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Sample records for alpha-1 foundation dna

  1. 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...

  2. 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.

  3. Purification, cDNA cloning, and expression of GDP-L-Fuc:Asn-linked GlcNAc alpha1,3-fucosyltransferase from mung beans.

    Science.gov (United States)

    Leiter, H; Mucha, J; Staudacher, E; Grimm, R; Glössl, J; Altmann, F

    1999-07-30

    Substitution of the asparagine-linked GlcNAc by alpha1,3-linked fucose is a widespread feature of plant as well as of insect glycoproteins, which renders the N-glycan immunogenic. We have purified from mung bean seedlings the GDP-L-Fuc:Asn-linked GlcNAc alpha1,3-fucosyltransferase (core alpha1,3-fucosyltransferase) that is responsible for the synthesis of this linkage. The major isoform had an apparent mass of 54 kDa and isoelectric points ranging from 6. 8 to 8.2. From that protein, four tryptic peptides were isolated and sequenced. Based on an approach involving reverse transcriptase-polymerase chain reaction with degenerate primers and rapid amplification of cDNA ends, core alpha1,3-fucosyltransferase cDNA was cloned from mung bean mRNA. The 2200-base pair cDNA contained an open reading frame of 1530 base pairs that encoded a 510-amino acid protein with a predicted molecular mass of 56.8 kDa. Analysis of cDNA derived from genomic DNA revealed the presence of three introns within the open reading frame. Remarkably, from the four exons, only exon II exhibited significant homology to animal and bacterial alpha1,3/4-fucosyltransferases which, though, are responsible for the biosynthesis of Lewis determinants. The recombinant fucosyltransferase was expressed in Sf21 insect cells using a baculovirus vector. The enzyme acted on glycopeptides having the glycan structures GlcNAcbeta1-2Manalpha1-3(GlcNAcbeta1-2Manalpha1- 6)Manbeta1-4GlcNAcbet a1-4GlcNAcbeta1-Asn, GlcNAcbeta1-2Manalpha1-3(GlcNAcbeta1-2Manalpha1- 6)Manbeta1-4GlcNAcbet a1-4(Fucalpha1-6)GlcNAcbeta1-Asn, and GlcNAcbeta1-2Manalpha1-3[Manalpha1-3(Manalpha1-6 )Manalpha1-6]Manbeta1 -4GlcNAcbeta1-4GlcNAcbeta1-Asn but not on, e.g. N-acetyllactosamine. The structure of the core alpha1,3-fucosylated product was verified by high performance liquid chromatography of the pyridylaminated glycan and by its insensitivity to N-glycosidase F as revealed by matrix-assisted laser desorption/ionization time of flight mass

  4. 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...

  5. 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...

  6. Foundations

    Science.gov (United States)

    Harteveld, Casper

    A building will more likely collapse if it does not have any proper foundations. Similarly, the design philosophy of Triadic Game Design (TGD) needs to reside on solid building blocks, otherwise the concept will collapse as well. In this level I will elaborate on these building blocks. First I will explain what the general idea of TGD is. It is a design philosophy, for sure, but one which stresses that an “optimum” needs to be found in a design space constituted by three different worlds: Reality, Meaning, and Play. Additionally, these worlds need to be considered simultaneously and be treated equally. The latter requires balancing the worlds which may result in different tensions, within and between two or three of the worlds. I continue by discussing each of the worlds and showing their perspective on the field of games with a meaningful purpose. From this, we clearly see that it is feasible to think of each world and that the idea makes sense. I substantiate this further by relating the notion of player and similar approaches to this framework. This level is quite a tough pill to swallow yet essential for finishing the other levels. Do not cheat or simply skip this level, but just take a big cup of coffee or tea and start reading it.

  7. The antagonistic effect of antipsychotic drugs on a HEK293 cell line stably expressing human alpha(1A1)-adrenoceptors

    DEFF Research Database (Denmark)

    Nourian, Zahra; Mulvany, Michael J; Nielsen, Karsten Bork;

    2008-01-01

    analysis showed higher transcription levels of alpha(1A1)- than of alpha(1A3)- and alpha(1A4)-adrenoceptors (1.6 and 5.8 times, respectively). We therefore chose to study the alpha(1A1)-adrenoceptor, and the cDNA encoding it was transfected into the Flp-In-293 (modified from HEK-293) cell line to produce...

  8. Biological chemistry as a foundation of DNA genealogy: the emergence of "molecular history".

    Science.gov (United States)

    Klyosov, A A

    2011-05-01

    foundation for "molecular history", in which the principal tool is high-technology analysis of DNA molecules of both our contemporaries and excavated ancient DNA samples, along with their biological kinetics.

  9. [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

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

    Science.gov (United States)

    Bishop, Michael J

    2007-01-01

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

  11. 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...

  12. Activation of two new alpha(1,3)fucosyltransferase activities in Chinese hamster ovary cells by 5-azacytidine.

    Science.gov (United States)

    Potvin, B; Stanley, P

    1991-01-01

    Several mammalian alpha(1,3)fucosyltransferases (alpha[1,3]Fuc-T) that synthesize carbohydrates containing alpha(1,3)fucosylated lactosamine units have been identified. Although Chinese hamster ovary (CHO) cells do not express alpha(1,3)Fuc-T activity, the rare mutants LEC11 and LEC12, isolated after mutagenesis or DNA transfection, each express an alpha(1,3)Fuc-T that may be distinguished by several criteria. Two new CHO mutants possessing alpha(1,3)Fuc-T activity (LEC29 and LEC30) have now been isolated after treatment of a CHO cell population with 5-azacytidine (5-AzaC), ethylnitrosourea (ENU), or 5-AzaC followed by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Like LEC12, both mutants possess an N-ethylmaleimide-resistant alpha(1,3)Fuc-T activity that can utilize a variety of acceptors and both express the Lewis X (Lex) determinant (Gal beta[1,4](Fuc alpha[1,3])GlcNAc beta 1)) but not the sialyl alpha(2,3)Lex determinant on cell-surface carbohydrates. However, LEC29 and LEC30 may be distinguished from LEC11 and LEC12, as well as from each other, on the basis of their unique patterns of lectin resistance and their abilities to bind the VIM-2 monoclonal antibody that recognizes carbohydrates terminating in NeuNAc alpha(2,3)Gal beta(1,4)GlcNAc beta(1,3)Gal beta(1,4)(Fuc alpha[1,3])GlcNAc beta and also by the different in vitro substrate specificities and kinetic properties of their respective alpha(1,3)Fuc-T activities. The combined data provide good evidence that the LEC29 and LEC30 alpha(1,3)Fuc-Ts are novel transferases encoded by distinct gene products. PMID:1724918

  13. 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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    R Croft Thomas

    Full Text Available 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 mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse.

  16. 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 ...

  17. 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...

  18. Urinary alpha1-antichymotrypsin: a biomarker of prion infection.

    Directory of Open Access Journals (Sweden)

    Gino Miele

    Full Text Available The occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. However, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. Sensitive biomarkers may help meeting this need. Here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. We found that alpha(1-antichymotrypsin (alpha(1-ACT was highly upregulated in brains of scrapie-infected mice. Furthermore, alpha(1-ACT levels were dramatically increased in urine of patients suffering from sporadic Creutzfeldt-Jakob disease, and increased progressively throughout the disease. Increased alpha(1-ACT excretion was also found in cases of natural prion disease of animals. Therefore measurement of urinary alpha(1-ACT levels may be useful for monitoring the efficacy of therapeutic regimens for prion disease, and possibly also for deferring blood and organ donors that may be at risk of transmitting prion infections.

  19. 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

  20. 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.

  1. 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.

  2. 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....

  3. 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 ...

  4. Effect of alpha1-blockers on stentless ureteroscopic lithotripsy

    Directory of Open Access Journals (Sweden)

    Jianguo Zhu

    2016-02-01

    Full Text Available ABSTRACT Objective To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. Materials and Methods From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents and group B (40 patients were treated by alpha1-adrenergic antagonists without stents. All cases of group B were treated with alpha1 blocker for 1 week. Results The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. Conclusions The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.

  5. 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...

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

    Science.gov (United States)

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

  7. alpha 1-Adrenoceptors modulate citalopram-induced serotonin release

    NARCIS (Netherlands)

    Rea, Kieran; Folgering, Joost; Westerink, Ben H. C.; Cremers, Thomas I. F. H.

    2010-01-01

    Previous studies suggest that noradrenaline may regulate serotonergic (5-HT) neurotransmission at the serotonin cell body and noradrenaline nerve terminal. Using microdialysis coupled to HPLC, we investigated the effects of alpha 1-adrenoceptor manipulation on extracellular serotonin levels in the v

  8. Effects of alpha 1-adrenoceptor antagonists on male sexual function

    NARCIS (Netherlands)

    M.M. van Dijk; J.J.M.C.H. de la Rosette; M.C. Michel

    2006-01-01

    alpha(1)-Adrenoceptor antagonists such as alfuzosin, doxazosin, tamsulosin and terazosin are first-line agents for the treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH), but are only second-line agents (doxazosin and terazosin only) for the treatment of arter

  9. Theoretical foundation and experimental proof of the accumulating transfer of tritium from water into DNA and other biomolecules in vitro and in vivo

    International Nuclear Information System (INIS)

    Theoretical foundation and experimental proof of the accumulating transfer of tritium from water into DNA and other biomolecules were presented using the data of experiments on fish sperm DNA and piglet's liver (in vitro tests) and maize and barley (in vivo tests). Heisenberg's uncertainty principle, which describes a fundamental property of matter, predicts the light hydrogen isotope to prefer strong hydrogen bridge positions (with large local uncertainty). In contrast, the heavy hydrogen isotope tritium originally localized in water, should finally be found in the exchangeable hydrogen bridge positions of proteins, carbohydrates and nucleotides which are definitely less strong than those of water. Fractionation factor of tritium and protonium measured between water and DNA as well as the mixture of biomolecules of liver confirm this conclusion and show tritium accumulation biomolecules. Furthermore, the elevated rate of natural increase in tritium concentration in tissue solids of growing maize and barley confirm the accumulating tritium transfer from water to biomolecules taking place in vivo

  10. Alpha-1 Antitrypsin Deficiency: Beyond the Protease/Antiprotease Paradigm.

    Science.gov (United States)

    Cosio, Manuel G; Bazzan, Erica; Rigobello, Chiara; Tinè, Mariaenrica; Turato, Graziella; Baraldo, Simonetta; Saetta, Marina

    2016-08-01

    From the discovery that alpha-1 antitrypsin (AAT) was an effective inhibitor of neutrophil elastase originated the classic paradigm of protease/antiprotease imbalance, linking lung destruction to the unopposed effect of proteases in patients with the deficiency. Notwithstanding its importance as an antiprotease, it has become evident that alpha-1 antitrypsin has important antiinflammatory and immune-regulatory activities, which may be critically involved in lung destruction. We review here recent evidence showing that, indeed, an important adaptive immune reaction is present in lungs with AAT deficiency, similar to the one seen in severe chronic obstructive pulmonary disease with normal AAT. On the basis of recent evidence from epidemiological, clinical, and pathogenetic studies, it is likely time to move on from the original protease/antiprotease hypothesis for the production of emphysema toward a more complex paradigm, involving the antiinflammatory and immune modulating functions of AAT. PMID:27564665

  11. Cloning, mRNA expression and bioinformatic analysis of full length type I collagen alpha 1 cDNA from grass carp (Ctenopharyngodon idellus)%草鱼Ⅰ型胶原蛋白α1基因cDNA全序列克隆、组织分布及其生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    刘邦辉; 郁二蒙; 王广军; 余德光; 谢骏; 王海英; 龚望宝

    2012-01-01

    Type I collagen, as a number of collagen family, is the most abundant collagen and major components of the extracellular matrices of all metazoan life, and plays crucial roles in differentiation, formation of collagen fibers and tissue remodeling after injury, etc. Type I collagen alpha 1(COL1A1) cDNA of grass carp (Ctenopharyngodon idella) was isolated through the RT-PCR and RACE approaches. The cDNA was 5 772-bp in length, including a 4 347-bp CDS (coding sequence) and encoded a polypeptide of 1 449 aa. The homology of COL1Al amino acid with relative species (zebrafish, goldfish, etc.) was as high as 93% with zebra fish and goldfish. The protein peptide molecular weight was 137.2 ku and theoretical pI was 5.44 using ProtParam software on line. The protein peptides of COL1A1 possessed 6 a-helixes, 12 β-sheets, others of ruleless coil regions, and 18 regions of triple helical repeats, 22 low complexity regions, 17 function domains. There were two calcium-binding sites and one zinc-binding site in the COL1A1 protein peptide. COL1A1 mRNA was determined in all the tested 8 tissues (muscle, intestine, hepatopancreas, gill, skin, fin, kidney and spleen) of grass carp by semi- quantitative RT-PCR, and the mRNAs expression in gill, kidney, skin and fin significantly higher than other tissues (P<0.05). The structure and bioinformat-ics characteristics of the COL1A1 from grass carp may help to further understand the function of COL1A1 gene in the repair process of damaged tissue in the grass carp.%利用PCR和RACE方法首次克隆了编码草鱼肌肉Ⅰ型胶原蛋白的α1基因(COL1A1)的cDNA全长序列,为5772 bp,其开放阅读框为4 347 bp,编码1448个氨基酸.BLAST同源性分析结果显示,草鱼COL1Al基因的氨基酸序列与斑马鱼、金鱼同源性较高,分别为93.90%和93.60%,呈现出较高的保守性.系统进化树分析表明,该基因与斑马鱼、金鱼处于同一支,亲缘性最近.生物信息学分析显示,草鱼COL1Al蛋白

  12. 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.)

  13. Alpha 1-antitrypsin and alpha 1-acid glycoprotein reduce the sensitivity of human dermal fibroblast to endotoxin

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To test the hypothesis that acute phase reactants, such as alpha 1-antitrypsin and alpha 1-acid glycoprotein, could protect mammalian cells from further damage.Methods: Human dermal fibroblasts (5 × 104) were cultured with DMEM plus 10% FBS at 37℃ in a 5% CO2incubator. Different doses of LPS (lipopolysaccharide) and/or acute phase reactants were added. After 24 hours, the cultured supernatant was aspirated, the cells were washed, fixed and stained by methylene blue. The unbound stain was washed off. The stained cells were solubilized in 0.1 mi of 1% Triton X-100. The absorbance of each well was measured using an ELISA spectrophotometer. The concentration of LPS which decreased the absorbance to 70% of the control LPS-free ) cultures was defined as LD30.Results: In order to achieve LD30 in the presence of acute phase proteins, it was necessary to alter the LPS concentrations. The LD30 of LPS treated with 0, 0.5, 2, 10mg/ml antitrypsin and 0, 0.5, 2, 10 mg/ml glycoprotein was 5.4, 6.5, 7.6, 14.2 mg/ml and 5.2, 5.9, 6.9, 10.5mg/ml, respectively. Statistically, with the treatment of more than 2 mg/ml antitrypsin or glycoprotein, LD30increased significantly.Conclusions: Our data show that fibroblasts are susceptible to the direct toxicity of LPS. Alpha 1-antitrypsin and alpha 1-acid glycoprotein can reduce the toxicity and/or increase the tolerance of mammalian cells to LPS., LD

  14. 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...

  15. Potential relevance of alpha(1-adrenergic receptor autoantibodies in refractory hypertension.

    Directory of Open Access Journals (Sweden)

    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies directed at the alpha(1-adrenergic receptor (alpha(1-AAB have been described in patients with hypertension. We implied earlier that alpha(1-AAB might have a mechanistic role and could represent a therapeutic target. METHODOLOGY/PRINCIPAL FINDINGS: To pursue the issue, we performed clinical and basic studies. We observed that 41 of 81 patients with refractory hypertension had alpha(1-AAB; after immunoadsorption blood pressure was significantly reduced in these patients. Rabbits were immunized to generate alpha(1-adrenergic receptor antibodies (alpha(1-AB. Patient alpha(1-AAB and rabbit alpha(1-AB were purified using affinity chromatography and characterized both by epitope mapping and surface plasmon resonance measurements. Neonatal rat cardiomyocytes, rat vascular smooth muscle cells (VSMC, and Chinese hamster ovary cells transfected with the human alpha(1A-adrenergic receptor were incubated with patient alpha(1-AAB and rabbit alpha(1-AB and the activation of signal transduction pathways was investigated by Western blot, confocal laser scanning microscopy, and gene expression. We found that phospholipase A2 group IIA (PLA2-IIA and L-type calcium channel (Cacna1c genes were upregulated in cardiomyocytes and VSMC after stimulation with both purified antibodies. We showed that patient alpha(1-AAB and rabbit alpha(1-AB result in protein kinase C alpha activation and transient extracellular-related kinase (EKR1/2 phosphorylation. Finally, we showed that the antibodies exert acute effects on intracellular Ca(2+ in cardiomyocytes and induce mesentery artery segment contraction. CONCLUSIONS/SIGNIFICANCE: Patient alpha(1-AAB and rabbit alpha(1-AB can induce signaling pathways important for hypertension and cardiac remodeling. Our data provide evidence for a potential clinical relevance for alpha(1-AAB in hypertensive patients, and the notion of immunity as a possible cause of hypertension.

  16. 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…

  17. Overexpression of Soluble Human Thymosin Alpha 1 in Escherichia coli

    Institute of Scientific and Technical Information of China (English)

    Pei-Fu CHEN; Hong-Ying ZHANG; Geng-Feng FU; Gen-Xing XU; Ya-Yi HOU

    2005-01-01

    Synthesized gene of human thymosin alpha 1 (Tα1) was inserted into pET-28a, pET-9c,pThioHis B, pGEX-2T or pBV222 and then inductively expressed in strains of Escherichia coli. Among the five expression systems, the BL21/pET-28a system provides the highest expression level of fusion protein in a soluble form, which is up to 70% of total expressed bacterial proteins as visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The resulting fusion protein purified through nickel affinity chromatography accounts for 2.53% of the wet bacterial pellet weight and reaches 94.5% purity by SDS-PAGE. These results indicate the potential of this expression system for high-throughput production of recombinant Tα1.

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

    Science.gov (United States)

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

    1981-01-01

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

  19. Apolipoprotein E and alpha1-antichymotrypsin polymorphism in Alzheimer's disease.

    Science.gov (United States)

    Nacmias, B; Tedde, A; Latorraca, S; Piacentini, S; Bracco, L; Amaducci, L; Guarnieri, B M; Petruzzi, C; Ortenzi, L; Sorbi, S

    1996-10-01

    A recent observation has shown that a common polymorphism in the alpha1-antichymotrypsin (ACT) gene modifies the apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker for AD. We analyzed the segregation of the ApoE and ACT polymorphism in sporadic and familial AD patients. In none of the sporadic AD patients did we find the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes. The frequency of ApoE epsilon4/epsilon4 homozygosity in the AD sample resulted highest for the ACT/ TT genotype (17.6%). Our data fail to confirm any additional association with AD beyond the ApoE epsilon4 allele with any ACT genotype, suggesting that ACT does not represent an additional risk factor for AD. PMID:8871590

  20. Implication of alpha1-antichymotrypsin polymorphism in familial Alzheimer's disease.

    Science.gov (United States)

    Nacmias, B; Marcon, G; Tedde, A; Forleo, P; Latorraca, S; Piacentini, S; Amaducci, L; Sorbi, S

    1998-03-13

    A common polymorphism in the alpha1-antichymotrypsin (ACT) gene has been shown to modify the Apolipoprotein E (ApoE) epsilon4-associated Alzheimer's disease (AD) risk identifying the combination of the ACT/AA and ApoE epsilon4/epsilon4 genotypes as a potential susceptibility marker for AD. Using the polymerase chain reaction, we analyzed the segregation of the ACT and ApoE polymorphisms in familial Alzheimer's disease (FAD) patients carrying mutations in Presenilin (PS) and APP genes and in both early onset (EO) and late onset (LO) FAD patients without known mutations. Our data suggest that ACT does not represent an additional risk factor for PS and APP mutated families. However, in LOFAD patients a high frequency of the combined ACT/AA and ApoE epsilon4/epsilon4 genotypes suggest that ACT may interact with ApoE and play a role in LOFAD. PMID:9572591

  1. The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits.

    Science.gov (United States)

    Morel, N; Buryi, V; Feron, O; Gomez, J P; Christen, M O; Godfraind, T

    1998-11-01

    1. CHO cells expressing the alpha(1C-a) subunit (cardiac isoform) and the alpha(1C-b) subunit (vascular isoform) of the voltage-dependent L-type Ca2+ channel were used to investigate whether tissue selectivity of Ca2+ channel blockers could be related to different affinities for alpha1C isoforms. 2. Inward current evoked by the transfected alpha1 subunit was recorded by the patch-clamp technique in the whole-cell configuration. 3. Neutral dihydropyridines (nifedipine, nisoldipine, (+)-PN200-110) were more potent inhibitors of alpha(1C-)b-subunit than of alpha(1C-a)-subunit. This difference was more marked at a holding potential of -100 mV than at -50 mV. SDZ 207-180 (an ionized dihydropyridine) exhibited the same potency on the two isoforms. 4. Pinaverium (ionized non-dihydropyridine derivative) was 2 and 4 fold more potent on alpha(1C-a) than on alpha(1C-b) subunit at Vh of -100 mV and -50 mV, respectively. Effects of verapamil were identical on the two isoforms at both voltages. 5. [3H]-(+)-PN 200-110 binding experiments showed that neutral dihydropyridines had a higher affinity for the alpha(1C-b) than for the alpha(1C-a) subunit. SDZ 207-180 had the same affinity for the two isoforms and pinaverium had a higher affinity for the alpha(1C-a) subunit than for the alpha(1C-b) subunit. 6. These results indicate marked differences among Ca2+ channel blockers in their selectivity for the alpha(1C-a) and alpha(1C-b) subunits of the Ca2+ channel. PMID:9846638

  2. 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

  3. Bucket foundations

    DEFF Research Database (Denmark)

    Foglia, Aligi; Ibsen, Lars Bo

    In this report, bearing behaviour and installation of bucket foundations are reviewed. Different methods and standards are compared with the experimental data presented in Foglia and Ibsen (2014a). The most important studies on these topics are suggested. The review is focused on the response...... of monopod bucket foundations supporting offshore wind turbines....

  4. Corporate Foundations

    DEFF Research Database (Denmark)

    Herlin, Heidi; Thusgaard Pedersen, Janni

    2013-01-01

    responsibility (CSR). The paper hence illuminates the fascinating and overlooked role of corporate foundations as potential bridges between business and civil society. It also informs theory on boundary organizations by clarifying challenges and limits of such institutions.......This paper aims to explore the potential of Danish corporate foundations as boundary organizations facilitating relationships between their founding companies and non-governmental organizations (NGOs). Hitherto, research has been silent about the role of corporate foundations in relation to cross......-sector partnerships. The results of this paper are based on interviews, participant observations, and organizational documents from a 19-month empirical study of a Danish corporate foundation. Findings suggest that corporate foundations have potential to act as boundary organizations and facilitate collaborative...

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

    Science.gov (United States)

    de Serres, F; Blanco, I

    2014-10-01

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

  6. 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

  7. 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

  8. Foundation Structure

    DEFF Research Database (Denmark)

    2009-01-01

    Method of installing a bucket foundation structure comprising one, two, three or more skirts, into soils in a controlled manner. The method comprises two stages: a first stage being a design phase and the second stage being an installation phase. In the first stage, design parameters are determined...... relating to the loads on the finished foundation structure; soil profile on the location; allowable installation tolerances, which parameters are used to estimate the minimum diameter and length of the skirts of the bucket. The bucket size is used to simulate load situations and penetration into foundation...

  9. The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits.

    OpenAIRE

    Morel, Nicole; Buryi, V; Feron, Olivier; Gomez, J. P.; Christen, M O; Godfraind, Theophile

    1998-01-01

    1. CHO cells expressing the alpha(1C-a) subunit (cardiac isoform) and the alpha(1C-b) subunit (vascular isoform) of the voltage-dependent L-type Ca2+ channel were used to investigate whether tissue selectivity of Ca2+ channel blockers could be related to different affinities for alpha1C isoforms. 2. Inward current evoked by the transfected alpha1 subunit was recorded by the patch-clamp technique in the whole-cell configuration. 3. Neutral dihydropyridines (nifedipine, nisoldipine, (+)-PN200-1...

  10. 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.)

  11. The experience with setting-up radioimmunoassay for alpha-1 fetoprotein

    International Nuclear Information System (INIS)

    The decisive factor in the preparation of radioimmunological alpha-1-fetoprotein determination, provided sufficient commercial or own antisera and standards are available for calibration, is the quality of the preparation for labelling. Alpha-1-fetoprotein was separated by affinity chromatography using Sepharose with alpha-1-fetoprotein-bound antibodies. The isolates thus obtained were labelled with 125I using enzyme and chloramine T and Iodogen techniques. The labelled alpha-1-fetoprotein can be used for RIA. In view of reduced immunoreactivity of the preparation, however, the performance of the radioimmunological determination has so far not matched the quality of imported kits. The technique is currently being optimized. (author)

  12. Glaucoma Foundation

    Science.gov (United States)

    ... Honors Presented at 2016 Think Tank Dinner The Glaucoma Foundation (TGF) has awarded Ursula Schlötzer-Schrehardt, PhD, ... Robert Ritch Award for Excellence and Innovation in Glaucoma for her distinguished career in glaucoma research. This ...

  13. Dysautonomia Foundation

    Science.gov (United States)

    ... disease most people have never heard of ... Familial Dysautonomia (FD) is a rare genetic neurological disorder that ... birth. (More about FD .) Research funded by the Dysautonomia Foundation has led to a number of breakthroughs ...

  14. 21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-lipoprotein immuno-logical test system. 866.5580 Section 866.5580 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN....5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An...

  15. Applied Foundations

    DEFF Research Database (Denmark)

    Kohlenbach, Ulrich

    2002-01-01

    A central theme in the foundations of mathematics, dating back to D. Hilbert, can be paraphrased by the following question "How is it that abstract methods (`ideal elements´) can be used to prove `real´ statements e.g. about the natural numbers and is this use necessary in principle?"......A central theme in the foundations of mathematics, dating back to D. Hilbert, can be paraphrased by the following question "How is it that abstract methods (`ideal elements´) can be used to prove `real´ statements e.g. about the natural numbers and is this use necessary in principle?"...

  16. Molecular cloning and characterization of a plant alpha1,3/4-fucosidase based on sequence tags from almond fucosidase I.

    Science.gov (United States)

    Zeleny, Reinhard; Leonard, Renaud; Dorfner, Georg; Dalik, Thomas; Kolarich, Daniel; Altmann, Friedrich

    2006-04-01

    Our work with almond peptide N-glycosidase A made us interested also in the alpha1,3/4-fucosidase which is used as a specific reagent for glycoconjugate analysis. The enzyme was purified to presumed homogeneity by a series of chromatographic steps including dye affinity and fast-performance anion exchange chromatography. The 63 kDa band was analyzed by tandem mass spectrometry which yielded several partial sequences. A homology search retrieved the hypothetical protein Q8GW72 from Arabidopsis thaliana. This protein has recently been described as being specific for alpha1,2-linkages. However, cDNA cloning and expression in Pichia pastoris of the A. thaliana fucosidase showed that it hydrolyzed fucose in 3- and 4-linkage to GlcNAc in Lewis determinants whereas neither 2-linked fucose nor fucose in 3-linkage to the innermost GlcNAc residue were attacked. This first cloning of a plant alpha1,3/4-fucosidase also confirmed the identity of the purified almond enzyme and thus settles the notorious uncertainty about its molecular mass. The alpha1,3/4-fucosidase from Arabidopsis exhibited striking sequence similarity with an enzyme of similar substrate specificity from Streptomyces sp. (Q9Z4I9) and with putative proteins from rice. PMID:16516937

  17. A non-Golgi alpha 1,2-fucosyltransferase that modifies Skp1 in the cytoplasm of Dictyostelium.

    Science.gov (United States)

    van Der Wel, H; Morris, H R; Panico, M; Paxton, T; North, S J; Dell, A; Thomson, J M; West, C M

    2001-09-01

    Skp1 is a subunit of the SCF-E3 ubiquitin ligase that targets cell cycle and other regulatory factors for degradation. In Dictyostelium, Skp1 is modified by a pentasaccharide containing the type 1 blood group H trisaccharide at its core. To address how the third sugar, fucose alpha1,2-linked to galactose, is attached, a proteomics strategy was applied to determine the primary structure of FT85, previously shown to copurify with the GDP-Fuc:Skp1 alpha 1,2-fucosyltransferase. Tryptic-generated peptides of FT85 were sequenced de novo using Q-TOF tandem mass spectrometry. Degenerate primers were used to amplify FT85 genomic DNA, which was further extended by a novel linker polymerase chain reaction method to yield an intronless open reading frame of 768 amino acids. Disruption of the FT85 gene by homologous recombination resulted in viable cells, which had altered light scattering properties as revealed by flow cytometry. FT85 was necessary and sufficient for Skp1 fucosylation, based on biochemical analysis of FT85 mutant cells and Escherichia coli that express FT85 recombinantly. FT85 lacks sequence motifs that characterize all other known alpha 1,2-fucosyltransferases and lacks the signal-anchor sequence that targets them to the secretory pathway. The C-terminal region of FT85 harbors motifs found in inverting Family 2 glycosyltransferase domains, and its expression in FT85 mutant cells restores fucosyltransferase activity toward a simple disaccharide substrate. Whereas most prokaryote and eukaryote Family 2 glycosyltransferases are membrane-bound and oriented toward the cytoplasm where they glycosylate lipid-linked or polysaccharide precursors prior to membrane translocation, the soluble, eukaryotic Skp1-fucosyltransferase modifies a protein that resides in the cytoplasm and nucleus. PMID:11423539

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  19. Modified equipartition calculation for supernova remnants. Cases \\alpha =0.5 and \\alpha =1

    CERN Document Server

    Arbutina, B; Vucetic, M M; Pavlovic, M Z; Vukotic, B

    2013-01-01

    The equipartition or minimum-energy calculation is a well-known procedure for estimating magnetic field strength and total energy in the magnetic field and cosmic ray particles by using only the radio synchrotron emission. In one of our previous papers we have offered a modified equipartition calculation for supernova remnants (SNRs) with spectral indices 0.5<\\alpha <1. Here we extend the analysis to SNRs with \\alpha =0.5 and \\alpha =1.

  20. 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...

  1. Phorbol esters promote alpha 1-adrenergic receptor phosphorylation and receptor uncoupling from inositol phospholipid metabolism.

    OpenAIRE

    Leeb-Lundberg, L M; Cotecchia, S; Lomasney, J W; DeBernardis, J F; Lefkowitz, R J; Caron, M G

    1985-01-01

    DDT1 MF-2 cells, which are derived from hamster vas deferens smooth muscle, contain alpha 1-adrenergic receptors (54,800 +/- 2700 sites per cell) that are coupled to stimulation of inositol phospholipid metabolism. Incubation of these cells with tumor-promoting phorbol esters, which stimulate calcium- and phospholipid-dependent protein kinase, leads to a marked attenuation of the ability of alpha 1-receptor agonists such as norepinephrine to stimulate the turnover of inositol phospholipids. T...

  2. Effect of extracellular pH on recombinant alpha1beta2gamma2 and alpha1beta2 GABAA receptors.

    Science.gov (United States)

    Mercik, Katarzyna; Pytel, Maria; Cherubini, Enrico; Mozrzymas, Jerzy W

    2006-08-01

    Recently, we have reported that extracellular protons allosterically modulated neuronal GABA(A) receptors [Mozrzymas, J.W., Zarnowska, E.D., Pytel, M., Mercik, K., 2003a. Modulation of GABA(A) receptors by hydrogen ions reveals synaptic GABA transient and a crucial role of desensitiztion process. Journal of Neuroscience 23, 7981-7992]. However, GABAARs in neurons are heterogeneous and the effect of hydrogen ions depends on the receptor subtype. In particular, gamma2 subunit sets the receptor sensibility to several modulators including protons. However, the mechanisms whereby protons modulate gamma2-containing and gamma2-free GABAARs have not been fully elucidated. To this end, current responses to ultrafast GABA applications were recorded for alpha1beta2gamma2 and alpha1beta2 receptors at different pH values. For both receptor types, increase in pH induced a decrease in amplitudes of currents elicited by saturating [GABA] but this effect was stronger for alpha1beta2 receptors. In the case of alpha1beta2gamma2 receptors, protons strongly affected the current time course due to a down regulation of binding and desensitization rates. This effect was qualitatively similar to that described in neurons. Protons strongly influenced the amplitude of alpha1beta2 receptor-mediated currents but the effect on their kinetics was weak suggesting a predominant direct non-competitive inhibition with a minor allosteric modulation. In conclusion, we provide evidence that extracellular protons strongly affect GABAA receptors and that, depending on the presence of the gamma2 subunit, the modulatory mechanisms show profound quantitative and qualitative differences.

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  4. Differential effects of angiostatin, endostatin and interferon-alpha(1) gene transfer on in vivo growth of human breast cancer cells.

    Science.gov (United States)

    Indraccolo, S; Gola, E; Rosato, A; Minuzzo, S; Habeler, W; Tisato, V; Roni, V; Esposito, G; Morini, M; Albini, A; Noonan, D M; Ferrantini, M; Amadori, A; Chieco-Bianchi, L

    2002-07-01

    The administration of different angiogenesis inhibitors by gene transfer has been shown to result in inhibition of tumor growth in animal tumor models, but the potency of these genes has been only partially evaluated in comparative studies to date. To identify the most effective anti-angiogenic molecule for delivery by retroviral vectors, we investigated the effects of angiostatin, endostatin and interferon(IFN)-alpha(1) gene transfer in in vivo models of breast cancer induced neovascularization and tumor growth. Moloney leukemia virus-based retroviral vectors for expression of murine angiostatin, endostatin and IFN-alpha(1) were generated, characterized, and used to transduce human breast cancer cell lines (MCF7 and MDA-MB435). Secretion of the recombinant proteins was confirmed by biological and Western blotting assays. Their production did not impair in vitro growth of these breast cancer cells nor their viability, and did not interfere with the expression of angiogenic factors. However, primary endothelial cell proliferation and migration in vitro were inhibited by supernatants of the transduced cells containing angiostatin, endostatin, and IFN-alpha(1). Stable gene transfer of the IFN-alpha(1) cDNA by retroviral vectors in both MCF7 and MDA-MB435 cells resulted in a marked and long-lasting inhibition of tumor growth in nude mice that was associated with reduced vascularization. Endostatin reduced the in vivo growth of MDA-MB435, but not MCF7 cells, despite similar levels of in vivo production, and angiostatin did not impair the in vivo growth of either cell line. These findings indicate heterogeneity in the therapeutic efficacy of angiostatic molecules delivered by viral vectors and suggest that gene therapy with IFN-alpha(1) and endostatin might be useful for treatment of breast cancer. PMID:12080381

  5. Inhibition of activated protein C by recombinant alpha 1-antitrypsin variants with substitution of arginine or leucine for methionine358

    NARCIS (Netherlands)

    Heeb, M.J.; Bischoff, Rainer; Courtney, M.; Griffin, J.H.

    1990-01-01

    alpha 1-Antitrypsin (alpha 1-AT) was recently identified as a major physiologic plasma inhibitor of activated protein C. The reaction with activated protein C of recombinant alpha 1-AT containing amino acid substitutions at the reactive center was studied. The substitution of Arg358 for Met, as obse

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

    Directory of Open Access Journals (Sweden)

    Mogilevski Grigori

    2004-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

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

  8. 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.

  9. Neuronal changes resulting in up-regulation of alpha-1 adrenoceptors after peripheral nerve injury

    Institute of Scientific and Technical Information of China (English)

    Peter D.Drummond

    2014-01-01

    Under normal conditions, the sympathetic neurotransmitter noradrenaline inhibits the pro-duction and release of pro-inlfammatory cytokines. However, after peripheral nerve and tissue injury, pro-inflammatory cytokines appear to induce the expression of the alpha1A-adreno-ceptor subtype on immune cells and perhaps also on other cells in the injured tissue. In turn, noradrenaline may act on up-regulated alpha1-adrenoceptors to increase the production of the pro-inflammatory cytokine interleukin-6. In addition, the release of inflammatory mediators and nerve growth factor from keratinocytes and other cells may augment the expression of al-pha1-adrenoceptors on peripheral nerve ifbers. Consequently, nociceptive afferents acquire an abnormal excitability to adrenergic agents, and inlfammatory processes build. These mechanisms could contribute to the development of sympathetically maintained pain in conditions such as post-herpetic neuralgia, cutaneous neuromas, amputation stump pain and complex regional pain syndrome.

  10. Proteomic identification of IPSE/alpha-1 as a major hepatotoxin secreted by Schistosoma mansoni eggs.

    Directory of Open Access Journals (Sweden)

    Maha-Hamadien Abdulla

    2011-10-01

    Full Text Available BACKGROUND: Eggs deposited in the liver of the mammalian host by the blood fluke parasite, Schistosoma mansoni, normally drive a T-helper-2 (Th2-mediated granulomatous response in immune-competent mice. By contrast, in mice deprived of T-cells and incapable of producing granulomata, egg-secreted proteins (ESP induce acute hepatic injury and death. Previous work has shown that one such ESP, the T2 ribonuclease known as omega-1, is hepatotoxic in vivo in that specific antisera to omega-1 prevent hepatocyte damage. METHODOLOGY/PRINCIPAL FINDINGS: Using an in vitro culture system employing mouse primary hepatocytes and alanine transaminase (ALT activity as a marker of heptocyte injury, we demonstrated that S. mansoni eggs, egg-secreted proteins (ESP, soluble-egg antigen (SEA, and omega-1 are directly hepatotoxic and in a dose-dependent manner. Depletion of omega-1 using a monoclonal antibody abolished the toxicity of pure omega-1 and diminished the toxicity in ESP and SEA by 47 and 33%, respectively. Anion exchange chromatography of ESP yielded one predominant hepatotoxic fraction. Proteomics of that fraction identified the presence of IPSE/alpha-1 (IL-4 inducing principle from S. mansoni eggs, a known activator of basophils and inducer of Th2-type responses. Pure recombinant IPSE/alpha-1 also displayed a dose-dependent hepatotoxicity in vitro. Monoclonal antibody depletion of IPSE/alpha-1 abolished the latter's toxicity and diminished the total toxicity of ESP and SEA by 32 and 35%, respectively. Combined depletion of omega-1 and IPSE/alpha-1 diminished hepatotoxicity of ESP and SEA by 60 and 58% respectively. CONCLUSIONS: We identified IPSE/alpha-1 as a novel hepatotoxin and conclude that both IPSE/alpha-1 and omega-1 account for the majority of the hepatotoxicity secreted by S. mansoni eggs.

  11. Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

    International Nuclear Information System (INIS)

    In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measured by autoradiography

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

    DEFF Research Database (Denmark)

    Andersen, J T

    1995-01-01

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

  13. [Effect of adrenal stress on activity of proteinase and alpha-1-proteinase inhibitor in rats].

    Science.gov (United States)

    Samokhina, L M; Kaliman, P A

    1994-01-01

    The effect of adrenal stress on the proteinase and alpha-1-proteinase inhibitor activities in blood serum and cytosols of the rat organs were investigated. The reliable change was marked only in the alpha-1-PI level research of lung tissue cytosol. The proteolysis suppression was revealed in the heart and kidney tissue, while the proteolysis activation was revealed in serum and less in the lung tissue cytosol. Changes in proteinase level in the myocardium and kidney tissue play the primary role in respect to those of the other research liquids under study. PMID:7747353

  14. Molecular determinants of desensitization and assembly of the chimeric GABA(A) receptor subunits (alpha1/gamma2) and (gamma2/alpha1) in combinations with beta2 and gamma2

    DEFF Research Database (Denmark)

    Elster, L; Kristiansen, U; Pickering, D S;

    2001-01-01

    )beta2gamma2 subunit combinations formed functional receptor complexes as shown by whole-cell patch-clamp recordings and [3H]muscimol and [3H]flunitrazepam binding. Moreover, the surface immunofluorescence staining of Sf-9 cells expressing the (alpha1/gamma2)-containing receptors was pronounced......Two gamma-aminobutyric acid(A) (GABA(A)) receptor chimeras were designed in order to elucidate the structural requirements for GABA(A) receptor desensitization and assembly. The (alpha1/gamma2) and (gamma2/alpha1) chimeric subunits representing the extracellular N-terminal domain of alpha1 or gamma......2 and the remainder of the gamma2 or alpha1 subunits, respectively, were expressed with beta2 and beta2gamma2 in Spodoptera frugiperda (Sf-9) cells using the baculovirus expression system. The (alpha1/gamma2)beta2 and (alpha1/gamma2)beta2gamma2 but not the (gamma2/alpha1)beta2 and (gamma2/alpha1...

  15. INOSITOL PHOSPHATES FORMED IN RAT AORTA AFTER ALPHA-1-ADRENOCEPTOR STIMULATION ARE INHIBITED BY FORSKOLIN

    NARCIS (Netherlands)

    MANOLOPOULOS, VG; PIPILISYNETOS, E; DENHERTOG, A; NELEMANS, A

    1991-01-01

    Rat aortic smooth muscle rings without endothelial cells were subjected to alpha-1-adrenoceptor stimulation. We measured the contractile state of the smooth muscle cells and the formation of inositol phosphates (InsPs) on receptor stimulation. Using different extracellular calcium-containing solutio

  16. Aspects of preanalytical variation of lactoferrin and elastase/alpha 1-protease inhibitor complexes

    DEFF Research Database (Denmark)

    Antonsen, S; Qvist, N; Wanscher, M

    1993-01-01

    A number of interesting applications of plasma elastase/alpha 1-protease inhibitor complexes (ELA-PI) and lactoferrin (LAC) have recently been suggested. However, the clinical utility of these components often seems to be low. This might be improved by minimizing the preanalytical variation...

  17. Alpha 1-acid glycoprotein has immunomodulatory effects in neonatal swine adipose tissue

    Science.gov (United States)

    Alpha 1-acid glycoprotein (AGP) is the most abundant protein in serum of neonatal swine. This protein functions as an immunomodulator in the pig. Recent work has demonstrated that adipose tissue can express AGP mRNA, as well as numerous cytokine mRNA. The present study was designed to determine i...

  18. 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

  19. Human CRISP-3 binds serum alpha(1)B-glycoprotein across species

    DEFF Research Database (Denmark)

    Udby, Lene; Johnsen, Anders H; Borregaard, Niels

    2010-01-01

    CRISP-3 was previously shown to be bound to alpha(1)B-glycoprotein (A1BG) in human serum/plasma. All mammalian sera are supposed to contain A1BG, although its presence in rodent sera is not well-documented. Since animal sera are often used to supplement buffers in experiments, in particular such...

  20. 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...

  1. The pharmacology of spontaneously open alpha 1 beta 3 epsilon GABA A receptor-ionophores.

    Science.gov (United States)

    Maksay, Gábor; Thompson, Sally A; Wafford, Keith A

    2003-06-01

    Human alpha(1)beta(3) epsilon GABA(A) receptors were expressed in Xenopus oocytes and examined using the conventional two-electrode voltage-clamp technique and compared to alpha(1)beta(3)gamma(2) receptors. The effects of several GABA(A) agonists were studied, and the allosteric modulation of the channel by a number of GABAergic modulators investigated. The presence of the epsilon subunit increased the potency and efficacy of direct activation by partial GABA(A) agonists (piperidine-4-sulphonic acid and thio-4-PIOL), pentobarbital and neuro-steroids. Direct activation by 3-hydroxylated neurosteroids was restricted to 3alpha epimers, while chirality at C5 was indifferent. The 3beta-sulfate esters of pregnenolone and dehydroepiandrosterone inhibited the spontaneous currents with efficacies higher, while bicuculline methiodide and SR 95531 did so lower than picrotoxin and TBPS. Furosemide, fipronil, triphenylcyanoborate and Zn(2+) blocked the spontaneous currents of alpha(1)beta(3) epsilon receptors with different efficacies. Flunitrazepam and 4'-chlorodiazepam inhibited the spontaneous currents with micromolar potencies. In conclusion, spontaneously active alpha(1)beta(3) epsilon GABA(A) receptors can be potentiated and blocked by GABAergic agents within a broad range of efficacy.

  2. The research on effect of radioactive material concentration and radiation to DNA plant. (The research on precedence foundation engineering field in fiscal 1998)

    Energy Technology Data Exchange (ETDEWEB)

    Nagara, S.; Tsurudome, K.; Tokizawa, T. [Environmental Research and Development Group, Ningyo Toge Environment Engineering Center, Japan Nuclear Cycle Development Inst., Kamisaibara, Okayama (Japan)

    1999-05-01

    For the purpose of effect of radioactive material concentration and radiation to DNA in plant, this study carried out laboratory experiment using soil from the Yotsugi mill-tailings dam which contained radionuclides such as uranium and radium. In present experiment, the Arabidopsis in which gene sequence had been clarified was used as a model plant, and the existence of the mutation of the gene was confirmed. In addition, the Imaging Plate method (IP) was applied to the detection of the radioactive material, and the applicability of IP for the analysis of the radioactive material migration was evaluated. In fiscal 1997, DNA amplification by the PCR (Polymerase Chain Reaction) method was carried out using DNA extracted from the Arabidopsis. The result showed that chalcone synthesis gene examined, when radiation and effect by the radioactive material are analyzed, could be amplified. From results of IP-image of the Arabidopsis which is grown in the soil from Yotsugi mill-tailings dam, it was able to be confirmed that radiation distribution in the plant body is measured, and the way opened it in the measuring method of the small radiation. This study promotes the experiment in the cooperation with Okayama Univ.. JNC was in charge of from the rearing of the plant to the DNA amplification operation. And Okayama Univ. was in charge of the operation that contains the DNA recombination experiment from sub-cloning to sequence. (author)

  3. 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

  4. The lipocalin alpha1-microglobulin protects erythroid K562 cells against oxidative damage induced by heme and reactive oxygen species.

    Science.gov (United States)

    Olsson, Magnus G; Olofsson, Tor; Tapper, Hans; Akerstrom, Bo

    2008-08-01

    Alpha(1)-microglobulin is a 26 kDa plasma and tissue glycoprotein that belongs to the lipocalin protein superfamily. Recent reports show that it is a reductase and radical scavenger and that it binds heme and has heme-degrading properties. This study has investigated the protective effects of alpha(1)-microglobulin against oxidation by heme and reactive oxygen species in the human erythroid cell line, K562. The results show that alpha(1)-microglobulin prevents intracellular oxidation and up-regulation of heme oxygenase-1 induced by heme, hydrogen peroxide and Fenton reaction-generated hydroxyl radicals in the culture medium. It also reduces the cytosol of non-oxidized cells. Endogeneous expression of alpha(1)-microglobulin was up-regulated by these oxidants and silencing of the alpha(1)-microglobulin expression increased the cytosol oxidation. alpha(1)-microglobulin also inhibited cell death caused by heme and cleared cells from bound heme. Binding of heme to alpha(1)-microglobulin increased the radical reductase activity of the protein as compared to the apo-protein. Finally, alpha(1)-microglobulin was localized mainly at the cell surface both when administered exogeneously and in non-treated cells. The results suggest that alpha(1)-microglobulin is involved in the defence against oxidative cellular injury caused by haemoglobin and heme and that the protein may employ both heme-scavenging and one-electron reduction of radicals to achieve this.

  5. Skin Cancer Foundation

    Science.gov (United States)

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the ... A "Sunscreen Gene"? Skin Cancer Facts & Statistics The Skin Cancer Foundation's Champions for Change Gala 2016 Learn ...

  6. ALPHA-1-ADRENOCEPTOR-MEDIATED CA2+-ENTRY FROM THE EXTRACELLULAR FLUID AND CA2+-RELEASE FROM INTRACELLULAR STORES - NO ROLE FOR ALPHA-1A,B-ADRENOCEPTOR SUBTYPES IN THE PITHED RAT

    NARCIS (Netherlands)

    SCHWIETERT, HR; MATHY, MJ; WILHELM, D; WILFFERT, B; PFAFFENDORF, M; VANZWIETEN, PA

    1992-01-01

    1 In the present study, we tested the hypothesis that in the pithed rat preparation two subtypes of the alpha-1-adrenoceptor are linked to two different signal transduction mechanisms, both of which contribute to vasoconstriction, one facilitating Ca2+-entry from the extracellular fluid (alpha-1A) a

  7. Investigation of the genes for RET and its ligand complex, GDNF/GFR alpha-1, in small cell lung carcinoma

    NARCIS (Netherlands)

    Mulligan, LM; Timmer, T; Ivanchuk, SM; Campling, BG; Young, LC; Rabbitts, PH; Sundaresan, [No Value; Hofstra, RMW; Eng, C

    1998-01-01

    RET is a receptor tyrosine kinase expressed in neuroendocrine cells and in tumors of these cell types. RET activation may be mediated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF family receptor alpha-1 (GFR alpha-1). Activating RET mutations are found i

  8. Apoptosis induction by doxazosin and other quinazoline alpha(1)-adrenoceptor antagonists: a new mechanism for cancer treatment?

    NARCIS (Netherlands)

    N. Kyprianou; T.B. Vaughan; M.C. Michel

    2009-01-01

    Doxazosin and related, quinazoline-based alpha(1)-adrenoceptor antagonists can induce apoptosis in prostate and various other normal, benign, smooth muscle, endothelial and malignant cells. Such apoptosis-inducing effects occur independently of alpha(1)-adrenoceptor antagonism and typically require

  9. Up-regulation of alpha1-microglobulin by hemoglobin and reactive oxygen species in hepatoma and blood cell lines.

    Science.gov (United States)

    Olsson, Magnus G; Allhorn, Maria; Olofsson, Tor; Akerström, Bo

    2007-03-15

    alpha(1)-Microglobulin is a 26-kDa glycoprotein synthesized in the liver, secreted to the blood, and rapidly distributed to the extravascular compartment of all tissues. Recent results show that alpha(1)-microglobulin has heme-binding and heme-degrading properties and it has been suggested that the protein is involved in the defense against oxidation by heme and reactive oxygen species. In the present study the influence of hemoglobin and reactive oxygen species (ROS) on the cellular expression of alpha(1)-microglobulin was investigated. Oxy- and methemoglobin, free heme, and Fenton reaction-induced hydroxyl radicals induced a dose-dependent up-regulation of alpha(1)-microglobulin on both mRNA and protein levels in hepatoma cells and an increased secretion of alpha(1)-microglobulin. The up-regulation was reversed by the addition of catalase and ascorbate, and by reacting hemoglobin with cyanide which prevents redox reactions. Furthermore, the blood cell lines U937 and K562 expressed alpha(1)-microglobulin at low levels, and this expression increased up to 11-fold by the addition of hemoglobin. These results suggest that alpha(1)-microglobulin expression is induced by ROS, arising from redox reactions of hemoglobin or from other sources and are consistent with the hypothesis that alpha(1)-microglobulin participates in the defense against oxidation by hemoglobin, heme, and reactive oxygen species.

  10. Altered hepatic vasopressin and alpha 1-adrenergic receptors after chronic endotoxin infusion

    Energy Technology Data Exchange (ETDEWEB)

    Roth, B.L.; Spitzer, J.A.

    1987-05-01

    Sepsis and septic shock are complicated by a number of hemodynamic and metabolic aberrations. These include catecholamine refractoriness and altered glucose metabolism. Recently, a nonshock rat model of continuous endotoxin infusion via an implanted osmotic pump was developed that reproduces some of the metabolic and cardiovascular findings of human sepsis. By using this model, we have found a decreased number of hepatic plasma membrane alpha 1-adrenergic and (Arg8)vasopressin receptors in rats continuously infused with endotoxin. There was a significant decrease in (/sup 3/H)prazosin (35 +/- 7%) and (/sup 3/H) (Arg8)vasopressin (43 +/- 8%) receptors after 30 h of continuous endotoxin infusion with no change in affinity. The ability of norepinephrine to form the high-affinity complex with alpha 1-adrenergic receptors was not altered after chronic endotoxin infusion. The results are consistent with the concept that alterations in receptor number might underlie certain of the metabolic consequences of chronic sepsis.

  11. Constraints on the Preferred-Frame {\\alpha}1, {\\alpha}2 parameters from Solar System planetary precessions

    CERN Document Server

    Iorio, Lorenzo

    2014-01-01

    Analytical expressions for the orbital precessions affecting the relative motion of the components of a local binary system induced by Lorentz-violating Preferred Frame Effects (PFE) are explicitly computed in terms of the PPN parameters {\\alpha}1, {\\alpha}2. A linear combination of the supplementary perihelion precessions of all the inner planets of the Solar System, able to remove the a-priori bias of unmodelled/mismodelled standard effects such as the general relativistic Lense-Thirring precessions and the classical rates due to the Sun's oblateness J2, allows to infer {\\alpha}1 <= 10^-6, {\\alpha}2 <= 10^-5. Such bounds should be improved in the near future after processing the data that are being collected by the MESSENGER spacecraft, currently orbiting Mercury. Further improvements may come in the mid-future from the approved BepiColombo mission to Mercury (Abridged).

  12. Mutation in collagen II alpha 1 isoforms delineates Stickler and Wagner syndrome phenotypes

    OpenAIRE

    Tran-Viet, Khanh-Nhat; Soler, Vincent; Quiette, Valencia; POWELL, CALDWELL; Yanovitch, Tammy; Metlapally, Ravikanth; Luo, Xiaoyan; Katsanis, Nicholas; Nading, Erica; Young, Terri L.

    2013-01-01

    Purpose Stickler syndrome is an arthro-ophthalmopathy with phenotypic overlap with Wagner syndrome. The common Stickler syndrome type I is inherited as an autosomal dominant trait, with causal mutations in collagen type II alpha 1 (COL2A1). Wagner syndrome is associated with mutations in versican (VCAN), which encodes for a chondroitin sulfate proteoglycan. A three-generation Caucasian family variably diagnosed with either syndrome was screened for sequence variants in the COL2A1 and VCAN gen...

  13. 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...

  14. Micturition in conscious rats with and without bladder outlet obstruction: role of spinal alpha 1-adrenoceptors.

    OpenAIRE

    Ishizuka, O; Persson, K.; Mattiasson, A.; Naylor, A; Wyllie, M.; Andersson, K.

    1996-01-01

    1. In normal rats and rats with bladder hypertrophy secondary to outflow obstruction, undergoing continuous cytometry, we examined the responses to the selective alpha 1-adrenoceptor antagonist doxazosin given intrathecally (i.t.) and intra-arterially (i.a.). In addition, we investigated the effects of the drug on L-dopa-induced bladder hyperactivity in normal, unobstructed rats. 2. Doxazosin 50 nmol (approximately 60 micrograms kg-1), given i.t., decreased micturition pressure in normal rats...

  15. An increased expression of Ca(2+) channel alpha(1A) subunit immunoreactivity in deep cerebellar neurons of rolling mouse Nagoya.

    Science.gov (United States)

    Sawada, K; Sakata-Haga, H; Ando, M; Takeda, N; Fukui, Y

    2001-12-01

    Rolling mouse Nagoya (RMN) is an ataxic mutant and carries a mutation in the gene coding for the alpha(1A) subunit of the P/Q-type Ca(2+) channel. We examined the immunohistochemical expression of the alpha(1A) subunit in deep cerebellar nuclei of RMN. The antibody used recognized residues 865-883 of the mouse alpha(1A) subunit not overlapping the altered sequences in RMN. In RMN, many neurons exhibited definite alpha(1A) subunit-staining in the medial nucleus, interposed nucleus, and lateral nucleus of deep cerebellar nuclei. The number of positive neurons in these nuclei was significantly higher in RMN than in controls. Increased expression of the alpha(1A) subunit in deep cerebellar neurons might compensate for the altered function of the P/Q-type Ca(2+) channel of RMN.

  16. Effect of alpha 1-adrenergic blockade on myocardial blood flow during exercise after myocardial infarction.

    Science.gov (United States)

    Herzog, C A; Dai, X Z; Bache, R J

    1991-08-01

    The effect of alpha 1-adrenergic blockade with prazosin on myocardial blood flow at rest and during two levels of treadmill exercise was assessed in 16 chronically instrumented dogs 9-14 days after myocardial infarction had been produced by occlusion of the left circumflex coronary artery. During resting conditions prazosin did not alter mean myocardial blood flow or the subendocardial-to-subepicardial flow ratio in either normally perfused or collateral-dependent myocardium. However, during exercise at comparable external work loads and comparable rate-pressure products, prazosin significantly increased blood flow to normally perfused (27% increase at the second level of exercise, P less than 0.001) and collateral-dependent myocardium (35% increase at the second level of exercise, P less than 0.001) compared with control. In addition, prazosin caused a small but significant decrease in the subendocardial-to-subepicardial flow ratio in both normal (1.27 +/- 0.04 to 1.19 +/- 0.04; P less than 0.01) and collateral-dependent myocardium (0.57 +/- 0.11 to 0.52 +/- 0.11; P less than 0.01) compared with control, reflecting a disproportionally greater increase in subepicardial flow in response to alpha 1-adrenergic blockade. These data demonstrate that alpha 1-adrenergic vasoconstriction inhibits coronary vasodilation during exercise, even in areas of collateral-dependent myocardium relatively early after coronary artery occlusion. PMID:1678929

  17. Modification of certain pharmacological effects of ethanol by lipophilic alpha-1 adrenergic agonists

    Energy Technology Data Exchange (ETDEWEB)

    Menon, M.K.; Dinovo, E.C.; Haddox, V.G.

    1987-09-28

    The influence of four centrally-acting alpha-1 adrenoceptor agonists, namely, 2(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), cirazoline, (-) 1,2,3,4-tetrahydro-8-methoxy-5-methylthio-2-naphthalenamine ((-)SKF 89748A) and 2-(2-methylindazol-4-imino)imidazolidine (Sgd 101/75) on the pharmacological effects of ethanol was investigated. All four drugs reduced the duration of ethanol-induced hypnosis in C57B1/6 mice, this effect being proportional to their relative potencies to exert central alpha-1 agonism. In prazosin-pretreated mice, St 587 failed to reduce the hypnotic effect of ethanol, which provided strong evidence for the role of alpha-1 agonism for the hypnosis reducing effect of St 587. Hyperactivity induced in C57B1/6 mice by a subhypnotic dose of ethanol and St 587 was reported earlier. In the present study, St 587, cirazoline and (-)SKF 89748A produced similar response, but no correlation between this effect and ethanol hypnosis blockade could be established. 19 references, 8 figures, 2 tables.

  18. Urine alpha-1-microglobulin reliability in the diagnosis of pyelonephritis: a systematic review

    Directory of Open Access Journals (Sweden)

    Anoush Azarfar

    2015-09-01

    Full Text Available Introduction:Pyelonephritis is known as kidney inflammation due to bacterial infection which should be diagnosed and treated promptly. In this article, we decided to systematically review the diagnostic value and reliability of evaluating urine excretion low molecular weight protein alpha-1-microglobulin (A1M. Methods: PubMed and Scopus were searched for the relevant articles about the efficacy of urine alpha-1-micriglobulin assays in the diagnosis of pyelonephritis in children. The search strategy was microglobulin AND pyelonephritis. No language and date limitations were included in this review. Results: A total of 16 articles were retrieved from PubMed and 23 articles from Scopus. After studying the abstracts, only 5 articles were selected, which specifically studied the efficacy of alpha-1-micrglobulin in the diagnosis of pyelonephritis in children.Discussion: A1M is not an acute phase protein but its concentration alters in several clinical conditions. Conclusion: Evaluating the urine concentration of A1M is a noninvasive and cost effective strategy with the diagnostic capability for urinary tract disorders such as early recognition of tubular damages during pyelonephritis.

  19. Distinct roles for laminin globular domains in laminin alpha1 chain mediated rescue of murine laminin alpha2 chain deficiency.

    Directory of Open Access Journals (Sweden)

    Kinga I Gawlik

    Full Text Available BACKGROUND: Laminin alpha2 chain mutations cause congenital muscular dystrophy with dysmyelination neuropathy (MDC1A. Previously, we demonstrated that laminin alpha1 chain ameliorates the disease in mice. Dystroglycan and integrins are major laminin receptors. Unlike laminin alpha2 chain, alpha1 chain binds the receptors by separate domains; laminin globular (LG domains 4 and LG1-3, respectively. Thus, the laminin alpha1 chain is an excellent tool to distinguish between the roles of dystroglycan and integrins in the neuromuscular system. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide insights into the functions of laminin alpha1LG domains and the division of their roles in MDC1A pathogenesis and rescue. Overexpression of laminin alpha1 chain that lacks the dystroglycan binding LG4-5 domains in alpha2 chain deficient mice resulted in prolonged lifespan and improved health. Importantly, diaphragm and heart muscles were corrected, whereas limb muscles were dystrophic, indicating that different muscles have different requirements for LG4-5 domains. Furthermore, the regenerative capacity of the skeletal muscle did not depend on laminin alpha1LG4-5. However, this domain was crucial for preventing apoptosis in limb muscles, essential for myelination in peripheral nerve and important for basement membrane assembly. CONCLUSIONS/SIGNIFICANCE: These results show that laminin alpha1LG domains and consequently their receptors have disparate functions in the neuromuscular system. Understanding these interactions could contribute to design and optimization of future medical treatment for MDC1A patients.

  20. Purification and properties of endo-alpha-1,3-glucanase from a Streptomyces chartreusis strain.

    Science.gov (United States)

    Takehara, T; Inoue, M; Morioka, T; Yokogawa, K

    1981-01-01

    An enzyme hydrolyzing the water-insoluble glucans produced from sucrose by Streptococcus mutans was purified from the culture concentrate of Streptomyces chartreusis strain F2 by ion-exchange chromatography on diethylaminoethyl cellulose and carboxymethyl cellulose columns and gel filtration on Bio-Gel A-1.5m. The purification achieved was 6.4-fold, with an overall yield of 27.3%. Electrophoresis of the purified enzyme protein gave a single band on a sodium dodecyl sulfate-polyacrylamide gel slab. Its molecular weight was estimated to be approximately 68,000, but there is a possibility that the native enzyme exists in an aggregated form or is an oligomer of the peptide subunits, have a molecular weight larger than 300,000. The pH optimum of the enzyme was 5.5 to 6.0, and its temperature optimum was 55 degrees C. The enzyme lost activity on heating at 65 degrees C for 10 min. The enzyme activity was completely inhibited by the presence of 1 mM Mn2+, Hg2+, Cu2+, Ag2+, or Merthiolate. The Km value for the water-insoluble glucan of S. mutans OMZ176 was an amount of glucan equivalent to 1.54 mM glucose, i.e., 0.89 mM in terms of the alpha-1,3-linked glucose residue. The purified enzyme was specific for glucans containing an alpha-1,3-glucosidic linkage as the major bond. The enzyme hydrolyzed the S. mutans water-insoluble glucans endolytically, and the products were oligosaccharides. These results indicate that the enzyme elaborated by S. chartreusis strain F2 is an endo-alpha-1,3-glucanase (EC 3.2.1.59). Images PMID:7462159

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

    Science.gov (United States)

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

    2014-02-01

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

  2. Renal and cardiac function during alpha1-beta-blockade in congestive heart failure

    DEFF Research Database (Denmark)

    Heitmann, M; Davidsen, U; Stokholm, K H;

    2002-01-01

    The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control...... of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function....

  3. Identification of the bovine $\\alpha$1-acid glycoprotein in colostrum and milk

    OpenAIRE

    Ceciliani, Fabrizio; Pocacqua, Vanessa; Provasi, Elena; Comunian, Claudio; Bertolini, Alessandra; Bronzo, Valerio; Moroni, Paolo; Sartorelli, Paola

    2005-01-01

    International audience $\\alpha$1-acid glycoprotein (AGP) is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. This paper presents the detection of bovine AGP (boAGP) in mammary secretions (colostrum and milk) and mammary gland tissue. Bovine AGP was detected by Western blotting in all the samples analysed, and could be quantified in colostrum at 162 (± 63.7) $\\mu$g/mL and 114.5 (...

  4. Induction of liver alpha-1 acid glycoprotein gene expression involves both positive and negative transcription factors.

    OpenAIRE

    Y. M. Lee; Tsai, W H; Lai, M Y; Chen, D S; Lee, S. C.

    1993-01-01

    Expression of the alpha-1 acid glycoprotein (AGP) gene is liver specific and acute phase responsive. Within the 180-bp region of the AGP promoter, at least five cis elements have been found to interact with trans-acting factors. Four of these elements (A, C, D, and E) interacted with AGP/EBP, a liver-enriched transcription factor, as shown by footprinting analysis and by an anti-AGP/EBP antibody-induced supershift in a gel retardation assay. Modification of these sites by site-directed mutage...

  5. Cooley's Anemia Foundation

    Science.gov (United States)

    Cooley's Anemia Foundation Leading the Fight against Thalassemia About Us Mission/Purpose History About Thomas Benton Cooley Medical Research ... Gabriella was diagnosed with thalassemia, and the Cooley’s Anemia Foundation continues to play an almost-daily role ...

  6. The Monopod Bucket Foundation

    DEFF Research Database (Denmark)

    Bakmar, Christian LeBlanc; Ahle, Kim; Nielsen, Søren A.;

    2009-01-01

    Following the successful installation of a prototype of a monopod bucket foundation, also called a “monopod suction caisson”, at Horns Rev 2 Offshore Wind Farm, Denmark, in 2009, DONG Energy is currently developing a commercialization strategy. The monopod bucket foundation is a promising foundat......, further research, development and prototype testing are required, before the monopod bucket foundation can be commercialized.......Following the successful installation of a prototype of a monopod bucket foundation, also called a “monopod suction caisson”, at Horns Rev 2 Offshore Wind Farm, Denmark, in 2009, DONG Energy is currently developing a commercialization strategy. The monopod bucket foundation is a promising...... foundation concept for offshore wind turbines and can be installed using suction assisted penetration, combined with other installation methods. This selfinstalling foundation concept, may avoid the use of expensive jack-ups and scour protection, and thus significantly reduces installation costs. However...

  7. American Vitiligo Research Foundation

    Science.gov (United States)

    ... life can acquire vitiligo Welcome to The American Vitiligo Foundation "Embracing Diversity" bracelets are available to help ... animal testing. Please Visit Our Donations Page American Vitiligo Research Foundation "We Walk By Faith, Not By ...

  8. Toxicology Education Foundation

    Science.gov (United States)

    ... bodies and our world. Welcome to the Toxicology Education Foundation! Our mission is to enhance public understanding ... TEF In the Classroom Our Goal The Toxicology Education Foundation seeks to help build the public's understanding ...

  9. Robert Wood Johnson Foundation

    Science.gov (United States)

    Robert Wood Johnson Foundation Search How We Work Our Focus Areas About RWJF Search Menu How We ... lives. Learn more For Grantees and Grantseekers The Robert Wood Johnson Foundation supports a wide array of ...

  10. Pulmonary Fibrosis Foundation

    Science.gov (United States)

    ... the most current news and updates from the Pulmonary Fibrosis Foundation. Life with PF Education & Support About PF ... open ! JOIN NOW We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources ...

  11. Cloning and comparative analysis of gene structure in promoter site of alpha-s1 casein gene in Naeinian goat and sheep

    Directory of Open Access Journals (Sweden)

    Mojtaba Najafi

    2014-12-01

    Full Text Available The 5′ end or alpha-S1 casein promoter has a significant role in milk protein gene expression. The understanding of the translation process of alpha-S1 casein mutants will provide us an opportunity to make the best selection in livestock providing more proteins in milk. Blood samples were taken from three hundred of Naeinian goats and sheep, and DNA extraction was done using modified salting out method. Polymerase chain reactions (PCR were carried out using a specific primer pairs for amplification a fragment of 1133 bp from part of 5′-UTR and exon 1 of alpha s1 casein gene. The AluI and HinfI restriction enzyme treatment of all samples provided the same homozygous AA genotype in both species. Subsequently, one sample of each species was selected and cloned, and the final sequences were analyzed by BioEdit, CLC genomic, Mega4 and DNASIS MAX software. Several polymorphisms are recognized between Naeinian goat and sheep that are presented on motif sites. In this research, the interested location, including exon I and a part of 5′, was analyzed, and genetic element comparisons were done between Naeinian goat and sheep. The number and location of probable binding sites can have a crucial role as a result of antagonistic and synergistic effects on gene regulation activities.

  12. Time course and extent of alpha 1-adrenoceptor density changes in rat heart after beta-adrenoceptor blockade.

    OpenAIRE

    Steinkraus, V.; Nose, M; H. Scholz; Thormählen, K.

    1989-01-01

    1. It has been suggested that impaired beta-adrenoceptor stimulation is a condition under which the functional role of cardiac alpha 1-adrenoceptors is enhanced. We therefore investigated the extent and time course of changes in alpha 1-adrenoceptor characteristics after chronic treatment with the beta-adrenoceptor blocker propranolol in rat heart. For comparison beta-adrenoceptors were also studied. The mechanism of the changes in adrenoceptor density was investigated with cycloheximide, an ...

  13. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

    OpenAIRE

    Glina, F.P.; Castro, P.M.V.; Monteiro, G.G.R.; G.C. Del Guerra; S Glina; M. Mazzurana; Bernardo, W.M.

    2015-01-01

    Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of alpha-1 ad...

  14. 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. ...

  15. 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

  16. Elevated levels of serum antibodies against alpha-1, 6-glucan in patients with systemic lupus erythematosus or rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    Hui Dai; Xiao-Ming Gao

    2011-01-01

    This study was undertaken to investigate whether levels of anti-alpha-1,6-glucan antibodies in human sera correlate with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE).Serum samples were collected from patients with SLE (n =30),RA (n =30) and healthy adult volunteers.IgG,IgA and IgM levels against alpha-1,6-glucan were measured using enzyme linked immunosorbent assays.Anti-alpha-1,6-glucan IgG prevalence was raised in patients with active SLE (73.3%)and RA (60%) compared with healthy controls (13.3%).Strong correlation between anti-alpha-1,6-glucan-IgG levels and anti-perinuclear factor (r =0.642; p< 0.05) in RA patients or anti-nuclear antibodies (r =0.675; p < 0.05)in SLE patients was observed.No significant differences in anti-alpha-1,6-glucan-lgA or-lgM levels were noted between different groups.We conclude that anti-alpha1,6-glucan-lgG levels were significantly elevated in patients with SLE or RA and positively correlated with disease activity.

  17. Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.

    Directory of Open Access Journals (Sweden)

    Katrin Wenzel

    Full Text Available BACKGROUND: Agonistic autoantibodies to the alpha(1-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A-adrenergic receptor and maintained them for one year. Alpha(1A-adrenergic antibodies (alpha(1A-AR-AB were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min. Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A-AR-AB could contribute to cardiovascular endorgan damage.

  18. Alpha1-acid glycoprotein post-translational modifications: a comparative two dimensional electrophoresis based analysis

    Directory of Open Access Journals (Sweden)

    P. Roncada

    2010-04-01

    Full Text Available Alpha1-acid glycoprotein (AGP is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. A proteomic approach based on two dimensional electrophoresis, immunoblotting and staining of 2DE gels with dyes specific for post-translational modifications (PTMs such as glycosylation and phosphorylation has been used to evaluate the differential interspecific protein expression of AGP purified from human, bovine and ovine sera. By means of these techniques, several isoforms have been identified in the investigated species: they have been found to change both with regard to the number of isoforms expressed under physiological condition and with regard to the quality of PTMs (i.e. different oligosaccharidic chains, presence/absence of phosphorilations. In particular, it is suggested that bovine serum AGP may have one of the most complex pattern of PTMs among serum proteins of mammals studied so far.

  19. Activity of alpha-1, 4-glucosidase in furazolidone-induced glycogenosis.

    Science.gov (United States)

    Czarnecki, C M; Salam, A; Caldwell, R; Jankus, E F

    1978-01-01

    Furazolidone (FZ) at 700 and 800 p.p.m. was added to feed mixtures fed turkey poults two and three weeks posthatching, respectively, to induce acute experimental cardiomyopathy. Poults in the control pen received the same ration but without FZ. From EKG data obtained at 2, 4, and 5 weeks of age, control unaffected and experimental affected poults were selected for sacrifice. Poults were sacrificed by cervical dislocation and appropriate samples of hepatic tissue were removed for assays of activity of alpha-1, 4-glucosidase. Results indicate that enzyme activity in affected FZ-treated poults is similar to that in unaffected control poults. Lack of significant differences in activity of this lysosomal enzyme suggests that FZ-induced glycogenosis may be related to the adult form of idiopathic generalized glucogenosis, the etiology of which remains unidentified. PMID:353772

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    James Patrick Chambers

    2011-12-01

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

  2. 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.

  3. Ligand-specific conformational changes in the alpha1 glycine receptor ligand-binding domain

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Lynch, Joseph W

    2009-01-01

    indicate that channel opening is accompanied by conformational rearrangements in both beta-sheets. In an attempt to resolve ligand-dependent movements in the ligand-binding domain, we employed voltage-clamp fluorometry on alpha1 glycine receptors to compare changes mediated by the agonist, glycine...... in the inner beta-sheet and pre-M1 domain that may be important for activation, desensitization, or both. In contrast, most labeled residues in loops C and F yielded fluorescence changes identical in magnitude for glycine and strychnine. A notable exception was H201C in loop C. This labeled residue responded...... differently to glycine and strychnine, thus underlining the importance of loop C in ligand discrimination. These results provide an important step toward mapping the domains crucial for ligand discrimination in the ligand-binding domain of glycine receptors and possibly other Cys loop receptors....

  4. 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

  5. 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

  6. Foundations for Critical Thinking

    Science.gov (United States)

    Bers, Trudy; Chun, Marc; Daly, William T.; Harrington, Christine; Tobolowsky, Barbara F.

    2015-01-01

    "Foundations for Critical Thinking" explores the landscape of critical-thinking skill development and pedagogy through foundational chapters and institutional case studies involving a range of students in diverse settings. By establishing a link between active learning and improved critical thinking, this resource encourages all higher…

  7. Modelling Foundations and Applications

    DEFF Research Database (Denmark)

    This book constitutes the refereed proceedings of the 8th European Conference on Modelling Foundations and Applications, held in Kgs. Lyngby, Denmark, in July 2012. The 20 revised full foundations track papers and 10 revised full applications track papers presented were carefully reviewed and sel...

  8. Functional characterisation of the human alpha1 glycine receptor in a fluorescence-based membrane potential assay

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Kristiansen, Uffe

    2004-01-01

    In the present study, we have created a stable HEK293 cell line expressing the human homomeric alpha1 glycine receptor (GlyR) and characterised its functional pharmacology in a conventional patch-clamp assay and in the FLIPR Membrane Potential (FMP) assay, a fluorescence-based high throughput...... and RU 5135>strychnine>brucine>PMBA=picrotoxin>atropine for the antagonists. The actions of three allosteric modulators at the alpha1 GlyR cell line were also characterised in the FMP assay. Micromolar concentrations of Zn2+ inhibited alpha1 GlyR signalling but in contrast to previous reports the metal...... not be suited for sophisticated studies of GlyR pharmacology and kinetics. However, the assay offers several advantages in studies of ligand-receptor interactions. Furthermore, the assay could be highly useful in the search for structurally novel ligands acting at GlyRs....

  9. Triple helix formation with the promoter of human alpha1(I) procollagen gene by an antiparallel triplex-forming oligodeoxyribonucleotide.

    OpenAIRE

    Nakanishi, M.; K. T. Weber; Guntaka, R V

    1998-01-01

    The promoters of alpha1(I) procollagen genes of vertebrates contain two contiguous stretches of polypyrimidine/polypurine sequences, referred to as C1 (-140 to -170) and C2 (-171 to -200). Antiparallel triplex-forming upstream oligonucleotides form efficient triplexes with C1. The C1 tract of human differs from rodent alpha1(I) promoters by 7 nt which are mainly A-->G transitions. Human triplex-forming oligodeoxyribonucleotide (TFO) formed stable triplexes efficiently with a K d of approximat...

  10. 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

  11. Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus.

    Science.gov (United States)

    Elshikha, Ahmed S; Lu, Yuanqing; Chen, Mong-Jen; Akbar, Mohammad; Zeumer, Leilani; Ritter, Andrea; Elghamry, Hanaa; Mahdi, Mahmoud A; Morel, Laurence; Song, Sihong

    2016-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder with a worldwide distribution and considerable mortality and morbidity. Although the pathogenesis of this disease remains elusive, over-reactive dendritic cells (DCs) play a critical role in the disease development. It has been shown that human alpha-1 antitrypsin (hAAT) has protective effects in type 1 diabetes and rheumatoid arthritis mouse models. In the present study, we tested the effect of AAT on DC differentiation and functions, as well as its protective effect in a lupus-prone mouse model. We showed that hAAT treatment significantly inhibited LPS (TLR4 agonist) and CpG (TLR9 agonist) -induced bone-marrow (BM)-derived conventional and plasmacytoid DC (cDC and pDC) activation and reduced the production of inflammatory cytokines including IFN-I, TNF-α and IL-1β. In MRL/lpr mice, hAAT treatment significantly reduced BM-derived DC differentiation, serum autoantibody levels, and importantly attenuated renal pathology. Our results for the first time demonstrate that hAAT inhibits DC activation and function, and it also attenuates autoimmunity and renal damage in the MRL/lpr lupus model. These results imply that hAAT has a therapeutic potential for the treatment of SLE in humans. PMID:27232337

  12. Alpha1 receptor coupling events initiated by methoxy-substituted tolazoline partial agonists

    International Nuclear Information System (INIS)

    A series of mono- and dimethyoxy substituted tolazoline derivatives, known to be partial agonists at the alpha1 receptor, were compared with the α1 selective full agonist phenylephrine (PE) on isolated strips of rabbit aorta Agonist activity was evaluated in contraction, 45Ca influx, 45Ca efflux, and 32P-Phospholipid labelling studies. Maximum contractile responses for the 2-, 3-, and 3, 5- methoxy substituted tolazoline derivatives (10-5M) were 53.8, 67.6 and 99.7% of the PE (10-5M) response respectively. These same partial agonists caused a stimulation of 45Ca influx to the extent of 64, 86, and 95% of the PE response respectively. In 45Ca efflux studies, (a measure of the intracellular Ca+2 release) the tolazolines caused: 30%, 63%, and 78% of the PE stimulated level. 32P-Phosphatidic acid (PA) labelling was measured as an index of PI turnover after α1 receptor stimulation. Compared to PE, the 2-, 3-, and 3,5- methoxy substituted tolazoline derivatives caused 22, 46, and 72% PA labelling. The above values are all in reasonable accord with the rank order or agonist activity shown in maximum contractile responses. The results of this investigation suggest that partial agonists stimulate α receptor coupling events at a level which is quantitatively comparable to their potencies in causing contraction of arterial smooth muscle

  13. 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.

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

    Science.gov (United States)

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

    2015-05-01

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

  15. 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.

  16. 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.

  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. 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.

  19. 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.

  20. 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

  1. Collagen Type XI Alpha 1 Expression in Intraductal Papillomas Predicts Malignant Recurrence

    Directory of Open Access Journals (Sweden)

    Javier Freire

    2015-01-01

    Full Text Available Despite the progress achieved in the treatment of breast cancer, there are still many unsolved clinical issues, being the diagnosis, prognosis, and treatment of papillary diseases, one of the highest challenges. Because of its unpredictable clinical behavior, treatment of intraductal papilloma has generated a great controversy. Even though considered as a benign lesion, it presents high rate of malignant recurrence. This is the reason why there are clinicians supporting a complete excision of the lesion, while others support an only expectant follow-up. Previous results of our group suggested that procollagen 11 alpha 1 (pro-COL11A1 expression correlates with infiltrating phenotype in breast lesions. We analyzed the correlation between expression of pro-COL11A1 in intraductal papilloma and their risk of malignant recurrence. Immunohistochemistry of pro-COL11A1 was performed in 62 samples of intraductal papilloma. Ten out 11 cases relapsed as carcinoma presents positive staining for COL11A1, while just 17 out of 51 cases with benign behaviour present immunostaining. There were significant differences (P<0.0001 when comparing patients with malignant recurrence versus nonmalignant relapse patients. These data suggest that pro-COL11A1 expression is a highly sensitive biomarker to predict malignant relapse of intraductal papilloma and it can be used as indicative factor for prevention programs.

  2. Collagen type I alpha 1 gene polymorphism in premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Vujović Svetlana

    2013-01-01

    Full Text Available Introduction. Premature ovarian failure (POF is characterized by amenorrhea, hypergonadotropism and hypoestrogenism in women bellow 40 years. Osteoporosis is one of the late complications of POF. Objective. To correlate collagen type I alpha1 (COLIA1 gene polymorphism with bone mineral density (BMD in women with POF. Methods. We determined the COLIA1 genotypes SS, Ss, ss in 66 women with POF. Single nucleotide polymorphism (G to T substitution within the Sp 1-binding site in the first intron of the COLIA1 gene was assessed by polymerase chain reaction (PCR followed by single-stranded conformation polymorphism (SSCP analysis. Bone mineral density (BMD was measured at the lumbar spine region by dual X-ray absorptiometry. Statistics: Kruskal-Wallis ANOVA, Chisquare test, Spearman correlation test. Results. The relative distribution of COLIA1 genotype alleles was SS - 54.4%, Ss - 41.0% and ss - 4.5%. No significant differences were found between genotype groups in body mass index, age, duration of amenorrhea or BMD. A significant positive correlation was observed between BMI and parity. Conclusion. The COLIA1 gene is just one of many genes influencing bone characteristics. It may act as a marker for differences in bone quantity and quality, bone fragility and accelerated bone loss in older women. However, in young women with POF, COLIA1 cannot identify those at higher risk for osteoporosis. [Projekat Ministarstva nauke Republike Srbije, br. ON 173056

  3. 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.

  4. Alpha (1,2)-fucosyltransferase M307A polymorphism improves piglet survival.

    Science.gov (United States)

    Kim, Kyungtae; Nguyen, Dinh Truong; Choi, Minkyung; Kim, Jin-Hoi; Seo, Han Geuk; Dadi, Hailu; Cha, Se-Yeoun; Seo, Kunho; Lee, Yun-Mi; Kim, Jong-Joo; Park, Chankyu

    2013-01-01

    To confirm the beneficial effects of alpha (1,2)-fucosyltransferase (FUT1) M307 (A) on piglet survival on commercial farms, we performed PCR-RFLP analysis of FUT1 M307 in successfully marketed (n = 245) and disease affected/deceased pigs during weaning (n = 252) at a commercial farm. We also evaluated the FUT1 genotypes of 190 healthy pigs from three different genetic backgrounds. The distribution of genotypes differed between the successfully marketed and disease affected/deceased pig groups. The frequency of the A allele, associated with resistance to edema and post-weaning diarrhea, was higher in the post-weaning survival group (0.21) than in the non-survival group (0.16, P piglet survival between AA and GG genotypes was 1.98; thus, piglet survival for individuals with the AA genotype was almost two-fold greater than for GG individuals. The FUT1 gene polymorphism can be used as an effective marker for selection programs to improve post-weaning piglet survival.

  5. Cerebral artery alpha-1 AR subtypes: high altitude long-term acclimatization responses.

    Directory of Open Access Journals (Sweden)

    Ravi Goyal

    Full Text Available In response to hypoxia and other stress, the sympathetic (adrenergic nervous system regulates arterial contractility and blood flow, partly through differential activities of the alpha1 (α1 - adrenergic receptor (AR subtypes (α1A-, α1B-, and α1D-AR. Thus, we tested the hypothesis that with acclimatization to long-term hypoxia (LTH, contractility of middle cerebral arteries (MCA is regulated by changes in expression and activation of the specific α1-AR subtypes. We conducted experiments in MCA from adult normoxic sheep maintained near sea level (300 m and those exposed to LTH (110 days at 3801 m. Following acclimatization to LTH, ovine MCA showed a 20% reduction (n = 5; P<0.05 in the maximum tension achieved by 10-5 M phenylephrine (PHE. LTH-acclimatized cerebral arteries also demonstrated a statistically significant (P<0.05 inhibition of PHE-induced contractility in the presence of specific α1-AR subtype antagonists. Importantly, compared to normoxic vessels, there was significantly greater (P<0.05 α1B-AR subtype mRNA and protein levels in LTH acclimatized MCA. Also, our results demonstrate that extracellular regulated kinase 1 and 2 (ERK1/2-mediated negative feedback regulation of PHE-induced contractility is modulated by α1B-AR subtype. Overall, in ovine MCA, LTH produces profound effects on α1-AR subtype expression and function.

  6. Collagen Type XI Alpha 1 Expression in Intraductal Papillomas Predicts Malignant Recurrence

    Science.gov (United States)

    Freire, Javier; García-Berbel, Lucia; García-Berbel, Pilar; Pereda, Saray; Azueta, Ainara; García-Arranz, Pilar; De Juan, Ana; Vega, Alfonso; Hens, Ángela; Enguita, Ana; Muñoz-Cacho, Pedro; Gómez-Román, Javier

    2015-01-01

    Despite the progress achieved in the treatment of breast cancer, there are still many unsolved clinical issues, being the diagnosis, prognosis, and treatment of papillary diseases, one of the highest challenges. Because of its unpredictable clinical behavior, treatment of intraductal papilloma has generated a great controversy. Even though considered as a benign lesion, it presents high rate of malignant recurrence. This is the reason why there are clinicians supporting a complete excision of the lesion, while others support an only expectant follow-up. Previous results of our group suggested that procollagen 11 alpha 1 (pro-COL11A1) expression correlates with infiltrating phenotype in breast lesions. We analyzed the correlation between expression of pro-COL11A1 in intraductal papilloma and their risk of malignant recurrence. Immunohistochemistry of pro-COL11A1 was performed in 62 samples of intraductal papilloma. Ten out 11 cases relapsed as carcinoma presents positive staining for COL11A1, while just 17 out of 51 cases with benign behaviour present immunostaining. There were significant differences (P < 0.0001) when comparing patients with malignant recurrence versus nonmalignant relapse patients. These data suggest that pro-COL11A1 expression is a highly sensitive biomarker to predict malignant relapse of intraductal papilloma and it can be used as indicative factor for prevention programs. PMID:26448946

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Utility of thymosin alpha-1 (Zadaxin) as a co-adjuvant in influenza vaccines: a review.

    Science.gov (United States)

    Panatto, D; Amicizia, D; Lai, P L; Camerini, R; De Rosa, A; Gasparini, R

    2011-09-01

    Influenza constitutes a serious problem for healthcare and social services worldwide, owing to its pattern and the severity of its complications in some categories of subjects at risk, such as the elderly and immunocompromised individuals. The only really effective means of combating influenza is vaccination. The elderly and immunocompromised subjects are refractory or low responders to vaccination. The need for ever more immunogenic and efficacious influenza vaccines, especially for subjects at risk, has prompted the development of adjuvated vaccines. With a view to enhancing the immune response in the elderly and in subjects at risk, the possibility of co-administering immunostimulants as Thymosin alpha-1 (Talpha1) with influenza vaccines has been investigated. Talpha1 is a biologically active peptide made up of 28 amino acids that can enhance T-cells, dendritic cell and antibody responses, modulate cytokines and chemokines production. Several studies were conducted and showed that Talpha1 ameliorate the performanc of influenza vaccination in elderly and subjects at risk. Although further studies on co-adjuvants are necessary, the future prospects of producing ever more efficacious influenza vaccines appear very promising.

  13. Children's Cardiomyopathy Foundation

    Science.gov (United States)

    Search The Children's Cardiomyopathy Foundation (CCF) is a national, non-profit organization focused on pediatric cardiomyopathy, a chronic disease of the heart muscle. CCF is dedicated to accelerating the search for ...

  14. Melanoma International Foundation

    Science.gov (United States)

    ... 501(c)(3) charity, also registered as a non-profit charity in the state of Pennsylvania, certificate #29498 © 2013 Melanoma International Foundation. All Rights Reserved. Privacy Policy | Terms of Use ...

  15. Restless Legs Syndrome Foundation

    Science.gov (United States)

    ... Into Relieved Are you experiencing symptoms linked to restless legs syndrome (RLS)? Find tools and support to help get ... I couldn’t sleep. Fortunately, I found the Restless Legs Syndrome Foundation and learned what type of doctor to ...

  16. Children's Brain Tumor Foundation

    Science.gov (United States)

    ... Become a monthly donor Volunteer Support LIMA Cares Sponsored by Jenna's Rainbow Foundation Jenna's Corner Online Community Username Password Not a member yet? Join Now Forgot password? CBTF Blog How do you all feel?? By: Tom | Sunday, ...

  17. Hepatitis B Foundation

    Science.gov (United States)

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 10 Other Languages . Resource Video See ...

  18. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... to make progress in “immunogenomics” Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  19. National Fragile X Foundation

    Science.gov (United States)

    ... Anthology Advocacy National Fragile X Foundation Advocacy Day STAR: Local Advocacy Agenda and Accomplishments Community Events International ... Feeding and Fragile X Toilet Training the Older Child Oppositional or Merely Anxious? Public or Private? Managing ...

  20. Foundation for Sarcoidosis Research

    Science.gov (United States)

    ... Clinical Trials Fail: FSR’s New Initiative to Bridge Gap between Industry Leaders, Researchers, and Patients Guest post ... 1 2 3 … 10 Next → Foundation for Sarcoidosis Research 1820 W. Webster Ave Suite 304 Chicago, Illinois ...

  1. Kessler Foundation Research Center

    Science.gov (United States)

    ... download directions in PDF format >> Map it with Google Maps Our other location 1199 Pleasant Valley Way West ... download directions in PDF format >> Map it with Google Maps email us @ info@kesslerfoundation.org Kessler Foundation 2015 © | ...

  2. Cleft Palate Foundation

    Science.gov (United States)

    ... Spanish , and Mandarin ! Information on Cleft Lip and Palate Our booklets and factsheets address a variety of ... Bear. –Paige with her Cleftline™ teddy bear– Cleft Palate Foundation 1504 East Franklin Street, Suite 102 Chapel ...

  3. The foundations of statistics

    CERN Document Server

    Savage, Leonard J

    1972-01-01

    Classic analysis of the foundations of statistics and development of personal probability, one of the greatest controversies in modern statistical thought. Revised edition. Calculus, probability, statistics, and Boolean algebra are recommended.

  4. National Psoriasis Foundation

    Science.gov (United States)

    ... handle bullies in the classroom. Previous Next National Psoriasis Foundation provides you with the help you need to best manage your psoriasis or psoriatic arthritis, while promoting research to find ...

  5. Morris Animal Foundation

    Science.gov (United States)

    ... the transmission of serious illnesses. Read more » Morris Animal Foundation Receives $750,000 Grant for Cancer Studies. ... Give Partners Become a Partner Meet Our Partners Animal Lovers Our Work Ways to Give Pet Health ...

  6. Mesothelioma Applied Research Foundation

    Science.gov (United States)

    ... Percentage Donations Tribute Wall Other Giving/Fundraising Opportunities Bitcoin Donation Form FAQs Help us raise awareness and ... Percentage Donations Tribute Wall Other Giving/Fundraising Opportunities Bitcoin Donation Form FAQs © 2013 Mesothelioma Applied Research Foundation, ...

  7. Prostate Cancer Foundation

    Science.gov (United States)

    ... P 2 rovocative Questions PCCTC Scientific Retreat Coffey-Holden Research News Faces of Prostate Cancer [4] Survivors ... Foundation News The Prostate Cancer Foundation’s 2016 Coffey-Holden Prostate Cancer Academy Meeting accelerates advances in the ...

  8. National Emphysema Foundation

    Science.gov (United States)

    ... August 15, 2016 A recent study finds that music therapy benefits chronic obstructive p... July 04, 2016 A new recommendation from US Preventive Services Task Force is encoura... Copyright © 2016, National Emphysema Foundation, all rights reserved home ...

  9. Identification of alpha-1 acid glycoprotein (AGP) as a potential marker of impaired growth in the newborn piglet

    Science.gov (United States)

    Two studies were conducted to investigate the relationship between the circulating levels of the acute phase proteins haptoglobin (HP) and alpha 1 acid glycoprotein (AGP) and growth potential in neonatal pigs. In runts, the circulating level of AGP, but not HP in serum of newborn piglets was higher...

  10. Plasma levels of alpha-1-antichymotrypsin are elevated in patients with chronic heart failure, but are of limited prognostic value

    NARCIS (Netherlands)

    Lok, S. I.; Lok, D. J.; van der Weide, P.; Winkens, B.; de la Porte, P. W. Bruggink-Andre; Doevendans, P. A.; de Weger, R. A.; van der Meer, P.; de Jonge, N.

    2014-01-01

    Background There is increasing interest in utilising novel markers of cardiovascular disease risk in patients with chronic heart failure (HF). Recently, it was shown that alpha-1-antichymotrypsin (ACT), an acute-phase protein and major inhibitor of cathpesin G, plays a role in the pathophysiology of

  11. 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.

  12. Corticosteroid regulation of Na(+),K(+)-ATPase alpha1-isoform expression in Atlantic salmon gill during smolt development

    DEFF Research Database (Denmark)

    Kiilerich, Pia; Pedersen, Sara H; Kristiansen, Karsten;

    2011-01-01

    cortisol had an enhanced capacity to stimulate alpha-1b as compared to DOC. Even though there was no demonstrable change in cortisol or DOC sensitivity in the gill, the magnitude of the hormonal effects were seasonally dependent. This is the first report of DOC-induced effects on osmoregulatory targets...

  13. Triiodothyronine causes rapid reversal of alpha 1/cyclic adenosine monophosphate synergism on brown adipocyte respiration and type II deiodinase activity.

    Science.gov (United States)

    Noronha, M; Raasmaja, A; Moolten, N; Larsen, P R

    1991-12-01

    Previous studies have shown that thyroid status affects the response of brown adipose tissue (BAT) to the sympathetic nervous system. For example, hypothyroidism is associated with the development of a marked synergism between alpha 1- and beta-adrenergic pathways to stimulate type II iodothyronine 5'-deiodinase activity. Hypothyroidism also attenuates the respiratory response (thermogenesis) of isolated brown adipocytes to norepinephrine. To explore the interactions of the sympathetic nervous system and thyroid status in these cells, we compared the thermogenic and 5'-deiodinase responses to adrenergic agonists in isolated brown adipocytes from hypothyroid rats during treatment with 3,5,3'-triiodothyronine (T3). The fivefold synergism of alpha 1- and beta-adrenergic catecholamines to increase the deiodinase activity was progressively reduced, reaching a control euthyroid value of unity after 5 days of T3 treatment. Hypothyroidism reduced both the O2max (twofold to threefold) and increased the concentration of agonist required for 50% stimulation (10-fold) for both norepinephrine and forskolin. In hypothyroid cells, there was a twofold synergism between the alpha 1-agonist cirazoline and forskolin to increase respiration, which was blocked by prazosin and reproduced by the calcium ionophore, A23187. This synergistic effect of the alpha 1-agonist was lost within 2 days of T3 administration. These studies identify a second Ca(2+)-dependent intra-adrenergic synergism, which functions to ameliorate the reduced cyclic adenosine monophosphate (cAMP) responsiveness of the hypothyroid brown adipocyte. PMID:1683679

  14. Up-regulation of alpha1A-adrenoceptors in rat mesenteric artery involves intracellular signal pathways

    DEFF Research Database (Denmark)

    Cao, Yong-Xiao; Xu, Cang-Bao; Luo, Guo-Gang;

    2006-01-01

    The aim of the present study was to investigate if there is an altered expression of alpha-adrenoceptors during organ culture of rat mesenteric artery segments by using a sensitive pharmacological method and molecular biological techniques. Noradrenalin (NA) induced contraction via alpha1-adrenoc...

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  16. Foundations of measurement

    CERN Document Server

    Suppes, Patrick

    1989-01-01

    Foundations of Measurement offers the most coherently organized treatment of the topics and issues central to measurement. Much of the research involved has been scattered over several decades and a multitude of journals--available in many instances only to specialties. With the publication of Volumes two and three of this important work, Foundations of Measurement is the most comprehensive presentation in the area of measurement.

  17. Foundational aspects of security

    DEFF Research Database (Denmark)

    Chatzikokolakis, Konstantinos; Mödersheim, Sebastian Alexander; Palamidessi, Catuscia;

    2014-01-01

    This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security.......This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security....

  18. Expression of mRNAs coding for the alpha 1 chain of type XIII collagen in human fetal tissues: comparison with expression of mRNAs for collagen types I, II, and III

    OpenAIRE

    1989-01-01

    This paper describes the topographic distribution of the multiple mRNAs coding for a novel human short-chain collagen, the alpha 1 chain of type XIII collagen. To identify the tissues and cells expressing these mRNAs, human fetal tissues of 15-19 gestational wk were studied by Northern and in situ hybridizations. The distribution pattern of the type XIII collagen mRNAs was compared with that of fibrillar collagen types I, II, and III using specific human cDNA probes for each collagen type. No...

  19. Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors.

    Science.gov (United States)

    Dreiling, Michelle; Bischoff, Sabine; Schiffner, Rene; Rupprecht, Sven; Kiehntopf, Michael; Schubert, Harald; Witte, Otto W; Nathanielsz, Peter W; Schwab, Matthias; Rakers, Florian

    2016-09-01

    Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.

  20. Alpha-1 Antitrypsin is Markedly Decreased Following Pulmonary F. tularensis Challenge

    Science.gov (United States)

    Chambers, James P.; Yu, Jieh-Juen; Jupelli, Madhulika; Weintraub, Susan T.; Lopez-Ribot, Jose L.; Valdes, James J.; Arulanandam, Bernard P.

    2011-01-01

    Neutrophils form the first line of defense during infection and are indispensable in this function. The neutrophil elastase is a key effector molecule of the innate immune system with potent antimicrobial activity against Gram-negative bacteria, spirochaetes, and fungi. However, the release of neutrophil elastase during bacterial infection must be checked otherwise its release in the extracellular milieu will result in damage to surrounding tissues. Alpha-1 antitrypsin is a small glycoprotein clade A serpine serine protease inhibitor and has been shown to increase in humans following bacterial and viral infection. Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of tularemia. Type A strains are the most virulent with an infectious dose as low as 10 colony forming units and a mortality rate of 30–60% among untreated cases of pneumonic tularemia. We report here significant reduction of this major inhibitor of the neutrophil elastase in plasma of F. tularensis LVS and F. tularensis (type A) SCHU S4 infected animals following pulmonary challenge. Associated with an imbalance of protease–antiprotease function at the alveolar level in lungs of infected animals, increased elastase activity was observed in lung lavage fluids accompanied by decrease lung function, i.e., loss of lung elastance with concomitant increase of pulmonary hysteresivity. Consistent with a competent acute phase response following F. tularensis LVS and F. tularensis (type A) SCHU S4 pulmonary challenge and proposed up-regulation of plasma haptoglobin during the course of the acute phase reaction, haptoglobin was observed significantly increased. These data suggest that unchecked neutrophil serine protease activity may arise from F. tularensis targeted reduction of plasma α1-antitrysin promoting lung tissue damage facilitating increased dissemination of this bacterium in infected animals. PMID:22919586

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

    Directory of Open Access Journals (Sweden)

    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.

  2. CONSTITUTIONAL FOUNDATIONS OF JURISDICTION

    Directory of Open Access Journals (Sweden)

    Alexandre Jamal Batista

    2016-06-01

    Full Text Available At the current stage of our State of Law there is no way to separate the study of the civil procedural law from the Federal Constitution, especially the jurisdiction, because it is in the Constitution that there are the legitimizing foundations of the jurisdiction institute. In this article, we carry on about the constitutional foundations of jurisdiction, such as: the principle of natural justice, principle of access to justice, principle of impartiality, principle of publicity, principle of motivation and principle of submission to res judicata. The conclusion is, after all, that jurisdiction, as one of the bulwarks of the citizen, finds in the “Citizen Constitution” of 1988 its foundations and decisive bases.

  3. Structures of NodZ [alpha]1,6-fucosyltransferase in complex with GDP and GDP-fucose

    Energy Technology Data Exchange (ETDEWEB)

    Brzezinski, Krzysztof; Dauter, Zbigniew; Jaskolski, Mariusz (NCI); (Polish)

    2012-03-26

    Rhizobial NodZ {alpha}1,6-fucosyltransferase ({alpha}1,6-FucT) catalyzes the transfer of the fucose (Fuc) moiety from guanosine 5'-diphosphate-{beta}-L-fucose to the reducing end of the chitin oligosaccharide core during Nod-factor (NF) biosynthesis. NF is a key signaling molecule required for successful symbiosis with a legume host for atmospheric nitrogen fixation. To date, only two {alpha}1,6-FucT structures have been determined, both without any donor or acceptor molecule that could highlight the structural background of the catalytic mechanism. Here, the first crystal structures of {alpha}1,6-FucT in complex with its substrate GDP-Fuc and with GDP, which is a byproduct of the enzymatic reaction, are presented. The crystal of the complex with GDP-Fuc was obtained through soaking of native NodZ crystals with the ligand and its structure has been determined at 2.35 {angstrom} resolution. The fucose residue is exposed to solvent and is disordered. The enzyme-product complex crystal was obtained by cocrystallization with GDP and an acceptor molecule, penta-N-acetyl-L-glucosamine (penta-NAG). The structure has been determined at 1.98 {angstrom} resolution, showing that only the GDP molecule is present in the complex. In both structures the ligands are located in a cleft formed between the two domains of NodZ and extend towards the C-terminal domain, but their conformations differ significantly. The structures revealed that residues in three regions of the C-terminal domain, which are conserved among {alpha}1,2-, {alpha}1,6- and protein O-fucosyltransferases, are involved in interactions with the sugar-donor molecule. There is also an interaction with the side chain of Tyr45 in the N-terminal domain, which is very unusual for a GT-B-type glycosyltransferase. Only minor conformational changes of the protein backbone are observed upon ligand binding. The only exception is a movement of the loop located between strand {beta}C2 and helix {alpha}C3. In addition

  4. Foundations of predictive analytics

    CERN Document Server

    Wu, James

    2012-01-01

    Drawing on the authors' two decades of experience in applied modeling and data mining, Foundations of Predictive Analytics presents the fundamental background required for analyzing data and building models for many practical applications, such as consumer behavior modeling, risk and marketing analytics, and other areas. It also discusses a variety of practical topics that are frequently missing from similar texts. The book begins with the statistical and linear algebra/matrix foundation of modeling methods, from distributions to cumulant and copula functions to Cornish--Fisher expansion and o

  5. Buckling of Bucket Foundations

    DEFF Research Database (Denmark)

    Madsen, Søren; Andersen, Lars Vabbersgaard; Ibsen, Lars Bo

    2012-01-01

    In this paper, the risk of structural buckling during installation of large-diameter bucket foundations is addressed using numerical methods. Imperfect geometries are introduced based on the pre-buckling mode shapes from a linear Eigenvalue buckling analysis. Various imperfect geometries are intr......In this paper, the risk of structural buckling during installation of large-diameter bucket foundations is addressed using numerical methods. Imperfect geometries are introduced based on the pre-buckling mode shapes from a linear Eigenvalue buckling analysis. Various imperfect geometries...

  6. Optimization Foundations and Applications

    CERN Document Server

    Miller, H Ronald

    2011-01-01

    A thorough and highly accessible resource for analysts in a broad range of social sciences. Optimization: Foundations and Applications presents a series of approaches to the challenges faced by analysts who must find the best way to accomplish particular objectives, usually with the added complication of constraints on the available choices. Award-winning educator Ronald E. Miller provides detailed coverage of both classical, calculus-based approaches and newer, computer-based iterative methods. Dr. Miller lays a solid foundation for both linear and nonlinear models and quickly moves on to dis

  7. Professional Windows Workflow Foundation

    CERN Document Server

    Kitta, Todd

    2007-01-01

    If you want to gain the skills to build Windows Workflow Foundation solutions, then this is the book for you. It provides you with a clear, practical guide on how to develop workflow-based software and integrate it into existing technology landscapes. Throughout the pages, you'll also find numerous real-world examples and sample code that will help you to get started quickly.Each major area of Windows Workflow Foundation is explored in depth along with some of the fundamentals operations related to generic workflow applications. You'll also find detailed coverage on how to develop workflow in

  8. TCP/IP foundations

    CERN Document Server

    Blank, Andrew G

    2006-01-01

    The world of IT is always evolving, but in every area there are stable, core concepts that anyone just setting out needed to know last year, needs to know this year, and will still need to know next year. The purpose of the Foundations series is to identify these concepts and present them in a way that gives you the strongest possible starting point, no matter what your endeavor. TCP/IP Foundations provides essential knowledge about the two protocols that form the basis for the Internet, as well as many other networks. What you learn here will benefit you in the short term, as you acquire and

  9. Foundations of Risk Analysis

    CERN Document Server

    Aven, Terje

    2012-01-01

    Foundations of Risk Analysis presents the issues core to risk analysis - understanding what risk means, expressing risk, building risk models, addressing uncertainty, and applying probability models to real problems. The author provides the readers with the knowledge and basic thinking they require to successfully manage risk and uncertainty to support decision making. This updated edition reflects recent developments on risk and uncertainty concepts, representations and treatment. New material in Foundations of Risk Analysis includes:An up to date presentation of how to understand, define and

  10. The resistance of delayed xenograft rejection to alpha(1,3)-galactosyltransferase gene inactivation and CD4 depletion in a mouse-to-rat model

    DEFF Research Database (Denmark)

    Hansen, Alastair B; Kirkeby, Svend; Aasted, Bent;

    2003-01-01

    that the reaction between alpha1,3Gal epitopes on donor endothelial cells and recipient anti-alpha1,3Gal antibodies (Abs) may damage the graft during DXR. Recipient anti-alpha1,3Gal Abs are produced by CD4-dependent B cells. To test the above-mentioned hypothesis, hearts from alpha1,3Gal-free mice (GT-Ko mice......), generated by alpha1,3-galacto-syltransferase gene disruption, were transplanted to anti-alpha1,3Gal antibody-free Lew/Mol rats. This model consists of an alpha1,3Gal/alpha1,3Gal-antibody-free environment, eliminating a possible influence of this specific system on DXR. A subgroup of recipients were......,3-galactosyltransferase gene inactivation and CD4 depletion. However, other Galalpha 1 epitopes and antibodies may play a role during DXR. Further studies are needed to elucidate the precise pathways leading to DXR....

  11. Foundations of Corporate Governance

    OpenAIRE

    Volonté, Christophe

    2012-01-01

    This paper outlines the foundations of corporate governance. The discussion includes a review on the modern corporation, transaction costs theory, agency costs theory, legal investor protection, investor protection by corporate governance and its various mechanisms, as well as an overview of the determinants of corporate governance.

  12. Foundation Fighting Blindness

    Science.gov (United States)

    ... Boston VisionWalk Kick Off 8th Annual Central Ohio Golf For Sight Golf Classic San Antonio/Austin Chapter Speaker Series Presentations ... Foundation Fighting Blindness’ 2015 Annual Report. Read More Learn more about the latest retinal research news and ...

  13. Sjogren's Syndrome Foundation

    Science.gov (United States)

    ... on Twitter, YouTube, Facebook, and Linkedin! anxiety © 2016 Sjögren’s Syndrome Foundation, Inc. 6707 Democracy Blvd, Ste 325, Bethesda, MD 20817 (Privacy Policy) 1-800 475-6473 · 301 530-4415 (Fax)

  14. Foundations of factor analysis

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

    Introduction Factor Analysis and Structural Theories Brief History of Factor Analysis as a Linear Model Example of Factor AnalysisMathematical Foundations for Factor Analysis Introduction Scalar AlgebraVectorsMatrix AlgebraDeterminants Treatment of Variables as Vectors Maxima and Minima of FunctionsComposite Variables and Linear Transformations Introduction Composite Variables Unweighted Composite VariablesDifferentially Weighted Composites Matrix EquationsMulti

  15. Impedance of Bucket Foundations

    DEFF Research Database (Denmark)

    Andersen, Lars; Ibsen, Lars Bo; Liingaard, Morten

    2008-01-01

    solutions, finding that the present boundary-element-finite-element model provides accurate results. The influence of the soil properties as well as the skirt length of the foundation is analysed, and each dynamic stiffness component is computed as function of a non-dimensional frequency....

  16. Foundations for Farming Website

    OpenAIRE

    Foundations for Farming

    2011-01-01

    Metadata only record This website provides information on the activities and outcomes of Foundations for Farming, an international NGO dedicated to promoting Conservation Agriculture as a means of poverty reduction and food security. The organization currently works in Zimbabwe, South Africa, and Malawi, hosting training sessions and facilitating the dissemination of Conservation Agriculture ideologies and practices.

  17. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

    Science.gov (United States)

    Glina, F.P.; Castro, P.M.V.; Monteiro, G.G.R.; Guerra, G.C. Del; Glina, S.; Mazzurana, M.; Bernardo, W.M.

    2015-01-01

    ABSTRACT Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of alpha-1 adrenergic blockers as medical expulsive treatment in children with distal ureterolithiasis. Evidence Acquisition: An electronic literature search was performed using the MEDLINE, COCHRANE, and LILACS databases. We further searched manually the references of the primary studies. Searches were concluded on October 4th, 2014. Articles were selected, independently and in pairs, by the respective titles and summaries. Any divergence was resolved by consensus. Evidence Synthesis: Alpha-1 adrenergic antagonists increased the probability of calculus expulsion by 27% (NNT=4). Calculi smaller than 5mm, increased by 33% (NNT=3). Larger than 5mm, increased by 34% (NNT=3). Conclusion: Alpha-1 adrenergic blocker use is related with a greater incidence of expulsion of ureteral calculi, smaller or greater than 5mm, and fewer episodes of pain when compared to ibuprofen. However it is necessary larger samples to enhance the power analysis of the expulsion of ureteral calculi larger than 5mm and the episodes of pain. Patient Summary: This review analyzed the outcome of alpha adrenergic antagonist in children with ureteral calculi. We conclude that it is the best medicine for use, since it helps the expulsion of the stone. PMID:26717117

  18. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    F.P. Glina

    2015-12-01

    Full Text Available Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of alpha-1 adrenergic blockers as medical expulsive treatment in children with distal ureterolithiasis. Evidence Acquisition: An electronic literature search was performed using the MEDLINE, COCHRANE, and LILACS databases. We further searched manually the references of the primary studies. Searches were concluded on October 4th, 2014. Articles were selected, independently and in pairs, by the respective titles and summaries. Any divergence was resolved by consensus. Evidence Synthesis: Alpha-1 adrenergic antagonists increased the probability of calculus expulsion by 27% (NNT=4. Calculi smaller than 5mm, increased by 33% (NNT=3. Larger than 5mm, increased by 34% (NNT=3. Conclusion: Alpha-1 adrenergic blocker use is related with a greater incidence of expulsion of ureteral calculi, smaller or greater than 5mm, and fewer episodes of pain when compared to ibuprofen. However it is necessary larger samples to enhance the power analysis of the expulsion of ureteral calculi larger than 5mm and the episodes of pain. Patient Summary: This review analyzed the outcome of alpha adrenergic antagonist in children with ureteral calculi. We conclude that it is the best medicine for use, since it helps the expulsion of the stone.

  19. Exclusion of the alpha 1(II) collagen structural gene as the mutant locus in type II Ehlers-Danlos syndrome.

    OpenAIRE

    Wordsworth, P; Ogilvie, D.; Smith, R.; Sykes, B

    1985-01-01

    We have used a high frequency site polymorphism within the human pro-alpha 1(II) collagen gene (COL2A1) in order to examine the segregation of this gene within a large pedigree with type II Ehlers-Danlos syndrome (EDS). The EDS gene and the collagen gene segregate independently within the pedigree and therefore COL2A1 can be excluded as the mutant locus.

  20. The use of alpha-1 adrenergic blockers in children with distal ureterolithiasis: a systematic review and meta-analysis

    OpenAIRE

    Glina, F.P.; Castro, P.M.V.; Monteiro, G.G.R.; G.C. Del Guerra; S. Glina; M. Mazzurana; W.M. Bernardo

    2015-01-01

    ABSTRACT Introduction: Urinary lithiasis is the main urologic cause of emergency treatment in adult patient. In the past years, the incidence in children population has increased. However, literature about the use of alpha-1 adrenergic blockers in pediatric population with distal ureterolithiasis is still scarce. The drug acts by decreasing ureter contractions, especially in the distal portion, facilitating calculus expulsion. Objective: This review has the objective to evaluate the use of al...

  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. 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...

  3. Effects of jump training on procollagen alpha(1)(i) mRNA expression and its relationship with muscle collagen concentration.

    Science.gov (United States)

    Ducomps, Christophe; Larrouy, Dominique; Mairal, Aline; Doutreloux, Jean-Paul; Lebas, Francois; Mauriege, Pascale

    2004-04-01

    The aim of this study was to examine the effects of a prolonged high-intensity exercise, jumping, on procollagen alpha(1)(I) mRNA level and collagen concentration in different muscles of trained (T) and control (C) rabbits. Procollagen alpha(1)(I) mRNA expression was much higher (2.8 to 23.5 times) in semimembranosus proprius (SMP), a slow-twitch oxidative muscle, than in extensor digitorum longus (EDL), rectus femoris (RF), and psoas major (Psoas) muscles, both fast-twitch mixed and glycolytic, whatever group was considered (p < 0.001). Procollagen alpha(1)(I) mRNA level also decreased significantly between 50 and 140 days in all muscles (0.001< p < 0.01). However, mRNA levels were 16 to 97% greater at 140 days in all muscles of T animals compared to C ones (0.01< p <0.05). Collagen concentrations of EDL and RF muscles were also higher (14 to 19%) in T than in C rabbits at 90 and 140 days (0.001 < p < 0.05). In the whole sample, collagen concentration was negatively associated with the procollagen alpha(1)(I) mRNA level in EDL and RF muscles (- 0.49 < r < (- 0.44, p < 0.05), while being positively related to mRNA expression in SMP and Psoas muscles (0.65 < r < 0.85, p < 0.01). It is concluded that jump training clearly restricts the decrease of procollagen (I) mRNA level and probably affects collagen synthesis level. In trained rabbit muscles, the maintenance of a better synthesis level could partly explain the higher collagen concentrations found in EDL and RF at 140 days. Nevertheless, the collagen degradation process seems to play the main role in the increase of total collagen concentration with age in EDL and RF muscles. PMID:15064425

  4. 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

  5. Grouting for Pile Foundation Improvement

    OpenAIRE

    Van der Stoel, A.E.C.

    2001-01-01

    The aim of this research was to examine the use of grouting methods for pile foundation improvement, a generic term that is used here to define both foundation renovation (increasing the bearing capacity of a pile foundation that has insufficient bearing capacity) and foundation protection (safeguarding the piles of the foundation against possible damage resulting from underground construction activities in the vicinity). A full-scale test, of which the general set-up and consistency check ar...

  6. Noradrenaline acting on alpha1-adrenoceptor mediates REM sleep deprivation-induced increased membrane potential in rat brain synaptosomes.

    Science.gov (United States)

    Das, Gitanjali; Mallick, Birendra Nath

    2008-01-01

    We hypothesized that one of the functions of REM sleep is to maintain brain excitability and therefore, REM sleep deprivation is likely to modulate neuronal transmembrane potential; however, so far there was no direct evidence to support the claim. In this study a cationic dye, 3,3'-diethylthiacarbocyanine iodide was used to estimate the potential in synaptosomal samples prepared from control and REM sleep deprived rat brains. The activity of Na-K-ATPase that maintains the transmembrane potential was also estimated in the same sample. Further, the roles of noradrenaline and alpha1-adrenoceptor in mediating the responses were studied both in vivo as well as in vitro. Rats were REM sleep deprived for 4 days by the classical flower-pot method; large platform and recovery controls were carried out in addition to free-moving control. The fluorescence intensity increased in samples prepared from REM sleep deprived rat brain as compared to control, which reflected synaptosomal depolarization after deprivation. The Na-K-ATPase activity also increased in the same deprived sample. Furthermore, both the effects were mediated by noradrenaline acting on alpha1-adrenoceptors in the brain. This is the first direct evidence showing that REM sleep deprivation indeed increased neuronal depolarization, which is the likely cause for increased brain excitability, thus supporting our hypothesis and the effect was mediated by noradrenaline acting through the alpha1-adrenoceptor.

  7. Netherlands foundation for radioastronomy

    International Nuclear Information System (INIS)

    A report of the board is followed by departmental reports from the Westerbork Telescope Group, Dwingeloo Telescope Group, Computer Group, Laboratory and Central Technical Services, Astronomy Group, Administration of the Foundation/General Affairs and Personnel Council. Astronomical reports describe radio astronomical research carried out by the Foundation staff and at the Kapteyn Laboratory Groningen, Leiden Observatory, Utrecht Observatory and the Laboratorio di Radioastronomia Bologna, Italy. Progress in the extension of the synthesis radio telescope and investigations into the possibility of substantially increasing the SRT data rate for solar observations, are outlined. Appendices shows the organisational structure, the names of the employees, the operating budget, the observing facilities at Westerbork and Dwingeloo, and the publications and reports published in 1978 and related to observations made with these facilities. (C.F.)

  8. Foundation doctors’ induction experiences

    OpenAIRE

    Miles, Susan; Kellett, Joanne; Leinster, Sam J.

    2015-01-01

    Background It is well established that trainee doctors struggle with the transition from medical school to starting work and feel unprepared for many aspects of their new role. There is evidence that suitable induction experiences improve competence and confidence, but available data indicate that trainee doctors on the UK Foundation Programme are commonly not experiencing useful inductions. The aim of the reported research was to explore trainee doctors’ experiences with induction during the...

  9. Foundations of image science

    CERN Document Server

    Barrett, Harrison H

    2013-01-01

    Winner of the 2006 Joseph W. Goodman Book Writing Award! A comprehensive treatment of the principles, mathematics, and statistics of image science In today's visually oriented society, images play an important role in conveying messages. From seismic imaging to satellite images to medical images, our modern society would be lost without images to enhance our understanding of our health, our culture, and our world. Foundations of Image Science presents a comprehensive treatment of the principles, mathematics, and st

  10. Foundations for Intrusion Prevention

    OpenAIRE

    Alderman, Ian D.; Parter, David W.; Rubin, Shai; Vernon, Mary K.

    2004-01-01

    We propose an infrastructure that helps a system administrator to identify a newly published vulnerability on the site hosts and to evaluate the vulnerability’s threat with respect to the administrator’s security priorities. The infrastructure foundation is the vulnerability semantics, a small set of attributes for vulnerability definition. We demonstrate that with a few attributes it is possible to define the majority of the known vulnerabilities in a way that (i) facilitates ...

  11. Mathematical foundations of thermodynamics

    CERN Document Server

    Giles, R; Stark, M; Ulam, S

    2013-01-01

    Mathematical Foundations of Thermodynamics details the core concepts of the mathematical principles employed in thermodynamics. The book discusses the topics in a way that physical meanings are assigned to the theoretical terms. The coverage of the text includes the mechanical systems and adiabatic processes; topological considerations; and equilibrium states and potentials. The book also covers Galilean thermodynamics; symmetry in thermodynamics; and special relativistic thermodynamics. The book will be of great interest to practitioners and researchers of disciplines that deal with thermodyn

  12. Foundations of Inference

    OpenAIRE

    Kevin H. Knuth; John Skilling

    2012-01-01

    We present a simple and clear foundation for finite inference that unites and significantly extends the approaches of Kolmogorov and Cox. Our approach is based on quantifying lattices of logical statements in a way that satisfies general lattice symmetries. With other applications such as measure theory in mind, our derivations assume minimal symmetries, relying on neither negation nor continuity nor differentiability. Each relevant symmetry corresponds to an axiom of quantification, and thes...

  13. Foundations of Mathematics

    OpenAIRE

    Chaitin, G. J.

    2002-01-01

    This article discusses what can be proved about the foundations of mathematics using the notions of algorithm and information. The first part is retrospective, and presents a beautiful antique, Godel's proof, the first modern incompleteness theorem, Turing's halting problem, and a piece of postmodern metamathematics, the halting probability Omega. The second part looks forward to the new century and discusses the convergence of theoretical physics and theoretical computer science and hopes fo...

  14. Fractal Topology Foundations

    OpenAIRE

    Porchon, Helene

    2012-01-01

    In this paper, we introduce the foundation of a fractal topological space constructed via a family of nested topological spaces endowed with subspace topologies, where the number of topological spaces involved in this family is related to the appearance of new structures on it. The greater the number of topological spaces we use, the stronger the subspace topologies we obtain. The fractal manifold model is brought up as an illustration of space that is locally homeomorphic to the fractal topo...

  15. Wronski's Foundations of Mathematics.

    Science.gov (United States)

    Wagner, Roi

    2016-09-01

    Argument This paper reconstructs Wronski's philosophical foundations of mathematics. It uses his critique of Lagrange's algebraic analysis as a vignette to introduce the problems that he raised, and argues that these problems have not been properly appreciated by his contemporaries and subsequent commentators. The paper goes on to reconstruct Wronski's mathematical law of creation and his notions of theory and techne, in order to put his objections to Lagrange in their philosophical context. Finally, Wronski's proof of his universal law (the expansion of a given function by any series of functions) is reviewed in terms of the above reconstruction. I argue that Wronski's philosophical approach poses an alternative to the views of his contemporary mainstream mathematicians, which brings up the contingency of their choices, and bridges the foundational concerns of early modernity with those of the twentieth-century foundations crisis. I also argue that Wronski's views may be useful to contemporary philosophy of mathematical practice, if they are read against their metaphysical grain. PMID:27573997

  16. Wronski's Foundations of Mathematics.

    Science.gov (United States)

    Wagner, Roi

    2016-09-01

    Argument This paper reconstructs Wronski's philosophical foundations of mathematics. It uses his critique of Lagrange's algebraic analysis as a vignette to introduce the problems that he raised, and argues that these problems have not been properly appreciated by his contemporaries and subsequent commentators. The paper goes on to reconstruct Wronski's mathematical law of creation and his notions of theory and techne, in order to put his objections to Lagrange in their philosophical context. Finally, Wronski's proof of his universal law (the expansion of a given function by any series of functions) is reviewed in terms of the above reconstruction. I argue that Wronski's philosophical approach poses an alternative to the views of his contemporary mainstream mathematicians, which brings up the contingency of their choices, and bridges the foundational concerns of early modernity with those of the twentieth-century foundations crisis. I also argue that Wronski's views may be useful to contemporary philosophy of mathematical practice, if they are read against their metaphysical grain.

  17. Foundations of chaotic mixing.

    Science.gov (United States)

    Wiggins, Stephen; Ottino, Julio M

    2004-05-15

    The simplest mixing problem corresponds to the mixing of a fluid with itself; this case provides a foundation on which the subject rests. The objective here is to study mixing independently of the mechanisms used to create the motion and review elements of theory focusing mostly on mathematical foundations and minimal models. The flows under consideration will be of two types: two-dimensional (2D) 'blinking flows', or three-dimensional (3D) duct flows. Given that mixing in continuous 3D duct flows depends critically on cross-sectional mixing, and that many microfluidic applications involve continuous flows, we focus on the essential aspects of mixing in 2D flows, as they provide a foundation from which to base our understanding of more complex cases. The baker's transformation is taken as the centrepiece for describing the dynamical systems framework. In particular, a hierarchy of characterizations of mixing exist, Bernoulli --> mixing --> ergodic, ordered according to the quality of mixing (the strongest first). Most importantly for the design process, we show how the so-called linked twist maps function as a minimal picture of mixing, provide a mathematical structure for understanding the type of 2D flows that arise in many micromixers already built, and give conditions guaranteeing the best quality mixing. Extensions of these concepts lead to first-principle-based designs without resorting to lengthy computations.

  18. Physicians and foundation hospitals.

    Science.gov (United States)

    Cooper, John; Black, Carol

    2003-01-01

    Foundation NHS Trusts will be constituted in the same way as Mutual Societies, and local people and patients will be invited to become subscribers. Subscribers will elect a board of governors who will appoint the non-executive directors of the Trusts. Foundation Trusts will be outside the performance management system, but will be subject to a regulator and to inspection. Contracts with commissioners will be legally enforceable. Issues discussed in the article include: financial borrowing; whether competition is being reintroduced; poaching staff; fears of a two-tier health service; fragmentation of the NHS; the impact on research and teaching; and the impact on the current 'target culture'. Local communities and patient groups may welcome involvement with their local hospitals, but special interest groups could be a danger. Foundation Trusts may bring back some of the better features of NHS Trusts as originally conceived, and offer better opportunities for clinicians to influence local policies and priorities. Fears of yet another organisational change are an important issue. Only time will tell whether the outcome will justify the effort the changes will involve. PMID:14703035

  19. Characterization of the casein gene complex in West African goats and description of a new alpha(s1)-casein polymorphism.

    Science.gov (United States)

    Caroli, A; Chiatti, F; Chessa, S; Rignanese, D; Ibeagha-Awemu, E M; Erhardt, G

    2007-06-01

    The analysis of casein polymorphisms was carried out in West Africa goat populations: Red Sokoto (n = 57), West African Dwarf Nigeria (n = 27), West African Dwarf Cameroon (n = 39), and Borno (n = 37). The 4 casein genes alpha(s1) (CSN1S1), beta (CSN2), alpha(s2) (CSN1S2), and kappa (CSN3) were typed at the DNA level. No null alleles were found in any of the genes analyzed. A PCR single-strand conformation polymorphism method was implemented for the identification of CSN1S1*F allele simultaneously with A/0(1), B/E, N and the new allele. The allele differed from CSN1S1*B by a synonymous transversion TCG-->TCT in the codon corresponding to Ser(66) of the mature protein. The new allele, named CSN1S1*B', occurred at a high frequency in all the populations, ranging from 0.295 (West African Dwarf Cameroon) to 0.405 (Borno). A greater frequency was found for alleles associated with high alpha(s1)-casein quantity, as has already been observed in the goat populations from the Mediterranean area. The intermediate E allele occurred only in the Red Sokoto and at a low frequency. The faint F allele occurred in 3 populations at frequencies lower than 0.03. Linkage disequilibrium occurred in all the populations, with highly significant differences in Borno, Red Sokoto, and West Africa Dwarf Nigeria, and significant differences in West Africa Dwarf Cameroon. Only 10 haplotypes showed frequencies > or =0.05 in at least 1 of the 4 populations considered, and the overall frequency was >0.1 only for 4 haplotypes: BAAB, B'ACA, ACAB, and BACA (in the order CSN1S1-CSN2-CSN1S2-CSN3). Haplotype BAAB, postulated as an ancestral haplotype in previous studies, was the most common haplotype in all breeds except Borno, where B'ACA was predominant. The results obtained are of considerable significance given that very little information exists on the subject for African goats. The high frequency of strong alleles in the calcium-sensitive caseins as well as the high linkage disequilibrium found

  20. Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats

    International Nuclear Information System (INIS)

    In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers

  1. GDP-fucose: beta-galactoside alpha1,2-fucosyltransferase, MFUT-II, and not MFUT-I or -III, is induced in a restricted region of the digestive tract of germ-free mice by host-microbe interactions and cycloheximide.

    Science.gov (United States)

    Lin, B; Hayashi, Y; Saito, M; Sakakibara, Y; Yanagisawa, M; Iwamori, M

    2000-09-27

    A shift from sialylation to fucosylation of mucosal glycoconjugates occurred in the mammalian digestive tract in the weaning period, but mice under germ-free conditions were found to express both fucosyl GM1 (FGM1) and fucosyl asialo GM1 (FGA1) in the stomach, cecum and colon, but not in the small intestine. By host-microbe interactions and administration of cycloheximide, FGA1 was quickly induced in the small intestine, but the concentrations of fucosylated glycolipids in the other regions were not altered significantly. Their expression coincided with the activity of GDP-fucose:GA1 alpha(1, 2)-fucosyltransferase (alpha1,2-FT), and we isolated a cDNA with an open reading frame encoding the murine alpha1,2-FT (MFUT-II) of 347 amino acids with a predicted molecular mass of 39.21 kDa. The intraperitoneal injection of cycloheximide induced the mRNA and activity of alpha1,2-FT (MFUT-II) in the small intestine of germ-free mice, whereas no change in the mRNA or activity was observed in the stomach, cecum and colon, indicating that expression of FGA1 in response to microbial colonization or cycloheximide is transcriptionally regulated in a restricted region of the murine digestive tract. At 24 h after the administration of cycloheximide, FGA1 was preferentially produced in the upper half of the duodenal microvilli. PMID:11018479

  2. Scour around Offshore Windturbine Foundations

    DEFF Research Database (Denmark)

    Larsen, Brian Juul; De Vos, Leen; Frigaard, Peter

    For the present report a testprogramme has been performed to determine the scour around offshore windturbine foundations.......For the present report a testprogramme has been performed to determine the scour around offshore windturbine foundations....

  3. Brain and Behavior Research Foundation.

    Science.gov (United States)

    ... View All > Donate DONATE TODAY! > The Brain & Behavior Research Foundation is committed to alleviating the suffering caused by ... in scientific research. Copyright © 2016 the brain & behavior research foundation Privacy Policy Legal Notices and Disclaimers

  4. American foundations : roles and contributions

    OpenAIRE

    Helmut K. Anheier; Hammack, David

    2010-01-01

    Foundations play an essential part in the philanthropic activity that defines so much of American life. No other nation provides its foundations with so much autonomy and freedom of action as does the United States. Liberated both from the daily discipline of the market and from direct control by government, American foundations understandably attract great attention. As David Hammack and Helmut Anheier note in this volume, "Americans have criticized foundations for... their alleged conservat...

  5. Wave Forces on Windturbine Foundations

    DEFF Research Database (Denmark)

    Larsen, Brian Juul; Frigaard, Peter

    A testprogramme has been performed to determine the wave forces on two types of foundations for an offshore windturbine. the tested foundation types are a monopile and cone. Furthermore the shaft of the cone has been tested.......A testprogramme has been performed to determine the wave forces on two types of foundations for an offshore windturbine. the tested foundation types are a monopile and cone. Furthermore the shaft of the cone has been tested....

  6. Regulation of coronary vascular tone via redox modulation in the alpha1-adrenergic-angiotensin-endothelin axis of the myocardium.

    Science.gov (United States)

    Yamaguchi, Osamu; Kaneshiro, Takashi; Saitoh, Shu-ichi; Ishibashi, Toshiyuki; Maruyama, Yukio; Takeishi, Yasuchika

    2009-01-01

    We hypothesized that alpha(1)-adrenoceptor stimulation of cardiac myocytes results in the production of an endothelin (ET)-releasing factor that stimulates the coronary vasculature to release ET and, by manipulating the redox state of cardiac and vascular cells, may influence the extent of alpha(1)-adrenergic-ET-1 vasoconstriction. Dihydroethidium (DHE) and dichlorodihydrofluorescein (DCF) intensities were increased by phenylephrine stimulation in isolated rat cardiac myocytes, which were enhanced by the mitochondrial electron transport chain complex I inhibitor rotenone (DHE: 20.4 +/- 1.2-fold and DCF: 25.2 +/- 0.9-fold, n = 8, P < 0.01, respectively) but not by the NADPH oxidase inhibitor apocynin. Olmesartan, an angiotensin II type 1 receptor antagonist, and enalaprilate did not change DHE and DCF intensities by phenylephrine. Next, we measured the vasoconstriction of isolated, pressurized rat coronary arterioles (diameter: 74 +/- 8 microm) in response to supernatant collected from isolated cardiac myocytes. The addition of supernatant from phenylephrine-stimulated myocytes to a 2-ml vessel bath (n = 8 each) caused volume-dependent vasoconstriction (500 microl: -14.8 +/- 2.2%). Olmesartan and TA0201, an ET type A receptor antagonist, converted vasoconstriction into vasodilation (8.5 +/- 1.2% and 10.5 +/- 0.5%, P < 0.01, respectively) in response to supernatant from phenylephrine-stimulated myocytes, which was eliminated with catalase. Vasoconstriction was weakened using supernatant from phenylephrine with rotenone-treated myocytes. Treatment of arterioles with apocynin to myocyte supernatant converted vasoconstriction into vasodilation (7.8 +/- 0.8%, P < 0.01). These results suggest that alpha(1)-adrenergic stimulation in cardiac myocytes produces angiotensin I and H(2)O(2) and that angiotensin releases ET-1 through NADPH oxidase in coronary arterioles. Thus, coronary vasoconstriction via the alpha-adrenergic-angiotensin-ET axis appears to require redox

  7. Lectin-like receptor for alpha 1-acid glycoprotein in the epithelium of the rat prostate gland and seminal vesicles

    DEFF Research Database (Denmark)

    Andersen, U O; Bøg-Hansen, T C; Kirkeby, S

    1996-01-01

    BACKGROUND: A receptor for alpha 1-acid glycoprotein glycoforms AGP-B and AGP-C in the epithelium of the rat prostate gland and seminal vesicles is described. METHODS: The interaction between AGP-glycoforms and their receptor is a lectin-like interaction confirmed by inhibition of the binding...... in rat prostate and seminal vesicles. The localization of the AGP lectin receptor is compared to the localization of glycoprotein AGP, and small differences are found. CONCLUSIONS: It is proposed the AGP receptors in the prostate and seminal vesicles belong to a group of lectins in the control...

  8. Mathematical foundations of elasticity

    CERN Document Server

    Marsden, Jerrold E

    1994-01-01

    This advanced-level study approaches mathematical foundations of three-dimensional elasticity using modern differential geometry and functional analysis. It is directed to mathematicians, engineers and physicists who wish to see this classical subject in a modern setting with examples of newer mathematical contributions. Prerequisites include a solid background in advanced calculus and the basics of geometry and functional analysis.The first two chapters cover the background geometry ― developed as needed ― and use this discussion to obtain the basic results on kinematics and dynamics of con

  9. Foundations of Power

    DEFF Research Database (Denmark)

    Lev, Amnon

    of state power. This sets the modern state apart from the societies of the Middle Ages in which civil authority was either seen to be founded in religion (Christian doctrine) or in custom (Roman law). In the age of the modern state, it is law, or rather, constitutional doctrine that serves as the medium...... legal thought arises out of the ruins of natural law and it argues that, even as 20th century legal thought has distanced itself from natural law, it has not ceased to return to its fundamental problem: the problem of the foundation of power....

  10. Web services foundations

    CERN Document Server

    Bouguettaya, Athman; Daniel, Florian

    2013-01-01

    Web services and Service-Oriented Computing (SOC) have become thriving areas of academic research, joint university/industry research projects, and novel IT products on the market. SOC is the computing paradigm that uses Web services as building blocks for the engineering of composite, distributed applications out of the reusable application logic encapsulated by Web services. Web services could be considered the best-known and most standardized technology in use today for distributed computing over the Internet.Web Services Foundations is the first installment of a two-book collection coverin

  11. Instant Zurb Foundation 4

    CERN Document Server

    Arévalo, Jorge

    2013-01-01

    A quick and easy guide that follows a practical approach to rapidly create responsive web pages using Foundation 4 framework, following the mobile-first philosophy.If you are a web developer who wants to get the most out of your HTML5/CSS/JavaScript skills, this book is ideal for you. It is assumed that you will have some experience with these languages, but for those who don't, you can also be up and running in an instant.

  12. Foundations of Inference

    Directory of Open Access Journals (Sweden)

    Kevin H. Knuth

    2012-06-01

    Full Text Available We present a simple and clear foundation for finite inference that unites and significantly extends the approaches of Kolmogorov and Cox. Our approach is based on quantifying lattices of logical statements in a way that satisfies general lattice symmetries. With other applications such as measure theory in mind, our derivations assume minimal symmetries, relying on neither negation nor continuity nor differentiability. Each relevant symmetry corresponds to an axiom of quantification, and these axioms are used to derive a unique set of quantifying rules that form the familiar probability calculus. We also derive a unique quantification of divergence, entropy and information.

  13. Problem solving in foundation engineering using foundationPro

    CERN Document Server

    Yamin, Mohammad

    2016-01-01

    This book is at once a supplement to traditional foundation engineering textbooks and an independent problem-solving learning tool. The book is written primarily for university students majoring in civil or construction engineering taking foundation analysis and design courses to encourage them to solve design problems. Its main aim is to stimulate problem solving capability and foster self-directed learning. It also explains the use of the foundationPro software, available at no cost, and includes a set of foundation engineering applications. Taking a unique approach, Dr. Yamin summarizes the general step-by-step procedure to solve various foundation engineering problems, illustrates traditional applications of these steps with longhand solutions, and presents the foundationPro solutions. The special structure of the book allows it to be used in undergraduate and graduate foundation design and analysis courses in civil and construction engineering. The book stands as valuable resource for students, faculty, ...

  14. Mathematical foundations of biomechanics.

    Science.gov (United States)

    Niederer, Peter F

    2010-01-01

    The aim of biomechanics is the analysis of the structure and function of humans, animals, and plants by means of the methods of mechanics. Its foundations are in particular embedded in mathematics, physics, and informatics. Due to the inherent multidisciplinary character deriving from its aim, biomechanics has numerous connections and overlapping areas with biology, biochemistry, physiology, and pathophysiology, along with clinical medicine, so its range is enormously wide. This treatise is mainly meant to serve as an introduction and overview for readers and students who intend to acquire a basic understanding of the mathematical principles and mechanics that constitute the foundation of biomechanics; accordingly, its contents are limited to basic theoretical principles of general validity and long-range significance. Selected examples are included that are representative for the problems treated in biomechanics. Although ultimate mathematical generality is not in the foreground, an attempt is made to derive the theory from basic principles. A concise and systematic formulation is thereby intended with the aim that the reader is provided with a working knowledge. It is assumed that he or she is familiar with the principles of calculus, vector analysis, and linear algebra. PMID:21303323

  15. Static Behaviour of Bucket Foundations

    DEFF Research Database (Denmark)

    Larsen, Kim André

    as well as large-scale tests on bucket foundations subjected to low vertical load are performed during this work. Numerical simulations of the tests performed are carried out using the Mohr Coulomb material model and the commercial finite element code ABAQUS. Based on the present work, the finite element......One new foundation concept in relation to offshore wind turbines is bucket foundations. The concept is known from the oil and gas industry, though the load conditions here are significantly different. The bucket foundation can be used as monopod or e.g. tripod foundations for offshore wind turbines....... The monopod concept is investigated in this thesis, regarding the static behaviour from loads relevant to offshore wind turbines. The main issue in this concept is the rotational stiffness of the foundation and the combined capacity dominated by moments. The vertical bearing capacity of bucket foundations...

  16. The alpha(1G)-subunit of a voltage-dependent Ca(2+) channel is localized in rat distal nephron and collecting duct

    DEFF Research Database (Denmark)

    Andreasen, D; Jensen, B L; Hansen, P B;

    2000-01-01

    , alpha(1G)-mRNA levels in kidney regions were determined as inner medulla >> outer medulla congruent with cortex. RT-PCR analysis of microdissected rat nephron segments revealed alpha(1G) expression in the distal convoluted tubule (DCT), in the connecting tubule and cortical collecting duct (CT...... at the apical plasma membrane domains of DCT cells, CT principal cells, and IMCD principal cells....

  17. In vivo binding in rat brain and radiopharmaceutical preparation of radioiodinated HEAT, an alpha-1 adrenoceptor ligand

    Energy Technology Data Exchange (ETDEWEB)

    Couch, M.W.; Greer, D.M.; Thonoor, C.M.; Williams, C.M.

    1988-03-01

    In vivo binding of (/sup 125/I)-2-(beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl tetralone) ((/sup 125/I)HEAT) to alpha-1 adrenoceptors in the rat brain was determined over 4 hr. Uptake in the thalamus and frontal cortex was approximately 0.1% injected dose per gram tissue. Thalamus/cerebellum ratios of 10:1 and frontal cortex/cerebellum ratios of 5:1 were found at 4 hr. Pretreatment with prazosin, an alpha-1 antagonist, completely inhibited the accumulation of (/sup 125/I)HEAT in thalamus and frontal cortex; yet uptake of radioactivity was not significantly affected by antagonists and agonists for other receptors classes (propranolol, beta-1; apomorphine, D-1; spiperone, D-2). Binding of (/sup 125/I)HEAT is saturable. At 4 hr, (/sup 125/I)HEAT or (/sup 123/I)HEAT was shown to be the only radioactive material in rat thalamus and frontal cortex. Iodine-123 HEAT and (/sup 125/I)HEAT were synthesized as radiopharmaceuticals within 3 hr in 99% radiochemical purity.

  18. Detection of bovine alpha-S1-casein in term and preterm human colostrum with proteomic techniques.

    Science.gov (United States)

    Orru, S; Di Nicola, P; Giuliani, F; Fabris, C; Conti, A; Coscia, A; Bertino, E

    2013-01-01

    Due to increased social awareness of allergens and population hyper-sensitization, the reported incidence of allergic reactions to food allergens has increased over the past two decades. Cow's milk proteins (CMPs) are among the most common food allergens. The aim of this study was to use proteomics techniques to investigate cow's milk allergens in both full-term human colostrum and in preterm newborns mothers where both groups showed no prior allergen detection -- in order to understand whether cows milk allergens could be a cause of sensitization established through lactation. The most relevant finding was the detection of the intact bovine alpha-S1-casein in both term and preterm colostrum. Using techniques detailed in this paper and which allowed for direct protein identification, beta-lactoglobulin was not detected in any of the colostrum samples. According to our results, bovine alpha 1 casein is considered a major cow's milk allergen, is readily secreted in human milk, and so could be considered a possible cause of sensitization in exclusively breastfed infants. PMID:23755758

  19. Reduction of the elastase inhibitory capacity of alpha 1-antitrypsin by peroxides in cigarette smoke: an analysis of brands and filters

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, A.B.; James, H.L.

    1982-07-01

    A procedure for measuring the oxidant content of aqueous condensates of tobacco cigarette smoke is described. The procedure was used in conjunction with analysis of the ability of the smoke solutions to inactivate the elastase inhibitory capacity (EIC) of alpha 1-antitrypsin. The ability of the smoke of a brand to inactivate alpha 1-antitrypsin correlates well with the known tar and nicotine and with the amount of oxidants as measured using o-dianisidine. Filters were found to remove about 73% of the oxidants from smoke. Smoke from a commercial nontobacco cigarette was also found to contain a significant amount of oxidants and to also destroy alpha 1-antitrypsin. Catalase and superoxide dismutase reduce the effect of solutions containing smoke on the EIC of alpha 1-antitrypsin, suggesting that peroxides and superoxide anions in smoke contribute to the oxidant capacity of the smoke. The extent of apparent oxidation by a given quantity of smoke condensate increases for as long as an hour from the time the condensate is collected. The addition of hydrogen peroxide to the smoke solution increases both its oxidant content and its ability to inactivate alpha 1-antitrypsin. These data suggest that occurrence of hydrogen peroxide caused by secretion from macrophages found in the small airways of smokers may contribute to a locally damaging environment for alpha 1-antitrypsin in the presence of cigarette smoke that could promote the development of centrilobular emphysema.

  20. Scientific foundations of engineering

    CERN Document Server

    McKnight, Stephen

    2015-01-01

    Providing an overview of the foundations of engineering from a fundamental scientific and physical perspective, this book reinforces the basic scientific and mathematical principles which underpin a range of engineering disciplines and applications. It covers the basics of physics, including quantum physics, as well as some key topics in chemistry, making it a valuable resource for both students and professionals looking to gain a more coherent and interdisciplinary understanding of engineering systems. Throughout, the focus is on common features of physical systems (such as mechanical and electronic resonance), showing how the same underlying principles apply to different disciplines. Problems are provided at the end of each chapter including conceptual questions and examples to demonstrate the practical application of fundamental scientific principles. These include real-world examples, which are solvable using computational packages such as MATLAB.

  1. The foundation of physicianship.

    Science.gov (United States)

    Fuks, Abraham; Brawer, James; Boudreau, J Donald

    2012-01-01

    Although the practice of medicine continually changes in response to new biomedical understanding, novel technologies, and evolving cultural contexts, the ethical foundations of the clinical relationship between patient and physician paradoxically remain constant. There are fundamental characteristics with respect to character, behavior, and responsibilities that are descriptive of and necessary to the role of healer and that underpin the notion of physicianship. This article discusses the underlying characteristics or virtues that are necessary to the practice of medicine from the perspectives of three different philosophic traditions: the Aristotelian idea of phronesis as developed in the work of Edmund Pellegrino; the notion of alterity as framed by Emmanuel Levinas; and the attributes necessary to healing as laid out in the kabbala.

  2. Foundations of Quantum Decoherence

    CERN Document Server

    Gamble, John

    2008-01-01

    The conventional interpretation of quantum mechanics, though it permits a correspondence to classical physics, leaves the exact mechanism of transition unclear. Though this was only of philosophical importance throughout the twentieth century, over the past decade new technological developments, such as quantum computing, require a more thorough understanding of not just the result of quantum emergence, but also its mechanism. Quantum decoherence theory is the model that developed out of necessity to deal with the quantum-classical transition explicitly, and without external observers. In this thesis, we present a self-contained and rigorously argued full derivation of the master equation for quantum Brownian motion, one of the key results in quantum decoherence theory. We accomplish this from a foundational perspective, only assuming a few basic axioms of quantum mechanics and deriving their consequences. We then consider a physical example of the master equation and show that quantum decoherence successfull...

  3. Foundations of signal processing

    CERN Document Server

    Vetterli, Martin; Goyal, Vivek K

    2014-01-01

    This comprehensive and engaging textbook introduces the basic principles and techniques of signal processing, from the fundamental ideas of signals and systems theory to real-world applications. Students are introduced to the powerful foundations of modern signal processing, including the basic geometry of Hilbert space, the mathematics of Fourier transforms, and essentials of sampling, interpolation, approximation and compression. The authors discuss real-world issues and hurdles to using these tools, and ways of adapting them to overcome problems of finiteness and localisation, the limitations of uncertainty and computational costs. Standard engineering notation is used throughout, making mathematical examples easy for students to follow, understand and apply. It includes over 150 homework problems and over 180 worked examples, specifically designed to test and expand students' understanding of the fundamentals of signal processing, and is accompanied by extensive online materials designed to aid learning, ...

  4. Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    The last day of March 1978 marked the completion of the first 3 years of operation of the Radiation Effects Research Foundation in Hiroshima and Nagasaki. RERF was established on 1 April 1975 as successor to the Atomic Bomb Casualty Commission which had been in continuous operation since 1947. This record of the first 3 years of operation consists of selected reports and other documents prepared in the course of conducting the business of RERF and includes a brief history, a late radiation effects that might be conducted at RERF. The wisdom and thought given to the research program and its operation by the Scientific Council and the Board of Directors is reflected in the minutes of their meetings which are included in the Appendix. (Mori, K.)

  5. Foundations of Geomagnetism

    Science.gov (United States)

    Jackson, Andy

    The study of the magnetic field of the Earth, or geomagnetism, is one of the oldest lines of scientific enquiry. Indeed, it has often been said that William Gilbert's De Magnete, published in 1600 and predating Isaac Newton's Principia by 87 years, can claim to be the first true scientific textbook; his study was essentially the first of academic rather than practical interest.What then, we may ask, has been accomplished in the nearly 400 intervening years up to the publication of Foundations of Geomagnetism? In short, a wealth of observational evidence, considerable physical understanding, and a great deal of mathematical apparatus have accrued, placing the subject on a much surer footing.The latter two categories are described in considerable detail, and with attendant rigor, in this book. The sphericity of the Earth means that a frequent theme in the book is the solution of the partial differential equations of electrodynamics in a spherical geometry.

  6. Intracellular Transactivation of Epidermal Growth Factor Receptor by alpha(1A)-Adrenoceptor Is Mediated by Phosphatidylinositol 3-Kinase Independently of Activation of Extracellular Signal Regulated Kinases 1/2 and Serine-Threonine Kinases in Chinese Hamster Ovary Cells

    NARCIS (Netherlands)

    Ulu, Nadir; Henning, Robert H.; Guner, Sahika; Zoto, Teuta; Duman-Dalkilic, Basak; Duin, Marry; Gurdal, Hakan

    2013-01-01

    Transactivation of epidermal growth factor receptor (EGFR) by alpha(1)-adrenoceptor (alpha(1)-AR) is implicated in contraction and hypertrophy of vascular smooth muscle (VSM). We examine whether all alpha(1)-AR subtypes transactivate EGFR and explore the mechanism of transactivation. Chinese hamster

  7. A study of Italian pediatric celiac disease patients confirms that the primary HLA association is to the DQ(alpha 1*0501, beta 1*0201) heterodimer.

    Science.gov (United States)

    Mazzilli, M C; Ferrante, P; Mariani, P; Martone, E; Petronzelli, F; Triglione, P; Bonamico, M

    1992-02-01

    Celiac disease (CD) has been recently reported to be primarily associated with the DQ(alpha 1*0501, beta 1*0201) heterodimer encoded in cis on DR3 haplotype and in trans in DR5,7 heterozygous individuals. The high incidence of DR5,7 heterozygotes, reflecting the high frequency of the DR5 allele in Italy, makes the analysis of the Italian CD patients critical. Polymerase chain reaction-amplified DNA from 50 CD patients and 50 controls, serologically typed for DR and DQw antigens, was hybridized with five DQA1-specific oligonucleotide probes detecting DQA1*0101 + 0102 + 0103, DQA1*0201, DQA1*0301 + 0302, DQA1*0401 + 0501 + 0601, and DQA1*0501 and a DQB1-sequence-specific oligonucleotide probe recognizing DQB1*0201 allele. As expected by the DR-DQ disequilibria, DQA1*0201 [62% in patients versus 26% in controls, relative risk (RR) = 5] and DQA1*0501 (96% versus 56%, RR = 19) show positive association with the disease. Of CD patients, 92% (50% DR3 and 42% DR5,7) compared to 18% of the controls carry both DQA1*0501 and DQB1*0201 alleles, so that the combination confers an RR of 52, higher than both the risks of the single alleles (DQA1*0501 RR = 19, DQB1*0201 RR = 30), confirming the primary role of the dimer in determining genetic predisposition to CD both in DR3 and in DR5,7 subjects. PMID:1563982

  8. Functional interactions of phospholemman (PLM) (FXYD1) with Na+,K+-ATPase. Purification of alpha1/beta1/PLM complexes expressed in Pichia pastoris.

    Science.gov (United States)

    Lifshitz, Yael; Lindzen, Moshit; Garty, Haim; Karlish, Steven J D

    2006-06-01

    Human FXYD1 (phospholemman, PLM) has been expressed in Pichia pastoris with porcine alpha1/His10-beta1 subunits of Na+,K+-ATPase or alone. Dodecyl-beta-maltoside-soluble complexes of alpha1/beta1/PLM have been purified by metal chelate chromatography, either from membranes co-expressing alpha1,His10-beta1, and PLM or by in vitro reconstitution of PLM with alpha1/His10-beta1 subunits. Comparison of functional properties of purified alpha1/His10-beta1 and alpha1/His10-beta1/PLM complexes show that PLM lowered K0.5 for Na+ ions moderately (approximately 30%) but did not affect the turnover rate or Km of ATP for activating Na+,K+-ATPase activity. PLM also stabilized the alpha1/His10-beta1 complex. In addition, PLM markedly (>3-fold) reduced the K0.5 of Na+ ions for activating Na+-ATPase activity. In membranes co-expressing alpha1/His10-beta1 with PLM the K0.5 of Na+ ions was also reduced, compared with the control, excluding the possibility that detergent or lipid in purified complexes compromise functional interactions. When expressed in HeLa cells with rat alpha1, rat PLM significantly raised the K0.5 of Na+ ions, whereas for a chimeric molecule consisting of transmembranes segments of PLM and extramembrane segments of FXYD4, the K0.5 of Na+ ions was significantly reduced, compared with the control. The opposite functional effects in P. pastoris and HeLa cells are correlated with endogenous phosphorylation of PLM at Ser68 or unphosphorylated PLM, respectively, as detected with antibodies, which recognize PLM phosphorylated at Ser68 (protein kinase A site) or unphosphorylated PLM. We hypothesize that PLM interacts with alpha1/His10-beta1 subunits at multiple locations, the different functional effects depending on the degree of phosphorylation at Ser68. We discuss the role of PLM in regulation of Na+,K+-ATPase in cardiac or skeletal muscle cells.

  9. The logical foundations of mathematics

    CERN Document Server

    Hatcher, William S

    1981-01-01

    The Logical Foundations of Mathematics offers a study of the foundations of mathematics, stressing comparisons between and critical analyses of the major non-constructive foundational systems. The position of constructivism within the spectrum of foundational philosophies is discussed, along with the exact relationship between topos theory and set theory.Comprised of eight chapters, this book begins with an introduction to first-order logic. In particular, two complete systems of axioms and rules for the first-order predicate calculus are given, one for efficiency in proving metatheorems, and

  10. Loss of Smyhc1 or Hsp90alpha1 function results in different effects on myofibril organization in skeletal muscles of zebrafish embryos.

    Directory of Open Access Journals (Sweden)

    Marta Codina

    Full Text Available BACKGROUND: Myofibrillogenesis requires the correct folding and assembly of sarcomeric proteins into highly organized sarcomeres. Heat shock protein 90alpha1 (Hsp90alpha1 has been implicated as a myosin chaperone that plays a key role in myofibrillogenesis. Knockdown or mutation of hsp90alpha1 resulted in complete disorganization of thick and thin filaments and M- and Z-line structures. It is not clear whether the disorganization of these sarcomeric structures is due to a direct effect from loss of Hsp90alpha1 function or indirectly through the disorganization of myosin thick filaments. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we carried out a loss-of-function analysis of myosin thick filaments via gene-specific knockdown or using a myosin ATPase inhibitor BTS (N-benzyl-p-toluene sulphonamide in zebrafish embryos. We demonstrated that knockdown of myosin heavy chain 1 (myhc1 resulted in sarcomeric defects in the thick and thin filaments and defective alignment of Z-lines. Similarly, treating zebrafish embryos with BTS disrupted thick and thin filament organization, with little effect on the M- and Z-lines. In contrast, loss of Hsp90alpha1 function completely disrupted all sarcomeric structures including both thick and thin filaments as well as the M- and Z-lines. CONCLUSION/SIGNIFICANCE: Together, these studies indicate that the hsp90alpha1 mutant phenotype is not simply due to disruption of myosin folding and assembly, suggesting that Hsp90alpha1 may play a role in the assembly and organization of other sarcomeric structures.

  11. 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.)

  12. 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...

  13. Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma

    DEFF Research Database (Denmark)

    Udby, Lene; Sørensen, Ole E; Pass, Jesper;

    2004-01-01

    -like substances found in lizard saliva or snake venom. Human CRISP-3 is present in exocrine secretions and in secretory granules of neutrophilic granulocytes and is believed to play a role in innate immunity. On the basis of the relatively high content of CRISP-3 in human plasma and the small size of the protein...... (28 kDa), we hypothesized that CRISP-3 in plasma was bound to another component. This was supported by size-exclusion chromatography and immunoprecipitation of plasma proteins. The binding partner was identified by mass spectrometry as alpha(1)B-glycoprotein (A1BG), which is a known plasma protein of......Human cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) belongs to a family of closely related proteins found in mammals and reptiles. Some mammalian CRISPs are known to be involved in the process of reproduction, whereas some of the CRISPs from reptiles are neurotoxin...

  14. Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I

    DEFF Research Database (Denmark)

    Teisner, B; Rasmussen, H B; Højrup, P;

    1992-01-01

    -PAGE analysis gave an M(r) = 27 kDa under reducing and non-reducing conditions for both forms, whereas the exact M(r) determined by mass spectrometry was 14,343 +/- 3 Da. FA2 was N-terminally blocked and after tryptic digestion the amino acid composition and sequences of the peptides showed identity...... with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated...... in fetal calf serum. Gel filtration with analysis of fractions by inhibition ELISA showed that the bovine homologue was present in the same molecular forms as those in human amniotic fluid, and immunohistochemical analysis with anti-human FA2 showed that its distribution in bovine skin was identical...

  15. Time-resolved fluorescence imaging (TRFI) for direct immunofluorescence of PSA and alpha-1-antichymotrypsin in prostatic tissue sections.

    Science.gov (United States)

    Bjartell, A; Siivola, P; Hulkko, S; Pettersson, K; Rundt, K; Lilja, H; Lövgren, T

    1999-05-01

    We have developed a direct immunofluorescence technique utilising chelates of the lanthanide ions europium and terbium conjugated to monoclonal IgGs (Mabs) against prostate-specific antigen (PSA) and alpha-1-antichymotrypsin (ACT) for the detection and quantification on the same tissue section. Strong signals without disturbance from tissue autofluorescence were demonstrated in paraffin sections of ten benign and six malignant prostate tissue specimens. The signal intensity increased linearly with the amount of labelled Mab until epitope saturation began. The highest concentrations of bound IgG in tissue sections were 27.3 fmol/pixel for ACT and 7.2 for PSA. Time-resolved fluorescence imaging (TRFI) offers an attractive method for histochemical studies based on specific and quantitative detection of fluorescent lanthanide chelates. PMID:12496823

  16. Foundations of resilience thinking.

    Science.gov (United States)

    Curtin, Charles G; Parker, Jessica P

    2014-08-01

    Through 3 broad and interconnected streams of thought, resilience thinking has influenced the science of ecology and natural resource management by generating new multidisciplinary approaches to environmental problem solving. Resilience science, adaptive management (AM), and ecological policy design (EPD) contributed to an internationally unified paradigm built around the realization that change is inevitable and that science and management must approach the world with this assumption, rather than one of stability. Resilience thinking treats actions as experiments to be learned from, rather than intellectual propositions to be defended or mistakes to be ignored. It asks what is novel and innovative and strives to capture the overall behavior of a system, rather than seeking static, precise outcomes from discrete action steps. Understanding the foundations of resilience thinking is an important building block for developing more holistic and adaptive approaches to conservation. We conducted a comprehensive review of the history of resilience thinking because resilience thinking provides a working context upon which more effective, synergistic, and systems-based conservation action can be taken in light of rapid and unpredictable change. Together, resilience science, AM, and EPD bridge the gaps between systems analysis, ecology, and resource management to provide an interdisciplinary approach to solving wicked problems.

  17. Toxin a from Clostridium difficile binds to rabbit erythrocyte glycolipids with therminal Gal. cap alpha. 1-3Gal. beta. 1-4GlcNaC sequences

    Energy Technology Data Exchange (ETDEWEB)

    Clark, G.F.; Krivan, H.; Wilkins, T.; Smith, D.F.

    1987-05-01

    Toxin A is one of two clostridial toxins implicated as the causative agent of pseudomembranous colitis in patients undergoing postoperative antibiotic therapy. Evidence that the carbohydrate binding determinant for this toxin is a glycoconjugate(s) with non-reducing Gal..cap alpha..1-3Gal..beta..1-4GlcNAc has recently been reported. Specific agglutination of rabbit erythrocytes by Toxin A is inhibited by bovine thyroglobulin and prevented by pretreatment of cells with ..cap alpha..-galactosidase. Total lipid extracts from rabbit erythrocytes were subjected to thin layer chromatography and the chromatogram overlaid with purified /sup 125/I-labeled Toxin A. Two major and several minor toxin-binding glycolipids were detected following autoradiography. The major toxin-binding glycolipids were identified as pentasaccharide- and decasaccharide-ceramides expressing terminal Gal..cap alpha..1-3Gal..beta..1-4GlcNAc sequences. Treatment of the toxin-binding glycolipids with ..cap alpha..-galactosidase abolished binding. Forsmann glycolipid, globoside, Gal..cap alpha..1-4 Gal..beta..1-4Glc-cer, and Gal..cap alpha..1-3Gal..beta..1-4Glc-cer did not bind the toxin. These observations are consistent with the proposed carbohydrate specificity of the toxin for the non-reducing terminal sequence, Gal..cap alpha..1-3Gal..beta..1-4GlcNAc.

  18. Corporate Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Thomsen, Steen

    1999-01-01

    Industrial foundations are self-governing non profit institutions that own business companies. This ownership structure is found in a fair number of Northern European companies, some of them successful world class competitors. Standard agency theory would predict foundation-owned companies...

  19. Antithetic Foundations of Economics

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2011-03-01

    Full Text Available This paper aims at decrypting the manner in which the foundations of Economics as a science and the meanings of the relevant explanatory formulas are being shaped. My analytical endeavor focuses on understanding the peculiarities of what is referred to as the object of study of the science known as Economics, an academic synthesis of concept-related breakthroughs regarding economicity. The explicit purpose of this analysis is to identify perennial benchmarks in economic cognition whereby this ensures its consistency. The implicit purpose is to shape a cognitive model in line with the specifics of the conceptual universe of Economics, as well as with the sources of the economic realities that are subject to a sui-generis relativism. The primary benefit of this endeavor consists in systemizing the conceptual prospects with an antithetic nature that allow for the explanations of the state of economic rationality and generate the understanding of what the source of economicity is and how it behaves. As such, the conclusions are marked by the stringent need of more precisely defining economic knowledge in order to match the changing nature of economic reality, as an expression that embraces the meeting point of two ontological vistas that are methodologically separated by some theories: human nature and human condition. Economics as a science thus features, apart from a conceptual substrate that needs to be spotted, an ontological background that needs to be revealed. The role played by this background appears to be most frequently ignored. The joint identification of both direct and contextual determinants for a sensitive area of humankind, i.e. the economy, is a direction to be followed by the royal path of rational knowledge.

  20. 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

  1. NEWS: Solid foundations?

    Science.gov (United States)

    2000-07-01

    Among the initiatives to be found at UK universities is a vocational award with the title `University Foundation Degree' at Nottingham Trent University. This qualification will be offered in 14 different subjects including four in the Faculty of Science and Mathematics, in the areas of applied biology, applied sciences, chemistry and physics. The courses will be available on a two-year full-time, three-year sandwich or a part-time basis. Set at a higher standard and specification than the Higher National Diplomas which it replaces, the UFD has been devised in consultation with industry and will cover the technical and specialist areas demanded by employers to combat skills shortages. The UFD in applied sciences concentrates on practical applications through laboratory, IT and project work, supported by lectures and seminars. At the end students can enter the employment market or transfer onto the second year of a degree course. Science-based careers including research and development would be the aim of those taking the UFD in physics. The first year develops the fundamentals of modern physics supported by studies in mathematics, IT and computer programming, whilst year 2 is vocational in nature with industrial problem solving and work experience as well as an academic theme associated with environmental aspects of the subject. Those who complete the UFD will be allowed automatic progression to a specified honours degree course and would normally be expected to study for a further two years for this award. However, those demonstrating an outstanding academic performance can transfer to the linked degree programme at the end of the first year via fast-track modules. Back in May the UK's Quality Assurance Agency (QAA) announced new standard benchmarks for degrees. These will be introduced into higher education institutions from 2002 to outline the knowledge, understanding and skills a student should gain from a particular higher education course. These benchmark

  2. Toxin A from Clostridium difficile binds to rabbit erythrocyte glycolipids with terminal Gal alpha 1-3Gal beta 1-4GlcNAc sequences

    International Nuclear Information System (INIS)

    The binding of Toxin A isolated from Clostridium difficile to rabbit erythrocyte glycolipids has been studied. Total lipid extracts from rabbit erythrocytes were subjected to thin-layer chromatography and toxin-binding glycolipids detected by using 125I-labeled Toxin A in a direct binding overlay technique. Two major and several minor toxin-binding glycolipids were detected in rabbit erythrocytes by this method. The results of structural analyses of the major toxin-binding glycolipids were consistent with a pentasaccharide-ceramide (Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer) and a branched decasaccharide-ceramide (Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3[Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6]Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer) previously identified as the two most abundant glycolipids in rabbit erythrocytes. 125I-Toxin A binding to these glycolipids could be inhibited by bovine thyroglobulin, monospecific antiserum to the toxin, or by treatment of the glycolipids with alpha-galactosidase. The absence of toxin interaction with isoglobotriaosylceramide (Gal alpha 1-3Gal beta 1-4Glc-Cer) isolated from canine intestine suggested that the GlcNAc residue present in the terminal Gal alpha 1-3Gal beta 1-4GLcNAc sequence common to all known toxin binding glycoconjugates is required for carbohydrate-specific recognition by Toxin A. These observations are consistent with the proposed carbohydrate binding specificity of Toxin A for the nonreducing terminal sequence, Gal alpha 1-3Gal beta 1-4GlcNAc

  3. Toxin A from Clostridium difficile binds to rabbit erythrocyte glycolipids with terminal Gal alpha 1-3Gal beta 1-4GlcNAc sequences

    Energy Technology Data Exchange (ETDEWEB)

    Clark, G.F.; Krivan, H.C.; Wilkins, T.D.; Smith, D.F.

    1987-08-15

    The binding of Toxin A isolated from Clostridium difficile to rabbit erythrocyte glycolipids has been studied. Total lipid extracts from rabbit erythrocytes were subjected to thin-layer chromatography and toxin-binding glycolipids detected by using /sup 125/I-labeled Toxin A in a direct binding overlay technique. Two major and several minor toxin-binding glycolipids were detected in rabbit erythrocytes by this method. The results of structural analyses of the major toxin-binding glycolipids were consistent with a pentasaccharide-ceramide (Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer) and a branched decasaccharide-ceramide (Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3(Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-6)Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc-Cer) previously identified as the two most abundant glycolipids in rabbit erythrocytes. /sup 125/I-Toxin A binding to these glycolipids could be inhibited by bovine thyroglobulin, monospecific antiserum to the toxin, or by treatment of the glycolipids with alpha-galactosidase. The absence of toxin interaction with isoglobotriaosylceramide (Gal alpha 1-3Gal beta 1-4Glc-Cer) isolated from canine intestine suggested that the GlcNAc residue present in the terminal Gal alpha 1-3Gal beta 1-4GLcNAc sequence common to all known toxin binding glycoconjugates is required for carbohydrate-specific recognition by Toxin A. These observations are consistent with the proposed carbohydrate binding specificity of Toxin A for the nonreducing terminal sequence, Gal alpha 1-3Gal beta 1-4GlcNAc.

  4. Psychological Foundations of Language

    Institute of Scientific and Technical Information of China (English)

    王敏

    2016-01-01

    语言在我们的进化史中只是新近才出现的一种现象,而导致这惊人发展的力量是什么尚不清楚。我们知道部分原因是特化于语言功能的脑结构的演变。语言行为,和所有的行为一样,要通过脑结构的作用,但因为语言极其微妙并涉及多个方面,所以要在大脑中有一个特别复杂的表征。我们会看到,我们语言能力的各个方面,不是纯粹的抽象物,而是在闹中有独立的,能具体说明的表征。另外,语言的心理学基础研究会扩展我们对语言理解,语言产生和语言习得的讨论。这篇文章首先对语言的心理学基础做了一个简单的介绍使我们对为什么要做这个研究有一个清晰的观点。然后讨论了大脑机制和语言。不同的语言技能涉及脑的不同部位,遭受脑受伤的个体常常只是在语言的某些方面表现缺陷。接着描述了语言进程的侧化,对脑裂病人和正常人的研究表明,对大部分人来说,脑的左半球控制语言,特别是句法过程和语言产生,而右半球则是语用方面和语言理解。最后,对关于大脑的智力,性别和遗传因素和语言的关系做了简要的描述。%The emergence of language occurred only recently in our evolutionary history,and the set of forces that led to this extraordinary de-velopment is not yet clear.We do know that part of the story concerns the evolution of brain mechanisms specialized for language functions.Lan-guage behavior,like all behavior,is mediated by brain structures,but because language is extremely subtle and multifaceted,it has a particularly complex representation in the brain.We will learn that various aspects of our language capacity are not mere abstractions but rather have separate and specifiable representations in the brain.Moreover,the study of the psychological foundations of language extends our discussion of language comprehension,production and

  5. Molecular mechanisms of benzodiazepine-induced down-regulation of GABAA receptor alpha 1 subunit protein in rat cerebellar granule cells.

    OpenAIRE

    Brown, M. J.; Bristow, D. R.

    1996-01-01

    1. Chronic benzodiazepine treatment of rat cerebellar granule cells induced a transient down-regulation of the gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit protein, that was dose-dependent (1 nM-1 microM) and prevented by the benzodiazepine antagonist flumazenil (1 microM). After 2 days of treatment with 1 microM flunitrazepam the alpha 1 subunit protein was reduced by 41% compared to untreated cells, which returned to, and remained at, control cell levels from 4-12 days of treat...

  6. Up-regulation of the integrin alpha 1/beta 1 in human neuroblastoma cells differentiated by retinoic acid: correlation with increased neurite outgrowth response to laminin.

    OpenAIRE

    Rossino, P; P. Defilippi; Silengo, L; Tarone, G.

    1991-01-01

    Retinoic acid (RA) is known to induce differentiation of neuroblastoma cells in vitro. Here we show that treatment of two human neuroblastoma cell lines, SY5Y and IMR32, with RA resulted in a fivefold increase of the integrin alpha 1/beta 1 expression. The effect was selective because expression of the alpha 3/beta 1 integrin, also present in these cells, was not increased. The up-regulation of the alpha 1/beta 1 differentiated SY5Y cells correlated with increased neurite response to laminin....

  7. 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....

  8. Polish Foundation for Energy Efficiency

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    The Polish Foundation for Energy Efficiency (FEWE) was established in Poland at the end of 1990. FEWE, as an independent and non-profit organization, has the following objectives: to strive towards an energy efficient national economy, and to show the way and methods by use of which energy efficiency can be increased. The activity of the Foundation covers the entire territory of Poland through three regional centers: in Warsaw, Katowice and Cracow. FEWE employs well-known and experienced specialists within thermal and power engineering, civil engineering, economy and applied sciences. The organizer of the Foundation has been Battelle Memorial Institute - Pacific Northwest Laboratories from the USA.

  9. Determination of human serum alpha1-acid glycoprotein and albumin binding of various marketed and preclinical kinase inhibitors.

    Science.gov (United States)

    Zsila, Ferenc; Fitos, Ilona; Bencze, Gyula; Kéri, György; Orfi, László

    2009-01-01

    There are about 380 protein kinase inhibitors in drug development as of today and 15 drugs have been marketed already for the treatment of cancer. This time 139 validated kinase targets are in the focus of drug research of pharmaceutical companies and big efforts are made for the development of new, druglike kinase inhibitors. Plasma protein binding is an important factor of the ADME profiling of a drug compound. Human serum albumin (HSA) and alpha(1)-acid glycoprotein (AAG) are the most relevant drug carriers in blood plasma. Since previous literature data indicated that AAG is the principal plasma binding component of some kinase inhibitors the present work focuses on the comprehensive evaluation of AAG binding of a series of marketed and experimental kinase inhibitors by using circular dichroism (CD) spectroscopy approach. HSA binding was also evaluated by affinity chromatography. Protein binding interactions of twenty-six kinase inhibitors are characterized. The contribution of AAG and HSA binding data to the pharmacokinetic profiles of the investigated therapeutic agents is discussed. Structural, biological and drug binding properties of AAG as well as the applicability of the CD method in studying drug-protein binding interactions are also briefly reviewed.

  10. Subcellular site of synthesis of the N-acetylgalactosamine (alpha 1-0) serine (or threonine) linkage in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Abeijon, C.; Hirschberg, C.B.

    1987-03-25

    We have studied the subcellular site of synthesis of the GalNAc(alpha-1-0) Ser/Thr linkage in rat liver. The specific and total activities of polypeptide:N-acetylgalactosaminyltransferase (using apomucin as exogenous acceptor) were highly enriched in membrane fractions derived from the Golgi apparatus; virtually no activity was detected in membranes from the rough and smooth endoplasmic reticulum. Vesicles of the above organelles (which were sealed and of the same membrane topographical orientation as in vivo) were able to translocate UDP-GalNAc into their lumen in an assay in vitro; the initial translocation rate into Golgi vesicles was 4-6-fold higher than that into vesicles from the rough and smooth endoplasmic reticulum. Translocation of UDP-GalNAc into Golgi vesicles was temperature dependent and saturable with an apparent Km of 8-10 microM. UDP-GalNAc labeled with different radioisotopes in the uridine and sugar was used to determine that the intact sugar nucleotide was being translocated in a reaction coupled to the exit of luminal UMP. Following translocation of UDP-GalNAc, transfer of GalNAc into endogenous macromolecular acceptors was detected in Golgi vesicles and not in those from the rough and smooth endoplasmic reticulum. The above results together with previous studies on the O-xylosylation of the linkage region of proteoglycans strongly suggest that, in rat liver, the bulk of O-glycosylation reactions occur in the Golgi apparatus.

  11. 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.

  12. Eukaryotic translation elongation factor 1-alpha 1 inhibits p53 and p73 dependent apoptosis and chemotherapy sensitivity.

    Directory of Open Access Journals (Sweden)

    Alvaro Blanch

    Full Text Available The p53 family of transcription factors is a key regulator of cell proliferation and death. In this report we identify the eukaryotic translation elongation factor 1-alpha 1 (eEF1A1 to be a novel p53 and p73 interacting protein. Previous studies have demonstrated that eEF1A1 has translation-independent roles in cancer. We report that overexpression of eEF1A1 specifically inhibits p53-, p73- and chemotherapy-induced apoptosis resulting in chemoresistance. Short-interfering RNA-mediated silencing of eEF1A1 increases chemosensitivity in cell lines bearing wild type p53, but not in p53 null cells. Furthermore, silencing of eEF1A1 partially rescues the chemoresistance observed in response to p53 or p73 knockdown, suggesting that eEF1A1 is a negative regulator of the pro-apoptotic function of p53 and p73. Thus, in the context of p53-family signaling, eEF1A1 has anti-apoptotic properties. These findings identify a novel mechanism of regulation of the p53 family of proteins by eEF1A1 providing additional insight into potential targets to sensitize tumors to chemotherapy.

  13. Ape1/Ref-1 induces glial cell-derived neurotropic factor (GDNF) responsiveness by upregulating GDNF receptor alpha1 expression.

    Science.gov (United States)

    Kim, Mi-Hwa; Kim, Hong-Beum; Acharya, Samudra; Sohn, Hong-Moon; Jun, Jae Yeoul; Chang, In-Youb; You, Ho Jin

    2009-04-01

    Apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1) dysregulation has been identified in several human tumors and in patients with a variety of neurodegenerative diseases. However, the function of Ape1/Ref-1 is unclear. We show here that Ape1/Ref-1 increases the expression of glial cell-derived neurotropic factor (GDNF) receptor alpha1 (GFRalpha1), a key receptor for GDNF. Expression of Ape1/Ref-1 led to an increase in the GDNF responsiveness in human fibroblast. Ape1/Ref-1 induced GFRalpha1 transcription through enhanced binding of NF-kappaB complexes to the GFRalpha1 promoter. GFRalpha1 levels correlate proportionally with Ape1/Ref-1 in cancer cells. The knockdown of endogenous Ape1/Ref-1 in pancreatic cancer cells markedly suppressed GFRalpha1 expression and invasion in response to GNDF, while overexpression of GFRalpha1 restored invasion. In neuronal cells, the Ape1/Ref-1-mediated increase in GDNF responsiveness not only stimulated neurite outgrowth but also protected the cells from beta-amyloid peptide and oxidative stress. Our results show that Ape1/Ref-1 is a novel physiological regulator of GDNF responsiveness, and they also suggest that Ape1/Ref-1-induced GFRalpha1 expression may play important roles in pancreatic cancer progression and neuronal cell survival.

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

    Directory of Open Access Journals (Sweden)

    Mohamad Khawandanah

    2014-01-01

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

  15. 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

    Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset...... a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated...... with an estimated effect of β = -0.068 g/L per minor allele (P = 1.20*10(-12)). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare...

  16. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools

  17. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providin gquality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in

  18. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in

  19. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>The Rural Development Foundation(RDF),founded in1996,is an Indian nonprofit organization with the mission of providingquality education for underprivileged rural children.RDF founded and continues to operate five schools and one junior college in

  20. The Swiss National Science Foundation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ Introduction The Swiss National Science Foundation (SNSF) is Switzerland's leading provider of scientific research funding.The SNSF annually supports some 7200 researchers, almost 80 percent of whom are aged 35 years or younger.

  1. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>The Rural Development Foundation (RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in Andhra

  2. Kaiser Family Foundation - Content Search

    Data.gov (United States)

    U.S. Department of Health & Human Services — Chartpacks, chartbooks, factsheets, reports, and slide presentations bring Kaiser Family Foundation information to life, and can be easily incorporated into your...

  3. Foundation for Film and Science

    Science.gov (United States)

    van der Veen, G.

    1976-01-01

    Provides a comprehensive discussion on the Stichting Film en Wetenschap, SFW (Foundation for Film and Science), in Utrecht. Various aspects of the use of audio-visual aids in university teaching are looked at in detail. (Editor/RK)

  4. Offshore Wind Turbine Foundation Design

    DEFF Research Database (Denmark)

    Passon, Patrik; Hvenekær Rasmussen, Jørgen

    continued into 2015 it is even more important to drive down the costs of energy for renewable energy sources such as offshore wind energy in order to arrive at a sustainable future on a global level.Cost of energy reductions for offshore wind turbines (OWTs) can be achieved by optimizations on different......-wave correlations are typically subjected to sequential load calculation approaches in an iterative and collaborative process between foundation designer and wind turbine manufacturer. Involvement of these different design parties may be motivated by various aspects such as introduction of state-of-the-art design...... in the specific context of OWTs and individual foundation type characteristics. For example, modelling and load calculation approaches for jacket type foundations of OWTs are often inherited from existing experiences of monopile type foundations or from their counterparts in the offshore oil & gas industry...

  5. Crohn's & Colitis Foundation of America

    Science.gov (United States)

    ... enabled to enjoy the full interactive experience. Crohn's & Colitis Foundation of America Find a Doctor Find a ... Local Chapters News Events Search: What are Crohn's & Colitis? What is Crohn's Disease What is Ulcerative Colitis ...

  6. Experimental Research of Engine Foundations

    Directory of Open Access Journals (Sweden)

    Violeta-Elena Chiţan

    2004-01-01

    Full Text Available This paper tries a compact presentation of experimental research of engine-foundations. The dynamic phenomena are so complex, that the vibrations cannot be estimated in the design stage. The design engineer of an engine foundation must foresee through a dynamic analysis of the vibrations, those measures that lead to the avoidance or limiting of the bad effects caused by the vibrations.

  7. Foundations of genetic algorithms 1991

    CERN Document Server

    FOGA

    1991-01-01

    Foundations of Genetic Algorithms 1991 (FOGA 1) discusses the theoretical foundations of genetic algorithms (GA) and classifier systems.This book compiles research papers on selection and convergence, coding and representation, problem hardness, deception, classifier system design, variation and recombination, parallelization, and population divergence. Other topics include the non-uniform Walsh-schema transform; spurious correlations and premature convergence in genetic algorithms; and variable default hierarchy separation in a classifier system. The grammar-based genetic algorithm; condition

  8. 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

  9. Physical Foundations of Cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, J M [University of Cambridge (United Kingdom)

    2006-02-07

    In 1952, Mme Yvonne Choquet-Bruhat published a major paper, Theoreme d'existence pour certains systemes d'equations aux derivees partielles non lineaires (Acta Math. 88 141-225), which laid the foundation for modern studies of the Cauchy problem in general relativity. The fiftieth anniversary of this event was celebrated with an eponymous Cargese Summer School in 2002. The proceedings of that summer school are summarized electronically (as audio, video, transparencies and lecture notes, where available) on a DVD archive included with this volume, and are also available on the internet. However the organizers decided that a separate volume describing the 'state of the art in mathematical general relativity' would be useful, and this book is the result. It includes some material not covered in the school and excludes some school material which has been covered adequately elsewhere. About one fifth of the book is devoted to a survey of Smoothness at Null Infinity and the Structure of Initial Data by Helmut Friedrich. This is a modern study of gravitational radiation, and the analysis of Einstein's equations. It is extremely helpful to survey all of this material, including some of the latest developments, using a consistent notation. This article is strongly recommended to anyone hoping to gain a foothold in this area. Lars Andersson has surveyed, in The Global Existence Problem in General Relativity, some results and conjectures about the global properties of 3+1-dimensional spacetimes with a compact Cauchy surface. Again it is very useful to have essentially all of the known results presented in a consistent notation. This material is not on the DVD. Yvonne Choquet-Bruhat has contributed a long research paper, Future Complete U(1) Symmetric Einsteinian Spacetimes, the Unpolarized Case. There is a non-linear stability theorem due to her and Vincent Moncrief in which spacetime is of the form M x R where M is a circle bundle over a compact

  10. Physical Foundations of Cosmology

    International Nuclear Information System (INIS)

    In 1952, Mme Yvonne Choquet-Bruhat published a major paper, Theoreme d'existence pour certains systemes d'equations aux derivees partielles non lineaires (Acta Math. 88 141-225), which laid the foundation for modern studies of the Cauchy problem in general relativity. The fiftieth anniversary of this event was celebrated with an eponymous Cargese Summer School in 2002. The proceedings of that summer school are summarized electronically (as audio, video, transparencies and lecture notes, where available) on a DVD archive included with this volume, and are also available on the internet. However the organizers decided that a separate volume describing the 'state of the art in mathematical general relativity' would be useful, and this book is the result. It includes some material not covered in the school and excludes some school material which has been covered adequately elsewhere. About one fifth of the book is devoted to a survey of Smoothness at Null Infinity and the Structure of Initial Data by Helmut Friedrich. This is a modern study of gravitational radiation, and the analysis of Einstein's equations. It is extremely helpful to survey all of this material, including some of the latest developments, using a consistent notation. This article is strongly recommended to anyone hoping to gain a foothold in this area. Lars Andersson has surveyed, in The Global Existence Problem in General Relativity, some results and conjectures about the global properties of 3+1-dimensional spacetimes with a compact Cauchy surface. Again it is very useful to have essentially all of the known results presented in a consistent notation. This material is not on the DVD. Yvonne Choquet-Bruhat has contributed a long research paper, Future Complete U(1) Symmetric Einsteinian Spacetimes, the Unpolarized Case. There is a non-linear stability theorem due to her and Vincent Moncrief in which spacetime is of the form M x R where M is a circle bundle over a compact orientable surface of genus

  11. On inequalities of Hermite-Hadamard type for co-ordinated \\((\\alpha_1,m_1\\-\\((\\alpha_2,m_2\\-convex functions

    Directory of Open Access Journals (Sweden)

    Shu-Ping Bai

    2015-11-01

    Full Text Available In the paper, the authors establish some Hermite-Hadamard type integral inequalities for co-ordinated \\((\\alpha_1,m_1\\-\\((\\alpha_2,m_2\\-convex functions on a rectangle of the plane \\(\\mathbb{R}_0^2\\.

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Amplification of the tetracycline resistance determinant of plasmid pAM alpha 1 in Streptococcus faecalis: dependence on host recombination machinery.

    OpenAIRE

    Yagi, Y.; Clewell, D B

    1980-01-01

    The plasmid pAM alpha 1 in Streptococcus faecalis was found to be severely impaired in its ability to exhibit amplification (generation of tandem repeats of the tetracycline resistance determinant during extended growth in the presence of tetracycline) when harbored by the recombination-deficient host cell UV202.

  14. 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

  15. 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

  16. 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

  17. Binding of peptides to HLA-DQ molecules: peptide binding properties of the disease-associated HLA-DQ(alpha 1*0501, beta 1*0201) molecule

    DEFF Research Database (Denmark)

    Johansen, B H; Buus, S; Vartdal, F;

    1994-01-01

    Peptide binding to DQ molecules has not previously been described. Here we report a biochemical peptide-binding assay specific for the DQ2 [i.e. DQ(alpha 1*0501, beta 1*0201)] molecule. This molecule was chosen since it shows a strong association to diseases such as celiac disease and insulin...

  18. Expansion of microsatellite in the thyroid hormone receptor-alpha1 gene linked to increased receptor expression and less aggressive thyroid cancer

    DEFF Research Database (Denmark)

    Onda, Masamitsu; Li, Daisy; Suzuki, Shinichi;

    2002-01-01

    PURPOSE: The purpose of this study was to determine whether the length of the THRA1 microsatellite, which resides in a noncoding portion of the thyroid hormone receptor-alpha1 gene, affects receptor expression and is linked to clinicopathological parameters in thyroid cancer. EXPERIMENTAL DESIGN:...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  20. Homology modeling of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABA receptor channels and Surflex-docking of fipronil.

    Science.gov (United States)

    Cheng, Jin; Ju, Xiu-Lian; Chen, Xiang-Yang; Liu, Gen-Yan

    2009-09-01

    To further explore the mechanism of selective binding of the representative gamma-aminobutyric acid receptors (GABARs) noncompetitive antagonist (NCA) fipronil to insect over mammalian GABARs, three-dimensional models of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABAR were generated by homology modeling, using the cryo-electron microscopy structure of the nicotinic acetylcholine receptor (nAChR) of Torpedo marmorata as a template. Fipronil was docked into the putative binding site of the human alpha 1 beta 2 gamma 2 and house fly beta 3 receptors by Surflex-docking, and the calculated docking energies are in agreement with experimental results. The GABA receptor antagonist fipronil exhibited higher potency with house fly beta 3 GABAR than with human alpha 1 beta 2 gamma 2 GABAR. Furthermore, analyses of Surflex-docking suggest that the H-bond interaction of fipronil with Ala2 and Thr6 in the second transmembrane segment (TM2) of these GABARs plays a relatively important role in ligand selective binding. The different subunit assemblies of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABARs may result in differential selectivity for fipronil.

  1. Human alpha galactosidase and alpha 1,2fucosyltransferase concordantly inhibit xenoreactivity of NIH 3T3 cells with human serum

    Institute of Scientific and Technical Information of China (English)

    YANJing-Lian; YULu-Yang; GUOLi-He

    2003-01-01

    AIM: To study the influence of the expression of human alpha galactosidase and alphal,2 fucosyltransferase on Galalpha 1,3 Gal and consequent xenoreactivity in NIH3T3 cells. METHODS: The expression levels of G antigen andH antigen and binding of human natural antibodies (IgG and IgM) and complement (C3c) to NIH3T3 cells wereanalyzed by flow cytometry. Western blot was employed to further determine the expression of glycoproteins of Gantigen. Cytolysis assay with normal human serum was performed by MTT assay. RESULTS: Western blotshowed that glycoproteins with molecular weight of 107 kDa, 98 kDa, 88 kDa, 56 kDa, 40 kDa, and 37 kDa wereinhibited and even abrogated totally in alpha galactosidase transfectants and alpha 1,2 fucosyltransferase transfectants.The combined transfection of the two enzymes led to a much stronger inhibition of the glycoproteins. The bindingof Gs-IB4 was decreased by 57.4% in alpha galactosidase transfectants, 28.8% in alpha 1,2 fucosyltransferasetransfectants, and 72.1% in combined transfectants, respectively. In contrast, UEA-1 binding was increased about6.7-fold, 6.0-fold, and 8.0-fold respectively. The xenoreactivity with human IgG was also reduced by 61.4%, 67.0%,and 73.4%, respectively in the three kinds of transfectants. The resistance to cytolysis mediated by human serumwas enhanced by 42.4% in alpha galactosidase transfectants, 51.9% in alpha 1,2 fucosyltranferase, and even65.5% in the combined transfectants. CONCLUSION: Although alpha galactosidase and alpha 1,2 fucosyltransferasehad different biochemical properties, they could inhibit the expression of Gal alpha 1,3 Gal synergistically, leading tostronger resistance of xenograft against cytolysis.

  2. Foundation on Economic Trends v. Bowen.

    Science.gov (United States)

    1989-10-01

    The National Enviromental Policy Act requires that government agencies make a detailed enviromental impact statement (EIS) for all research significantly affecting the environment. These statements must be supplemented if the project substantially changes or if new information is obtained. The Foundation on Economic Trends argued that three developments in recombinant DNA research will significantly alter the enviromental impact, thereby mandating a new EIS by the National Institutes of Health (NIH). These developments are cloning oncogenic viruses, engineering the human immunodeficiency virus into cells not normally susceptible to it, and introducing AIDS genetic codes into mice. The U.S. District Court, District of Columbia, held that the first two projects do not pose a greater risk and that the enviromental assessment being prepared by NIH on the third satisfies the requirements of the National Enviromental Policy Act. PMID:11648296

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

    Science.gov (United States)

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

    2015-10-01

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

  4. Entrapment of alpha1-acid glycoprotein in high-performance affinity columns for drug-protein binding studies.

    Science.gov (United States)

    Bi, Cong; Jackson, Abby; Vargas-Badilla, John; Li, Rong; Rada, Giana; Anguizola, Jeanethe; Pfaunmiller, Erika; Hage, David S

    2016-05-15

    A slurry-based method was developed for the entrapment of alpha1-acid glycoprotein (AGP) for use in high-performance affinity chromatography to study drug interactions with this serum protein. Entrapment was achieved based on the physical containment of AGP in hydrazide-activated porous silica supports and by using mildly oxidized glycogen as a capping agent. The conditions needed for this process were examined and optimized. When this type of AGP column was used in binding studies, the association equilibrium constant (Ka) measured by frontal analysis at pH 7.4 and 37°C for carbamazepine with AGP was found to be 1.0 (±0.5)×10(5)M(-1), which agreed with a previously reported value of 1.0 (±0.1)×10(5)M(-1). Binding studies based on zonal elution were conducted for several other drugs with such columns, giving equilibrium constants that were consistent with literature values. An entrapped AGP column was also used in combination with a column containing entrapped HSA in a screening assay format to compare the binding of various drugs to AGP and HSA. These results also agreed with previous data that have been reported in literature for both of these proteins. The same entrapment method could be extended to other proteins and to the investigation of additional types of drug-protein interactions. Potential applications include the rapid quantitative analysis of biological interactions and the high-throughput screening of drug candidates for their binding to a given protein.

  5. Efficacy of three different alpha 1-adrenergic blockers and hyoscine N-butylbromide for distal ureteral stones

    Directory of Open Access Journals (Sweden)

    M. Cenk Gurbuz

    2011-04-01

    Full Text Available PURPOSE: To evaluate hyoscine N-butyl bromide (HBB and three different alpha-1 blockers in the treatment of distal ureteral stones. MATERIALS AND METHODS: A total of 140 patients with stones located in the distal tract of the ureter with stone diameters of 5 to 10mm were enrolled in the present study and were randomized into 4 equal groups. Group 1 received HBB, Group 2 received alfuzosin, Group 3 received doxazosin and Group 4 received terazosin. The subjects were prescribed diclofenac injection (75 mg intramuscularly on demand for pain relief and were followed-up after two weeks with x-rays of the kidneys, ureters, bladder and urinary ultrasonography every week. The number of pain episodes, analgesic dosage and the number of days of spontaneous passage of the calculi through the ureter were also recorded. RESULTS: The average stone size for groups 1, 2, 3 and 4 was comparable (6.13, 5.83, 5.59 and 5.48 mm respectively. Stone expulsion was observed in 11%, 52.9%, 62%, and 46% in groups 1, 2, 3 and 4 respectively. The average time to expulsion was 10.55 ± 6.21 days in group 1, 7.38 ± 5.55 days in group 2, 7.85 ± 5.11 days in group 3 and 7.45 ± 5.32 days in group 4. Alpha blockers were found to be superior to HBB (p < 0.05. CONCLUSIONS: Medical treatment of distal ureteral calculi with alfuzosin, doxazosin and terazosin resulted in a signi?cantly increased stone-expulsion rate and decreased expulsion time when compared with HBB. HBB seems to have a negative effect on stone-expulsion rate.

  6. 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.

  7. Scour Development around Bucket Foundations

    DEFF Research Database (Denmark)

    Stroescu, Ionut Emanuel; Frigaard, Peter Bak; Fejerskov, Morten

    2015-01-01

    The design without scour protection is a sensitive topic to most offshore developers, especially in the North Sea. However, newer research show that this concept is realistic if exists extended comprehension of the scour and backfill phenomena. The present paper shows comparative results for mono......The design without scour protection is a sensitive topic to most offshore developers, especially in the North Sea. However, newer research show that this concept is realistic if exists extended comprehension of the scour and backfill phenomena. The present paper shows comparative results...... for monopile and Bucket Foundation; using experimental analysis and real scour surveys around offshore installed Bucket Foundations. The main finding reflect that Bucket Foundation is a candidate for design without scour protection behaving like scour protected monopoles, in a variety of environmental...

  8. Macroelement modeling of shallow foundations

    CERN Document Server

    Chatzigogos, Charisis; Salençon, J

    2008-01-01

    The paper presents a new macroelement model for shallow foundations. The model is defined through a non-linear constitutive law written in terms of some generalized force and displacement parameters. The linear part of this constitutive law comes from the dynamic impedances of the foundation. The non-linear part comprises two mechanisms. One is due to the irreversible elastoplastic soil behavior: it is described with a bounding surface hypoplastic model, adapted for the description of the cyclic soil response. An original feature of the formulation is that the bounding surface is considered independently of the surface of ultimate loads of the system. The second mechanism is the detachment that can take place at the soil-footing interface (foundation uplift). It is totally reversible and non-dissipative and can thus be described by a phenomenological non-linear elastic model. The macroelement is qualitatively validated by application to soil-structure interaction analyses of simple real structures.

  9. Characteristic Behavior of Bucket Foundations

    DEFF Research Database (Denmark)

    Barari, Amin

    The world is currently facing serious problems brought about by oil dependence. Reducing oil consumption provides an opportunity to increase competitiveness, technological development, and progress. Wind energy is currently the most costcompetitive form of renewable energy, and there are strong...... the design of offshore wind turbine foundations. The work was divided into two main research efforts: geotechnical engineering experiments to gain insight into the behavior of offshore bucket foundations, and development of methods to improve the study of infiltration into unsaturated soils, an important...

  10. Professional Team Foundation Server 2012

    CERN Document Server

    Blankenship, Ed; Holliday, Grant; Keller, Brian

    2012-01-01

    A comprehensive guide to using Microsoft Team Foundation Server 2012 Team Foundation Server has become the leading Microsoft productivity tool for software management, and this book covers what developers need to know to use it effectively. Fully revised for the new features of TFS 2012, it provides developers and software project managers with step-by-step instructions and even assists those who are studying for the TFS 2012 certification exam. You'll find a broad overview of TFS, thorough coverage of core functions, a look at extensibility options, and more, written by Microsoft ins

  11. Physical foundations of technical acoustics

    CERN Document Server

    Malecki, I

    1969-01-01

    Physical Foundations of Technical Acoustics discusses theoretical foundations of acoustical engineering. It is not so much a technical compendium as a systematic statement of physical laws so conceived that technologists might find in it all the information they need to become acquainted with the physical meaning and mathematical expression of phenomena they encounter in their work. To facilitate the acquirement of notions, which lie beyond a layman's grasp, the plan of narration adopted consists in beginning with the simplest idealized cases and then gradually moving on to the truest possibl

  12. On the foundation of Mechanics

    CERN Document Server

    Alonso-Blanco, Ricardo J

    2014-01-01

    This note is an extended version of "A note on the foundations of Mechanics", arXiv: 1404.1321 [math-ph]. A presentation of its contents was given in a talk in memorial homage to the professor Juan B. Sancho Guimer\\'a. For this reason, it was written in spanish language. The matter of the note is a systematic foundation of the most classical part of Mechanics. The content by sections is: 0)Notions and basic results, 1)Conservative systems 2) Time. Time constraints, 3) Proper time. Relativistic forces, 4)Electromagnetic fields, 5) On the Hamilton-Noether Principle, 6) Schr\\"odinger equation.

  13. ITIL Foundation exam study guide

    CERN Document Server

    Gallacher, Liz

    2012-01-01

    Everything you need to prepare for the ITIL exam The ITIL (Information Technology Infrastructure Library) exam is the ultimate certification for IT service management. This essential resource is a complete guide to preparing for the ITIL Foundation exam and includes everything you need for success. Organized around the ITIL Foundation syllabus, the study guide addresses the ITIL Service Lifecycles, the ITIL processes, roles, and functions, and also thoroughly explains how the Service Lifecycle provides effective and efficient IT services. Offers an introduction to IT service management and ITI

  14. Professional Team Foundation Server 2010

    CERN Document Server

    Blankenship, Ed; Holliday, Grant; Keller, Brian

    2011-01-01

    Authoritative guide to TFS 2010 from a dream team of Microsoft insiders and MVPs!Microsoft Visual Studio Team Foundation Server (TFS) has evolved until it is now an essential tool for Microsoft?s Application Lifestyle Management suite of productivity tools, enabling collaboration within and among software development teams. By 2011, TFS will replace Microsoft?s leading source control system, VisualSourceSafe, resulting in an even greater demand for information about it. Professional Team Foundation Server 2010, written by an accomplished team of Microsoft insiders and Microsoft MVPs, provides

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

    Directory of Open Access Journals (Sweden)

    Gian Andri Thun

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

  16. 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

  17. Bucket Foundation Response Under Various Displacement Rates

    DEFF Research Database (Denmark)

    Vaitkunaite, Evelina; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

    2016-01-01

    The present testing program aims at showing the pore pressure response around a bucket foundation skirt as well as the load and displacement change due to ten different displacement rates. Research findings are useful for a numerical model calibration focusing on the design of the upwind foundation...... in a multi-bucket foundation system. The foundation model is at a scale of approximately 1:20 prototype foundation size. The tests are performed in a pressure tank with the foundation model installed in dense sand. Based on the data, the conclusion is that the bucket foundation design in a storm case should...

  18. Student Alumni Associations and Foundations.

    Science.gov (United States)

    Alberger, Patricia L., Ed.

    Papers from a conference on student alumni programs and foundations are presented. Contents are as follows: "How Student Alumni Programs Can Serve Your Institution," by Larry Weiss; "How to Start a Student Alumni Organization," by William Harlan; "Getting the Right Students: How, When, and Where" (Harlan); "Building Your Budget From Scratch," by…

  19. Theoretical foundations for collaboration engineering

    NARCIS (Netherlands)

    Kolfschoten, G.L.

    2007-01-01

    Collaboration is often presented as the solution to numerous problems in business and society. However, collaboration is challenging, and collaboration support is not an off-the-shelf-product. This research offers theoretical foundations for Collaboration Engineering. Collaboration Engineering is an

  20. The Governance of Industrial Foundations

    DEFF Research Database (Denmark)

    Børsting, Christa; Kuhn, Johan; Poulsen, Thomas;

    We study turnover among executives and directors in companies owned by Danish industrial foundations, which are held to be long term owners. Executives are members of the management board (direktionen), whereas directors a members of the supervisiory board (bestyrelsen). As expected, we find...

  1. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology. Rather than

  2. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>The Rural Development Foundation (RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providingquality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in AndhraPradesh State,taking a unique holistic approach to education through innovative programs and methodology. Rather than using the con-

  3. Cushing's Support and Research Foundation

    Science.gov (United States)

    ... News in Southern California aired a segment on Cushing's Disease. VIEW THE VIDEO > Have You Had an EMS Experience for Adrenal Insufficiency? The CARES Foundation is looking for stories from patients who have had ... Spotlight Diagnosing Cushing's Webinar On May 7, 2016 Dr. James Findling ...

  4. Urban heritage, building maintenance: foundations

    NARCIS (Netherlands)

    Verhoef, L.G.W.

    1999-01-01

    What do we understand by the term 'foundations'? This general idea may embody the literal ' groundwork' that provides support for a building and may possibly include the entire structural works that serve to pre vent subsidence. Remarkably, in this definition the word 'groundwork' incorporates both

  5. Does Macroeconomics Need Microeconomic Foundations?

    OpenAIRE

    Da Silva, Sergio

    2009-01-01

    The author argues that it is microeconomics that needs foundations, not macroeconomics. Preferences need to be built on biology, and, in particular, on neuroscience. In contrast, macroeconomics could benefit from rationalizations of aggregate economic phenomena by non-equilibrium statistical physics.

  6. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    <正>The Rural Development Foundation(RDF),founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children.RDF founded and continues to operate five schools and one junior college in Andhra

  7. Foundations of Responsibility for Children

    Science.gov (United States)

    Dillen, Annemie

    2008-01-01

    Children's vulnerability asks for people taking up responsibility for children. In this contribution, three different ways of thinking on foundations of (ethical and spiritual) responsibility for children are discussed, namely, a liberalist, a social-constructivist and a naturalist paradigm. The author argues that cultural and natural elements are…

  8. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providingquality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college inAndhra Pradesh State,

  9. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    <正>The Rural Development Foundation(RDF),founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children.RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology.Rather than using the

  10. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>The Rural Development Foundation(RDF),founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children.RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology.Rather than using the con-

  11. Behavior Modeling -- Foundations and Applications

    DEFF Research Database (Denmark)

    This book constitutes revised selected papers from the six International Workshops on Behavior Modelling - Foundations and Applications, BM-FA, which took place annually between 2009 and 2014. The 9 papers presented in this volume were carefully reviewed and selected from a total of 58 papers...

  12. Team Foundation Server 2013 customization

    CERN Document Server

    Beeming, Gordon

    2014-01-01

    This book utilizes a tutorial based approach, focused on the practical customization of key features of the Team Foundation Server for collaborative enterprise software projects.This practical guide is intended for those who want to extend TFS. This book is for intermediate users who have an understanding of TFS, and basic coding skills will be required for the more complex customizations.

  13. Principles for Foundations of Education.

    Science.gov (United States)

    Britt, John

    The significance of the foundations of education approach to teaching is apparent in the ideas of John Henry Newman, Karl Jaspers, Jose Ortega y Gasset, and Mortimer Adler. Newman maintained that there is a circle of knowledge and once this unity is ignored the result is distortion in the learners and in the knowledge. To retain the whole, the…

  14. DNA methylation and transcription in a distal region upstream from the bovine AlphaS1 casein gene after once or twice daily milking.

    Directory of Open Access Journals (Sweden)

    Minh Nguyen

    Full Text Available Once daily milking (ODM induces a reduction in milk production when compared to twice daily milking (TDM. Unilateral ODM of one udder half and TDM of the other half, enables the study of underlying mechanisms independently of inter-individual variability (same genetic background and of environmental factors. Our results show that in first-calf heifers three CpG, located 10 kb upstream from the CSN1S1 gene were methylated to 33, 34 and 28%, respectively, after TDM but these levels were higher after ODM, 38, 38 and 33%, respectively. These methylation levels were much lower than those observed in the mammary gland during pregnancy (57, 59 and 50%, respectively or in the liver (74, 78 and 61%, respectively. The methylation level of a fourth CpG (CpG4, located close by (29% during TDM was not altered after ODM. CpG4 methylation reached 39.7% and 59.5%, during pregnancy or in the liver, respectively. CpG4 is located within a weak STAT5 binding element, arranged in tandem with a second high affinity STAT5 element. STAT5 binding is only marginally modulated by CpG4 methylation, but it may be altered by the methylation levels of the three other CpG nearby. Our results therefore shed light on mechanisms that help to explain how milk production is almost, but not fully, restored when TDM is resumed (15.1 ± 0.2 kg/day instead of 16.2 ± 0.2 kg/day, p<0.01. The STAT5 elements are 100 bp away from a region transcribed in the antisense orientation, in the mammary gland during lactation, but not during pregnancy or in other reproductive organs (ovary or testes. We now need to clarify whether the transcription of this novel RNA is a consequence of STAT5 interacting with the CSN1S1 distal region, or whether it plays a role in the chromatin structure of this region.

  15. DNA Methylation and Transcription in a Distal Region Upstream from the Bovine AlphaS1 Casein Gene after Once or Twice Daily Milking

    Science.gov (United States)

    Nguyen, Minh; Boutinaud, Marion; Pétridou, Barbara; Gabory, Anne; Pannetier, Maëlle; Chat, Sophie; Bouet, Stephan; Jouneau, Luc; Jaffrezic, Florence; Laloë, Denis; Klopp, Christophe; Brun, Nicolas; Kress, Clémence; Jammes, Hélène; Charlier, Madia; Devinoy, Eve

    2014-01-01

    Once daily milking (ODM) induces a reduction in milk production when compared to twice daily milking (TDM). Unilateral ODM of one udder half and TDM of the other half, enables the study of underlying mechanisms independently of inter-individual variability (same genetic background) and of environmental factors. Our results show that in first-calf heifers three CpG, located 10 kb upstream from the CSN1S1 gene were methylated to 33, 34 and 28%, respectively, after TDM but these levels were higher after ODM, 38, 38 and 33%, respectively. These methylation levels were much lower than those observed in the mammary gland during pregnancy (57, 59 and 50%, respectively) or in the liver (74, 78 and 61%, respectively). The methylation level of a fourth CpG (CpG4), located close by (29% during TDM) was not altered after ODM. CpG4 methylation reached 39.7% and 59.5%, during pregnancy or in the liver, respectively. CpG4 is located within a weak STAT5 binding element, arranged in tandem with a second high affinity STAT5 element. STAT5 binding is only marginally modulated by CpG4 methylation, but it may be altered by the methylation levels of the three other CpG nearby. Our results therefore shed light on mechanisms that help to explain how milk production is almost, but not fully, restored when TDM is resumed (15.1±0.2 kg/day instead of 16.2±0.2 kg/day, p<0.01). The STAT5 elements are 100 bp away from a region transcribed in the antisense orientation, in the mammary gland during lactation, but not during pregnancy or in other reproductive organs (ovary or testes). We now need to clarify whether the transcription of this novel RNA is a consequence of STAT5 interacting with the CSN1S1 distal region, or whether it plays a role in the chromatin structure of this region. PMID:25369064

  16. Next generation DNA led technologies

    CERN Document Server

    Jyothsna, G; Kashyap, Amita

    2016-01-01

    This brief highlights advances in DNA technologies and their wider applications. DNA is the source of life and has been studied since a generation, but very little is known as yet. Several sophisticated technologies of the current era have laid their foundations on the principle of DNA based mechanisms. DNA based technologies are bringing a new revolution of Advanced Science and Technology. Forensic Investigation, Medical Diagnosis, Paternity Disputes, Individual Identity, Health insurance, Motor Insurance have incorporated the DNA testing and profiling technologies for settling the issues.

  17. The Structure and Function of an Arabinan-specific [alpha]-1,2-Arabinofuranosidase Identified from Screening the Activities of Bacterial GH43 Glycoside Hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Cartmell, Alan; McKee, Lauren S.; Pena, Maria J.; Larsbrink, Johan; Brumer, Harry; Kaneko, Satoshi; Ichinose, Hitomi; Lewis, Richard J.; Vikso-Nielsen, Anders; Gilbert, Harry; Marles-Wright, Jon (Newcastle); (National Food Research Institute); (Novozymes A/S); (RITS); (Georgia)

    2012-03-26

    Reflecting the diverse chemistry of plant cell walls, microorganisms that degrade these composite structures synthesize an array of glycoside hydrolases. These enzymes are organized into sequence-, mechanism-, and structure-based families. Genomic data have shown that several organisms that degrade the plant cell wall contain a large number of genes encoding family 43 (GH43) glycoside hydrolases. Here we report the biochemical properties of the GH43 enzymes of a saprophytic soil bacterium, Cellvibrio japonicus, and a human colonic symbiont, Bacteroides thetaiotaomicron. The data show that C. japonicus uses predominantly exo-acting enzymes to degrade arabinan into arabinose, whereas B. thetaiotaomicron deploys a combination of endo- and side chain-cleaving glycoside hydrolases. Both organisms, however, utilize an arabinan-specific {alpha}-1,2-arabinofuranosidase in the degradative process, an activity that has not previously been reported. The enzyme can cleave {alpha}-1,2-arabinofuranose decorations in single or double substitutions, the latter being recalcitrant to the action of other arabinofuranosidases. The crystal structure of the C. japonicus arabinan-specific {alpha}-1,2-arabinofuranosidase, CjAbf43A, displays a five-bladed {beta}-propeller fold. The specificity of the enzyme for arabinan is conferred by a surface cleft that is complementary to the helical backbone of the polysaccharide. The specificity of CjAbf43A for {alpha}-1,2-L-arabinofuranose side chains is conferred by a polar residue that orientates the arabinan backbone such that O2 arabinose decorations are directed into the active site pocket. A shelflike structure adjacent to the active site pocket accommodates O3 arabinose side chains, explaining how the enzyme can target O2 linkages that are components of single or double substitutions.

  18. MCDF-RCI predictions for structure and width of $K\\alpha_{1,2}$ x-ray line of Al and Si

    CERN Document Server

    Kozioł, Karol

    2014-01-01

    Multiconfiguration Dirac-Fock and Relativistic Configuration Interaction methods have been employed to predict the structure and the width of $K\\alpha_{1,2}$ x-ray lines of Al and Si. The influences of electron correlation and inclusion of possible satellite contributions on spectra structure have been studied. The widths of $K$ and $L_{2,3}$ atomic levels of Al and Si have been also computed.

  19. Investigation of the Relationship Between Clinical and EEG Findings of Photosensitive Epilepsy and GABA Receptor Alpha 1 Subunit (GABRA1) Gene Mutations

    OpenAIRE

    Yavuz, E.N.; Demirkan, A.; Moen, S.; Ozdemir, O.; Catal, S.; Bebek, N.; Ozbek, U; Baykan, B.

    2011-01-01

    Objective: Although photosensitive epilepsy (PE) is commonly observed, its pathophysiology has not been clarified yet. However, relevant literature indicates that genetic factors play an important role. Our aim was to investigate whether there is a relationship between the clinical and electroencephalographic (EEG) features and the possible mutations/polymorphisms in the GABA receptor alpha 1 subunit (GABRA1) gene in patients with PE by scanning this gene. Methods: 54 patients diagnosed as ha...

  20. Identification of a GH110 subfamily of alpha 1,3-galactosidases: novel enzymes for removal of the alpha 3Gal xenotransplantation antigen

    DEFF Research Database (Denmark)

    Liu, Qiyong P; Yuan, Huaiping; Bennett, Eric P;

    2008-01-01

    Bacteroides fragilis had exquisite substrate specificity for the branched blood group B structure Galalpha1-3(Fucalpha1-2)Gal, whereas linear oligosaccharides terminated by alpha1,3-linked galactose such as the immunodominant xenotransplantation epitope Galalpha1-3Galbeta1-4GlcNAc did not serve as substrates...... mechanism. The novel GH110 subfamily offers enzymes with highly improved performance in enzymatic removal of the immunodominant alpha3Gal xenotransplantation epitope....

  1. Foundations of scientific research (Foundations of Research Activities)

    OpenAIRE

    Glazunov, N. M.

    2012-01-01

    During years 2008 to 2011 author gives several courses on Foundations of Scientific Research at Computer Science Faculty of the National Aviation University in Kiev. This text presents material to lectures of the courses. It consists of 18 sections and some ideas of the manual can be seen from their titles. These include: General notions about scientific research. Ontologies and upper ontologies. Ontologies of object domains. Examples of Research Activity. Some Notions of the Theory of Finite...

  2. Comparison of the effect of alpha1- and alpha2-adrenoceptor agonists and antagonists on muscle contractility of the rabbit abdominal aorta in vitro.

    Science.gov (United States)

    Gnus, Jan; Rusiecka, Agnieszka; Czerski, Albert; Zawadzki, Wojciech; Witkiewicz, Wojciech; Hauzer, Willy

    2013-01-01

    The aim of the study was to demonstrate the effect of selected agonists and antagonists of alpha-adrenergic receptors on muscle contractility of the rabbit abdominal aorta in vitro with particular emphasis on alpha2-adrenergic receptor subtypes. The study was conducted on 30 New Zealand breed rabbits from which specimens of the abdominal aorta were collected. The sections were set up in an automatic water bath in a Krebs-Henseleit buffer at 37 degrees C. The experiments showed that alpha1-adrenergic receptors played the main role in the contractile response ofthe rabbit abdominal aorta. Stimulation of alpha1-adrenergic receptor by administration ofphenylephrine resulted in an increase in smooth muscle tonus ofthe rabbit abdominal aorta by an average of 4.75 mN. The reaction after stimulation of alpha2-adrenergic receptors by similar doses of their agonists was much weaker. Prolonged tissue response time and time needed to reach maximum tonus for alpha2-adrenergic receptor agonists were observed. The obtained results confirm the thesis that the alpha1-adrenergic receptor is the most important factor controlling the contractility of the rabbit abdominal aorta, but the alpha2-adrenergic receptor is also involved in maintaining muscle tissue tonus. PMID:23767297

  3. Boosting of synaptic potentials and spine Ca transients by the peptide toxin SNX-482 requires alpha-1E-encoded voltage-gated Ca channels.

    Directory of Open Access Journals (Sweden)

    Andrew J Giessel

    Full Text Available The majority of glutamatergic synapses formed onto principal neurons of the mammalian central nervous system are associated with dendritic spines. Spines are tiny protuberances that house the proteins that mediate the response of the postsynaptic cell to the presynaptic release of glutamate. Postsynaptic signals are regulated by an ion channel signaling cascade that is active in individual dendritic spines and involves voltage-gated calcium (Ca channels, small conductance (SK-type Ca-activated potassium channels, and NMDA-type glutamate receptors. Pharmacological studies using the toxin SNX-482 indicated that the voltage-gated Ca channels that signal within spines to open SK channels belong to the class Ca(V2.3, which is encoded by the Alpha-1E pore-forming subunit. In order to specifically test this conclusion, we examined the effects of SNX-482 on synaptic signals in acute hippocampal slices from knock-out mice lacking the Alpha-1E gene. We find that in these mice, application of SNX-482 has no effect on glutamate-uncaging evoked synaptic potentials and Ca influx, indicating that that SNX-482 indeed acts via the Alpha-1E-encoded Ca(V2.3 channel.

  4. Ancient DNA

    DEFF Research Database (Denmark)

    Willerslev, Eske; Cooper, Alan

    2004-01-01

    ancient DNA, palaeontology, palaeoecology, archaeology, population genetics, DNA damage and repair......ancient DNA, palaeontology, palaeoecology, archaeology, population genetics, DNA damage and repair...

  5. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  6. Characteristic Behavior of Bucket Foundations

    DEFF Research Database (Denmark)

    Barari, Amin

    The world is currently facing serious problems brought about by oil dependence. Reducing oil consumption provides an opportunity to increase competitiveness,technological development, and progress. Wind energy is currently the most cost-competitive form of renewable energy, and there are strong...... engineering experiments to gain insight into the behavior of offshore bucket foundations, and development of methods to improve the study of infiltration intounsaturated soils, an important problem in geo-environmental engineering. The outcomes of the research have the potential to directly or indirectly...... reduce the risks and costsrelated to offshore geotechnics. The thesis examines: 1.Characteristic Behavior of Bucket Foundations 2. Modeling of Water Flow through Porous Media The outcomes of each of the research contributions are summarized in four research articles, either directly or indirectly...

  7. Linear programming foundations and extensions

    CERN Document Server

    Vanderbei, Robert J

    2001-01-01

    Linear Programming: Foundations and Extensions is an introduction to the field of optimization. The book emphasizes constrained optimization, beginning with a substantial treatment of linear programming, and proceeding to convex analysis, network flows, integer programming, quadratic programming, and convex optimization. The book is carefully written. Specific examples and concrete algorithms precede more abstract topics. Topics are clearly developed with a large number of numerical examples worked out in detail. Moreover, Linear Programming: Foundations and Extensions underscores the purpose of optimization: to solve practical problems on a computer. Accordingly, the book is coordinated with free efficient C programs that implement the major algorithms studied: -The two-phase simplex method; -The primal-dual simplex method; -The path-following interior-point method; -The homogeneous self-dual methods. In addition, there are online JAVA applets that illustrate various pivot rules and variants of the simplex m...

  8. Cognitive Foundations for Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Greitzer, Frank L.; Noonan, Christine F.; Franklin, Lyndsey

    2011-02-25

    In this report, we provide an overview of scientific/technical literature on information visualization and VA. Topics discussed include an update and overview of the extensive literature search conducted for this study, the nature and purpose of the field, major research thrusts, and scientific foundations. We review methodologies for evaluating and measuring the impact of VA technologies as well as taxonomies that have been proposed for various purposes to support the VA community. A cognitive science perspective underlies each of these discussions.

  9. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology. Rather than using the conventional method of rote memorization,RDF focuses on cultivating critical thinking skills and

  10. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>The Rural Development Foundation(RDF),founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children.RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology.Rather than using the conventional method of rote memorization,RDF focuses on cultivating critical thinking skills and encouraging students to understand and

  11. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    <正>The Rural Development Foundation(RDF),founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children.RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology.Rather than using the conventional method of rote memorization,RDF focuses on cultivating critical thinking skills and encouraging students to understand and

  12. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology. Rather than using the conventional method of rote memorization,RDF focuses on cultivating critical thinking skills and encouraging students to

  13. The Art of DNA Strings: Sixteen Years of DNA Coding Theory

    OpenAIRE

    Limbachiya, Dixita; Rao, Bansari; Gupta, Manish K.

    2016-01-01

    The idea of computing with DNA was given by Tom Head in 1987, however in 1994 in a seminal paper, the actual successful experiment for DNA computing was performed by Adleman. The heart of the DNA computing is the DNA hybridization, however, it is also the source of errors. Thus the success of the DNA computing depends on the error control techniques. The classical coding theory techniques have provided foundation for the current information and communication technology (ICT). Thus it is natur...

  14. Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: A randomized controlled study

    Institute of Scientific and Technical Information of China (English)

    Jing You; Virasakdi Chongsuvivatwong; Hutcha Sriplung; Alan Geater; Yan-Wei Qiao; Rong-Xue Wu; Lin Zhuang; Hong-Ying Cheng; Shou-Ming Yan; Lan Yu; Jun-Hua Huang; Bao-Zhang Tang; Meng-Ling Huang; Yong-Liang Ma

    2006-01-01

    AIM: To observe the efficiency and safety of thymosin-α1treatment in patients with hepatitis B e antigen (HBeAg)and HBV DNA positive chronic hepatitis.METHODS: Sixty-two patients were randomly divided into groups A and B. The patients in group A received subcutaneous injection of 1.6 mg thymosin-α1, twice a week (T-α1 group) for six months, and the patients in group B received 5 MU interferon alpha (IFN-α) each day for fifteen days, then three times weekly (IFN-α group)for six months. The results between two groups treated with and the group untreated with IFN-α which was followed up for 12 mo (historical control group consisting of 30 patients) were compared, and three groups were comparable between each other (P > 0.05) at baseline (age, sex, clinical history, biochemical, and serological parameters).RESULTS: At the end of treatment, complete response,which was defined as alanine aminotransferase (ALT)normalization and HBV DNA and HBeAg loss, occurred in 9 of 29 (31.0%) patients in the T-α1 group and in 15 of 33 (45.5%) patients in the IFN-α group (x2= 1.36, P >0.05). After a follow-up period of six months, a complete response was observed in 14 of 29 (48.3%) patients in the T-α1 group and in 9 of 33 (27.3%) patients in the IFN-α group (x2= 2.93, P > 0.05). Compared with the results observed in the historical control (HC) group untreated with IFN-α which was followed up for 12 mo,the rate of complete response was significantly higher in IFN-α group at the end of therapy (1 of 30 vs 15 of 33,x2 = 14.72, P < 0.001) and in the T-α1 group at the end of follow-up (1 of 30 vs 14 of 29, x2 = 15.71, P < 0.001).In T-α1 and IFN-α treatment groups, the area under (the plasma concentration time) curve (AUC) of negative HBV DNA and HBeAg was 34%, 17%, 31% and 19% smaller than that in the HC group. By the end of the followup period, the proportions of ALT normalization and negative HBV DNA in the T-α1 group were significantly higher than those in the

  15. Run-up on Offshore Windturbine Foundations

    DEFF Research Database (Denmark)

    De Vos, Leen; Larsen, Brian Juul; Frigaard, Peter

    For the present report a testprogramme has been performed to determine the run-up on offshore windturbine foundations.......For the present report a testprogramme has been performed to determine the run-up on offshore windturbine foundations....

  16. Progeria Research Foundation Diagnostic Testing Program

    Science.gov (United States)

    ... Testing The PRF Diagnostic Testing Program The Progeria Research Foundation, in association with a CLIA-approved diagnostics lab, ... please contact Dr. Leslie Gordon at The Progeria Research Foundation at info@progeriaresearch.org quick links Donate Now ...

  17. Founding a Foundation: A Mini Case Study.

    Science.gov (United States)

    Lake, Dale B.

    1981-01-01

    Lists factors contributing to the need for increased fund raising in community colleges. Discusses advantages of a foundation as a means of obtaining private funds. Delineates specifics of establishing, organizing, and implementing the Kalamazoo Valley Community College Foundation. (DMM)

  18. Compressor Foundation Analysis Tool(COFANTO)

    NARCIS (Netherlands)

    Eijk, A.; Lentzen, S.S.K; Zuada Coelho, B.E.; Galanti, F.M.B.

    2012-01-01

    Reciprocating compressors are generally supported on a heavy concrete foundation. In spite of the large inertia and stiffness of the foundation, problems can occur due to interaction between the mechanical installation and the foundation. Two types of problems may occur. In the first type, the inter

  19. Philanthropy and Private Foundations: Expanding Revenue Sources

    Science.gov (United States)

    Drummer, Carlee; Marshburn, Roxann

    2014-01-01

    As community colleges seek new revenue streams, philanthropic organizations, including college foundations and private funders, have already begun to influence both revenues and college programming. This chapter discusses the current role of philanthropy, especially private foundations such as the Lumina Foundation for Education and the Bill and…

  20. Crystal growth under bridge foundation

    OpenAIRE

    Ramon Tarragona, Anna; Alonso Pérez de Agreda, Eduardo

    2012-01-01

    W(H)YDOC PhD Prize 2012, durant el 4th International Workshop of Young Doctors in Geomechanics W(H)YDOC 2012. A high-speed railway viaduct experienced a sustained heave at high rates after its construction. The pillars of the bridge are founded on an Eocene hard anhydritic-gypsiferous claystone by means of massive foundations. Field investigations identified an active layer below the piles’ tips where expansions occur as a result of gypsum crystal growth in discontinuities from supersatura...

  1. Foundations of combinatorics with applications

    CERN Document Server

    Bender, Edward A

    2006-01-01

    This introduction to combinatorics, the foundation of the interaction between computer science and mathematics, is suitable for upper-level undergraduates and graduate students in engineering, science, and mathematics.The four-part treatment begins with a section on counting and listing that covers basic counting, functions, decision trees, and sieving methods. The following section addresses fundamental concepts in graph theory and a sampler of graph topics. The third part examines a variety of applications relevant to computer science and mathematics, including induction and recursion, sorti

  2. Quantum mechanics foundations and applications

    CERN Document Server

    Swanson, Donald Gary

    2006-01-01

    Progressing from the fundamentals of quantum mechanics (QM) to more complicated topics, Quantum Mechanics: Foundations and Applications provides advanced undergraduate and graduate students with a comprehensive examination of many applications that pertain to modern physics and engineering.Based on courses taught by the author, this textbook begins with an introductory chapter that reviews historical landmarks, discusses classical theory, and establishes a set of postulates. The next chapter demonstrates how to find the appropriate wave functions for a variety of physical systems in one dimens

  3. About The Rural Development Foundation

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    <正>The Rural Development Foundation (RDF),founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools and one junior college in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and methodology. Rather than using the conventional method of rote memorization,RDF focuses on cultivating critical thinking skills and encouraging students to understand and apply concepts. RDF does this through special programs such as Social Awareness,Youth Empowerment,

  4. Foundations of cryptography a primer

    CERN Document Server

    Goldreich, Oded

    2014-01-01

    Foundations of Cryptography surveys the main paradigms, approaches and techniques used to conceptualize, define and provide solutions to natural cryptographic problems. The author starts by presenting some of the central tools; that is, computational difficulty (in the form of one-way functions), pseudorandomness, and zero-knowledge proofs. Based on these tools, the emphasis is shifted to the treatment of basic applications such as encryption and signature schemes as well as the design of general secure cryptographic protocols. The author has created a unique overview that includes well over 1

  5. Letter to European Science Foundation

    Directory of Open Access Journals (Sweden)

    2006-06-01

    Full Text Available Département de Linguistique AppliquéeEt de Didactique des languesDirecteur : Claude Springerhttp://dladl.u-strasbg.fr Dr. Rüdiger KleinEUROCORES Programme CoordinatorEuropean Science Foundation1, quai Lezay MarnésiaBP 90015F-67080 Strasbourg Cedex Strasbourg, le 22 mai 2006 Dear colleague, The Editorial Board of the journal ALSIC (Apprentissage des langues et système d’information et de communication which comprises 45 people from universities in 9 different countries was astonished to note...

  6. Foundations of wireless and electronics

    CERN Document Server

    Scroggie, M G

    1984-01-01

    Foundations of Wireless and Electronics, 10th Edition covers the cathode-ray and microwave tubes; modern pulse methods; f.m. detectors; basic processes of transmission; and reception, computers, and non-sinusoidal signal amplification. The book starts by giving a general overview of a complete electronic system, electricity and circuits, capacitance, and inductance. The text also discusses alternating currents (a.c.), including the frequency and phase of a.c.; the capacitance and inductance in a.c. circuits; and the capacitance and inductance in a series. Diodes, triode, transistor equivalent

  7. Foundational issues in evolution education

    Science.gov (United States)

    Smith, Mike U.; Siegel, Harvey; McInerney, Joseph D.

    1995-01-01

    There is a great need for effective evolution education. This paper reviews some of the evidence that demonstrates that need and analyzes some of the foundational semantic, epistemological, and philosophical issues involved. This analysis is used to provide a functional understanding of the distinction between science and non-science. Special emphasis is placed the scientific meaning of the terms theory, hypothesis, fact, proof, evidence, and truth, focusing on the difference between religious belief and acceptance of a scientific theory. Science is viewed as theologically neutral and as not mutually exclusive from religion. Finally, a number of practical recommendations to the classroom biology teacher are presented.

  8. Ensemble Methods Foundations and Algorithms

    CERN Document Server

    Zhou, Zhi-Hua

    2012-01-01

    An up-to-date, self-contained introduction to a state-of-the-art machine learning approach, Ensemble Methods: Foundations and Algorithms shows how these accurate methods are used in real-world tasks. It gives you the necessary groundwork to carry out further research in this evolving field. After presenting background and terminology, the book covers the main algorithms and theories, including Boosting, Bagging, Random Forest, averaging and voting schemes, the Stacking method, mixture of experts, and diversity measures. It also discusses multiclass extension, noise tolerance, error-ambiguity a

  9. The shifting foundations of nursing.

    Science.gov (United States)

    Law, Kate; Aranda, Kay

    2010-08-01

    In this paper we argue that the concerns generated by the development of Foundation Degrees and the Assistant and Associate Practitioner roles have rekindled some of the unresolved debates regarding the status and identity of nursing and nurses. Through the application of the sociological theories of professionalisation and nostalgia we have identified the shifting and unresolved nature of nursing. We argue that these theories continue to have resonance in the current climate of change and 'upskilling' of the health care workforce and argue, that the shifts illuminated are perhaps so significant as to demonstrate that we have entered a post-nursing era.

  10. Electromagnetic foundations of electrical engineering

    CERN Document Server

    Faria, J A Brandao

    2008-01-01

    The applications of electromagnetic phenomena within electrical engineering have been evolving and progressing at a fast pace. In contrast, the underlying principles have been stable for a long time and are not expected to undergo any changes. It is these electromagnetic field fundamentals that are the subject of discussion in this book with an emphasis on basic principles, concepts and governing laws that apply across the electrical engineering discipline. Electromagnetic Foundations of Electrical Engineering begins with an explanation of Maxwell's equations, from which the fundament

  11. Microsoft Windows Identity Foundation Cookbook

    CERN Document Server

    Chanda, Sandeep

    2012-01-01

    This book is written in a simple, easy to understand format, with lots of screenshots and step-by-step explanations.If you are a .NET developer looking forward to building access control in your applications using claims-based identity, then this is the best guide for you. This book is also an excellent choice for professionals and IT administrators trying to enable Single Sign-On across applications within the enterprise, and in the cloud spanning interoperable platforms. No previous knowledge on the subject is necessary, however a strong foundation in the C# programming language and .NET Fra

  12. 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

  13. Role of glycine residues highly conserved in the S2-S3 linkers of domains I and II of voltage-gated calcium channel alpha(1) subunits.

    Science.gov (United States)

    Teng, Jinfeng; Iida, Kazuko; Ito, Masanori; Izumi-Nakaseko, Hiroko; Kojima, Itaru; Adachi-Akahane, Satomi; Iida, Hidetoshi

    2010-05-01

    The pore-forming component of voltage-gated calcium channels, alpha(1) subunit, contains four structurally conserved domains (I-IV), each of which contains six transmembrane segments (S1-S6). We have shown previously that a Gly residue in the S2-S3 linker of domain III is completely conserved from yeasts to humans and important for channel activity. The Gly residues in the S2-S3 linkers of domains I and II, which correspond positionally to the Gly in the S2-S3 linker of domain III, are also highly conserved. Here, we investigated the role of the Gly residues in the S2-S3 linkers of domains I and II of Ca(v)1.2. Each of the Gly residues was replaced with Glu or Gln to produce mutant Ca(v)1.2s; G182E, G182Q, G579E, G579Q, and the resulting mutants were transfected into BHK6 cells. Whole-cell patch-clamp recordings showed that current-voltage relationships of the four mutants were the same as those of wild-type Ca(v)1.2. However, G182E and G182Q showed significantly smaller current densities because of mislocalization of the mutant proteins, suggesting that Gly(182) in domain I is involved in the membrane trafficking or surface expression of alpha(1) subunit. On the other hand, G579E showed a slower voltage-dependent current inactivation (VDI) compared to Ca(v)1.2, although G579Q showed a normal VDI, implying that Gly(579) in domain II is involved in the regulation of VDI and that the incorporation of a negative charge alters the VDI kinetics. Our findings indicate that the two conserved Gly residues are important for alpha(1) subunit to become functional.

  14. The effects of salt-induced hypertension on alpha1-adrenoreceptor expression and cardiovascular physiology in the rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Chen, Xi; Moon, Thomas W; Olson, Kenneth R; Dombkowski, Ryan A; Perry, Steve F

    2007-09-01

    Experiments were conducted on rainbow trout to determine the impact of dietary salt on arterial blood pressure. After 4-6 wk, fish fed a salt-enriched diet exhibited a 37% elevation of dorsal aortic pressure (from 23.8 +/- 1.2 to 32.6 +/- 1.4 mmHg) and an 18% increase in ventral aortic pressure (from 33.0 +/- 1.5 to 38.9 +/- 1.3 mmHg). The hypertension presumably reflected the increase in cardiac output (from 31.0 +/- 0.8 to 36.4 +/- 2.2 ml.min(-1).kg(-1)) because systemic and branchial resistances were statistically unaltered by salt feeding. The chronic hypertension was associated with a decrease in the pressor responses of the systemic vasculature to catecholamines and hypercapnia in the salt-fed fish. The reduction in alpha-adrenergic responsiveness of the systemic vasculature is consistent with desensitization or loss of functional alpha-adrenoceptors (alpha-ARs). In support of this idea, the salt-fed fish exhibited significantly decreased levels of alpha(1D)-AR mRNA in the dorsal aorta and the afferent (ABA) and efferent branchial arteries (EBA). In contrast, however, the results obtained from norepinephrine dose-response curves for EBA and ABA vascular rings in vitro did not provide evidence for loss of function of branchial artery alpha(1)-ARs in the salt-fed fish. Indeed, the EC(50) for the EBA norepinephrine dose-response curve was significantly reduced (from 3.75 x 10(-7) to 2.12 x 10(-7) M) in the salt-fed fish, indicating an increase in the binding affinity of the alpha(1)-ARs.

  15. Reversal of acquired resistance to adriamycin in CHO cells by tamoxifen and 4-hydroxy tamoxifen: role of drug interaction with alpha 1 acid glycoprotein.

    OpenAIRE

    Chatterjee, M.; Harris, A. L.

    1990-01-01

    Tamoxifen and 4-OH tamoxifen were used to reverse multidrug resistance (MDR) in CHO cells with acquired resistance to adriamycin (CHO-Adrr). Because alpha 1 acid glycoprotein (AAG) can bind a range of calcium channel blockers that also reverse MDR and rises in malignancy, its interactions with tamoxifen and 4-OH tamoxifen were also studied. Tamoxifen decreased the IC50 of 10 microM adriamycin 4.8-fold in the parent CHO-K1 cell line and 16-fold in CHO-Adrr. Similarly 4-OH tamoxifen decreased t...

  16. Antiparallel polypurine phosphorothioate oligonucleotides form stable triplexes with the rat alpha1(I) collagen gene promoter and inhibit transcription in cultured rat fibroblasts.

    OpenAIRE

    Joseph, J.; Kandala, J C; Veerapanane, D; K. T. Weber; Guntaka, R V

    1997-01-01

    The rat alpha1(I) collagen promoter contains a unique polypurine-polypyrimidine sequence between -141 and -200 upstream of the transcription start site. The polypurine sequence from -171 to -200 (C2) is on the coding strand and the adjacent polypurine sequence from -141 to -170 (C1) is on the non-coding strand. Earlier we demonstrated triplex formation with a polypurine 30 nt parallel triplex-forming oligonucleotide (TFO) corresponding to C1 and inhibition of transcriptional activity of the r...

  17. GFAP and alpha1a-AR staining and nuclear morphometry of oligodendrogliomas by confocal microscopy and image analysis: useful parameters for predicting survival in oligodendrogliomas

    Directory of Open Access Journals (Sweden)

    Uranga-Ocio José A

    2008-07-01

    Full Text Available Abstract Objective This study attempts to evaluate the GFAP and alpha1a-AR staining and morphometrical nuclear features of oligodendrogliomas and their prognostic implications as compared to present histopathology classification and their survival outcome. Study design Surgical specimens from 24 patients with oligodendrogliomas during the period 1981–2000 were included. These cases were classified into two groups defined by the grade of the neoplasm: Group I: oligodendrogliomas grade II; Group II: oligodendrogliomas grade III and two groups based on the outcome status: Group of the alive cases and group of the death cases. Death rate for the groups were obtained by patients' charts. Descriptive statistics were used to examine the groups with respect to the morphometrical nuclear variables; area, perimeter, aspect, axes (major and minor, diameters (max, mean and min., radius (max. and min. margination, ratio of perimeter-area, roundness and sizes (length and width. In addition, an immunofluorescence method for GFAP and 1a-AR were performed and their area, density and intensity of staining were analyzed. Results Semiautomated quantitative morphometrical results showed that the variables of nuclear area (GII 48.87 μm2 vs. GIII 43.45 μm2 p-value = 0.02, aspect (GII 1.39 vs. GIII 1.55 p-value = 0.03, axis minor (GII 6.66 μm vs. GIII 6.01 μm p-value = 0.003, diameter minor (GII 5.93 μm vs. GIII 5.27 μm p-value = 0.002, radius minor (GII 2.64 μm vs. GIII 2.25 μm p-value = 0,003, perimeter-area (GII 0.0007 vs. GIII 0.0006 p-value = 0.04, size width (GII 6.60 μm vs. GIII 5.96 μm p-value = 0,003, and density of alpha1a-AR staining (GII 121.38 vs. GIII 146.03 p-value = 0.05 were statistically significant in regard of grade; and that the sum of density of GFAP (p-value = 0.01 and the intensity of alpha1a-AR (p-value = 0.01 were statistically significant in predicting survival. Conclusion These results suggest that some nuclear morphometrical

  18. Instability of Bucket Foundations during Installation

    DEFF Research Database (Denmark)

    Madsen, Søren; Andersen, Lars Vabbersgaard; Ibsen, Lars Bo

    The bucket foundation is an upcoming technology for offshore wind turbines. The bucket foundation is a large cylindrical monopod foundation constructed as a thin steel shell structure. A bucket foundation does not require heavy installation equipment since it is installed by suction forces. The...... combination of a thin shell structure and suction forces leads to the fact that instability, in form of buckling, becomes a crucial issue during installation. The hydrostatic buckling pressure of the bucket foundation is addressed using three-dimensional, non-linear finite element analysis. The results of the...

  19. Stiffness Formulation of Flexible Bucket Foundation

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Liingaard, Morten; Larsen, Kim André

    as a substructure with predetermined properties. The interaction between the foundation and structure is expressed purely in terms of force and moment resultants, and their conjugate displacements and rotations. The Macro Model modelling the Bucket Foundation is suitable for implementation in an......The response of offshore wind turbines e.g. static, eigen frequencies and eigen modes, are affected by elastic properties of the foundation and the subsoil. The Elastic Macro Model is developed to evaluate the soil-structure interaction of flexible bucket foundations for offshore wind turbines so...... that it can be properly included and analysed in a composite structure-foundation system. The typical approach for analysing the structure-foundation system is to use a finite-element method. Such an approach is, however, inefficient and time consuming. The Elastic Macro Model describes the foundation...

  20. DNA-Conjugated Organic Chromophores in DNA Stacking Interactions

    DEFF Research Database (Denmark)

    Filichev, Vyacheslav V.; Pedersen, Erik Bjerregaard

    2009-01-01

    Since the discovery of the intercalation of acridine derivatives into DNA (1961), chemists have synthesized many intercalators tethered to DNA. Advances in the chemical synthesis of modified nucleosides along with progress in oligonucleotide synthesis have made it possible to introduce organic...... review presents those efforts in the design of intercalators/organic chromophores as oligonucleotide conjugates that form a foundation for the generation of novel nucleic acid architectures...

  1. Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membranes.

    OpenAIRE

    Skinner, M P; Raines, E W; Ross, R.

    1994-01-01

    Vascular smooth muscle cells (SMCs) in the media of normal arteries express alpha 1 beta 1 integrin with no detectable alpha 2 beta 1 as determined by immunocytochemistry. In contrast, immunoprecipitation of integrins expressed by human SMCs cultured from medial explants shows strong expression of alpha 2 beta 1 and no expression of alpha 1 beta 1. The apparent reciprocal expression of these two collagen and laminin receptors was confirmed by flow cytometric analysis of fluorescent labeled ce...

  2. 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.

  3. Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

    Science.gov (United States)

    Confort, C; Rochefort, H; Vignon, F

    1995-09-01

    The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion.

  4. Long-Term Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Børsting, Christa Winther; Kuhn, Johan Moritz; Poulsen, Thomas;

    2016-01-01

    the hypothesis that time horizons are influenced by ownership structures and particularly that industrial foundations promote longtermism. Policymakers which are interested in promoting longtermism should allow and perhaps even encourage the creation of industrial foundations. More generally they should consider...... in Denmark. Industrial foundations are independent legal entities without owners or members typically with the dual objective of preserving the company and using excess profits for charity. We use a unique Danish data set to examine the governance of foundation-owned companies. We show that they are long......-term in several respects. Foundations hold on to their shares for longer. Foundation-owned companies replace managers less frequently. They have more conservative capital structures with less leverage. Their companies survive longer. Their business decisions appear to be more long term. This paper supports...

  5. The Heart and Stroke Foundation of Ontario

    OpenAIRE

    Graham, Anthony F.

    1987-01-01

    The Heart and Stroke Foundation of Ontario is a non-profit volunteer-driven organization that is active in supporting research and education programs with the ultimate goal of reducing death and disability from heart disease and stroke. The Foundation has over 65 chapters across the province, a full-time staff of 130, and over 70,000 volunteers involved in various programs and fund-raising activities. Several of the Foundation's programs offer direct assistance to family physicians and their ...

  6. Adaptive plasticity model for bucket foundations

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Barari, Amin; Larsen, Kim A.

    2014-01-01

    Based on experimental investigations, the literature proposes different methods for modeling the behavior and capacity of foundations subjected to combined loading. Generally, two methods are used to predict the behavior of foundations: traditional approaches and hardening plasticity solutions....... The first method is only capable of determining the capacity of the foundations and not the prepeak behavior. Thus, a new strain-hardening criterion is developed by calibrating failure criteria by employing data from small-scale tests on bucket foundations subjected to static loads. The shape of the yield...

  7. Monopod Bucket Foundations Under Cyclic Lateral Loading

    DEFF Research Database (Denmark)

    Foglia, Aligi; Ibsen, Lars Bo

    2016-01-01

    The monopod bucket foundation has the potential to become a cost-reducing substructure for offshore wind turbines. To avoid problems during the energy converter operation, the long-term effect of cyclic loading must be considered in the design of the foundation. In this paper, a 1-g testing rig...... is adopted to extend the knowledge of bucket foundations under lateral cyclic loading. The test setup is described, and a comprehensive experimental campaign is presented. The effect of some important system parameters on the long-term plastic rotation is analysed. Key aspects of the cyclic load behavior...... of bucket foundations are discussed....

  8. 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

  9. Relativistic navigation a theoretical foundation

    CERN Document Server

    Turyshev, S G

    1996-01-01

    We present a theoretical foundation for relativistic astronomical measurements in curved space-time. In particular, we discuss a new iterative approach for describing the dynamics of an astronomical N-body system. To do this, we generalize the Fock-Chandrasekhar method of the weak-field and slow-motion approximation (WFSMA) and develop a theory of relativistic reference frames (RF) for a gravitationally bounded many-extended-body problem. In any proper RF constructed in the immediate vicinity of an arbitrary body, the N-body solutions of the gravitational field equations are presented as a sum of the Riemann-flat inertial space-time, the gravitational field generated by the body itself, the unperturbed solutions for each body in the system transformed to the coordinates of this proper RF, and the gravitational interaction term. We develop the basic concept of a general theory of the celestial RFs applicable to a wide class of metric theories of gravity with an arbitrary model of matter distribution. We apply ...

  10. Linkage of the gene that encodes the alpha 1 chain of type V collagen (COL5A1) to type II Ehlers-Danlos syndrome (EDS II).

    Science.gov (United States)

    Loughlin, J; Irven, C; Hardwick, L J; Butcher, S; Walsh, S; Wordsworth, P; Sykes, B

    1995-09-01

    Ehlers-Danlos syndrome (EDS) is a group of heritable disorders of connective tissue with skin, ligaments and blood vessels being the main sites affected. The commonest variant (EDS II) exhibits an autosomal dominant mode of inheritance and is characterized by joint hypermobility, cigarette paper scars, lax skin and excessive bruising. As yet no gene has been linked to EDS II, nor has linkage been established to a specific region of the genome. However, several candidate genes encoding proteins of the extracellular matrix have been excluded. Using an intragenic simple sequence repeat polymorphism, we report linkage of the COL5A1 gene, which encodes the alpha 1(V) chain of type V collagen, to EDS II. A maximum LOD score (Zmax) for linkage of 8.3 at theta = 0.00 was generated for a single large pedigree.

  11. The role of proteases, endoplasmic reticulum stress and SERPINA1 heterozygosity in lung disease and alpha-1 anti-trypsin deficiency.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2012-02-01

    The serine proteinase inhibitor alpha-1 anti-trypsin (AAT) provides an antiprotease protective screen throughout the body. Mutations in the AAT gene (SERPINA1) that lead to deficiency in AAT are associated with chronic obstructive pulmonary diseases. The Z mutation encodes a misfolded variant of AAT that is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum of hepatocytes and other AAT-producing cells. Until recently, it was thought that loss of antiprotease function was the major cause of ZAAT-related lung disease. However, the contribution of gain-of-function effects is now being recognized. Here we describe how both loss- and gain-of-function effects can contribute to ZAAT-related lung disease. In addition, we explore how SERPINA1 heterozygosity could contribute to smoking-induced chronic obstructive pulmonary diseases and consider the consequences.

  12. Insulin-like growth factors (IGFs) stimulate the release of alpha 1-antichymotrypsin and soluble IGF-II/mannose 6-phosphate receptor from MCF7 breast cancer cells.

    Science.gov (United States)

    Confort, C; Rochefort, H; Vignon, F

    1995-09-01

    The growth of hormone-responsive MCF7 human breast cancer cells is controlled by steroid hormones and growth factors. By metabolic labeling of cells grown in steroid- and growth factor-stripped serum conditions, we show that insulin-like growth factors (IGF-I and IGF-II) increase by approximately 5-fold the release of several proteins including cathepsin D, alpha 1-antichymotrypsin, and soluble forms of the multifunctional IGF-II/mannose 6-phosphate (M6P) receptor. Two soluble forms of IGF-II/M6P receptors were detected, one major (approximately 260 kilodaltons) and one minor (approximately 85 kilodaltons) that probably represents a proteolytic fragment of the larger soluble molecule. IGFs increased receptor release in a dose-dependent fashion with 50-60% of newly synthesized receptor released at 5-10 nM IGFs. The release of IGF-II/M6P receptors correlated with the levels of secreted cathepsin D in different human breast cancer cells or in rats stable transfectants that are constitutively expressing variable levels of human cathepsin D. IGFs had a stronger effect on IGF-II/M6P receptor release, whereas estradiol treatment preferentially enhanced the release of protease and antiprotease. We thus demonstrate that in human breast cancer cells, IGFs not only act as strong mitogens but also regulate release of alpha 1-antichymotrypsin, IGF-II/M6P-soluble receptor, and cathepsin D; three proteins that potentially regulate cell proliferation and/or invasion. PMID:7649082

  13. Cleaving DNA with DNA

    Science.gov (United States)

    Carmi, Nir; Balkhi, Shameelah R.; Breaker, Ronald R.

    1998-03-01

    A DNA structure is described that can cleave single-stranded DNA oligonucleotides in the presence of ionic copper. This ``deoxyribozyme'' can self-cleave or can operate as a bimolecular complex that simultaneously makes use of duplex and triplex interactions to bind and cleave separate DNA substrates. Bimolecular deoxyribozyme-mediated strand scission proceeds with a kobs of 0.2 min-1, whereas the corresponding uncatalyzed reaction could not be detected. The duplex and triplex recognition domains can be altered, making possible the targeted cleavage of single-stranded DNAs with different nucleotide sequences. Several small synthetic DNAs were made to function as simple ``restriction enzymes'' for the site-specific cleavage of single-stranded DNA.

  14. Liberating Foundations of Art and Design

    Science.gov (United States)

    Lerner, Fern

    2012-01-01

    Research concerning the basic course known as Foundations of Art and Design strengthens the pedagogical approach for K-16 art and design education. The version of Foundations introduced to America by Josef Albers, although hardly changed, is shown to have continued, timeless relevance. Next, a sequential, implicit logic is revealed in linking the…

  15. Scour and Scour Protection for Windturbine Foundations

    DEFF Research Database (Denmark)

    Larsen, Brian Juul; Frigaard, Peter

    A test programme has been performed to determine the necessary scour protection around a various types of foundation for an offshore windturbine. Furthermore the unprotected scour depths have been investigated.......A test programme has been performed to determine the necessary scour protection around a various types of foundation for an offshore windturbine. Furthermore the unprotected scour depths have been investigated....

  16. Wave Forces on Offshore Windturbine Foundations

    DEFF Research Database (Denmark)

    Larsen, Brian Juul; Frigaard, Peter

    The present report on the wave forces is the first report on the Borkum Riff project. A testprogramme has been performed to dertermine the wave forces on windturbine foundations.......The present report on the wave forces is the first report on the Borkum Riff project. A testprogramme has been performed to dertermine the wave forces on windturbine foundations....

  17. Scour and Scour Protection for Bucket Foundations

    DEFF Research Database (Denmark)

    Larsen, Brian Juul; Frigaard, Peter

    A test programme has been performed to determine the scour around a bucket foundation for an offshore windturbine. furthermore the necessary scour protection has been investigated.......A test programme has been performed to determine the scour around a bucket foundation for an offshore windturbine. furthermore the necessary scour protection has been investigated....

  18. Prototype bucket foundation for wind turbines

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Liingaard, Morten

    The first full scale prototype bucket foundation for wind turbines has been installed in October 2002 at Aalborg University offshore test facility in Frederikshavn, Denmark. The suction caisson and the wind turbine have been equipped with an online monitoring system, consisting of 15 accelerometers...... capable of simulating dynamic frequency dependent behaviour of the structure-foundation system....

  19. Density functional theory: Foundations reviewed

    Energy Technology Data Exchange (ETDEWEB)

    Kryachko, Eugene S., E-mail: eugene.kryachko@ulg.ac.be [Bogolyubov Institute for Theoretical Physics, Kiev, 03680 (Ukraine); Ludeña, Eduardo V., E-mail: popluabe@yahoo.es [Centro de Química, Instituto Venezolano de Investigaciones Científicas, IVIC, Apartado 21827, Caracas 1020-A (Venezuela, Bolivarian Republic of); Prometheus Program, Senescyt (Ecuador); Grupo Ecuatoriano para el Estudio Experimental y Teórico de Nanosistemas, GETNano, USFQ, N104-E, Quito (Ecuador); Escuela Politécnica Superior del Litoral, ESPOL, Guayaquil (Ecuador)

    2014-11-10

    Guided by the above motto (quotation), we review a broad range of issues lying at the foundations of Density Functional Theory, DFT, a theory which is currently omnipresent in our everyday computational study of atoms and molecules, solids and nano-materials, and which lies at the heart of modern many-body computational technologies. The key goal is to demonstrate that there are definitely the ways to improve DFT. We start by considering DFT in the larger context provided by reduced density matrix theory (RDMT) and natural orbital functional theory (NOFT), and examine the implications that N-representability conditions on the second-order reduced density matrix (2-RDM) have not only on RDMT and NOFT but, also, by extension, on the functionals of DFT. This examination is timely in view of the fact that necessary and sufficient N-representability conditions on the 2-RDM have recently been attained. In the second place, we review some problems appearing in the original formulation of the first Hohenberg–Kohn theorem which is still a subject of some controversy. In this vein we recall Lieb’s comment on this proof and the extension to this proof given by Pino et al. (2009), and in this context examine the conditions that must be met in order that the one-to-one correspondence between ground-state densities and external potentials remains valid for finite subspaces (namely, the subspaces where all Kohn–Sham solutions are obtained in practical applications). We also consider the issue of whether the Kohn–Sham equations can be derived from basic principles or whether they are postulated. We examine this problem in relation to ab initio DFT. The possibility of postulating arbitrary Kohn–Sham-type equations, where the effective potential is by definition some arbitrary mixture of local and non-local terms, is discussed. We also deal with the issue of whether there exists a universal functional, or whether one should advocate instead the construction of problem

  20. Forward the Foundation: Local Education Foundations Offer an Alternative Source for School Funding

    Science.gov (United States)

    Brooks-Young, Susan

    2007-01-01

    February's column "Going Corporate" discussed ideas for approaching private foundations for funding. Some districts take this idea several steps further by partnering with the community and local businesses to establish a not-for-profit foundation, or local education foundation (LEF). It probably comes as no surprise that the idea of forming a LEF…

  1. Monopod bucket foundations under cyclic lateral loading

    DEFF Research Database (Denmark)

    Foglia, Aligi; Ibsen, Lars Bo

    The monopod bucket foundation can be a cost-reducing sub-structure for offshore wind turbines. To avoid problems during the turbine operation, the long-term effect of cyclic loading must be considered in the design of the foundation. In this paper a 1g testing rig is adopted to extend the knowledge...... on bucket foundations under lateral cyclic loading. The test setup is described in detail and a comprehensive experimental campaign is presented. The foundation is subjected to cyclic overturning moment, cyclic horizontal loading and constant vertical loading, acting on the same plane for thousands...... of cycles. Three buckets with different embedment ratios are tested. The data interpretation is focused on the long-term permanent rotation of the foundation and, particularly, on understanding how the controlling variables influence the potential for rotation accumulation. New and more general parameters...

  2. Advanced Laboratory Setup for Testing Offshore Foundations

    DEFF Research Database (Denmark)

    Nielsen, Søren Dam; Ibsen, Lars Bo; Nielsen, Benjaminn Nordahl

    2016-01-01

    This paper describes a test setup for testing small-scale offshore foundations under realistic conditions of high pore-water pressure and high impact loads. The actuator, used for loading has enough capacity to apply sufficient force and displacement to achieve both drained and undrained failure...... modes for small-scale offshore foundations. Results from trial tests on two small-scale bucket foundations, subjected to transient or cyclic loading, are presented. Tests showed that cavitation limits the undrained bearing capacity. Hence, a high pore-water pressure is important for simulating offshore...

  3. Foundations for a theory of gravitation theories

    Science.gov (United States)

    Thorne, K. S.; Lee, D. L.; Lightman, A. P.

    1972-01-01

    A foundation is laid for future analyses of gravitation theories. This foundation is applicable to any theory formulated in terms of geometric objects defined on a 4-dimensional spacetime manifold. The foundation consists of (1) a glossary of fundamental concepts; (2) a theorem that delineates the overlap between Lagrangian-based theories and metric theories; (3) a conjecture (due to Schiff) that the Weak Equivalence Principle implies the Einstein Equivalence Principle; and (4) a plausibility argument supporting this conjecture for the special case of relativistic, Lagrangian-based theories.

  4. Philosophical foundations of interpretations of quantum mechanics

    CERN Document Server

    Bezlepkin, Evgeny

    2016-01-01

    It is demonstrated that the reason for the diversity of interpretations of quantum mechanics is that they are not connected by continuity relations with classical physics, and also the reason is the impossibility of operationalist definition of the vector of state. The problem lies in the incompatibility of the philosophical foundations of interpretations, which results in the difficulty of building a unified picture of the world. To solve the problem, we identify general philosophical foundation of interpretations of quantum mechanics and built their classification. We also show that in more general theories, the part of which is quantum mechanics, it is possible to integrate (reconcile) the philosophical foundations of interpretations.

  5. Rapid eye movement sleep loss induces neuronal apoptosis in the rat brain by noradrenaline acting on alpha 1-adrenoceptor and by triggering mitochondrial intrinsic pathway

    Directory of Open Access Journals (Sweden)

    Bindu I Somarajan

    2016-03-01

    Full Text Available Many neurodegenerative disorders are associated with rapid eye movement sleep (REMS-loss, however the mechanism was unknown. As REMS-loss elevates noradrenaline (NA level in the brain as well as induces neuronal apoptosis and degeneration, in this study we have delineated the intracellular molecular pathway involved in REMS deprivation (REMSD associated NA-induced neuronal apoptosis. Rats were REMS deprived for 6 days by the classical flower-pot method, suitable controls were conducted and the effects on apoptosis markers evaluated. Further, the role of NA was studied by one, intraperitoneal (i.p. injection of NA-ergic alpha1-adrenoceptor antagonist prazosin (PRZ and two, by down-regulation of NA synthesis in locus coeruleus (LC neurons by local microinjection of tyrosine hydroxylase siRNA (TH-siRNA. Immunoblot estimates showed that the expressions of pro-apoptotic proteins viz. Bcl2-associated death promoter (BAD protein, apoptotic protease activating factor-1 (Apaf-1, cytochrome c, caspase9, caspase3 were elevated in the REMS-deprived rat brains, while caspase8 level remained unaffected; PRZ treatment did not allow elevation of these pro-apoptotic factors. Further, REMSD increased cytochrome c expression, which was prevented if the NA synthesis from the LC neurons was blocked by microinjection of TH-siRNA in vivo into the LC during REMSD in freely moving normal rats. Mitochondrial damage was re-confirmed by transmission electron microscopy (TEM, which showed distinctly swollen mitochondria with disintegrated cristae, chromosomal condensation and clumping along the nuclear membrane and all these changes were prevented in PRZ treated rats. Combining findings of this study along with earlier reports we propose that upon REMSD NA level increases in the brain as the LC NA-ergic REM-OFF neurons do not cease firing and TH is up-regulated in those neurons. This elevated NA acting on alpha1-adrenoceptors damages mitochondria causing release of

  6. Attenuation of KATP channel-opener induced shortening of repolarization time by alpha 1-adrenoceptor antagonist during ischemia in canine heart.

    Science.gov (United States)

    Tanabe, T; Aikawa, M; Deguchi, Y; Yoshioka, K; Handa, S

    2000-06-01

    The purpose of the study was to determine whether a new KATP channel opener, Y 26763 (Y), can influence the electrophysiological properties in the ischemic myocardium as well as to determine whether the blunting effect of the alpha 1-adrenoceptor antagonist bunazosin (BN) on an ischemia-induced shortening of repolarization time can be related to the KATP channel activity. The anterior descending branch of the left coronary artery was ligated four times for 5 minutes, separated by 15 minutes of reperfusion (stages 1-4) to test the dose-dependent effect of drugs on repolarization. Dogs received either vehicle (n = 9), Y (0.4, 2.0, and 4.0 micrograms/kg at stages 2, 3, and 4, respectively, with 0.4 microgram/kg/min drip infusion at each of stages 2-4, n = 7), BN (0.1 mg at each of stages 2-4, n = 8), or a combination of these two drugs (BN + Y, the same dose of BN and Y in groups BN and Y, respectively, n = 9). Drugs were administered into the left atrium. The monophasic action potential (MAP) and regional electrograms were recorded. The MAP90 and the duration of the slow deflections (DSD) of the regional electrogram were used as markers of repolarization. The Vmax of the MAP and the rapid deflections (DRD) of the regional electrogram were used as markers of conduction. Y augmented an ischemia-induced shortening of MAP90 and DSD in proportion to an increase in the dose given and the plasma concentration (P DRD in the ischemic zone between periods before and after an increase in each drug dose in the four groups. None of the seven dogs developed ventricular tachycardia (VT)/ventricular fibrillation (VF) in the Y group, whereas two of the eight dogs in the BN group, three of the nine dogs in the BN + Y group, and three of the nine dogs in the control group developed VT/VF. These results suggest that the alpha 1-adrenergic blocker bunazosin blunts the shortening effect of KATP channel activator on repolarization time, and that the KATP channel opener Y may be

  7. Radioimmunoassay of thymosin alpha 1

    International Nuclear Information System (INIS)

    The present invention relates to an immunoassay for thymosin α1, a heat stable, acidic polypeptide composed of 28 amino acid residues. This immunopotentiating hormone is a component of thymosin fraction 5 and also has been found to be present in the blood of mammalian subjects. The immunogen utilized to prepare the antibody for the instant assay is readily obtained by covalently bonding thymosin α1 to a conventional immunological carrier material. Thymosin α1 may be radioisotopically labelled with tritium, carbon 14 or iodine 125

  8. Astrophysics. An introduction into theory and foundations

    International Nuclear Information System (INIS)

    The following topics are covered: general and physical foundations, star burning, Jeans instability, protostars, radiation transport, stellar energy sources, models for burning stars and compact objects, white dwarfs, neutron stars, pulsars and black holes, stability theory, collapsing objects

  9. Sartre: A Possible Foundation for Educational Theory.

    Science.gov (United States)

    Burstow, Bonnie

    1983-01-01

    The claim by Khemais Benhamida and others that Jean-Paul Sartre's philosophy is too hostile and restrictive to serve as the foundation of progressive educational theory is based on an incomplete understanding of the philosopher's work. (IS)

  10. Corporatism As A Totalitaristic Foundation And Practicism

    OpenAIRE

    Slobodan Lakic

    2012-01-01

    Based on the liberal concept of management and generating profit, capitalism disappeared from the world economic and political scene during the Great Economic Crisis. The expansion of mega corporations, primarily from the USA, was enabled by Anglo-Saxon fascist political-economic world order and state favoring - global control mechanism. The fascist order was in propulsion owing to a combination of leftist economic and political foundations and rightist oppressive practicism. As a foundation ...

  11. Nordic Corporate Governance and Industrial Foundations

    DEFF Research Database (Denmark)

    Thomsen, Steen

    The Nordic countries have attracted considerable attention in recent years as a benchmark for good governance. However, while the political governance characteristics of the Nordic model – particularly the welfare state - are well understood, its corporate governance characteristics remain elusive...... to the international audience. This paper therefore reviews the Nordic corporate governance model with special emphasis on a unique ownership structure, industrial foundations (foundations that own business companies). Rather than a meticulous description of details it emphasizes the Nordic model as a mode...

  12. Transforming a foundation into a cooperative

    Directory of Open Access Journals (Sweden)

    Juan Ramón Manzano Malaxechevarría

    2013-12-01

    Full Text Available The author charts a path between entities that meet needs in the general interest such as foundations and others which are neither entities of general interest nor have purely mercantile legal personality such as cooperatives. Transforming a foundation into a cooperative calls for a broad interpretation of the principle of free will that the legislation wishes to foster.Received: 12.02.2013Accepted: 20.04.2013

  13. CENTRIFUGAL VIBRATION TEST OF RC PILE FOUNDATION

    Science.gov (United States)

    Higuchi, Shunichi; Tsutsumiuchi, Takahiro; Otsuka, Rinna; Ito, Koji; Ejiri, Joji

    It is necessary that nonlinear responses of structures are clarified by soil-structure interaction analysis for the purpose of evaluating the seismic performances of underground structure or foundation structure. In this research, centrifuge shake table tests of reinforced concrete pile foundation installed in the liquefied ground were conducted. Then, finite element analyses for the tests were conducted to confirm an applicability of the analytical method by comparing the experimental results and analytical results.

  14. Foundations of microprogramming architecture, software and applications

    CERN Document Server

    Agrawala, Ashok K

    1976-01-01

    Foundations of Microprogramming: Architecture, Software, and Applications discusses the foundations and trends in microprogramming, focusing on the architectural, software, and application aspects of microprogramming. The book reviews microprocessors, microprogramming concepts, and characteristics, as well as the architectural features in microprogrammed computers. The text explains support software and the different hierarchies or levels of languages. These include assembler languages which are mnemonic or symbolic representation of machine commands; the procedure oriented machine-dependent;

  15. Health legacy foundations: a new census.

    Science.gov (United States)

    Niggel, Sabrina Jones; Brandon, William P

    2014-01-01

    Health care merger and acquisition activity has increased since enactment of the Affordable Care Act in 2010. Proceeds from transactions involving nonprofit hospitals, health systems, and health plans will endow philanthropic foundations, collectively known as health legacy foundations. Building on work by Grantmakers In Health, we undertook a systematic search for these foundations and generated a newly updated, comprehensive database. We found 306 organizations in forty-three states that have been endowed with proceeds from the sale, merger, lease, joint venture, or other restructuring of nonprofit health care assets. These health legacy foundations had $26.2 billion in assets in 2010. Concentrated in the southern United States, foundations originating from hospitals and specialty care facilities (86.6 percent) held mean assets of $64.7 million per funder and typically restricted grants to local communities. Foundations formed from health plans (13.4 percent) held higher mean assets ($222 million), usually served larger areas, and were more likely to engage in health care advocacy. Recent transactions involving smaller and stand-alone nonprofit hospitals will infuse many more communities with unprecedented charitable wealth. PMID:24395949

  16. Foundations on Expansive Soils; A Review

    Directory of Open Access Journals (Sweden)

    Behzad Kalantari

    2012-09-01

    Full Text Available This study describes various types of foundation designs to be considered for structural engineering projects when the subsoil foundation consists of expansive or swelling soils. Among civil and architectural engineers expansive soils are known to be difficult foundation materials and problematic. These type of soils swell when they are subjected to moistures and shrink due to moisture loss. Because of this different behaviour upon wetting and drying, they cause minor to major structural damages to pavements as well as buildings. Every year millions of dollars spent dealing with the consequences of swelling soils. For design of foundations on swelling soil, it is first essential to recognize and evaluate the soil based on its swelling potential, and then determining the most proper foundation design that can be constructed on this problematic soil. In general, this study presents some of the most common techniques to evaluate the swelling potential of expansive soils. Also, it discusses problems associated with swelling soil, classification of structural damages caused to buildings, and various foundation designs to combat the problems based on the degree of detrimental effects of swelling potential to civil engineering projects.

  17. The foundation of self-esteem.

    Science.gov (United States)

    Bailey, Joseph A

    2003-05-01

    Self-esteem is a simplistic term for varied and complex mental states pertaining to how one views oneself. It takes but little research in the voluminous literature to see the vagueness and inconsistencies in its various definitions. Even more problematic is the uncertainty concerning its foundational components. The importance of having a solid definition and specific ideas about the foundational components of self-esteem is that both pave the way to recognizing its causes; to predicting effects from those causes; and to organizing the trouble-shooting process for locating those philosophical flaws or psychological scars which lead to low self-esteem. The purpose of this paper is to offer a common ground for thinking about self-esteem at its most basic level. In order to distinguish the "basic level" from the rest of the components of self-esteem, let us liken it to a skyscraper building. Here, the focus is on the building's "underground foundation" and the base upon which that foundation rests. The base is a definition that allows for the assessment of the foundation. The underground foundation itself consists of the mental building blocks called self-meaning, self-identity, self-image, and self-concepts. To help illustrate their interactions, a few of the "masks" and "faces" of self-esteem will be mentioned. What is not being addressed is the "above ground structure"--those theories and manifestations dealt with by most mental health specialists.

  18. On-column entrapment of alpha1-acid glycoprotein for studies of drug-protein binding by high-performance affinity chromatography.

    Science.gov (United States)

    Anguizola, Jeanethe; Bi, Cong; Koke, Michelle; Jackson, Abby; Hage, David S

    2016-08-01

    An on-column approach for protein entrapment was developed to immobilize alpha1-acid glycoprotein (AGP) for drug-protein binding studies based on high-performance affinity chromatography. Soluble AGP was physically entrapped by using microcolumns that contained hydrazide-activated porous silica and by employing mildly oxidized glycogen as a capping agent. Three on-column entrapment methods were evaluated and compared to a previous slurry-based entrapment method. The final selected method was used to prepare 1.0 cm × 2.1 mm I.D. affinity microcolumns that contained up to 21 (±4) μg AGP and that could be used over the course of more than 150 sample applications. Frontal analysis and zonal elution studies were performed on these affinity microcolumns to examine the binding of various drugs with the entrapped AGP. Site-selective competition studies were also conducted for these drugs. The results showed good agreement with previous observations for these drug-protein systems and with binding constants that have been reported in the literature. The entrapment method developed in this study should be useful for future work in the area of personalized medicine and in the high-throughput screening of drug interactions with AGP or other proteins. Graphical abstract On-column protein entrapment using a hydrazide-activated support and oxidized glycogen as a capping agent.

  19. In Vivo Clearance of Alpha-1 Acid Glycoprotein Is Influenced by the Extent of Its N-Linked Glycosylation and by Its Interaction with the Vessel Wall

    Directory of Open Access Journals (Sweden)

    Teresa R. McCurdy

    2012-01-01

    Full Text Available Alpha-1 acid glycoprotein (AGP is a highly glycosylated plasma protein that exerts vasoprotective effects. We hypothesized that AGP’s N-linked glycans govern its rate of clearance from the circulation, and followed the disappearance of different forms of radiolabeled human AGP from the plasma of rabbits and mice. Enzymatic deglycosylation of human plasma-derived AGP (pdAGP by Peptide: N-Glycosidase F yielded a mixture of differentially deglycosylated forms (PNGase-AGP, while the introduction of five Asn to Gln mutations in recombinant Pichia pastoris-derived AGP (rAGP-N(5Q eliminated N-linked glycosylation. PNGase-AGP was cleared from the rabbit circulation 9-fold, and rAGP-N(5Q, 46-fold more rapidly than pdAGP, primarily via a renal route. Pichia pastoris-derived wild-type rAGP differed from pdAGP in expressing mannose-terminated glycans, and, like neuraminidase-treated pdAGP, was more rapidly removed from the rabbit circulation than rAGP-N(5Q. Systemic hyaluronidase treatment of mice transiently decreased pdAGP clearance. AGP administration to mice reduced vascular binding of hyaluronic acid binding protein in the liver microcirculation and increased its plasma levels. Our results support a critical role of N-linked glycosylation of AGP in regulating its in vivo clearance and an influence of a hyaluronidase-sensitive component of the vessel wall on its transendothelial passage.

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

    Directory of Open Access Journals (Sweden)

    Guilherme Baldo

    2008-01-01

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

  1. 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.

  2. Association of collagen type I alpha1 (COLIA1) Sp1 polymorphism with osteoporotic fracture in Caucasian post-menopausal women: a meta-analysis.

    LENUS (Irish Health Repository)

    Ji, G-R

    2012-01-06

    This study was designed to summarize quantitatively the evidence for a relationship between collagen type I alpha1 (COLIA1) Sp1 polymorphism and osteoporotic fracture risk in Caucasian post-menopausal women. This meta-analysis included 16 studies, which analysed 2294 patients with fractures and 10 285 controls. The combined results showed that there was a significant difference in genotype distribution (SS odds ratio [OR] 0.72; Ss OR 1.18; ss OR 1.97) between patients with fractures and controls. When stratifying by the fracture site, it was found that: (i) patients with vertebral fractures had a significantly higher frequency of the Ss genotype and a lower frequency of the SS genotype than controls; and (ii) patients with non-vertebral fractures had a significantly higher frequency of the ss genotype and a lower frequency of the SS genotype than controls. This meta-analysis suggests that the COLIA1 Sp1 polymorphism may be associated with osteoporotic fracture in Caucasian post-menopausal women.

  3. 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.

  4. Neutral alpha-1,4-glucosidase and fructose levels contribute to discriminating obstructive and nonobstructive azoospermia in Chinese men with azoospermia.

    Science.gov (United States)

    Lei, B; Xing, R; Zhou, X; Lv, D; Wan, B; Shu, F; Zhong, L; Wu, H; Mao, X

    2016-08-01

    Nowadays, whether neutral alpha-1,4-glucosidase (NAG) and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese azoospermic patients remains unclear. In this study, we retrospectively analysed the levels of NAG and fructose in 229 patients with obstructive azoospermia and 415 patients with nonobstructive azoospermia from three different medical central. Results indicated that NAG and fructose levels in patients with nonobstructive azoospermia were significantly higher compared with those with obstructive azoospermia (P fructose defined by the World Health Organization (WHO, 2010), decreased level of NAG was observed in 77.3% of patients with obstructive azoospermia, which was significantly higher than those with nonobstructive azoospermia (55.2%, P fructose was observed in 48.0% of patients with obstructive azoospermia, which is also obviously higher than those with nonobstructive azoospermia (31.8%, P fructose was only recorded in 3.7% of patients with SCO syndrome, 5.0% of patients with severe hypospermatogenesis and 18.2% of patients with maturation arrest. Therefore, our results indicated that NAG and fructose levels are contributed to discriminating obstructive and nonobstructive azoospermia in Chinese patients based on the histological types of testes. PMID:26610429

  5. Physical and linkage mapping of the human and murine genes for the [alpha]1 chain of type IX collagen (COL9A1)

    Energy Technology Data Exchange (ETDEWEB)

    Warman, M.L. (Harvard Medical School, Boston, MA (United States) Children' s Hospital/Harvard Medical School, Boston, MA (United States)); Tiller, G.E.; Polumbo, P.A. (Vanderbilt Univ. Medical Center, Nashville, TN (United States)); Seldin, M.F.; Rochelle, J.M. (Duke Univ. Medical Center, Durham, NC (United States)); Knoll, J.H.M.; Cheng, Sou De (Children' s Hospital/Harvard Medical School, Boston, MA (United States)); Olsen, B.R. (Harvard Medical School, Boston, MA (United States))

    1993-09-01

    The IX collagen, a member of the FACIT family of extracellular matrix proteins, is a heterotrimer composed of three genetically distinct [alpha] chains. The cDNAs for the human and mouse [alpha]1(IX) chains have been cloned. In this paper the authors confirm the mapping of the human COL9A1 gene to chromosome 6q12-q13 by fluorescence in situ hybridization utilizing two genomic clones which also contain short tandem repeat polymorphisms. They also report the characterization of these repeats and their incorporation into the chromosome 6 linkage map. The COL9A1 locus shows no recombination with the marker D6Z1 (Z = 27.61 at [theta] = 0) and identifies the most likely locus order of KRAS1P-[D6Z1-COL9A1]-D6S30. In addition, using an interspecific backcross panel, they have mapped murine Col9a1 to mouse chromosome 1. Together with other comparative mapping results, these data suggest that the pericentric region of human chromosome 6 is homologous to the most proximal segment of mouse chromosome 1. These data may facilitate linkage studies with COL9A1 (or col9a1) as a candidate gene for hereditary chondrodysplasias and osteoarthritis. 35 refs., 2 figs., 2 tabs.

  6. Phosphorylation-independent dual-site binding of the FHA domain of KIF13 mediates phosphoinositide transport via centaurin [alpha]1

    Energy Technology Data Exchange (ETDEWEB)

    Tong, Yufeng; Tempel, Wolfram; Wang, Hui; Yamada, Kaori; Shen, Limin; Senisterra, Guillermo A.; MacKenzie, Farrell; Chishti, Athar H.; Park, Hee-Won (Toronto); (UICM)

    2011-11-07

    Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin {alpha}1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)P2). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule.

  7. Elicitor and resistance-inducing activities of beta-1,4 cellodextrins in grapevine, comparison with beta-1,3 glucans and alpha-1,4 oligogalacturonides.

    Science.gov (United States)

    Aziz, Aziz; Gauthier, Adrien; Bézier, Annie; Poinssot, Benoît; Joubert, Jean-Marie; Pugin, Alain; Heyraud, Alain; Baillieul, Fabienne

    2007-01-01

    Cellodextrins (CD), water-soluble derivatives of cellulose composed of beta-1,4 glucoside residues, have been shown to induce a variety of defence responses in grapevine (Vitis vinifera L.) cells. The larger oligomers of CD rapidly induced transient generation of H2O2 and elevation in free cytosolic calcium, followed by a differential expression of genes encoding key enzymes of the phenylpropanoid pathway and pathogenesis-related (PR) proteins as well as stimulation of chitinase and beta-1,3 glucanase activities. Most of these defence reactions were also induced by linear beta-1,3 glucans (betaGlu) and alpha-1,4 oligogalacturonides (OGA) of different degree of polymerization (DP), but the intensity of some reactions induced by CD was different when compared with betaGlu and OGA effects. Moreover, desensitization assays using H2O2 production showed that cells treated with CD remained fully responsive to a second application of OGA, suggesting a different mode of perception of these oligosaccharides by grape cells. None of CD, betaGlu, or OGA induced HSR gene expression nor did they induce cell death. In accordance with elicitor activity in grapevine cells, CD-incubated leaves challenged with Botrytis cinerea also resulted in a significant reduction of the disease. Data suggest that CD could operate via other distinct reaction pathways than betaGlu and OGA. They also highlight the requirement of a specific DP for each oligosaccharide to induce the defence response. PMID:17322548

  8. The effect of age and teat order on alpha1-acid glycoprotein, neutrophil-to-lymphocyte ratio, cortisol, and average daily gain in commercial growing pigs.

    Science.gov (United States)

    Stull, C L; Kachulis, C J; Farley, J L; Koenig, G J

    1999-01-01

    The objectives of the study were to evaluate age and teat order on a performance trait, average daily gain, and on physiological stress indicators, alpha1-acid glycoprotein (AGP), neutrophil-to-lymphocyte ratio (N:L), and cortisol in commercial growing pigs from weaning to market age. Pigs (n = 129) from five commercial California farms were weighed and blood-sampled at 28-d intervals from 28 to 168 d of age. Laboratory assays were performed from blood samples to quantify cortisol, AGP, and N:L. Age and facility effects (P.05), were found for all three physiological traits and ADG. Pigs that routinely suckled from teats 1, 4, or 6 (numbered from anterior to posterior on the upper teat bank) had similar (P>.05) ADG and BW throughout the production cycle. No correlation (P> .05) was found between cortisol, AGP, and N:L. The use of these physiological and production traits as stress and health indices of growing pigs in commercial facilities has limitations in comparing data between facilities or different ages of pigs. PMID:10064029

  9. 75 FR 45600 - African Development Foundation, Board of Directors Meeting

    Science.gov (United States)

    2010-08-03

    ...; ] AFRICAN DEVELOPMENT FOUNDATION African Development Foundation, Board of Directors Meeting Time: Tuesday, August 17, 2010, 8:30 a.m. to 1 p.m. Place: African Development Foundation, Conference Room, 1400...

  10. 75 FR 2844 - African Development Foundation, Board of Directors Meeting

    Science.gov (United States)

    2010-01-19

    ...; ] AFRICAN DEVELOPMENT FOUNDATION African Development Foundation, Board of Directors Meeting Time: Tuesday, January 26, 2010, 8:30 a.m. to 1 p.m. Place: African Development Foundation, Conference Room, 1400...

  11. 75 FR 14418 - African Development Foundation, Board of Directors Meeting

    Science.gov (United States)

    2010-03-25

    ...; ] AFRICAN DEVELOPMENT FOUNDATION African Development Foundation, Board of Directors Meeting Time: Tuesday, April 13, 2010, 9:30 a.m. to 1 p.m. Place: African Development Foundation, Conference Room, 1400...

  12. Beyond food: a foundation species facilitates its own predator

    NARCIS (Netherlands)

    Agüera, A.; van de Koppel, J.; Jansen, J.M.; Smaal, A.C.; Bouma , T.J.

    2015-01-01

    Facilitation by foundation species can play a critical role in structuring ecological communities. As environmental stress increases, generally more organisms become dependent on the stress buffering provided by foundation species. As such, foundation species may even facilitate their own predators,

  13. Concept Study of Foundation Systems for Wave Energy Converters

    DEFF Research Database (Denmark)

    Molina, Salvador Devant; Vaitkunaite, Evelina; Ibsen, Lars Bo

    Analysis of possible foundation solution for Wave Energy Converters (WEC) is presented by investigating and optimizing novel foundation systems recently developed for offshore wind turbines. Gravity based, pile and bucket foundations are innovative foundation systems that are analyzed. Concept...... studies for all three foundation systems, geotehcnical design methods of foundations and discussion about the differences in the means of structural design, installation and cost are presented in the paper....

  14. Development of a monoclonal antibody to urinary degradation products from the C-terminal telopeptide alpha 1 chain of type I collagen. Application in an enzyme Immunoassay and comparison to CrossLaps(TM) ELISA

    DEFF Research Database (Denmark)

    C, Fledelius; I, Kolding; P, Quist;

    1997-01-01

    A monoclonal antibody MAbA7 was raised against a synthetic peptide having a sequence (EKAHDGGR) specific for a part of the C-telopeptide alpha 1 chain of type I collagen. MAbA7 was labelled with horseradish peroxide and used in a competitive one-step enzyme-linked immunosorbent assay (ELISA...

  15. The phenotypic features of osteogenesis imperfecta resulting from a mutation of the carboxyl-terminal pro alpha 1(I) propeptide that impairs the assembly of type I procollagen and formation of the extracellular matrix

    NARCIS (Netherlands)

    Cole, WG; Chow, CW; Bateman, JF; Sillence, DO

    1996-01-01

    The features of a baby with lethal perinatal osteogenesis imperfecta (OI-II), resulting from the substitution of tryptophan 94 by cysteine in the carboxyl-terminal propeptide of pro alpha 1(I) chains of type I procollagen, were studied. The limbs and torso were of normal length, shape, and proportio

  16. Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways.

    Science.gov (United States)

    Wang, Sen; Xu, Dong-Jie; Cai, Jing-Bo; Huang, Yuan-Zhu; Zou, Jian-Gang; Cao, Ke-Jiang

    2009-04-17

    Ventricular tachyarrhythmias are often precipitated by physical or emotional stress, indicating a link between increased adrenergic stimulation and cardiac ion channel activity. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of delayed rectifier potassium current, I(kr), a crucial component for action potential repolarization. To evaluate the correlation between increased alpha(1)-adrenergic activity and the rapid component of cardiac I(kr), whole-cell patch-clamp recording was performed in isolated guinea-pig ventricular myocytes. Stimulation of alpha(1)-adrenoceptors using phenylephrine (0.1 nM-100 microM) reduced I(kr) current in a dose-dependent manner at 37 degrees C. Phenylephrine (0.1 microM) reduced I(kr) current to 66.83+/-3.16%. Chelerythrine (1 microM), a specific inhibitor of protein kinase C (PKC) completely inhibited the changes in I(kr) trigged by 0.1 microM phenylephrine. KT5720 (2.5 microM), a specific inhibitor of protein kinase A (PKA) partially inhibited the current decrease induced by 0.1 microM phenylephrine. Both chelerythrine and KT5720 drastically reduced the phenylephrine-induced effects, indicating possible involvement of PKC and PKA in the alpha(1)-adrenergic inhibition of I(kr). Our data suggest a link between I(kr) and the alpha(1)-adrenoceptor, involving activation of PKC and PKA in arrhythmogenesis.

  17. Vascular smooth muscle cells express the alpha(1A) subunit of a P-/Q-type voltage-dependent Ca(2+)Channel, and It is functionally important in renal afferent arterioles

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Jensen, Boye L.; Andreasen, D;

    2000-01-01

    in rat aorta, brain, aortic smooth muscle cells (A7r5), VSMCs, and mesangial cells. Immunolabeling with an anti-alpha(1A) antibody was positive in acid-macerated, microdissected preglomerular vessels and in A7r5 cells. Patch-clamp experiments on aortic A7r5 cells showed 22+/-4% (n=6) inhibition of inward...

  18. Close-up of the alpha-1,3-Gal epitope as defined by a monoclonal chimeric IgE and human serum using saturation transfer difference (STD) NMR

    DEFF Research Database (Denmark)

    Plum, Melanie; Michel, Yvonne; Wallach, Katharina;

    2011-01-01

    Anaphylaxis mediated by carbohydrate structures is a controversially discussed phenomenon. Nevertheless, IgE with specificity for the xenotransplantation antigen alpha-1,3-Gal (alpha-Gal) are associated with a delayed type of anaphylaxis providing evidence for the clinical relevance of carbohydrate...

  19. Bucket foundations under lateral cyclic loading

    DEFF Research Database (Denmark)

    Foglia, Aligi

    To enable a prosperous development of offshore wind energy, economically feasible technologies must be developed. The monopod bucket foundation is likely to become a cost-effective sub-structure for offshore wind turbines and has the potential to make offshore wind more cost-competitive in the en......To enable a prosperous development of offshore wind energy, economically feasible technologies must be developed. The monopod bucket foundation is likely to become a cost-effective sub-structure for offshore wind turbines and has the potential to make offshore wind more cost......-competitive in the energy market. This thesis addresses issues concerning monopod bucket foundations in the hope of providing tools and ideas that could be used to optimize the design of this sub-structure. The work is focussed on the behaviour of bucket foundations under lateral cyclic loading. Other related...... with the loading rate. Though, there is no difference in the initial stiffness. Pore pressure transducers inside and around the foundations recorded the distribution of the pore water pressure during loading.Horizontal and rotational displacements are not found to be influenced by the loading rate. A comprehensive...

  20. Insights into carbohydrate recognition by Narcissus pseudonarcissus lectin: the crystal structure at 2 A resolution in complex with alpha1-3 mannobiose.

    Science.gov (United States)

    Sauerborn, M K; Wright, L M; Reynolds, C D; Grossmann, J G; Rizkallah, P J

    1999-07-01

    Carbohydrate recognition by monocot mannose-binding lectins was studied via the crystal structure determination of daffodil (Narcissus pseudonarcissus) lectin. The lectin was extracted from daffodil bulbs, and crystallised in the presence of alpha-1,3 mannobiose. Molecular replacement methods were used to solve the structure using the partially refined model of Hippeastrum hybrid agglutinin as a search model. The structure was refined at 2.0 A resolution to a final R -factor of 18.7 %, and Rfreeof 26.7 %. The main feature of the daffodil lectin structure is the presence of three fully occupied binding pockets per monomer, arranged around the faces of a triangular beta-prism motif. The pockets have identical topology, and can bind mono-, di- or oligosaccharides. Strand exchange forms tightly bound dimers, and higher aggregation states are achieved through hydrophobic patches on the surface, completing a tetramer with internal 222-symmetry. There are therefore 12 fully occupied binding pockets per tetrameric cluster. The tetramer persists in solution, as shown with small-angle X-ray solution scattering. Extensive sideways and out-of-plane interactions between tetramers, some mediated via the ligand, make up the bulk of the lattice contacts.A fourth binding site was also observed. This is unique and has not been observed in similar structures. The site is only partially occupied by a ligand molecule due to the much lower binding affinity. A comparison with the Galanthus nivalis agglutinin/mannopentaose complex suggests an involvement of this site in the recognition mechanism for naturally occurring glycans.

  1. Interaction of new kinase inhibitors cabozantinib and tofacitinib with human serum alpha-1 acid glycoprotein. A comprehensive spectroscopic and molecular Docking approach

    Science.gov (United States)

    Ajmal, Mohammad Rehan; Abdelhameed, Ali Saber; Alam, Parvez; Khan, Rizwan Hasan

    2016-04-01

    In the current study we have investigated the interaction of newly approved kinase inhibitors namely Cabozantinib (CBZ) and Tofacitinib (TFB) with human Alpha-1 acid glycoprotein (AAG) under simulated physiological conditions using fluorescence quenching measurements, circular dichroism, dynamic light scattering and molecular docking methods. CBZ and TFB binds to AAG with significant affinity and the calculated binding constant for the drugs lie in the order of 104. With the increase in temperature the binding constant values decreased for both CBZ and TFB. The fluorescence resonance energy transfer (FRET) from AAG to CBZ and TFB suggested the fluorescence intensity of AAG was quenched by the two studied drugs via the formation of a non-fluorescent complex in the static manner. The molecular distance r value calculated from FRET is around 2 nm for both drugs, fluorescence spectroscopy data was employed for the study of thermodynamic parameters, standard Gibbs free energy change at 300K was calculated as - 5.234 kcal mol- 1 for CBZ-AAG interaction and - 6.237 kcal mol- 1 for TFB-AAG interaction, standard enthalpy change and standard entropy change for CBZ-AAG interaction are - 9.553 kcal mol- 1 and - 14.618 cal mol- 1K- 1 respectively while for AAG-TFB interaction, standard enthalpy and standard entropy change was calculated as 4.019 kcal mol- 1 and 7.206 cal mol- 1K- 1 respectively. Protein binding of the two drugs caused the tertiary structure alterations. Dynamic light scattering measurements demonstrated the reduction in the hydrodynamic radii of the protein. Furthermore molecular docking results suggested the Hydrophobic interaction and hydrogen bonding were the interactive forces in the binding process of CBZ to AAG while in case of TFB only hydrophobic interactions were found to be involved, overlap of the binding site for two studied drugs on the AAG molecule was revealed by docking results.

  2. Use of alpha-1 adrenoceptor antagonists in patients who underwent low-dose-rate brachytherapy for prostate cancer - a randomized controlled trial of silodosin versus naftopidil -

    International Nuclear Information System (INIS)

    To evaluate the effect of two different alpha-1 adrenoceptor antagonists on lower urinary tract symptoms in patients who underwent LDR-brachytherapy. A total of 141 patients who had been clinically diagnosed with localized prostate cancer and underwent LDR-brachytherapy were enrolled. Patients were randomized and allocated to two groups (silodosin 8 mg vs. naftopidil 75 mg). The primary endpoint was a change in the international prostate symptom score (IPSS) at 3 months after seed implantation. Secondary endpoints included the recovery rate of IPSS at 12 months after seed implantation, the change in IPSS and overactive bladder symptom score, uroflowmetric parameters, and frequency volume chart (FVC). To determine independent variables that can predict IPSS recovery, logistic regression analysis was carried out. The mean change in the IPSS at 3 months after seed implantation in both groups was ⊿10.6 (naftopidil) and ⊿10.4 (silodosin), respectively. There was not a significant difference between the two groups (p=0.728). An increase in urinary frequency and a decrease in total urinated volume and mean voided volume were observed in FVC for 12 months after seed implantation. Multivariate analysis revealed that the urethral dose (UD30) was an independent predictive parameter of IPSS recovery. Patients with UD30 < 200Gy showed a higher recovery rate of IPSS at 12 months after seed implantation. There was no significant difference of serial change in IPSS between silodosin and naftopidil during the first year after seed implantation. A lower dose on the urethra was an independent predictor of IPSS recovery at 12 months after seed implantation

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

    Science.gov (United States)

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

    2014-07-01

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

  4. Relation between increased anxiety and reduced expression of alpha1 and alpha2 subunits of GABA(A) receptors in Wfs1-deficient mice.

    Science.gov (United States)

    Raud, Sirli; Sütt, Silva; Luuk, Hendrik; Plaas, Mario; Innos, Jürgen; Kõks, Sulev; Vasar, Eero

    2009-08-28

    Mutations in the coding region of the WFS1 gene cause Wolfram syndrome, a rare multisystem neurodegenerative disorder of autosomal recessive inheritance. In clinical studies a relation between mutations in the Wfs1 gene and increased susceptibility for mood disorders has been established. According to our previous studies, mice lacking Wfs1 gene displayed increased anxiety in stressful environment. As the GABA-ergic system plays a significant role in the regulation of anxiety, we analyzed the expression of GABA-related genes in the forebrain structures of wild-type and Wfs1-deficient mice. Experimentally naïve Wfs1-deficient animals displayed a significant down-regulation of alpha1 (Gabra1) and alpha2 (Gabra2) subunits of GABA(A) receptors in the temporal lobe and frontal cortex. Exposure of wild-type mice to the elevated plus-maze decreased levels of Gabra1 and Gabra2 genes in the temporal lobe. A similar tendency was also established in the frontal cortex of wild-type animals exposed to behavioral test. In Wfs1-deficient mice the elevated plus-maze exposure did not induce further changes in the expression of Gabra1 and Gabra2 genes. By contrast, the expression of Gad1 and Gad2 genes, enzymes responsible for the synthesis of GABA, was not significantly affected by the exposure of mice to the elevated plus-maze or by the invalidation of Wfs1 gene. Altogether, the present study demonstrates that increased anxiety of Wfs1-deficient mice is probably linked to reduced expression of Gabra1 and Gabra2 genes in the frontal cortex and temporal lobe. PMID:19477223

  5. Differences between Mice and Humans in Regulation and the Molecular Network of Collagen, Type III, Alpha-1 at the Gene Expression Level: Obstacles that Translational Research Must Overcome

    Directory of Open Access Journals (Sweden)

    Lishi Wang

    2015-07-01

    Full Text Available Collagen, type III, alpha-1 (COL3A1 is essential for normal collagen I fibrillogenesis in many organs. There are differences in phenotypes of mutations in the COL3A1 gene in humans and mutations in mice. In order to investigate whether the regulation and gene network of COL3A1 is the same in healthy populations of mice and humans, we compared the quantitative trait loci (QTL that regulate the expression level of COL3A1 and the gene network of COL3A1 pathways between humans and mice using whole genome expression profiles. Our results showed that, for the regulation of expression of Col3a1 in mice, an eQTL on chromosome (Chr 12 regulates the expression of Col3a1. However, expression of genes in the syntenic region on human Chr 7 has no association with the expression level of COL3A1. For the gene network comparison, we identified 44 top genes whose expression levels are strongly associated with that of Col3a1 in mice. We next identified 41 genes strongly associated with the expression level of COL3A1 in humans. There are a few but significant differences in the COL3A1 gene network between humans and mice. Several genes showed opposite association with expression of COL3A1. These genes are known to play important roles in development and function of the extracellular matrix of the lung. Difference in the molecular pathway of key genes in the COL3A1 gene network in humans and mice suggest caution should be used in extrapolating results from models of human lung diseases in mice to clinical lung diseases in humans. These differences may influence the efficacy of drugs in humans whose development employed mouse models.

  6. Identification of the collagen type 1 alpha 1 gene (COL1A1) as a candidate survival-related factor associated with hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death especially among Asian and African populations. It is urgent that we identify carcinogenesis-related genes to establish an innovative treatment strategy for this disease. Triple-combination array analysis was performed using one pair each of HCC and noncancerous liver samples from a 68-year-old woman. This analysis consists of expression array, single nucleotide polymorphism array and methylation array. The gene encoding collagen type 1 alpha 1 (COL1A1) was identified and verified using HCC cell lines and 48 tissues from patients with primary HCC. Expression array revealed that COL1A1 gene expression was markedly decreased in tumor tissues (log2 ratio –1.1). The single nucleotide polymorphism array showed no chromosomal deletion in the locus of COL1A1. Importantly, the methylation value in the tumor tissue was higher (0.557) than that of the adjacent liver tissue (0.008). We verified that expression of this gene was suppressed by promoter methylation. Reactivation of COL1A1 expression by 5-aza-2′-deoxycytidine treatment was seen in HCC cell lines, and sequence analysis identified methylated CpG sites in the COL1A1 promoter region. Among 48 pairs of surgical specimens, 13 (27.1%) showed decreased COL1A1 mRNA expression in tumor sites. Among these 13 cases, 10 had promoter methylation at the tumor site. The log-rank test indicated that mRNA down-regulated tumors were significantly correlated with a poor overall survival rate (P = 0.013). Triple-combination array analysis successfully identified COL1A1 as a candidate survival-related gene in HCCs. Epigenetic down-regulation of COL1A1 mRNA expression might have a role as a prognostic biomarker of HCC

  7. Topics in modern physics theoretical foundations

    CERN Document Server

    Walecka, John Dirk

    2013-01-01

    While the two previous books entitled Introduction to Modern Physics: Theoretical Foundations and Advanced Modern Physics: Theoretical Foundations exposed the reader to the foundations and frontiers of today's physics, the goal of this third volume is to cover in some detail several topics omitted in the essentially linear progression of the first two. This book is divided into three parts. Part 1 is on quantum mechanics. Analytic solutions to the Schrödinger equation are developed for some basic systems. The analysis is then formalized, concluding with a set of postulates for the theory. Part 2 is on applications of quantum mechanics: approximation methods for bound states, scattering theory, time-dependent perturbation theory, and electromagnetic radiation and quantum electrodynamics. Part 3 covers some selected topics in relativistic quantum field theory: discrete symmetries, the Heisenberg picture, and the Feynman rules for quantum chromodynamics. The three volumes in this series taken together provide ...

  8. Al- Khwarizmi and axiomatic foundation of algebra

    International Nuclear Information System (INIS)

    This paper intends to investigate the axiomatic foundations of algebra, as they were presented in the book of algebra of al-Khwarizmi (9 th century), and as they were developed in many subsequent Arabic works. The paper gives also a description of algebra evolution towards a discipline independent ofgeometry and arithmetic: the two disciplines whosemarriage had led to its birth.By an in depth reading of some details in the text of al Khwarizmi , we concluded that this mathematician intended to lay down the axiomatic foundations of that new discipline. His resort to arithmetical and geometrical means was a way of making his theory more accessible. He used them to justify the axioms: those that were not explicitly introduced per se, and those that were remained implicit. The paper also relies on some unedited writingsof al-Khwarizmi's successors, which could shedlight on the ways they used to consolidate the foundations of algebra and improve its methods. (author)

  9. The theoretical foundations of quantum mechanics

    CERN Document Server

    Baaquie, Belal E

    2013-01-01

    The Theoretical Foundations of Quantum Mechanics addresses fundamental issues that are not discussed in most books on quantum mechanics. This book focuses on analyzing the underlying principles of quantum mechanics and explaining the conceptual and theoretical underpinning of quantum mechanics. In particular, the concepts of quantum indeterminacy, quantum measurement and quantum superposition are analyzed to clarify the concepts that are implicit in the formulation of quantum mechanics. The Schrodinger equation is never solved in the book. Rather, the discussion on the fundamentals of quantum mechanics is treated in a rigorous manner based on the mathematics of quantum mechanics. The new concept of the interplay of empirical and trans-empirical constructs in quantum mechanics is introduced to clarify the foundations of quantum mechanics and to explain the counter-intuitive construction of nature in quantum mechanics. The Theoretical Foundations of Quantum Mechanics is aimed at the advanced undergraduate and a...

  10. Dynamic Properties of Offshore Wind Turbine Foundations

    DEFF Research Database (Denmark)

    Damgaard, Mads

    ages structurally over its service life. Well-covered in the field of earthquake engineering, the dynamic response of civil engineering structures is highly dependent on the impedance of the soil–foundation system. For offshore wind turbine applications, however, the hysteretical and geometrical......, there is a general consensus that offshore wind-generated electricity is still too expensive to be competitive with conventional energy sources. As a consequence, the overall weight of the turbine and foundation is kept to a minimum resulting in a flexible and dynamically active structural system—even at low...... frequencies. The highly variable and cyclic loads on the rotor, tower and foundation, caused by wind and wave loads as well as low-frequent excitations from the rotor blades, all demand special fatigue design considerations and create an even greater demand for a fuller appreciation of how the wind turbine...

  11. Analysis of foundations on reinforced soil

    Science.gov (United States)

    Brown, B. S.; Poulos, H. G.

    1980-10-01

    A finite element model of reinforced earth is used to investigate the increase in bearing capacity and stiffness of a foundation due to the placement of reinforcement in the soil. The analysis is used to examine the effect of reinforcement on the load settlement behavior of a strip foundation founded on a c-theta soil. It is shown that the improvement in foundation performance depends on both the number of reinforcing layers and on the concentration (surface area per unit width of footing) of the reinforcement. The case of a footing on a reinforced soil mass overlying a cavity or a very soft zone is also analyzed, and the reinforced soil is shown to result in a significant improvement in footing performance.

  12. Expert Meeting Report. Foundations Research Results

    Energy Technology Data Exchange (ETDEWEB)

    Ojczyk, C. [Univ. of Minnesota, St. Paul, MN (United States); Huelman, P. [Univ. of Minnesota, St. Paul, MN (United States); Carmody, J. [Univ. of Minnesota, St. Paul, MN (United States)

    2013-05-01

    The NorthernSTAR Building America Partnership held an expert meeting on Foundations–Research Results on November 15, 2011, in Minneapolis, MN. Audience participation was actively encouraged during each presentation to uncover needs and promote dialog among researchers and industry professionals. Key results were: greater understanding of the role of moisture transport through foundation and insulation materials and its potential impact on building durability; greater understanding of the role of foundation type in the process of selecting an insulation system for energy performance and building durability; need for research to quantify the risks associated with insulation processes to better enable users to weigh costs and benefits against the existing conditions of a home; need for improved performance modeling capabilities that address variations in foundation types and soil conditions.

  13. Kellogg Foundation Initiative: Rewriting the Way Foundations Do Business in Indian Country.

    Science.gov (United States)

    Boyer, Paul

    2000-01-01

    Describes the multi-million dollar initiative announced by W. K. Kellogg Foundation in 1995 to support the Native American Higher Education Initiative, and how the Kellogg initiative deserves attention from the nation as a whole because it is attempting to fundamentally rewrite the way foundations do business with Indian communities. (VWC)

  14. Relativity foundations & philosophy of science & technology

    CERN Document Server

    Angel, Roger B

    1980-01-01

    Relativity: The Theory and its Philosophy provides a completely self-contained treatment of the philosophical foundations of the theory of relativity. It also surveys the most essential mathematical techniques and concepts that are indispensable to an understanding of the foundations of both the special and general theories of relativity. In short, the book includes a crash course in applied mathematics, ranging from elementary trigonometry to the classical tensor calculus.Comprised of 11 chapters, this book begins with an introduction to fundamental mathematical concepts such as sets, relatio

  15. History on foundation of Korea nuclear power

    International Nuclear Information System (INIS)

    This reports the history on foundation of Korea nuclear power from 1955 to 1980, which is divided ten chapters. The contents of this book are domestic and foreign affairs before foundation of nuclear power center, establishment of nuclear power and research center, early activity and internal conflict about nuclear power center, study for nuclear power business and commercialization of the studying ordeal over nuclear power administration and new phase, dispute for jurisdiction on nuclear power business and the process, permission for nuclear reactor, regulation and local administration, the process of deliberation and decision of reactor 3. 4 in Yonggwang, introduction of nuclear reprocessing facilities and activities for social organization.

  16. Cyber warfare building the scientific foundation

    CERN Document Server

    Jajodia, Sushil; Subrahmanian, VS; Swarup, Vipin; Wang, Cliff

    2015-01-01

    This book features a wide spectrum of the latest computer science research relating to cyber warfare, including military and policy dimensions. It is the first book to explore the scientific foundation of cyber warfare and features research from the areas of artificial intelligence, game theory, programming languages, graph theory and more. The high-level approach and emphasis on scientific rigor provides insights on ways to improve cyber warfare defense worldwide. Cyber Warfare: Building the Scientific Foundation targets researchers and practitioners working in cyber security, especially gove

  17. Impact of foundation properties on seismic response

    International Nuclear Information System (INIS)

    Seismic response of the NPP structures depends on the foundation properties twice. First, “free-field excitation” depends on soil/rock layering; second, soil-structure interaction also depends on soil/rock profile. Extreme cases of soil foundation profile are homogeneous half-space and soil layer resting on rigid rock. These two site profiles are principally different in behavior. Each particular site is usually somewhere in between. It is important to know the type of site in order to predict seismic response of NPP structures. (author)

  18. Mastering Microsoft SharePoint Foundation 2010

    CERN Document Server

    Callahan, C A

    2011-01-01

    Everything IT professionals need to create collaborative solutions. SharePoint Foundation 2010 is the newest version of a powerful collaboration tool used in many Exchange-enabled organizations. This book gets network professionals and business application administrators up to speed on the updates, features, and installation procedures, preparing them to create powerful collaboration structures for their companies.: Microsoft SharePoint Foundation 2010 is the successor to Windows SharePoint Services 3.0 and is used with Microsoft Office SharePoint Server to enable collaboration; this guide pre

  19. Vibration Based Wind Turbine Tower Foundation Design Utilizing Soil-Foundation-Structure Interaction

    Science.gov (United States)

    Al Satari, P. E. Mohamed; Hussain, S. E. Saif

    2008-07-01

    Wind turbines have been used to generate electricity as an alternative energy source to conventional fossil fuels. This case study is for multiple wind towers located at different villages in Alaska where severe arctic weather conditions exist. The towers are supported by two different types of foundations; large mat or deep piles foundations. Initially, a Reinforced Concrete (RC) mat foundation was utilized to provide the system with vertical and lateral support. Where soil conditions required it, a pile foundation solution was devised utilizing a 30″ thick RC mat containing an embedded steel grillage of W18 beams supported by 20″-24″ grouted or un-grouted piles. The mixing and casting of concrete in-situ has become the major source of cost and difficulty of construction at these remote Alaska sites. An all-steel foundation was proposed for faster installation and lower cost, but was found to impact the natural frequencies of the structural system by significantly softening the foundation system. The tower-foundation support structure thus became near-resonant with the operational frequencies of the wind turbine leading to a likelihood of structural instability or even collapse. A detailed 3D Finite-Element model of the original tower-foundation-pile system with RC foundation was created using SAP2000. Soil springs were included in the model based on soil properties obtained from the geotechnical consultant. The natural frequency from the model was verified against the tower manufacturer analytical and the experimental values. Where piles were used, numerous iterations were carried out to eliminate the need for the RC and optimize the design. An optimized design was achieved with enough separation between the natural and operational frequencies to prevent damage to the structural system eliminating the need for any RC encasement to the steel foundation or grouting to the piles.

  20. Implementation of a new Foundations Concept for Offshore Wind Farms

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo

    2008-01-01

    The foundation principles for the recent major offshore wind farm projects in Europe have been dominated by two types of foundation solutions, the gravitational foundation and the monopile. A fully operational 3.0 MW offshore wind turbine was installed on a prototype of the bucket foundation...

  1. Effects of Ionic Dependence of DNA Persistence Length on the DNA Condensation at Room Temperature

    Science.gov (United States)

    Mao, Wei; Liu, Yan-Hui; Hu, Lin; Xu, Hou-Qiang

    2016-05-01

    DNA persistence length is a key parameter for quantitative interpretation of the conformational properties of DNA and related to the bending rigidity of DNA. A series of experiments pointed out that, in the DNA condensation process by multivalent cations, the condensed DNA takes elongated coil or compact globule states and the population of the compact globule states increases with an increase in ionic concentration. At the same time, single molecule experiments carried out in solution with multivalent cations (such as spermidine, spermine) indicated that DNA persistence length strongly depends on the ionic concentration. In order to revolve the effects of ionic concentration dependence of persistence length on DNA condensation, a model including the ionic concentration dependence of persistence length and strong correlation of multivalent cation on DNA is provided. The autocorrelation function of the tangent vectors is found as an effective way to detect the ionic concentration dependence of toroidal conformations. With an increase in ion concentration, the first periodic oscillation contained in the autocorrelation function shifts, the number of segment contained in the first periodic oscillation decreases gradually. According to the experiments, the average long-axis length is defined to estimate the ionic concentration dependence of condensation process further. The relation between long-axis length and ionic concentration matches the experimental results qualitatively. Supported by National Natural Science Foundation of China under Grant Nos. 11047022, 11204045, 11464004 and 31360215; The Research Foundation from Ministry of Education of China (212152), Guizhou Provincial Tracking Key Program of Social Development (SY20123089, SZ20113069); The General Financial Grant from the China Postdoctoral Science Foundation (2014M562341); The Research Foundation for Young University Teachers from Guizhou University (201311); The West Light Foundation (2015) and College

  2. Interactive data visualization foundations, techniques, and applications

    CERN Document Server

    Ward, Matthew; Keim, Daniel

    2015-01-01

    Interactive Data Visualization: Foundations, Techniques, and Applications, Second Edition provides all the theory, details, and tools necessary to build visualizations and systems involving the visualization of data. In color throughout, it explains basic terminology and concepts, algorithmic and software engineering issues, and commonly used techniques and high-level algorithms. Full source code is provided for completing implementations.

  3. Excavationless Exterior Foundation Insulation Field Study

    Energy Technology Data Exchange (ETDEWEB)

    Schirber, T.; Mosiman, G.; Ojczyk, C.

    2014-10-01

    Building science research supports installing exterior (soil side) foundation insulation as the optimal method to enhance the hygrothermal performance of new homes. With exterior foundation insulation, water management strategies are maximized while insulating the basement space and ensuring a more even temperature at the foundation wall. However, such an approach can be very costly and disruptive when applied to an existing home, requiring deep excavation around the entire house. The NorthernSTAR Building America Partnership team implemented an innovative, minimally invasive foundation insulation upgrade technique on an existing home. The approach consisted of using hydrovac excavation technology combined with a liquid insulating foam. The team was able to excavate a continuous 4" wide by 4' to 5' deep trench around the entire house, 128 linear feet, except for one small part under the stoop that was obstructed with concrete debris. The combination pressure washer and vacuum extraction technology also enabled the elimination of large trenches and soil stockpiles normally produced by backhoe excavation. The resulting trench was filled with liquid insulating foam, which also served as a water-control layer of the assembly. The insulation was brought above grade using a liquid foam/rigid foam hybrid system and terminated at the top of the rim joist. Cost savings over the traditional excavation process ranged from 23% to 50%. The excavationless process could result in even greater savings since replacement of building structures, exterior features, utility meters, and landscaping would be minimal or non-existent in an excavationless process.

  4. Excavationless Exterior Foundation Insulation Field Study

    Energy Technology Data Exchange (ETDEWEB)

    Schirber, T. [NorthernSTAR, Minneaplolis, MN (United States); Mosiman, G. [NorthernSTAR, Minneaplolis, MN (United States); Ojczyk, C. [NorthernSTAR, Minneaplolis, MN (United States)

    2014-09-01

    Building science research supports installing exterior (soil side) foundation insulation as the optimal method to enhance the hygrothermal performance of new homes. With exterior foundation insulation, water management strategies are maximized while insulating the basement space and ensuring a more even temperature at the foundation wall. However, such an approach can be very costly and disruptive when applied to an existing home, requiring deep excavation around the entire house. The NorthernSTAR Building America Partnership team implemented an innovative, minimally invasive foundation insulation upgrade technique on an existing home. The approach consisted of using hydrovac excavation technology combined with liquid insulating foam. The team was able to excavate a continuous 4 inches wide by 4 feet to 5 feet deep trench around the entire house, 128 linear feet, except for one small part under the stoop that was obstructed with concrete debris. The combination pressure washer and vacuum extraction technology also enabled the elimination of large trenches and soil stockpiles normally produced by backhoe excavation. The resulting trench was filled with liquid insulating foam, which also served as a water-control layer of the assembly. The insulation was brought above grade using a liquid foam/rigid foam hybrid system and terminated at the top of the rim joist. Cost savings over the traditional excavation process ranged from 23% to 50%. The excavationless process could result in even greater savings since replacement of building structures, exterior features, utility meters, and landscaping would be minimal or non-existent in an excavationless process.

  5. Towards Axiomatic Foundations for Defuzzification Theory

    OpenAIRE

    Thiele, Helmut

    1998-01-01

    The starting point of the paper presented are the well-known defuzzification procedures on the one hand and approaches to axiomatize the concept of defuzzification, on the other hand. We present a new attempt to build up an axiomatic foundation for defuzzification theory using the theory of groups and the theory of partially ordered sets, and in particular, the theory of GALOIS connections.

  6. Theoretical Foundations for Website Design Courses.

    Science.gov (United States)

    Walker, Kristin

    2002-01-01

    Considers how theoretical foundations in website design courses can facilitate students learning the genres of Internet communication. Proposes ways that theories can be integrated into website design courses. Focuses on two students' website portfolios and ways they utilize genre theory and activity theory discussed in class to produce websites…

  7. Scientific foundations of structural policy analysis

    OpenAIRE

    Svetlana Grygoriyeva

    2015-01-01

    This article analyses the theoretical foundations of scientific investigation of the interrelation of sectoral (technological) and institutional aspects of structural policy in Ukraine. In the article it is substantiated the concept modernization of metallurgy and mechanical engineering sectors. This concept considers the modernization of metallurgy and mechanical engineering as a single institutional and technological complex.

  8. The Philosophical Foundations of Lifelong Learning.

    Science.gov (United States)

    Michopoulos, Aristotle

    The current lifelong learning movement, the new force toward global education, owes much to the League of Nations and the United Nations that sponsored an expanded multiracial "polis." Its philosophical foundations go back, however, to ancient China, India, and especially Greece, where philosophers and scientists got their creative stimulus from…

  9. Vibrations of machine foundations and surrounding soil

    NARCIS (Netherlands)

    Van Koten, H.; Hoogenboom, P.C.J.

    2012-01-01

    Rotating or pulsing machines are often placed on concrete foundations supported by soil. The machines cause vibrations in the building and in the surrounding soil. This paper provides information, formulas and calculation examples to predict these vibrations. The formulas have been experimentally te

  10. The Philosophical Foundations of Modern Medicine

    CERN Document Server

    Lee, Dr Keekok

    2011-01-01

    An exploration of the philosophical foundation of modern medicine which explains why such a medicine possesses the characteristics it does and where precisely its strengths as well as its weaknesses lie. Written in plain English, it should be accessible to anyone who is intellectually curious, lay persons and medical professionals alike.

  11. Theoretical Foundations of Rorschach by Piotrowski.

    Science.gov (United States)

    Daly, William C.

    2005-01-01

    The writer has tried to lift the veil of mystery from the Rorschach Cards by uncovering in simple form the ten basic principles of Zygmunt Protrowski which can be considered the foundation stones of Rorschach; they are composed of psycho-justifications as well as meaningful administrative procedures allowing the reader broader understanding of…

  12. Binary Relations as a Foundation of Mathematics

    NARCIS (Netherlands)

    Kuper, J.; Barendsen, E.; Capretta, V.; Geuvers, H.; Niqui, M.

    2007-01-01

    We describe a theory for binary relations in the Zermelo-Fraenkel style. We choose for ZFCU, a variant of ZFC Set theory in which the Axiom of Foundation is replaced by an axiom allowing for non-wellfounded sets. The theory of binary relations is shown to be equi-consistent ZFCU by constructing a mo

  13. Response of Rubble Foundation to Dynamic Loading

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Ibsen, Lars Bo

    1994-01-01

    The soil beneath vertical monolithic structures is subjected to a combination of static load due to the submerged weight of the structure and stochastic non-stationary loads as a result of the wave loads on the vertical wall. The stress conditions in the soil below a foundation exposed to both...

  14. Theoretical Foundations of Learning Environments. Second Edition

    Science.gov (United States)

    Jonassen, David, Ed.; Land, Susan, Ed.

    2012-01-01

    "Theoretical Foundations of Learning Environments" provides students, faculty, and instructional designers with a clear, concise introduction to the major pedagogical and psychological theories and their implications for the design of new learning environments for schools, universities, or corporations. Leading experts describe the most important…

  15. Excavations and Foundations in Soft Soils

    Science.gov (United States)

    Kempfert, Hans-Georg; Gebreselassie, Berhane

    The book reviews the experiences with, as well as recent developments and research results on excavations and foundations in and on soft soil deposits. Geotechnical design and execution of civil engineering structures on very soft soils are usually associated with substantial difficulties.

  16. Observed variations of monopile foundation stiffness

    DEFF Research Database (Denmark)

    Kallehave, Dan; Thilsted, C.L.; Diaz, Alberto Troya

    2015-01-01

    The soil-structure stiffness of monopile foundations for offshore wind turbines has a high impact on the fatigue loading during normal operating conditions. Thus, a robust design must consider the evolution of pile-soil stiffness over the lifetime of the wind farm. This paper present and discuss ...

  17. Corner Office Interview: Gates Foundation's Deborah Jacobs

    Science.gov (United States)

    Miller, Rebecca

    2010-01-01

    U.S. libraries gave the world a top talent when Deborah Jacobs left her transformational role as City Librarian of Seattle in 2008 to head the Bill & Melinda Gates Foundation's Global Libraries program, the international sibling to the U.S. Libraries program. The initiative fosters national-scale projects with grantees in transitioning countries…

  18. Foundations of computer science : lecture notes

    OpenAIRE

    Escardó, Martín

    2005-01-01

    Lecture given at Foundations of Computer Science, 2nd term In this part of the module are studied data structures and algorithms. The firts module have been treated some data structures (e.g. arrays, lists, stacks, queues) and some algorithms (e.g. linear search and binary search).

  19. Perfect Bayesian equilibrium. Part II: epistemic foundations

    OpenAIRE

    Bonanno, Giacomo

    2011-01-01

    In a companion paper we introduced a general notion of perfect Bayesian equilibrium which can be applied to arbitrary extensive-form games. The essential ingredient of the proposed definition is the qualitative notion of AGM-consistency. In this paper we provide an epistemic foundation for AGM-consistency based on the AGM theory of belief revision.

  20. Readiness, Behavior, and Foundational Mathematics Course Success

    Science.gov (United States)

    Li, Kevin; Zelenka, Richard; Buonaguidi, Larry; Beckman, Robert; Casillas, Alex; Crouse, Jill; Allen, Jeff; Hanson, Mary Ann; Acton, Tara; Robbins, Steve

    2013-01-01

    This study examines the effects of math readiness and student course behavior (e.g., attendance, participation, homework completion) on knowledge gain and course success using two samples of students enrolled in foundational skills (noncredit-bearing) mathematics courses. As hypothesized, entering student mathematics readiness and course behavior…

  1. About The Rural Developm ent Foundation

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    <正>The Rural Development Foundation ( RDF) ,founded in 1996,is an Indian nonprofit organization with the mission of providing quality education for underprivileged rural children. RDF founded and continues to operate five schools and one juniorcollege in Andhra Pradesh State,taking a unique holistic approach to education through innovative programs and

  2. Physico-mathematical foundations of relativistic cosmology

    CERN Document Server

    Soares, Domingos

    2013-01-01

    I briefly present the foundations of relativistic cosmology, which are, General Relativity Theory and the Cosmological Principle. I discuss some relativistic models, namely, "Einstein static universe" and "Friedmann universes". The classical bibliographic references for the relevant tensorial demonstrations are indicated whenever necessary, although the calculations themselves are not shown.

  3. Response of Rubble Foundation to Dynamic Loading

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Ibsen, Lars Bo

    1993-01-01

    The soil beneath vertical monolithic structures is subjected to a combination of static load due to the submerged weight of the structure and stochastic non-stationary loads as a result of the wave loads on the vertical wall. The stress conditions in the soil below a foundation exposed to both st...

  4. Vibrations of a pipe on elastic foundations

    Indian Academy of Sciences (India)

    S V Lilkova-Markova; D S Lolov

    2004-06-01

    A cantilevered pipe subjected to external transverse (or lateral) force is investigated. Two cases of elastic foundations are considered: rotational and both linear and rotational. The major findings are the variations in frequency with flow velocity and displacements at different points and times.

  5. The Foundations of Modern Time Series Analysis

    CERN Document Server

    Mills, Professor Terence C

    2011-01-01

    This book develops the analysis of Time Series from its formal beginnings in the 1890s through to the publication of Box and Jenkins' watershed publication in 1970, showing how these methods laid the foundations for the modern techniques of Time Series analysis that are in use today.

  6. Foundational Academic Development: Building Collegiality across Divides?

    Science.gov (United States)

    Clarke, Catherine; Reid, Jacqueline

    2013-01-01

    There is limited research into the effectiveness of non-accredited foundational courses for new academic staff. An ongoing issue is that of attention and anxiety overload in the critical first period of employment when the challenges of establishing oneself in a new collegial environment are most acute. Approaches to addressing this issue may be…

  7. Industrial Foundations in the Danish Economy

    DEFF Research Database (Denmark)

    Thomsen, Steen

    -owned companies account for 5-10% of the Danish economy depending on measurement. However, they constitute the bulk of Danish stock market capitalization and R&D expenditure, and they also contribute disproportionally to international business activity. Finally the industrial foundations make charitable donations...

  8. The Emotional Foundations of Social Understanding

    Science.gov (United States)

    Warren, Heather K.; Denham, Susanne A.; Bassett, Hideko H.

    2008-01-01

    The infant and toddler years are a watershed of development in the emotional domain. These skills lay the foundation for positive social interactions, and ultimately, academic and life success. This article describes the development of three skills that are central in creating successful relationships: expressing emotion, understanding emotion,…

  9. Mining Foundations, Trust and Funds : A Sourcebook

    OpenAIRE

    World Bank, (WB)

    2010-01-01

    Mining operations increasingly exist in remote parts of developing countries, and with the combined challenges in public services delivery and development assistance, this is drawing the mining sector further into catalyzing development at local, regional and national levels. Responding to this multifaceted trend, the mining sector has increasingly turned to foundations, trusts and funds a...

  10. Foundation: Transforming data bases into knowledge bases

    Science.gov (United States)

    Purves, R. B.; Carnes, James R.; Cutts, Dannie E.

    1987-01-01

    One approach to transforming information stored in relational data bases into knowledge based representations and back again is described. This system, called Foundation, allows knowledge bases to take advantage of vast amounts of pre-existing data. A benefit of this approach is inspection, and even population, of data bases through an intelligent knowledge-based front-end.

  11. Status of Supersymmetry: Foundations and Applications

    CERN Document Server

    Ferrara, Sergio

    2011-01-01

    We review some aspects of the foundations of supersymmetry as a conjectural in­variance of the Laws of Nature. This symmetry bypasses the Coleman-Mandula Theorem by enlarging the funda­mental space -time symmetries to the Superworld. Application of supersymmetry to particle physics requires its spontaneous breaking, as it happens for the electroweak symmetry of the Standard Model.

  12. Three Essays on Foundation Owned Firms in Germany

    OpenAIRE

    Draheim, Matthias

    2016-01-01

    This dissertation consists of three research papers on foundation owned firms in Germany, which are structured into three chapters. All chapters and their respective main research results are briefly summarized below.There are several prominent examples of foundation owned firms, such as Aldi, Bosch, Lidl, ThyssenKrupp, and ZF Friedrichshafen. Foundation owned firms are firms that are fully or partially owned by a foundation. A foundation is a legal entity without owners that is set up by a ...

  13. Pile foundation of nuclear power plant structures

    International Nuclear Information System (INIS)

    The subject of pile foundation used for nuclear power plant structures, considering the experience gained by the designers of the Angra Nuclear Power Plant, Units 2 and 3 in Brazil is dealt with. The general concept of the pile foundations, including types and execution of the piles, is described briefly. Then the two basic models, i.e. the static model and the dynamic one, used in the design are shown, and the pertinent design assumptions as related to the Angra project are mentioned. The criteria which established the loading capacity of the piles are discussed and the geological conditions of the Angra site are also explained briefly, justifying the reasons why pile foundations are necessary in this project. After that, the design procedures and particularly the tools - i.e. the computer programs - are described. It is noted that the relatively simple but always time consuming job of loading determination calculations can be computerized too, as it was done on this project through the computer program SEASA. The interesting aspects of soil/structure interaction, applicable to static models, are covered in detail, showing the theoretical base wich was used in the program PILMAT. Then the advantage resulting from computerizing of the job of pile reinforcement design are mentioned, describing briefly the jobs done by the two special programs PILDES and PILTAB. The point is stressed that the effort computerizing the structural design of this project was not so much due to the required accuracy of the calculations, but mainly due to the need to save on the design time, as to allow to perform the design task within the relatively tight time schedule. A conclusion can be drawn that design of pile foundations for nuclear power plant structures is a more complex task than the design of bearing type of foundation for the same structures, but that the task can be always made easier when the design process can be computerized. (Author)

  14. Dna Sequencing

    Science.gov (United States)

    Tabor, Stanley; Richardson, Charles C.

    1995-04-25

    A method for sequencing a strand of DNA, including the steps off: providing the strand of DNA; annealing the strand with a primer able to hybridize to the strand to give an annealed mixture; incubating the mixture with four deoxyribonucleoside triphosphates, a DNA polymerase, and at least three deoxyribonucleoside triphosphates in different amounts, under conditions in favoring primer extension to form nucleic acid fragments complementory to the DNA to be sequenced; labelling the nucleic and fragments; separating them and determining the position of the deoxyribonucleoside triphosphates by differences in the intensity of the labels, thereby to determine the DNA sequence.

  15. Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin.

    Directory of Open Access Journals (Sweden)

    Benjamin M Scott

    Full Text Available In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2-P1 yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352-356 (P7-P3 was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7-P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1 as a serpin amenable to phage display and suggest the utility of this approach for the selection

  16. Lipid raft facilitated ligation of K-{alpha}1-tubulin by specific antibodies on epithelial cells: Role in pathogenesis of chronic rejection following human lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Tiriveedhi, Venkataswarup; Angaswamy, Nataraju [Department of Surgery, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Weber, Joseph [Department of Medicine, Washington University School of Medicine, St. Louis, MO (United States); Mohanakumar, T., E-mail: kumart@wustl.edu [Department of Surgery, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States)

    2010-08-20

    Research highlights: {yields} Addition of KAT Abs (+) sera to NHBE culture causes upregulation of growth factors. {yields} Cholesterol depletion causes down regulation of growth factor expression. {yields} Cholesterol depletion is accompanied by loss of membrane bound caveolin. {yields} Thus, we demonstrate lipid raft are critical for efficient ligation of the KAT Abs. -- Abstract: Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-{alpha}1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4 {+-} 1.1-, 3.2 {+-} 0.9-, and 3.4 {+-} 1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of {beta}-methyl cyclodextran ({beta}MCD) had significantly reduced growth factor expression (1.3 {+-} 0.3, vs {beta}MCD untreated being 6.4 {+-} 1.1-fold

  17. Oncostatin M, but not interleukin-6 or leukemia inhibitory factor, stimulates expression of alpha1-proteinase inhibitor in A549 human alveolar epithelial cells.

    Science.gov (United States)

    Sallenave, J M; Tremblay, G M; Gauldie, J; Richards, C D

    1997-06-01

    Alpha-1 proteinase inhibitor (A1-Pi) is the main serine proteinase inhibitor found in human plasma and is a potent elastase inhibitor in various tissues, including lung. A1-Pi is expressed and induced in liver during inflammatory responses but can also be produced by epithelial cells. Since hepatocyte A1-Pi production is stimulated by interleukin-6 (IL-6) and other gp130-cytokines, such as leukemia inhibitory factor (LIF) and oncostatin M (OM), we investigated the role of these cytokines in regulating A1-Pi in lung epithelial cells. We show that OM, a monocyte and T cell product, can specifically and potently induce A1-Pi production in lung-derived A549 alveolar (epithelial) cells, as well as in liver-derived HepG2 cells. Both A1-Pi protein (as detected by ELISA and Western blots) and mRNA levels were enhanced 20-fold to 30-fold in A549 cells. OM was also able to stimulate the expression of tissue inhibitor of metalloproteinase-1 in these cells. Interestingly, other members of the IL-6 family (IL-6 and LIF) had little or no effect on A549 cells, and proinflammatory cytokines, such as IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) also had no stimulatory effect on A1-Pi synthesis in A549 cells. Costimulation with IL-1 beta resulted in a decrease in A1-Pi production from OM-stimulated A549 cells. However, IL-6 production was synergistically enhanced. OM was also able to stimulate A1-Pi production from a bronchial epithelial primary cell line, whereas an intestinal epithelial cell line HT29 responded to IL-6 but not OM. These results suggest that lung levels A1-Pi could be derived not only from liver and inflammatory cells but also from epithelial cells, which can be upregulated on stimulation by OM. This may have implications for regulation of local activity of human neutrophil elastase (HNE) in such diseases as emphysema and cystic fibrosis. PMID:9198001

  18. SUSTAINABLE CONCRETE FOR WIND TURBINE FOUNDATIONS.

    Energy Technology Data Exchange (ETDEWEB)

    BERNDT,M.L.

    2004-06-01

    The use of wind power to generate electricity continues to grow, especially given commitments by various countries throughout the world to ensure that a significant percentage of energy comes from renewable sources. In order to meet such objectives, increasingly larger turbines with higher capacity are being developed. The engineering aspects of larger turbine development tend to focus on design and materials for blades and towers. However, foundations are also a critical component of large wind turbines and represent a significant cost of wind energy projects. Ongoing wind research at BNL is examining two areas: (a) structural response analysis of wind turbine-tower-foundation systems and (b) materials engineering of foundations. This work is investigating the dynamic interactions in wind turbine systems, which in turn assists the wind industry in achieving improved reliability and more cost efficient foundation designs. The results reported herein cover initial studies of concrete mix designs for large wind turbine foundations and how these may be tailored to reduce cost and incorporate sustainability and life cycle concepts. The approach taken was to investigate material substitutions so that the environmental, energy and CO{sub 2}-impact of concrete could be reduced. The use of high volumes of ''waste'' materials in concrete was examined. These materials included fly ash, blast furnace slag and recycled concrete aggregate. In addition, the use of steel fiber reinforcement as a means to improve mechanical properties and potentially reduce the amount of bar reinforcement in concrete foundations was studied. Four basic mixes were considered. These were: (1) conventional mix with no material substitutions, (2) 50% replacement of cement with fly ash, (3) 50% replacement of cement with blast furnace slag and (4) 25% replacement of cement with fly ash and 25% replacement with blast furnace slag. Variations on these mixes included the addition of 1

  19. Purification and biological activity of recombinant thymosin alpha 1%重组胸腺素α1的分离纯化和活性测定

    Institute of Scientific and Technical Information of China (English)

    石继红; 张英起; 赵宁; 颜真; 韩苇; 赵永同

    2001-01-01

    目的 利用融合表达载体pThioHisA的重组质粒pThioHisA-Tα1④, 转化大肠杆菌TOP10得到的工程菌,来分离纯化表达的胸腺素α1(thymosin alpha 1,T α1). 方法 将高效表达融合蛋白 的工程菌用细胞破碎器裂解,经80℃热处理,离心上清采用Q-Sepharose FF阴离子交换色谱纯化融合蛋白. 融合蛋白经CNBr裂 解后用常压离子交换色谱纯化Tα1单体. 应用SDS-PAGE,2L-Tricine-SDS-PAGE和HPLC进行鉴定. 结果 [ HTSS SDS-PAGE分析表明菌体表达的融合蛋白占菌体总蛋白的400 g*kg-1. 经2L-Tricine-SDS-PAGE分析证实,融合蛋白可裂 解出Tα1单体,裂解物经简单的离子色谱可以纯化出Tα1单体,HPLC鉴定纯化出的Tα1纯度可达950 g*kg-1以上. 利用3H-TdR进行的生物活性测定表明,在致有丝分裂原ConA存在的条件下,融合蛋白和Tα1单体均具有刺激小鼠脾淋巴细胞 分裂增殖的能力,与化学合成的Tα1相比具有相似的生物活性. 结论 该方法是分离纯化Tα1 简便易行,经济有效的方法;同时也为Tα1的分离纯化和大规模的开发生产奠定了基础.%AIM To purify and prepare thymosin alpha 1 (Tα 1). METHODS The engineering bacteria TOP10 including recombinant plasmid of a fusion expression vector pThioHisA with the tandem Tα 1 gene of 4 repeats (Tα1④) was used. after bacter ia lysated by Bionee Cell Disruoter, the lysate was incubat ed in the temperature of 80℃ for 10 minutes, and cooled quickly. By Q-Sepharose Fast Flow chromatography, the fusio n protein was purified from the supernatant of the lysate. At the concentrion of 0.5 mol*L-1 CNBr cleavage of the fusion protein in 700 mL*L-1 formic acid, Tα1 was purified by ion exchange methods of SP-Sepharose Fast Flow and Q-Sepharose Fast Flow. T hese were identified by SDS-PAGE, 2L-Tricine-SDS-PAGE and HPLC. RESULTS SDS-PAGE analysis showed an induced expression fusion protein band which consititued 400 g

  20. Method of Installing a Foundation in the Sea Bed and Such Foundation

    DEFF Research Database (Denmark)

    2015-01-01

    The invention relates to a seabed foundation 11) for an offshore facility, comprising a primary pressure chamber 17) connected to a primary pump 1S) and one or more secondary pressure chambers 19) connected to one or more secondary pumps 110).According to an embodiment of the invention, said...... primary pump is a suction pump and said secondary pump is a pressure pump. The invention further relates to a method 112) of installing said foundation on the seabed 119), which comprises the steps of activating 114) said primary pump to create negative pressure in the primary pressure chamber 17), so...... that the foundation sinks into the seabed, and activating 115) said one or more secondary pumps 110) to create positive pressures in the secondary pressure chambers 19), so as to control the alignment of the foundation with respect to a substantially horizontal axis 116)during the sinking into the seabed....