods use the compositing equation to estimate alpha at a pixel from pairs of foreground (F) and background (B) samples. The quality of the matte depends on the selected (F,B) pairs. In this paper, the matting problem is reinterpreted as a sparse coding of pixel features, wherein the sum of the codes gives the estimate of the alpha matte from a set of unpaired F and B samples. A non-parametric probabilistic segmentation provides a certainty measure on the pixel belonging to foreground or background, based on which a dictionary is formed for use in sparse coding. By removing the restriction to conform to (F,B) pairs, this method allows for better alpha estimation from multiple F and B samples. The same framework is extended to videos, where the requirement of temporal coherence is handled effectively. Here, the dictionary is formed by samples from multiple frames. A multi-frame graph model, as opposed to a single image as for image matting, is proposed that can be solved efficiently in closed form. Quantitative and qualitative evaluations on a benchmark dataset are provided to show that the proposed method outperforms current state-of-the-art in image and video matting.

  9. Evolution and seismology of alpha Centauri

    CERN Document Server

    Montalban, J; Montalban, Josefina; Miglio, Andrea

    2005-01-01

    Solar-like oscillations detected in both components of the binary system alpha Centauri provide strong constraints on the fundamental parameters of the stellar system. We model alpha Centauri by means of a Levenberg-Marquardt minimization algorithm including seismic and classical constraints. Computations, that were perfomed decreasing significanly the weight of alpha Cen B seismic data in the calibration procedure, predict small separations in good agreement with new observations of solar-like oscillations in alpha Cen B by Bedding (these proceedings).

  10. Astrophysical reaction rate for $\\alpha(\\alpha n,\\gamma)$

    CERN Document Server

    Sumiyoshi, K; Goko, S; Kajino, T

    2002-01-01

    We study the astrophysical reaction rate for the formation of $^{9}$Be through the three body reaction $\\alpha(\\alpha n,\\gamma)$. This reaction is one of the key reactions which could bridge the mass gap at A = 8 nuclear systems to produce intermediate-to-heavy mass elements in alpha- and neutron-rich environments such as r-process nucleosynthesis in supernova explosions, s-process nucleosynthesis in asymptotic giant branch (AGB) stars, and primordial nucleosynthesis in baryon inhomogeneous cosmological models. To calculate the thermonuclear reaction rate in a wide range of temperatures, we numerically integrate the thermal average of cross sections assuming a two-steps formation through a metastable $^{8}$Be. Off-resonant and on-resonant contributions from the ground state in $^{8}$Be are taken into account. As input cross section, we adopt the latest experimental data by photodisintegration of $^{9}$Be with laser-electron photon beams, which covers all relevant resonances in $^{9}$Be. We provide the reactio...

  11. THE ALPHA/BETA-HYDROLASE FOLD

    NARCIS (Netherlands)

    OLLIS, DL; CHEAH, E; CYGLER, M; FROLOW, F; FRANKEN, SM; HAREL, M; REMINGTON, SJ; SILMAN, [No Value; SCHRAG, J; SUSSMAN, JL; VERSCHUEREN, KHG; GOLDMAN, A

    1992-01-01

    We have identified a new protein fold-the alpha/beta-hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta-sheet, not barrel, of eight beta-sheets connected by alpha-helices. These

  12. Effectiveness of Alpha Biofeedback Therapy: Negative Results.

    Science.gov (United States)

    Watson, Charles G.; Herder, Joseph

    1980-01-01

    Assessed the utility of alpha biofeedback training in the treatment of patients (N=66). Biofeedback and placebo biofeedback groups were given alpha or mock-alpha training sessions. Improvement on 54 variables was compared to that of no-treatment controls. Only a chance number of significant changes appeared among the groups. (Author)

  13. Enzyme replacement therapy for alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J

    2013-01-01

    Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intrave...... intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment....

  14. Refinement of the $n-\\alpha$ and $p-\\alpha$ fish-bone potential

    CERN Document Server

    Smith, E; Papp, Z

    2012-01-01

    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the $n-\\alpha$ and $p-\\alpha$ fish-bone potential by simultaneously fitting to the experimental phase shifts. We found that with a double Gaussian parametrization of the local potential can describe the $n-\\alpha$ and $p-\\alpha$ phase shifts for all partial waves.

  15. Nature of the pygmy dipole resonance in Ce-140 studied in (alpha, alpha 'gamma) experiments

    NARCIS (Netherlands)

    Savran, D.; Babilon, M.; van den Berg, A. M.; Harakeh, M. N.; Hasper, J.; Matic, A.; Wortche, H. J.; Zilges, A.

    2006-01-01

    A concentration of electric-dipole excitations below the particle threshold, which is frequently denoted as the pygmy dipole resonance, has been studied in the semimagic nucleus Ce-140 in (alpha, alpha(')gamma) experiments at E-alpha=136 MeV. The technique of alpha-gamma coincidence experiments allo

  16. Separation of the subtypes of type V collagen molecules, [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha 3(V), by chain composition-dependent affinity for heparin: single alpha 1(V) chain shows intermediate heparin affinity between those of the type V collagen subtypes composed of [alpha 1(V)]2 alpha 2(V) and of alpha 1(V) alpha 2(V) alpha 3(V).

    Science.gov (United States)

    Mizuno, K; Hayashi, T

    1996-11-01

    The heparin affinities of heat-treated type V collagen alpha-chains and the triple-helical molecules were evaluated in terms of the NaCl concentration required for prevention of binding to a heparin-Sepharose column. After heat treatment, alpha 1(V) chain required approximately two-fold higher NaCl concentration to pass through the column than the other two chains, alpha 2(V) and alpha 3(V). Thus, the heparin affinity of alpha 1(V) may be approximately two-fold higher than those of the other alpha (V)-chains. The type V collagen molecules in triple-helical conformation were separated into two fractions at 170 mM NaCl in 20 mM phosphate buffer, pH 7.2, containing 2 M urea; bound and non-bound. The ratio of the three alpha-chains, alpha 1(V): alpha 2(V): alpha 3(V) was 2 : 1 : 0 and 1 : 1 : 1 in the bound and flow-through fractions, respectively, on analysis by SDS-PAGE. The differential affinity of the two fractions could be accounted for by the number of alpha 1(V) chains in the triple-helical molecule, if these fractions contained triple-helical subtypes with the chain compositions of [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha 3(V), respectively. From the comparison of the NaCl concentration required for prevention of the binding, [alpha 1(V)]2, alpha 2(V) had about two-fold higher affinity than alpha 1(V) alpha 2(V) alpha 3(V), and the separated alpha 1(V) chain showed an intermediate affinity. A possible explanation for difference in heparin affinity among the subtypes of molecules and the separated alpha-chains is that the heparin affinity of type V collagen molecule is governed by the number of alpha 1(V) chains contained in the molecule and that steric restraint in a triple-helical conformation weakens the binding of alpha 1(V) chain to heparin.

  17. Crystalline anhydrous {alpha},{alpha}-trehalose (polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose: A calorimetric study

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Susana S. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: susanapinto@ist.utl.pt; Diogo, Herminio P. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: hdiogo@ist.utl.pt; Moura-Ramos, Joaquim J. [Centro de Quimica-Fisica Molecular, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail: mouraramos@ist.utl.pt

    2006-09-15

    The mean values of the standard massic energy of combustion of crystalline anhydrous {alpha},{alpha}-trehalose (C{sub 12}H{sub 22}O{sub 11}, polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose (C{sub 12}H{sub 26}O{sub 13}) measured by static-bomb combustion calorimetry in oxygen, at the temperature T=298.15K, are {delta}{sub c}u{sup o}=-(16434.05+/-4.50)J.g{sup -1} and {delta}{sub c}u{sup o}=-(14816.05+/-3.52)J.g{sup -1}, respectively. The standard (p{sup o}=0.1MPa) molar enthalpy of formation of these compounds were derived from the corresponding standard molar enthalpies of combustion, respectively, {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 22}O{sub 11},cr)=-(2240.9+/-3.9)kJ.mol{sup -1}, and {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 26}O{sub 13},cr)=-(2832.6+/-3.6)kJ.mol{sup -1}. The values of the standard enthalpies of formation obtained in this work, together with data on enthalpies of solution at infinite dilution ({delta}{sub sol}H{sup {approx}}) for crystalline dihydrate and amorphous anhydrous trehalose, allow a better insight on the thermodynamic description of the trehalose system which can provide, together with the future research on the subject, a contribution for understanding the metabolism in several organisms, as well as the phase transition between the different polymorphs.

  18. Alpha voltaic batteries and methods thereof

    Science.gov (United States)

    Raffaelle, Ryne P. (Inventor); Jenkins, Phillip (Inventor); Wilt, David (Inventor); Scheiman, David (Inventor); Chubb, Donald (Inventor); Castro, Stephanie (Inventor)

    2011-01-01

    An alpha voltaic battery includes at least one layer of a semiconductor material comprising at least one p/n junction, at least one absorption and conversion layer on the at least one layer of semiconductor layer, and at least one alpha particle emitter. The absorption and conversion layer prevents at least a portion of alpha particles from the alpha particle emitter from damaging the p/n junction in the layer of semiconductor material. The absorption and conversion layer also converts at least a portion of energy from the alpha particles into electron-hole pairs for collection by the one p/n junction in the layer of semiconductor material.

  19. Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches

    OpenAIRE

    1994-01-01

    Collagen IV is a major component of vertebrate basal laminae (BLs). Studies in humans have revealed a family of genes encoding alpha 1- alpha 6 collagen IV chains and implicated alpha 3-alpha 6 in disease processes (Goodpasture and Alport syndromes and diffuse leiomyomatosis). To extend studies of these components to an experimentally accessible animal, we cloned cDNAs encoding partial collagen alpha 3, alpha 4, and alpha 5(IV) chains from the mouse. Ribonuclease protection assays showed that...

  20. Further Precise Determinations of $\\alpha_s$ from Lattice QCD

    CERN Document Server

    Davies, C T H; Lepage, G P; McCallum, P; Shigemitsu, J; Sloan, J

    1997-01-01

    We present a new determination of the strong coupling constant from lattice QCD simulations. We use four different short-distance quantities to obtain the coupling, three different (infrared) meson splittings to tune the simulation parameters, and a wide range of lattice spacings, quark masses, and lattice volumes to test for systematic errors. Our final result consists of ten different determinations of $\\alpha^{(3)}_{P}(8.2 GeV)$, which agree well with each other and with our previous results. The most accurate of these, when evolved perturbatively to the $Z^0$ mass, gives obtained from other recent lattice simulations.

  1. Double-real corrections at O(alpha alpha_s) to single gauge boson production

    CERN Document Server

    Bonciani, Roberto; Mondini, Roberto; Vicini, Alessandro

    2016-01-01

    We consider the O(alpha alpha_s) corrections to single on-shell gauge boson production at hadron colliders. We concentrate on the contribution of all the subprocesses where the gauge boson is accompanied by the emission of two additional real partons and we evaluate the corresponding total cross sections. The latter are divergent quantities, because of soft and collinear emissions, and are expressed as Laurent series in the dimensional regularization parameter. The total cross sections are evaluated by means of reverse unitarity, i.e. expressing the phase-space integrals in terms of two-loop forward box integrals with cuts on the final state particles. The results are reduced to a combination of Master Integrals, which eventually are evaluated in terms of Generalized Polylogarithms. The presence of internal massive lines in the Feynman diagrams, due to the exchange of electroweak gauge bosons, causes the appearance of 14 Master Integrals which were not previously known in the literature and have been evaluate...

  2. Folding model study of the elastic $\\alpha + \\alpha$ scattering at low energies

    CERN Document Server

    Tan, Ngo Hai; Khoa, Dao T

    2014-01-01

    The folding model analysis of the elastic $\\alpha + \\alpha$ scattering at the incident energies below the reaction threshold of 34.7 MeV (in the lab system) has been done using the well-tested density dependent versions of the M3Y interaction and realistic choices for the $^4$He density. Because the absorption is negligible at the energies below the reaction threshold, we were able to probe the $\\alpha + \\alpha$ optical potential at low energies quite unambiguously and found that the $\\alpha + \\alpha$ overlap density used to construct the density dependence of the M3Y interaction is strongly distorted by the Pauli blocking. This result gives possible explanation of a long-standing inconsistency of the double-folding model in its study of the elastic $\\alpha + \\alpha$ and $\\alpha$-nucleus scattering at low energies using the same realistic density dependent M3Y interaction.

  3. Case study on human α1-antitrypsin: Recombinant protein titers obtained by commercial ELISA kits are inaccurate

    DEFF Research Database (Denmark)

    Hansen, Henning Gram; Kildegaard, Helene Faustrup; Min Lee, Gyun;

    2016-01-01

    Accurate titer determination of recombinant proteins is crucial for evaluating protein production cell lines and processes. Even though enzyme-linked immunosorbent assay (ELISA) is the most widely used assay for determining protein titer, little is known about the accuracy of commercially availab...

  4. Streptococcal pyogenic exotoxin B (SpeB) boosts the contact system via binding of a-1 antitrypsin

    DEFF Research Database (Denmark)

    Meinert Niclasen, Louise; Olsen, Johan G; Dagil, Robert

    2011-01-01

    The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after...

  5. Scale setting for alpha_s beyond leading order

    CERN Document Server

    Hornbostel, K; Morningstar, C J

    2003-01-01

    We present a general procedure for incorporating higher-order information into the scale-setting prescription of Brodsky, Lepage and Mackenzie. In particular, we show how to apply this prescription when the leading coefficient or coefficients in a series in the strong coupling alpha_s are anomalously small and the original prescription can give an unphysical scale. We give a general method for computing an optimum scale numerically, within dimensional regularization, and in cases when the coefficients of a series are known. We apply it to the heavy quark mass and energy renormalization in lattice NRQCD, and to a variety of known series. Among the latter, we find significant corrections to the scales for the ratio of e+e- to hadrons over muons, the ratio of the quark pole to MSbar mass, the semi-leptonic B-meson decay width, and the top decay width. Scales for the latter two decay widths, expressed in terms of MSbar masses, increase by factors of five and thirteen, respectively, substantially reducing the size...

  6. Recoil-alpha-fission and recoil-alpha-alpha-fission events observed in the reaction Ca-48 + Am-243

    CERN Document Server

    Forsberg, U; Andersson, L -L; Di Nitto, A; Düllmann, Ch E; Gates, J M; Golubev, P; Gregorich, K E; Gross, C J; Herzberg, R -D; Hessberger, F P; Khuyagbaatar, J; Kratz, J V; Rykaczewski, K; Sarmiento, L G; Schädel, M; Yakushev, A; Åberg, S; Ackermann, D; Block, M; Brand, H; Carlsson, B G; Cox, D; Derkx, X; Dobaczewski, J; Eberhardt, K; Even, J; Fahlander, C; Gerl, J; Jäger, E; Kindler, B; Krier, J; Kojouharov, I; Kurz, N; Lommel, B; Mistry, A; Mokry, C; Nazarewicz, W; Nitsche, H; Omtvedt, J P; Papadakis, P; Ragnarsson, I; Runke, J; Schaffner, H; Schausten, B; Shi, Y; Thörle-Pospiech, P; Torres, T; Traut, T; Trautmann, N; Türler, A; Ward, A; Ward, D E; Wiehl, N

    2015-01-01

    Products of the fusion-evaporation reaction Ca-48 + Am-243 were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum f\\"ur Schwerionenforschung. Amongst the detected thirty correlated alpha-decay chains associated with the production of element Z=115, two recoil-alpha-fission and five recoil-alpha-alpha-fission events were observed. The latter are similar to four such events reported from experiments performed at the Dubna gas-filled separator. Contrary to their interpretation, we propose an alternative view, namely to assign eight of these eleven decay chains of recoil-alpha(-alpha)-fission type to start from the 3n-evaporation channel 115-288. The other three decay chains remain viable candidates for the 2n-evaporation channel 115-289.

  7. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  8. Linearized Bekenstein Varying Alpha Models

    CERN Document Server

    Pina-Avelino, P; Oliveira, J C

    2004-01-01

    We study the simplest class of Bekenstein-type, varying $\\alpha$ models, in which the two available free functions (potential and gauge kinetic function) are Taylor-expanded up to linear order. Any realistic model of this type reduces to a model in this class for a certain time interval around the present day. Nevertheless, we show that no such model is consistent with all existing observational results. We discuss possible implications of these findings, and in particular clarify the ambiguous statement (often found in the literature) that ``the Webb results are inconsistent with Oklo''.

  9. The Alpha Magnetic Spectrometer (AMS)

    Energy Technology Data Exchange (ETDEWEB)

    Alcaraz, J.; Alpat, B.; Ambrosi, G.; Anderhub, H.; Ao, L.; Arefiev, A.; Azzarello, P.; Babucci, E.; Baldini, L.; Basile, M.; Barancourt, D.; Barao, F.; Barbier, G.; Barreira, G.; Battiston, R.; Becker, R.; Becker, U.; Bellagamba, L.; Bene, P.; Berdugo, J.; Berges, P.; Bertucci, B.; Biland, A.; Bizzaglia, S.; Blasko, S.; Boella, G.; Boschini, M.; Bourquin, M.; Brocco, L.; Bruni, G.; Buenerd, M.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Camps, C.; Cannarsa, P.; Capell, M.; Casadei, D.; Casaus, J.; Castellini, G.; Cecchi, C.; Chang, Y.H.; Chen, H.F.; Chen, H.S.; Chen, Z.G.; Chernoplekov, N.A.; Chiueh, T.H.; Chuang, Y.L.; Cindolo, F.; Commichau, V.; Contin, A. E-mail: contin@bo.infn.it; Crespo, P.; Cristinziani, M.; Cunha, J.P. da; Dai, T.S.; Deus, J.D.; Dinu, N.; Djambazov, L.; DAntone, I.; Dong, Z.R.; Emonet, P.; Engelberg, J.; Eppling, F.J.; Eronen, T.; Esposito, G.; Extermann, P.; Favier, J.; Fiandrini, E.; Fisher, P.H.; Fluegge, G.; Fouque, N.; Galaktionov, Yu.; Gervasi, M.; Giusti, P.; Grandi, D.; Grimm, O.; Gu, W.Q.; Hangarter, K.; Hasan, A.; Hermel, V.; Hofer, H.; Huang, M.A.; Hungerford, W.; Ionica, M.; Ionica, R.; Jongmanns, M.; Karlamaa, K.; Karpinski, W.; Kenney, G.; Kenny, J.; Kim, W.; Klimentov, A.; Kossakowski, R.; Koutsenko, V.; Kraeber, M.; Laborie, G.; Laitinen, T.; Lamanna, G.; Laurenti, G.; Lebedev, A.; Lee, S.C.; Levi, G.; Levtchenko, P.; Liu, C.L.; Liu, H.T.; Lopes, I.; Lu, G.; Lu, Y.S.; Luebelsmeyer, K.; Luckey, D.; Lustermann, W.; Mana, C.; Margotti, A.; Mayet, F.; McNeil, R.R.; Meillon, B.; Menichelli, M.; Mihul, A.; Mourao, A.; Mujunen, A.; Palmonari, F.; Papi, A.; Park, I.H.; Pauluzzi, M.; Pauss, F.; Perrin, E.; Pesci, A.; Pevsner, A.; Pimenta, M.; Plyaskin, V.; Pojidaev, V.; Postolache, V.; Produit, N.; Rancoita, P.G.; Rapin, D.; Raupach, F.; Ren, D.; Ren, Z.; Ribordy, M.; Richeux, J.P.; Riihonen, E.; Ritakari, J.; Roeser, U.; Roissin, C.; Sagdeev, R.; Sartorelli, G.; Schultz von Dratzig, A.; Schwering, G.; Scolieri, G.; Seo, E.S.; Shoutko, V.

    2002-02-01

    The Alpha Magnetic Spectrometer (AMS) is a large acceptance (0.65 sr m{sup 2}) detector designed to operate in the International Space Station (ISS) for three years. The purposes of the experiment are to search for cosmic antimatter and dark matter and to study the composition and energy spectrum of the primary cosmic rays. A 'scaled-down' version has been flown on the Space Shuttle Discovery for 10 days in June 1998. The complete AMS is programmed for installation on the ISS in October 2003 for an operational period of 3 yr. This contribution reports on the experimental configuration that will be installed on the ISS.

  10. The Alpha Magnetic Spectrometer (AMS)

    CERN Document Server

    Alcaraz, J; Ambrosi, G; Anderhub, H; Ao, L; Arefev, A; Azzarello, P; Babucci, E; Baldini, L; Basile, M; Barancourt, D; Barão, F; Barbier, G; Barreira, G; Battiston, R; Becker, R; Becker, U; Bellagamba, L; Bene, P; Berdugo, J; Berges, P; Bertucci, B; Biland, A; Bizzaglia, S; Blasko, S; Bölla, G; Boschini, M; Bourquin, Maurice; Brocco, L; Bruni, G; Buénerd, M; Burger, J D; Burger, W J; Cai, X D; Camps, C; Cannarsa, P; Capell, M; Casadei, D; Casaus, J; Castellini, G; Cecchi, C; Chang, Y H; Chen, H F; Chen, H S; Chen, Z G; Chernoplekov, N A; Tzi Hong Chiueh; Chuang, Y L; Cindolo, F; Commichau, V; Contin, A; Crespo, P; Cristinziani, M; Cunha, J P D; Dai, T S; Deus, J D; Dinu, N; Djambazov, L; Dantone, I; Dong, Z R; Emonet, P; Engelberg, J; Eppling, F J; Eronen, T; Esposito, G; Extermann, P; Favier, Jean; Fiandrini, E; Fisher, P H; Flügge, G; Fouque, N; Galaktionov, Yu; Gervasi, M; Giusti, P; Grandi, D; Grimm, O; Gu, W Q; Hangarter, K; Hasan, A; Hermel, V; Hofer, H; Huang, M A; Hungerford, W; Ionica, M; Ionica, R; Jongmanns, M; Karlamaa, K; Karpinski, W; Kenney, G; Kenny, J; Kim, W; Klimentov, A; Kossakowski, R; Koutsenko, V F; Kraeber, M; Laborie, G; Laitinen, T; Lamanna, G; Laurenti, G; Lebedev, A; Lee, S C; Levi, G; Levchenko, P M; Liu, C L; Liu, H T; Lopes, I; Lu, G; Lü, Y S; Lübelsmeyer, K; Luckey, D; Lustermann, W; Maña, C; Margotti, A; Mayet, F; McNeil, R R; Meillon, B; Menichelli, M; Mihul, A; Mourao, A; Mujunen, A; Palmonari, F; Papi, A; Park, I H; Pauluzzi, M; Pauss, Felicitas; Perrin, E; Pesci, A; Pevsner, A; Pimenta, M; Plyaskin, V; Pozhidaev, V; Postolache, V; Produit, N; Rancoita, P G; Rapin, D; Raupach, F; Ren, D; Ren, Z; Ribordy, M; Richeux, J P; Riihonen, E; Ritakari, J; Röser, U; Roissin, C; Sagdeev, R; Sartorelli, G; Schwering, G; Scolieri, G; Seo, E S; Shoutko, V; Shoumilov, E; Siedling, R; Son, D; Song, T; Steuer, M; Sun, G S; Suter, H; Tang, X W; Ting, Samuel C C; Ting, S M; Tornikoski, M; Torsti, J; Ulbricht, J; Urpo, S; Usoskin, I; Valtonen, E; Vandenhirtz, J; Velcea, F; Velikhov, E P; Verlaat, B; Vetlitskii, I; Vezzu, F; Vialle, J P; Viertel, Gert M; Vitè, Davide F; Gunten, H V; Wallraff, W; Wang, B C; Wang, J Z; Wang, Y H; Wiik, K; Williams, C; Wu, S X; Xia, P C; Yan, J L; Yan, L G; Yang, C G; Yang, M; Ye, S W; Yeh, P; Xu, Z Z; Zhang, H Y; Zhang, Z P; Zhao, D X; Zhu, G Y; Zhu, W Z; Zhuang, H L; Zichichi, A; Zimmermann, B

    2002-01-01

    The Alpha Magnetic Spectrometer (AMS) is a large acceptance (0.65 sr m sup 2) detector designed to operate in the International Space Station (ISS) for three years. The purposes of the experiment are to search for cosmic antimatter and dark matter and to study the composition and energy spectrum of the primary cosmic rays. A 'scaled-down' version has been flown on the Space Shuttle Discovery for 10 days in June 1998. The complete AMS is programmed for installation on the ISS in October 2003 for an operational period of 3 yr. This contribution reports on the experimental configuration that will be installed on the ISS.

  11. Orthopositronium lifetime at O({alpha}) and O({alpha}{sup 3} ln {alpha}) in closed form

    Energy Technology Data Exchange (ETDEWEB)

    Kniehl, B.A.; Kotikov, A.V.; Veretin, O.L. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik

    2009-09-15

    Recently, the O({alpha}) and O({alpha}{sup 3} ln{alpha}) radiative corrections to the orthopositronium lifetime have been presented in closed analytical form, in terms of basic irrational numbers that can be evaluated numerically to arbitrary precision [Phys. Rev. Lett. 101, 193401 (2008)]. Here, we present the details of this calculation and reveal the nature of these new constants. We also list explicit transformation formulas for generalized polylogarithms of weight four, which may be useful for other applications. (orig.)

  12. Selective sorting of alpha-granule proteins.

    Science.gov (United States)

    Italiano, J E; Battinelli, E M

    2009-07-01

    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. A majority of this vast array of secreted proteins are stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on the mechanisms of alpha-granule biogenesis and secretion, with a particular emphasis on recent findings that clearly demonstrate that platelets contain distinct subpopulations of alpha-granules that undergo differential release during activation. We consider the implications of this new paradigm of platelet secretion, discuss mechanisms of alpha-granule biogenesis, and review the molecular basis of transport and delivery of alpha-granules to assembling platelets.

  13. The alpha,alpha-(1-->1) linkage of trehalose is key to anhydrobiotic preservation.

    Science.gov (United States)

    Albertorio, Fernando; Chapa, Vanessa A; Chen, Xin; Diaz, Arnaldo J; Cremer, Paul S

    2007-08-29

    This study compares the efficacy of six disaccharides and glucose for the preservation of solid supported lipid bilayers (SLBs) upon exposure to air. Disaccharide molecules containing an alpha,alpha-(1-->1) linkage, such as alpha,alpha-trehalose and alpha,alpha-galacto-trehalose, were found to be effective at retaining bilayer structure in the absence of water. These sugars are known to crystallize in a clam shell conformation. Other saccharides, which are found to crystallize in more open structures, did not preserve the SLB structure during the drying process. These included the nonreducing sugar, sucrose, as well as maltose, lactose, and the monosaccharide, glucose. In fact, even close analogs to alpha,alpha-trehalose, such as alpha,beta-trehalose, which connects its glucopyranose rings via a (1-->1) linkage in an axial, equatorial fashion, permitted nearly complete delamination and destruction of supported bilayers upon exposure to air. Lipids with covalently attached sugar molecules such as ganglioside GM1, lactosyl phosphatidylethanolamine, and glucosylcerebroside were also ineffective at preserving bilayer structure. The liquid crystalline-to-gel phase transition temperature of supported phospholipid bilayers was tested in the presence of sugars in a final set of experiments. Only alpha,alpha-trehalose and alpha,alpha-galacto-trehalose depressed the phase transition temperature, whereas the introduction of other sugar molecules into the bulk solution caused the phase transition temperature of the bilayer to increase. These results point to the importance of the axial-axial linkage of disaccharides for preserving SLB structure.

  14. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...... of rat MIP-1 alpha. The resulting product shared 92% and 90% homology with the known murine sequence at the cDNA level and protein level, respectively. Recombinant rat MIP-1 alpha exhibited dose-dependent chemotactic activity for both rat and human monocytes and neutrophils, which could be blocked...... by anti-murine MIP-1 alpha Ab. Rat MIP-1 alpha mRNA and protein expression were determined as a function of time in both injury models. A time-dependent increase in MIP-1 alpha mRNA in lung extracts was observed in both models. In the LPS model, MIP-1 alpha protein could also be detected...

  15. $\\alpha_{s}$ from the (revised) ALEPH data for $\\tau$ decay

    CERN Document Server

    Boito, Diogo; Maltman, Kim; Osborne, James; Peris, Santiago

    2014-01-01

    We present a new analysis of $\\alpha_s$ from hadronic $\\tau$ decays based on the recently revised ALEPH data. The analysis is based on a strategy which we previously applied to the OPAL data. We critically compare our strategy to the one traditionally used and comment on the main differences. Our analysis yields the values $\\alpha_s(m_\\tau^2)=0.296\\pm 0.010$ using fixed-order perturbation theory, and $\\alpha_s(m_\\tau^2)=0.310\\pm 0.014$ using contour-improved perturbation theory. Averaging these values with our previously obtained values from the OPAL data, we find $\\alpha_s(m_\\tau^2)=0.303\\pm 0.009$, respectively, $\\alpha_s(m_\\tau^2)=0.319\\pm 0.012$, as the most reliable results for $\\alpha_s$ from $\\tau$ decays currently available.

  16. EEG, alpha waves and coherence

    Science.gov (United States)

    Ascolani, Gianluca

    This thesis addresses some theoretical issues generated by the results of recent analysis of EEG time series proving the brain dynamics are driven by abrupt changes making them depart from the ordinary Poisson condition. These changes are renewal, unpredictable and non-ergodic. We refer to them as crucial events. How is it possible that this form of randomness be compatible with the generation of waves, for instance alpha waves, whose observation seems to suggest the opposite view the brain is characterized by surprisingly extended coherence? To shed light into this apparently irretrievable contradiction we propose a model based on a generalized form of Langevin equation under the influence of a periodic stimulus. We assume that there exist two different forms of time, a subjective form compatible with Poisson statistical physical and an objective form that is accessible to experimental observation. The transition from the former to the latter form is determined by the brain dynamics interpreted as emerging from the cooperative interaction among many units that, in the absence of cooperation would generate Poisson fluctuations. We call natural time the brain internal time and we make the assumption that in the natural time representation the time evolution of the EEG variable y(t) is determined by a Langevin equation perturbed by a periodic process that in this time representation is hardly distinguishable from an erratic process. We show that the representation of this random process in the experimental time scale is characterized by a surprisingly extended coherence. We show that this model generates a sequence of damped oscillations with a time behavior that is remarkably similar to that derived from the analysis of real EEG's. The main result of this research work is that the existence of crucial events is not incompatible with the alpha wave coherence. In addition to this important result, we find another result that may help our group, or any other research

  17. Carbohydrate composition of the alpha-subunit of human choriogonadotropin (hCG alpha) and the free alpha molecules produced in pregnancy: most free alpha and some combined hCG alpha molecules are fucosylated.

    Science.gov (United States)

    Blithe, D L

    1990-06-01

    The carbohydrate compositions of pregnancy-derived hCG alpha (dissociated from intact hCG) and free alpha-subunit were analyzed using a combination of chemical analysis, lectin affinity chromatography, and glycosidase sensitivity. For direct compositional analysis, parallel samples were hydrolyzed in trifluoroacetic acid and analyzed for sialic acid and neutral sugars without prior derivatization. Separation of the monosaccharides was achieved by HPLC on a Dionex CarboPac column eluted at high pH, and the resolved monosaccharides were quantified by pulsed amperometric detection. The amounts of sugar that were found relative to peptide indicated the presence of two N-linked oligosaccharides per molecule on both hCG alpha and free alpha. Free alpha contained 2.5-fold higher amounts of sialic acid and galactose as well as a higher amount of N-acetylglucosamine than did hCG alpha. Free alpha also contained a 6-fold higher amount of fucose than did hCG alpha (1.2 vs. 0.2 residues of fucose/molecule). Serial fractionation of intact hCG alpha and free alpha molecules by lectin affinity chromatography indicated that virtually all of the hCG alpha-subunits contained at least one Concanavalin-A (Con-A)-binding site, whereas as many as 32% of the free alpha molecules could not bind to Con-A. Chromatography on Lens culinaris (Lch) resulted in 12% binding of hCG alpha and approximately 72% binding of free alpha (80-85% of the Con-A-bound free alpha and 47-48% of the Con-A-nonbound free alpha bound to Lch). Endoglycosidase-H (endo-H) treatment of hCG alpha released a portion of the oligosaccharides. The endo-H-released material appeared to be a monoantennary hybrid based on DEAE-binding properties and carbohydrate composition. In contrast to hCG alpha, free alpha was completely resistant to endo-H treatment. Incubation of endo-H-resistant hCG alpha with glycopeptidase-A resulted in the release of two components, which could be separated into monoantennary and biantennary

  18. PLE CATALYZED HYDROLYZES OF ALPHA-SUBSTITUTED ALPHA-HYDROXY ESTERS - THE INFLUENCE OF THE SUBSTITUENTS

    NARCIS (Netherlands)

    MOORLAG, H; KELLOGG, RM

    1991-01-01

    The enzymatic hydrolyses of a variety of alpha-substituted mandelic and lactic esters using pig liver esterase (PLE) have been investigated. High to moderate enantioselectivity was found for various alpha-substituted mandelic esters, whereas PLE showed low to no enantioselectivity for alpha-substitu

  19. Matching coefficients for alpha_s and m_b to O(alpha_s^2) in the MSSM

    CERN Document Server

    Bauer, A; Salomon, J

    2009-01-01

    We compute the exact two-loop matching coefficients for the strong coupling constant alpha_s and the bottom-quark mass m_b within the Minimal Supersymmetric Standard Model (MSSM), taking into account O(alpha_s^2) contributions from Supersymmetric Quantum Chromodynamics (SQCD). We find that the explicit mass pattern of the supersymmetric particles has a significant impact on the predictions of alpha_s and m_b at high energies. Further on, the three-loop corrections exceed the uncertainty due to the current experimental accuracy. In case of the the running bottom-quark mass, they can reach in the large tan(beta) regime up to 30% from the tree-level value.

  20. Local Varying-Alpha Theories

    CERN Document Server

    Barrow, John D

    2014-01-01

    In a recent paper we demonstrated how the simplest model for varying alpha may be interpreted as the effect of a dielectric material, generalized to be consistent with Lorentz invariance. Unlike normal dielectrics, such a medium cannot change the speed of light, and its dynamics obey a Klein-Gordon equation. This work immediately suggests an extension of the standard theory, even if we require compliance with Lorentz invariance. Instead of a wave equation, the dynamics may satisfy a local algebraic relation involving the permittivity and the properties of the electromagnetic field, in analogy with more conventional dielectric (but still preserving Lorentz invariance). We develop the formalism for such theories and investigate some phenomenological implications. The problem of the divergence of the classical self-energy can be solved, or at least softened, in this framework. Some interesting new cosmological solutions for the very early universe are found, including the possibility of a bounce, inflation and e...

  1. Alpha Shape Topology of the Cosmic Web

    NARCIS (Netherlands)

    Weygaert, Rien van de; Platen, Erwin; Vegter, Gert; Eldering, Bob; Kruithof, Nico

    2010-01-01

    We study the topology of the Megaparsec Cosmic Web on the basis of the Alpha Shapes of the galaxy distribution. The simplicial complexes of the alpha shapes are used to determine the set of Betti numbers (βk, k = 1, . . . , D), which represent a complete characterization of the topology of a manifol

  2. The ALPHA detector : Module Production and Assembly

    CERN Document Server

    Andresen, G; Bowe, P D; Cesar, C L; Chapman, S; Charlton, M; Fajans, J; Fujiwara, M C; Gill, D R; Hangst, J S; Hydomako, R; Jenkins, M J; Kurchaninov, L; Madsen, N; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Robicheaux, F; Sarid, E; Silveira, D M; Storey, J W; Thompson, R I; van der Werf, D P; Wurtele, J S; Yamazaki, Y; Ashkezari, M D; Baquero-Ruiz, M; Butler, E; Deller, A; Eriksson, S; Friesen, T; Gutierrez, A; Hardy, W N; Hayden, M E; Humphries, A J; Jonsell, S; McKenna, J T K; Menary, S; Pusa, P; Sampson, J; Seddon, D; Seif el Nasr, S; So, C; Thornhill, J; Wells, D; Jorgensen, L V

    2012-01-01

    ALPHA is one of the experiments situated at CERN's Antiproton Decelerator (AD). A Silicon Vertex Detector (SVD) is placed to surround the ALPHA atom trap. The main purpose of the SVD is to detect and locate antiproton annihilation events by means of the emitted charged pions. The SVD system is presented with special focus given to the design, fabrication and performance of the modules.

  3. Bayesian Meta-Analysis of Coefficient Alpha

    Science.gov (United States)

    Brannick, Michael T.; Zhang, Nanhua

    2013-01-01

    The current paper describes and illustrates a Bayesian approach to the meta-analysis of coefficient alpha. Alpha is the most commonly used estimate of the reliability or consistency (freedom from measurement error) for educational and psychological measures. The conventional approach to meta-analysis uses inverse variance weights to combine…

  4. Remote Associates Test and Alpha Brain Waves

    Science.gov (United States)

    Haarmann, Henk J.; George, Timothy; Smaliy, Alexei; Dien, Joseph

    2012-01-01

    Previous studies found that performance on the remote associates test (RAT) improves after a period of incubation and that increased alpha brain waves over the right posterior brain predict the emergence of RAT insight solutions. We report an experiment that tested whether increased alpha brain waves during incubation improve RAT performance.…

  5. ALPHA experiment facility and Prof. Jeffrey Hangst.

    CERN Multimedia

    Maximilien Brice

    2010-01-01

    Picture 01-07: General views of the ALPHA experiment Picture 5: Andrea Gutierrez, a PhD student from UBC, transfers liquid helium from a storage dewar into the cryostat containing the superconducting magnetic trap used by the ALPHA experiment.Picture 08-11: Jeffery Hangst, spokesperson for ALPHA Picture 12: The ALPHA silicon detector, which surrounds the trapping resion and is used for imaging antiproton annihilations (Credit University of Liverpool) Picture 13: Untrapped antihydrogen atoms annihilating on the inner surface of the ALPHA trap. These are measured by the ALPHA annihilation detector. The events are concentrated at the electrode radius of about 22.3 mm. The coordinates are defined in the Nature article, Figure 1b. Picture 14: The electrodes (gold) for the ALPHA Penning trap being inserted into the vacuum chamber and cryostat assembly. This is the trap used to combine or "mix" positrons and antiprotons to make antihydrogen. (Credit: Niels Madsen ALPHA/Swansea.) Picture 15: Top, a diagram of the...

  6. Measurement of the angle alpha at BABAR

    CERN Document Server

    Pérez, A

    2009-01-01

    We present recent measurements of the CKM angle alpha using data collected by the BABAR detector at the PEP-II asymmetric-energy e^+e^- collider at the SLAC National Accelerator Laboratory, operating at the Upsilon(4S) resonance. We present constraints on alpha from B->pipi, B->rhorho and B->rhopi decays.

  7. Atypical Alpha Asymmetry in Adults with ADHD

    Science.gov (United States)

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

    2009-01-01

    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  8. Psychiatric Symptoms in Alpha-Mannosidosis

    Science.gov (United States)

    Malm, D.; Pantel, J.; Linaker, O. M.

    2005-01-01

    Alpha-mannosidosis is characterized by mild to moderate intellectual disability (ID), moderate to severe neurosensory hearing loss, frequent infections, psychomotor disturbances and skeletal dysmorphism. For the first time, a panel of nine alpha-mannosidosis patients with psychiatric symptoms is presented. The clinical picture has several…

  9. Confidence Intervals for Cronbach's Coefficient Alpha Values

    NARCIS (Netherlands)

    A.J. Koning (Alex); Ph.H.B.F. Franses (Philip Hans)

    2003-01-01

    textabstractCoefficient Alpha, which is widely used in empirical research, estimates the reliability of a test consisting of parallel items. In practice it is difficult to compare values of alpha across studies as it depends on the number of items used. In this paper we provide a simple solution, wh

  10. Teaching Calculus with Wolfram|Alpha

    Science.gov (United States)

    Dimiceli, Vincent E.; Lang, Andrew S. I. D.; Locke, LeighAnne

    2010-01-01

    This article describes the benefits and drawbacks of using Wolfram|Alpha as the platform for teaching calculus concepts in the lab setting. It is a result of our experiences designing and creating an entirely new set of labs using Wolfram|Alpha. We present the reasoning behind our transition from using a standard computer algebra system (CAS) to…

  11. Anomalous atomic volume of alpha-Pu

    DEFF Research Database (Denmark)

    Kollar, J.; Vitos, Levente; Skriver, Hans Lomholt

    1997-01-01

    .3%. The comparison between the LDA and GGA results show that the anomalously large atomic volume of alpha-Pu relative to alpha-Np can be ascribed to exchange-correlation effects connected with the presence of low coordinated sites in the structure where the f electrons are close to the onset of localization...

  12. Folate receptor {alpha} regulates cell proliferation in mouse gonadotroph {alpha}T3-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Congjun; Evans, Chheng-Orn [Department of Neurosurgery and Laboratory of Molecular Neurosurgery and Biotechnology, Emory University, School of Medicine, Atlanta, Georgia (United States); Stevens, Victoria L. [Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia (United States); Owens, Timothy R. [Emory University, School of Medicine, Atlanta, Georgia (United States); Oyesiku, Nelson M., E-mail: noyesik@emory.edu [Department of Neurosurgery and Laboratory of Molecular Neurosurgery and Biotechnology, Emory University, School of Medicine, Atlanta, Georgia (United States)

    2009-11-01

    We have previously found that the mRNA and protein levels of the folate receptor alpha (FR{alpha}) are uniquely over-expressed in clinically human nonfunctional (NF) pituitary adenomas, but the mechanistic role of FR{alpha} has not fully been determined. We investigated the effect of FR{alpha} over-expression in the mouse gonadotroph {alpha}T3-1 cell line as a model for NF pituitary adenomas. We found that the expression and function of FR{alpha} were strongly up-regulated, by Western blotting and folic acid binding assay. Furthermore, we found a higher cell growth rate, an enhanced percentage of cells in S-phase by BrdU assay, and a higher PCNA staining. These observations indicate that over-expression of FR{alpha} promotes cell proliferation. These effects were abrogated in the same {alpha}T3-1 cells when transfected with a mutant FR{alpha} cDNA that confers a dominant-negative phenotype by inhibiting folic acid binding. Finally, by real-time quantitative PCR, we found that mRNA expression of NOTCH3 was up-regulated in FR{alpha} over-expressing cells. In summary, our data suggests that FR{alpha} regulates pituitary tumor cell proliferation and mechanistically may involve the NOTCH pathway. Potentially, this finding could be exploited to develop new, innovative molecular targeted treatment for human NF pituitary adenomas.

  13. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J

    1998-06-29

    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  14. Alpha macroglobulins and the low-density-lipoprotein-related protein alpha-2-macroglobulin receptor in experimental renal fibrosis

    NARCIS (Netherlands)

    van Goor, H; Diamond, [No Value; Ding, GH; Kaysen, GA

    1999-01-01

    In this study, we evaluated the location of non-specific proteinase inhibitors and their receptor in experimental glomerular and interstitial fibrosis. The alpha macroglobulins alpha-2-macroglobulin (alpha 2M) and alpha-1-inhibitor 3 (alpha 1I3) are proteinase inhibitors, including metalloproteinase

  15. Radiative corrections to the muonium hyperfine structure; 1, the $\\alpha^{2}$ (Z$\\alpha$) correction

    CERN Document Server

    Kinoshita, T

    1995-01-01

    This is the first of a series of papers on a systematic application of the NRQED bound state theory of Caswell and Lepage to higher-order radiative corrections to the hyperfine structure of the muonium ground state. This paper describes the calculation of the \\alpha^2 (Z\\alpha) radiative correction. Our result for the complete \\alpha^2 (Z\\alpha) correction is 0.424(4) kHz, which reduces the theoretical uncertainty significantly. The remaining uncertainty is dominated by that of the numerical evaluation of the nonlogarithmic part of the \\alpha (Z\\alpha )^2 term and logarithmic terms of order \\alpha^4. These terms will be treated in the subsequent papers.

  16. The fratricide of alpha-Omega dynamos by their alpha-squared siblings

    CERN Document Server

    Hubbard, Alexander; Brandenburg, Axel

    2011-01-01

    Context. Helically forced magneto-hydrodynamic shearing-sheet turbulence can support different large-scale dynamo modes, although the {\\alpha} - {\\Omega} mode is generally expected to dominate because it is the fastest growing. In an {\\alpha} - {\\Omega} dynamo, most of the field amplification is produced by the shear. As differential rotation is an ubiquitous source of shear in astrophysics, such dynamos are believed to be the source of most astrophysical large-scale magnetic fields. Aims. We study the stability of oscillatory migratory {\\alpha} - {\\Omega} type dynamos in turbulence simulations. Methods. We use shearing-sheet simulations of hydromagnetic turbulence that is helically forced at a wavenumber that is about three times larger than the lowest wavenumber in the domain so that both {\\alpha} - {\\Omega} and {\\alpha}2 dynamo action is possible. Results. After initial dominance and saturation, the {\\alpha} - {\\Omega} mode is found to be destroyed by an orthogonal {\\alpha}2 mode sustained by the helical t...

  17. [Contents and its change during storage of alpha-solanine and alpha-chaconine in potatoes].

    Science.gov (United States)

    Shindo, Tetsuya; Ushiyama, Hirofumi; Kan, Kimiko; Yasuda, Kazuo; Saito, Kazuo

    2004-10-01

    Contents of alpha-solanine and alpha-chaconine in native species of potato (May Queen, Danshaku and Waseshiro), and in species (Jagakids Red '90 (Red) and Jagakids Purple '90 (Purple)) on the market, and their change during storage at room temparature were investigated. alpha-Solanine and alpha-chaconine were extracted from potatoes with methanol, cleaned up by using a Sep-Pak Plus C18 cartridge, and then subjected to HPLC. The recoveries of alpha-solanine and alpha-chaconine from potatoes were both more than 96%, and the quantitation limits were both 2 microg/g. alpha-Solanine and alpha-chaconine were detected in periderm in all samples at the levels of 260-320 microg/g in May Queen,190-240 microg/g in Danshaku, 43-63 microg/g in Waseshiro, 140-200 microg/g in Red and 84-130 microg/g in Purple, respectively. alpha-Solanine and alpha-chaconine were detected in the cortex in all samples of May Queen and Danshaku at the levels of 2.7-12 microg/g and 5.8-31 microg/g, respectively. Contents of alpha-solanine and alpha-chaconine in the cortex of May Queen and Danshaku were less than 10% of those in the periderm. When potatoes were stored for 90 days at room temparature in a dark place, no marked change in the contents of alpha-solanine and alpha-chaconine was observed in any of the potato samples.

  18. Involvement of central alpha1-adrenoceptors on renal responses to central moxonidine and alpha-methylnoradrenaline.

    Science.gov (United States)

    de Andrade, Carina A F; de Andrade, Glaucia M F; De Paula, Patricia M; De Luca, Laurival A; Menani, José V

    2009-04-01

    Moxonidine (alpha2-adrenoceptor/imidazoline receptor agonist) injected into the lateral ventricle induces diuresis, natriuresis and renal vasodilation. Moxonidine-induced diuresis and natriuresis depend on central imidazoline receptors, while central alpha1-adrenoceptors are involved in renal vasodilation. However, the involvement of central alpha1-adrenoceptors on diuresis and natriuresis to central moxonidine was not investigated yet. In the present study, the effects of moxonidine, alpha-methylnoradrenaline (alpha2-adrenoceptor agonist) or phenylephrine (alpha1-adrenoceptor agonist) alone or combined with previous injections of prazosin (alpha1-adrenoceptor antagonist), yohimbine or RX 821002 (alpha2-adrenoceptor antagonists) intracerebroventricularly (i.c.v.) on urinary sodium, potassium and volume were investigated. Male Holtzman rats (n = 5-18/group) with stainless steel cannula implanted into the lateral ventricle and submitted to gastric water load (10% of body weight) were used. Injections of moxonidine (20 nmol) or alpha-methylnoradrenaline (80 nmol) i.c.v. induced natriuresis (196 +/- 25 and 171 +/- 30, respectively, vs. vehicle: 101 +/- 9 microEq/2 h) and diuresis (9.0 +/- 0.4 and 12.3 +/- 1.6, respectively, vs. vehicle: 5.2 +/- 0.5 ml/2 h). Pre-treatment with prazosin (320 nmol) i.c.v. abolished the natriuresis (23 +/- 4 and 76 +/- 11 microEq/2 h, respectively) and diuresis (5 +/- 1 and 7.6 +/- 0.8 ml/2 h, respectively) produced by i.c.v. moxonidine or alpha-methylnoradrenaline. RX 821002 (320 nmol) i.c.v. abolished the natriuretic effect of alpha-methylnoradrenaline, however, yohimbine (320 nmol) did not change renal responses to moxonidine. Phenylephrine (80 nmol) i.c.v. induced natriuresis and kaliuresis that were blocked by prazosin. Therefore, the present data suggest that moxonidine and alpha-methylnoradrenaline acting on central imidazoline receptors and alpha2-adrenoceptors, respectively, activate central alpha1-adrenergic mechanisms to

  19. Mapping High-Velocity H-alpha and Lyman-alpha Emission from Supernova 1987A

    Science.gov (United States)

    France, Kevin; McCray, Richard; Fransson, Claes; Larsson, Josefin; Frank, Kari A.; Burrows, David N.; Challis, Peter; Kirshner, Robert P.; Chevalier, Roger A.; Garnavich, Peter; Heng, Kevin; Lawrence, Stephen S.; Lundqvist, Peter; Smith, Nathan; Sonneborn, George

    2015-01-01

    We present new Hubble Space Telescope images of high-velocity H-alpha and Lyman-alpha emission in the outer debris of SN 1987A. The H-alpha images are dominated by emission from hydrogen atoms crossing the reverse shock. For the first time we observe emission from the reverse shock surface well above and below the equatorial ring, suggesting a bipolar or conical structure perpendicular to the ring plane. Using the H-alpha imaging, we measure the mass flux of hydrogen atoms crossing the reverse shock front, in the velocity intervals (-7,500 < V(sub obs) < -2,800 km/s) and (1,000 < V(sub obs) < 7,500 km/s), ?M(sub H) = 1.2 × 10(exp -3) M/ y. We also present the first Lyman-alpha imaging of the whole remnant and new Chandra X-ray observations. Comparing the spatial distribution of the Lyman-alpha and X-ray emission, we observe that the majority of the high-velocity Lyman-alpha emission originates interior to the equatorial ring. The observed Lyman-alpha/H-alpha photon ratio, R(L-alpha/H-alpha) approx. = 17, is significantly higher than the theoretically predicted ratio of approx. = 5 for neutral atoms crossing the reverse shock front. We attribute this excess to Lyman-alpha emission produced by X-ray heating of the outer debris. The spatial orientation of the Lyman-alpha and X-ray emission suggests that X-ray heating of the outer debris is the dominant Lyman-alpha production mechanism in SN 1987A at this phase in its evolution.

  20. A new alpha chain hemoglobin variant: Hb Al-Hammadi Riyadh [alpha75(EF4)Asp-->Val (alpha2)].

    Science.gov (United States)

    Burnichon, Nelly; Lacan, Philippe; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Mowafy, Mohammed; Couprie, Nicole; Francina, Alain

    2006-01-01

    A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC-->GTC); alpha75(EF4)Asp-->Val (alpha2)] corresponding to an A-->T transversion on the second exon of the alpha2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.

  1. $Q_{\\alpha}$-Normal Families and entire functions

    CERN Document Server

    Gul, Shai

    2010-01-01

    For every countable ordinal number $\\alpha$ we construct an entire function $f=f_\\alpha$ such that the family $\\left\\{f(nz):n\\in\\mathbb{N}\\right\\}$ is exactly $Q_\\alpha$-normal in the unit disk.

  2. Feasibility of commercial space manufacturing, production of pharmaceuticals. Volume 2: Technical analysis

    Science.gov (United States)

    1978-01-01

    A technical analysis on the feasibility of commercial manufacturing of pharmaceuticals in space is presented. The method of obtaining pharmaceutical company involvement, laboratory results of the separation of serum proteins by the continuous flow electrophoresis process, the selection and study of candidate products, and their production requirements is described. The candidate products are antihemophilic factor, beta cells, erythropoietin, epidermal growth factor, alpha-1-antitrypsin and interferon. Production mass balances for antihemophelic factor, beta cells, and erythropoietin were compared for space versus ground operation. A conceptual description of a multiproduct processing system for space operation is discussed. Production requirements for epidermal growth factor of alpha-1-antitrypsin and interferon are presented.

  3. Lucid dreaming and alpha activity: a preliminary report.

    Science.gov (United States)

    Ogilvie, R D; Hunt, H T; Tyson, P D; Lucescu, M L; Jeakins, D B

    1982-12-01

    10 good dream recallers spent 2 nights in the sleep lab during which they were awakened 4 times per night from REM sleep, twice during their highest alpha activity in REM, and twice during low REM alpha. 5 were given alpha feedback training prior to sleep onset. Arousals from high alpha REM sleep yielded significantly higher lucidity ratings. Alpha feedback had no effect upon lucidity or REM alpha levels. Similarities between lucid dreams and meditative phenomena are discussed.

  4. Lyman alpha emission in starburst galaxies

    Science.gov (United States)

    Kunth, Daniel

    1999-07-01

    We propose to perform a deep study of Ly-alpha emission and destruction in 3 star-forming galaxies. These objects have been already observed with the GHRS and exhibit a variety of situations, with Ly-alpha showing P Cyg profiles, secondary emissions or even a deep damped absorption line with no emission. They also span a range of intrinsic properties: IZW18 is a gas-rich, metal deficient dust free dwarf galaxy, Haro 2 has a simple morphology while IRAS 08339+6517 is a luminous IRAS starburst galaxy with more dust and complex Ly- alpha profile. The use of STIS will allow for the first time to study the geometrical/kinematical configuration of the ionized and neutral gas across the galaxies nuclear regions and pin point the effects of porosity and the kinematical structure of the ISM, that may play the key roles {in addition to dust} in the detectability of the line. This study will have important impact for cosmology since Ly-alpha emitters are nowaday found at high-re dshift. We strongly emphasize that since Ly-alpha is primarely a diagnostic of the ISM, a full understanding of how the ISM and Ly-alpha are related is a necessary step before we can hope to correlate Ly-alpha to the cosmic star-formation rate. Our results will be interpreted against the model of superbubble evolution developed with G. Tenorio Tagle.

  5. Diagnostics for PLX-alpha

    Science.gov (United States)

    Gilmore, Mark; Hsu, Scott

    2015-11-01

    The goal of the Plasma Liner eXperiment PLX-alpha at Los Alamos National Laboratory is to establish the viability of creating a spherically imploding plasma liner for MIF and HED applications, using a spherical array of supersonic plasma jets launched by innovative contoured-gap coaxial plasma guns. PLX- α experiments will focus in particular on establishing the ram pressure and uniformity scalings of partial and fully spherical plasma liners. In order to characterize these parameters experimentally, a suite of diagnostics is planned, including multi-camera fast imaging, a 16-channel visible interferometer (upgraded from 8 channels) with reconfigurable, fiber-coupled front end, and visible and VUV high-resolution and survey spectroscopy. Tomographic reconstruction and data fusion techniques will be used in conjunction with interferometry, imaging, and synthetic diagnostics from modeling to characterize liner uniformity in 3D. Diagnostic and data analysis design, implementation, and status will be presented. Supported by the Advanced Research Projects Agency - Energy - U.S. Department of Energy.

  6. Lyman Alpha Spicule Observatory (LASO)

    Science.gov (United States)

    Chamberlin, P. C.; Allred, J. C.; Airapetian, V.; Gong, Q.; Mcintosh, S. W.; De Pontieu, B.; Fontenla, J. M.

    2011-12-01

    The Lyman Alpha Spicule Observatory (LASO) sounding rocket will observe small-scale eruptive events called "Rapid Blue-shifted Events" (RBEs) [Rouppe van der Voort et al., 2009], the on-disk equivalent of Type-II spicules, and extend observations that explore their role in the solar coronal heating problem [De Pontieu et al., 2011]. LASO utilizes a new and novel optical design to simultaneously observe two spatial dimensions at 4.2" spatial resolution (2.1" pixels) over a 2'x2' field of view with high spectral resolution of 66mÅ (33mÅ pixels) across a broad 20Å spectral window. This spectral window contains three strong chromospheric and transition region emissions and is centered on the strong Hydrogen Lyman-α emission at 1216Å. This instrument makes it possible to obtain new data crucial to the physical understanding of these phenomena and their role in the overall energy and momentum balance from the upper chromosphere to lower corona. LASO was submitted March 2011 in response to the ROSES SHP-LCAS call.

  7. Measurements of $\\alpha_s$ in $pp$ Collisions at the LHC

    CERN Document Server

    Warburton, Andreas; The ATLAS collaboration

    2015-01-01

    The coupling of the strong force, $\\alpha_s$, is deemed to be a fundamental parameter of Nature, and, beyond the quark masses, constitutes the only free parameter in the QCD Lagrangian. Provided is an overview of CERN Large Hadron Collider (LHC) measurements of $\\alpha_s(M_Z)$ evaluated at the $Z$-boson mass and of the running of $\\alpha_s(Q)$ as a function of energy-momentum transfer $Q$. The measurements were performed by the ATLAS and CMS Collaborations using proton-proton ($pp$) collisions with centre-of-mass energies of 7 TeV and data samples with time-integrated luminosities of up to 5 fb$^{-1}$. Four different categories of observable were used in the described extractions of $\\alpha_s$: inclusive jet cross sections, 3-jet to 2-jet inclusive cross-section ratios, 3-jet mass cross sections, and top-quark pair production cross sections. These results, which include the first NNLO measurement of $\\alpha_s$ at a hadron collider and the first determinations of $\\alpha_s$ at energy scales above 1 TeV, are co...

  8. Generalized dual symmetry of nonabelian theories and the freezing of \\alpha_s

    CERN Document Server

    Das, C R; Nielsen, H B

    2006-01-01

    The quantum Yang-Mills theory, describing a system of fields with non-dual (chromo-electric g) and dual (chromo-magnetic \\tilde g) charges and revealing the generalized dual symmetry, is developed by analogy with the Zwanziger formalism in QED. The renormalization group equations (RGEs) for pure nonabelian theories are analysed for both constants, \\alpha = g^2 / 4\\pi and \\tilde\\alpha = {\\tilde g}^2 / 4\\pi. The pure SU(3) \\times \\widetilde{SU(3)} gauge theory is investigated as an example. We consider not only monopoles, but also dyons. The behaviour of the total SU(3) \\beta-function is investigated in the whole region of \\alpha \\equiv \\alpha_s: 0 \\le \\alpha < \\infty. It is shown that this \\beta-function is antisymmetric under the interchange \\alpha \\leftrightarrow 1/\\alpha and is given by the well-known perturbative expansion not only for \\alpha \\ll 1, but also for \\alpha \\gg 1. Using an idea of the Maximal Abelian Projection by t' Hooft, we considered the formation of strings - the ANO flux tubes - in the...

  9. $\\alpha_s$ from the updated ALEPH data for hadronic $\\tau$ decays

    CERN Document Server

    Boito, Diogo; Maltman, Kim; Osborne, James; Peris, Santiago

    2015-01-01

    We extract the strong coupling $\\alpha_s(m_\\tau^2)$ from the recently updated ALEPH non-strange spectral functions obtained from hadronic $\\tau$ decays. We apply a self-consistent analysis method, first tested in the analysis of OPAL data, to extract $\\alpha_s(m_\\tau^2)$ and non-perturbative contributions. The analysis yields $\\alpha_s^{\\rm FO}(m_\\tau^2)=0.296\\pm0.010 $, using Fixed Order Perturbation Theory (FOPT), and $\\alpha^{\\rm CI}_s(m_\\tau^2)= 0.310\\pm0.014$, using Contour Improved Perturbation Theory (CIPT). The weighted average of these results with those previously obtained from OPAL data give $\\alpha_s^{\\rm FO}(m_\\tau^2)=0.303\\pm 0.009$ and $\\alpha_s^{\\rm CI}(m_\\tau^2)=0.319\\pm 0.012$, which gives, after evolution to the $Z$ boson mass scale, $\\alpha^{\\rm FO}_s(m_Z^2)=0.1165\\pm0.0012 $ and $\\alpha_s^{\\rm CI}(m_Z^2)=0.1185\\pm0.0015 $, respectively. We observe that non-perturbative effects limit the accuracy with which $\\alpha_s$ can be extracted from $\\tau$ decay data.

  10. Collagen alpha5 and alpha2(IV) chain coexpression: analysis of skin biopsies of Alport patients.

    Science.gov (United States)

    Patey-Mariaud de Serre, N; Garfa, M; Bessiéres, B; Noël, L H; Knebelmann, B

    2007-08-01

    Alport syndrome is a collagen type IV disease caused by mutations in the COL4A5 gene with the X-linked form being most prevalent. The resultant alpha5(IV) collagen chain is a component of the glomerular and skin basement membranes (SBMs). Immunofluorescent determination of the alpha5(IV) chain in skin biopsies is the procedure of choice to identify patients. In 30% of patients, however, the mutant protein is still found in the SBM resulting in a normal staining pattern. In order to minimize or eliminate false results, we compared the distribution of the alpha2(IV) chain (another SBM component) and the alpha5(IV) chain by standard double label immunofluorescence (IF) and by confocal laser scanning microscopy. The study was performed on 55 skin biopsies of patients suspected of Alports and five normal control specimens. In normal skin, IF showed the classical linear pattern for both collagens along the basement membrane. Additionally, decreased alpha5(IV) was found in the bottom of the dermal papillary basement membrane. Confocal analysis confirmed the results and show alpha5(IV) focal interruptions. In suspected patients, both techniques showed the same rate of abnormal alpha5(IV) expression: segmental in women and absent in men. Our results show a physiological variation of alpha5(IV) location with focal interruptions and decreased expression in the bottom of the dermal basement membrane. Comparison of alpha5(IV) with alpha2(IV) expression is simple and eliminates technical artifacts.

  11. Variable displacement alpha-type Stirling engine

    Science.gov (United States)

    Homutescu, V. M.; Bălănescu, D. T.; Panaite, C. E.; Atanasiu, M. V.

    2016-08-01

    The basic design and construction of an alpha-type Stirling engine with on load variable displacement is presented. The variable displacement is obtained through a planar quadrilateral linkage with one on load movable ground link. The physico-mathematical model used for analyzing the variable displacement alpha-type Stirling engine behavior is an isothermal model that takes into account the real movement of the pistons. Performances and power adjustment capabilities of such alpha-type Stirling engine are calculated and analyzed. An exemplification through the use of the numerical simulation was performed in this regard.

  12. First Attempts at Antihydrogen Trapping in ALPHA

    CERN Document Server

    Andresen, G B; Bowe, P D; Bray, C C; Butler, E; Cesar, C L; Chapman, S; Charlton, M; Fajans, J; Funakoshi, R; Gill, D R; Hangst, J S; Hardy, W N; Hayano, R S; Hayden, M E; Humphries, A J; Hydomako, R; Jenkins, M J; Jørgensen, L V; Kurchaninov, L; Lambo, R; Madsen, N; Nolan, P; Olchanski, K; Olin, A; Page, R D; Povilus, A; Pusa, P; Robicheaux, F; Sarid, E; Seif El Nasr, S; Silveira, D M; Storey, J W; Thompson, R I; Van der Werf, D P; Wasilenko, L; Wurtele, J S; Yamazaki, Y; Fujiwara, M C

    2008-01-01

    We discuss aspects of antihydrogen studies, that relate to particle physics ideas and techniques, within the context of the ALPHA experiment at CERN's Antiproton Decelerator facility. We review the fundamental physics motivations for antihydrogen studies, and their potential physics reach. We argue that initial spectroscopy measurements, once antihydrogen is trapped, could provide competitive tests of CPT, possibly probing physics at the Planck Scale. We discuss some of the particle detection techniques used in ALPHA. Preliminary results from commissioning studies of a partial system of the ALPHA Si vertex detector are presented, the results of which highlight the power of annihilation vertex detection capability in antihydrogen studies.

  13. On $\\alpha$-roughly weighted games

    CERN Document Server

    Freixas, Josep

    2011-01-01

    Very recently Gvozdeva, Hemaspaandra, and Slinko (2011) have introduced three hierarchies for simple games in order to measure the distance of a given simple game to the class of weighted voting games or roughly weighted voting games. Their third class $\\mathcal{C}_\\alpha$ consists of all simple games permitting a weighted representation such that each winning coalition has a weight of at least 1 and each losing coalition a weight of at most $\\alpha$. We continue their work and contribute some new results on the possible values of $\\alpha$ for a given number of voters.

  14. Alpha decay chains from superheavy nuclei

    CERN Document Server

    Samanta, C

    2008-01-01

    Magic islands for extra-stable nuclei in the midst of the sea of fission-instability were predicted to be around Z=114, 124 or, 126 with N=184, and Z=120, with N=172. Whether these fission-survived superheavy nuclei with high Z and N would live long enough for detection or, undergo alpha-decay in a very short time remains an open question. Alpha-decay half lives of nuclei with 130 118 are found to have alpha-decay half lives of the order of microseconds or, less.

  15. Synthesis of alpha-phosphorylated alpha,beta-unsaturated imines and their selective reduction to vinylogous and saturated alpha-aminophosphonates.

    Science.gov (United States)

    Palacios, Francisco; Vicario, Javier; Maliszewska, Agnieszka; Aparicio, Domitila

    2007-03-30

    An efficient synthesis of alpha,beta-unsaturated imines derived from alpha-aminophosphonates is achieved through aza-Wittig reaction of P-trimethyl phosphazenes with beta,gamma-unsaturated alpha-ketophosphonates. Selective 1,2-reduction of such 1-azadienes affords beta,gamma-unsaturated alpha-aminophosphonates, phosphorylated analogs of vinylglycines, which are hydrogenated to yield saturated alpha-aminophosphonate derivatives.

  16. Lambda alpha, Sigma alpha and Xi alpha potentials derived from the SU6 quark-model baryon-baryon interaction

    CERN Document Server

    Fujiwara, Y; Suzuki, Y

    2006-01-01

    We calculate Lambda alpha, Sigma alpha and Xi alpha potentials from the nuclear-matter G-matrices of the SU6 quark-model baryon-baryon interaction. The alpha-cluster wave function is assumed to be a simple harmonic-oscillator shell-model wave function. A new method is proposed to derive the direct and knock-on terms of the interaction Born kernel from the hyperon-nucleon G-matrices, with explicit treatments of the nonlocality and the center-of-mass motion between the hyperon and alpha. We find that the SU6 quark-model baryon-baryon interactions, FSS and fss2, yield a reasonable bound-state energy for 5 He Lambda, -3.18 -- -3.62 MeV, in spite of the fact that they give relatively large depths for the Lambda single-particle potentials, 46 -- 48 MeV, in symmetric nuclear matter. An equivalent local potential derived from the Wigner transform of the nonlocal Lambda alpha kernel shows a strong energy dependence for the incident Lambda-particle, indicating the importance of the strangeness-exchange process in the o...

  17. Is coefficient alpha robust to nonnormal data?

    Directory of Open Access Journals (Sweden)

    Yanyan eSheng

    2012-02-01

    Full Text Available Coefficient alpha has been a widely used measure by which internal consistency reliability is assessed. In addition to essential tau-equivalence and uncorrelated errors, normality has been noted as another important assumption for alpha. Earlier work on evaluating this assumption considered either exclusively nonnormal error score distributions, or limited conditions. In view of this and the availability of advanced methods for generating univariate nonnormal data, Monte Carlo simulations were conducted to show that nonnormal distributions for true or error scores do create problems for using alpha to estimate the internal consistency reliability. The sample coefficient alpha is affected by leptokurtic true score distributions, or skewed and/or kurtotic error score distributions. Increased sample sizes, not test lengths, help improve the accuracy, bias or precision of using it with nonnormal data.

  18. The QSE-reduced $\\alpha$ Network

    CERN Document Server

    Hix, W R; Wheeler, J C; Thielemann, F K

    1998-01-01

    Examination of the process of silicon burning, the burning stage that leads to the production of the iron peak nuclei, reveals that the nuclear evolution is dominated by large groups of nuclei in mutual equilibrium. These quasi-equilibrium (QSE) groups form well in advance of the global Nuclear Statistical Equilibrium (NSE). We present an improved ``minimal'' nuclear network, which takes advantage of quasi-equilibrium in order to calculate the nuclear evolution and energy generation while further reducing the computational cost compared to a conventional \\alpha-chain network. During silicon burning, the resultant \\emph{QSE-reduced} \\alpha network is twice as fast as the full \\alpha network it replaces and requires the tracking of only half as many abundance variables, without significant loss of accuracy. When the QSE-reduced \\alpha network is used in combination with a conventional an accurate approximation for all of the burning stages from He burning to NSE, while tracking only 7 abundances. These reductio...

  19. T-branes and $\\alpha'$-corrections

    CERN Document Server

    Marchesano, Fernando

    2016-01-01

    We study $\\alpha'$-corrections in multiple D7-brane configurations with non-commuting profiles for their transverse position fields. We focus on T-brane systems, crucial in F-theory GUT model building. There $\\alpha'$-corrections modify the D-term piece of the BPS equations which, already at leading order, require a non-primitive Abelian worldvolume flux background. We find that $\\alpha'$-corrections may either i) leave this flux background invariant, ii) modify the Abelian non-primitive flux profile, or iii) deform it to a non-Abelian profile. The last case typically occurs when primitive fluxes, a necessary ingredient to build 4d chiral models, are added to the system. We illustrate these three cases by solving the $\\alpha'$-corrected D-term equations in explicit examples, and describe their appearance in more general T-brane backgrounds. Finally, we discuss implications of our findings for F-theory GUT local models.

  20. Strichartz estimates on $alpha$-modulation spaces

    Directory of Open Access Journals (Sweden)

    Weichao Guo

    2013-05-01

    Full Text Available In this article, we consider some dispersive equations, including Schrodinger equations, nonelliptic Schrodinger equations, and wave equations. We develop some Strichartz estimates in the frame of alpha-modulation spaces.

  1. Solar Imagery - Chromosphere - H-Alpha

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Collection includes a variety of H-alpha photographic datasets contributed by a number of national and private solar observatories located worldwide. Solar...

  2. Energy dependence of event shapes and of $\\alpha_s$ at LEP 2

    CERN Document Server

    Abreu, P; Adye, T; Adzic, P; Albrecht, Z; Alderweireld, T; Alekseev, G D; Alemany, R; Allmendinger, T; Allport, P P; Almehed, S; Amaldi, Ugo; Amapane, N; Amato, S; Anassontzis, E G; Andersson, P; Andreazza, A; Andringa, S; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barbiellini, Guido; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Beillière, P; Belokopytov, Yu A; Belous, K S; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Bizouard, M A; Bloch, D; Blom, H M; Bonesini, M; Bonivento, W; Boonekamp, M; Booth, P S L; Borgland, A W; Borisov, G; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Boyko, I; Bozovic, I; Bozzo, M; Branchini, P; Brenke, T; Brenner, R A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschbeck, Brigitte; Buschmann, P; Cabrera, S; Caccia, M; Calvi, M; Camporesi, T; Canale, V; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Chapkin, M M; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cieslik, K; Collins, P; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crépé, S; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Davenport, Martyn; Da Silva, W; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Min, A; De Paula, L S; Dijkstra, H; Di Ciaccio, Lucia; Dolbeau, J; Doroba, K; Dracos, M; Drees, J; Dris, M; Duperrin, A; Durand, J D; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Ellert, M; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fanourakis, G K; Fassouliotis, D; Fayot, J; Feindt, Michael; Fenyuk, A; Ferrari, P; Ferrer, A; Ferrer-Ribas, E; Ferro, F; Fichet, S; Firestone, A; Flagmeyer, U; Föth, H; Fokitis, E; Fontanelli, F; Franek, B J; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gamblin, S; Gandelman, M; García, C; Gaspar, C; Gaspar, M; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Ghodbane, N; Gil, I; Glege, F; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; González-Caballero, I; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Grahl, J; Graziani, E; Green, C; Grimm, H J; Gris, P; Grosdidier, G; Grzelak, K; Günther, M; Guy, J; Hahn, F; Hahn, S; Haider, S; Hallgren, A; Hamacher, K; Hansen, J; Harris, F J; Hedberg, V; Heising, S; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Heuser, J M; Higón, E; Holmgren, S O; Holt, P J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hughes, G J; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, P E; Joram, C; Juillot, P; Kapusta, F; Karafasoulis, K; Katsanevas, S; Katsoufis, E C; Keränen, R; Kersevan, Borut P; Khomenko, B A; Khovanskii, N N; Kiiskinen, A P; King, B J; Kinvig, A; Kjaer, N J; Klapp, O; Klein, H; Kluit, P M; Kokkinias, P; Koratzinos, M; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Krammer, Manfred; Kriznic, E; Krstic, J; Krumshtein, Z; Kubinec, P; Kurowska, J; Kurvinen, K L; Lamsa, J; Lane, D W; Langefeld, P; Lapin, V; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Leinonen, L; Leisos, A; Leitner, R; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Lethuillier, M; Libby, J; Liko, D; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; Lopes, J H; López, J M; López-Fernandez, R; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Mahon, J R; Maio, A; Malek, A; Malmgren, T G M; Maltezos, S; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Masik, J; Mazzucato, F; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; McPherson, G; Meroni, C; Meyer, W T; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Moch, M; Møller, R; Mönig, K; Monge, M R; Moreau, X; Morettini, P; Morton, G A; Müller, U; Münich, K; Mulders, M; Mulet-Marquis, C; Muresan, R; Murray, W J; Muryn, B; Myatt, Gerald; Myklebust, T; Naraghi, F; Nassiakou, M; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Némécek, S; Neufeld, N; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nikolenko, M; Nomokonov, V P; Normand, Ainsley; Nygren, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Orazi, G; Österberg, K; Ouraou, A; Paganoni, M; Paiano, S; Pain, R; Paiva, R; Palacios, J; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Pegoraro, M; Peralta, L; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Phillips, H T; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Ratoff, P N; Read, A L; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Reinhardt, R; Renton, P B; Resvanis, L K; Richard, F; Rídky, J; Rinaudo, G; Røhne, O M; Romero, A; Ronchese, P; Rosenberg, E I; Rosinsky, P; Roudeau, Patrick; Rovelli, T; Royon, C; Ruhlmann-Kleider, V; Ruiz, A; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sampsonidis, D; Sannino, M; Schneider, H; Schwemling, P; Schwering, B; Schwickerath, U; Schyns, M A E; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Sekulin, R L; Shellard, R C; Sheridan, A; Siebel, M; Simard, L C; Simonetto, F; Sissakian, A N; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Sopczak, André; Sosnowski, R; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stanic, S; Stevenson, K; Stocchi, A; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tegenfeldt, F; Terranova, F; Thomas, J; Timmermans, J; Tinti, N; Tkatchev, L G; Todorova-Nová, S; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tzamarias, S; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; Van der Velde, C; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Van Lysebetten, A; Van Vulpen, I B; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Verzi, V; Vilanova, D; Vitale, L; Vlasov, E; Vodopyanov, A S; Vollmer, C F; Voulgaris, G; Vrba, V; Wahlen, H; Walck, C; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G R; Winter, M; Witek, M; Wolf, G; Yi, J; Yushchenko, O P; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zucchelli, G C; Zumerle, G

    1999-01-01

    Infrared and collinear safe event shape distributions and their mean values are determined using the data taken at ve di erent centre of mass energies above $M_Z$ with the DELPHI detector at LEP. From the event shapes, the strong coupling $\\alpha_s$ is extracted in $O(\\alpha^2_s)$, NLLA and a combined scheme using hadronisation corrections evaluated with fragmentation model generators as well as using an analytical power ansatz. Comparing these measurements to those obtained at MZ, the energy dependence (running) of $\\alpha_s$ is accessible. The logarithmic energy slope of the inverse strong coupling is measured to be $d\\alpha_{s}^{-1}/d log(E_{cm}) = 1.39 \\pm 0.34(stat) \\pm 0.17(syst)$, in good agreement with the QCD expectation of 1.27.

  3. Improved parametrization of the unified model for alpha decay and alpha capture

    CERN Document Server

    Denisov, V Yu; Sedykh, I Yu

    2015-01-01

    The updated data for the ground-state-to-ground-state alpha-transition half-lives in 401 nuclei and the alpha capture cross sections of 40Ca, 44Ca, 59Co, 208Pb and 209Bi are well described in the framework of the unified model for alpha-decay and alpha-capture. The updated values of the alpha decay half-lives, the binding energies of nuclei, the spins of parent and daughter nuclei, and the surface deformation parameters are used for the reevaluation of the model parameters. The data for the ground-state-to-ground-state alpha-decay half-lives are also well described by the empirical relationships.

  4. Investigation of the Pygmy Dipole Resonance in ({alpha},{alpha}{sup '}{gamma}) coincidence experiments

    Energy Technology Data Exchange (ETDEWEB)

    Savran, D. [Institut fuer Kernphysik, TU Darmstadt, Schlossgartenstrasse 9, D-64289 Darmstadt (Germany); Babilon, M. [Institut fuer Kernphysik, TU Darmstadt, Schlossgartenstrasse 9, D-64289 Darmstadt (Germany); Berg, A.M. van den [Kernfysisch Versneller Instituut, Rijksuniversiteit Groningen, Zernikelaan 25, NL-9747 AA Groningen (Netherlands); Harakeh, M.N. [Kernfysisch Versneller Instituut, Rijksuniversiteit Groningen, Zernikelaan 25, NL-9747 AA Groningen (Netherlands); Hasper, J. [Institut fuer Kernphysik, TU Darmstadt, Schlossgartenstrasse 9, D-64289 Darmstadt (Germany); Woertche, H.J. [Kernfysisch Versneller Instituut, Rijksuniversiteit Groningen, Zernikelaan 25, NL-9747 AA Groningen (Netherlands); Zilges, A. [Institut fuer Kernphysik, TU Darmstadt, Schlossgartenstrasse 9, D-64289 Darmstadt (Germany)

    2007-05-15

    We report on first results from experiments using the ({alpha},{alpha}{sup '}{gamma}) reaction at E{sub {alpha}}=136 MeV to investigate bound electric dipole (E1) excitations building the so-called Pygmy Dipole Resonance (PDR) in the semi-magic nucleus {sup 140}Ce. The method of ({alpha},{alpha}{sup '}{gamma}) allows the separation of E1 excitations from states of higher multipolarity, provides an excellent energy resolution and therefore allows a detailed analysis for each single state. Studying bound E1 excitations in {alpha}-scattering experiments at intermediate energies becomes feasible for the first time even in nuclei with a high level density. The surprising results of the first experiment on {sup 140}Ce point to a splitting of the PDR in this nucleus.

  5. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, A R;

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with immunoinflammatory diseases and cytokine-dependent tumours....

  6. Lattice measurement of \\alpha_s with a realistic charm quark

    CERN Document Server

    Blossier, B; Brinet, M; De Soto, F; Du, X; Morenas, V; Pene, O; Petrov, K; Rodriguez-Quintero, J

    2012-01-01

    We report on an estimate of \\alpha_s, renormalised in the MSbar scheme at the tau and Z^0 mass scales, by means of lattice QCD. Our major improvement compared to previous lattice calculations is that, for the first time, no perturbative treatment at the charm threshold has been required since we have used statistical samples of gluon fields built by incorporating the vacuum polarisation effects of u/d, s and c sea quarks. Extracting \\alpha_s in the Taylor scheme from the lattice measurement of the ghost-ghost-gluon vertex, we obtain \\alpha_s^{MSbar}(m^2_Z)=0.1200(14) and \\alpha_s^{MSbar}(m^2_tau)=0.339(13).

  7. The ALPHA Experiment a Cold Antihydrogen Trap

    CERN Document Server

    Bertsche, W; Bowe, P D; Cesar, C L; Chapman, S; Charlton, M; Chartier, M; Deutsch, A; Fajans, J; Fujiwara, M C; Funakoshi, R; Gill, D; Gomberoff, K; Grote, D P; Hangst, J S; Hayano, R S; Jenkins, M; Jørgensen, L V; Madsen, N; Miranda, D; Nolan, P; Ochanski, K; Olin, A; Page, R D; Posada, L G C; Robicheaux, F; Sarid, E; Telle, H H; Vay, J L; Wurtele, J; van der Werf, D P; Yamazaki, Y

    2005-01-01

    The ALPHA experiment aims to trap antihydrogen as the next crucial step towards a precise CPT test, by a spectroscopic comparison of antihydrogen with hydrogen. The experiment will retain the salient techniques developed by the ATHENA collaboration during the previous phase of antihydrogen experiments at the antiproton decelerator (AD) at CERN. The collaboration has identified the key problems in adding a neutral antiatom trap to the previously developed experimental configuration. The solutions identified by ALPHA are described in this paper.

  8. Self-assembling, dynamic alphaPNAs

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2009-01-01

    In the recent report published in Science, Ghadiri and coworkers describe dynamic tPNAs, alphaPNA derivatives with a nucleobase attached via a thioester bond that are a step forward toward self-repairing and replicating molecules.......In the recent report published in Science, Ghadiri and coworkers describe dynamic tPNAs, alphaPNA derivatives with a nucleobase attached via a thioester bond that are a step forward toward self-repairing and replicating molecules....

  9. Selective sorting of alpha-granule proteins

    OpenAIRE

    Italiano, J.E.; Battinelli, E. M.

    2009-01-01

    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. The majority of this vast array of secreted proteins is stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on th...

  10. Lectin interactions with alpha-galactosylated xenoantigens

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Moe, Dennis

    2002-01-01

    alpha-Galactosylated xenoantigens (Galalpha1-3Galbeta1-4GlcNAcbeta1 and Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) are often detected with the alpha-Gal specific lectin Griffonia simplicifolia 1 isolectin B4 (GS1 B4). However, this lectin exhibits a broad and variable specificity for carboh...

  11. Scaling Property in the Alpha Predominant EEG

    CERN Document Server

    Lin, D C; Kwan, H; Lin, Der Chyan; Sharif, Asif; Kwan, Hon

    2004-01-01

    The $\\alpha$ predominant electroencephalographic (EEG) recording of the human brain during eyes open and closed is studied using the zero-crossing time statistics. A model is presented to demonstrate and compare the key characteristics of the brain state. We found the zero-crossing time statistic is more accurate than the power spectral analysis and the detrend fluctuation analysis. Our results indicate different EEG fractal scaling in eyes closed and open for individuals capable of strong $\\alpha$ rhythm.

  12. Measurement of the angle alpha at BABAR

    Energy Technology Data Exchange (ETDEWEB)

    Perez, A.; /Orsay, LAL

    2009-06-25

    The authors present recent measurements of the CKM angle {alpha} using data collected by the BABAR detector at the PEP-II asymmetric-energy e{sup +}e{sup -} collider at the SLAC National Accelerator Laboratory, operating at the {Upsilon}(4S) resonance. They present constraints on {alpha} from B {yields} {pi}{pi}, B {yields} {rho}{rho} and B {yields} {rho}{pi} decays.

  13. EEG alpha power and creative ideation ☆

    OpenAIRE

    2014-01-01

    Neuroscientific studies revealed first insights into neural mechanisms underlying creativity, but existing findings are highly variegated and often inconsistent. Despite the disappointing picture on the neuroscience of creativity drawn in recent reviews, there appears to be robust evidence that EEG alpha power is particularly sensitive to various creativity-related demands involved in creative ideation. Alpha power varies as a function of creativity-related task demands and the originality of...

  14. Alpha-emitters for medical therapy workshop

    Energy Technology Data Exchange (ETDEWEB)

    Feinendegen, L.E.; McClure, J.J.

    1996-12-31

    A workshop on ``Alpha-Emitters for Medical Therapy`` was held May 30-31, 1996 in Denver Colorado to identify research goals and potential clinical needs for applying alpha-particle emitters and to provide DOE with sufficient information for future planning. The workshop was attended by 36 participants representing radiooncology, nuclear medicine, immunotherapy, radiobiology, molecular biology, biochemistry, radiopharmaceutical chemistry, dosimetry, and physics. This report provides a summary of the key points and recommendations arrived at during the conference.

  15. Neurophysiological assessment of alpha pattern coma.

    OpenAIRE

    1980-01-01

    Somatosensory evoked potentials, blink reflexes, and H wave reflexes, were recorded on several days from three patients with alpha pattern coma. Coma was secondary to cardiac arrest in two cases and to brainstem infarction in one. Results are compatible with damage to the brainstem reticular formation with sparing of thalamo-cortical circuits as the main physiopathological characteristic of alpha pattern coma. This condition should not be regarded as a discrete entity when establishing the pr...

  16. [Studies on determination of alpha-amylase with p-nitrophenyl-alpha-D-maltotetraoside].

    Science.gov (United States)

    Kruse-Jarres, J D; Schott, F J; Klein, B; Rastetter, N; Wallenfels, K

    1982-11-01

    Nitrophenylmaltodextrins are alpha-amylase substrates which allow a continuous determination with a zero order kinetics over a period of at least 10 min, without deviations from linearity. Only one auxiliary enzyme is necessary. Practicability and clinical evidence of alpha-amylase determinations by means of p-nitrophenyl-alpha-D-maltotetraoside are demonstrated. The interserial precision of 0.84% cannot conceal an only moderate correlation with previous methods. This fact, however, does not negate the advantages.

  17. Therapeutic use of alpha-emitters

    Energy Technology Data Exchange (ETDEWEB)

    Lassmann, M. [Klinik und Poliklinik fuer Nuklearmedizin der Univ. Wuerzburg (Germany)

    2005-07-01

    In recent years there is a growing interest in the therapeutic use of {alpha}-emitters for patient treatment, {alpha}-particles have much higher energy and their range is only a few cell diameters. Their high LET and the limited ability of cells to repair DNA damage from {alpha}-radiation explain their high relative biological effectiveness and cytotoxicity. Potential {alpha}-emitting isotopes for therapeutic applications are {sup 224}Ra, {sup 223}Ra, {sup 213}Bi and {sup 211}At. The treatment with {alpha}-particles is focused upon targeted cancer therapy using radiolabeled monoclonal antibodies, on palliation of bone metastases or upon pain relief in patients with ankylosing spondylitis (AS). Examples for targeted cancer therapy are the treatment of melanoma with {sup 213}Bi and non-Hodgkin lymphoma with {sup 211}At. For metastatic bone pain palliation {sup 223}Ra was applied in a phase I clinical trial. For amelioration of pain in AS-patients {sup 224}Ra-chloride is used. This radiopharmaceutical is licensed for this particular application in Germany. Today there are some potential clinical applications for {alpha}-emitters although most of them are in the state of scientific, non-routine investigations. In-vivo dosimetry for risk assessment associated with this treatment is even more difficult to perform than for therapies using beta-emitting radiopharmaceuticals. (orig.)

  18. Compatibility of $\\alpha_s(M_\\tau)$ with $\\alpha_s(M_Z)$

    OpenAIRE

    Steele, T. G.; Elias, V.

    1998-01-01

    The current phenomenological determinations of $\\alpha_s(M_\\tau)$ and $\\alpha_s(M_Z)$ are shown to be only marginally consistent with the QCD evolution of the strong coupling constant between $M_Z$ and $M_\\tau$. This motivates a revised estimate of $\\alpha_s(M_\\tau)$ since the perturbative series used to extract $\\alpha_s(M_\\tau)$ from the $\\tau$ hadronic width exhibits slow convergence. Pad\\'e summation techniques provide an estimate of these unknown higher-order effects, leading to the revi...

  19. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup;

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...

  20. Mapping High-velocity H-alpha and Lyman-alpha Emission from Supernova 1987A

    OpenAIRE

    France, Kevin; McCray, Richard; Fransson, Claes; Larsson, Josefin; Frank, Kari A.; Burrows, David N.; Challis, Peter; Kirshner, Robert P.; Chevalier, Roger A.; Garnavich, Peter; Heng, Kevin; Lawrence, Stephen S.; Lundqvist, Peter; Smith, Nathan; Sonneborn, George

    2015-01-01

    We present new {\\it Hubble Space Telescope} images of high-velocity H-$\\alpha$ and Lyman-$\\alpha$ emission in the outer debris of SN~1987A. The H-$\\alpha$ images are dominated by emission from hydrogen atoms crossing the reverse shock. For the first time we observe emission from the reverse shock surface well above and below the equatorial ring, suggesting a bipolar or conical structure perpendicular to the ring plane. Using the H$\\alpha$ imaging, we measure the mass flux of hydrogen atoms cr...

  1. H-alpha features with hot onsets III. Fibrils in Lyman-alpha and with ALMA

    CERN Document Server

    Rutten, Robert J

    2016-01-01

    In H-alpha most of the solar surface is covered by a dense canopy of long opaque fibrils, but predictions for quiet-Sun observations with ALMA have ignored this fact. Comparison with Ly-alpha suggests that the large opacity of H-alpha fibrils is caused by hot precursor events. Application of a recipe that assumes momentary Saha-Boltzmann extinction during their hot onset to millimeter wavelengths suggests that ALMA will observe the H-alpha fibril canopy, not acoustic shocks underneath, and will yield data more interesting than if this canopy were transparent.

  2. Synthesis of tritiated 1-alpha-methadol and 1-alpha-acetylmethadol

    Energy Technology Data Exchange (ETDEWEB)

    Thang, D.C.; Nam, N.H.; Pontikis, R. (Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Fernand Widal, 75 - Paris (France)); Pichat, L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

    1982-04-01

    dl-Methadone was resolved by crystallization of its ammonium d- ..cap alpha.. -bromocamphor-..pi..-sulfonate salt to give d-methadone. The latter in ethyl acetate solution was reduced with tritium gas to 1-..cap alpha..-methadol /sup 3/H in presence of Adams platinum oxide at normal temperature and pressure. Acetylation of 1-..cap alpha..-carbinol hydrochloride by means of acetyl chloride afforded 1-..cap alpha..-acetylmethadol /sup 3/H, specific activity: 20 Ci/mMole. The positions and extent of tritium labelling were determined by /sup 3/H NMR spectroscopy.

  3. Alpha 1-blockers vs 5 alpha-reductase inhibitors in benign prostatic hyperplasia. A comparative review

    DEFF Research Database (Denmark)

    Andersen, J T

    1995-01-01

    During recent years, pharmacological treatment of symptomatic benign prostatic hyperplasia (BPH) has become the primary treatment choice for an increasing number of patients. The 2 principal drug classes employed are alpha 1-blockers and 5 alpha-reductase inhibitors. Current information from...... of patients who will respond well to alpha 1-blockers have yet to be identified, and data concerning the long term effects of these drugs are not yet available. 5 alpha-Reductase inhibitors have a slow onset of effect, but treatment leads to improvement in symptoms, reduction of the size of the prostate gland...... or unwilling to undergo surgical resection of the prostate will benefit from such therapy....

  4. Anti-IL-1alpha autoantibodies in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Forslind, K; Svensson, Birte; Svenson, M;

    2001-01-01

    To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA).......To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA)....

  5. Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane

    Science.gov (United States)

    Gyoneva, Lazarina

    The glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is alpha3(IV)alpha4(IV)alpha5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the alpha3(IV)alpha4(IV)alpha5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the alpha3(IV)alpha4(IV)alpha5(IV) chains present and missing. The experiments showed basement membranes containing alpha3(IV)alpha4(IV)alpha5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the alpha3(IV)alpha4(IV)alpha5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the alpha3(IV)alpha4(IV)alpha5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the alpha3(IV)alpha4(IV)alpha5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of alpha3(IV)alpha4(IV)alpha

  6. Recent advances in the discovery of alpha1-adrenoceptor agonists.

    Science.gov (United States)

    Bishop, Michael J

    2007-01-01

    The alpha(1) adrenoceptors are three of nine well-characterized receptors that are activated by epinephrine and norepinephrine. Agonists acting at the alpha(1) adrenoceptors produce numerous physiological effects, and are used therapeutically for several indications. Many known alpha(1) adrenoceptor agonists are alpha(1A) selective, but the discovery of highly selective alpha(1B) and alpha(1D) adrenoceptor agonists has proven to be an extremely difficult goal to achieve. This review will focus on recent advances in the discovery, development and clinical utility of subtype-specific alpha(1) agonists as well as contributions to our understanding of agonist-receptor interactions.

  7. Pharmacologic specificity of alpha-2 adrenergic receptor subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Petrash, A.; Bylund, D.

    1986-03-01

    The authors have defined alpha-2 adrenergic receptor subtypes in human and rat tissues using prazosin as a subtype selective drug. Prazosin has a lower affinity (250 nM) at alpha-2A receptor and a higher affinity (5 nM) at alpha-2B receptors. In order to determine if other adrenergic drugs are selective for one or the other subtypes, the authors performed (/sup 3/H)yohimbine inhibition experiments with various adrenergic drugs in tissues containing alpha-2A, alpha-2B or both subtypes. Oxymetazoline, WB4101 and yohimbine were found to be 80-, 20- and 10-fold more potent at alpha-2A receptors than at alpha-2B receptors. Phentolamine, adazoxan, (+)- and (-)-mianserin, clonidine, (+)-butaclamol, (-)- and (+)-norepinephrine, epinephrine, dopamine and thioridazine were found to have equal affinities for the two subtypes. These results further validate the subdivision of alpha-2 adrenergic receptors into alpha-2A and alpha-2B subtypes.

  8. [Individual alpha activity of electroencephalogram and nonverbal creativity].

    Science.gov (United States)

    Bazanova, O M; Aftanas, L I

    2007-01-01

    The main objective of present correlational investigation was to clarify relationships between nonverbal creativity indices and individual electroencephalogram alpha activity indices: individual alpha peak frequency, alpha band width, magnitude of alpha desynchronization and alpha spindle indices such as duration, amplitude, variability and skewness. The EEG was recorded in 98 healthy male right-handed subjects. Scores of nonverbal creativity (i. e., fluency, originality, and flexibility) were assessed using the Torrance test of nonverbal performance. The study showed that fluency in creative performance was associated with individual alpha peak frequency and alpha spindles duration, whereas originality and plasticity--with individual alpha band width and spindle amplitude variability. The findings also show that both highest and lowest individual alpha peak frequency indices are associated with enhanced scores of originality. It is suggested that individual alpha activity indices could be presented as individual predictors of fluency, plasticity and originality of nonverbal creativity.

  9. Endometrial receptivity: expression of alpha3beta1, alpha4beta1 and alphaVbeta1 endometrial integrins in women with impaired fertility.

    Science.gov (United States)

    Skrzypczak, J; Mikołajczyk, M; Szymanowski, K

    2001-11-01

    Advances in immunohistochemical methods with the specificity of poly- and monoclonal antibodies allow the description of the endometrial receptivity, which is characterized by the ability of secretion of phase specific proteins and glikoproteins by epithelial and stromal cells. We studied the differences in the expression of alpha3beta1, alpha4beta1 and alphaVbeta1 integrins in endometrium of women with recurrent miscarriages and women with unexplained infertility. The endometrial tissue was collected during hysteroscopy performed between 7th and 9th day after ovulation. The immunohistochemical evaluation of alpha3beta1, alpha4beta1 and alphaVbeta1 integrin expression was determined in all endometrial biopsies. Staining intensity of alpha3beta1 in glandular epithelium and endometrial stroma was similar in both groups. In women with recurrent miscarriages we noted a lower concentrations of the alpha4beta1 and alphaVbeta1 integrins during the midluteal phase than in women with unexplained infertility. Moreover, integrins alpha4beta1 and alphaVbeta1 were expressed more frequently in glandular epithelium and endometrial stroma of women with unexplained infertility than those of women with recurrent miscarriages. However, alphaV(2)1 staining in endometrial stroma was stronger than that of alpha4beta1. It can be concluded, that these integrins may play an important role in the implantation process.

  10. Alpha Channeling in Rotating Plasma with Stationary Waves

    Energy Technology Data Exchange (ETDEWEB)

    A. Fetterman and N.J. Fisch

    2010-02-15

    An extension of the alpha channeling effect to supersonically rotating mirrors shows that the rotation itself can be driven using alpha particle energy. Alpha channeling uses radiofrequency waves to remove alpha particles collisionlessly at low energy. We show that stationary magnetic fields with high nθ can be used for this purpose, and simulations show that a large fraction of the alpha energy can be converted to rotation energy.

  11. {alpha}-nucleus potentials and photon-induced nucleosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Galaviz, D. E-mail: redondo@ikp.tu-darmstadt.de; Babilon, M.; Fueloep, Zs.; Gyuerky, Gy.; Hillier, R.; Mate, Z.; Mohr, P.; Rauscher, T.; Somorjai, E.; Zilges, A.; Zolnai, L

    2003-05-05

    New data for the {sup 112,124}Sn({alpha},{alpha}){sup 112,124}Sn reaction have been measured and are presently analyzed. Results of the {sup 112} Sn x {alpha} potential at the energy E{sub c.m.} {approx} 14 MeV are presented. The determination of this {alpha}-nucleus potential may allow a prediction of the {sup 112}Sn({alpha},{gamma}){sup 116}Te cross section.

  12. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    OpenAIRE

    Maryam Rakhshandehroo; Bianca Knoch; Michael Müller; Sander Kersten

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPAR alpha serves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPAR alpha binds and is activated by numerous fatty acids and fatty acid-derived compounds. PPAR alpha governs biologi...

  13. Infusions of 3alpha,5alpha-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3alpha,5alpha-THP in midbrain, hippocampus, diencephalon, and cortex of female rats.

    Science.gov (United States)

    Frye, Cheryl A; Rhodes, Madeline E

    2008-02-11

    17beta-Estradiol (E2) and progesterone (P4) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P4 metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), modulates lordosis of E2-primed rodents; 3alpha,5alpha-THP can also influence anxiety and social behaviors. To examine if 3alpha,5alpha-THP in the VTA mediates socio-sexual behaviors, we infused 3alpha,5alpha-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E2, P4, dihydroprogesterone (DHP), and 3alpha,5alpha-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3alpha,5alpha-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3alpha,5alpha-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3alpha,5alpha-THP, but neither E2 nor P4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3alpha,5alpha-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

  14. The biological effects of five feline IFN-alpha subtypes.

    Science.gov (United States)

    Baldwin, Susan L; Powell, Tim D; Sellins, Karen S; Radecki, Steven V; Cohen, J John; Milhausen, Michael J

    2004-06-01

    IFN-alpha has been shown to induce both antiviral and antiproliferative activities in animals. This report describes the biological activity of five recently identified feline IFN-alpha subtypes expressed in the Chinese hamster ovary (CHO) cell line (rfeIFN-alpha1[CHO], rfeIFN-alpha2[CHO], rfeIFN-alpha3[CHO], rfeIFN-alpha5[CHO] and rfeIFN-alpha6[CHO]) and the feIFN-alpha6 subtype expressed in and purified from Pichia pastoris (rfeIFN-alpha6[P. pastoris]). The rfeIFN-alpha[CHO] subtypes were tested for antiviral activity against either Vesicular stomatitis virus (VSV) or feline calicivirus (FCV) infected feline embryonic fibroblast cell line (AH927) or Crandell feline kidney cell line (CRFK). Antiviral activity was induced against both VSV and FCV infected AH927 cells and VSV infected CRFK cells by all five of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris]. In addition, the IFN-alpha inducible Mx gene (associated with antiviral activity) was upregulated in vivo 24 h following treatment with rfeIFN-alpha6[P. pastoris], compared to baseline levels seen prior to treatment. All of the rfeIFN-alpha[CHO] subtypes and rfeIFN-alpha6[P. pastoris] exhibited antiproliferative activity in the FeT-J cell line (an IL-2 independent feline T-cell line). Both necrosis and apoptosis were observed in rfeIFN-alpha6[P. pastoris]-treated FeT-J cells. The rfeIFN-alpha3[CHO] subtype consistently exhibited lower antiviral and antiproliferative activity compared to that observed with the other four rfeIFN-alpha[CHO] subtypes. In summary, this paper demonstrates that five previously described feIFN-alpha subtypes induce both antiviral and antiproliferative activities in vitro and are capable of upregulating the feMx gene in vivo.

  15. Lyman-alpha emission in star-forming galaxies

    Science.gov (United States)

    Hartmann, Lee W.; Huchra, John P.; Geller, Margaret J.; O'Brien, Paul; Wilson, Robert

    1988-01-01

    IUE observations of five blue, low-metallicity, star-forming galaxies sufficiently redshifted to permit detection of Lyman-alpha are reported. The galaxies with metallicities 0.1 time solar or more have weak or absent Lyman-alpha emission. There is evidence for increasing Lyman-alpha emission with decreasing metallicity. The reduction of Lyman-alpha fluxes from recombination values is attributed to absorption of multiply scattered Lyman-alpha by dust.

  16. Consistent Measurements of $\\alpha_{s}$ from Precise Oriented Event Shape Distributions

    CERN Document Server

    Abreu, P.; Adye, T.; Adzic, P.; Albrecht, Z.; Alderweireld, T.; Alekseev, G.D.; Alemany, R.; Allmendinger, T.; Allport, P.P.; Almehed, S.; Amaldi, U.; Amapane, N.; Amato, S.; Anassontzis, E.G.; Andersson, P.; Andreazza, A.; Andringa, S.; Antilogus, P.; Apel, W.D.; Arnoud, Y.; Asman, B.; Augustin, J.E.; Augustinus, A.; Baillon, P.; Bambade, P.; Barao, F.; Barbiellini, G.; Barbier, R.; Bardin, D.Yu.; Barker, G.J.; Baroncelli, A.; Battaglia, M.; Baubillier, M.; Becks, K.H.; Begalli, M.; Behrmann, A.; Beilliere, P.; Belokopytov, Yu.; Benekos, N.C.; Benvenuti, A.C.; Berat, C.; Berggren, M.; Bertini, D.; Bertrand, D.; Besancon, M.; Bigi, M.; Bilenky, Mikhail S.; Bizouard, M.A.; Bloch, D.; Blom, H.M.; Bonesini, M.; Bonivento, W.; Boonekamp, M.; Booth, P.S.L.; Borgland, A.W.; Borisov, G.; Bosio, C.; Botner, O.; Boudinov, E.; Bouquet, B.; Bourdarios, C.; Bowcock, T.J.V.; Boyko, I.; Bozovic, I.; Bozzo, M.; Branchini, P.; Brenke, T.; Brenner, R.A.; Bruckman, P.; Brunet, J.M.; Bugge, L.; Buran, T.; Burgsmuller, T.; Buschbeck, B.; Buschmann, P.; Cabrera, S.; Caccia, M.; Calvi, M.; Camporesi, T.; Canale, V.; Carena, F.; Carroll, L.; Caso, C.; Castillo Gimenez, M.V.; Cattai, A.; Cavallo, F.R.; Chabaud, V.; Charpentier, P.; Chaussard, L.; Checchia, P.; Chelkov, G.A.; Chierici, R.; Chochula, P.; Chorowicz, V.; Chudoba, J.; Cieslik, K.; Collins, P.; Contri, R.; Cortina, E.; Cosme, G.; Cossutti, F.; Cowell, J.H.; Crawley, H.B.; Crennell, D.; Crepe-Renaudin, Sabine; Crosetti, G.; Cuevas Maestro, J.; Czellar, S.; Davenport, M.; Da Silva, W.; Deghorain, A.; Della Ricca, G.; Delpierre, P.; Demaria, N.; De Angelis, A.; De Boer, W.; De Clercq, C.; De Lotto, B.; De Min, A.; De Paula, L.; Dijkstra, H.; Di Ciaccio, L.; Dolbeau, J.; Doroba, K.; Dracos, M.; Drees, J.; Dris, M.; Duperrin, A.; Durand, J.D.; Eigen, G.; Ekelof, T.; Ekspong, G.; Ellert, M.; Elsing, M.; Engel, J.P.; Erzen, B.; Espirito Santo, M.C.; Fanourakis, G.; Fassouliotis, D.; Fayot, J.; Feindt, M.; Ferrari, P.; Ferrer, A.; Ferrer-Ribas, E.; Ferro, F.; Fichet, S.; Firestone, A.; Flagmeyer, U.; Foeth, H.; Fokitis, E.; Fontanelli, F.; Franek, B.; Frodesen, A.G.; Fruhwirth, R.; Fulda-Quenzer, F.; Fuster, J.; Galloni, A.; Gamba, D.; Gamblin, S.; Gandelman, M.; Garcia, C.; Gaspar, C.; Gaspar, M.; Gasparini, U.; Gavillet, P.; Gazis, Evangelos; Gele, D.; Ghodbane, N.; Gil Botella, Ines; Glege, F.; Gokieli, R.; Golob, B.; Gomez-Ceballos, G.; Goncalves, P.; Gonzalez Caballero, I.; Gopal, G.; Gorn, L.; Gracco, V.; Grahl, J.; Graziani, E.; Green, C.; Grimm, H.J.; Gris, P.; Grosdidier, G.; Grzelak, K.; Gunther, M.; Guy, J.; Hahn, F.; Hahn, S.; Haider, S.; Hallgren, A.; Hamacher, K.; Hansen, J.; Harris, F.J.; Hedberg, V.; Heising, S.; Hernandez, J.J.; Herquet, P.; Herr, H.; Hessing, T.L.; Heuser, J.M.; Higon, E.; Holmgren, S.O.; Holt, P.J.; Hoorelbeke, S.; Houlden, M.; Hrubec, J.; Huet, K.; Hughes, G.J.; Hultqvist, K.; Jackson, John Neil; Jacobsson, R.; Jalocha, P.; Janik, R.; Jarlskog, C.; Jarlskog, G.; Jarry, P.; Jean-Marie, B.; Johansson, Erik Karl; Jonsson, P.; Joram, C.; Juillot, P.; Kapusta, Frederic; Karafasoulis, K.; Katsanevas, S.; Katsoufis, E.C.; Keranen, R.; Kersevan, B.P.; Khomenko, B.A.; Khovansky, N.N.; Kiiskinen, A.; King, B.; Kinvig, A.; Kjaer, N.J.; Klapp, O.; Klein, Hansjorg; Kluit, P.; Kokkinias, P.; Koratzinos, M.; Kourkoumelis, C.; Kuznetsov, O.; Krammer, M.; Kriznic, E.; Krumshtein, Z.; Kubinec, P.; Kurowska, J.; Kurvinen, K.; Lamsa, J.W.; Lane, D.W.; Langefeld, P.; Laugier, J.P.; Lauhakangas, R.; Leder, G.; Ledroit, Fabienne; Lefebure, V.; Leinonen, L.; Leisos, A.; Leitner, R.; Lemonne, J.; Lenzen, G.; Lepeltier, V.; Lesiak, T.; Lethuillier, M.; Libby, J.; Liko, D.; Lipniacka, A.; Lippi, I.; Lorstad, B.; Loken, J.G.; Lopes, J.H.; Lopez, J.M.; Lopez-Fernandez, R.; Loukas, D.; Lutz, P.; Lyons, L.; MacNaughton, J.; Mahon, J.R.; Maio, A.; Malek, A.; Malmgren, T.G.M.; Maltezos, S.; Malychev, V.; Mandl, F.; Marco, J.; Marco, R.; Marechal, B.; Margoni, M.; Marin, J.C.; Mariotti, C.; Markou, A.; Martinez-Rivero, C.; Martinez-Vidal, F.; Marti i Garcia, S.; Masik, J.; Mastroyiannopoulos, N.; Matorras, F.; Matteuzzi, C.; Matthiae, G.; Mazzucato, F.; Mazzucato, M.; McCubbin, M.; McKay, R.; McNulty, R.; McPherson, G.; Meroni, C.; Meyer, W.T.; Migliore, E.; Mirabito, L.; Mitaroff, W.A.; Mjornmark, U.; Moa, T.; Moch, M.; Moller, Rasmus; Monig, Klaus; Monge, M.R.; Moreau, X.; Morettini, P.; Morton, G.; Muller, U.; Munich, K.; Mulders, M.; Mulet-Marquis, C.; Muresan, R.; Murray, W.J.; Muryn, B.; Myatt, G.; Myklebust, T.; Naraghi, F.; Nassiakou, M.; Navarria, F.L.; Navas, Sergio; Nawrocki, K.; Negri, P.; Nemecek, S.; Neufeld, N.; Nicolaidou, R.; Nielsen, B.S.; Niezurawski, P.; Nikolenko, M.; Nomokonov, V.; Normand, A.; Nygren, A.; Olshevsky, A.G.; Onofre, A.; Orava, R.; Orazi, G.; Osterberg, K.; Ouraou, A.; Paganoni, M.; Paiano, S.; Pain, R.; Paiva, R.; Palacios, J.; Palka, H.; Papadopoulou, T.D.; Papageorgiou, K.; Pape, L.; Parkes, C.; Parodi, F.; Parzefall, U.; Passeri, A.; Passon, O.; Pegoraro, M.; Peralta, L.; Pernicka, M.; Perrotta, A.; Petridou, C.; Petrolini, A.; Phillips, H.T.; Pierre, F.; Pimenta, M.; Piotto, E.; Podobnik, T.; Pol, M.E.; Polok, G.; Poropat, P.; Pozdnyakov, V.; Privitera, P.; Pukhaeva, N.; Pullia, A.; Radojicic, D.; Ragazzi, S.; Rahmani, H.; Ratoff, P.N.; Read, Alexander L.; Rebecchi, P.; Redaelli, Nicola Giuseppe; Regler, M.; Reid, D.; Reinhardt, R.; Renton, P.B.; Resvanis, L.K.; Richard, F.; Ridky, J.; Rinaudo, G.; Rodrigo, German; Rohne, O.; Romero, A.; Ronchese, P.; Rosenberg, E.I.; Rosinsky, P.; Roudeau, P.; Rovelli, T.; Royon, C.; Ruhlmann-Kleider, V.; Ruiz, A.; Saarikko, H.; Sacquin, Y.; Sadovsky, A.; Sajot, G.; Salt, J.; Sampsonidis, D.; Sannino, M.; Schneider, H.; Schwemling, P.; Schwering, B.; Schwickerath, U.; Schyns, M.A.E.; Scuri, Fabrizio; Seager, P.; Sedykh, Yu.; Segar, A.M.; Sekulin, R.; Shellard, R.C.; Sheridan, A.; Siebel, M.; Simard, L.; Simonetto, F.; Sisakian, A.N.; Smadja, G.; Smirnova, O.; Smith, G.R.; Sopczak, A.; Sosnowski, R.; Spassoff, T.; Spiriti, E.; Sponholz, P.; Squarcia, S.; Stanescu, C.; Stanic, S.; Stevenson, K.; Stocchi, A.; Strauss, J.; Strub, R.; Stugu, B.; Szczekowski, M.; Szeptycka, M.; Tabarelli, T.; Tegenfeldt, F.; Terranova, F.; Thomas, J.; Timmermans, Jan; Tinti, N.; Tkachev, L.G.; Todorova, S.; Tomaradze, A.; Tome, B.; Tonazzo, A.; Tortora, L.; Transtromer, G.; Treille, D.; Tristram, G.; Trochimczuk, M.; Troncon, C.; Tsirou, A.; Turluer, M.L.; Tyapkin, I.A.; Tzamarias, S.; Ullaland, O.; Valenti, G.; Vallazza, E.; Vander Velde, C.; Van Apeldoorn, G.W.; Van Dam, Piet; Van Doninck, Walter; Van Eldik, J.; Van Lysebetten, A.; Van Remortel, N.; Van Vulpen, I.; Vassilopoulos, N.; Vegni, G.; Ventura, L.; Venus, W.; Verbeure, F.; Verlato, M.; Vertogradov, L.S.; Verzi, V.; Vilanova, D.; Vitale, L.; Vodopianov, A.S.; Vollmer, C.; Voulgaris, G.; Vrba, V.; Wahlen, H.; Walck, C.; Weiser, C.; Wicke, D.; Wickens, J.H.; Wilkinson, G.R.; Winter, M.; Witek, M.; Wolf, G.; Yi, J.; Zalewska, A.; Zalewski, P.; Zavrtanik, D.; Zevgolatakos, E.; Zimine, N.I.; Zucchelli, G.C.; Zumerle, G.

    2000-01-01

    An updated analysis using about 1.5 million events recorded at $\\sqrt{s} =M_Z$ with the DELPHI detector in 1994 is presented. Eighteen infrared and collinear safe event shape observables are measured as a function of the polar angle of the thrust axis. The data are compared to theoretical calculations in${\\cal O} (\\alpha_s^2)$ including the event orientation. A combined fit of $\\alpha_s$ and of the renormalization scale $x_{\\mu}$ in $\\cal O(\\alpha_s^2$)yields an excellent description of the high statistics data. The weighted average from 18 observables including quark mass effects and correlations is $\\alpha_s(M_Z^2) = 0.1174 \\pm 0.0026$. The final result, derived from the jet cone energy fraction, the observable with the smallest theoretical and experimental uncertainty, is $\\alpha_s(M_Z^2) = =0:1180 0:0006(exp:) 0:0013(hadr:) 0:0008(scale) 0:0007(mass). Further studies include an s determination using theoretical predictions in the next-to-leading log approximation (NLLA), matched NLLA and O(\\alpha^{2}_{s})...

  17. On the Diffuse Lyman-alpha Halo Around Lyman-alpha Emitting Galaxies

    CERN Document Server

    Lake, Ethan; Cen, Renyue; Sadoun, Raphael; Momose, Rieko; Ouchi, Masami

    2015-01-01

    Ly$\\alpha$ photons scattered by neutral hydrogen atoms in the circumgalactic media or produced in the halos of star-forming galaxies are expected to lead to extended Ly$\\alpha$ emission around galaxies. Such low surface brightness Ly$\\alpha$ halos (LAHs) have been detected by stacking Ly$\\alpha$ images of high-redshift star-forming galaxies. We study the origin of LAHs by performing radiative transfer modeling of nine $z=3.1$ Lyman-Alpha Emitters (LAEs) in a high resolution hydrodynamic galaxy formation simulation. We develop a method of computing the mean Ly$\\alpha$ surface brightness profile of each LAE by effectively integrating over many different observing directions. Without adjusting any parameters, our model yields an average Ly$\\alpha$ surface brightness profile in remarkable agreement with observations. We find that observed LAHs can not be accounted for solely by photons originating from the central LAE and scattered to large radii by hydrogen atoms in the circumgalactic gas. Instead, Ly$\\alpha$ em...

  18. ALPHA spokesperson Jeffrey Hangst gives a tour of the new ALPHA-2

    CERN Multimedia

    CERN Video Productions

    2012-01-01

    While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.

  19. Changes in vascular alpha 1- and alpha 2-adrenoceptor responsiveness by selegiline treatment.

    Science.gov (United States)

    Pelat, M; Verwaerde, P; Tran, M A; Berlan, M; Senard, J M; Montastruc, J L

    2001-08-01

    Pharmacoepidemiological studies have reported an excess of mortality with selegiline, a MAO B inhibitor used in the treatment of Parkinson's disease. The mechanism of this putative adverse effect remains unknown but an interaction with the sympathetic nervous system was suggested. The aim of the present study was to investigate the influence of selegiline (10 mg/daily, orally during one week) on vascular alpha1- and alpha2-adrenoceptor responsiveness in conscious unrestrained dogs. Selegiline significantly increased resting values of both systolic and diastolic blood pressures and noradrenaline plasma levels (HPLC) without changing heart rate. Moreover, spectral analysis of systolic blood pressure (Fast Fourier Transformation) showed that selegiline increased the relative energy of a low frequency band without modifying the total spectrum. ED 50 calculated from dose-pressor response curves with phenylephrine (after beta-blockade by propranolol), an index of alpha1-adrenoceptor response or with noradrenaline (after alpha1- and beta blockade by prazosin plus propranolol), an index of alpha2-adrenoceptor response, were significantly higher after selegiline. Selegiline failed to modify the number of platelet alpha2-adrenoceptors measured by [(3)H] RX 821002 binding. Yohimbine-induced increase in noradrenaline release was significantly more marked after selegiline. These results support the evidence that selegiline induces a vascular alpha1- and alpha2-adrenoceptor-hyposensitivity that can be explained by the increase in noradrenaline release elicited by the drug.

  20. Radiative-nonrecoil corrections of order alpha^2 (Z alpha)^5 to the Lamb shift

    CERN Document Server

    Dowling, Matthew; Piclum, Jan H; Czarnecki, Andrzej

    2009-01-01

    We present results for the corrections of order alpha^2 (Z alpha)^5 to the Lamb shift. We compute all the contributing Feynman diagrams in dimensional regularization and a general covariant gauge using a mixture of analytical and numerical methods. We confirm results obtained by other groups and improve their precision. Values of the 32 master integrals for this and similar problems are provided.

  1. Cortical Alpha Oscillations Predict Speech Intelligibility

    Science.gov (United States)

    Dimitrijevic, Andrew; Smith, Michael L.; Kadis, Darren S.; Moore, David R.

    2017-01-01

    Understanding speech in noise (SiN) is a complex task involving sensory encoding and cognitive resources including working memory and attention. Previous work has shown that brain oscillations, particularly alpha rhythms (8–12 Hz) play important roles in sensory processes involving working memory and attention. However, no previous study has examined brain oscillations during performance of a continuous speech perception test. The aim of this study was to measure cortical alpha during attentive listening in a commonly used SiN task (digits-in-noise, DiN) to better understand the neural processes associated with “top-down” cognitive processing in adverse listening environments. We recruited 14 normal hearing (NH) young adults. DiN speech reception threshold (SRT) was measured in an initial behavioral experiment. EEG activity was then collected: (i) while performing the DiN near SRT; and (ii) while attending to a silent, close-caption video during presentation of identical digit stimuli that the participant was instructed to ignore. Three main results were obtained: (1) during attentive (“active”) listening to the DiN, a number of distinct neural oscillations were observed (mainly alpha with some beta; 15–30 Hz). No oscillations were observed during attention to the video (“passive” listening); (2) overall, alpha event-related synchronization (ERS) of central/parietal sources were observed during active listening when data were grand averaged across all participants. In some participants, a smaller magnitude alpha event-related desynchronization (ERD), originating in temporal regions, was observed; and (3) when individual EEG trials were sorted according to correct and incorrect digit identification, the temporal alpha ERD was consistently greater on correctly identified trials. No such consistency was observed with the central/parietal alpha ERS. These data demonstrate that changes in alpha activity are specific to listening conditions. To our

  2. Role of Frontal Alpha Oscillations in Creativity

    Science.gov (United States)

    Lustenberger, Caroline; Boyle, Michael R.; Foulser, A. Alban; Mellin, Juliann M.; Fröhlich, Flavio

    2015-01-01

    Creativity, the ability to produce innovative ideas, is a key higher-order cognitive function that is poorly understood. At the level of macroscopic cortical network dynamics, recent EEG data suggests that cortical oscillations in the alpha frequency band (8 – 12 Hz) are correlated with creative thinking. However, whether alpha oscillations play a fundamental role in creativity has remained unknown. Here we show that creativity is increased by enhancing alpha power using 10 Hz transcranial alternating current stimulation (10Hz-tACS) of the frontal cortex. In a study of 20 healthy participants with a randomized, balanced cross-over design, we found a significant improvement of 7.4% in the Creativity Index measured by the Torrance Test of Creative Thinking, a comprehensive and most frequently used assay of creative potential and strengths. In a second similar study with 20 subjects, 40Hz-tACS was used in instead of 10Hz-tACS to rule out a general “electrical stimulation” effect. No significant change in the Creativity Index was found for such frontal gamma stimulation. Our results suggest that alpha activity in frontal brain areas is selectively involved in creativity; this enhancement represents the first demonstration of specific neuronal dynamics that drive creativity and can be modulated by non-invasive brain stimulation. Our findings agree with the model that alpha recruitment increases with internal processing demands and is involved in inhibitory top-down control, which is an important requirement for creative ideation. PMID:25913062

  3. H-alpha Photometry of Abell 2390

    CERN Document Server

    Balogh, M L; Balogh, Michael L.; Morris, Simon L.

    2000-01-01

    We present the results of a search for strong H-alpha emission line galaxies (rest frame equivalent widths greater than 50 A) in the z=0.23 cluster Abell 2390. The survey contains 1189 galaxies over 270 square arcminutes, and is 50% complete at M_r=-17.5+5 log h. The fraction of galaxies in which H-alpha is detected at the 2sigma level rises from 0.0 in the central regions (excluding the cD galaxy) to 12.5+/-8% at R200. For 165 of the galaxies in our catalogue, we compare the H-alpha equivalent widths with their [OII] equivalent widths, from the CNOC1 spectra. The fraction of strong H-alpha emission line galaxies is consistent with the fraction of strong [OII] emission galaxies in the CNOC1 sample: only 2+/-1% have no detectable [OII] emission and yet significant (>2sigma) H-alpha equivalent widths. Dust obscuration, non-thermal ionization, and aperture effects are all likely to contribute to this non-correspondence of emission lines. We identify six spectroscopically 'secure' k+a galaxies (W(OII)5 A); at lea...

  4. Alpha methyldopa induced hepatotoxicity in pregnancy

    Directory of Open Access Journals (Sweden)

    Padmasri Ramalingappa

    2014-06-01

    Full Text Available We report a case of gestational hepatitis due to alpha-methyldopa and briefly review the literature on alpha-methyldopa-induced hepatotoxicity in pregnancy. A 32 year old woman, primigravida with 34 weeks of gestation with pre eclampsia, presented with symptoms of nausea, dark coloured urine and jaundice. She was on alpha methyldopa (Aldomet 250 mg thrice a day since the last five weeks. Laboratory investigations revealed raised bilirubin, serum aspartate transaminases and serum alanine transaminases. Platelets were normal. Peripheral smear did not show haemolysis. With the exclusion of viral, haemolytic and obstructive causes, drug induced jaundice was considered as a differential diagnosis. Alpha methyldopa was withdrawn and replaced with nifedipine for her pre eclampsia treatment. Her repeat bilirubin level done two weeks later showed a drop. She went into labour at 38 weeks and delivered vaginally. In postpartum follow up her liver tests returned to normal in two weeks, about six weeks after stopping methyldopa. Hepatotoxicity should be considered as one of the adverse drug reaction of alpha methyldopa. It is not possible at present to predict which patients will develop liver disease following the administration of this drug. An awareness of the possibility of methyldopa induced hepatotoxicity should be present in the clinician's mind and liver function tests should be done at regular intervals. The occasional occurrence of this harmful side effect is not a contraindication to the use of this antihypertensive agent. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 805-807

  5. H-alpha Observations of MKW10

    Science.gov (United States)

    Johnson, Harold; Coble, Kimberly A.; Koopmann, Rebecca A.; Durbala, Adriana; Undergraduate ALFALFA Team

    2016-01-01

    As part of the Undergraduate ALFALFA Team project looking at clusters and groups of galaxies to investigate the effects of environment on star formation, we analyzed H-alpha and R-band observations of the group MKW10 from the WIYN 0.9-m telescope with MOSAIC camera at Kitt Peak. We continuum-subtract the H-alpha images by scaling and subtracting the broadband R images. This process includes: determining the seeing of each image by calculating the FWHM values of several stars in the image; convolving all images to the worst seeing; stacking images for each filter; subtracting sky background; scaling the R image to H-alpha; and subtracting the scaled R from H-alpha. We then use the H-alpha-continuum-subtracted image to perform surface photometry of individual galaxies in MKW10. The data will be used to determine star formation rates and distributions of galaxies in this group environment and will be compared to results for galaxies in other UAT group and cluster environments. Analysis is ongoing.This work has been supported by NSF grant AST-1211005 and the Illinois Space Grant Consortium.

  6. Measurements of $\\alpha_{s}$ with the DELPHI detector at LEP

    CERN Document Server

    Flagmeyer, U

    2000-01-01

    The data collected with DELPHI during the LEP1 period is used to perform a simultaneous fit to the strong coupling constant alpha /sub s/ in 2/sup nd/ order perturbation theory and to the renormalisation scale x/sub mu /. The results are compared to alpha /sub s/ fits in 2 /sup nd/ order perturbation theory with fixed scale x/sub mu / and to other theoretically motivated scale setting methods. To determine the energy dependence of alpha /sub s/, event shape distributions and their mean values are measured for square root (s)=48 GeV to 189 GeV. The strong coupling alpha /sub s/ is extracted in O( alpha /sub s //sup 2/). Next to leading log approximation (NLLA) and in a combined scheme using - evaluated with fragmentation model generators, and an analytical power ansatz. (16 refs).

  7. Benchmarking the External Surrogate Ratio Method using the (alpha,alpha' f) reaction at STARS

    Energy Technology Data Exchange (ETDEWEB)

    Lesher, S R; Bernstein, L A; Ai, H; Beausang, C W; Bleuel, D; Burke, J T; Clark, R M; Fallon, P; Gibelin, J; Lee, I Y; Lyles, B F; Macchiavelli, A O; McMahan, M A; Moody, K J; Norman, E B; Phair, L; Rodriguez-Vieitez, E; Wiedeking, M

    2008-01-09

    We measured the ratio of the fission probabilities of {sup 234}U* relative to {sup 236}U* formed via an ({alpha},{alpha}{prime}) direct reactions using the STARS array at the 88-inch cyclotron at the Lawrence Berkeley National Laboratory. This ratio has a shape similar to the ratio of neutron capture probabilities from {sup 233}U(n; f) and {sup 235}U(n; f), indicating the alpha reactions likely formed a compound nucleus. This result indicates that the ratios of fission exit channel probabilities for two actinide nuclei populated via ({alpha}, {alpha}{prime}) can be used to determine an unknown fission cross section relative to a known one. The validity of the External Surrogate Ratio Method (ESRM) is tested and the results support the conclusions of Burke et al. [1].

  8. Efficient synthesis of 1-azadienes derived from alpha-aminoesters. Regioselective preparation of alpha-dehydroamino acids, vinylglycines, and alpha-amino acids.

    Science.gov (United States)

    Palacios, Francisco; Vicario, Javier; Aparicio, Domitila

    2006-09-29

    An efficient synthesis of 1-azadienes derived from alpha-aminoesters is achieved through an aza-Wittig reaction of phosphazenes with beta,gamma-unsaturated alpha-ketoesters. Regioselective 1,2-reduction of these functionalized 1-azadienes affords vinylglycine derivatives, while conjugative 1,4-reduction gives alpha-dehydroamino acid compounds. Reduction of both the carbon-carbon and the imine-carbon-nitrogen double bonds leads to the formation of alpha-amino acid derivatives.

  9. Review on alpha sub s at LEP

    CERN Document Server

    Wicke, D

    2000-01-01

    To measure the strong coupling alpha sub s from event shape observables two ingredients are necessary: a perturbative prediction containing the dependence of observables on alpha sub s and a description of the hadronisation process to match the perturbative prediction with the hadronic data. As perturbative prediction O(alpha sup 2 sub s), NLLA and combined calculations are available. Beside the well known Monte-Carlo based models also analytical predictions, so called power corrections, exist to describe the hadronisation. Advantages and disadvantages of the different resulting methods for determining the strong coupling and its energy dependence will be discussed, the newest DELPHI results will be presented, and an overview of the LEP results will be included.

  10. ALPHA MIS: Reference manual. Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    Lovin, J.K.; Haese, R.L.; Heatherly, R.D.; Hughes, S.E.; Ishee, J.S.; Pratt, S.M.; Smith, D.W.

    1992-02-01

    ALPHA is a powerful and versatile management information system (MIS) initiated and sponsored and by the Finance and Business Management Division of Oak Ridge National Laboratory, who maintain and develop it in concert with the Business Systems Division for its Information Center. A general-purpose MIS, ALPHA allows users to access System 1022 and System 1032 databases to obtain and manage information. From a personal computer or a data terminal, Energy Systems employees can use ALPHA to control their own report reprocessing. Using four general commands (Database, Select, Sort, and Report) they can (1) choose a mainframe database, (2) define subsets within it, (3) sequentially order a subset by one or more variables, and (4) generate a report with their own or a canned format.

  11. Iron modulates the alpha chain of fibrinogen.

    Science.gov (United States)

    Nielsen, Vance G; Jacobsen, Wayne K

    2016-04-01

    Iron-bound fibrinogen has been noted to accelerate plasmatic coagulation in patients with divergent conditions involving upregulation of heme oxygenase activity, including hemodialysis, Alzheimer's disease, sickle cell anemia, and chronic migraine. Our goal was to determine if a site of iron-fibrinogen interaction was on the alpha chain. Using thrombelastography, we compared the coagulation kinetic profiles of plasma exposed to 0-10 µM ferric chloride after activation of coagulation with thrombin generated by contact activation of plasma with the plastic sample cup or by exposure to 1 µg/ml of Calloselasma rhodostoma venom (rich in ancrod activity), which causes coagulation via polymerization of alpha chain monomers. Venom mediated coagulation always occurred before thrombin activated thrombus formation, and ferric chloride always diminished the time of onset of coagulation and increased the velocity of clot growth. Iron enhances plasmatic coagulation kinetics by modulating the alpha chain of fibrinogen.

  12. Lyman-alpha Absorption from Heliosheath Neutrals

    CERN Document Server

    Wood, B E; Linsky, J L; Malama, Y G; Wood, Brian E.; Izmodenov, Vladislav V.; Linsky, Jeffrey L.; Malama, Yury G.

    2006-01-01

    We assess what information HST observations of stellar Ly-alpha lines can provide on the heliosheath, the region of the heliosphere between the termination shock and heliopause. To search for evidence of heliosheath absorption, we conduct a systematic inspection of stellar Ly-alpha lines reconstructed after correcting for ISM absorption (and heliospheric/astrospheric absorption, if present). Most of the stellar lines are well centered on the stellar radial velocity, as expected, but the three lines of sight with the most downwind orientations relative to the ISM flow (Chi1 Ori, HD 28205, and HD 28568) have significantly blueshifted Ly-alpha lines. Since it is in downwind directions where heliosheath absorption should be strongest, the blueshifts are almost certainly caused by previously undetected heliosheath absorption. We make an initial comparison between the heliosheath absorption and the predictions of a pair of heliospheric models. A model with a complex multi-component treatment of plasma within the he...

  13. Synthesis of peptide .alpha.-thioesters

    Science.gov (United States)

    Camarero, Julio A.; Mitchell, Alexander R.; De Yoreo, James J.

    2008-08-19

    Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.

  14. Alpha indirect conversion radioisotope power source

    Energy Technology Data Exchange (ETDEWEB)

    Sychov, Maxim [TRACE Photonics Inc., 1680 West Polk, Charleston, IL 61920 (United States)], E-mail: msychov@yahoo.com; Kavetsky, Alexandr; Yakubova, Galina; Walter, Gabriel; Yousaf, Shahid; Lin, Qian; Chan, Doris; Socarras, Heather; Bower, Kenneth [TRACE Photonics Inc., 1680 West Polk, Charleston, IL 61920 (United States)

    2008-02-15

    Advantages of radioisotope-powered electric generators include long service life, wide temperature range operation and high-energy density. We report development of a long-life generator based on indirect conversion of alpha decay energy. Prototyping used 300 mCi Pu-238 alpha emitter and AlGaAs photovoltaic cells designed for low light intensity conditions. The alpha emitter, phosphor screens, and voltaic arrays were assembled into a power source with the following characteristics: I{sub sc}=14 {mu}A; U{sub oc}=2.3 V; power output -21 {mu}W. Using this prototype we have powered an eight-digit electronic calculator and wrist watch.

  15. Existence of six-$\\alpha$ linear structure

    CERN Document Server

    Iwata, Yoritaka; Itagaki, Naoyuki; Maruhn, Joachim A; Otsuka, Takaharu

    2014-01-01

    The stable existence of a six-$\\alpha$ linear structure in highly excited states of $^{24}$Mg is studied based on a systematic Cranked Hartree-Fock calculation with various Skyrme-type interactions. Its stability is examined by allowing the transition of the cluster structure to the shell-model like structure. Especially, the six-$\\alpha$ linear state is exposed to two major instabilities: the bending motion, which is the main path for the transition to low-lying states, and the spin-orbit interaction, which is the driving force to break the $\\alpha$ clusters and enhance the independent motion of the nucleons. The linear structure with large angular momentum is obtained as a meta-stable stationary state.

  16. Relativistic effects in Lyman-alpha forest

    CERN Document Server

    Iršič, Vid; Viel, Matteo

    2015-01-01

    We present the calculation of the Lyman-alpha (Lyman-$\\alpha$) transmitted flux fluctuations with full relativistic corrections to the first order. Even though several studies exist on relativistic effects in galaxy clustering, this is the first study to extend the formalism to a different tracer of underlying matter at unique redshift range ($z = 2 - 5$). Furthermore, we show a comprehensive application of our calculations to the Quasar- Lyman-$\\alpha$ cross-correlation function. Our results indicate that the signal of relativistic effects can be as large as 30% at Baryonic Acoustic Oscillation (BAO) scale, which is much larger than anticipated and mainly due to the large differences in density bias factors of our tracers. We construct an observable, the anti-symmetric part of the cross- correlation function, that is dominated by the relativistic signal and offers a new way to measure the relativistic terms at relatively small scales. The analysis shows that relativistic effects are important when considerin...

  17. Varying Alpha and the Electroweak Model

    CERN Document Server

    Kimberly, D; Kimberly, Dagny; Magueijo, Joao

    2003-01-01

    Inspired by recent claims for a varying fine structure constant, alpha, we investigate the effect of ``promoting coupling constants to variables'' upon various parameters of the standard model. We first consider a toy model: Proca's theory of the massive photon. We then explore the electroweak theory with one and two dilaton fields. We find that a varying alpha unavoidably implies varying W and Z masses. This follows from gauge invariance, and is to be contrasted with Proca' theory. For the two dilaton theory the Weinberg angle is also variable, but Fermi's constant and the tree level fermion masses remain constant unless the Higgs' potential becomes dynamical. We outline some cosmological implications.

  18. X-rays from Alpha Centauri

    Science.gov (United States)

    Nugent, J.; Garmire, G.

    1978-01-01

    HEAO 1 observations of soft X-ray emission from a point source in the vicinity of Alpha Cen are reported. The source, designated H1437-61, is tentatively identified with Alpha Cen, and an X-ray luminosity comparable to that of the sun in an active state is estimated. A temperature of about 500,000 K and an emission integral of 5 x 10 to the 50th per cu cm are obtained. Coronal emission is suggested as the X-ray-producing mechanism.

  19. Parallel Genetic Algorithm for Alpha Spectra Fitting

    Science.gov (United States)

    García-Orellana, Carlos J.; Rubio-Montero, Pilar; González-Velasco, Horacio

    2005-01-01

    We present a performance study of alpha-particle spectra fitting using parallel Genetic Algorithm (GA). The method uses a two-step approach. In the first step we run parallel GA to find an initial solution for the second step, in which we use Levenberg-Marquardt (LM) method for a precise final fit. GA is a high resources-demanding method, so we use a Beowulf cluster for parallel simulation. The relationship between simulation time (and parallel efficiency) and processors number is studied using several alpha spectra, with the aim of obtaining a method to estimate the optimal processors number that must be used in a simulation.

  20. Enteric alpha defensins in norm and pathology

    Directory of Open Access Journals (Sweden)

    Lisitsyn Nikolai A

    2012-01-01

    Full Text Available Abstract Microbes living in the mammalian gut exist in constant contact with immunity system that prevents infection and maintains homeostasis. Enteric alpha defensins play an important role in regulation of bacterial colonization of the gut, as well as in activation of pro- and anti-inflammatory responses of the adaptive immune system cells in lamina propria. This review summarizes currently available data on functions of mammalian enteric alpha defensins in the immune defense and changes in their secretion in intestinal inflammatory diseases and cancer.

  1. Interferon-alpha caused reversible parkinsonism.

    Science.gov (United States)

    Lu, Chieh-Sheng; Kao, Wei-Yau; Lin, Jiann-Chyun; Chang, Ping-Ying

    2015-01-01

    Interferon has been used to treat chronic viral hepatitis and several malignancies. However, it may cause various neuropsychiatric adverse effects including parkinsonism. We report a rare case of interferon alpha-2a therapy-related parkinsonism in a 67-year-old man with metastatic papillary renal cell carcinoma and our experience of using Tc-99m-TRODAT-1 single photon emission computed tomography (SPECT) as a tool for evaluation of parkinsonism. Physicians should be alert to the possibility of interferon alpha-2a-related parkinsonism.

  2. Workshop on Precision Measurements of alphas

    CERN Document Server

    Bethke, S; Kluth, S; Schieck, J; Stewart, I W; Aoki, S; Beneke, M; Blumlein, J; Brambilla, N; Brodsky, S; Descotes-Genon, S; Erler, J; Forte, S; Gehrmann, T; Golterman, M; Hashimoto, S; Kronfeld, A; Kuhn, J; Lepage, P; Martin, A; Mateu, V; Menke, S; Nomura, Y; Pahl, C; Petriello, F; Pich, A; Rabbertz, K; Salam, G; Schulz, H; Sommer, R; Steinhauser, M; Webber, B; Yuan, CP; Zanderighi, G

    2011-01-01

    These are the proceedings of the "Workshop on Precision Measurements of alphas" held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of alphas(mZ) in the MS-bar scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, tau-decays, electroweak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

  3. Dipole oscillation modes in $\\alpha$-clustering light nuclei

    CERN Document Server

    He, W B; Cao, X G; Cai, X Z; Zhang, G Q

    2016-01-01

    The alpha cluster states are discussed in an extended quantum molecular dynamics (EQMD) model frame. Different alpha cluster structures are studied in details, such as $^8$Be two-alpha cluster structure, $^{12}$C triangle structure, $^{12}$C chain structure, $^{16}$O chain structure, $^{16}$O kite structure, and $^{16}$O square structure. The properties like width of wave packets for different alpha clusters, momentum distribution, and the binding energy among alpha clusters are studied. It is also discussed how the $\\alpha$ cluster degree of freedom affects nuclear collective vibrations. The different $\\alpha$ cluster configurations in $^{12}$C and $^{16}$O have corresponding characteristic spectra of GDR and the coherence of different alpha clusters's dipole oscillation are described in details. The number and centroid energies of peaks in the GDR spectra can be reasonably explained by the geometrical and dynamical symmetries of $\\alpha$-clustering configurations. The GDR can be regarded as a very effective...

  4. Green Pea Galaxies Reveal Secrets of Ly$\\alpha$ Escape

    CERN Document Server

    Yang, Huan; Gronke, Max; Rhoads, James E; Jaskot, Anne; Zheng, Zhenya; Dijkstra, Mark

    2015-01-01

    Star-formation in galaxies generates a lot of Ly$\\alpha$ photons. Understanding the escape of Ly$\\alpha$ photons from galaxies is a key issue in studying high redshift galaxies and probing cosmic reionization with Ly$\\alpha$. To understand Ly$\\alpha$ escape, it is valuable to study analogs of high redshift Ly$\\alpha$ emitters in nearby universe. However, most nearby analogs have too small a Ly$\\alpha$ equivalent width and escape fraction compared to high redshift Ly$\\alpha$ emitters. One different group of nearby analogs are "Green Pea" galaxies, selected by their high equivalent width optical emission lines. Here we show that Green Pea galaxies have strong Ly$\\alpha$ emission lines and high Ly$\\alpha$ escape fraction (see also Henry et al. 2015), providing an opportunity to solve Ly$\\alpha$ escape problem. Green Peas have a Ly$\\alpha$ equivalent width distribution similar to high redshift Ly$\\alpha$ emitters. The Ly$\\alpha$ escape fraction correlates with many quantities of Ly$\\alpha$ profile, especially the...

  5. The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha.

    Science.gov (United States)

    Yang, Qian; Nagano, Tomokazu; Shah, Yatrik; Cheung, Connie; Ito, Shinji; Gonzalez, Frank J

    2008-01-01

    To determine the impact of the species difference between rodents and humans in response to peroxisome proliferators (PPs) mediated by peroxisome proliferator-activated receptor (PPAR)alpha, PPAR alpha-humanized transgenic mice were generated using a P1 phage artificial chromosome (PAC) genomic clone bred onto a ppar alpha-null mouse background, designated hPPAR alpha PAC. In hPPAR alpha PAC mice, the human PPAR alpha gene is expressed in tissues with high fatty acid catabolism and induced upon fasting, similar to mouse PPAR alpha in wild-type (Wt) mice. Upon treatment with the PP fenofibrate, hPPAR alpha PAC mice exhibited responses similar to Wt mice, including peroxisome proliferation, lowering of serum triglycerides, and induction of PPAR alpha target genes encoding enzymes involved in fatty acid metabolism in liver, kidney, and heart, suggesting that human PPAR alpha (hPPAR alpha) functions in the same manner as mouse PPAR alpha in regulating fatty acid metabolism and lowering serum triglycerides. However, in contrast to Wt mice, treatment of hPPAR alpha PAC mice with fenofibrate did not cause significant hepatomegaly and hepatocyte proliferation, thus indicating that the mechanisms by which PPAR alpha affects lipid metabolism are distinct from the hepatocyte proliferation response, the latter of which is only induced by mouse PPAR alpha. In addition, a differential regulation of several genes, including the oncogenic let-7C miRNA by PPs, was observed between Wt and hPPAR alpha PAC mice that may contribute to the inherent difference between mouse and human PPAR alpha in activation of hepatocellular proliferation. The hPPAR alpha PAC mouse model provides an in vivo platform to investigate the species difference mediated by PPAR alpha and an ideal model for human risk assessment PPs exposure.

  6. Plant alpha-amylase inhibitors and their interaction with insect alpha-amylases.

    Science.gov (United States)

    Franco, Octávio L; Rigden, Daniel J; Melo, Francislete R; Grossi-De-Sá, Maria F

    2002-01-01

    Insect pests and pathogens (fungi, bacteria and viruses) are responsible for severe crop losses. Insects feed directly on the plant tissues, while the pathogens lead to damage or death of the plant. Plants have evolved a certain degree of resistance through the production of defence compounds, which may be aproteic, e.g. antibiotics, alkaloids, terpenes, cyanogenic glucosides or proteic, e.g. chitinases, beta-1,3-glucanases, lectins, arcelins, vicilins, systemins and enzyme inhibitors. The enzyme inhibitors impede digestion through their action on insect gut digestive alpha-amylases and proteinases, which play a key role in the digestion of plant starch and proteins. The natural defences of crop plants may be improved through the use of transgenic technology. Current research in the area focuses particularly on weevils as these are highly dependent on starch for their energy supply. Six different alpha-amylase inhibitor classes, lectin-like, knottin-like, cereal-type, Kunitz-like, gamma-purothionin-like and thaumatin-like could be used in pest control. These classes of inhibitors show remarkable structural variety leading to different modes of inhibition and different specificity profiles against diverse alpha-amylases. Specificity of inhibition is an important issue as the introduced inhibitor must not adversely affect the plant's own alpha-amylases, nor the nutritional value of the crop. Of particular interest are some bifunctional inhibitors with additional favourable properties, such as proteinase inhibitory activity or chitinase activity. The area has benefited from the recent determination of many structures of alpha-amylases, inhibitors and complexes. These structures highlight the remarkable variety in structural modes of alpha-amylase inhibition. The continuing discovery of new classes of alpha-amylase inhibitor ensures that exciting discoveries remain to be made. In this review, we summarize existing knowledge of insect alpha-amylases, plant alpha

  7. Functional contribution of alpha3L8' to the neuronal nicotinic alpha3 receptor.

    Science.gov (United States)

    Nieves-Cintrón, Madeline; Caballero-Rivera, Daniel; Silva, Walter I; Navedo, Manuel F; Lasalde-Dominicci, José A

    2008-10-01

    The role of position L8', located in transmembrane domain 1 of the neuronal nicotinic alpha3 subunit, was characterized by using two-electrode voltage clamp in Xenopus oocytes. Four amino acids (Ala, Ser, Phe, and Tyr) were inserted at this conserved position, and the mutant subunit was coexpressed with either wild-type beta2 or beta4 subunits. These substitutions led to significant alterations in the pharmacodynamic parameters of cholinergic agents, resulting in loss of function. Ala and Ser substitutions resulted in losses in agonist (ACh, nicotine, and DMPP) potency and intrinsic activity at both alpha3beta2 and alpha3beta4 receptors. Similarly, significant changes in antagonist potency were produced by the Ala and Ser substitutions. Phe and Tyr mutations did not alter the receptor's EC(50) for ACh or nicotine but reduced the EC(50) for DMPP at both receptors. The Phe mutation also reduced the intrinsic activity of all agonists tested at both receptors. The Tyr mutation, though, led to a decrease in intrinsic activity for all agonists at the alpha3beta2 receptor, yet resulted in no changes for DMPP, a decrease for nicotine, and an increase for ACh at the alpha3beta4 receptor. The most dramatic changes in the receptor's functional properties were produced by substitutions that introduced the largest changes in amino acid volume. Additional replacements (Gly, Thr, and Val) suggested an inverse correlation between amino acid volume at position alpha3L8' and EC(50) for alpha3beta4 nAChRs; however, alpha3beta2 nAChRs displayed a nonlinear correlation. These data demonstrate that structural alterations at position alpha3L8' could propagate to the agonist-binding site.

  8. \\alpha-Discounting Multi-Criteria Decision Making (\\alpha-D MCDM)

    CERN Document Server

    Smarandache, Florentin

    2010-01-01

    In this paper we introduce a new method called \\alpha-Discounting Multi-Criteria Decision Making (\\alpha-D MCDM), which is an aletrnative and extension of Saaty's Analytical Hierarchy Process (AHP). It works for any set of preferences that can be transformed into a system of homogeneous linear equations. A degree of consistency (and implicitly a degree of inconsistency) of a decision-making problem are defined. \\alpha-D MCDM is then generalized to a set of preferences that can be transformed into a system of linear and/or non-linear equations and/or inequalities. Many consistent, weak inconsistent, and strong inconsistent examples are given.

  9. Aspergillus nidulans alpha-galactosidase of glycoside hydrolase family 36 catalyses the formation of alpha-galacto-oligosaccharides by transglycosylation.

    Science.gov (United States)

    Nakai, Hiroyuki; Baumann, Martin J; Petersen, Bent O; Westphal, Yvonne; Hachem, Maher Abou; Dilokpimol, Adiphol; Duus, Jens Ø; Schols, Henk A; Svensson, Birte

    2010-09-01

    The alpha-galactosidase from Aspergillus nidulans (AglC) belongs to a phylogenetic cluster containing eukaryotic alpha-galactosidases and alpha-galacto-oligosaccharide synthases of glycoside hydrolase family 36 (GH36). The recombinant AglC, produced in high yield (0.65 g.L(-1) culture) as His-tag fusion in Escherichia coli, catalysed efficient transglycosylation with alpha-(1-->6) regioselectivity from 40 mm 4-nitrophenol alpha-d-galactopyranoside, melibiose or raffinose, resulting in a 37-74% yield of 4-nitrophenol alpha-D-Galp-(1-->6)-D-Galp, alpha-D-Galp-(1-->6)-alpha-D-Galp-(1-->6)-D-Glcp and alpha-D-Galp-(1-->6)-alpha-D-Galp-(1-->6)-D-Glcp-(alpha1-->beta2)-d-Fruf (stachyose), respectively. Furthermore, among 10 monosaccharide acceptor candidates (400 mm) and the donor 4-nitrophenol alpha-D-galactopyranoside (40 mm), alpha-(1-->6) linked galactodisaccharides were also obtained with galactose, glucose and mannose in high yields of 39-58%. AglC did not transglycosylate monosaccharides without the 6-hydroxymethyl group, i.e. xylose, L-arabinose, L-fucose and L-rhamnose, or with axial 3-OH, i.e. gulose, allose, altrose and L-rhamnose. Structural modelling using Thermotoga maritima GH36 alpha-galactosidase as the template and superimposition of melibiose from the complex with human GH27 alpha-galactosidase supported that recognition at subsite +1 in AglC presumably requires a hydrogen bond between 3-OH and Trp358 and a hydrophobic environment around the C-6 hydroxymethyl group. In addition, successful transglycosylation of eight of 10 disaccharides (400 mm), except xylobiose and arabinobiose, indicated broad specificity for interaction with the +2 subsite. AglC thus transferred alpha-galactosyl to 6-OH of the terminal residue in the alpha-linked melibiose, maltose, trehalose, sucrose and turanose in 6-46% yield and the beta-linked lactose, lactulose and cellobiose in 28-38% yield. The product structures were identified using NMR and ESI-MS and five of the 13

  10. Cosmological attractors from alpha-scale supergravity

    NARCIS (Netherlands)

    Roest, Diederik; Scalisi, Marco

    2015-01-01

    The Planck value of the spectral index can be interpreted as n(s) = 1 - 2/N in terms of the number of e-foldings N. An appealing explanation for this phenomenological observation is provided by alpha-attractors: the inflationary predictions of these supergravity models are fully determined by the cu

  11. Alpha-actinin structure and regulation.

    Science.gov (United States)

    Sjöblom, B; Salmazo, A; Djinović-Carugo, K

    2008-09-01

    Alpha-actinin is a cytoskeletal actin-binding protein and a member of the spectrin superfamily, which comprises spectrin, dystrophin and their homologues and isoforms. It forms an anti-parallel rod-shaped dimer with one actin-binding domain at each end of the rod and bundles actin filaments in multiple cell-type and cytoskeleton frameworks. In non-muscle cells, alpha-actinin is found along the actin filaments and in adhesion sites. In striated, cardiac and smooth muscle cells, it is localized at the Z-disk and analogous dense bodies, where it forms a lattice-like structure and stabilizes the muscle contractile apparatus. Besides binding to actin filaments alpha-actinin associates with a number of cytoskeletal and signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, rendering it important structural and regulatory roles in cytoskeleton organization and muscle contraction. This review reports on the current knowledge on structure and regulation of alpha-actinin.

  12. Alpha Background Rejection in Bolometer Detectors

    Science.gov (United States)

    Deporzio, Nicholas

    2016-03-01

    This study presents the modification of bolometer detectors used in particle searches to veto or otherwise reject alpha radiation background and the statistical advantages of doing so. Several techniques are presented in detail - plastic film scintillator vetoes, metallic film ionization vetoes, and scintillating bolometer vetoes. Plastic scintillator films are cooled to bolometer temperatures and bombarded with 1.4MeV to 6.0MeV alpha particles representative of documented detector background. Photomultipliers detect this scintillation light and produce a veto signal. Layered metallic films of a primary metal, dielectric, and secondary metal, such as gold-polyethylene-gold films, are cooled to milli-kelvin temperatures and biased to produce a current signal veto when incident 1.4MeV to 6.0MeV alpha particles ionize conduction paths through the film. Modified Zinc Molybdate Bolometers are used to produce scintillation light when stimulated by alpha background. Calibration of veto signal to background energy is presented. Results are used to quantify the statistical impact of such modifications on bolometer searches.

  13. Alpha particles diffusion due to charge changes

    Energy Technology Data Exchange (ETDEWEB)

    Clauser, C. F., E-mail: cesar.clauser@ib.edu.ar; Farengo, R. [Centro Atómico Bariloche and Instituto Balseiro, Comisión Nacional de Energía Atómica and Universidad Nacional de Cuyo, Av. Bustillo 9500, 8400 Bariloche (Argentina)

    2015-12-15

    Alpha particles diffusion due to charge changes in a magnetized plasma is studied. Analytical calculations and numerical simulations are employed to show that this process can be very important in the pedestal-edge-SOL regions. This is the first study that presents clear evidence of the importance of atomic processes on the diffusion of alpha particles. A simple 1D model that includes inelastic collisions with plasma species, “cold” neutrals, and partially ionized species was employed. The code, which follows the exact particle orbits and includes the effect of inelastic collisions via a Monte Carlo type random process, runs on a graphic processor unit (GPU). The analytical and numerical results show excellent agreement when a uniform background (plasma and cold species) is assumed. The simulations also show that the gradients in the density of the plasma and cold species, which are large and opposite in the edge region, produce an inward flux of alpha particles. Calculations of the alpha particles flux reaching the walls or divertor plates should include these processes.

  14. Syndecan-4 associates with alpha-actinin

    DEFF Research Database (Denmark)

    Greene, Daniel K; Tumova, Sarka; Couchman, John R;

    2002-01-01

    during the formation of focal adhesions. To date, a direct link between syndecan-4 and the cytoskeleton has remained elusive. We now demonstrate by Triton X-100 extraction immunoprecipitation and in vitro binding assays that the focal adhesion component alpha-actinin interacts with syndecan-4 in a beta...

  15. Alpha particle radiography of small insects

    Energy Technology Data Exchange (ETDEWEB)

    Chingshen Su [National Tsing Hua Univ., Hsinchu (Taiwan) Inst. of Nuclear Science

    1993-12-31

    Radiographies of ants, mosquitoes, cockroaches and small bugs have been done with a radioisotope {sup 244}Cm alpha source. Energy of alpha particles was varied by attenuating the 5.81 MeV alpha particles with adjustable air spacings from the source to the sample. The LR-115 was used to register radiographs. The image of the insect registered on the LR-115 was etched out in a 2.5 N NaOH solution at 52{sup o}C for certain minutes, depending on various irradiation conditions for the insects. For larger insects, a scanning device for the alpha particle irradiation has been fabricated to take the radiograph of whole body of the insect, and the scanning period can be selected to give desired irradiation dosage. A CCDTV camera system connected to a microscope interfaced to an IBM/AT computer is used to register the microscopic image of the radiograph and to print it out with a video copy processor. (Author).

  16. Interferon alpha association with neuromyelitis optica

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Voss, Anne; Steenstrup, Troels;

    2013-01-01

    Interferon-alpha (IFN- α ) has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN- α in neuromyelitis optica (NMO) patients. Thirty-six NMO and 41 multiple sclerosis (MS) patients from a population...

  17. Synthesis of stabilized alpha-helical peptides.

    Science.gov (United States)

    Bernal, Federico; Katz, Samuel G

    2014-01-01

    Stabilized alpha-helical (SAH) peptides are valuable laboratory tools to explore important protein-protein interactions. Whereas most peptides lose their secondary structure when isolated from the host protein, stapled peptides incorporate an all-hydrocarbon "staple" that reinforces their natural alpha-helical structure. Thus, stapled peptides retain their functional ability to bind their native protein targets and serve multiple experimental uses. First, they are useful for structural studies such as NMR or crystal structures that map and better define binding sites. Second, they can be used to identify small molecules that specifically target that interaction site. Third, stapled peptides can be used to test the importance of specific amino acid residues or posttranslational modifications to the binding. Fourth, they can serve as structurally competent bait to identify novel binding partners to specific alpha-helical motifs. In addition to markedly improved alpha-helicity, stapled peptides also display resistance to protease cleavage and enhanced cell permeability. Most importantly, they are useful for intracellular experiments that explore the functional consequences of blocking particular protein interactions. Because of their remarkable stability, stapled peptides can be applied to whole-animal, in vivo studies. Here we describe a protocol for the synthesis of a peptide that incorporates an all-hydrocarbon "staple" employing a ring-closing olefin metathesis reaction. With proper optimization, stapled peptides can be a fundamental, accurate laboratory tool in the modern chemical biologist's armory.

  18. First stars in Damped Lyman Alpha systems

    NARCIS (Netherlands)

    Salvadori, Stefania; Ferrara, Andrea

    2011-01-01

    In order to characterize Damped Lyman Alpha systems (DLAs) potentially host- ing first stars, we present a novel approach to investigate DLAs in the context of Milky Way (MW) formation, along with their connection with the most metal-poor stars and local dwarf galaxies. The merger tree method previo

  19. Superparamagnetic relaxation in alpha-Fe particles

    DEFF Research Database (Denmark)

    Bødker, Franz; Mørup, Steen; Pedersen, Michael Stanley;

    1998-01-01

    The superparamagnetic relaxation time of carbon-supported alpha-Fe particles with an average size of 3.0 Mm has been studied over a large temperature range by the use of Mossbauer spectroscopy combined with AC and DC magnetization measurements. It is found that the relaxation time varies with tem...

  20. Understanding a Widely Misunderstood Statistic: Cronbach's "Alpha"

    Science.gov (United States)

    Ritter, Nicola L.

    2010-01-01

    It is important to explore score reliability in virtually all studies, because tests are not reliable. The present paper explains the most frequently used reliability estimate, coefficient alpha, so that the coefficient's conceptual underpinnings will be understood. Researchers need to understand score reliability because of the possible impact…

  1. A method for extracting $cos\\alpha$

    CERN Document Server

    Grinstein, B; Rothstein, I Z; Grinstein, Benjamin; Nolte, Detlef R.; Rothstein, Ira Z.

    2000-01-01

    We show that it is possible to extract the weak mixing angle alpha via a measurement of the rate for B^+(-) -> \\pi^+(-) e^+e^-. The sensitivity to cos(alpha) results from the interference between the long and short distance contributions. The short distance contribution can be computed, using heavy quark symmetry, in terms of semi-leptonic form factors. More importantly, we show that, using Ward identities and a short distance operator product expansion, the long distance contribution can be calculated without recourse to light cone wave functions when the invariant mass of the lepton pair, q^2, is much larger than LQCDs. We find that for q^2 > 2 GeV^2 the branching fraction is approximately 1 * 10^{-8}|V_{td}/0.008|^2. The shape of the differential rate is very sensitive to the value of cos(alpha) at small values of q^2 with dGamma /dq^2 varying up to 50% in the interval -1< cos(alpha)< 1 at q^2= 2 GeV^2. The size of the variation depends upon the ratio V_{ub}/V_{td}.

  2. EEG alpha power and creative ideation☆

    Science.gov (United States)

    Fink, Andreas; Benedek, Mathias

    2014-01-01

    Neuroscientific studies revealed first insights into neural mechanisms underlying creativity, but existing findings are highly variegated and often inconsistent. Despite the disappointing picture on the neuroscience of creativity drawn in recent reviews, there appears to be robust evidence that EEG alpha power is particularly sensitive to various creativity-related demands involved in creative ideation. Alpha power varies as a function of creativity-related task demands and the originality of ideas, is positively related to an individuals’ creativity level, and has been observed to increase as a result of creativity interventions. Alpha increases during creative ideation could reflect more internally oriented attention that is characterized by the absence of external bottom-up stimulation and, thus, a form of top-down activity. Moreover, they could indicate the involvement of specific memory processes such as the efficient (re-)combination of unrelated semantic information. We conclude that increased alpha power during creative ideation is among the most consistent findings in neuroscientific research on creativity and discuss possible future directions to better understand the manifold brain mechanisms involved in creativity. PMID:23246442

  3. Alpha and Beta at the B Factories

    Energy Technology Data Exchange (ETDEWEB)

    Finocchiaro, Giuseppe; /Frascati

    2007-10-15

    We review recent experimental results on time-dependent CP asymmetries in the B system from the BABAR and Belle experiments. Measurements of the {alpha} and {beta} angles of the Unitarity Triangle of the CKM matrix are discussed. These measurements constitute stringent tests of the Standard Model, and are also used to search for new physics.

  4. EEG alpha power and creative ideation.

    Science.gov (United States)

    Fink, Andreas; Benedek, Mathias

    2014-07-01

    Neuroscientific studies revealed first insights into neural mechanisms underlying creativity, but existing findings are highly variegated and often inconsistent. Despite the disappointing picture on the neuroscience of creativity drawn in recent reviews, there appears to be robust evidence that EEG alpha power is particularly sensitive to various creativity-related demands involved in creative ideation. Alpha power varies as a function of creativity-related task demands and the originality of ideas, is positively related to an individuals' creativity level, and has been observed to increase as a result of creativity interventions. Alpha increases during creative ideation could reflect more internally oriented attention that is characterized by the absence of external bottom-up stimulation and, thus, a form of top-down activity. Moreover, they could indicate the involvement of specific memory processes such as the efficient (re-)combination of unrelated semantic information. We conclude that increased alpha power during creative ideation is among the most consistent findings in neuroscientific research on creativity and discuss possible future directions to better understand the manifold brain mechanisms involved in creativity.

  5. Alpha thalassaemia-mental retardation, X linked

    Directory of Open Access Journals (Sweden)

    Gibbons Richard

    2006-05-01

    Full Text Available Abstract X-linked alpha thalassaemia mental retardation (ATR-X syndrome in males is associated with profound developmental delay, facial dysmorphism, genital abnormalities and alpha thalassaemia. Female carriers are usually physically and intellectually normal. So far, 168 patients have been reported. Language is usually very limited. Seizures occur in about one third of the cases. While many patients are affectionate with their caregivers, some exhibit autistic-like behaviour. Patients present with facial hypotonia and a characteristic mouth. Genital abnormalities are observed in 80% of children and range from undescended testes to ambiguous genitalia. Alpha-thalassaemia is not always present. This syndrome is X-linked recessive and results from mutations in the ATRX gene. This gene encodes the widely expressed ATRX protein. ATRX mutations cause diverse changes in the pattern of DNA methylation at heterochromatic loci but it is not yet known whether this is responsible for the clinical phenotype. The diagnosis can be established by detection of alpha thalassaemia, identification of ATRX gene mutations, ATRX protein studies and X-inactivation studies. Genetic counselling can be offered to families. Management is multidisciplinary: young children must be carefully monitored for gastro-oesophageal reflux as it may cause death. A number of individuals with ATR-X are fit and well in their 30s and 40s.

  6. Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues.

    Science.gov (United States)

    Eason, M G; Liggett, S B

    1993-07-01

    At present, molecular cloning and pharmacological studies have delineated three human alpha 2-adrenergic receptor (alpha 2AR) subtypes, alpha 2C10, alpha 2C4, and alpha 2C2. Assignment of the alpha 2AR subtypes to specific functions has been limited by an unclear definition of tissue alpha 2AR expression outside of the central nervous system. It has been suggested that alpha 2C4 expression is confined to the brain, that alpha 2C2 expression is only in the liver and kidney, and that there is nearly ubiquitous expression of alpha 2C10. However, this is based on studies of a limited number of rat tissues or on studies using non-species-specific approaches. Therefore, to define alpha 2C10, alpha 2C4, and alpha 2C2 tissue expression, we used reverse transcription of total RNA isolated from 20 human tissues, followed by amplification of alpha 2AR cDNA using the polymerase chain reaction. This technique provided two advantages: high sensitivity and, with the use of subtype-specific oligonucleotide primers and probes, differentiation between the alpha 2AR subtypes. The tissues studied were aorta, vena cava, heart (epicardium and endocardium), lung, skeletal muscle, liver, pancreas (head and tail), fat (perinephric and subcutaneous), kidney (cortex and medulla), prostate, stomach, ileum, jejunum, colon, adrenal gland, and spleen. We found that the majority of these tissues expressed alpha 2C10, with the exceptions being the head of the pancreas, subcutaneous fat, colon, and spleen. In marked distinction to other studies, however, we found a prolific expression of the alpha 2C4 and alpha 2C2 subtypes. Expression of alpha 2C4 was found in all tissues with the exception of liver, fat, stomach, and colon, and a virtually ubiquitous expression of alpha 2C2 was found, with the exception of epicardium. Of all tissues studied, only colon and subcutaneous fat expressed a single alpha 2AR subtype, which was alpha 2C2. Thus, the alpha 2AR subtypes do not have a confined expression but

  7. Alpha decay of {sup 181}Pb

    Energy Technology Data Exchange (ETDEWEB)

    Davids, C.N.; Henderson, D.J.; Hermann, R. [and others

    1995-08-01

    The {alpha}-decay energy of {sup 181}Pb was measured as 7211(10) keV and 7044(15). In the first study the isotope was produced in {sup 90}Zr bombardments of {sup 94}Mo and, after traversing a velocity filter, implanted in a position-sensitive Si detector; no half life for {sup 181}Pb was reported. In the second study the isotope was produced in {sup 40}Ca bombardments of {sup 144}Sm and transported to a position in front of a Si(Au) surface barrier detector with a fast He-gas-jet capillary system; an estimate of 50 ms was determined for the {sup 181}Pb half life. Recently we investigated {sup 181}Pb {alpha} decay at ATLAS as part of a survey experiment in which a l-pnA beam of 400-MeV {sup 92}Mo was used to irradiate targets of {sup 89}Y, {sup 90,92,94}Zr, and {sup 92}Mo to examine yields for one- and two-nucleon evaporation products from symmetric cold-fusion reactions. Recoiling nuclei of interest were passed through the Fragment Mass Analyzer and implanted in a double-sided silicon strip detector for {alpha}-particle assay. With the {sup 90}Zr target we observed a group at 7065(20) keV which was correlated with A = 181 recoils and had a half life of 45(20) ms. Our new results for {sup 181}Pb therefore agreed with those of the second study. There was no indication in the {sup 90}Zr + {sup 92}Mo data of the 7211(10)-keV {alpha} particles seen by Keller et al. The interested reader is referred to the 1993 atomic mass evaluation wherein the input {alpha}-decay energies and resultant masses of the light Pb isotopes (including {sup 181}Pb) are discussed.

  8. The fibrinogen cleavage product Aα-Val360, a specific marker of neutrophil elastase activity in vivo

    DEFF Research Database (Denmark)

    Carter, Richard I; Mumford, Richard A; Treonze, Kelly M

    2011-01-01

    Alpha-1-antitrypsin (A1AT) deficiency is the only recognised genetic risk factor for chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. Since A1AT is the major inhibitor of neutrophil elastase (NE), this enzyme has become widely implicated in the p...

  9. INVITRO RELEASE OF NEUTROPHIL ELASTASE, MYELOPEROXIDASE AND BETA-GLUCURONIDASE IN PATIENTS WITH EMPHYSEMA AND HEALTHY-SUBJECTS

    NARCIS (Netherlands)

    RENKEMA, TEJ; POSTMA, DS; NOORDHOEK, JA; SLUITER, HJ; KAUFFMAN, HF

    1991-01-01

    Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha-1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin

  10. Feasibility of commercial space manufacturing, production of pharmaceuticals. Volume 3: Product data

    Science.gov (United States)

    1978-01-01

    The feasibility of commercial manufacturing of pharmaceuticals in space is analyzed and the study results are presented. The chronology of the study process is discussed. The separation of serum proteins by the continuous flow electrophoresis process is investigated. The production requirements of twelve candidate products including antihemophilic factor, beta cells, erythropoietin, epidermal growth factor, alpha-1-antitrypsin, and interferon are evaluated.

  11. Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies

    DEFF Research Database (Denmark)

    Castaldi, P J; Demeo, D L; Hersh, C P;

    2010-01-01

    with COPD. Using data from the Alpha-1 Antitrypsin Genetic Modifiers Study, the accuracy and power of two different approaches to model smoking were compared by performing a simulation study of a genetic variant with a range of gene-by-smoking interaction effects. Results Non-linear relationships between...

  12. A 17.6 kbp region located upstream of the rabbit WAP gene directs high level expression of a functional human protein variant in transgenic mouse milk

    NARCIS (Netherlands)

    Bischoff, Rainer; Degryse, E.; Perraud, F.; Dalemans, W.; Ali-Hadji, D.; Thepot, D.; Devinoy, E.; Houdebine, L.M.; Pavirani, A.

    1992-01-01

    We have investigated whether DNA regions present in the rabbit whey acidic protein (WAP) promoter/5' flanking sequence could potentially confer, in vivo, high level expression of reporter genes. Transgenic mice were generated expressing a variant of human alpha 1-antitrypsin, which has inhibitory ac

  13. Markers of early disease and prognosis in COPD

    DEFF Research Database (Denmark)

    Dahl, Morten; Nordestgaard, Børge G

    2009-01-01

    vary substantially over time. This review explores potential markers of early disease and prognosis in COPD by examining genetic markers in the alpha(1)-antitrypsin, cystic fibrosis transmembrane conductance regulator (CFTR), and MBL-2 genes, and by examining the biochemical markers fibrinogen and C...

  14. The measurement of $\\alpha_s$ from event shapes with the DELPHI detector at the highest LEP energies

    CERN Document Server

    Abdallah, J; Adam, W; Adzic, P; Albrecht, T; Alderweireld, T; Alemany-Fernandez, R; Allmendinger, T; Allport, P P; Amaldi, Ugo; Amapane, N; Amato, S; Anashkin, E; Andreazza, A; Andringa, S; Anjos, N; Antilogus, P; Apel, W D; Arnoud, Y; Ask, S; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Ballestrero, A; Bambade, P; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Ben-Haim, E; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Berntzon, L; Bertrand, D; Besançon, M; Besson, N; Bloch, D; Blom, M; Bluj, M; Bonesini, M; Boonekamp, M; Booth, P S L; Borisov, G; Botner, O; Bouquet, B; Bowcock, T J V; Boyko, I; Bracko, M; Brenner, R; Brodet, E; Brückman, P; Brunet, J M; Bugge, L; Buschmann, P; Calvi, M; Camporesi, T; Canale, V; Carena, F; Castro, N; Cavallo, F R; Chapkin, M M; Charpentier, P; Checchia, P; Chierici, R; Shlyapnikov, P; Chudoba, J; Chung, S U; Cieslik, K; Collins, P; Contri, R; Cosme, G; Cossutti, F; Costa, M J; Crennell, D J; Cuevas-Maestro, J; D'Hondt, J; Dalmau, J; Da Silva, T; Da Silva, W; Della Ricca, G; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Maria, N; De Min, A; De Paula, L S; Di Ciaccio, Lucia; Di Simone, A; Doroba, K; Drees, J; Dris, M; Eigen, G; Ekelöf, T J C; Ellert, M; Elsing, M; Espirito-Santo, M C; Fanourakis, G K; Fassouliotis, D; Feindt, M; Fernández, J; Ferrer, A; Ferro, F; Flagmeyer, U; Föth, H; Fokitis, E; Fulda-Quenzer, F; Fuster, J A; Gandelman, M; García, C; Gavillet, P; Gazis, E N; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; Graziani, E; Grosdidier, G; Grzelak, K; Guy, J; Haag, C; Hallgren, A; Hamacher, K; Hamilton, K; Haug, S; Hauler, F; Hedberg, V; Hennecke, M; Herr, H; Hoffman, J; Holmgren, S O; Holt, P J; Houlden, M A; Hultqvist, K; Jackson, J N; Jarlskog, G; Jarry, P; Jeans, D; Johansson, E K; Johansson, P D; Jonsson, P; Joram, C; Jungermann, L; Kapusta, F; Katsanevas, S; Katsoufis, E C; Kernel, G; Kersevan, Borut P; Kerzel, U; Kiiskinen, A P; King, B T; Kjaer, N J; Kluit, P; Kokkinias, P; Kourkoumelis, C; Kuznetsov, O; Krumshtein, Z; Kucharczyk, M; Lamsa, J; Leder, G; Ledroit, F; Leinonen, L; Leitner, R; Lemonne, J; Lepeltier, V; Lesiak, T; Liebig, W; Liko, D; Lipniacka, A; Lopes, J H; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J; Malek, A; Maltezos, S; Mandl, F; Marco, J; Marco, R; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Masik, J; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Mazzucato, F; Mazzucato, M; McNulty, R; Meroni, C; Migliore, E; Mitaroff, W A; Mjörnmark, U; Moa, T; Moch, M; Mönig, K; Monge, R; Montenegro, J; Moraes, D; Moreno, S; Morettini, P; Müller, U; Münich, K; Mulders, M; Mundim, L M; Murray, W; Muryn, B; Myatt, Gerald; Myklebust, T; Nassiakou, M; Navarria, Francesco Luigi; Nawrocki, K; Nicolaidou, R; Nikolenko, M; Oblakowska-Mucha, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Oyanguren, A; Paganoni, M; Paiano, S; Palacios, J P; Palka, H; Papadopoulou, T D; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Peralta, L; Perepelitsa, V F; Perrotta, A; Petrolini, A; Piedra, J; Pieri, L; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Poireau, V; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Pukhaeva, N; Pullia, Antonio; Rames, J; Ramler, L; Read, A; Rebecchi, P; Rehn, J; Reid, D; Reinhardt, R; Renton, P B; Richard, F; Rídky, J; Rivero, M; Rodríguez, D; Romero, A; Ronchese, P; Roudeau, Patrick; Rovelli, T; Ruhlmann-Kleider, V; Ryabtchikov, D; Sadovskii, A; Salmi, L; Salt, J; Savoy-Navarro, A; Schwickerath, U; Segar, A; Sekulin, R L; Siebel, M; Sissakian, A N; Smadja, G; Smirnova, O G; Sokolov, A; Sopczak, A; Sosnowski, R; Spassoff, Tz; Stanitzki, M; Stocchi, A; Strauss, J; Stugu, B; Szczekowski, M; Szeptycka, M; Szumlak, T; Tabarelli de Fatis, T; Taffard, A C; Tegenfeldt, F; Timmermans, J; Tkatchev, L G; Tobin, M; Todorovova, S; Tomé, B; Tonazzo, A; Tortosa, P; Travnicek, P; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Turluer, M L; Tyapkin, I A; Tyapkin, P; Tzamarias, S; Uvarov, V; Valenti, G; van Dam, P; Van Eldik, J; Van Lysebetten, A; Van Remortel, N; Van Vulpen, I B; Vegni, G; Veloso, F; Venus, W A; Verdier, P; Verzi, V; Vilanova, D; Vitale, L; Vrba, V; Wahlen, H; Washbrook, A J; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G; Winter, M; Witek, M; Yushchenko, O P; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zhuravlov, V; Zimin, N I; Zinchenko, A I; Zupan, M

    2004-01-01

    Hadronic event shape distributions are determined from data in e+e- collisions between 183 and 207 GeV. From these the strong coupling alpha_s is extracted in O(alpha_s^2), NLLA and matched O(alpha_s^2)+NLLA theory. Hadronisation corrections evaluated with fragmentation model generators as well as an analytical power ansatz are applied. Comparing these measurements to those obtained at and around M_Z allows a combined measurement of alpha_s from all DELPHI data and a test of the energy dependence of the strong coupling.

  15. Degradation of the potato glycoalkaloids--alpha-solanine and alpha-chaconine in groundwater.

    Science.gov (United States)

    Jensen, Pia H; Jacobsen, Ole S; Henriksen, Trine; Strobel, Bjarne W; Hansen, Hans Christian B

    2009-06-01

    The potato glycoalkaloids alpha-chaconine and alpha-solanine are produced in high amounts in potato plants from where release to soil takes place. Degradation of the compounds in groundwater was investigated, as their fate in the terrestrial environment is unknown. Abiotic and microbial degradation were followed in groundwater sampled from below a potato field and spiked with the glycoalkaloids (115 nmol/l). Degradation was primarily microbial and the glycoalkaloids were degraded within 21-42 days. The metabolites beta(1)-solanine, gamma-solanine, and solanidine were formed from alpha-solanine, while beta-chaconine, gamma-chaconine and solanidine were detected from alpha-chaconine. Thus, indigenous groundwater microorganisms are capable of degrading the glycoalkaloids.

  16. Constraints on the Preferred-Frame {\\alpha}1, {\\alpha}2 parameters from Solar System planetary precessions

    CERN Document Server

    Iorio, Lorenzo

    2014-01-01

    Analytical expressions for the orbital precessions affecting the relative motion of the components of a local binary system induced by Lorentz-violating Preferred Frame Effects (PFE) are explicitly computed in terms of the PPN parameters {\\alpha}1, {\\alpha}2. A linear combination of the supplementary perihelion precessions of all the inner planets of the Solar System, able to remove the a-priori bias of unmodelled/mismodelled standard effects such as the general relativistic Lense-Thirring precessions and the classical rates due to the Sun's oblateness J2, allows to infer {\\alpha}1 <= 10^-6, {\\alpha}2 <= 10^-5. Such bounds should be improved in the near future after processing the data that are being collected by the MESSENGER spacecraft, currently orbiting Mercury. Further improvements may come in the mid-future from the approved BepiColombo mission to Mercury (Abridged).

  17. Dynamical Screening Effect on $\\alpha$-$\\alpha$ Resonant Scattering and Thermal Nuclear Scattering Rate

    CERN Document Server

    Yao, Xiaojun; Müller, Berndt

    2016-01-01

    We study the dynamical screening effect in the QED plasma on the $\\alpha$-$\\alpha$ scattering at the $^8$Be resonance. Dynamical screening leads to an imaginary part of the potential which results in a thermal width for the resonance and dominates over the previously considered static screening effect. As a result, both the resonance energy and width increase with the plasma temperature. Furthermore, dynamical screening can have a huge impact on the $\\alpha$-$\\alpha$ thermal nuclear scattering rate. For example, when the temperature is around $10$ keV, the rate is suppressed by a factor of about $900$. We expect similar thermal suppressions of nuclear reaction rates to occur in nuclear reactions dominated by an above threshold resonance with a thermal energy. Dynamical screening effects on nuclear reactions can be relevant to cosmology and astrophysics.

  18. Precision determination of alpha_s using an unbiased global NLO parton set

    CERN Document Server

    Lionetti, Simone; Bertone, Valerio; Cerutti, Francesco; Del Debbio, Luigi; Forte, Stefano; Guffanti, Alberto; Latorre, Jose I; Rojo, Juan; Ubiali, Maria

    2011-01-01

    We determine the strong coupling alpha_s from a next-to-leading order analysis of processes used for the NNPDF2.1 parton determination, which includes data from neutral and charged current deep-inelastic scattering, Drell-Yan and inclusive jet production. We find alpha_s(M_Z)=0.1191+-0.0006 (exp), where the uncertainty includes all statistical and systematic experimental uncertainties, but not purely theoretical uncertainties. We study the dependence of the results on the dataset, by providing further determinations based respectively on deep-inelastic data only, and on HERA data only. The deep-inelastic fit gives the consistent result alpha_s(M_Z)=0.1177+-0.0009(exp), but the result of the HERA-only fit is only marginally consistent. We provide evidence that individual data subsets can have runaway directions due to poorly determined PDFs, thus suggesting that a global dataset is necessary for a reliable determination.

  19. Interaction of alphaVbeta3 and alphaVbeta6 integrins with human parechovirus 1.

    Science.gov (United States)

    Seitsonen, Jani; Susi, Petri; Heikkilä, Outi; Sinkovits, Robert S; Laurinmäki, Pasi; Hyypiä, Timo; Butcher, Sarah J

    2010-09-01

    Human parechovirus (HPEV) infections are very common in early childhood and can be severe in neonates. It has been shown that integrins are important for cellular infectivity of HPEV1 through experiments using peptide blocking assays and function-blocking antibodies to alpha(V) integrins. The interaction of HPEV1 with alpha(V) integrins is presumably mediated by a C-terminal RGD motif in the capsid protein VP1. We characterized the binding of integrins alpha(V)beta(3) and alpha(V)beta(6) to HPEV1 by biochemical and structural studies. We showed that although HPEV1 bound efficiently to immobilized integrins, alpha(V)beta(6) bound more efficiently than alpha(V)beta(3) to immobilized HPEV1. Moreover, soluble alpha(V)beta(6), but not alpha(V)beta(3), blocked HPEV1 cellular infectivity, indicating that it is a high-affinity receptor for HPEV1. We also showed that HPEV1 binding to integrins in vitro could be partially blocked by RGD peptides. Using electron cryo-microscopy and image reconstruction, we showed that HPEV1 has the typical T=1 (pseudo T=3) organization of a picornavirus. Complexes of HPEV1 and integrins indicated that both integrin footprints reside between the 5-fold and 3-fold symmetry axes. This result does not match the RGD position predicted from the coxsackievirus A9 X-ray structure but is consistent with the predicted location of this motif in the shorter C terminus found in HPEV1. This first structural characterization of a parechovirus indicates that the differences in receptor binding are due to the amino acid differences in the integrins rather than to significantly different viral footprints.

  20. Catalytic enantioselective Michael addition reactions of alpha-nitroesters to alpha,beta-unsaturated ketones

    NARCIS (Netherlands)

    Keller, E; Veldman, N; Spek, AL; Feringa, BL

    1997-01-01

    Enantioselective Michael additions of alpha-nitroesters 2a-d with alpha,beta-unsaturated ketones were carried out in the presence of a catalytic amount of chiral Al-Li-(R,R')-2,2'-dihydroxy-1,1'-binaphthyl ('AlLiBINOL') complex prepared in situ from LiAlH4 and 2.45 equiv. of (R,R')-BINOL. The enanti

  1. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof

    1992-01-01

    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  2. Estimation of Time-Varying Autoregressive Symmetric Alpha Stable

    Data.gov (United States)

    National Aeronautics and Space Administration — In the last decade alpha-stable distributions have become a standard model for impulsive data. Especially the linear symmetric alpha-stable processes have found...

  3. Effects of tumor necrosis factor-alpha (TNF alpha) in epidermal keratinocytes revealed using global transcriptional profiling.

    Science.gov (United States)

    Banno, Tomohiro; Gazel, Alix; Blumenberg, Miroslav

    2004-07-30

    Identification of tumor necrosis factor-alpha (TNF alpha) as the key agent in inflammatory disorders, e.g. rheumatoid arthritis, Crohn's disease, and psoriasis, led to TNF alpha-targeting therapies, which, although avoiding many of the side-effects of previous drugs, nonetheless causes other side-effects, including secondary infections and cancer. By controlling gene expression, TNF alpha orchestrates the cutaneous responses to environmental damage and inflammation. To define TNF alpha action in epidermis, we compared the transcriptional profiles of normal human keratinocytes untreated and treated with TNF alpha for 1, 4, 24, and 48 h by using oligonucleotide microarrays. We found that TNF alpha regulates not only immune and inflammatory responses but also tissue remodeling, cell motility, cell cycle, and apoptosis. Specifically, TNF alpha regulates innate immunity and inflammation by inducing a characteristic large set of chemokines, including newly identified TNF alpha targets, that attract neutrophils, macrophages, and skin-specific memory T-cells. This implicates TNF alpha in the pathogenesis of psoriasis, fixed drug eruption, atopic and allergic contact dermatitis. TNF alpha promotes tissue repair by inducing basement membrane components and collagen-degrading proteases. Unexpectedly, TNF alpha induces actin cytoskeleton regulators and integrins, enhancing keratinocyte motility and attachment, effects not previously associated with TNF alpha. Also unanticipated was the influence of TNF alpha upon keratinocyte cell fate by regulating cell-cycle and apoptosis-associated genes. Therefore, TNF alpha initiates not only the initiation of inflammation and responses to injury, but also the subsequent epidermal repair. The results provide new insights into the harmful and beneficial TNF alpha effects and define the mechanisms and genes that achieve these outcomes, both of which are important for TNF alpha-targeted therapies.

  4. Extended Ly$\\alpha$ emission around quasars with eclipsing damped Ly$\\alpha$ systems

    CERN Document Server

    Fathivavsari, Hassan; Noterdaeme, Pasquier; Pâris, Isabelle; Finley, Hayley; López, Sebastian; Srianand, Raghunathan

    2016-01-01

    We present spectroscopic observations of six high redshift ($z_{\\rm em}$ $>$ 2) quasars, which have been selected for their Lyman $\\alpha$ (Ly$\\alpha$) emission region being only partially covered by a strong proximate ($z_{\\rm abs}$ $\\sim$ $z_{\\rm em}$) coronagraphic damped Ly$\\alpha$ system (DLA). We detected spatially extended Ly$\\alpha$ emission envelopes surrounding these six quasars, with projected spatial extent in the range 26 $\\le$ $d_{\\rm Ly\\alpha}$ $\\le$ 51 kpc. No correlation is found between the quasar ionizing luminosity and the Ly$\\alpha$ luminosity of their extended envelopes. This could be related to the limited covering factor of the extended gas and/or due to the AGN being obscured in other directions than towards the observer. Indeed, we find a strong correlation between the luminosity of the envelope and its spatial extent, which suggests that the envelopes are probably ionized by the AGN. The metallicity of the coronagraphic DLAs is low and varies in the range $-$1.75 $<$ [Si/H] $<...

  5. Silicon vertex detector upgrade in the ALPHA experiment

    Energy Technology Data Exchange (ETDEWEB)

    Amole, C. [Department of Physics and Astronomy, York University, Toronto, ON, M3J 1P3 (Canada); Andresen, G.B. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Ashkezari, M.D. [Department of Physics, Simon Fraser University, Burnaby, BC, V5A 1S6 (Canada); Baquero-Ruiz, M. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Bertsche, W. [School of Physics and Astronomy, University of Manchester, M13 9PL Manchester (United Kingdom); The Cockcroft Institute, Daresbury Laboratory, WA4 4AD Warrington (United Kingdom); Burrows, C. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); Butler, E. [Physics Department, CERN, CH-1211 Geneva 23 (Switzerland); Capra, A. [Department of Physics and Astronomy, York University, Toronto, ON, M3J 1P3 (Canada); Cesar, C.L. [Instituto de Física, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-972 (Brazil); Chapman, S. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Charlton, M.; Deller, A.; Eriksson, S. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); Fajans, J. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Lawrence Berkeley National Laboratory, Berkeley, CA 94720 (United States); Friesen, T. [Department of Physics and Astronomy, University of Calgary, Calgary, Alberta T2N 1N4 (Canada); Fujiwara, M.C. [Department of Physics and Astronomy, University of Calgary, Calgary, Alberta T2N 1N4 (Canada); TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Gill, D.R. [TRIUMF, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Gutierrez, A. [Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, V6T 1Z4 (Canada); and others

    2013-12-21

    The Silicon Vertex Detector (SVD) is the main diagnostic tool in the ALPHA-experiment. It provides precise spatial and timing information of antiproton (antihydrogen) annihilation events (vertices), and most importantly, the SVD is capable of directly identifying and analysing single annihilation events, thereby forming the basis of ALPHA's analysis. This paper describes the ALPHA SVD and its upgrade, installed in the ALPHA's new neutral atom trap.

  6. Silicon vertex detector upgrade in the ALPHA experiment

    CERN Document Server

    Amole, C; Ashkezari, M.D; Baquero-Ruiz, M; Bertsche, W; Burrows, C; Butler, E; Capra, A; Cesar, C.L; Chapman, S; Charlton, M; Deller, A; Eriksson, S; Fajans, J; Friesen, T; Fujiwara, M.C; Gill, D.R; Gutierrez, A; Hangst, J.S; Hardy, W.N; Hayden, M.E; Humphries, A.J; Isaac, C.A; Jonsell, S; Kurchaninov, L; Little, A; Madsen, N; McKenna, J.T.K; Menary, S; Napoli, S.C; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Pusa, P; Rasmussen, C.Ø; Robicheaux, F; Sacramento, R.L; Sampson, J.A; Sarid, E; Seddon, D; Silveira, D.M; So, C; Stracka, S; Tharp, T; Thompson, R.I; Thornhill, J; Tooley, M.P; Van Der Werf, D.P; Wells, D

    2013-01-01

    The Silicon Vertex Detector (SVD) is the main diagnostic tool in the ALPHA-experiment. It provides precise spatial and timing information of antiproton (antihydrogen) annihilation events (vertices), and most importantly, the SVD is capable of directly identifying and analysing single annihilation events, thereby forming the basis of ALPHA ' s analysis. This paper describes the ALPHA SVD and its upgrade, installed in the ALPHA ' s new neutral atom trap.

  7. Towards Antihydrogen Confinement with the ALPHA Antihydrogen Trap

    CERN Document Server

    Fujiwara, M C; Bertsche, W; Boston, A; Bowe, P D; Cesar, C L; Chapman, S; Charlton, M; Chartier, M; Deutsch, A; Fajans, J; Funakoshi, R; Gill, D R; Gomberoff, K; Hangst, J S; Hardy, W N; Hayano, R S; Hydomako, R; Jenkins, M J; Jørgensen, L V; Kurchaninov, L; Madsen, N; Nolan, P; Olchanski, K; Olin, A; Page, R D; Povilus, A; Robicheaux, F; Sarid, E; Silveira, D M; Storey, J W; Thompson, R I; Van der Werf, D P; Wurtele, J S; Yamazaki, Y

    2006-01-01

    ALPHA is an international project that has recently begun experimentation at CERN's Antiproton Decelerator (AD) facility. The primary goal of ALPHA is stable trapping of cold antihydrogen atoms with the ultimate goal of precise spectroscopic comparisons with hydrogen. We discuss the status of the ALPHA project and the prospects for antihydrogen trapping.

  8. Peroxisome Proliferator-Activated Receptor Alpha Target Genes

    NARCIS (Netherlands)

    Rakhshandehroo, M.; Knoch, B.; Müller, M.R.; Kersten, A.H.

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPAR alpha serves as a molecular target for hypolip

  9. Alpha Models for 3D Eulerian mean fluid circulation

    Energy Technology Data Exchange (ETDEWEB)

    Holm, D.D. [Los Alamos National Laboratory, Los Alamos, NM (United States). Center for Nonlinear Studies and Theoretical Division

    1999-12-01

    The study provides the known analytical properties of the alpha models, including an outline of their derivation and the associated assumptions, their simplification for the case of constant dispersion length (alpha) and their conservation properties. Interpretations of nonlinear dynamics of viscous alpha models are also showed and the differences one might expect from the dynamics of the Navier-Stokes equations are indicated.

  10. Acute toxicity of high doses of the glycoalkaloids, alpha-solanine and alpha-chaconine, in the Syrian Golden hamster

    DEFF Research Database (Denmark)

    Langkilde, Søren; Schrøder, Malene; Stewart, Derek

    2008-01-01

    Sprouted, stressed, or spoiled potato tubers have reportedly led to human acute intoxication, coma, and death when consumed in high amounts. These effects have been attributed to glycoalkaloids (GAs), primarily alpha-solanine and alpha-chaconine, naturally present in all potatoes. The level of GAs...... in potato tubers has previously been shown to increase substantially as a result of improper handling and postharvest storage. A short-term study was performed to investigate the dose-response profile of alpha-solanine and alpha-chaconine alone or in combination, administered daily by oral gavage to Syrian...... Golden hamsters. Daily doses of 100 mg of alpha-solanine [kg body weight (BW)](-1) induced death in two of four hamsters within 4 days, when administered by gavage to female Syrian hamsters. Doses of 100 mg of alpha-chaconine alone or alpha-solanine and alpha-chaconine combined in a ratio of 1...

  11. Varying alpha and the electroweak model

    Energy Technology Data Exchange (ETDEWEB)

    Kimberly, Dagny; Magueijo, Joao

    2004-03-25

    Inspired by recent claims for a varying fine structure constant, alpha, we investigate the effect of 'promoting coupling constants to variables' upon various parameters of the standard model. We first consider a toy model: Proca theory of the massive photon. We then explore the electroweak theory with one and two dilaton fields. We find that a varying alpha unavoidably implies varying W and Z masses. This follows from gauge invariance, and is to be contrasted with Proca theory. For the two dilaton theory the Weinberg angle is also variable, but Fermi's constant and the tree level fermion masses remain constant unless the Higgs potential becomes dynamical. We outline some cosmological implications.

  12. Gravitational waves in $\\alpha-$attractors

    CERN Document Server

    Kumar, K Sravan; Moniz, Paulo Vargas; Das, Suratna

    2015-01-01

    We study inflation in the $\\alpha-$attractor model under a non-slow-roll dynamics with an ansatz proposed by Gong \\& Sasaki \\cite{Gong:2015ypa} of assuming $N=N\\left(\\phi\\right)$. Under this approach, we construct a class of local shapes of inflaton potential that are different from the T-models. We find this type of inflationary scenario predicts an attractor at $n_{s}\\sim0.967$ and $r\\sim0.00055$. In our approach, the non-slow-roll inflaton dynamics are related to the $\\alpha-$parameter which is the curvature of K\\"ahler geometry in the SUGRA embedding of this model.

  13. Alpha self-absorption in monazite dusts.

    Science.gov (United States)

    Terry, K W

    1995-10-01

    Measurements have been made of the self-absorption effects in monazite of alpha particles of the 232Th decay series. Samples of six size fractions of monazite were deposited on filters at different dust concentrations and then the gross alpha activity determined. Self-absorption effects were negligible in monazite particles up to 8 microns diameter provided dust concentrations were less than 1 mg cm-2. Significant self-absorption effects occurred for both larger particle sizes and higher dust loadings. As reported AMAD values in the mineral sands industry range up to 15 microns, which is equivalent to an actual mean size of 8 microns diameter monazite particle, minimal self-absorption occurs in samples collected in air monitoring programs conducted in the industry provided that dust concentrations on the filters are less than 1 mg cm-2.

  14. Do marine bacteria degrade. alpha. -hexachlorocyclohexane stereoselectively

    Energy Technology Data Exchange (ETDEWEB)

    Faller, J.; Huehnerfuss, H.; Koenig, W.A.; Krebber, R.; Ludwig, P. (Univ. Hamburg (West Germany))

    1991-04-01

    The enantiomeric ratio of a chiral organic pollutant has been determined gas chromatographically for the first time at low concentrations as encountered in a North Sea water sample by using heptakis (3-O-butyryl-2,6-di-O-pentyl)-{beta}-cyclodextrin as a chiral stationary phase. As an example, the separation of the enantiomers of {alpha}-hexachlorocyclo-hexane ({alpha}-HCH) is shown herein. However, the method is expected to be generally applicable to many environmental problems that are related to chiral biogenic and anthropogenic substances and chiral degradation products. The potential of this experimental approach for a discrimination between enzymatic and nonenzymatic processes in marine and terrestric ecosystems is discussed.

  15. Source preparations for alpha and beta measurements

    Energy Technology Data Exchange (ETDEWEB)

    Holm, E. [Risoe National Lab., Roskilde (Denmark)

    2001-01-01

    Regarding alpha particle emitters subject for environmental studies, electrodeposition or co-precipitation as fluorides are the most common methods. For electro deposition stainless steel is generally used as cathode material but also other metals such as Ni, Ag, and Cu showed promising results. The use of other anode material than platinum, such as graphite should be investigated. For other purposes such as optimal resolution other more sophisticated methods are used but often resulting in poorer recovery. For beta particle emitters the type of detection system will decide the source preparation. Similar methods as for alpha particle emitters, electrodeposition or precipitation techniques can be used. Due to the continuous energy distribution of the beta pulse height distribution a high resolution is not required. Thicker sources from the precipitates or a stable isotopic carrier can be accepted but correction for absorption in the source must be done. (au)

  16. Sneutrino Inflation with $\\alpha$-attractors

    CERN Document Server

    Kallosh, Renata; Roest, Diederik; Wrase, Timm

    2016-01-01

    Sneutrino inflation employs the fermionic partners of the inflaton and stabilizer field as right-handed neutrinos to realize the seesaw mechanism for light neutrino masses. A crucial ingredient in existing constructions for sneutrino (multi-)natural inflation is an unbroken discrete shift symmetry. We demonstrate that a similar construction applies to $\\alpha$-attractor models. In this case the hyperbolic geometry protects the neutrino Yukawa couplings to the inflaton field, and the masses of leptons and Higgs fields, from blowing up when the inflaton is super-Planckian. We find that the predictions for $n_s$ and $r$ for $\\alpha$-attractor cosmological models, compatible with the current cosmological data, are preserved in the presence of the neutrino sector.

  17. Bakers' asthma caused by alpha amylase.

    Science.gov (United States)

    Valdivieso, R; Subiza, J; Subiza, J L; Hinojosa, M; de Carlos, E; Subiza, E

    1994-10-01

    Two bakers with bronchial asthma and two with rhinoconjunctivitis are described. Prick and RAST tests were positive with wheat flour in all of them, but the challenge test (nasal or bronchial) with wheat flour extract was positive only in one asthmatic baker. The prick test, RAST, and nasal or bronchial challenge done with alpha amylase extract (a glycolytic enzyme obtained from Aspergillus oryzae and used as a flour additive) were positive in all four patients. Our results support previous data indicating that alpha amylase used in bakeries is an important antigen that could cause respiratory allergy in bakers. It can function as sole causative allergen or in addition with other allergens used in the baking industry.

  18. Alpha Decay, Shell Structure, and New Elements

    Institute of Scientific and Technical Information of China (English)

    REN Zhong-Zhou; TAI Fei; SHEN Wen-Qing

    2003-01-01

    We systematically analyze the experimental data of alpha decay in even-even heavy nuclei far from stabilityand find that the Geiger-Nuttall law breaks for an isotopic chain when its neutron number is across a magic numberor there is a deformed subshell. This break can be used to identify new magic numbers of superheavy nuclei. It is alsodiscovered that there is a new linear relation between the logarithm of half-life and the reciprocal of the square root ofdecay energy for N = 126 and N = 152 isotones. It could be a new law of alpha decay for nuclei with magic neutronnumbers but the physics behind it is to be explored. The significance of these researches for the search of new elementsis discussed.

  19. Alpha Decay, Shell Structure, and New Elements

    Institute of Scientific and Technical Information of China (English)

    PENZhong-Zhou; TAIFei; SHENWen-Qing

    2003-01-01

    We systematically analyze the experimental data of alpha decay in even-even heavy nuclei far from stability and find that the Geiger-Nuttall law brea~s for an isotopic chain when its neutron number is across a marc number or there is a deformed subshell. This break can be used to identify new magic numbers of superheavy nuclei. It is also discovered that there is a new linear relation between the logarithm of half-life and the reciprocal of the square root of decay energy for N = 126 and N = 152 isotones. It could be a new law of alpha decay for nuclei with magic neutron numbers but the physics behind it is to be explored. The significance of these researches for the search of new elements is discussed.

  20. Possibilities of life around Alpha Centauri B

    CERN Document Server

    Gonzalez, Antolin; Hearnshaw, John

    2014-01-01

    We make a preliminary assessment on the habitability of potential rocky exoplanets around Alpha Centauri B. We use several indexes: the Earth Similarity Index, a mathematical model for photosynthesis, and a biological productivity model. Considering the atmospheres of the exoplanets similar to current Earth's atmosphere, we find consistent predictions of both the Earth Similarity Index and the biological productivity model. The mathematical model for photosynthesis clearly failed because does not consider the temperature explicitly. For the case of Alpha Centauri B, several simulation runs give 11 planets in the habitable zone. Applying to them above mentioned indexes, we select the five exoplanets more prone for photosynthetic life; showing that two of them in principle have better conditions than Earth for this kind of life.

  1. The Alpha Magnetic Spectrometer Silicon Tracker

    CERN Document Server

    Burger, W J

    1999-01-01

    The Alpha Magnetic Spectrometer (AMS) is designed as a independent module for installation on the International Space Station Alpha (ISSA) in the year 2002 for an operational period of three years. The principal scientific objectives are the searches for antimatter and dark matter in cosmic rays. The AMS uses 5.5 m sup 2 of silicon microstrip sensors to reconstruct charged particle trajectories in the field of a permanent magnet. The detector design and construction covered a 3 yr period which terminated with a test flight on the NASA space shuttle Discovery during June 2-12, 1988. In this contribution, we describe the shuttle version of the AMS silicon tracker, including preliminary results of the tracker performance during the flight. (author)

  2. The predominantly nonhydrolytic action of alpha amylases on alpha-maltosyl fluoride.

    Science.gov (United States)

    Okada, G; Genghof, D S; Hehre, E J

    1979-06-01

    Crystalline alpha amylases from a number of sources utilized alpha-maltosyl fluoride as a glycosyl donor and acceptor at high rates (approximately 10 to approximately 1550 mumol/min/mg of protein, for 30 mM substrate). All enzymes catalyzed conversion of this compound into maltooligosaccharides in preference to causing its hydrolysis. Maltotetraosyl flouride and maltooligosaccharides of d.p. 3 to 6+ accounted for 75--93% (by weight) of early reaction-products. At a late stage, the yield of maltooligosaccharides was 2--5 times that of maltose, with chains as long as 12 D-glucosyl residues formed by one amylase (from Asp. oryzae), which utilized alpha-maltosyl fluoride as a donor and as an acceptor at extremely high rates. These results indicate that alpha amylases have a substantial capacity for binding two molecules of this small substrate in a distinctive way, with the C--F glycosylic bond of one and the free C-4 hydroxyl group of the other located in the region of the enzyme's catalytic groups, therby favoring glycosylation of the suitably positioned acceptor over solvent water. Hydrolysis is assumed to prevail when only a single substrate molecule or segment binds to alpha amylase with a (1 linked to 4)-alpha-D-glucosidic linkage of glycosylic C--F bond positioned at the catalytic center. The present demonstration that glycosyl-transfer reactions can be dominantly expressed by alpha amylases, given an appropriate substrate, illustrates the inadequacy of the usual characterization of these enzymes as hydrolases that produce overwhelming hydrolysis of all substrates.

  3. Proceedings, High-Precision $\\alpha_s$ Measurements from LHC to FCC-ee

    Energy Technology Data Exchange (ETDEWEB)

    d' Enterria, David [CERN; Skands, Peter Z. [Monash U.

    2015-01-01

    This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experimental uncertainties associated to each extraction method, the improvements expected from LHC data in the coming years, and future perspectives achievable in $e^+e^-$ collisions at the Future Circular Collider (FCC-ee) with $\\cal{O}$(1--100 ab$^{-1}$) integrated luminosities yielding 10$^{12}$ Z bosons and jets, and 10$^{8}$ W bosons and $\\tau$ leptons, are thoroughly reviewed. The current uncertainty of the (preliminary) 2015 strong coupling world-average value, $\\alpha_s(m_Z)$ = 0.1177 $\\pm$ 0.0013, is about 1\\%. Some participants believed this may be reduced by a factor of three in the near future by including novel high-precision observables, although this opinion was not universally shared. At the FCC-ee facility, a factor of ten reduction in the $\\alpha_s$ uncertainty should be possible, mostly thanks to the huge Z and W data samples available.

  4. Biomarkers of Alpha Particle Radiation Exposure

    Science.gov (United States)

    2014-04-01

    Increased forensic capability through the development of biological tools to help identify those involved should be an integral to a national strategy... forensics capabilities and emergency preparedness response plans through the detection of those exposed to alpha-particle emitting radioactive...exposure and stored at -40°C before being processed next day. Plasma was analysed using the Piccolo Express Chemistry Analyser (Fisher Scientific

  5. Properties of observed Ly-$\\alpha$ forest

    OpenAIRE

    Demianski, M.; Doroshkevich, A.; Turchaninov, V.

    2000-01-01

    The main observed properties of Ly-$\\alpha$ absorbers are investigated on the basis of theoretical model of formation and evolution of DM structure elements. This model is generally consistent with simulations of absorbers formation and with statistical description of structure evolution based on the Zel'dovich theory. The analysis of redshift variations of comoving linear number density of absorbers was performed in our previous paper. We show that the observed characteristics of Doppler par...

  6. Heterodiffusion coefficients in alpha-iron

    Energy Technology Data Exchange (ETDEWEB)

    Katsika-Tsigourakou, Vassiliki, E-mail: vkatsik@phys.uoa.g [Department of Solid State Physics, Faculty of Physics, University of Athens, Panepistimiopolis Zografos, 15784 Athens (Greece); Skordas, Efthimios S. [Department of Solid State Physics, Faculty of Physics, University of Athens, Panepistimiopolis Zografos, 15784 Athens (Greece)

    2010-04-01

    The diffusion of tungsten in alpha-iron is important for the application of ferritic-iron alloys to thermal power plants. These data, over a wide temperature range across the Curie temperature, have been recently reported. We show that these diffusion coefficients can be satisfactory reproduced in terms of the bulk elastic and expansivity data by means of a thermodynamical model that interconnects point defects parameters with bulk qualities.

  7. Alpha-beta bidirectional associative memories

    OpenAIRE

    María Elena Acevedo Mosqueda; Cornelio Yáñez Márquez

    2006-01-01

    Most models of Bidirectional associative memories intend to achieve that all trained pattern correspond to stable states; however, this has not been possible. Also, none of the former models has been able to recall all the trained patterns. In this work we introduce a new model of bidirectional associative memory which is not iterative and has no stability problems. It is based on the Alpha-Beta associative memories. This model allows perfect recall of all trained patterns, with no ambiguity ...

  8. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

    Science.gov (United States)

    Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

    2007-09-01

    Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

  9. Hypoxia inducible factor-1-alpha (HIF-1 alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis

    NARCIS (Netherlands)

    Brouwer, E.; Gouw, A. S. H.; Posthumus, M. D.; van Leeuwen, M. A.; Boerboom, A. L.; Bijzet, J.; Limburg, P. C.; Kallenberg, C. G. M.; Westra, J.; Bos, R

    2009-01-01

    Objectives Despite the important role of the transcription factor HIF-1 alpha in angiogenesis and inflammation, only a few studies on HIF-1 alpha expression have been performed in RA patients. The aim of the present study was to identify the layer in synovial tissue of RA patients where HIF1 alpha i

  10. The Alpha Dynamo Effects in Laboratory Plasmas

    Energy Technology Data Exchange (ETDEWEB)

    Hantao Ji; Stewart C. Prager

    2001-10-16

    A concise review of observations of the alpha dynamo effect in laboratory plasmas is given. Unlike many astrophysical systems, the laboratory pinch plasmas are driven magnetically. When the system is overdriven, the resultant instabilities cause magnetic and flow fields to fluctuate, and their correlation induces electromotive forces along the mean magnetic field. This alpha-effect drives mean parallel electric current, which, in turn, modifies the initial background mean magnetic structure towards the stable regime. This drive-and-relax cycle, or the so-called self-organization process, happens in magnetized plasmas in a timescale much shorter than resistive diffusion time, thus it is a fast and unquenched dynamo process. The observed alpha-effect redistributes magnetic helicity (a measure of twistedness and knottedness of magnetic field lines) but conserves its total value. It can be shown that fast and unquenched dynamos are natural consequences of a driven system where fluctuations are statistically either not stationary in time or not homogeneous in space, or both. Implications to astrophysical phenomena will be discussed.

  11. Parallax and masses of alpha Centauri revisited

    CERN Document Server

    Pourbaix, Dimitri

    2016-01-01

    Context. Despite the thorough work of van Leeuwen (2007), the parallax of alpha Centauri is still far from being carved in stone. Any derivation of the individual masses is therefore uncertain, if not questionable. And yet, that does not prevent this system from being used for calibration purpose in several studies. Aims. Obtaining more accurate model-free parallax and individual masses of this system. Methods. With HARPS, the radial velocities are not only precise but also accurate. Ten years of HARPS data are enough to derive the complement of the visual orbit for a full 3D orbit of alpha Cen. Results. We locate alpha Cen (743 mas) right where Hipparcos (ESA 1997) had put it, i.e. slightly further away than derived by Soderhjelm (1999). The components are thus a bit more massive than previously thought (1.13 and 0.97 Msun for A and B respectively). These values are now in excellent agreement with the latest asteroseismologic results.

  12. $\\alpha$-cluster ANCs for nuclear astrophysics

    CERN Document Server

    Avila, M L; Koshchiy, E; Baby, L T; Belarge, J; Kemper, K W; Kuchera, A N; Santiago-Gonzalez, D

    2014-01-01

    Background. Many important $\\alpha$-particle induced reactions for nuclear astrophysics may only be measured using indirect techniques due to small cross sections at the energy of interest. One of such indirect technique, is to determine the Asymptotic Normalization Coefficients (ANC) for near threshold resonances extracted from sub-Coulomb $\\alpha$-transfer reactions. This approach provides a very valuable tool for studies of astrophysically important reaction rates since the results are practically model independent. However, the validity of the method has not been directly verified. Purpose. The aim of this letter is to verify the technique using the $^{16}$O($^6$Li,$d$)$^{20}$Ne reaction as a benchmark. The $^{20}$Ne nucleus has a well known $1^-$ state at excitation energy of 5.79 MeV with a width of 28 eV. Reproducing the known value with this technique is an ideal opportunity to verify the method. Method. The 1$^-$ state at 5.79 MeV is studied using the $\\alpha$-transfer reaction $^{16}$O($^6$Li,$d$)$^...

  13. $\\alpha$ Centauri A in the far infrared

    CERN Document Server

    Liseau, R; Olofsson, G; Bryden, G; Marshall, J P; Ardila, D; Aran, A Bayo; Danchi, W C; del Burgo, C; Eiroa, C; Ertel, S; Fridlund, M C W; Krivov, A V; Pilbratt, G L; Roberge, A; Thébault, P; Wiegert, J; White, G J

    2012-01-01

    Chromospheres and coronae are common phenomena on solar-type stars. Understanding the energy transfer to these heated atmospheric layers requires direct access to the relevant empirical data. Study of these structures has, by and large, been limited to the Sun thus far. The region of the temperature reversal can be directly observed only in the far infrared and submm. We aim at the determination of the characteristics of the atmosphere in the region of the temperature minimum of the solar sister star alpha Cen A. For the nearby binary system alpha Centauri, stellar parameters are known with high accuracy from measurements. For the basic model parameters Teff, log g and [Fe/H], we interpolate in the grid of GAIA/PHOENIX stellar model atmospheres and compute the corresponding model for the G2 V star alpha Cen A. Comparison with photometric measurements shows excellent agreement between observed photospheric data in the optical and infrared. For longer wavelengths, the modelled spectral energy distribution is co...

  14. Alpha Particle Physics Experiments in the Tokamak Fusion Test Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Budny, R.V.; Darrow, D.S.; Medley, S.S.; Nazikian, R.; Zweben, S.J.; et al.

    1998-12-14

    Alpha particle physics experiments were done on the Tokamak Fusion Test Reactor (TFTR) during its deuterium-tritium (DT) run from 1993-1997. These experiments utilized several new alpha particle diagnostics and hundreds of DT discharges to characterize the alpha particle confinement and wave-particle interactions. In general, the results from the alpha particle diagnostics agreed with the classical single-particle confinement model in magnetohydrodynamic (MHD) quiescent discharges. Also, the observed alpha particle interactions with sawteeth, toroidal Alfvén eigenmodes (TAE), and ion cyclotron resonant frequency (ICRF) waves were roughly consistent with theoretical modeling. This paper reviews what was learned and identifies what remains to be understood.

  15. Multimode fiber with z-dependent alpha-value.

    Science.gov (United States)

    Marcuse, D

    1979-07-01

    The width of the impulse response of multimode fibers with power law index profiles depends on the alpha-value of the power law exponent. For constant alpha, optimum pulse width is achievable only in a very narrow range of values centered around alpha = 2 - (12/5)Delta. We show in this paper that the optimum width of the impulse response is achievable for fibers with nonoptimum alpha-values provided alpha varies slowly along the fiber and deviates on average by equal amounts to either side of its (constant) optimum value.

  16. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    Science.gov (United States)

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  17. Bioisosteric phentolamine analogs as potent alpha-adrenergic antagonists.

    Science.gov (United States)

    Hong, Seoung-Soo; Bavadekar, Supriya A; Lee, Sang-Il; Patil, Popat N; Lalchandani, S G; Feller, Dennis R; Miller, Duane D

    2005-11-01

    The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described. Replacement of the carbon next to the imidazoline ring of phentolamine with a nitrogen atom provides compounds (2, 3) that are about 1.6 times and 4.1 times more potent functionally than phentolamine on rat alpha1-adrenergic receptors, respectively. In receptor binding assays, the affinities of phentolamine and its bioisosteric analogs were determined on the human embryonic kidney (HEK) and Chinese Hamster ovary (CHO) cell lines expressing the human alpha1- and alpha2-AR subtypes, respectively. Analogs 2 and 3, both, displayed higher binding affinities at the alpha2- versus the alpha1-ARs, affinities being the least at the alpha1B-AR. Binding affinities of the methoxy ether analog 2 were greater than those of the phenolic analog 3 at all six alpha-AR subtypes. One of the nitrogen atoms in the imidazoline ring of phentolamine was replaced with an oxygen atom to give compounds 4 and 5, resulting in a 2-substituted oxazoline ring. The low functional antagonist activity on rat aorta, and binding potencies of these two compounds on human alpha1A- and alpha2A-AR subtypes indicate that a basic functional group is important for optimum binding to the alpha1- and alpha2A-adrenergic receptors.

  18. Functional and genomic analyses of alpha-solenoid proteins.

    Directory of Open Access Journals (Sweden)

    David Fournier

    Full Text Available Alpha-solenoids are flexible protein structural domains formed by ensembles of alpha-helical repeats (Armadillo and HEAT repeats among others. While homology can be used to detect many of these repeats, some alpha-solenoids have very little sequence homology to proteins of known structure and we expect that many remain undetected. We previously developed a method for detection of alpha-helical repeats based on a neural network trained on a dataset of protein structures. Here we improved the detection algorithm and updated the training dataset using recently solved structures of alpha-solenoids. Unexpectedly, we identified occurrences of alpha-solenoids in solved protein structures that escaped attention, for example within the core of the catalytic subunit of PI3KC. Our results expand the current set of known alpha-solenoids. Application of our tool to the protein universe allowed us to detect their significant enrichment in proteins interacting with many proteins, confirming that alpha-solenoids are generally involved in protein-protein interactions. We then studied the taxonomic distribution of alpha-solenoids to discuss an evolutionary scenario for the emergence of this type of domain, speculating that alpha-solenoids have emerged in multiple taxa in independent events by convergent evolution. We observe a higher rate of alpha-solenoids in eukaryotic genomes and in some prokaryotic families, such as Cyanobacteria and Planctomycetes, which could be associated to increased cellular complexity. The method is available at http://cbdm.mdc-berlin.de/~ard2/.

  19. Determination of $\\alpha_{s}$ using Jet Rates at LEP with the OPAL detector

    CERN Document Server

    Abbiendi, G.; Akesson, P.F.; Alexander, G.; Anagnostou, G.; Anderson, K.J.; Asai, S.; Axen, D.; Bailey, I.; Barberio, E.; Barillari, T.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Boeriu, O.; Bock, P.; Boutemeur, M.; Braibant, S.; Brown, Robert M.; Burckhart, H.J.; Campana, S.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, D.G.; Ciocca, C.; Csilling, A.; Cuffiani, M.; Dado, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Etzion, E.; Fabbri, F.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Gagnon, P.; Gary, John William; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harel, A.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herten, G.; Heuer, R.D.; Hill, J.C.; Horvath, D.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanzaki, J.; Karlen, D.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kramer, T.; Krasznahorkay, A.; Krieger, P.; von Krogh, J.; Kuhl, T.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Lellouch, D.; Lettso, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, A.; Ludwig, J.; Mader, W.; Marcellini, S.; Martin, A.J.; Mashimo, T.; Mattig, Peter; McKenna, J.; McPherson, R.A.; Meijers, F.; Menges, W.; Merritt, F.S.; Mes, H.; Meyer, Niels T.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Nanjo, H.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Roney, J.M.; Rossi, A.M.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schorner-Sadenius, T.; Schroder, Matthias; Schumacher, M.; Seuster, R.; Shears, T.G.; Shen, B.C.; Sherwood, P.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spano, F.; Stahl, A.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vollmer, C.F.; Vannerem, P.; Vertesi, R.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija

    2006-01-01

    Hadronic events produced in e+e- collisions by the LEP collider and recorded by the OPAL detector were used to form distributions based on the number of reconstructed jets. The data were collected between 1995 and 2000 and correspond to energies of 91 GeV, 130-136 GeV and 161-209 GeV. The jet rates were determined using four different jet-finding algorithms (Cone, JADE, Durham and Cambridge). The differential two-jet rate and the average jet rate with the Durham and Cambridge algorithms were used to measure alpha(s) in the LEP energy range by fitting an expression in which order alpah_2s calculations were matched to a NLLA prediction and fitted to the data. Combining the measurements at different centre-of-mass energies, the value of alpha_s (Mz) was determined to be alpha(s)(Mz)=0.1177+-0.0006(stat.)+-0.0012$(expt.)+-0.0010(had.)+-0.0032

  20. Systematics of alpha decay half-life: new evaluations for alpha-emitter nuclides

    Energy Technology Data Exchange (ETDEWEB)

    Medeiros, E.L.; Rodrigues, M.M.N.; Duarte, S.B.; Tavares, O.A.P. E-mail: emil.cbpf.br

    2006-06-15

    A semiempirical model based on the quantum mechanical tunnelling mechanism of alpha emission from nuclei has been used to systematize the alpha decay half-lives of a set of 336 nuclides, comprising all the alpha-emitter nuclides whose T{sub 1/2} {sup a}lpha-data for ground-state to ground-state transitions of mutual angular momentum l = 0 are known. With a minimum of data rejection (only {approx} 5% of cases), the procedure has been successful in reproducing quite satisfactorily (within a factor {approx} 2) most of the cases ({approx} 80%) investigated. The few significant discrepancies found between measured and calculated results are analysed and discussed. Also reported is the prediction from the model for possible new alpha-emitter nuclides, namely {sup 180} W, {sup 184} Os, and {sup 228} Ra for which cases the calculated partial alpha decay half-lives fall within the range of half-lives measurable by the current techniques. (author)

  1. Probing surface distribution of $\\alpha$-cluster in $^{20}$Ne via $\\alpha$-transfer reaction

    CERN Document Server

    Fukui, Tokuro; Suhara, Tadahiro; Kanada-En'yo, Yoshiko; Ogata, Kazuyuki

    2015-01-01

    Direct evidence of the $\\alpha$-cluster development in bound states has not been obtained yet although a number of experimental studies were carried out to extract the information of the clustering. In particular in conventional analyses of $\\alpha$-transfer reactions, there exist a few significant problems on reaction models, which are insufficient to qualitatively discuss the cluster structure. We aim to verify the development of the $\\alpha$-cluster structure from observables. As the first application, it is argued to extract the spatial information of the cluster structure of the $^{20}$Ne nucleus in its ground state through the cross section of the $\\alpha$-transfer reaction $^{16}$O($^6$Li,~$d$)$^{20}$Ne. For the analysis of the transfer reaction, we work with the coupled-channels Born approximation (CCBA) approach, in which the breakup effect of $^6$Li is explicitly taken into account by means of the continuum-discretized coupled-channels method (CDCC) based on the three-body $\\alpha + d + {}^{16}$O mo...

  2. $\\alpha_s$ analyses from hadronic tau decays with OPAL and ALEPH data

    CERN Document Server

    Boito, Diogo; Maltman, Kim; Peris, Santiago

    2016-01-01

    Recently, we extracted the strong coupling, $\\alpha_s(m_\\tau^2)$, from the revised ALEPH data for non-strange hadronic tau decays. Our analysis is based on a method previously used for the determination of the strong coupling from OPAL data. In our strategy, we employ different moments of the spectral functions both with and without pinching, including Duality Violations, in order to obtain fully self-consistent analyses that do not rely on untested assumptions (such as the smallness of higher dimension contributions in the OPE). Here we discuss the $\\alpha_s$ values obtained from the ALEPH and the OPAL data, the robustness of the analysis, as well as non-perturbative contributions from DVs and the OPE. We show that, although the $\\alpha_s$ determination is sound, non-perturbative effects limit the accuracy with which one can extract the strong coupling from tau decay data. Finally, we discuss the compatibility of the data sets and the possibility of a combined analysis.

  3. Extreme alpha-clustering in the 18O nucleus

    CERN Document Server

    Johnson, E D; Goldberg, V Z; Brown, S; Robson, D; Crisp, A M; Cottle, P D; Fu, C; Giles, J; Green, B W; Kemper, K W; Lee, K; Roeder, B T; Tribble, R E

    2009-01-01

    The structure of the 18O nucleus at excitation energies above the alpha decay threshold was studied using 14C+alpha resonance elastic scattering. A number of states with large alpha reduced widths have been observed, indicating that the alpha-cluster degree of freedom plays an important role in this N not equal Z nucleus. However, the alpha-cluster structure of this nucleus is very different from the relatively simple pattern of strong alpha-cluster quasi-rotational bands in the neighboring 16O and 20Ne nuclei. A 0+ state with an alpha reduced width exceeding the single particle limit was identified at an excitation energy of 9.9+/-0.3 MeV. We discuss evidence that states of this kind are common in light nuclei and give possible explanations of this feature.

  4. Expression of Integrin Alpha10 Is Induced in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ann-Kathrin Wenke

    2007-01-01

    Full Text Available Recently, integrin alpha10 was described as a collagen type II-binding integrin expressed mainly in chondrocytes. However, by array studies we detected integrin alpha10 also to be upregulated in malignant melanoma compared to primary melanocytes. Subsequent analysis of melanoma cell lines and melanoma tumor samples confirmed this finding. Further, we demonstrated that expression of integrin alpha10 is controlled by AP-2 and Ets-1, two transcription factors known to be involved in melanoma development and progression. To investigate the functional relevance of integrin alpha10, expression was downregulated via stable antisense transfection. Proliferation assays and colony forming assays revealed no differences comparing antisense integrin alpha10 cell clones with control and wild type melanoma cells, respectively. However, antisense integrin alpha10 cell clones and Mel Im cells treated with an inhibitory antibody against integrin alpha10 showed a reduced migratory potential.

  5. Determination of {alpha}-nucleus potentials by {alpha}-elastic scattering and its implications for the {gamma}-process

    Energy Technology Data Exchange (ETDEWEB)

    Galaviz, D. E-mail: redondo@ikp.tu-darmstadt.de; Babilon, M.; Fueloep, Zs.; Gyuerky, Gy.; Mate, Z.; Hillier, R.; Mohr, P.; Rauscher, T.; Somorjai, E.; Zilges, A.; Zolnai, L

    2003-05-19

    Complete angular distributions for the reactions {sup 112,124}Sn({alpha},{alpha}){sup 112,124}Sn have been measured at different energies around the Coulomb barrier. Preliminary results for the {sup 112}Sn x {alpha} and {sup 124}Sn x {alpha} potentials at the energy E{sub c.m.} {approx} 19 MeV are presented. The full determination of the a-nucleus potential for both nuclides may also help to understand the behaviour of {alpha}-nucleus potentials along an isotopic chain.

  6. A measurement of $\\alpha_{s}$ (M$_{Z}^{2}$) from the Gross Llewellyn Smith sum rule

    CERN Document Server

    Harris, D A; Auchincloss, P S; De Barbaro, P; Bazarko, A O; Bernstein, R H; Bodek, A; Bolton, T; Budd, H; Conrad, J; Drucker, R B; Johnson, R A; Kim, J H; King, B J; Kinnel, T; Koizumi, G; Koutsoliotas, S; Lamm, M J; Lefmann, W C; Marsh, W; McFarland, K S; McNulty, C; Mishra, S R; Naples, D; Nienaber, P; Nussbaum, M; Oreglia, M J; Perera, L; Quintas, P Z; Romosan, A; Sakumoto, W K; Schumm, B A; Sciulli, F J; Seligman, W G; Shaevitz, M H; Smith, W H; Spentzouris, P; Steiner, R; Stern, E G; Vakili, M; Yang, U K

    1995-01-01

    The Gross Llewellyn Smith sum rule has been measured at different values of four-momentum transfer squared (Q^{2}) by combining the precise CCFR neutrino data with data from other deep-inelastic scattering experiments at lower values of Q^{2}. A comparison with the {\\cal O}(\\alpha^{3}_{s}) predictions of perturbative QCD yields a determination of \\alpha_{s} and its dependence on Q^{2} in the range 1\\,GeV^2 < Q^{2} < 20 \\,GeV^{2}. Low \\qsq\\ tests have greater sensitivity to \\alfs(\\mztwo) than high \\qsq\\ tests, since at low Q^2, \\alpha_s is large and changing rapidly.

  7. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Maëlle Lempereur

    2016-01-01

    Full Text Available Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L. which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box. In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells. Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif.

  8. Expression of G alpha 16, a G-protein alpha subunit specific for hematopoiesis in acute leukemia.

    Science.gov (United States)

    Pfeilstöcker, M; Karlic, H; Salamon, J; Krömer, E; Mühlberger, H; Pavlova, B; Selim, U; Tüchler, H; Fritsch, G; Kneissl, S; Heinz, R; Pitterman, E; Paukovits, M R

    1996-07-01

    G-proteins are essential in signal transduction pathways. A G-protein alpha subunit termed G alpha 16 was found to be exclusively expressed in hematopoietic cell lines. In cells derived from patients, G alpha 16 expression has been detected in progenitor- and pre-B ALL cells and also in peripheral blood stem cells (PBSC). In this study, we analyzed G alpha 16 expression using a RT-PCR technique by testing elutriated blood cells from normal donors, PBSC from breast cancer patients and bone marrow or peripheral blood cells from acute leukemia patients. Both of two ALL patients and 15/16 AML patients expressed G alpha 16. In elutriation experiments, G alpha 16 expression was found in fractions containing the highest number of precursor cells but was absent in mature T and B cell fractions. In addition, CD34-enriched PBSC were positive for G alpha 16 expression. Further in vitro experiments using the cell line KG1 showed that G alpha 16 expression was not affected by the growth inhibiting hemoregulatory peptide pEEDCK which has a sequence homology present within G alpha 16. Taken together, these data demonstrate that G alpha 16 is expressed in various normal and malignant hematopietic progenitors but not in their differentiated counterparts. G alpha 16 could play a vital role in signal transduction pathways controlling proliferation in early normal and malignant hematopoiesis.

  9. Expression and Purification of PI3 Kinase {alpha} and Development of an ATP Depletion and an AlphaScreen PI3 Kinase Activity Assay

    DEFF Research Database (Denmark)

    Boldyreff, Brigitte; Rasmussen, Tine L; Jensen, Hans H

    2008-01-01

    -terminal His-tag and the p85alpha regulatory domain in Sf9 insect cells. The complex consisting of p110alpha and p85alpha was purified by nickel affinity chromatography. The authors established an adenosine triphosphate (ATP) depletion assay to measure the activity of p110alpha/p85alpha. The assay...

  10. Test of the Flavour Independence of $\\alpha_{s}$ using Next-to-Leading Order Calculations for Heavy Quarks

    CERN Document Server

    Abbiendi, G; Alexander, Gideon; Allison, J; Altekamp, N; Anderson, K J; Anderson, S; Arcelli, S; Asai, S; Ashby, S F; Axen, D A; Azuelos, Georges; Ball, A H; Barberio, E; Barlow, R J; Batley, J Richard; Baumann, S; Bechtluft, J; Behnke, T; Bell, K W; Bella, G; Bellerive, A; Bentvelsen, Stanislaus Cornelius Maria; Bethke, Siegfried; Betts, S; Biebel, O; Biguzzi, A; Bloodworth, Ian J; Bock, P; Böhme, J; Bonacorsi, D; Boutemeur, M; Braibant, S; Bright-Thomas, P G; Brigliadori, L; Brown, R M; Burckhart, Helfried J; Capiluppi, P; Carnegie, R K; Carter, A A; Carter, J R; Chang, C Y; Charlton, D G; Chrisman, D; Ciocca, C; Clarke, P E L; Clay, E; Cohen, I; Conboy, J E; Cooke, O C; Couchman, J; Couyoumtzelis, C; Coxe, R L; Cuffiani, M; Dado, S; Dallavalle, G M; Davis, R; De Jong, S; de Roeck, A; Dervan, P J; Desch, Klaus; Dienes, B; Dixit, M S; Dubbert, J; Duchovni, E; Duckeck, G; Duerdoth, I P; Estabrooks, P G; Etzion, E; Fabbri, Franco Luigi; Fanfani, A; Fanti, M; Faust, A A; Fiedler, F; Fierro, M; Fleck, I; Frey, A; Fürtjes, A; Futyan, D I; Gagnon, P; Gary, J W; Gascon-Shotkin, S M; Gaycken, G; Geich-Gimbel, C; Giacomelli, G; Giacomelli, P; Gibson, V; Gibson, W R; Gingrich, D M; Glenzinski, D A; Goldberg, J; Gorn, W; Grandi, C; Graham, K; Gross, E; Grunhaus, Jacob; Gruwé, M; Hajdu, C; Hanson, G G; Hansroul, M; Hapke, M; Harder, K; Harel, A; Hargrove, C K; Harin-Dirac, M; Hauschild, M; Hawkes, C M; Hawkings, R; Hemingway, Richard J; Herndon, M; Herten, G; Heuer, R D; Hildreth, M D; Hill, J C; Hobson, P R; Höcker, Andreas; Hoffman, K; Homer, R James; Honma, A K; Horváth, D; Hossain, K R; Howard, R; Hüntemeyer, P; Igo-Kemenes, P; Imrie, D C; Ishii, K; Jacob, F R; Jawahery, A; Jeremie, H; Jimack, Martin Paul; Jones, C R; Jovanovic, P; Junk, T R; Kanaya, N; Kanzaki, J I; Karlen, D A; Kartvelishvili, V G; Kawagoe, K; Kawamoto, T; Kayal, P I; Keeler, Richard K; Kellogg, R G; Kennedy, B W; Kim, D H; Klier, A; Kobayashi, T; Kobel, M; Kokott, T P; Kolrep, M; Komamiya, S; Kowalewski, R V; Kress, T; Krieger, P; Von Krogh, J; Kühl, T; Kyberd, P; Lafferty, G D; Landsman, Hagar Yaël; Lanske, D; Lauber, J; Lawson, I; Layter, J G; Lellouch, Daniel; Letts, J; Levinson, L; Liebisch, R; List, B; Littlewood, C; Lloyd, A W; Lloyd, S L; Loebinger, F K; Long, G D; Losty, Michael J; Lü, J; Ludwig, J; Liu, D; Macchiolo, A; MacPherson, A L; Mader, W F; Mannelli, M; Marcellini, S; Martin, A J; Martin, J P; Martínez, G; Mashimo, T; Mättig, P; McDonald, W J; McKenna, J A; McKigney, E A; McMahon, T J; McPherson, R A; Meijers, F; Méndez-Lorenzo, P; Merritt, F S; Mes, H; Michelini, Aldo; Mihara, S; Mikenberg, G; Miller, D J; Mohr, W; Montanari, A; Mori, T; Nagai, K; Nakamura, I; Neal, H A; Nisius, R; O'Neale, S W; Oakham, F G; Odorici, F; Ögren, H O; Okpara, A N; Oreglia, M J; Orito, S; Pásztor, G; Pater, J R; Patrick, G N; Patt, J; Pérez-Ochoa, R; Petzold, S; Pfeifenschneider, P; Pilcher, J E; Pinfold, James L; Plane, D E; Poffenberger, P R; Poli, B; Polok, J; Przybycien, M B; Quadt, A; Rembser, C; Rick, Hartmut; Robertson, S; Robins, S A; Rodning, N L; Roney, J M; Rosati, S; Roscoe, K; Rossi, A M; Rozen, Y; Runge, K; Runólfsson, O; Rust, D R; Sachs, K; Saeki, T; Sahr, O; Sang, W M; Sarkisyan-Grinbaum, E; Sbarra, C; Schaile, A D; Schaile, O; Scharff-Hansen, P; Schieck, J; Schmitt, S; Schöning, A; Schröder, M; Schumacher, M; Schwick, C; Scott, W G; Seuster, R; Shears, T G; Shen, B C; Shepherd-Themistocleous, C H; Sherwood, P; Siroli, G P; Sittler, A; Skuja, A; Smith, A M; Snow, G A; Sobie, Randall J; Söldner-Rembold, S; Spagnolo, S; Sproston, M; Stahl, A; Stephens, K; Steuerer, J; Stoll, K; Strom, D; Ströhmer, R; Surrow, B; Talbot, S D; Taras, P; Tarem, S; Teuscher, R; Thiergen, M; Thomas, J; Thomson, M A; Torrence, E; Towers, S; Trigger, I; Trócsányi, Z L; Tsur, E; Turner-Watson, M F; Ueda, I; Van Kooten, R; Vannerem, P; Verzocchi, M; Voss, H; Wäckerle, F; Wagner, A; Ward, C P; Ward, D R; Watkins, P M; Watson, A T; Watson, N K; Wells, P S; Wermes, N; Wetterling, D; White, J S; Wilson, G W; Wilson, J A; Wyatt, T R; Yamashita, S; Zacek, V; Zer-Zion, D

    1999-01-01

    We present a test of the flavour independence of the strong coupling constant for charm and bottom quarks with respect to light (uds) quarks, based on a hadronic event sample obtained with the OPAL detector at LEP. Five observables related to global event shapes were used to measure alpha_s in three flavour tagged samples (uds, c and b). The event shape distributions were fitted by Order(alpha_s**2) calculations of jet production taking into account mass effects for the c and b quarks. We find: = 0.997 +- 0.038(stat.) +- 0.030(syst.) +- 0.012(theory) and = 0.993 +- 0.008(stat.) +- 0.006(syst.) +- 0.011(theory) for the ratios alpha_s(charm)/alpha_s(uds) and alpha_s(b)/alpha_s(uds) respectively.

  11. Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C

    DEFF Research Database (Denmark)

    Hauser, Goran; Awad, Tahany; Thorlund, Kristian

    2014-01-01

    : We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS until October 2013. We also searched conference abstracts, journals, and grey...... literature. SELECTION CRITERIA: We included randomised clinical trials comparing peginterferon alpha-2a versus peginterferon alpha-2b given with or without co-intervention(s) (for example, ribavirin) for chronic hepatitis C. Quasi-randomised studies and observational studies as identified by the searches...

  12. Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s

    CERN Document Server

    Abramowicz, H; Adamczyk, L; Adamus, M; Adler, V; Aghuzumtsyan, G; Allfrey, P D; Antonioli, P; Antonov, A; Arneodo, M; Bailey, D S; Bamberger, A; Barakbaev, A N; Barbagli, G; Barbi, M; Bari, G; Barreiro, F; Bartsch, D; Basile, M; Behrens, U; Bell, M A; Bellagamba, L; Bellan, P M; Benen, A; Bertolin, A; Bhadra, S; Bloch, I; Bold, T; Boos, E G; Borras, K; Boscherini, D; Freiburgi, B; Brock, I; Brook, N H; Brugnera, R; Brümmer, N; Bruni, A; Bruni, G; Bussey, P J; Butterworth, J M; Büttner, C; Bylsma, B; Caldwell, A; Capua, M; Cara Romeo, G; Carli, T; Carlin, R; Catterall, C D; Chekanov, S; Chwastowski, J; Ciborowski, J; Ciesielski, R; Cifarelli, Luisa; Cindolo, F; Cole, J E; Collins-Tooth, C; Contin, A; Cooper-Sarkar, A M; Coppola, N; Corradi, M; Corriveau, F; Costa, M; Cottrell, A; Cui, Y; D'Agostini, G; Dal Corso, F; Danilov, P; De Pasquale, S; Dementiev, R K; Derrick, M; Devenish, R C E; Dhawan, S; Dobur, D; Dolgoshein, B A; Doyle, A T; Drews, G; Durkin, L S; Dusini, S; Eisenberg, Y; Ermolov, P F; Eskreys, Andrzej; Everett, A; Ferrando, J; Ferrero, M I; Figiel, J; Foster, B; Foudas, C; Fourletov, S; Fourletova, J; Fry, C; Gabareen, A; Galas, A; Gallo, E; Garfagnini, A; Geiser, A; Genta, C; Gialas, I; Giusti, P; Gladilin, L K; Gladkov, D; Glasman, C; Goers, S; Goncalo, R; González, O; Gosau, T; Göttlicher, P; Grabowska-Bold, I; Grigorescu, G; Grijpink, S; Grzelak, G; Gutsche, O; Gwenlan, C; Haas, T; Hain, W; Hall-Wilton, R; Hamatsu, R; Hamilton, J; Hanlon, S; Hart, C; Hartmann, H; Hartner, G; Heaphy, E A; Heath, G P; Helbich, M; Hilger, E; Hochman, D; Holm, U; Horn, C; Iacobucci, G; Iga, Y; Irrgang, P; Jakob, P; Jiménez, M; Jones, T W; Kagawa, S; Kahle, B; Kaji, H; Kananov, S; Karshon, U; Karstens, F; Kataoka, M; Katkov, I I; Kcira, D; Keramidas, A; Khein, L A; Kim, J Y; Kind, O; Kisielewska, D; Kitamura, S; Koffeman, E; Kohno, T; Kooijman, P; Koop, T; Korzhav--, I A; Kotanski, A; Kötz, U; Kowal, A M; Kowal--, H; Kramberger, G; Kreisel, A; Krumnack, N; Kulinski, P; Kuze, M; Kuzmin, V A; Labarga, L; Lammers, S; Lelas, D; Levchenko, B B; Levy, A; Li, L; Lightwood, M S; Lim, H; Limentani, S; Ling, T Y; Liu, C; Liu, X; Löhr, B; Lohrmann, E; Loizides, J H; Long, K R; Longhin, A; Lukasik, J; Lukina, O Yu; Luzniak, P; Ma, K J; Maddox, E; Magill, S; Malka, J; Mankel, R; Margotti, A; Marini, G; Martin, J F; Mastroberardino, A; Matsuzawa, K; Mattingly, M C K; Melzer-Pellmann, I A; Menary, S R; Metlica, F; Meyer, U; Miglioranzi, S; Milite, M; Mirea, A; Monaco, V; Montanari, A; Musgrave, B; Nagano, K; Namsoo, T; Nania, R; Nguyen, C N; Nigro, A; Ning, Y; Noor, U; Notz, D; Nowak, R J; Nuncio-Quiroz, A E; Oh, B Y; Olkiewicz, K; Ota, O; Padhi, S; Palmonari, F; Patel, S; Paul, E; Pavel, Usan; Pawlak, J M; Pelfer, P G; Pellegrino, A; Pesci, A; Piotrzkowski, K; Plamondon, M; Plucinsky, P P; Pokrovskiy, N S; Polini, A; Proskuryakov, A S; Przybycien, M B; Rautenberg, J; Raval, A; Reeder, D D; Ren, Z; Renner, R; Repond, J; Ri, Y D; Rinaldi, L; Robins, S; Rosin, M; Ruspa, M; Ryan, P; Sacchi, R; Salehi, H; Santamarta, R; Sartorelli, G; Savin, A A; Saxon, D H; Schagen, S; Schioppa, M; Schlenstedt, S; Schleper, P; Schmidke, W B; Schneekloth, U; Schörner-Sadenius, T; Sciulli, F; Shcheglova, L M; Skillicorn, I O; Slominski, W; Smith, W H; Soares, M; Solano, A; Son, D; Sosnovtsev, V V; Stairs, D G; Stanco, L; Standage, J; Stifutkin, A; Stonjek, S; Stopa, P; Stösslein, U; Straub, P B; Suchkov, S; Susinno, G; Suszycki, L; Sutiak, J; Sutton, M R; Sztuk, J; Szuba, D; Szuba, J; Tapper, A D; Targett--, C; Tassi, E; Tawara, T; Terron, J; Tiecke, H G; Tokushuku, K; Tsurugai, T; Turcato, M; Tymieniecka, T; Tyszkiewicz, A; Ukleja, A; Ukleja, J; Vázquez, M; Vlasov, N N; Voss, K C; Walczak, R; Walsh, R; Wang, M; Whitmore, J J; Whyte, J; Wichmann, K; Wick, K; Wiggers, L; Wills, H H; Wing, M; Wlasenko, M; Wolf, G; Yagues-Molina, A G; Yamada, S; Yamazaki, Y; Yoshida, R; Youngman, C; Za, L; Zambrana, M; Zeuner, W; Zhautykov, B O; Zhou, C; Zichichi, A; Ziegler, A; Zotkin, D S; Zotkin, S A; De Favereau, J; De Wolf, E; Del Peso, J

    2005-01-01

    Multijet production rates in neutral current deep inelastic scattering have been measured in the range of exchanged boson virtualities 10 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD calculations describe the data well. The value of the strong coupling constant alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections, is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.) {+0.0064}_{-0.0046}(th.)

  13. Li production in alpha-alpha reactions. [relation to gamma ray observation

    Science.gov (United States)

    Kozlovsky, B.; Ramaty, R.

    1974-01-01

    The cross section for Li-7 production in alpha-alpha reactions is shown to be increased by about a factor of 2 due to the excitation levels of Li-7 and Be-7 at 478 keV and 431 keV, respectively. The cross section for Li-6 production, however, remains the same as calculated on the basis of the detailed balance principle. The lines at 478 keV and 431 keV may link Li-7 production to feasible gamma-ray observations.

  14. Involvement of central alpha1- and alpha2-adrenoceptors on cardiovascular responses to moxonidine.

    Science.gov (United States)

    Moreira, Thiago S; Takakura, Ana C; Menani, José V; Colombari, Eduardo

    2007-06-01

    In the present study we compared the effects produced by moxonidine (alpha2-adrenoceptor/imidazoline agonist) injected into the 4th cerebral ventricle and into the lateral cerebral ventricle on mean arterial pressure, heart rate and on renal, mesenteric and hindquarter vascular resistances, as well as the possible action of moxonidine on central alpha1- or alpha2-adrenoceptors to produce cardiovascular responses. Male Holtzman rats (n=7-8) anesthetized with urethane (0.5 g/kg, intravenously-i.v.) and alpha-chloralose (60 mg/kg, i.v.) were used. Moxonidine (5, 10 and 20 nmol) injected into the 4th ventricle reduced arterial pressure (-19+/-5, -30+/-7 and -43+/-8 mmHg vs. vehicle: 2+/-4 mmHg), heart rate (-10+/-6, -16+/-7 and -27+/-9 beats per minute-bpm, vs. vehicle: 4+/-5 bpm), and renal, mesenteric and hindquarter vascular resistances. Moxonidine (5, 10 and 20 nmol) into the lateral ventricle only reduced renal vascular resistance (-77+/-17%, -85+/-13%, -89+/-10% vs. vehicle: 3+/-4%), without changes on arterial pressure, heart rate and mesenteric and hindquarter vascular resistances. Pre-treatment with the selective alpha2-adrenoceptor antagonist yohimbine (80, 160 and 320 nmol) injected into the 4th ventricle attenuated the hypotension (-32+/-5, -25+/-4 and -12+/-6 mmHg), bradycardia (-26+/-11, -23+/-5 and -11+/-6 bpm) and the reduction in renal, mesenteric and hindquarter vascular resistances produced by moxonidine (20 nmol) into the 4th ventricle. Pre-treatment with yohimbine (320 nmol) into the lateral ventricle did not change the renal vasodilation produced by moxonidine (20 nmol) into the lateral ventricle. The alpha1-adrenoceptor antagonist prazosin (320 nmol) injected into the 4th ventricle did not affect the cardiovascular effects of moxonidine. However, prazosin (80, 160 and 320 nmol) into the lateral ventricle abolished the renal vasodilation (-17+/-4, -6+/-9 and 2+/-11%) produced by moxonidine. The results indicate that the decrease in renal vascular

  15. R-matrix and K-matrix analysis of elastic $\\alpha - \\alpha$ scattering

    CERN Document Server

    Humblet, J; Langanke, K

    1998-01-01

    The R- and K-matrix parametrizations are analyzed and compared for the elastic alpha-alpha scattering at center-of-mass energies below 40 MeV. The two parametrizations differ in their definitions of the resonance energy which can lead to quite different results. The physical values of the best-fit parameters are compared with those computed for a potential model. The existence of a broad resonance near 9 MeV is not supported by the data or by the potential model. We discuss the positive and negative aspects for both parametrizations.

  16. Pharmacological profiles of a novel alpha 1-adrenoceptor agonist, PNO-49B, at alpha 1-adrenoceptor subtypes.

    Science.gov (United States)

    Muramatsu, I; Ohmura, T; Kigoshi, S

    1995-01-01

    The effects of a newly synthesized compound, PNO-49B, (R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide hydrochloride, on alpha 1-adrenoceptor subtypes were examined in various tissues in which the following distribution of alpha 1-adrenoceptor subtypes has been suggested: dog carotid artery (alpha 1B), dog mesenteric artery (alpha 1N), rabbit thoracic aorta (alpha 1B + alpha 1L), rat liver (alpha 1B), rat vas deferens (alpha 1A + alpha 1L), rat cerebral cortex (alpha 1A + alpha 1B) and rat thoracic aorta (controversial subtype). PNO-49B (0.1-100 microM) produced concentration-dependent contractions in dog mesenteric artery, rabbit thoracic aorta, rat thoracic aorta and rat vas deferens; and the maximal amplitudes of contraction were almost the same as or slightly less than those of noradrenaline. By contrast, the maximal response to PNO-49B in dog carotid artery was markedly smaller than the response to noradrenaline. In rabbit thoracic aorta, the contractile response to PNO-49B was not affected by inactivation of the alpha 1B subtype with chloroethylclonidine (CEC), although the response to noradrenaline was attenuated by that treatment. The dissociation constants (KA) of PNO-49B were not different among the rat thoracic aorta, dog carotid and mesenteric arteries and rabbit thoracic aorta (CEC-pretreated). The contractile responses to PNO-49B were inhibited competitively by prazosin, HV723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)-ethyl)- amino(propyl)benzeneacetonitrile fumarate) and by WB4101 (2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4- benzodioxane).(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Proteasomal degradation of TRIM5alpha during retrovirus restriction.

    Directory of Open Access Journals (Sweden)

    Christopher James Rold

    2008-05-01

    Full Text Available The host protein TRIM5alpha inhibits retroviral infection at an early post-penetration stage by targeting the incoming viral capsid. While the detailed mechanism of restriction remains unclear, recent studies have implicated the activity of cellular proteasomes in the restriction of retroviral reverse transcription imposed by TRIM5alpha. Here, we show that TRIM5alpha is rapidly degraded upon encounter of a restriction-susceptible retroviral core. Inoculation of TRIM5alpha-expressing human 293T cells with a saturating level of HIV-1 particles resulted in accelerated degradation of the HIV-1-restrictive rhesus macaque TRIM5alpha protein but not the nonrestrictive human TRIM5alpha protein. Exposure of cells to HIV-1 also destabilized the owl monkey restriction factor TRIMCyp; this was prevented by addition of the inhibitor cyclosporin A and was not observed with an HIV-1 virus containing a mutation in the capsid protein that relieves restriction by TRIMCyp IVHIV. Likewise, human TRIM5alpha was rapidly degraded upon encounter of the restriction-sensitive N-tropic murine leukemia virus (N-MLV but not the unrestricted B-MLV. Pretreatment of cells with proteasome inhibitors prevented the HIV-1-induced loss of both rhesus macaque TRIM5alpha and TRIMCyp proteins. We also detected degradation of endogenous TRIM5alpha in rhesus macaque cells following HIV-1 infection. We conclude that engagement of a restriction-sensitive retrovirus core results in TRIM5alpha degradation by a proteasome-dependent mechanism.

  18. Alpha-resonance structure in $^{11}$C studied via resonant scattering of $^{7}$Be+$\\alpha$ and $^{7}$Be($\\alpha$, $p$) reaction

    CERN Document Server

    Yamaguchi, H; Wakabayashi, Y; Kubono, S; Hashimoto, T; Hayakawa, S; Kawabata, T; Iwasa, N; Teranishi, T; Kwon, Y K; Binh, D N; Khiem, L H; Duy, N N

    2012-01-01

    The resonance structure in $^{11}$C is particularly of interest with regard to the astrophysical $^{7}$Be($\\alpha$, $\\gamma$) reaction, relevant at high temperature, and to the $\\alpha$-cluster structure in $^{11}$C. The measurement was to determine unknown resonance parameters for the high excited states of $^{11}$C. In particular, the $\\alpha$ decay width can be useful information to discuss $\\alpha$ cluster structure in $^{11}$C. New measurements of the $^{7}$Be+$\\alpha$ resonant scattering and the $^{7}$Be($\\alpha$, $p$)$^{10}$B reaction in inverse kinematics were performed for center-of-mass energy up to 5.5 MeV, and the resonances at excitation energies of 8.9--12.7 MeV in the compound $^{11}$C nucleus were studied. Inelastic scattering of $^{7}$Be+$\\alpha$ and the $^{7}$Be($\\alpha$, $p_1$)$^{10}$B$^*$ reaction were also studied with a simultaneous $\\gamma$-ray measurement. The measurements were performed at the low-energy RI beam facility CRIB (CNS Radioactive Ion Beam separator) of the Center for Nucl...

  19. Lyman-alpha observations of astrospheres

    CERN Document Server

    Linsky, Jeffrey L

    2014-01-01

    Charge-exchange reactions between outflowing stellar wind protons and interstellar neutral hydrogen atoms entering a stellar astrosphere produce a region of piled-up-decelerated neutral hydrogen called the hydrogen wall. Absorption by this gas, which is observed in stellar Lyman-alpha emission lines, provides the only viable technique at this time for measuring the mass-loss rates of F-M dwarf stars. We describe this technique, present an alternative way for understanding the relation of mass-loss rate with X-ray emission, and identify several critical issues.

  20. Towards Antihydrogen Trapping and Spectroscopy at ALPHA

    CERN Document Server

    Butler, Eoin; Ashkezari, Mohammad D; Baquero-Ruiz, Marcelo; Bertsche, William; Bowe, Paul D; Bray, Crystal C; Cesar, Claudio L; Chapman, Steven; Charlton, Michael; Fajans, Joel; Friesen, Tim; Fujiwara, Makoto C; Gill, David R; Hangst, Jeffrey S; Hardy, Walter N; Hayano, Ruyugo S; Hayden, Michael E; Humphries, Andrew J; Hydomako, Richard; Jonsell, Svante; Kurchaninov, Leonid; Lambo, Ricardo; Madsen, Niels; Menary, Scott; Nolan, Paul; Olchanski, Konstantin; Olin, Art; Povilus, Alexander; Pusa, Petteri; Robicheaux, Francis; Sarid, Eli; Silveira, Daniel M; So, Chukman; Storey, James W; Thompson, Robert I; van der Werf, Dirk P; Wilding, Dean; Wurtele, Jonathan S; Yamazaki, Yasunori

    2011-01-01

    Spectroscopy of antihydrogen has the potential to yield high-precision tests of the CPT theorem and shed light on the matter-antimatter imbalance in the Universe. The ALPHA antihydrogen trap at CERN's Antiproton Decelerator aims to prepare a sample of antihydrogen atoms confined in an octupole-based Ioffe trap and to measure the frequency of several atomic transitions. We describe our techniques to directly measure the antiproton temperature and a new technique to cool them to below 10 K. We also show how our unique position-sensitive annihilation detector provides us with a highly sensitive method of identifying antiproton annihilations and effectively rejecting the cosmic-ray background.

  1. Alpha Channeling in a Rotating Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Abraham J. Fetterman and Nathaniel J. Fisch

    2008-09-23

    The wave-particle α-channeling effect is generalized to include rotating plasma. Specifically, radio frequency waves can resonate with α particles in a mirror machine with E × B rotation to diffuse the α particles along constrained paths in phase space. Of major interest is that the α-particle energy, in addition to amplifying the RF waves, can directly enhance the rotation energy which in turn provides additional plasma confinement in centrifugal fusion reactors. An ancillary benefit is the rapid removal of alpha particles, which increases the fusion reactivity.

  2. Alpha decay from fission isomeric states

    Energy Technology Data Exchange (ETDEWEB)

    Poenaru, D.N.; Ivascu, M. (Institutul de Fizica si Inginerie Nucleara, Bucharest (Romania))

    1981-07-01

    Alpha-decay half-lives from shape isomeric states of some even-even isotopes of U, Pu and Cm nuclei are calculated by using fission theory in the parametrisation of a spheroid intersected with a sphere. The potential barrier was calculated in the framework of the liquid-drop model of Myers and Swiatecki (Art. Fys.; 36: 343 (1967)) extended for systems with different charge densities; a phenomenological shell correction was introduced. The WKB computed lifetimes are many orders of magnitude longer than that of the spontaneous fission process, in agreement with experimental results.

  3. Alpha particle collective Thomson scattering in TFTR

    Energy Technology Data Exchange (ETDEWEB)

    Machuzak, J.S.; Woskov, P.P.; Rhee, D.Y.; Gilmore, J. [Massachusetts Inst. of Tech., Cambridge, MA (United States). Plasma Fusion Center; Bretz, N.L.; Park, H.K. [Princeton Univ., NJ (United States). Plasma Physics Lab.; Aamodt, R.E.; Cheung, P.Y.; Russell, D.A. [Lodestar Research Corp., Boulder, CO (United States); Bindslev, H. [JET Joint Undertaking, Abingdon (United Kingdom)

    1993-11-01

    A collective Thomson scattering diagnostic is being implemented on TFTR to measure alpha particle, energetic and thermal ion densities and velocity distributions. A 60 GHz, 0.1-1 kW gyrotron will be used as the transmitter source, and the scattering geometry will be perpendicular to the magnetic field in the extraordinary mode polarization. An enhanced scattered signal is anticipated from fluctuations in the lower hybrid frequency range with this scattering geometry. Millimeter wave collective Thomson scattering diagnostics have the advantage of larger scattering angles to decrease the amount of stray light, and long, high power, modulated pulses to obtain improved signal to noise through synchronous detection techniques.

  4. Clinical significance of human alpha-fetoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Yachnin, S.

    1978-01-01

    Deviations from the normal of alpha-fetoprotein (AFP) concentrations in fetal serum, amniotic fluid, maternal serum and adult human serum can be explained by understanding the normal physiology and the pathophysiology of AFP synthesis and metabolism. AFP is the prototype of oncofetal markers. Emphasis is given to the usefulness of elevated serum AFP levels in the diagnosis and management of primary hepatomas and tumors of germ cell origin. The ability to detect neural tube defects early in gestation by monitoring maternal serum and amniotic fluid AFP concentrations is discussed.

  5. Alpha resonant scattering for astrophysical reaction studies

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, H.; Kahl, D.; Nakao, T. [Center for Nuclear Study (CNS), University of Tokyo, RIKEN campus, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Wakabayashi, Y.; Kubano, S. [The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Hashimoto, T. [Research Center for Nuclear Physics (RCNP), Osaka University, 10-1 Mihogaoka, Ibaraki, Osaka 567-0047 (Japan); Hayakawa, S. [Istituto Nazionale Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS), Via S. Sofia 62, 95125 Catania (Italy); Kawabata, T. [Department of Physics, Kyoto University, Kita-Shirakawa, Kyoto 606-8502 (Japan); Iwasa, N. [Department of Physics, Tohoku University, Aoba, Sendai, Miyagi 980-8578 (Japan); Teranishi, T. [Department of Physics, Kyushu University, 6-10-1 Hakozaki, Fukuoka 812-8581 (Japan); Kwon, Y. K. [Institute for Basic Science, 70, Yuseong-daero 1689-gil, Yuseong-gu, Daejeon 305-811 (Korea, Republic of); Binh, D. N. [30 MeV Cyclotron Center, Tran Hung Dao Hospital, Hoan Kiem District, Hanoi (Viet Nam); Khiem, L. H.; Duy, N. G. [Institute of Physics, Vietnam Academy of Science and Technology, 18 Hong Quoc Viet, Nghia do, Hanoi (Viet Nam)

    2014-05-02

    Several alpha-induced astrophysical reactions have been studied at CRIB (CNS Radioactive Ion Beam separator), which is a low-energy RI beam separator at Center for Nuclear Study (CNS) of the University of Tokyo. One of the methods to study them is the α resonant scattering using the thick-target method in inverse kinematics. Among the recent studies at CRIB, the measurement of {sup 7}Be+α resonant scattering is discussed. Based on the result of the experiment, we evaluated the contributions of high-lying resonances for the {sup 7}Be(α,γ) reaction, and proposed a new cluster band in {sup 11}C.

  6. H$\\alpha$ kinematics of KPG 390

    CERN Document Server

    Repetto, P; Fuentes-Carrera, R Gabbasov I

    2009-01-01

    In this work we present scanning Fabry-Perot H$\\alpha$ observations of the isolated interacting galaxy pair NGC 5278/79 obtained with the PUMA Fabry-Perot interferometer. We derived velocity fields, various kinematic parameters and rotation curves for both galaxies. Our kinematical results together with the fact that dust lanes have been detected in both galaxies, as well as the analysis of surface brightness profiles along the minor axis, allowed us to determine that both components of the interacting pair are trailing spirals.

  7. Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

    Science.gov (United States)

    Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

    2004-01-16

    Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

  8. A cis-proline in alpha-hemoglobin stabilizing protein directs the structural reorganization of alpha-hemoglobin.

    Science.gov (United States)

    Gell, David A; Feng, Liang; Zhou, Suiping; Jeffrey, Philip D; Bendak, Katerina; Gow, Andrew; Weiss, Mitchell J; Shi, Yigong; Mackay, Joel P

    2009-10-23

    alpha-Hemoglobin (alphaHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with alphaHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting alphaHb to a conformation in which the heme is coordinated at both axial positions by histidine side chains (bis-histidyl coordination). Currently, the detailed mechanism by which AHSP induces structural changes in alphaHb has not been determined. Here, we present x-ray crystallography, NMR spectroscopy, and mutagenesis data that identify, for the first time, the importance of an evolutionarily conserved proline, Pro(30), in loop 1 of AHSP. Mutation of Pro(30) to a variety of residue types results in reduced ability to convert alphaHb. In complex with alphaHb, AHSP Pro(30) adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in alphaHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the alphaHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of alphaHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops.

  9. On the Relative Ages of the $\\alpha$-Rich and $\\alpha$-Poor Stellar Populations in the Galactic Halo

    CERN Document Server

    Hawkins, Keith; Gilmore, Gerry; Masseron, Thomas

    2014-01-01

    We study the ages of $\\alpha$-rich and $\\alpha$-poor stars in the halo using a sample of F and G dwarfs from the Sloan Digital Sky Survey (SDSS). To separate stars based on [$\\alpha$/Fe], we have developed a new semi-empirical spectral-index based method and applied it to the low-resolution, moderate signal-to-noise SDSS spectra. The method can be used to estimate the [$\\alpha$/Fe] directly providing a new and widely applicable way to estimate [$\\alpha$/Fe] from low-resolution spectra. We measured the main-sequence turnoff temperature and combined it with the metallicities and a set of isochrones to estimate the age of the $\\alpha$-rich and $\\alpha$-poor populations in our sample. We found all stars appear to be older than 8 Gyr confirming the idea that the Galactic halo was formed very early on. A bifurcation appears in the age-metallicity relation such that in the low metallicity regime the $\\alpha$-rich and $\\alpha$-poor populations are coeval while in the high metallicity regime the $\\alpha$-rich populati...

  10. Immunostimulatory effects of natural human interferon-alpha (huIFN-alpha) on carps Cyprinus carpio L.

    Science.gov (United States)

    Watanuki, Hironobu; Chakraborty, Gunimala; Korenaga, Hiroki; Kono, Tomoya; Shivappa, R B; Sakai, Masahiro

    2009-10-15

    Human interferon-alpha (huIFN-alpha) is an important immunomodulatory substance used in the treatment and prevention of numerous infectious and immune-related diseases in animals. However, the immunostimulatory effects of huIFN-alpha in fish remain to be investigated. In the current study, the immune responses of the carp species Cyprinus carpio L. to treatment with huIFN-alpha were analyzed via measurement of superoxide anion production, phagocytic activity and the expression of cytokine genes including interleukin-1beta, tumor necrosis factor-alpha and interleukin 10. Low doses of huIFN-alpha were administered orally once a day for 3 days, and sampling was carried out at 1, 3 and 5 days post-treatment. Our results indicate that a low dose of huIFN-alpha significantly increased phagocytic activity and superoxide anion production in the carp kidney. The huIFN-alpha-treated fish also displayed a significant upregulation in cytokine gene expression. The current study demonstrates the stimulatory effects of huIFN-alpha on the carp immune system and highlights the immunomodulatory role of huIFN-alpha in fish.

  11. Stochastic model error in the LANS-alpha and NS-alpha deconvolution models of turbulence

    CERN Document Server

    Olson, Eric

    2015-01-01

    This paper reports on a computational study of the model error in the LANS-alpha and NS-alpha deconvolution models of homogeneous isotropic turbulence. The focus is on how well the model error may be characterized by a stochastic force. Computations are also performed for a new turbulence model obtained as a rescaled limit of the deconvolution model. The technique used is to plug a solution obtained from direct numerical simulation of the incompressible Navier--Stokes equations into the competing turbulence models and to then compute the time evolution of the resulting residual. All computations have been done in two dimensions rather than three for convenience and efficiency. When the effective averaging length scale in any of the models is $\\alpha_0=0.01$ the time evolution of the root-mean-squared residual error grows as $\\sqrt t$. This growth rate is consistent with the hypothesis that the model error may be characterized by a stochastic force. When $\\alpha_0=0.20$ the residual error grows linearly. Linea...

  12. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein

    Science.gov (United States)

    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David

    2016-09-01

    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

  13. An alpha particle instrument with alpha, proton, and X-ray modes for planetary chemical analyses

    Science.gov (United States)

    Economou, T. E.; Turkevich, A. L.

    1976-01-01

    The interaction of alpha particles with matter is employed in a compact instrument that could provide rather complete in-situ chemical analyses of surfaces and thin atmospheres of extraterrestrial bodies. The instrument is a miniaturized and improved version of the Surveyor lunar instrument. The backscattering of alpha particles and (alpha, p) reactions provide analytical data on the light elements (carbon-iron). An X-ray mode that detects the photons produced by the alpha sources provides sensitivity and resolution for the chemical elements heavier than about silicon. The X-rays are detected by semiconductor detectors having a resolution between 150 and 250 eV at 5.9 keV. Such an instrument can identify and determine with good accuracy 99 percent of the atoms (except hydrogen) in rocks. For many trace elements, the detecting sensitivity is a few ppm. Auxiliary sources could be used to enhance the sensitivities for elements of special interest. The instrument could probably withstand the acceleration involved in semi-hard landings.

  14. Tumor Necrosis Factor alpha (TNF{alpha}) regulates CD40 expression through SMAR1 phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kamini; Sinha, Surajit; Malonia, Sunil Kumar; Chattopadhyay, Samit, E-mail: samit@nccs.res.in

    2010-01-08

    CD40 plays an important role in mediating inflammatory response and is mainly induced by JAK/STAT phosphorylation cascade. TNF{alpha} is the key cytokine that activates CD40 during inflammation and tumorigenesis. We have earlier shown that SMAR1 can repress the transcription of Cyclin D1 promoter by forming a HDAC1 dependent repressor complex. In this study, we show that SMAR1 regulates the transcription of NF-{kappa}B target gene CD40. SMAR1 recruits HDAC1 and forms a repressor complex on CD40 promoter and keeps its basal transcription in check. Further, we show that TNF{alpha} stimulation induces SMAR1 phosphorylation at Ser-347 and promotes its cytoplasmic translocation, thus releasing its negative effect. Concomitantly, TNF{alpha} induced phosphorylation of STAT1 at Tyr-701 by JAK1 facilitates its nuclear translocation and activation of CD40 through p300 recruitment and core Histone-3 acetylation. Thus, TNF{alpha} mediated regulation of CD40 expression occurs by dual phosphorylation of SMAR1 and STAT1.

  15. Workshop on High-precision $\\alpha_s$ measurements from LHC to FCC-ee

    CERN Document Server

    S. Alekhin; d'Enterria, David; A. Banfi; S. Bethke; J. Blümlein; K.G. Chetyrkin; D. d’Enterria; G. Dissertori; X. Garcia i Tormo; A. H. Hoang; M. Klasen; T. Klijnsma; S. Kluth; J.-L. Kneur; B.A. Kniehl; D. W. Kolodrubetz; J. Kühn; P. Mackenzie; B. Malaescu; V. Mateu; L. Mihaila; S. Moch; K. Mönig; R. Pérez-Ramos; A. Pich; J. Pires; K. Rabbertz; G. P. Salam; F. Sannino; J. Soto i Riera; M. Srebre; I. W. Stewart

    2015-01-01

    This document provides a writeup of all contributions to the workshop on "High precision measurements of $\\alpha_s$: From LHC to FCC-ee" held at CERN, Oct. 12--13, 2015. The workshop explored in depth the latest developments on the determination of the QCD coupling $\\alpha_s$ from 15 methods where high precision measurements are (or will be) available. Those include low-energy observables: (i) lattice QCD, (ii) pion decay factor, (iii) quarkonia and (iv) $\\tau$ decays, (v) soft parton-to-hadron fragmentation functions, as well as high-energy observables: (vi) global fits of parton distribution functions, (vii) hard parton-to-hadron fragmentation functions, (viii) jets in $e^\\pm$p DIS and $\\gamma$-p photoproduction, (ix) photon structure function in $\\gamma$-$\\gamma$, (x) event shapes and (xi) jet cross sections in $e^+e^-$ collisions, (xii) W boson and (xiii) Z boson decays, and (xiv) jets and (xv) top-quark cross sections in proton-(anti)proton collisions. The current status of the theoretical and experiment...

  16. Increased sensitivity to interferon-alpha in psoriatic T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Lovato, Paola; Skov, Lone

    2005-01-01

    disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers......Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important...... role in host defense against infections, but recent data have also implicated IFN-alpha in psoriasis. Thus, IFN-alpha induces or aggravates psoriasis in some patients, and mice lacking a transcriptional attenuator of IFN-alpha/beta signaling spontaneously develop a psoriasis-like inflammatory skin...

  17. CMB and reheating constraints to \\alpha-attractor inflationary models

    CERN Document Server

    Eshaghi, Mehdi; Riazi, Nematollah; Kiasatpour, Ahmad

    2016-01-01

    After Planck 2013, a broad class of inflationary models called \\alpha-attractors was developed which has universal observational predictions. For small values of the parameter \\alpha, the models have good consistency with the recent CMB data. In this work, we first calculate analytically (and verify numerically) the predictions of these models for spectral index, n_s and tensor-to-scalar ratio, r and then using BICEP2/Keck 2015 data we impose constraints on \\alpha-attractors. Then, we study the reheating in \\alpha-attractors. The reheating temperature, T_{re} and the number of e-folds during reheating, N_{re} are calculated as functions of n_s. Using these results, we determine the range of free parameter \\alpha for two clasees of \\alpha-attractors which satisfy the constraints of recent CMB data.

  18. [Bifunctional inhibitor of alpha-amylase/trypsin from wheat grain].

    Science.gov (United States)

    Islamov, R A; Furusov, O V

    2007-01-01

    A trypsin inhibitor, isolated from whole-wheat grain (Triticum aestivum L.) by the method of bio-specific chromatography on trypsin-Sepharose, was potent in inhibiting human salivary alpha-amylase. The bi-functional alpha-amylase/trypsin inhibitor was characterized by a narrow specificity for other alpha-amylases and proteinases. The high thermostability of the inhibitor was lost in the presence of SH group-reducing agents. The inhibitor-trypsin complex retained its activity against alpha-amylase. The inhibitor-alpha-amylase complex was active against trypsin. Studies of the enzyme kinetics demonstrated that the inhibition of alpha-amylase and trypsin was noncompetitive. Our results suggest the existence of two independent active sites responsible for the interaction with the enzymes.

  19. H$\\alpha$ and EUV observations of a partial CME

    CERN Document Server

    Christian, Damian J; Antolin, Patrick; Mathioudakis, Mihalis

    2015-01-01

    We have obtained H$\\alpha$ high spatial and time resolution observations of the upper solar chromosphere and supplemented these with multi-wavelength observations from the Solar Dynamic Observatory (SDO) and the {\\it Hinode} ExtremeUltraviolet Imaging Spectrometer (EIS). The H$\\alpha$ observations were conducted on 11 February 2012 with the Hydrogen-Alpha Rapid Dynamics Camera (HARDcam) instrument at the National Solar Observatory's Dunn Solar Telescope. Our H$\\alpha$ observations found large downflows of chromospheric material returning from coronal heights following a failed prominence eruption. We have detected several large condensations ("blobs") returning to the solar surface at velocities of $\\approx$200 km s$^{-1}$ in both H$\\alpha$ and several SDO AIA band passes. The average derived size of these "blobs" in H$\\alpha$ is 500 by 3000 km$^2$ in the directions perpendicular and parallel to the direction of travel, respectively. A comparison of our "blob" widths to those found from coronal rain, indicate...

  20. Characterizing Lyman Alpha Scattering in Nearby Galaxies

    Science.gov (United States)

    Bridge, Joanna; Hayes, Matthew; Melinder, Jens; Östlin, Göran; Gronwall, Caryl

    2017-01-01

    The hydrogen emission line of Lyman alpha (Lyα) has long been recognized as key to studying high redshift star-forming galaxies. However, due to the resonance of the emission line, the path that a Lyα photon takes from emission to eventual escape from the galaxy is essentially a mystery. This scattering poses a problem for using Lyα as a key emission feature of galaxies because it results in Lyα not being observed in all star-forming galaxies, and, in galaxies where it is observed, the place where the photon is originally emitted and where it is observed are two very different things. We discuss here how the Lyman-Alpha Reference Sample (LARS) provides a unique sample of 14 nearby (0.02 Space Telescope imaging. We compare the Lyα/Hα ratios with those expected from pure dust attenuation models, finding that in some cases significant positive departures are found on small scales, consistent with geometrical effects being important on sizes comparable to the HII regions. We then develop a simple scattering model in which we are able to estimate the average path length a Lyα photon travels with respect to non-resonant radiation, and quantifiy the excess dust optical depth to which Lyα radiation may be susceptible.

  1. GHRS Observations of the Lyman $\\alpha$ Forest

    CERN Document Server

    Morris, S L

    1996-01-01

    I review the results obtained using the GHRS on low redshift Lyman alpha absorbers. Until the advent of HST and the GHRS, the existence of such absorbers was doubted. The confirmation of their existence, in one of the first GHRS GTO team results to be published, must rank as one of the HSTs most interesting results. The GHRS resolution allows us to probe equivalent widths well below those detectable with the FOS, and has led to a number of interesting new questions. One example is the apparent disagreement between the GHRS result that there are many Lyman alpha absorbers which are not associated with luminous galaxies, and FOS studies which suggest that all such absorbers have a nearby galaxy causing them. This almost certainly shows that the equivalent width (or column density) range reachable by the GHRS includes gas from a wide range of causes, and not only the halos of luminous galaxies. With these data, we are seeing the debris left over from Galaxy formation, material flung out from galaxy interactions ...

  2. MFTF-. cap alpha. + T progress report

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, W.D. (ed.)

    1985-04-01

    Early in FY 1983, several upgrades of the Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) were proposed to the fusion community. The one most favorably received was designated MFTF-..cap alpha..+T. The engineering design of this device, guided by LLNL, has been a principal activity of the Fusion Engineering Design Center during FY 1983. This interim progress report represents a snapshot of the device design, which was begun in FY 1983 and will continue for several years. The report is organized as a complete design description. Because it is an interim report, some parts are incomplete; they will be supplied as the design study proceeds. As described in this report, MFTF-..cap alpha..+T uses existing facilities, many MFTF-B components, and a number of innovations to improve on the physics parameters of MFTF-B. It burns deuterium-tritium and has a central-cell Q of 2, a wall loading GAMMA/sub n/ of 2 MW/m/sup 2/ (with a central-cell insert module), and an availability of 10%. The machine is fully shielded, allows hands-on maintenance of components outside the vacuum vessel 24 h after shutdown, and has provisions for repair of all operating components.

  3. Oral phentolamine: an alpha-1, alpha-2 adrenergic antagonist for the treatment of erectile dysfunction.

    Science.gov (United States)

    Goldstein, I

    2000-03-01

    Phentolamine mesylate is an alpha-1 and alpha-2 selective adrenergic receptor antagonist which has undergone clinical trials for erectile dysfunction treatment. Biochemical and physiological studies in human erectile tissue have revealed a high affinity of phentolamine for alpha-1 and alpha-2 adrenergic receptors. Based on pharmacokinetic studies, it is suggested that 30-40 min following oral ingestion of 40 or 80 mg of phentolamine (Vasomax), the mean plasma phentolamine concentrations are sufficient to occupy the alpha-1 and -2 adrenergic receptors in erectile tissue and thereby result in inhibition of adrenergic-mediated physiologic activity. In large multi-center, placebo-controlled pivotal phase III clinical trials, the mean change in the erectile function domain of the International Index of Erectile Function scores (Questions 1-5 and 15) from screening to the end of treatment was significantly higher following use of active drug (40 mg and 80 mg) compared to placebo. Three to four times as many patients receiving phentolamine reported being satisfied or very satisfied compared with those receiving placebo. At doses of 40 mg and 80 mg respectively, 55% and 59% of men were able to achieve vaginal penetration with 51% and 53% achieving penetration on 75% of attempts. The correction of erectile dysfunction or improvement to a less severe category of dysfunction was experienced by 53% of men with the 80 mg dose and 40% with the 40 mg dose of phentolamine. All trends of response were the same regardless of any concomitant medication. There were no severe adverse events. At 40 mg, 7.7% experienced rhinitis and fewer than 3.1% experienced any other side effect of treatment. Phentolamine is safe, well tolerated and efficacious for the treatment of erectile dysfunction.

  4. Waves for Alpha-Channeling in Mirror Machines

    Energy Technology Data Exchange (ETDEWEB)

    A. I. Zhmoginov and N. J. Fisch

    2009-07-08

    Alpha-channeling can, in principle, be implemented in mirror machines via exciting weaklydamped modes in the ion cyclotron frequency range with perpendicular wavelengths smaller than the alpha particle gyroradius. Assuming quasi-longitudinal or quasi-transverse wave propagation, we search systematically for suitable modes in mirror plasmas. Considering two device designs, a proof-of-principle facility and a fusion rector prototype, we in fact identify candidate modes suitable for alpha-channeling.

  5. Context based Coding of Quantized Alpha Planes for Video Objects

    DEFF Research Database (Denmark)

    Aghito, Shankar Manuel; Forchhammer, Søren

    2002-01-01

    In object based video, each frame is a composition of objects that are coded separately. The composition is performed through the alpha plane that represents the transparency of the object. We present an alternative to MPEG-4 for coding of alpha planes that considers their specific properties....... Comparisons in terms of rate and distortion are provided, showing that the proposed coding scheme for still alpha planes is better than the algorithms for I-frames used in MPEG-4....

  6. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    Energy Technology Data Exchange (ETDEWEB)

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  7. Sourcing Dark Matter and Dark Energy from $\\alpha$-attractors

    OpenAIRE

    Mishra, Swagat S.; Sahni, Varun; Shtanov, Yuri(Department of Physics, Taras Shevchenko National University, Kiev, Ukraine)

    2017-01-01

    Recently, Kallosh and Linde have drawn attention to a new family of superconformal inflationary potentials, subsequently called $\\alpha$-attractors. The $\\alpha$-attractor family can interpolate between a large class of inflationary models. It also has an important theoretical underpinning within the framework of supergravity. We demonstrate that the $\\alpha$-attractors have an even wider appeal since they may describe dark matter and perhaps even dark energy. The dark matter associated with ...

  8. Scintillation of thin tetraphenyl butadiene films under alpha particle excitation

    Energy Technology Data Exchange (ETDEWEB)

    Pollmann, Tina, E-mail: tina@owl.phy.queensu.c [Department of Physics, Engineering Physics, and Astronomy, Queens University, Kingston, Ontario, K7L 3N6 (Canada); Boulay, Mark; Kuzniak, Marcin [Department of Physics, Engineering Physics, and Astronomy, Queens University, Kingston, Ontario, K7L 3N6 (Canada)

    2011-04-11

    The alpha induced scintillation of the wavelength shifter 1,1,4,4-tetraphenyl-1,3-butadiene (TPB) was studied to improve the understanding of possible surface alpha backgrounds in the DEAP dark matter search experiment. We found that vacuum deposited thin TPB films emit 882{+-}210 photons per MeV under alpha particle excitation. The scintillation pulse shape consists of a double exponential decay with lifetimes of 11{+-}5 and 275{+-}10ns.

  9. alpha-synuclein and LRRK2: partners in crime.

    Science.gov (United States)

    Tong, Youren; Shen, Jie

    2009-12-24

    In this issue of Neuron, Lin et al. report that LRRK2 modulates age-related neurodegeneration caused by overexpression of alpha-synuclein in the forebrain of transgenic mice. Overexpression of LRRK2 accelerates the progression of alpha-synuclein-mediated neuropathological changes, whereas deletion of LRRK2 alleviates these alterations. The results reveal an interesting interaction between alpha-synuclein and LRRK2, two gene products linked to dominantly inherited Parkinson's disease.

  10. Evidence for Alpha Receptors in the Human Ureter

    Science.gov (United States)

    Madeb, Ralph; Knopf, Joy; Golijanin, Dragan; Bourne, Patricia; Erturk, Erdal

    2007-04-01

    An immunohistochemical and western blot expression analysis of human ureters was performed in order to characterize the alpha-1-adrenergic receptor distribution along the length of the human ureteral wall. Mapping the distribution will assist in understanding the potential role alpha -1-adrenergic receptors and their subtype density might have in the pathophysiology of ureteral colic and stone passage. Patients diagnosed with renal cancer or bladder cancer undergoing nephrectomy, nephroureterectomy, or cystectomy had ureteral specimens taken from the proximal, mid, distal and tunneled ureter. Tissues were processed for fresh frozen examination and fixed in formalin. None of the ureteral specimens were involved with cancer. Serial histologic sections and immunohistochemical studies were performed using antibodies specific for alpha-1-adrenergic receptor subtypes (alpha 1a, alpha 1b, alpha 1d). The sections were examined under a light microscope and scored as positive or negative. In order to validate and quantify the alpha receptor subtypes along the human ureter. Western blotting techniques were applied. Human ureter stained positively for alpha -1-adrenergic receptors. Immunostaining appeared red, with intense reaction in the smooth muscle of the ureter and endothelium of the neighboring blood vessels. There was differential expression between all the receptors with the highest staining for alpha-1D subtype. The highest protein expression for all three subtypes was in the renal pelvis and decreased with advancement along the ureter to the distal ureter. At the distal ureter, there was marked increase in expression as one progressed towards the ureteral orifice. The same pattern of protein expression was exhibited for all three alpha -1-adrenergic receptor subtypes. We provide preliminary evidence for the ability to detect and quantify the alpha-1-receptor subtypes along the human ureter which to the best of our knowledge has never been done with

  11. Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: Evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin.

    Science.gov (United States)

    Kawataki, Tomoyuki; Yamane, Tetsu; Naganuma, Hirofumi; Rousselle, Patricia; Andurén, Ingegerd; Tryggvason, Karl; Patarroyo, Manuel

    2007-11-01

    Glioma cell infiltration of brain tissue often occurs along the basement membrane (BM) of blood vessels. In the present study we have investigated the role of laminins, major structural components of BMs and strong promoters of cell migration. Immunohistochemical studies of glioma tumor tissue demonstrated expression of alpha2-, alpha3-, alpha4- and alpha5-, but not alpha1-, laminins by the tumor vasculature. In functional assays, alpha3 (Lm-332/laminin-5)- and alpha5 (Lm-511/laminin-10)-laminins strongly promoted migration of all glioma cell lines tested. alpha1-Laminin (Lm-111/laminin-1) displayed lower activity, whereas alpha2 (Lm-211/laminin-2)- and alpha4 (Lm-411/laminin-8)-laminins were practically inactive. Global integrin phenotyping identified alpha3beta1 as the most abundant integrin in all the glioma cell lines, and this laminin-binding integrin exclusively or largely mediate the cell migration. Moreover, pretreatment of U251 glioma cells with blocking antibodies to alpha3beta1 integrin followed by intracerebral injection into nude mice inhibited invasion of the tumor cells into the brain tissue. The cell lines secreted Lm-211, Lm-411 and Lm-511, at different ratios. The results indicate that glioma cells secrete alpha2-, alpha4- and alpha5-laminins and that alpha3- and alpha5-laminins, found in brain vasculature, selectively promote glioma cell migration. They identify alpha3beta1 as the predominant integrin and laminin receptor in glioma cells, and as a brain invasion-mediating integrin.

  12. Unique copper-induced oligomers mediate alpha-synuclein toxicity.

    Science.gov (United States)

    Wright, Josephine A; Wang, Xiaoyan; Brown, David R

    2009-08-01

    Parkinson's disease and a number of other neurodegenerative diseases have been linked to either genetic mutations in the alpha-synuclein gene or show evidence of aggregates of the alpha-synuclein protein, sometimes in the form of Lewy bodies. There currently is no clear evidence of a distinct neurotoxic species of alpha-synuclein to explain the death of neurons in these diseases. We undertook to assess the toxicity of alpha-synuclein via exogenous application in cell culture. Initially, we showed that only aggregated alpha-synuclein is neurotoxic and requires the presence copper but not iron. Other members of the synuclein family showed no toxicity in any form and inherited point mutations did not alter the effective toxic concentration of alpha-synuclein. Through protein fractionation techniques, we were able to isolate an oligomeric species responsible for the toxicity of alpha-synuclein. This oligomeric species has a unique stellate appearance under EM and again, requires association with copper to induce cell death. The results allow us to suggest that the toxic species of alpha-synuclein in vivo could possibly be these stellate oligomers and not fibrils. Our data provide a link between the recently noted association of copper and alpha-synuclein and a potential role for the combination in causing neurodegeneration.

  13. The visibility of Lyman Alpha Emitters during reionization

    CERN Document Server

    Dayal, Pratika; Ferrara, Andrea

    2010-01-01

    We present the first Lyman Alpha Emitter (LAE) study that combines: (i) cosmological SPH simulations run using GADGET-2, (ii) radiative transfer simulations (CRASH), and (iii) a previously developed LAE model. This complete LAE model accounts for the intrinsic LAE Lyman Alpha/continuum luminosity, dust enrichment and Lyman Alpha transmission through the intergalactic medium (IGM), to quantify the effects of reionization, dust and velocity fields on the Lyman Alpha and UV Luminosity Functions (LF). We find that a model neglecting dust sorely fails to reproduce either the slope or the magnitude of the observed Lyman Alpha and UV LFs. Clumped dust is required to simultaneously fit the observed UV and Lyman Alpha LFs, such that the intrinsic Lyman Alpha-to-continuum luminosity is enhanced by a factor f_alpha/f_c ~ 1.5 (3.7) excluding (including) peculiar velocities. The higher value including velocity fields arises since LAEs reside in large potential wells and inflows decrease their Lyman Alpha transmission. For...

  14. alpha-thalassemia mutations in Khuzestan Province, Southwest Iran.

    Science.gov (United States)

    Zandian, Khodamorad; Nateghi, Jamal; Keikhaie, Bijan; Pedram, Mohammad; Hafezi-Nejad, Nima; Hadavi, Valeh; Oberkanins, Christian; Azarkeivan, Azita; Law, Hai-Yang; Najmabadi, Hossein

    2008-01-01

    Although alpha-thalassemia (alpha-thal) is the most common hereditary hemoglobin (Hb) disorder in Iran, no comprehensive data are so far available on the prevalence of the disease in the province of Khuzestan in Southwest Iran. This study investigates the spectrum of alpha-thal mutations in this region. One hundred and twenty-one subjects from Khuzestan Province, Iran, were initially tested for the three most common Iranian alpha-thal mutations (- alpha3.7, -alpha4.2, and --MED) by gap-polymerase chain reaction (gap-PCR). Reverse hybridization test strips and DNA sequencing were used to identify additional alpha-globin mutations. A total of 131 mutated alpha-globin alleles were identified in these patients. Of the 13 mutations that were detected in Khuzestan Province, Iran, the - alpha3.7 single gene deletion was the most frequently identified variant, representing 62.6% of the total; we also observed significant numbers of individuals with compound heterozygous mutations. On the basis of our results, we strongly recommend screening for the most common mutations to improve the molecular diagnosis of anemia in this region.

  15. Biophysical Modeling of Alpha Rhythms During Halothane-Induced Unconsciousness.

    Science.gov (United States)

    Vijayan, Sujith; Ching, ShiNung; Purdon, Patrick L; Brown, Emery N; Kopell, Nancy J

    2013-01-01

    During the induction of general anesthesia there is a shift in power from the posterior regions of the brain to the frontal cortices; this shift in power is called anteriorization. For many anesthetics, a prominent feature of anteriorization is a shift specifically in the alpha band (8-13 Hz) from posterior to frontal cortices. Here we present a biophysical computational model that describes thalamocortical circuit-level dynamics underlying anteriorization of the alpha rhythm in the case of halothane. Halothane potentiates GABAA and increases potassium leak conductances. According to our model, an increase in potassium leak conductances hyperpolarizes and silences the high-threshold thalamocortical (HTC) cells, a specialized subset of thalamocortical cells that fire at the alpha frequency at relatively depolarized membrane potentials (>-60 mV) and are thought to be the generators of quiet awake occipital alpha. At the same time the potentiation of GABAA imposes an alpha time scale on both the cortical and the thalamic component of the frontal portion of our model. The alpha activity in the frontal component is further strengthened by reciprocal thalamocortical feedback. Thus, we argue that the dual molecular targets of halothane induce the anteriorization of the alpha rhythm by increasing potassium leak conductances, which abolishes occipital alpha, and by potentiating GABAA, which induces frontal alpha. These results provide a computational modeling formulation for studying highly detailed biophysical mechanisms of anesthetic action in silico.

  16. [Extraction and properties of microcapsulated alpha-chymotrypsin].

    Science.gov (United States)

    Aĭsina, R B; Kazanskaia, N F; Lukasheva, E V; Berezin, I V

    1976-09-01

    A method of microencapsulating of the proteolytic enzyme alpha-chymotrypsin into semi-permeable nylon membranes is worked out. The membrane is a polimer of 1,6-hexamethylenediamine and sebacoyl chloride. alpha-Chymotrypsin is enclosed into the capsule together with polyethyleneimine, capable of joining the walls of microcapsules and making the membrane more stable. The optimal concentrations of polyenthyleneimine and alpha-chymotrypsin are 5% and 1% correspondingly. The highest yield of microencapsulated enzyme was obtained for completely acetylated delta-chymotrypsin. The kinetic properties of microencapsulated alpha-chymotrypsin change very slightly as compared to those of the native one.

  17. Modeling of non-stationary autoregressive alpha-stable processe

    Data.gov (United States)

    National Aeronautics and Space Administration — In the literature, impulsive signals are mostly modeled by symmetric alpha-stable processes. To represent their temporal dependencies, usually autoregressive models...

  18. Measurements of escaping alphas in the TFTR DT experiments

    Energy Technology Data Exchange (ETDEWEB)

    Zweben, S.J.; Darrow, D.S.; Herrmann, H.W.

    1995-03-01

    Alpha particle loss to the wall of TFTR has been measured during the initial TFTR DT run period. These measurements were made with the same lost alpha scintillator detector system used previously for DD fusion products, except for a switch of the scintillator material from zinc sulfide (P31) to yttrium aluminate (P46) to insure a linear response up to the maximum alpha flux expected in DT. The alpha loss signals in DT are {approx} 100 times larger than the DD fusion product loss signals, as expected from the neutron rates and the relative sensitivity to DT vs. DD fusion products.

  19. Ly$\\alpha$ and UV Sizes of Green Pea Galaxies

    CERN Document Server

    Yang, Huan; Rhoads, James E; Leitherer, Claus; Wofford, Aida; Jiang, Tianxing; Wang, Junxian

    2016-01-01

    Green Peas are nearby analogs of high-redshift Ly$\\alpha$-emitting galaxies. To probe their Ly$\\alpha$ escape, we study the spatial profiles of Ly$\\alpha$ and UV continuum emission of 24 Green Pea galaxies using the Cosmic Origins Spectrograph (COS) on Hubble Space Telescope (HST). We extract the spatial profiles of Ly$\\alpha$ emission from their 2D COS spectra, and of UV continuum from both the 2D spectra and NUV images. The Ly$\\alpha$ emission shows more extended spatial profiles than the UV continuum in most Green Peas. The deconvolved Full Width Half Maximum (FWHM) of the Ly$\\alpha$ spatial profile is about 2 to 4 times that of the UV continuum in most cases. The Ly$\\alpha$ light shows significant offsets from the UV continuum in four galaxies and central absorption in one galaxy. We also compare the spatial profiles of Ly$\\alpha$ photons at blueshifted and redshifted velocities in eight Green Peas with sufficient data quality, and find the blue wing of the Ly$\\alpha$ line has a larger spatial extent than...

  20. Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin;

    2009-01-01

    The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At.......The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At....