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Sample records for alpha 1-antitrypsin

  1. Alpha-1 Antitrypsin Test

    Science.gov (United States)

    ... helpful? Also known as: Alpha 1 -antitrypsin; A1AT; AAT Formal name: Alpha 1 Antitrypsin; α1-antitrypsin Related ... know? How is it used? Alpha-1 antitrypsin (AAT) testing is used to help diagnose alpha-1 ...

  2. How Is Alpha-1 Antitrypsin Deficiency Diagnosed?

    Science.gov (United States)

    ... Alpha-1 Antitrypsin Deficiency Diagnosed? Alpha-1 antitrypsin (AAT) deficiency usually is diagnosed after you develop a ... related to the condition. Your doctor may suspect AAT deficiency if you have signs or symptoms of ...

  3. How Is Alpha-1 Antitrypsin Deficiency Treated?

    Science.gov (United States)

    ... Alpha-1 Antitrypsin Deficiency Treated? Alpha-1 antitrypsin (AAT) deficiency has no cure, but its related lung ... pulmonary disease). If you have symptoms related to AAT deficiency, your doctor may recommend: Medicines called inhaled ...

  4. What Causes Alpha-1 Antitrypsin Deficiency?

    Science.gov (United States)

    ... this page from the NHLBI on Twitter. What Causes Alpha-1 Antitrypsin Deficiency? Alpha-1 antitrypsin (AAT) ... develop. The most common faulty gene that can cause AAT deficiency is called PiZ. If you inherit ...

  5. [Alpha-1 antitrypsin deficiency: diagnosis and treatment].

    Science.gov (United States)

    Camelier, Aquiles A; Winter, Daniel Hugo; Jardim, José Roberto; Barboza, Carlos Eduardo Galvão; Cukier, Alberto; Miravitlles, Marc

    2008-07-01

    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 implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The mutation most commonly associated with the clinical disease is the Z allele, which causes polymerization and accumulation within hepatocytes. The accumulation of and the consequent reduction in the serum levels of alpha-1 antitrypsin cause, respectively, liver and lung disease, the latter occurring mainly as early emphysema, predominantly in the lung bases. Diagnosis involves detection of low serum levels of alpha-1 antitrypsin as well as phenotypic confirmation. In addition to the standard treatment of chronic obstructive pulmonary disease, specific therapy consisting of infusion of purified alpha-1 antitrypsin is currently available. The clinical efficacy of this therapy, which appears to be safe, has yet to be definitively established, and its cost-effectiveness is also a controversial issue that is rarely addressed. Despite its importance, in Brazil, there are no epidemiological data on the prevalence of the disease or the frequency of occurrence of deficiency alleles. Underdiagnosis has also been a significant limitation to the study of the disease as well as to appropriate treatment of patients. It is hoped that the creation of the Alpha One International Registry will resolve these and other important issues. PMID:18695797

  6. Who Is at Risk for Alpha-1 Antitrypsin Deficiency?

    Science.gov (United States)

    ... for Alpha-1 Antitrypsin Deficiency? Alpha-1 antitrypsin (AAT) deficiency occurs in all ethnic groups. However, the ... most often in White people of European descent. AAT deficiency is an inherited condition. "Inherited" means the ...

  7. Immunoassay of serum alpha-1 antitrypsin level in uveitis.

    OpenAIRE

    Gupta, A K; Sarin, G. S.

    1984-01-01

    The serum alpha-1 antitrypsin level was measured in 60 patients with endogenous uveitis, 27 patients with phacoallergic endophthalmitis, 12 patients with phacolytic glaucoma, and 58 healthy subjects. Thirty-four patients with endogenous uveitis were also followed up for 6 months after treatment, and the serum alpha-1 antitrypsin level was measured again. There was a significant rise in the serum alpha-1 antitrypsin level in cases of endogenous uveitis and phacoallergic endophthalmitis but no ...

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

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    2010-01-01

    We reviewed the benefits and harms of augmentation therapy with alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency and lung disease. We searched for randomised trials comparing augmentation therapy with placebo or no treatment in PubMed and ClinicalTrials (7 January 2010). Two...

  9. Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease. People who smoke are more seriously affected and have a greater risk of dying from the disease.......Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease. People who smoke are more seriously affected and have a greater risk of dying from the disease....

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

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    2010-01-01

    We reviewed the benefits and harms of augmentation therapy with alpha-1 antitrypsin in patients with alpha-1 antitrypsin deficiency and lung disease. We searched for randomised trials comparing augmentation therapy with placebo or no treatment in PubMed and ClinicalTrials (7 January 2010). Two...... (difference 1.14 g/l; 95% confidence interval 0.14 to 2.14; p = 0.03) over the total course of the trials. Augmentation therapy with alpha-1 antitrypsin cannot be recommended in view of the lack of evidence of clinical benefit and the cost of treatment....

  11. Alpha-1 Antitrypsin and Lung Cell Apoptosis.

    Science.gov (United States)

    Serban, Karina A; Petrache, Irina

    2016-04-01

    Discovery of alpha-1 antitrypsin (A1AT) as the principal circulating inhibitor of neutrophil elastase was critical to the appreciation of protease/antiprotease imbalance involvement in the pathogenesis of emphysema. Additional targets of A1AT have been uncovered, along with their contribution to alveolar wall destruction induced by cigarette smoke exposure. We highlight in this report mechanisms of A1AT antiapoptotic effects on structural lung endothelial cells. This function was largely dependent on uptake of the protein from the circulation via clathrin- and, in part, caveolae-mediated endocytosis and on specific interactions with cysteine proteases such as capsase-3, -6, and -7. Exposures to cigarette smoke diminished A1AT intracellular uptake and its anticaspase action, suggesting that even in A1AT-suficient individuals, cigarette smoke may weaken the serpin's endothelial prosurvival effect. In addition, cigarette smoke exposure or genetic mutations known to induce posttranslational modifications such as oxidation or polymerization may alter A1AT bidirectional intracellular traffic in endothelial cells and thus determine its functional bioavailability in certain lung compartments. Uncovering and harnessing the A1AT canonical and noncanonical mechanisms will advance our understanding of the pathogenesis of emphysema and may provide means to improve the effectiveness of therapies in both A1AT-sufficient and A1AT-deficient individuals. PMID:27115949

  12. Treatment of Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Strange, Charlie; Beiko, Tatsiana

    2015-08-01

    Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that creates multiple unique phenotypes of chronic obstructive pulmonary disease. While bronchospasm, cough, dyspnea, and sputum production all occur with AATD, the phenotypic differences require a computed tomographic (CT) scan to decipher. The availability of augmentation therapy in the United States since 1989 has generated both controversy and evidence that informs the science of usual chronic obstructive pulmonary disease (COPD). Because of the predominance of emphysema in AATD, much of the best evidence concerning biomarkers of emphysema progression comes from this population. Imaging measurement of emphysema progression, impact of emphysema phenotypes on hyperinflation and dynamic hyperinflation, and correlation with traditional spirometric measures of COPD progression are required to understand the impact of AAT therapies. These studies are important for better understanding of usual COPD pathogenesis. Significantly, there are no adequately powered research studies to determine if augmentation therapy is helpful for the non-emphysema phenotypes of AATD. Specifically, phenotypes of chronic bronchitis, asthma predominant disease, and bronchiectasis will require targeted research studies to define optimal therapy. PMID:26238635

  13. Delivery of Alpha-1 Antitrypsin to Airways.

    Science.gov (United States)

    Griese, Matthias; Scheuch, Gerhard

    2016-08-01

    Treatment with exogenous alpha-1 antitrypsin (AAT), a potent serine protease inhibitor, was developed originally for chronic obstructive pulmonary disease associated with AAT deficiency; however, other lung conditions involving neutrophilic inflammation and proteolytic tissue injury related to neutrophil elastase and other serine proteases may also be considered for AAT therapy. These conditions include bronchiectasis caused by primary ciliary dyskinesia, cystic fibrosis, and other diseases associated with an increased free elastase activity in the airways. Inhaled AAT may be a viable option to counteract proteolytic tissue damage. This form of treatment requires efficient drug delivery to the targeted pulmonary compartment. Aerosol technology meeting this requirement is currently available and offers an alternative therapeutic approach to systemic AAT administration. To date, early studies in humans have shown biochemical efficacy and have established the safety of inhaled AAT. However, to bring aerosol AAT therapy to patients, large phase 3 protocols in carefully selected patient populations (i.e., subgroups of patients with AAT deficiency, cystic fibrosis, or other lung diseases with bronchiectasis) will be needed with clinical end points in addition to the measurement of proteolytic activity in the airway. The outcomes likely will have to include lung function, lung structure assessed by computed tomography imaging, disease exacerbations, health status, and mortality. PMID:27564672

  14. How Can Alpha-1 Antitrypsin Deficiency Be Prevented?

    Science.gov (United States)

    ... Prevented? You can't prevent alpha-1 antitrypsin (AAT) deficiency because the condition is inherited (passed from ... children through genes). If you inherit two faulty AAT genes, you'll have AAT deficiency. Even so, ...

  15. 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...... (rs1800790, G>A) and FGB -448 (rs4220, G>A) and had plasma fibrinogen measured. Furthermore, 13 405 individuals were genotyped for the SERPINA1 S-allele (rs17580) and the Z-allele (rs28929474) and had measurements of plasma alpha(1)-antitrypsin. Exacerbations were defined as hospital admissions or...... 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...

  16. Alpha-1-antitrypsin studies: canine serum and canine surfactant protein

    International Nuclear Information System (INIS)

    Canine serum alpha-1-antitrypsin was isolated by gel filtration and affinity chromatography and characterized by polyacrylamide gel electrophoresis and immunoelectrophoresis. Measurement of the trypsin inhibitory capacity of the separated protein indicated a ninefold concentration of functional trypsin inhibitor during the isolation procedure. Electrophoresis demonstrated the presence of a single protein with alpha-globulin mobility and a molecular weight near that of human alpha-1-antitrypsin. The trypsin inhibitory capacity of pulmonary surfactant protein from five Beagle dogs was measured, related to total surfactant protein concentration, and compared with similar measurements on whole serum from the same animals. Results indicated a variable concentration of trypsin inhibitor in the canine pulmonary surfactant protein. However, the concentration in the surfactant protein was always significantly higher than that in the corresponding serum sample. Preliminary experiments designed to separate the trypsin inhibitory fraction(s) from the other surfactant proteins by gel filtration chromatography indicated that the trypsin inhibitor was probably a single protein with a molecular weight near that of alpha-1-antitrypsin. (U.S.)

  17. SlimQuick™ - associated hepatotoxicity in a woman with alpha-1 antitrypsin heterozygosity

    OpenAIRE

    Weinstein, Douglas H; Twaddell, William S.; Raufman, Jean-Pierre; Philosophe, Benjamin; Mindikoglu, Ayse L

    2012-01-01

    Green tea (Camellia sinensis)-associated hepatotoxicity is reported. However, the presence of alpha-1 antitrypsin MZ phenotype as a predisposing factor to green tea-associated drug-induced liver injury (DILI) is unknown. A previously healthy woman with alpha-1 antitrypsin MZ phenotype who took SlimQuick™, an herbal supplement containing green tea extract, developed severe hepatotoxicity requiring corticosteroid treatment. Green tea-associated hepatotoxicity is reviewed and alpha-1 antitrypsin...

  18. 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...... selenium positively associated with sputum AAT (P=0.004 and P=0.002, respectively). In analyses stratified by town, these relationships remained significant only in Ajo, with the higher arsenic exposure. Reduction in AAT may be a means by which arsenic induces respiratory disease, and selenium may protect...

  19. Fluorescent antibody studies of alpha-1-antitrypsin in adult human lung

    International Nuclear Information System (INIS)

    The distribution of alpha-1-antitrypsin in frozen sections prepared from four specimens of human lung was determined by the indirect fluorescent antibody technique. Three of the specimens were obtained directly from surgical procedures and were peripheral tissue excised with tumors. Specific fluorescence for alpha-1-antitrypsin was observed lining the terminal airways and alveoli throughout the sections from two of the cases. In the other cases, a few focal areas of specific fluorescence were observed. The results of this study indicate that alpha-1-antitrypsin may be distributed in lung in association with pulmonary surfactant and that local tissue concentrations of alpha-1-antitrypsin are variable. (U.S.)

  20. 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

  1. Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy.

    Science.gov (United States)

    Wozniak, Joanna; Wandtke, Tomasz; Kopinski, Piotr; Chorostowska-Wynimko, Joanna

    2015-11-01

    Alpha-1 antitrypsin (AAT) is a protease inhibitor belonging to the serpin family. A number of identified mutations in the SERPINA1 gene encoding this protein result in alpha-1 antitrypsin deficiency (AATD). A decrease in AAT serum concentration or reduced biological activity causes considerable risk of chronic respiratory and liver disorders. As a monogenic disease, AATD appears to be an attractive target for gene therapy, particularly for patients with pulmonary dysfunction, where augmentation of functional AAT levels in plasma might slow down respiratory disease development. The short AAT coding sequence and its activity in the extracellular matrix would enable an increase in systemic serum AAT production by cellular secretion. In vitro and in vivo experimental AAT gene transfer with gamma-retroviral, lentiviral, adenoviral, and adeno-associated viral (AAV) vectors has resulted in enhanced AAT serum levels and a promising safety profile. Human clinical trials using intramuscular viral transfer with AAV1 and AAV2 vectors of the AAT gene demonstrated its safety, but did not achieve a protective level of AAT >11 μM in serum. This review provides an in-depth critical analysis of current progress in AATD gene therapy based on viral gene transfer. The factors affecting transgene expression levels, such as site of administration, dose and type of vector, and activity of the immune system, are discussed further as crucial variables for optimizing the clinical effectiveness of gene therapy in AATD subjects. PMID:26413996

  2. A rare case of alpha 1-antitrypsin deficiency associated with hypogammaglobulinemia and recurrent pulmonary thrombosis

    Directory of Open Access Journals (Sweden)

    Raghav Gupta

    2014-01-01

    Full Text Available Alpha 1-antitrypsin (AAT belongs to the family of serpins (serine protease inhibitors. Loop sheet polymerization is the pathology behind serpinopathies which encompasses AAT, anti-thrombin III and neuroserpin deficiency. To the best of our knowledge, we report the first case of alpha 1-antitrypsin deficiency associated with hypogammaglobulinemia and recurrent pulmonary thrombosis without any concomitant use of drugs.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Alpha-1-antitrypsin deficiency: increasing awareness and improving diagnosis.

    Science.gov (United States)

    Greulich, Timm; Vogelmeier, Claus F

    2016-02-01

    Alpha-1-antitrypsin deficiency (AATD) is a hereditary disorder that is characterized by a low serum level of alpha-1-antitrypsin (AAT). The loss of anti-inflammatory and antiproteolytic functions, together with pro-inflammatory effects of polymerized AAT contribute to protein degradation and increased inflammation resulting in an increased risk of developing chronic obstructive pulmonary disease (COPD) and emphysema, especially in smokers. AATD is a rare disease that is significantly underdiagnosed. According to recent data that are based on extrapolations, in many countries only 5-15% of homozygous individuals have been identified. Furthermore, the diagnostic delay typically exceeds 5 years, resulting in an average age at diagnosis of about 45 years. Although the American Thoracic Society/European Respiratory Society recommendations state that all symptomatic adults with persistent airway obstruction should be screened, these recommendations are not being followed. Potential reasons for that include missing knowledge about the disease and the appropriate tests, and the low awareness of physicians with regard to the disorder. Once the decision to initiate testing has been made, a screening test (AAT serum level or other) should be performed. Further diagnostic evaluation is based on the following techniques: polymerase chain reaction (PCR) for frequent and clinically important mutations, isoelectric focusing (IEF) with or without immunoblotting, and sequencing of the gene locus coding for AAT. Various diagnostic algorithms have been published for AATD detection (severe deficiency or carrier status). Modern laboratory approaches like the use of serum separator cards, a lateral flow assay to detect the Z-protein, and a broader availability of next-generation sequencing are recent advances, likely to alter existing algorithms. PMID:26341117

  5. [The interaction of human alpha 1-antitrypsin with human plasmin].

    Science.gov (United States)

    Sakurama, S

    1984-01-01

    The interaction of alpha 1-antitrypsin (alpha 1-AT) with plasmin was investigated, and the molecular weight of the inhibitor was also re-evaluated. The value of molecular weight of alpha 1-AT determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) method showed a difference depending on the presence or absence of the reducing agent, resulting in 72,000 dalton before reduction and 59,000 dalton after reduction. Conclusively, the molecular weight of alpha 1-AT was appropriate to be 59,000 dalton from considering the molecular shape of the protein. The interaction of alpha 1-AT with plasmin was analysed by SDS-PAGE method. Unreduced analysis revealed that two kinds of complexes with different molecular weight (the major of 155,000 dalton and the minor of 140,000 dalton) were formed time dependently, suggesting that the former was a native complex and the latter was a degraded product. Reduced analysis disclosed that the light chain of plasmin involved the complex formation with the inhibitor, and a peptide of 16,000 dalton appeared during the reaction. From these observations, the mechanism of action was summarized as follows. First, alpha 1-AT inhibited all of the plasmin activities by forming a 1: 1 stoichiometric complex with the enzyme, presumably with the active center of the enzyme, whose complex is undissociable in the presence of denaturing or reducing agents or both. Secondly, the native complex broke into a degraded product and a released peptide by limited proteolysis with the free plasmin which existed in the reaction mixture even with an excess of alpha 1-AT due to the reaction of complex formation being time consuming. The clinical significance of alpha 1-AT on fibrinolysis was also subject for discussion. PMID:6232193

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

    Directory of Open Access Journals (Sweden)

    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

  7. Alpha-1 antitrypsin is a potential biomarker for hepatitis B

    Directory of Open Access Journals (Sweden)

    Chen Zhi

    2011-06-01

    Full Text Available Abstract Background Function exertion of specific proteins are key factors in disease progression, thus the systematical identification of those specific proteins is a prerequisite to understand various diseases. Though many proteins have been verified to impact on hepatitis, no systematical protein screening has been documented to hepatitis B virus (HBV induced hepatitis, hindering the comprehensive understanding to this severe disease. Aim To identify the major proteins in the progression of HBV infection from mild stage to severe stage. Methods We performed an integrated strategy by combining two-dimensional electrophoresis (2-DE, peptide mass fingerprinting (PMF analysis, and tissue microarray techniques to screen the functional proteins and detect the localization of those proteins. Results Interestingly, MS/MS identification revealed the expression level of alpha-1 antitrypsin (AAT was significantly elevated in serum samples from patients with severe chronic hepatitis. Immunoblotting with a specific AAT antibody confirmed that AAT is highly expressed in serum samples from patients with hepatic carcinoma and severe chronic hepatitis. Furthermore, we observed that AAT is with highest expression in normal tissue and cells, but lowest in hepatic carcinoma and severe chronic hepatitis tissues and cells, suggesting the specific secretion of AAT from tissues and cells to serum. Conclusion These results suggest the possibility of AAT as a potential biomarker for hepatitis B in diagnosis.

  8. Alpha 1 Antitrypsin Deficiency in Infants with Neonatal Cholestasis

    Directory of Open Access Journals (Sweden)

    Maryam Monajemzadeh

    2013-10-01

    Full Text Available Objective: Alpha1-antitrypsin deficiency (A1ATD is the most important indication for liver transplantation in children. The gene frequencies vary in different ethnic groups. In the present study, we attempt to determine the frequencies of the most common defective alleles, Z and S, in Iranian children suffering from idiopathic neonatal cholestasis. Eighty-seven infants were typed for Z and S alleles.Methods: In a single center study, 87 consecutive liver biopsies from infants with cholestasis were reviewed and patients with neonatal cholestasis enrolled in the study and cases with confirmed biliary tract atresia excluded. Formalin fixed paraffin embedded blocks were used for DNA extraction. AAT genotype was determined by polymerase chain reaction (PCR assay and amplification of the two most common deficiency variants, S and Z alleles, and then sequencing of PCR products.Findings: There were 48 (55.2% males and 39 (44.8% females, with a median age of 60 days. Out of 87 of the study subject, 2 (2.2% were heterozygous for the S allele, and no ZZ, SS or MZ individual was found in the patients. No other polymorphism was found in the sequencing results.Conclusion: In comparison to other populations, AAT deficiency seems not to be an important etiologic factor for neonatal cholestatic liver disease in Iran; however, further studies are recommended to estimate the true mutant gene frequencies.

  9. Alpha-1 Antitrypsin Investigations Using Animal Models of Emphysema.

    Science.gov (United States)

    Ni, Kevin; Serban, Karina A; Batra, Chanan; Petrache, Irina

    2016-08-01

    Animal models of disease help accelerate the translation of basic science discoveries to the bedside, because they permit experimental interrogation of mechanisms at relatively high throughput, while accounting for the complexity of an intact organism. From the groundbreaking observation of emphysema-like alveolar destruction after direct instillation of elastase in the lungs to the more clinically relevant model of airspace enlargement induced by chronic exposure to cigarette smoke, animal models have advanced our understanding of alpha-1 antitrypsin (AAT) function. Experimental in vivo models that, at least in part, replicate clinical human phenotypes facilitate the translation of mechanistic findings into individuals with chronic obstructive pulmonary disease and with AAT deficiency. In addition, unexpected findings of alveolar enlargement in various transgenic mice have led to novel hypotheses of emphysema development. Previous challenges in manipulating the AAT genes in mice can now be overcome with new transgenic approaches that will likely advance our understanding of functions of this essential, lung-protective serine protease inhibitor (serpin). PMID:27564666

  10. What Are the Signs and Symptoms of Alpha-1 Antitrypsin Deficiency?

    Science.gov (United States)

    ... first lung-related symptoms of alpha-1 antitrypsin (AAT) deficiency may include shortness of breath, less ability ... and weight loss. Some people who have severe AAT deficiency develop emphysema (em-fi-SE-ma)—often ...

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

    DEFF Research Database (Denmark)

    Hersh, C P; Dahl, Morten; Ly, N P; Berkey, C S; Nordestgaard, B G; Silverman, E K

    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.......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....

  12. Deficiency Mutations of Alpha-1 Antitrypsin. Effects on Folding, Function, and Polymerization.

    Science.gov (United States)

    Haq, Imran; Irving, James A; Saleh, Aarash D; Dron, Louis; Regan-Mochrie, Gemma L; Motamedi-Shad, Neda; Hurst, John R; Gooptu, Bibek; Lomas, David A

    2016-01-01

    Misfolding, polymerization, and defective secretion of functional alpha-1 antitrypsin underlies the predisposition to severe liver and lung disease in alpha-1 antitrypsin deficiency. We have identified a novel (Ala336Pro, Baghdad) deficiency variant and characterized it relative to the wild-type (M) and Glu342Lys (Z) alleles. The index case is a homozygous individual of consanguineous parentage, with levels of circulating alpha-1 antitrypsin in the moderate deficiency range, but is a biochemical phenotype that could not be classified by standard methods. The majority of the protein was present as functionally inactive polymer, and the remaining monomer was 37% active relative to the wild-type protein. These factors combined indicate an 85 to 95% functional deficiency, similar to that seen with ZZ homozygotes. Biochemical, biophysical, and computational studies further defined the molecular basis of this deficiency. These studies demonstrated that native Ala336Pro alpha-1 antitrypsin could populate the polymerogenic intermediate-and therefore polymerize-more readily than either wild-type alpha-1 antitrypsin or the Z variant. In contrast, folding was far less impaired in Ala336Pro alpha-1 antitrypsin than in the Z variant. The data are consistent with a disparate contribution by the "breach" region and "shutter" region of strand 5A to folding and polymerization mechanisms. Moreover, the findings demonstrate that, in these variants, folding efficiency does not correlate directly with the tendency to polymerize in vitro or in vivo. They therefore differentiate generalized misfolding from polymerization tendencies in missense variants of alpha-1 antitrypsin. Clinically, they further support the need to quantify loss-of-function in alpha-1 antitrypsin deficiency to individualize patient care. PMID:26091018

  13. Alpha-1 Antitrypsin Therapy in Cystic Fibrosis and the Lung Disease Associated with Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    McElvaney, Noel G

    2016-04-01

    Cystic fibrosis and alpha-1 antitrypsin (AAT) deficiency are two of the commonest lethal hereditary lung diseases affecting white individuals. Although having quite different phenotypic extrapulmonary presentations, the lung disease associated with these conditions is exemplified by a neutrophil-dominated inflammation in which neutrophil elastase plays a major role. In AAT deficiency the diminution of the anti-neutrophil elastase protection, due to diminished AAT levels in the lung, predisposes the lung to an unopposed neutrophil elastase attack, whereas, in cystic fibrosis, the levels of AAT and other antiproteases are normal, but the neutrophil elastase burden is so large that it overwhelms the normal anti-neutrophil elastase protection. With this as background, it seems logical to augment the anti-neutrophil elastase defenses of the lung in both conditions using exogenous AAT. The type of AAT, the route of administration, and the physiologic, radiologic, and clinical readouts for this type of therapy are discussed, along with the similarities and differences between the two conditions and their responses to AAT therapy. PMID:27115956

  14. Survival in severe alpha-1-antitrypsin deficiency (PiZZ

    Directory of Open Access Journals (Sweden)

    Nilsson Jan-Åke

    2010-04-01

    Full Text Available Abstract Background Previous studies of the natural history of alpha-1-antitrypsin (AAT deficiency are mostly based on highly selected patients. The aim of this study was to analyse the mortality of PiZZ individuals. Methods Data from 1339 adult PiZZ individuals from the Swedish National AAT Deficiency Registry, followed from 1991 to 2008, were analysed. Forty-three percent of these individuals were identified by respiratory symptoms (respiratory cases, 32% by liver diseases and other diseases (non-respiratory cases and 25% by screening (screened cases. Smoking status was divided into two groups: smokers 737 (55% and 602 (45% never-smokers. Results During the follow-up 315 individuals (24% died. The standardised mortality rate (SMR for respiratory cases was 4.70 (95% Confidence Interval (CI 4.10-5.40, 3.0 (95%CI 2.35-3.70 for the non-respiratory cases and 2.30 (95% CI 1.46-3.46 for the screened cases. The smokers had a higher mortality risk than never-smokers, with a SMR of 4.80 (95%CI 4.20-5.50 for the smokers and 2.80(95%CI 2.30-3.40 for the never-smokers. The Rate Ratio (RR was 1.70 (95% CI 1.35-2.20. Also among the screened cases, the mortality risk for the smokers was significantly higher than in the general Swedish population (SMR 3.40 (95% CI 1.98-5.40. Conclusion Smokers with severe AAT deficiency, irrespective of mode of identification, have a significantly higher mortality risk than the general Swedish population.

  15. Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency: an update.

    Science.gov (United States)

    Blanco, I; Lipsker, D; Lara, B; Janciauskiene, S

    2016-04-01

    Neutrophilic panniculitis associated with alpha-1-antitrypsin deficiency (AATD) is a very rare disease. Its estimated prevalence is 1 in 1000 subjects with severe AATD (usually white individuals with a Pi*ZZ genotype). It is manifested clinically by painful recurrent ulcerating subcutaneous nodules, and characterized histologically by dense infiltrates of neutrophils in the deep dermis and connective-tissue septae, with secondary lobular panniculitis. It may be the only clinical manifestation of AATD, although it can also occur together with the classical pulmonary or hepatic manifestations of the disease. AATD-associated panniculitis is not only very rare but may also be significantly underdiagnosed. The physician managing a case of panniculitis with a clinical presentation suggestive of AATD and a compatible skin biopsy should measure serum AAT concentration and, if low, determine the AAT phenotype by isoelectric focusing. If uncertainty remains, the SERPINA1 gene should be sequenced to identify the genotype. If AATD is diagnosed, AATD testing of first-degree family members should be performed in order to take appropriate preventive and therapeutic measures, including genetic counselling, education on inheritance, risk arising from tobacco smoke, occupational exposure to pollutants and hepatotoxic substances, and the provision of information on clinical management. Cases of panniculitis in which conventional therapy with dapsone has failed may be managed with intravenous augmentative therapy using human AAT. The current manuscript addresses the fundamental concepts of the pathogenesis of AATD-associated panniculitis and describes the clinical presentation and management of cases in order to reduce underdiagnosis and improve outcomes. PMID:26595240

  16. 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.

  17. 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.

  18. Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha-1 Foundation DNA and Tissue Bank

    OpenAIRE

    Tonelli, Adriano

    2009-01-01

    Adriano R Tonelli1, Farshid Rouhani1, Ning Li2, Pam Schreck1, Mark L Brantly11Alpha-1 Research Program, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, 2Department of Epidemiology and Biostatistics, University of Florida, Gainesville, Florida, USAIntroduction: Intravenous augmentation therapy with purified intravenous alpha-1 antitrypsin replaces the deficient protein and is the only currently approved treatment for alpha-1 antitrypsin deficiency (AAT...

  19. [Role of alpha 1-antitrypsin and alpha-2 macroglobulin in hepatopathies].

    Science.gov (United States)

    Triolo, L; Mian, G; Magris, D; Novello, E; D'Agnolo, B

    1979-02-18

    Two pictures of alpha 1-antitrypsin deficiency, one associated with alpha 2-macroglobulin deficiency and one isolated case of the latter deficiency have been observed in three patients suffering from cirrhosis of the liver and/or hepatoma. On the basis of these cases, the literature on the subject is reviewed. The unusually high incidence of such anti-enzymatic deficiencies (three cases in the first eleven patients studied) in severe liver pathology, calls for a reassessment of such research and suggests that these tests should be carried out on a routine basis in cases of cryptogenetic cirrhosis and probably for long-term prognosis in cases of viral hepatitis. PMID:86175

  20. 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

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

    OpenAIRE

    de Serres Frederick; Lara Beatriz; Blanco Ignacio

    2011-01-01

    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

  2. New variants of alpha 1-antitrypsin: comparison of Pi typing techniques.

    OpenAIRE

    Cox, D. W.

    1981-01-01

    Four new rare inherited variants (Pi types) of alpha 1-antitrypsin (alpha 1-protease inhibitor) are described. Each variant has been compared with previously reported genetic variants by several techniques used for Pi typing: isoelectric focusing in polyacrylamide gel, starch gel electrophoresis, and agarose gel electrophoresis. Some variants are identical or very similar by one technique but can be clearly distinguished by another technique. Crossed immunoelectrophoresis and gel immunofixati...

  3. C3, factor B, alpha-1-antitrypsin in neonatal septicaemia with sclerema.

    OpenAIRE

    Pelet, B

    1980-01-01

    C3, factor B, and alpha-1-antitrypsin were determined in newborn infants with septicaemia and sclerema, associated with suspected infections, ABO or Rh incompatibility, and hyperbilirubinaemia of unknown origin, during and after treatment with exchange transfusion. Activation products from C3 and factor B, the clearance of the transfused C3, and its synthesis by the recipient were determined also. Infected newborn infants had low levels of C3 and factor B, but a normal amount of alpha-1-antit...

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

    OpenAIRE

    AL-Bayaty, Fouad H.; NorAdinar Baharuddin; Mahmood A. Abdulla; Hapipah Mohd Ali; Arkilla, Magaji B.; ALBayaty, Mustafa F.

    2013-01-01

    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 alpha < 0.05. ...

  5. Risk factors for symptom onset in PI*Z alpha-1 antitrypsin deficiency

    OpenAIRE

    Mayer, Annyce S; James K. Stoller; Vedal, Sverre; Ruttenber, A James; Strand, Matt; Sandhaus, Robert A.; Newman, Lee S

    2006-01-01

    Background In an early study of highly symptomatic patients with PI*Z alpha-1 antitrypsin deficiency (AAT), tobacco smoking was identified as a risk factor by comparing the age of symptom onset in smokers and nonsmokers. Age of symptom onset has not been well studied in relationship to other environmental exposures. Methods Environmental exposures were assessed in 313 PI*Z adults through retrospective self-administered questionnaire. Age of onset of symptoms with and without these exposures w...

  6. Heterozygosity for the alpha1-antitrypsin Z allele may confer genetic risk of cholangiocarcinoma

    OpenAIRE

    Mihalache, Florentina; HÖBLINGER, AKSANA; Grünhage, Frank; Krawczyk, Marcin; Gärtner, Barbara C.; Acalovschi, Monica; Sauerbruch, Tilman; Lammert, Frank; Zimmer, Vincent

    2010-01-01

    Abstract Background & Aim: Alpha1-antitrypsin (?1AT) deficiency caused by Z allele homozygosity represents a risk factor for hepatocellular carcinoma. Previous studies have implicated ?1AT Z heterozygosity in cholangiocarcinogenesis. We assessed the ?common? Z and S alleles as well as the promoter variant rs8004738 for association with cholangiocarcinoma (CCA). Patients & Methods: We genotyped 182 Caucasian patients and 350 controls for rs28929474 (Z), rs17580 (S) and the varia...

  7. The parallel lives of alpha1-antitrypsin deficiency and pulmonary alveolar proteinosis

    OpenAIRE

    Trapnell, Bruce C.; Luisetti, Maurizio

    2013-01-01

    In 1963, five cases of alpha1-antitrypsin deficiency were reported in the scientific literature, as well as an attempt to treat pulmonary alveolar proteinosis by a massive washing of the lung (whole lung lavage). Now, fifty years later, it seems the ideal moment not only to commemorate these publications, but also to point out the influence both papers had in the following decades and how knowledge on these two fascinating rare respiratory disorders progressed over the years. This paper is th...

  8. Prognosis of patients with alpha1-antitrypsine deficiency on long-term oxygen therapy

    DEFF Research Database (Denmark)

    Ringbaek, Thomas J; Seersholm, Niels; Perch, Michael;

    2014-01-01

    INTRODUCTION: Data on patients with alpha1-antitrypsine deficiency (AATD) on long-term oxygen therapy (LTOT) is sparse. The aim of this study was to present the incidence of patients with AATD on LTOT, and compare their characteristics, comorbidities and prognosis (lung transplantation, termination.......001). CONCLUSIONS: Compared with COPD without AATD, AATD patients are younger, more often males, have a lower prevalence of cardio-vascular diseases and diabetes mellitus, and higher prevalence of osteoporosis. Moreover, they have better prognosis, partly due to greater chance of receiving a lung transplantation....

  9. Pulmonary Physiology of Chronic Obstructive Pulmonary Disease, Cystic Fibrosis, and Alpha-1 Antitrypsin Deficiency.

    Science.gov (United States)

    Stockley, James A; Stockley, Robert A

    2016-04-01

    Cystic fibrosis is predominantly an airway disease with marked bronchiectatic changes associated with inflammation, chronic colonization, and progressive airflow obstruction. The condition can be identified in childhood and monitored with detectable airway changes early in life while conventional spirometry remains in the normal range. Alpha-1 antitrypsin deficiency can also be detected early in life through blood spot and genetic testing and leads (in some) to the development of airflow obstruction and a predominant emphysema phenotype with bronchiectatic changes in about 30%. Early detection also allows the natural history of the pulmonary physiological changes to be determined. Chronic obstructive pulmonary disease is usually detected late in the disease process when significant damage has occurred. The condition consists of varying combinations of airway disease, bronchiectasis, colonization, and emphysema. Lessons learned from the physiological evolution of airway disease in cystic fibrosis and the emphysema of alpha-1 antitrypsin deficiency provide strategies to enable early detection of chronic obstructive pulmonary disease in general and its phenotypes. PMID:27115945

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

    OpenAIRE

    Chotirmall, Sanjay

    2015-01-01

    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...

  11. DNA polymorphisms of the human alpha 1 antitrypsin gene in normal subjects and in patients with pulmonary emphysema.

    OpenAIRE

    Hodgson, I; Kalsheker, N

    1987-01-01

    Alpha 1 antitrypsin deficiency predisposes subjects to developing pulmonary emphysema and childhood liver cirrhosis. We have studied restriction fragment length polymorphisms (RFLPs) of the alpha 1 antitrypsin gene in a normal population and a group of patients with pulmonary emphysema. We have identified five RFLPs with eight restriction enzymes. The most frequent polymorphisms have been detected with the enzymes MspI, PstI, and TaqI at frequencies of 46.8%, 6.4%, and 5.0% respectively in th...

  12. Familial alpha 1 antitrypsin deficiency cases that are diagnosed in adulthood.

    Science.gov (United States)

    Atayan, Y; Çağın, Y F; Erdoğan, M A; Bestas, R; Aladag, M

    2016-01-01

    Alpha 1 antitrypsin (AAT) deficiency is a hereditary disorder leading to severe lung and liver diseases worldwide. An accumulation of insoluble heterodimer AAT molecules in hepatocytes is the main cause of liver disorders. The most commonly detected allele worldwide is the PIMM allele, which fulfills the AAT function. The most common missing variant is PiZZ. Serum AAT level is a beneficial but not a reliable determinant for diagnosis. Liver biopsy yields more reliable results. AAT deficiency has no specific treatment. The only treatment modality in children with end stage liver disease is the hepatic transplant. We wanted to present in our article four cases from same family, diagnosed alpha-1 antitrypsindeficiency in adulthood. PMID:26852765

  13. Infected tracheal diverticulum: a rare association with alpha-1 antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Cecília Beatriz Alves Amaral

    2014-12-01

    Full Text Available Tracheal diverticulum, defined as a benign outpouching of the tracheal wall, is rarely diagnosed in clinical practice. It can be congenital or acquired in origin, and most cases are asymptomatic, typically being diagnosed postmortem. We report a case of a 69-year-old woman who was hospitalized after presenting with fever, fatigue, pleuritic chest pain, and a right neck mass complicated by dysphagia. Her medical history was significant: pulmonary emphysema (alpha-1 antitrypsin deficiency; bronchiectasis; and thyroidectomy. On physical examination, she presented diminished breath sounds and muffled heart sounds, with a systolic murmur. Laboratory tests revealed elevated inflammatory markers, a CT scan showed an air-filled, multilocular mass in the right tracheal wall, and magnetic resonance imaging confirmed the CT findings. Fiberoptic bronchoscopy failed to reveal any abnormalities. Nevertheless, the patient was diagnosed with tracheal diverticulum. The treatment approach was conservative, consisting mainly of antibiotics. After showing clinical improvement, the patient was discharged.

  14. 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.

  15. [Hereditary deficiency of alpha 1- antitrypsin in rats due to evolving chronic lung pathology].

    Science.gov (United States)

    Soloveva, N A; Grishaeva, O N; Parik, Iu Ia; Kosova, E Iu; Korolenko, T A

    1994-01-01

    W/SSM rats which are characterized by hereditary abnormal changes in the lungs, hepato- and splenomegalia and some other disturbances have also alpha 1-antitrypsin (AAT) deficiency. A study of AAT in these rats by means of isoelectrofocusing and immunoblotting with anti-AAT antibodies labelled with peroxidase has demonstrated that deficiency of the protease inhibitor is not associated with any disturbances of its synthesis or any changes of its electrophoretic properties. A higher activity of lysosomal glycosidases and proteinases was found in the liver and leukocytes of W/SSM rats. It is suggested that AAT deficiency is due to its modification under the influence of lysosomal enzymes. The described biochemical distances seem to be associated with an increased hexose transport into the cells, which is controlled by a mutant gene. PMID:7513577

  16. 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

  17. Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease.

    Science.gov (United States)

    Schaefer, Benedikt; Haschka, David; Finkenstedt, Armin; Petersen, Britt-Sabina; Theurl, Igor; Henninger, Benjamin; Janecke, Andreas R; Wang, Chia-Yu; Lin, Herbert Y; Veits, Lothar; Vogel, Wolfgang; Weiss, Günter; Franke, Andre; Zoller, Heinz

    2015-11-01

    Liver disease due to alpha-1-antitrypsin deficiency (A1ATD) is associated with hepatic iron overload in a subgroup of patients. The underlying cause for this association is unknown. The aim of the present study was to define the genetics of this correlation and the effect of alpha-1-antitrypsin (A1AT) on the expression of the iron hormone hepcidin. Full exome and candidate gene sequencing were carried out in a family with A1ATD and hepatic iron overload. Regulation of hepcidin expression by A1AT was studied in primary murine hepatocytes. Cells co-transfected with hemojuvelin (HJV) and matriptase-2 (MT-2) were used as a model to investigate the molecular mechanism of this regulation. Observed familial clustering of hepatic iron overload with A1ATD suggests a genetic cause, but genotypes known to be associated with hemochromatosis were absent. Individuals homozygous for the A1AT Z-allele with environmental or genetic risk factors such as steatosis or heterozygosity for the HAMP non-sense mutation p.Arg59* presented with severe hepatic siderosis. In hepatocytes, A1AT induced hepcidin mRNA expression in a dose-dependent manner. Experiments in overexpressing cells show that A1AT reduces cleavage of the hepcidin inducing bone morphogenetic protein co-receptor HJV via inhibition of the membrane-bound serine protease MT-2. The acute-phase protein A1AT is an inducer of hepcidin expression. Through this mechanism, A1ATD could be a trigger of hepatic iron overload in genetically predisposed individuals or patients with environmental risk factors for hepatic siderosis. PMID:26310624

  18. Expression of modified gene encoding functional human alpha-1-antitrypsin protein in transgenic tomato plants.

    Science.gov (United States)

    Agarwal, Saurabh; Singh, Rahul; Sanyal, Indraneel; Amla, D V

    2008-10-01

    Transgenic plants offer promising alternative for large scale, sustainable production of safe, functional, recombinant proteins of therapeutic and industrial importance. Here, we report the expression of biologically active human alpha-1-antitrypsin in transgenic tomato plants. The 1,182 bp cDNA sequence of human AAT was strategically designed, modified and synthesized to adopt codon usage pattern of dicot plants, elimination of mRNA destabilizing sequences and modifications around 5' and 3' flanking regions of the gene to achieve high-level regulated expression in dicot plants. The native signal peptide sequence was substituted with modified signal peptide sequence of tobacco (Nicotiana tabacum) pathogenesis related protein PR1a, sweet potato (Ipomoea batatas) sporamineA and with dicot-preferred native signal peptide sequence of AAT gene. A dicot preferred translation initiation context sequence, 38 bp alfalfa mosaic virus untranslated region were incorporated at 5' while an endoplasmic reticulum retention signal (KDEL) was incorporated at 3' end of the gene. The modified gene was synthesized by PCR based method using overlapping oligonucleotides. Tomato plants were genetically engineered by nuclear transformation with Agrobacterium tumefaciens harbouring three different constructs pPAK, pSAK and pNAK having modified AAT gene with different signal peptide sequences under the control of CaMV35S duplicated enhancer promoter. Promising transgenic plants expressing recombinant AAT protein upto 1.55% of total soluble leaf protein has been developed and characterized. Plant-expressed recombinant AAT protein with molecular mass of around approximately 50 kDa was biologically active, showing high specific activity and efficient inhibition of elastase activity. The enzymatic deglycosylation established proper glycosylation of the plant-expressed recombinant AAT protein in contrast to unglycosylated rAAT expressed in E. coli ( approximately 45 kDa). Our results demonstrate

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.

  1. Suspecting and Testing for Alpha-1 Antitrypsin Deficiency-An Allergist's and/or Immunologist's Perspective.

    Science.gov (United States)

    Craig, Timothy J

    2015-01-01

    Alpha-1 antitrypsin deficiency (AATD) is a hereditary, monogenic disorder with no unique clinical features. AATD can be difficult to diagnose as patients commonly present with respiratory symptoms often mistaken for other respiratory syndromes such as asthma or smoking-related chronic obstructive pulmonary disease. In addition, symptoms related to AATD may also affect other organs, including the liver, vasculature, and skin. The severity of AATD varies between individuals, and in severe cases, the irreversible lung damage can develop into emphysema. Early diagnosis is critical to enable the implementation of lifestyle changes and therapeutic options that can slow further deterioration of pulmonary tissue. Once AATD is suspected, a range of tests are available (serum alpha-1 proteinase inhibitor [A1-PI] level measurement, phenotyping, genotyping, gene sequencing) for confirming AATD. Currently, intravenous infusion of A1-PI is the only therapy that directly addresses the underlying cause of AATD, and has demonstrated efficacy in a recent randomized, placebo-controlled trial. This review discusses the etiology, testing, and management of AATD from the allergist's and/or immunologist's perspective. It aims to raise awareness of the condition among physicians who care for people with obstructive lung disorders and are therefore likely to see patients with obstructive lung disease that may, in fact, prove to be AATD. PMID:26032475

  2. 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.

  3. Is There a Therapeutic Role for Selenium in Alpha-1 Antitrypsin Deficiency?

    Directory of Open Access Journals (Sweden)

    Noel G. McElvaney

    2013-03-01

    Full Text Available Selenium is an essential trace mineral of fundamental importance to human health. Much of its beneficial influence is attributed to its presence within selenoproteins, a group of proteins containing the rare amino acid selenocysteine. There are 25 known human selenoproteins including glutathione peroxidases, thioredoxin reductases and selenoproteins. Selenoprotein S (SEPS1 is an endoplasmic reticulum (ER resident selenoprotein involved in the removal of misfolded proteins from the ER. SEPS1 expression can be induced by ER stress, an event that is associated with conformational disorders and occurs due to accumulation of misfolded proteins within the ER. Alpha-1 antitrypsin (AAT deficiency, also known as genetic emphysema, is a conformational disorder in which the roles of ER stress, SEPS1 and selenium have been investigated. SEPS1 can relieve ER stress in an in vitro model of AAT deficiency by reducing levels of active ATF6 and inhibiting grp78 promoter- and NFκB activity; some of these effects are enhanced in the presence of selenium supplementation. Other studies examining the molecular mechanisms by which selenium mediates its anti-inflammatory effects have identified a role for prostaglandin 15d-PGJ2 in targeting NFκB and PPARγ. Together these ER stress-relieving and anti-inflammatory properties suggest a therapeutic potential for selenium supplementation in genetic emphysema.

  4. 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. PMID:26647313

  5. [Alpha-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)].

    Science.gov (United States)

    Ljujic, M; Mijatovic, S; Bulatovic, M Z; Mojic, M; Maksimovic-Ivanic, D; Radojkovic, D; Topic, A

    2016-01-01

    Alpha-1-antitrypsin (AAT), an acute phase protein, is the principal circulatory anti-protease. This multifunctional protein is encoded by the SERPINA1 gene. Although AAT was recognised as a potential tumour marker, its role in cancer biology remains unknown. Given that it has been demonstrated that AAT has an anti-apoptotic property against non-malignant cells, we aimed to investigate whether AAT affects apoptosis in a colon cancer cell line (HCT116). The presence of AAT in the HCT116 cell culture antagonized cytotoxicity of blockers of MEK1/2, PI3K/Akt pathways as well as NF-κB. The dominantly recovered cell viability was observed in the co-treatment with MEK1/2 inhibitor U0126. In addition, it was revealed that AAT almost completely abolished U0126-induced apoptosis through maintenance of the autophagy process. Our study revealed for the first time that the observed cyto-protection triggered by AAT was accompanied by sustained autophagy which opposed apoptosis. These results may contribute to understanding of the role of AAT in cancer development and evaluation of efficacy of cancer therapy. PMID:27028823

  6. 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.

  7. 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.

  8. Intestinal apoprotein biosynthesis: alpha-1-antitrypsin identified as a constituent of rat lymph chylomicrons

    International Nuclear Information System (INIS)

    Apolipoproteins synthesized in the intestine can serve as a source of constituents for plasma lipoproteins and play an important role in the pathways of lipoprotein formation, interconversion, and catabolism. In the present study, apolipoproteins synthesized by the intestine were identified in mesenteric lymph following intraduodenal administration of lipid and [14C]-leucine to rats. The study was undertaken to assess differences in the rate of appearance of newly synthesized apolipoproteins into chylomicron and VLDL particles of rat mesenteric lymph and to determine if there is a sex-related influence on this process. Examination of qualitative and quantitative differences in apolipoprotein profiles, [14C]-leucine labeling patterns, and the specific activities of the individual apolipoproteins secreted with either chylomicrons or VLDL distinguish the two particles and their pathways of assembly. A protein of molecular weight 54,000 daltons was recovered with the chylomicrons. The protein was shown to be synthesized by rat liver hepatocytes, and immunoprecipitation studies with rat intestinal cells incubated with 35S-methionine included this organ as a source of alpha-1-antitrypsin

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

    Science.gov (United States)

    Blaurock, Nancy; Schmerler, Diana; Hünniger, Kerstin; Kurzai, Oliver; Ludewig, Katrin; Baier, Michael; Brunkhorst, Frank Martin; Imhof, Diana; Kiehntopf, Michael

    2016-01-01

    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. PMID:27382189

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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. PMID:27296827

  12. Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress

    Directory of Open Access Journals (Sweden)

    Yaling eFeng

    2016-05-01

    Full Text Available Preeclampsia (PE and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Historical role of alpha-1-antitrypsin deficiency in respiratory and hepatic complications.

    Science.gov (United States)

    Zuo, Li; Pannell, Benjamin K; Zhou, Tingyang; Chuang, Chia-Chen

    2016-09-10

    Alpha-1-antitrypsin (AAT) deficiency is a heritable disease that is commonly associated with complications in the respiratory and hepatic systems. AAT acts as a regulatory enzyme that primarily inhibits neutrophil elastase activity thus protecting tissues from proteolytic damage after inflammation. This paper provides a historical review of the discovery, classification, phenotypic expression, and treatment of AAT deficiency. While its pattern of inheritance has been long understood, the underlying mechanism between AAT deficiency and related diseases remains to be elucidated. Most commonly, AAT deficiency is associated with the development of emphysema in the lungs as well as various liver injuries. Cigarette smoke has been shown to be particularly detrimental in AAT deficient individuals during the development of lung disease. Therefore, understanding familial history may be beneficial when educating patients regarding lifestyle choices. While numerous AAT deficient phenotypes exist in the human populations, only specific variants have been proven to markedly predispose individuals to lung and liver disorders. The exact relationship between AAT levels and the aforementioned diseases is an essential area of further research. It is imperative that clinicians and researchers alike strive to standardize diagnostic criteria and develop safe and effective therapies for this genetic disease. PMID:26768576

  16. 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.

  17. Circulating alpha1-antitrypsin in the general population: Determinants and association with lung function

    Directory of Open Access Journals (Sweden)

    Berger Wolfgang

    2008-04-01

    Full Text Available Abstract Background Severe alpha1-antitrypsin (AAT deficiency associated with low AAT blood concentrations is an established genetic COPD risk factor. Less is known about the respiratory health impact of variation in AAT serum concentrations in the general population. We cross-sectionally investigated correlates of circulating AAT concentrations and its association with FEV1. Methods In 5187 adults (2669 females with high-sensitive c-reactive protein (CRP levels ≤ 10 mg/l from the population-based Swiss SAPALDIA cohort, blood was collected at the time of follow-up examination for measuring serum AAT and CRP. Results Female gender, hormone intake, systolic blood pressure, age in men and in postmenopausal women, as well as active and passive smoking were positively, whereas alcohol intake and BMI inversely correlated with serum AAT levels, independent of CRP adjustment. We observed an inverse association of AAT with FEV1 in the total study population (p Conclusion The results of this population-based study reflect a complex interrelationship between tobacco exposure, gender related factors, circulating AAT, systemic inflammatory status and lung function.

  18. Tissue-specific expression of the human alpha 1-antitrypsin gene is controlled by multiple cis-regulatory elements.

    OpenAIRE

    Shen, R F; Li, Y.; Sifers, R N; Wang, H.; Hardick, C; Tsai, S. Y.; Woo, S L

    1987-01-01

    Human alpha 1-antitrypsin (AAT) is expressed in the liver, and a 318 bp fragment immediately flanking the CAP site of the gene was found to be sufficient to drive the expression of a reporter gene (CAT) specifically in hepatoma cells. The enhancing activity however, was orientation-dependent. The DNA fragment was separated into a distal region and a proximal region. A "core enhancer" sequence GTGGTTTC is present within the distal region and is capable of activity enhancement in both orientati...

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

    OpenAIRE

    Nikolić Aleksandra; Divac Aleksandra; Stanković Marija; Dinić Jelena; Lukić Snežana; Anđelić-Jelić Marina; Popović Dragan; Radojković Dragica

    2010-01-01

    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...

  20. The influence of cigarette smoking on gingival bleeding and serum concentrations of haptoglobin and alpha 1-antitrypsin.

    Science.gov (United States)

    Al-Bayaty, Fouad H; Baharuddin, Noradinar; Abdulla, Mahmood A; Ali, Hapipah Mohd; Arkilla, Magaji B; ALBayaty, Mustafa F

    2013-01-01

    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. PMID:24286083

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Oxidized alpha-1 antitrypsin as a predictive risk marker of opisthorchiasis-associated cholangiocarcinoma.

    Science.gov (United States)

    Jamnongkan, Wassana; Techasen, Anchalee; Thanan, Raynoo; Duenngai, Kunyarat; Sithithaworn, Paiboon; Mairiang, Eimorn; Loilome, Watcharin; Namwat, Nisana; Pairojkul, Chawalit; Yongvanit, Puangrat

    2013-04-01

    The oxidized alpha-1 antitrypsin (ox-A1AT) is one modified form of A1AT, generated via oxidation at its active site by free radicals released from inflammatory cells which subsequently are unable to inhibit protease enzymes. The presence of ox-A1AT in human serum has been used as oxidative stress indicator in many diseases. As oxidative/nitrative damage is one major contributor in opisthorchiasis-driven cholangiocarcinogenesis, we determined A1AT and ox-A1AT expression in human cholangiocarcinoma (CCA) tissue using immunohistochemical staining and measured serum ox-A1AT levels by ELISA. A1AT and ox-A1AT were found to be expressed in the tumor of CCA patients. The group with high expression has a significant poor prognosis. Serum levels of ox-A1AT were also significantly higher in groups of patients with heavy Opisthorchis viverrini infection, advanced periductal fibrosis (APF) and CCA when compared with healthy controls (P < 0.001). Odds ratio (OR) analysis implicated high ox-A1AT levels as a risk predictor for APF and CCA (P < 0.001; OR = 140.5 and 22.0, respectively). In conclusion, as APF may lead to hepatobiliary diseases and an increased risk of CCA development, our results identified ox-A1AT as a potential risk indicator for opisthorchiasis-associated CCA. This marker could now be explored for screening of subjects living in endemic areas where the prevalence of opisthorchiasis still remains high. PMID:23188705

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  5. Tumor necrosis factor-α driven inflammation in alpha-1 antitrypsin deficiency: a new model of pathogenesis and treatment.

    Science.gov (United States)

    Hurley, Killian; Reeves, Emer P; Carroll, Tomás P; McElvaney, Noel G

    2016-02-01

    Alpha-1 antitrypsin (AAT) deficiency (AATD) has traditionally been thought of as a genetic disorder characterized by lung destruction and early emphysema in a low AAT, and high neutrophil elastase (NE) environment in the lungs of affected individuals. Recently, a growing body of evidence has emerged to support the hypothesis that tumor necrosis factor alpha (TNF-α) is essential in the pathogenesis of both genetic AATD and non-genetic chronic obstructive pulmonary disease (COPD). Reports have highlighted the importance of TNF-α driven immune cell dysfunction in the development of lung disease in AATD. The authors discuss the role of AAT as a key modulator of TNF-α signaling firstly in the setting of AATD and secondly in other conditions where AAT augmentation therapy has potential utility as a novel therapy. PMID:26634397

  6. Relationship between alpha-1 antitrypsin deficient genotypes S and Z and lung cancer in Jordanian lung cancer patients

    International Nuclear Information System (INIS)

    Alpha-1 antitrypsin (alpha1-AT) is a secretory glycoprotein produced mainly in the liver and monocytes. It is the most abundant serine protease inhibitor in human plasma. It predominantly inhibits neutrophil elastase thus, it prevents the breakdown of lung tissue. The deficiency of alpha1-AT is an inherited disorder characterized by reduced serum level of alpha1-AT. Protease inhibitors Z (PiZ) and protease inhibitors S (PiS) are the most common deficient genotypes of alpha1-AT. The aim of this study is to test the relationship between alpha1-AT deficient genotypes S and Z and lung cancer in Jordanian lung cancer patients. We obtained the samples used in this study from 100 paraffin embedded tissue blocks of the lung cancer patients from Prince Iman Research Center and Laboratory Sciences at King Hussein Medical Center, Amman, Jordan. Analyses of the Z and S genotypes of alpha1-AT were performed by polymerase chain reaction and restriction fragment length polymorphism techniques at Jordan University of Science and Technology during 2003 and 2004. We demonstrated that all lung cancer patients were of M genotype, and no Z or S genotypes were detected. There is no relationship between alpha1-AT deficient genotypes S and Z and lung cancer in patients involved in this study. (author)

  7. Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis.

    Science.gov (United States)

    Wang, Qian; Du, Jianjun; Yu, Pengfei; Bai, Bin; Zhao, Zhanwei; Wang, Shiqi; Zhu, Junjie; Feng, Quanxin; Gao, Yun; Zhao, Qingchuan; Liu, Chaoxu

    2015-01-01

    Hepatic steatosis (HS) can exacerbate acute pancreatitis (AP). This study aimed to investigate the relation between α1-antitrypsin (AAT) and acute pancreatitis when patients have HS. Using proteomic profiling, we identified 18 differently expressed proteins pots in the serum of rats with or without HS after surgical establishment of AP. AAT was found to be one of the significantly down-regulated proteins. AAT levels were significantly lower in hepatic steatosis acute pancreatitis (HSAP) than in non-HSAP (NHSAP) (P AAT in the serum of 240 patients with HSAP, NHSAP, fatty liver disease (FLD), or no disease. Compared with healthy controls, serum AAT levels in patients with NHSAP were significantly higher (P AAT levels were significantly lower (P AAT levels (r = -0.85, P AAT in patients with HSAP are correlated with disease severity and AAT may represent a potential target for therapies aiming to improve pancreatitis. PMID:26634430

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Tumor necrosis factor alpha and alpha-1 antitrypsin gene variants in Serbian pediatric arterial ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Đorđević Valentina

    2013-01-01

    Full Text Available The etiology of arterial ischemic stroke (AIS in children is complex, and different from that in adults. Although rare, stroke in children is an important cause of mortality and morbidity. There is increasing evidence that genetic factors, including inflammation mediators, have a role in occurrence and outcome of stroke. We have chosen to assess the role of polymorphism -308G/A in the promoter of tumor necrosis factor α (TNFα gene and S and Z mutations in alpha 1-antitrypsin (AAT gene in the etiology of stroke in children. TNFα polymorphism affects plasma levels of this proinflamatory cytokine, and this could contribute to stroke pathology. It has been shown that increased AAT concentration may present a risk for AIS in children. Since S and Z mutations in AAT gene reduce its levels in plasma they could have a protective role in pediatric stroke. In this study twenty six children with AIS and 100 unrelated individuals from Serbian general population were investigated by PCR/RFLP for these gene variations. No statistically significant difference was observed between patients and general population in distribution of genotypes for -308G/A TNFα polymorphism, so its contributory role in the etiology of stroke was not evident in our group of patients. None of the tested AAT gene mutations were found in patients, which is in concordance with the proposed protective role of deficient AAT variants. AIS is a multifactorial disease, with many genes having a modest role in its pathophysiology, so further analyses of their combined effect are needed to elucidate genetic risk factors in the etiology and outcome of stroke in pediatric patients.

  10. Regional distribution of ventilation and perfusion in patients with obstructive pulmonary disease and alpha1-antitrypsin deficiency

    International Nuclear Information System (INIS)

    Regional distribution of pulmonary ventilation and perfusion has been determined of 13 patients with chronic obstructive pulmonary disease (COPD). Eight patients had alpha1-antitrypsin deficiency (α1ATD). Ventilation studies were carried out using xenon-133 (133Xe) and krypton-81m (sup(81m)Kr) gases. Trapping indices were determined from the wash-out part of the xenon ventilation studies. Results obtained from patients were compared with those of normal controls. Ventilation studies with sup(81m)Kr showed pulmonary changes more clearly than did 133Xe studies and the trapping of radio-xenon was more extensive in lung bases than in apices whether or not the patients had α1 ATD. The distribution of perfusion followed a pattern similar to that of ventilation, but did not differ statistically from that of the normal controls. (orig.)

  11. 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

    stimulation. A1AT 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......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...... with azurophile granules in neutrophils indicative of A1AT expression being restricted to the promyelocyte stage. We examined the localization and production of A1AT in healthy donor neutrophils and found A1AT to be a constituent of all granule subtypes and to be released from neutrophils following...

  12. Correction: Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency.

    NARCIS (Netherlands)

    Stolk, J.; Veldhuisen, B.; Annovazzi, L.; Zanone, C.; Versteeg, E.M.M.; Kuppevelt, A.H.M.S.M. van; Nieuwenhuizen, W.; Iadarola, P.; Berden, J.H.M.; Luisetti, M.

    2006-01-01

    BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longi

  13. Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

    NARCIS (Netherlands)

    Stolk, J; Veldhuisen, B; Annovazzi, L; Zanone, C; Versteeg, EM; van Kuppevelt, TH; Nieuwenhuizen, W; Iadarola, P; Luisetti, M

    2005-01-01

    Background: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longi

  14. Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency.

    NARCIS (Netherlands)

    Stolk, J.; Veldhuisen, B.; Annovazzi, L.; Zanone, C.; Versteeg, E.M.M.; Kuppevelt, A.H.M.S.M. van; Nieuwenhuizen, W.; Iadarola, P.; Luisetti, M.

    2005-01-01

    BACKGROUND: The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longi

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

    Directory of Open Access Journals (Sweden)

    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

  16. Tissue-specific expression of the human alpha 1-antitrypsin gene is controlled by multiple cis-regulatory elements.

    Science.gov (United States)

    Shen, R F; Li, Y; Sifers, R N; Wang, H; Hardick, C; Tsai, S Y; Woo, S L

    1987-10-26

    Human alpha 1-antitrypsin (AAT) is expressed in the liver, and a 318 bp fragment immediately flanking the CAP site of the gene was found to be sufficient to drive the expression of a reporter gene (CAT) specifically in hepatoma cells. The enhancing activity however, was orientation-dependent. The DNA fragment was separated into a distal region and a proximal region. A "core enhancer" sequence GTGGTTTC is present within the distal region and is capable of activity enhancement in both orientations when complemented by the proximal region in the sense orientation. The results strongly suggest that there are multiple cis-acting elements in the human AAT gene that confer cell specificity for its expression. Nuclear proteins prepared from the hepatoma cells bound specifically to the proximal region in a band-shifting assay that was resistant to competition by the globin promoter DNA. Foot-printing analysis showed a protected domain within the proximal region that contains a nearly perfect palindromic sequence TGGTTAATATTCACCA, which may be important in the regulation of AAT expression in the liver. PMID:2823229

  17. Corticosteroid-binding globulin cleavage is paradoxically reduced in alpha-1 antitrypsin deficiency: Implications for cortisol homeostasis.

    Science.gov (United States)

    Nenke, Marni A; Holmes, Mark; Rankin, Wayne; Lewis, John G; Torpy, David J

    2016-01-15

    High-affinity corticosteroid-binding globulin (haCBG) is cleaved by neutrophil elastase (NE) resulting in permanent transition to the low cortisol-binding affinity form (laCBG), thereby increasing cortisol availability at inflammatory sites. Alpha-1 antitrypsin (AAT) is the major inhibitor of NE. AAT deficiency (AATD) predisposes patients to early-onset emphysema due to increased proteolytic destruction from the inherent proteinase-antiproteinase imbalance. We hypothesized that AATD may result in increased CBG cleavage in vivo. We collected demographic data and blood samples from 10 patients with AATD and 28 healthy controls measuring total CBG and haCBG levels by parallel in-house ELISAs, as well as AAT, total and free cortisol levels. haCBG was higher (median [range]); 329 [210-551] vs. 250 [175-365] nmol/L; PAAT levels (P<0.05, R=-0.64). Paradoxically, proteolytic cleavage of CBG was reduced in AATD, despite the recognized increase in NE activity. This implies that NE activity is not the mechanism for systemic CBG cleavage in basal, low inflammatory conditions. Relatively low levels of laCBG may have implications for cortisol action in AATD. PMID:26522656

  18. A protein structural approach to the solution of biological problems: alpha 1-antitrypsin as a recent example.

    Science.gov (United States)

    Lomas, D A; Carrell, R W

    1993-09-01

    alpha 1-Antitrypsin is a circulating serine proteinase inhibitor that protects the lungs against proteolysis by the enzyme neutrophil elastase. Most northern Europeans have only the normal M form, but some 4% are heterozygotes for the Z deficiency mutant. This mutant is characterized by the substitution of a positively charged lysine residue for a negatively charged glutamic acid at position 342 and results in normal gene translation but reduced protein secretion into the plasma. The plasma levels of antitrypsin in homozygotes are only 15% of normal, the other 85% being retained in the endoplasmic reticulum of the hepatocyte. This review describes the effect of the Z mutation on the structure and function of antitrypsin and illustrates the importance of understanding protein structure in solving the mechanism of Z antitrypsin retention within the liver. We demonstrate that antitrypsin accumulation in the liver results from a unique interaction between antitrypsin molecules. The Z mutation perturbs the gap between the third and fifth strands of the A sheet, allowing the reactive center loop of one molecule to insert into the A sheet of a second. This loop-sheet polymerization results in the formation of chains of protein which form insoluble inclusions in the endoplasmic reticulum, resulting in hepatocellular damage and cirrhosis. In addition, the Z mutation results in a distortion of the circular dichroic spectrum, a rearrangement of the reactive center loop with respect to the A sheet, and a reduction in association rate constant with the cognate proteinase neutrophil elastase. PMID:8214081

  19. Serum concentration of alpha-1 antitrypsin is significantly higher in colorectal cancer patients than in healthy controls

    International Nuclear Information System (INIS)

    The association between alpha-1 antitrypsin (AAT) deficiency and colorectal cancer (CRC) is currently controversial. The present study compares AAT serum concentrations and gene frequencies between a group of CRC patients and a control group of healthy unrelated people (HUP). 267 CRC subjects (63% males, 72 ± 10 years old) were enlisted from a Hospital Clinic setting in Asturias, Spain. The HUP group comprised 327 subjects (67% males, mean age 70 ± 7.5 years old) from the same geographical region. Outcome measures were AAT serum concentrations measured by nephelometry, and AAT phenotyping characterization by isoelectric focusing. Significantly higher serum concentrations were found among CRC (208 ± 60) than in HUP individuals (144 ± 20.5) (p = 0.0001). No differences were found in the phenotypic distribution of the Pi*S and Pi*Z allelic frequencies (p = 0.639), although the frequency of Pi*Z was higher in CRC (21%) than in HUP subjects (15%). The only statistically significant finding in this study was the markedly higher AAT serum concentrations found in CRC subjects compared with HUP controls, irrespective of whether their Pi* phenotype was normal (Pi*MM) or deficient (Pi*MS, Pi*MZ and Pi*SZ). Although there was a trend towards the more deficient Pi* phenotype the more advanced the tumor, the results were inconclusive due to the small sample size. Consequently, more powerful studies are needed to reach firmer conclusions on this matter

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Alpha-1 Antitrypsin Deficiency

    Science.gov (United States)

    ... a Healthy Liver In the Field Call to Action - Change Tomorrow, Give Today Liver Lowdown Sept 2013 Recovery Month Path to Wellness ... Patient Story-Lynette In the Field Call to Action 5 Things About Hep Healthy Summer Tips Liver Lowdown June 2013 Liver Lowdown July/Aug 2014 ...

  2. 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....

  3. 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

  4. The clinical significance of determination of serum leptin, c-reactive protein and alpha 1-antitrypsin levels in patients with breast cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of changes of serum leptin, C-reactive protein and alpha 1-antitrypsin (α1-AT)levels in patients with breast cancer. Methods: Serum leptin(with radioimmunoassay)and CRP, α1-AT (with ELISA)levels were determined in 79 patients with breast cancer and 60 controls. Results: Serum levels of leptin, CRP and α1-AT in breast cancer patients were significantly higher than those in the controls (all P1-AT levels patients with breast cancer might be related with progression of the disease, each played independent biological roles. (authors)

  5. Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

    Directory of Open Access Journals (Sweden)

    Nieuwenhuizen Willem

    2005-05-01

    Full Text Available Abstract Background The burden of proteinases from inflammatory cells in the lung of subjects with type Pi ZZ of alpha-1-antitrypsin deficiency is higher than in those without the deficiency. Cross-sectional studies have shown increased levels of biomarkers of extracellular matrix degradation in vivo. Longitudinal variability of these biomarkers is unknown but desirable for clinical studies with proteinase inhibitors. Methods We measured three different types of biomarkers, including desmosines, elastase-formed fibrinogen fragments and heparan sulfate epitope JM403, in plasma and urine for a period of 7 weeks in a group of 12 patients who participated in a placebo-controlled study to assess the safety of a single inhalation of hyaluronic acid. Results Effect of study medication on any of the biomarkers was not seen. Baseline desmosines in plasma and urine correlated with baseline CO diffusion capacity (R = 0.81, p = 0.01 and R = 0.65, p = 0.05. Mean coefficient of variation within patients (CVi for plasma and urine desmosines was 18.7 to 13.5%, respectively. Change in urinary desmosine levels correlated significantly with change in plasma desmosine levels (R = 0.84, p Conclusion We found acceptable variability in our study parameters, indicating the feasibility of their use in an evaluation of biochemical efficacy of alpha-1-antitrypsin augmentation therapy in Pi Z subjects.

  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. Diagnosis of. alpha. sub 1 -antitrypsin deficiency by enzymatic amplification of human genomic DNA and direct sequencing of polymerase chain reaction products

    Energy Technology Data Exchange (ETDEWEB)

    Newton, C.R.; Graham, A.; Powell, S.; Gammack, A.; Riley, J.; Markham, A.F. (ICI Diagnostics, Cheshire (England)); Kalsheker, N. (Univ. of Wales, Cardiff (Wales))

    1988-09-12

    The authors have compared sequencing of cloned polymerase chain reaction (PCR) products and the direct sequencing of PCR products in the examination of individuals from six families affected with {alpha}{sub 1}-antitrypsin (AAT) deficiency. In families where paternity was in question they confirmed consanguinity by DNA fingerprinting using a panel of locus-specific minisatellite probes. They demonstrate that direct sequencing of PCR amplification products is the method of choice for the absolutely specific diagnosis of AAT deficiency and can distinguish normals, heterozygotes and homozygotes in a single, rapid and facile assay. Furthermore, they demonstrate the reproducibility of the PCR and a rapid DNA isolation procedure. They have also shown that two loci can be simultaneously amplified and that the PCR product from each locus can be independently examined by direct DNA sequencing.

  9. 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; Deng, Chunqin; Wencker, Marion; Stockley, Robert A

    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 with...... AATD (n = 77) were randomised to weekly infusions of 60 mg/kg human AAT (Prolastin) or placebo over 2 to 2.5 years. Lung volume was included as a covariate in an endpoint analysis and a comparison was made of different CT densitometric indices (15th percentile lung density [PD15], mean lung density...... analysis. TRIAL REGISTRATION: Registered in ClinicalTrials.gov as 'Antitrypsin (AAT) to Treat Emphysema in AAT-Deficient Patients'; ClinicalTrials.gov Identifier: NCT00263887....

  10. Emergence of a Stage-Dependent Human Liver Disease Signature with Directed Differentiation of Alpha-1 Antitrypsin-Deficient iPS Cells

    Directory of Open Access Journals (Sweden)

    Andrew A. Wilson

    2015-05-01

    Full Text Available Induced pluripotent stem cells (iPSCs provide an inexhaustible source of cells for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs of iPSCs derived from diseased versus normal human cohorts as they emerge during in vitro directed differentiation. Using iPSCs generated from a cohort carrying mutations (PiZZ in the gene responsible for alpha-1 antitrypsin (AAT deficiency, we find that the global transcriptomes of PiZZ iPSCs diverge from normal controls upon differentiation to hepatic cells. Expression of 135 genes distinguishes PiZZ iPSC-hepatic cells, providing potential clues to liver disease pathogenesis. The disease-specific cells display intracellular accumulation of mutant AAT protein, resulting in increased autophagic flux. Furthermore, we detect beneficial responses to the drug carbamazepine, which further augments autophagic flux, but adverse responses to known hepatotoxic drugs. Our findings support the utility of iPSCs as tools for drug development or prediction of toxicity.

  11. 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.

  12. 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.

  13. Role of α-1-antitrypsin and oxidative stress in emphysema

    Directory of Open Access Journals (Sweden)

    Anita M Raut, Suryakar AN, Smita D Mhaisekar, Dilip Mhaisekar

    2013-02-01

    Full Text Available In the lungs, deficiency of alpha-1antitrypsin can lead to the development of emphysema. Emphysema involves destruction of the lung’s air sacs (alveoli, where oxygen from the air is exchanged for carbon dioxide in the blood. Alpha 1-antitrypsin is a protein produced by the liver and that circulates in the blood. Among other functions, the protein protects the lungs so they can function properly. In people with the disorder, the liver produces too little or no alpha 1 -antitrypsin. Without enough alpha-1 antitrypsin, neutrophil elastase is free to destroy air sac tissue. 60 emphysema patients were included in the study. 100 healthy non-smokers’ were served as controls. Their baseline clinical examination, Alpha 1- antitrysin (AAT, malondialdehyde (MDA and vitamin E were measured. The mean levels of Alpha 1 antitrysin and vitamin E in the patients at baseline were lower (P< 0.001 than the controls. The malondialdehyde were high (P<0.001 in the emphysema patients compared to controls. We found decreased levels of Alpha 1- antitrysin and vitamin E and increased levels of malondialdehyde (MDA. Thus the present study confirmed the existence of oxidative stress and altered levels of alpha 1- antitrypsin in emphysema patients.

  14. Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry

    Directory of Open Access Journals (Sweden)

    Stolk Jan

    2010-10-01

    Full Text Available Abstract Background Two randomised, double-blind, placebo-controlled trials have investigated the efficacy of IV alpha-1 antitrypsin (AAT augmentation therapy on emphysema progression using CT densitometry. Methods Data from these similar trials, a 2-center Danish-Dutch study (n = 54 and the 3-center EXAcerbations and CT scan as Lung Endpoints (EXACTLE study (n = 65, were pooled to increase the statistical power. The change in 15th percentile of lung density (PD15 measured by CT scan was obtained from both trials. All subjects had 1 CT scan at baseline and at least 1 CT scan after treatment. Densitometric data from 119 patients (AAT [Alfalastin® or Prolastin®], n = 60; placebo, n = 59 were analysed by a statistical/endpoint analysis method. To adjust for lung volume, volume correction was made by including the change in log-transformed total lung volume as a covariate in the statistical model. Results Mean follow-up was approximately 2.5 years. The mean change in lung density from baseline to last CT scan was -4.082 g/L for AAT and -6.379 g/L for placebo with a treatment difference of 2.297 (95% CI, 0.669 to 3.926; p = 0.006. The corresponding annual declines were -1.73 and -2.74 g/L/yr, respectively. Conclusions The overall results of the combined analysis of 2 separate trials of comparable design, and the only 2 controlled clinical trials completed to date, has confirmed that IV AAT augmentation therapy significantly reduces the decline in lung density and may therefore reduce the future risk of mortality in patients with AAT deficiency-related emphysema. Trial registration The EXACTLE study was registered in ClinicalTrials.gov as 'Antitrypsin (AAT to Treat Emphysema in AAT-Deficient Patients'; ClinicalTrials.gov Identifier: NCT00263887.

  15. Inhibitory effect of a mixture containing vitamin C, lysine, proline, epigallocatechin gallate, zinc and alpha-1-antitrypsin on lung carcinogenesis induced by benzo(a pyrene in mice

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    Ahmed Mohamed Ibrahim

    2013-01-01

    Full Text Available Background: This study was aimed to evaluate protective and therapeutic effects of a specific mixture, containing vitamin C, lysine, proline, epigallocatechin gallate and zinc, as well as alpha-1-antitrypsin protein on lung tumorigenesis induced by benzo(a pyrene [B(aP] in mice. Materials and Methods: Swiss albino mice were divided into two main experiments, experiment (1 the mice were injected with 100 mg/kg B(aP and lasted for 28 weeks, while experiment (2 the mice were injected with 8 doses each of 50 mg/kg B(aP and lasted for 16 weeks. Each experiment (1 and 2 divided into five groups, group (I received vehicle, group (II received the protector mixture, group (III received the carcinogen B(aP, group (IV received the protector together with the carcinogen (simultaneously and group (V received the carcinogen then the protector (consecutively. Results: Total sialic acid, thiobarbituric acid reactive substances, vascular epithelial growth factor, hydroxyproline levels, as well as elastase and gelatinase activities showed significant elevation in group (III in the two experiments comparing to control group (P < 0.001. These biochemical alterations were associated with histopathological changes. Administration of the protector in group IV and group V causes significant decrease in such parameters with improvement in histopathological alterations with improvement in histopathological alterations when compared with group III in the two experiments (P < 0.001. Conclusion: The present protector mixture has the ability to suppress neoplastic alteration and restore the biochemical and histopathological parameters towards normal on lung carcinogenesis induced by benzo(a pyrene in mice. Furthermore, the present mixture have more protective rather than therapeutic action.

  16. Polymorphisms in the HPC/ELAC-2 and alpha 1-antitrypsin genes that correlate with human diseases in a North Indian population.

    Science.gov (United States)

    Sobti, Ranbir C; Thakur, Hitender; Gupta, Lipsy; Janmeja, Ashok K; Seth, Amlesh; Singh, Sharwan K

    2011-06-01

    Two genes HPC/ELAC-2 and AAT were studied in north Indian population. HPC/ELAC-2 was studied in prostate cancer cases and AAT was studied in COPD patients. HPC/ELAC-2 is considered as an important cancer-susceptibility gene in prostate cancer. There are two common polymorphisms of this gene, i.e., Ser217Leu and Ala541Thr. Alpha 1 antitrypsin is a highly polymorphic anti-elastase enzyme, especially active in the protection of alveoli and liver. In the present study, we observed the distribution of two deficient alleles PiZ and Pi S in COPD patients. We extracted the DNA from 157 prostate cancer cases, 200 COPD patients, 170 BPH and 370 healthy controls. The polymorphisms were studied by PCR-RFLP technique. The mutant genotype (Leu/Leu) of HPC/ELAC-2 was present in 9.6, 7.6 and 5.9% of BPH, cancer cases and healthy controls, respectively. Higher risk of Ser/Leu as well as Leu/Leu had shown when compared to healthy controls. That was about 1.5 and 1.7-fold (OR = 1.55; 95% CI = 0.96-2.51; OR = 1.70; 95% CI = 0.74-3.92), respectively. Risk was found to be increased in smokers and those consuming non-vegetarian diet. Our results suggest that the HPC/ELAC-2 polymorphisms, especially in localized cases, could help to predict prostate cancer risk and confirm its high prevalence of the leu/leu allele in north Indian population. Considering heterozygous PiZ genotype, we obtained an OR of 3.82 (P = 0.03). Multivariate analysis adjusted by age sex and drinking habit showed 4.15-fold increased risk for COPD in PiZ heterozygous individuals. No increased risk was observed in the individuals carrying PiS alleles. PMID:20119870

  17. Altered glycosylation, expression of serum haptoglobin and alpha-1-antitrypsin in chronic hepatitis C, hepatitis C induced liver cirrhosis and hepatocellular carcinoma patients.

    Science.gov (United States)

    Mondal, Gautam; Saroha, Ashish; Bose, Partha Pratim; Chatterjee, B P

    2016-04-01

    Liver cirrhosis with hepatitis C viral infection (HCV-LC) causes high risk to develop hepatocellular carcinoma (HCC). Besides diagnosis of liver cirrhosis by biochemical test, imaging techniques, assessment of structural liver damage by biopsy shows several disadvantages. Our aim was to monitor the changes in the expression level of serum proteins and their glycosylation pattern among chronic hepatitis C (HCV-CH), HCV-LC and HCC patients with respect to controls. 2D gel electrophoresis of HCV-CH, HCV-LC and HCC patients' sera showed several protein spots, which were identified by LC-MS. The change in the expression of two prominent protein spots, haptoglobin (Hp) and alpha 1-antitrypsin (AAT) was evaluated by western blot and ELISA. The changes in glycosylation pattern of these serum proteins were assayed using different lectins. Increased level of Hp and AAT was observed in HCV-LC and HCC patients' group whereas those were found to be present less in HCV-CH patient groups with respect to control as determined by ELISA using monoclonal antibodies. Decreased level of sialylation in both Hp and AAT was observed in HCV-LC and HCV-CH patients' group whereas increased level of sialylation was observed in HCC patient groups by ELISA using Sambucus nigra agglutinin. On the other hand increased level of fucosylation in two serum glycoproteins was observed in HCV-LC and HCC patients' group using Lens culinarris agglutinin. High glycan branching was found in HCV-LC and HCC patient groups in Hp but not in HCV-CH as determined by Datura stramonium agglutinin. However, there was no such change observed in glycan branching in AAT of HCV-CH and HCV-LC patients' groups, to the contrary high glycan branching was observed in HCC patients' group. Increased level of exposed galactose in both serum proteins was observed in both HCC patients' group as determined by Ricinus communis agglutinin. The present glycoproteomics study could predict the progression of HCV-CH, HCV-LC and HCC

  18. Diagnóstico tardío de déficit de α-1-antitripsina Delayed diagnosis of alpha-1 antitrypsin deficiency

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    P. Rodríguez

    2011-04-01

    Full Text Available El déficit de alfa-1 antitripsina (D-AAT es una enfermedad genética, relativamente frecuente en poblaciones de origen europeo. Frecuentemente está infradiagnosticada, con largos retrasos entre el inicio de los síntomas respiratorios y el diagnóstico definitivo. El D-AAT puede diagnosticarse con la determinación de los niveles séricos de esta proteína, y, cuando están por debajo del rango normal debe ser confirmado con el fenotipo. El seguimiento correcto de la progresión de la enfermedad debe realizarse en todos los casos, ya que se asocia con mejor pronóstico. Presentamos el caso de una mujer de 69 años, con infecciones respiratorias de repetición y sintomatología asmática. Los niveles de AAT estaban por debajo de la normalidad, confirmándose posteriormente el fenotipo ZZ. El retraso diagnóstico de nuestra paciente parece reforzar la necesidad de alertar a los médicos sobre esta enfermedad, frecuentemente asociada con síntomas de asma o EPOC.Alpha-1 antitrypsin deficiency (AAT-D is a genetic disease, relatively common in populations of European ancestry. AAT-D remains undiagnosed in many patients, and there are often long delays between the onset of respiratory symptoms and diagnosis. AAT-D can be readily diagnosed by measurement of the serum or plasma protein level, which should be confirmed by assessing the genotype or protein phenotype when AAT levels are below the normal range. Close monitoring for the development or progression of lung disease or liver disease is required, and can improve the prognosis. We show the case of a 69 year old woman with recurrent respiratory infections and asthma symptoms. The serum levels of AAT were below the normal range, and ZZ genotype was confirmed. The delayed diagnosis of our patient seems to emphasize the need to remind the doctors about AAT-D, frequently associated with asthma or COPD symptoms.

  19. Alpha-1 Antitrypsin Deficiency PI*Z and PI*S Gene Frequency Distribution Using on Maps of the World by an Inverse Distance Weighting (IDW) Multivariate Interpolation Method

    OpenAIRE

    Blanco, Ignacio; de Serres, Frederick J; Cárcaba, Victoriano; Lara, Beatríz; Fernández-Bustillo, Enrique

    2012-01-01

    1.Background Currently, there is a remarkable lack of genetic epidemiological studies on alpha 1-antitrypsin (AAT) deficiency in about half of the 193 countries of the World. This fact impedes the establishment of a true prevalence pattern of this deleterious hereditary disorder in extensive regions of human population. 2.Objectives The aim of the present study was to generate detailed maps of the frequency distribution of the two most frequent AAT deficiency alleles (i.e., PI*S and PI*Z) in ...

  20. Therapy with Plasma Purified Alpha1-Antitrypsin (Prolastin®) Induces Time-Dependent Changes in Plasma Levels of MMP-9 and MPO

    OpenAIRE

    Koepke, Janine; Dresel, Marc; Schmid, Severin; Greulich, Timm; Beutel, Björn; Schmeck, Bernd; Vogelmeier, Claus Franz; Janciauskiene, Sabina; Koczulla, Andreas Rembert

    2015-01-01

    The common Z mutation (Glu342Lys) of α1-antitrypsin (A1AT) results in the polymerization and intracellular retention of A1AT protein. The concomitant deficiency of functional A1AT predisposes PiZZ subjects to early onset emphysema. Clinical studies have implied that, among the biomarkers associated with emphysema, matrix metalloproteinase 9 (MMP-9) is of particular importance. Increased plasma MMP-9 levels are proposed to predict the decline of lung function as well as greater COPD exacerbati...

  1. 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...... from individuals who are normal, heterozygous, or homozygous for the mutations. We show that the two assays can be performed with purified genomic DNA as well as with boiled blood spots. The new assays were validated by parallel testing with a technique in which PCR is combined with allele......-specific oligonucleotide (ASO) probes. In all cases tested the results obtained by the different techniques were in accordance. The new assays can be used for prenatal diagnostics and can be performed directly with boiled tissue samples. Because the new assays are easy to perform and reliable, we conclude that they are...

  2. Krüppel-like zinc finger proteins in end-stage COPD lungs with and without severe alpha1-antitrypsin deficiency

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    Koczulla A-Rembert

    2012-05-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is influenced by environmental and genetic factors. An important fraction of COPD cases harbor a major genetic determinant, inherited ZZ (Glu342Lys α1-antitrypsin deficiency (AATD. A study was undertaken to investigate gene expression patterns in end-stage COPD lungs from patients with and without AATD. Methods Explanted lungs of end-stage ZZ AATD-related (treated and non-treated with AAT augmentation therapy and “normal” MM COPD, and liver biopsies from patients suffering from liver cirrhosis with and without ZZ AATD were used for gene expression analysis by Affymetrix microarrays or RT-PCR. Results A total of 162 genes were found to be differentially expressed (p-value ≤ 0.05 and |FC| ≥ 2 between MM and ZZ COPD patients. Of those, 134 gene sets were up-regulated and 28 were down-regulated in ZZ relative to MM lung tissue. A subgroup of genes, zinc finger protein 165, snail homolog 1 (Drosophila (SNAI1, and Krüppel-like transcription factors (KLFs 4 (gut, 9 and 10, perfectly segregated ZZ and MM COPD patients. The higher expression of KLF 9 and KLF10 has been verified in the replication cohort with AATD-related end-stage lung emphysema and liver cirrhosis. Furthermore, higher expression of KLF9, SNAI1 and DEFA1 was found in ZZ COPD lungs without augmentation therapy relative to MM COPD or ZZ COPD with augmentation therapy. Conclusions These results reveal the involvement of transcriptional regulators of the zinc-finger family in COPD pathogenesis and provide deeper insight into the pathophysiological mechanisms of COPD with and without AATD.

  3. Therapy with plasma purified alpha1-antitrypsin (Prolastin® induces time-dependent changes in plasma levels of MMP-9 and MPO.

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    Janine Koepke

    Full Text Available The common Z mutation (Glu342Lys of α1-antitrypsin (A1AT results in the polymerization and intracellular retention of A1AT protein. The concomitant deficiency of functional A1AT predisposes PiZZ subjects to early onset emphysema. Clinical studies have implied that, among the biomarkers associated with emphysema, matrix metalloproteinase 9 (MMP-9 is of particular importance. Increased plasma MMP-9 levels are proposed to predict the decline of lung function as well as greater COPD exacerbations in A1AT deficiency-associated emphysema. The aim of the present study was to investigate the effect of A1AT therapy (Prolastin on plasma MMP-9 and myeloperoxidase (MPO levels. In total 34 PiZZ emphysema patients were recruited: 12 patients without and 22 with weekly intravenous (60 mg/kg body weight A1AT therapy. The quantitative analysis of A1AT, MMP-9 and MPO was performed in serum and in supernatants of blood neutrophils isolated from patients before and after therapy. Patients with Prolastin therapy showed significantly lower serum MMP-9 and MPO levels than those without therapy. However, parallel analysis revealed that a rapid infusion of Prolastin is accompanied by a transient elevation of plasma MMP-9 and MPO levels. Experiments with freshly isolated blood neutrophils confirmed that therapy with Prolastin causes transient MMP-9 and MPO release. Prolastin induced the rapid release of MMP-9 and MPO when added directly to neutrophil cultures and this reaction was associated with the presence of IgA in A1AT preparation. Our data support the conclusion that changes in plasma levels of MMP-9 and MPO mirror the effect of Prolastin on blood neutrophils.

  4. 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.

  5. Progression of Emphysema Evaluated by MRI Using Hyperpolarized 3He (HP 3He) Measurements in Patients with Alpha-1-Antitrypsin (A1AT) Deficiency Compared with CT and Lung Function Tests

    Energy Technology Data Exchange (ETDEWEB)

    Stavngaard, T.; Vejby Soegaard, L. (Danish Research Center for Magnetic Resonance, Copenhagen Univ. Hospital Hvidovre, Hvidovre (Denmark)); Batz, M. (Inst. of Physics, Johannes Gutenberg Univ., Mainz (Germany)); Schreiber, L.M. (Dept. of Interventional and Diagnostic Radiology, Johannes Gutenberg Univ. Medical School, Mainz (Germany)); Dirksen, A. (Dept. of Respiratory Medicine, Gentofte Hospital, Univ. of Copenhagen, Copenhagen (Denmark))

    2009-11-15

    Background: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV1) being the most accepted and used measurement. However, FEV1 is insensitive in detecting mild/slow progression of emphysema because of low reproducibility as compared to yearly decline. Purpose: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) 3He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. Material and Methods: Nine patients with severe A1AT deficiency were studied over a period of 2 years (baseline, year 1, and year 2) with HP 3He MRI using apparent diffusion coefficient (ADC), lung function tests (FEV1 and carbon monoxide lung diffusion capacity [DL,CO]), and computed tomography (CT) using densitometric parameters (15th percentile density [CT-PD15] and relative area of emphysema below -910 HU [CT-RA-910]). Results: Seven patients were scanned three times, one patient two times, and one patient only at baseline. The mean increase in ADC values from first to last HP 3He MR scanning was 3.8% (0.014 cm2/s [SD 0.024 cm2/s]; not significant). The time trends for FEV1, DL,CO, CT-PD15, and CT-RA-910 were all statistically significant. We found a high correlation between ADC and DL,CO (P<0.001). Conclusion: This pilot study indicates the possible use of nonionizing HP 3He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results

  6. Progression of Emphysema Evaluated by MRI Using Hyperpolarized 3He (HP 3He Measurements in Patients with Alpha-1-Antitrypsin (A1AT) Deficiency Compared with CT and Lung Function Tests

    International Nuclear Information System (INIS)

    Background: The progression of emphysema is traditionally measured by pulmonary function test, with forced expiratory volume in 1 s (FEV1) being the most accepted and used measurement. However, FEV1 is insensitive in detecting mild/slow progression of emphysema because of low reproducibility as compared to yearly decline. Purpose: To investigate the progression of emphysema over a period of 2 years using diffusion-weighted hyperpolarized (HP) 3He magnetic resonance imaging (MRI) in patients with alpha-1-antitrypsin (A1AT) deficiency. Material and Methods: Nine patients with severe A1AT deficiency were studied over a period of 2 years (baseline, year 1, and year 2) with HP 3He MRI using apparent diffusion coefficient (ADC), lung function tests (FEV1 and carbon monoxide lung diffusion capacity [DL,CO]), and computed tomography (CT) using densitometric parameters (15th percentile density [CT-PD15] and relative area of emphysema below -910 HU [CT-RA-910]). Results: Seven patients were scanned three times, one patient two times, and one patient only at baseline. The mean increase in ADC values from first to last HP 3He MR scanning was 3.8% (0.014 cm2/s [SD 0.024 cm2/s]; not significant). The time trends for FEV1, DL,CO, CT-PD15, and CT-RA-910 were all statistically significant. We found a high correlation between ADC and DL,CO (P3He MRI for monitoring the progression of emphysema. However, in the future, larger studies are needed to confirm these preliminary results

  7. Living with Alpha-1 Antitrypsin Deficiency

    Science.gov (United States)

    ... include flower and tree pollen, ash, allergens, air pollution, wood burning stoves, paint fumes, and fumes from ... protein foods, such as lean meats, poultry without skin, seafood, processed soy products, nuts, seeds, beans, and ...

  8. Augmentation therapy for alpha-1 antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stockley, Robert A; Miravitlles, Marc; Vogelmeier, Claus

    2013-01-01

    combination of age, physiological impairment, exacerbation history and rate of decline in spirometry and other measures of emphysema may be used to improve therapeutic decision making, until a reliable predictive biomarker of the evolution of lung impairment can be identified. In addition, individual...

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

    Science.gov (United States)

    ... in Genetics Coverage & Reimbursement of Genetic Tests Genetic Discrimination Human Subjects Research Informed Consent for Genomics Research ... symptoms can include repeated respiratory infections, fatigue, rapid heartbeat upon standing, vision problems and unintentional weight loss. ...

  10. 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

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

    Directory of Open Access Journals (Sweden)

    Joanna Chorostowska-Wynimko

    2015-03-01

    Full Text Available α1-antitrypsin deficiency (AATD is a significantly under-recognised autosomal genetic disorder with <10% of affected 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.

  12. 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

  13. Alpha One Foundation

    Science.gov (United States)

    ... Tested Find Support Find Doctor What Is Alpha-1? Alpha-1 Antitrypsin Deficiency (Alpha-1) is a ... results for inhaled augmentation More News Our Number One Goal: Find a cure for Alpha-1. Website ...

  14. Prevalence of α-1-Antitrypsin gene mutations in Saudi Arabia

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    Badr Aljarallah

    2011-01-01

    Full Text Available Background/Aim: α-1 antitrypsin (AAT deficiency results from mutations of the protease inhibitor (PI. The AAT gene is mapped on chromosome 14 and has been associated with chronic liver disease and chronic obstructive pulmonary disease (COPD. Objective: To determine the frequency of AAT mutations on S and Z carrier alleles in healthy Saudi individuals from Qassim Province in Saudi Arabia. Patients and Methods : A total of 158 healthy, unrelated participants from Qassim Province were recruited. They were genotyped for the two AAT-deficiency alleles, PIFNx01S and PIFNx01Z, using polymerase chain reaction, with primers designed throughout to mediate site-directed mutagenesis. Results: Of the 158 subjects, 11.39% were carriers for the S mutation (i.e., had the MS genotype, whereas 2.53% were carriers for the Z mutation (i.e., had the MZ genotype. The SZ genotype was present in 3.8% of subjects, while the homozygous genotype SS was present in 1.9% of subjects. No subjects showed the ZZ mutant genotype. Accordingly, frequency of the mutant S and Z alleles of AAT gene was 9.49% and 3.19%, respectively. Conclusion: The results obtained showed a high prevalence of the AAT deficiency allele in the Saudi population. This probably warrants adoption of a screening program for at-risk individuals, so that they might initiate adequate prophylactic measures.

  15. α1-Antitrypsin deficiency • 3: Clinical manifestations and natural history

    OpenAIRE

    Needham, M; Stockley, R

    2004-01-01

    A review of the clinical manifestations of α1-antitrypsin (AAT) deficiency, including lung disease and liver disease, and risk factors affecting the rate of decline in lung function in AAT deficient patients.

  16. [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. PMID:22008137

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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; Sandhaus, Robert A; Seersholm, Niels; Stocks, James M; Stoel, Berend C; Huang, Liping; Yao, Zhenling; Edelman, Jonathan M; McElvaney, Noel G

    2015-01-01

    four (5%) in the placebo group. One death occurred in the A1PI group (respiratory failure) and three occurred in the placebo group (sepsis, pneumonia, and metastatic breast cancer). INTERPRETATION: Measurement of lung density with CT at TLC alone provides evidence that purified A1PI augmentation slows......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...... than spirometry is, so we aimed to assess the efficacy of augmentation treatment with this measure. METHODS: The RAPID study was a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial of A1PI treatment in patients with α1 antitrypsin deficiency. We recruited eligible non...

  19. A Novel Antiapoptotic Role for α1-Antitrypsin in the Prevention of Pulmonary Emphysema

    OpenAIRE

    Petrache, Irina; Fijalkowska, Iwona; Zhen, Lijie; Medler, Terry R.; Brown, Emile; Cruz, Pedro; Choe, Kang-Hyeon; Taraseviciene-Stewart, Laimute; Scerbavicius, Robertas; Shapiro, Lee; Zhang, Bing; Song, Sihong; Hicklin, Dan; Voelkel, Norbert F.; Flotte, Terence

    2006-01-01

    Rationale: There is growing evidence that alveolar cell apoptosis plays an important role in emphysema pathogenesis, a chronic inflammatory lung disease characterized by alveolar destruction. The association of α1-antitrypsin deficiency with the development of emphysema has supported the concept that protease/antiprotease imbalance mediates cigarette smoke–induced emphysema.

  20. A single-chain variable fragment intrabody prevents intracellular polymerization of Z α 1-antitrypsin while allowing its antiproteinase activity

    OpenAIRE

    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.

    2015-01-01

    Mutant Z α 1-antitrypsin (E342K) accumulates as polymers within the endoplasmic reticulum (ER) of hepatocytes predisposing to liver disease, whereas low levels of circulating Z α 1-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 α 1-antitrypsin that comply with both requirements. We report the generation of an mAb (4B12...

  1. α1-antitrypsin increases interleukin-1 receptor antagonist production during pancreatic islet graft transplantation.

    Science.gov (United States)

    Abecassis, Avishag; Schuster, Ronen; Shahaf, Galit; Ozeri, Eyal; Green, Ross; Ochayon, David E; Rider, Peleg; Lewis, Eli C

    2014-07-01

    Although islet transplantation for individuals with type 1 diabetes has been shown to yield superior blood glucose control, it remains inadequate for long-term control. This is partly due to islet injuries and stresses that can lead to beta cell loss. Inhibition of excess IL-1β activity might minimize islet injuries, thus preserving function. The IL-1 receptor antagonist (IL-1Ra), an endogenous inhibitor of IL-1β, protects islets from cytokine-induced necrosis and apoptosis. Therefore, an imbalance between IL-1β and IL-1Ra might influence the courses of allogeneic and autoimmune responses to islets. Our group previously demonstrated that the circulating serine-protease inhibitor human alpha-1-antitrypsin (hAAT), the levels of which increase in circulation during acute-phase immune responses, exhibits anti-inflammatory and islet-protective properties, as well as immunomodulatory activity. In the present study, we sought to determine whether the pancreatic islet allograft-protective activity of hAAT was mediated by IL-1Ra induction. Our results demonstrated that hAAT led to a 2.04-fold increase in IL-1Ra expression in stimulated macrophages and that hAAT-pre-treated islet grafts exhibited a 4.851-fold increase in IL-1Ra transcript levels, which were associated with a moderate inflammatory profile. Unexpectedly, islets that were isolated from IL-1Ra-knockout mice and pre-treated with hAAT before grafting into wild-type mice yielded an increase in intragraft IL-1Ra expression that was presumably derived from infiltrating host cells, albeit in the absence of hAAT treatment of the host. Indeed, hAAT-pre-treated islets generated hAAT-free conditioned medium that could induce IL-1Ra production in cultured macrophages. Finally, we demonstrated that hAAT promoted a distinct phosphorylation and nuclear translocation pattern for p65, a key transcription factor required for IL-1Ra expression. PMID:25000533

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

    OpenAIRE

    McElvaney, Noel G.

    2015-01-01

    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...

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

    OpenAIRE

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

    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 wit...

  4. Rare case of eosinophilic granulomatosis with polyangiitis in two patients with α-1-antitrypsin deficiency (PiSZ).

    Science.gov (United States)

    Moxey, Jordan Maureen; Low, Emma Victoria; Turner, Alice Margaret

    2016-01-01

    We present two cases of eosinophilic granulomatosis with polyangiitis occurring with α-1-antitrypsin deficiency, both PiSZ phenotype. The simultaneous occurrence of these two conditions has seldom been described in the literature, despite evidence of an association between α-1-antitrypsin deficiency and other forms of vasculitis. Both patients had pulmonary involvement and reported intermittent exacerbations of vasculitic symptoms. Both patients were managed on low-dose oral steroids and azathioprine remaining well with occasional exacerbations. It is important to consider whether there is an association between eosinophilic granulomatosis with polyangiitis and α-1-antitrypsin deficiency, as this may lead to more severe pulmonary symptoms during exacerbations. If a genetic association between the two conditions is found, clinicians should be aware of the possible need to screen for α-1-antitrypsin deficiency in appropriate patients. PMID:27118743

  5. 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

  6. 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. PMID:25757566

  7. Mysteries of α1-antitrypsin deficiency: emerging therapeutic strategies for a challenging disease

    Directory of Open Access Journals (Sweden)

    Raafe Ghouse

    2014-04-01

    Full Text Available The classical form of α1-antitrypsin deficiency (ATD is an autosomal co-dominant disorder that affects ~1 in 3000 live births and is an important genetic cause of lung and liver disease. The protein affected, α1-antitrypsin (AT, is predominantly derived from the liver and has the function of inhibiting neutrophil elastase and several other destructive neutrophil proteinases. The genetic defect is a point mutation that leads to misfolding of the mutant protein, which is referred to as α1-antitrypsin Z (ATZ. Because of its misfolding, ATZ is unable to efficiently traverse the secretory pathway. Accumulation of ATZ in the endoplasmic reticulum of liver cells has a gain-of-function proteotoxic effect on the liver, resulting in fibrosis, cirrhosis and/or hepatocellular carcinoma in some individuals. Moreover, because of reduced secretion, there is a lack of anti-proteinase activity in the lung, which allows neutrophil proteases to destroy the connective tissue matrix and cause chronic obstructive pulmonary disease (COPD by loss of function. Wide variation in the incidence and severity of liver and lung disease among individuals with ATD has made this disease one of the most challenging of the rare genetic disorders to diagnose and treat. Other than cigarette smoking, which worsens COPD in ATD, genetic and environmental modifiers that determine this phenotypic variability are unknown. A limited number of therapeutic strategies are currently available, and liver transplantation is the only treatment for severe liver disease. Although replacement therapy with purified AT corrects the loss of anti-proteinase function, COPD progresses in a substantial number of individuals with ATD and some undergo lung transplantation. Nevertheless, advances in understanding the variability in clinical phenotype and in developing novel therapeutic concepts is beginning to address the major clinical challenges of this mysterious disorder.

  8. Selenoprotein S/SEPS1 Modifies Endoplasmic Reticulum Stress in Z Variant α1-Antitrypsin Deficiency*

    OpenAIRE

    Kelly, Emer; Catherine M. Greene; Carroll, Tomás P; Noel G. McElvaney; O'Neill, Shane J

    2009-01-01

    Z α1-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...

  9. 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.

  10. Molecular evolution of serpins: homologous structure of the human α1-antichymotrypsin and α1-antitrypsin genes

    International Nuclear Information System (INIS)

    α1-Antichymotrypsin belongs to a supergene family that includes α1-antitrypsin, antithrombin III, ovalbumin, and angiotensinogen. The human chromosomal α1-antichymotrypsin gene has been cloned and its molecular structure established. The gene is approximately 12 kb in length and contains five exons and four introns. The locations of the introns within the α1-antichymotrypsin gene are identical with those of the human α1-antitrypsin and angiotensinogen genes. Other members of this supergene family contain introns located at nonhomologous positions of the genes. The homologous organization of the α1-antichymotrypsin and α1-antitrypsin genes corresponds with the high degree of homology between their protein sequences and suggest that these loci arose by recent gene duplication. A model is presented for the evolution of both the genomic structure and the protein sequences of the serine protease inhibitor superfamily

  11. 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.

  12. Alpha 1-antitrypsin Siiyama (Ser53-->Phe). Further evidence for intracellular loop-sheet polymerization.

    OpenAIRE

    D. A. Lomas; Finch, J. T.; Seyama, K.; Nukiwa, T; Carrell, R W

    1993-01-01

    Antitrypsin Siiyama is a rare example of the deficiency variants of antitrypsin that accumulate in the endoplasmic reticulum of the hepatocyte. The common example is Z antitrypsin, which has a mutation (Glu342-->Lys) at the junction of the head of the fifth strand of the A sheet and the base of the reactive center loop. It was previously shown that Z antitrypsin spontaneously polymerizes due to the insertion of the reactive center loop of one molecule into the A sheet of a second. The mutatio...

  13. 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...

  14. Assembly of bioactive multilayered nanocoatings on pancreatic islet cells: incorporation of α1-antitrypsin into the coatings.

    Science.gov (United States)

    Zhi, Zheng-Liang; Singh, Jashandeep; Austin, Amazon L F; Hope, David C D; King, Aileen J; Persaud, Shanta J; Jones, Peter M

    2015-07-01

    A spontaneous multilayer deposition approach for presenting therapeutic proteins onto pancreatic islet surfaces, using a heparin polyaldehyde and glycol chitosan alternating layering scheme, has been developed to enable the nanoscale engineering of a microenvironment for transplanted cells. The nanocoating incorporating α1-antitrypsin, an anti-inflammatory protein, exhibited effective anti-coagulant activities in vitro. PMID:26051448

  15. Unusual Acute Sequelae of α1-Antitrypsin Deficiency: A Myriad of Symptoms With One Common Cure.

    Science.gov (United States)

    Franciosi, Alessandro N; McCarthy, Cormac; Carroll, Tomas P; McElvaney, Noel G

    2015-11-01

    Panniculitis associated with α1-antitrypsin deficiency (AATD) is well documented but rare. We report the first case, to our knowledge, of successful induction of clinical remission of AATD-related panniculitis following a single 120-mg/kg dose administration of plasma-purified α1-antitrypsin (AAT). A 23-year-old man with known PiZZ AATD presented to the hospital with a diffusely swollen and tender right upper limb. This was associated with subcutaneous induration, and a discrepancy of 5 cm in upper limb circumference at the mid arm was noted. There was no convincing precipitant for cellulitis or an infectious cause, and inflammatory markers were raised, with a C-reactive protein (CRP) level of 93.9 mg/L and erythrocyte sedimentation rate (ESR) of 71 mm/h. Doppler ultrasonography ruled out DVT. No antimicrobials or antiinflammatory medications were administered during or prior to admission. Biopsy specimens of the right upper limb revealed extensive panniculitis with neutrophils, foamy macrophages, and fat necrosis. A diagnosis of AATD-associated panniculitis was made. Following this, a single IV dose of 120 mg/kg of plasma-purified AAT was administered. By day 7 post AAT infusion, CRP level had normalized to 4.6 mg/L and ESR had dropped to 22 mm/h. Limb circumference discrepancy on day 7 was 1 cm. There was no tenderness to palpation or induration, and a clinical remission of panniculitis was observed. We report the first case, to our knowledge, of clinical remission following a single treatment with IV AAT at a dose of 120 mg/kg. This opens avenues to more timely and effective treatment of the more severe presentations of AAT-associated panniculitis. PMID:26527439

  16. Directing membrane chromatography to manufacture α1-antitrypsin from human plasma fraction IV.

    Science.gov (United States)

    Fan, Jinxin; Luo, Jianquan; Song, Weijie; Chen, Xiangrong; Wan, Yinhua

    2015-12-01

    The surging demand for plasma proteins, mainly driven by the growing market and the development of new therapeutic indications, is promoting manufacturers to improve the throughput of plasma proteins. Due to the inherent convective mass transfer, membrane chromatography has been proved to be an efficient approach for extracting a small amount of target proteins from large-volume feed. In this study, α1-antitrypsin (AAT) was extracted from human plasma fraction IV by a two-step membrane chromatography. An anion-exchange membrane chromatography (AEMC) was used to capture the plasma proteins in bind/elute mode, and the obtained effluent was further polished by a hydrophobic interaction membrane chromatography (HIMC) in flow-through mode. Under optimal conditions, the recovery and purity of AAT achieved 87.0% and 0.58 AAT/protein (g/g) by AEMC, respectively. After the precise polishing by HIMC, the purity of AAT was 1.22 AAT/protein (g/g). The comparison results showed that membrane chromatography outperformed column chromatography in both steps because of its high throughput. This two-step membrane chromatography could obtain an AAT recovery of 83.3% and an activity recovery of 91.4%. The outcome of this work not only offers an alternative process for protein purification from plasma, but also provides guidelines for manufacturing product from a large-volume feed with multi-components by membrane chromatography. PMID:26518493

  17. 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.

  18. Deletion of Serpina1a, a murine α1-antitrypsin ortholog, results in embryonic lethality.

    Science.gov (United States)

    Wang, Dongmei; Wang, Weimin; Dawkins, Paul; Paterson, Trevor; Kalsheker, Noor; Sallenave, Jean-Michel; Houghton, A McGarry

    2011-06-01

    Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States Approximately 1% to 2% of COPD patients suffer from α(1)-antitrypsin (A1AT) deficiency, the major inheritable predisposition to COPD/emphysema. To further study the role of A1AT deficiency in the pathogenesis of COPD/emphysema, the authors attempted to generate null-mutant mice for Serpina1a, 1 of 2 A1AT orthologs in mice. Here the authors show that targeted deletion of Serpina1a results in embryonic lethality prior to 8.5 days post conception (dpc). The results are surprising given that A1AT-null humans exist and therefore do not require this gene product for normal development. The Serpina1 gene cluster is substantially different between mouse and man. Through gene duplication, mice have 3 to 5 (depending on the strain) highly homologous proteinase inhibiting (Pi) genes, 2 of which inhibit neutrophil elastase. Despite the abundance of Pi genes in mice, Serpina1a serves a critical, nonredundant function during early mouse development. A1AT-deficient mice have been highly sought after to study emphysema, cancer, and liver disease, and as a model to perfect gene replacement therapy. These results highlight important differences between human and murine serpins and point to the difficulty inherent to using gene-targeted mice to study this common human genetic disease. PMID:21574874

  19. 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. PMID:25961766

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Astute, Assertive, and Alpha-1: Quantifying Empowerment in a Rare Genetic Community

    Science.gov (United States)

    Finn, Symma

    2008-01-01

    We investigated empowerment in the Alpha-1 Antitrypsin Deficiency (Alpha-1) community, a rare, genetic disease network in the United States. The research was motivated by nine years of observations in the community. After observing what seemed to be a heightened amount of activism among Alpha-1 community members, I had hypothesized that this…

  6. Long-term experience in the treatment of α1-antitrypsin deficiency: 25 years of augmentation therapy

    Directory of Open Access Journals (Sweden)

    Helmut Teschler

    2015-03-01

    Full Text Available Although it is often under-recognised, α1-antitrypsin deficiency (AATD represents one of the most common genetic respiratory disorders worldwide. Since the publication of studies in the late 1980s, which demonstrated that plasma-derived augmentation therapy with intravenous α1-antitrypsin (AAT can reverse the biochemical deficiencies in serum and lung fluid that characterise emphysema, augmentation therapy has become the cornerstone of patient management. This article, with a focus on experience gained in clinical practice in Germany, provides an overview of some of the research highlights and clinical experience gained in the use of augmentation therapy for AATD during the past 25 years, and briefly discusses the potential role of AAT augmentation therapy in lung transplant recipients. Additionally, the goals of AAT augmentation therapy will be discussed, namely to delay the progression of emphysema, reduce the frequency of exacerbations and improve health-related quality of life. Beyond pulmonary disease, there is recent growing evidence to indicate that AATD could also play a role in rare disorders such as panniculitis, granulomatosis with polyangiitis and ulcerative colitis.

  7. 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. PMID:26749278

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

    Science.gov (United States)

    Gosai, Sager J; Kwak, Joon Hyeok; Luke, Cliff J; Long, Olivia S; King, Dale E; Kovatch, Kevin J; Johnston, Paul A; Shun, Tong Ying; Lazo, John S; Perlmutter, David H; Silverman, Gary A; Pak, Stephen C

    2010-01-01

    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. PMID:21103396

  9. 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.

  10. 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

    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......Assessment of emphysema-modifying therapy is difficult, but newer outcome measures offer advantages over traditional methods. The EXAcerbations and Computed Tomography scan as Lung End-points (EXACTLE) trial explored the use of computed tomography (CT) densitometry and exacerbations for the......-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...

  11. Reactivity of alpha 1-antitrypsin mutants against proteolytic enzymes of the kallikrein-kinin, complement, and fibrinolytic systems

    NARCIS (Netherlands)

    Patston, P.A.; Roodi, N.; Schifferli, J.A.; Bischoff, Rainer; Courtney, M.; Schapira, M.

    1990-01-01

    Increased extracellular proteolysis because of unregulated activation of blood coagulation, complement, and fibrinolysis is observed in thrombosis, shock, and inflammation. In the present study, we have examined whether the plasma kallikrein-kinin system, the classical pathway of complement, and the

  12. Rosuvastatin Alters the Proteome of High Density Lipoproteins: Generation of alpha-1-antitrypsin Enriched Particles with Anti-inflammatory Properties.

    Science.gov (United States)

    Gordon, Scott M; McKenzie, Benjamin; Kemeh, Georgina; Sampson, Maureen; Perl, Shira; Young, Neal S; Fessler, Michael B; Remaley, Alan T

    2015-12-01

    Statins lower plasma cholesterol by as much as 50%, thus reducing future cardiovascular events. However, the physiological effects of statins are diverse and not all are related to low density lipoprotein cholesterol (LDL-C) lowering. We performed a small clinical pilot study to assess the impact of statins on lipoprotein-associated proteins in healthy individuals (n = 10) with normal LDL-C (J774 macrophages, demonstrated that the association of A1AT with HDL enhances its antiprotease activity, preventing elastase induced production of tumor necrosis factor α. In conclusion, we show that statins can significantly alter the protein composition of both LDL and HDL and our studies reveal a novel functional relationship between A1AT and HDL. The up-regulation of A1AT on HDL enhances its anti-inflammatory functionality, which may contribute to the non-lipid lowering beneficial effects of statins. PMID:26483418

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

    OpenAIRE

    Aquiles A Camelier; Daniel Hugo Winter; José Roberto Jardim; Carlos Eduardo Galvão Barboza; Alberto Cukier; Marc Miravitlles

    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...

  14. 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; Kvist, Peter Helding; Bjerrum, Jacob Tveiten

    2015-01-01

    (Mayo score) and from 40 healthy controls were analyzed by multiplex enzyme-linked immunosorbent assay for 78 potential disease biomarkers. Using the statistical software SIMCA-P+ and GraphPad Prism, multivariate statistical analyses were conducted to identify a limited number of biomarkers to assess...

  15. 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

    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...... 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...

  16. The BLT1 Inhibitory Function of α-1 Antitrypsin Augmentation Therapy Disrupts Leukotriene B4 Neutrophil Signaling.

    Science.gov (United States)

    O'Dwyer, Ciara A; O'Brien, M Emmet; Wormald, Mark R; White, Michelle M; Banville, Nessa; Hurley, Killian; McCarthy, Cormac; McElvaney, Noel G; Reeves, Emer P

    2015-10-15

    Leukotriene B4 (LTB4) contributes to many inflammatory diseases, including genetic and nongenetic forms of chronic obstructive pulmonary disease. α-1 Antitrypsin (AAT) deficiency (AATD) is characterized by destruction of lung parenchyma and development of emphysema, caused by low AAT levels and a high neutrophil burden in the airways of affected individuals. In this study we assessed whether AATD is an LTB4-related disease and investigated the ability of serum AAT to control LTB4 signaling in neutrophils. In vitro studies demonstrate that neutrophil elastase is a key player in the LTB4 inflammatory cycle in AATD, causing increased LTB4 production, and associated BLT1 membrane receptor expression. AATD patients homozygous for the Z allele were characterized by increased neutrophil adhesion and degranulation responses to LTB4. We demonstrate that AAT can bind LTB4 and that AAT/LTB4 complex formation modulates BLT1 engagement and downstream signaling events, including 1,4,5-triphosphate production and Ca(2+) flux. Additionally, treatment of ZZ-AATD individuals with AAT augmentation therapy decreased plasma LTB4 concentrations and reduced levels of membrane-bound neutrophil elastase. Collectively, these results provide a mechanism by which AAT augmentation therapy impacts on LTB4 signaling in vivo, and not only reinforces the utility of this therapy for resolving inflammation in AATD, but supports useful future clinical applications in treatment of other LTB4-related diseases. PMID:26371243

  17. Ubiquitin ligase gp78 increases solubility and facilitates degradation of the Z variant of α-1-antitrypsin

    International Nuclear Information System (INIS)

    Deficiency of circulating α-1-antitrypsin (AAT) is the most widely recognized abnormality of a proteinase inhibitor that causes lung disease. AAT-deficiency is caused by mutations of the AAT gene that lead to AAT protein retention in the endoplasmic reticulum (ER). Moreover, the mutant AAT accumulated in the ER predisposes the homozygote to severe liver injuries, such as neonatal hepatitis, juvenile cirrhosis, and hepatocellular carcinoma. Despite the fact that mutant AAT protein is subject to ER-associated degradation (ERAD), yeast genetic studies have determined that the ubiquitination machinery, Hrd1/Der3p-cue1p-Ubc7/6p, which plays a prominent role in ERAD, is not involved in degradation of mutant AAT. Here we report that gp78, a ubiquitin ligase (E3) pairing with mammalian Ubc7 for ERAD, ubiquitinates and facilitates degradation of ATZ, the classic deficiency variant of AAT having a Z mutation (Glu 342 Lys). Unexpectedly, gp78 over-expression also significantly increases ATZ solubility. p97/VCP, an AAA ATPase essential for retrotranslocation of misfolded proteins from the ER during ERAD, is involved in gp78-mediated degradation of ATZ. Surprisingly, unlike other ERAD substrates that cause ER stress leading to apoptosis when accumulated in the ER, ATZ, in fact, increases cell proliferation when over-expressed in cells. This effect can be partially inhibited by gp78 over-expression. These data indicate that gp78 assumes multiple unique quality control roles over ATZ, including the facilitation of degradation and inhibition of aggregation of ATZ

  18. 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.

  19. 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; Kjeldgaard, Morten; Huntington, James A.; Jensen, Jan Kristian

    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...... within hepatocytes, causing their destruction. Recently, it was proposed that Z-α1AT polymerizes by a C-terminal domain swap. In this study, small-angle x-ray scattering (SAXS) was used to characterize Z-α1AT polymers in solution. The data show that the Z-α1AT trimer, tetramer, and pentamer all form ring...

  20. The effect of methotrexate and azathioprine on the serum levels of IgA-a1-antitrypsin complex in juvenile chronic arthritis

    Directory of Open Access Journals (Sweden)

    J.K. Lacki

    1997-06-01

    Full Text Available In the present study we investigated the influence of methotrexate (MTX and azathioprine (AZA on the serum levels of the IgA-a1-antitrypsin (IgA-AT complex in patients with the systemic form of juvenile chronic arthritis (JCA. Fifty-six JCA patients (22 treated with MTX, 18 treated with AZA, and 16 not treated with any immunosuppressive agent were enrolled in the study. MTX dosage ranged from 0.3 to 0.5 mg kg-1 week-1, while AZA was given daily at an average dose of 1 mg/kg. MTX was given for 13 months (SD = 7 months whereas AZA for 11 months (SD = 6 months. The average value of the complex was higher in JCA patients than in both control groups (0.74 ± 0.73 U vs 0.37 ± 0.13 U (control children, Pa1-acid-glycoprotein (r = 0.45, Pa1-antichymotrypsin (r = 0.52, Pa1-antitrypsin (r = 0.40, P<0.01 and IgA (r = 0.56, P<0.01 was established

  1. Serum alpha-antitrypsin in patients with lung cancer or abnormal sputum cytology

    Energy Technology Data Exchange (ETDEWEB)

    Harris, C.C.; Cohen, M.H.; Connor, R.; Primack, A.; Saccomanno, G.; Talamo, R.C.

    1976-10-01

    Scrum alpha/sub 1/-antitrypsin Pi types and trypsin inhibitory capacity (TIC) were measured in 72 patients with lung cancer and in 196 patients with abnormal sputum cytology but no clinical evidence of lung cancer to determine if a genetic deficiency of alpha/sub 1/-antitrypsin (AAT) predisposes to lung cancer. The distributions of Pi types in these two groups of patients and healthy adults are similar. Serum TIC and AAT concentrations are elevated in lung cancer patients. However, patients with abnormal sputum cytology and no clinical lung cancer have normal levels of serum TIC and AAT. A genetic deficiency of AAT probably does not produce a state of increased susceptibility to the carcinogenic effects of respiratory carcinogens such as tobacco smoke.

  2. 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.

  3. Sulphation of proteins secreted by a human hepatoma-derived cell line. Sulphation of N-linked oligosaccharides on alpha 2HS-glycoprotein.

    Science.gov (United States)

    Hortin, G; Green, E D; Baenziger, J U; Strauss, A W

    1986-01-01

    Several human glycoproteins, including alpha 1-antitrypsin, alpha 1-acid glycoprotein, transferrin, caeruloplasmin and alpha 2HS-glycoprotein, synthesized by the hepatoma-derived cell line HepG2 were observed to contain covalently linked sulphate. These proteins were estimated to contain about 0.1 mol of sulphate/mol of protein. The most abundant of the sulphated glycoproteins, alpha 2HS-glycoprotein, was analysed in detail. All of the sulphate on this protein was attached to N-linked oligosaccharides which contained sialic acid and resisted release by endoglycosidase H. Several independent analytical approaches established that approx. 10% of the molecules of alpha 2HS-glycoprotein contained sulphate. Our results suggest that a number of human plasma proteins contain small amounts of sulphate linked to oligosaccharides. Images Fig. 1. Fig. 2. Fig. 3. PMID:3017304

  4. On the structure, function and biosynthesis of human inter-. alpha. inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Swaim, M.W.

    1989-01-01

    Human inter-{alpha} inhibitor (I{alpha}I) is a {approx}200-kD serum glycoprotein with serine proteinase-inhibitory activity whose physiologic role remains unclear. I{alpha}I is related to smaller inhibitors found in physiologic fluids and is a complex of {approx}40-kD light and {approx}90-kD heavy chains. I{alpha}I proteinase-inhibitory activity resides exclusively in the light chain, which has tandem Kunitz inhibitory domains with methionine and arginine residues, respectively, at position P{sub 1}. The inhibitory activity of the reactive centers was heretofore uncharacterized. Cis-dichlorodiammineplatinum (II) (cis-DDP) reacts with sulfur containing residues in a limited and selective fashion. In preliminary studies, cis-DDP was evaluated as a reagent to modify the methionine reactive centers of two other plasma proteinase inhibitors, {alpha}{sub 1}-antitrypsin and {alpha}{sub 2}-antiplasmin. Cis-DDP readily abolished the proteinase-inhibitory activity of both proteins. Methionine oxidation, papain digestion, and platinum binding assays showed that cis-DDP inactivates {alpha}-antitrypsin by binding exclusively to its reactive-center methionine. Cis-DDP partially eliminated I{alpha}I inhibitory activity against cathepsin G and neutrophil elastase but did not affect inhibition of trypsin or chymotrypsin. Conversely, reaction with the arginine-modifying reagent 2,3-butanedione afforded complete loss of activity against trypsin and chymotrypsin but partial loss of activity against cathepsin G and elastase. Employment of both reagents eliminated inhibition of cathepsin G and elastase. Thus eathepsin G and elastase are apparently inhibited at either reactive center. Trypsin and chymotrypsin are inhibited exclusively at the arginine reactive center.

  5. Coefficient Alpha

    OpenAIRE

    Panayiotis Panayides

    2013-01-01

    Heavy reliance on Cronbach’s alpha has been standard practice in many validation studies. However, there seem to be two misconceptions about the interpretation of alpha. First, alpha is mistakenly considered as an indication of unidimensionality and second, that the higher the value of alpha the better. The aim of this study is to clarify these misconceptions with the use of real data from the educational setting. Results showed that high alpha values can be obtained in multidimensional scale...

  6. A 32 year old male with idiopathic hepatic encephalopathy and necrotic lower extremity

    Directory of Open Access Journals (Sweden)

    Schmitz ED

    2010-11-01

    Full Text Available A 32 year old with undiagnosed alpha-1 antitrypsin deficiency had an unusual initial presentation of acute liver failure, septic shock; adult respiratory distress syndrome and what appeared to be a left lower extremity soft tissue infection. Skin biopsy revealed panniculitis. Because of the diagnosis of panniculitis, an alpha-1 antitrypsin level was ordered and demonstrated alpha-1 antitrypsin deficiency with a ZZ phenotype. The patient recovered with antibiotics and supportive therapy. This case illustrates that alpha-1 antitrypsin deficiency can present other that the more usual adult presentation of progressive emphysema. Unexplained panniculitis should prompt investigation of alpha-1 antitrypsin deficiency in the adult patient.

  7. 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 ...

  8. $\\alpha_s$ 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.

  9. The $\\alpha-\\alpha$ fishbone potential revisited

    CERN Document Server

    Day, J P; Elhanafy, M; Smith, E; Woodhouse, R; Papp, Z

    2011-01-01

    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the $\\alpha-\\alpha$ fishbone potential by simultaneously fitting to two-$\\alpha$ resonance energies, experimental phase shifts and three-$\\alpha$ binding energies. We found that essentially a simple gaussian can provide a good description of two-$\\alpha$ and three-$\\alpha$ experimental data without invoking three-body potentials.

  10. Alpha spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Felix; Wilsenach, Heinrich; Zuber, Kai [IKTP TU-Dresden, Dresden (Germany)

    2014-07-01

    Alpha decays from long living isotopes are one of the limiting backgrounds for experiments searching for rare decays with stringent background constrains, such as neutrinoless double beta decay experiments. It is thus very important to accurately measure the half-lives of these decays, in order to properly model their background contribution. Therefore, it is important to be able to measure half-lives from alpha decays of the order of 1 x 10{sup 15} yr. A measurement of such a long lived decay imposes, however, a series of challenges, where the correct discrimination between background and true signal is critical. There is also a more general interest in such long living half-life measurements, as their value depends crucially on the underlying nuclear model. This work proposes a setup to measure long lived alpha decays, based on the design of the Frisch-Grid ionisation chamber. It is shown that the proposed design provides a good separation of signal and background events. It is also demonstrated that, with pulse shape analysis, it is possible to constrain the source position of the decay, further improving the quality of the data. A discussion of the characterisation of the detector is also presented as well as some results obtained with calibration sources.

  11. Alpha spectroscopy

    International Nuclear Information System (INIS)

    Alpha decays from long living isotopes are one of the limiting backgrounds for experiments searching for rare decays with stringent background constrains, such as neutrinoless double beta decay experiments. It is thus very important to accurately measure the half-lives of these decays, in order to properly model their background contribution. Therefore, it is important to be able to measure half-lives from alpha decays of the order of 1 x 1015 yr. A measurement of such a long lived decay imposes, however, a series of challenges, where the correct discrimination between background and true signal is critical. There is also a more general interest in such long living half-life measurements, as their value depends crucially on the underlying nuclear model. This work proposes a setup to measure long lived alpha decays, based on the design of the Frisch-Grid ionisation chamber. It is shown that the proposed design provides a good separation of signal and background events. It is also demonstrated that, with pulse shape analysis, it is possible to constrain the source position of the decay, further improving the quality of the data. A discussion of the characterisation of the detector is also presented as well as some results obtained with calibration sources.

  12. Chronic obstructive pulmonary disease

    Science.gov (United States)

    ... airways disease; Chronic obstructive lung disease; Chronic bronchitis; Emphysema; Bronchitis - chronic ... a protein called alpha-1 antitrypsin can develop emphysema. Other risk factors for COPD are: Exposure to ...

  13. Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments.

    Science.gov (United States)

    Stolk, Jan; Cooper, Brendan G; Stoel, Berend; Rames, Alexis; Rutman, Olga; Soliman, Sherif; Stockley, Robert

    2010-12-01

    Emphysema is characterized by the destruction of alveolar wall and enlargement of alveolar airspaces, resulting in a reduction of the total lung gas exchange area, loss of lung elastic recoil and hyperinflation. The REPAIR study (Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry) is the first proof-of-concept study of a new potential disease-modifying drug, Palovarotene©, an orally active, gamma selective retinoid agonist in patients with emphysema secondary to alpha-1-antitrypsin deficiency (AATD) as a model population for the general smoke-induced emphysema population. This article describes the study design as well as the effectiveness of the quality control that was implemented on the key efficacy endpoints, based on data derived from the placebo-treated subjects. In this multicentre, multinational study the implementation of standardized procedures included: careful site selection, use of trained staff, regular monitoring and machine calibration, use of biological controls and regular feedback to sites by an independent quality control centre. All of these procedures resulted in high-quality measurements of lung density, spirometry, static lung volumes and gas transfer. It was also confirmed that CT lung density was the most sensitive endpoint followed by TLco, FEV(1) and RV measured by body box. PMID:20926506

  14. Ab initio alpha-alpha scattering.

    Science.gov (United States)

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

    2015-12-01

    Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  15. Ab initio alpha-alpha scattering

    Science.gov (United States)

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

    2015-12-01

    Processes such as the scattering of alpha particles (4He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei—nuclei with even and equal numbers of protons and neutrons—is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the ‘adiabatic projection method’ to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of

  16. 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...

  17. Review of alpha_s determinations

    CERN Document Server

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupling is found to be alpha_s(M_Z^2)= 0.1186 \\pm 0.0007.

  18. Review of alpha_s determinations

    OpenAIRE

    Pich, Antonio

    2013-01-01

    The present knowledge on the strong coupling is briefly summarized. The most precise determinations of alpha_s, at different energies, are reviewed and compared at the Z mass scale, using the predicted QCD running. The impressive agreement achieved between experimental measurements and theoretical predictions constitutes a beautiful and very significant test of Asymptotic Freedom, establishing QCD as the fundamental theory of the strong interaction. The world average value of the strong coupl...

  19. World Summary of $\\alpha_s$ (2015)

    CERN Document Server

    Bethke, Siegfried; Salam, Gavin P

    2015-01-01

    This is a preliminary update of the measurements of α s and the determination of the world average value of α s (M Z 2 ) presented in the 2013/2014 edition of the Review of Particle Properties [1]. A number of studies which became available since late 2013 provide new results for each of the (previously 5, now) 6 subclasses of measurements for which pre-average values of $\\alpha_s (M_Z^2)$ are determined.

  20. 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.

  1. 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.

  2. 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...

  3. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter

    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....

  4. UniProt search blastx result: AK287588 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK287588 J065045K19 P01010|A1AT_PAPAN Alpha-1-antitrypsin precursor (Alpha-1 protease inhibitor) ... 1-antiproteinase) (AAT) (Fragment) - Papio anubis (Olive ... baboon) 1.00E-17 ...

  5. 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

    OpenAIRE

    Heliane Guerra Serra; Carmen Sílvia Bertuzzo; Mônica Corso Pereira; Cláudio Lúcio Rossi; Walter Pinto Júnior; Ilma Aparecida Paschoal

    2008-01-01

    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 i...

  6. Production of glycosylated physiologically normal human α1-antitrypsin by mouse fibroblasts modified by insertion of a human α1-antitrypsin cDNA using a retroviral vector

    International Nuclear Information System (INIS)

    α2-Antitrypsin (α1AT) deficiency is a hereditary disorder characterized by reduced serum levels of α1AT, resulting in destruction of the lower respiratory tract by neutrophil elastase. As an approach to augment α1AT levels in this disorder with physiologically normal human α1AT, the authors have integrated a full-length normal human α1AT cDNA into the genome of mouse fibroblasts. To accomplish this, the retroviral vector N2 was modified by inserting the simian virus 40 early promoter followed by the α1AT cDNA. Southern analysis demonstrated that the intact cDNA was present in the genome of selected clones of the transfected murine fibroblasts psi2 and infected NIH 3T3. The clones produced three mRNA transcripts containing human α1AT sequences, secreted an α1AT molecule recognized by an anti-human α1AT antibody, with the same molecular mass as normal human α1AT and that complexed with and inhibited human neutrophil elastase. The psi2 produced α1AT was glycosylated, and when infused intravenously into mice, it had a serum half-life similar to normal α1AT purified from human plasma and markedly longer than that of nonglycosylated human α1AT cDNA-directed yeast-produced α1AT. These studies demonstrate the feasibility of using a retroviral vector to insert the normal human α1AT cDNA into non-α1AT-producing cells, resulting in the synthesis and secretion of physiologically normal α1AT

  7. Targeted Alpha Therapy: From Alpha to Omega

    International Nuclear Information System (INIS)

    This review covers the broad spectrum of Targeted Alpha Therapy (TAT) research in Australia; from in vitro and in vivo studies to clinical trials. The principle of tumour anti-vascular alpha therapy (TAVAT) is discussed in terms of its validation by Monte Carlo calculations of vascular models and the potential role of biological dosimetry is examined. Summmary of this review is as follows: 1. The essence of TAT 2. Therapeutic objectives 3. TAVAT and Monte Carlo microdosimetry 4. Biological dosimetry 5. Preclinical studies 6. Clinical trials 7. What next? 8. Obstacles. (author)

  8. Alpha-particle diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Young, K.M.

    1991-01-01

    This paper will focus on the state of development of diagnostics which are expected to provide the information needed for {alpha}- physics studies in the future. Conventional measurement of detailed temporal and spatial profiles of background plasma properties in DT will be essential for such aspects as determining heating effectiveness, shaping of the plasma profiles and effects of MHD, but will not be addressed here. This paper will address (1) the measurement of the neutron source, and hence {alpha}-particle birth profile, (2) measurement of the escaping {alpha}-particles and (3) measurement of the confined {alpha}-particles over their full energy range. There will also be a brief discussion of (4) the concerns about instabilities being generated by {alpha}-particles and the methods necessary for measuring these effects. 51 refs., 10 figs.

  9. Imaging alpha particle detector

    Science.gov (United States)

    Anderson, D.F.

    1980-10-29

    A method and apparatus for detecting and imaging alpha particles sources is described. A dielectric coated high voltage electrode and a tungsten wire grid constitute a diode configuration discharge generator for electrons dislodged from atoms or molecules located in between these electrodes when struck by alpha particles from a source to be quantitatively or qualitatively analyzed. A thin polyester film window allows the alpha particles to pass into the gas enclosure and the combination of the glass electrode, grid and window is light transparent such that the details of the source which is imaged with high resolution and sensitivity by the sparks produced can be observed visually as well. The source can be viewed directly, electronically counted or integrated over time using photographic methods. A significant increase in sensitivity over other alpha particle detectors is observed, and the device has very low sensitivity to gamma or beta emissions which might otherwise appear as noise on the alpha particle signal.

  10. The alpha channeling effect

    Energy Technology Data Exchange (ETDEWEB)

    Fisch, N. J.

    2015-12-10

    Alpha particles born through fusion reactions in a tokamak reactor tend to slow down on electrons, but that could take up to hundreds of milliseconds. Before that happens, the energy in these alpha particles can destabilize on collisionless timescales toroidal Alfven modes and other waves, in a way deleterious to energy confinement. However, it has been speculated that this energy might be instead be channeled into useful energy, so as to heat fuel ions or to drive current. Such a channeling needs to be catalyzed by waves Waves can produce diffusion in energy of the alpha particles in a way that is strictly coupled to diffusion in space. If these diffusion paths in energy-position space point from high energy in the center to low energy on the periphery, then alpha particles will be cooled while forced to the periphery. The energy from the alpha particles is absorbed by the wave. The amplified wave can then heat ions or drive current. This process or paradigm for extracting alpha particle energy collisionlessly has been called alpha channeling. While the effect is speculative, the upside potential for economical fusion is immense. The paradigm also operates more generally in other contexts of magnetically confined plasma.

  11. Local versus nonlocal $\\alpha\\alpha$ interactions in $3\\alpha$ description of $^{12}$C

    CERN Document Server

    Suzuki, Y; Descouvemont, P; Fujiwara, Y; Matsumura, H; Orabi, M; Theeten, M

    2008-01-01

    Local $\\alpha \\alpha$ potentials fail to describe $^{12}$C as a $3\\alpha$ system. Nonlocal $\\alpha \\alpha$ potentials that renormalize the energy-dependent kernel of the resonating group method allow interpreting simultaneously the ground state and $0^+_2$ resonance of $^{12}$C as $3\\alpha$ states. A comparison with fully microscopic calculations provides a measure of the importance of three-cluster exchanges in those states.

  12. Bremsstrahlung in $\\alpha$ Decay

    CERN Document Server

    Takigawa, N; Hagino, K; Ono, A; Brink, D M

    1999-01-01

    A quantum mechanical analysis of the bremsstrahlung in $\\alpha$ decay of $^{210}$Po is performed in close reference to a semiclassical theory. We clarify the contribution from the tunneling, mixed, outside barrier regions and from the wall of the inner potential well to the final spectral distribution, and discuss their interplay. We also comment on the validity of semiclassical calculations, and the possibility to eliminate the ambiguity in the nuclear potential between the alpha particle and daughter nucleus using the bremsstrahlung spectrum.

  13. Unified model for alpha-decay and alpha-capture

    International Nuclear Information System (INIS)

    A unified model for alpha-decay and alpha-capture is discussed. Simultaneously the half-lives for alpha-transition between ground states as well as ground and excited states and alpha-capture cross-sections by spherical magic or near-magic nuclei are well described in the framework of this model. Using these data the alpha-nucleus potential is obtained. The simple empirical relations for handy evaluation of the half-lives for alpha-transition, which take into account both the angular momentum and parity of alpha-transition, are presented

  14. 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.&...

  15. Alpha Particle Diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, Ray, K.

    2009-05-13

    The study of burning plasmas is the next frontier in fusion energy research, and will be a major objective of the U.S. fusion program through U.S. collaboration with our international partners on the ITER Project. For DT magnetic fusion to be useful for energy production, it is essential that the energetic alpha particles produced by the fusion reactions be confined long enough to deposit a significant fraction of their initial ~3.5 MeV energy in the plasma before they are lost. Development of diagnostics to study the behavior of energetic confined alpha particles is a very important if not essential part of burning plasma research. Despite the clear need for these measurements, development of diagnostics to study confined the fast confined alphas to date has proven extremely difficult, and the available techniques remain for the most part unproven and with significant uncertainties. Research under this grant had the goal of developing diagnostics of fast confined alphas, primarily based on measurements of the neutron and ion tails resulting from alpha particle knock-on collisions with the plasma deuterium and tritium fuel ions. One of the strengths of this approach is the ability to measure the alphas in the hot plasma core where the interesting ignition physics will occur.

  16. Resting alpha activity predicts learning ability in alpha neurofeedback

    OpenAIRE

    Wenya eNan; Feng eWan; Mang I eVai; Agostinho eRosa

    2014-01-01

    Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the tr...

  17. Alpha particles in fusion research

    International Nuclear Information System (INIS)

    This collection of 39 (mostly view graph) presentations addresses various aspects of alpha particle physics in thermonuclear fusion research, including energy balance and alpha particle losses, transport, the influence of alpha particles on plasma stability, helium ash, the transition to and sustainment of a burning fusion plasma, as well as alpha particle diagnostics. Refs, figs and tabs

  18. 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.

  19. 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.

  20. Alpha and evangelical conversion

    OpenAIRE

    Stout, A.; Dein, S.

    2013-01-01

    A semi-structured interview study was conducted among 11 ‘Born Again’ Christians eliciting their conversion narratives. Informants emphasised the importance of embodying the Holy Spirit and developing a personal relationship with Christ in the process of conversion. The Alpha Course played an important role in this process.

  1. Alpha-mannosidosis

    DEFF Research Database (Denmark)

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

    2015-01-01

    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 to...

  2. The $\\alpha_S$ Dependence of Parton Distributions

    OpenAIRE

    Martin, A. D.; Stirling, W. J.; Roberts, R G

    1995-01-01

    We perform next-to-leading order global analyses of deep inelastic and related data for different fixed values of $\\alpha_S (M_Z^2)$. We present sets of parton distributions for six values of $\\alpha_S$ in the range 0.105 to 0.130. We display the $(x, Q^2)$ domains with the largest parton uncertainty and we discuss how forthcoming data may be able to improve the determination of the parton densities.

  3. Specific Genetic Disorders

    Science.gov (United States)

    ... links from the National Institutes of Health. Specific Genetic Disorders Many human diseases have a genetic component. ... Condition in an Adult The Undiagnosed Diseases Program Genetic Disorders Achondroplasia Alpha-1 Antitrypsin Deficiency Antiphospholipid Syndrome ...

  4. Genetics Home Reference: alpha thalassemia

    Science.gov (United States)

    ... for Disease Control and Prevention Centre for Genetics Education (Australia) Cooley's Anemia Foundation: Fact sheet about alpha thalassemia Disease InfoSearch: Alpha-Thalassemia Genomics Education Programme (UK) Information Center for Sickle Cell and ...

  5. $\\alpha$-minimal Banach spaces

    CERN Document Server

    Rosendal, Christian

    2011-01-01

    A Banach space with a Schauder basis is said to be $\\alpha$-minimal for some countable ordinal $\\alpha$ if, for any two block subspaces, the Bourgain embeddability index of one into the other is at least $\\alpha$. We prove a dichotomy that characterises when a Banach space has an $\\alpha$-minimal subspace, which contributes to the ongoing project, initiated by W. T. Gowers, of classifying separable Banach spaces by identifying characteristic subspaces.

  6. Resting alpha activity predicts learning ability in alpha neurofeedback

    Directory of Open Access Journals (Sweden)

    Wenya eNan

    2014-07-01

    Full Text Available Individuals differ in their ability to learn how to regulate the alpha activity by neurofeedback. This study aimed to investigate whether the resting alpha activity is related to the learning ability of alpha enhancement in neurofeedback and could be used as a predictor. A total of 25 subjects performed 20 sessions of individualized alpha neurofeedback in order to learn how to enhance activity in the alpha frequency band. The learning ability was assessed by three indices respectively: the training parameter changes between two periods, within a short period and across the whole training time. It was found that the resting alpha amplitude measured before training had significant positive correlations with all learning indices and could be used as a predictor for the learning ability prediction. This finding would help the researchers in not only predicting the training efficacy in individuals but also gaining further insight into the mechanisms of alpha neurofeedback.

  7. Alpha scintillation radon counting

    International Nuclear Information System (INIS)

    Radon counting chambers which utilize the alpha-scintillation properties of silver activated zinc sulfide are simple to construct, have a high efficiency, and, with proper design, may be relatively insensitive to variations in the pressure or purity of the counter filling. Chambers which were constructed from glass, metal, or plastic in a wide variety of shapes and sizes were evaluated for the accuracy and the precision of the radon counting. The principles affecting the alpha-scintillation radon counting chamber design and an analytic system suitable for a large scale study of the 222Rn and 226Ra content of either air or other environmental samples are described. Particular note is taken of those factors which affect the accuracy and the precision of the method for monitoring radioactivity around uranium mines

  8. Rossi Alpha Method

    International Nuclear Information System (INIS)

    The Rossi Alpha Method has proved to be valuable for the determination of prompt neutron lifetimes in fissile assemblies having known reproduction numbers at or near delayed critical. This workshop report emphasizes the pioneering applications of the method by Dr. John D. Orndoff to fast-neutron critical assemblies at Los Alamos. The value of the method appears to disappear for subcritical systems where the Rossi-α is no longer an α-eigenvalue

  9. 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.

  10. Alpha-globin loci in homozygous beta-thalassemia intermedia.

    Science.gov (United States)

    Triadou, P; Lapoumeroulie, C; Girot, R; Labie, D

    1983-01-01

    Homozygous beta-thalassemia intermediate (TI) differs from thalassemia major (TM) in being less severe clinically. Associated alpha-thalassemia could account for the TI phenotype by reducing the alpha/non-alpha chain imbalance. We have analyzed the alpha loci of 9 TI and 11 TM patients by restriction endonuclease mapping. All the TM and 7 of the TI patients have the normal complement of four alpha-globin genes (alpha alpha/alpha alpha). One TI patient has three alpha-globin genes (alpha alpha/-alpha), and another TI patient has five alpha genes (alpha alpha/alpha alpha alpha). PMID:6305827

  11. Unfolding domains of recombinant fusion alpha alpha-tropomyosin.

    OpenAIRE

    Ishii, Y; Hitchcock-DeGregori, S.; Mabuchi, K; Lehrer, S S

    1992-01-01

    The thermal unfolding of the coiled-coil alpha-helix of recombinant alpha alpha-tropomyosin from rat striated muscle containing an additional 80-residue peptide of influenza virus NS1 protein at the N-terminus (fusion-tropomyosin) was studied with circular dichroism and fluorescence techniques. Fusion-tropomyosin unfolded in four cooperative transitions: (1) a pretransition starting at 35 degrees C involving the middle of the molecule; (2) a major transition at 46 degrees C involving no more ...

  12. Bi209 alpha activity

    International Nuclear Information System (INIS)

    The study for measuring Bi209 alpha activity is presented. Ilford L4 nuclear emulsion pellicles loaded with bismuth citrate to obtain a load of 100 mg/cm3 of dry emulsion, were prepared. Other pellicles were prepared with the same. Ilford L4 gel to estimate the background radiation. To observe 'fading' effect, pellicles loaded with bismuth were submitted to neutrons of high energy, aiming to record recoil proton tracks. The pellicles were confined in nitrogen atmosphere at temperature lower than -100C. The Bi209 experimental half-life was obtained and compared with the estimated theoretical data. (M.C.K.)

  13. Background canceling surface alpha detector

    International Nuclear Information System (INIS)

    A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone. 5 figs

  14. Alpha activity measurement with lsc

    International Nuclear Information System (INIS)

    Recently, we showed that the alpha activity in liquid samples can be measured using a liquid scintillation analyzer without alpha/beta discrimination capability. The purpose of this work was to evaluate the performances of the method and to optimize the procedure of the sample preparation. A series of tests was performed to validate the procedure of alpha emitting radionuclides extraction in aqueous samples with Actinide Resin, especially regarding to the contact time required to extract all alpha nuclides. The main conclusions were that a minimum 18 hours stirring time is needed to achieve a percent recovery of the alpha nuclides grater than 90% and that the counting efficiency of alphas measurements with LSC is nearly 100%. (authors)

  15. Robust Estimation of Cronbach's Alpha

    OpenAIRE

    Christmann, A.; Van Aelst, Stefan

    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 question- naires. 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,...

  16. Alpha glucosidase inhibitors.

    Science.gov (United States)

    Kalra, Sanjay

    2014-04-01

    Alpha glucosidase inhibitors (AGIs) are a unique class of anti-diabetic drugs. Derived from bacteria, these oral drugs are enzyme inhibitors which do not have a pancreato -centred mechanism of action. Working to delay carbohydrate absorption in the gastrointestinal tract, they control postprandial hyperglycaemia and provide unquestioned cardiovascular benefit. Specially suited for a traditional Pakistani carbohydrate-rich diet, AGIs have been termed the 'untapped diamonds' of diabetology. The use of these oral antidiabetic drugs (OADs) that target pathophysiology in the early stages of type 2 diabetes, notably to reduce postprandial hyperglycaemia and hyperinsulinaemia will inevitably increase with time. This review describes the history of their development, mechanism of action, basic and clinical pharmacology, and suggests practical, evidence-based guidance for their optimal use. PMID:24864650

  17. Insurance - Piper Alpha ''et al''

    International Nuclear Information System (INIS)

    This paper opens with some brief information about the Piper Alpha loss, how the loss was handled and its final cost. More importantly, it discusses the effect of the Piper Alpha loss on the world insurance market including the oil insurance captives such as O.I.L Limited. Finally, the insurance market current status and prognosis for the future are considered. (Author)

  18. Long-range alpha detector

    International Nuclear Information System (INIS)

    Historically, alpha-particle and alpha-contamination detectors have been limited by the very short range of alpha particles in air and by relatively poor sensitivity even if the particles are intercepted. Alpha detectors have had to be operated in a vacuum or in close proximity to the source if reasonable efficiency is desired. Alpha particles interact with the ambient air, producing ionization in the air at the rate of ∼30,000 ion pairs per mega-electron-volt of alpha energy. These charges can be transported over significant distances (several meters) in a moving current of air generated by a small fan. An ion chamber located in front of the fan measures the current carried by the moving ions. The long-range alpha detector (LRAD) offers several advantages over more traditional alpha detectors. First and foremost, it can operate efficiently even if the contamination is not easily accessible. Second, ions generated by contamination in crevices and other unmonitorable locations can be detected if the airflow penetrates those areas. Third, all of the contamination on a large surface will generate ions that can be detected in a single detector; hence, the detector's sensitivity to distributed sources is not limited by the size of the probe. Finally, a simple ion chamber can detect very small electric currents, making this technique potentially quite sensitive

  19. Alpha particle emitters in medicine

    International Nuclear Information System (INIS)

    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 (211At) and natural bismuth-212 (212Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 (223Ra) 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

  20. The Lyman alpha reference sample

    DEFF Research Database (Denmark)

    Hayes, M.; Östlin, G.; Schaerer, D.; Verhamme, A.; Mas-Hesse, J.M.; Adamo, A.; Atek, H.; Cannon, J.M.; Duval, F.; Guaita, L.; Herenz, E.C.; Kunth, D.; Laursen, Peter; Melinder, J.; Orlitová, I.; Otí-Floranes, H.; Sandberg, A.

    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

  1. Alpha Schottky junction energy source

    Science.gov (United States)

    Litz, Marc S.; Fan, Zhaoyang; Carroll, James J.; Bayne, Stephen

    2012-06-01

    Isotope batteries offer solutions for long-lived low-power sensor requirements. Alpha emitting isotopes have energy per decay 103 times that of beta emitters. Alpha particles are absorbed within 20 μm of most materials reducing shielding mitigation. However, damage to materials from the alphas limits their practical use. A Schottky Barrier Diode (SBD) geometry is considered with an alpha emitting contact-layer on a diamond-like crystal semiconductor region. The radiation tolerance of diamond, the safety of alpha particles, combined with the internal field of the SBD is expected to generate current useful for low-power electronic devices over decades. Device design parameters and calculations of the expected current are described.

  2. 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...

  3. Synthesis of a precursor for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha,17 beta-diol 17-glucuronide

    International Nuclear Information System (INIS)

    Starting from 11 beta-hydroxytestosterone, the synthesis of a strategic precursor, C-9 (11) unsaturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide (9a), for the preparation of 9 alpha,11 alpha-tritiated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide has been achieved. The authors optimized the reaction conditions for catalytic reduction employing hydrogen and subsequent base hydrolysis followed by purification on Amberlite XAD-2 resin to obtain the saturated 5 alpha-androstane-3 alpha, 17 beta-diol 17-glucuronide

  4. Measurement of $\\alpha_{s}$ with Radiative Hadronic Events

    CERN Document Server

    Abbiendi, G; Åkesson, 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, K W; Bell, P J; Bella, G; Bellerive, A; Benelli, G; Bethke, S; Biebel, O; Boeriu, O; Bock, P; Boutemeur, M; Braibant, S; Brown, R 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; Dallavalle, M; de Roeck, A; De Wolf, E A; Desch, K; Dienes, B; 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, J W; Geich-Gimbel, C; Giacomelli, G; Giacomelli, P; Giunta, M; Goldberg, J; Gross, E; Grunhaus, J; Gruwé, M; Sen-Gupta, A; Hajdu, C; Hamann, M; Hanson, G G; Harel, A; Hauschild, M; Hawkes, C M; Hawkings, R; Herten, G; Heuer, R D; Hill, J C; Horváth, 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; Krasznahorkays, A Jr; Krieger, P; Von Krogh, J; Kühl, T; Kupper, M; Lafferty, G D; Landsman, H; Lanske, D; Lellouch, D; Letts, J; Levinson, L; Lillich, J; Lloyd, S L; Loebinger, F K; Lü, J; Ludwig, A; Ludwig, J; Mader, W; Marcellini, S; Martin, A J; Mashimo, T; Mättig, P; McKenna, J; McPherson, R A; Meijers, F; Menges, W; Merritt, F S; Mes, H; Meyer, N; Michelini, A; Mihara, S; Mikenberg, G; Miller, D J; Mohr, W; Mori, T; Mutter, A; Nagai, K; Nakamura, I; Nanjo, H; Neal, H A; O'Neale, S W; Oh, A; Oreglia, M J; Orito, S; Pahl, C; Pásztor, G; Pater, J R; Pilcher, J E; Pinfold, J L; Plane, D 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-Grinbaum, E; Schaile, A D; Schaile, O; Scharff-Hansen, P; Schiecks, J; Schörner-Sadenius, T; Schröder, M; Schumacher, M; Seuster, R; Shears, T G; Shen, B C; Sherwood, P; Skuja, A; Smith, A M; Sobie, R J; Söldner-Rembold, S; Spanó, F; Stahl, A; Strom, D; Ströhmer, R; Tarem, S; Tasevsky, M; Teuscher, R; Thomson, M A; Torrence, E; Toya, D; Trigger, I; Trócsányi, Z L; Tsur, E; Turner-Watson, M F; Ueda, I; Ujvári, 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, L

    2008-01-01

    Hadronic final states with a hard isolated photon are studied using data taken at centre-of-mass energies around the mass of the Z0 boson with the OPAL detector at LEP. The strong coupling alpha S is extracted by comparing data and QCD predictions for event shape observables at average reduced centre-of-mass energies ranging from 24 GeV to 78 GeV, and the energy dependence of alpha S is studied. Our results are consistent with the running of alpha S as predicted by QCD and show that within the uncertainties of our analysis event shapes in hadronic Z0 decays with hard and isolated photon radiation can be described by QCD at reduced centre-of-mass energies. Combining all values from different event shape observables and energies gives alpha S (Mz)=0.1182 pm 0.0015(stat.) pm 0.0101(syst.).

  5. What Powers Lyman alpha Blobs?

    OpenAIRE

    Ao, Y.; Matsuda, 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.

    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 rad...

  6. Sparse Coding for Alpha Matting

    OpenAIRE

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

    2016-01-01

    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 measur...

  7. Dynamic fibrils in Ly alpha

    CERN Document Server

    Koza, J; Vourlidas, A

    2008-01-01

    The solar chromosphere and transition region are highly structured regimes of large complexity. A recent breakthrough concerns the identification of dynamic fibrils seen in Halpha. An aim is to find out whether dynamic fibrils are also observable in Ly alpha. We use a brief sequence of four high-resolution Ly alpha filtergrams of the solar limb taken by the Very high Angular resolution ULtraviolet Telescope (VAULT) to identify 50 dynamic fibrils, measure their top trajectories, and fit these with parabolas. Most fibril tops move supersonically. Their decelerations vary from sub- to superballistic. About half show outward acceleration, which may be an artifact from the poor sampling. The similarity between these dynamic fibrils observed in Ly alpha and the ones observed in Halpha suggests that the magnetoacoustic shock excitation proposed for the Halpha dynamic fibrils is also valid for the Ly alpha ones.

  8. 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.

  9. Alpha thalassaemia in British people.

    OpenAIRE

    Higgs, D R; Ayyub, H.; Clegg, J B; Hill, A V; Nicholls, R D; Teal, H; Wainscoat, J.S. (James S.); Weatherall, D. J.

    1985-01-01

    Although alpha thalassaemia is rare in north Europeans, it has been identified in British people with no known foreign ancestry. Twelve such patients were studied, of whom eight shared a distinctive molecular defect, which was clearly different from defects seen in subjects of Mediterranean or South East Asian origin. A rare but specific form of alpha thalassaemia is therefore present in the British population. In addition, two patients from families of mixed racial origin were encountered wh...

  10. Alpha Particle Emission in Fission

    International Nuclear Information System (INIS)

    Soon after it was discovered that alpha particles are occasionally emitted in fission, it was concluded, on the basis of the energy and angular distributions of these particles, that they are emitted from the space between the fragments at times close to that of the snapping of the neck that connects them. It is shown that, independent of any (still unknown) dynamic features of the alpha-particle ejection process, the energy required to emit alpha particles from between the fragments at the indicated time is barely available. Presumably the rareness of alpha particles in fission, and the apparent absence of still heavier ''third'' particles, is associated with the marginal energy supply at the time of actual fragment division. The fact that the total kinetic energy release in so-called ternary fission is roughly equal to that in normal binary fission instead of being about 20 MeV larger is shown to imply that the mean fragment separation at the division time is larger in ternary fission. This is interpreted to indicate that alpha particles are emitted with greatest probability n those fissions where ample energy happens to be provided through the stretching of an abnormally long neck between the fragments before they actually divide. It is suggested that the release of the alpha particles is a sudden rather than adiabatic process. (author)

  11. Alpha particle physics for ITER

    International Nuclear Information System (INIS)

    The paper is devoted to the analysis of a variety of physical processes which, in the ITER EDA configuration, determine the nature of alpha particle heating in the plasma interior and alpha particle losses to the first wall. The paper consists of results from the alpha particle toroidal field (TF) ripple loss calculations and an analysis of alpha particle collective effects including Alfven modes, sawtooth stabilization, etc. It is shown that the ripple loss in the present ITER configuration is only a few per cent, which cannot directly affect the achievement of ignition. In spite of the up-down asymmetry, the loss fraction does not strongly depend on the toroidal drift direction. However, the heat load is highly localized and can be as high as 1 MW/m2 on the top of the protective limiters. Preliminary calculations of toroidicity induced Alfven eigenmode (TAE) stability indicate that high n numbers may be unstable, but the computational tools, needed for reliable quantitative predictions, are still in a state of development. The likelihood of appreciable alpha particle loss will depend on whether TAE modes produce stochastic alpha particle diffusion or not. The effect of fast particles on the m = 1 mode is also discussed. (author). 15 refs, 2 figs, 1 tab

  12. Systematics of Alpha-Radioactivity

    Energy Technology Data Exchange (ETDEWEB)

    Perlman, I.; Ghiorso, A.; Seaborg, G.T.

    1949-09-12

    Correlations of alpha-decay energies in terms of mass number and atomic number have been made for all of the alpha-emitting species now numbering over 100. For each element isotopes show increase in alpha-energy with decrease in mass number except in the region of 126 neutrons where there is an explainable reversal. This reversal has the effect of creating a region of relatively low alpha-energy and long half-life at low mass numbers for such elements as astatine, emanation, francium, and possibly higher elements as had been noted already for bismuth and polonium. Methods and examples of using alpha-decay data to define the energy surface in the heavy element region are discussed. The regularities in alpha-decay are used for predictions of nuclear properties including prediction of the beta-stable nuclides among the heavy elements. The half-life vs. energy correlations show that the even-even nuclides conform well with existing alpha-decay theory, but all nuclear types with odd nucleons show prohibited decay. The reason for this prohibition is not found in spin changes in the alpha-emission but in the assembly of the components of the alpha particle, and this theory is discussed further in terms of observations made on nuclides having two or more alpha-groups. Using most of the even-even nuclei to define 'normal nuclear radius' calculations are now able to show the shrinkage in the regions of lead and of 126 neutrons to amount to about 10%. The much greater change in 'effective radius' for bismuth isotopes can be dissociated into the effects of odd nucleons superimposed on the actual decrease in nuclear radius. The simple expression r = 1.48 A{sup 1/3} {center_dot} 10{sup -13} cm seems to fit the data for the even-even nuclei outside of the region of 126 neutrons better than more complex functions.

  13. $\\alpha $ -Skew $\\pi $ -McCoy Rings

    OpenAIRE

    Areej M. Abduldaim; Chen, Sheng

    2013-01-01

    As a generalization of $\\alpha $ -skew McCoy rings, we introduce the concept of $\\alpha $ -skew $\\pi $ -McCoy rings, and we study the relationships with another two new generalizations, $\\alpha $ -skew ${\\pi }_{1}$ -McCoy rings and $\\alpha $ -skew ${\\pi }_{2}$ -McCoy rings, observing the relations with $\\alpha $ -skew McCoy rings, $\\pi $ -McCoy rings, $\\alpha $ -skew Armendariz rings, $\\pi $ -regular rings, and other kinds of rings. Also, we investigate conditions such that $\\alpha $ -skew ${...

  14. Gaseous alpha emitter diffusion studies using alpha track method

    International Nuclear Information System (INIS)

    Using a very accurate and sensitive analysis method such as alpha track method, the SSNTD group was able to undertake studies on the atomic and molecular processes taking place at low speed and/or very low concentrations, such as diffusion of gaseous alpha radionuclides in gaseous media. For practical application reasons, we began to study the diffusion in air for gaseous alpha radionuclides and aerosols carrying solid alpha radionuclides. The used alpha radionuclides were: Rn-222, as gaseous radionuclide and its solid descendants genetically related, attached to different particles from air, as radioactive aerosols. The source was included into an air tight device with a very well known volume. After 40 days, the radioactive equilibrium was established for all descendants, so that in the device there were the Rn-222 and its descendants, each of them having the same activity. The relative amount/activity ratio of each decay product, at any duration, for any initial mass of Ra-226 parent radionuclide, were calculated using the code UURASE, based on the Bateman general equations, for computing the U-238 radioactive series gamma accumulation. This was adapted for alpha accumulation as ALFAURASE programme. The device which contains the Ra-226 source can be coupled to the calibration system or to the diffusion system, without destroying the radioactive equilibrium. At this coupling, only the radioactive concentration is changed due to the variation of the volume. First of all the device was used for calibrating the CR-39 track detectors for both Rn-222 gaseous radionuclide and aerosol concentration measurements using, in the coupled calibration system, a special 'detector-container' equipped/or not with a filter used for radioactive aerosol stopping. The track detectors CR-39 were etched in NaOH 30%, for 7 hours at 70 deg. C and their studies were performed by optical microscopy using a stereo-microscope Wild M7S and a binocular Zeiss Jena microscope. (authors)

  15. Contribution to the study of the alpha-alpha interaction

    International Nuclear Information System (INIS)

    The new variable energy cyclotron at Berkeley that can accelerate an alpha beam up to an energy of 130 MeV and the mass production of lithium diffused junctions have enabled us to perform 2 series of measurement, in the first one we use alpha beams with an energy ranging between 50 and 120 MeV to study alpha-alpha forces in the second one we use the flexibility of the variable energy cyclotron the resonances around 40 MeV, region that can not yet be reached by tandem accelerators. This work is divided into 6 chapters. The first chapter is dedicated to the formalism of partial wave analysis and the theory of the compound nucleus. In the second chapter the author presents the 88 cyclotron at Berkeley and the diffusion chamber, the alpha detectors are lithium diffused junctions made of silicon. The third chapter deals with the experimental methods used and the issue of the reduction of the volume of data. In the fourth chapter the results obtained in the upper part of the energy range are described in terms of complex shifts that allow the description of the α-α interaction at high energy. The very low impact parameter has enabled us to find 2 new components (l=6 and l=8) of the rotational spectrum and to define a more accurate phenomenological potential. The fifth chapter is dedicated to the narrow resonances we have found between 12 and 27 MeV. We present in the last chapter a calculation of the binding energy of C12 in which we have considered the 12C nucleus as formed by 3 alpha particles interacting with each other through the phenomenological potential defined above

  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. On the transfer of serum proteins to the rat intestinal juice

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, G H; Olsen, J;

    1994-01-01

    The in vivo pattern of serum proteins in the rat small-intestinal juice was characterized by crossed immunoelectrophoresis. Immunoglobulins and albumin, alpha-1-antitrypsin, transferrin, and orosomucoid were present. Larger serum proteins were absent (ceruloplasmin, haptoglobin, alpha-1-macroglob......The in vivo pattern of serum proteins in the rat small-intestinal juice was characterized by crossed immunoelectrophoresis. Immunoglobulins and albumin, alpha-1-antitrypsin, transferrin, and orosomucoid were present. Larger serum proteins were absent (ceruloplasmin, haptoglobin, alpha-1...... proteins in the intestinal juice is a selective passage through the capillary wall followed by passive intercellular transport via delivery of the serum in the interstitial space during disintegration of the enterocytes....

  18. Space Station alpha joint bearing

    Science.gov (United States)

    Everman, Michael R.; Jones, P. Alan; Spencer, Porter A.

    1987-01-01

    Perhaps the most critical structural system aboard the Space Station is the Solar Alpha Rotary Joint which helps align the power generation system with the sun. The joint must provide structural support and controlled rotation to the outboard transverse booms as well as power and data transfer across the joint. The Solar Alpha Rotary Joint is composed of two transition sections and an integral, large diameter bearing. Alpha joint bearing design presents a particularly interesting problem because of its large size and need for high reliability, stiffness, and on orbit maintability. The discrete roller bearing developed is a novel refinement to cam follower technology. It offers thermal compensation and ease of on-orbit maintenance that are not found in conventional rolling element bearings. How the bearing design evolved is summarized. Driving requirements are reviewed, alternative concepts assessed, and the selected design is described.

  19. ALPHA: antihydrogen and fundamental physics

    Science.gov (United States)

    Madsen, Niels

    2014-02-01

    Detailed comparisons of antihydrogen with hydrogen promise to be a fruitful test bed of fundamental symmetries such as the CPT theorem for quantum field theory or studies of gravitational influence on antimatter. With a string of recent successes, starting with the first trapped antihydrogen and recently resulting in the first measurement of a quantum transition in anti-hydrogen, the ALPHA collaboration is well on its way to perform such precision comparisons. We will discuss the key innovative steps that have made these results possible and in particular focus on the detailed work on positron and antiproton preparation to achieve antihydrogen cold enough to trap as well as the unique features of the ALPHA apparatus that has allowed the first quantum transitions in anti-hydrogen to be measured with only a single trapped antihydrogen atom per experiment. We will also look at how ALPHA plans to step from here towards more precise comparisons of matter and antimatter.

  20. Conditioning of alpha bearing wastes

    International Nuclear Information System (INIS)

    Alpha bearing wastes are generated during the reprocessing of spent fuel, mixed oxide fuel fabrication, decommissioning and other activities. The safe and effective management of these wastes is of particular importance owing to the radiotoxicity and long lived characteristics of certain transuranic (TRU) elements. The management of alpha bearing wastes involves a number of stages which include collection, characterization, segregation, treatment, conditioning, transport, storage and disposal. This report describes the currently available matrices and technologies for the conditioning of alpha wastes and relates them to their compatibility with the other stages of the waste management process. The selection of a specific immobilization process is dependent on the waste treatment state and the subsequent handling, transport, storage and disposal requirements. The overall objectives of immobilization are similar for all waste producers and processors, which are to produce: (a) Waste forms with sufficient mechanical, physical and chemical stability to satisfy all stages of handling, transport and storage (referred to as the short term requirements), and (b) Waste forms which will satisfy disposal requirements and inhibit the release of radionuclides to the biosphere (referred to as the long term requirements). Cement and bitumen processes have already been successfully applied to alpha waste conditioning on the industrial scale in many of the IAEA Member States. Cement systems based on BFS and pozzolanic cements have emerged as the principal encapsulation matrices for the full range of alpha bearing wastes. Alternative technologies, such as polymers and ceramics, are being developed for specific waste streams but are unlikely to meet widespread application owing to cost and process complexity. The merits of alpha waste conditioning are improved performance in transport, storage and disposal combined with enhanced public perception of waste management operations. These

  1. Alpha decay of At-194

    OpenAIRE

    Andreev, Andrei; Antalic, S; Ackermann, D.; Bianco, L.; Franchoo, S.; S. Heinz; F. P. Hessberger; Hofmann, S.; Huyse, Marc; Kojouharov, I.; Kindler, B.; Lommel, B.; Mann, R.; Nishio, K; R.D.Page

    2009-01-01

    Detailed alpha-decay studies of the neutron-deficient isotope At-194 have been performed in the complete fusion reaction Fe-56+Pr-141 -> At-194+3n at the velocity filter SHIP. Two alpha-decaying isomeric states with half-lives of T-1/2(At-194(m1))=310(8) ms and T-1/2(At-194(m2))=253(10) ms were identified in this nucleus. Their complex decays to the states in the daughter nucleus Bi-190 are discussed in the article. We propose that similar to the case of the neighboring At-191,At-192,At-193,A...

  2. Test chamber for alpha spectrometry

    Science.gov (United States)

    Larsen, Robert P.

    1977-01-01

    Alpha emitters for low-level radiochemical analysis by measurement of alpha spectra are positioned precisely with respect to the location of a surface-barrier detector by means of a chamber having a removable threaded planchet holder. A pedestal on the planchet holder holds a specimen in fixed engagement close to the detector. Insertion of the planchet holder establishes an O-ring seal that permits the chamber to be pumped to a desired vacuum. The detector is protected against accidental contact and resulting damage.

  3. Influence of the repulsive coefficient {alpha} and approximate corresponding states in Mie {alpha}-6 and exponential {alpha}-6 fluids

    Energy Technology Data Exchange (ETDEWEB)

    Galliero, Guillaume [Universite de Marne-la-Vallee, Laboratoire d' Etude des Transferts d' Energie et de Matiere (EA 2546), Bat. Lavoisier, Cite Descartes, Champs-sur-Marne, F-77454 Marne-la-Vallee Cedex 2 (France)], E-mail: galliero@univ-mlv.fr; Boned, Christian; Baylaucq, Antoine [Universite de Pau et des Pays de l' Adour, Laboratoire des Fluides Complexes (UMR-5150), BP 1155, F-64013 Pau Cedex (France); Montel, Francois [TOTAL, CSTJF, Avenue Larribau, F-64018 Pau (France)

    2007-03-30

    Non-equilibrium molecular dynamics (NEMD) simulations of the Mie {alpha}-6 and the exponential {alpha}-6 (exp {alpha}-6) fluids have been carried out for 42 thermodynamic states. Various repulsive coefficients have been studied, {alpha} ranging from 9 to 14 for the Mie {alpha}-6 potentials and from 11 to 16 for the exp {alpha}-6 ones, which corresponds to a total of 603 points of simulation of stable phases. The simulations have shown that, for a given set of reduced temperature and density (using an appropriate scaling procedure), the reduced pressure varies linearly with {radical}({alpha}-6) for the Mie {alpha}-6 potentials and with {radical}({alpha}-7) for the exp {alpha}-6 potentials. Concerning the viscosity, it is shown that, for both potential families, the variation is linear with {alpha}. Thus, an approximate corresponding states scheme exists on pressure and on viscosity for fluids modelled by both potentials families, but only for each property separately. In addition, it appears that, approximate corresponding states exist between fluids modelled by a Mie {alpha}-6 potential and an exp ({alpha} + 2)-6 one for pressure, and between fluids modelled by a Mie {alpha}-6 potential and an exp ({alpha} + 2.5)-6 one for viscosity. So, despite obvious similarities, the influence of the shape of the potential on pressure and on viscosity is not strictly the same. Hence, a complete perfect corresponding states scheme (including both the pressure and the viscosity) seems hardly feasible between fluids modelled by the Mie {alpha}-6 and the exp {alpha}-6 potential families.

  4. 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 ...

  5. Alcoholism, Alpha Production, and Biofeedback

    Science.gov (United States)

    Jones, Frances W.; Holmes, David S.

    1976-01-01

    Electroencephalograms of 20 alcoholics and 20 nonalcoholics were obtained. Data indicated that alcoholics produced less alpha than nonalcoholics. In one training condition subjects were given accurate biofeedback, whereas in the other condition subjects were given random (noncontingent) feedback. Accurate biofeedback did not result in greater…

  6. Alpha Testing Escape from Diab

    Science.gov (United States)

    Alpha testing was conducted of sessions 2 and 3 from Diab to assess whether the activities worked as expected, and whether children in the target ages enjoyed it. Data include both RA observations of child performance while playing the games and cognitive interview responses from the players after t...

  7. A synopsis of collective alpha effects and implications for ITER

    Energy Technology Data Exchange (ETDEWEB)

    Sigmar, D.J.

    1990-10-01

    This paper discusses the following: Alpha Interaction with Toroidal Alfven Eigenmodes; Alpha Interaction with Ballooning Modes; Alpha Interaction with Fishbone Oscillations; and Implications for ITER.

  8. Calibration of sources for alpha spectroscopy systems

    International Nuclear Information System (INIS)

    This paper describes the calibration methodology for measuring the total alpha activity of plane and thin sources with the Alpha Spectrometer for Silicon Detector in the Nuclear Measures and Dosimetry laboratory at IEAv/CTA. (author)

  9. Monitor for alpha beta contamination of hands

    International Nuclear Information System (INIS)

    The following specifications of hands alpha beta contamination monitor are presented: the position of the hands, the detection and separation of alpha and beta, the information processing, the programming, the results presentation and general characteristics. (A.L.B.)

  10. \\alpha $ $^m $ Continuous Maps in Topological Spaces

    OpenAIRE

    Mathew, Milby; Parimelazhagan, R.; S Jafari

    2016-01-01

    The main aim of the present paper is to introduce new classes of functions called $ \\alpha $ $^m $ continuous maps and $ \\alpha $ $^m $ irresolute maps. We obtain some characterizations of these classes and properties are studied.

  11. 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....

  12. Automated High-Content Live Animal Drug Screening Using C. elegans Expressing the Aggregation Prone Serpin α1-antitrypsin Z

    OpenAIRE

    Gosai, Sager J.; Joon Hyeok Kwak; Cliff J Luke; Long, Olivia S.; King, Dale E.; Kovatch, Kevin J.; Johnston, Paul A.; Tong Ying Shun; Lazo, John S.; Perlmutter, David H.; Silverman, Gary A.; Pak, Stephen C.

    2010-01-01

    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. elegan...

  13. 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...... systemic spreading. Addition of SpeB to human plasma increased plasma-mediated bacterial killing and prolonged coagulation time through the intrinsic pathway of coagulation. This effect was independent of the enzymatic activity of SpeB and was mediated by a non-covalent medium-affinity binding and...

  14. Damped Lyman-Alpha Galaxies

    CERN Document Server

    Turnshek, D A; Lane, W; Monier, E M; Nestor, D; Bergeron, J; Briggs, F; Smette, A

    2000-01-01

    Some results from an imaging program to identify low-redshift (0.09alpha (DLA) galaxies are presented. The standard paradigm that was widely accepted a decade ago, that DLA galaxies are the progenitors of luminous disk galaxies, is now being seriously challenged. The indisputable conclusion from imaging studies at low redshift is that the morphological types of DLA galaxies are mixed and that they span a range in luminosities and surface brightnesses.

  15. Diabetes and alpha lipoic acid

    OpenAIRE

    IssyLaher

    2011-01-01

    Diabetes mellitus is a multi-faceted metabolic disorder where there is increased oxidative stress that contributes to the pathogenesis of this debilitating disease. This has prompted several investigations into the use of antioxidants as a complementary therapeutic approach. Alpha lipoic acid, a naturally occurring dithiol compound which plays an essential role in mitochondrial bioenergetic reactions, has gained considerable attention as an antioxidant for use in managing diabetic complicatio...

  16. Diabetes and Alpha Lipoic Acid

    OpenAIRE

    Golbidi, Saeid; Badran, Mohammad; Laher, Ismail

    2011-01-01

    Diabetes mellitus is a multi-faceted metabolic disorder where there is increased oxidative stress that contributes to the pathogenesis of this debilitating disease. This has prompted several investigations into the use of antioxidants as a complementary therapeutic approach. Alpha lipoic acid, a naturally occurring dithiol compound which plays an essential role in mitochondrial bioenergetic reactions, has gained considerable attention as an antioxidant for use in managing diabetic complicatio...

  17. $Gamma(H\\to b\\bar{b})$ to order $\\alpha\\alpha_s$

    CERN Document Server

    Mihaila, Luminita; Steinhauser, Matthias

    2015-01-01

    We compute the decay rate of the Standard Model Higgs boson to bottom quarks to order $\\alpha\\alpha_s$. We apply the optical theorem and calculate the imaginary part of three-loop corrections to the Higgs boson propagator using asymptotic expansions in appropriately chosen mass ratios. The corrections of order $\\alpha\\alpha_s$ are of the same order of magnitude as the ${\\cal O}(\\alpha_s^3)$ QCD corrections but have the opposite sign.

  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. Innovations in Los Alamos alpha box design

    International Nuclear Information System (INIS)

    Destructive examinations of irradiated fuel pins containing plutonium fuel must be performed in shielded hot cells with strict provisions for containing the plutonium. Alpha boxes provide containment for the plutonium, toxic fission products, and other hazardous highly radioactive materials. The alpha box contains windows for viewing and a variety of transfer systems specially designed to allow transfers in and out of the alpha box without spread of the hazardous materials that are contained in the box. Alpha boxes have been in use in the Wing 9 hot cells at Los Alamos National Laboratory for more than 20 years. Features of the newly designed alpha boxes are presented

  20. Innovations in Los Alamos alpha box design

    Energy Technology Data Exchange (ETDEWEB)

    Ledbetter, J.M.; Dowler, K.E.; Cook, J.H.

    1985-01-01

    Destructive examinations of irradiated fuel pins containing plutonium fuel must be performed in shielded hot cells with strict provisions for containing the plutonium. Alpha boxes provide containment for the plutonium, toxic fission products, and other hazardous highly radioactive materials. The alpha box contains windows for viewing and a variety of transfer systems specially designed to allow transfers in and out of the alpha box without spread of the hazardous materials that are contained in the box. Alpha boxes have been in use in the Wing 9 hot cells at Los Alamos National Laboratory for more than 20 years. Features of the newly designed alpha boxes are presented.

  1. Alpha particles detection in nitrocellulose

    International Nuclear Information System (INIS)

    The method for the manufacturing of the detection films follows these steps: preparation of the mass which includes nitrocellulose in the form of cotton as raw material ethyl acetate, cellosolve acetate, isopropyl and butyl alcohols as solvents and dioctyl phtalate as plasticiser; dilution of the paste; pouring of the diluted mass; and drying of the detection films. The results obtained experimentally are: The determination of the development times of the different thicknesses of the manufactured films. Response linearity of the detectors, variation of the number of tracks according to the distance of the source to the detector. Sizes of the diameter of the tracks depending of the distance detector-alpha emmission source. As a conclusion we can say the the nitrocellulose detectors are specific for alpha radiation; the more effective thicknesses in uranium prospecting works were those of 60 microns, since for the laboratory works the thicknesses of 30 to 40 microns were the ideal; the development technique of the detection films is simple and cheap and can be realized even in another place than the laboratory; this way of the manufacturing of nitrocellulose detection film sensitive to alpha nuclear radiation is open to future research. (author)

  2. The Behaviour of Varying-Alpha Cosmologies

    CERN Document Server

    Barrow, John D; Magueijo, J

    2002-01-01

    We determine the behaviour of a time-varying fine structure 'constant' $\\alpha (t)$ during the early and late phases of universes dominated by the kinetic energy of changing $\\alpha (t)$, radiation, dust, curvature, and lambda, respectively. We show that after leaving an initial vacuum-dominated phase during which $\\alpha$ increases, $\\alpha$ remains constant in universes like our own during the radiation era, and then increases slowly, proportional to a logarithm of cosmic time, during the dust era. If the universe becomes dominated by negative curvature or a positive cosmological constant then $\\alpha$ tends rapidly to a constant value. The effect of an early period of de Sitter or power-law inflation is to drive $\\alpha$ to a constant value. Various cosmological consequences of these results are discussed with reference to recent observational studies of the value of $\\alpha$ from quasar absorption spectra and to the existence of life in expanding universes.

  3. Identification of noncollagenous sites encoding specific interactions and quaternary assembly of alpha 3 alpha 4 alpha 5(IV) collagen: implications for Alport gene therapy.

    Science.gov (United States)

    Kang, Jeong Suk; Colon, Selene; Hellmark, Thomas; Sado, Yoshikazu; Hudson, Billy G; Borza, Dorin-Bogdan

    2008-12-12

    Defective assembly of alpha 3 alpha 4 alpha 5(IV) collagen in the glomerular basement membrane causes Alport syndrome, a hereditary glomerulonephritis progressing to end-stage kidney failure. Assembly of collagen IV chains into heterotrimeric molecules and networks is driven by their noncollagenous (NC1) domains, but the sites encoding the specificity of these interactions are not known. To identify the sites directing quaternary assembly of alpha 3 alpha 4 alpha 5(IV) collagen, correctly folded NC1 chimeras were produced, and their interactions with other NC1 monomers were evaluated. All alpha1/alpha 5 chimeras containing alpha 5 NC1 residues 188-227 replicated the ability of alpha 5 NC1 to bind to alpha3NC1 and co-assemble into NC1 hexamers. Conversely, substitution of alpha 5 NC1 residues 188-227 by alpha1NC1 abolished these quaternary interactions. The amino-terminal 58 residues of alpha3NC1 encoded binding to alpha 5 NC1, but this interaction was not sufficient for hexamer co-assembly. Because alpha 5 NC1 residues 188-227 are necessary and sufficient for assembly into alpha 3 alpha 4 alpha 5 NC1 hexamers, whereas the immunodominant alloantigenic sites of alpha 5 NC1 do not encode specific quaternary interactions, the findings provide a basis for the rational design of less immunogenic alpha 5(IV) collagen constructs for the gene therapy of X-linked Alport patients. PMID:18930919

  4. $\\alpha_s$ extractions from CMS (status and plans)

    CERN Document Server

    Rabbertz, Klaus

    2015-01-01

    Numerous extractions of the strong coupling constant have been performed at hadron colliders, in particular from jet cross sections. The latest results achieved by the experiments at the $ep$ collider HERA, at the $p\\bar{p}$ collider Tevatron, and at the $pp$ collider LHC are reported with emphasis on the CMS experiment for the latter. Future prospects for precision determinations of $\\alpha_s(M_Z)$ and for testing the running of the strong coupling beyond the TeV range are discussed.

  5. 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.

  6. The 2009 Wolrd Average of $\\alpha_s (M_Z)$

    CERN Document Server

    Bethke, Siegfried

    2009-01-01

    Measurements of $\\alpha_s$, the coupling strength of the Strong Interaction between quarks and gluons, are summarised and an updated value of the world average of $\\alpha_s (M_Z)$ is derived. Building up on previous reviews, special emphasis is laid on the most recent determinations of $\\alpha_s$. These are obtained from $\\tau$-decays, from global fits of electroweak precision data and from measurements of the proton structure function $\\F_2$, which are based on perturbative QCD calculations up to $O(\\alpha_s^4)$; from hadronic event shapes and jet production in $\\epem$ annihilation, based on $O(\\alpha_s^3) $ QCD; from jet production in deep inelastic scattering and from $\\Upsilon$ decays, based on $O(\\alpha_s^2) $ QCD; and from heavy quarkonia based on unquenched QCD lattice calculations. Applying pragmatic methods to deal with possibly underestimated errors and/or unknown correlations, the world average value of $\\alpha_s (M_Z)$ results in $\\alpha_s (M_Z) = 0.1184 \\pm 0.0007$. The measured values of $\\alpha...

  7. 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.

  8. Targeted alpha therapy for cancer

    Science.gov (United States)

    Allen, Barry J.; Raja, Chand; Rizvi, Syed; Li, Yong; Tsui, Wendy; Zhang, David; Song, Emma; Qu, Chang Fa; Kearsley, John; Graham, Peter; Thompson, John

    2004-08-01

    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 213Bi-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 µCi in human

  9. 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.

  10. The Alpha Magnetic Spectrometer (AMS)

    International Nuclear Information System (INIS)

    The Alpha Magnetic Spectrometer (AMS) is a large acceptance (0.65 sr m2) 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. 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.

  12. Genomic organization of the bovine alpha-S1 casein gene.

    OpenAIRE

    Koczan, D; Hobom, G.; Seyfert, H.M.

    1991-01-01

    We report the sequence of the complete bovine alpha-s1 casein gene eludicating for the first time the genomic organization of an alpha-s type casein gene. Extending over 17508 bp the gene is split into 19 exons, ranging in size from 24 bp to 385 bp. Except for the translational stop codon not a single coding triplet of the alpha-s1 reading frame is disrupted by any of the splice junctions, which all confirm to known splice consensus sequences. Nine out of 16 coding exons begin with a 'GAX' co...

  13. Nanodosimetry of radon alpha particles

    International Nuclear Information System (INIS)

    It is currently accepted that energy deposition at the nanometer level (rather than conventional microdosimetry) determines the biological effects of ionizing radiation. Many previously established experimental techniques (e.g., the Rossi proportional counter) or theoretical methods (e.g., simplified calculations using the continuous slowing-down approximation (CSDA)) are inapplicable to the study of nanodosimetry. The peculiarities of the geometry of exposure to radon progeny further complicate the problem. This is because the conditions under which several open-quotes classicalclose quotes models of radiation action are obtained (e.g., the alpha-beta formulation of the Theory of Dual Radiation Action, which is built on microdosimetry) are no longer valid. It thus becomes clear that not only new techniques but new concepts are required to describe the effects of radon alpha particles. In this paper we discuss a number of computational aspects specific to radon nanodosimetry. In particular, we describe the novel concept of open-quotes associated surfaceclose quotes (AS) which is necessary for efficiently converting Monte-Carlo-generated particle tracks to nanodosimetric spectra. The AS is the analog of Lea's associated volume, applied to radiation sources subject to the geometrical restrictions of internal exposure. We systematically analyze factors affecting the nanodosimetry of radon progeny, such as the distance between the radioactive source and the sensitive volume, the size of the sensitive volume, and CSDA versus full Monte-Carlo track generation

  14. Nanodosimetry of radon alpha particles

    Energy Technology Data Exchange (ETDEWEB)

    Zaider, M. [Columbia Univ. New York, NY (United States); Varma, M.N. [U.S. Department of Energy, Washington, DC (United States)

    1992-12-31

    It is currently accepted that energy deposition at the nanometer level (rather than conventional microdosimetry) determines the biological effects of ionizing radiation. Many previously established experimental techniques (e.g., the Rossi proportional counter) or theoretical methods (e.g., simplified calculations using the continuous slowing-down approximation (CSDA)) are inapplicable to the study of nanodosimetry. The peculiarities of the geometry of exposure to radon progeny further complicate the problem. This is because the conditions under which several {open_quotes}classical{close_quotes} models of radiation action are obtained (e.g., the alpha-beta formulation of the Theory of Dual Radiation Action, which is built on microdosimetry) are no longer valid. It thus becomes clear that not only new techniques but new concepts are required to describe the effects of radon alpha particles. In this paper we discuss a number of computational aspects specific to radon nanodosimetry. In particular, we describe the novel concept of {open_quotes}associated surface{close_quotes} (AS) which is necessary for efficiently converting Monte-Carlo-generated particle tracks to nanodosimetric spectra. The AS is the analog of Lea`s associated volume, applied to radiation sources subject to the geometrical restrictions of internal exposure. We systematically analyze factors affecting the nanodosimetry of radon progeny, such as the distance between the radioactive source and the sensitive volume, the size of the sensitive volume, and CSDA versus full Monte-Carlo track generation.

  15. Confidence Intervals for Cronbach's Coefficient Alpha Values

    OpenAIRE

    Koning, Alex; 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, which amounts to computing the confidence intervals of an alpha, as these intervals automatically account for differences across the numbers of items. We also give appropriate statistics to test for ...

  16. Confidence Intervals for Cronbach's Coefficient Alpha Values

    OpenAIRE

    Koning, A. J.; Franses, Ph.H.B.F.

    2003-01-01

    Coefficient 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, which amounts to computing the confidence intervals of an alpha, as these intervals automatically account for differences across the numbers of items. We also give appropriate statistics to test for significant ...

  17. Conformons in alpha-helical proteins

    CERN Document Server

    Atanasov, Victor

    2009-01-01

    We propose the conformon as a quantum of conformational change for energy transfer in alpha-helical proteins. The underlying mechanism of interaction between the quantum of excitation and the conformational degrees of freedom is nonlinear and leads to solitary wave packets of conformational energy. The phenomenon is specific to alpha-helices and not to beta-sheets in proteins due to the three strands of hydrogen bonds constituting the alpha-helical backbone.

  18. Quantum time scales in alpha tunneling

    CERN Document Server

    Kelkar, N G; Nowakowski, M

    2008-01-01

    The theoretical treatment of alpha decay by Gamow is revisited by investigating the quantum time scales in tunneling. The time spent by an alpha particle in front of the barrier and traversing it before escape is evaluated using microscopic alpha nucleus potentials. The half-life of a nucleus is shown to correspond to the time spent by the alpha knocking in front of the barrier. Calculations for medium and super heavy nuclei show that from a multitude of available tunneling time definitions, the transmission dwell time gives the bulk of the lifetime of the decaying state, in most cases.

  19. Prospects for alpha particle studies on TFTR

    International Nuclear Information System (INIS)

    TFTR is expected to produce approximately 5 MW of alpha heating during the D/T Q ≅ 1 phase of operation in 1990. At that point the collective confinement properties and the heating effects of alpha particles become accessible for study for the first time. This paper outlines the potential performance of TFTR with respect to alpha particle production, the diagnostics which will be available for alpha particle measurements, and the physics issues which can be studied both before and during D/T operation

  20. [Alpha-linolenic acid and cardiovascular diseases].

    Science.gov (United States)

    Ristić-Medić, Danijela; Ristić, Gordana; Tepsić, Vesna

    2003-01-01

    IMPORTANCE AND METABOLISM OF ALPHA-LINOLENIC ACID: Alpha-linolenic acid is an essential fatty acid which cannot be produced in the body and must be taken by food. Both in animals and humans, alpha-linolenic acid is desaturated and elongated into eicosapentaenoic and docosahexaenoic acid. It is also incorporated into plasma and tissue lipids and its conversion is affected by levels of linoleic acid. POTENTIAL ROLE IN PATHOGENESIS OF CARDIOVASCULAR DISEASES: Diet enriched in n-3 fatty acids, especially alpha-linolenic acid, reduces the incidence of cardiac death. Studies have shown that alpha linolenic acid prevents ventricular fibrillation which is the main cause of cardiac death. Studies in rats suggest that alpha-linolenic acid may be more effective in preventing ventricular fibrillations than eicosapentaenoic and docosahexaenoic acid. Furthermore, alpha-linolenic acid is the main fatty acid decreasing platalet aggregation which is an important step in thrombosis i.e. non-fatal myocardial infarction and stroke. DIETARY SOURCES AND NUTRITION RECOMMENDATIONS: Dietary sources include flaxseed and flaxseed oil, canola oil, soybean and soybean oil, pumpkin seed and pumpkin oil, walnuts and walnut oil. Strong evidence supports beneficial effects of alpha-linolenic acid and its dietary sources should be incorporated into balanced diet for prevention of cardiovascular diseases. The recommended daily intake is 2 g with a ratio of 5/1 for linoleic/alpha-linolenic acid. PMID:15510909

  1. Alpha particle problems in shielded support systems

    International Nuclear Information System (INIS)

    Alpha particle confinement is considered in the case of internal conductor systems with magnetically shielded supports. The treatment includes problems of energy transfer to the background plasma, the balance between radiation losses and alpha particle heating, mirror confinement in the main poloidal field, the cut-off and shielding conditions at the supports, ambipolar electric fields, wall interaction, and support location. With a proper and technically realizable choice of parameter values, it should become possible to achieve alpha particle heating as well as to manage the reactor technological problems due to alpha particle interaction with the supports. (Auth.)

  2. Quantum Estimates of Alpha Emitter Life Time

    Directory of Open Access Journals (Sweden)

    B. Santoso

    2006-01-01

    Full Text Available Quantum estimates of several alpha radioactive life time have been made using the probability of quantum tunneling through the nuclear potential barrier. It is assumed that for a given nucleus with mass number A and isotopic number Z, there exists an alpha particle moving freely back and forth in the nucleus with mass and isotopic numbers A -4 and Z-2. If the probability of penetrating the nuclear potential barrier is Τ, then after N times (N=1/Τ hitting the barrier an alpha particle is emitted. To obtain the elapsed time for emitting an alpha particle requires N times τ0, where τ0 is the time travel for alpha across the nuclear diameter, which is dependent on alpha energy. It is assumed here that this kinetic energy is the same as the emitted energy. The emitting alpha kinetic energies here are calculated by the difference of the masses of the parent and daughter nuclei and the alpha particles. They are in closed agreement with the experimental observations. While the alpha radioactive life time are not the same order of magnitudes but give the same linearity on the logarithmic scale as function of the inverse square root of energy.

  3. $\\alpha_{s}$ 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.

  4. $\\alpha$-curvatures and $\\alpha$-flows on low dimensional triangulated manifolds

    OpenAIRE

    Ge, Huabin; Xu, Xu

    2015-01-01

    In this paper, we introduce two discrete curvature flows, which are called $\\alpha$-flows on two and three dimensional triangulated manifolds. For triangulated surface $M$, we introduce a new normalization of combinatorial Ricci flow (first introduced by Bennett Chow and Feng Luo \\cite{CL1}), aiming at evolving $\\alpha$ order discrete Gauss curvature to a constant. When $\\alpha\\chi(M)\\leq0$, we prove that the convergence of the flow is equivalent to the existence of constant $\\alpha$-curvatur...

  5. alpha-nucleus potentials, alpha-decay half-lives, and shell closures for superheavy nuclei

    OpenAIRE

    Mohr, Peter

    2006-01-01

    Systematic alpha-nucleus folding potentials are used to analyze alpha-decay half-lives of superheavy nuclei. Preformation factors of about several per cent are found for all nuclei under study. The systematic behavior of the preformation factors and the volume integrals of the potentials allows to predict alpha-decay energies and half-lives for unknown nuclei. Shell closures can be determined from measured alpha-decay energies using the discontinuity of the volume integral at shell closures. ...

  6. 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.

  7. Expression of the alpha 1, alpha 2 and alpha 3 isoforms of the GABAA receptor in human alcoholic brain.

    Science.gov (United States)

    Lewohl, J M; Crane, D I; Dodd, P R

    1997-03-14

    The expression of the alpha 1, alpha 2 and alpha 3 isoforms of the GABAA receptor was studied in the superior frontal and motor cortices of 10 control, 10 uncomplicated alcoholic and 7 cirrhotic alcoholic cases matched for age and post-mortem delay. The assay was based on competitive RT/PCR using a single set of primers specific to the alpha class of isoform mRNA species, and was normalized against a synthetic cRNA internal standard. The assay was shown to be quantitative for all three isoform mRNA species. Neither the patient's age nor the post-mortem interval significantly affected the expression of any isoform in either cortical area. The profile of expression was shown to be significantly different between the case groups, particularly because alpha 1 expression was raised in both groups of alcoholics of controls. The two groups of alcoholics could be differentiated on the basis of regional variations in alpha 1 expression. In frontal cortex, alpha 1 mRNA expression was significantly increased when uncomplicated alcoholics were compared with control cases whereas alcoholic-cirrhotic cases were not significantly different from either controls or uncomplicated alcoholic cases. In the motor cortex, alpha 1 expression was elevated only when alcoholic-cirrhotic cases were compared with control cases. There was no significant difference between case groups or areas for any other isoform. PMID:9098573

  8. Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume

    Science.gov (United States)

    Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.

    2015-01-01

    Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…

  9. Alpha-Synuclein Binds to the Inner Membrane of Mitochondria in an alpha-Helical Conformation

    NARCIS (Netherlands)

    Robotta, M.; Gerding, H.R.; Vogel, A.; Hauser, K.; Schildknecht, S.; Karreman, C.; Leist, M.; Subramaniam, V.; Drescher, M.

    2014-01-01

    The human alpha-Synuclein (alphaS) protein is of significant interest because of its association with Parkinson's disease and related neurodegenerative disorders. The intrinsically disordered protein (140 amino acids) is characterized by the absence of a well-defined structure in solution. It displa

  10. 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.

  11. 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...

  12. 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

  13. Coefficient Alpha Bootstrap Confidence Interval under Nonnormality

    Science.gov (United States)

    Padilla, Miguel A.; Divers, Jasmin; Newton, Matthew

    2012-01-01

    Three different bootstrap methods for estimating confidence intervals (CIs) for coefficient alpha were investigated. In addition, the bootstrap methods were compared with the most promising coefficient alpha CI estimation methods reported in the literature. The CI methods were assessed through a Monte Carlo simulation utilizing conditions…

  14. DT results of TFTR's alpha collector

    International Nuclear Information System (INIS)

    An escaping alpha collector probe has been developed for TFTR's DT phase to complement the results of the lost alpha scintillator detectors which have been operating on TFTR since 1988. Measurements of the energy distribution of escaping alphas have been made by measuring the range of alphas implanted into nickel foils located within the alpha collector. Exposed samples have been analyzed for 4 DT plasma discharges at plasma currents of 1.0 and 1.8 MA. The results at 1.0 MA are in good agreement with predictions for first orbit alpha loss at 3.5 MeV. The 1.8 MA results, however, indicate a large anomalous loss of partially thermalized alphas at an energy ∼30% below the birth energy and at a total fluence nearly an order of magnitude above expected first orbit loss. This anomalous loss is not observed with the lost alpha scintillator detectors in DT plasmas but does resemble the anomalous delayed loss seen in DD plasmas. Several potential explanations for this loss process are examined. None of the candidate explanations proposed thus far are fully consistent with the anomalous loss observations

  15. 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...

  16. Single-field $\\alpha$-attractors

    CERN Document Server

    Linde, Andrei

    2015-01-01

    I describe a simple class of $\\alpha$-attractors, generalizing the single-field GL model of inflation in supergravity. The new class of models is defined for $0<\\alpha \\lesssim 1$, providing a good match to the present cosmological data. I also present a generalized version of these models which can describe not only inflation but also dark energy and supersymmetry breaking.

  17. Sensitivity of alpha-decay to the real alpha-nucleus potential

    International Nuclear Information System (INIS)

    The information which can be obtained from studies of low energy alpha-particle scattering from heavy nuclei and from alpha-decay is discussed. The sensitivity of calculated widths and lifetimes for alpha-decay to the real nuclear potential is examined in detail using a formalism based on the unified theory of nuclear reactions. It is shown that a combined study of alpha-decay and alpha-particle scattering at energies near the Coulomb barrier should give a very precise determination of the barrier height and radius, although there is a more uniquely defined separation distance some way beyond the barrier. (orig.)

  18. A low-energy determination of $\\alpha_s$ at three loops

    CERN Document Server

    Vairo, Antonio

    2015-01-01

    We review one of the most accurate low-energy determinations of $\\alpha_s$. Comparing at short distances the QCD static energy at three loops and resummation of the next-to-next-to leading logarithms with its determination in 2+1-flavor lattice QCD, we obtain $\\alpha_s(1.5~{\\rm GeV})=0.336^{+0.012}_{-0.008}$, which corresponds to $\\alpha_s(M_Z)=0.1166^{+0.0012}_{-0.0008}$. We discuss future perspectives.

  19. Practical alpha detectors for site characterization

    International Nuclear Information System (INIS)

    The authors have and are developing a series of practical alpha detectors for alpha characterization. These include soil surface monitors, pipe and duct monitors, air quality and radon monitors, tool monitors, and sample monitors. Two types of these monitors have been transferred to industry thus far for commercialization. Several of these systems have been fully field tested: for example, the soil surface monitor has been used to characterize 11 sites for 7 customers at 3 DOE facilities. Using a new but simple technology, these alpha detectors can be put to use in many areas where conventional alpha probes are impractical or insufficiently sensitive. Use of these alpha detectors in site characterization at the Uranium in Soil Integrated Demonstration at Fernald, at Los Alamos, and elsewhere will be discussed as well as their commercialization and possible further applications

  20. An Alpha Schottky Junction Power Source

    Science.gov (United States)

    Litz, Marc; Carroll, James; Henriquez, Stan

    2011-10-01

    Isotope batteries present solutions for long-lived low power sources. Compact sensors, and electronic circuit boards can be powered for the lifetime of infrastructure. Alpha sources are practical for safety reasons because of the limited distance before energy absorption in materials, and the high energy (~5MeV) per particle. Damage to materials from the alphas limits the practical use. A Schottky diode geometry is created from an alpha foil on a diamond-like crystal. A power source is proposed that takes advantage of the radiation damage tolerance of diamond, combined with the short range of the alpha radiation. The internal field of the Schottky barrier creates a current through the diode from electron-hole pairs created by alpha bombardment in the gap. Calculations of the expected current, circuit model results, and design parameters for a device are described.

  1. Folding model analysis of alpha radioactivity

    CERN Document Server

    Basu, D N

    2003-01-01

    Radioactive decay of nuclei via emission of $\\alpha$ particles has been studied theoretically in the framework of a superasymmetric fission model using the double folding (DF) procedure for obtaining the $\\alpha$-nucleus interaction potential. The DF nuclear potential has been obtained by folding in the density distribution functions of the $\\alpha$ nucleus and the daughter nucleus with a realistic effective interaction. The M3Y effective interaction has been used for calculating the nuclear interaction potential which has been supplemented by a zero-range pseudo-potential for exchange along with the density dependence. The nuclear microscopic $\\alpha$-nucleus potential thus obtained has been used along with the Coulomb interaction potential to calculate the action integral within the WKB approximation. This subsequently yields microscopic calculations for the half lives of $\\alpha$ decays of nuclei. The density dependence and the exchange effects have not been found to be very significant. These calculations...

  2. 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.

  3. Direct Alpha Analysis for Forensic Samples (DAAFS)

    International Nuclear Information System (INIS)

    The goal of the DAAFS project is to deliver a field deployable direct alpha sample spectrometry system. This system is designed to rectify current gaps in pure alpha emitting material detection. The system comprises, firstly, an evaluation of multiple innovative methods for rapid on-site sample collection of difficult to detect alpha RN contamination. Secondly, the incorporation of an experimental alpha spectrometry analysis software suite, 'ADAM', is provided for performing the required on-site deconvolution of the complex alpha spectra arising from the direct sample measurement. Software simulation of collected alpha spectra will be handled by 'AASI', which will simulate alpha spectra as a training and analysis verification tool. Thirdly, a Concept of Operations (ConOps) for the system implementation in RN field teams is included. This combination of the swipe methodology, advanced swipe treatment equipment, mobile field laboratories, and the state of the art analysis software suite will provide RN response teams with the capability to identify and rapidly (i.e., hours as opposed to days) quantify low activity and difficult to detect alpha emitters. Further expert analysis support is available to field teams by sharing of raw spectral data via email with off-site laboratories. The proposed system provides the solution to this identified capability gap, specifically, a field-deployable real-time alpha detection system. The system comprises: a non-destructive particle sampler, standardized swipe sampling methods, a self-contained field alpha spectrometry system and an integrated data management/communications tool allowing for real-time raw-data tracking and data sharing. This system also provides responders with the type/quantity of RN material for improved safeguards, forensics, and contamination mitigation applications. (author)

  4. Catalytic Mechanism of Human Alpha-galactosidase

    Energy Technology Data Exchange (ETDEWEB)

    Guce, A.; Clark, N; Salgado, E; Ivanen, D; Kulinskaya, A; Brumer, H; Garman, S

    2010-01-01

    The enzyme {alpha}-galactosidase ({alpha}-GAL, also known as {alpha}-GAL A; E.C. 3.2.1.22) is responsible for the breakdown of {alpha}-galactosides in the lysosome. Defects in human {alpha}-GAL lead to the development of Fabry disease, a lysosomal storage disorder characterized by the buildup of {alpha}-galactosylated substrates in the tissues. {alpha}-GAL is an active target of clinical research: there are currently two treatment options for Fabry disease, recombinant enzyme replacement therapy (approved in the United States in 2003) and pharmacological chaperone therapy (currently in clinical trials). Previously, we have reported the structure of human {alpha}-GAL, which revealed the overall structure of the enzyme and established the locations of hundreds of mutations that lead to the development of Fabry disease. Here, we describe the catalytic mechanism of the enzyme derived from x-ray crystal structures of each of the four stages of the double displacement reaction mechanism. Use of a difluoro-{alpha}-galactopyranoside allowed trapping of a covalent intermediate. The ensemble of structures reveals distortion of the ligand into a {sup 1}S{sub 3} skew (or twist) boat conformation in the middle of the reaction cycle. The high resolution structures of each step in the catalytic cycle will allow for improved drug design efforts on {alpha}-GAL and other glycoside hydrolase family 27 enzymes by developing ligands that specifically target different states of the catalytic cycle. Additionally, the structures revealed a second ligand-binding site suitable for targeting by novel pharmacological chaperones.

  5. Human podocytes adhere to the KRGDS motif of the alpha3alpha4alpha5 collagen IV network.

    Science.gov (United States)

    Borza, Corina M; Borza, Dorin-Bogdan; Pedchenko, Vadim; Saleem, Moin A; Mathieson, Peter W; Sado, Yoshikazu; Hudson, Heather M; Pozzi, Ambra; Saus, Juan; Abrahamson, Dale R; Zent, Roy; Hudson, Billy G

    2008-04-01

    Podocyte adhesion to the glomerular basement membrane is required for proper function of the glomerular filtration barrier. However, the mechanism whereby podocytes adhere to collagen IV networks, a major component of the glomerular basement membrane, is poorly understood. The predominant collagen IV network is composed of triple helical protomers containing the alpha3alpha4alpha5 chains. The protomers connect via the trimeric noncollagenous (NC1) domains to form hexamers at the interface. Because the NC1 domains of this network can potentially support integrin-dependent cell adhesion, it was determined whether individual NC1 monomers or alpha3alpha4alpha5 hexamers support podocyte adhesion. It was found that, although human podocytes did not adhere to NC1 domains proper, they did adhere via integrin alphavbeta3 to a KRGDS motif located adjacent to alpha3NC1 domains. Because the KRGDS motif is a site of phosphorylation, its interactions with integrin alphavbeta3 may play a critical role in cell signaling in physiologic and pathologic states. PMID:18235087

  6. 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. PMID:7162915

  7. Osmotic fragility test in heterozygotes for alpha and beta thalassaemia.

    OpenAIRE

    Maccioni, L; Cao, A

    1985-01-01

    This study shows that the combination of heterozygous beta thalassaemia and deletion heterozygous (-alpha/alpha alpha) or homozygous (-alpha/-alpha) alpha+ thalassaemia may result in the production of erythrocytes which have normal mean volume and haemoglobinisation but decreased osmotic fragility. Based on this finding and previous studies, which have shown that beta thalassaemia screening by the osmotic fragility test may miss a significant proportion of beta thalassaemia heterozygotes, we ...

  8. Lyman alpha radiation in external galaxies

    Science.gov (United States)

    Neufeld, David A.; Mckee, Christopher F.

    1990-01-01

    The Ly alpha line of atomic hydrogen is often a luminous component of the radiation emitted by distant galaxies. Except for those galaxies which have a substantial central source of non-stellar ionizing radiation, most of the Ly alpha radiation emitted by galaxies is generated within regions of the interstellar medium which are photoionized by starlight. Conversely, much of the energy radiated by photoionized regions is carried by the Ly alpha line. Only hot, massive stars are capable of ionizing hydrogen in the interstellar medium which surrounds them, and because such stars are necessarily short-lived, Ly alpha emission traces regions of active star formation. Researchers argue that the strength of the Ly alpha emission observed from external galaxies may be used to estimate quantitatively the dust content of the emitting region, while the Ly alpha line profile is sensitive to the presence of shock waves. Interstellar dust particles and shock waves are intimately associated with the process of star formation in two senses. First, both dust particles and shock waves owe their existence to stellar activity; second, they may both serve as agents which facilitate the formation of stars, shocks by triggering gravitational instabilities in the interstellar gas that they compress, and dust by shielding star-forming molecular clouds from the ionizing and dissociative effects of external UV radiation. By using Ly alpha observations as a probe of the dust content in diffuse gas at high redshift, we might hope to learn about the earliest epochs of star formation.

  9. Remote Optical Detection of Alpha Radiation

    International Nuclear Information System (INIS)

    Alpha emitting radiation sources are typically hard to detect with conventional detectors due to the short range of alpha particles in the air. However, previous studies have shown that remote detection of alpha radiation is possible by measuring the ionization-induced fluorescence of air molecules. The alpha-induced ultraviolet (UV) light is mainly emitted by molecular nitrogen and its fluorescence properties are well known. The benefit of this method is the long range of UV photons in the air. Secondly, the detection is possible also under a strong beta and gamma radiation backgrounds as they do not cause localized molecular excitation. In this work, the optical detection was studied using two different detection schemes; spectral separation of fluorescence from the background lighting and coincidence detection of UV photons originating from a single radiative decay event. Our spectrally integrated measurements have shown that one alpha decay event yields up to 400 fluorescence photons in the air and all these UV photons are induced in a 5 ns time-window. On the other hand, the probability of a background coincidence event in 5 ns scale is very rare compared to the number of background photons. This information can be applied in fluorescence coincidence filtering to discriminate the alpha radiation initiated fluorescence signal from much more intense background lighting. A device called HAUVA (Handheld Alpha UV Application) was built during this work for demonstration purposes. HAUVA utilizes spectral filtering and it is designed to detect alpha emitters from a distance of about 40 cm. Using specially selected room lighting, the device is able to separate 1 kBq alpha emitter from the background lighting with 1 second integration time. (author)

  10. Naturally-occurring alpha activity

    International Nuclear Information System (INIS)

    In view of the difficulties of assessing the significance of man-made radioactivity it is important to study for comparison the background of natural radioactivity against which the human race has evolved and lives. It is also important to define the present levels of activity so that it will be possible to detect and study as quickly as possible any changes which may occur owing to the release into the environment of new radioactive materials. Moreover, by the study of the behaviour of natural radioactivity light may be shed upon that of the artificially produced isotopes and a number of analogies traced between the two groups. These concepts have led to studies of naturally-occurring radioactive materials alongside a programme of research into fission products in food, water and air, as well as studies of the metabolism of both sets of materials in the human body. Since the last report there has been a useful increase in our knowledge of natural radioactivity in the biosphere, and its levels relative to the new man-made activities. These studies have necessitated technical developments, particularly in the methods of measuring and identifying alpha-ray emitters, to which group many of the more important natural radioactive materials belong

  11. Diabetes and alpha lipoic acid

    Directory of Open Access Journals (Sweden)

    IssyLaher

    2011-11-01

    Full Text Available Diabetes mellitus is a multi-faceted metabolic disorder where there is increased oxidative stress that contributes to the pathogenesis of this debilitating disease. This has prompted several investigations into the use of antioxidants as a complementary therapeutic approach. Alpha lipoic acid, a naturally occurring dithiol compound which plays an essential role in mitochondrial bioenergetic reactions, has gained considerable attention as an antioxidant for use in managing diabetic complications. Lipoic acid quenches reactive oxygen species, chelates metal ions, and reduces the oxidized forms of other antioxidants such as vitamin C, vitamin E and glutathione. It also boosts antioxidant defense system through Nrf2-mediated antioxidant gene expression and by modulation of peroxisome proliferator activated receptors-regulated genes. ALA inhibits nuclear factor kappa B and activates AMPK in skeletal muscles, which in turn have a plethora of metabolic consequences. These diverse actions suggest that a lipoic acid acts by multiple mechanisms, many of which have only been uncovered recently. In this review we briefly summarize the known biochemical properties of lipoic acid and then discussed the oxidative mechanisms implicated in diabetic complications and the mechanisms by which lipoic acid may ameliorate these reactions. The findings of some of the clinical trials in which lipoic acid administration has been tested in diabetic patients during the last 10 years are summarized. It appears that the clearest benefit of lipoic acid supplementation is in patients with diabetic neuropathy.

  12. 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.

  13. Growth behaviors in the range $e^{r^\\alpha}$

    OpenAIRE

    Brieussel, Jérémie

    2011-01-01

    For every $\\alpha \\leq \\beta$ in a left neighborhood $[\\alpha_0,1]$ of 1, a group $G(\\alpha,\\beta)$ is constructed, the growth function of which satisfies $\\limsup \\frac{\\log \\log b_{G(\\alpha,\\beta)}(r)}{\\log r}=\\alpha$ and $\\liminf \\frac{\\log \\log b_{G(\\alpha,\\beta)}(r)}{\\log r}=\\beta$. When $\\alpha=\\beta$, this provides an explicit uncountable collection of groups with growth functions strictly comparable. On the other hand, oscillation in the case $\\alpha < \\beta$ explains the existence of...

  14. $\\alpha_s$ 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.

  15. 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.

  16. Alpha spectral analysis via artificial neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Kangas, L.J.; Hashem, S.; Keller, P.E.; Kouzes, R.T. [Pacific Northwest Lab., Richland, WA (United States); Troyer, G.L. [Westinghouse Hanford Co., Richland, WA (United States)

    1994-10-01

    An artificial neural network system that assigns quality factors to alpha particle energy spectra is discussed. The alpha energy spectra are used to detect plutonium contamination in the work environment. The quality factors represent the levels of spectral degradation caused by miscalibration and foreign matter affecting the instruments. A set of spectra was labeled with a quality factor by an expert and used in training the artificial neural network expert system. The investigation shows that the expert knowledge of alpha spectra quality factors can be transferred to an ANN system.

  17. Lyman alpha airglow observations from SORCE SOLSTICE

    Science.gov (United States)

    Dolinar, E.; Snow, M.; Holsclaw, G.; Thomas, G. E.; Woods, T. N.

    2010-12-01

    The Solar Stellar Irradiance Comparison Experiment (SOLSTICE) instrument on board the Solar Radiation Climate Experiment (SORCE) spacecraft in low Earth orbit observes stars every orbit for in-flight calibration. It also observes several star-free regions of the sky near the wavelength of Lyman alpha to correct for airglow emission in the stellar measurements. Although the airglow measurements are only taken during the eclipse portion of the orbit, the look directions cover nearly the entire anti-sunward hemisphere. This seven-year record of Lyman alpha airglow observations (2003-2010) shows the response of the Hydrogen geocorona to changes in the solar Lyman alpha irradiance over the solar cycle.

  18. Alpha particle confinement in tandem mirrors

    International Nuclear Information System (INIS)

    Mechanisms leading to loss of alpha particles from non-axisymmetric tandem mirrors are considered. Stochastic diffusion due to bounce-drift resonances, which can cause rapid radial losses of high-energy alpha particles, can be suppressed by imposing a 20% rise in axisymmetric fields before the quadrupole transition sections. Alpha particles should then be well-confined until thermal energies when they enter the resonant plateau require. A fast code for computation of drift behavior in reactors is described. Sample calculations are presented for resonant particles in a proposed coil set for the Tandem Mirror Next Step

  19. Alpha spectral analysis via artificial neural networks

    International Nuclear Information System (INIS)

    An artificial neural network system that assigns quality factors to alpha particle energy spectra is discussed. The alpha energy spectra are used to detect plutonium contamination in the work environment. The quality factors represent the levels of spectral degradation caused by miscalibration and foreign matter affecting the instruments. A set of spectra was labeled with a quality factor by an expert and used in training the artificial neural network expert system. The investigation shows that the expert knowledge of alpha spectra quality factors can be transferred to an ANN system

  20. Enzymatic synthesis of l-menthyl alpha-maltoside and l-menthyl alpha-maltooligosides from l-menthyl alpha-glucoside by cyclodextrin glucanotransferase.

    Science.gov (United States)

    Do, Hiroyuki; Sato, Toshiyuki; Kirimura, Kohtaro; Kino, Kuniki; Usami, Shoji

    2002-01-01

    l-Menthyl alpha-D-glucopyranosyl-(1-->4)-alpha-d-glucopyranoside (alpha-MenG2), a novel glycoside of l-menthol, was synthesized enzymatically and its physicochemical properties were characterized. Production of alpha-MenG2 from l-menthyl alpha-d-glucopyranoside (alpha-MenG) was attempted since we had already succeeded in the high-yield production of alpha-MenG using a Xanthomonas campestris enzyme (Nakagawa H., et al. J. Biosci. Bioeng., 89, 138-144, 2000). Through production tests on enzymes, it was confirmed that cyclodextrin glucanotransferase (CGTase) from Bacillus macerans produced l-menthyl alpha-D-maltooligosides (alpha-MenG(n)), containing alpha-MenG2, from alpha-MenG and soluble starch. When 10 ml of a 10 mM citrate-10 mM phosphate buffer (pH 6.0) containing 150 mg of alpha-MenG, 3 g of soluble starch and CGTase was shaken at 70 degrees C for 24 h, a total of 81.8% alpha-MenG was reacted. The molar conversion yields of alpha-MenG2 and alpha-MenG(n) with alpha-glucose degrees of polymerization of 3-18, based on the amount of alpha-MenG supplied, reached 16.1% and 65.7%, respectively. For efficient production of alpha-MenG2, the reaction mixture was treated with alpha-amylase of Aspergillus oryzae, and alpha-MenG(n) were mainly converted into alpha-MenG2: finally, the molar conversion yield of alpha-MenG2 reached 74.2% based on the amount of alpha-MenG supplied. alpha-MenG2 was purified and its molecular structure was confirmed by 13C-NMR, 1H-NMR and two-dimensional HMBC (heteronuclear multiple-bond coherence). alpha-MenG2 and its aqueous solution tasted bitter and a little sweet at first, but in a few minutes, a refreshing flavor and sweetness spread. At 20 degrees C the solubility of alpha-MenG2 in pure water was 29.6 g/100 ml, approximately 1570-fold that of alpha-MenG. PMID:16233280

  1. Determination of alpha_s and W boson leptonic branching ratio from the W and Z cross sections

    CERN Document Server

    Xiao, Weichen

    2016-01-01

    We try to determine the strong coupling alpha_s and the W boson leptonic branching ratio from the W and Z boson production cross section through pp collisions in the LHC. We run the MCFM program together with LHAPDF or HERAPDF les to extract the theoretical prediction of cross sections at different alpha_s in different experiments. We compare the predicted values and the experimental results to do a precise measurement of alpha_s and the branching ratio.

  2. Isolated Photons at Hadron Colliders at O($\\alpha alpha_s^2$) (I): Spin Averaged Case

    OpenAIRE

    Gordon, L. E.

    1996-01-01

    The cross sections for isolated and non-isolated prompt photon production with unpolarized hadron beams are studied at order $\\alpha\\alpha_s^2$. Two methods of performing the calculations are compared. One uses purely analytic techniques and the second uses a combination of analytic and Monte Carlo techniques to perform the phase-space integrations. The results of the analytic and Monte Carlo methods are compared both before and after isolation cuts are placed on the photon. Fragmentation con...

  3. 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...

  4. 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).

  5. An alpha-omega-dynamo with an alpha-effect due to magnetostrophic waves

    Science.gov (United States)

    Schmitt, D.

    1987-03-01

    The effects of the latitude dependence of the dynamic alpha-effect on the solution of equations of alpha-omega-dynamos are investigated. The equations of kinematic rotationally symmetric alpha-omega-dynamos are evaluated using the spherical solar dynamo model of Deinzer and Stix (1971), in which the induction effects, differential rotation, and alpha-effect act in two separate infinitesimal thin shells. Butterfly diagrams are derived and analyzed. It is observed that the diagram has two branches: the ordinary sunspot branch, migrating from midlatitudes toward the equator during the cycle, and the polar branch, which migrates from the midlatitudes toward the pole. It is also found that, in order to obtain the correct propagation direction of the two dynamos, the alpha of the magnetostrophic waves requires a rotation decreasing with depth. The influence of various locations of the induction layers of alpha- and omega-effect are examined.

  6. 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.

  7. Perturbative expansion of tau hadronic spectral function moments and alpha_s extractions

    CERN Document Server

    Beneke, Martin; Jamin, Matthias

    2012-01-01

    Various moments of the hadronic spectral functions have been employed in the determination of the strong coupling alpha_s from tau decays. In this work we study the behaviour of their perturbative series under different assumptions for the large-order behaviour of the Adler function, extending previous work on the tau hadronic width. We find that the moments can be divided into a small number of classes, whose characteristics depend only on generic features of the moment weight function and Adler function series. Some moments that are commonly employed in alpha_s analyses from tau decays should be avoided because of their perturbative instability. This conclusion is corroborated by a simplified alpha_s extraction from individual moments. Furthermore, under reasonable assumptions for the higher-order behaviour of the perturbative series, fixed-order perturbation theory (FOPT) provides the preferred framework for the renormalization group improvement of all moments that show good perturbative behaviour. Finally...

  8. On Cronbach’s Alpha as the Mean of All Possible k-Split Alphas

    Directory of Open Access Journals (Sweden)

    Matthijs J. Warrens

    2014-01-01

    Full Text Available Coefficient alpha is the most commonly used internal consistency reliability coefficient. Alpha is the mean of all possible k-split alphas if the items are divided into k parts of equal size. This result gives proper interpretations of alpha: interpretations that also hold if (some of its assumptions are not valid. Here we consider the cases where the items cannot be split into parts of equal size. It is shown that if a k-split is made such that the items are divided as evenly as possible, the difference between alpha and the mean of all possible k-split alphas can be made arbitrarily small by increasing the number of items.

  9. 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.

  10. Alpha decay property of Pb parent

    International Nuclear Information System (INIS)

    In this work, the half-lives of alpha decay have been calculated from 182-210Pb nuclei, both in two sphere approximation and taking care the deformation effects and compared with the available theoretical and experimental data

  11. High resolution alpha particle spectrometry through collimation

    International Nuclear Information System (INIS)

    Alpha particle spectrometry with collimation is a useful method for identifying nuclear materials among various nuclides. A mesh type collimator reduces the low energy tail and broadened energy distribution by cutting off particles with a low incidence angle. The relation between the resolution and the counting efficiency can be investigated by changing a ratio of the mesh hole diameter and the collimator thickness. Through collimation, a target particle can be distinguished by a PIPS® detector under a mixture of various nuclides. - Highlights: • Alpha particle spectrometry with collimation a useful method for identifying nuclear materials among various radionuclides. • A collimator cut off alpha particles with low angle emitted from a source. • We confirm that that a collimator improves the resolution of alpha spectra through both simulation and experiments

  12. Alpha particles spectrometer with photodiode PIN

    International Nuclear Information System (INIS)

    The radiation propagates in form of electromagnetic waves or corpuscular radiation; if the radiation energy causes ionization in environment that crosses it is considered ionizing radiation. To detect radiation several detectors types are used, if the radiation are alpha particles are used detectors proportional type or trace elements. In this work the design results, construction and tests of an alpha particles spectrometer are presented, which was designed starting from a photodiode PIN type. The system design was simulated with a code for electronic circuits. With results of simulation phase was constructed the electronic phase that is coupled to a multichannel analyzer. The resulting electronic is evaluated analyzing the electronic circuit performance before an alphas triple source and alpha radiation that produce two smoke detectors of domestic use. On the tests phase we find that the system allows obtain, in a multichannel, the pulses height spectrum, with which we calibrate the system. (Author)

  13. 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...

  14. Neutron-induced alpha radiography

    International Nuclear Information System (INIS)

    A new radiography technique to inspect thin samples was developed. Low energy alpha particles, generated by a boron based screen under thermal neutron irradiation, are used as penetrating radiation. The solid state nuclear track detector CR-39 has been used to register the image. The interaction of the α - particles with the CR-39 gives rise to damages which under an adequate chemical etching became tracks the basic units forming the image. A digital system was developed for data acquisition and data analysis as well as for image processing. The irradiation and etching conditions to obtain the best radiography are 1,3 hours and 25 minutes at 70 deg C respectively. For such conditions samples having 10 μm in thickness can be inspected with a spatial resolution of 32 μm. The use of the digital system has reduced the time spent for data acquisition and data analysis and has improved the radiography image visualization. Furthermore, by using the digital system, it was possible to study several new parameters regarding the tracks which are very important to understand and study the image formation theory in solid state nuclear track detectors, the one used in this thesis. Some radiography images are also shown which demonstrate the potential of the proposed radiography technique. When compared with the other radiography techniques already in use to inspect thin samples, the present one developed in the present paper allows a smaller time to obtain the image, it is not necessary to handle liquid radioactive substances, the detector is insensitive to β, γ, X-ray and visible light. (author)

  15. Alpha thalassaemia-mental retardation, X linked

    OpenAIRE

    Gibbons Richard

    2006-01-01

    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 pres...

  16. Alpha particle spectroscopy by gridded ionization chamber

    International Nuclear Information System (INIS)

    A gridded ionization chamber has been constructed with the aim of determining its ultimate energy resolution in alpha spectroscopy, utilizing a cooled FET pre-amplifier of the type normally employed with semiconductor detectors. With suitable mechanical collimation of the alpha particles, their fine structure has been measured with an energy resolution of -11.5 keV (fwhm), achieved using an Ar + 0.75% C2H2 mixture as the filling gas. (orig.)

  17. Abundances in Damped Ly-alpha Galaxies

    OpenAIRE

    Molaro, Paolo

    2005-01-01

    Damped Ly_alpha galaxies provide a sample of young galaxies where chemical abundances can be derived throughout the whole universe with an accuracy comparable to that for the local universe. Despite a large spread in redshift, HI column density and metallicity, DLA galaxies show a remarkable uniformity in the elemental ratios rather suggestive of similar chemical evolution if not of an unique population. These galaxies are characterized by a moderate, if any, enhancement of alpha-elements ove...

  18. Alpha emitters in Chernobyl hot particles

    International Nuclear Information System (INIS)

    The alpha radioactive component of hot particles from the Chernobyl fallout was analysed for cases studied previously by gamma spectroscopy. Correlations established from the absolute alpha activity determination and high resolution analysis provided information on actinides release during accident and on some aspects of the Chernobyl reactor fuel composition. Unexpected features revealed during the analysis of one specific particle are presented. 11 refs., 5 figs., 5 tabs. (author)

  19. Processing. alpha. -mercuric iodide by zone refining

    Energy Technology Data Exchange (ETDEWEB)

    Burger, A.; Morgan, S.H.; Henderson, D.O.; Biao, Y.; Zhang, K.; Silberman, E. (Fisk Univ., Nashville, TN (United States). Dept. of Physics); Nason, D.; van den Berg, L.; Ortale-Baccash, C.; Cross, E. (EG and G Energy Measurements, Inc., Goleta, CA (United States). Santa Barbara Operations)

    1992-01-01

    An investigation is being conducted on zone refining {alpha}-mercuric iodide. Analytical studies using differential scanning calorimetry and anion chromatography indicate that impurities are segregated mainly at the end where zone travel terminates. Early results indicate that single crystals can be readily grown from zone refined material, and the effects of the process on the performance of radiation detectors fabricated from {alpha}-mercuric iodide are being evaluated.

  20. Phototransferred thermoluminescence and exoemission in alpha alumina

    Energy Technology Data Exchange (ETDEWEB)

    Iacconi, P.; Lapraz, D.; Alessandri-Fraccaro, M.F.; Addi, D. (Univ. de Nice-Sophia Antipolis (France). Lab. d' Emission Electronique et de Luminescence)

    1990-01-01

    {alpha}-Al{sub 2}O{sub 3}, irradiated by ionising radiation and submitted to UV illumination, presents a phototransfer phenomenon that is characterised by thermoluminescence (TL) and by thermostimulated exoelectronic emission (TSEE). The TL and the TSEE glow curves of {alpha}-alumina from -196 to 700{sup 0}C are compared, to parallel one phototransfer observation with another and to draw various conclusions concerning the stability of the traps involved in dosimetric applications. (author).

  1. ON An Infra-\\(\\alpha\\)-Open Sets

    OpenAIRE

    Hakeem Othman; Md Hanif Page

    2016-01-01

    In this paper, we define a new class of set in general topology called an infra- \\(\\alpha\\) open set and we investigate fundamental properties by using this new class. The relation between infra-\\(\\alpha\\)-open set and other topological sets are studied. Moreover, In the light of this new definition, we also define some generalization of continuous mappings and discuss the relations between these new classes of mappings and other continuous mappings. Basic properties of these new mappings...

  2. Neurophysiological assessment of alpha pattern coma.

    OpenAIRE

    Obeso, J A; Iragui, M I; Marti-Masso, J. F.; Maravi, E; Teijeira, J M; Carrera, N; Teijeria, J

    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...

  3. 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.

  4. Alpha-emitters for medical therapy workshop

    International Nuclear Information System (INIS)

    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

  5. Remote Associates Test and Alpha Brain Waves

    OpenAIRE

    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. Participants received two blocks of RAT items (RAT1 and RAT2), with the second block consisting of items that were not solved during the first block. Pa...

  6. 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....

  7. Alpha emitters in Chernobyl hot particles

    Energy Technology Data Exchange (ETDEWEB)

    Broda, R.; Kubica, B.; Szeglowski, Z.; Zuber, K. (Institute of Nuclear Physics, Krakow (Poland))

    1989-01-01

    The alpha radioactive component of hot particles from the Chernobyl fallout was analyzed for cases studied previously by gamma spectroscopy. Correlations established from the absolute alpha activity determination and high resolution analysis provided information on the release of actinides during the accident and on some aspects of the Chernobyl reactor fuel composition. Unexpected features revealed during the analysis of one specific particle are presented. (orig.).

  8. Effects of $\\alpha$-cluster breaking on 3$\\alpha$ cluster structures in $^{12}$C

    OpenAIRE

    Suhara, Tadahiro; Kanada-En'yo, Yoshiko

    2014-01-01

    To clarify the effects of $\\alpha$-cluster breaking on 3$\\alpha$ cluster structures in $^{12}$C, we investigate $^{12}$C using a hybrid model that combines the Brink-Bloch cluster model with the $p_{3/2}$ subshell closure wave function. We have found that $\\alpha$-cluster breaking caused by spin-orbit force significantly changes cluster structures of excited $0^{+}$ states through orthogonality to lower states. Spatially developed cluster components of the $0^{+}_{2}$ state are reduced. The $...

  9. Probing surface distributions of $\\alpha$ clusters in $^{20}$Ne via $\\alpha$-transfer reaction

    OpenAIRE

    Fukui, Tokuro; Taniguchi, Yasutaka; Suhara, Tadahiro; Kanada-En'yo, Yoshiko; Ogata, Kazuyuki

    2015-01-01

    Direct evidence of the $\\alpha$-cluster manifestation 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 fi...

  10. 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; Diamant, M; Nansen, A; Rieneck, K; Otterness, I G; Bendtzen, K

    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 vaccinat...

  11. Alpha nuclides in nuclear power plants

    International Nuclear Information System (INIS)

    In a joint research project of VGB and AREVA NP GmbH the behavior of alpha nuclides in nuclear power plants has been investigated since 2005. The main source of alpha nuclides is core contamination with fissile material (so called tramp uranium or tramp fuel) which deposits on fuel rod surfaces and leads to the build-up of transuranium nuclides. Such alpha-nuclides are of special interest for health physics due to their high biological effectiveness. Having very high dose factors they lead to high dose weighting in case of incorporation. At NPC 2008 first results of the joint research project were presented concerning tramp fuel and its impact to alpha nuclides. The present publication will cover the ongoing results of this research project. A special focus is taken to deduce recommendations which allow plant operation personal to recognize situations in advance which can lead to enhanced appearance of alpha nuclides. Depending on the fuel conditions in the core and the activity level of fission products of the reactor coolant a better prediction of the alpha situation at the following outage and maintenance can be deduced. (author)

  12. Alpha-emitting radioisotopes production for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Kwon Soo [Korea Institutet of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-02-15

    This review discusses the production of alpha-particle-emitting radionuclides in radioimmunotherapy. Radioimmunotherapy labeled with alpha-particle is expected to be very useful for the treatment of monocellular cancer (e.g. leukemia) and micrometastasis at an early stage, residual tumor remained in tissues after chemotherapy and tumor resection, due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha particle. Despite of the expected effectiveness of alpha-particle in radioimmunotherapy, its clinical research has not been activated by the several reasons, shortage of a suitable a-particle development and a reliable radionuclide production and supply system, appropriate antibody and chelator development. Among them, the establishment of radionuclide development and supply system is a key factor to make an alpha-immunotherapy more popular in clinical trial. Alpha-emitter can be produced by several methods, natural radionuclides, reactor irradiation, cyclotron irradiation, generator system and elution. Due to the sharply increasing demand of {sup 213}Bi, which is a most promising radionuclide in radioimmunotherapy and now has been produced with reactor, the cyclotron production system should be developed urgently to meet the demand.

  13. Alpha-dispersion in human tissue

    Science.gov (United States)

    Grimnes, Sverre; Martinsen, Ørjan G.

    2010-04-01

    Beta dispersion is found in living tissue in the kilohertz - megahertz range and is caused by the cellular structure of biological materials with low frequency properties caused by cell membranes. Alpha dispersion is found in the hertz range and the causes are not so well known. Alpha dispersions are the first to disappear when tissue dies. Tissue data have often been based upon excised specimen from animals and are therefore not necessarily representative for human tissue alpha dispersions. Here we present data obtained with non-invasive skin surface electrodes for different segments of the living human body. We found alpha dispersions in all cases; the ankle-wrist results had the smallest. Large alpha dispersions were found where the distance between the electrodes and muscle masses was small, e.g. on the calf. Further studies on electrode technique and reciprocity, electrode positioning, statistical variations, gender, age and bodily constitutions are necessary in order to reveal more about the alpha dispersion, its appearance and disappearance.

  14. Lorentz alpha orbit calculation in search of position suitable for escaping alpha particle diagnostics in ITER

    International Nuclear Information System (INIS)

    The Lorentz orbit code is developed to understand escaping alpha particle orbits and to contribute to the design of an escaping alpha particle probe in ITER. The code follows the full gyromotion of an alpha particle in ITER equilibrium, considering the toroidal field magnetic field ripple produced by the finite number of toroidal field coils as well as full three-dimensional first wall panels placed at the outboard side of the torus. It is shown that alpha particles that exist in the peripheral region and have banana orbits intersect the first wall placed at the outboard side on the lower plane. (author)

  15. The Lyman alpha reference sample. VII. Spatially resolved H$\\alpha$ kinematics

    CERN Document Server

    Herenz, Edmund Christian; Orlitova, Ivana; Hayes, Matthew; Östlin, Göran; Cannon, John M; Roth, Martin M; Bik, Arjan; Pardy, Stephen; Otí-Floranes, Héctor; Mas-Hesse, J Miguel; Adamo, Angela; Atek, Hakim; Duval, Florent; Guaita, Lucia; Kunth, Daniel; Laursen, Peter; Melinder, Jens; Puschnig, Johannes; Rivera-Thorsen, Thøger E; Schaerer, Daniel; Verhamme, Anne

    2015-01-01

    We present integral field spectroscopic observations with the Potsdam Multi Aperture Spectrophotometer of all 14 galaxies in the $z\\sim 0.1$ Lyman Alpha Reference Sample (LARS). We produce 2D line of sight velocity maps and velocity dispersion maps from the Balmer $\\alpha$ (H$\\alpha$) emission in our data cubes. These maps trace the spectral and spatial properties of the LARS galaxies' intrinsic Ly$\\alpha$ radiation field. We show our kinematic maps spatially registered onto the Hubble Space Telescope H$\\alpha$ and Lyman $\\alpha$ (Ly$\\alpha$) images. Only for individual galaxies a causal connection between spatially resolved H$\\alpha$ kinematics and Ly$\\alpha$ photometry can be conjectured. However, no general trend can be established for the whole sample. Furthermore, we compute non-parametric global kinematical statistics -- intrinsic velocity dispersion $\\sigma_0$, shearing velocity $v_\\mathrm{shear}$, and the $v_\\mathrm{shear}/\\sigma_0$ ratio -- from our kinematic maps. In general LARS galaxies are charac...

  16. On Cronbach’s Alpha as the Mean of All Possible k-Split Alphas

    OpenAIRE

    Matthijs J. Warrens

    2014-01-01

    Coefficient alpha is the most commonly used internal consistency reliability coefficient. Alpha is the mean of all possible k-split alphas if the items are divided into k parts of equal size. This result gives proper interpretations of alpha: interpretations that also hold if (some of) its assumptions are not valid. Here we consider the cases where the items cannot be split into parts of equal size. It is shown that if a k-split is made such that the items are divided as evenly as possible, t...

  17. 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; Diamant, Marcus; Nansen, A; Rieneck, K; Otterness, I G; Bendtzen, K

    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...... 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...... induced 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...

  18. 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.

  19. 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.

  20. 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)....

  1. Alpha Com eclipse observing campaign

    Science.gov (United States)

    Waagen, Elizabeth O.

    2014-12-01

    Drs. Matthew W. Muterspaugh and Gregory W. Henry (Tennessee State University) have requested AAVSO observers' ssistance in monitoring the possible Algol-like binary star alpha Com before, during, and after the eclipse they have predicted for mid-to-late January 2015. The PIs will be using the Fairborn Observatory automated photometric telescopes on Mt. Hopkins, but they are requesting additional observations not only to supplement theirs but also specifically to have good coverage in the event of bad weather at Mt. Hopkins. Alf Com has a 26-year period and is 4.32V at maximum. The expected amplitude of the eclipse is about 0.8 magnitude and the duration somewhere between 28 and 45 hours. The eclipse is predicted for January 25 ± three days (JD 2457047 ± 3). Muterspaugh at al. first calculated the possibility of a 2015 eclipse in 2010 (AJ). Muterspaugh and Henry recently published an article with updated information (arXiv 2014). V and/or R photometry (other bands welcome) is requested, with a minimal cadence of one measurement/2 hours, to make sure the eclipse is caught right as it begins and to ensure having multiple data points on any unseen objects that might eclipse as well. During eclipse, continuous observations are important. Infrared (H-band) observations could be interesting, should the CHARA array image the event. The precision photometry in the weeks before and after the eclipse is requested in order to catch possible evidence for planets or other materials around the eclipsing star. Updated astrometry from the current epoch would greatly improve the eclipse preductions. Charts with comparison star sequence for alf Com may be created using the AAVSO Variable Star Plotter (http://www.aavso.org/vsp). The PIs recommend using the comparison stars HD 113848 (39 Com, HR 4946, HIP 63948, V=5.990, B-V=0.39, F4V) and HD 114520 (HIP 64312, V=6.820, B-V=0.46,F2II). Observations should be submitted to the AAVSO International Database. See AAVSO Alert Notice 506

  2. Mapping the X(+1) binding site of the Grb2-SH2 domain with alpha,alpha-disubstituted cyclic alpha-amino acids.

    Science.gov (United States)

    García-Echeverría, C; Gay, B; Rahuel, J; Furet, P

    1999-10-18

    A series of phosphopeptides containing alpha,alpha-disubstituted cyclic alpha-amino acids (Ac(n)c, 3 activity as antagonists of the Grb2-SH2 domain has been determined in competitive binding assays. The SAR data obtained have been interpreted by using models constructed from the X-ray structure of the ligand-bound Grb2-SH2 domain. The used of alpha,alpha-disubstituted cyclic alpha-amino acids to map the binding pockets of proteins expands the classical alanine scan concept and takes advantage of the known conformational preferences of these amino acids. PMID:10571147

  3. In vitro anti-inflammatory activities of new steroidal antedrugs: [16alpha,17alpha-d] Isoxazoline and [16alpha,17alpha-d]-3'-hydroxy-iminoformyl isoxazoline derivatives of prednisolone and 9alpha-fluoroprednisolone.

    Science.gov (United States)

    Park, Kwan-K; Ko, Dong-H; You, Z; Khan, M Omar F; Lee, Henry J

    2006-03-01

    A series of new anti-inflammatory steroidal antedrugs with C-16,17-isoxazoline ring system were synthesized and their pharmacological activities were evaluated. We reported earlier that these compounds are promising antedrugs based on the results of 5-day rat croton oil ear edema assay. In the present study, most of these compounds showed high binding affinities to the glucocorticoid receptor of liver cytosol. 21-acetyloxy-9alpha-fluoro-11beta-hydroxy-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d] isoxazoline (FP-ISO-21AC) and 11beta,21-dihydroxy-9alpha-fluoro-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d] isoxazoline (FP-ISO-21OH) were found 5.0-, 5.3-fold more potent than prednisolone, respectively. Inhibitory effects of the antedrugs on the nitric oxide (NO) production were assessed using LPS-stimulated RAW 264.7 murine macrophage cells. All these steroidal antedrugs exhibited concentration-dependent inhibition of NO production, but their relative potencies were lower than prednisolone. In vitro metabolism study in rat plasma showed that FP-ISO-21AC and 21-acetyloxy-9alpha-fluoro-11beta-hydroxy-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d]-3'-hydroxyiminoformyl isoxazoline (FP-OXIM-21AC) were hydrolyzed rapidly, with the half-lives of 2.1 and 4.2 min, respectively. The half-lives of FP-ISO-21OH and 11beta,21-dihydroxy-9alpha-fluoro-3,20-dioxo-1,4-pregnadieno [16alpha,17alpha-d]-3'-hydroxyiminoformyl isoxazoline (FP-OXIM-21OH) were 92.2 and 110.2 min, respectively. PMID:16309722

  4. [The permeability of the hemato-encephalic barrier and the proteolytic potential of the cerebrospinal fluid in severe craniocerebral trauma].

    Science.gov (United States)

    Churliaev, Iu A; Nikiforova, N V; Lutsik, A A; Kuksinskiĭ, V A; Lykova, O F; Martynenkov, V Ia; Karpenko, V S

    1999-01-01

    To study blood-brain barrier permeability and proteolytic changes in in patients with severe brain injury and to evaluate their impact on its course and outcome, the concentrations of albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin were examined in 58 victims by enzyme immunoassay. The control group comprised 20 patients examined for lumbar discal hernia. The studies indicate that early severe brain injury showed blood-brain barrier dysfunction whose severity can be detected by the spinal fluid levels of albumin, plasminogen, and alpha 2-macroglobulin. Proteolytic changes in spinal fluid are determined by its albumin, plasminogen (plasmin), alpha 2-macroglobulin, alpha 2-antiplasmin, and alpha 1-antitrypsin concentrations and affect the development of secondary brain lesion and they are of practical value. PMID:10696680

  5. 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.

  6. The Lyman-alpha signature of the first galaxies

    OpenAIRE

    Smith, Aaron; Safranek-Shrader, Chalence; Bromm, Volker; Milosavljević, Miloš

    2014-01-01

    We present the Cosmic Lyman-$\\alpha$ Transfer code (COLT), a massively parallel Monte-Carlo radiative transfer code, to simulate Lyman-$\\alpha$ (Ly$\\alpha$) resonant scattering through neutral hydrogen as a probe of the first galaxies. We explore the interaction of centrally produced Ly$\\alpha$ radiation with the host galactic environment. Ly$\\alpha$ photons emitted from the luminous starburst region escape with characteristic features in the line profile depending on the density distribution...

  7. 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.

  8. Crystallization and melt behaviour of isotactic poly((4-alpha,alpha-dimethyl-benzyl)phenyl methacrylate)

    NARCIS (Netherlands)

    vanEkenstein, GORA; Tan, YY

    1997-01-01

    The crystallization and melting behaviour of practically 100% isotactic poly((4-alpha,alpha-dimethylbenzyl) phenyl methacrylate) has been studied by d.s.c. and light microscopy. Crystallization from the melt seemed to be non-spherulitic. The maximum crystallization rate, which could only be determin

  9. Alpha particle radiography of ants using a 244Cm alpha source

    International Nuclear Information System (INIS)

    Alpha particles emitted from a radioisotope 244Cm were used for the radiography of ants. Cellulose nitrate films, LR-115 from Kodak Pathe, were used as solid state nuclear track detectors to make the radiographs. Alpha particles of energies from 3.5 to 5.5 MeV were obtained by varying the air spacing between the 244Cm and the sample with stainless steel spacers of thickness from 2.4 to 0.5 cm to slow the 5.81 MeV alpha particles from the 244Cm by air. The resulting radiographs of the ants put on the LR-115 films and irradiated by alpha particles of different energies show that only the profiles of the ants were obtained when the ants were exposed to alpha particles of energies lower than 3.5 MeV, and almost all parts of the ant except a portion in the head were penetrated by alpha particles of energies higher than 5.0 MeV to register high density alpha tracks on the LR-115. The details of the internal organs of the ant can be shown clearly by radiography with alpha particles of energies between 4.0 and 5.0 MeV. (author)

  10. 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...

  11. 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, 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; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; 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; 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 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; Fanourakis, G K; Fassouliotis, D; Fayot, J; Feindt, Michael; 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; 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; Kourkoumelis, C; Kuznetsov, O; Krammer, Manfred; Kriznic, E; Krumshtein, Z; Kubinec, P; Kurowska, J; Kurvinen, K L; Lamsa, J; Lane, D W; Langefeld, P; 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; Masik, J; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; 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; Nicolaidou, R; Nielsen, B S; Niezurawski, P; Nikolenko, M; Nomokonov, V P; Normand, Ainsley; Nygren, A; 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; Rodrigo, Germán; 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; 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; Strauss, J; 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; 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 Remortel, N; 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; 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; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, 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})...

  12. Syntheses of alpha-tocopheryl glycosides by glucosidases.

    Science.gov (United States)

    Ponrasu, Thangavel; Charles, Rajachristu Einstein; Sivakumar, Ramaiah; Divakar, Soundar

    2008-08-01

    Enzymatic syntheses of water-soluble alpha-tocopheryl glycosides were carried out in di-isopropyl ether using amyloglucosidase from Rhizopus mold or beta-glucosidase isolated from sweet almond. Optimum conditions for the amyloglucosidase were: alpha-tocopherol 0.5 mmol, D-glucose 0.5 mmol, 400 activity unit (AU) amyloglucosidase, 0.2 mM pH 7 phosphate buffer and 72 h; and for the beta-glucosidase: alpha-tocopherol 0.5 mmol, D: -glucose 0.5 mmol, 110 AU beta-glucosidase, 0.1 mM pH 6 phosphate buffer and 72 h. Out of 11 carbohydrates employed, amyloglucosidase reacted only with D-glucose to give 50% of 6-O-(alpha-D-glucopyranosyl)alpha-tocopherol. However, the beta-glucosidase gave 6-O-(beta-D-glucopyranosyl)alpha-tocopherol, 6-O-(alpha-D-galactopyranosyl)alpha-tocopherol, 6-O-(beta-D-galactopyranosyl)alpha-tocopherol, 6-O-(alpha-D-mannopyranosyl)alpha-tocopherol and 6-O-(beta-D-mannopyranosyl)alpha-tocopherol in yields ranging from 10-25%. Water solubility of 6-O-(alpha-D-glucopyranosyl)alpha-tocopherol was 26 g/l at 25 degrees C. alpha-Tocopheryl glycosides showed antioxidant activities with IC(50) values from 0.5 to 1 mM and angiotensin-converting enzyme (ACE) inhibitory activity with IC(50) values from 1.3 to 2.6 mM. PMID:18368294

  13. 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...... 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...... and improvement in objective parameters for bladder outflow obstruction. Approximately 30 to 50% of patients will respond to treatment with 5 alpha-reductase inhibitors. The definitive role of pharmacological treatment in symptomatic BPH remains to be established, although it seems that patients unfit...

  14. Alpha decay favoured isotopes of some superheavy nuclei: Spontaneous fission versus alpha decay

    CERN Document Server

    Kiren, O V; Bubbly, S G

    2013-01-01

    Spontaneous fission and alpha decay are the main decay modes for superheavy nuclei. The superheavy nuclei which have small alpha decay half-life compared to spontaneous fission half-life will survive fission and can be detected in the laboratory through alpha decay. We have studied the alpha decay half-life and spontaneous half-life of some superheavy elements in the atomic range Z = 100-130. Spontaneous fission half-lives of superheavy nuclei have been calculated using the phenomenological formula and the alpha decay half-lives using Viola-Seaborg-Sobiczewski formula (Sobiczewski et al. 1989), semi empirical relation of Brown (1992) and formula based on generalized liquid drop model proposed by Dasgupta-Schubert and Reyes (2007). The results are reported here.

  15. 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).

  16. Non-adiabatic dynamics in 10Be with the microscopic alpha+alpha+n+n model

    CERN Document Server

    Ito, M

    2006-01-01

    The alpha+6He low-energy reactions and the structural changes of 10Be in the microscopic alpha+alpha+n+n model are studied by the generalized two-center cluster model with the Kohn-Hulthen-Kato variation method. It is found that, in the inelastic scattering to the alpha+6He(2+) channel, characteristic enhancements are expected as the results of the parity-dependent non-adiabatic dynamics. In the positive parity state, the enhancement originates from the no-adiabatic eigenstate generated by the radial excitation of the relative motion between two alpha-cores. On the other hand, the enhancement in the negative parity state is induced by the Landau-Zener level-crossing. These non-adiabatic processes are discussed in connection to the formation of the inversion doublet in the compound system of 10Be.

  17. 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.

  18. 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

  19. Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    List, K; Jensen, O N; Bugge, T H;

    2000-01-01

    alpha(1)-antitrypsin. We suggest that mouse glandular kallikrein mGK-6 is an activator of pro-uPA in the mouse urinary tract in vivo. Since this kallikrein is expressed in a number of tissues and also occurs in plasma, it can also be considered a candidate for a physiological pro-uPA activator in other...

  20. 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...

  1. Emphysema and COPD in a young woman

    OpenAIRE

    Kevin Conroy; Graham Miller; Mark Shipley

    2014-01-01

    A 28-year old woman presented with a progressive cough and breathlessness. She had a family history of early onset COPD. Spirometry demonstrated airflow obstruction with no reversibility. An HRCT showed extensive centrolobular emphysema with an upper lobe predominance. Blood tests including an Alpha1 Antitrypsin level were normal.

  2. 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...

  3. L-alpha-glycerylphosphorylcholine inhibits the transfer function of phosphatidylinositol transfer protein alpha.

    Science.gov (United States)

    Komatsu, Hiroaki; Westerman, Jan; Snoek, Gerry T; Taraschi, Theodore F; Janes, Nathan

    2003-12-30

    Phosphatidylinositol transfer protein alpha (PITP-alpha) is a bifunctional phospholipid transfer protein that is highly selective for phosphatidylinositol (PtdIns) and phosphatidylcholine (PtdCho). Polar lipid metabolites, including L-alpha-glycerylphosphorylcholine (GroPCho), increasingly have been linked to changes in cellular function and to disease. In this study, polar lipid metabolites of PtdIns and PtdCho were tested for their ability to influence PITP-alpha activity. GroPCho inhibited the ability of PITP-alpha to transfer PtdIns or PtdCho between liposomes. The IC(50) of both processes was dependent on membrane composition. D-myo-inositol 1-phosphate and glycerylphosphorylinositol modestly enhanced PITP-alpha-mediated phospholipid transfer. Choline, phosphorylcholine (PCho), CDP-choline, glyceryl-3-phosphate, myo-inositol and D-myo-inositol 1,4,5-trisphosphate had little effect. Membrane surface charge was a strong determinant of the GroPCho inhibition with the inhibition being greatest for highly anionic membranes. GroPCho was shown to enhance the binding of PITP-alpha to anionic vesicles. In membranes of low surface charge, phosphatidylethanolamine (PtdEtn) was a determinant enabling the GroPCho inhibition. Anionic charge and PtdEtn content appeared to increase the strength of PITP-alpha-membrane interactions. The GroPCho-enhanced PITP-alpha-membrane binding was sufficient to cause inhibition, but not sufficient to account for the extent of inhibition observed. Processes associated with strengthened PITP-alpha-membrane binding in the presence of GroPCho appeared to impair the phospholipid insertion/extraction process. PMID:14729069

  4. The Story of Alpha - In Three Parts

    Science.gov (United States)

    Hautecoeur, Jean-Paul

    2001-09-01

    The article presents a retrospective history of the ALPHA series of publications. This action-research project (later called "cooperative research") on literacy and basic education is divided into three periods of seven years each. The first one, "Construction", involved assisting the nascent literacy movement in Québec and Canada by given it a theoretical, critical and ideological basis. In the second period, "Ruptures", the project distanced itself somewhat from the literacy movement, whose success, according to the author, was dubious. During the same period ALPHA systematised its critical function and internationalised its field of research. The third phase, "Wanderings", involved a different research paradigm, in which the project explored basic education at community level in connection with local development initiatives. This biographical/autobiographical account ends with the last publication ALPHA 2000, evincing an ecological vision for alternative education and sustainable communities, partly documented in the Arab countries.

  5. 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.

  6. 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...

  7. 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. PMID:26782808

  8. Calculation of nuclear radius using alpha decay

    International Nuclear Information System (INIS)

    Using a Quantum Theory approach for the Alpha-Decay process, a formula is deduced for determination of the nuclear radius of the s-state, that is, a nuclear model with a spherical shell. The hypothesis that it is possible to individualize the alpha particle and the daughter nucleus at the moment of the alpha particle emission is considered. In considered in these conditions, the treatment of a two body problem considered as point particles, repelling each other by Coulomb's Law. Using the new values of the fundamental physical constants, experimentally determinated, by substitution of their numerical values in the proposed, new values of nuclear radii are obtained. These values are compared with those found in the literature. (author)

  9. 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.

  10. 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.

  11. Anomalous atomic volume of alpha-Pu

    DEFF Research Database (Denmark)

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

    1997-01-01

    We have performed full charge-density calculations for the equilibrium atomic volumes of the alpha-phase light actinide metals using the local density approximation (LDA) and the generalized gradient approximation (GGA). The average deviation between the experimental and the GGA atomic radii is 1.......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. This effect is correctly described in the GGA but not in the LDA....

  12. Alpha activity measurements in Anarak copper mine

    International Nuclear Information System (INIS)

    Alpha radiations in the ground arises from the decay of naturally occurring uranium and thorium, which are widely distributed in soils and rocks. According to Environmental Protection Agency (EPA) reports, the highest of alpha activity is found in locations near copper mines. In this study, the amounts of natural activity of alpha emitters for 31 samples of surface soil of Talmesi Anarak mine, located in center of Iran, are measured by Nuclear Track method. Having virtually zero background and exposure time, are advantages of this method. After sampling, all of the 31 samples were transferred to laboratory to place CR-39 detectors vertically in them. In next step, CR-39 detectors were etched in NaOH 6 M, aqueous solution at 70 °C for 4 h. Then, number of tracks per area unit was counted by an optical microscope. The amounts of alpha activity were calculated in all samples and range of minimum 1.40E + 04 to maximum 3.03E + 05 Bq/kg .And also the activity of Th-232 and U-238 are measured by alpha-track method. Moreover “equivalent uranium” (eU) and “equivalent thorium” (eTh) by Hp-Ge detector, were calculated. - Highlights: ► We studied measuring the alpha activity in soils samples near copper mine by CR-39. ► According to experiments and mechanism of track formation, 2 formulas have introduced. ► We studied the accuracy of 2 formulas and present the optimal formula. ► Our results show these formulas are the same. ► Also we could calculate the concentration of U-238 and Th-232 by results of CR-39

  13. 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...

  14. Alpha-beta discrimination in LENA

    International Nuclear Information System (INIS)

    Alpha emitting isotopes, mainly 210Po, provide a background for the detection of 7Be neutrinos in LENA (Low Energy Neutrino Astronomy). This background can be reduced by a pulse shape analysis, as alpha particles and electrons have a different typical pulse shape, caused by the different energy deposition per unit path length ((dE)/(dx)). Thus, the efficiency of this method was analyzed by a detailed Monte Carlo study. Several scintillators as well as the influence of the photomultiplier performance on the discrimination efficiency were investigated.

  15. Alpha-nuclides in nuclear power plants

    International Nuclear Information System (INIS)

    The behaviour of alpha-nuclides in nuclear power plants is subject of the investigations presented. The source of alpha-nuclides is a contamination with fissile material (so called tramp uranium or tramp fuel) which deposits on fuel rod surfaces and leads to the build-up of transuranium nuclides. The determination of a defect situation with fuel release as well as the quantification of the fissile material contamination background is given for BWR and PWR plants. The quantification of the fuel release and the tramp uranium background can be calculated with different, measurable nuclides in BWR and PWR plants. (orig.)

  16. 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.

  17. Re-visiting the Piper Alpha accident

    OpenAIRE

    Dykesteen, Mette Kahrs

    2013-01-01

    The main objective of this thesis has been to re-visit the Piper Alpha accident using the latest version of the FLACS simulation code. In 1988/89 simulations of the gas explosion in the C Module of Piper Alpha were performed by Jan Roar Bakke and Idar Storvik at Christian Michelsen Institute, in conjunction with the investigation after the accident. For these simulations the computer code FLACS was used [1, 2]. In this thesis, the same simulation cases have been looked into, and the results o...

  18. Radiological hazards of alpha-contaminated waste

    International Nuclear Information System (INIS)

    The radiological hazards of alpha-contaminated wastes are discussed in this overview in terms of two components of hazard: radiobiological hazard, and radioecological hazard. Radiobiological hazard refers to human uptake of alpha-emitters by inhalation and ingestion, and the resultant dose to critical organs of the body. Radioecological hazard refers to the processes of release from buried wastes, transport in the environment, and translocation to man through the food chain. Besides detailing the sources and magnitude of hazards, this brief review identifies the uncertainties in their estimation, and implications for the regulatory process

  19. Personal alpha contamination simulator and detector

    International Nuclear Information System (INIS)

    A simulated radiation source and a compatible detector system are disclosed. The combination is useful in training for detecting alpha radiation contamination. A flexible, soft iron plate or first permanent magnet in the detector system responds to a second magnet that is employed to represent an alpha radiation source. Where the first permanent magnet is used, an iron member may be adopted in lieu of the second magnet. The simulated source is affixed to the subject's clothing or body. When the detector system is brought into proximity with the simulated radiation source, the soft plate or first magnet responds and affects a strain gage which in turn provides an electronic indication

  20. Task motivation influences alpha suppression following errors.

    Science.gov (United States)

    Compton, Rebecca J; Bissey, Bryn; Worby-Selim, Sharoda

    2014-07-01

    The goal of the present research is to examine the influence of motivation on a novel error-related neural marker, error-related alpha suppression (ERAS). Participants completed an attentionally demanding flanker task under conditions that emphasized either speed or accuracy or under conditions that manipulated the monetary value of errors. Conditions in which errors had greater motivational value produced greater ERAS, that is, greater alpha suppression following errors compared to correct trials. A second study found that a manipulation of task difficulty did not affect ERAS. Together, the results confirm that ERAS is both a robust phenomenon and one that is sensitive to motivational factors. PMID:24673621

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

    CERN Document Server

    France, Kevin; 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 crossing the reverse shock front, in the velocity intervals ($-$7,500~$<$~$V_{obs}$~$<$~$-$2,800 km s$^{-1}$) and (1,000~$<$~$V_{obs}$~$<$~7,500 km s$^{-1}$), $\\dot{M_{H}}$ = 1.2~$\\times$~10$^{-3}$ M$_{\\odot}$ yr$^{-1}$. 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...

  2. A practical alpha particle irradiator for studying internal alpha particle exposure.

    Science.gov (United States)

    Lee, Ki-Man; Lee, Ui-Seob; Kim, Eun-Hee

    2016-09-01

    An alpha particle irradiator has been built in the Radiation Bioengineering Laboratory at Seoul National University (SNU) to investigate the cellular responses to alpha emissions from radon and the progeny. This irradiator is designed to have the energy of alpha particles entering target cells similar to that of alpha emissions from the radon progeny Po-218 and Po-214 residing in the human respiratory tract. For the SNU alpha particle irradiator, an irradiation system is equipped with cell dishes of 4µm thick Mylar bottom and a special setup of cells on slide for gamma-H2AX assay. Dose calibration for the alpha particle irradiator was performed by dual approaches, detection and computer simulation, in consideration of the source-to-target distance (STD) and the size of a cell dish. The uniformity of dose among cells in a dish is achieved by keeping the STD and the size of cell dish in certain ranges. The performance of the SNU alpha particle irradiator has been proven to be reliable through the gamma-H2AX assay with the human lung epithelial cells irradiated. PMID:27475622

  3. Instrument for measuring total alpha particle energies of alpha emitters in ambient air

    Energy Technology Data Exchange (ETDEWEB)

    Kronenberg, S.; Brucker, G.J.; Cummings, B.; Bechtel, E.; Gentner, F.; Horne, S

    2000-11-11

    This paper describes the design, fabrication, testing and evaluation of a self-reading, carbon fiber, electrometer-type instrument. It is used for measuring the total energy of alpha particles emitted in air by progenies of {sup 222}Rn ({sup 218}Po, {sup 214}Pb, and {sup 214}Bi), and sometimes by other types of alpha emitters (e.g. {sup 212}Pb, {sup 238}U, and {sup 239}Pu). The purpose of these measurements is to assess the energy delivered by alpha emission from these sources to the lung tissue. A sample (charged progenies attached to aerosols) is collected on filter paper from a known volume of air and placed on the instrument. The discharge rate indicates the alpha energy in MeV l{sup -1} of air per min that is produced by the alpha emitters. The calibration procedure shows that the instrument has an energy sensitivity for alpha particles of 800.5 MeV/scale unit. The range of the readout scale is 30 units. Measurements of alpha contamination in air were made using this instrument in buildings, private homes and in a standard chamber. The value of the radon concentration in this chamber is traceable back to the US Environmental Protection Agency (EPA) and to the National Institute of Standards and Technology (NIST)

  4. Phenomenological Alpha-Alpha Interactions and its Application on 16O Nucleus

    International Nuclear Information System (INIS)

    The thesis includes the study of alpha-alpha interactions and apply them to the nucleus of the 16 O by using Hartree-Fock method for bosons. The used potentials are Ali-Bodmer potential, Modified Woods- Saxon potential, Fish-Bone I (FB-I) and Fish-Bone II (FB-II) potential. Also, the properties of nuclear structure of 16 O nucleus are calculated such as binding energy, form factor and root mean square radius. The results we have obtained were compared with previous results in the same field of research topic. This work requires knowledge of different kinds of potentials and the difference between the phenomenological and microscopic interactions and research in Hartree-Fock method and nuclear models, especially shell model. The content of the present thesis can be summarized as the following: The first Chapter, (Introduction), presents detailed informations about the nuclear structure, clustering, alpha clustering and nuclear models especially the shell model. Also, a review of previous researches in the research topic ( phenomenological alpha- alpha interactions). The second chapter, (Alpha-Alpha interactions), many types of phenomenological alpha-alpha interactions and its various forms are displayed, including what has been used in the thesis.The third chapter, (Derivation of Hartree-Fock Method for Bosons), illustrates the theoretical calculations which have been used in the thesis, the derivation of the Hartree-Fock method for bosons, the variational method and the derivation of binding energy, form factor and root mean square radius equations. the fourth chapter, (Numerical Results and Discussion), includes the present theoretical results of the nuclear structure of 16 O nucleus using the previous four potentials, and comparing our present results with the experimental and previous theoretical ones.

  5. A survey of the alpha-nucleon interaction

    International Nuclear Information System (INIS)

    A survey of the alpha-nucleon interaction is made. The experimental work on angular distributions of differential scattering cross-sections and polarizations in proton-alpha and neutron-alpha scattering is described. The phenomenological approach which includes the study of both local and non-local potentials reproducing the experimental alpha-nucleon scattering data, is discussed. Basic studies of the alpha-nucleon interaction attempting to build an interaction between an alpha particle and a nucleon from first principles are then described. A critical discussion of the results with some concluding remarks suggesting the direction for further investigation is made. (author)

  6. Anti-integral extensions $ {R[{\\alpha}]/R$

    OpenAIRE

    Kiyoshi Baba; Ken-Ichi Yoshida

    2004-01-01

    Let $ R $ be an integral domain and $ \\alpha $ an anti-integral element of degree $ d $ over $ R $. In the paper [3] we give a condition for $ \\alpha^2-a$ to be a unit of $ R[\\alpha] $. In this paper we will generalize the result to an arbitrary positive integer $n$ and give a condition, in terms of the ideal $ I_{[\\alpha]}^{n}D(\\sqrt[n]{a}) $ of $ R $, for $ \\alpha^{n}-a$ to be a unit of $ R[\\alpha] $.

  7. 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.

  8. Alpha particle diagnostics using impurity pellet injection

    International Nuclear Information System (INIS)

    We have proposed using impurity injection to measure the energy distribution of the fast confined alpha particles in a reacting plasma. The ablation cloud surrounding the injected pellet is thick enough that an equilibrium fraction Fo∞(E) of the incident alphas should be neutralized as they pass through the cloud. By observing neutrals created in the large spatial region of the cloud which is expected to be dominated by the helium-like ionization state, e.g., Li+ ions, we can determine the incident alpha distribution dnHe2+/dE from the measured energy distribution of neutral helium atoms. Initial experiments were performed on TEXT in which we compared pellet penetration with our impurity pellet ablation model, and measured the spatial distribution of various ionization states in carbon pellet clouds. Experiments have recently begun on TFTR with the goal of measuring the alpha particle energy distribution during D-T operation in 1993--94. A series of preliminary experiments are planned to test the diagnostic concept. The first experiments will observe neutrals from beam-injected deuterium ions and the high energy 3He tail produced during ICH minority heating on TFTR interacting with the cloud. We will also monitor by line radiation the charge state distributions in lithium, boron, and carbon clouds

  9. 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

  10. The Alpha Constant from Relativistic Groups

    CERN Document Server

    González-Martin, G R

    2000-01-01

    The value of the alpha constant, known to be equal to an algebraic expression in terms of pi and entire numbers related to certain group volumes, is derived from the relativistic structure group of a geometric unified theory, its subgroups and corresponding symmetric space quotients.

  11. 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.

  12. Production of alpha-amylase by yeast

    Energy Technology Data Exchange (ETDEWEB)

    Thomse, K.K.

    1987-01-01

    The enzyme alpha-amylase confers to an organism the enzymatic activity for the degradation of polyglucosides with alpha-1,4 glycosidic bonds such as starch and glycogen which are among the major storage compounds in plants and animals. Most alpha-amylases are single polypeptides of molecular weights around 50,000 dalton. They are generally found in the digestive tract of animals and in germinating seeds. Among the products released upon enzymatic degradation of polyglucosides maltose, a sugar that can be utilized as carbon source by yeast, is a major constituent. A cDNA segment complementary to mouse salivary amylase messenger RNA has been inserted into the yeast expression vector pMA56 behind the promoter of the gene encoding alcohol dehydrogenase I of yeast. Yeast transformants harboring plasmids with the normal orientation of the promoter and the mouse amylase cDNA gene produce amylase and release the enzyme in free form into the culture medium. Approximately 90% of the amylase activity is found in the medium. Yeast strains carrying MAL allele and transformed with a plasmid which directed the synthesis of mouse alpha-amylase were tested on plates containing starch and in batch fermentations using different high molecular weight sugars and oligosaccharides as carbon source. The results of these experiments will be discussed. (Refs. 21).

  13. Varying-Alpha Cosmologies with Potentials

    CERN Document Server

    Barrow, John D

    2008-01-01

    We generalize the Bekenstein-Sandvik-Barrow-Magueijo (BSBM) model for the variation of the fine structure 'constant', $\\alpha ,$ to include an exponential or inverse power-law self-potential for the scalar field $% \\phi $ which drives the time variation of $\\alpha $, and consider the dynamics of $\\phi$ in such models. We find solutions for the evolution of $\\phi $ or $\\alpha $ in matter-, radiation- and dark-energy-dominated cosmic eras. In general, the evolution of $\\phi $ is well determined solely by either the self-potential or the coupling to matter, depending on the model parameters. The results are general and applicable to other models where the evolution of a scalar field is governed by a matter coupling and a self-potential. We find that the existing astronomical data stringently constrains the possible evolution of $\\alpha $ between redshifts $z\\simeq 1-3.5$ and the present, and this leads to very strong limit on the allowed deviation of the potential from that of a pure cosmological constant.

  14. Superparamagnetic relaxation in alpha-Fe particles

    DEFF Research Database (Denmark)

    Bødker, Franz; Mørup, Steen; Pedersen, Michael Stanley; Svedlindh, P.; Jonsson, G.T.; Garcia-Palacios, J.L.; Lazaro, F.J.

    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...

  15. Electronic key system using alpha detection

    International Nuclear Information System (INIS)

    We have developed the new electronic key system utilizes random pulse from alpha-particle detection with PIN photo diode. The random pulse by natural decay of alpha source is stable under the every outside environment like as temperature, pressure, an electromagnetic wave, and so on. The stable and un-predicted signals of the random pulses are the most suitable as a source of authentication signal for the electric key system. The program made of manufacture side forms the key code under current electronic key. Therefore, the manufacture must keep the code data secret for long time. The new electronic key always identify between key body and each key by the original pulse data from alpha particles. It is reduce the control cost of security remarkably. Moreover, back ground noise can be ignored in the circuit and it doesn't need to enlarge a total number of activity. The activity of the alpha source is about 10-100 Bq in one module. (author)

  16. Statistical process control for alpha spectroscopy

    International Nuclear Information System (INIS)

    Statistical process control(SPC) allows for the identification of problems in alpha spectroscopy processes before they occur, unlike standard laboratory Q C which only identifies problems after a process fails. SPC tools that are directly applicable to alpha spectroscopy include individual X-charts and X-bar charts, process capability plots, and scatter plots. Most scientists are familiar with the concepts the and methods employed by SPC. These tools allow analysis of process bias, precision, accuracy and reproducibility as well as process capability. Parameters affecting instrument performance are monitored and analyzed using SPC methods. These instrument parameters can also be compared to sampling, preparation, measurement, and analysis Q C parameters permitting the evaluation of cause effect relationships. Three examples of SPC, as applied to alpha spectroscopy , are presented. The first example investigates background contamination using averaging to show trends quickly. A second example demonstrates how SPC can identify sample processing problems, analyzing both how and why this problem occurred. A third example illustrates how SPC can predict when an alpha spectroscopy process is going to fail. This allows for an orderly and timely shutdown of the process to perform preventative maintenance, avoiding the need to repeat costly sample analyses. 7 figs., 2 tabs

  17. 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.

  18. Measurement of alpha emitters in radioactive waste

    International Nuclear Information System (INIS)

    The alpha emitters measurement in radioactive waste (10-2Ci/T) is essential for a good fissil materials management. This paper describes 3 classes of devices: device using a neutronic passive counting, device using a neutronic activation and detection of fission gamma, device using a neutronic activation and detection of prompt neutrons fission

  19. Interactive alpha spectroscopy on personal computers

    International Nuclear Information System (INIS)

    An interactive alpha spectroscopy program is described for the Microsoft Windows environment on personal computers. The program supports multiple sample types for tailoring analysis procedures and the simultaneous graphical representation of data being analysed and live data being collected. Both simple ROI area calculations and sophisticated multiplet analysis capabilities are supported by the package. (orig.)

  20. E-PERM alpha surface monitor

    Energy Technology Data Exchange (ETDEWEB)

    Fricke, V.

    1999-12-16

    Innovative Technology Summary Reports are designed to provide potential users with the information they need to quickly determine if a technology would apply to a particular environmental management problem. They are also designed for readers who may recommend that a technology be considered by prospective users. Each report describes a technology, system, or process that has been developed and tested with funding from DOE's Office of Science and Technology (OST). The E-PERM{reg{underscore}sign} Alpha Surface Monitor is an integrating electret ion chamber innovative technology used to measure alpha radiation on surfaces of materials. The technology is best used on surfaces with low contamination levels such as areas with potential for free release, but can also be used in areas with higher levels of contamination. Measurement accuracy and production of the E-PERM {reg{underscore}sign} Alpha Surface Monitor compared favorably with the baseline technology. The innovative technology cost is approximately 28% higher than the baseline with an average unit cost per reading costing %6.04 vs. $4.36; however, the flexibility of the E-PERM{reg{underscore}sign} Alpha Surface Monitor may offer advantages in ALARA, reduction of operator error, waste minimization, and measurement accuracy.

  1. Alpha particle effects on MHD ballooning

    International Nuclear Information System (INIS)

    During the period, as the first step towards the goal of detail understanding of the effects of alpha particle on MHD Ballooning Modes, a new numerical approach to investigate the stability of low-frequency fluctuations in high temperature tokamaks was developed by solving the gyrokinetic equations for the ion and electron directly as an initial value problem. The advantage of this approach is the inclusion of many important kinetic features of the problem without approximations and computationally more economical than particle-pushing simulation. The ion-temperature-gradient-mode was investigated to benchmark this new simulation technique. Previous results in literature were recovered. Both the adiabatic electron model and the full drift-kinetic electron model are studied. Numerical result shows that the full drift-kinetic electron model is more unstable. The development of subcycling technique to handle the fast electron bounce time is particularly significant to apply this new approach to the alpha particle problem since alpha particle bounce frequency is also significantly higher than the mode frequency. This new numerical technique will be the basis of future study of the microstability in high temperature tokamaks with alpha particles (or any energetic species). 15 refs., 13 figs

  2. ALPHA THERMOLUMINESCENCE DOSIMETRY IN DATING OF POTTERY

    Institute of Scientific and Technical Information of China (English)

    王维达; 夏君定

    1994-01-01

    This article describes the measurement of internal alpha dose-rate in pottery using ultrathin CaSO4:Tm theromoluminescence dosimeter,Among the advantages of the technique are not only convenience,accuracy,lowcost,but also the beta dose-rate from pottery can be obtained at the same time.

  3. 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…

  4. 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...

  5. Method of making nanocrystalline alpha alumina

    Science.gov (United States)

    Siegel, Richard W.; Hahn, Horst; Eastman, Jeffrey A.

    1992-01-01

    Method of making selected phases of nanocrystalline ceramic materials. Various methods of controlling the production of nanocrystalline alpha alumina and titanium oxygen phases are described. Control of the gas atmosphere and use of particular oxidation treatments give rise to the ability to control the particular phases provided in the aluminum/oxygen and titanium/oxygen system.

  6. Alpha thermoluminescence dosimetry in dating of pottery

    International Nuclear Information System (INIS)

    The article describes the measurement of internal alpha dose-rate in pottery using ultrathin CaSO4: Tm thermoluminescence dosimeter. The advantages of the technique are not only convenience, accuracy, low cost, but also the beta dose-rate from pottery can be obtained at the same time

  7. Alpha decay chain of 292116 nucleus

    International Nuclear Information System (INIS)

    Study of superheavy nuclides is of current interest for theoretical physicists as well experimentalists. The present work describes the alpha decay chain of 292116 terminating at 224Pb with corresponding half-lives. Some of these nuclides are reportedly superdeformed but yet stable

  8. The alloantigenic sites of alpha3alpha4alpha5(IV) collagen: pathogenic X-linked alport alloantibodies target two accessible conformational epitopes in the alpha5NC1 domain.

    Science.gov (United States)

    Kang, Jeong Suk; Kashtan, Clifford E; Turner, A Neil; Heidet, Laurence; Hudson, Billy G; Borza, Dorin-Bogdan

    2007-04-01

    Anti-glomerular basement membrane (GBM) antibody nephritis is caused by an autoimmune or alloimmune reaction to the NC1 domains of alpha3alpha4alpha5(IV) collagen. Some patients with X-linked Alport syndrome (XLAS) develop post-transplant nephritis mediated by pathogenic anti-GBM alloantibodies to collagen IV chains present in the renal allograft but absent from the tissues of the patient. In this work, the epitopes targeted by alloantibodies from these patients were identified and characterized. All XLAS alloantibodies recognized conformational epitopes in the NC1 domain of alpha5(IV) collagen, which were mapped using chimeric alpha1/alpha5 NC1 domains expressed in mammalian cells. Allograft-eluted alloantibodies mainly targeted two conformational alloepitopes mapping to alpha5NC1 residues 1-45 and 114-168. These regions also encompassed the major epitopes of circulating XLAS alloantibodies, which in some patients additionally targeted alpha5NC1 residues 169-229. Both kidney-eluted and circulating alloantibodies to alpha5NC1 distinctively targeted epitopes accessible in the alpha3alpha4alpha5NC1 hexamers of human GBM, unlike anti-GBM autoantibodies, which targeted sequestered alpha3NC1 epitopes. The results identify two immunodominant alpha5NC1 epitopes as major alloantigenic sites of alpha3alpha4alpha5(IV) collagen specifically implicated in the pathogenesis of post-transplant nephritis in XLAS patients. The contrast between the accessibility of these alloepitopes and the crypticity of autoepitopes indicates that distinct molecular forms of antigen may initiate the immunopathogenic processes in the two forms of anti-GBM disease. PMID:17293596

  9. 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

  10. 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.

  11. Development of thermal conditioning technology for Alpha-containment wastes: Alpha-contaminated waste incineration technology

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Joon Hyung; Kim, Jeong Guk; Yang, Hee Chul; Choi, Byung Seon; Jeong, Myeong Soo

    1999-03-01

    As the first step of a 3-year project named 'development of alpha-contaminated waste incineration technology', the basic information and data were reviewed, while focusing on establishment of R and D direction to develop the final goal, self-supporting treatment of {alpha}- wastes that would be generated from domestic nuclear industries. The status on {alpha} waste incineration technology of advanced states was reviewed. A conceptual design for {alpha} waste incineration process was suggested. Besides, removal characteristics of volatile metals and radionuclides in a low-temperature dry off-gas system were investigated. Radiation dose assessments and some modification for the Demonstration-scale Incineration Plant (DSIP) at Korea Atomic Energy Research Institute (KAERI) were also done.

  12. Measurement of total alpha activity in water; Messung der Gesamt-Alpha-Aktivitaet in Wasser

    Energy Technology Data Exchange (ETDEWEB)

    Eikenberg, Jost [Paul Scherrer Institut (PSI), Villigen (Switzerland). Abt. fuer Strahlenschutz und Sicherheit; Florschuetz, Bernd [Hessisches Landesamt fuer Umwelt und Geologie, Kassel (Germany). Dezernat 15 - Strahlenschutz; Salvamoser, Josef [Institut fuer Angewandte Isotopen-, Gas- und Umweltuntersuchungen, Woerthsee (Germany); Steinkopff, Thomas [Deutscher Wetterdienst, Offenbach am Main (Germany); Wilhelm, Christoph [Karlsruher Institut fuer Technologie (KIT), Eggenstein-Leopoldshafen (Germany). Sicherheitsmanagement - Analytische Labore; Wisser, Sascha [FCI, Mainz (Germany)

    2014-04-01

    The article describes the measurement of the total alpha activity in an (evaporated) liquid sample, and the various sample preparation methods for measurements with proportional counters or LSC. (orig.)

  13. 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.

  14. 3D Lyman-alpha radiation transfer. I. Understanding Lyman-alpha line profile morphologies

    OpenAIRE

    Verhamme, Anne; Schaerer, Daniel; Maselli, Antonella

    2006-01-01

    Using a Monte Carlo technique, we have developed a 3D lyman-alpha radiation transfer code allowing for prescribed arbitrary hydrogen density, ionisation, temperature structures, and dust distribution, and arbitrary velocity fields and UV photon sources. We have examined the lyman-alpha line profiles predicted for several simple geometrical configurations and their dependence on the main input parameters. Overall, we find line profiles reaching from doubly peaked symmetric emission to symmetri...

  15. Determination of \\alpha_s from Event Shapes and Power Corrections

    OpenAIRE

    Wicke, Daniel

    1997-01-01

    The size of non-perturbative corrections to event shape observables is predicted to fall like a power of the inverse centre of mass energy. These power corrections are investigated for different observables from e+e-annihilation and compared to the theoretical predictions. Using the latest DELPHI high energy data advantages of determining \\alpha_s from these predictions are discussed and compared to conventional methods.

  16. Order (alpha^2 Gamma, alpha^3 Gamma) Binding Effects in Orthopositronium Decay

    OpenAIRE

    Hill, Richard J.; Lepage, G. Peter

    2000-01-01

    We present a new, simplified analysis of the low-energy electron-positron interaction, and use the resulting effective theory to calculate the binding effects that contribute to the decay rate, Gamma, of orthopositronium, through Order(alpha^3 ln(alpha) Gamma). We express the total decay rate in terms of the annihilation rate for a free electron and positron at threshold, which has just recently been computed to sufficient precision. Our result corrects errors in a previous analysis.

  17. Perturbative expansion of tau hadronic spectral function moments and alpha_s extractions

    OpenAIRE

    Beneke, Martin; Boito, Diogo; Jamin, Matthias

    2012-01-01

    Various moments of the hadronic spectral functions have been employed in the determination of the strong coupling alpha_s from tau decays. In this work we study the behaviour of their perturbative series under different assumptions for the large-order behaviour of the Adler function, extending previous work on the tau hadronic width. We find that the moments can be divided into a small number of classes, whose characteristics depend only on generic features of the moment weight function and A...

  18. DEPENDENT-ALPHA CALCULATOR: TESTING THE DIFFERENCES BETWEEN DEPENDENT COEFFICIENTS ALPHA

    OpenAIRE

    Sabry M. ABD-EL-FATTAH; Hala K. HASSAN

    2011-01-01

    Coefficient alpha (α) was first introduced by Lee J. Cronbach in 1951 and since then it continues to serve as a valuable index of reliability within different areas of research. According to the Social Sciences Citation Index, between 1951 and 2010, Cronbach’s seminar article (Cronbach, 1951) was cited 6,912 times by other published articles and numerous other publications often cite secondary sources in support of the use of coefficient alpha.

  19. 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...

  20. 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...

  1. 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] $<...

  2. Expression of alpha-amylase in Bacillus licheniformis.

    OpenAIRE

    Rothstein, D. M.; Devlin, P E; Cate, R. L.

    1986-01-01

    In Bacillus licheniformis, alpha-amylase production varied more than 100-fold depending on the presence or absence of a catabolite-repressing carbon source in the growth medium. alpha-Amylase was produced during the growth phase and not at the onset of the stationary phase. Induction of alpha-amylase correlated with synthesis of mRNA initiating at the promoter of the alpha-amylase gene.

  3. A Meta-analysis of Cronbach's Coefficient Alpha.

    OpenAIRE

    Robert A. Peterson

    1994-01-01

    Despite some limitations, Cronbach's coefficient alpha remains the most widely used measure of scale reliability. The purpose of this article was to empirically document the magnitudes of alpha coefficients obtained in behavioral research, compare these obtained values with guidelines and recommendations set forth by individuals such as Nunnally (1967, 1978), and provide insights into research design characteristics that may influence the size of coefficient alpha. Average reported alpha coef...

  4. 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.

  5. 211 Po alpha decay level scheme

    International Nuclear Information System (INIS)

    The fine structure of alpha decay was discovered by Rosenblum in 1929 by measuring the range of the emitted particle in the air. Usually, attempts to investigate this phenomenon were effected theoretically by calculating the overlaps between the wave function of the parent and the antisymmetric product between the wave functions of the nascent fragments for different configurations after the scission. However, quantitatively this phenomenon was not explained rigorously. In earlier papers, a theory based on the Landau--Zener effect was developed in order to describe quantitatively the cluster decay fine structure phenomenon. It was claimed that the same effect can also direct the fine structure in the case of alpha decay. It was also evidenced that the fine structure can be explained as the promotion of the unpaired nucleon on upper levels belonging to the daughter during the decay process in the field created by the emitted nascent fragment. In this context, the first step in the construction of such a theory for alpha decay is to develop a two-centre diagram of the levels during the whole decay process beginning with the levels of the parent nucleus, following the energetic variations of these levels up to the final configuration given by the separated daughter and alpha particle. Of course, in our representation it is only intended to treat the alpha cluster with a smooth potential in order to estimate the influence of the emitted particle on the daughter levels during the decay and it is not assumed that the oscillator well is appropriate for the description of an alpha nucleus. The Landau-Zener promotion mechanism takes place between levels belonging to the nascent heavy nucleus, so that only the influence of the potential attributed to the alpha particle is taken into consideration. The level scheme is plotted for a nuclear shape parametrisation given by two intersected spheres of different radii as described. The parent and the daughter do not have pronounced

  6. Gravitational lensing by damped Ly-alpha absorbers

    NARCIS (Netherlands)

    Smette, A; Claeskens, JF; Surdej, J

    1997-01-01

    Assuming that (i) damped Ly-alpha absorbers (DLAs) arise in present-day-like spiral galaxies which are immersed in isothermal dark matter halos, (ii) that these galaxies obey the Tully-Fisher sigma/sigma* = (L/L*)(1/alpha TF) and the Holmberg R-L/R* = (L/L*)(alpha H) relations, and (iii) that they f

  7. alpha-Thalassemia mutation analyses in Mazandaran province, North Iran.

    Science.gov (United States)

    Tamaddoni, Ahmad; Hadavi, Valeh; Nejad, Nima Hafezi; Khosh-Ain, Atefeh; Siami, Rita; Aghai-Meibodi, Jalil; Almadani, Navid; Oberkanins, Christian; Law, Hai-Yang; Najmabadi, Hossein

    2009-01-01

    Two hundred and fifty-five patients from Mazandaran Province, Iran, all presenting with hypochromic and microcytic anemia, were selected for alpha-thalassemia (alpha-thal) mutation screening. We detected a total of 274 alpha-globin mutations in 227 (89%) of these patients. Among the 21 different alpha-globin alleles found, the -alpha(3.7) (44.9%), polyadenylation signal 2 (poly A2) (AATAAA>AATGAA) (18.2%), -alpha(4.2) (9.1%), alpha(IVS-I(-5 nt)) (6.5%), - -(MED) (4.3%), and alpha(codon 19 (-G)) (4%) were the most frequent. The other 15 mutations included variants that had not yet been observed in Iran, such as Hb Bleuland [alpha108(G15)ThrAsn, ACC>AAC (alpha2)], as well as a novel mutation on the alpha2 gene, also not described to date [3 ' untranslated region (3 'UTR) nucleotide (nt) 46 (C>A)]. These comprehensive new data are useful for establishing a screening strategy for the effective control of alpha-thal in Mazandaran Province. PMID:19373587

  8. Strong absorption model analysis of alpha scattering

    International Nuclear Information System (INIS)

    Angular distribution of alpha-particles at several energies, Eα = 21 ∼ 85.6 MeV from a number of nuclei between 20Ni and 119Sn, extending to wide angular range up to ∼ 160 deg. C in some cases, have been analyzed in terms of three-parameter strong absorption model of Frahn and Venter. Interaction radius and surface diffuseness are obtained from the parameter values rendering the best fit to the elastic scattering data. The inelastic scattering of alpha-particles from a number of nuclei, leading to quadrupole and octupole excitations has also been studied giving the deformation parameters βL. (author). 14 refs, 7 figs, 3 tabs

  9. Alpha-contaminated waste management workshop

    International Nuclear Information System (INIS)

    These proceedings are published to provide a record of the oral presentations made at the DOE Alpha-Contaminated Workshop held in Gaithersburg, Maryland, on August 10-13, 1982. The papers are transcriptions of these oral presentations and, as such, do not contain as significant detail as will be found in the reviewed papers to be published in the periodical Nuclear and Chemical Waste Management in the first issue for 1983. These transcriptions have been reviewed by the speakers and some illustrations have been provided, but these contain only the preliminary information that will be provided in the technical papers to be published in the periodical. These papers have been grouped under the following headings: source terms; disposal technology and practices for alpha-contaminated waste; risk analyses and safety assessments. These papers in addition to those dealing with legislative and regulatory aspects have been abstracted and indexed for the Energy Data Base

  10. Intercomparison of alpha particle spectrometry software packages

    International Nuclear Information System (INIS)

    Software has reached an important level as the 'logical controller' at different levels, from a single instrument to an entire computer-controlled experiment. This is also the case for software packages in nuclear instruments and experiments. In particular, because of the range of applications of alpha-particle spectrometry, software packages in this field are often used. It is the aim of this intercomparison to test and describe the abilities of four such software packages. The main objectives of the intercomparison were the ability of the programs to determine the peak areas and the peak area uncertainties, and the statistical control and stability of reported results. In this report, the task, methods and results of the intercomparison are presented in order to asist the potential users of such software and to stimulate the development of even better alpha-particle spectrum analysis software

  11. Discovery of a shell around Alpha Lyrae

    Science.gov (United States)

    Aumann, H. H.; Beichman, C. A.; Gillett, F. C.; De Jong, T.; Houck, J. R.; Low, F. J.; Neugebauer, G.; Walker, R. G.; Wesselius, P. R.

    1984-01-01

    IRAS observations of Alpha Lyrae reveal a large infrared excess beyond 12 microns. The excess over an extrapolation of a 10,000 K blackbody is a factor of 1.3 at 25 microns, 7 at 60 microns, and 16 at 100 microns. The source of 60 microns emission has a diameter of about 20 arcsec. This is the first detection of a large infrared excess from a main-sequence star without significant mass loss. The most likely origin of the excess is thermal radiation from solid particles more than a millimeter in radius, located approximately 85 AU from Alpha Lyr and heated by the star to an equilibrium temperature of 85 K. These results provide the first direct evidence outside of the solar system for the growth of large particles from the residual of the prenatal cloud of gas and dust.

  12. 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.

  13. 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.

  14. The Alpha Magnetic Spectrometer Silicon Tracker

    International Nuclear Information System (INIS)

    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 m2 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)

  15. The Ups and Downs of Alpha Centauri

    Science.gov (United States)

    Ayres, Thomas

    2014-11-01

    Nearby Alpha Centauri is destined for a pivotal chapter in human history, as first stop of future starfarers from Earth: 3x closer than the next nearest star; three very different objects to visit -- Alpha Cen A (G2V), B (K1V), and C (M6V); and B hosts an Earth-mass companion, albeit in a hot, lifeless orbit. For its part, Chandra has been keeping intent watch on the high-energy starspot cycles of AB, with semi-annual pointings over the past decade. Only HRC-I can separate AB as they plunge toward a close approach of 4" in 2016; and LETGS has countered that an abrupt 50x drop in XMM count rate of sun-like A in early 2005, ominously reported as the "darkening of the solar twin," simply is a soft sensitivity issue, not an unprecedented, inexplicable case of corona interrupta.

  16. Alpha Resonant States in 13C

    International Nuclear Information System (INIS)

    The 9Be(6Li,d)13C reaction was used to investigate alpha resonant states in 13C up to 15 MeV of excitation. The reaction was measured at a bombarding energy of 25.5 MeV employing the Sao Paulo Pelletron-Enge-Spectrograph facility and the nuclear emulsion detection technique. An energy resolution of 50 keV was obtained. Several narrow alpha resonant states not previously measured were detected, in particular the one at the (3α+n) threshold populated by an L = 2 transfer, revealing a 9Be+α component for the 1/2- cluster state candidate at this threshold. Experimental angular distributions are presented in comparison with DWBA predictions.

  17. 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)

  18. 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.

  19. Source preparations for alpha and beta measurements

    International Nuclear Information System (INIS)

    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)

  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 Fission of Thorium with Alpha Particles

    Energy Technology Data Exchange (ETDEWEB)

    Newton, Amos S.

    1948-04-15

    The fission distribution of fission of thorium with alpha particle of average energy 37.5 Mev has been measured by the chemical method. The distribution found shows that the characteristic dip in the fission yield mass spectrum has been raised to within a factor of two of the peaks compared to a factor of 600 in slow neutron fission of U{sup 235}. The raise in the deip has caused a corresponding lowering in fission yield of these elements at the peaks. The cross section for fission of thorium with 37.5 Mev alphas was found to be about 0.6 barn, and the threshold for fission was found to be 23 to 24 Mev.

  2. Registration probability of alphas in cellulose nitrate

    International Nuclear Information System (INIS)

    Registration 'thresholds' of alpha particles in cellulose nitrate plastic present a statistical behaviour. The effect depends on etching conditions. It is particularly large in strong etching conditions, in which registration is transposed to high energies: up to 7.7 MeV for the conditions and energies studied. 'Registration probability' expresses more adequately the effect of registration constraints. The study of registration probability indicates that the 'target theory' can describe the effect. The parameters of target theory, m (number of targets) and D0 (the equivalent of biological dose D37) were found to be: m = 5 and D0 = 3 x 107 erg cm-3. Dose distribution around the trajectory of alphas of various energies is estimated. It is also deduced that track development takes place when the required dose for registration is deposited at a distance r >= 20 A from particle trajectory. (author)

  3. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

    Science.gov (United States)

    Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

    2015-01-01

    The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. PMID:26154585

  4. 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. PMID:17640976

  5. 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.

  6. The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin

    DEFF Research Database (Denmark)

    Goldfinger, L E; Hopkinson, S B; deHart, G W;

    1999-01-01

    function-inhibiting antibodies, we provide evidence that LN5 and its two integrin receptors (alpha6beta4 and alpha3beta1) appear necessary for wound healing to occur in MCF-10A cell culture wounds. We propose a model for healing of wounded epithelial tissues based on these results....... epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 subunit as a consequence of proteolytic processing. Antibody 12C4 stains throughout the matrix of...... cover the wound site. A similar phenomenon is observed in human skin wounds, since we also detect expression of the unprocessed alpha3 laminin subunit at the leading tip of the sheet of epidermal cells that epithelializes skin wounds in vivo. In addition, using alpha3 laminin subunit and integrin...

  7. A new seismic analysis of Alpha Centauri

    CERN Document Server

    Thoul, A; Noels, A; Vatovez, B; Briquet, M; Dupret, M A; Montalban, J

    2003-01-01

    Models of alpha Cen A & B have been computed using the masses determined by Pourbaix et al. (2002) and the data derived from the spectroscopic analysis of Neuforge and Magain (1997). The seismological data obtained by Bouchy and Carrier (2001, 2002) do help improve our knowledge of the evolutionary status of the system. All the constraints are satisfied with a model which gives an age of about 6 Gyr for the binary.

  8. Alpha Emitting Radionuclides and Radiopharmaceuticals for Therapy

    International Nuclear Information System (INIS)

    Today, cancer treatments mainly rely on surgery or external beam radiation to remove or destroy bulky tumors. Chemotherapy is given when tumours cannot be removed or when dissemination is suspected. However, these approaches cannot permanently treat all cancers and relapse occurs in up to 50% of the patients’ population. Radioimmunotherapy (RIT) and peptide receptor radionuclide therapy (PRRT) are effective against some disseminated and metastatic diseases, although they are rarely curative. Most preclinical and clinical developments in this field have involved electron-emitting radionuclides, particularly iodine-131, yttrium-90 and lutetium-177. The large range of the electrons emitted by these radionuclides reduces their efficacy against very small tumour cell clusters or isolated tumour cells present in residual disease and in many haematological tumours (leukaemia, myeloma). The range of alpha particles in biological tissues is very short, less than 0.1 mm, which makes alpha emitters theoretically ideal for treatment of such isolated tumour cells or micro-clusters of malignant cells. Thus, over the last decade, a growing interest for the use of alpha-emitting radionuclides has emerged. Research on targeted alpha therapy (TAT) began years ago in Nantes through cooperation between Subatech, a nuclear physics laboratory, CRCNA, a cancer research centre with a nuclear oncology team and ITU (Karlsruhe, Germany). CD138 was demonstrated as a potential target antigen for Multiple Myeloma, which is a target of huge clinical interest particularly suited for TAT because of the disseminated nature of the disease consisting primarily of isolated cells and small clusters of tumour cells mainly localized in the bone marrow. Thus anti-CD138 antibodies were labelled with bismuth-213 from actinium-225/bismuth-213 generators provided by ITU and used to target multiple myeloma cells. In vitro studies showed cell cycle arrest, synergism with chemotherapy and very little induction

  9. Effect of Pilates Training on Alpha Rhythm

    OpenAIRE

    Zhijie Bian; Hongmin Sun; Chengbiao Lu; Li Yao; Shengyong Chen; Xiaoli Li

    2013-01-01

    In this study, the effect of Pilates training on the brain function was investigated through five case studies. Alpha rhythm changes during the Pilates training over the different regions and the whole brain were mainly analyzed, including power spectral density and global synchronization index (GSI). It was found that the neural network of the brain was more active, and the synchronization strength reduced in the frontal and temporal regions due to the Pilates training. These results support...

  10. Weather Radar Signals with Alpha Stable Distributions

    OpenAIRE

    Lagha, Mohand; Bensebti, Messaoud

    2007-01-01

    This work, treats about a modeling of the weather precipitation echoes detected by a weather pulse Doppler radar. The methods used for the simulation of the Doppler spectrum, and I & Q signals representing the precipitations radar echoes, is based on a macroscopic models, i.e. random processes with assigned spectra. We propose global model, with a power spectrum having a range of statistical distributions ranging between Cauchy and Gauss called alpha-stable model. The results obtained shows t...

  11. Alpha particles energy straggling in noble gases

    International Nuclear Information System (INIS)

    The comparison of the calculated spectra by the Monte-Carlo simulation with the experimental alpha-particles spectra after their passage through noble gases target has good agreement for Ar, Kr, and Xe and significant deviation for He and Ne. These agreement or disagreement of the calculated and experimental spectra were ascribed to adequacy or inadequacy of the applied Bohr's charged particles energy loss formula for the specific medium. (author)

  12. Targeting folate receptor alpha for cancer treatment

    OpenAIRE

    Cheung, Anthony; Bax, Heather J.; Josephs, Debra H; Ilieva, Kristina M.; Pellizzari, Giulia; Fittall, Matthew; Grigoriadis, Anita; Figini, Mariangela; Canevari, Silvana; Spicer, James F; Tutt, Andrew N; Karagiannis, Sophia N.

    2016-01-01

    Promising targeted treatments and immunotherapy strategies in oncology and advancements in our understanding of molecular pathways that underpin cancer development have reignited interest in the tumor-associated antigen Folate Receptor alpha (FRα). FRα is a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Its overexpression in tumors such as ovarian, breast and lung cancers, low and restricted distribution in normal tissues, alongside emerging insights into tumor-promoting functi...

  13. Dark Energy from $\\alpha$-Attractors

    CERN Document Server

    Linder, Eric V

    2015-01-01

    A class of inflation theories called $\\alpha$-attractors has been investigated recently with interesting properties interpolating between quadratic potentials, the Starobinsky model, and an attractor limit. Here we examine their use for late time cosmic acceleration. We generalize the class and demonstrate how it can interpolate between thawing and freezing dark energy, and reduce the fine tuning of initial conditions, allowing $w\\approx-1$ for a prolonged period or as a de Sitter attractor.

  14. Determination of alpha radionuclides in fish

    International Nuclear Information System (INIS)

    In atmospheric water, external water and undercurrent the occurrence of radionuclides is usual. It is an important factor of quality of the environment. Plants ingest radionuclides from water and with they everyone. And it arises radioactivity infest food-chain. Radiotoxicity of this radionuclides is very deer sometimes. The sensitive radiochemical procedures for their determination are necessarily important. The poster presents the combined procedure used at our laboratory for determination of alpha radionuclides in biological samples. (authors)

  15. Effects of internally deposited alpha emitters

    International Nuclear Information System (INIS)

    This study seeks to identify and quantify the human health effects of occupational exposures to radium, use the health effects data from the radium study to predict responses to other alpha-emitting and/or bone-seeking radionuclides at occupational exposure levels and above, and predict the effects of these radionuclides, specifically environmental radium and its daughters, at nonoccupational exposure levels. 14 refs

  16. The Alpha-1A Adrenergic Receptor in the Rabbit Heart

    OpenAIRE

    R Croft Thomas; Cowley, Patrick M.; Abhishek Singh; Bat-Erdene Myagmar; Swigart, Philip M.; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mR...

  17. The expression of nicotinic receptor alpha7 during cochlear development

    OpenAIRE

    Rogers, Scott W.; Myers, Elizabeth J.; Gahring, Lorise C.

    2012-01-01

    Nicotinic acetylcholine receptor alpha7 expression was examined in the developing and adult auditory system using mice that were modified through homologous recombination to coexpress either GFP (alpha7GFP) or Cre (alpha7Cre), respectively. The expression of alpha7GFP is first detected at embryonic (E) day E13.5 in cells of the spiral prominence. By E14.5, sensory regions including the putative outer hair cells and Deiters' cells express alpha7GFP as do solitary efferent fibers. This pattern ...

  18. Elucidating the spectrum of alpha-thalassemia mutations in Iran.

    Science.gov (United States)

    Hadavi, Valeh; Taromchi, Amir Hossein; Malekpour, Mahdi; Gholami, Behjat; Law, Hai-Yang; Almadani, Navid; Afroozan, Fariba; Sahebjam, Farhad; Pajouh, Parisa; Kariminejad, Roxana; Kariminejad, Mohammad Hassan; Azarkeivan, Azita; Jafroodi, Maryam; Tamaddoni, Ahmad; Puehringer, Helene; Oberkanins, Christian; Najmabadi, Hossein

    2007-07-01

    Alpha thalassemia (alpha-thal) is one of the most common hemoglobin (Hb) disorders in the world. Alpha-globin genes are located on chromosome 16. The majority of alpha-thal mutations are deletions but point mutations are found as well. Since the Iranian population is a mixture of different ethnic groups, frequency and distribution of alpha-globin mutations in various regions of the country need to be clarified. These findings can contribute to a wider understanding of this disorder. PMID:17606454

  19. Synthesis and reactivity of {alpha}-phenylseleno-{beta}-substituted styrenes: preparation of (Z)-allyl alcohols, (E)-{alpha}-phenyl-{alpha},{beta}-unsaturated aldehydes and {alpha}-aryl acetophenones

    Energy Technology Data Exchange (ETDEWEB)

    Lenardao, Eder J.; Jacob, Raquel G.; Silva, Thiago B. da [Universidade Federal de Pelotas, RS (Brazil). Dept. de Quimica Analitica e Inorganica]. E-mail: lenardao@ufpel.edu.br; Cella, Rodrigo [Santa Maria Univ., RS (Brazil). Dept. de Quimica; Perin, Gelson [Universidade Federal de Pelotas, RS (Brazil). Dept. de Quimica Organica

    2006-09-15

    A new and efficient method was developed to prepare {alpha}-phenylseleno-{beta}-substituted styrenes by reaction of diethyl {alpha}-phenylseleno benzylphosphonate with NaH and aldehydes. Selenium-lithium exchange by reaction with n-BuLi yielded the vinyl lithium species, which were captured with several electrophiles, like aldehydes and DMF, affording exclusively (Z)-allyl alcohols, and (E)-{alpha}-phenyl-{alpha}-{beta}-unsaturated aldehydes, respectively in good yields. The hydrolysis of the vinyl selenides in presence of TiCl{sub 4} allowed the corresponding {alpha}-aryl acetophenones. (author)

  20. 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......-galactophilic lectins to alpha-galactosylated neoglycoproteins. The lectins were: Euonymus europaeus agglutinin (EEA), Griffonia simplicifolia 1 isolectin B4 (GS1 B4), Maclura pomifera agglutinin (MPA) and Pseudomonas aeruginosa agglutinin (PA-IL). Although both GS1 B4 and MPA strongly bound glycoconjugates terminating...... in Gal there seems to be some differentiation in their sugar binding preferences. MPA was the only lectin that showed high affinity for the pentasaccharide Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc and for the Galalpha-glycans on non-primate thyroglobulin. The length of the xenoantigenic...