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Sample records for adenosine deaminase ada

  1. CSF ADENOSINE DEAMINASE (ADA ACTIVITY IN PATIENTS WITH MENINGITIS

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    Justin

    2016-05-01

    Full Text Available Meningitis is inflammation of the meninges (pia, arachnoid and dura mater covering the brain and the spinal cord. ADA is an enzyme in the purine salvage pathway which is found in abundance in active T-lymphocytes. Hence, an attempt was made to estimate the CSF ADA level in patients with suspected meningitis and throw light on its use in differentiating the various types of meningitis. AIMS AND OBJECTIVES To estimate the level of CSF adenosine deaminase level in different types of meningitis. To assess its usefulness in differentiating the various types (bacterial, viral and tuberculous of meningitis. MATERIALS AND METHODS The study was conducted at the medical wards of Govt. Rajaji Hospital, Madurai, a prospective analytical study from a period of April 2012 to September 2012. OBSERVATION AND RESULTS Tuberculous meningitis occurred more in the age group of 21–40 years. Bacterial meningitis was seen mainly in patients < 20 years of age. Viral meningitis was seen in all age groups. CSF ADA level was highest in tuberculous meningitis, the mean value being 24.5 U/L. The mean value of ADA in bacterial meningitis was 4.54 U/L and viral meningitis patients had lowest mean ADA value of 2.65 U/L. CONCLUSION In our study, 50 patients with meningitis admitted in Government Rajaji Hospital from April 2012 to September 2012 were evaluated. Meningitis predominantly affected people in the age group of 20-40 years in our study with a male: female ratio of 1.9:1. Cases of tuberculous meningitis constituted 48% of the study group and bacterial and viral meningitis were 26% each. CSF protein values were higher and sugar values lower in patients with tuberculous and bacterial meningitis. CSF cell counts were higher in patients with bacterial meningitis.

  2. Autoimmune dysregulation and purine metabolism in adenosine deaminase (ADA)-deficiency

    OpenAIRE

    Aisha Vanessa Sauer; Immacolata eBrigida; Nicola eCarriglio; Alessandro eAiuti

    2012-01-01

    Genetic defects in the adenosine deaminase (ADA) gene are among the most common causes for severe combined immunodeficiency (SCID). ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT), enzyme replacement therapy with bovine ADA (PEG-ADA) or hematopoietic stem cell gene therapy (HSC-GT). Although ...

  3. Platelet aggregation and serum adenosine deaminase (ADA) activity in pregnancy associated with diabetes, hypertension and HIV.

    Science.gov (United States)

    Leal, Claudio A M; Leal, Daniela B R; Adefegha, Stephen A; Morsch, Vera M; da Silva, José E P; Rezer, João F P; Schrekker, Clarissa M L; Abdalla, Faida H; Schetinger, Maria R C

    2016-07-01

    Platelet aggregation and adenosine deaminase (ADA) activity were evaluated in pregnant women living with some disease conditions including hypertension, diabetes mellitus and human immunodeficiency virus infection. The subject population is consisted of 15 non-pregnant healthy women [control group (CG)], 15 women with normal pregnancy (NP), 7 women with hypertensive pregnancy (HP), 10 women with gestational diabetes mellitus (GDM) and 12 women with human immunodeficiency virus-infected pregnancy (HIP) groups. The aggregation of platelets was checked using an optical aggregometer, and serum ADA activity was determined using the colorimetric method. After the addition of 5 µM of agonist adenosine diphosphate, the percentage of platelet aggregation was significantly (p pregnancy and pregnancy-associated diseases suggest that platelet aggregation and ADA activity could serve as peripheral markers for the development of effective therapy in the maintenance of homeostasis and some inflammatory process in these pathophysiological conditions. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27273565

  4. Autoimmune dysregulation and purine metabolism in adenosine deaminase (ADA-deficiency

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    Aisha Vanessa Sauer

    2012-08-01

    Full Text Available Genetic defects in the adenosine deaminase (ADA gene are among the most common causes for severe combined immunodeficiency (SCID. ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT, enzyme replacement therapy with bovine ADA (PEG-ADA or hematopoietic stem cell gene therapy (HSC-GT. Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment.A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T and B cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties.

  5. Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances

    OpenAIRE

    Li, Gen; Nakagome, Izumi; Hirono, Shuichi; Itoh, Tomoo; Fujiwara, Ryoichi

    2015-01-01

    Cordycepin, which is an analogue of a nucleoside adenosine, exhibits a wide variety of pharmacological activities including anticancer effects. In this study, ADA1- and ADA2-expressing HEK293 cells were established to determine the major ADA isoform responsible for the deamination of cordycepin. While the metabolic rate of cordycepin deamination was similar between ADA2-expressing and Mock cells, extensive metabolism of cordycepin was observed in the ADA1-expressing cells with K m and V max v...

  6. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus;

    2007-01-01

    Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated familie...... the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation....

  7. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry.

    Science.gov (United States)

    Sanchez, Juan J; Monaghan, Gemma; Børsting, Claus; Norbury, Gail; Morling, Niels; Gaspar, H Bobby

    2007-05-01

    Inherited adenosine deaminase (ADA) deficiency is a rare metabolic disorder that causes immunodeficiency, varying from severe combined immunodeficiency (SCID) in the majority of cases to a less severe form in a small minority of patients. Five patients of Somali origin from four unrelated families, with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb upstream of the ADA transcription start site. All patients were homozygous for the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7. Among 207 Somali immigrants to Denmark, the frequency of ADA c7C>T and the maximum likelihood estimate of the frequency of the haplotype ADA-7T/ADA-239G/ADA-425G/AluVpA7 were both 0.012 (carrier frequency 2.4%). Based on the analysis of AluVpA alleles, the ADA c7C/T mutation was estimated to be approximately 7,100 years old. Approximately 1 out of 5 - 10000 Somali children will be born with ADA deficiency due to an ADA c7C/T mutation, although within certain clans the frequency may be significantly higher. ADA-SCID may be a frequent immunodeficiency disorder in Somalia, but will be underdiagnosed due to the prevailing socioeconomic and nutritional deprivation.

  8. Comparative study of adenosine deaminase activity, insulin resistance and lipoprotein(a) among smokers and healthy non-smokers

    OpenAIRE

    Ramesh Ramasamy; Sathish Babu Murugaiyan; Arulkumaran U.; Sathiya R.; Kuzhandai Velu V.; Niranjan Gopal

    2016-01-01

    Background: Adenosine deaminase also known as adenosine aminohydrolase involved in purine metabolism. Its primary function is development and maintenance of immune system. The main objective of the study was to estimate adenosine deaminase (ADA) enzyme and find its correlation with lipoprotein(a) and insulin resistance among smokers and healthy non-smokers. Methods: Fifty smokers and fifty healthy non-smokers were selected based on WHO definition. ADA, lipid profile and glucose was estimat...

  9. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency

    NARCIS (Netherlands)

    Hassan, Amel; Booth, Claire; Brightwell, Alex; Allwood, Zoe; Veys, Paul; Rao, Kanchan; Hoenig, Manfred; Friedrich, Wilhelm; Gennery, Andrew; Slatter, Mary; Bredius, Robbert; Finocchi, Andrea; Cancrini, Caterina; Aiuti, Alessandro; Porta, Fulvio; Lanfranchi, Arnalda; Ridella, Michela; Steward, Colin; Filipovich, Alexandra; Marsh, Rebecca; Bordon, Victoria; Al-Muhsen, Saleh; Al-Mousa, Hamoud; Alsum, Zobaida; Al-Dhekri, Hasan; Al Ghonaium, Abdulaziz; Speckmann, Carsten; Fischer, Alain; Mahlaoui, Nizar; Nichols, Kim E.; Grunebaum, Eyal; Al Zahrani, Daifulah; Roifman, Chaim M.; Boelens, Jaap; Davies, E. Graham; Cavazzana-Calvo, Marina; Notarangelo, Luigi; Gaspar, H. Bobby

    2012-01-01

    Deficiency of the purine salvage enzyme adenosine deaminase leads to SCID (ADA-SCID). Hematopoietic cell transplantation (HCT) can lead to a permanent cure of SCID; however, little data are available on outcome of HCT for ADA-SCID in particular. In this multicenter retrospective study, we analyzed o

  10. Lower frequency of the low activity adenosine deaminase allelic variant (ADA1*2 in schizophrenic patients Diminuição da frequência da variante alélica de baixa atividade da adenosina desaminase (ADA1*2 em pacientes esquizofrênicos

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    Gustavo Pimentel Dutra

    2010-09-01

    Full Text Available OBJECTIVE: Adenosine may play a role in the pathophysiology of schizophrenia, since it modulates the release of several neurotransmitters such as glutamate, dopamine, serotonin and acetylcholine, decreases neuronal activity by pos-synaptic hyperpolarization and inhibits dopaminergic activity. Adenosine deaminase participates in purine metabolism by converting adenosine into inosine. The most frequent functional polymorphism of adenosine deaminase (22G→A (ADA1*2 exhibits 20-30% lower enzymatic activity in individuals with the G/A genotype than individuals with the G/G genotype. The aim of this study was to evaluate the ADA polymorphism 22G→A (ADA1*2 in schizophrenic patients and healthy controls. METHOD: The genotypes of the ADA 22G→A were identified with allele-specific PCR strategy in 152 schizophrenic patients and 111 healthy individuals. RESULTS: A significant decrease in the frequency of the G/A genotype was seen in schizophrenic patients (7/152 - 4.6% relative to controls (13/111 - 11.7%, p = 0.032, OR = 2.6. CONCLUSION: These results suggest that the G/A genotype associated with low adenosine deaminase activity and, supposingly, with higher adenosine levels is less frequent among schizophrenic patients.OBJETIVO: A adenosina pode ter um papel importante na fisiopatologia da esquizofrenia, uma vez que modula a liberação de vários neurotransmissores, tais como glutamato, dopamina, serotonina e acetilcolina, diminui a atividade neuronal por hiperpolarização pós-sináptica e inibe a atividade dopaminérgica. A adenosina desaminase participa do metabolismo das purinas pela conversão de adenosina em inosina. O mais frequente polimorfismo funcional da adenosina desaminase (22G →A (ADA1*2 exibe uma diminuição de 20-30% da atividade funcional em indivíduos com genótipo G/A quando comparados com indivíduos com o genótipo G/G. O objetivo deste estudo foi avaliar o polimorfismo 22G→A (ADA1*2 em pacientes esquizofrênicos e em

  11. COMPARISION OF ADENOSINE DEAMINASE [ADA] LEVELS WITH CYTO-CHEMICAL ANALYSIS OF PLEURAL FLUIDS TO DIFFERENTIATE TUBERCULAR AND NON â TUBERCULAR EFFUSIONS

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    Choukimath M Sharanabasav

    2013-12-01

    Full Text Available This study is intended to utilize biochemical parameters like ADA and protein levels in comparison with cell count and cell type in pleural fluid to differentiate tubercular and non-tubercular effusions. We have analyzed a total of 208 cases and among them 59.61% cases were ADA positive and 40.39% cases were ADA negative, and 156 cases were exudates and 52 cases were transudates. Categorized these effusions into 4 groups taking consideration of ADA, cell count, lymphocyte and protein levels as exudate with ADA positive, exudate with ADA negative, transudate with ADA positive and transudate with ADA negative. This study has shown promising results to diagnose tuberculosis with immediate and cost effectiveness that can be undertaken by any basic laboratory, in a endemic areas and developing countries like India

  12. Adenosine Deaminase Activity in Chronic Lymphocytic Leukemia and Healthy Subjects

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    Ghaderi, Bayazid; Amini, Sabrieh; Maroofi, Farzad; Jalali, Chiya; Javanmardi, Mitra; Roshani, Daem; Abdi, Mohammad

    2016-01-01

    Background B cell chronic lymphocytic leukemia is one of the most frequent hematologic malignancies in the world. Cellular surface CD markers and serum Beta-2-microglobulin may be used as a prognostic tool in CLL patients. Objectives In the present study we introduce serum adenosine deaminase as a diagnostic marker in CLL. Materials and Methods Blood samples were collected from B-CLL and healthy subjects. White blood cell, red blood cell and platelet count and blood Erythrocyte sedimentation rate was recorded and serum Beta-2-microglobulin, Lactate dehydrogenase and total ADA enzyme activity were determined. Results Serum ADA activity was significantly higher in patients group than that of controls. ADA had a significant and direct correlation with B2M, WBC, LDH and ESR. However, there was not any relation between ADA and the stages of disease. Diagnostic cut-off, sensitivity and specificity of the serum ADA test were 27.97 U/L, 91% and 94%, respectively. Conclusions A higher ADA activity in patients group and its correlation with CLL markers were seen in our study. High diagnostic value of serum ADA in our study suggests that it might be considered as a useful screening tool among the other markers in CLL.

  13. Serum adenosine deaminase activity and its isoenzyme in patients treated for tuberculosis

    International Nuclear Information System (INIS)

    Objective: Increased serum adenosine deaminase (ADA) activity, mainly associated with tuberculosis can also occur in a number of other diseases thus negatively affecting the diagnostic utility of ADA measurements in tuberculosis. The aim of the study was to determine whether or not the combined use of the activity of ADA, its isoenzymes and differential cell counts would provide a more efficient means of diagnosing tuberculosis than the use of ADA levels alone. Results: Data suggested significant (p0.75) of ADA/sub 2/ADA was found to be better indicator of tuberculosis. Lymphocyte neutrophil ratio (L/N)> 0.69 gave additional benefit to increase the sensitivity and specificity for the use of ADA as marker in diagnosing tuberculosis. Conclusion: The combined use of activity of ADA, its isoenzymes and total and differential cell counts is a better indicator and gives better understanding to diagnose and evaluate tuberculosis and response to therapy. (author)

  14. A 24-Year Enzyme Replacement Therapy in an Adenosine-deaminase-Deficient Patient.

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    Tartibi, Hana M; Hershfield, Michael S; Bahna, Sami L

    2016-01-01

    Severe combined immunodeficiency (SCID) is a fatal childhood disease unless immune reconstitution is performed early in life, with either hematopoietic stem cell transplantation or gene therapy. One of its subtypes is caused by adenosine deaminase (ADA) enzyme deficiency, which leads to the accumulation of toxic metabolites that impair lymphocyte development and function. With the development of polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) enzyme replacement therapy, many ADA-deficient children with SCID who could not receive a hematopoietic stem cell transplantation or gene therapy survived and had longer and healthier lives. We report a 24-year course of treatment in a patient who was diagnosed with ADA deficiency at 4 months of age. The patient was treated with PEG-ADA, which was the only therapy available for him. The patient's plasma ADA level was regularly monitored and the PEG-ADA dose adjusted accordingly. This treatment has resulted in near-normalization of lymphocyte counts, and his clinical course has been associated with only minor to moderate infections. Thus far, he has had no manifestations of autoimmune or lymphoproliferative disorders. This patient is among the longest to be maintained on PEG-ADA enzyme replacement therapy. PMID:26684479

  15. Modulating effect of adenosine deaminase on function of adenosine A1receptors

    Institute of Scientific and Technical Information of China (English)

    Wan-chun SUN; Yan CAO; Lei JIN; Li-zhen WANG; Fan MENG; Xing-zu ZHU

    2005-01-01

    Aim: To study the modulating effect of adenosine deaminase (ADA) on yhe adenosine A1 receptor (A1R) in HEK293 cells stably expressing the human A1R.Methods: cDNA was amplified by RT-PCR using total RNA from human embryo brain tissue as the template. The PCR products were subcloned into the plasmid pcDNA3 and cloned into the plasmid pcDNA3.1. The cloned A1R cDNA was sequenced and stably expressed in HEK293 cells. The modulating effect of adenosine deaminase on A1R was studied by using [3H]DPCPX binding assay and an intracellular calcium assay. Results: HEK293 cells stably expressing human A1R were obtained. Saturation studies showed that the KD value and Bmax value of [3H]DPCPX were 1.6±0.2 nmol/L and 1.819±0.215 nmol/g of protein respectively, in the absence of ecto-ADA respectively, and 1.3±0.2 nmol/L and 1.992±0.130 nmol/g of protein in the presence of ecto-ADA respectively, suggesting that the KD value and Bmax value of [3H]DPCPX were unaffected by ecto-ADA. In the case of [3H]DPCPX competition curves obtained from intact cells or membranes, A1R agonist CCPA/[3H]DPCPX competition curve could be fitted well to a one-site model in the absence of ecto-ADA and a two-site model in the presence of ecto ADA with a KH value of 0.74 (0.11-4.8) nmol/L (intact cells) or 1.8 (0.25-10) nmol/L (membrane) and a KL value of 0.94 (0.62-1.41) μmol/L (intact cells) or 0.77 (0.29-0.99) μmol/L (membrane). The KL value is not significantly different from the IC50 value of 0.84(0.57-1.23) μmol/L (intact cells) or 0.84 (0.63-1.12) μmol/L (membrane) obtained in the absence of ecto-ADA. Similar results were obtained from the CPA/[3H]DPCPX competition curve in the absence or presence of ecto-ADA on intact cells or membranes. Intracellular calcium assay demonstrated that the EC50 value of CPA were 10 (5-29) nmol/L and 94 (38-229) nmol/L in the presence or absence of ecto-ADA, respectively. Conclusion: A1R stably expressed in the HEK293 cells display a low affinity for agonists in

  16. Genetics Home Reference: adenosine monophosphate deaminase deficiency

    Science.gov (United States)

    ... links) CLIMB: Children Living with Inherited Metabolic Diseases Muscular Dystrophy Association: Myoadenylate Deaminase Deficiency Genetic Testing Registry (1 link) Muscle AMP deaminase deficiency ...

  17. Adenosine deaminase activity in serum and lymphocytes of rats infected with Sporothrix schenckii.

    Science.gov (United States)

    Castro, Verônica S P; Pimentel, Victor C; Da Silva, Aleksandro S; Thomé, Gustavo R; Wolkmer, Patrícia; Castro, Jorge L C; Costa, Márcio M; da Silva, Cássia B; Oliveira, Daniele C; Alves, Sydney H; Schetinger, Maria R C; Lopes, Sonia T A; Mazzanti, Cinthia M

    2012-07-01

    Sporotrichosis is a fungal infection of subcutaneous or chronic evolution, inflammatory lesions characterized by their pyogranulomatous aspect, caused by the dimorphic fungus Sporothrix schenckii. Adenosine deaminase (ADA) is a "key" enzyme in the purine metabolism, promoting the deamination of adenosine, an important anti-inflammatory molecule. The increase in ADA activity has been demonstrated in several inflammatory conditions; however, there are no data in the literature associated with this fungal infection. The objective of this study was to evaluate the activity of serum ADA (S-ADA) and lymphocytes (L-ADA) of rats infected with S. schenckii. We used seventy-eight rats divided into two groups. In the first experiment, rats were infected subcutaneously and in the second experiment, infected intraperitoneally. Blood samples for hematologic evaluation and activities of S-ADA and L-ADA were performed at days 15, 30, and 40 post-infection (PI) to assess disease progression. In the second experiment, it was observed an acute decrease in activity of S-ADA and L-ADA (P schenckii alters the activities of S-ADA in experimentally infected rats, demonstrating the involvement of this enzyme in the pathogenesis of sporotrichosis.

  18. Increased level of soluble adenosine deaminase in bone marrow of visceral leishmaniasis patients: an inverse relation with parasite load.

    Science.gov (United States)

    Rai, Ambak K; Kumar, Prabin; Saini, Sheetal; Thakur, Chandreshwar P; Seth, Tulika; Mitra, Dipendra K

    2016-09-01

    Adenosine deaminase (ADA) which degrades adenosine to inosine, is known to be pro-inflammatory molecule in many diseases. Adenosine suppresses the functioning of the immune system and thus promotes dissemination of the parasite. In our previous finding, the level of soluble ADA in serum of visceral leishmaniasis (VL) was found to be increased as compared to healthy controls. However, it cannot be fairly interpreted unless their level is demonstrated at the disease site, where the parasite resides. We designed this study to correlate the level of soluble ADA (sADA) with parasitic load at the disease site i.e. bone marrow (BM). We found increased levels of sADA in BM as compared to the unaffected BM. Furthermore, a significant inverse correlation is observed between the parasite load and level of sADA at the disease site. PMID:27447233

  19. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency.

    OpenAIRE

    Montiel-Equihua, Claudia A; Thrasher, Adrian J.; Bobby Gaspar, H

    2009-01-01

    Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a pr...

  20. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

    OpenAIRE

    Thrasher, Adrian

    2009-01-01

    Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a pr...

  1. Comparison of interferon-gamma release assays and adenosine deaminase of pleural fluid for the diagnosis of pleural tuberculosis

    Institute of Scientific and Technical Information of China (English)

    刘菲

    2014-01-01

    Objective To compare the diagnostic performance of interferon gamma releasing assays(T-SPOT.TB)and adenosine deaminase(ADA)in pleural tuberculosis,and therefore to evaluate the value of T-SPOT.TB in a high tuberculosis burden country.Methods From June 2011to November 2012,111 patients with pleural fluid in Beijing Chest Hospital,Capital Medical University were

  2. The investigation of Adenosine Deaminase activity in patients with Mycosis Fungoides

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    Yılmaz Ulaş

    2013-12-01

    Full Text Available Aim: Mycosis fungoides (MF is a cutaneous T cell lymphoma. The clinical and histophological diagnosis of early mycosis fungoides is usually diffucult. There is no special laboratory method for the diagnosis of MF disease and this is the most important problem in diagnosis and also follow up the effectiveness of treatment. Adenosine deaminase (ADA activity is a non-specific marker of T cell activation. In the present study, we aimed to investigate the levels of plasma and tissue ADA in patients with mycosis fungoides and to determine if ADA is an activation criteria for this disease. Materials and Medhods: The levels of ADA activities in both plasma and tissues were spectrophotometrically measured in 40 patients with MF and compared to those of 33 healthy subjects. Moreover, a subgroup analysis regarding ADA activities was performed in 17 patients who achieved complete remission after different kinds of treatments. Results: Patients with MF had more significantly elevated plasma and tissue ADA activity levels than those of control groups (respectively p0.05; MF patients in remission were found to have higher plasma levels of ADA activities than those of controls (p<0.001. Conclusion: These findings of the current study may provide an important clinical support for showing the roles of plasma and tissue ADA activity levels to predict disease activity in MF patients. In addition, levels of ADA activity measurements might be a marker to follow up in MF patients.

  3. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY

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    Iván Darío BRAVO-TOBAR

    2015-10-01

    Full Text Available SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA and C-reactive protein serum levels (CRP in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35, II (n = 29, and III (n = 18. A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.

  4. A Case of Hypogammaglobulinemia with Enteroviral Meningoencephalitis, Associated with Increased Adenosine Deaminase in Cerebrospinal Fluid

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    Alborizi Abdolvahab

    2009-06-01

    Full Text Available We describe the development of enterovirus meningoencephalitis associated with increased adenosine deaminase in cerebrospinal fluid of a 12-year-old boy, a known case of hypogamaglobulinemia despite monthly replacement of IVIg.The patient was referred to our center with fever, headache and vomiting for 10 days. CSF analysis was compatible with aseptic meningoencephalitis but high CSF protein (>200mg/dl and high level of adenosine deaminase in CSF (30IU/L were against the diagnosis of simple viral meningoencephalitis. Nested PCR of CSF for entrovirus was positive. Treatment with daily high-dose IVIg was commenced, with significant clinical improvement. For patients with increased ADA and lymphocytic pleocytosis in CSF, differential diagnoses should include enteroviral meningitis. Antibodies, although crucial, cannot on their own prevent enteroviral infection in some hypogamaglbulinemic patients.

  5. Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker.

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    Herbschleb-Voogt, E; Ten Kate, J; Meera Khan, P

    1983-01-01

    Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues. PMID:6133497

  6. Serum Adenosine deaminase activity and C-reactive protein levels in unstable angina

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    Rani Surekha

    2003-01-01

    Full Text Available In unstable angina (USA patients, immunological responses contributing to inflammation play a vital role in plaque rupture and thrombosis causing stroke. In the present study an attempt is made to estimate the levels of adenosine deaminase activity, an immunoenzyme marker and C-reactive protein, a marker of inflammation in USA patients. 45 patients presenting USA and 50 age and sex matched healthy controls were included in the study. Serum ADA activity was measured spectrophotometrically at 630nm and serum C-reactive protein was detected using Avitex CRP kit, which is a rapid latex agglutination test. The Mean ADA levels were 41.15 ± 11.04 in patients and 20.71±5.63 in controls and 66.6% of patients and none of the controls were positive to CRP. The present study observed the importance of ADA as a serum marker in addition to CRP for assessing the immune response in USA patients.

  7. Mutations in the human adenosine deaminase gene that affect protein structure and RNA splicing

    International Nuclear Information System (INIS)

    Adenosine deaminase deficiency is one cause of the genetic disease severe combined immunodeficiency. To identify mutations responsible for ADA deficiency, the authors synthesized cDNAs to ADA mRNAs from two cell lines, GM2756 and GM2825A, derived from ADA-deficient immunodeficient patients. Sequence analysis of GM2756 cDNA clones revealed a different point mutation in each allele that causes amino acid changes of alanine to valine and arginine to histidine. One allele of GM2825A also has a point mutation that causes an alanine to valine substitution. The other allele of GM2825A was found to produce an mRNA in which exon 4 had been spliced out but had no other detrimental mutations. S1 nuclease mapping of GM2825A mRNA showed equal abundance of the full-length ADA mRNA and the ADA mRNA that was missing exon 4. Several of the ADA cDNA clones extended 5' of the major initiation start site, indicating multiple start sites for ADA transcription. The point mutations in GM2756 and GM2825A and the absence of exon 4 in GM2825A appear to be directly responsible for the ADA deficiency. Comparison of a number of normal and mutant ADA cDNA sequences showed a number of changes in the third base of codons. These change do not affect the amino acid sequence. Analyses of ADA cDNAs from different cell lines detected aberrant RNA species that either included intron 7 or excluded exon 7. Their presence is a result of aberrant splicing of pre-mRNAs and is not related to mutations that cause ADA deficiency

  8. Influence of hemodialysis on the plasma concentration of adenosine deaminase in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Eduardo O. Chielle

    2015-06-01

    Full Text Available ABSTRACT Introduction: Over the past years there has been a significant increase in hospitalizations and treatments due to kidney complications that eventually resulted in the increased number of patients on dialysis. The adenosine deaminase (ADA enzyme mediates the formation of some defense cells of the organism and is therefore a marker of inflammation. Objective: The objective of this study was to evaluate biomarkers of renal function and serum ADA of hemodialysis patients. Materials and methods: Blood samples were collected from 80 patients – 40 women and 40 men – between 19 and 60 years old, before and after the completion of hemodialysis. Results: There was a significant difference in levels of creatinine, urea and ADA in pre- and post-hemodialysis periods (p < 0.0001. There was a significant increase in post-dialysis ADA regardless of sex; however there was a significantly greater increase in men. Conclusion: The results showed a reduction in urea and creatinine parameters, evidencing the main purpose of hemodialysis. This study suggests that the determination of ADA activity could be used to monitor inflammation in hemodialysis patients, however wider and more specific studies are needed to show the effectiveness of serum ADA activity as an inflammatory marker in patients with chronic kidney disease.

  9. Purine metabolic enzymes in lymphocytes. III. Effects of immunosuppressants on adenosine deaminase and purine nucleoside phosphorylase activities

    OpenAIRE

    Kurashige, Satonori; Akuzawa, Yuki; Yoshida, Toshiharu; Kodama, Kazue

    1983-01-01

    Mice were treated with a single injection of 6-mercaptopurine riboside (6MP-R), predonine or cyclophosphamide (CY), and the effects of these immunosuppressants on blastogenic responses to phytohemagglutinin P (PHA-P) or bacterial lipopoly saccharide (LPS) and on adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) activities were studied with spleen lymphocytes. The retardation of blastogenic responses to both PHA-P and LPS were associated with the retardation of both intracellu...

  10. MicroRNA-146b-3p Regulates Retinal Inflammation by Suppressing Adenosine Deaminase-2 in Diabetes

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    Sadanand Fulzele

    2015-01-01

    Full Text Available Hyperglycemia- (HG- Amadori-glycated albumin- (AGA- induced activation of microglia and monocytes and their adherence to retinal vascular endothelial cells contribute to retinal inflammation leading to diabetic retinopathy (DR. There is a great need for early detection of DR before demonstrable tissue damages become irreversible. Extracellular adenosine, required for endogenous anti-inflammation, is regulated by the interplay of equilibrative nucleoside transporter with adenosine deaminase (ADA and adenosine kinase. ADA, including ADA1 and ADA2, exists in all organisms. However, because ADA2 gene has not been identified in mouse genome, how diabetes alters adenosine-dependent anti-inflammation remains unclear. Studies of pig retinal microglia and human macrophages revealed a causal role of ADA2 in inflammation. Database search suggested miR-146b-3p recognition sites in the 3′-UTR of ADA2 mRNA. Coexpression of miR-146b-3p, but not miR-146-5p or nontargeting miRNA, with 3′-UTR of the ADA2 gene was necessary to suppress a linked reporter gene. In the vitreous of diabetic patients, decreased miR-146b-3p is associated with increased ADA2 activity. Ectopic expression of miR-146b-3p suppressed ADA2 expression, activity, and TNF-α release in the AGA-treated human macrophages. These results suggest a regulatory role of miR-146b-3p in diabetes related retinal inflammation by suppressing ADA2.

  11. Modulatory effect of iron chelators on adenosine deaminase activity and gene expression in Trichomonas vaginalis.

    Science.gov (United States)

    Primon-Barros, Muriel; Rigo, Graziela Vargas; Frasson, Amanda Piccoli; Santos, Odelta dos; Smiderle, Lisiane; Almeida, Silvana; Macedo, Alexandre José; Tasca, Tiana

    2015-11-01

    Trichomonas vaginalis is a flagellate protozoan that parasitises the urogenital human tract and causes trichomoniasis. During the infection, the acquisition of nutrients, such as iron and purine and pyrimidine nucleosides, is essential for the survival of the parasite. The enzymes for purinergic signalling, including adenosine deaminase (ADA), which degrades adenosine to inosine, have been characterised in T. vaginalis. In the evaluation of the ADA profile in different T. vaginalis isolates treated with different iron sources or with limited iron availability, a decrease in activity and an increase in ADA gene expression after iron limitation by 2,2-bipyridyl and ferrozine chelators were observed. This supported the hypothesis that iron can modulate the activity of the enzymes involved in purinergic signalling. Under bovine serum limitation conditions, no significant differences were observed. The results obtained in this study allow for the assessment of important aspects of ADA and contribute to a better understanding of the purinergic system in T. vaginalis and the role of iron in establishing infection and parasite survival.

  12. Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency

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    Claudia A Montiel-Equihua

    2009-12-01

    Full Text Available Claudia A Montiel-Equihua, Adrian J Thrasher, H Bobby GasparCentre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UKAbstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID and especially adenosine deaminase (ADA-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.Keywords: adenosine deaminase, severe combined immunodeficiency, gene therapy, hematopoietic stem cell, retrovirus, clinical trial

  13. Cerebrospinal fluid adenosine deaminase activity: A complimentary tool in the early diagnosis of tuberculous meningitis

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    Taori Girdhar M

    2006-03-01

    Full Text Available Abstract Background Tuberculous meningitis (TBM is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB. The diagnosis of TBM is often difficult. A reliable, cost-effective and rapid diagnostic test, which can be performed in any standard pathology laboratory, could be of help in the diagnosis of TBM. In the present study we measured the adenosine deaminase (ADA activity in cerebrospinal fluid (CSF of TBM and non-TBM patients. Method ADA activity in CSF was determined according to a method based on the Berthlot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically. Results The CSF ADA activity from TBM patients was compared with CSF ADA from non-TBM infectious meningitis patients, and from patients with non-infectious neurological disorders. The mean CSF ADA activity was found to be significantly higher in CSF of TBM patients, 14.31 ± 3.87 (2.99–26.94, mean ± SD with range, than in the CSF from non-TBM infectious meningitis, 9.25 ± 2.14 (4.99–13.96 and from the non-infectious neurological disorders group, 2.71 ± 1.96 (0.00–7.68, P Conclusion This study demonstrated that ADA activity in the CSF of TBM patients, using a cut-off value 11.39 U/L/min, can be useful for the early differential diagnosis of TBM. This test can be performed in any pathology laboratory where more sophisticated methods are not available.

  14. Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2'-deoxycoformycin.

    OpenAIRE

    Hershfield, M S; Kurtzberg, J; Harden, E; Moore, J O; Whang-Peng, J; Haynes, B. F.

    1984-01-01

    Selective failure of lymphoid development occurs in genetic deficiency of adenosine deaminase (ADA). We examined the in vivo effects of a potent inhibitor of ADA, 2'-deoxycoformycin, which was used to treat a patient with refractory acute leukemia. Unexpectedly, within 7 days of starting treatment, the leukemic phenotype underwent complete conversion from T lymphoblastic to promyelocytic, with kinetics that suggested a precursor-product relationship between the two cell populations. Pretreatm...

  15. DNA-templated silver nanoclusters based label-free fluorescent molecular beacon for the detection of adenosine deaminase.

    Science.gov (United States)

    Zhang, Kai; Wang, Ke; Xie, Minhao; Zhu, Xue; Xu, Lan; Yang, Runlin; Huang, Biao; Zhu, Xiaoli

    2014-02-15

    A general and reliable fluorescent molecular beacon is proposed in this work utilizing DNA-templated silver nanoclusters (AgNCs). The fluorescent molecular beacon has been employed for sensitive determination of the concentration of adenosine deaminase (ADA) and its inhibition. A well-designed oligonucleotide containing three functional regions (an aptamer region for adenosine assembly, a sequence complementary to the region of the adenosine aptamer, and an inserted six bases cytosine-loop) is adopted as the core element in the strategy. The enzymatic reaction of adenosine catalyzed by ADA plays a key role as well in the regulation of the synthesis of the DNA-templated AgNCs, i.e. the signal indicator. The intensity of the fluorescence signal may thereby determine the concentration of the enzyme and its inhibitor. The detection limit of the ADA can be lowered to 0.05 UL(-1). Also, 100 fM of a known inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA) is enough to present distinguishable fluorescence emission. Moreover, since the fluorescent signal indicator is not required to be bound with the oligonucleotide, this fluorescent molecular beacon may integrate the advantages of both the label-free and signal-on strategies.

  16. Development of a capillary electrophoresis method for analyzing adenosine deaminase and purine nucleoside phosphorylase and its application in inhibitor screening.

    Science.gov (United States)

    Qi, Yanfei; Li, Youxin; Bao, James J

    2016-08-01

    A novel capillary electrophoresis (CE) method was developed for simultaneous analysis of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) in red blood cells (RBCs). The developed method considered and took advantage of the natural conversion from the ADA product, inosine to hypoxanthine. The transformation ratio was introduced for ADA and PNP analysis to obtain more reliable results. After optimizing the enzymatic incubation and electrophoresis separation conditions, the determined activities of ADA and PNP in 12 human RBCs were 0.237-0.833 U/ml and 9.013-10.453 U/ml packed cells, respectively. The analysis of ADA in mice RBCs indicated that there was an apparent activity difference between healthy and hepatoma mice. In addition, the proposed method was also successfully applied in the inhibitor screening from nine traditional Chinese medicines, and data showed that ADA activities were strongly inhibited by Rhizoma Chuanxiong and Angelica sinensis. The inhibition effect of Angelica sinensis on ADA is first reported here and could also inhibit PNP activity. PMID:27173606

  17. Oxidative Stress Biomarkers and Adenosine Deaminase over the Alopecic Area of the Patients with Alopecia Areata

    Science.gov (United States)

    Öztürk, Perihan; Arıcan, Özer; Kurutaş, Ergül Belge; Mülayim, Kamil

    2016-01-01

    Background: Alopecia areata (AA) is an autoimmune, T-cell mediated, and chronic inflammatory disorder. The pathological mechanisms of disease are unclear, but oxidative stress may be involved. To our knowledge, no studies have examined the oxidative stress levels or biomarkers within the lesional area and skin surface in patients with AA. Similarly, adenosine deaminase (ADA) has not been characterized in AA. Aims: Therefore, we aimed to define ADA levels and the factors involved in oxidative stress from scalp-scrapes of patients with AA. Study Design: Case-control study. Method: A total of 60 patients (30 diagnosed AA patients and 30 healthy controls) were included in the study. ADA as well as oxidative stress factors, including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analyzed from scalp-scrapes in both groups and quantified by spectrophotometry. Results: Activities of SOD (p=0.000), CAT (p=0.033), and ADA (p=0.004) as well as levels of GSH (p=0.000) and MDA (p=0.032) in patients with AA were higher than the controls statistically significant. Conclusion: Based on these results, factors associated with oxidative stress were elevated in AA patient scalp-scrapes compared to controls and may have a defined role the disease pathogenesis. Alterations in the activities of antioxidant enzymes from AA patient scraping samples may be a local effect of elevated oxidative stress levels. In this disease, oxidative stress may affect not only hair follicle but also any layers of the skin.

  18. Serum adenosine deaminase as oxidative stress marker in type 2 diabetes mellitus

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    Shashikala Magadi Dasegowda

    2015-05-01

    Results: The study observed an increased level of serum adenosine deaminase, malondialdehyde and decreased levels of total antioxidant capacity in type 2 diabetes mellitus compared to controls. Serum adenosine deaminase levels in type 2 diabetics were 50.77 +/- 6.95 and in controls was 17.86 +/- 4.04. Serum Malondialdehyde levels in type 2 diabetics was 512.13 +/- 70.15 and in controls was 239.32 +/- 23.97. Serum total antioxidant levels in type 2 diabetics was 0.39+/-0.15 and in controls was 1.66+/-0.25. Positive correlation was seen between serum adenosine deaminase and malondialdehyde and it was statistically significant. Statistically significant negative correlation was seen between serum adenosine deaminase and total antioxidant capacity. Conclusion: Adenosine deaminase can be used as oxidative stress marker. Their increased levels indicate oxidative stress in type 2 diabetes mellitus. Therefore, estimation of serum adenosine deaminase levels help in early prediction and prevention of long term complications occurring due to oxidative stress in diabetics, thereby decreasing the mortality and morbidity in them. [Int J Res Med Sci 2015; 3(5.000: 1195-1198

  19. Evaluation of Serum Adenosine Deaminase and Retinol in patients with Laryngeal Cancer

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    R.B Metgudmath

    2013-12-01

    Full Text Available Laryngeal cancers account for 4% of all head and neck cancers in India. The disease process has better prognosis if it is diagnosed early. In view of this the objective of the study was to assess the reliability of serum enzyme marker adenosine deaminase and non-enzymatic anti-oxidant retinol in laryngeal cancer patients as supportive parameters for diagnostic purpose. Materials and methods:-25 clinically and histopathologically confirmed patients of laryngeal cancer in age group of 45-65 years were included in the study and 25 healthy subjects with in the same age group served as controls. Results:-The level of serum ADA was significantly elevated in laryngeal cancer patients in comparison to controls whereas retinol levels were significantly decreased. Conclusion: - Lipid per-oxidation as a result of cancer leads to membrane damage and an increase in cytoplasmic ADA. It is also associated with a decrease in levels of non-enzymatic antioxidant retinol. These biochemical parameters may be used as supportive parameters for diagnostic purpose and may add further for prognostic information. Further studies are required on a larger sample size to explore strategies by which normal levels of anti-oxidant can be maintained by a retinol rich diet which may play a role in reducing the morbidity and mortality due to cancer.

  20. Syzygium cumini extract decrease adenosine deaminase, 5'nucleotidase activities and oxidative damage in platelets of diabetic patients.

    Science.gov (United States)

    De Bona, Karine S; Bellé, Luziane P; Sari, Marcel H; Thomé, Gustavo; Schetinger, Maria R C; Morsch, Vera M; Boligon, Aline; Athayde, Margareth L; Pigatto, Aline S; Moretto, Maria B

    2010-01-01

    Diabetes mellitus, a chronic metabolic disorder, has assumed epidemic proportions and its long-term complications can have devastating consequences. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Syzygium cumini is being widely used to treat diabetes by the traditional practitioners over many centuries. Adenosine deaminase (ADA) and 5'-Nucleotidase (5'NT) are enzymes of purine nucleoside metabolism that play an important role in the regulation of adenosine (Ado) levels. In this study, we investigated the effect of Syzygium cumini aqueous leaves extract (ASc) on ADA and 5'NT activities and on parameters of oxidative stress under in vitro conditions, using platelets of patients with Type 2 diabetes mellitus. Platelet-Rich Plasma (PRP) was assayed by ADA, 5'NT, Catalase (CAT), Superoxide Dismutase (SOD) activities and Thiobarbituric acid reactive substances (TBARS) levels. We observed that ADA, 5'NT activities and TBARS levels were significantly higher when compared to the control group, and ASc (100 and 200 μg/mL) prevented these effects. Our study demonstrates that ASc was able to remove oxidant species generated in diabetic conditions and modulates in the Ado levels. Then, ASc may promote a compensatory response in platelet function, improving the susceptibility-induced by the diabetes mellitus. PMID:21063110

  1. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma.

    Science.gov (United States)

    ten Kate, J; van den Ingh, H F; Khan, P M; Bosman, F T

    1986-04-15

    Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi-quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane-associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well-differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor. PMID:3957458

  2. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    Science.gov (United States)

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process. PMID:2573631

  3. Effects of PUVA and Narrowband UVB on Tissue and Serum Adenosine Deaminase Levels of Patients with Psoriasis

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    Sinem Öztürk

    2013-12-01

    Full Text Available Objective: Adenosine deaminase (ADA, which is accepted as a non-specific marker of T cell activation in psoriasis, has been shown to have an important role in determining activity of disease and efficacy of treatments. This is the first study investigating the levels of ADA in lesional skins of patients with psoriasis. Methods: Thirty-four patients; 26 with chronic plaque type and eight with guttate psoriasis were enrolled in this study. Patients were treated with PUVA or narrowband UVB. Contol group consisted of 25 patients who had an amputation of any extremity because of trauma. In this study, ADA activities were measured in plasma and tissue samples of patients and control group. Psoriasis Area and Severity Index (PASI scores of patients were determined. Results: Plasma and tissue ADA levels of patients with psoriasis were higher than control group (p0.05. Conclusion: These results support the immunological mechanisms showing activation of T cell acts in the pathogenesis of psoriasis and also this study suggests that the levels of plasma and tissue ADA are reliable laboratory parameters in follow-up of the disease.

  4. STUDY OF ADENOSINE DEAMINASE AND LYMPHOCYTE/NEUTROPHIL RATIO IN COMBINATION AS DIAGNOSTIC TOOL FOR TUBERCULAR PLEURAL EFFUSION

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    Md. Faizur

    2015-10-01

    Full Text Available Adenosine deaminase, considered one of the key enzyme of purine metabolism, has been used in work up of lymphocytic pleural effusion. Low level of ADA 50IU/L specially when combined with Lymphocytic/neutrophil ratio >0.75 in pleural fluid is useful test in the diagnosis of tubercular pleurisy. AIM AND OBJECTIVE: To suggest a better diagnostic tool in the diagnosis of pleural effusion of tubercular origin by estimating the activity of ADA along with L/N ratio in pleural effusion. METHOD: Biochemical, cytological and microbiology studies were done by obtaining pleural fluid by thoracocentesis in 100 patients after excluding pleural effusion cases of malignancy, transudative effusion. RESULT: 84 cases were tubercular and had high level of ADA in comparison to rest of 16 non-tubercular cases. At level of 50 IU/L of ADA activity test had sensitivity of 97.6%, specificity 87.5%, positive predictive value 97.6%, negative predictive value 87.5%which increased to 100% and 92.8%, 98.6%, and 100% respectively in combination with test of Lymphocytic/Neutrophilic ratio >0.75. CONCLUSION: ADA level with L/N ratio can be important investigation in diagnosis of tubercular pleural effusion cases.

  5. Recombinant adeno-associated virus-mediated gene transfer for the potential therapy of adenosine deaminase-deficient severe combined immune deficiency.

    Science.gov (United States)

    Silver, Jared N; Elder, Melissa; Conlon, Thomas; Cruz, Pedro; Wright, Amy J; Srivastava, Arun; Flotte, Terence R

    2011-08-01

    Severe combined immune deficiency due to adenosine deaminase (ADA) deficiency is a rare, potentially fatal pediatric disease, which results from mutations within the ADA gene, leading to metabolic abnormalities and ultimately profound immunologic and nonimmunologic defects. In this study, recombinant adeno-associated virus (rAAV) vectors based on serotypes 1 and 9 were used to deliver a secretory version of the human ADA (hADA) gene to various tissues to promote immune reconstitution following enzyme expression in a mouse model of ADA deficiency. Here, we report that a single-stranded rAAV vector, pTR2-CB-Igκ-hADA, (1) facilitated successful gene delivery to multiple tissues, including heart, skeletal muscle, and kidney, (2) promoted ectopic expression of hADA, and (3) allowed enhanced serum-based enzyme activity over time. Moreover, the rAAV-hADA vector packaged in serotype 9 capsid drove partial, prolonged, and progressive immune reconstitution in ADA-deficient mice. Overview Summary Gene therapies for severe combined immune deficiency due to adenosine deaminase (ADA) deficiency (ADA-SCID) over two decades have exclusively involved retroviral vectors targeted to lymphocytes and hematopoietic progenitor cells. These groundbreaking gene therapies represented an unprecedented revolution in clinical medicine but in most cases did not fully correct the immune deficiency and came with the potential risk of insertional mutagenesis. Alternatively, recombinant adeno-associated virus (rAAV) vectors have gained attention as valuable tools for gene transfer, having demonstrated no pathogenicity in humans, minimal immunogenicity, long-term efficacy, ease of administration, and broad tissue tropism (Muzyczka, 1992 ; Flotte et al., 1993 ; Kessler et al., 1996 ; McCown et al., 1996 ; Lipkowitz et al., 1999 ; Marshall, 2001 ; Chen et al., 2003 ; Conlon and Flotte, 2004 ; Griffey et al., 2005 ; Pacak et al., 2006 ; Stone et al., 2008 ; Liu et al., 2009 ; Choi et al., 2010

  6. The Effect of Acute Exercise upon Adenosin Deaminase Oxidant and Antioxidant Activity

    Science.gov (United States)

    Kafkas, M. Emin; Karabulut, Aysun Bay; Sahin, Armagan; Otlu, Onder; Savas, Seyfi; Aytac, Aylin

    2012-01-01

    The purpose of this study was to determine the changes of MDA, glutation (GSH), Adenozine deaminase (ADA) and superoxidase dismutaze (SOD) levels with exercise training in obese middle-aged women (body mass index, MMI [greater than or equal to] 30.0). Twelve obese middle-aged women participated in this study. The descriptive statistics of some of…

  7. SIGNIFICANCE OF ADENOSINE DEAMINASE SERUM CONCENTRATIONS IN THE DIAGNOSIS OF EXTRA-PULMONARY TUBERCULOSIS

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    Stevanovic G,

    2011-06-01

    Full Text Available Extra pulmonary tuberculosis (EPTB is a growing problem worldwide. Due to the nature of the disease, the diversity of clinical pictures as well as its minor epidemiological importance, the diagnosis is difficult and often late.In addition to standard TB diagnostic techniques use of new biochemical (surrogate markers are increased. With this work we wanted to examine the usefulness of serum adenosine deaminase levels as a diagnostic parameter for EPTB.The work included 116 patients with fever of unknown origin in which tuberculosis or infectious mononucleosis was not proven and 51 person who had proven EPTB. Correlated adenosine deaminase levels between these two groups we obtained significantly higher values ​​in patients with EPTB. The calculated sensitivity was 0.56, specificity 0.89, positive predictive value 0.80 and negative predictive value 0.72. Certain reducing of the values observed during anti TB therapy. In previous studies the diagnostic importance of adenosine deaminase in the diagnosis of tuberculosis serosityes was demonstrated. The significance of serum levels in diagnosis is rarely evaluated during EPTB. Our findings are similar to the results of authors who have conducted such testing in the pediatric population.Increased concentrations of serum adenosine deaminase have shown the potential of usable screening test and can be used as an indicative EPTB parameter. To fully assess its diagnostic significance require future clinical research.

  8. Dietary Supplementation of Ginger and Turmeric Rhizomes Modulates Platelets Ectonucleotidase and Adenosine Deaminase Activities in Normotensive and Hypertensive Rats.

    Science.gov (United States)

    Akinyemi, Ayodele Jacob; Thomé, Gustavo Roberto; Morsch, Vera Maria; Bottari, Nathieli B; Baldissarelli, Jucimara; de Oliveira, Lizielle Souza; Goularte, Jeferson Ferraz; Belló-Klein, Adriane; Oboh, Ganiyu; Schetinger, Maria Rosa Chitolina

    2016-07-01

    Hypertension is associated with platelet alterations that could contribute to the development of cardiovascular complications. Several studies have reported antiplatelet aggregation properties of ginger (Zingiber officinale) and turmeric (Curcuma longa) with limited scientific basis. Hence, this study assessed the effect of dietary supplementation of these rhizomes on platelet ectonucleotidase and adenosine deaminase (ADA) activities in Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) induced hypertensive rats. Animals were divided into seven groups (n = 10): normotensive control rats; induced (l-NAME hypertensive) rats; hypertensive rats treated with atenolol (10 mg/kg/day); normotensive and hypertensive rats treated with 4% supplementation of turmeric or ginger, respectively. After 14 days of pre-treatment, the animals were induced with hypertension by oral administration of l-NAME (40 mg/kg/day). The results revealed a significant (p < 0.05) increase in platelet ADA activity and ATP hydrolysis with a concomitant decrease in ADP and AMP hydrolysis of l-NAME hypertensive rats when compared with the control. However, dietary supplementation with turmeric or ginger efficiently prevented these alterations by modulating the hydrolysis of ATP, ADP and AMP with a concomitant decrease in ADA activity. Thus, these activities could suggest some possible mechanism of the rhizomes against hypertension-derived complications associated to platelet hyperactivity. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27151061

  9. Combined detections of interleukin 27, interferon-γ, and adenosine deaminase in pleural effusion for diagnosis of tuberculous pleurisy

    Institute of Scientific and Technical Information of China (English)

    WU Yan-bin; YE Zhi-jian; QIN Sou-ming; WU Cong; CHEN Yi-qiang; SHI Huan-zhong

    2013-01-01

    Background Previous studies reported interleukin-27 (IL-27),interferon-γ (IFN-γ),or adenosine deaminase (ADA) alone plays a helpful role in diagnosing tuberculous pleural effusion (TPE).The present study aims at comparing the diagnostic accuracy of pleural IL-27,IFN-γ,and ADA,and investigate the diagnostic accuracy of the combination of IL-27,IFN-γ,or/and ADA for differentiating TPE from pleural effusions with the other etiologies.Methods The concentrations of IL-27,IFN-γ and ADA were simultaneously determined in pleural fluids and sera from 40 patients with TPE; 26 with malignant pleural effusion,seven with infectious pleural effusion,and eight with transudative pleural effusion by enzyme linked immunosorbent assay and colorimetric method.The corresponding biochemical indexs were also simultaneously determined.Results The concentrations of pleural IL-27 and IFN-γ in the tuberculous group were significantly higher than those in the malignant,infectious,and transudative groups.The concentrations of ADA in TPE were significantly higher than those in MPE or transudative effusions,while much lower than those in infectious effusions.Among these three biomarkers,IL-27 was the most effective for TPE diagnosis,with the cut off value of 900.8 ng/L.IL-27 had a high sensitivity of 95% and specificity of 97.6% for differential diagnosis of TPE from non-TPEs.Combinations of IL-27,IFN-γ and ADA measurements further increased the sensitivity or specificity up to 100%.Conclusions Compared to non-TPEs,IL-27,IFN-γ and ADA all simultaneously increased in TPE; and among these three rapid detection methods,IL-27 appeared to be the best for distinguishing tuberculous from non-TPEs,especially from MPE.Combinations of the three markers (IL-27,IFN-γ and ADA) yielded the highest sensitivity and specificity.These findings suggest that the applications of a new biomarker,IL-27,alone or with IFN-γ and ADA,may contribute to more efficient diagnosis strategies in the management

  10. Diagnostic value of serum adenosine deaminase levels in sputum smear negative pulmonary tuberculosis patients in Nepalese population

    Institute of Scientific and Technical Information of China (English)

    Anil Chander; Chandrika Devi Shrestha

    2012-01-01

    Objective: To assess the levels of adenosine deaminase (ADA) in serum in patients with sputum smear negative pulmonary tuberculosis (SNPTB) and to compare it with serum ADA levels in patients with non-tuberculous pulmonary disease - chronic obstructive pulmonary disease (COPD) and with healthy control group and to explore its validity as a diagnostic marker in serum in SNPTB patients.Methods:Three groups of study populations were made. Group I: SNPTB - 142 cases, Group II:non-tubercular pulmonary disease - COPD - 40 cases, Group III: healthy controls - 80 cases. Serum samples were collected and ADA assay was done by the method of Guisti and Galanti. Results: ADA levels (Mean±SD, U/L) in the three groups were as follows: Group I: 42.26±21.22, Group II: 23.31±8.22, Group III: 18.88±6.67. Difference between Group I and Group III was statistically significant (P < 0.0001). The test showed a high specificity 91.25% (95% confidence interval - CI 83.00 - 95.7) and a sensitivity of 83.10% (95% CI 76.08-88.37) in Group I. Positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and accuracy in Group I were 94.00%, 69.52%, 9.49, 0.18 and 82.43% respectively.Conclusions: Overall assessment of the use of serum ADA levels as a diagnostic biochemical marker in smear-negative pulmonary tuberculosis patients showed promising results. Studies with a larger population group are required to validate its use as a routine diagnostic test in these cases.

  11. Analysis of cerebrospinal fluid adenosine deaminase levels in meningitis

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    Vyankatesh T. Anchinmane

    2016-09-01

    Results: The mean ADA levels in CSF were highest in TBM patients as compared to PM and AM. The sensitivity, specificity and accuracy of ADA were 96.15%, 92% and 94.11% respectively for detection TBM cases from non-tuberculous meningitis cases. Conclusions: Since ADA test is simple, rapid and inexpensive, it can be used as rapid diagnostic test for differential diagnosis of CSF and confirmation of TBM cases. [Int J Res Med Sci 2016; 4(9.000: 3855-3857

  12. Efficient, low-cost protein factories: expression of human adenosine deaminase in baculovirus-infected insect larvae.

    OpenAIRE

    Medin, J A; Hunt, L; Gathy, K; Evans, R K; Coleman, M S

    1990-01-01

    Human adenosine deaminase (EC 3.5.4.4), a key purine salvage enzyme essential for immune competence, has been overproduced in Spodoptera frugiperda cells and in Trichoplusia ni (cabbage looper) larvae infected with recombinant baculovirus. The coding sequence of human adenosine deaminase was recombined into a baculovirus immediately downstream from the strong polyhedrin gene promoter. Approximately 60 hr after infection of insect cells with the recombinant virus, maximal levels of intracellul...

  13. Magnetically assisted fluorescence ratiometric assays for adenosine deaminase using water-soluble conjusated polymers

    Institute of Scientific and Technical Information of China (English)

    HE Fang; YU MingHui; WANG Shu

    2009-01-01

    A magnetically assisted fluorescence ratiometric technique has been developed for adenosine deami-nase assays with high sensitivity using water-soluble cationic conjugated polymers (CCPs).The assay contains three elements:a biotin-labeled aptamer of adenosine (biotin-aptamer),a signaling probe single-stranded DNA-tagged fiuorescein at terminus (ssDNA-FI) and a CCP.The specific binding of adenosine to biotin-aptamer makes biotin-aptamer and ssDNA-FI unhybridized,and the ssDNA-FI is washed out after streptavidin-coated magnetic beads are added and separated from the assay solution under magnetic field.In this case,after the addition of CCP to the magnetic beads solution,the fluo-rescence resonance energy transfer (FRET) from CCP to fluorescein is inefficient.Upon adding adenosine deaminase,the adenosine is converted into inosine,and the biotin-aptamer is hybridized with ssDNA-FI to form doubled stranded DNA (biotin-dsDNA-FI).The ssONA-FI is attached to the mag-netic beads at the separation step,and the addition of CCP to the magnetic beads solution leads to efficient FRET from CCP to fluorescein.Thus the adenosine deaminase activity can be monitored by fluorescence spectra in view of the intensity decrease of CCP emission or the increase of fluorescein emission in aqueous solutions.The assay integrates surface-functionalized magnetic particles with significant amplification of detection signal of water-soluble cationic conjugated polymers.

  14. Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1.

    Science.gov (United States)

    Naval-Macabuhay, Isaac; Casanova, Víctor; Navarro, Gemma; García, Felipe; León, Agathe; Miralles, Laia; Rovira, Cristina; Martinez-Navio, José M; Gallart, Teresa; Mallol, Josefa; Gatell, José M; Lluís, Carme; Franco, Rafael; McCormick, Peter J; Climent, Núria

    2016-02-01

    Regulatory T cells have an important role in immune suppression during HIV-1 infection. As regulatory T cells produce the immunomodulatory molecule adenosine, our aim here was to assess the potential of adenosine removal to revert the suppression of anti-HIV responses exerted by regulatory T cells. The experimental setup consisted of ex vivo cocultures of T and dendritic cells, to which adenosine deaminase, an enzyme that hydrolyzes adenosine, was added. In cells from healthy individuals, adenosine hydrolysis decreased CD4(+)CD25(hi) regulatory T cells. Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine receptor agonist, significantly decreased CD4(+)CD25(lo) cells, confirming a modulatory role of adenosine acting via adenosine receptors. In autologous cocultures of T cells with HIV-1-pulsed dendritic cells, addition of adenosine deaminase led to a significant decrease of HIV-1-induced CD4(+)CD25(hi) forkhead box p3(+) cells and to a significant enhancement of the HIV-1-specific CD4(+) responder T cells. An increase in the effector response was confirmed by the enhanced production of CD4(+) and CD8(+) CD25(-)CD45RO(+) memory cell generation and secretion of Th1 cytokines, including IFN-γ and IL-15 and chemokines MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5. These ex vivo results show, in a physiologically relevant model, that adenosine deaminase is able to enhance HIV-1 effector responses markedly. The possibility to revert regulatory T cell-mediated inhibition of immune responses by use of adenosine deaminase, an enzyme that hydrolyzes adenosine, merits attention for restoring T lymphocyte function in HIV-1 infection. PMID:26310829

  15. G22A Polymorphism of Adenosine Deaminase and its Association with Biochemical Characteristics of Gestational Diabetes Mellitus in an Iranian Population

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    Mohammad Ali Takhshid

    2015-03-01

    Full Text Available Adenosine deaminase (ADA is an important regulator of insulin action. The single nucleotide polymorphism (SNP G22A in the ADA gene decreases enzymatic activity of ADA. The aim of this study was to investigate the relationship between the SNP G22A and blood glycemic control, insulin resistance, and obesity of gestational diabetes mellitus (GDM patients in an Iranian population. SNP G22A was determined in women with GDM (N=70 and healthy pregnant women (control, N=70 using polymerase chain reaction-restriction fragment length polymorphism. Fasting plasma glucose (FPG, hemoglobin A1C (HbA1c, plasma insulin levels and plasma lipids were measured using commercial kits. Homeostasis model of assessment for insulin resistance (HOMA-IR was calculated. The distribution of genotypes and alleles among GDM patients was similar to that of the control group. FPG and HbA1c were significantly higher in GDM patients with GG genotype compared with GDM patients with GA+AA genotype and non-GDM patients. The frequency of GG genotype was significantly higher in obese GDM patients compared to lean GDM patients. The SNP G22A in the ADA gene was not associated with the risk of GDM in our population. GG genotype was associated with poor glycemic control and obesity in GDM patients.

  16. Aqueous seed extract of Syzygium cumini inhibits the dipeptidyl peptidase IV and adenosine deaminase activities, but it does not change the CD26 expression in lymphocytes in vitro.

    Science.gov (United States)

    Bellé, Luziane Potrich; Bitencourt, Paula Eliete Rodrigues; Abdalla, Faida Husein; Bona, Karine Santos de; Peres, Alessandra; Maders, Liési Diones Konzen; Moretto, Maria Beatriz

    2013-03-01

    Syzygium cumini (Sc) have been intensively studied in the last years due its beneficial effects including anti-diabetic and anti-inflammatory potential. Thus, the aim of this study was to evaluate the effect of aqueous seed extract of Sc (ASc) in the activity of enzymes involved in lymphocyte functions. To perform this study, we isolated lymphocytes from healthy donors. Lymphocytes were exposed to 10, 30, and 100 mg/mL of ASc during 4 and 6 h and adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), and acetylcholinesterase (AChE) activities as well as CD26 expression and cellular viability were evaluated. ASc inhibited the ADA and DPP-IV activities without alteration in the CD26 expression (DPP-IV protein). No alterations were observed in the AChE activity or in the cell viability. These results indicate that the inhibition of the DPP-IV and ADA activities was dependent on the time of exposition to ASc. We suggest that ASc exhibits immunomodulatory properties probably via the pathway of DPP-IV-ADA complex, contributing to the understanding of these proceedings in the purinergic signaling. PMID:22798209

  17. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

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    Cátia Vieira

    2014-01-01

    Full Text Available Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis lacks adenosine neuromodulation, which may contribute to acceleration of gastrointestinal transit. The loss of adenosine neuromodulation results from deficient accumulation of the nucleoside at the myenteric synapse despite the fact that the increases in ATP release were observed. Disparity between ATP outflow and adenosine deficit in postinflammatory ileitis is ascribed to feed-forward inhibition of ecto-5′-nucleotidase/CD73 by high extracellular ATP and/or ADP. Redistribution of NTPDase2, but not of NTPDase3, from ganglion cell bodies to myenteric nerve terminals leads to preferential ADP accumulation from released ATP, thus contributing to the prolonged inhibition of muscle-bound ecto-5′-nucleotidase/CD73 and to the delay of adenosine formation at the inflamed neuromuscular synapse. On the other hand, depression of endogenous adenosine accumulation may also occur due to enhancement of adenosine deaminase activity. Both membrane-bound and soluble forms of ecto-5′-nucleotidase/CD73 and adenosine deaminase were detected in the inflamed myenteric plexus. These findings provide novel therapeutic targets for inflammatory gut motility disorders.

  18. [The involvement of adenosine and adenosine deaminase in experimental myocardial infarct].

    Science.gov (United States)

    Stratone, A; Busuioc, A; Roşca, V; Bazgan, L; Popa, M; Hăulică, I

    1989-01-01

    By the ligature of the left coronary artery in the rat anesthetized with nembutal (10 mg/100 i.p.) a significant increase of the 5'-nucleotidase activity (Wooton method) was noticed 10 minutes after the left ventricle infarction (from an average value of 1038.5 +/- 187 mU/g tissue to 1537 +/- 225 mU/g fresh tissue). The adenosine desaminase levels spectrophotometrically determined by Denstedt technique, do not appear significantly modified 10 or 30 minutes after the left ventricle infarction. The chromatographically determined adenosine levels, by HPLC technique, decrease from the average value of 11.63 +/- 1.4 micrograms/mg PT to 8.60 +/- 1.0 micrograms/mg PT 30 minutes after infarction. The observed changes are explained by the conditions of hypoxia in the infarcted ventricle which lead to the raise in adenosine levels by activating the 5'-nucleotidase and their depression by a very fast metabolism of the same substance.

  19. Comparative study of adenosine deaminase activity, insulin resistance and lipoprotein(a among smokers and healthy non-smokers

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    Ramesh Ramasamy

    2016-06-01

    Conclusions: Adenosine deaminase activity was increased in patients in response to nicotine which is the key component of cigarette smoke. These findings indicate that nicotine and carbon monoxide can alter lipoprotein synthesis and also modify LDL to oxidized form which can lead to ischemic heart disease. [Int J Res Med Sci 2016; 4(6.000: 1950-1953

  20. Determination of serum adenosine deaminase and xanthine oxidase levels in patients with crimean-congo hemorrhagic fever

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    V. Kenan Celik

    2010-01-01

    Full Text Available OBJECTIVE: Crimean-Congo hemorrhagic fever is an acute viral hemorrhagic fever with a high mortality rate. Despite increasing knowledge about hemorrhagic fever viruses, little is known about the pathogenesis of Crimean-Congo hemorrhagic fever. In this study, we measured serum adenosine deaminase and xanthine oxidase levels in Crimean-Congo hemorrhagic fever patients. METHODS: Serum adenosine deaminase levels were measured with a sensitive colorimetric method described by Giusti and xanthine oxidase levels by the method of Worthington in 30 consecutive hospitalized patients (mean age 42.6 ± 21.0. Laboratory tests confirmed their diagnoses of Crimean-Congo hemorrhagic fever. Thirty-five subjects (mean age 42.9 ± 19.1 served as the control group. RESULTS: There was a significant difference in adenosine deaminase and xanthine oxidase levels between cases and controls (p0.05. CONCLUSION: Adenosine deaminase and xanthine oxidase levels were increased in patients with Crimean-Congo hemorrhagic fever. Elevated serum xanthine oxidase activity in patients with Crimean-Congo hemorrhagic fever may be associated with reactive oxygen species generated by the xanthine/xanthine oxidase system during inflammatory responses. In addition, elevated lipid peroxidation may contribute to cell damage and hemorrhage. The association of cell damage and hemorrhage with xanthine oxidase activity should be further investigated in large-scale studies.

  1. Ectonucleotidases and adenosine deaminase activity in laying hens naturally infected by Salmonella Gallinarum and their effects on the pathogenesis of the disease.

    Science.gov (United States)

    Boiago, Marcel M; Baldissera, Matheus D; Doleski, Pedro H; Bottari, Nathieli B; do Carmo, Guilherme M; Araujo, Denise N; Giuriatti, Jessica; Baggio, Vanessa; Leal, Daniela B R; Casagrande, Renata A; Wisser, Cláudia S; Stefani, Lenita M; da Silva, Aleksandro S

    2016-04-01

    Salmonella Gallinarum is the etiologic agent of fowl typhoid that affects chickens and turkeys causing egg production drops, infertility, lower hatchability, high mortality, and as a consequence severe economic losses to the poultry industry. The alterations in NTPDase and adenosine deaminase (ADA) activities have been demonstrated in several inflammatory conditions; however, there are no data in the literature associated with this infection. Thus, the aim of this study was to evaluate the activities of NTPDase, 5'nucleotidase, and ADA in serum and hepatic tissue of laying hens naturally infected by Salmonella Gallinarum. Liver and serum samples were collected of 27 laying hens (20 S. Gallinarum infected and 7 uninfected). NTPDase and 5'-nucleotidase activities in serum were increased (P laying hens naturally infected by S. Gallinarum; as well as increased (P laying hens. Histopathological analyses revealed that S. Gallinarum caused fibrinoid necrosis in liver and spleen associated with infiltrates of heterophils, macrophages, lymphocytes, and plasma cells. Considering that NTPDase and ADA are involved in the cell-mediated immunity, this study suggests that activities of these enzymes could be important biomarkers to determine the severity of inflammatory and immune responses in salmonellosis, contributing to clarify the pathogenesis of the disease. PMID:26911648

  2. A combination of the QuantiFERON-TB Gold In-Tube assay and the detection of adenosine deaminase improves the diagnosis of tuberculous pleural effusion.

    Science.gov (United States)

    Liu, Yuanyuan; Ou, Qinfang; Zheng, Jian; Shen, Lei; Zhang, Bingyan; Weng, Xinhua; Shao, Lingyun; Gao, Yan; Zhang, Wenhong

    2016-01-01

    The differential diagnosis of tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) remains difficult despite the availability of numerous diagnostic tools. The current study aimed to evaluate the performance of the whole blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and conventional laboratory biomarkers in differential diagnosis of TPE and MPE in high tuberculosis prevalence areas. A total of 117 patients with pleural effusions were recruited, including 91 with TPE and 26 with MPE. All of the patients were tested with QFT-GIT, and the conventional biomarkers in both blood and pleural effusion were detected. The level of antigen-stimulated QFT-GIT in the whole blood of TPE patients was significantly higher than that of MPE (2.89 vs 0.33 IU/mL, PGIT for the diagnosis of TPE were 93.0% and 60.0%, respectively. Among the biomarkers in blood and pleural effusion, pleural adenosine deaminase (ADA) was the most prominent biomarker, with a cutoff value of 15.35 IU/L. The sensitivity and specificity for the diagnosis of TPE were 93.4% and 96.2%, respectively. The diagnostic classification tree from the combination of these two biomarkers was 97.8% sensitive and 92.3% specific. Ultimately, the combination of whole blood QFT-GIT with pleural ADA improved both the specificity and positive predictive value to 100%. Thus, QFT-GIT is not superior to pleural ADA in the differential diagnosis of TPE and MPE. Combined whole blood QFT-GIT and pleural ADA detection can improve the diagnosis of TPE. PMID:27485497

  3. Activity of cholinesterases, pyruvate kinase and adenosine deaminase in rats experimentally infected by Fasciola hepatica: Influences of these enzymes on inflammatory response and pathological findings.

    Science.gov (United States)

    Baldissera, Matheus D; Bottari, Nathieli B; Mendes, Ricardo E; Schwertz, Claiton I; Lucca, Neuber J; Dalenogare, Diessica; Bochi, Guilherme V; Moresco, Rafael N; Morsch, Vera M; Schetinger, Maria R C; Rech, Virginia C; Jaques, Jeandre A; Da Silva, Aleksandro S

    2015-11-01

    The aim of this study was to investigate acetylcholinesterase (AChE) in total blood and liver tissue; butyrylcholinesterase (BChE) in serum and liver tissue; adenosine deaminase (ADA) in serum and liver tissue; and pyruvate kinase (PK) in liver tissue of rats experimentally infected by Fasciola hepatica. Animals were divided into two groups with 12 animals each, as follows: group A (uninfected) and group B (infected). Samples were collected at 20 (A1 and B1;n=6 each) and 150 (A2 and B2; n=6 each) days post-infection (PI). Infected animals showed an increase in AChE activity in whole blood and a decrease in AChE activity in liver homogenates (P<0.05) at 20 and 150 days PI. BChE and PK activities were decreased (P<0.05) in serum and liver homogenates of infected animals at 150 days PI. ADA activity was decreased in serum at 20 and 150 days PI, while in liver homogenates it was only decreased at 150 days PI (P<0.05). Aspartate aminotransferase and alanine aminotransferase activities in serum were increased (P<0.05), while concentrations of total protein and albumin were decreased (P<0.05) when compared to control. The histological analysis revealed fibrous perihepatitis and necrosis. Therefore, we conclude that the liver fluke is associated with cholinergic and purinergic dysfunctions, which in turn may influence the pathogenesis of the disease.

  4. A 30-year-old female Behçet's disease patient with recurrent pleural and pericardial effusion and elevated adenosine deaminase levels: case report.

    Science.gov (United States)

    Choi, Joon Young; Kim, Sung-Hwan; Kwok, Seung-Ki; Jung, Jung Im; Lee, Kyo-Young; Kim, Tae-Jung; Kang, Ji Young

    2016-07-01

    Behçet's disease is a systemic disease which may involve various organs. We describe a case of a patient diagnosed as pleuropericardial involvement of Behçet's disease. A 30-year-old woman visited our clinic presented with left pleuritic chest pain for s days. She had been diagnosed as Behçet's disease and admitted to our clinic due to pericardial and pleural effusion repeatedly in past two years. In the previous studies, effusion analysis revealed to be lympho-dominant exudate with high adenosine deaminase level. Acid-fast bacilli (AFB) culture and polymerase chain reaction (PCR) for mycobacterial tuberculosis (M.TB) were negative in the pericardial tissue, and pathologic finding showed mild endothelitis with micro-thrombi formation in the lumen. The patient had been treated with antituberculous medication for a year. In the current admission, chest computed tomography (CT) again showed left pleural effusion without other significant lesion. Pleural fluid analysis was similar with the previous study. Video-assisted thoracoscopic pleural biopsy was performed to obtain the definite diagnosis. Pathology confirmed the diagnosis as pleuropericardial involvement of Behçet's disease, and we treated the patient with oral steroid in the out-patient department. Pleuropericardial involvement of Behçet's disease may mimic TB pleurisy or pericarditis due to high adenosine deaminase (ADA) level in effusion analysis. Clinicians should keep in mind that Behçet's disease may manifest as pleural or pericardial effusion, and pathologic confirmation could be helpful for the definite diagnosis. PMID:27499994

  5. Diagnostic value of combinative detection of serum carcinoembryonic antigen(CEA),adenosine deaminase(ADA),lactate dehydrogenase(LDH) and ESR in differential diagnosis of pleural effusion%联合检测CEA、ADA、LDH及血沉对胸腔积液性质判断的临床意义

    Institute of Scientific and Technical Information of China (English)

    夏静; 闫雪波; 刘荣玉

    2013-01-01

    Objective To establish the diagnostic value of combinative detection of serum CEA,serum and pleural fluid LDH,pleural fluid ADA and ESR in different pleural effusion patients. Methods From December 2011 to June 2012 ,89 cases of in-patients with pleural effusion in the First Affiliated Hospital of Anhui Medical University were chosen,including 25 cases of tuberculous effusion( TE ),42 patients with malignant pleural effusion( MPE ) and 22 cases of inflammatory patients with pleural effusion( IPE ). The levels of serum CEA were examined by electrochemilumin-escence immunoassay method, serum LDH by the enzymatic( L method ), pleural fluid LDH and ADA by rating method and ESR by Westergren. Results The serum CEA of malignant pleural effusion patients is higher than that of TE and IPE patients;The serum and pleural fluid LDH levels in TE,MPE,IPE patients showed no significant difference,but the three pleural effusion LDH levels were significantly higher than the normal range, and the ratio of pleural effusion and serum LDH in patients with TE was significantly higher than that of patients with MPE; The pleural fluid ADA levels of TE were significantly higher than those of the MPE and IPE; The IPE patients ESR levels were significantly higher than those of TE and MPE patients, and ESR levels of TE patients were significantly higher than those of MPE patients. Conclusion Combined detection of serum CEA, pleural fluid and serum LDH, pleural fluid ADA and ESR has great significance in judging the nature of pleural fluid.%目的 探讨联合检测血清癌胚抗原(CEA)、血清及胸水乳酸脱氢酶(LDH)、胸水腺苷脱氨酶(ADA)及血沉对胸腔积液性质判断的临床意义.方法 以安徽医科大学第一附属医院2011年12月至2012年6月89例住院胸腔积液患者为研究对象,其中25例结核性胸腔积液患者,42例恶性胸腔积液患者,22例炎性胸腔积液患者;采用电化学发光免疫分析法测定血清CEA,酶法(L法)测定血

  6. Association of G22A and A4223C ADA1 gene polymorphisms and ADA activity with PCOS.

    Science.gov (United States)

    Salehabadi, Mahshid; Farimani, Marzieh; Tavilani, Heidar; Ghorbani, Marzieh; Poormonsefi, Faranak; Poorolajal, Jalal; Shafiei, Gholamreza; Ghasemkhani, Neda; Khodadadi, Iraj

    2016-06-01

    Adenosine deaminase-1 (ADA1) regulates the concentration of adenosine as the main modulator of oocyte maturation. There is compelling evidence for the association of ADA1 gene polymorphisms with many diseases but the importance of ADA1 polymorphisms in polycystic ovary syndrome (PCOS) has not been studied before. This study investigates serum total ADA activity (tADA), ADA1 and ADA2 isoenzyme activities, and genotype and allele frequencies of G22A and A4223C polymorphisms in healthy and PCOS women. In this case-control study 200 PCOS patients and 200 healthy women were enrolled. Genomic DNA was extracted from whole blood and the PCR-RFLP technique was used to determine the G22A and A4223C variants. The genotype frequencies were calculated and the association between polymorphic genotypes and enzyme activities were determined. tADA activity was significantly lower in the PCOS group compared with the control group (27.76±6.0 vs. 39.63±7.48, respectively). PCOS patients also showed reduced activity of ADA1 and ADA2. PCOS was not associated with G22A polymorphism whereas AA, AC, and CC genotypes of A4223C polymorphism were found distributed differently between the control and the PCOS women where the C allele showed a strong protective role for PCOS (odds ratio=1.876, p=0.033). The present study for the first time showed that lower ADA activity may be involved in pathogenesis of PCOS by maintaining a higher concentration of adenosine affecting follicular growth. As a novel finding, we also showed great differences in genotype distribution and allele frequencies of A4223C polymorphism between groups indicating a protective role for C allele against PCOS. AbbreviationsADA: adenosine deaminase PCOS: polycystic ovary syndrome PCR-RFLP: polymerase chain reaction-restriction fragment length polymorphism tADA: total adenosine deaminase.

  7. Mitochondrial Damage and Apoptosis Induced by Adenosine Deaminase Inhibition and Deoxyadenosine in Human Neuroblastoma Cell Lines.

    Science.gov (United States)

    Garcia-Gil, Mercedes; Tozzi, Maria Grazia; Balestri, Francesco; Colombaioni, Laura; Camici, Marcella

    2016-07-01

    The treatment with deoxycoformycin, a strong adenosine deaminase inhibitor, in combination with deoxyadenosine, causes apoptotic cell death of two human neuroblastoma cell lines, SH-SY5Y and LAN5. Herein we demonstrate that, in SH-SY5Y cells, this combination rapidly decreases mitochondrial reactive oxygen species and, in parallel, increases mitochondrial mass, while, later, induces nuclear fragmentation, and activation of caspase-8, -9, and -3. In previous papers we have shown that a human astrocytoma cell line, subjected to the same treatment, undergoes apoptotic death as well. Therefore, both astrocytoma and neuroblastoma cell lines undergo apoptotic death following the combined treatment with deoxycoformycin and deoxyadenosine, but several differences have been found in the mode of action, possibly reflecting a different functional and metabolic profile of the two cell lines. Overall this work indicates that the neuroblastoma cell lines, like the line of astrocytic origin, are very sensitive to purine metabolism perturbation thus suggesting new therapeutic approaches to nervous system tumors. J. Cell. Biochem. 117: 1671-1679, 2016. © 2015 Wiley Periodicals, Inc. PMID:26659614

  8. Adenosine deaminase complexing protein (ADCP) expression and metastatic potential in prostatic adenocarcinomas.

    Science.gov (United States)

    Dinjens, W N; Ten Kate, J; Kirch, J A; Tanke, H J; Van der Linden, E P; Van den Ingh, H F; Van Steenbrugge, G J; Meera Khan, P; Bosman, F T

    1990-03-01

    The expression of the adenosine deaminase complexing protein (ADCP) was investigated by immunohistochemistry in the normal and hyperplastic human prostate, in 30 prostatic adenocarcinomas, and in seven human prostatic adenocarcinoma cell lines grown as xenografts in athymic nude mice. In the normal and hyperplastic prostate, ADCP was localized exclusively in the apical membrane and the apical cytoplasm of the glandular epithelial cells. In prostatic adenocarcinomas, four distinct ADCP expression patterns were observed: diffuse cytoplasmic, membranous, both cytoplasmic and membranous, and no ADCP expression. The expression patterns were compared with the presence of metastases. We found an inverse correlation between membranous ADCP immunoreactivity and metastatic propensity. Exclusively membranous ADCP immunoreactivity occurred only in non-metastatic tumours. In contrast, the metastatic tumours showed no or diffuse cytoplasmic ADCP immunoreactivity. This suggests that immunohistochemical detection of ADCP might predict the biological behaviour of prostatic cancer. However, the occurrence of membranous ADCP immunoreactivity in the xenograft of a cell line (PC-EW), derived from a prostatic carcinoma metastasis, indicates that not only the tendency to metastasize modulates ADCP expression. PMID:1692338

  9. The G22A Polymorphism of the ADA Gene and Susceptibility to Autism Spectrum Disorders

    Science.gov (United States)

    Hettinger, Joe A.; Liu, Xudong; Holden, Jeanette Jeltje Anne

    2008-01-01

    Inborn errors of purine metabolism have been implicated as a cause for some cases of autism. This hypothesis is supported by the finding of decreased adenosine deaminase (ADA) activity in the sera of some children with autism and reports of an association of the A allele of the ADA G22A (Asp8Asn) polymorphism in individuals with autism of…

  10. Adenosine deaminase isoenzymes estimation -as a diagnostic tool for tuberculous pleural effusions

    Institute of Scientific and Technical Information of China (English)

    Nalla NK; Prasad CE; Gopalakrishniah V; Somayajulu VL; Lakshmi K Chelluri

    2009-01-01

    Objective:To assess the efficacy of ADA isoenzyme estimation over that of total ADA level in pleural fluid and serum as a more efficient diagnostic indicator in tuberculous pleural effusions in high prevalence country like India.Methods:The efficacy was analysed in total thirty four patients of pleural effusions.Total ADA was esti-mated by Guitsi and Galanti Calorimetric method and ADA isoenzymes with and without EHNA[Erythro-9-(2-hydroxy-3-nonyl)adenine]a potent ADA1 inhibitor using the same method.Results:The results demonstrated a statistically significant values of ADA2 in serum (P <0.001 ),pleural fluid (P =0.000)and significant value for the ratio of pleural fluid ADA2 /serum ADA2 (P <0.001 )and pleural fluid ADA1 /ADA2 (P <0. 005).The sensitivity and specificity values of pleural fluid ADA2 is 81.8 % and 91.6 % (cut off value 60 IU /L for Tuberculous effusions),serum ADA2 95.4 % and 66 % (cut off value 70 IU /L for tuberculous effu-sions).ADA2 is an isoenzyme,which is significantly raised in tuberculous pleural effusions both in the serum and pleural fluid.Conclusion:Estimation of ADA isoenzymes is redundant as a diagnostic aid over total ADA estimation in view of the limited improvements both in specificity and sensitivity patterns and also in term of cost-benefit ratio.

  11. Pleural effusion adenosine deaminase: a candidate biomarker to discriminate between Gram-negative and Gram-positive bacterial infections of the pleural space

    Directory of Open Access Journals (Sweden)

    Ruolin Li

    2016-05-01

    Full Text Available OBJECTIVES: Delay in the treatment of pleural infection may contribute to its high mortality. In this retrospective study, we aimed to evaluate the diagnostic accuracy of pleural adenosine deaminase in discrimination between Gram-negative and Gram-positive bacterial infections of the pleural space prior to selecting antibiotics. METHODS: A total of 76 patients were enrolled and grouped into subgroups according to Gram staining: 1 patients with Gram-negative bacterial infections, aged 53.2±18.6 years old, of whom 44.7% had empyemas and 2 patients with Gram-positive bacterial infections, aged 53.5±21.5 years old, of whom 63.1% had empyemas. The pleural effusion was sampled by thoracocentesis and then sent for adenosine deaminase testing, biochemical testing and microbiological culture. The Mann-Whitney U test was used to examine the differences in adenosine deaminase levels between the groups. Correlations between adenosine deaminase and specified variables were also quantified using Spearman’s correlation coefficient. Moreover, receiver operator characteristic analysis was performed to evaluate the diagnostic accuracy of pleural effusion adenosine deaminase. RESULTS: Mean pleural adenosine deaminase levels differed significantly between Gram-negative and Gram-positive bacterial infections of the pleural space (191.8±32.1 U/L vs 81.0±16.9 U/L, p<0.01. The area under the receiver operator characteristic curve was 0.689 (95% confidence interval: 0.570, 0.792, p<0.01 at the cutoff value of 86 U/L. Additionally, pleural adenosine deaminase had a sensitivity of 63.2% (46.0-78.2%; a specificity of 73.7% (56.9-86.6%; positive and negative likelihood ratios of 2.18 and 0.50, respectively; and positive and negative predictive values of 70.6% and 66.7%, respectively. CONCLUSIONS: Pleural effusion adenosine deaminase is a helpful alternative biomarker for early and quick discrimination of Gram-negative from Gram-positive bacterial infections of the

  12. Crystallization and preliminary X-ray crystallographic analysis of the tRNA-specific adenosine deaminase from Streptococcus pyogenes

    Energy Technology Data Exchange (ETDEWEB)

    Ku, Min-Je [Functional Proteomics Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Lee, Won-Ho [Functional Proteomics Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Biotechnology and Genetic Engineering, Korea University, Seoul 136-701 (Korea, Republic of); Nam, Ki-hyun; Rhee, Kyeong-hee [Biomedical Research Center, Life Science Division, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Lee, Ki-Seog [Biotechnology and Genetic Engineering, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Eunice EunKyung [Biomedical Research Center, Life Science Division, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Yu, Myung-Hee [Functional Proteomics Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Hwang, Kwang Yeon, E-mail: hwangky@kist.re.kr [Biomedical Research Center, Life Science Division, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791 (Korea, Republic of); Functional Proteomics Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791 (Korea, Republic of)

    2005-04-01

    The tRNA-specific adenosine deaminase from the pathogenic bacteria S. pyogenes has been overexpressed and crystallized. The tRNA-specific adenosine deaminase from the pathogenic bacteria Streptococcus pyogenes (spTAD) has been overexpressed in Escherichia coli and crystallized in the presence of Zn{sup 2+} ion at 295 K using ammonium sulfate as a precipitant. Flash-cooled crystals of spTAD diffracted to 2.0 Å using 30%(v/v) glycerol as a cryoprotectant. X-ray diffraction data have been collected to 2.0 Å using synchrotron radiation. The crystal belongs to the tetragonal space group P4{sub 2}2{sub 1}2, with unit-cell parameters a = b = 81.042, c = 81.270 Å. The asymmetric unit contains one subunit of spTAD, with a corresponding crystal volume per protein weight (V{sub M}) of 3.3 Å{sup 3} Da{sup −1} and a solvent content of 62.7%.

  13. 肝病患者血清腺苷脱氨酶检测的临床意义%Study of the serum adenosine deaminase level in patients with hepatitis

    Institute of Scientific and Technical Information of China (English)

    马士恒; 杨彦改; 常亚青; 谢晓华

    2013-01-01

    Objective To study the level of serum adenosine deaminase in patients viral hepatitis. Methods The adenosine deaminase and liver function indexes of the patients were determined by OLYMPUS AU400. Results The rates of increasing serum adenosine deaminase in acute hepatitis,chronic hepatitis, cirrhosis, hepatitis gravis were 55%, 43.8%, 87.9%and 70%, respectively. It was higher in cirrhosis than acute hepatitis, chronic hepatitis(P=0.008, 0.000, respectively). The level of serum adenosine deaminase in cirrhosis patients was higher than that in acute hepatitis patients, chronic hepatitis patients(P=0.003). The serum adenosine deaminase was correlated positively with serum asparate aminotransferase, globulin, the width of portal vein and the thickness of apleen(r=0.214, 0.376, 0.424, 0.306, respectively), it was correlated negatively with serum albumin and cholinesterase (r=-0.405,-0.351, respectively). Conclusion In patients with viral hepatitis, the higher serum adenosine deaminase expressed the decrease of liver synthesization function, it could not reflect the harm of liver cells and cholestasis perfectly.%  目的研究病毒性肝炎患者血清腺苷脱氨酶(ADA)水平.方法应用全自动生化分析仪检测各型病毒性肝炎患者血清ADA及各项肝功能指标.结果急性肝炎、慢性肝炎、肝炎后肝硬化、重型肝炎患者血清ADA升高比例分别为55%、43.8%、87.9%及70%,肝炎后肝硬化组显著高于急性肝炎组、慢性肝炎组(P分别为0.008、0.000).肝炎后肝硬化组ADA血清水平亦显著高于急性肝炎组、慢性肝炎组(P均为0.003).病毒性肝炎患者血清ADA与门冬氨酸转氨酶、球蛋白、门静脉宽度、脾脏厚度呈显著正相关(r分别为0.214、0.376、0.424、0.306),与白蛋白、胆碱脂酶呈显著负相关(r分别为-0.405、-0.351).结论在病毒性肝炎患者中,血清ADA升高主要反映肝脏储备合成功能逐渐降低,而不能很好反映肝细胞受损及胆汁淤积.

  14. Adenosine modulation of [Ca2+]i in cerebellar granular cells: multiple adenosine receptors involved.

    Science.gov (United States)

    Vacas, Javier; Fernández, Mercedes; Ros, Manuel; Blanco, Pablo

    2003-12-01

    Elimination of adenosine by addition of adenosine deaminase (ADA) to the media leads to alterations in intracellular free calcium concentration ([Ca(2+)](i)) in cerebellar granular cells. Adenosine deaminase brings about increases or decreases in [Ca(2+)](i) depending on the previous activation state of the cell. These effects are dependent on the catalytic activity of adenosine deaminase, since its previous catalytic inactivation with Hg(2+) prevents the above-mentioned changes in intracellular calcium. Extracellular calcium is required for the increase in [Ca(2+)](i) promoted by ADA. This rise is insensitive to thapsigargin, but sensitive to micromolar concentrations of Ni(2+). Toxins specific for L, N and P/Q calcium channels do not overtly reduce this effect. N(6)-Cyclopentyl adenosine (CPA), an A(1) receptor agonist, produces a partial reversion of ADA effects, while CGS21680, A(2A)/A(2B) receptor agonist, slightly enhances them. Expression of A(1), A(2A), A(2B) and A(3) adenosine receptor mRNAs was detected in cerebellar granular cell cultures. These results suggest that adenosine modulate [Ca(2+)](i) in cerebellar granule cells through different adenosine receptor subtypes which, at least in part, seem to act through R-type calcium channels.

  15. Dosagem sérica de adenosina deaminase em lúpus eritematoso sistêmico: ausência de associação com atividade de doença Levels of serum adenosine deaminase in systemic lupus erythematosus: lack of association with disease activity

    Directory of Open Access Journals (Sweden)

    Isabella Lima

    2005-10-01

    Full Text Available O lúpus eritematoso sistêmico (LES é uma doença inflamatória auto-imune, que evolui intercalando períodos de atividade e remissão. OBJETIVO: avaliar a associação da dosagem sérica de adenosina deaminase (ADA e atividade do LES, segundo os critérios do SLEDAI 2K - Systemic lupus erythematosus disease activity index. MÉTODOS: avaliou-se 82 pacientes com LES atendidos em um hospital de referência para o tratamento do LES em Salvador, BA, Brasil. A atividade de doença foi determinada pelo SLEDAI 2K e a dosagem sérica da ADA realizada por colorimetria. RESULTADOS: oitenta e uma pacientes (98,78% eram do sexo feminino e a idade média foi de 35,07±11,73 anos. O escore de SLEDAI médio foi de 11,66±5,89; a média de ADA sérica foi de 38,24±13,61U/l; C3 de 91,93±27,39 mg/dl; C4 de 15,17±5,77 mg/dl e a pesquisa de anticorpos anti-DNA nativo (aDNAn foi positiva em 31 casos (37,8%. Não houve correlação entre os níveis séricos de ADA e escore do SLEDAI. A ADA sérica correlacionou-se inversamente com C4 (r=-0,336 e p=0,001. CONCLUSÕES: no presente estudo a dosagem sérica de ADA não se associou a atividade de doença segundo os critérios do SLEDAI 2K, sugerindo que esse teste não deve ser utilizado como marcador de atividade de doença em LES. Esse resultado diverge da maioria dos trabalhos publicados, o que pode ser explicado pela dificuldade de padronização da técnica de dosagem da ADA ou por diferença nas diversas populações estudadas.Systemic lupus erythematosus (SLE is an autoimmune inflammatory disease, with a variable course and characterized by periods of remissions and exacerbations. OBJECTIVE: To evaluate the association between serum adenosine deaminase (ADA levels and disease activity in SLE. METHODS: Eighty two SLE patients seen at Santa Izabel Hospital in Salvador, BA, Brazil, were studied. Disease activity was measured by SLEDAI 2K- Systemic Lupus Erythematosus Disease Activity Index, and serum ADA was

  16. The genetics of feto-placental development: A study of acid phosphatase locus 1 and adenosine deaminase polymorphisms in a consecutive series of newborn infants

    Directory of Open Access Journals (Sweden)

    Bergamaschi Antonio

    2008-09-01

    Full Text Available Abstract Background Acid phosphatase locus 1 and adenosine deaminase locus 1 polymorphisms show cooperative effects on glucose metabolism and immunological functions. The recent observation of cooperation between the two systems on susceptibility to repeated spontaneous miscarriage prompted us to search for possible interactional effects between these genes and the correlation between birth weight and placental weight. Deviation from a balanced development of the feto-placental unit has been found to be associated with perinatal morbidity and mortality and with cardiovascular diseases in adulthood. Methods We examined 400 consecutive newborns from the Caucasian population of Rome. Birth weight, placental weight, and gestational length were registered. Acid phosphatase locus 1 and adenosine deaminase locus 1 phenotypes were determined by starch gel electrophoresis and correlation analysis was performed by SPSS programs. Informed verbal consent to participate in the study was obtained from the mothers. Results Highly significant differences in birth weight-placental weight correlations were observed among acid phosphatase locus 1 phenotypes (p = 0.005. The correlation between birth weight and placental weight was markedly elevated in subjects carrying acid phosphatase locus 1 phenotypes with medium-low F isoform concentration (A, CA and CB phenotypes compared to those carrying acid phosphatase locus 1 phenotypes with medium-high F isoform concentration (BA and B phenotypes (p = 0.002. Environmental and developmental variables were found to exert a significant effect on birth weight-placental weight correlation in subjects with medium-high F isoform concentrations, but only a marginal effect was observed in those with medium-low F isoform concentrations. The correlation between birth weight and placental weight is higher among carriers of the adenosine deaminase locus 1 allele*2, which is associated with low activity, than in homozygous adenosine

  17. Two Cases of Severe Combined Immunodeficiency Caused By Adenosine Deaminase Deficiency

    Directory of Open Access Journals (Sweden)

    Turkan Patiroglu

    2014-08-01

    Full Text Available Severe Combined Immune Deficiency (SCID is a primary immune deficiency disorder manifested with severe infections upon first months of life, which is characterized by diverse genetic defects in T and B lymphocyte functions and occasionally in NK cells. ADA deficiency is a form of SCID progressing with severe lymphopenia and immune deficiency caused by toxic metabolites of ADA. Bone marrow transplantation (BMT is the only curative treatment although prophylactic anti-microbial therapy, intravenous immunoglobulin (IVIG and enzyme replacement can achieve transient improvements. Early diagnosis before development of severe infections and organ injury and referral to pediatric immunology clinics will make considerable contributions to prognosis. Here, we presented 2 cousins with SCID who had positive family history with deceased sibling; presented with tanning at skin, severe neonatal infections and Q246X (c736C>T non-sense mutation in exon 8 in ADA gene  in order to emphasize this rare mutation and pediatric emergencies associated with this disorder.

  18. Escherichia coli ASKA Clone Library Harboring tRNA-Specific Adenosine Deaminase (tadA Reveals Resistance towards Xanthorrhizol

    Directory of Open Access Journals (Sweden)

    Yogiara

    2015-09-01

    Full Text Available Xanthorrhizol is a potent antimicrobial compound isolated from the rhizome of Curcuma xanthorrhiza. However, the mechanism of xanthorrhizol action is unknown. To screen for probable target(s, we introduced the ASKA pooled-plasmid library into Escherichia coli W3110 imp4213 and enriched the library for resistant clones with increasing concentrations of xanthorrhizol. After three rounds of enrichment, we found nine genes that increased xanthorrhizol resistance. The resistant clones were able to grow in LB medium containing 256 µg/mL xanthorrhizol, representing a 16-fold increase in the minimum inhibitory concentration. Subsequent DNA sequence analysis revealed that overexpression of tadA, galU, fucU, ydeA, ydaC, soxS, nrdH, yiiD, and mltF genes conferred increased resistance towards xanthorrhizol. Among these nine genes, tadA is the only essential gene. tadA encodes a tRNA-specific adenosine deaminase. Overexpression of E. coli W3110 imp4213 (pCA24N-tadA conferred resistance to xanthorrhizol up to 128 µg/mL. Moreover, overexpression of two tadA mutant enzymes (A143V and F149G led to a twofold increase in the MIC. These results suggest that the targets of xanthorrhizol may include tadA, which has never before been explored as an antibiotic target.

  19. 结核性脑膜炎患儿脑脊髓液中腺苷脱氨酶活性测定的临床意义%Clinical Significance of Cerebrospinal Fluid Adenosine Deaminase of Children with Tuberculous Meningitis

    Institute of Scientific and Technical Information of China (English)

    程金玲

    2012-01-01

      目的:评价结核性脑膜炎患儿脑脊髓液中腺苷脱氨酶(CSF-ADA)活性对临床诊断意义及疗效判断价值.方法:选择122例住院患儿为研究对象,56例结核性脑膜炎患者为A组;66例非结核性脑膜炎患者为对照组,其中细菌性脑膜炎32例为B组,病毒性脑膜炎34例为C组,采用酶耦联Trinder法测定患儿治疗前CSF-ADA活性,56例结核性脑膜炎患儿于抗结核治疗后2周和6周时分别检测CSF-ADA.结果:A组CSF-ADA活性为(11.8±4.4)U/L,B组为(6.1±2.8)U/L,C组为(4.9±3.1)U/L,与A组比较差异有统计学意义(F=45.150, P=0.000).取CSF-ADA≥8 U/L作为临界值时鉴别结核性脑膜炎与非结核性脑膜炎价值最高,灵敏度为87.72%,特异度为90.77%.随着患儿病情好转,CSF-ADA活性逐渐降低.结论:CSF-ADA活性≥8U/L可作为诊断结核性脑膜炎的一项辅助诊断指标,抗结核治疗后CSF-ADA活性可作为疗效判断的参考指标.%  Objective: Evaluation of tuberculous meningitis with cerebrospinal fluid of adenosine deaminase(CSF-ADA)activity to clinical diagnosis significance and effect of value judgment. Method: To choose 122 cases hospitalized children as the research object,56 cases of tuberculous meningitis was the case group(group A). 66 cases of meningitis of n/med tuberculosis sex as control group,including bacterial meningitis 32 cases(group B),and viral meningitis 34 cases(C group),using enzyme coupling Trinder spectrometry to analyze CSF-ADA activity before treatment. 56 cases of tuberculous meningitis in antitubercular treatment children after 2 weeks and six weeks respectively detection CSF-ADA. Result:The CSF-ADA activity of group A was(11.8±4.4)U/L,compared with group B(6.1±2.8)U/L,group C(4.9±3.1)U/L,there was a significant difference meaning(F=45.150,P=0.000). Taking the CSF-ADA ≥ 8 U/L as critical value in identification of tuberculous meningitis had the highest value,and sensitivity was 87.72% and specificity was 90

  20. Serum activities of adenosine deaminase, dipeptidyl peptidase IV and prolyl endopeptidase in patients with fibromyalgia: diagnostic implications.

    Science.gov (United States)

    Čulić, Ognjen; Cordero, Mario D; Žanić-Grubišić, Tihana; Somborac-Bačura, Anita; Pučar, Lara Batičić; Detel, Dijana; Varljen, Jadranka; Barišić, Karmela

    2016-10-01

    Fibromyalgia (FM) is a chronic pain syndrome with number of symptoms that present challenge in terms of diagnosis and treatment. Patients with FM show abnormal profile of purines in plasma. In this work, we measured serum activities of enzymes involved in purine metabolism, namely total adenosine deaminase (ADE) and its isoforms (ADE1 and ADE2), ecto-ATPase, and 5'-nucleotidase (5'-NT). We also measured activity of dipeptidyl peptidase IV (DPPIV) and prolyl endopeptidase (PEP). Spectrophotometric and fluorometric methods were used for enzyme activity determinations. Enzyme activities were measured in sera of 24 patients with FM that were not undergoing pharmacological treatment during the study. Control group comprised 32 healthy control subjects. Significantly higher activities of total ADE (P = 0.025) and ADE2 (P = 0.011) were observed in FM patients, while no significant differences in ADE1, ecto-ATPase, and 5'-NT activities (P > 0.05) were found when compared to healthy controls. Moreover, increase in the activity of DPPIV (P = 0.015) and lower activity of PEP (P = 0.011) were also found in the FM group. ROC analysis pointed to different diagnostic sensitivities/specificities for individual enzyme activities measured as follows: ADE (50.0/87.5), ADE2 (41.7/90.6), DPPIV (62.5/71.9), and PEP (83.3/62.5). ADE2 and PEP were shown to be independent predictors of FM, while combination of the two gives AUC of 0.786 (95 % confidence interval of 0.656-0.885, P < 0.05). Our results are showing that serum activities of ADE2 and PEP could be useful as biomarkers for FM diagnosis. However, relatively low diagnostic sensitivity of ADE2 and specificity of PEP must be taken into account.

  1. The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

    Science.gov (United States)

    la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

    2014-01-01

    Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine <0.09μmol/L, adenosine <1.61μmol/L). We also developed a second tier test to distinguish true positives from false positives and improve the positive predictive value of an initial abnormal result. In the first 18 months, the pilot project has identified a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program.

  2. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

    OpenAIRE

    Cátia Vieira; Maria Teresa Magalhães-Cardoso; Fátima Ferreirinha; Isabel Silva; Ana Sofia Dias; Julie Pelletier; Jean Sévigny; Paulo Correia-de-Sá

    2014-01-01

    Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis ...

  3. CSF ADA Determination in Early Diagnosis of Tuberculous Meningitis in HIV-Infected Patients.

    Science.gov (United States)

    Ghosh, Gopal Chandra; Sharma, Brijesh; Gupta, B B

    2016-01-01

    Tuberculous and Cryptococcal meningitis are common in HIV patients. A highly specific and sensitive rapid test for diagnosis of Tuberculous meningitis especially in setting of HIV is not available in developing countries where the burden of disease is high. We measured ADA (adenosine deaminase) levels using spectrophotometric method in the CSF of HIV patients with meningitis to differentiate Tuberculous meningitis from meningitis due to other causes. Kruskal-Wallis test was used to compare ADA values between tuberculous meningitis (TBM) and nontuberculous (non-TB) meningitis patients and a receiver-operating characteristic (ROC) analysis curve was drawn from these values. Levels of ADA in the CSF of patients with TBM were significantly higher than those in patients with meningitis due to other causes. CSF ADA level determination with a cut-off value of 6 IU/L was found to be highly specific and fairly sensitive test for the diagnosis of TBM in HIV positive patients. PMID:27144055

  4. Observation on the activities of alpha-L-fucosidase,alkaline phosphatase and adenosine deaminase in pregnant women%妊娠女性α-L-岩藻糖苷酶、碱性磷酸酶和腺苷脱氨酶活性观察

    Institute of Scientific and Technical Information of China (English)

    王玮玮; 孙伟才; 周惠玉

    2014-01-01

    目的:妊娠期女性观察血清α-L-岩藻糖苷酶(AFU)、碱性磷酸酶(ALP)及腺苷脱氨酶(ADA)活性的变化及其与妊娠周期的相关性。方法分别检测352例体检正常的不同妊娠期女性(妊娠组,其中早期妊娠210例、晚期妊娠142例)及322例因不孕就诊且尚未妊娠的体检正常的女性(非妊娠组)血清 AFU、ALP、ADA 活性。对所有对象均进行动态监测(早期妊娠组于妊娠第14、22、30及38周分别检测,晚期妊娠组于妊娠第38及40周检测,非妊娠组于就诊时、就诊后第8及24周检测)并做比较。结果妊娠组血清 ALP、AFU 活性明显高于非妊娠组(P =0.000),ADA 活性则低于非妊娠组(P =0.000)。晚期妊娠组血清 ALP、AFU 活性明显高于早期妊娠组(P =0.000),但 ADA 活性两组间差异无统计学意义(P >0.05)。对早期妊娠组的动态监测显示,随着妊娠周期的增加,AFU 及 ALP 活性逐渐升高,但 ADA 基本无变化。晚期妊娠组第38周及第40周血清 AFU、ALP、ADA 活性差异均无统计学意义(P >0.05)。对非妊娠组的动态监测显示,与就诊时比较,就诊后第8周 ALP、ADA 活性差异有统计学意义(P =0.000),就诊后第24周 ADA 活性差异有统计学意义;与就诊后第8周比较,就诊后第24周 ALP、AFU、ADA 活性差异均有统计学意义(P <0.05)。结论妊娠期女性血清 AFU 及 ALP 活性明显升高,且随孕周的增加,升高趋势越明显。%Objective To observe the activity changes of alpha-L-fucosidase (AFU),alkaline phosphatase (ALP) and adenosine deaminase (ADA)in pregnant women and their correlations with pregnant period.Methods The activities of AFU,ALP and ADA were determined in 352 pregnant women (210 cases with early-stage pregnancy and 142 cases with late-stage pregnancy)and 322 unpregnant women.Dynamic monitoring was performed (early-stage pregnancy

  5. Dosagem da atividade da adenosina deaminase no líquido pleural para o diagnóstico da tuberculose pleural Pleural fluid adenosine deaminase detection for the diagnosis of pleural tuberculosis

    OpenAIRE

    Morrys Casagrande Kaisemann; Afrânio Lineu Kritski; Maria de Fátima C Pereira; Anete Trajman

    2004-01-01

    INTRODUÇÃO: O diagnóstico da tuberculose pleural permanece um desafio, pois a sensibilidade dos testes tradicionais é baixa. O exame histopatológico da pleura é o método mais preciso, com até 80% de sensibilidade. A dosagem da adenosina deaminase foi introduzida mais recentemente, mas sua utilidade no diagnóstico da tuberculose pleural no Brasil não foi suficientemente esclarecida. OBJETIVO: Verificar a sensibilidade e a especificidade de um método experimental de dosagem da atividade da aden...

  6. Overexpression of adenosine deaminase acting on RNA 1 in chordoma tissues is associated with chordoma pathogenesis by reducing miR-125a and miR-10a expression

    Science.gov (United States)

    KUANG, LEI; LV, GUOHUA; WANG, BING; LI, LEI; DAI, YULIANG; LI, YAWEI

    2015-01-01

    Chordoma is a rare, slow-growing primary malignant neoplasm of the axial skeleton, which arises from the remnants of the notochord. Emerging evidence suggests that microRNAs (miRs) are dysregulated in chordoma tissues and crucially involved in chordoma pathogenesis. In the present study, the expression of 11 candidate miRs were analyzed in chordoma tissues and miR-10a and miR-125a were found to be significantly downregulated compared with controls. Notably, the expression of the primary transcripts, pri-miR-125a and pri-miR-10a was unaltered, suggesting that disturbed microRNA expression may be induced by altered pri-miRNA processing. Previous studies have indicated that disturbed adenosine deaminase acting on RNA (ADAR) expression is able to alter mRNA and miRNA adenosine to inosine (A-to-I) levels associated with cancer pathogenesis. Therefore, the expression of ADAR1 and ADAR2 was analyzed in chordoma tissues. It was found that ADAR1 was significantly overexpressed, which was accompanied by enhanced pre-miR-10a and pri-miR-125a A-to-I editing. These findings suggest that ADAR2 overexpression causes enhanced pre-miR-10a and pri-miR-125a A-to-I editing, which alters mature miR-10a and miR-125a expression and may contribute to chordoma pathogenesis. PMID:25673044

  7. 脑脊液腺苷脱氨酶对结核性脑膜炎患者病情程度和疾病预后的预测价值%Predictive value of cerebrospinal fluid adenosine deaminase for degree of illness and disease prognosis of patients with tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    吴素芳; 彭素珍; 郑淑芳; 黄镇丰

    2014-01-01

    目的:探讨脑脊液腺苷脱氨酶(ADA)对结核性脑膜炎患者病情程度和疾病预后的预测作用。方法选取135例脑膜炎患者,其中结核性脑膜炎(结核组)50例,病毒性脑膜炎(病毒组)45例,细菌性脑膜炎(细菌组)40例,同期选取50例健康体检者(对照组)。全部研究对象采用酶显色检测法检测ADA水平,并进行比较。结核组患者根据全身性炎症反应程度进行分组,分为未合并败血症组、合并轻度败血症组和合并重症败血症组,比较三组ADA水平,分析脑脊液ADA在结核性脑膜炎患者病情、预后评估中的价值。结果结核组脑脊液ADA水平明显高于病毒组、细菌组和对照组,组间比较差异有统计学意义(P<0.05),合并重症败血症组ADA水平明显高于未合并败血症组和合并轻度败血症组,组间比较差异有统计学意义(P<0.05),治疗后3、6、9周ADA水平显著低于入院时,差异有统计学意义(P<0.05),且预后不良组ADA水平明显高于预后良好组(P<0.05)。结论脑脊液ADA在结核性脑膜炎的诊断中具有重要的意义,在病情和疾病预后的预测方面具有可靠的价值。%Objective To investigate the predictive effect of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for tubercular meningitis patients severity and prognosis of the disease. Methods 135 cases of meningitis were selected, and included 50 cases of tubercular meningitis (the tuberculosis group), 45 cases of viral meningitis (the virus group), 40 cases of bacterial meningitis (the bacterial group). 50 healthy subjects were selected as the control group in the same period. The ADA levels of all research objects were detected by enzyme color detection and were compared. TB patients grouped according to systemic inflammatory reaction degree, who were divided into the unincorporated sepsis groups, the mild sepsis group and the combining severe sepsis group, the ADA levels of the three

  8. Cloning of the cDNA encoding adenosine 5'-monophosphate deaminase 1 and its mRNA expression in Japanese flounder Paralichthys olivaceus

    Science.gov (United States)

    Jiang, Keyong; Sun, Shujuan; Liu, Mei; Wang, Baojie; Meng, Xiaolin; Wang, Lei

    2013-01-01

    AMP deaminase catalyzes the conversion of AMP into IMP and ammonia. In the present study, a full-length cDNA of AMPD1 from skeletal muscle of Japanese flounder Paralichthys olivaceus was cloned and characterized. The 2 526 bp cDNA contains a 5'-UTR of 78 bp, a 3'-UTR of 237 bp and an open reading frame (ORF) of 2 211 bp, which encodes a protein of 736 amino acids. The predicted protein contains a highly conserved AMP deaminase motif (SLSTDDP) and an ATP-binding site sequence (EPLMEEYAIAAQVFK). Phylogenetic analysis showed that the AMPD1 and AMPD3 genes originate from the same branch, but are evolutionarily distant from the AMPD2 gene. RT-PCR showed that the flounder AMPD1 gene was expressed only in skeletal muscle. QRT-PCR analysis revealed a statistically significant 2.54 fold higher level of AMPD1 mRNA in adult muscle (750±40 g) compared with juvenile muscle (7.5±2 g) ( Panimals.

  9. Avaliação da adenosina desaminase no diagnóstico da tuberculose pleural: uma metanálise brasileira Evaluation of adenosine deaminase in the diagnosis of pleural tuberculosis: a Brazilian meta-analysis

    Directory of Open Access Journals (Sweden)

    Patrizio Morisson

    2008-04-01

    Full Text Available OBJETIVO: Avaliar trabalhos brasileiros resumindo a acurácia da adenosina desaminase no diagnóstico da tuberculose pleural, com o intuito de contribuir para a concretização do exame como rotina na investigação dos derrames pleurais. MÉTODOS: Depois de realizada uma busca por trabalhos brasileiros referentes à dosagem da adenosina desaminase no líquido pleural, estes foram avaliados e incluídos no estudo. A análise dos dados foi feita por meio da curva summary receiver operating characteristic (SROC que possibilitou a reunião dos estudos quanto a acurácia para o diagnóstico. Com os valores globais de sensibilidade e especificidade foi aplicado o teorema de Bayes para calcular as probabilidades pós-teste em diferentes prevalências da doença. RESULTADOS: Entre 1987 e 2005 foram encontrados 25 estudos contendo informações suficientes que poderiam ser utilizadas na metanálise. Após avaliação, foram incluídos nove estudos, totalizando 1.674 pacientes. De acordo com a curva SROC, foi encontrada uma sensibilidade de 91,8% (IC95%: 89,8-93,6% e uma especificidade de 88,4% (IC95%: 86,0-90,5%, com uma área abaixo da curva de 0,969. O odds ratio global foi de 112,0 (IC95%: 51,6-243,2. Considerando uma prevalência da tuberculose pleural de 50% (considerada neutra, a probabilidade do diagnóstico pós-teste positivo é de 88,7% e sua exclusão após resultado negativo de 91,5%. CONCLUSÕES: Apesar das diferenças encontradas entre os estudos, é possível concluir que a adenosina desaminase possui alta acurácia no diagnóstico da tuberculose pleural, devendo ser utilizada de rotina em sua investigação.OBJECTIVE: To evaluate Brazilian studies by summarizing the accuracy of adenosine deaminase in the diagnosis of pleural tuberculosis, with the objective of lending support to the movement to make the test part of the routine investigation of pleural effusions. METHODS: A search for Brazilian studies related to the determination of

  10. Syzygium cumini is more effective in preventing the increase of erythrocytic ADA activity than phenolic compounds under hyperglycemic conditions in vitro.

    Science.gov (United States)

    De Bona, Karine S; Bonfanti, Gabriela; Bitencourt, Paula E R; Cargnelutti, Lariane O; da Silva, Priscila S; da Silva, Thainan P; Zanette, Régis A; Pigatto, Aline S; Moretto, Maria B

    2014-06-01

    Syzygium cumini (S. cumini) is a plant known for its antidiabetic properties. The aim of this study was to evaluate the effect of Sc aqueous leaf extract (ASc) on adenosine deaminase (ADA) activity in erythrocytes (RBCs) exposed to high glucose concentrations (30 mM) in vitro. We also investigated the effects of the main phenolic compounds found in ASc (gallic acid, rutin, and chlorogenic acid) and the effects of insulin, caffeine, and dipyridamole, which are substances involved in the adenosine metabolism, on ADA activity in vitro. Blood samples were obtained from healthy volunteers and a suspension of RBCs was used for the determination of ADA activity. The results showed that: (1) the effect of ASc on ADA activity was more significant than the combination of phenolic compounds; (2) insulin, caffeine, or dipyridamole prevented high glucose increase of ADA activity at doses as low as 50 μU/mL, 25 μM, and 1 μM, respectively; (3) the inhibitory effect caused by ASc on erythrocyte ADA activity remained practically the same after the combination of the extract with insulin or caffeine; (4) when RBCs were exposed to ASc plus dipyridamole, this chemical attenuated the effect of ASc on ADA activity, suggesting an antagonism or a competition with ASc by the same site of action. Therefore, ASc was more effective in preventing the increase in ADA activity than phenolic compounds, suggesting that ASc may collaborate to improve endothelial dysfunction, antioxidant, anti-inflammatory, and antithrombotic properties of adenosine by affecting its metabolism. The results of this study help to provide evidence of the empirically supported benefits of the use of S. cumini in diabetes. PMID:24407852

  11. Biochemical detection of E-ADA on Neospora caninum tachyzoites and the effects of a specific enzymatic inhibitor

    Directory of Open Access Journals (Sweden)

    Alexandre A. Tonin

    2015-01-01

    Full Text Available Objective. This study aimed to investigate the presence and activity of the ecto adenosine deaminase (E-ADA enzyme in tachyzoites of Neospora caninum (Nc-1 strain, as well as to assess the activity of a well-known E-ADA inhibitor, the deoxycoformycin. Materials and methods. The parasites were grown in cell culture, being subsequently separated in a pellet of tachyzoites, on which the E-ADA activity was tested using the concentrations 0 (control, 0.2, 0.4 and 0.8 mg mL-1. Results. The E-ADA showed high activity, progressively increasing its activity according to the enhancement of the protein concentration. The test was carried out with different concentrations of deoxycoformycin, showing that it was able to inhibit the E-ADA present on the free form of the parasite. Conclusions. Based on these results we conclude that the E-ADA is present on tachyzoites of N. caninum, and deoxycoformycin is able to inhibit this enzyme. In this sense, knowing the negative impact of N. caninum on reproductive issue in cattle (mainly abortion, might it is an alternative in order to deal with this parasitic infection.

  12. Monogenic polyarteritis: the lesson of ADA2 deficiency.

    Science.gov (United States)

    Caorsi, Roberta; Penco, Federica; Schena, Francesca; Gattorno, Marco

    2016-01-01

    The deficiency of Adenosine Deaminase 2 (DADA2) is a new autoinflammatory disease characterised by an early onset vasculopathy with livedoid skin rash associated with systemic manifestations, CNS involvement and mild immunodeficiency.This condition is secondary to autosomal recessive mutations of CECR1 (Cat Eye Syndrome Chromosome Region 1) gene, mapped to chromosome 22q11.1, that encodes for the enzymatic protein adenosine deaminase 2 (ADA2). By now 19 different mutations in CECR1 gene have been detected.The pathogenetic mechanism of DADA2 is still unclear. ADA2 in a secreted protein mainly expressed by cells of the myeloid lineage; its enzymatic activity is higher in conditions of hypoxia, inflammation and oncogenesis. Moreover ADA2 is able to induce macrophages proliferation and differentiation; it's deficiency is in fact associated with a reduction of anti-inflammatory macrophages (M2). The deficiency of ADA2 is also associated with an up-regulation of neutrophils-expressed genes and an increased secretion of pro-inflammatory cytokines. The mild immunodeficiency detected in many DADA2 patients suggests a role of this protein in the adaptive immune response; an increased mortality of B cells and a reduction in the number of memory B cells, terminally differentiated B cells and plasmacells has been described in many patients. The lack of the protein is associated with endothelium damage; however the function of this protein in the endothelial homeostasis is still unknown.From the clinical point of view, this disease is characterized by a wide spectrum of severity. Chronic or recurrent systemic inflammation with fever, elevation of acute phase reactants and skin manifestations (mainly represented by livedo reticularis) is the typical clinical picture. While in some patients the disease is mild and skin-limited, others present a severe, even lethal, disease with multi-organ involvement; the CNS involvement is rather common with ischemic or hemorrhagic strokes. In

  13. Validação laboratorial de um método automatizado de dosagem da atividade de adenosina desaminase em líquido pleural e em líquido cefalorraquidiano Laboratorial validation of an automated assay for the determination of adenosine deaminase activity in pleural fluid and cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Márcia Cristina Feres

    2008-12-01

    determination of adenosine deaminase (ADA activity in pleural fluid (PF and cerebrospinal fluid (CSF, comparing it with a conventional method (the modified Giusti method. METHODS: In total, 134 samples were selected from among those tested in our laboratory: 94 PF samples and 40 CSF samples. The ADA activity was determined using the two methods. Inter- and intra-assay precision was determined, linear regression analysis was performed, simple concordance tests were conducted, and the means of the differences were calculated. RESULTS: The correlation coefficients for PF and CSF samples were, respectively, 0.96 and 0.95. Inter-assay precision was determined using 21 replicates at 3 different activity levels: low, medium and high. The percentage coefficient of variation (%CV was, respectively, 5.9, 8.1 and 5.8 for PF samples, compared with 21.9, 18.6 and 13.8 for CSF samples. Intra-assay precision in %CV was 1.3 and 11.7, respectively, for PF and CSF samples. The concordance between the methods in PF and CRF samples was, respectively, 96.8% and 100%, considering the reference values for the diagnosis of TB to be 40 U/L (conventional and 30 U/L (automated in PF samples, versus 9 U/L (for both methods in CSF samples. CONCLUSIONS: The results validate the use of the automated method of determining ADA activity in PF and CSF samples as an alternative to the conventional method.

  14. 脑脊液免疫球蛋白、乳酸脱氢酶及腺苷脱氨酶检测在成人颅内感染鉴别诊断中的临床意义%Clinical significance of immunoglobulins, lactatedehydrogenase ,and adenosine deaminase detection in differential diagnosis of intracranial infections in adults

    Institute of Scientific and Technical Information of China (English)

    张丽琴

    2012-01-01

    OBJECTIVE To investigate the changes of immunoglobulin (Ig), lactate dehydrogenase(LDH), and adenosine deaminase(ADA) in cerebrospinal fluid (CSF)of the adults with intracranial infections and explore the clinical significance.METHODS Totally 17 patients with tuberculous meningitis, 19 patients with purulent meningitis, and 21 patients with viral meningitis were recruited in this study.The levels of LDH, ADA, and Ig in CSF from.each patient were measured and compared with the control group.RESULTS The concentrations of LDH, ADA, IgM, IgG.and IgA in CSF of the patients with purulent meningitis were(85.60±18.11)U/L,(2.59 ±0.52)U/L,(63.85±13.44)mg/L,(92.55±35.18)mg/L,and (20.60±8.75)mg/L,respectively ; the levels of LDA, ADA, IgM, IgG, and IgA in CSF of the patients with tuberculous meningitis were(78.80±22.38)U/L, (11.83±2.65)U/L, (18.90±8.62)mg/L, (180.69±42.28)mg/L, and(41.63±ll.42)mg/L, respectively) the levels of LDA, ADA, IgM, IgG, and IgA in CSF of the patients with viral meningitis were(22.43±9.56)U/L, (2.66±0.64)U/L, (5.83±1.34)mg/L,(20.90±10.35)mg/L,and(7.20±2.30)mg/L, respectively; of the three groups of adults with intracranial infectious diseases, the levels of IgM, IgG, IgA, and LDH in CSF of the patients with tuberculous meningitis or purulent meningitis were significantly higher than those in the patients with viral meningitis(P<0.01), the levels of IgG and IgA in CSF of the patients with tuberculous meningitis increased most significantly, the level of IgM in CSF of the patients with purulent meningitis increased most significantly, the activity of ADA of the tuberculous meningitis group was significantly higher than control group and other two groups(P<0.01 ); no statistical significance was found when between the indexes of viral meningitis group and control group.CONCLUSION The blood brain barriers of adult patients have been injured in varying degreest the detection of Ig, LDH in CSF is helpful to clinical diagnosis and

  15. The effect of renal stones on serum adenosine aminohydrolase and AMP-aminohydrolase in Malaysia

    Institute of Scientific and Technical Information of China (English)

    Faridah; Yusof; Atheer; Awad; Mehde; Wesen; Adel; Mehdi; Hamid; Ghazali; Azlina; Abd; Rahman

    2015-01-01

    Objective: To verify possible associations between adenosine aminohydrolase(ADA) and AMP-aminohydrolase(AMPDA) to E3 SUMO-protein ligase NSE2(NSMCE2) in patients with renal stones. And to isolate, purify and characterize ADA in patients with renal stones and healthy group.Methods: A total of 60 renal stones patients and 50 control were enrolled in a case-control study. The blood urea, creatinine, uric acid, protein, albumin, ADA and AMPDA were measured by colorimetric tests. The serum NSMCE2 was measured by ELISA.Results: Serum ADA, AMPDA and specii c activity of enzymes showed signii cant decrease(P < 0.05) in patients with renal stones compared to control group, mean levels of sera NSMCE2 and uric acid had a signii cant increase(P < 0.01 and P < 0.05, respectively) in patients compared to control group.Conclusions: The present study suggests that ADA, AMP deaminase and NSMCE2 can be used as a indicator to monitor the DNA damage and inl ammation disorders in the patients with kidney stones.

  16. Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors

    Science.gov (United States)

    Roseti, Cristina; Martinello, Katiuscia; Fucile, Sergio; Piccari, Vanessa; Mascia, Addolorata; Di Gennaro, Giancarlo; Quarato, Pier Paolo; Manfredi, Mario; Esposito, Vincenzo; Cantore, Gianpaolo; Arcella, Antonella; Simonato, Michele; Fredholm, Bertil B.; Limatola, Cristina; Miledi, Ricardo; Eusebi, Fabrizio

    2008-01-01

    We examined how the endogenous anticonvulsant adenosine might influence γ-aminobutyric acid type A (GABAA) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 μM), GABAA receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABAA-current (IGABA) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced IGABA run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated IGABA run-down in ≈40% and ≈20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 μM) potentiated IGABA run-down but only in ≈20% of tested oocytes. CGS15943 administration again decreased IGABA run-down in patch-clamped neurons from either human or rat neocortex slices. IGABA run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABAA-receptor stability is tonically influenced by A2A but not by A1 receptors. IGABA run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2–A3 receptors alter the stability of GABAA receptors, which could offer therapeutic opportunities. PMID:18809912

  17. Diagnostic value of combined detection of serum ADA,TBA and AFU in liver diseases%血清ADA、TBA和AFU联合检测在肝脏疾病临床诊疗中的价值

    Institute of Scientific and Technical Information of China (English)

    徐万清; 龚扬彬; 肖毅; 熊杰

    2011-01-01

    目的:探讨血清腺苷脱氨酶(Adenosine deaminase,ADA)、总胆汁酸(Total bilious acid,TBA)和α-L-岩藻糖苷酶(α-L-Fucosidase,AFU)联合检测对肝脏疾病的诊断价值.方法:分别测定急性肝炎组、慢性活动性肝炎组、慢性迁延性肝炎组、肝硬化组、肝癌组及健康对照组血清ADA、TBA、AFU、丙氨酸氨基转移酶(ALT)及γ-谷氨酰转移酶(γ-GT).结果:相对于健康对照组,ADA和TBA在各型肝炎及肝硬化中均有不同程度的升高,而肝癌患者的AFU明显升高,ADA和TBA无明显升高.结论:联合检测血清ADA、TBA和AFU在肝脏疾病的诊断和鉴别诊断中具有更高价值.%Objective: To investigate the diagnostic value of combined detection of serum Adenosine deaminase (ADA) , Total bilious acid (TBA) and a - L - Fucosidase (AFU) in patients suffering from liver diseases. Methods; Serum ADA,TBA,AFU and ALT, γ - GT among actute hepatitis group, chronic active hepatitis group, chronic persistent hepatitis group, cirrhosis group, hepatic cancer and healthy contrast group were determined respectively. Results; Compared with healthy contrast group, ADA and TBA increased differently in actute hepatitis group, chronic active hepatitis group, chronic persistent hepatitis group and cirrhosis group. AFU improved significantly in the patients with hepatic cancer, but the results of ADA and TBA were similar to those of healthy controls. Conclusion; The associated tests of AD A, TBA and AFU are helpful to improve the diagnosis and differential diagnosis of liver diseases.

  18. Ecto- and cytosolic 5'-nucleotidases in normal and AMP deaminase-deficient human skeletal muscle

    DEFF Research Database (Denmark)

    Hanisch, Frank; Hellsten, Ylva; Zierz, Stephan

    2006-01-01

    In skeletal muscle, adenosine monophosphate (AMP) is mainly deaminated by AMP deaminase. However, the C34T mutation in the AMPD1 gene severely reduces AMP deaminase activity. Alternatively, intracellular AMP is dephosphorylated to adenosine via cytosolic AMP 5'-nucleotidase (cN-I). In individuals...... with a homozygous C34T mutation, cN-I might be a more important pathway for AMP removal. We determined activities of AMP deaminase, cN-I, total cytosolic 5'-nucleotidase (total cN), ecto-5'-nucleotidase (ectoN) and whole homogenate 5'-nucleotidase activity in skeletal muscle biopsies from patients with...

  19. Adenosine (ADO) released during orthodromic stimulation of the frog sympathetic ganglion inhibits phosphatidylinositol turnover (PI) associated with synaptic transmission

    International Nuclear Information System (INIS)

    The authors have previously demonstrated that 3H-purine release was enhanced during synaptic activation of the prelabelled frog sympathetic ganglion. In addition, during orthodromic stimulation, there is an increased 3H-inositol release (an index of PI) that occurs during the poststimulation period and not during the period of stimulation. They hypothesized that endogenous ADO inhibits PI turnover during orthodromic stimulation. To test this hypothesis (1) they performed experiments to directly measure ADO release in the extracellular fluid by placing the ganglion in a 5 μl drop of Ringer's and let it come to equilibrium with the interstitial fluid, (2) they destroyed endogenous ADO by suffusing adenosine deaminase (ADA) during the stimulation period. Their results show (1) orthodromic stimulation increases release of ADO into the bathing medium, (2) ADA induced an increase of PI during the stimulation period in contrast to an increase seen only during the poststimulation period when ADA was omitted. They conclude that there is dual control of PI during synaptic activity, a stimulatory effect (cause unknown) and a short lived inhibitory effect that is probably caused by adenosine

  20. Investigation on the diagnosis significance of C reactive protein and adenosine deaminase in cerebrospinal fluid among children with meningitis%脑脊液C反应蛋白和腺苷脱氨酶检测在小儿脑膜炎中的诊断价值探讨

    Institute of Scientific and Technical Information of China (English)

    徐仁荣; 张慧华; 朱华丽

    2015-01-01

    Objective To determine C reactive protein and adenosine deaminase in cerebrospinal fluid,and to investigate the clinical diagnosis significance for tuberculosis meningitis,purulent meningitis and viral meningitis. Methods A total of 31 5 children with meningitis (1 02 cases of tuberculosis meningitis,1 08 cases of purulent meningitis and 1 05 cases of viral meningitis)were enrolled,96 children undergoing operation without meningitis were enrolled as control group,and their cerebrospinal fluid samples were collected.The levels of C reactive protein and adenosine deaminase were determined,and the results were compared.Results C reactive protein and adenosine deaminase in control and viral meningitis groups were significantly lower than those in tuberculosis and purulent meningitis groups (P 0.05 ).C reactive protein in purulent meningitis group was higher than that in tuberculosis meningitis group(P <0.05 ),and adenosine deaminase was lower than that in tuberculosis meningitis group (P <0.05).C reactive protein in purulent meningitis group was positive,and the positive rate was 1 00%.There were 63 positive cases in tuberculosis meningitis group,and the positive rate was 61 .76%.That in viral meningtis was negative.Conclusions In cerebrospinal fluid,C reactive protein and adenosine deaminase determinations have important reference significance for the differential diagnosis of bacterial meningitis (purulent meningitis and tuberculosis meningitis)and viral meningitis.Adenosine deaminase may be a good indicator for the diagnosis of tuberculosis meningitis,in order to provide the reference for the early diagnosis of various types of meningitis.%目的:探讨小儿脑脊液C反应蛋白和腺苷脱氨酶在结核性脑膜炎、化脓性脑膜炎和病毒性脑膜炎早期诊断中的临床意义。方法分别检测315例小儿脑膜炎患儿(包括结核性脑膜炎102例、化脓性脑膜炎108例、病毒性脑膜炎105例)及96例非脑膜炎外科手术

  1. Enzymatic production of 5'-inosinic acid by AMP deaminase from a newly isolated Aspergillus oryzae.

    Science.gov (United States)

    Li, Shubo; Chen, Leitao; Hu, Yangjun; Fang, Guohui; Zhao, Mouming; Guo, Yuan; Pang, Zongwen

    2017-02-01

    5'-adenylic acid deaminase (AMP deaminase), an important enzyme for the food industry, can catalyze the irreversible hydrolysis of adenosine monophosphate (AMP) to inosine monophosphate (IMP) and ammonia. In this study, a new strain was screened that efficiently produces 3191.6U/g of AMP deaminase at 32°C. After purification, the optimal temperature and pH of the AMP deaminase were found to be 40°C and 6.0, respectively, but it was partially inhibited by Fe(3+), Cu(2+), Al(3+), and Zn(2+). With amplification of the AMP deaminase production system, 6mL of crude enzyme could produce 2.00mg/g of IMP from 2.04mg/g of dried yeast with an 84.8% molar yield after 40min. These results provide a new insight into AMP deaminase production and offer a potential platform for producing 5'-IMP. PMID:27596420

  2. Ada & the Analytical Engine.

    Science.gov (United States)

    Freeman, Elisabeth

    1996-01-01

    Presents a brief history of Ada Byron King, Countess of Lovelace, focusing on her primary role in the development of the Analytical Engine--the world's first computer. Describes the Ada Project (TAP), a centralized World Wide Web site that serves as a clearinghouse for information related to women in computing, and provides a Web address for…

  3. Software engineering capability for Ada (GRASP/Ada Tool)

    Science.gov (United States)

    Cross, James H., II

    1995-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada Source code. A new Motif compliant graphical user interface has been developed for the GRASP/Ada prototype.

  4. 腺苷脱氨酶、C型凝集素及丝氨酸蛋白酶抑制剂基因在白纹伊蚊唾液腺中的表达%Expression of the Genes of Adenosine Deaminase, C-lectin and Serpin in the Salivary Gland of Aedes albopictus

    Institute of Scientific and Technical Information of China (English)

    吴家红; 程金芝; 陈璐; 孙宇

    2010-01-01

    目的 了解腺苷脱氨酶(adenosine deal-flinase,ADA)基因、C型凝集素(C-lectin)基因和丝氨酸蛋白酶抑制剂(serine protease inhibitor,serpin)基因在白纹伊蚊唾液腺中的表达情况.方法 分别制备未吸血雌蚊唾液腺(SG组) 和吸血雌蚊唾液腺(BSG组)、雌蚊躯体(无头无唾液腺,C组)和雄蚊组织(无头含唾液腺,M组)的总RNA,采用实时荧光定量RT.PCR技术,以β肌动蛋白(β-actin)基因作为内参,根据GenBank公布的ADA、C-lectin和Serpin基因序列设计特异性引物进行RT-PCR.分析以上基因在不同组织中的表达情况.结果 与雌蚊躯体和雄蚊组织中相对表达量相比,ADA基因在雌蚊唾液腺中的表达分别提高了545倍和123倍(P<0.01);C-lectin基因在雌蚊唾液腺中的表达分别提高了3 929倍和4 973倍(P<0.01);Serpin基因在雌蚊唾液腺中的表达分别提高了1 911倍和2 978倍(P<0.01).吸血前后雌蚊唾液腺中ADA、C-lectin和Serpin等3个基因的表达差异无统计学意义(P>0.05).结论 ADA在蚊虫组织中均有表达,在雌蚊唾液腺中高表达;C-lectin和serpin基因在雌蚊唾液腺中特异高表达.

  5. Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.

    Science.gov (United States)

    Tostes, Rita C; Giachini, Fernanda R C; Carneiro, Fernando S; Leite, Romulo; Inscho, Edward W; Webb, R Clinton

    2007-08-01

    This study tested the hypothesis that adenosine, in murine corpora cavernosa, produces direct relaxation of smooth muscle cells and inhibition of contractile responses mediated by sympathetic nerve stimulation. Penes were excised from anesthetized male C57BL/6 mice, dissected, and cavernosal strips were mounted to record isometric force. Adenosine, 2-chloroadenosine (stable analog of adenosine), and 2-phenylaminoadenosine (CV1808) (A2(A)/A2(B) agonist) produced concentration-dependent relaxations of phenylephrine-contracted tissues. Relaxation to 2-chloroadenosine was inhibited, in a concentration-dependent manner, by 2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261; A2(A) antagonist; 10(-9)-10(-6) M) and N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamida (MRS1706; A2(B) antagonist; 10(-8)-10(-6) M). The combination of both antagonists abrogated 2-chloroadenosine-induced relaxation. Electrical field stimulation (EFS; 1-32 Hz) of adrenergic nerves produced frequency-dependent contractions that were inhibited by compounds that increase adenosine levels, such as 5'-iodotubercidin (adenosine kinase inhibitor), erythro-9-(2-hydroxy-3-nonyl)adenine (adenosine deaminase inhibitor), and dipyridamole (inhibitor of adenosine transport). The adenosine A1 receptor agonist N(6)-cyclopentyladenosine (C8031) right-shifted contractile responses to EFS, with a significant inhibitory effect at 10(-6) M. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine (C101) (10(-7) M) enhanced contractile responses to EFS and eliminated the inhibitory effects of 5'-iodotubercidin. Dipyridamole and 5'-iodotubercidin had no effect on adenosine-mediated relaxation. In summary, adenosine directly relaxes cavernosal smooth muscle cells, by the activation of A2(A)/A2(B) receptor subtypes. In addition, adenosine negatively modulates sympathetic neurotransmission, by A1 receptor

  6. Introduction to Image Algebra Ada

    Science.gov (United States)

    Wilson, Joseph N.

    1991-07-01

    Image Algebra Ada (IAA) is a superset of the Ada programming language designed to support use of the Air Force Armament Laboratory's image algebra in the development of computer vision application programs. The IAA language differs from other computer vision languages is several respects. It is machine independent, and an IAA translator has been implemented in the military standard Ada language. Its image operands and operations can be used to program a range of both low- and high-level vision algorithms. This paper provides an overview of the image algebra constructs supported in IAA and describes the embodiment of these constructs in the IAA extension of Ada. Examples showing the use of IAA for a range of computer vision tasks are given. The design of IAA as a superset of Ada and the implementation of the initial translator in Ada represent critical choices. The authors discuss the reasoning behind these choices as well as the benefits and drawbacks associated with them. Implementation strategies associated with the use of Ada as an implementation language for IAA are also discussed. While one can look on IAA as a program design language (PDL) for specifying Ada programs, it is useful to consider IAA as a separate language superset of Ada. This admits the possibility of directly translating IAA for implementation on special purpose architectures. This paper explores strategies for porting IAA to various architectures and notes the critical language and implementation features for porting to different architectures.

  7. High-throughput assay of adenosine in fermentation broth based on enzyme catalysis%酶法高通量测定发酵液中的腺苷含量

    Institute of Scientific and Technical Information of China (English)

    李宁; 董会娜; 祖昕; 张大伟; 吴勇杰

    2015-01-01

    腺苷是合成阿糖腺苷、腺苷酸(AMP)、三磷酸腺苷(ATP)的主要原料,是一种重要的医药原料.目前,微生物发酵生产腺苷越来越受到重视,会产生大量的发酵液样品需要检测.基于腺苷脱氨酶(ADA)建立了一种快速、高通量检测发酵液腺苷的方法.实验结果表明,响应面方法优化检测试剂浓度为碳酸钠-碳酸氢钠34.20mmol/L-27.40 mmol/L,亚硝基铁氰化钠3.35 g/L,次氯酸钠的有效氯为0.172 5%,百里香酚6.64 g/L.该方法检测灵敏,检测限为0.025~6 mmol/L,能够满足发酵检测和高通量筛选的需要.%Adenosine is the main raw material for the production of vidarabine,adenosine monophosphate (AMP) and adenosinetriphosphate (ATP).Adenosine is also an important pharmaceutical raw materials.At present,microbial fermentation production of adenosoine will produce large amounts of fermentation samples to be detected A rapid high -throughput method for detecting adenosine in fermentation broth based on adenosine deaminase (ADA)was estabished.Using response surface model analysis to determine the optimum concentration of four substances,the results showed sodium carbonate-sodium bicarbonate 34.20 mmol/L-27.40 mmol/L,sodium nitropmssid 3.35 g/L,the effective chlorine of sodium hypochlorite 0.172 5%,thymol 6.64 g/L.The limit of detection was between 0.025 mmo1/L and 6 mmo1/L,this method is sensitive and can meet the needs of the fermentation detection and high-throughput screening.

  8. ARE: Ada Rendering Engine

    Directory of Open Access Journals (Sweden)

    Stefano Penge

    2009-10-01

    Full Text Available E' ormai pratica diffusa, nello sviluppo di applicazioni web, l'utilizzo di template e di potenti template engine per automatizzare la generazione dei contenuti da presentare all'utente. Tuttavia a volte la potenza di tali engine è€ ottenuta mescolando logica e interfaccia, introducendo linguaggi diversi da quelli di descrizione della pagina, o addirittura inventando nuovi linguaggi dedicati.ARE (ADA Rendering Engine è€ pensato per gestire l'intero flusso di creazione del contenuto HTML/XHTML dinamico, la selezione del corretto template, CSS, JavaScript e la produzione dell'output separando completamente logica e interfaccia. I templates utilizzati sono puro HTML senza parti in altri linguaggi, e possono quindi essere gestiti e visualizzati autonomamente. Il codice HTML generato è€ uniforme e parametrizzato.E' composto da due moduli, CORE (Common Output Rendering Engine e ALE (ADA Layout Engine.Il primo (CORE viene utilizzato per la generazione OO degli elementi del DOM ed è pensato per aiutare lo sviluppatore nella produzione di codice valido rispetto al DTD utilizzato. CORE genera automaticamente gli elementi del DOM in base al DTD impostato nella configurazioneIl secondo (ALE viene utilizzato come template engine per selezionare automaticamente in base ad alcuni parametri (modulo, profilo utente, tipologia del nodo, del corso, preferenze di installazione il template HTML, i CSS e i file JavaScript appropriati. ALE permette di usare templates di default e microtemplates ricorsivi per semplificare il lavoro del grafico.I due moduli possono in ogni caso essere utilizzati indipendentemente l'uno dall'altro. E' possibile generare e renderizzare una pagina HTML utilizzando solo CORE oppure inviare gli oggetti CORE al template engine ALE che provvede a renderizzare la pagina HTML. Viceversa è possibile generare HTML senza utilizzare CORE ed inviarlo al template engine ALECORE è alla prima release ed è€ già utilizzato all

  9. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

    OpenAIRE

    Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro

    2009-01-01

    Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent ...

  10. Using Ada: The deeper challenges

    Science.gov (United States)

    Feinberg, David A.

    1986-01-01

    The Ada programming language and the associated Ada Programming Support Environment (APSE) and Ada Run Time Environment (ARTE) provide the potential for significant life-cycle cost reductions in computer software development and maintenance activities. The Ada programming language itself is standardized, trademarked, and controlled via formal validation procedures. Though compilers are not yet production-ready as most would desire, the technology for constructing them is sufficiently well known and understood that time and money should suffice to correct current deficiencies. The APSE and ARTE are, on the other hand, significantly newer issues within most software development and maintenance efforts. Currently, APSE and ARTE are highly dependent on differing implementer concepts, strategies, and market objectives. Complex and sophisticated mission-critical computing systems require the use of a complete Ada-based capability, not just the programming language itself; yet the range of APSE and ARTE features which must actually be utilized can vary significantly from one system to another. As a consequence, the need to understand, objectively evaluate, and select differing APSE and ARTE capabilities and features is critical to the effective use of Ada and the life-cycle efficiencies it is intended to promote. It is the selection, collection, and understanding of APSE and ARTE which provide the deeper challenges of using Ada for real-life mission-critical computing systems. Some of the current issues which must be clarified, often on a case-by-case basis, in order to successfully realize the full capabilities of Ada are discussed.

  11. The AdaBoost Flow

    CERN Document Server

    Lykov, A; Vaninsky, K

    2011-01-01

    We introduce a dynamical system which we call the AdaBoost flow. The flow is defined by a system of ODEs with control. We show how by a suitable choice of control AdaBoost algorithm of Schapire and Freund and arc-gv algorithm of Breiman can be embedded in the AdaBoost flow. We also show how previously studied by Schapire and Singer confidence rated prediction can be obtained from our continuous time approach. We introduce a new continuous time algorithm which we call superBoost and describe its properties. The AdaBoost flow equations coincide with the equations of dynamics of the nonperiodic Toda system written in terms of spectral variables. This establishes a connection between two seemingly unrelated fields of boosting algorithms and classical integrable models. Finally we explain similarity of the AdaBoost flow with Perelman's ideas to control Ricci flow.

  12. Ada Structure Design Language (ASDL)

    Science.gov (United States)

    Chedrawi, Lutfi

    1986-01-01

    An artist acquires all the necessary tools before painting a scene. In the same analogy, a software engineer needs the necessary tools to provide their design with the proper means for implementation. Ada provide these tools. Yet, as an artist's painting needs a brochure to accompany it for further explanation of the scene, an Ada design also needs a document along with it to show the design in its detailed structure and hierarchical order. Ada could be self-explanatory in small programs not exceeding fifty lines of code in length. But, in a large environment, ranging from thousands of lines and above, Ada programs need to be well documented to be preserved and maintained. The language used to specify an Ada document is called Ada Structure Design Language (ASDL). This language sets some rules to help derive a well formatted Ada detailed design document. The rules are defined to meet the needs of a project manager, a maintenance team, a programmer and a systems designer. The design document templates, the document extractor, and the rules set forth by the ASDL are explained in detail.

  13. Update of GRASP/Ada reverse engineering tools for Ada

    Science.gov (United States)

    Cross, James H., II

    1993-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional pretty printed Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype CSD generator (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3,e two update phases were completed. Update'92 focused on the initial analysis of evaluation data collected from software engineering students at Auburn University and the addition of significant enhancements to the user interface. Update'93 (the current update) focused on the statistical analysis of the data collected in the previous update and preparation of Version 3.4 of the prototype for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical

  14. Adenosine and adenosine receptors: Newer therapeutic perspective

    Directory of Open Access Journals (Sweden)

    Manjunath S

    2009-01-01

    Full Text Available Adenosine, a purine nucleoside has been described as a ′retaliatory metabolite′ by virtue of its ability to function in an autocrine manner and to modify the activity of a range of cell types, following its extracellular accumulation during cell stress or injury. These effects are largely protective and are triggered by binding of adenosine to any of the four adenosine receptor subtypes namely A1, A2a, A2b, A3, which have been cloned in humans, and are expressed in most of the organs. Each is encoded by a separate gene and has different functions, although overlapping. For instance, both A1 and A2a receptors play a role in regulating myocardial oxygen consumption and coronary blood flow. It is a proven fact that adenosine plays pivotal role in different physiological functions, such as induction of sleep, neuroprotection and protection against oxidative stress. Until now adenosine was used for certain conditions like paroxysmal supraventricular tachycardia (PSVT and Wolff Parkinson White (WPW syndrome. Now there is a growing evidence that adenosine receptors could be promising therapeutic targets in a wide range of conditions including cardiac, pulmonary, immunological and inflammatory disorders. After more than three decades of research in medicinal chemistry, a number of selective agonists and antagonists of adenosine receptors have been discovered and some have been clinically evaluated, although none has yet received regulatory approval. So this review focuses mainly on the newer potential role of adenosine and its receptors in different clinical conditions.

  15. Ada Linear-Algebra Program

    Science.gov (United States)

    Klumpp, A. R.; Lawson, C. L.

    1988-01-01

    Routines provided for common scalar, vector, matrix, and quaternion operations. Computer program extends Ada programming language to include linear-algebra capabilities similar to HAS/S programming language. Designed for such avionics applications as software for Space Station.

  16. GRASP/Ada 95: Reverse Engineering Tools for Ada

    Science.gov (United States)

    Cross, James H., II

    1996-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped an algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD), and a new visualization for a fine-grained complexity metric called the Complexity Profile Graph (CPG). By synchronizing the CSD and the CPG, the CSD view of control structure, nesting, and source code is directly linked to the corresponding visualization of statement level complexity in the CPG. GRASP has been integrated with GNAT, the GNU Ada 95 Translator to provide a comprehensive graphical user interface and development environment for Ada 95. The user may view, edit, print, and compile source code as a CSD with no discernible addition to storage or computational overhead. The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada 95 source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. The current update has focused on the design and implementation of a new Motif compliant user interface, and a new CSD generator consisting of a tagger and renderer. The Complexity Profile Graph (CPG) is based on a set of functions that describes the context, content, and the scaling for complexity on a statement by statement basis. When combined graphicafly, the result is a composite profile of complexity for the program unit. Ongoing research includes the development and refinement of the associated functions, and the development of the CPG generator prototype. The current Version 5.0 prototype provides the capability for the user to generate CSDs and CPGs from Ada 95 source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for

  17. Paranoia.Ada: Sample output reports

    Science.gov (United States)

    1986-01-01

    Paranoia.Ada is a program to diagnose floating point arithmetic in the context of the Ada programming language. The program evaluates the quality of a floating point arithmetic implementation with respect to the proposed IEEE Standards P754 and P854. Paranoia.Ada is derived from the original BASIC programming language version of Paranoia. The Paranoia.Ada replicates in Ada the test algorithms originally implemented in BASIC and adheres to the evaluation criteria established by W. M. Kahan. Paranoia.Ada incorporates a major structural redesign and employs applicable Ada architectural and stylistic features.

  18. ART-Ada design project, phase 2

    Science.gov (United States)

    Lee, S. Daniel; Allen, Bradley P.

    1990-01-01

    Interest in deploying expert systems in Ada has increased. An Ada based expert system tool is described called ART-Ada, which was built to support research into the language and methodological issues of expert systems in Ada. ART-Ada allows applications of an existing expert system tool called ART-IM (Automated Reasoning Tool for Information Management) to be deployed in various Ada environments. ART-IM, a C-based expert system tool, is used to generate Ada source code which is compiled and linked with an Ada based inference engine to produce an Ada executable image. ART-Ada is being used to implement several expert systems for NASA's Space Station Freedom Program and the U.S. Air Force.

  19. Isolation and properties of AMP deaminase from jumbo squid (Dosidicus gigas) mantle muscle from the Gulf of California, Mexico.

    Science.gov (United States)

    Marquez-Rios, E; Pacheco-Aguilar, R; Castillo-Yañez, F J; Figueroa-Soto, C G; Ezquerra-Brauer, J M; Gollas-Galvan, T

    2008-09-01

    Adenosine monophosphate (AMP) deaminase was purified from jumbo squid mantle muscle by chromatography in cellulose phosphate, Q-Fast and 5'-AMP sepharose. Specific activity of 2.5U/mg protein, 4.5% recovery and 133.68 purification fold were obtained at the end of the experiment. SDS-PAGE showed a single band with 87kDa molecular mass, native PAGE proved a band of 178kDa, whereas gel filtration detected a 180kDa protein, suggesting the homodimeric nature of this enzyme, in which subunits are not linked by covalent forces. Isoelectric focusing of this enzyme showed a pI of 5.76, which agrees with pI values of AMP deaminase from other invertebrate organisms. AMP deaminase presented a kinetic sigmoidal plot with Vmax of 1.16μM/min/mg, Km of 13mM, Kcat of 3.48μM.s(-1) and a Kcat/Km of 267 (mol/L)(-1).s(-1). The apparent relative low catalytic activity of jumbo squid muscle AMP deaminase in the absence of positive effectors is similar to that reported for homologous enzymes in other invertebrate organisms. PMID:26050167

  20. 腺苷脱氨酶用于结核性与肿瘤性胸腹水鉴别诊断的meta分析%Meta-analysis of determination of adenosine deaminase for differential diagnosis of tuberculose and tumorous pleural fluid and ascites

    Institute of Scientific and Technical Information of China (English)

    董春富; 朱以军

    2005-01-01

    目的 评价腺苷脱氨酶(ADA)用于结核性与肿瘤性胸腹水诊断的价值.方法 对入选的8篇文献(3篇腹水文献和5篇胸水文献)进行齐性检验、两个均数之差的合并及meta统计分析.结果 腹水标本结核组ADA含量比肿瘤组高1.559 4~6.206 6倍标准差;胸水标本结核组ADA含量比肿瘤组高0.627 3~3.264 7倍标准差,差异均有显著性(P<0.001).结论 ADA检测是鉴别诊断结核性与肿瘤性胸腹水的快速、简便、特异、敏感的方法.

  1. Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder.

    Science.gov (United States)

    Silva-Ramos, M; Silva, I; Faria, M; Magalhães-Cardoso, M T; Correia, J; Ferreirinha, F; Correia-de-Sá, P

    2015-12-01

    This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [(3)H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [(3)H]ACh was higher (P bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A(1) immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A1 inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL(-1)) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A(1) receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A(1) receptor activation might be useful to control bladder overactivity in BPH patients. PMID:26521170

  2. Adenosine Receptors and Asthma

    OpenAIRE

    Wilson, Constance N; Nadeem, Ahmed; Spina, Domenico; Brown, Rachel; Page, Clive P.; Jamal Mustafa, S.

    2009-01-01

    The pathophysiological processes underlying respiratory diseases like asthma are complex, resulting in an overwhelming choice of potential targets for the novel treatment of this disease. Despite this complexity, asthmatic subjects are uniquely sensitive to a range of substances like adenosine, thought to act indirectly to evoke changes in respiratory mechanics and in the underlying pathology, and thereby to offer novel insights into the pathophysiology of this disease. Adenosine is of partic...

  3. ART/Ada design project, phase 1

    Science.gov (United States)

    1989-01-01

    An Ada-Based Expert System Building Tool Design Research Project was conducted. The goal was to investigate various issues in the context of the design of an Ada-based expert system building tool. An attempt was made to achieve a comprehensive understanding of the potential for embedding expert systems in Ada systems for eventual application in future projects. The current status of the project is described by introducing an operational prototype, ART/Ada. How the project was conducted is explained. The performance of the prototype is analyzed and compared with other related works. Future research directions are suggested.

  4. Separation of effects of adenosine on energy metabolism from those on cyclic AMP in rat thymic lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Nordeen, S.K.; Young, D.A.

    1977-08-10

    In rat thymic lymphocytes incubated for 2 h without exogenous energy-providing substrate, adenosine may be substituted for glucose as a means of maximally restoring energy metabolism and those cellular functions whose rates are sensitive to small changes in the energy balance, such as protein synthesis and uridine utilization for RNA synthesis. Since effects of adenosine in thymocytes and other cells have frequently been attributed to changes in cyclic AMP, this report investigates its possible involvement in these glucose-like restorative actions of adenosine. Although the same range of doses of adenosine effective at raising cyclic AMP also elicit roughly parallel stimulations of protein synthesis and uridine utilization, further results dissociate the restorative actions from those on cyclic AMP. (a) Other purine nucleosides mimic the glucose-like actions of adenosine without increasing cyclic AMP; (b) conversely, prostaglandin E/sub 1/ mimics the cyclic AMP response without restoring energy metabolism or energy-dependent functions; and (c) potentiation of the cyclic AMP response, either by inhibiting phosphodiesterase or adenosine deaminase, does not enhance the restorative response to a range of doses of adenosine. Finally, cyclic AMP-mediated glycogenolysis cannot account for the glucose-like effects since addition of adenosine increases, not decreases, levels of glycogen.

  5. Paranoia.Ada: A diagnostic program to evaluate Ada floating-point arithmetic

    Science.gov (United States)

    Hjermstad, Chris

    1986-01-01

    Many essential software functions in the mission critical computer resource application domain depend on floating point arithmetic. Numerically intensive functions associated with the Space Station project, such as emphemeris generation or the implementation of Kalman filters, are likely to employ the floating point facilities of Ada. Paranoia.Ada appears to be a valuabe program to insure that Ada environments and their underlying hardware exhibit the precision and correctness required to satisfy mission computational requirements. As a diagnostic tool, Paranoia.Ada reveals many essential characteristics of an Ada floating point implementation. Equipped with such knowledge, programmers need not tremble before the complex task of floating point computation.

  6. A small evaluation suite for Ada compilers

    Science.gov (United States)

    Wilke, Randy; Roy, Daniel M.

    1986-01-01

    After completing a small Ada pilot project (OCC simulator) for the Multi Satellite Operations Control Center (MSOCC) at Goddard last year, the use of Ada to develop OCCs was recommended. To help MSOCC transition toward Ada, a suite of about 100 evaluation programs was developed which can be used to assess Ada compilers. These programs compare the overall quality of the compilation system, compare the relative efficiencies of the compilers and the environments in which they work, and compare the size and execution speed of generated machine code. Another goal of the benchmark software was to provide MSOCC system developers with rough timing estimates for the purpose of predicting performance of future systems written in Ada.

  7. The development of a program analysis environment for Ada: Reverse engineering tools for Ada

    Science.gov (United States)

    Cross, James H., II

    1991-01-01

    The Graphical Representations of Algorithms, Structures, and Processes for Ada (GRASP/Ada) has successfully created and prototyped a new algorithm level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and thus improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under the Virtual Memory System (VMS) on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. In Phase 3 of the project, the prototype was prepared for limited distribution (GRASP/Ada Version 3.0) to facilitate evaluation. The user interface was extensively reworked. The current prototype provides the capability for the user to generate CSD from Ada source code in a reverse engineering mode with a level of flexibility suitable for practical application.

  8. Adenosine and sleep

    International Nuclear Information System (INIS)

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A1 receptors, 3H-L-PIA binding was measured. The Bmax values for 3H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in 3H-L-PIA binding resulted from REM sleep deprivation and not from stress

  9. Adenosine and sleep

    Energy Technology Data Exchange (ETDEWEB)

    Yanik, G.M. Jr.

    1987-01-01

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A/sub 1/ receptors, /sup 3/H-L-PIA binding was measured. The Bmax values for /sup 3/H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in /sup 3/H-L-PIA binding resulted from REM sleep deprivation and not from stress.

  10. Disease: H00092 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ferentiation, along with direct or indirect impairment of B-cell development and function. Adenosine deaminase (ADA) deficiency accou...nts for about half of the autosomal recessive forms of S

  11. Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes.

    Science.gov (United States)

    Kocbuch, Katarzyna; Sakowicz-Burkiewicz, Monika; Grden, Marzena; Szutowicz, Andrzej; Pawelczyk, Tadeusz

    2009-01-01

    In diabetes several aspects of immunity are altered, including the immunomodulatory action of adenosine. Our study was undertaken to investigate the effect of different glucose and insulin concentrations on activities of adenosine metabolizing enzymes in human B lymphocytes line SKW 6.4. The activity of adenosine deaminase in the cytosolic fraction was very low and was not affected by different glucose concentration, but in the membrane fraction of cells cultured with 25 mM glucose it was decreased by about 35% comparing to the activity in cells maintained in 5 mM glucose, irrespective of insulin concentration. The activities of 5'-nucleotidase (5'-NT) and ecto-5'-NT in SKW 6.4 cells depended on insulin concentration, but not on glucose. Cells cultured with 10(-8) M insulin displayed an about 60% lower activity of cytosolic 5'-NT comparing to cells maintained at 10(-11) M insulin. The activity of ecto-5'-NT was decreased by about 70% in cells cultured with 10(-8) M insulin comparing to cells grown in 10(-11) M insulin. Neither insulin nor glucose had an effect on adenosine kinase (AK) activity in SKW 6.4 cells or in human B cells isolated from peripheral blood. The extracellular level of adenosine and inosine during accelerated catabolism of cellular ATP depended on glucose, but not on insulin concentration. Concluding, our study demonstrates that glucose and insulin differentially affect the activities of adenosine metabolizing enzymes in human B lymphocytes, but changes in those activities do not correlate with the adenosine level in cell media during accelerated ATP catabolism, implying that nucleoside transport is the primary factor determining the extracellular level of adenosine.

  12. Experiences with Ada in an embedded system

    Science.gov (United States)

    Labaugh, Robert J.

    1988-01-01

    Recent experiences with using Ada in a real time environment are described. The application was the control system for an experimental robotic arm. The objectives of the effort were to experiment with developing embedded applications in Ada, evaluating the suitability of the language for the application, and determining the performance of the system. Additional objectives were to develop a control system based on the NASA/NBS Standard Reference Model for Telerobot Control System Architecture (NASREM) in Ada, and to experiment with the control laws and how to incorporate them into the NASREM architecture.

  13. The detection significance of CD64,Cys-C and ADA levels in cerebrospinal fluid of patients with tuberculous meningitis%结核性脑膜炎患者脑脊液 CD64 Cys-C 及 ADA 水平的检测意义

    Institute of Scientific and Technical Information of China (English)

    钟晶; 尚鹏程; 吴张君; 朱玛; 毕雷; 李由平; 李青峰

    2015-01-01

    目的:分析结核性脑膜炎患者脑脊液中性粒细胞表面膜糖蛋白(CD64)、血清胱抑素C(Cys‐C)及腺苷脱氨酶(ADA )水平的检测意义。方法选取我院193例住院患者为对象,结核性脑膜炎102例,化脓性脑膜炎35例,病毒性脑膜炎30例,非感染性神经系统疾病26例,免疫透射比浊法检测4组Cys‐C、流式细胞术检测CD64、酶标法检测ADA ,比较4组CD64、Cys‐C及ADA水平,并比较单一指标检测与联合检查结核性脑膜炎的诊断符合率。结果结核性脑膜炎患者Cys‐C、ADA、CD64均显著高于非感染性神经系统疾病患者(P<0.05),结核性脑膜炎组、化脓性脑膜炎组、病毒性脑膜炎组3项指标呈递减趋势,病毒性脑膜炎与非感染性神经系统疾病组CD64、Cys‐C比较差异无统计学意义(P>0.05),结核性脑膜炎组与化脓性脑膜炎组Cys‐C比较差异无统计学意义(P>0.05),其他组间比较差异均有统计学意义(P<0.05);Cys‐C、ADA、CD64诊断符合率分别为78.43%、60.73%、70.59%,联合诊断符合率98.04%,显著高于单一诊断。结论 CD64、Cys‐C及 ADA均为结核性脑膜炎的有效检测指标,联合检查有助于提高结核性脑膜炎的诊断准确率及与其他类型脑膜炎的鉴别,具有较高的临床应用价值。%Objective To study the detection significance of neutral granulocyte surface film glycoprotein (CD64) ,serum cystatin C (Cys‐C ) and adenosine deaminase (ADA ) levels in cerebrospinal fluid of patients with tuberculous meningi‐tis.Methods 193 cases of patients admitted to our hospital were selected as subjects ,among whom 102 cases of tuberculous meningitis ,35 cases of purulent meningitis and 30 cases of viral meningitis ,and 26 cases of non‐infectious neurological disea‐ses. Cys‐C levels of the four groups were detected by immunoturbidimetry ,CD64 by flow cytometry and ADA by enzyme

  14. Pleural effusion: Role of pleural fluid cytology, adenosine deaminase level, and pleural biopsy in diagnosis

    Directory of Open Access Journals (Sweden)

    Biswajit Biswas

    2016-01-01

    Full Text Available Objective: The present study is designed to evaluate the role of pleural fluid analysis in diagnosing pleural diseases and to study the advantages and disadvantages of thoracocentasis and pleural biopsy. Materials and Methods: We prospectively included 66 consecutive indoor patients over a duration of 1 year. Pleural fluid was collected and cytological smears were made from the fluid. Plural biopsy was done in the same patient by Cope needle. Adequate pleural biopsy tissue yielding specific diagnosis was obtained in 47 (71.2% cases. Results: Tuberculosis was the commonest nonneoplastic lesion followed by chronic nonspecific pleuritis comprising 60% and 33.3% of the nonneoplastic cases respectively and tuberculosis was predominantly diagnosed in the younger age group. Majority (70.8% of malignancy cases were in the age group of >50-70. Adenocarcinoma was found to be the commonest (66.7% malignant neoplasm in the pleurae followed by small-cell carcinoma (20.8%. Conclusion: Pleural biopsy is a useful and minimally invasive procedure. It is more sensitive and specific than pleural fluid smears.

  15. Adenosine and Sleep

    OpenAIRE

    Bjorness, Theresa E.; Greene, Robert W.

    2009-01-01

    Over the last several decades the idea that adenosine (Ado) plays a role in sleep control was postulated due in large part to pharmacological studies that showed the ability of Ado agonists to induce sleep and Ado antagonists to decrease sleep. A second wave of research involving in vitro cellular analytic approaches and subsequently, the use of neurochemical tools such as microdialysis, identified a population of cells within the brainstem and basal forebrain arousal centers, with activity t...

  16. Software engineering and Ada in design

    Science.gov (United States)

    Oneill, Don

    1986-01-01

    Modern software engineering promises significant reductions in software costs and improvements in software quality. The Ada language is the focus for these software methodology and tool improvements. The IBM FSD approach, including the software engineering practices that guide the systematic design and development of software products and the management of the software process are examined. The revised Ada design language adaptation is revealed. This four level design methodology is detailed including the purpose of each level, the management strategy that integrates the software design activity with the program milestones, and the technical strategy that maps the Ada constructs to each level of design. A complete description of each design level is provided along with specific design language recording guidelines for each level. Finally, some testimony is offered on education, tools, architecture, and metrics resulting from project use of the four level Ada design language adaptation.

  17. The effects of N-acylhomoserine lactones, β-lactam antibiotics and adenosine on biofilm formation in the multi-β-lactam antibiotic-resistant bacterium Acidovorax sp. strain MR-S7.

    Science.gov (United States)

    Kusada, Hiroyuki; Hanada, Satoshi; Kamagata, Yoichi; Kimura, Nobutada

    2014-07-01

    Bacteria in the natural ecosystem frequently live as adherent communities called biofilms. Some chemical compounds are known to affect biofilm formation. We investigated the effect of exogenous small molecules, N-acylhomoserine lactones (AHLs), β-lactam antibiotics, and adenosine, on biofilm formation in the β-lactam antibiotic-resistant bacterium Acidovorax sp. strain MR-S7. Biofilm formation was induced by the addition of various types of AHL isomers and β-lactam antibiotics, whereas the addition of adenosine strongly interfered with the biofilm formation. A gene (macP) encoding adenosine deaminase (that converts adenosine to inosine controlling intracellular adenosine concentration) was successfully cloned from MR-S7 genome and heterologously expressed in Escherichia coli. The purified MacP protein clearly catalyzed the deamination of adenosine to produce inosine. A transcriptional analysis revealed that biofilm-inducing molecules, an AHL and a β-lactam antibiotic, strongly induced not only biofilm formation but also adenosine deaminase gene expression, suggesting that an elaborate gene regulation network for biofilm formation is present in the β-lactam antibiotic-resistant bacterium studied here.

  18. Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection

    Science.gov (United States)

    Doria, Margherita; Neri, Francesca; Gallo, Angela; Farace, Maria Giulia; Michienzi, Alessandro

    2009-01-01

    Adenosine deaminases that act on dsRNA (ADARs) are enzymes that target double-stranded regions of RNA converting adenosines into inosines (A-to-I editing) thus contributing to genome complexity and fine regulation of gene expression. It has been described that a member of the ADAR family, ADAR1, can target viruses and affect their replication process. Here we report evidence showing that ADAR1 stimulates human immuno deficiency virus type 1 (HIV-1) replication by using both editing-dependent and editing-independent mechanisms. We show that over-expression of ADAR1 in HIV-1 producer cells increases viral protein accumulation in an editing-independent manner. Moreover, HIV-1 virions generated in the presence of over-expressed ADAR1 but not an editing-inactive ADAR1 mutant are released more efficiently and display enhanced infectivity, as demonstrated by challenge assays performed with T cell lines and primary CD4+ T lymphocytes. Finally, we report that ADAR1 associates with HIV-1 RNAs and edits adenosines in the 5′ untranslated region (UTR) and the Rev and Tat coding sequence. Overall these results suggest that HIV-1 has evolved mechanisms to take advantage of specific RNA editing activity of the host cell and disclose a stimulatory function of ADAR1 in the spread of HIV-1. PMID:19651874

  19. An Embedded Rule-Based Diagnostic Expert System in Ada

    Science.gov (United States)

    Jones, Robert E.; Liberman, Eugene M.

    1992-01-01

    Ada is becoming an increasingly popular programming language for large Government-funded software projects. Ada with it portability, transportability, and maintainability lends itself well to today's complex programming environment. In addition, expert systems have also assumed a growing role in providing human-like reasoning capability expertise for computer systems. The integration is discussed of expert system technology with Ada programming language, especially a rule-based expert system using an ART-Ada (Automated Reasoning Tool for Ada) system shell. NASA Lewis was chosen as a beta test site for ART-Ada. The test was conducted by implementing the existing Autonomous Power EXpert System (APEX), a Lisp-based power expert system, in ART-Ada. Three components, the rule-based expert systems, a graphics user interface, and communications software make up SMART-Ada (Systems fault Management with ART-Ada). The rules were written in the ART-Ada development environment and converted to Ada source code. The graphics interface was developed with the Transportable Application Environment (TAE) Plus, which generates Ada source code to control graphics images. SMART-Ada communicates with a remote host to obtain either simulated or real data. The Ada source code generated with ART-Ada, TAE Plus, and communications code was incorporated into an Ada expert system that reads the data from a power distribution test bed, applies the rule to determine a fault, if one exists, and graphically displays it on the screen. The main objective, to conduct a beta test on the ART-Ada rule-based expert system shell, was achieved. The system is operational. New Ada tools will assist in future successful projects. ART-Ada is one such tool and is a viable alternative to the straight Ada code when an application requires a rule-based or knowledge-based approach.

  20. Adenosine modulates hypoxia-induced responses in rat PC12 cells via the A2A receptor.

    Science.gov (United States)

    Kobayashi, S; Conforti, L; Pun, R Y; Millhorn, D E

    1998-04-01

    1. The present study was undertaken to determine the role of adenosine in mediating the cellular responses to hypoxia in rat phaeochromocytoma (PC12) cells, an oxygen-sensitive clonal cell line. 2. Reverse transcriptase polymerase chain reaction studies revealed that PC12 cells express adenosine deaminase (the first catalysing enzyme of adenosine degradation) and the A2A and A2B adenosine receptors, but not the A1 or A3 adenosine receptors. 3. Whole-cell current- and voltage-clamp experiments showed that adenosine attenuated the hypoxia-induced membrane depolarization. The hypoxia-induced suppression of the voltage-sensitive potassium current (IK(V)) was markedly reduced by adenosine. Furthermore, extracellularly applied adenosine increased the peak amplitudes of IK(V) in a concentration-dependent manner. This increase was blocked by pretreatment not only with a non-specific adenosine receptor antagonist, 8-phenyltheophylline (8-PT), but also with a selective A2A receptor antagonist, ZM241385. 4. Ca2+ imaging studies using fura-2 acetoxymethyl ester (fura-2 AM) revealed that the increase in intracellular free Ca2+ during hypoxic exposure was attenuated significantly by adenosine. Voltage-clamp studies showed that adenosine inhibited the voltage-dependent Ca2+ currents (ICa) in a concentration-dependent fashion. This inhibition was also abolished by both 8-PT and ZM241385. 5. The modulation of both IK(V) and ICa by adenosine was prevented by intracellular application of an inhibitor of protein kinase A (PKA), PKA inhibitor fragment (6-22) amide. In addition, the effect of adenosine on either IK(V) or ICa was absent in PKA-deficient PC12 cells. 6. These results indicate that the modulatory effects of adenosine on the hypoxia-induced membrane responses of PC12 cells are likely to be mediated via activation of the A2A receptor, and that the PKA pathway is required for these modulatory actions. We propose that this modulation serves to regulate membrane excitability in

  1. Imaging Adenosine Triphosphate (ATP).

    Science.gov (United States)

    Rajendran, Megha; Dane, Eric; Conley, Jason; Tantama, Mathew

    2016-08-01

    Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provide valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities.

  2. LAS DOS TRÍADAS DEBEJARANO

    Directory of Open Access Journals (Sweden)

    Jorge Iván González

    Full Text Available El artículo diseute "dos tríadas" que propone Bejarano para calificar a la teoría económica actual. La primera tríada tiene que ver con el realismo, la pertinencia y la relevancia de la teoría. Y la segunda tríada con sus dimensiones política, institucional y moral. El artículo centra la atención en esta segunda tríada, argumentando que la teoría no es apolítica, ainstitucional y amoral como afirma Bejarano. El examen crítico de la posición de Bejarano se sustenta en algunas de las tesis de: Walras, Marshall, Hicks, vickrey, Samuelson y Arrow.This article discusses the "two triads" that Bejarano has proposed in order to describe present economic theory. The first triad refers to the realism, pertinence and relevance of the theory. The second triad to its political, institutional and moral dimension. The article centers its attention on this second triad, arguing that the theory is not apolitical, uninstitutional and amoral as Bejarano states. The critical examination of Bejarano's proposition is supported on thesis of Walras, Marshall, Hicks, Vickrey, Samuelson and Arrow.

  3. Alma Flor Ada: Writer, Translator, Storyteller.

    Science.gov (United States)

    Brodie, Carolyn S.

    2003-01-01

    Discusses the work of children's author Alma Flor Ada, a Cuban native who has won awards honoring Latino writers and illustrators. Includes part of an interview that explores her background, describes activity ideas, and presents a bibliography of works written by her (several title published in both English and Spanish) as well as sources of…

  4. Is Your Queuing System ADA-Compliant?

    Science.gov (United States)

    Lawrence, David

    2002-01-01

    Discusses the Americans with Disabilities (ADA) and Uniform Federal Accessibility Standards (UFAS) regulations regarding public facilities' crowd control stanchions and queuing systems. The major elements are protruding objects and wheelchair accessibility. Describes how to maintain compliance with the regulations and offers a list of additional…

  5. 49 CFR 37.125 - ADA paratransit eligibility: Process.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false ADA paratransit eligibility: Process. 37.125... INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.125 ADA paratransit eligibility: Process. Each public entity required to provide complementary paratransit service...

  6. 49 CFR 37.123 - ADA paratransit eligibility: Standards.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false ADA paratransit eligibility: Standards. 37.123... INDIVIDUALS WITH DISABILITIES (ADA) Paratransit as a Complement to Fixed Route Service § 37.123 ADA paratransit eligibility: Standards. (a) Public entities required by § 37.121 of this subpart to...

  7. Ada education in a software life-cycle context

    Science.gov (United States)

    Clough, Anne J.

    1986-01-01

    Some of the experience gained from a comprehensive educational program undertaken at The Charles Stark Draper Lab. to introduce the Ada language and to transition modern software engineering technology into the development of Ada and non-Ada applications is described. Initially, a core group, which included manager, engineers and programmers, received training in Ada. An Ada Office was established to assume the major responsibility for training, evaluation, acquisition and benchmarking of tools, and consultation on Ada projects. As a first step in this process, and in-house educational program was undertaken to introduce Ada to the Laboratory. Later, a software engineering course was added to the educational program as the need to address issues spanning the entire software life cycle became evident. Educational efforts to date are summarized, with an emphasis on the educational approach adopted. Finally, lessons learned in administering this program are addressed.

  8. Ada (trademark) projects at NASA. Runtime environment issues and recommendations

    Science.gov (United States)

    Roy, Daniel M.; Wilke, Randall W.

    1988-01-01

    Ada practitioners should use this document to discuss and establish common short term requirements for Ada runtime environments. The major current Ada runtime environment issues are identified through the analysis of some of the Ada efforts at NASA and other research centers. The runtime environment characteristics of major compilers are compared while alternate runtime implementations are reviewed. Modifications and extensions to the Ada Language Reference Manual to address some of these runtime issues are proposed. Three classes of projects focusing on the most critical runtime features of Ada are recommended, including a range of immediately feasible full scale Ada development projects. Also, a list of runtime features and procurement issues is proposed for consideration by the vendors, contractors and the government.

  9. The OPEN-ADAS Approach to Atomic Data Provision

    International Nuclear Information System (INIS)

    Dr O'Mullane of University of Strathclyde presented an overview of the ADAS project (Atomic Data and Analysis Structure, http://www.adas.ac.uk/) and of OPEN-ADAS (http://open.adas.ac.uk/). ADAS is maintained as a self-funding consortium of fusion laboratories. The project provides an interconnected set of computer codes and data collections for modeling the radiating properties of ions and atoms in plasmas. The ADAS data fall into 3 broad classes: 1) Fundamental data such as A- values, cross-sections and effective collision strengths obtained from ADAS collaborators, the literature or data centres. 2) Derived data processed for modeling such as electron temperature and density dependent effective emission coefficients, effective ionization/recombination rates, radiated power and spectral emissivities. 3) Driver data which allow complete regeneration of all ADAS derived data in conjunction with the various ADAS codes. ADAS data uses high quality data as well as baseline data for fall-back when high quality data is not available. The data is mostly embedded in codes and the update without expert help is problematic. The ADAS data formats (adf) are precisely defined and Fortran codes are supplied to read the data sets for easy access. IDL can be used for interactive manipulation. The OPEN-ADAS project is a joint development between the ADAS Project and the IAEA to make the extensive fundamental and derived atomic data for fusion more widely available. It is designed to appeal to both plasma modelers and those interested in the detailed atomic physics. It has been searchable through the Google Scholar and appears in citations, which gives greater visibility and credits to the data producers. The OPEN-ADAS server was replaced due to a series of attacks since June 2011 and was off-line for 8 weeks. The new service removed the registration requirement and hence the user statistics is limited.

  10. Uneven distribution of nucleoside transporters and intracellular enzymatic degradation prevent transport of intact [14C] adenosine across the sheep choroid plexus epithelium as a monolayer in primary culture

    Directory of Open Access Journals (Sweden)

    Misirlic Dencic Sonja T

    2006-03-01

    Full Text Available Abstract Background Efflux transport of adenosine across the choroid plexus (CP epithelium might contribute to the homeostasis of this neuromodulator in the extracellular fluids of the brain. The aim of this study was to explore adenosine transport across sheep CP epithelial cell monolayers in primary culture. Methods To explore transport of adenosine across the CP epithelium, we have developed a method for primary culture of the sheep choroid plexus epithelial cells (CPEC on plastic permeable supports and analysed [14C] adenosine transport across this cellular layer, [14C] adenosine metabolism inside the cells, and cellular uptake of [14C] adenosine from either of the chambers. The primary cell culture consisted of an enriched epithelial cell fraction from the sheep fourth ventricle CP and was grown on laminin-precoated filter inserts. Results and conclusion CPEC grew as monolayers forming typical polygonal islands, reaching optical confluence on the third day after the seeding. Transepithelial electrical resistance increased over the time after seeding up to 85 ± 9 Ω cm2 at day 8, while permeability towards [14C] sucrose, a marker of paracellular diffusion, simultaneously decreased. These cells expressed some features typical of the CPEC in situ, including three nucleoside transporters at the transcript level that normally mediate adenosine transport across cellular membranes. The estimated permeability of these monolayers towards [14C] adenosine was low and the same order of magnitude as for the markers of paracellular diffusion. However, inhibition of the intracellular enzymes, adenosine kinase and adenosine deaminase, led to a significant increase in transcellular permeability, indicating that intracellular phosphorylation into nucleotides might be a reason for the low transcellular permeability. HPLC analysis with simultaneous detection of radioactivity revealed that [14C] radioactivity which appeared in the acceptor chamber after the

  11. Characterization of unexplored amidohydrolase enzyme-pterin deaminase.

    Science.gov (United States)

    Jayaraman, Angayarkanni; Thandeeswaran, Murugesan; Priyadarsini, Ulaganathan; Sabarathinam, Shanmugam; Nawaz, K A Ayub; Palaniswamy, Muthusamy

    2016-06-01

    Pterin deaminase is an amidohydrolase enzyme hydrolyzing pteridines to form lumazine derivatives and ammonia. The enzyme captured the attention of scientists as early as 1959 and had been patented for its application as an anticancer agent. It is ubiquitously present in prokaryotes and has been reported in some eukaryotes such as honey bee, silkworm and rats. The enzyme has been observed to have a spectrum of substrates with the formation of respective lumazines. The role of the substrates of the enzyme in various metabolic pathways warrants a significant role in the biological activity of both prokaryotes and eukaryotes. Even though the functions of the enzyme have been explored in prokaryotes, their niche in the eukaryotic system is not clear. There is very few information on the structural and functional properties of the enzyme. This review has been congregated to emphasize the significance of pterin deaminase and analyzes the lacunae in understanding the biological characters of the enzyme. PMID:27094187

  12. AID/APOBEC cytosine deaminase induces genome-wide kataegis

    Directory of Open Access Journals (Sweden)

    Lada Artem G

    2012-12-01

    Full Text Available Abstract Clusters of localized hypermutation in human breast cancer genomes, named “kataegis” (from the Greek for thunderstorm, are hypothesized to result from multiple cytosine deaminations catalyzed by AID/APOBEC proteins. However, a direct link between APOBECs and kataegis is still lacking. We have sequenced the genomes of yeast mutants induced in diploids by expression of the gene for PmCDA1, a hypermutagenic deaminase from sea lamprey. Analysis of the distribution of 5,138 induced mutations revealed localized clusters very similar to those found in tumors. Our data provide evidence that unleashed cytosine deaminase activity is an evolutionary conserved, prominent source of genome-wide kataegis events. Reviewers This article was reviewed by: Professor Sandor Pongor, Professor Shamil R. Sunyaev, and Dr Vladimir Kuznetsov.

  13. APOBEC deaminases-mutases with defensive roles for immunity

    Institute of Scientific and Technical Information of China (English)

    Courtney; PROCHNOW; Ronda; BRANSTEITTER

    2009-01-01

    In recent years, tremendous progress has been made in the elucidation of the biological roles and molecular mechanisms of the apolioprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of enzymes. The APOBEC family of cytidine deaminases has important functional roles within the adaptive and innate immune system. Activation induced cytidine deaminase (AID) plays a central role in the biochemical steps of somatic hypermutation and class switch recombination during antibody maturation, and the APOBEC 3 enzymes are able to inhibit the mobility of retroelements and the replication of retroviruses and DNA viruses, such as the human immunodeficiency virus type-1 and hepatitis B virus. Recent advances in structural and functional studies of the APOBEC enzymes provide new biochemical insights for how these enzymes carry out their biological roles. In this review, we provide an overview of these recent advances in the APOBEC field with a special emphasis on AID and APOBEC3G.

  14. Chronic hypoxia enhances adenosine release in rat PC12 cells by altering adenosine metabolism and membrane transport.

    Science.gov (United States)

    Kobayashi, S; Zimmermann, H; Millhorn, D E

    2000-02-01

    Acute exposure to hypoxia causes a release of adenosine (ADO) that is inversely related to the O2 levels in oxygen-sensitive pheochromocytoma (PC12) cells. In the current study, chronic exposure (48 h) of PC12 cells to moderate hypoxia (5% O2) significantly enhanced the release of ADO during severe, acute hypoxia (1% O2). Investigation into the intra- and extracellular mechanisms underpinning the secretion of ADO in PC12 cells chronically exposed to hypoxia revealed changes in gene expression and activities of several key enzymes associated with ADO production and metabolism, as well as the down-regulation of a nucleoside transporter. Decreases in the enzymatic activities of ADO kinase and ADO deaminase accompanied by an increase in those of cytoplasmic and ecto-5'-nucleotidases bring about an increased capacity to produce intra- and extracellular ADO. This increased potential to generate ADO and decreased capacity to metabolize ADO indicate that PC12 cells shift toward an ADO producer phenotype during hypoxia. The reduced function of the rat equilibrative nucleoside transporter rENT1 also plays a role in controlling extracellular ADO levels. The hypoxia-induced alterations in the ADO metabolic enzymes and the rENT1 transporter seem to increase the extracellular concentration of ADO. The biological significance of this regulation is unclear but is likely to be associated with modulating cellular activity during hypoxia. PMID:10646513

  15. A visual language for ADA program unit specifications

    OpenAIRE

    Gordon, Christopher Todd

    1990-01-01

    This thesis describes a visual programming language designed to describe and generate Ada program unit specifications. The author first describes the foundations for the work, and gives a brief introduction to some of the features of the language. Most of the thesis is dedicated to describing the visual representation for each portion of an Ada package specification. The BNF grammar of an Ada package specification is used as a basis for organization. By organizing the the...

  16. ART/Ada design project, phase 1: Project plan

    Science.gov (United States)

    Allen, Bradley P.

    1988-01-01

    The plan and schedule for Phase 1 of the Ada based ESBT Design Research Project is described. The main platform for the project is a DEC Ada compiler on VAX mini-computers and VAXstations running the Virtual Memory System (VMS) operating system. The Ada effort and lines of code are given in tabular form. A chart is given of the entire project life cycle.

  17. Enzymatic conformational fluctuations along the reaction coordinate of cytidine deaminase

    OpenAIRE

    Noonan, Ryan C.; Carter, Charles W.; Bagdassarian, Carey K.

    2002-01-01

    Analysis of the crystal structures for cytidine deaminase complexed with substrate analog 3-deazacytidine, transition-state analog zebularine 3,4-hydrate, and product uridine establishes significant changes in the magnitude of atomic-scale fluctuations along the (approximate) reaction coordinate of this enzyme. Differences in fluctuations between the substrate analog complex, transition-state analog complex, and product complex are monitored via changes in corresponding crystallographic tempe...

  18. Ada and its impact on the scientific user

    International Nuclear Information System (INIS)

    The Ada programming language is the result of a collective effort to design a common language for programming real-time systems. The design of Ada was initiated by the United States Department of Defense (DoD) in 1975. Ada combines facilities found in most classical languages like Fortran, PL/I, Pascal, and Basic together with many features formerly found only in experimental languages. It is argued that these features make Ada a very decent tool not only for writing real-time programs but also for the development of software in the scientific sector. (orig.)

  19. Accommodating Uncertainty in ADAS Models and Data

    International Nuclear Information System (INIS)

    The Atomic Data and Analysis Structure (ADAS) is an interconnected set of computer codes and data collections for modelling the radiating properties of ions and atoms in plasmas and for assisting in the analysis and interpretation of spectral measurements. Fundamental atomic data is mediated via collisional-radiative population models to produce the effective coefficients for practical use in impurity transport modelling, influx estimation, beam stopping efficiency and active charge exchange quantification. Away from the coronal picture, the simple connection between fundamental processes and the derived population or emissivity is lost. Instead these coefficients become dependent on many fundamental processes with unknown weightings. The challenge is threefold: to develop methods for assigning an uncertainty to the fundamental data, to propagate these through the population models and to enable techniques to utilize within plasmas models atomic data that comes with an accompanying error surface. Pure atomic properties, such as energy levels and some transition probabilities, are measurable and are known to high precision. However most of the fundamental data required for fusion work, such as excitation and state selective charge transfer cross sections, ionisation and recombination rates (for both electron and ion drivers) remain the result of theoretical calculations and this is not likely to change. The envelope of variation between different methods and calculations is the simplest approach to ascribing an error and is useful in identifying both the principal contributors to the final quantity of interest and to assess its domain of influence. A more refined approach, based on variation of the control parameters of the fundamental ab initio codes, is adopted for this smaller set of significant cross sections. The error for the derived quantities is computed via a statistical sampling methodology assuming an error distribution within the ascribed uncertainty

  20. Regulation of adenosine levels during cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Stephanie CHU; Wei XIONG; Dali ZHANG; Hanifi SOYLU; Chao SUN; Benedict C ALBENSI; Fiona E PARKINSON

    2013-01-01

    Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events,and attenuates the excitotoxic neuronal injury.Adenosine is produced both intracellularly and extracellularly,and nucleoside transport proteins transfer adenosine across plasma membranes.Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption,cellular release of ATP,metabolism of extracellular ATP (and other adenine nucleotides),adenosine influx,adenosine efflux and adenosine metabolism.Recent studies have used genetically modified mice to investigate the relative contributions of intra-and extracellular pathways for adenosine formation.The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase.From these studies,we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures,but not in hippocampal slices or in vivo mice exposed to ischemic conditions.

  1. Alma Flor Ada and the Quest for Change

    Science.gov (United States)

    Manna, Anthony, L.; Hill, Janet; Kellogg, Kathy

    2004-01-01

    Alma Flor Ada, a folklorist, novelist, scholar, teacher, and children's book author has passionate dedication to education for social justice, equality, and peace. As a faculty member at the University of San Francisco, Ada has developed programs that help students and others transform their lives and has written several bilingual legends and…

  2. L-Arginine Intake Effect on Adenine Nucleotide Metabolism in Rat Parenchymal and Reproductive Tissues

    Directory of Open Access Journals (Sweden)

    G. Kocic

    2012-01-01

    Full Text Available L-arginine is conditionally essetcial amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolism: 5′-nucleotidase (5′-NU, adenosine deaminase (ADA, AMP deaminase, and xanthine oxidase (XO, during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme, 5′-NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased 5′-NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.

  3. First International Conference on Ada (R) Programming Language Applications for the NASA Space Station, volume 1

    Science.gov (United States)

    Bown, Rodney L. (Editor)

    1986-01-01

    Topics discussed include: test and verification; environment issues; distributed Ada issues; life cycle issues; Ada in Europe; management/training issues; common Ada interface set; and run time issues.

  4. Characterization of the Escherichia coli codBA operon encoding cytosine permease and cytosine deaminase

    DEFF Research Database (Denmark)

    Danielsen, S; Kilstrup, M; Barilla, K;

    1992-01-01

    The nucleotide sequence of a 3.1 kb segment carrying the cytosine deaminase gene (codA) from Escherichia coli was determined. The sequence revealed the presence of two open reading frames, the first (codB) specifying a highly hydrophobic polypeptide and the second specifying cytosine deaminase. A...

  5. ACTIVATION OF A CRYPTIC D-SERINE DEAMINASE (DSD) GENE FROM PSEUDOMONAS CEPACIA 17616

    Science.gov (United States)

    D-serine inhibits growth of P. cepacia 17616; however, resistant mutants able to express an ordinarily cryptic D-serine deaminase (dsd) gene were isolated readily. The resistant strains formed high levels of a D-serine deaminase active on D-threonine as well as D-serine. IS eleme...

  6. ART/Ada design project, phase 1. Task 1 report: Overall design

    Science.gov (United States)

    Allen, Bradley P.

    1988-01-01

    The design methodology for the ART/Ada project is introduced, and the selected design for ART/Ada is described in detail. The following topics are included: object-oriented design, reusable software, documentation techniques, impact of Ada, design approach, and differences between ART-IM 1.5 and ART/Ada 1.0 prototype. Also, Ada generator and ART/Ada runtime systems are discussed.

  7. Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues

    DEFF Research Database (Denmark)

    Jørgensen, P E; Erlandsen, E J; Poulsen, Steen Seier;

    2000-01-01

    Porphobilinogen deaminase (PBGD) is an enzyme involved in the synthesis of heme. Acute intermittent porphyria (AIP) is an inherited disease resulting from a reduced activity of PBGD. The symptoms seem to be due to a neurological dysfunction. Attacks of AIP are often provoked by conditions where...... the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest...

  8. Identification, Expression, and Characterization of Escherichia coli Guanine Deaminase

    OpenAIRE

    Maynes, Jason T.; Yuan, Richard G.; Snyder, Floyd F.

    2000-01-01

    Using the human cDNA sequence corresponding to guanine deaminase, the Escherichia coli genome was scanned using the Basic Local Alignment Search Tool (BLAST), and a corresponding 439-residue open reading frame of unknown function was identified as having 36% identity to the human protein. The putative gene was amplified, subcloned into the pMAL-c2 vector, expressed, purified, and characterized enzymatically. The 50.2-kDa protein catalyzed the conversion of guanine to xanthine, having a Km of ...

  9. Regulation of Activation Induced Deaminase (AID) by Estrogen.

    Science.gov (United States)

    Pauklin, Siim

    2016-01-01

    Regulation of Activation Induced Deaminase (AID) by the hormone estrogen has important implications for understanding adaptive immune responses as well as the involvement of AID in autoimmune diseases and tumorigenesis. This chapter describes the general laboratory techniques for analyzing AID expression and activity induced by estrogen, focusing on the isolation and preparation of cells for hormone treatment and the subsequent analysis of AID responsiveness to estrogen at the RNA level and for determining the regulation of AID activity via estrogen by analyzing Ig switch circle transcripts and mutations in switch region loci.

  10. An adenosine A(2A) antagonist injected in the NTS reverses thermal prolongation of the LCR in decerebrate piglets.

    Science.gov (United States)

    Xia, Luxi; Bartlett, Donald; Leiter, J C

    2008-12-31

    Hyperthermia prolongs the laryngeal chemoreflex (LCR). Under normothermic conditions, adenosine antagonists shorten and adenosine A(2A) (Ad-A(2A)) agonists prolong the LCR. Therefore, we tested the hypothesis that SCH-58261, an Ad-A(2A) receptor antagonist, would prevent thermal prolongation of the LCR when injected unilaterally within the nucleus of the solitary tract (NTS). We studied decerebrate piglets aged 4-13 days. We elicited the LCR by injecting 0.1ml of water into the larynx and recorded integrated phrenic nerve activity. The laryngeal chemoreflex was prolonged when the body temperature of each piglet was raised approximately 2.5 degrees C, and SCH-58261 reversed the thermal prolongation of the LCR when injected into the NTS (n=13), but not when injected in the nucleus ambiguus (n=9). Injections of vehicle alone into the NTS did not alter the thermal prolongation of the LCR (n=9). We conclude that activation of adenosine receptors, perhaps located on GABAergic neurons in the NTS, contributes to thermal prolongation of the LCR.

  11. New insights into 1-aminocyclopropane-1-carboxylate (ACC deaminase phylogeny, evolution and ecological significance.

    Directory of Open Access Journals (Sweden)

    Francisco X Nascimento

    Full Text Available The main objective of this work is the study of the phylogeny, evolution and ecological importance of the enzyme 1-aminocyclopropane-1-carboxylate (ACC deaminase, the activity of which represents one of the most important and studied mechanisms used by plant growth-promoting microorganisms. The ACC deaminase gene and its regulatory elements presence in completely sequenced organisms was verified by multiple searches in diverse databases, and based on the data obtained a comprehensive analysis was conducted. Strain habitat, origin and ACC deaminase activity were taken into account when analyzing the results. In order to unveil ACC deaminase origin, evolution and relationships with other closely related pyridoxal phosphate (PLP dependent enzymes a phylogenetic analysis was also performed. The data obtained show that ACC deaminase is mostly prevalent in some Bacteria, Fungi and members of Stramenopiles. Contrary to previous reports, we show that ACC deaminase genes are predominantly vertically inherited in various bacterial and fungal classes. Still, results suggest a considerable degree of horizontal gene transfer events, including interkingdom transfer events. A model for ACC deaminase origin and evolution is also proposed. This study also confirms the previous reports suggesting that the Lrp-like regulatory protein AcdR is a common mechanism regulating ACC deaminase expression in Proteobacteria, however, we also show that other regulatory mechanisms may be present in some Proteobacteria and other bacterial phyla. In this study we provide a more complete view of the role for ACC deaminase than was previously available. The results show that ACC deaminase may not only be related to plant growth promotion abilities, but may also play multiple roles in microorganism's developmental processes. Hence, exploring the origin and functioning of this enzyme may be the key in a variety of important agricultural and biotechnological applications.

  12. AdaBoost分类问题的理论推导%Theory deduction of AdaBoost classification

    Institute of Scientific and Technical Information of China (English)

    严超; 王元庆; 李久雪; 张兆扬

    2011-01-01

    为解决AdaBoost算法在二分类问题及多分类问题上缺乏共同的理论基础,算法系列的系统性难以得到理论诠释这一问题,首先,从算法思想的层面对AdaBoost算法与最优贝叶斯推理的关系进行了探讨;然后对AdaBoost算法的训练流程及相关参量进行了定量分析;最后从基本不等式定理入手,重点推导了AdaBoost算法由二分类问题向多分类问题延展的理论依据,探讨了AdaBoost算法的本质.总结并证明了AdaBoost算法的2条理论基础:当非负数之和是一个定值时,其差值越大则其乘积越小;非负数的算术平均数大于等于它们的几何平均数.并且分别就二分类问题和多分类问题对AdaBoost算法的应用提出了优化策略.%AdaBoost two-classification and AdaBoost multi-classification lack mutual theory principals, so the unity of AdaBoost algorithm could not be represented theorically. To solve this problem , firstly, the connection of AdaBoost algorithm and Bayes Inference is probed; secondly, the training process and relative parameters of AdaBoost algorithm are analyzed quantitatively; thirdly, with fundamental inequality principals, the extension process of AdaBoost algorithm from two-classification application to multi-classification application is reasoned. Two intrinsic theories are summarized and proved: if the sum of some non-negative numbers is fixed, their product will become smaller when their values difference become greater; arithmetic average of some non-negative numbers is greater than their geometric average. In addition, some improvements to two-classification and multi-classification applications are suggested.

  13. Visualization design and verification of Ada tasking using timing diagrams

    Science.gov (United States)

    Vidale, R. F.; Szulewski, P. A.; Weiss, J. B.

    1986-01-01

    The use of timing diagrams is recommended in the design and testing of multi-task Ada programs. By displaying the task states vs. time, timing diagrams can portray the simultaneous threads of data flow and control which characterize tasking programs. This description of the system's dynamic behavior from conception to testing is a necessary adjunct to other graphical techniques, such as structure charts, which essentially give a static view of the system. A series of steps is recommended which incorporates timing diagrams into the design process. Finally, a description is provided of a prototype Ada Execution Analyzer (AEA) which automates the production of timing diagrams from VAX/Ada debugger output.

  14. Adenosine, Energy Metabolism, and Sleep

    Directory of Open Access Journals (Sweden)

    Tarja Porkka-Heiskanen

    2003-01-01

    Full Text Available While the exact function of sleep remains unknown, it is evident that sleep was developed early in phylogenesis and represents an ancient and vital strategy for survival. Several pieces of evidence suggest that the function of sleep is associated with energy metabolism, saving of energy, and replenishment of energy stores. Prolonged wakefulness induces signs of energy depletion in the brain, while experimentally induced, local energy depletion induces increase in sleep, similarly as would a period of prolonged wakefulness. The key molecule in the induction of sleep appears to be adenosine, which induces sleep locally in the basal forebrain.

  15. Bahan pemutih gigi dengan sertifikat ADA/ISO (Tooth bleaching material with ADA/ISO certificate

    Directory of Open Access Journals (Sweden)

    Asti Meizarini

    2005-06-01

    Full Text Available Bleaching of teeth for cosmetic reasons is a popular aspect of cosmetic dentistry because patients realize the aesthetical benefits of these products. The dentist as a clinician's practitioner must be knowledgeable of the products and their application techniques. Bleaching materials which are safe and effective are the ADA accepted or manufactured by those which have already haved ISO certificate. Dentist must have enough knowledge about in-office bleaching prescribed for home-use bleaching including their contra indication and side effects, to advise the patients and provide effective bleaching services.

  16. Latvian PR people are world class / Ada Parr

    Index Scriptorium Estoniae

    Parr, Ada

    2004-01-01

    Suhtekorraldusfirma Porter Novelli rahvusvahelise partnerluse juht suhtekorralduse osatähtsuse kasvust ettevõtete äritegevuses, suhtekorraldusturu olukorrast ja teenuste kvaliteedi tasemest Baltimaades. Vt. samas: Ada Parr recommends

  17. A report on NASA software engineering and Ada training requirements

    Science.gov (United States)

    Legrand, Sue; Freedman, Glenn B.; Svabek, L.

    1987-01-01

    NASA's software engineering and Ada skill base are assessed and information that may result in new models for software engineering, Ada training plans, and curricula are provided. A quantitative assessment which reflects the requirements for software engineering and Ada training across NASA is provided. A recommended implementation plan including a suggested curriculum with associated duration per course and suggested means of delivery is also provided. The distinction between education and training is made. Although it was directed to focus on NASA's need for the latter, the key relationships to software engineering education are also identified. A rationale and strategy for implementing a life cycle education and training program are detailed in support of improved software engineering practices and the transition to Ada.

  18. Las drogas diseñadas

    Directory of Open Access Journals (Sweden)

    Eddie Alvarado Vargas

    1998-12-01

    Full Text Available Cada vez cobra más fuerza la clasificación de las drogas que las divide en psictrópicos y estupefacientes y en Costa Rica se ha añadido la sustancia inhalable. Se hace una ligera definición sobre lo que es una droga y la diferencia con las sustancias indispensables para el organismo como son el agua, el oxígeno y los alimentos las cuales son necesarias para el mismo. En el mundo cada vez es mayor el número de estas sustancias fiscalizadas, y que es considerada una acción delictiva en determinadas ocasiones. Convenios internacionales que deben ser ratificados por las naciones exige que se especifique previamente el objeto material del Delito. Las Drogas Diseñadas son aquellas que por algún cambio realizado en un laboratorio sobre su molécula, tienen los efectos muchas veces superiores a la droga madre, pero que por no estar en la lista de drogas fiscalizadas en el momento de aparición de la misma, va permitiendo que, mientras se agrega a la lista de las mencionadas drogas fiscalizadas, estos actos queden impunes con gran daño por la Salud Pública y del individuo durante mucho tiempo. Costa Rica no escapa de esta realidad por lo que el "narcotraficante" siempre irá adelante con nuevas drogas diseñadas causando grandes estragos, mientras las mismas poco a poco se van incluyendo en la lista de sustancias fiscalizadas. Se hace mención sobre posibles soluciones, entre ellas está incluir en las listas de los convenios internacionales, decretos y reglamentos, nueva terminología que incluya las posibles variaciones de las moléculas de las sustancias fiscalizadas.Every time takes greater force the clasification of drugs, which are divided in psichotropics and stupefacients, and in Costa Rica a new classification has been added: inhalable sustances. A light definition of what a drug is and the difference between the indispensable sustances for the organism like the water, oxigen and food which are necesary for life.Every time the number

  19. GRASP/Ada: Graphical Representations of Algorithms, Structures, and Processes for Ada. The development of a program analysis environment for Ada: Reverse engineering tools for Ada, task 2, phase 3

    Science.gov (United States)

    Cross, James H., II

    1991-01-01

    The main objective is the investigation, formulation, and generation of graphical representations of algorithms, structures, and processes for Ada (GRASP/Ada). The presented task, in which various graphical representations that can be extracted or generated from source code are described and categorized, is focused on reverse engineering. The following subject areas are covered: the system model; control structure diagram generator; object oriented design diagram generator; user interface; and the GRASP library.

  20. Hydraulic Capacity of an ADA Compliant Street Drain Grate

    Energy Technology Data Exchange (ETDEWEB)

    Lottes, Steven A. [Argonne National Lab. (ANL), Argonne, IL (United States); Bojanowski, Cezary [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-01

    Resurfacing of urban roads with concurrent repairs and replacement of sections of curb and sidewalk may require pedestrian ramps that are compliant with the American Disabilities Act (ADA), and when street drains are in close proximity to the walkway, ADA compliant street grates may also be required. The Minnesota Department of Transportation ADA Operations Unit identified a foundry with an available grate that meets ADA requirements. Argonne National Laboratory’s Transportation Research and Analysis Computing Center used full scale three dimensional computational fluid dynamics to determine the performance of the ADA compliant grate and compared it to that of a standard vane grate. Analysis of a parametric set of cases was carried out, including variation in longitudinal, gutter, and cross street slopes and the water spread from the curb. The performance of the grates was characterized by the fraction of the total volume flow approaching the grate from the upstream that was captured by the grate and diverted into the catch basin. The fraction of the total flow entering over the grate from the side and the fraction of flow directly over a grate diverted into the catch basin were also quantities of interest that aid in understanding the differences in performance of the grates. The ADA compliant grate performance lagged that of the vane grate, increasingly so as upstream Reynolds number increased. The major factor leading to the performance difference between the two grates was the fraction of flow directly over the grates that is captured by the grates.

  1. Extracellular Adenosine Protects against Streptococcus pneumoniae Lung Infection by Regulating Pulmonary Neutrophil Recruitment.

    Science.gov (United States)

    Bou Ghanem, Elsa N; Clark, Stacie; Roggensack, Sara E; McIver, Sally R; Alcaide, Pilar; Haydon, Philip G; Leong, John M

    2015-08-01

    An important determinant of disease following Streptococcus pneumoniae (pneumococcus) lung infection is pulmonary inflammation mediated by polymorphonuclear leukocytes (PMNs). We found that upon intratracheal challenge of mice, recruitment of PMNs into the lungs within the first 3 hours coincided with decreased pulmonary pneumococci, whereas large numbers of pulmonary PMNs beyond 12 hours correlated with a greater bacterial burden. Indeed, mice that survived infection largely resolved inflammation by 72 hours, and PMN depletion at peak infiltration, i.e. 18 hours post-infection, lowered bacterial numbers and enhanced survival. We investigated host signaling pathways that influence both pneumococcus clearance and pulmonary inflammation. Pharmacologic inhibition and/or genetic ablation of enzymes that generate extracellular adenosine (EAD) (e.g. the ectoenzyme CD73) or degrade EAD (e.g. adenosine deaminase) revealed that EAD dramatically increases murine resistance to S. pneumoniae lung infection. Moreover, adenosine diminished PMN movement across endothelial monolayers in vitro, and although inhibition or deficiency of CD73 had no discernible impact on PMN recruitment within the first 6 hours after intratracheal inoculation of mice, these measures enhanced PMN numbers in the pulmonary interstitium after 18 hours of infection, culminating in dramatically elevated numbers of pulmonary PMNs at three days post-infection. When assessed at this time point, CD73-/- mice displayed increased levels of cellular factors that promote leukocyte migration, such as CXCL2 chemokine in the murine lung, as well as CXCR2 and β-2 integrin on the surface of pulmonary PMNs. The enhanced pneumococcal susceptibility of CD73-/- mice was significantly reversed by PMN depletion following infection, suggesting that EAD-mediated resistance is largely mediated by its effects on PMNs. Finally, CD73-inhibition diminished the ability of PMNs to kill pneumococci in vitro, suggesting that EAD alters

  2. Two Arabidopsis orthologs of the transcriptional coactivator ADA2 have distinct biological functions.

    Science.gov (United States)

    Hark, Amy T; Vlachonasios, Konstantinos E; Pavangadkar, Kanchan A; Rao, Sumana; Gordon, Hillary; Adamakis, Ioannis-Dimosthenis; Kaldis, Athanasios; Thomashow, Michael F; Triezenberg, Steven J

    2009-02-01

    Histone acetylation is an example of covalent modification of chromatin structure that has the potential to regulate gene expression. Gcn5 is a prototypical histone acetyltransferase that associates with the transcriptional coactivator Ada2. In Arabidopsis, two genes encode proteins that resemble yeast ADA2 and share approximately 45% amino acid sequence identity. We previously reported that plants harboring a T-DNA insertion in the ADA2b gene display a dwarf phenotype with developmental defects in several organs. Here we describe T-DNA insertion alleles in the ADA2a gene, which result in no dramatic growth or developmental phenotype. Both ADA2a and ADA2b are expressed in a variety of plant tissues; moreover, expression of ADA2a from a constitutive promoter fails to complement the ada2b-1 mutant phenotype, consistent with the hypothesis that the two proteins have distinct biochemical roles. To further probe the cellular roles of ADA2a and ADA2b, we studied the response of the transcriptional coactivator mutants to abiotic stress. Although ada2b seedlings display hypersensitivity to salt and abscisic acid and altered responses to low temperature stress, the responses of ada2a seedlings to abiotic stress generally parallel those of wildtype plants. Intriguingly, ada2a;ada2b double mutant plants display an intermediate, gcn5-like phenotype, suggesting that ADA2a and ADA2b each work independently with GCN5 to affect genome function in Arabidopsis.

  3. ART/Ada design project, phase 1. Task 3 report: Test plan

    Science.gov (United States)

    Allen, Bradley P.

    1988-01-01

    The plan is described for the integrated testing and benchmark of Phase Ada based ESBT Design Research Project. The integration testing is divided into two phases: (1) the modules that do not rely on the Ada code generated by the Ada Generator are tested before the Ada Generator is implemented; and (2) all modules are integrated and tested with the Ada code generated by the Ada Generator. Its performance and size as well as its functionality is verified in this phase. The target platform is a DEC Ada compiler on VAX mini-computers and VAX stations running the VMS operating system.

  4. Remolding Diversified Objects in Ada95: Toward A-Object Pattern

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Ada provides full capacities of supporting object-orientation,but the diversified objects patterned in Ada are so intricate that Ada95's aim would be demolished. In order to complement the disfigurement that Ada does lack for a pr istine notion of class, this paper presents a remolded object pattern known as A -object, an Ada-based class description language A-ObjAda aiming at support f or A-object pattern and the related approach for key algorithms and implementation . In consequent, A-ObjAda hereby promotes Ada with highlighted object-orientati on , which not only effectively exploits the capacities in Ada95, but also rational ly hides befuddling concepts from Ada95.

  5. Alternative transcription and splicing of the human porphobilinogen deaminase gene

    International Nuclear Information System (INIS)

    Porphobilinogen deaminase is a cytosolic enzyme involved in the heme biosynthetic pathway. Two isoforms of PBGD, encoded by two mRNAs differing solely in their 5' end, are known: one is found in all cells and the other is present only in erythroid cells. The authors have previously shown that the human PBGD is encoded by a single gene and have now cloned and characterized this gene, which is split into 15 exons spread over 10 kilobases of DNA. They demonstrate that the two mRNAs arise from two overlapping transcription units. The first one (upstream) is active in all tissues and its promoter has some of the structural features of a housekeeping promoter; the second, located 3 kilobases downstream, is active only in erythroid cells and its promoter displays structural homologies with the β-globin gene promoters

  6. Optical Aptasensors for Adenosine Triphosphate

    Science.gov (United States)

    Ng, Stella; Lim, Hui Si; Ma, Qian; Gao, Zhiqiang

    2016-01-01

    Nucleic acids are among the most researched and applied biomolecules. Their diverse two- and three-dimensional structures in conjunction with their robust chemistry and ease of manipulation provide a rare opportunity for sensor applications. Moreover, their high biocompatibility has seen them being used in the construction of in vivo assays. Various nucleic acid-based devices have been extensively studied as either the principal element in discrete molecule-like sensors or as the main component in the fabrication of sensing devices. The use of aptamers in sensors - aptasensors, in particular, has led to improvements in sensitivity, selectivity, and multiplexing capacity for a wide verity of analytes like proteins, nucleic acids, as well as small biomolecules such as glucose and adenosine triphosphate (ATP). This article reviews the progress in the use of aptamers as the principal component in sensors for optical detection of ATP with an emphasis on sensing mechanism, performance, and applications with some discussion on challenges and perspectives. PMID:27446501

  7. AdaNET phase 0 support for the AdaNET Dynamic Software Inventory (DSI) management system prototype. Catalog of available reusable software components

    Science.gov (United States)

    Hanley, Lionel

    1989-01-01

    The Ada Software Repository is a public-domain collection of Ada software and information. The Ada Software Repository is one of several repositories located on the SIMTEL20 Defense Data Network host computer at White Sands Missile Range, and available to any host computer on the network since 26 November 1984. This repository provides a free source for Ada programs and information. The Ada Software Repository is divided into several subdirectories. These directories are organized by topic, and their names and a brief overview of their topics are contained. The Ada Software Repository on SIMTEL20 serves two basic roles: to promote the exchange and use (reusability) of Ada programs and tools (including components) and to promote Ada education.

  8. TO ESTIMATE SERUM ADA LEVELS IN BCG VACCINATED CHILDREN

    Directory of Open Access Journals (Sweden)

    Manjunatha Babu

    2015-04-01

    Full Text Available BACKGROUND: Tuberculosis is an important cause of morbidity and mortality in both adults and children, especially in developing countries. For prevention of childhood tuberculosis, BCG vaccination is advocated. Protection is attained 4 - 6 weeks after BCG vaccination a nd is mainly due to cell mediated immunity. After BCG vaccination almost 12 to 15% of neonates do not develop scar but have positive cell mediated immune response. ADA estimation is simple and inexpensive method to assess the cell mediated immunity. OBJECT IVE: To estimate serum ADA levels in children with and without BCG scar, after receiving BCG vaccination. MATERIAL AND METHODS: This prospective observational study was conducted at a tertiary care hospital for a period of 2 years. Babies in post natal ward and infants up to the age of 12 weeks attending well baby clinic for BCG vaccination were included in the study. Serum ADA lev els were estimated before BCG vaccination and 12 - 14 weeks after the vaccination. ADA levels were estimated by colorimetric method. Presence or absence of BCG scar was noted at 12 - 14 weeks of age. RESULTS: A total of 75 babies followed up, of which only 60 babies noted to have scar and in rest 15 babies there was no scar noticed. Twenty unvaccinated babies at 12 weeks of age were included as controls. The Mean ADA levels are significantly elevated after BCG vaccination (34 . 12 ± 3 . 28 U/L in comparison to le vels before vaccination (12 . 55± 2 . 64 U/L with p value 0. 06. CONCLUSION: After BCG vaccination, there is increase in serum ADA levels indicating adequ ate immunity. Increase in ADA levels in children without scar after BCG vaccination may indicate the probability of adequate immunity.

  9. Adenosine in the tuberomammillary nucleus inhibits the histaminergic system via A1 receptors and promotes non-rapid eye movement sleep.

    Science.gov (United States)

    Oishi, Yo; Huang, Zhi-Li; Fredholm, Bertil B; Urade, Yoshihiro; Hayaishi, Osamu

    2008-12-16

    Adenosine has been proposed to promote sleep through A(1) receptors (A(1)R's) and/or A(2A) receptors in the brain. We previously reported that A(2A) receptors mediate the sleep-promoting effect of prostaglandin D(2), an endogenous sleep-inducing substance, and that activation of these receptors induces sleep and blockade of them by caffeine results in wakefulness. On the other hand, A(1)R has been suggested to increase sleep by inhibition of the cholinergic region of the basal forebrain. However, the role and target sites of A(1)R in sleep-wake regulation remained controversial. In this study, immunohistochemistry revealed that A(1)R was expressed in histaminergic neurons of the rat tuberomammillary nucleus (TMN). In vivo microdialysis showed that the histamine release in the frontal cortex was decreased by microinjection into the TMN of N(6)-cyclopentyladenosine (CPA), an A(1)R agonist, adenosine or coformycin, an inhibitor of adenosine deaminase, which catabolizes adenosine to inosine. Bilateral injection of CPA into the rat TMN significantly increased the amount and the delta power density of non-rapid eye movement (non-REM; NREM) sleep but did not affect REM sleep. CPA-promoted sleep was observed in WT mice but not in KO mice for A(1)R or histamine H(1) receptor, indicating that the NREM sleep promoted by A(1)R-specific agonist depended on the histaminergic system. Furthermore, the bilateral injection of adenosine or coformycin into the rat TMN increased NREM sleep, which was completely abolished by coadministration of 1,3-dimethyl-8-cyclopenthylxanthine, a selective A(1)R antagonist. These results indicate that endogenous adenosine in the TMN suppresses the histaminergic system via A(1)R to promote NREM sleep.

  10. Role of Activation-Induced Cytidine Deaminase in the Development of Oral Squamous Cell Carcinoma

    OpenAIRE

    Yosuke Nakanishi; Satoru Kondo; Naohiro Wakisaka; Akira Tsuji; Kazuhira Endo; Shigeyuki Murono; Makoto Ito; Kouichi Kitamura; Masamichi Muramatsu; Tomokazu Yoshizaki

    2013-01-01

    PURPOSE: In humans, activation-induced cytidine deaminase (AID) expression results due to inflammation and this deaminase activity is also involved in carcinogenesis. The aim of this study is to investigate the correlation between AID expression and the clinical classification of oral cancer tissues. EXPERIMENTAL DESIGN: The current study investigated the correlation between AID expression and the clinical classification of oral cancer tissues from 27 patients who underwent surgical resection...

  11. Mast cell adenosine receptors function: a focus on the A3 adenosine receptor and inflammation

    Directory of Open Access Journals (Sweden)

    Noam eRudich

    2012-06-01

    Full Text Available Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease (COPD patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells, as an attractive drug candidate. Four subtypes (A1, A2a, A2b and A3 of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R in mediating hyper responsiveness to adenosine in mast cells, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human mast cells. The relevance of mouse studies to the human is discussed.

  12. Adenosine triphosphate inhibition of yeast trehalase.

    Science.gov (United States)

    Panek, A D

    1969-09-01

    Yeast trehalase has been found to be inhibited non-competitively by adenosine triphosphate. Such a biological control could explain the accumulation of trehalose during the stationary phase of the growth curve. PMID:5370287

  13. Electrocardiographic profile of adenosine pharmacological stress testing

    OpenAIRE

    Sun, Hao; TIAN, YUEQIN; ZHENG, LIHUI; Pan, Qingrong; XIE, BOQIA

    2015-01-01

    Adenosine stress testing in conjunction with radionuclide myocardial perfusion imaging has become a common approach for the detection of coronary artery diseases in patients who are unable to perform adequate levels of exercise. However, specific electrocardiographic alterations during the test have been rarely described. Using a Chinese population, the aim of the present study was to provide a detailed electrocardiographic profile of adenosine stress testing. The study population included 1,...

  14. An automated quality assessor for Ada object-oriented designs

    Science.gov (United States)

    Bailin, Sidney C.

    1988-01-01

    A tool for evaluating object-oriented designs (OODs) for Ada software is described. The tool assumes a design expressed as a hierarchy of object diagrams. A design of this type identifies the objects of a system, an interface to each object, and the usage relationships between objects. When such a design is implemented in Ada, objects become packages, interfaces become package specifications, and usage relationships become Ada `with' clauses and package references. An automated quality assessor has been developed that is based on flagging undesirable design constructs. For convenience, distinctions are made among three levels of severity: questionable, undesirable, and hazardous. A questionable construct is one that may well be appropriate. An undesirable construct is one that should be changed because it is potentially harmful to the reliability, maintainability, or reusability of the software. A hazardous construct is one that is undesirable and that introduces a high level of risk.

  15. V Olimpíada Brasileira de Astronomia

    Science.gov (United States)

    Villas da Rocha, J. F.; Canalle, J. B. G.; Wuesnche, C. A.; de Medeiros, J. R., Silva, A. V. R.; Lavouras, D. F.; Dottori, H. A.; Maia, M. A. G.; Vieira Martins, R.; Poppe, P. C. R.

    2003-08-01

    Neste trabalho apresentamos os resultados da V Olimpíada Brasileira de Astronomia, a qual ocorreu em 11/05/2002 em todos os estabelecimentos de ensino fundamental ou médio previamente cadastrados. Participaram do evento 60.338 alunos distribuídos por 1469 escolas pertencentes a todos os Estados brasileiros. Uma equipe de 5 alunos foi escolhida para representar o Brasil na VII Olimpíada Internacional de Astronomia que ocorreu na Rússia em 2002 e dois de nossos alunos ganharam a medalha de bronze naquele evento.

  16. GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

    Science.gov (United States)

    Cross, James H., II

    1990-01-01

    The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

  17. State prisons are covered by ADA, 7th Circuit rules.

    Science.gov (United States)

    1997-07-25

    Prison inmate [name removed] sued the Indiana Department of Corrections, claiming it violated the Americans with Disabilities Act (ADA) by denying him access to education programs, the library, and the dining hall because he is blind. The 7th U.S. Circuit Court of Appeals rejected the district court's decision to dismiss the case based on the grounds that the ADA does not apply to prison inmates. The court held that the Department of Corrections cannot exclude an inmate with a disability from prison programs unless the accommodation caused an undue burden on the system. PMID:11364516

  18. An Ada run-time control architecture for telerobots

    Science.gov (United States)

    Balaram, J.; Rodriguez, G.

    1987-01-01

    This paper describes the architecture and Ada language implementation of a process-level run-time control subystem for the Jet Propulsion Laboratory (JPL) telerobot system. The concept of run-time control in a combined robot-teleoperation environment is examined and the telerobot system at JPL is described. An Ada language implementation of the JPL Telerobot Run-Time Controller (RTC) is described by highlighting the functional behavior of the subsystem, defining the internal modules, and providing a functional flow time sequence of internal module activity.

  19. AdaBoost分类算法的数学分析%The Mathematical Analysis of AdaBoost Algorithm

    Institute of Scientific and Technical Information of China (English)

    王兵

    2014-01-01

    This article provides a gentle introduction to the AdaBoost algorithm, and the mathematical analysis of how to draft classifiers and assign a weight for them, finally form a strong classifier through a set of weak classifiers.%本文对AdaBoost算法进行了介绍,并从整个数学推导过程中分析怎样挑选分类器并设置权值,最终通过一组弱分类器组合构成强分类器。

  20. Adenosine stress protocols for myocardial perfusion imaging

    Directory of Open Access Journals (Sweden)

    Baškot Branislav

    2008-01-01

    Full Text Available Background/Aim. Treadmill test combined with myocardial perfusion scintigraphy (MPS is a commonly used technique in the assessment of coronary artery disease. There are many patients, however, who may not be able to undergo treadmill test. Such patients would benefit from pharmacological stress procedures combined with MPS. The most commonly used pharmacological agents for cardiac stress are coronary vasodilatators (adenosine, dipyridamol and catecholamines. Concomitant low-level treadmill exercise with adenosine pharmacologic stress (AdenoEX during MPS has become commonly used in recent years. A number of studies have demonstrated a beneficial impact of AdenoEX protocol. The aim of the study was, besides introducing into practice the two types of protocols of pharmatological stress test with adenosine, as a preparation for MPS, to compare and monitor the frequency of their side effects to quality, acquisition, as well as to standardize the onset time of acquisition (diagnostic imaging for both protocols. Methods. A total of 130 patients underwent pharmacological stress test with adenosine (vasodilatator. In 108 of the patients we performed concomitant exercise (AdenoEX of low level (50W by a bicycle ergometar. In 28 of the patients we performed Adenosine abbreviated protocol (AdenoSCAN. Side effects of adenosine were followed and compared between the two kinds of protocols AdenoEX and AdenoSCAN. Also compared were image quality and suggested time of acquisition after the stress test. Results. Numerous side effects were found, but being short-lived they did not require any active interventions. The benefit of AdenoEX versus AdenoSCAN included decreased side effects (62% vs 87%, improved safety and patients tolerance, improved target-to-background ratios because of less subdiaphragmatic activity, earlier acquisition, and improved sensitivity. Conclusion. The safety and efficacy of adenosine pharmacological stress is even better with concomitant

  1. Myeloprotection by Cytidine Deaminase Gene Transfer in Antileukemic Therapy

    Directory of Open Access Journals (Sweden)

    Nico Lachmann

    2013-03-01

    Full Text Available Gene transfer of drug resistance (CTX-R genes can be used to protect the hematopoietic system from the toxicity of anticancer chemotherapy and this concept recently has been proven by overexpression of a mutant O6-methylguaninemethyltransferase in the hematopoietic system of glioblastoma patients treated with temozolomide. Given its protection capacity against such relevant drugs as cytosine arabinoside (ara-C, gemcitabine, decitabine, or azacytidine and the highly hematopoiesis-specific toxicity profile of several of these agents, cytidine deaminase (CDD represents another interesting candidate CTX-R gene and our group recently has established the myeloprotective capacity of CDD gene transfer in a number of murine transplant studies. Clinically, CDD overexpression appears particularly suited to optimize treatment strategies for acute leukemias and myelodysplasias given the efficacy of ara-C (and to a lesser degree decitabine and azacytidine in these disease entities. This article will review the current state of the art with regard to CDD gene transfer and point out potential scenarios for a clinical application of this strategy. In addition, risks and potential side effects associated with this approach as well as strategies to overcome these problems will be highlighted.

  2. Techniques and implementation of the embedded rule-based expert system using Ada

    Science.gov (United States)

    Liberman, Eugene M.; Jones, Robert E.

    1991-01-01

    Ada is becoming an increasingly popular programming language for large Government-funded software projects. Ada with its portability, transportability, and maintainability lends itself well to today's complex programming environment. In addition, expert systems have also assured a growing role in providing human-like reasoning capability and expertise for computer systems. The integration of expert system technology with Ada programming language, specifically a rule-based expert system using an ART-Ada (Automated Reasoning Tool for Ada) system shell is discussed. The NASA Lewis Research Center was chosen as a beta test site for ART-Ada. The test was conducted by implementing the existing Autonomous Power EXpert System (APEX), a Lisp-base power expert system, in ART-Ada. Three components, the rule-based expert system, a graphics user interface, and communications software make up SMART-Ada (Systems fault Management with ART-Ada). The main objective, to conduct a beta test on the ART-Ada rule-based expert system shell, was achieved. The system is operational. New Ada tools will assist in future successful projects. ART-Ada is one such tool and is a viable alternative to the straight Ada code when an application requires a rule-based or knowledge-based approach.

  3. Supreme Court to hear ADA suit involving arbitration clause.

    Science.gov (United States)

    1998-03-20

    The U.S. Supreme Court agreed to review a third case under the Americans with Disabilities Act (ADA) this year. The Supreme Court previously agreed to hear [name removed] v. [Name removed], involving a dentist who refused to treat an HIV-positive patient in his office. The second case is Pennsylvania Department of Corrections v. [Name removed], in which the State asserts that the ADA does not apply to prisons. The third involves whether an arbitration clause in a labor union's collective bargaining agreement prevents a court from hearing a union member's discrimination claim. [Name removed] longshoreman [name removed] alleges that the [name removed] and several employers violated the ADA when they refused to help him for employment referral. [Name removed] previously settled a workers' compensation disability claim with [name removed] and Terminal Co., his employer. Three years later he applied for work at the International Longshoreman's Association hiring hall and was referred to four different employers. The employers discovered he had received a worker's compensation settlement and would no longer accept [name removed] for employment referral. The case is important because union members can continue to file ADA charges with the EEOC and the outcomes will vary depending on the circuit where the union member happens to file the claim. PMID:11365192

  4. ADA and multi-microprocessor real-time simulation

    Science.gov (United States)

    Feyock, S.; Collins, W. R.

    1983-01-01

    The selection of a high-order programming language for a real-time distributed network simulation is described. The additional problem of implementing a language on a possibly changing network is addressed. The recently designed language ADA (trademarked by DoD) was chosen since it provides the best model of the underlying application to be simulated.

  5. A Pre-Allocation Strategy for Implement ADA95's Distrbuted Computing

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to realize distributed computing of Ada95, this paper discusses Ada95's distributed system model and an implement model of Ada95's distributed computing—workstation cluster model. Under this model, we presents a pre-allocation strategy for allocating the computation quantity of distributed units evenly among workstations and also reducing the communication expense between those distributed units.

  6. Mechanish of dTTP Inhibition of the Bifunctional dCTP Deaminase:dUTPase Encoded by Mycobacterium tuberculosis

    DEFF Research Database (Denmark)

    Helt, Signe Smedegaard; Thymark, Majbritt; Harris, Pernille;

    2008-01-01

    Recombinant deoxycytidine triphosphate (dCTP) deaminase from Mycobacterium tuberculosis was produced in Escherichia coli and purified. The enzyme proved to be a bifunctional dCTP deaminase:deoxyuridine triphosphatase. As such, the M. tuberculosis enzyme is the second bifunctional enzyme to be cha...

  7. A graphically oriented specification language for automatic code generation. GRASP/Ada: A Graphical Representation of Algorithms, Structure, and Processes for Ada, phase 1

    Science.gov (United States)

    Cross, James H., II; Morrison, Kelly I.; May, Charles H., Jr.; Waddel, Kathryn C.

    1989-01-01

    The first phase of a three-phase effort to develop a new graphically oriented specification language which will facilitate the reverse engineering of Ada source code into graphical representations (GRs) as well as the automatic generation of Ada source code is described. A simplified view of the three phases of Graphical Representations for Algorithms, Structure, and Processes for Ada (GRASP/Ada) with respect to three basic classes of GRs is presented. Phase 1 concentrated on the derivation of an algorithmic diagram, the control structure diagram (CSD) (CRO88a) from Ada source code or Ada PDL. Phase 2 includes the generation of architectural and system level diagrams such as structure charts and data flow diagrams and should result in a requirements specification for a graphically oriented language able to support automatic code generation. Phase 3 will concentrate on the development of a prototype to demonstrate the feasibility of this new specification language.

  8. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  9. Biological function of activation-induced cytidine deaminase (AID).

    Science.gov (United States)

    Kumar, Ritu; DiMenna, Lauren J; Chaudhuri, Jayanta; Evans, Todd

    2014-01-01

    Activation-induced Cytidine Deaminase (AID) is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  10. AdaBoost for Improved Voice-Band Signal Classification

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A good voice-band signal classification can not only enable the safe application of speech coding techniques,the implementation of a Digital Signal Interpolation (DSI)system, but also facilitate network administration and planning by providing accurate voice-band traffic analysis.A new method is proposed to detect and classify the presence of various voice-band signals on the General Switched Telephone Network ( GSTN ). The method uses a combination of simple base classifiers through the AdaBoost algorithm. The conventional classification features for voiceband data classification are combined and optimized by the AdaBoost algorithm and spectral subtraction method.Experiments show the simpleness, effectiveness, efficiency and flexibility of the method.

  11. Olimpíadas e geopolítica

    Directory of Open Access Journals (Sweden)

    João Fábio Bertonha

    2008-09-01

    Full Text Available

    o artigo trata de competições esportivas,

    em especial as olimpíadas. Nelas, valorizam-se o

    nacionalismo e o poder dos países.

  12. Extracting Objects from Ada83 Programs: A Case Study

    Institute of Scientific and Technical Information of China (English)

    XU Baowen; ZHOU Yuming

    2001-01-01

    Reengineering legacy systems written in conventional procedural languages to equivalent OO systems makes software more maintainable and reliable. This paper proposes a method for extracting objects from legacy Ada83 systems using module features. First, metrics are developed to measure module cohesion. Then, effects on cohesion from changing module components are analyzed and rules about how to extract inheritance relations among objects are given. At the end of this paper, an object-extracting algorithm using module features is proposed.

  13. Bernoulli Numbers: from Ada Lovelace to the Debye Functions

    OpenAIRE

    Sparavigna, Amelia Carolina

    2016-01-01

    Jacob Bernoulli owes his fame for the numerous contributions to calculus and for his discoveries in the field of probability. Here we will discuss one of his contributions to the theory of numbers, the Bernoulli numbers. They were proposed as a case study by Ada Lovelace in her analysis of Menabrea's report on Babbage Analytical Engine. It is probable that it was this Lovelace's work, that inspired Hans Thirring in using the Bernoulli numbers in the calculus of the Debye functions.

  14. AN ADA LINEAR ALGEBRA PACKAGE MODELED AFTER HAL/S

    Science.gov (United States)

    Klumpp, A. R.

    1994-01-01

    This package extends the Ada programming language to include linear algebra capabilities similar to those of the HAL/S programming language. The package is designed for avionics applications such as Space Station flight software. In addition to the HAL/S built-in functions, the package incorporates the quaternion functions used in the Shuttle and Galileo projects, and routines from LINPAK that solve systems of equations involving general square matrices. Language conventions in this package follow those of HAL/S to the maximum extent practical and minimize the effort required for writing new avionics software and translating existent software into Ada. Valid numeric types in this package include scalar, vector, matrix, and quaternion declarations. (Quaternions are fourcomponent vectors used in representing motion between two coordinate frames). Single precision and double precision floating point arithmetic is available in addition to the standard double precision integer manipulation. Infix operators are used instead of function calls to define dot products, cross products, quaternion products, and mixed scalar-vector, scalar-matrix, and vector-matrix products. The package contains two generic programs: one for floating point, and one for integer. The actual component type is passed as a formal parameter to the generic linear algebra package. The procedures for solving systems of linear equations defined by general matrices include GEFA, GECO, GESL, and GIDI. The HAL/S functions include ABVAL, UNIT, TRACE, DET, INVERSE, TRANSPOSE, GET, PUT, FETCH, PLACE, and IDENTITY. This package is written in Ada (Version 1.2) for batch execution and is machine independent. The linear algebra software depends on nothing outside the Ada language except for a call to a square root function for floating point scalars (such as SQRT in the DEC VAX MATHLIB library). This program was developed in 1989, and is a copyrighted work with all copyright vested in NASA.

  15. Software tools to aid Pascal and Ada program design

    Energy Technology Data Exchange (ETDEWEB)

    Jankowitz, H.T.

    1987-01-01

    This thesis describes a software tool which analyses the style and structure of Pascal and Ada programs by ensuring that some minimum design requirements are fulfilled. The tool is used in much the same way as a compiler is used to teach students the syntax of a language, only in this case issues related to the design and structure of the program are of paramount importance. The tool operates by analyzing the design and structure of a syntactically correct program, automatically generating a report detailing changes that need to be made in order to ensure that the program is structurally sound. The author discusses how the model gradually evolved from a plagiarism detection system which extracted several measurable characteristics in a program to a model that analyzed the style of Pascal programs. In order to incorporate more-sophistical concepts like data abstraction, information hiding and data protection, this model was then extended to analyze the composition of Ada programs. The Ada model takes full advantage of facilities offered in the language and by using this tool the standard and quality of written programs is raised whilst the fundamental principles of program design are grasped through a process of self-tuition.

  16. Internalization and desensitization of adenosine receptors.

    NARCIS (Netherlands)

    Klaasse, E.C.; IJzerman, A.P.; Grip, W.J. de; Beukers, M.W.

    2008-01-01

    Until now, more than 800 distinct G protein-coupled receptors (GPCRs) have been identified in the human genome. The four subtypes of the adenosine receptor (A(1), A(2A), A(2B) and A(3) receptor) belong to this large family of GPCRs that represent the most widely targeted pharmacological protein clas

  17. Isolation and characterization of human liver guanine deaminase.

    Science.gov (United States)

    Gupta, N K; Glantz, M D

    1985-01-01

    Guanine deaminase (EC 3.5.4.3, guanine aminohydrolase [GAH]) was purified 3248-fold from human liver to homogeneity with a specific activity of 21.5. A combination of ammonium sulfate fractionation, and DEAE-cellulose, hydroxylapatite, and affinity chromatography with guanine triphosphate ligand were used to purify the enzyme. The enzyme was a dimer protein of a molecular weight of 120,000 with each subunit of 59,000 as determined by gel filtration and sodium dodecyl sulfate-gel electrophoresis. Isoelectric focusing gave a pI of 4.76. It was found to be an acidic protein, as evidenced by the amino acid analysis, enriched with glutamate, aspartate, alanine and glycine. It showed a sharp pH optimum of 8.0. The apparent Km for guanine was determined to be 1.53 X 10(-5) M at pH 6.0 and 2 X 10(-4) M for 8-azaguanine as a substrate at pH 6.0. The enzyme was found to be sensitive to p-hydroxymercuribenzoate inhibition with a Ki of 1.53 X 10(-5) M and a Ki of 5 X 10(-5) M with 5-aminoimidazole-4-carboxamide as an inhibitor. The inhibition with iodoacetic acid showed only a 7% loss in the activity at 1 X 10(-4) M and a 24% loss at 1 X 10(-3) M after 30 min of incubation, whereas p-hydroxymercuribenzoate incubation for 30 min resulted in a 91% loss of activity at a concentration of 1 X 10(-4) M. Guanine was the substrate for all of the inhibition studies. The enzyme was observed to be stable up to 40 degrees C, with a loss of almost all activity at 65 degrees C with 30 min incubation. Two pKa values were obtained at 5.85 and 8.0. Analysis of the N-terminal amino acid proved to be valine while the C-terminal residue was identified as alanine. PMID:3966794

  18. Adenosine: An immune modulator of inflammatory bowel diseases

    Institute of Scientific and Technical Information of China (English)

    Jeff Huaqing Ye; Vazhaikkurichi M Rajendran

    2009-01-01

    Inflammatory bowel disease (IBD) is a common and lifelong disabling gastrointestinal disease. Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response. Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models. High extracellular adenosine suppresses and resolves chronic inflammation in IBD models. High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis. Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells, respectively. Increased extracellular adenosine levels activate the A2a receptor, which would reduce cytokines responsible for chronic inflammation.

  19. Improved cytotoxic effects of Salmonella-producing cytosine deaminase in tumour cells

    Science.gov (United States)

    Mesa-Pereira, Beatriz; Medina, Carlos; Camacho, Eva María; Flores, Amando; Santero, Eduardo

    2015-01-01

    In order to increase the cytotoxic activity of a Salmonella strain carrying a salicylate-inducible expression system that controls cytosine deaminase production, we have modified both, the vector and the producer bacterium. First, the translation rates of the expression module containing the Escherichia coli codA gene cloned under the control of the Pm promoter have been improved by using the T7 phage gene 10 ribosome binding site sequence and replacing the original GUG start codon by AUG. Second, to increase the time span in which cytosine deaminase may be produced by the bacteria in the presence of 5-fluorocytosine, a 5-fluorouracyl resistant Salmonella strain has been constructed by deleting its upp gene sequence. This new Salmonella strain shows increased cytosine deaminase activity and, after infecting tumour cell cultures, increased cytotoxic and bystander effects under standard induction conditions. In addition, we have generated a purD mutation in the producer strain to control its intracellular proliferation by the presence of adenine and avoid the intrinsic Salmonella cell death induction. This strategy allows the analysis and comparison of the cytotoxic effects of cytosine deaminase produced by different Salmonella strains in tumour cell cultures. PMID:25227763

  20. The circadian regulation of sleep: impact of a functional ADA-polymorphism and its association to working memory improvements.

    Directory of Open Access Journals (Sweden)

    Carolin F Reichert

    Full Text Available Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers, previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM sleep and slow wave sleep concomitant with reduced power between 8-16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is

  1. Event-based Implicit Invocation Decentralized in Ada

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Nowadays more and more attraction is drawn by the event-basedimplicit invocation - one of useful architectural patterns, because of its loose couplin g between components in the architecture and reactive integration in software sys tems. Analyzing object-oriented interaction with objects, this paper, based upo n the principle of software architecture, presents an approach on event-based ob j ect model with Ada exception handler. Consequently it is possible for us to impr ove, with adding specific architectural patterns, traditional programming langua ges into architectural description languages.

  2. Large distributed control system using ADA in fusion research

    Energy Technology Data Exchange (ETDEWEB)

    Woodruff, J. P., LLNL

    1998-04-21

    Construction of the National Ignition Facility laser at Lawrence Livermore National Laboratory features a large distributed control system constructed using object-oriented software engineering techniques. Control of 60,000 devices is effected using a network of some 500 computers that run software written in Ada and communicating through CORBA. The project has completed its final design review; implementation of the first of five planned increments will be delivered at the end of fiscal year 1998. Preliminary measures of the distributed controls performance confirm the design decisions reported in this paper, and the measurement and supporting simulation of full system performance continue.

  3. ADaPPT: Enterprise Architecture Thinking for Information Systems Development

    Directory of Open Access Journals (Sweden)

    Hanifa Shah

    2011-01-01

    Full Text Available Enterprises have architecture: whether it is visible or invisible is another matter. An enterprises' architecture determines the way in which it works to deliver its business objectives and the way in which it can change to continue to meet its evolving business objectives. Enterprise architectural thinking can facilitate effective strategic planning and information systems development. This paper reviews enterprise architecture (EA and its concepts. It briefly considers EA frameworks. It describes the ADaPPT (Aligning Data, People, Processes and Technology EA approach as a means to managing organisational complexity and change. Future research directions are discussed.

  4. Adenosine receptors and asthma in humans

    OpenAIRE

    Wilson, C N

    2008-01-01

    According to an executive summary of the GINA dissemination committee report, it is now estimated that approximately 300 million people (5% of the global population or 1 in 20 persons) have asthma. Despite the scientific progress made over the past several decades toward improving our understanding of the pathophysiology of asthma, there is still a great need for improved therapies, particularly oral therapies that enhance patient compliance and that target new mechanisms of action. Adenosine...

  5. Chemoelectrical energy conversion of adenosine triphosphate

    Science.gov (United States)

    Sundaresan, Vishnu Baba; Sarles, Stephen Andrew; Leo, Donald J.

    2007-04-01

    Plant and animal cell membranes transport charged species, neutral molecules and water through ion pumps and channels. The energy required for moving species against established concentration and charge gradients is provided by the biological fuel - adenosine triphosphate (ATP) -synthesized within the cell. The adenosine triphosphatase (ATPases) in a plant cell membrane hydrolyze ATP in the cell cytoplasm to pump protons across the cell membrane. This establishes a proton gradient across the membrane from the cell exterior into the cell cytoplasm. This proton motive force stimulates ion channels that transport nutrients and other species into the cell. This article discusses a device that converts the chemical energy stored in adenosine triphosphate into electrical power using a transporter protein, ATPase. The V-type ATPase proteins used in our prototype are extracted from red beet(Beta vulgaris) tonoplast membranes and reconstituted in a bilayer lipid membrane or BLM formed from POPC and POPS lipids. A pH7 medium that can support ATP hydrolysis is provided on both sides of the membrane and ATP is dissolved in the pH7 buffer on one side of the membrane. Hydrolysis of ATP results in the formation of a phosphate ion and adenosine diphosphate. The energy from the reaction activates ATPase in the BLM and moves a proton across the membrane. The charge gradient established across the BLM due to the reaction and ion transport is converted into electrical current by half-cell reference electrodes. The prototype ATPase cell with an effective BLM area of 4.15 mm2 carrying 15 μl of ATPase proteins was observed to develop a steady state peak power output of 70 nW, which corresponds to a specific power of 1.69 μW/cm2 and a current density of 43.4 μA/cm2 of membrane area.

  6. Aminopyrimidine derivatives as adenosine antagonists / Janke Kleynhans

    OpenAIRE

    Kleynhans, Janke

    2013-01-01

    Aims of this project - The aim of this study was to design and synthesise novel 2-aminopyrimidine derivatives as potential adenosine A1 and A2A receptor antagonists. Background and rationale - Parkinson’s disease is the second most common neurodegenerative disorder (after Alzheimer’s disease) and is characterised by the selective death of the dopaminergic neurons of the nigro-striatal pathway. Distinctive motor symptoms include bradykinesia, muscle rigidity and tremor, while non-m...

  7. TCP-ADaLR: TCP with adaptive delay and loss response for broadband GEO satellite networks

    OpenAIRE

    Omueti, Modupe Omogbohun

    2007-01-01

    Transmission Control Protocol (TCP) performance degrades in broadband geostationary satellite networks due to long propagation delays and high bit error rates. In this thesis, we propose TCP with algorithm modifications for adaptive delay and loss response (TCP-ADaLR) to improve TCP performance. TCP-ADaLR incorporates delayed acknowledgement mechanism recommended for Internet hosts. We evaluate and compare the performance of TCP-ADaLR, TCP SACK, and TCP NewReno, with and without delayed ackno...

  8. Disfungsi Keluarga dalam Novel Cinta Masih Ada Karya Embart Nugroho: Suatu Tinjauan Sosiologi Sastra

    OpenAIRE

    Lestari, Aprillia

    2015-01-01

    Sastra adalah Karya sastra merupakan ungkapan ide manusia dari pengalaman pribadi. Salah satu karya sastra yang dianggap sebagai cerminan kehidupan nyata adalah novel. Penelitian ini membahas tentang penyebab dan dampak disfungsi keluarga pada novel Cinta Masih Ada. Tujuan penelitian ini adalah untuk Mendeskripsikan penyebab disfungsi keluarga yang terdapat pada novel Cinta Masih Ada dan Mendeskripsikan dampak-dampak disfungsi keluarga yang terdapat pada novel Cinta Masih Ada karya Embart Nug...

  9. N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors

    Science.gov (United States)

    Fang, Ming; Chai, Yiqiu; Chen, Guanjv; Wang, Huidong; Huang, Bo

    2016-01-01

    The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32–35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR. PMID:27668428

  10. Effects of adenosine agonist R-phenylisopropyl-adenosine on halothane anesthesia and antinociception in rats

    Institute of Scientific and Technical Information of China (English)

    Hai-chun MA; Yan-fen WANG; Chun-sheng FENG; Hua ZHAO; Shuji DOHI

    2005-01-01

    Aim: To investigate the antinociceptive effect of adenosine agonist Rphenylisopropyl-adenosine (R-PIA) given to conscious rats by intracerebroventricular (ICV) and intrathecal (IT), and identify the effect of R-PIA on minimum alveolar concentration (MAC) of halothane with pretreatment of A1 receptor an tagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or K+ channel blocker 4-aminopyridine (4-AP). Methods: Sprague-Dawley rats were implanted with 24 gauge stainless steel guide cannula using stereotaxic apparatus and ICV method, and an IT catheter (PE-10, 8.5 cm) was inserted into the lumbar subarachnoid space, while the rats were under pentobarbital anesthesia. After one week of recovery from surgery, rats were randomly assigned to one of the following protocols: MAC of halothane, or tail-flick latency. All measurements were performed after R-PIA (0.8-2.0 μg) microinjection into ICV and IT with or without pretreatment of DPCPX or 4-AP. Results: Microinjection of adenosine agonist R PIA in doses of 0.8-2.0 μg into ICV and IT produced a significant dose- and time dependent antinociceptive action as reflected by increasing latency times and ICV administration of adenosine agonist R-PIA (0.8 μg) reducing halothane anes thetic requirements (by 29%). The antinociception and reducing halothane requirements effected by adenosine agonist R-PIA was abolished by DPCPX and 4-AP. Conclusion: ICV and IT administration of adenosine agonist R-PIA produced an antinociceptive effect in a dose-dependent manner and decreased hal othane MAC with painful stimulation through activation of A1 receptor subtype, and the underlying mechanism involves K+ channel activation.

  11. Rationale for the proposed standard for a generic package of primitive functions for Ada

    Energy Technology Data Exchange (ETDEWEB)

    Dritz, K.W.

    1990-12-01

    This paper supplements the Proposed Standard for a Generic Package of Primitive Functions for Ada,'' written by the ISO- IEC/JTC1/SC22/WG9 (Ada) Numerics Rapporteur Group. Based on recommendations made jointly by the ACM SIGAda Numerics Working Group and the Ada-Europe Numerics Working Group, the proposed primitive functions standard is the second of several anticipated secondary standards to address the interrelated issues of portability, efficiency, and robustness of numerical software written in Ada. Its purpose, features, and developmental history are outlined in this commentary. 16 refs.

  12. ART/Ada design project, phase 1. Task 2 report: Detailed design

    Science.gov (United States)

    Allen, Bradley P.

    1988-01-01

    Various issues are studied in the context of the design of an Ada based expert system building tool. Using an existing successful design as a starting point, the impact is analyzed of the Ada language and Ada development methodologies on that design, the Ada system is redesigned, and its performance is analyzed using both complexity-theoretic and empirical techniques. The algorithms specified in the overall design are refined, resolving and documenting any open design issues, identifying each system module, documenting the internal architecture and control logic, and describing the primary data structures involved in the module.

  13. The Impact of Ada and Object-Oriented Design in NASA Goddard's Flight Dynamics Division

    Science.gov (United States)

    Waligora, Sharon; Bailey, John; Stark, Mike

    1996-01-01

    This paper presents the highlights and key findings of 10 years of use and study of Ada and object-oriented design in NASA Goddard's Flight Dynamics Division (FDD). In 1985, the Software Engineering Laboratory (SEL) began investigating how the Ada language might apply to FDD software development projects. Although they began cautiously using Ada on only a few pilot projects, they expected that, if the Ada pilots showed promising results, the FDD would fully transition its entire development organization from FORTRAN to Ada within 10 years. However, 10 years later, the FDD still produced 80 percent of its software in FORTRAN and had begun using C and C++, despite positive results on Ada projects. This paper presents the final results of a SEL study to quantify the impact of Ada in the FDD, to determine why Ada has not flourished, and to recommend future directions regarding Ada. Project trends in both languages are examined as are external factors and cultural issues that affected the infusion of this technology. The detailed results of this study were published in a formal study report in March of 1995. This paper supersedes the preliminary results of this study that were presented at the Eighteenth Annual Software Engineering Workshop in 1993.

  14. Assessing the effects of heavy metals in ACC deaminase and IAA production on plant growth-promoting bacteria.

    Science.gov (United States)

    Carlos, Mendoza-Hernández José; Stefani, Perea-Vélez Yazmin; Janette, Arriola-Morales; Melani, Martínez-Simón Sara; Gabriela, Pérez-Osorio

    2016-01-01

    This study poses a methodology in order to simultaneously quantify ACC deaminase and IAA levels in the same culture medium. Ten bacterial strains isolated from plant rhizosphere naturally settled in mining residues were chosen. These bacterial strains were characterized as PGPB, and all of them showed at least three characteristics (indole-3 acetic acid and siderophore production, ACC deaminase enzyme activity, and inorganic phosphate solubilization). Taxonomic identification showed that the strains belong to Enterobacter, Serratia, Klebsiella, and Escherichia genera. Similarly, both the ACC deaminase enzyme activity and the IAA synthesis in the presence of Cu, As, Pb, Ni, Cd, and Mn were measured. The results showed that both the ACC deaminase enzyme activity and the IAA synthesis were higher with the Pb, As, and Cu treatments than with the Escherichia N16, Enterobacter K131, Enterobacter N9, and Serratia K120 control treatments. On the other hand, Ni, Cd, and Mn negatively affected both the ACC deaminase enzyme activity and the IAA production on every bacterium except on the Klebsiella Mc173 strain. Serratia K120 bacterium got a positive correlation between ACC deaminase and IAA in the presence of every heavy metal, and it also promoted Helianthus annuus plant growth, showing a potential use in phytoremediation systems. PMID:27296962

  15. A metabolic immune checkpoint: adenosine in tumor microenvironment

    Directory of Open Access Journals (Sweden)

    Akio eOhta

    2016-03-01

    Full Text Available Within tumors, some areas are less oxygenated than others. Since their home ground is under chronic hypoxia, tumor cells adapt to this condition by activating aerobic glycolysis; however, this hypoxic environment is very harsh for incoming immune cells. Deprivation of oxygen limits availability of energy sources and induces accumulation of extracellular adenosine in tumors. Extracellular adenosine, upon binding with adenosine receptors on the surface of various immune cells, suppresses pro-inflammatory activities. In addition, signaling through adenosine receptors upregulates a number of anti-inflammatory molecules and immunoregulatory cells, leading to the establishment of a long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine, tumors can discourage anti-tumor immune responses no matter how the response was induced, whether it was spontaneous or artificially introduced with a therapeutic intention. Preclinical studies have shown the significance of adenosine in tumor survival strategy by demonstrating tumor regression after inactivation of adenosine receptors, inhibition of adenosine-producing enzymes or reversal of tissue hypoxia. These promising results indicate a potential use of the inhibitors of the hypoxia-adenosine pathway for cancer immunotherapy.

  16. Pretreatment with adenosine and adenosine A1 receptor agonist protects against intestinal ischemia-reperfusion injury in rat

    Institute of Scientific and Technical Information of China (English)

    V Haktan Ozacmak; Hale Sayan

    2007-01-01

    AIM: To examine the effects of adenosine and A1 receptor activation on reperfusion-induced small intestinal injury.METHODS: Rats were randomized into groups with sham operation, ischemia and reperfusion, and systemic treatments with either adenosine or 2-chloro-N6-cyclopentyladenosine, A1 receptor agonist or 8-cyclopentyl-1,3-dipropylxanthine, A1 receptor antagonist, plus adenosine before ischemia. Following reperfusion, contractions of ileum segments in response to KCl, carbachol and substance P were recorded. Tissue myeloperoxidase,malondialdehyde, and reduced glutathione levels were measured.RESULTS: Ischemia significantly decreased both contraction and reduced glutathione level which were ameliorated by adenosine and agonist administration. Treatment also decreased neutrophil infiltration and membrane lipid peroxidation. Beneficial effects of adenosine were abolished by pretreatment with A1 receptor antagonist.CONCLUSION: The data suggest that adenosine and A1 receptor stimulation attenuate ischemic intestinal injury via decreasing oxidative stress, lowering neutrophil infiltration, and increasing reduced glutathione content.

  17. Identification of small molecule compounds with higher binding affinity to guanine deaminase (cypin) than guanine

    OpenAIRE

    Fernández, José R.; Sweet, Eric S; Welsh, William J.; Firestein, Bonnie L

    2010-01-01

    Guanine deaminase (GDA; cypin) is an important metalloenzyme that processes the first step in purine catabolism, converting guanine to xanthine by hydrolytic deamination. In higher eukaryotes, GDA also plays an important role in the development of neuronal morphology by regulating dendritic arborization. In addition to its role in the maturing brain, GDA is thought to be involved in proper liver function since increased levels of GDA activity have been correlated with liver disease and transp...

  18. Mechanism of protection of adenosine from sulphate radical anion and repair of adenosine radicals by caffeic acid in aqueous solution

    Indian Academy of Sciences (India)

    M Sudha Swaraga; L Charitha; M Adinarayana

    2005-07-01

    The photooxidation of adenosine in presence of peroxydisulphate (PDS) has been studied by spectrophotometrically measuring the absorbance of adenosine at 260 nm. The rates of oxidation of adenosine by sulphate radical anion have been determined in the presence of different concentrations of caffeic acid. Increase in [caffeic acid] is found to decrease the rate of oxidation of adenosine suggesting that caffeic acid acts as an efficient scavenger of $SO_{4}^{\\bullet-}$ and protects adenosine from it. Sulphate radical anion competes for adenosine as well as for caffeic acid. The quantum yields of photooxidation of adenosine have been calculated from the rates of oxidation of adenosine and the light intensity absorbed by PDS at 254 nm, the wavelength at which PDS is activated to sulphate radical anion. From the results of experimentally determined quantum yields (exptl) and the quantum yields calculated (cal) assuming caffeic acid acting only as a scavenger of $SO_{4}^{\\bullet-}$ show that exptl values are lower than cal values. The ' values, which are experimentally found quantum yield values at each caffeic acid concentration and corrected for $SO_{4}^{\\bullet-}$ scavenging by caffeic acid, are also found to be greater than exptl values. These observations suggest that the transient adenosine radicals are repaired by caffeic acid in addition to scavenging of sulphate radical anions.

  19. Electroacupuncture improves neuropathic pain Adenosine,adenosine 5'-triphosphate disodium and their receptors perhaps change simultaneously

    Institute of Scientific and Technical Information of China (English)

    Wen Ren; Wenzhan Tu; Songhe Jiang; Ruidong Cheng; Yaping Du

    2012-01-01

    Applying a stimulating current to acupoints through acupuncture needles-known as electroacupuncture-has the potential to produce analgesic effects in human subjects and experimental animals.When acupuncture was applied in a rat model,adenosine 5'-triphosphate disodium in the extracellular space was broken down into adenosine,which in turn inhibited pain transmission by means of an adenosine A1 receptor-dependent process.Direct injection of an adenosine A1 receptor agonist enhanced the analgesic effect of acupuncture.The analgesic effect of acupuncture appears to be mediated by activation of A1 receptors located on ascending nerves.In neuropathic pain,there is upregulation of P2X purinoceptor 3(P2X3)receptor expression in dorsal root ganglion neurons.Conversely,the onset of mechanical hyperalgesia was diminished and established hyperalgesia was significantly reversed when P2X3 receptor expression was downregulated.The pathways upon which electroacupuncture appear to act are interwoven with pain pathways,and electroacupuncture stimuli converge with impulses originating from painful areas.Electroacupuncture may act via purinergic A1 and P2X3 receptors simultaneously to induce an analgesic effect on neuropathic pain.

  20. Beyond SHM and CSR: AID and related cytidine deaminases in the host response to viral infection.

    Science.gov (United States)

    Rosenberg, Brad R; Papavasiliou, F Nina

    2007-01-01

    As the primary effector of immunoglobulin somatic hypermutation (SHM) and class switch recombination (CSR), activation-induced cytidine deaminase (AID) serves an important function in the adaptive immune response. Recent advances have demonstrated that AID and a group of closely related cytidine deaminases, the APOBEC3 proteins, also act in the innate host response to viral infection. Antiviral activity was first attributed to APOBEC3G as a potent inhibitor of HIV. It is now apparent that the targets of the APOBEC3 proteins extend beyond HIV, with family members acting against a wide variety of viruses as well as host-encoded retrotransposable genetic elements. Although it appears to function through a different mechanism, AID also possesses antiviral properties. Independent of its antibody diversification functions, AID protects against transformation by Abelson murine leukemia virus (Ab-MLV), an oncogenic retrovirus. Additionally, AID has been implicated in the host response to other pathogenic viruses. These emerging roles for the AID/APOBEC cytidine deaminases in viral infection suggest an intriguing evolutionary connection of innate and adaptive immune mechanisms.

  1. Bacteria with ACC deaminase can promote plant growth and help to feed the world.

    Science.gov (United States)

    Glick, Bernard R

    2014-01-20

    To feed all of the world's people, it is necessary to sustainably increase agricultural productivity. One way to do this is through the increased use of plant growth-promoting bacteria; recently, scientists have developed a more profound understanding of the mechanisms employed by these bacteria to facilitate plant growth. Here, it is argued that the ability of plant growth-promoting bacteria that produce 1-aminocyclopropane-1-carboxylate (ACC) deaminase to lower plant ethylene levels, often a result of various stresses, is a key component in the efficacious functioning of these bacteria. The optimal functioning of these bacteria includes the synergistic interaction between ACC deaminase and both plant and bacterial auxin, indole-3-acetic acid (IAA). These bacteria not only directly promote plant growth, they also protect plants against flooding, drought, salt, flower wilting, metals, organic contaminants, and both bacterial and fungal pathogens. While a considerable amount of both basic and applied work remains to be done before ACC deaminase-producing plant growth-promoting bacteria become a mainstay of plant agriculture, the evidence indicates that with the expected shift from chemicals to soil bacteria, the world is on the verge of a major paradigm shift in plant agriculture. PMID:24095256

  2. Large distributed control system using Ada in fusion research

    International Nuclear Information System (INIS)

    Construction of the National Ignition Facility laser at Lawrence Livermore National Laboratory features a distributed control system that uses object-oriented software engineering techniques. Control of 60,000 devices is effected using a network of some 500 computers. The software is being written in Ada and communicates through CORBA. Software controls are implemented in two layers: individual device controllers and a supervisory layer. The software architecture provides services in the form of frameworks that address issues common to event-driven control systems. Those services are allocated to levels that strictly prescribe their interdependency so the levels are separately reusable. The project has completed its final design review. The delivery of the first increment takes place in October 1998. Keywords Distributed control system, object-oriented development, CORBA, application frameworks, levels of abstraction

  3. Inclusion of geriatric nutrition in ADA-approved undergraduate programs.

    Science.gov (United States)

    Shoaf, L R; Jensen, H M

    1989-09-01

    All ADA Plan IV programs were surveyed to determine whether geriatric nutrition was included in their curriculums. Of the 268 Plan IV programs, 66% responded. Less than one-fifth of the programs offered or planned to offer a specific geriatric nutrition course. An overview of geriatric nutrition occurred most frequently in a human nutrition course. A practicum/clinical experience or a course other than nutrition most frequently provided in-depth study, if such was available. Nursing homes and congregate meal sites were the primary locations for experiences with the geriatric population. Major activities with that age group included (a) taking diet histories, (b) making nutrition assessments, and (c) providing diet instruction. In some programs, didactic and experiential training with the geriatric population may not be adequate to prepare dietetic undergraduate students to meet the health care needs of that growing segment of society. PMID:2768741

  4. Large distributed control system using Ada in fusion research

    Energy Technology Data Exchange (ETDEWEB)

    Van Arsdall, P J; Woodruff, J P

    1998-08-11

    Construction of the National Ignition Facility laser at Lawrence Livermore National Laboratory features a distributed control system that uses object-oriented software engineering techniques. Control of 60,000 devices is effected using a network of some 500 computers. The software is being written in Ada and communicates through CORBA. Software controls are implemented in two layers: individual device controllers and a supervisory layer. The software architecture provides services in the form of frameworks that address issues common to event-driven control systems. Those services are allocated to levels that strictly prescribe their interdependency so the levels are separately reusable. The project has completed its final design review. The delivery of the first increment takes place in October 1998. Keywords Distributed control system, object-oriented development, CORBA, application frameworks, levels of abstraction

  5. 基于AdaCostBoost算法的网络钓鱼检测%Phishing Detection System Based on AdaCostBoost Algorithm

    Institute of Scientific and Technical Information of China (English)

    曾传璜; 李思强; 张小红

    2015-01-01

    针对日益严重的网络钓鱼攻击,提出机器学习的方法进行钓鱼网站的检测和判断。首先,根据URL提取敏感特征,然后,采用AdaBoost算法进行训练出分类器,再用训练好的分类器对未知URL检测识别。最后,针对非平衡代价问题,采用了改进后的 AdaBoost 算法--AdaCostBoost,加入代价因子的计算。实验结果表明,文中提出的网络钓鱼检测方法,具有较优的检测性能。%For increasing serious phishing attacks, machine-learning method is proposed to detect phishing webs. Firstly, sensitive features are extracted from the URL, then, using AdaBoost algorithm to get the trained classifier, and then the classifier is used to detect unknown URLs. Finally, considering of non-equilibrium problems of AdaBoost, the paper puts forward the improved learning algorithm called AdaCostBoost, which contains computation of cost factors. According to the experiment result, the proposed phishing detection method has better detection performance.

  6. High-dose adenosine overcomes the attenuation of myocardial perfusion reserve caused by caffeine.

    OpenAIRE

    Reyes, E.; Loong, C Y; Harbinson, Mark; Donovan, J; Anagnostopoulos, C.; Underwood, S. R.

    2008-01-01

    Objectives:We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation.Background:Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose.Methods:Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (bas...

  7. 76 FR 79065 - Recordkeeping and Reporting Requirements Under Title VII, the ADA and GINA

    Science.gov (United States)

    2011-12-21

    ... Employment Opportunity Commission 29 CFR Part 1602 Recordkeeping and Reporting Requirements Under Title VII..., revised as of July 1, 2011, in Part 1602, remove the words ``section 709(c) of title VII or section 107 of the ADA'' and add in their place the words ``section 709(c) of title VII, section 107 of the ADA,...

  8. NRPA Law Review. Combat Karate Class Illustrates ADA "Direct Threat" Exception.

    Science.gov (United States)

    Kozlowski, James C.

    2000-01-01

    Describes the Americans with Disabilities Act (ADA), which prohibits discrimination against people with disabilities, highlighting a lawsuit involving a boy with AIDS who was barred from a traditional combat-oriented martial arts school. Courts ruled that his exclusion did not violate the ADA because he posed significant health and safety risks to…

  9. Storage management in Ada. Three reports. Volume 1: Storage management in Ada as a risk to the development of reliable software. Volume 2: Relevant aspects of language. Volume 3: Requirements of the language versus manifestations of current implementations

    Science.gov (United States)

    Auty, David

    1988-01-01

    The risk to the development of program reliability is derived from the use of a new language and from the potential use of new storage management techniques. With Ada and associated support software, there is a lack of established guidelines and procedures, drawn from experience and common usage, which assume reliable behavior. The risk is identified and clarified. In order to provide a framework for future consideration of dynamic storage management on Ada, a description of the relevant aspects of the language is presented in two sections: Program data sources, and declaration and allocation in Ada. Storage-management characteristics of the Ada language and storage-management characteristics of Ada implementations are differentiated. Terms that are used are defined in a narrow and precise sense. The storage-management implications of the Ada language are described. The storage-management options available to the Ada implementor and the implications of the implementor's choice for the Ada programmer are also described.

  10. Comorbidities in Neurology: Is Adenosine the Common Link?

    Science.gov (United States)

    Boison, Detlev; Aronica, Eleonora

    2015-01-01

    Comorbidities in Neurology represent a major conceptual and therapeutic challenge. For example, temporal lobe epilepsy (TLE) is a syndrome comprised of epileptic seizures and comorbid symptoms including memory and psychiatric impairment, depression, and sleep dysfunction. Similarly, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are accompanied by various degrees of memory dysfunction. Patients with AD have an increased likelihood for seizures, whereas all four conditions share certain aspects of psychosis, depression, and sleep dysfunction. This remarkable overlap suggests common pathophysiological mechanisms, which include synaptic dysfunction and synaptotoxicity, as well as glial activation and astrogliosis. Astrogliosis is linked to synapse function via the tripartite synapse, but astrocytes also control the availability of gliotransmitters and adenosine. Here we will specifically focus on the ‘adenosine hypothesis of comorbidities’ implying that astrocyte activation, via overexpression of adenosine kinase (ADK), induces a deficiency in the homeostatic tone of adenosine. We present evidence from patient-derived samples showing astrogliosis and overexpression of ADK as common pathological hallmark of epilepsy, AD, PD, and ALS. We discuss a transgenic ‘comorbidity model’, in which brain-wide overexpression of ADK and resulting adenosine deficiency produces a comorbid spectrum of seizures, altered dopaminergic function, attentional impairment, and deficits in cognitive domains and sleep regulation. We conclude that dysfunction of adenosine signaling is common in neurological conditions, that adenosine dysfunction can explain comorbid phenotypes, and that therapeutic adenosine augmentation might be effective for the treatment of comorbid symptoms in multiple neurological conditions. PMID:25979489

  11. Digital data sets that describe aquifer characteristics of the Vamoosa-Ada aquifer in east-central Oklahoma

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized water-level elevation contours for the Vamoosa-Ada aquifer in east-central Oklahoma. The Vamoosa-Ada aquifer is an important...

  12. Digital data sets that describe aquifer characteristics of the Vamoosa-Ada aquifer in east-central Oklahoma

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized polygons of constant hydraulic conductivity values for the Vamoosa-Ada aquifer in east-central Oklahoma. The Vamoosa-Ada aquifer...

  13. Digital data sets that describe aquifer characteristics of the Vamoosa-Ada aquifer in east-central Oklahoma

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized polygons of constant recharge values for the Vamoosa-Ada aquifer, in east-central Oklahoma. The Vamoosa-Ada aquifer is an...

  14. Digital data sets that describe aquifer characteristics of the Vamoosa-Ada aquifer in east-central Oklahoma

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This data set consists of digitized aquifer boundaries for the Vamoosa-Ada aquifer in east-central Oklahoma. The Vamoosa-Ada aquifer is an important source of water...

  15. A High-Affinity Adenosine Kinase from Anopheles Gambiae

    Energy Technology Data Exchange (ETDEWEB)

    M Cassera; M Ho; E Merino; E Burgos; A Rinaldo-Matthis; S Almo; V Schramm

    2011-12-31

    Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (K{sub m} = 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site, but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap{sub 4}A (2.0 {angstrom} resolution) reveals interactions for adenosine and ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg{sup 2+} ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layer {alpha}/{beta}/{alpha} sandwich, and a small cap domain in contact with adenosine. The specificity and tight binding for adenosine arise from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168, and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64, and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. The structure is more similar to that of human adenosine kinase (48% identical) than to that of AK from Toxoplasma gondii (31% identical). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role for this enzyme in the maintenance of the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects.

  16. The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity

    OpenAIRE

    Kubilay Oransay; Nil Hocaoglu; Mujgan Buyukdeligoz; Yesim Tuncok; Sule Kalkan

    2014-01-01

    Aim: We investigated the role of adenosine in citalopram-induced cardiotoxicity. Materials and Methods: Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A 1 receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A 2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour...

  17. 基于改进的AdaBoost人脸检测算法的研究%Research on Face Detection Based on Improved AdaBoost Algorithm

    Institute of Scientific and Technical Information of China (English)

    丁知平

    2013-01-01

    Face detection is a fundamental research theme in the topic of computer vision ,and it has a broad application in many fields such as video surveillance,automatic face recognition,etc. To improve the detection speed of AdaBoost based face detection algorithm, proposes a rapid im-proved AdaBoost based face detection algorithm. Experiments shows that, compared with the current algorithm less features are selected in the inspection, and a high detection correct rate is achieved with the proposed algorithm.%  人脸检测是计算机视觉领域的基础研究,在视频监控、自动人脸识别等领域有着重要应用价值。针对传统的AdaBoost算法用于人脸检测时需要的特征数目多、检测速度慢的问题,提出一种基于改进的AdaBoost人脸检测算法。实验结果表明,相对于传统的AdaBoost人脸检测算法,该算法使用较少的特征即可达到较高的检测准确率,检测速度得到显著提高。

  18. Prevention of adenosine A2A receptor activation diminishes beat-to-beat alternation in human atrial myocytes.

    Science.gov (United States)

    Molina, Cristina E; Llach, Anna; Herraiz-Martínez, Adela; Tarifa, Carmen; Barriga, Montserrat; Wiegerinck, Rob F; Fernandes, Jacqueline; Cabello, Nuria; Vallmitjana, Alex; Benitéz, Raúl; Montiel, José; Cinca, Juan; Hove-Madsen, Leif

    2016-01-01

    Atrial fibrillation (AF) has been associated with increased spontaneous calcium release from the sarcoplasmic reticulum and linked to increased adenosine A2A receptor (A2AR) expression and activation. Here we tested whether this may favor atrial arrhythmogenesis by promoting beat-to-beat alternation and irregularity. Patch-clamp and confocal calcium imaging was used to measure the beat-to-beat response of the calcium current and transient in human atrial myocytes. Responses were classified as uniform, alternating or irregular and stimulation of Gs-protein coupled receptors decreased the frequency where a uniform response could be maintained from 1.0 ± 0.1 to 0.6 ± 0.1 Hz; p < 0.01 for beta-adrenergic receptors and from 1.4 ± 0.1 to 0.5 ± 0.1 Hz; p < 0.05 for A2ARs. The latter was linked to increased spontaneous calcium release and after-depolarizations. Moreover, A2AR activation increased the fraction of non-uniformly responding cells in HL-1 myocyte cultures from 19 ± 3 to 51 ± 9 %; p < 0.02, and electrical mapping in perfused porcine atria revealed that adenosine induced electrical alternans at longer cycle lengths, doubled the fraction of electrodes showing alternation, and increased the amplitude of alternations. Importantly, protein kinase A inhibition increased the highest frequency where uniform responses could be maintained from 0.84 ± 0.12 to 1.86 ± 0.11 Hz; p < 0.001 and prevention of A2AR-activation with exogenous adenosine deaminase selectively increased the threshold from 0.8 ± 0.1 to 1.2 ± 0.1 Hz; p = 0.001 in myocytes from patients with AF. In conclusion, A2AR-activation promotes beat-to-beat irregularities in the calcium transient in human atrial myocytes, and prevention of A2AR activation may be a novel means to maintain uniform beat-to-beat responses at higher beating frequencies in patients with atrial fibrillation.

  19. RESEARCH for Face Detection on Improved Algorithm of AdaBoost

    Directory of Open Access Journals (Sweden)

    Chen Hong

    2016-01-01

    Full Text Available Face detection is basic research in computer visual field, it has important application value in the fields of cameras and surveillance and Automatic face recognition. Because traditional algorithm of AdaBoost has the problem that it needs more features and the detection speed is slow when it is used to detect face, so a improved algorithm of AdaBoost is presented. The experiment results shows that compared with traditional algorithm of AdaBoost, lower features are used in the improved algorithm and higher accuracy rate can be get and the speed of detection is improved Significantly.

  20. AdaBoost-based algorithm for network intrusion detection.

    Science.gov (United States)

    Hu, Weiming; Hu, Wei; Maybank, Steve

    2008-04-01

    Network intrusion detection aims at distinguishing the attacks on the Internet from normal use of the Internet. It is an indispensable part of the information security system. Due to the variety of network behaviors and the rapid development of attack fashions, it is necessary to develop fast machine-learning-based intrusion detection algorithms with high detection rates and low false-alarm rates. In this correspondence, we propose an intrusion detection algorithm based on the AdaBoost algorithm. In the algorithm, decision stumps are used as weak classifiers. The decision rules are provided for both categorical and continuous features. By combining the weak classifiers for continuous features and the weak classifiers for categorical features into a strong classifier, the relations between these two different types of features are handled naturally, without any forced conversions between continuous and categorical features. Adaptable initial weights and a simple strategy for avoiding overfitting are adopted to improve the performance of the algorithm. Experimental results show that our algorithm has low computational complexity and error rates, as compared with algorithms of higher computational complexity, as tested on the benchmark sample data. PMID:18348941

  1. Biochemistry and Genetics of ACC deaminase: A weapon to 'stress ethylene' produced in plants

    Directory of Open Access Journals (Sweden)

    Rajnish Prakash Singh

    2015-09-01

    Full Text Available 1-aminocyclopropane-1-carboxylate deaminase (ACCD, a pyridoxal phosphate dependent enzyme, is widespread in diverse bacterial and fungal species. Owing to ACCD activity, certain plant associated bacteria help plant to grow under biotic and abiotic stresses by decreasing level of 'stress ethylene' which is inhibitory to plant growth. ACCD breaks down ACC, an immediate precursor of ethylene, to ammonia and α-ketobutyrate which can be further metabolized by bacteria for their growth. ACC deaminase is an inducible enzyme whose synthesis is induced in presence of its substrate ACC. This enzyme, encoded by gene AcdS, is under tight regulation and regulated differentilly under different environmental conditions. Regulatory elements of gene AcdS are comprised of regulatory gene encoding LRP protein and other regulator elements which are activated differentially under aerobic and anaerobic conditions. Role of some additional regulatory genes such as AcdB or LysR may also be required for expression of AcdS. Phylogenetic analysis of AcdS has revealed that distribution of this gene among different bacteria might have resulted from vertical gene transfer with occasional horizontal gene transfer. Application of bacterial AcdS gene has been extended by developing transgenic plants with ACCD gene which showed increased tolerance to biotic and abiotic stresses in plants. Moreover, distribution of ACCD gene or its homologs in wide range of species belonging to all three domains indicate alternative role of ACCD in physiology of an organism. Therefore, this review is an attempt to explore current knowledge of bacterial ACC deaminase mediated physiological effects in plants, mode of enzyme action, genetics, and distribution in different species and ecological role of ACCD and, future research avenues to develop transgenic plants expressing foreign AcdS gene to cope with biotic and abiotic stressors. Systemic identification of regulatory circuits would be highly

  2. Structural, kinetic, and mutational studies of the zinc ion environment in tetrameric cytidine deaminase

    DEFF Research Database (Denmark)

    Johansson, Eva; Neuhard, Jan; Willemoës, Martin;

    2004-01-01

    The zinc-containing cytidine deaminase (CDA, EC 3.5.4.5) is a pyrimidine salvage enzyme catalyzing the hydrolytic deamination of cytidine and 2'-deoxycytidine forming uridine and 2'-deoxyuridine, respectively. Homodimeric CDA (D-CDA) and homotetrameric CDA (T-CDA) both contain one zinc ion per...... subunit coordinated to the catalytic water molecule. The zinc ligands in D-CDA are one histidine and two cysteine residues, whereas in T-CDA zinc is coordinated to three cysteines. Two of the zinc coordinating cysteines in T-CDA form hydrogen bonds to the conserved residue Arg56, and this residue together...

  3. Cloning, expression, and purification of cytidine deaminase from Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Vincenzetti, Silvia; Cambi, Alessandra; Neuhard, Jan;

    1999-01-01

    plasma-optical emission spectroscopy analysis indicated that the enzyme contains 1 mol of zinc atom per mole of subunit. The kinetic properties of AT-CDA1 both toward the natural substrates and with analogs indicated that the catalytic mechanism of the plant enzyme is probably very similar to that of the......The complementary DNA (cDNA) coding forArabidopsis thalianacytidine deaminase 1 (AT-CDA1) was obtained from the amplifiedA. thalianacDNA expression library, provided by R. W. Davis (Stanford University, CA). AT-CDA1 cDNA was subcloned into the expression vector pTrc99-A and the protein, expressed...

  4. Significance of the D-serine-deaminase and D-serine metabolism of Staphylococcus saprophyticus for virulence.

    Science.gov (United States)

    Korte-Berwanger, Miriam; Sakinc, Türkan; Kline, Kimberly; Nielsen, Hailyn V; Hultgren, Scott; Gatermann, Sören G

    2013-12-01

    Staphylococcus saprophyticus is the only species of Staphylococcus that is typically uropathogenic and possesses a gene coding for a D-serine-deaminase (DsdA). As D-serine is prevalent in urine and toxic or bacteriostatic to many bacteria, it is not surprising that the D-serine-deaminase gene is found in the genome of uropathogens. It has been suggested that D-serine-deaminase or the ability to respond to or to metabolize D-serine is important for virulence. For uropathogenic Escherichia coli (UPEC), a high intracellular D-serine concentration affects expression of virulence factors. S. saprophyticus is able to grow in the presence of high D-serine concentrations; however, its D-serine metabolism has not been described. The activity of the D-serine-deaminase was verified by analyzing the formation of pyruvate from D-serine in different strains with and without D-serine-deaminase. Cocultivation experiments were performed to show that D-serine-deaminase confers a growth advantage to S. saprophyticus in the presence of D-serine. Furthermore, in vivo coinfection experiments showed a disadvantage for the ΔdsdA mutant during urinary tract infection. Expression analysis of known virulence factors by reverse transcription-quantitative PCR (RT-qPCR) showed that the surface-associated lipase Ssp is upregulated in the presence of D-serine. In addition, we show that S. saprophyticus is able to use D-serine as the sole carbon source, but interestingly, D-serine had a negative effect on growth when glucose was also present. Taken together, D-serine metabolism is associated with virulence in S. saprophyticus, as at least one known virulence factor is upregulated in the presence of D-serine and a ΔdsdA mutant was attenuated in virulence murine model of urinary tract infection.

  5. JOB OPPORTUNITIES (SUBSURFACE PROTECTION AND REMEDIATION DIVISION, ADA, OKLAHOMA, NATIONAL RISK MANAGEMENT RESEARCH LABORATORY)

    Science.gov (United States)

    This page lists job opportunities at NRMRL's Subsurface Protection and Remediation Division (SPRD) located in Ada, Oklahoma. These include both EPA Postdoctoral Positions and National Research Council Postdoctoral Positions.SPRD's research programs include basic studies to enha...

  6. The implications of the ADA Amendments Act of 2008 for residency training program administration.

    Science.gov (United States)

    Regenbogen, Alexandra; Recupero, Patricia R

    2012-01-01

    The Americans with Disabilities Act (ADA) is rarely invoked by medical residents in training. Dr. Martin Jakubowski, a family medicine resident with Asperger's disorder, was dismissed for communicating poorly with patients, peers, and supervisors and for issuing dangerous medical orders. In an attempt to become reinstated, he sued under the ADA (Jakubowski v. The Christ Hospital), arguing that the program had failed to make reasonable accommodation for his disability. The Sixth Circuit Court of Appeals ruled in favor of the hospital, finding that although the doctor was disabled under the ADA, he had failed to demonstrate that he was otherwise qualified for the position. This article comments on the ADA Amendments Act of 2008, the Equal Employment Opportunity Commission (EEOC) guidelines from 2011 and their application to medical residency training, and the Accreditation Council for Graduate Medical Education (ACGME) core competencies as essential job functions. PMID:23233478

  7. Modulation of bladder function by luminal adenosine turnover and A1 receptor activation

    OpenAIRE

    Prakasam, H. Sandeep; Herrington, Heather; Roppolo, James R.; Jackson, Edwin K.; Apodaca, Gerard

    2012-01-01

    The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed ...

  8. Inhibition of uptake of adenosine into human blood platelets

    NARCIS (Netherlands)

    Lips, J.P.M.; Sixma, J.J.; Trieschnigg, A.C.

    1980-01-01

    Adenosine transport into human blood platelets is mediated by two independent systems with different affinities. Both systems transport only purine nucleosides and no pyrimidine nucleosides. In experiments with differently substituted purine nucleosides, purines and analogues, differences in carrier

  9. A-D-A small molecules for solution-processed organic photovoltaic cells.

    Science.gov (United States)

    Ni, Wang; Wan, Xiangjian; Li, Miaomiao; Wang, Yunchuang; Chen, Yongsheng

    2015-03-25

    A-D-A small molecules have drawn more and more attention in solution-processed organic solar cells due to the advantages of a diversity of structures, easy control of energy levels, etc. Recently, a power conversion efficiency of nearly 10% has been achieved through careful material design and device optimization. This feature article reviews recent representative progress in the design and application of A-D-A small molecules in organic photovoltaic cells.

  10. ADAS on COTS with OpenCL: A Case Study with Lane Detection

    OpenAIRE

    Kai Huang, Biao Hu, Long Chen, Alois Knoll, Zhihua Wang

    2016-01-01

    The concept of autonomous cars is driving a boost for car electronics and the size of automotive semiconductor market is foreseen to double by 2025. How to benefit from this boost is an interesting question. This article presents a case study to test the feasibility of using OpenCL as the programming language and COTS components as the underlying platforms for ADAS development. For representative ADAS applications, a scalable lane detection is developed that can tune the trade-off be...

  11. Software fault tree analysis of an automated control system device written in Ada

    OpenAIRE

    Winter, Mathias William.

    1995-01-01

    Software Fault Tree Analysis (SFTA) is a technique used to analyze software for faults that could lead to hazardous conditions in systems which contain software components. Previous thesis works have developed three Ada-based, semi-automated software analysis tools, the Automated Code Translation Tool (ACm) an Ada statement template generator, the Fault Tree Editor (Fm) a graphical fault tree editor, and the Fault Isolator (Fl) an automated software fault tree isolator. These previous works d...

  12. Soil microorganisms numbers in the tailing deposition ModADA areas of Freeport Indonesia, Timika, Papua

    OpenAIRE

    IRNANDA AIKO FIFI DJUUNA; MARIA MASORA; PRATITA PURADYATMIKA

    2011-01-01

    Djuuna IAF, Masora M, Puradyatmika P (2011) Soil microorganisms numbers in the tailing deposition ModADA areas of Freeport Indonesia, Timika, Papua. Biodiversitas 12: 198-203. The objective of this study was to examine the number and distribution of bacteria, fungi and actinomycetes in the inactive tailing deposition areas of Freeport Indonesia Mining and Gold Company, Timika. One hundred ninety eight composite samples (0-20 cm) were taken from four location of inactive tailing ModADA (Modifi...

  13. Distribution of adenosine receptors in human sclera fibroblasts

    OpenAIRE

    Cui, Dongmei; Trier, Klaus; Chen, Xiang; Zeng, Junwen; Yang, Xiao; Hu, Jianmin; Ge, Jian

    2008-01-01

    Purpose Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF). Methods Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines...

  14. Vector-matrix-quaternion, array and arithmetic packages: All HAL/S functions implemented in Ada

    Science.gov (United States)

    Klumpp, Allan R.; Kwong, David D.

    1986-01-01

    The HAL/S avionics programmers have enjoyed a variety of tools built into a language tailored to their special requirements. Ada is designed for a broader group of applications. Rather than providing built-in tools, Ada provides the elements with which users can build their own. Standard avionic packages remain to be developed. These must enable programmers to code in Ada as they have coded in HAL/S. The packages under development at JPL will provide all of the vector-matrix, array, and arithmetic functions described in the HAL/S manuals. In addition, the linear algebra package will provide all of the quaternion functions used in Shuttle steering and Galileo attitude control. Furthermore, using Ada's extensibility, many quaternion functions are being implemented as infix operations; equivalent capabilities were never implemented in HAL/S because doing so would entail modifying the compiler and expanding the language. With these packages, many HAL/S expressions will compile and execute in Ada, unchanged. Others can be converted simply by replacing the implicit HAL/S multiply operator with the Ada *. Errors will be trapped and identified. Input/output will be convenient and readable.

  15. Constructing a working taxonomy of functional Ada software components for real-time embedded system applications

    Science.gov (United States)

    Wallace, Robert

    1986-01-01

    A major impediment to a systematic attack on Ada software reusability is the lack of an effective taxonomy for software component functions. The scope of all possible applications of Ada software is considered too great to allow the practical development of a working taxonomy. Instead, for the purposes herein, the scope of Ada software application is limited to device and subsystem control in real-time embedded systems. A functional approach is taken in constructing the taxonomy tree for identified Ada domain. The use of modular software functions as a starting point fits well with the object oriented programming philosophy of Ada. Examples of the types of functions represented within the working taxonomy are real time kernels, interrupt service routines, synchronization and message passing, data conversion, digital filtering and signal conditioning, and device control. The constructed taxonomy is proposed as a framework from which a need analysis can be performed to reveal voids in current Ada real-time embedded programming efforts for Space Station.

  16. Mutational analysis of the nucleotide binding site of Escherichia coli dCTP deaminase

    DEFF Research Database (Denmark)

    Thymark, Majbritt; Johansson, Eva; Larsen, Sine;

    2007-01-01

    In Escherichia coli and Salmonella typhimurium about 80% of the dUMP used for dTMP synthesis is derived from deamination of dCTP. The dCTP deaminase produces dUTP that subsequently is hydrolyzed by dUTPase to dUMP and diphosphate. The dCTP deaminase is regulated by dTTP that inhibits the enzyme by...... detectable activity with a 30- and 140-fold reduction in k(cat), respectively. Furthermore, S111T and E138D both showed altered dTTP inhibition compared to wild-type enzyme. S111T was almost insensitive to the presence of dTTP. With the E138D enzyme the dTTP dependent increase in cooperativity of d......CTP saturation was absent, although the dTTP inhibition itself was still cooperative. Modeling of the active site of the S111T enzyme indicated that this enzyme is restricted in forming the inactive dTTP binding conformer due to steric hindrance by the additional methyl group in threonine. The crystal structure...

  17. Isolation and characterization of novel bacteria containing acc deaminase from the rhizosphere resource on dry-farming lands

    International Nuclear Information System (INIS)

    Soil-microbe-plant interactions are known to be intricate and they can greatly influence the crop vigor and yield. Plant growth promoting rhizobacteria (PGPR) containing ACC deaminase can markedly affect plant metabolic processes under stress conditions. In the present study, we isolated 300 bacterial strains from the rhizosphere of maize or apple grown in drought-hit soil including four different locations of the Loess Plateau, China. Of all isolated strains, four with ACC deaminase activity (ranging from 28.88 to 155.12 nmol alpha-ketobutyrate mg-1 h-1) were further studied by determining their biological characters and sequencing the 16S rRNA gene. All four strains showed positive performance in terms of arabinose, citrate utilization, urease, indol, glucose and melibiose. In connection with the results of biochemical characters and phylogenetic analysis, these strains commonly belong to three different genera: Klebsiella, Pseudomonas and Raoultella and four different species: Klebsiella oxytoca, Klebsiella variicola, Pseudomonas fluorescens and Raoultella planticola. Although some researchers have reported their performance under stress conditions, we are the first to report Klebsiella oxytoca, Klebsiella variicola and Raoultella planticola containing ACC deaminase under drought stress. These findings are a reasonable explanation to their superb ability of causing stress-resistance in maize (Zea mays) or apple (Malus domestica) plants. The presence of diverse PGPR possessing potential ACC deaminase activity may be beneficial for enhancing crop production under different stress conditions. (author)

  18. Characterization of 1-Aminocyclopropane-1-Carboxylate (ACC) Deaminase-Containing Pseudomonas spp. in the Rhizosphere of Salt-Stressed Canola

    NARCIS (Netherlands)

    Akhgar, A.; Arzanlou, M.; Bakker, Peter; Hamidpour, M.

    2014-01-01

    When exposed to biotic or abiotic stress conditions, plants produce ethylene from its immediate precursor 1-aminocyclopropane-1- carboxylate (ACC), leading to retarded root growth and senescence. Many plant growth-promoting rhizobacteria contain the enzyme ACC deaminase and this enzyme can cleave AC

  19. Short Communication: Rhizosphere bacteria containing ACC-deaminase conferred drought tolerance in wheat grown under semi-arid climate

    Directory of Open Access Journals (Sweden)

    Masood Ahmad Shakir

    2012-05-01

    Full Text Available Certain rhizobacteria have the potential of lowering endogenous ethylene levels in plants because of their 1- aminocyclopropane-1-carboxylate (ACC-deaminase activity and promoting root growth. This mechanism is of great agronomic significance under stress environments, which are known to induce accelerated production of ethylene. Thirty rhizobacteria were isolated from rhizosphere of wheat (Triticum aestivum L. growing in the Southern Punjab, a semi-arid region of Pakistan. Rhizobacteria were screened for ACC-deaminase activity and their potential to confer drought tolerance in wheat crop. Results of laboratory study revealed that selected rhizobacteria lowered endogenous ethylene levels in the rhizosphere as measured by Gas Chromatograph. Axenic studies showed that inoculation increased root-shoot length, root-shoot mass and lateral root number of the inoculated plants by 141, 44, 196, 52 and 30%, respectively, over control. Better-developed roots because of inoculation with plant growth promoting rhizobacteria (PGPR helped plants, a better crop stand that enhanced moisture and nutrient feeding volume resulting-in improved growth and yields of wheat crop. Two-year multi-location field trials inferred optimum yields with low delta water in semi-arid climate by PGPR containing ACC-deaminase. The enzyme ACC-deaminase probably lowered harmful ethylene levels which partially eliminated drought stress consequently utilizing soil moisture from lower profiles through proliferated roots.

  20. 1-Aminocyclopropane-1-Carboxylate Deaminase from Pseudomonas stutzeri A1501 Facilitates the Growth of Rice in the Presence of Salt or Heavy Metals.

    Science.gov (United States)

    Han, Yunlei; Wang, Rui; Yang, Zhirong; Zhan, Yuhua; Ma, Yao; Ping, Shuzhen; Zhang, Liwen; Lin, Min; Yan, Yongliang

    2015-07-01

    1-Aminocyclopropane-1-carboxylate (ACC) deaminase, which is encoded by some bacteria, can reduce the amount of ethylene, a root elongation inhibitor, and stimulate the growth of plants under various environmental stresses. The presence of ACC deaminase activity and the regulation of ACC in several rhizospheric bacteria have been reported. The nitrogen-fixing Pseudomonas stutzeri A1501 is capable of endophytic association with rice plants and promotes the growth of rice. However, the functional identification of ACC deaminase has not been performed. In this study, the proposed effect of ACC deaminase in P. stutzeri A1501 was investigated. Genome mining showed that P. stutzeri A1501 carries a single gene encoding ACC deaminase, designated acdS. The acdS mutant was devoid of ACC deaminase activity and was less resistant to NaCl and NiCl2 compared with the wild-type. Furthermore, inactivation of acdS greatly impaired its nitrogenase activity under salt stress conditions. It was also observed that mutation of the acdS gene led to loss of the ability to promote the growth of rice under salt or heavy metal stress. Taken together, this study illustrates the essential role of ACC deaminase, not only in enhancing the salt or heavy metal tolerance of bacteria but also in improving the growth of plants, and provides a theoretical basis for studying the interaction between plant growth-promoting rhizobacteria and plants. PMID:25674802

  1. 基于Online AdaBoost的偏振图像目标跟踪%Polarization image object tracking based on Online AdaBoost

    Institute of Scientific and Technical Information of China (English)

    邢晨; 薛模根; 袁广林; 王峰

    2011-01-01

    根据偏振图像的特点,文章提出一种基于在线AdaBoost的目标跟踪方法.该方法以最小二乘回归作为弱分类器,以强度、偏振度和边缘方向特征组成的向量为其输入;通过AdaBoost算法将多个弱分类器集成为强分类器,并在跟踪过程中利用AdaBoost算法对强分类器进行在线更新,以适应目标与背景的变化;利用强分类器生成当前置信图,在置信图上利用粒子滤波估计目标的状态.实验结果表明,该方法能够在复杂背景下稳定地跟踪目标.%A polarization image object tracking method is proposed based on Online Adaboost. The least square regression is used as the weak classifier, with feature vectors of intensity, polarization degree and margin direction chosen for the input. The ensemble of weak classifiers is integrated into a strong classifier by AdaBoost algorithm, and this strong classifier is updated online by AdaBoost algorithm during tracking in order to adapt to the change of the object or the background. Current confidence map is given by using the strong classifier, and based on this map the new state of the object is estimated by using particle filter. Experimental results show that the proposed method is robust and efficient in polarization image object tracking on complex background.

  2. Role of A3 adenosine receptor in diabetic neuropathy.

    Science.gov (United States)

    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc.

  3. Intracoronary adenosine improves myocardial perfusion in late reperfused myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Myocardial perfusion associates with clinical syndromes and prognosis.Adenosine could improve myocardial perfusion of acute myocardial infarction within 6 hours,but few data are available on late perfusion of myocardial infarction (MI).This study aimed at quantitatively evaluating the value of intracoronary adenosine improving myocardial perfusion in late reperfused MI with myocardial contrast echocardiography(MCE).Methods Twenty-six patients with anterior wall infarcts were divided randomly into 2 groups:adenosine group(n=12) and normal saline group(n=14).Their history of myocardial infarction was about 3-12 weeks.Adenosine or normalsaline was given when the guiding wire crossed the lesion through percutaneous coronary intervention(PCI),then the balloon was dilated and stent(Cypher/Cypher select)was implanted at the lesion.Contrast pulse sequencing MCE with Sonovue contrast via the coronary route was done before PCI and 30 minutes after PCI.Video densitometry and contrast filled-blank area were calculated with the CUSQ off-line software.Heart function and cardiac events were followed up within 30 days.Results Perfusion in the segments of the criminal occlusive coronary artery in the adenosine group was better than that in the saline group(5.71±0.29 vs 4.95±1.22,P<0.05).Ischemic myocardial segment was deminished significantly afterPCI,but the meliorated area was bigger in the adenosine group than in the saline group((1.56±0.60)cm2 vs(1.02±0.56) cm2,P<0.05).The video densitometry in critical segments was also improved significantly in the adenosine group (5.53±0.36 vs 5.26±0.35,P<0.05).Left ventricular ejection fraction(LVEF)was improved in all patients after PCI,but EF was not significant between the two groups((67±6)% vs(62±7)%,P>0.05).There was no in-hospital or 30-day major adverse cardiac event(MACE)in the adenosine group but 3 MACE in the saline group in 30 days after PCI.Conclusions Adenosine could improve myocardial microvascular

  4. Antagonism by theophylline of respiratory inhibition induced by adenosine.

    Science.gov (United States)

    Eldridge, F L; Millhorn, D E; Kiley, J P

    1985-11-01

    The effects on respiration of an analogue of adenosine, L-2-N6-(phenylisopropyl)adenosine (PIA), and of the methylxanthine, theophylline, were determined in 19 vagotomized glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. Integrated phrenic nerve activity was used to represent respiratory output. Our results show that PIA, whether given systemically or into the third cerebral ventricle, depressed respiration. Systemically administered theophylline stimulated respiration. Theophylline given intravenously, or into the third ventricle not only reversed the depressive effects of previously administered PIA but caused further increases of respiration above the control level. Prior systemic administration of theophylline blocked both respiratory and hypotensive effects of subsequently administered PIA. Effects of either agent on medullary extracellular fluid pH did not explain the results. We conclude that the adenosine analogue PIA, acts to inhibit neurons in the brain that are involved in the control of respiration and that its effects are blocked by theophylline. We suggest that adenosine acts as a tonic modulator of respiration and that theophylline stimulates breathing by competitive antagonism of adenosine at neuronal receptor sites. PMID:4066573

  5. Adenosine A1 receptor agonists inhibit trigeminovascular nociceptive transmission

    DEFF Research Database (Denmark)

    Goadsby, P J; Hoskin, K L; Storer, R J;

    2002-01-01

    There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg/kg, intraperit......There is a considerable literature to suggest that adenosine A1 receptor agonists may have anti-nociceptive effects, and we sought to explore the role of adenosine A1 receptors in a model of trigeminovascular nociceptive transmission. Cats were anaesthetized (alpha-chloralose 60 mg...... from the external jugular vein to determine levels of calcitonin gene-related peptide (CGRP) release before and after drug administration. Intravenous administration of the highly selective adenosine A1 receptor agonist, GR79236 (3-100 microg/kg) had a dose-dependent inhibitory effect on SSS...... 33 +/- 2 pmol/l (n = 6) to 64 +/- 3 pmol/l, an effect substantially reduced by pre-treatment with GR79236 (30 microg/kg; P agonist, GR190178 (30-1000 microg/kg i.v.), also inhibited SSS-evoked neuronal activity in a dose-dependent fashion...

  6. Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells.

    Science.gov (United States)

    Katz, Adam J; Tholpady, Ashok; Tholpady, Sunil S; Shang, Hulan; Ogle, Roy C

    2005-03-01

    Adult human subcutaneous adipose tissue contains cells with intriguing multilineage developmental plasticity, much like marrow-derived mesenchymal stem cells. Putative stem or progenitor cells from fat have been given many different names in the literature, reflecting an early and evolving consensus regarding their phenotypic characterization. The study reported here used microarrays to evaluate over 170 genes relating to angiogenesis and extracellular matrix in undifferentiated, early-passage human adipose-derived adherent stromal (hADAS) cells isolated from three separate donors. The hADAS populations unanimously transcribed 66% of the screened genes, and 83% were transcribed by at least two of the three populations. The most highly transcribed genes relate to functional groupings such as cell adhesion, matrix proteins, growth factors and receptors, and proteases. The transcriptome of hADAS cells demonstrated by this work reveals many similarities to published profiles of bone marrow mesenchymal stem cells (MSCs). In addition, flow analysis of over 24 hADAS cell surface proteins (n = 7 donors) both confirms and expands on the existing literature and reveals strong intergroup correlation, despite an inconsistent nomenclature and the lack of standardized protocols for cell isolation and culture. Finally, based on flow analysis and reverse transcription polymerase chain reaction studies, our results suggest that hADAS cells do not express several proteins that are implicated as markers of "stemness" in other stem cell populations, including telomerase, CD133, and the membrane transporter ABCG2.

  7. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    International Nuclear Information System (INIS)

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

  8. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Atsushi; Marusawa, Hiroyuki, E-mail: maru@kuhp.kyoto-u.ac.jp; Chiba, Tsutomu [Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

    2011-06-22

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  9. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID during Inflammation-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tsutomu Chiba

    2011-06-01

    Full Text Available Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID, a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  10. Nonimmunoglobulin target loci of activation-induced cytidine deaminase (AID) share unique features with immunoglobulin genes.

    Science.gov (United States)

    Kato, Lucia; Begum, Nasim A; Burroughs, A Maxwell; Doi, Tomomitsu; Kawai, Jun; Daub, Carsten O; Kawaguchi, Takahisa; Matsuda, Fumihiko; Hayashizaki, Yoshihide; Honjo, Tasuku

    2012-02-14

    Activation-induced cytidine deaminase (AID) is required for both somatic hypermutation and class-switch recombination in activated B cells. AID is also known to target nonimmunoglobulin genes and introduce mutations or chromosomal translocations, eventually causing tumors. To identify as-yet-unknown AID targets, we screened early AID-induced DNA breaks by using two independent genome-wide approaches. Along with known AID targets, this screen identified a set of unique genes (SNHG3, MALAT1, BCL7A, and CUX1) and confirmed that these loci accumulated mutations as frequently as Ig locus after AID activation. Moreover, these genes share three important characteristics with the Ig gene: translocations in tumors, repetitive sequences, and the epigenetic modification of chromatin by H3K4 trimethylation in the vicinity of cleavage sites.

  11. A clinicopathological study of tuberculous pleural effusion in a tertiary care hospital

    OpenAIRE

    Amitabha Basu; Indranil Chakrabarti; Nilanjana Ghosh; Subrata Chakraborty

    2012-01-01

    Context: Tuberculosis is a major contributor of exudative pleural effusion which is the second most common extra-pulmonary manifestation of tuberculosis following tubercular lymphadenitis. Aims: To re-evaluate the time tested and easily available investigation of closed pleural biopsy and its relation with pleural fluid adenosine deaminase (ADA) level and cytological findings in the clinically suspected cases of tuberculous pleural effusion. Materials and Methods: A total of 44 cases of suspe...

  12. Estimating the genetic divergence and identification of three trichinella species by isoenzyme analysis

    OpenAIRE

    Šnábel V.; Malakauskas A.; Dubinský P.; Kapel C.M.O.

    2001-01-01

    Isoenzyme-based approach was applied to compare Trichinella spiralis, T. britovi and T. pseudospiralis species. Among 13 enzyme systems examined, esterase (EST), malic enzyme (ME) and phosphoglucomutase (PGM) have been found as fully diagnostic, with no common allele in species studied. Adenosine deaminase (ADA), adenylate kinase (AK), hexokinase (HK), peptidase leucyl-alanine (PEP-C) and fructose-bis-phosphatase (FBP) have been capable of distinguishing the two species from resulting profile...

  13. Thallium-201 scintigraphy of the myocardium in connection with adenosine

    International Nuclear Information System (INIS)

    It is shown that thallium-201 SPECT studies of the myocardium performed subsequent to intravenous infusion of adenosine provide results at least as valuable as those from exercise thallium-201 scintigraphy in the diagnosis of coronary artery disease. The infusion of adenosine offers great advantages over exercise studies in that it is a standardized procedure uninfluenced by a patient's physical fitness, which can thus be used in all cases. There are quite a number of clinically tolerable untoward reactions that may be associated with discomfort but do not warrant discontinuation of the procedure. Serious, verifiable side-effects are rare and disappear immediately on termination of the infusion. The most recent research in this field has shown that newly developed compounds of 99mTc are also suitable for radionuclide studies of the myocardium with adenosine vasodilation. (orig.)

  14. An enhanced Ada run-time system for real-time embedded processors

    Science.gov (United States)

    Sims, J. T.

    1991-01-01

    An enhanced Ada run-time system has been developed to support real-time embedded processor applications. The primary focus of this development effort has been on the tasking system and the memory management facilities of the run-time system. The tasking system has been extended to support efficient and precise periodic task execution as required for control applications. Event-driven task execution providing a means of task-asynchronous control and communication among Ada tasks is supported in this system. Inter-task control is even provided among tasks distributed on separate physical processors. The memory management system has been enhanced to provide object allocation and protected access support for memory shared between disjoint processors, each of which is executing a distinct Ada program.

  15. Role of adenosine as adjunctive therapy in acute myocardial infarction.

    Science.gov (United States)

    Forman, Mervyn B; Stone, Gregg W; Jackson, Edwin K

    2006-01-01

    Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio-protective effects of adenosine are supported by its role as a mediator of pre- and post-conditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk-patients undergoing reperfusion therapy. PMID:16961725

  16. Transplantation and optimization of AdaBoost face detection algorithm on DSP%AdaBoost人脸检测算法在DSP上的移植与优化

    Institute of Scientific and Technical Information of China (English)

    朱明; 陆小锋; 陆亨立; 李莹娇; 张东升

    2014-01-01

    This paper transplants the AdaBoost algorithm proposed by Viola from PC platform to TMS320DM642 platform. The transplantation solves the compile problem caused by the difference between PC and DSP platform. The algorithm optimization is proceeding in CCS compiler which is provided by Texas Instruments. The paper optimizes the AdaBoost algorithm by the optimization of C code and the project settings, and a lot of experiments are done to give out the optimi-zation solution. It plays a guiding role in the implementation of real-time feature in embedded DM642 platform.%将Viola等人提出的AdaBoost人脸检测算法由PC机移植到TMS320DM642嵌入式平台,采用EMCV (Embedded Computer Vision Library)移植方案,将PC平台的OpenCV(Open Source Computer Vision Library)视觉库中有关AdaBoost算法的模块修改使之适应嵌入式DSP平台。该移植工作主要解决了OpenCV在嵌入式平台的不兼容问题以及不同体系架构的编译器环境和库文件导致的编译和链接错误。优化工作在TI的编译器CCS中进行,在编译器平台下进行C语言的项目及程序优化,并进行了大量实验数据的对比,给出了优化的方案,对实现系统的实时性有指导性作用。

  17. AdaBoost人脸检测算法在DSP上的移植与优化%Transplantation and optimization of AdaBoost face detection algorithm on DSP

    Institute of Scientific and Technical Information of China (English)

    朱明; 陆小锋; 陆亨立; 李莹娇; 张东升

    2014-01-01

    将Viola等人提出的AdaBoost人脸检测算法由PC机移植到TMS320DM642嵌入式平台,采用EMCV (Embedded Computer Vision Library)移植方案,将PC平台的OpenCV(Open Source Computer Vision Library)视觉库中有关AdaBoost算法的模块修改使之适应嵌入式DSP平台。该移植工作主要解决了OpenCV在嵌入式平台的不兼容问题以及不同体系架构的编译器环境和库文件导致的编译和链接错误。优化工作在TI的编译器CCS中进行,在编译器平台下进行C语言的项目及程序优化,并进行了大量实验数据的对比,给出了优化的方案,对实现系统的实时性有指导性作用。%This paper transplants the AdaBoost algorithm proposed by Viola from PC platform to TMS320DM642 platform. The transplantation solves the compile problem caused by the difference between PC and DSP platform. The algorithm optimization is proceeding in CCS compiler which is provided by Texas Instruments. The paper optimizes the AdaBoost algorithm by the optimization of C code and the project settings, and a lot of experiments are done to give out the optimi-zation solution. It plays a guiding role in the implementation of real-time feature in embedded DM642 platform.

  18. Investigating real-time activation of adenosine receptors by bioluminescence resonance energy transfer technique

    Science.gov (United States)

    Huang, Yimei; Yang, Hongqin; Zheng, Liqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

    2013-02-01

    Adenosine receptors play important roles in many physiological and pathological processes, for example regulating myocardial oxygen consumption and the release of neurotransmitters. The activations of adenosine receptors have been studied by some kinds of techniques, such as western blot, immunohistochemistry, etc. However, these techniques cannot reveal the dynamical response of adenosine receptors under stimulation. In this paper, bioluminescence resonance energy transfer technique was introduced to study the real-time activation of adenosine receptors by monitoring the dynamics of cyclic adenosine monophosphate (cAMP) level. The results showed that there were significant differences between adenosine receptors on real-time responses under stimulation. Moreover, the dynamics of cAMP level demonstrated that competition between adenosine receptors existed. Taken together, our study indicates that monitoring the dynamics of cAMP level using bioluminescence resonance energy transfer technique could be one potential approach to investigate the mechanism of competitions between adenosine receptors.

  19. N-terminal and C-terminal cytosine deaminase domain of APOBEC3G inhibit hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)

    Yan-Chang Lei; Dong-Liang Yang; Yong-Jun Tian; Hong-Hui Ding; Bao-Ju Wang; Yan Yang; You-Hua Hao; Xi-Ping Zhao; Meng-Ji Lu; Fei-Li Gong

    2006-01-01

    AIM: To investigate the effect of human apolipoprotein B mRNA-editing enzyme catalytic-polypeptide 3G(APOBEC3G) and its N-terminal or C-terminal cytosine deaminase domain-mediated antiviral activity against hepatitis B virus (HBV) in vitro and in vivo.METHODS: The mammalian hepatoma cells HepG2 and HuH7 were cotransfected with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vector and 1.3-fold-overlength HBV DNA as well as the linear monomeric HBV of genotype B and C. For in vivo study, an HBV vector-based mouse model was used in which APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain expression vectors were co-delivered with 1.3-fold-overlength HBV DNA via high-volume tail vein injection. Levels of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) in the media of the transfected cells and in the sera of mice were determined by ELISA.The expression of hepatitis B virus core antigen (HBcAg)in the transfected cells was determined by Western blot analysis. Core-associated HBV DNA was examined by Southern blot analysis. Levels of HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by quantitative PCR and quantitative RT-PCR analysis, respectively.RESULTS: Human APOBEC3G exerted an anti-HBV activity in a dose-dependent manner in HepG2 cells,and comparable suppressive effects were observed on genotype B and C as that of genotype A. Interestingly,the N-terminal or C-terminal cytosine deaminase domain alone could also inhibit HBV replication in HepG2 cells as well as Huh7 cells. Consistent with in vitro results, the levels of HBsAg in the sera of mice were dramatically decreased, with more than 50 times decrease in the levels of serum HBV DNA and core-associated RNA in the liver of mice treated with APOBEC3G and its N-terminal or C-terminal cytosine deaminase domain as compared to the controls.CONCLUSION: Our findings provide probably the first

  20. Phosphorylation of adenosine with trimetaphosphate under simulated prebiotic conditions.

    Science.gov (United States)

    Cheng, Changmei; Fan, Chang; Wan, Rong; Tong, Chunyuan; Miao, Zhiwei; Chen, Jing; Zhao, Yufen

    2002-06-01

    The phosphorylation of adenosine with trimetaphosphate in solution, in solid phase and using wet-dry cycles was carried out and it was found that wet-dry cycles were the most efficient. The catalytic effects of some metal ions on the phosphorylation were also studied and it was discovered that Ni(II) is the most effective. The combination of wet-dry cycles (4 cycles) and catalysis by Ni(II) led to an unprecedented high conversion of adenosine to phosphorylated products (30%) near neutral pH. The main phosphorylated products were 2',3'-cyclic AMP (10.4%) and 5'-ATP (13.0%). PMID:12227426

  1. No role of interstitial adenosine in insulin-mediated vasodilation

    DEFF Research Database (Denmark)

    Dela, F; Stallknecht, B

    1999-01-01

    healthy subjects (H) and in four subjects with a complete, high (C5-C6/7) spinal cord injury (SCI) a hyperinsulinaemic (480 mU min-1 kg-1), isoglycaemic clamp was performed. SCI subjects were included as it has been proposed that adenosine and adenine nucleotides may be released from nerve endings in the...... skeletal muscle. Adenosine concentrations in the extracellular fluid (ECF) of skeletal muscle in the thigh were measured by means of the microdialysis technique. Leg blood flow (LBF) was measured by termodilution. In response to insulin infusion, LBF always increased (P < 0.05) (from 228 +/- 25 and 318...

  2. Why do premature newborn infants display elevated blood adenosine levels?

    Science.gov (United States)

    Panfoli, Isabella; Cassanello, Michela; Bruschettini, Matteo; Colella, Marina; Cerone, Roberto; Ravera, Silvia; Calzia, Daniela; Candiano, Giovanni; Ramenghi, Luca

    2016-05-01

    Our preliminary data show high levels of adenosine in the blood of very low birth weight (VLBW) infants, positively correlating to their prematurity (i.e. body weight class). This prompted us to look for a mechanism promoting such impressive adenosine increase. We hypothesized a correlation with oxygen challenge. In fact, it is recognized that either oxygen lack or its excess contribute to the pathogenesis of the injuries of prematurity, such as retinopathy (ROP) and periventricular white matter lesions (PWMI). The optimal concentration of oxygen for resuscitation of VLBW infants is currently under revision. We propose that the elevated adenosine blood concentrations of VLBW infants recognizes two sources. The first could be its activity-dependent release from unmyelinated brain axons. Adenosine in this respect would be an end-product of the hypometabolic VLBW newborn unmyelinated axon intensely firing in response to the environmental stimuli consequent to premature birth. Adenosine would be eventually found in the blood due to blood-brain barrier immaturity. In fact, adenosine is the primary activity-dependent signal promoting differentiation of premyelinating oligodendrocyte progenitor cells (OPC) into myelinating cells in the Central Nervous System, while inhibiting their proliferation and inhibiting synaptic function. The second, would be the ecto-cellular ATP synthesized by the endothelial cell plasmalemma exposed to ambient oxygen concentrations due to premature breathing, especially in lung. ATP would be rapidly transformed into adenosine by the ectonucleotidase activities such as NTPDase I (CD39), and NT5E (CD73). An ectopic extra-mitochondrial aerobic ATP synthetic ability was reported in many cell plasma-membranes, among which endothelial cells. The potential implications of the cited hypotheses for the neonatology area would be great. The amount of oxygen administration for reviving of newborns would find a molecular basis for its assessment. VLBW

  3. Tween 20-stabilized gold nanoparticles combined with adenosine triphosphate-BODIPY conjugates for the fluorescence detection of adenosine with more than 1000-fold selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Hung, Szu-Ying; Shih, Ya-Chen [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); Tseng, Wei-Lung, E-mail: tsengwl@mail.nsysu.edu.tw [Department of Chemistry, National Sun Yat-sen University, Taiwan (China); School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Taiwan (China); Center for Nanoscience and Nanotechnology, National Sun Yat-sen University, Taiwan (China); Center for Stem Cell Research, Kaohsiung Medical University, Taiwan (China)

    2015-02-01

    Graphical abstract: A simple, enzyme-free, label-free, sensitive and selective system was developed for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles as an efficient quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate and as a recognition element for adenosine. - Highlights: • The proposed method can detect adenosine with more than 1000-fold selectivity. • The analysis of adenosine is rapid (∼6 min) using the proposed method. • This method provided better sensitivity for adenosine as compared to aptamer-based sensors. • This method can be applied for the determination of adenosine in urine. - Abstract: This study describes the development of a simple, enzyme-free, label-free, sensitive, and selective system for detecting adenosine based on the use of Tween 20-stabilized gold nanoparticles (Tween 20-AuNPs) as an efficient fluorescence quencher for boron dipyrromethene-conjugated adenosine 5′-triphosphate (BODIPY-ATP) and as a recognition element for adenosine. BODIPY-ATP can interact with Tween 20-AuNPs through the coordination between the adenine group of BODIPY-ATP and Au atoms on the NP surface, thereby causing the fluorescence quenching of BODIPY-ATP through the nanometal surface energy transfer (NSET) effect. When adenosine attaches to the NP surface, the attached adenosine exhibits additional electrostatic attraction to BODIPY-ATP. As a result, the presence of adenosine enhances the efficiency of AuNPs in fluorescence quenching of BODIPY-ATP. The AuNP-induced fluorescence quenching of BODIPY-ATP progressively increased with an increase in the concentration of adenosine; the detection limit at a signal-to-noise ratio of 3 for adenosine was determined to be 60 nM. The selectivity of the proposed system was more than 1000-fold for adenosine over any adenosine analogs and other nucleotides. The proposed system combined with a phenylboronic acid-containing column was successfully applied to the

  4. Methyl phosphotriesters in alkylated DNA are repaired by the Ada regulatory protein of E. coli.

    OpenAIRE

    McCarthy, T.V.; Lindahl, T

    1985-01-01

    The E. coli ada+ gene product that controls the adaptive response to alkylating agents has been purified to apparent homogeneity using an overproducing expression vector system. This 39 kDa protein repairs 0(6)-methylguanine and 0(4)-methylthymine residues in alkylated DNA by transfer of the methyl group from the base to a cysteine residue in the protein itself. The Ada protein also corrects one of the stereoisomers of methyl phosphotriesters in DNA by the same mechanism, while the other isom...

  5. The role of transcriptional coactivator ADA2b in Arabidopsis abiotic stress responses.

    Science.gov (United States)

    Vlachonasios, Konstantinos E; Kaldis, Athanasios; Nikoloudi, Adriana; Tsementzi, Despoina

    2011-10-01

    Plant growth and crop production can be greatly affected by common environmental stresses such as drought, high salinity and low temperatures. Gene expression is affected by several abiotic stresses. Stress-inducible genes are regulated by transcription factors and epigenetic mechanisms such as histone modifications. In this Mini-Review, we have explored the role of transcriptional adaptor ADA2b in Arabidopsis responses to abiotic stress. ADA2b is required for the expression of genes involved in abiotic stress either by controlling H3 and H4 acetylation in the case of salt stress or affecting nucleosome occupancy in low temperatures response.

  6. An Ada implementation of the network manager for the advanced information processing system

    Science.gov (United States)

    Nagle, Gail A.

    1986-01-01

    From an implementation standpoint, the Ada language provided many features which facilitated the data and procedure abstraction process. The language supported a design which was dynamically flexible (despite strong typing), modular, and self-documenting. Adequate training of programmers requires access to an efficient compiler which supports full Ada. When the performance issues for real time processing are finally addressed by more stringent requirements for tasking features and the development of efficient run-time environments for embedded systems, the full power of the language will be realized.

  7. The Spectrum Sensing Algorithm Based AdaBoost in Cognitive Radio

    Science.gov (United States)

    Tian, Deyong; Wang, Xin

    To solve the low detection rate of the primary user in the cognitive radio environment, we propose a spectrum sensing method based on AdaBoost in the case of low SNR. In this paper, a set of received signal spectrum features are first calculated and extracted the discriminant feature vector as training samples and testing samples for classification. Finally, we utilize the trained AdaBoost to detect the primary user. Test result shows that the proposed algorithm is not affected by uncertainty factors of noise and has high performance to classification detection compared with ANN, SVM and maximum-minimum eigenvalue (MME).

  8. ACC (1-Aminocyclopropane-1-Carboxylate) Deaminase Activity, a Widespread Trait in Burkholderia Species, and Its Growth-Promoting Effect on Tomato Plants▿

    OpenAIRE

    Onofre-Lemus, Janette; Hernández-Lucas, Ismael; Girard, Lourdes; Caballero-Mellado, Jesús

    2009-01-01

    The genus Burkholderia includes pathogens of plants and animals and some human opportunistic pathogens, such as the Burkholderia cepacia complex (Bcc), but most species are nonpathogenic, plant associated, and rhizospheric or endophytic. Since rhizobacteria expressing ACC (1-aminocyclopropane-1-carboxylate) deaminase may enhance plant growth by lowering plant ethylene levels, in this work we investigated the presence of ACC deaminase activity and the acdS gene in 45 strains, most of which are...

  9. Cytotoxic purine nucleoside analogues bind to A1, A2A and A3 adenosine receptors

    OpenAIRE

    Jensen, Kyle; Johnson, L’Aurelle A.; Jacobson, Pamala A.; Kachler, Sonja; Kirstein, Mark N.; Lamba, Jatinder; Klotz, Karl-Norbert

    2012-01-01

    Fludarabine, clofarabine and cladribine are anti-cancer agents which are analogues of the purine nucleoside adenosine. These agents have been associated with cardiac and neurological toxicities. Because these agents are analogues of adenosine, they may act through adenosine receptors to elicit their toxic effects. The objective of this study was to evaluate the ability of cytotoxic nucleoside analogues to bind and activate adenosine receptor subtypes (A1, A2A, A2B, and A3). Radioligand bindin...

  10. Development of coronary vasospasm during adenosine-stress myocardial perfusion CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Jeong Gu; Choi, Seong Hoon; Kang, Byeong Seong; Bang, Min Aeo; Kwon, Woon Jeong [Dept. of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan (Korea, Republic of)

    2015-06-15

    Adenosine is a short-acting coronary vasodilator, and it is widely used during pharmacological stress myocardial perfusion imaging. It has a well-established safety profile, and most of its side effects are known to be mild and transient. Until now, coronary vasospasm has been rarely reported as a side effect of adenosine during or after adenosine stress test. This study reports a case of coronary vasospasm which was documented on stress myocardial perfusion CT imaging during adenosine stress test.

  11. Characterization and optimization of 1-Aminocyclopropane-1-Carboxylate Deaminase (ACCD activity in different rhizospheric PGPR along with Microbacterium sp. strain ECI-12A

    Directory of Open Access Journals (Sweden)

    Ashok Kumar

    2013-03-01

    Full Text Available A total of nine strains of plant growth promoting rhizobacteria were analyzed for ACC deaminase activity, where highest ACC deaminase activity was found in Klebsiella sp strain ECI-10A (539.1 nmol α-keto butyrate/ mg protein/ h and lowest in Microbacterium sp strain ECI-12A (122.0 nmol α-keto butyrate/ mg protein/ h. Although Microbacterium sp strain ECI-12A showed lowest level of ACC deaminase activity, but, the species of Microbacterium isolated from rhizosphere is the first report. Microbacterium sp strain ECI-12A was also analyzed under varying conditions of time, amount of 1-Aminocyclopropane-1- carboxylate (ACC, and temperature for optimization of the ACC deaminase activity. The optimum activity was recorded with the supplementation of 5mM ACC at 30oC temperature after 24h of culture growth. All the nine strains showed acdS gene in the PCR amplification of that gene. No any rhizospheric Microbacterium species showing ACC deaminase activity have been reported earlier, therefore, we report here ACC deaminase activity in Microbacterium sp ECI-12A isolated from rice rhizosphere is a novel finding.

  12. The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias.

    Science.gov (United States)

    Welihinda, Ajith A; Kaur, Manmeet; Greene, Kelly; Zhai, Yongjiao; Amento, Edward P

    2016-06-01

    Inosine is an endogenous purine nucleoside that is produced by catabolism of adenosine. Adenosine has a short half-life (approximately 10s) and is rapidly deaminated to inosine, a stable metabolite with a half-life of approximately 15h. Resembling adenosine, inosine acting through adenosine receptors (ARs) exerts a wide range of anti-inflammatory and immunomodulatory effects in vivo. The immunomodulatory effects of inosine in vivo, at least in part, are mediated via the adenosine A2A receptor (A2AR), an observation that cannot be explained fully by in vitro pharmacological characterization of inosine at the A2AR. It is unclear whether the in vivo effects of inosine are due to inosine or a metabolite of inosine engaging the A2AR. Here, utilizing a combination of label-free, cell-based, and membrane-based functional assays in conjunction with an equilibrium agonist-binding assay we provide evidence for inosine engagement at the A2AR and subsequent activation of downstream signaling events. Inosine-mediated A2AR activation leads to cAMP production with an EC50 of 300.7μM and to extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation with an EC50 of 89.38μM. Our data demonstrate that inosine produces ERK1/2-biased signaling whereas adenosine produces cAMP-biased signaling at the A2AR, highlighting pharmacological differences between these two agonists. Given the in vivo stability of inosine, our data suggest an additional, previously unrecognized, mechanism that utilizes inosine to functionally amplify and prolong A2AR activation in vivo. PMID:26903141

  13. DMPD: Shaping of monocyte and macrophage function by adenosine receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17056121 Shaping of monocyte and macrophage function by adenosine receptors. Hasko ...tml) (.csml) Show Shaping of monocyte and macrophage function by adenosine receptors. PubmedID 17056121 Titl...e Shaping of monocyte and macrophage function by adenosine receptors. Authors Has

  14. Protein preparation and preliminary X-ray crystallographic analysis of a putative glucosamine 6-phosphate deaminase from Streptococcus mutants

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Guan-Jing; Li, Lan-Fen; Li, Dan; Liu, Cong [National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing 100871 (China); Wei, Shi-Cheng, E-mail: kqsc-wei@bjmu.edu.cn [Peking University School of Stomatology, Beijing 100081 (China); Liang, Yu-He, E-mail: kqsc-wei@bjmu.edu.cn; Su, Xiao-Dong [National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing 100871 (China)

    2007-09-01

    A glucosamine 6-phosphate deaminase homologue from S. mutans was expressed, purified and crystallized. Diffraction data have been collected to 2.4 Å resolution. The SMU.636 protein from Streptococcus mutans is a putative glucosamine 6-phosphate deaminase with 233 residues. The smu.636 gene was PCR-amplified from S. mutans genomic DNA and cloned into the expression vector pET-28a(+). The resultant His-tagged fusion protein was expressed in Escherichia coli and purified to homogeneity in two steps. Crystals of the fusion protein were obtained by the hanging-drop vapour-diffusion method. The crystals diffracted to 2.4 Å resolution and belong to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 53.83, b = 82.13, c = 134.70 Å.

  15. Searching Inhibitors of Adenosine Kinase by Simulation Methods

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-Xin; ZHANG Xing-Long; DONG Xi-Cheng; CHEN Min-Bo

    2006-01-01

    Searching new inhibitors of adenosine kinase (AK) is still drawing attention of experimental scientists. A better and solid model is here proposed by means of simulation methods from different ways, the direct analysis of receptor itself, the conventional 3D-QSAR methods and the integration of docking method and the conventional QSAR analysis.

  16. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... disorders. (b) Classification. Class I (general controls)....

  17. Vasoconstrictor and vasodilator effects of adenosine in the kidney

    DEFF Research Database (Denmark)

    Hansen, Pernille B; Schnermann, Jurgen

    2003-01-01

    that the steady-state response to the increase of plasma adenosine levels above normal resulting from the infusion is global renal vasorelaxation that is the result of A2AR activation in most parts of the renal vasculature, including larger renal arteries, juxtamedullary afferent arterioles, efferent arterioles...

  18. Implementation of Ada protocols on Mil-STD-1553 B data bus

    Science.gov (United States)

    Ruhman, Smil; Rosemberg, Flavia

    1986-01-01

    Standardization activity of data communication in avionic systems started in 1968 for the purpose of total system integration and the elimination of heavy wire bundles carrying signals between various subassemblies. The growing complexity of avionic systems is straining the capabilities of MIL-STD-1553 B (first issued in 1973), but a much greater challenge to it is posed by Ada, the standard language adopted for real-time, computer embedded-systems. Hardware implementation of Ada communication protocols in a contention/token bus or token ring network is proposed. However, during the transition period when the current command/response multiplex data bus is still flourishing and the development environment for distributed multi-computer Ada systems is as yet lacking, a temporary accomodation of the standard language with the standard bus could be very useful and even highly desirable. By concentrating all status informtion and decisions at the bus controller, it was found to be possible to construct an elegant and efficient harware impelementation of the Ada protocols at the bus interface. This solution is discussed.

  19. 76 FR 57013 - Recordkeeping and Reporting Requirements Under Title VII, the ADA, and GINA

    Science.gov (United States)

    2011-09-15

    ... proposed modifications of its recordkeeping and reporting provisions under title VII, the ADA, and GINA. (76 FR 31892, June 2, 2011). No requests to present oral testimony at a hearing concerning the... COMMISSION 29 CFR Part 1602 RIN 3046-AA89 Recordkeeping and Reporting Requirements Under Title VII, the...

  20. Anemia nos pacientes com insuficiência cardíaca avançada

    Directory of Open Access Journals (Sweden)

    Juliano Cardoso

    2010-10-01

    Full Text Available FUNDAMENTO: Anemia está associada à pior evolução nos pacientes com insuficiência cardíaca (IC. Entretanto, há poucos estudos sobre a anemia nos pacientes com IC avançada. OBJETIVO: Avaliar as características da anemia na IC em fase avançada. MÉTODOS: Foram incluídos 99 pacientes hospitalizados para compensação de IC (CF IV/NYHA, com idade > 18 anos e FEVE 12 g/dl. A anemia foi marcador independente de mau prognóstico na análise multivariada (mortalidade 47% vs 24,6%, p = 0,016, risco relativo 2,54. CONCLUSÃO: Anemia acomete, aproximadamente, 1/3 dos pacientes com IC avançada, e a deficiência de ferro é uma importante etiologia. Pacientes anêmicos são mais idosos e apresentaram função renal mais deteriorada. A melhora da congestão não foi suficiente para melhorar a anemia na maioria dos casos. Nos pacientes com IC avançada, a anemia é marcador independente de mau prognóstico.

  1. Automatic player detection and recognition in images using AdaBoost

    NARCIS (Netherlands)

    Mahmood, Zahid; Ali, Tauseef; Khattak, Shadid

    2012-01-01

    In this work we developed an augmented reality sports broadcasting application for enhanced end-user experience. The proposed system consists of three major steps. In the first step each player is detected using AdaBoost Algorithm. In second step, same algorithm is used to detect face in each player

  2. NTP pattern of avian embryonic red cells: role of RNA degradation and AMP deaminase/5'-nucleotidase activity.

    Science.gov (United States)

    Baumann, Rosemarie; Gotz, Robert; Dragon, Stefanie

    2003-03-01

    During terminal erythroid differentiation, degradation of RNA is a potential source for nucleotide triphosphates (NTPs) that act as allosteric effectors of hemoglobin. In this investigation, we assessed the developmental profile of RNA and purine/pyrimidine trinucleotides in circulating embryonic chick red blood cells (RBC). Extensive changes of the NTP pattern are observed which differ significantly from what is observed for adult RBC. The biochemical mechanisms have not been identified yet. Therefore, we studied the role of AMP deaminase and IMP/GMP 5'-nucleotidase, which are key enzymes for the regulation of the purine nucleotide pool. Finally, we tested the effect of major NTPs on the oxygen affinity of embryonic/adult hemoglobin. The results are as follows. 1) Together with ATP, UTP and CTP serve as allosteric effectors of hemoglobin. 2) Degradation of erythroid RNA is apparently a major source for NTPs. 3) Developmental changes of nucleotide content depend on the activities of key enzymes (AMP deaminase, IMP/GMP 5'-nucleotidase, and pyrimidine 5'-nucleotidase). 4) Oxygen-dependent hormonal regulation of AMP deaminase adjusts the red cell ATP concentration and therefore the hemoglobin oxygen affinity.

  3. The Rickettsia prowazekii invasion gene homolog (invA) encodes a Nudix hydrolase active on adenosine (5')-pentaphospho-(5')-adenosine.

    Science.gov (United States)

    Gaywee, Jariyanart; Xu, WenLian; Radulovic, Suzana; Bessman, Maurice J; Azad, Abdu F

    2002-03-01

    The genomic sequence of Rickettsia prowazekii, the obligate intracellular bacterium responsible for epidemic typhus, reveals an uncharacterized invasion gene homolog (invA). The deduced protein of 18,752 Da contains a Nudix signature, the specific motif found in the Nudix hydrolase family. To characterize the function of InvA, the gene was cloned and overexpressed in Escherichia coli. The expressed protein was purified to near homogeneity and subsequently tested for its enzymatic activity against a series of nucleoside diphosphate derivatives. The purified InvA exhibits hydrolytic activity toward dinucleoside oligophosphates (Np(n)N; n > or = 5), a group of cellular signaling molecules. At optimal pH 8.5, the enzyme actively degrades adenosine (5')-pentaphospho-(5')-adenosine into ATP and ADP with a K(m) of 0.1 mM and k(cat) of 1.9 s(-1). Guanosine (5')-pentaphospho-(5')-guanosine and adenosine-(5')-hexaphospho (5')-adenosine are also substrates. Similar to other Nudix hydrolases, InvA requires a divalent metal cation, Mg(2+) or Zn(2+), for optimal activity. These data suggest that the rickettsial invasion protein likely plays a role in controlling the concentration of stress-induced dinucleoside oligophosphates following bacterial invasion.

  4. Adenosine contributes to blood flow regulation in the exercising human leg by increasing prostaglandin and nitric oxide formation

    DEFF Research Database (Denmark)

    Mortensen, Stefan; Nyberg, Michael; Thaning, Pia;

    2009-01-01

    Adenosine can induce vasodilation in skeletal muscle, but to what extent adenosine exerts its effect via formation of other vasodilators and whether there is redundancy between adenosine and other vasodilators remain unclear. We tested the hypothesis that adenosine, prostaglandins, and NO act in...

  5. Adaptive evolution of threonine deaminase in plant defense against insect herbivores

    Energy Technology Data Exchange (ETDEWEB)

    Gonzales-Vigil, Eliana; Bianchetti, Christopher M.; Phillips, Jr., George N.; Howe, Gregg A. (MSU); (UW)

    2011-11-07

    Gene duplication is a major source of plant chemical diversity that mediates plant-herbivore interactions. There is little direct evidence, however, that novel chemical traits arising from gene duplication reduce herbivory. Higher plants use threonine deaminase (TD) to catalyze the dehydration of threonine (Thr) to {alpha}-ketobutyrate and ammonia as the committed step in the biosynthesis of isoleucine (Ile). Cultivated tomato and related Solanum species contain a duplicated TD paralog (TD2) that is coexpressed with a suite of genes involved in herbivore resistance. Analysis of TD2-deficient tomato lines showed that TD2 has a defensive function related to Thr catabolism in the gut of lepidopteran herbivores. During herbivory, the regulatory domain of TD2 is removed by proteolysis to generate a truncated protein (pTD2) that efficiently degrades Thr without being inhibited by Ile. We show that this proteolytic activation step occurs in the gut of lepidopteran but not coleopteran herbivores, and is catalyzed by a chymotrypsin-like protease of insect origin. Analysis of purified recombinant enzymes showed that TD2 is remarkably more resistant to proteolysis and high temperature than the ancestral TD1 isoform. The crystal structure of pTD2 provided evidence that electrostatic interactions constitute a stabilizing feature associated with adaptation of TD2 to the extreme environment of the lepidopteran gut. These findings demonstrate a role for gene duplication in the evolution of a plant defense that targets and co-opts herbivore digestive physiology.

  6. Camouflage Patterning in Maize Leaves Results from a Defect in Porphobilinogen Deaminase

    Institute of Scientific and Technical Information of China (English)

    Mingshu Huang; Thomas L.Slewinski; R.Frank Baker; Diane Janick-Buckner; Brent Buckner; Gurmukh S.Johal; David M.Braun

    2009-01-01

    Maize leaves are produced from polarized cell divisions that result in clonal cell lineages arrayed along the long axis of the leaf.We utilized this stereotypical division pattern to identify a collection of mutants that form chloroplast pigmentation sectors that violate the clonal cell lineages.Here,we describe the camouflage1 (cf1) mutant,which develops nonclonal,yellow-green sectors in its leaves.We cloned the cf1 gene by transposon tagging and determined that it encodes porphobilinogen deaminase (PBGD),an enzyme that functions early in chlorophyll and heme biosynthesis.While PBGD has been characterized biochemically,no viable mutations in this gene have been reported in plants.To investigate the in vivo function of PBGD,we characterized the cf1 mutant.Histological analyses revealed that of 1 yellow sectors display the novel phenotype of bundle sheath cell-specific death.Light-shift experiments determined that constant light suppressed cf1 sector formation,a dark/light transition is required to induce yellow sectors,and that sectors form only during a limited time of leaf development.Biochemical experiments determined that cf1 mutant leaves have decreased PBGD activity and increased levels of the enzyme substrate in both green and yellow regions.Furthermore,the cf1 yellow regions displayed a reduction in catalase activity.A threshold model is hypothesized to explain the cf1 variegation and incorporates photosynthetic cell differentiation,reactive oxygen species scavenging,and PBGD function.

  7. Tetrahydrouridine inhibits cell proliferation through cell cycle regulation regardless of cytidine deaminase expression levels.

    Directory of Open Access Journals (Sweden)

    Naotake Funamizu

    Full Text Available Tetrahydrouridine (THU is a well characterized and potent inhibitor of cytidine deaminase (CDA. Highly expressed CDA catalyzes and inactivates cytidine analogues, ultimately contributing to increased gemcitabine resistance. Therefore, a combination therapy of THU and gemcitabine is considered to be a potential and promising treatment for tumors with highly expressed CDA. In this study, we found that THU has an alternative mechanism for inhibiting cell growth which is independent of CDA expression. Three different carcinoma cell lines (MIAPaCa-2, H441, and H1299 exhibited decreased cell proliferation after sole administration of THU, while being unaffected by knocking down CDA. To investigate the mechanism of THU-induced cell growth inhibition, cell cycle analysis using flow cytometry was performed. This analysis revealed that THU caused an increased rate of G1-phase occurrence while S-phase occurrence was diminished. Similarly, Ki-67 staining further supported that THU reduces cell proliferation. We also found that THU regulates cell cycle progression at the G1/S checkpoint by suppressing E2F1. As a result, a combination regimen of THU and gemcitabine might be a more effective therapy than previously believed for pancreatic carcinoma since THU works as a CDA inhibitor, as well as an inhibitor of cell growth in some types of pancreatic carcinoma cells.

  8. Target DNA sequence directly regulates the frequency of activation-induced deaminase-dependent mutations.

    Science.gov (United States)

    Chen, Zhangguo; Viboolsittiseri, Sawanee S; O'Connor, Brian P; Wang, Jing H

    2012-10-15

    Activation-induced deaminase (AID) catalyses class switch recombination (CSR) and somatic hypermutation (SHM) in B lymphocytes to enhance Ab diversity. CSR involves breaking and rejoining highly repetitive switch (S) regions in the IgH (Igh) locus. S regions appear to be preferential targets of AID. To determine whether S region sequence per se, independent of Igh cis regulatory elements, can influence AID targeting efficiency and mutation frequency, we established a knock-in mouse model by inserting a core Sγ1 region into the first intron of proto-oncogene Bcl6, which is a non-Ig target of SHM. We found that the mutation frequency of the inserted Sγ1 region was dramatically higher than that of the adjacent Bcl6 endogenous sequence. Mechanistically, S region-enhanced SHM was associated with increased recruitment of AID and RNA polymerase II, together with Spt5, albeit to a lesser extent. Our studies demonstrate that target DNA sequences influence mutation frequency via regulating AID recruitment. We propose that the nucleotide sequence preference may serve as an additional layer of AID regulation by restricting its mutagenic activity to specific sequences despite the observation that AID has the potential to access the genome widely.

  9. Evolution of class switch recombination function in fish activation-induced cytidine deaminase, AID.

    Science.gov (United States)

    Wakae, Koshou; Magor, Brad G; Saunders, Holly; Nagaoka, Hitoshi; Kawamura, Akemi; Kinoshita, Kazuo; Honjo, Tasuku; Muramatsu, Masamichi

    2006-01-01

    Following activation of mammalian B cells, class switch recombination (CSR) and somatic hypermutation (SHM) of the Ig heavy chain (IgH) gene can improve the functions of the expressed antibodies. Activation-induced cytidine deaminase (AID) is the only known B cell-specific protein required for inducing CSR and SHM in mammals. Lower vertebrates have an AID homologue, and there is some evidence of SHM in vivo. However there is no evidence of CSR in the cartilaginous or bony fishes, and this may be due in part to a lack of cis-elements in the IgH gene that are the normal targets of AID-mediated recombination. We have tested whether bony fish (zebrafish and catfish) AID can mediate CSR and SHM in mammalian cells. As expected, ectopic expression of fish AID in mouse fibroblasts resulted in mutations in an introduced SHM reporter gene, indicating that fish AID can mediate SHM. Unexpectedly, expression of fish AID in mouse AID-/- B cells induced surface IgG expression as well as switched transcripts from Ig gene loci, clearly indicating that the fish AID protein can mediate CSR, at least in mouse cells. These results suggest that the AID protein acquired the ability to mediate CSR before the IgH locus evolved the additional exon clusters and switch regions that are the targets of recombination. We discuss how pleiotropic functions of specific domains within the AID protein may have facilitated the early evolution of CSR in lower vertebrates.

  10. Structural analysis of the activation-induced deoxycytidine deaminase required in immunoglobulin diversification.

    Science.gov (United States)

    Pham, Phuong; Afif, Samir A; Shimoda, Mayuko; Maeda, Kazuhiko; Sakaguchi, Nobuo; Pedersen, Lars C; Goodman, Myron F

    2016-07-01

    Activation-induced deoxycytidine deaminase (AID) initiates somatic hypermutation (SHM) and class-switch recombination (CSR) by deaminating C→U during transcription of Ig-variable (V) and Ig-switch (S) region DNA, which is essential to produce high-affinity antibodies. Here we report the crystal structure of a soluble human AID variant at 2.8Å resolution that favors targeting WRC motifs (W=A/T, R=A/G) in vitro, and executes Ig V SHM in Ramos B-cells. A specificity loop extending away from the active site to accommodate two purine bases next to C, differs significantly in sequence, length, and conformation from APOBEC proteins Apo3A and Apo3G, which strongly favor pyrimidines at -1 and -2 positions. Individual amino acid contributions to specificity and processivity were measured in relation to a proposed ssDNA binding cleft. This study provides a structural basis for residue contributions to DNA scanning properties unique to AID, and for disease mutations in human HIGM-2 syndrome. PMID:27258794

  11. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Yi, E-mail: yihooyi@gmail.com; Ericsson, Ida, E-mail: ida.ericsson@ntnu.no; Doseth, Berit, E-mail: berit.doseth@ntnu.no; Liabakk, Nina B., E-mail: nina.beate.liabakk@ntnu.no; Krokan, Hans E., E-mail: hans.krokan@ntnu.no; Kavli, Bodil, E-mail: bodil.kavli@ntnu.no

    2014-03-10

    Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation.

  12. The Role of Histidine-Proline-Rich Glycoprotein as Zinc Chaperone for Skeletal Muscle AMP Deaminase

    Directory of Open Access Journals (Sweden)

    Maria Ranieri-Raggi

    2014-05-01

    Full Text Available Metallochaperones function as intracellular shuttles for metal ions. At present, no evidence for the existence of any eukaryotic zinc-chaperone has been provided although metallochaperones could be critical for the physiological functions of Zn2+ metalloenzymes. We propose that the complex formed in skeletal muscle by the Zn2+ metalloenzyme AMP deaminase (AMPD and the metal binding protein histidine-proline-rich glycoprotein (HPRG acts in this manner. HPRG is a major plasma protein. Recent investigations have reported that skeletal muscle cells do not synthesize HPRG but instead actively internalize plasma HPRG. X-ray absorption spectroscopy (XAS performed on fresh preparations of rabbit skeletal muscle AMPD provided evidence for a dinuclear zinc site in the enzyme compatible with a (μ-aqua(μ-carboxylatodizinc(II core with two histidine residues at each metal site. XAS on HPRG isolated from the AMPD complex showed that zinc is bound to the protein in a dinuclear cluster where each Zn2+ ion is coordinated by three histidine and one heavier ligand, likely sulfur from cysteine. We describe the existence in mammalian HPRG of a specific zinc binding site distinct from the His-Pro-rich region. The participation of HPRG in the assembly and maintenance of skeletal muscle AMPD by acting as a zinc chaperone is also demonstrated.

  13. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

    Science.gov (United States)

    Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

    2016-04-01

    Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver. PMID:26908609

  14. Activation-induced cytidine deaminase (AID) is localized to subnuclear domains enriched in splicing factors

    International Nuclear Information System (INIS)

    Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and found that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation

  15. Activation-induced deoxycytidine deaminase (AID) co-transcriptional scanning at single-molecule resolution

    Science.gov (United States)

    Senavirathne, Gayan; Bertram, Jeffrey G.; Jaszczur, Malgorzata; Chaurasiya, Kathy R.; Pham, Phuong; Mak, Chi H.; Goodman, Myron F.; Rueda, David

    2015-12-01

    Activation-induced deoxycytidine deaminase (AID) generates antibody diversity in B cells by initiating somatic hypermutation (SHM) and class-switch recombination (CSR) during transcription of immunoglobulin variable (IgV) and switch region (IgS) DNA. Using single-molecule FRET, we show that AID binds to transcribed dsDNA and translocates unidirectionally in concert with RNA polymerase (RNAP) on moving transcription bubbles, while increasing the fraction of stalled bubbles. AID scans randomly when constrained in an 8 nt model bubble. When unconstrained on single-stranded (ss) DNA, AID moves in random bidirectional short slides/hops over the entire molecule while remaining bound for ~5 min. Our analysis distinguishes dynamic scanning from static ssDNA creasing. That AID alone can track along with RNAP during transcription and scan within stalled transcription bubbles suggests a mechanism by which AID can initiate SHM and CSR when properly regulated, yet when unregulated can access non-Ig genes and cause cancer.

  16. Activation-induced cytidine deaminase deficiency causes organ-specific autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Koji Hase

    Full Text Available Activation-induced cytidine deaminase (AID expressed by germinal center B cells is a central regulator of somatic hypermutation (SHM and class switch recombination (CSR. Humans with AID mutations develop not only the autosomal recessive form of hyper-IgM syndrome (HIGM2 associated with B cell hyperplasia, but also autoimmune disorders by unknown mechanisms. We report here that AID-/- mice spontaneously develop tertiary lymphoid organs (TLOs in non-lymphoid tissues including the stomach at around 6 months of age. At a later stage, AID-/- mice develop a severe gastritis characterized by loss of gastric glands and epithelial hyperplasia. The disease development was not attenuated even under germ-free (GF conditions. Gastric autoantigen -specific serum IgM was elevated in AID-/- mice, and the serum levels correlated with the gastritis pathological score. Adoptive transfer experiments suggest that autoimmune CD4+ T cells mediate gastritis development as terminal effector cells. These results suggest that abnormal B-cell expansion due to AID deficiency can drive B-cell autoimmunity, and in turn promote TLO formation, which ultimately leads to the propagation of organ-specific autoimmune effector CD4+ T cells. Thus, AID plays an important role in the containment of autoimmune diseases by negative regulation of autoreactive B cells.

  17. Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice.

    Science.gov (United States)

    Witts, Emily C; Nascimento, Filipe; Miles, Gareth B

    2015-10-01

    Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925-1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output. PMID:26311185

  18. Adenosine receptors and stress : Studies using methylmercury, caffeine and hypoxia

    OpenAIRE

    Björklund, Olga

    2008-01-01

    Brain development is a precisely organized process that can be disturbed by various stress factors present in the diet (e.g. exposure to xenobiotics) as well as insults such as decreased oxygen supply. The consequent adverse changes in nervous system function may not necessarily be apparent until a critical age when neurodevelopmental defects may be unmasked by a subsequent challenge. Adenosine and its receptors (AR) (A1, A2A, A2B and A3) which participate in the brain stres...

  19. Myocardial energy metabolism in ischemic preconditioning, role of adenosine catabolism

    OpenAIRE

    Kavianipour, Mohammad

    2002-01-01

    Brief episodes of ischemia and reperfusion render the myocardium more resistant to necrosis from a subsequent, otherwise lethal ischemic insult. This phenomenon is called ischemic preconditioning(IP). Today, much is known about the signalling pathways involved in IP; however, the details of the final steps leading to cardioprotection, remain elusive. Adenosine (a catabolite of ATP) plays a major role in the signalling pathways of IP. Following IP there is an unexplained discrepancy between an...

  20. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    Science.gov (United States)

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  1. Real-time multi-camera video acquisition and processing platform for ADAS

    Science.gov (United States)

    Saponara, Sergio

    2016-04-01

    The paper presents the design of a real-time and low-cost embedded system for image acquisition and processing in Advanced Driver Assisted Systems (ADAS). The system adopts a multi-camera architecture to provide a panoramic view of the objects surrounding the vehicle. Fish-eye lenses are used to achieve a large Field of View (FOV). Since they introduce radial distortion of the images projected on the sensors, a real-time algorithm for their correction is also implemented in a pre-processor. An FPGA-based hardware implementation, re-using IP macrocells for several ADAS algorithms, allows for real-time processing of input streams from VGA automotive CMOS cameras.

  2. Reinforced AdaBoost Learning for Object Detection with Local Pattern Representations

    OpenAIRE

    Younghyun Lee; Han, David K.; Hanseok Ko

    2013-01-01

    A reinforced AdaBoost learning algorithm is proposed for object detection with local pattern representations. In implementing Adaboost learning, the proposed algorithm employs an exponential criterion as a cost function and Newton’s method for its optimization. In particular, we introduce an optimal selection of weak classifiers minimizing the cost function and derive the reinforced predictions based on a judicial confidence estimate to determine the classification results. The weak classifie...

  3. VIII Olimpíada Brasileira de Astronomia e Astronáutica

    Science.gov (United States)

    Garcia Canalle, João Batista; Villas da Rocha, Jaime Fernando; Wuensche de Souza, Carlos Alexandre; Pereira Ortiz, Roberto; Aguilera, Nuricel Villalonga; Padilha, Maria De Fátima Catta Preta; Pessoa Filho, José Bezerra; Soares Rodrigues, Ivette Maria

    2007-07-01

    Neste trabalho apresentamos as motivações pelas quais organizamos, em conjunto, pela primeira vez, a Olimpíada Brasileira de Astronomia incluindo a Astronáutica, em colaboração com a Agência Espacial Brasileira. Esta ampliação contribuiu para atrair ainda mais alunos, professores, escolas e patrocinadores para participarem desta Olimpíada. Em 2005 participaram da VIII Olimpíada Brasileira de Astronomia e Astronáutica (VIII OBA) 187.726 alunos distribuídos por 3.229 escolas, pertencentes a todos os estados brasileiros, incluindo o Distrito Federal. O crescimento em número de alunos participantes foi 52,4% maior do que em 2004. Em abril de 2005 organizamos, em Itapecerica da Serra, SP, um curso para os 50 alunos previamente selecionados e participantes da VII OBA e ao final selecionamos, dentre eles, uma equipe de 5 alunos, os quais representaram o Brasil na X Olimpíada Internacional de Astronomia, na China, em outubro de 2005. Ganhamos, pela primeira vez, uma medalha de ouro naquele evento. Em Agosto de 2005, organizamos a VIII Escola de Agosto para 50 alunos e respectivos professores, em Águas de Lindóia, SP, juntamente com a XXXI reunião anual da Sociedade Astronômica Brasileira (SAB). Em novembro de 2005 realizamos a I Jornada Espacial, em São José dos Campos, com 22 alunos e 22 professores selecionados dentre os participantes que melhores resultados obtiveram nas questões de Astronáutica da VIII OBA. Neste trabalho detalhamos os resultados da VIII OBA bem como as ações subseqüentes.

  4. Model-Based Software Engineering and Ada: Synergy for the Development of Safety-Critical Systems

    OpenAIRE

    Blotz, Andree; Huber, Franz; Loetzbeyer, Heiko; Pretschner, Alexander; Slotosch, Oscar; Zaengerl, Hans-Peter

    2002-01-01

    In this paper we outline a software development process for safety-critical systems that aims at combining some of the specific strengths of model-based development with those of programming language based development using safety-critical subsets of Ada. Model-based software development and model-based test case generation techniques are combined with code generation techniques and tools providing a transition from model to code both for a system itself and for its test cases. This allows de...

  5. ADA2 deficiency: case report of a new phenotype and novel mutation in two sisters.

    Science.gov (United States)

    Uettwiller, F; Sarrabay, G; Rodero, M P; Rice, G I; Lagrue, E; Marot, Y; Deiva, K; Touitou, I; Crow, Y J; Quartier, P

    2016-01-01

    The objective of this paper is to: describe the phenotype compound heterozygote for mutations in CECR1 in two children. We describe the clinical and immunological phenotype, including the assessment of ADA2 activity, cytokine expression, interferon-stimulated and neutrophil-stimulated gene signatures, and the results of CECR1 sequencing. The first patient presented with intermittent fever, cutaneous vasculitis, myalgia and muscle inflammation on MRI leading to a provisional diagnosis of periarteritis nodosa. Subsequently, two cerebral lacunar lesions were identified following a brain stroke. Clinical features improved on anti-tumour necrosis factor therapy. The first patient's sister demonstrated early-onset, long-lasting anaemia with mild biological inflammation; at the ages of 3 and 5 years, she had presented 2 acute, transient neurological events with lacunar lesions on MRI. CECR1 sequencing identified both sisters to be compound heterozygous for a p.Tyr453Cys mutation and a previously undescribed deletion of exon 7. ADA2 activity was reduced by 50%. Neutrophil-stimulated genes were not overexpressed, but interferon-stimulated genes were. The expression of a panel of other cytokine transcripts was not significantly altered. In conclusion, searching for CECR1 mutation or assessing ADA2 activity should be considered in patients with an atypical presentation of inflammatory disease. PMID:27252897

  6. AdaFF: Adaptive Failure-Handling Framework for Composite Web Services

    Science.gov (United States)

    Kim, Yuna; Lee, Wan Yeon; Kim, Kyong Hoon; Kim, Jong

    In this paper, we propose a novel Web service composition framework which dynamically accommodates various failure recovery requirements. In the proposed framework called Adaptive Failure-handling Framework (AdaFF), failure-handling submodules are prepared during the design of a composite service, and some of them are systematically selected and automatically combined with the composite Web service at service instantiation in accordance with the requirement of individual users. In contrast, existing frameworks cannot adapt the failure-handling behaviors to user's requirements. AdaFF rapidly delivers a composite service supporting the requirement-matched failure handling without manual development, and contributes to a flexible composite Web service design in that service architects never care about failure handling or variable requirements of users. For proof of concept, we implement a prototype system of the AdaFF, which automatically generates a composite service instance with Web Services Business Process Execution Language (WS-BPEL) according to the users' requirement specified in XML format and executes the generated instance on the ActiveBPEL engine.

  7. Using Ada to implement the operations management system in a community of experts

    Science.gov (United States)

    Frank, M. S.

    1986-01-01

    An architecture is described for the Space Station Operations Management System (OMS), consisting of a distributed expert system framework implemented in Ada. The motivation for such a scheme is based on the desire to integrate the very diverse elements of the OMS while taking maximum advantage of knowledge based systems technology. Part of the foundation of an Ada based distributed expert system was accomplished in the form of a proof of concept prototype for the KNOMES project (Knowledge-based Maintenance Expert System). This prototype successfully used concurrently active experts to accomplish monitoring and diagnosis for the Remote Manipulator System. The basic concept of this software architecture is named ACTORS for Ada Cognitive Task ORganization Scheme. It is when one considers the overall problem of integrating all of the OMS elements into a cooperative system that the AI solution stands out. By utilizing a distributed knowledge based system as the framework for OMS, it is possible to integrate those components which need to share information in an intelligent manner.

  8. Ada (R) assessment: An important issue within European Columbus Support Technology Programme

    Science.gov (United States)

    Vielcanet, P.

    1986-01-01

    Software will be more important and more critical for Columbus than for any ESA previous project. As a simple comparison, overall software size has been in the range of 100 K source statements for EXOSAT, 500 K for Spacelab, and will probably reach several million lines of code for Columbus (all element together). Based on past experience, the total development cost of software can account for about 10 pct to 15 pct of the total space project development cost. The Ada technology may support the strong software engineering principles needed for Columbus, provided that technology is sufficiently mature and industry plans are meeting the Columbus project schedule. Over the past 3 years, Informatique Internationale has conducted a coherent program based on Ada technology assessment studies and experiments, for ESA and CNES. This specific research and development program benefits from 15 years experience in the field of space software development and is supported by the overall software engineering expertise of the company. The assessment and experiments of Ada software engineering by Informatique Internationale are detailed.

  9. Cytosine Deaminase/5-Fluorocytosine Exposure Induces Bystander and Radiosensitization Effects in Hypoxic Glioblastoma Cells in vitro

    International Nuclear Information System (INIS)

    Purpose: Treatment of glioblastoma (GBM) is limited by therapeutic ratio; therefore, successful therapy must be specifically cytotoxic to cancer cells. Hypoxic cells are ubiquitous in GBM, and resistant to radiation and chemotherapy, and, thus, are logical targets for gene therapy. In this study, we investigated whether cytosine deaminase (CD)/5-fluorocytosine (5-FC) enzyme/prodrug treatment induced a bystander effect (BE) and/or radiosensitization in hypoxic GBM cells. Methods and Materials: We stably transfected cells with a gene construct consisting of the SV40 minimal promoter, nine copies of a hypoxia-responsive element, and the yeast CD gene. During hypoxia, a hypoxia-responsive element regulates expression of the CD gene and facilitates the conversion of 5-FC to 5-fluorouracil, a highly toxic antimetabolite. We used colony-forming efficiency (CFE) and immunofluorescence assays to assess for BE in co-cultures of CD-expressing clone cells and parent, pNeo- or green fluorescent protein-stably transfected GBM cells. We also investigated the radiosensitivity of CD clone cells treated with 5-FC under hypoxic conditions, and we used flow cytometry to investigate treatment-induced cell cycle changes. Results: Both a large BE and radiosensitization occurred in GBM cells under hypoxic conditions. The magnitude of the BE depended on the number of transfected cells producing CD, the functionality of the CD, the administered concentration of 5-FC, and the sensitivity of cell type to 5-fluorouracil. Conclusion: Hypoxia-inducible CD/5-FC therapy in combination with radiation therapy shows both a pronounced BE and a radiosensitizing effect under hypoxic conditions

  10. RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase.

    Science.gov (United States)

    Liang, Guoxin; Kitamura, Kouichi; Wang, Zhe; Liu, Guangyan; Chowdhury, Sajeda; Fu, Weixin; Koura, Miki; Wakae, Kousho; Honjo, Tasuku; Muramatsu, Masamichi

    2013-02-01

    Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. The mechanism by which AID triggers SHM and CSR has been explained by two distinct models. In the DNA deamination model, AID converts cytidine bases in DNA into uridine. The uridine is recognized by the DNA repair system, which produces DNA strand breakages and point mutations. In the alternative model, RNA edited by AID is responsible for triggering CSR and SHM. However, RNA deamination by AID has not been demonstrated. Here we found that C-to-T and G-to-A mutations accumulated in hepatitis B virus (HBV) nucleocapsid DNA when AID was expressed in HBV-replicating hepatic cell lines. AID expression caused C-to-T mutations in the nucleocapsid DNA of RNase H-defective HBV, which does not produce plus-strand viral DNA. Furthermore, the RT-PCR products of nucleocapsid viral RNA from AID-expressing cells exhibited significant C-to-T mutations, whereas viral RNAs outside the nucleocapsid did not accumulate C-to-U mutations. Moreover, AID was packaged within the nucleocapsid by forming a ribonucleoprotein complex with HBV RNA and the HBV polymerase protein. The encapsidation of the AID protein with viral RNA and DNA provides an efficient environment for evaluating AID's RNA and DNA deamination activities. A bona fide RNA-editing enzyme, apolipoprotein B mRNA editing catalytic polypeptide 1, induced a similar level of C-to-U mutations in nucleocapsid RNA as AID. Taken together, the results indicate that AID can deaminate the nucleocapsid RNA of HBV.

  11. Mutation Processes in 293-Based Clones Overexpressing the DNA Cytosine Deaminase APOBEC3B.

    Directory of Open Access Journals (Sweden)

    Monica K Akre

    Full Text Available Molecular, cellular, and clinical studies have combined to demonstrate a contribution from the DNA cytosine deaminase APOBEC3B (A3B to the overall mutation load in breast, head/neck, lung, bladder, cervical, ovarian, and other cancer types. However, the complete landscape of mutations attributable to this enzyme has yet to be determined in a controlled human cell system. We report a conditional and isogenic system for A3B induction, genomic DNA deamination, and mutagenesis. Human 293-derived cells were engineered to express doxycycline-inducible A3B-eGFP or eGFP constructs. Cells were subjected to 10 rounds of A3B-eGFP exposure that each caused 80-90% cell death. Control pools were subjected to parallel rounds of non-toxic eGFP exposure, and dilutions were done each round to mimic A3B-eGFP induced population fluctuations. Targeted sequencing of portions of TP53 and MYC demonstrated greater mutation accumulation in the A3B-eGFP exposed pools. Clones were generated and microarray analyses were used to identify those with the greatest number of SNP alterations for whole genome sequencing. A3B-eGFP exposed clones showed global increases in C-to-T transition mutations, enrichments for cytosine mutations within A3B-preferred trinucleotide motifs, and more copy number aberrations. Surprisingly, both control and A3B-eGFP clones also elicited strong mutator phenotypes characteristic of defective mismatch repair. Despite this additional mutational process, the 293-based system characterized here still yielded a genome-wide view of A3B-catalyzed mutagenesis in human cells and a system for additional studies on the compounded effects of simultaneous mutation mechanisms in cancer cells.

  12. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations.

    Science.gov (United States)

    Sawai, Yugo; Kodama, Yuzo; Shimizu, Takahiro; Ota, Yuji; Maruno, Takahisa; Eso, Yuji; Kurita, Akira; Shiokawa, Masahiro; Tsuji, Yoshihisa; Uza, Norimitsu; Matsumoto, Yuko; Masui, Toshihiko; Uemoto, Shinji; Marusawa, Hiroyuki; Chiba, Tsutomu

    2015-08-15

    Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC.

  13. Rezension: Ada Lovelace. Die Pionierin der Computertechnik und ihre Nachfolgerinnen von Sybille Krämer (Hg.)

    OpenAIRE

    Bettina Schabschneider

    2015-01-01

    Ein aktueller von Sybille Krämer herausgegebener Sammelband beleuchtet die Bedeutung der Computertechnik-Pionierin Ada Lovelace. Bettina Schabschneider hat den Band einer detaillierten Lektüre unterzogen und für die MEDIENIMPULSE rezensiert …

  14. Intracellular signalling pathways in the vasoconstrictor response of mouse afferent arterioles to adenosine

    DEFF Research Database (Denmark)

    Hansen, Pernille B. Lærkegaard; Friis, Ulla Glenert; Uhrenholt, Torben Rene;

    2007-01-01

    calcium from the sarcoplasmic reticulum (SR), stimulated presumably by IP(3), is involved in the adenosine contraction mechanism of the afferent arteriole. In agreement with this notion is the observation that 2 aminoethoxydiphenyl borate (100 microM) blocked the adenosine-induced constriction whereas the...... protein kinase C inhibitor calphostin C had no effect. The calcium-activated chloride channel inhibitor IAA-94 (30 microM) inhibited the adenosine-mediated constriction. Patch clamp experiments showed that adenosine treatment induced a depolarizing current in preglomerular smooth muscle cells which was....... METHODS AND RESULTS: Adenosine (10(-7) M) significantly increased the intracellular calcium concentration in mouse isolated afferent arterioles measured by fura-2 fluorescence. Pre-treatment with thapsigargin (2 microM) blocked the vasoconstrictor action of adenosine (10(-7) M) indicating that release of...

  15. [Effects of dopamine and adenosine on regulation of water-electrolyte exchange in Amoeba proteus].

    Science.gov (United States)

    Bagrov, Ia Iu; Manusova, N B

    2014-01-01

    Dopamine and adenosine both regulate transport of sodium chloride in the renal tubules in mammals. We have studied the effect of dopamine and adenosine on spontaneous activity of contractile vacuole of Amoeba proteous. Both substances stimulated contractile vacuole. The effect of dopamine was suppressed by D2 receptor antagonist, haloperidol, but not by D1 antagonist, SCH 39166. Adenylate cyclase inhibitor, 2.5-dideoxyadenosine, suppressed the effect of dopamine, but not of adenosine. Inhibitor of protein kinase C, staurosporine, in contrast, blocked the effect of adenosine, but not dopamine. Notably, dopamine opposed effect of adenosine and vice versa. These results suggest that similar effects of dopamine and adenosine could be mediated by different intracellulare mechanisms.

  16. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

    2015-01-01

    Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP......) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18...

  17. Contraction induced secretion of VEGF from skeletal muscle cells is mediated by adenosine

    DEFF Research Database (Denmark)

    Høier, Birgitte; Olsen, Karina; Nyberg, Michael Permin;

    2010-01-01

    The role of adenosine and contraction for secretion of VEGF in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted into the thigh muscle of seven male subjects and dialysate was collected at rest, during infusion of adenosine...... and contraction caused secretion of VEGF (pcontraction induced secretion of VEGF protein was abolished by the A(2B) antagonist enprofyllin and markedly reduced by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells...... and that the contraction induced secretion of VEGF is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent....

  18. HIV-1 Vif versus the APOBEC3 cytidine deaminases: an intracellular duel between pathogen and host restriction factors.

    Science.gov (United States)

    Wissing, Silke; Galloway, Nicole L K; Greene, Warner C

    2010-10-01

    The Vif protein of HIV is essential for the effective propagation of this pathogenic retrovirus in vivo. Vif acts by preventing virion encapsidation of two potent antiviral factors, the APOBEC3G and APOBEC3F cytidine deaminases. Decreased encapsidation in part involves Vif-mediated recruitment of a ubiquitin E3 ligase complex that promotes polyubiquitylation and proteasome-mediated degradation of APOBEC3G/F. The resultant decline in intracellular levels of these enzymes leads to decreased encapsidation of APOBECG/F into budding virions. This review discusses recent advances in our understanding of the dynamic interplay of Vif with the antiviral APOBEC3 enzymes. PMID:20538015

  19. NF-IL6 (C/EBPβ) induces HIV-1 replication by inhibiting cytidine deaminase APOBEC3G

    OpenAIRE

    Shigemi M Kinoshita; Taguchi, Shizuka

    2008-01-01

    T cell activation is crucial for the productive HIV-1 infection of primary T cells; however, little is known about the host molecules involved in this process. We show that the host transcription factor NF-IL6 (also called C/EBPβ) renders primary CD4+ T cells highly permissive for HIV-1 replication. NF-IL6 facilitates reverse transcription of the virus by binding to and inhibiting the antiviral cytidine deaminase APOBEC3G. A mutation in NF-IL6 at Ser-288 weakened its binding to APOBEC3G and s...

  20. RNA binding to APOBEC3G induces the disassembly of functional deaminase complexes by displacing single-stranded DNA substrates

    OpenAIRE

    Polevoda, Bogdan; McDougall, William M.; Tun, Bradley N.; Cheung, Michael; Salter, Jason D.; Friedman, Alan E.; Smith, Harold C.

    2015-01-01

    APOBEC3G (A3G) DNA deaminase activity requires a holoenzyme complex whose assembly on nascent viral reverse transcripts initiates with A3G dimers binding to ssDNA followed by formation of higher-order A3G homo oligomers. Catalytic activity is inhibited when A3G binds to RNA. Our prior studies suggested that RNA inhibited A3G binding to ssDNA. In this report, near equilibrium binding and gel shift analyses showed that A3G assembly and disassembly on ssDNA was an ordered process involving A3G d...

  1. Implementación de un framework de componente en el lenguaje de programación Ada

    OpenAIRE

    Hernández Villalón, Francisco José

    2013-01-01

    El objetivo principal de este proyecto es la traducción de FrameworkAda 2005 y mantener la compatibilidad entre las dos implementaciones de Framework que se realizaron anteriormente C++ y Java. Cabe destacar que la implementación en Java es el Framework de partida de donde derivan estas dos últimas C++ y Ada 2005. Escuela Técnica Superior de Ingeniería Industrial Universidad Politécnica de Cartagena

  2. Topical adenosine increases the proportion of thick hair in Caucasian men with androgenetic alopecia.

    Science.gov (United States)

    Iwabuchi, Tokuro; Ideta, Ritsuro; Ehama, Ritsuko; Yamanishi, Haruyo; Iino, Masato; Nakazawa, Yosuke; Kobayashi, Takashi; Ohyama, Manabu; Kishimoto, Jiro

    2016-05-01

    Adenosine is an effective treatment for androgenetic alopecia (AGA) in Japanese men and women. Adenosine exerts its effects by significantly increasing the proportion of thick hair. In this study, we assessed the clinical outcome of adenosine treatment for 6 months in 38 Caucasian men. The change in proportion of thick hair (≥60 μm) compared with baseline in the adenosine group was significantly higher than that in the placebo group (P thick hair in Caucasian men with AGA as well as in Japanese men and women.

  3. Comparison of the novel vasodilator uridine triphosphate and adenosine for the measurement of fractional flow reserve

    DEFF Research Database (Denmark)

    Sivertsen, Jacob; Jensen, Jan Skov; Galatius, Søren;

    2014-01-01

    AIM: Examination of the fractional flow reserve (FFR) responses of intravenous (IV) adenosine with increasing doses of intracoronary (IC) adenosine versus IC uridine triphosphate (UTP) in patients with coronary artery disease. METHODS AND RESULTS: We measured FFR in 25 patients during continuous IV...... and IC infusion (using a microcatheter in the coronary ostium). Standard IV adenosine infusion (140 μg/kg/min) was compared to 8 equimolar incremental doses of IC UTP and IC adenosine (20, 40, 60, 80, 160, 240, 320 and 640 μg/min) in a randomized order. Across all doses, ΔFFR[IC UTP - IC adenosine......] was -0.038 ± 0.008, Pdose of IC UTP, FFR was significantly lower (FFR[IC UTP] = 0.62 ± 0.04) than during IV adenosine (FFR[IV adenosine] = 0.72 ± 0.05; P=.02) and IC adenosine (FFR[IC adenosine] = 0.68 ± 0.05; P=.03). Furthermore, UTP had significantly fewer side effects compared...

  4. Research on Classification of Neuron Morphology Based on AdaBoost%基于AdaBoost的神经元形态分类的研究

    Institute of Scientific and Technical Information of China (English)

    陆良虎; 毕硕本; 葛荐; 闫荞荞; 颜坚

    2011-01-01

    根据神经元形态的几何特征,使用AdaBoost算法对其进行分类,采用决策树、贝叶斯和关联规则分类模型作为基分类器。算法首先采用直接面向纽舍分类器分类精度提升的集成学刁算法选取基分类器,其次利用分类过程中生成样本的孱升权值来调整前K次(K〉1)被错误分类样本的权重,并提留双重阎值法对样本的最终投票表决结果进行判定。对20个测试样本进行分类,得出高可信度分类数为18个。%According to the geometric characteristics of neuron morphology, neurons were classified by AdaBoost algorithm, in which the decision tree, Bayesian and association rules classification model were used as base classifiers Firstly, the improvement of the classification precision of combined classifier directly oriented ensemble learning algorithms were adopted to select the base classifier. Secondly, cumulative weights of the sample generated during the classification were used to adjust the weights of misclassified samples in the former K (K〉 1) classification processes, and the dual threshold values for final voting results of samples were set. The 20 test samples were classified by AadBoost algorithm, and the results show that the number of highly reliable classification is 18.

  5. First-In-Class Small Molecule Inhibitors of the Single-Strand DNA Cytosine Deaminase APOBEC3G

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ming; Shandilya, Shivender M.D.; Carpenter, Michael A.; Rathore, Anurag; Brown, William L.; Perkins, Angela L.; Harki, Daniel A.; Solberg, Jonathan; Hook, Derek J.; Pandey, Krishan K.; Parniak, Michael A.; Johnson, Jeffrey R.; Krogan, Nevan J.; Somasundaran, Mohan; Ali, Akbar; Schiffer, Celia A.; Harris, Reuben S. (Pitt); (UMASS, MED); (SLUHSC); (UCSF); (UMM)

    2012-04-04

    APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput screening identified 34 compounds that inhibit APOBEC3G catalytic activity. Twenty of 34 small molecules contained catechol moieties, which are known to be sulfhydryl reactive following oxidation to the orthoquinone. Located proximal to the active site, C321 was identified as the binding site for the inhibitors by a combination of mutational screening, structural analysis, and mass spectrometry. Bulkier substitutions C321-to-L, F, Y, or W mimicked chemical inhibition. A strong specificity for APOBEC3G was evident, as most compounds failed to inhibit the related APOBEC3A enzyme or the unrelated enzymes E. coli uracil DNA glycosylase, HIV-1 RNase H, or HIV-1 integrase. Partial, but not complete, sensitivity could be conferred to APOBEC3A by introducing the entire C321 loop from APOBEC3G. Thus, a structural model is presented in which the mechanism of inhibition is both specific and competitive, by binding a pocket adjacent to the APOBEC3G active site, reacting with C321, and blocking access to substrate DNA cytosines.

  6. Killing effect of adenoviral mediated cytosine deaminase gene on human pancreatic cancer cell line PaTu 8988

    Institute of Scientific and Technical Information of China (English)

    PAN Xue; LI Zhao-shen; XU Guo-ming; CUI Long; ZHANG Su-zhen; GONG Yan-fang; TU Zhen-xing

    2001-01-01

    Objective: To evaluate the in vitro killing effects of cytosine deaminase gene mediated by adenovirus vector on human pancreatic carcinoma. Methods: Cytosine Deaminase (CD) gene was cloned into pAdTrack-CMV-CD, pAdTrack-CMV-CD and pAdEasy-1 were recombined in bacteria, and the products containing green fluorescent protein (GFP)were propagated in 293 cells and purified by cesium chloride gradient centrifugation. Human pancreatic carcinoma cell line 8988 were infected with this virus, then 5-FC was added; XTT assay was used to estimate the relative numbers of viable cells. Results: The positive clones were confirmed by using endonuclease digestion, and the titer of the virus containing CD gene was 2 × 1011 pfu/ml. It was found that 5-FC possessed significant cytotoxic activities for CD gene transfected 8988cell line, but had little effects on non-transfected pancreatic carcinoma cells. Conclusion: CD gene mediated by adenovirus has a high infectivity and is efficient for killing cultured pancreatic carcinoma cells, indicating suicide gene may be effective for pancreatic cancer in furure.

  7. Selection of efficient salt-tolerant bacteria containing ACC deaminase for promotion of tomato growth under salinity stress

    Directory of Open Access Journals (Sweden)

    Kannika Chookietwattana* and Kedsukon Maneewan

    2012-05-01

    Full Text Available For successful application of plant growth promoting bacteria (PGPB in salt-affected soil, bioinoculant with salt-tolerant property is required in order to provide better survival and perform well in the field. The present study aimed to select the most efficient salt-tolerant bacterium containing 1-aminocyclopropane-1-carboxylic acid (ACC deaminase from eighty four bacterial strains and to investigate the effects of the selected bacterium on the germination and growth of tomato (Licopersicon esculentum Mill. cv. Seeda under saline conditions. The Bacillus licheniformis B2r was selected for its ability to utilize ACC as a sole nitrogen source under salinity stress. It also showed a high ACC deaminase activity at 0.6 M NaCl salinity. Tomato plants inoculated with the selected bacterium under various saline conditions (0, 30, 60, 90 and 120 mM NaCl revealed a significant increase in the germination percentage, germination index, root length, and seedling dry weight especially at salinity levels ranging from 30-90 mM NaCl. The work described in this report is an important step in developing an efficient salt-tolerant bioinoculant to facilitate plant growth in saline soil.

  8. ADAR proteins: structure and catalytic mechanism.

    Science.gov (United States)

    Goodman, Rena A; Macbeth, Mark R; Beal, Peter A

    2012-01-01

    Since the discovery of the adenosine deaminase (ADA) acting on RNA (ADAR) family of proteins in 1988 (Bass and Weintraub, Cell 55:1089-1098, 1988) (Wagner et al. Proc Natl Acad Sci U S A 86:2647-2651, 1989), we have learned much about their structure and catalytic mechanism. However, much about these enzymes is still unknown, particularly regarding the selective recognition and processing of specific adenosines within substrate RNAs. While a crystal structure of the catalytic domain of human ADAR2 has been solved, we still lack structural data for an ADAR catalytic domain bound to RNA, and we lack any structural data for other ADARs. However, by analyzing the structural data that is available along with similarities to other deaminases, mutagenesis and other biochemical experiments, we have been able to advance the understanding of how these fascinating enzymes function. PMID:21769729

  9. Novos materiais de construção com tecnologias avançadas

    OpenAIRE

    Lucas, S.; Cunha, Sandra Raquel Leite; Senff, L.; Paiva, H.; Aguiar, J. L. Barroso de; J. A. Labrincha; Ferreira, V. M.

    2014-01-01

    Este artigo pretende apenas dar um contributo, assinalando alguns exemplos em que se tem vindo a trabalhar e que refletem o uso de tecnologias avançadas na formulação e funcionalidade de materiais de construção tradicionais. Um exemplo claro é o uso de aditivos que induzem novas funções e que muitos deles pertencem ao grupo denominado como nanomateriais. A sua adição coloca quase sempre problemas de incorporação e que requerem um trabalho de ajuste das formulações e comportamen...

  10. Detección de fatiga en conductores mediante fusión de sistemas ADAS

    OpenAIRE

    García Daza, Iván

    2011-01-01

    Se ha identificado la somnolencia como una de las causas más importante de accidentes de tráfico, ya que se encuentra implicada en el 20% de los mismos, por lo que existe un interés creciente en encontrar sistemas ADAS (Advanced Driver Assistance Systems) capaces de detectar el estado de fatiga del conductor para prevenir posibles accidentes. En esta tesis se propone una técnica, basada en el procesado de imágenes monoculares consistente en la detección, seguimiento y caracterización de la ap...

  11. Development of Ada language control software for the NASA power management and distribution test bed

    Science.gov (United States)

    Wright, Ted; Mackin, Michael; Gantose, Dave

    1989-01-01

    The Ada language software developed to control the NASA Lewis Research Center's Power Management and Distribution testbed is described. The testbed is a reduced-scale prototype of the electric power system to be used on space station Freedom. It is designed to develop and test hardware and software for a 20-kHz power distribution system. The distributed, multiprocessor, testbed control system has an easy-to-use operator interface with an understandable English-text format. A simple interface for algorithm writers that uses the same commands as the operator interface is provided, encouraging interactive exploration of the system.

  12. Addressing the Regression Test Problem with Change Impact Analysis for Ada

    OpenAIRE

    Jones, Andrew V.

    2016-01-01

    The regression test selection problem--selecting a subset of a test-suite given a change--has been studied widely over the past two decades. However, the problem has seen little attention when constrained to high-criticality developments and where a "safe" selection of tests need to be chosen. Further, no practical approaches have been presented for the programming language Ada. In this paper, we introduce an approach to solving the selection problem given a combination of both static and dyn...

  13. A razão comunicativa nas sociedades avançadas

    OpenAIRE

    Martins, Moisés de Lemos

    2005-01-01

    O desenvolvimento das indústrias culturais (produtos informáticos, multimedia -televisão, telefone e computador integrados -, publicidade, moda, música, dança, turismo e férias) tomou hegemónica no nosso tempo a cultura de massas. A culminação deste processo, que inclui os media, fez confluir num mesmo sentido a comunicação, o consumo e o lazer, fechando deste modo o ciclo da estruturação da sociedade moderna. É meu intuito analisar o modo como nas sociedades avançadas a comunicação ...

  14. AN ESCHERICHIA-COLI STRAIN DEFICIENT FOR BOTH EXONUCLEASE-V AND DEOXYCYTIDINE TRIPHOSPHATE DEAMINASE SHOWS ENHANCED SENSITIVITY TO IONIZING-RADIATION

    NARCIS (Netherlands)

    ESTEVENON, AM; KOOISTRA, J; SICARD, N

    1995-01-01

    An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores th

  15. 1-Aminocyclopropane-1-carboxylic acid (ACC) deaminase-containing rhizobacteria protect Ocimum sanctum plants during waterlogging stress via reduced ethylene generation.

    Science.gov (United States)

    Barnawal, Deepti; Bharti, Nidhi; Maji, Deepamala; Chanotiya, Chandan Singh; Kalra, Alok

    2012-09-01

    Ocimum sanctum grown as rain-fed crop, is known to be poorly adapted to waterlogged conditions. Many a times the crop suffers extreme damages because of anoxia and excessive ethylene generation due to waterlogging conditions present under heavy rain. The usefulness of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase-containing plant growth promoting rhizobacteria was investigated under waterlogging stress. The comparison of herb yield and stress induced biochemical changes of waterlogged and non-waterlogged plants with and without ACC deaminase-containing microbiological treatments were monitored in this study. Ten plant growth promoting rhizobacteria strains containing ACC-deaminase were isolated and characterized. Four selected isolates Fd2 (Achromobacter xylosoxidans), Bac5 (Serratia ureilytica), Oci9 (Herbaspirillum seropedicae) and Oci13 (Ochrobactrum rhizosphaerae) had the potential to protect Ocimum plants from flood induced damage under waterlogged glass house conditions. Pot experiments were conducted to evaluate the potential of these ACC deaminase-containing selected strains for reducing the yield losses caused by waterlogging conditions. Bacterial treatments protected plants from waterlogging induced detrimental changes like stress ethylene production, reduced chlorophyll concentration, higher lipid peroxidation, proline concentration and reduced foliar nutrient uptake. Fd2 (A. xylosoxidans) induced maximum waterlogging tolerance as treated waterlogged plants recorded maximum growth and herb yield (46.5% higher than uninoculated waterlogged plants) with minimum stress ethylene levels (53% lower ACC concentration as compared to waterlogged plants without bacterial inoculation) whereas under normal non-waterlogged conditions O. rhizosphaerae was most effective in plant growth promotion. PMID:22846334

  16. Sensitization of prostate cancer cell lines to 5-fluorocytosine induced by a replication incompetent adenoviral vector carrying a cytosine deaminase transcription unit

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To investigate the efficiency of cytosine deaminase adenoviral/5-fluorocytosine system on prostate cancer cell lines. METHODS: Cell culture, infectivity test and sensitivity test, observing the bystander effect and animal model experiment were carried out. RESULTS: All the established prostate cancer cell lines were eventually infectable, but ratio of vector/cell and time of exposed at which infection occurs was dependent on the cell lines. The expression of transfered cytosine deaminase gene peaked at different days, but persisted beyond 11 days. The prostate cell lines were sensitized to the 5-fluorocytosine by infection with the cytosine deaminase gene adenoviral vector, and only 5% of the LNCap and 10% of the RM-1 cells infected were required for 100% cell death. In the animal model, there was significant eradiation of tumor growth at the ratio of 400 vector particles/cell and with the systematic treatment of 5-fluorocytosine. CONCLUSION: The adenoviral vector carrying a cytosine deaminase transcription unit can sensitize the prostate cancer cell lines to 5-fluorocytosine, and the system can significantly inhibit the growth of prostatic tumor in mice.

  17. Genetically Controlled Upregulation of Adenosine A(1) Receptor Expression Enhances the Survival of Primary Cortical Neurons

    NARCIS (Netherlands)

    Serchov, Tsvetan; Atas, Hasan-Cem; Normann, Claus; van Calker, Dietrich; Biber, Knut

    2012-01-01

    Adenosine has a key endogenous neuroprotective role in the brain, predominantly mediated by the adenosine A(1) receptor (A(1)R). This has been mainly explored using pharmacological tools and/or receptor knockout mice strains. It has long been suggested that the neuroprotective effects of A(1)R are i

  18. Activation of A(2) adenosine receptors dilates cortical efferent arterioles in mouse

    DEFF Research Database (Denmark)

    Al-Mashhadi, Rozh H; Skøtt, Ole; Vanhoutte, Paul M;

    2009-01-01

    that the adenosine-induced vasodilatation was inhibited by the A(2)-specific receptor blocker 3,7-dimethyl-1-propargylxanthine. In the presence of this inhibitor, adenosine failed to alter the basal vessel diameter of quiescent efferent arterioles. Using primer-specific polymerase chain reaction we found...

  19. Adenosine receptors in COPD and asymptomatic smokers : effects of smoking cessation

    NARCIS (Netherlands)

    Versluis, Mieke; ten Hacken, Nick; Postma, Dirkje; Barroso, Begona; Rutgers, Bea; Geerlings, Marie; Willemse, Brigitte; Timens, Wim; Hylkema, Machteld

    2009-01-01

    Our group has shown that 1-year smoking cessation persisted or increased airway inflammation in chronic obstructive pulmonary disease (COPD). We compared adenosine and adenosine receptor (AR) expression in COPD and asymptomatic smokers (AS) before and after 1-year smoking cessation. Sputum cytospins

  20. Treatment of paroxysmal supraventricular tachycardia with intravenous injection of adenosine triphosphate.

    OpenAIRE

    Saito, D.; Ueeda, M; Abe, Y.; Tani, H; Nakatsu, T.; Yoshida, H.; Haraoka, S; Nagashima, H

    1986-01-01

    Intravenous adenosine triphosphate rapidly terminated all 11 episodes of paroxysmal supraventricular tachycardia in 10 patients. Eight patients reported side effects but these resolved within 20 seconds and did not require treatment. Adenosine triphosphate is a suitable agent for the rapid termination of paroxysmal supraventricular tachycardia.

  1. Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Nesterov, Sergey V; Kemppainen, Jukka;

    2007-01-01

    Evidence from both animal and human studies suggests that adenosine plays a role in the regulation of exercise hyperemia in skeletal muscle. We tested whether adenosine also plays a role in the regulation of blood flow (BF) distribution and heterogeneity among and within quadriceps femoris (QF...

  2. Adenosine signaling and the energetic costs of induced immunity.

    Directory of Open Access Journals (Sweden)

    Brian P Lazzaro

    2015-04-01

    Full Text Available Life history theory predicts that trait evolution should be constrained by competing physiological demands on an organism. Immune defense provides a classic example in which immune responses are presumed to be costly and therefore come at the expense of other traits related to fitness. One strategy for mitigating the costs of expensive traits is to render them inducible, such that the cost is paid only when the trait is utilized. In the current issue of PLOS Biology, Bajgar and colleagues elegantly demonstrate the energetic and life history cost of the immune response that Drosophila melanogaster larvae induce after infection by the parasitoid wasp Leptopilina boulardi. These authors show that infection-induced proliferation of defensive blood cells commands a diversion of dietary carbon away from somatic growth and development, with simple sugars instead being shunted to the hematopoetic organ for rapid conversion into the raw energy required for cell proliferation. This metabolic shift results in a 15% delay in the development of the infected larva and is mediated by adenosine signaling between the hematopoietic organ and the central metabolic control organ of the host fly. The adenosine signal thus allows D. melanogaster to rapidly marshal the energy needed for effective defense and to pay the cost of immunity only when infected.

  3. Adenosine Amine Congener as a Cochlear Rescue Agent

    Directory of Open Access Journals (Sweden)

    Srdjan M. Vlajkovic

    2014-01-01

    Full Text Available We have previously shown that adenosine amine congener (ADAC, a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg was administered intraperitoneally to Wistar rats (8–10 weeks old at intervals (6–72 hours after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours. Hearing sensitivity was assessed using auditory brainstem responses (ABR before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz. Pharmacokinetic studies demonstrated a short (5 min half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.

  4. Novel trypanocidal analogs of 5'-(methylthio)-adenosine.

    Science.gov (United States)

    Sufrin, Janice R; Spiess, Arthur J; Marasco, Canio J; Rattendi, Donna; Bacchi, Cyrus J

    2008-01-01

    The purine nucleoside 5'-deoxy-5'-(hydroxyethylthio)-adenosine (HETA) is an analog of the polyamine pathway metabolite 5'-deoxy-5'-(methylthio)-adenosine (MTA). HETA is a lead structure for the ongoing development of selectively targeted trypanocidal agents. Thirteen novel HETA analogs were synthesized and examined for their in vitro trypanocidal activities against bloodstream forms of Trypanosoma brucei brucei LAB 110 EATRO and at least one drug-resistant Trypanosoma brucei rhodesiense clinical isolate. New compounds were also assessed in a cell-free assay for their activities as substrates of trypanosome MTA phosphorylase. The most potent analog in this group was 5'-deoxy-5'-(hydroxyethylthio)-tubercidin, whose in vitro cytotoxicity (50% inhibitory concentration [IC50], 10 nM) is 45 times greater than that of HETA (IC50, 450 nM) against pentamidine-resistant clinical isolate KETRI 269. Structure-activity analyses indicate that the enzymatic cleavage of HETA analogs by trypanosome MTA phosphorylase is not an absolute requirement for trypanocidal activity. This suggests that additional biochemical mechanisms are associated with the trypanocidal effects of HETA and its analogs.

  5. Distribution of adenosine receptors in human sclera fibroblasts

    Science.gov (United States)

    Cui, Dongmei; Trier, Klaus; Chen, Xiang; Zeng, Junwen; Yang, Xiao; Hu, Jianmin

    2008-01-01

    Purpose Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF). Methods Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines and in the frozen human scleral sections. ADOR protein expression in HSF and human sclera was confirmed by western blot analysis of cell lysates. Results ADORs were expressed in both HSF and human sclera. This was confirmed by western blot. ADORA1 expression was concentrated in the nucleus. ADORA2A was concentrated mainly in one side of the cytoplasm, and ADORA2B was found both in the nucleus and the cytoplasm. ADORA3 was expressed weakly in the cytoplasm. Conclusions All four subtypes of ADOR were found in HSF and may play a role in scleral remodeling. PMID:18385786

  6. Cloning, expression and pharmacological characterization of rabbit adenosine A1 and A3 receptors.

    Science.gov (United States)

    Hill, R J; Oleynek, J J; Hoth, C F; Kiron, M A; Weng, W; Wester, R T; Tracey, W R; Knight, D R; Buchholz, R A; Kennedy, S P

    1997-01-01

    The role of adenosine A1 and A3 receptors in mediating cardioprotection has been studied predominantly in rabbits, yet the pharmacological characteristics of rabbit adenosine A1 and A3 receptor subtypes are unknown. Thus, the rabbit adenosine A3 receptor was cloned and expressed, and its pharmacology was compared with that of cloned adenosine A1 receptors. Stable transfection of rabbit A1 or A3 cDNAs in Chinese hamster ovary-K1 cells resulted in high levels of expression of each of the receptors, as demonstrated by high-affinity binding of the A1/A3 adenosine receptor agonist N6-(4-amino-3-[125I]iodobenzyl)adenosine (125I-ABA). For both receptors, binding of 125I-ABA was inhibited by the GTP analog 5'-guanylimidodiphosphate, and forskolin-stimulated cyclic AMP accumulation was inhibited by the adenosine receptor agonist (R)-phenylisopropyladenosine. The rank orders of potency of adenosine receptor agonists for inhibition of 125I-ABA binding were as follows: rabbit A1, N6-cyclopentyladenosine = (R)-phenylisopropyladenosine > N-ethylcarboxamidoadenosine > or = I-ABA > or = N6-2-(4-aminophenyl) ethyladenosine > > N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide > N6-(4-amino-3-benzyl)adenosine; rabbit A3, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide > or = I-ABA > > N-ethylcarboxamidoadenosine > N6-2-(4-aminophenyl) ethyladenosine = N6-cyclopentyladenosine = (R)-phenylisopropyladenosine > N6-(4-amino-3-benzyl)adenosine. The adenosine receptor antagonist rank orders were as follow: rabbit A1, 8-cyclopentyl-1,3-dipropylxanthine > 1,3- dipropyl-8-(4-acrylate)phenylxanthine > or = xanthine amine congener > > 8-(p-sulfophenyl)theophylline; rabbit A3, xanthine amine congener > 1,3-dipropyl-8-(4-acrylate)phenylxanthine > or = 8-cyclopentyl-1,3-dipropylxanthine > > 8-(p-sulfophenyl)theophylline. These observations confirm the identity of the expressed proteins as A1 and A3 receptors. The results will facilitate further in-depth studies of the roles of A1 and A3 receptors in

  7. Distinct Roles for the A2B Adenosine Receptor in Acute and Chronic Stages of Bleomycin-Induced Lung Injury

    OpenAIRE

    Yang ZHOU; Schneider, Daniel J.; Morschl, Eva; Song, Ling; Pedroza, Mesias; Karmouty-Quintana, Harry; Le, Thuy.; Sun, Chun-Xiao; Blackburn, Michael R.

    2010-01-01

    Adenosine is an extracellular signaling molecule that is generated in response to cell injury where it orchestrates tissue protection and repair. Whereas adenosine is best known for promoting anti-inflammatory activities during acute injury responses, prolonged elevations can enhance destructive tissue remodeling processes associated with chronic disease states. The generation of adenosine and the subsequent activation of the adenosine 2B receptor (A2BR) is an important processes in the regul...

  8. Reconstruction of the adenosine system by bone marrow-derived mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Huicong Kang; Qi Hu; Xiaoyan Liu; Yinhe Liu; Feng Xu; Xiang Li; Suiqiang Zhu

    2012-01-01

    In the present study, we transplanted bone marrow-derived mesenchymal stem cells into the CA3 area of the hippocampus of chronic epilepsy rats kindled by lithium chloride-pilocarpine. Immunofluorescence and western blotting revealed an increase in adenosine A1 receptor expression and a decrease in adenosine A2a receptor expression in the brain tissues of epileptic rats 3 months after transplantation. Moreover, the imbalance in the A1 adenosine receptor/A2a adenosine receptor ratio was improved. Electroencephalograms showed that frequency and amplitude of spikes in the hippocampus and frontal lobe were reduced. These results suggested that mesenchymal stem cell transplantation can reconstruct the normal function of the adenosine system in the brain and greatly improve epileptiform discharges.

  9. Comparison of exogenous adenosine and voluntary exercise on human skeletal muscle perfusion and perfusion heterogeneity

    DEFF Research Database (Denmark)

    Heinonen, Ilkka H.A.; Kemppainen, Jukka; Kaskinoro, Kimmo;

    2010-01-01

    Adenosine is a widely used pharmacological agent to induce a 'high flow' control condition to study the mechanisms of exercise hyperemia, but it is not known how well adenosine infusion depicts exercise-induced hyperemia especially in terms of blood flow distribution at the capillary level in human...... muscle. Additionally, it remains to be determined what proportion of adenosine-induced flow elevation is specifically directed to muscle only. In the present study we measured thigh muscle capillary nutritive blood flow in nine healthy young men using positron emission tomography at rest and during...... femoral artery infusion of adenosine (1 mg * min(-1) * litre thigh volume(-1)), which has previously been shown to induce maximal whole thigh blood flow of ~8 L/min. This response was compared to the blood flow induced by moderate-high intensity one-leg dynamic knee extension exercise. Adenosine increased...

  10. Adenosine stimulates DNA fragmentation in human thymocytes by Ca(2+)-mediated mechanisms.

    Science.gov (United States)

    Szondy, Z

    1994-12-15

    Incubation of human thymocytes with an optimum concentration of adenosine and its receptor site agonist, 2-chloroadenosine, induced increases in intracellular cyclic AMP (cAMP) (from a resting 0.6 +/- 0.1 to 4.1 +/- 0.2 pmol/10(7) cells within 5 min) and Ca2+ (from the resting 85 +/- 7 nM to a peak of 210 +/- 25 nM) levels and resulted in internucleosomal DNA fragmentation and cell death (apoptosis). Other adenosine analogues were also effective at inducing DNA fragmentation, the order of potency being 2-p-(carboxyethylphenylethylamino)-5'-carboxyamidoadenosine 13399-13402], at 60 ng/ml concentration also prevented adenosine-induced DNA fragmentation when added prior to adenosine. This suggested a complex cross-talk between the adenosine-triggered signal transduction cascade and the activation state of protein kinase C in regulating apoptosis of human thymocytes. PMID:7818494

  11. Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Frandsen, Ulrik

    1997-01-01

    in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P muscle cells...... found to have ecto-forms of several enzymes involved in nucleotide metabolism, including ATPases capable of converting extracellular ATP to ADP and AMP. 5. Adenosine added to the cell medium was taken up by muscle cells and incorporated into the adenine nucleotide pool so that after 30 min of incubation......, over 95% of the adenosine label was present in ATP, ADP and AMP. A similar extent of incorporation of adenosine into the nucleotide pool was evident in the endothelial cells. 6. The present data suggest that contracting muscle cells induce an elevation in the extracellular adenosine concentration...

  12. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production.

  13. Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage:the neuroprotective effects of adenosine triphosphate against apoptosis

    Institute of Scientific and Technical Information of China (English)

    Na Lu; Baoying Wang; Xiaohui Deng; Honggang Zhao; Yong Wang; Dongliang Li

    2014-01-01

    After hypoxia, ischemia, or inlfammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, lfow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations (2, 4, 6, 8, 10 mmol/L) over time (1, 2, 3, and 6 hours) on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SY5Y cells. The enhanced autophagy ifrst appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.

  14. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    Science.gov (United States)

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production. PMID:16023100

  15. Transcriptome and proteome analyses of adaptive responses to methyl methanesulfonate in Escherichia coli K-12 and ada mutant strains

    Directory of Open Access Journals (Sweden)

    Lee Sang Yup

    2009-09-01

    Full Text Available Abstract Background The Ada-dependent adaptive response system in Escherichia coli is important for increasing resistance to alkylation damage. However, the global transcriptional and translational changes during this response have not been reported. Here we present time-dependent global gene and protein expression profiles following treatment with methyl methanesulfonate (MMS in E. coli W3110 and its ada mutant strains. Results Transcriptome profiling showed that 1138 and 2177 genes were differentially expressed in response to MMS treatment in the wild-type and mutant strains, respectively. A total of 81 protein spots representing 76 nonredundant proteins differentially expressed were identified using 2-DE and LC-MS/MS. In the wild-type strain, many genes were differentially expressed upon long-exposure to MMS, due to both adaptive responses and stationary phase responses. In the ada mutant strain, the genes involved in DNA replication, recombination, modification and repair were up-regulated 0.5 h after MMS treatment, indicating its connection to the SOS and other DNA repair systems. Interestingly, expression of the genes involved in flagellar biosynthesis, chemotaxis, and two-component regulatory systems related to drug or antibiotic resistance, was found to be controlled by Ada. Conclusion These results show in detail the regulatory components and pathways controlling adaptive response and how the related genes including the Ada regulon are expressed with this response.

  16. Involvement of adenosine A2a receptor in intraocular pressure decrease induced by 2-(1-octyn-1-yl)adenosine or 2-(6-cyano-1-hexyn-1-yl)adenosine.

    Science.gov (United States)

    Konno, Takashi; Murakami, Akira; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-04-01

    The aim of the present study is to clarify the mechanism for the decrease in intraocular pressure by 2-alkynyladenosine derivatives in rabbits. The receptor binding analysis revealed that 2-(1-octyn-1-yl)adenosine (2-O-Ado) and 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) selectively bound to the A(2a) receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A(2a)-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or the adenosine A(2b)-receptor antagonist alloxazine. In addition, 2-O-Ado and 2-CN-Ado caused an increase in outflow facility, which was inhibited by CSC, but not by DPCPX or alloxazine. Moreover, 2-O-Ado and 2-CN-Ado increased cAMP in the aqueous humor, and the 2-O-Ado-induced an increase in cAMP was inhibited by CSC. These results suggest that 2-O-Ado and 2-CN-Ado reduced intraocular pressure via an increase in outflow facility. The ocular hypotension may be mainly mediated through the activation of adenosine A(2a) receptor, although a possible involvement of adenosine A(1) receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma.

  17. Involvement of adenosine A2a receptor in intraocular pressure decrease induced by 2-(1-octyn-1-yl)adenosine or 2-(6-cyano-1-hexyn-1-yl)adenosine.

    Science.gov (United States)

    Konno, Takashi; Murakami, Akira; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-04-01

    The aim of the present study is to clarify the mechanism for the decrease in intraocular pressure by 2-alkynyladenosine derivatives in rabbits. The receptor binding analysis revealed that 2-(1-octyn-1-yl)adenosine (2-O-Ado) and 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) selectively bound to the A(2a) receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A(2a)-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or the adenosine A(2b)-receptor antagonist alloxazine. In addition, 2-O-Ado and 2-CN-Ado caused an increase in outflow facility, which was inhibited by CSC, but not by DPCPX or alloxazine. Moreover, 2-O-Ado and 2-CN-Ado increased cAMP in the aqueous humor, and the 2-O-Ado-induced an increase in cAMP was inhibited by CSC. These results suggest that 2-O-Ado and 2-CN-Ado reduced intraocular pressure via an increase in outflow facility. The ocular hypotension may be mainly mediated through the activation of adenosine A(2a) receptor, although a possible involvement of adenosine A(1) receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma. PMID:15821340

  18. Real-time monitoring of extracellular adenosine using enzyme-linked microelectrode arrays.

    Science.gov (United States)

    Hinzman, Jason M; Gibson, Justin L; Tackla, Ryan D; Costello, Mark S; Burmeister, Jason J; Quintero, Jorge E; Gerhardt, Greg A; Hartings, Jed A

    2015-12-15

    Throughout the central nervous system extracellular adenosine serves important neuroprotective and neuromodulatory functions. However, current understanding of the in vivo regulation and effects of adenosine is limited by the spatial and temporal resolution of available measurement techniques. Here, we describe an enzyme-linked microelectrode array (MEA) with high spatial (7500 µm(2)) and temporal (4 Hz) resolution that can selectively measure extracellular adenosine through the use of self-referenced coating scheme that accounts for interfering substances and the enzymatic breakdown products of adenosine. In vitro, the MEAs selectively measured adenosine in a linear fashion (r(2)=0.98±0.01, concentration range=0-15 µM, limit of detection =0.96±0.5 µM). In vivo the limit of detection was 0.04±0.02 µM, which permitted real-time monitoring of the basal extracellular concentration in rat cerebral cortex (4.3±1.5 µM). Local cortical injection of adenosine through a micropipette produced dose-dependent transient increases in the measured extracellular concentration (200 nL: 6.8±1.8 µM; 400 nL: 19.4±5.3 µM) [P<0.001]. Lastly, local injection of dipyridamole, which inhibits transport of adenosine through equilibrative nucleoside transporter, raised the measured extracellular concentration of adenosine by 120% (5.6→12.3 µM) [P<0.001]. These studies demonstrate that MEAs can selectively measure adenosine on temporal and spatial scales relevant to adenosine signaling and regulation in normal and pathologic states. PMID:26183072

  19. Specificity of synergistic coronary flow enhancement by adenosine and pulsatile perfusion in the dog.

    Science.gov (United States)

    Pagliaro, P; Senzaki, H; Paolocci, N; Isoda, T; Sunagawa, G; Recchia, F A; Kass, D A

    1999-10-01

    1. Coronary flow elevation from enhanced perfusion pulsatility is synergistically amplified by adenosine. This study determined the specificity of this interaction and its potential mechanisms. 2. Mean and phasic coronary flow responses to increasing pulsatile perfusion were assessed in anaesthetized dogs, with the anterior descending coronary artery servoperfused to regulate real-time physiological flow pulsatility at constant mean pressure. Pulsatility was varied between 40 and 100 mmHg. Hearts ejected into the native aorta whilst maintaining stable loading. 3. Increasing pulsatility elevated mean coronary flow +11.5 +/- 1.7 % under basal conditions. Co-infusion of adenosine sufficient to raise baseline flow 66 % markedly amplified this pulsatile perfusion response (+82. 6 +/- 14.3 % increase in mean flow above adenosine baseline), due to a leftward shift of the adenosine-coronary flow response curve at higher pulsatility. Flow augmentation with pulsatility was not linked to higher regional oxygen consumption, supporting direct rather than metabolically driven mechanisms. 4. Neither bradykinin, acetylcholine nor verapamil reproduced the synergistic amplification of mean flow by adenosine and higher pulsatility, despite being administered at doses matching basal flow change with adenosine. 5. ATP-sensitive potassium (KATP) activation (pinacidil) amplified the pulse-flow response 3-fold, although this remained significantly less than with adenosine. Co-administration of the phospholipase A2 inhibitor quinacrine virtually eliminated adenosine-induced vasodilatation, yet synergistic interaction between adenosine and pulse perfusion persisted, albeit at a reduced level. 6. Thus, adenosine and perfusion pulsatility specifically interact to enhance coronary flow. This synergy is partially explained by KATP agonist action and additional non-flow-dependent mechanisms, and may be important for modulating flow reserve during exercise or other high output states where

  20. Overexpression, purification and crystallographic analysis of a unique adenosine kinase from Mycobacterium tuberculosis

    International Nuclear Information System (INIS)

    Adenosine kinase from M. tuberculosis has been overexpressed, purified and crystallized in the presence of adenosine. Structure determination using molecular replacement with diffraction data collected at 2.2 Å reveals a dimeric structure. Adenosine kinase from Mycobacterium tuberculosis is the only prokaryotic adenosine kinase that has been isolated and characterized. The enzyme catalyzes the phosphorylation of adenosine to adenosine monophosphate and is involved in the activation of 2-methyladenosine, a compound that has demonstrated selective activity against M. tuberculosis. The mechanism of action of 2-methyladenosine is likely to be different from those of current tuberculosis treatments and this compound (or other adenosine analogs) may prove to be a novel therapeutic intervention for this disease. The M. tuberculosis adenosine kinase was overexpressed in Escherichia coli and the enzyme was purified with activity comparable to that reported previously. The protein was crystallized in the presence of adenosine using the vapour-diffusion method. The crystals diffracted X-rays to high resolution and a complete data set was collected to 2.2 Å using synchrotron radiation. The crystal belonged to space group P3121, with unit-cell parameters a = 70.2, c = 111.6 Å, and contained a single protein molecule in the asymmetric unit. An initial structural model of the protein was obtained by the molecular-replacement method, which revealed a dimeric structure. The monomers of the dimer were related by twofold crystallographic symmetry. An understanding of how the M. tuberculosis adenosine kinase differs from the human homolog should aid in the design of more potent and selective antimycobacterial agents that are selectively activated by this enzyme

  1. Generic Ada code in the NASA space station command, control and communications environment

    Science.gov (United States)

    Mcdougall, D. P.; Vollman, T. E.

    1986-01-01

    The results of efforts to apply powerful Ada constructs to the formatted message handling process are described. The goal of these efforts was to extend the state-of-technology in message handling while at the same time producing production-quality, reusable code. The first effort was initiated in September, 1984 and delivered in April, 1985. That product, the Generic Message Handling Facility, met initial goals, was reused, and is available in the Ada Repository on ARPANET. However, it became apparent during its development that the initial approach to building a message handler template was not optimal. As a result of this initial effort, several alternate approaches were identified, and research is now on-going to identify an improved product. The ultimate goal is to be able to instantly build a message handling system for any message format given a specification of that message format. The problem lies in how to specify the message format, and one that is done, how to use that information to build the message handler. Message handling systems and message types are described. The initial efforts, its results and its shortcomings are detailed. The approach now being taken to build a system which will be significantly easier to implement, and once implemented, easier to use, is described. Finally, conclusions are offered.

  2. ADA1 and NET1 Genes of Yeast Mediate Both Chromosome Maintenance and Mitochondrial $\\rho^{-}$ Mutagenesis

    CERN Document Server

    Koltovaya, N A; Tchekhouta, I A; Devin, A B

    2002-01-01

    An increase in the mitochondrial (mt) rho^- mutagenesis is a well-known respose of yeast cells to mutations in the numerous nuclear genes as well as to various kinds of stress. Notwithstanding the extensive studies during several decades the biological significance of this response is not yet fully understood. The genetic approach to solution of this subject includes the study of genes that are required for the high incidence of spontaneous rho^- mutants. Previously we found that mutations in certain nuclear genes including CDC28, the central cell-cycle regulation gene, may decrease the spontaneous rho^- mutability and simultaneously affect maintenance of the yeast chromosomes and plasmids. The present work provides data on identification of two more genes, resembling CDC28 in this respect. These genes NET1 and ADA1 mediate important regulatory protein-protein interactions in the yeast cell. The effects of net1 and ada1 mutations on the maintenance of yeast mt genome, chromosomes and plasmids as well as on ce...

  3. Integrating automated structured analysis and design with Ada programming support environments

    Science.gov (United States)

    Hecht, Alan; Simmons, Andy

    1986-01-01

    Ada Programming Support Environments (APSE) include many powerful tools that address the implementation of Ada code. These tools do not address the entire software development process. Structured analysis is a methodology that addresses the creation of complete and accurate system specifications. Structured design takes a specification and derives a plan to decompose the system subcomponents, and provides heuristics to optimize the software design to minimize errors and maintenance. It can also produce the creation of useable modules. Studies have shown that most software errors result from poor system specifications, and that these errors also become more expensive to fix as the development process continues. Structured analysis and design help to uncover error in the early stages of development. The APSE tools help to insure that the code produced is correct, and aid in finding obscure coding errors. However, they do not have the capability to detect errors in specifications or to detect poor designs. An automated system for structured analysis and design TEAMWORK, which can be integrated with an APSE to support software systems development from specification through implementation is described. These tools completement each other to help developers improve quality and productivity, as well as to reduce development and maintenance costs. Complete system documentation and reusable code also resultss from the use of these tools. Integrating an APSE with automated tools for structured analysis and design provide capabilities and advantages beyond those realized with any of these systems used by themselves.

  4. Effect of adenosine and adenosine receptor antagonist on Müller cell potassium channel in Rat chronic ocular hypertension models.

    Science.gov (United States)

    Yang, Zijian; Huang, Ping; Liu, Xiaohong; Huang, Shouyue; Deng, Lianfu; Jin, Zhe; Xu, Shuo; Shen, Xi; Luo, Xunda; Zhong, Yisheng

    2015-01-01

    Müller cells are principal glial cells in rat retina and have attracted much attention in glaucoma studies. However, it is not clear whether adenosine and adenosine receptor (AR) antagonists play any roles in the regulation of potassium channels in Müller cells and subsequently in the promotion of glutamine synthetase (GS) and L-Glutamate/L-Aspartate Transporter (GLAST) functions. We found that chronic ocular hypertension (COH) in rat down-regulated Müller cells Kir2.1, Kir4.1, TASK-1, GS and GLAST expressions and attenuated the peak of inward potassium current. Retinal ganglion cells (RGC) count was lower in the COH rats than that in the sham operation animals. Intravitreal injection of selective A2A AR antagonist SCH442416 up-regulated Müller cell Kir4.1, TASK-1, GS and GLAST expressions and enhanced inward potassium currents compared with those in the COH rats with vehicle control. Meanwhile, the RGC count was higher following intravitreal injection of SCH442416 in the COH rats than that after vehicle injection. The fact that PKA inhibitor H-89 blocked these SCH442416 effects suggested that the PKA signaling pathway was involved in the observed ocular responses following the intravitreal SCH442416 injection. PMID:26063641

  5. Killing effect of coexpressing cytosine deaminase and thymidine kinase on rat vascular smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    曹慧青; 孟宪敏; 刘冬青; 赵秀文; 丁金凤

    2004-01-01

    Background Vascular smooth muscle cell (VSMC) proliferation following arterial injury plays a critical role in a variety of vascular proliferative disorders, such as atherosclerosis and restenosis after balloon angioplasty. Herpes simplex virus-thymidine kinase (HSV-TK)/ganciclovir (GCV) and E.coli cytosine deaminase (CD)/5-fluorocytosine (5-Fc) suicide gene systems have been successfully employed in cardiovascular gene therapy, respectively. We reasoned that coexpression of both HSV-TK with CD suicide genes would lead to increased cell killing. To test this imagine, the adenoviral vectors expressing TK and/or CD genes were developed and tested on vascular smooth muscle cells. Methods Adenoviral vectors, including Ad-EF1α-CD-cytomegolovirus (CMV)-TK coexpressing both CD and TK double suicide genes, Ad-EF1α-CD and Ad-CMV-TK expressing CD and TK respectively, and control vector Ad-CMV-LacZ, were constructed and prepared with homologous recombination in RecA+E.coli cells. Integration and expression of CD and/or TK gene were identified by PCR and Western blot. Primary cultured VSMCs were infected at a multiplicity of infection (MOI) of 20 with exposure to their matching prodrugs 5-Fc and GCV. Cell mortality was measured by methyl thiazolyl tetrazolium (MTT) assays. Flow cytometry analysis was used to detect cell death. Apoptotic cells were analyzed using Hoechst 33342 fluorescence dye as a DNA probe. Genomic DNA cleavage of apoptotic VSMCs was tested by agarose gel electrophoresis. Results Recombinant adenovirus expressing CD and/or TK suicide genes were successfully constructed. Both single and double suicide genes could be integrated into adenoviral genome and expressed. Cytotoxic effects of Ad-EF1α-CD-CMV-TK double suicide genes combined with 5-Fc and GCV were higher than those of Ad-CMV-TK and Ad-EF1α-CD single gene groups. The rate of cell survival was only (9±3)% in the Ad-EF1α-CD-CMV-TK group, but (37±3)% in the Ad-CMV-TK and (46±4)% in the Ad-EF1

  6. Random mutagenesis MAPPIT analysis identifies binding sites for Vif and Gag in both cytidine deaminase domains of Apobec3G.

    Directory of Open Access Journals (Sweden)

    Isabel Uyttendaele

    Full Text Available The mammalian two-hybrid system MAPPIT allows the detection of protein-protein interactions in intact human cells. We developed a random mutagenesis screening strategy based on MAPPIT to detect mutations that disrupt the interaction of one protein with multiple protein interactors simultaneously. The strategy was used to detect residues of the human cytidine deaminase Apobec3G that are important for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins. The strategy is able to identify the previously described head-to-head homodimerization interface in the N-terminal domain of Apobec3G. Our analysis further detects two new potential interaction surfaces in the N-and C-terminal domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization.

  7. Random mutagenesis MAPPIT analysis identifies binding sites for Vif and Gag in both cytidine deaminase domains of Apobec3G.

    Science.gov (United States)

    Uyttendaele, Isabel; Lavens, Delphine; Catteeuw, Dominiek; Lemmens, Irma; Bovijn, Celia; Tavernier, Jan; Peelman, Frank

    2012-01-01

    The mammalian two-hybrid system MAPPIT allows the detection of protein-protein interactions in intact human cells. We developed a random mutagenesis screening strategy based on MAPPIT to detect mutations that disrupt the interaction of one protein with multiple protein interactors simultaneously. The strategy was used to detect residues of the human cytidine deaminase Apobec3G that are important for its homodimerization and its interaction with the HIV-1 Gag and Vif proteins. The strategy is able to identify the previously described head-to-head homodimerization interface in the N-terminal domain of Apobec3G. Our analysis further detects two new potential interaction surfaces in the N-and C-terminal domain of Apobec3G for interaction with Vif and Gag or for Apobec3G dimerization. PMID:22970171

  8. An Escherichia coli strain deficient for both exonuclease V and deoxycytidine triphosphate deaminase shows enhanced sensitivity to ionizing radiation.

    Science.gov (United States)

    Estèvenon, A M; Kooistra, J; Sicard, N

    1995-02-20

    An Escherichia coli mutant lacking deoxycytidine triphosphate deaminase (Dcd) activity and an unknown function encoded by a gene designated ior exhibits sensitivity to ionizing radiation whereas dcd mutants themselves are not sensitive. A DNA fragment from an E. coli genomic library that restores the wild type level of UV and gamma ray resistance to this mutant has been cloned in the multicopy vector pBR322. Comparison of its restriction map with the physical map of the E. coli chromosome revealed complete identity to the recBD genes. ior affects ATP-dependent exonuclease activity, suggesting that it is an allele of recB. This mutation alone does not confer sensitivity to UV and gamma radiation, indicating that lack of Dcd activity is also required for expression of radiation sensitivity.

  9. Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance.

    Science.gov (United States)

    Cantaert, Tineke; Schickel, Jean-Nicolas; Bannock, Jason M; Ng, Yen-Shing; Massad, Christopher; Oe, Tyler; Wu, Renee; Lavoie, Aubert; Walter, Jolan E; Notarangelo, Luigi D; Al-Herz, Waleed; Kilic, Sara Sebnem; Ochs, Hans D; Nonoyama, Shigeaki; Durandy, Anne; Meffre, Eric

    2015-11-17

    Activation-induced cytidine deaminase (AID), the enzyme-mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID+ immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells.

  10. Cytidine deaminases from B. subtilis and E. coli: compensating effects of changing zinc coordination and quaternary structure.

    Science.gov (United States)

    Carlow, D C; Carter, C W; Mejlhede, N; Neuhard, J; Wolfenden, R

    1999-09-21

    Cytidine deaminase from E. coli is a dimer of identical subunits (M(r) = 31 540), each containing a single zinc atom. Cytidine deaminase from B. subtilis is a tetramer of identical subunits (M(r) = 14 800). After purification from an overexpressing strain, the enzyme from B. subtilis is found to contain a single atom of zinc per enzyme subunit by flame atomic absorption spectroscopy. Fluorescence titration indicates that each of the four subunits contains a binding site for the transition state analogue inhibitor 5-fluoro-3,4-dihydrouridine. A region of amino acid sequence homology, containing residues that are involved in zinc coordination in the enzyme from E. coli, strongly suggests that in the enzyme from B. subtilis, zinc is coordinated by the thiolate side chains of three cysteine residues (Cys-53, Cys-86, and Cys-89) [Song, B. H., and Neuhard, J. (1989) Mol. Gen. Genet. 216, 462-468]. This pattern of zinc coordination appears to be novel for a hydrolytic enzyme, and might be expected to reduce the reactivity of the active site substantially compared with that of the enzyme from E. coli (His-102, Cys-129, and Cys-132). Instead, the B. subtilis and E. coli enzymes are found to be similar in their activities, and also in their relative binding affinities for a series of structurally related inhibitors with binding affinities that span a range of 6 orders of magnitude. In addition, the apparent pK(a) value of the active site is shifted upward by less than 1 unit. Sequence alignments, together with model building, suggest one possible mechanism of compensation.

  11. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.

    Science.gov (United States)

    Masino, S A; Kawamura, M; Wasser, C D; Wasser, C A; Pomeroy, L T; Ruskin, D N

    2009-09-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  12. Role of adenosine signalling and metabolism in β-cell regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Andersson, Olov, E-mail: olov.andersson@ki.se

    2014-02-01

    Glucose homeostasis, which is controlled by the endocrine cells of the pancreas, is disrupted in both type I and type II diabetes. Deficiency in the number of insulin-producing β cells – a primary cause of type I diabetes and a secondary contributor of type II diabetes – leads to hyperglycemia and hence an increase in the need for insulin. Although diabetes can be controlled with insulin injections, a curative approach is needed. A potential approach to curing diabetes involves regenerating the β-cell mass, e.g. by increasing β-cell proliferation, survival, neogenesis or transdifferentiation. The nucleoside adenosine and its cognate nucleotide ATP have long been known to affect insulin secretion, but have more recently been shown to increase β-cell proliferation during homeostatic control and regeneration of the β-cell mass. Adenosine is also known to have anti-inflammatory properties, and agonism of adenosine receptors can promote the survival of β-cells in an inflammatory microenvironment. In this review, both intracellular and extracellular mechanisms of adenosine and ATP are discussed in terms of their established and putative effects on β-cell regeneration. - Highlights: • A potential way to cure diabetes is to regenerate the β-cell mass by promoting cell survival, proliferation or neogenesis. • Adenosine may promote β-cell regeneration through several cellular mechanisms. • Adenosine and its cognate nucleotide ATP can each promote β-cell proliferation. • Do adenosine and ATP interact in promoting β-cell proliferation?.

  13. Susceptibility to seizure-induced sudden death in DBA/2 mice is altered by adenosine.

    Science.gov (United States)

    Faingold, Carl L; Randall, Marc; Kommajosyula, Srinivasa P

    2016-08-01

    Sudden unexpected death in epilepsy (SUDEP) is rare but is an important public health burden due to the number of patient years lost. Respiratory dysfunction following generalized convulsive seizure is a common sequence of events in witnessed SUDEP cases. The DBA/2 mouse model of SUDEP exhibits generalized convulsive audiogenic seizures (AGSz), which result in seizure-induced respiratory arrest (S-IRA) in ∼75% of these animals, while the remaining DBA/2 mice exhibit AGSz without S-IRA. SUDEP induction may involve actions of adenosine, which is released during generalized seizures in animals and patients and is known to depress respiration. This study examined the effects of systemic administration of agents that alter the actions of adenosine on the incidence of S-IRA in DBA/2 mice. DBA/2 mice that consistently exhibited AGSz without S-IRA showed a significantly increased incidence of S-IRA following treatment with 5-iodotubercidin, which blocks adenosine metabolism. Treatment of DBA/2 mice that consistently exhibited AGSz followed by S-IRA with a non-selective adenosine antagonist, caffeine, or an A2A adenosine receptor subtype-selective antagonist (SCH 442416) significantly reduced S-IRA incidence. By contrast, an A1 adenosine receptor antagonist (DPCPX) was not effective in reducing S-IRA incidence. These findings suggest that preventative approaches for SUDEP should consider agents that reduce the actions of adenosine. PMID:27259068

  14. The neuro-glial properties of adipose-derived adult stromal (ADAS cells are not regulated by Notch 1 and are not derived from neural crest lineage.

    Directory of Open Access Journals (Sweden)

    Philip C Wrage

    Full Text Available We investigated whether adipose-derived adult stromal (ADAS are of neural crest origin and the extent to which Notch 1 regulates their growth and differentiation. Mouse ADAS cells cultured in media formulated for neural stem cells (NSC displayed limited capacity for self-renewal, clonogenicity, and neurosphere formation compared to NSC from the subventricular zone in the hippocampus. Although ADAS cells expressed Nestin, GFAP, NSE and Tuj1 in vitro, exposure to NSC differentiation supplements did not induce mature neuronal marker expression. In contrast, in mesenchymal stem cell (MSC media, ADAS cells retained their ability to proliferate and differentiate beyond 20 passages and expressed high levels of Nestin. In neuritizing cocktails, ADAS cells extended processes, downregulated Nestin expression, and displayed depolarization-induced Ca(2+ transients but no spontaneous or evoked neural network activity on Multi-Electrode Arrays. Deletion of Notch 1 in ADAS cell cultures grown in NSC proliferation medium did not significantly alter their proliferative potential in vitro or the differentiation-induced downregulation of Nestin. Co-culture of ADAS cells with fibroblasts that stably expressed the Notch ligand Jagged 1 or overexpression of the Notch intracellular domain (NICD did not alter ADAS cell growth, morphology, or cellular marker expression. ADAS cells did not display robust expression of neural crest transcription factors or genes (Sox, CRABP2, and TH; and lineage tracing analyses using Wnt1-Cre;Rosa26R-lacZ or -EYFP reporter mice confirmed that fewer than 2% of the ADAS cell population derived from a Wnt1-positive population during development. In summary, although media formulations optimized for MSCs or NSCs enable expansion of mouse ADAS cells in vitro, we find no evidence that these cells are of neural crest origin, that they can undergo robust terminal differentiation into functionally mature neurons, and that Notch 1 is likely to be

  15. SMARTPHONE-BASED APPROACH TO ADVANCED DRIVER ASSISTANCE SYSTEM (ADAS RESEARCH AND DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    I. B. Lashkov

    2015-11-01

    Full Text Available Subject of Research.The paper deals with findings and presents asmartphone-based approach to advanced driver assistance system (ADAS research and development.The approach is based on the data of smartphone cameras and sensors. The line of researchis associated with the developmentof mobile advanced driver assistance system (ADAS. Method.The proposedapproach isbased on the use of driver'sand vehicle behavior ontologies. Current ADAS systems can be divided into two main categories according to the method of implementation: mobile applications, manually installed by the driver from the application stores, and safetyhardware and softwaresystems,integrated into vehicles by manufacturesor in the automotive service centers.Mobile application installed on the smartphone uses the built-in rear and front-facing cameras and sensors to monitor both the road and vehicles ahead, and at the same time the driver in order to prevent traffic collisions. The service consists of components for objects recognition in the images obtained with cameras, and components for traffic situation analysis. Main Results. The driver safety mobile application has been developedfor the use on mobile phones.The mobile phone is mounted on the windshield of a car.In case of dangerous event occurrence, the application engine will make an audible or vibration signal to inform the driver to be concentratedand more vigilant. For example, road obstacles, rear-end and stationary vehicle accidents are the most common accident types.The mobile application detects whether a crash is imminent by computing the ‘Time To Contact’ (TTC taking into account host vehicle speed, relative speed and relative acceleration.If the driver doesn’t maintain safe minimum distance with the car immediately ahead, the mobile application will alert the driver by displaying an attention icon with an audible alert. The dual-camera sensing application is designed to help the drivers increase the trip safety

  16. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Nakazawa, Taisuke; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-02-01

    Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by N(G)-nitro-L-arginine methyl ester. There were no differences in the responses to pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of K(ATP) channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in

  17. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    Science.gov (United States)

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists. PMID:25063794

  18. Adenosine Modulates the Oocyte Developmental Competence by Exposing Stages and Synthetic Blocking during In Vitro Maturation.

    Science.gov (United States)

    Cheon, Yong-Pil

    2016-06-01

    Purine metabolism is known factor for nuclear maturation of oocytes through both follicle cells and oocyte itself. However, it is largely unknown the roles of purine metabolism in the oocyte competence for fertilization and early development. In this study, the effects of adenosine in oocyte competence for development were examined using adenosine and its synthetic inhibitors. Adenosine treatment from GV intact stage for 18 hr (fGV) caused of decrease the fertilization rate but of increase the cleavage rate compared from the other stage treatment groups. Hadacidin did not effect on fertilization rate but increased cleavage rate without stage specificity. Adenosine did not block the effects of hadacidin with the exception of fGV group. By the inhibition of purine synthetic pathways the fertilization rate was decreased in the fGV and fGVB groups but increased in the fMII group. Exogenous adenosine caused of decrease fertilization rate in the fGVB group but increase in the fMII group. Cleavage rate was dramatically increased in the adenosine treatment with synthetic inhibitors. It means that the metabolism of purine has stage specific effects on fertilization and cleavage. Exogenous adenosine had only can improve oocyte developmental competence when it treated at GV intact stage. On the other hand, endogenous synthesis in all maturation stage caused of increase the cleavage rate without effects on fertilization. These data suggest that adenosine at GV stage as a paracrine fashion and inhibitions of endogenous adenosine in all stage improve oocyte developmental competence.. PMID:27660830

  19. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors.

    Science.gov (United States)

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2014-09-15

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as the exogenous agonists do. Our previous study showed that adenosine is released into the NTS during severe hemorrhage and contributes to reciprocal changes of renal (decreases) and adrenal (increases) sympathetic nerve activity observed in this setting. Both A1 and A2a adenosine receptors are involved. Therefore, we tested the hypothesis that, during severe hemorrhage, CCR control of the two sympathetic outputs is attenuated by adenosine naturally released into the NTS. We compared renal and adrenal sympathoinhibitory responses evoked by right atrial injections of 5HT3 receptor agonist phenylbiguanide (2-8 μg/kg) under control conditions, during hemorrhage, and during hemorrhage preceded by blockade of NTS adenosine receptors with bilateral microinjections of 8-(p-sulfophenyl) theophylline (1 nmol/100 nl) in urethane/chloralose anesthetized rats. CCR-mediated inhibition of renal and adrenal sympathetic activity was significantly attenuated during severe hemorrhage despite reciprocal changes in the baseline activity levels, and this attenuation was removed by bilateral blockade of adenosine receptors in the caudal NTS. This confirmed that adenosine endogenously released into the NTS has a similar modulatory effect on integration of cardiovascular reflexes as stimulation of NTS adenosine receptors with exogenous agonists.

  20. Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats.

    Science.gov (United States)

    Scaramuzzi, R J; Baker, D J

    2003-10-01

    Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age. PMID:14633184

  1. Receptor crosstalk: haloperidol treatment enhances A2A adenosine receptor functioning in a transfected cell model

    OpenAIRE

    Trincavelli, Maria Letizia; Cuboni, Serena; Catena Dell’Osso, Mario; Maggio, Roberto; Klotz, Karl-Norbert; Novi, Francesca; Panighini, Anna; Daniele, Simona; Martini, Claudia

    2010-01-01

    A2A adenosine receptors are considered an excellent target for drug development in several neurological and psychiatric disorders. It is noteworthy that the responses evoked by A2A adenosine receptors are regulated by D2 dopamine receptor ligands. These two receptors are co-expressed at the level of the basal ganglia and interact to form functional heterodimers. In this context, possible changes in A2A adenosine receptor functional responses caused by the chronic blockade/activation of D2 dop...

  2. Adenosine concentrations in the interstitium of resting and contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Maclean, D.; Rådegran, G.;

    1998-01-01

    BACKGROUND: Adenosine has been proposed to be a locally produced regulator of blood flow in skeletal muscle. However, the fundamental questions of to what extent adenosine is formed in skeletal muscle tissue of humans, whether it is present in the interstitium, and where it exerts its vasodilatory...... effect remain unanswered. METHODS AND RESULTS: The interstitial adenosine concentration was determined in the vastus lateralis muscle of healthy humans via dialysis probes inserted in the muscle. The probes were perfused with buffer, and the dialysate samples were collected at rest and during graded knee...... concentration and a higher FaBF (2.22+/-0.18 L/min; PATP, ADP, and AMP increased from...

  3. The role of adenosine A2A receptors on neuromuscular transmission upon ageing

    OpenAIRE

    Pousinha, Paula Isabel Antunes, 1978-

    2012-01-01

    Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2012 Adenosine is a neuromodulator with important actions in the nervous system. The activation of adenosine A2A receptors has been shown to modulate the action of other receptors. Considering that it was observed an interaction between adenosine A2A receptors and TrkB receptors in hippocampus, I hypothesized that the activation of A2A receptors could also facilitate BDNF actions on ne...

  4. The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells

    DEFF Research Database (Denmark)

    Hayashi, M.; Inagaki, A.; Novak, Ivana;

    2016-01-01

    Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl− chann...

  5. Adenosine A2A receptor binding profile of two antagonists, ST1535 and KW6002: consideration on the presence of atypical adenosine A2A binding sites

    Directory of Open Access Journals (Sweden)

    Teresa Riccioni

    2010-08-01

    Full Text Available Adenosine A2A receptors seem to exist in typical (more in striatum and atypical (more in hippocampus and cortex subtypes. In the present study, we investigated the affinity of two adenosine A2A receptor antagonists, ST1535 [2 butyl -9-methyl-8-(2H-1,2,3-triazol 2-yl-9H-purin-6-xylamine] and KW6002 [(E-1,3-diethyl-8-(3,4-dimethoxystyryl-7-methyl-3,7-dihydro-1H-purine-2,6,dione] to the “typical” and “atypical” A2A binding sites. Affinity was determined by radioligand competition experiments in membranes from rat striatum and hippocampus. Displacement of the adenosine analog [3H]CGS21680 [2-p-(2-carboxyethylphenethyl-amino-5’-N-ethylcarbox-amidoadenosine] was evaluated in the absence or in the presence of either CSC [8-(3-chlorostyryl-caffeine], an adenosine A2A antagonist that pharmacologically isolates atypical binding sites, or DPCPX (8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor antagonist that pharmacologically isolates typical binding site. ZM241385 [84-(2-[7-amino-2-(2-furyl [1,2,4]-triazol[2,3-a][1,3,5]triazin-5-yl amino]ethyl phenol] and SCH58261 [(5-amino-7-(β-phenylethyl-2-(8-furylpyrazolo(4,3-e-1,2,4-triazolo(1,5-c pyrimidine], two other adenosine A2A receptor antagonists, which were reported to differently bind to atypical and typical A2A receptors, were used as reference compounds. ST1535, KW6002, ZM241385 and SCH58261 displaced [3H]CGS21680 with higher affinity in striatum than in hippocampus. In hippocampus, no typical adenosine A2A binding was detected, and ST1535 was the only compound that occupied atypical A2A adenosine receptors. Present data are explained in terms of heteromeric association among adenosine A2A, A2B and A1 receptors, rather than with the presence of atypical A2A receptor subtype.

  6. Evolution of the Cañadas edifice and its implications for the origin of the Cañadas Caldera (Tenerife, Canary Islands)

    Science.gov (United States)

    Ancochea, E.; Huertas, M. J.; Cantagrel, J. M.; Coello, J.; Fúster, J. M.; Arnaud, N.; Ibarrola, E.

    1999-02-01

    The volcano-stratigraphic and geochronologic data presented in this work show that the Tenerife central zone has been occupied during the last 3 Ma by shield or central composite volcanoes which reached more than 3000 m in height. The last volcanic system, the presently active Teide-Pico Viejo Complex began to form approximately 150 ka ago. The first Cañadas Edifice (CE) volcanic activity took place between about 3.5 Ma and 2.7 Ma. The CE-I is formed mainly by basalts, trachybasalts and trachytes. The remains of this phase outcrop in the Cañadas Wall (CW) sectors of La Angostura (3.5-3.0 Ma and 3.0-2.7 Ma), Boca de Tauce (3.0 Ma), and in the bottom of some external radial ravines (3.5 Ma). The position of its main emission center was located in the central part of the CC. The volcano could have reached 3000 m in height. This edifice underwent a partial destruction by failure and flank collapse, forming debris-avalanches during the 2.6-2.3 Ma period. The debris-avalanche deposits can be seen in the most distal zones in the N flank of the CE-I (Tigaiga Breccia). A new volcanic phase, whose deposits overlie the remains of CE-I and the former debris-avalanche deposits, constituted a new volcanic edifice, the CE-II. The dyke directions analysis and the morphological reconstruction suggest that the CE-II center was situated somewhat westward of the CE-I, reaching some 3200 m in height. The CE-II formations are well exposed on the CW, especially at the El Cedro (2.3-2.00 Ma) sector. They are also frequent in the S flank of the edifice (2.25-1.89 Ma) in Tejina (2.5-1.87 Ma) as well as in the Tigaiga massif to the N (2.23 Ma). During the last periods of activity of CE-II, important explosive eruptions took place forming ignimbrites, pyroclastic flows, and fall deposits of trachytic composition. Their ages vary between 1.5 and 1.6 Ma (Adeje ignimbrites, to the W). In the CW, the Upper Ucanca phonolitic Unit (1.4 Ma) could be the last main episode of the CE-II. Afterwards

  7. Lessons learned applying CASE methods/tools to Ada software development projects

    Science.gov (United States)

    Blumberg, Maurice H.; Randall, Richard L.

    1993-01-01

    This paper describes the lessons learned from introducing CASE methods/tools into organizations and applying them to actual Ada software development projects. This paper will be useful to any organization planning to introduce a software engineering environment (SEE) or evolving an existing one. It contains management level lessons learned, as well as lessons learned in using specific SEE tools/methods. The experiences presented are from Alpha Test projects established under the STARS (Software Technology for Adaptable and Reliable Systems) project. They reflect the front end efforts by those projects to understand the tools/methods, initial experiences in their introduction and use, and later experiences in the use of specific tools/methods and the introduction of new ones.

  8. Poéticas del cuerpo monstruoso en la Ilíada y la Odisea

    Directory of Open Access Journals (Sweden)

    Mariano Nava Contreras

    2009-10-01

    Full Text Available Si bien la tradición ha considerado que los poemas homéricos son una fuente determinante en la creación y el desarrollo de la estética griega clásica fundamentada en los ideales de belleza y armonía, también es posible identificar allí una estética de la fealdad y de lo monstruoso, basada en la desmesura y la deformidad. A través de una revisión de la descripción de criaturas como Gorgona, Quimera, Escila, los Cíclopes o el Can Cerbero, es posible elaborar una poética de lo monstruoso que opera en la Ilíada y la Odisea como recurso patémico, pero también como instrumento narrativo.

  9. Determination of Gender and Age Based on Pattern of Human Motion Using AdaBoost Algorithms

    Science.gov (United States)

    Handri, Santoso; Nomura, Shusaku; Nakamura, Kazuo

    Automated human identification by their walking behavior is a challenge attracting much interest among machine vision researchers. However, practical systems for such identification remain to be developed. In this study, a machine learning approach to understand human behavior based on motion imagery was proposed as the basis for developing pedestrian safety information systems. At the front end, image and video processing was performed to separate foreground from background images. Shape-width was then analyzed using 2D discrete wavelet transformation to extract human motion features. Finally, an adaptive boosting (AdaBoost) algorithm was performed to classify human gender and age into its class. The results demonstrated capability of the proposed systems to classify gender and age highly accurately.

  10. Distribution of Isotopic and Environmental Tracers in Groundwater, Northern Ada County, Southwestern Idaho

    Science.gov (United States)

    Adkins, Candice B.; Bartolino, James R.

    2010-01-01

    Residents of northern Ada County, Idaho, depend on groundwater for domestic and agricultural uses. The population of this area is growing rapidly and groundwater resources must be understood for future water-resource management. The U.S. Geological Survey, in cooperation with the Idaho Department of Water Resources, used a suite of isotopic and environmental tracers to gain a better understanding of groundwater ages, recharge sources, and flowpaths in northern Ada County. Thirteen wells were sampled between September and October 2009 for field parameters, major anions and cations, nutrients, oxygen and hydrogen isotopes, tritium, radiocarbon, chlorofluorocarbons, and dissolved gasses. Well depths ranged from 30 to 580 feet below land surface. Wells were grouped together based on their depth and geographic location into the following four categories: shallow aquifer, intermediate/deep aquifer, Willow Creek aquifer, and Dry Creek aquifer. Major cations and anions indicated calcium-bicarbonate and sodium-bicarbonate water types in the study area. Oxygen and hydrogen isotopes carried an oxygen-18 excess signature, possibly indicating recharge from evaporated sources or water-rock interactions in the subsurface. Chlorofluorocarbons detected modern (post-1940s) recharge in every well sampled; tritium data indicated modern water (post-1951) in seven, predominantly shallow wells. Nutrient concentrations tended to be greater in wells signaling recent recharge based on groundwater age dating, thus confirming the presence of recent recharge in these wells. Corrected radiocarbon results generated estimated residence times from modern to 5,100 years before present. Residence time tended to increase with depth, as confirmed by all three age-tracers. The disagreement among residence times indicates that samples were well-mixed and that the sampled aquifers contain a mixture of young and old recharge. Due to a lack of data, no conclusions about sources of recharge could be drawn

  11. La díada en el desarrollo de la condición humana

    Directory of Open Access Journals (Sweden)

    Carmen Rosalía Solla

    2011-05-01

    Full Text Available Este artículo tiene como propósito realizar una disertación sobre la díada como estrategia socializadora que coadyuva al desarrollo de la condición humana, entendiendo ésta como la fuerza viva de interrelacionarse con su semejante, respetarlo, amarlo y ser empático son ese otro que está ahí para ser el complemento de uno. Esta investigación se desarrolla como un estudio documental, de tipo expositivo, ya que en éste se presentan los estudios de Valles (2004, Hernández y Cortés (2009, Solla (2003/2010 y, Rodríguez (2009 y se hace referencia a las teorías de Gadamer (1997, Heidegger (2003 y Bronfenbrenner (1987 como soportes al estudio de las relaciones complementarias, específicamente de la díada. Los trabajos antes mencionados se exponen en forma dialógica para que así uno sea complemento del otro. El artículo está compuesto por varias partes que guían al lector a entender al individuo desde su unicidad hasta la necesidad de complementarse con el otro quien le ayuda a ratificar su condición humana. Finalmente, se concluye que el ser humano, desde la relación diádica, abre su ser para desplegarse en el otro; promueve la interrelación, la comunicación, la cohesión, la afectividad, la reciprocidad, la solidaridad, el respeto y la dialógica; trabaja con su semejante y posibilita la formación de comunidades cohesionadas.

  12. 77 FR 45962 - Approval and Promulgation of State Implementation Plans: Idaho; Boise-Northern Ada County Air...

    Science.gov (United States)

    2012-08-02

    ... County Air Quality Maintenance Area Second 10-Year Carbon Monoxide Maintenance Plan AGENCY: Environmental... County Air Quality Maintenance Area Second 10- year Carbon Monoxide Limited Maintenance Plan submitted by... Maintenance Area. The Northern Ada County Area attained the CO national ambient air quality standards...

  13. Dynamic Allocation Strategy Based on Pre-allocation and Agent to Implement Ada95's Distributed Computing

    Institute of Scientific and Technical Information of China (English)

    ZhuFu-xi; FuJian-ming; WuChan-le; CaoZheng

    2003-01-01

    This paper discusses the model of how the Agent is applied to implement distributed computing of Ada95 and presents a dynamic allocation strategy for distributed computing that based on pre-allocationand Agent. The aim of this strategy is realizing dynamic equilibrium allocation.

  14. Reliability prediction for the vehicles equipped with advanced driver assistance systems (ADAS and passive safety systems (PSS

    Directory of Open Access Journals (Sweden)

    Balbir S. Dhillon

    2012-10-01

    Full Text Available The human error has been reported as a major root cause in road accidents in today’s world. The human as a driver in road vehicles composed of human, mechanical and electrical components is constantly exposed to changing surroundings (e.g., road conditions, environmentwhich deteriorate the driver’s capacities leading to a potential accident. The auto industries and transportation authorities have realized that similar to other complex and safety sensitive transportation systems, the road vehicles need to rely on both advanced technologies (i.e., Advanced Driver Assistance Systems (ADAS and Passive Safety Systems (PSS (e.g.,, seatbelts, airbags in order to mitigate the risk of accidents and casualties. In this study, the advantages and disadvantages of ADAS as active safety systems as well as passive safety systems in road vehicles have been discussed. Also, this study proposes models that analyze the interactions between human as a driver and ADAS Warning and Crash Avoidance Systems and PSS in the design of vehicles. Thereafter, the mathematical models have been developed to make reliability prediction at any given time on the road transportation for vehicles equipped with ADAS and PSS. Finally, the implications of this study in the improvement of vehicle designs and prevention of casualties are discussed.

  15. La tríada oscura de la personalidad: maquiavelismo, narcisismo y psicopatía. Una mirada evolutiva

    Directory of Open Access Journals (Sweden)

    Fernando Renee González Moraga

    2015-08-01

    Full Text Available Se aborda la denominada Tríada Oscura de la Personalidad -Tríada- (maquiavelismo, narcisismo subclínico y psicopatía subclínica desde una mirada evolutiva. El objetivo de esta investigación es revisar la evidencia que han presentado los teóricos evolucionistas sobre la Tríada, desde un acercamiento a la mirada evolutiva. Para esto, se indaga en las principales características de cada uno de estos rasgos, los instrumentos que se han utilizado para evaluarlos y las principales áreas en donde se han estudiado. La mirada evolutiva plantea que los rasgos de la Tríada son dimensionales y varían de acuerdo con las diversas estrategias que utilizan los sujetos para adaptarse a las características socioambientales en las que se desarrollan. Estos rasgos se caracterizan por presentar violencia psicológica, inhibición moral, manipulación, baja amabilidad, insensibilidad, egoísmo y dificultad para mentalizar en contextos de interacción interpersonal y social.

  16. Rezension: Ada Lovelace. Die Pionierin der Computertechnik und ihre Nachfolgerinnen von Sybille Krämer (Hg.

    Directory of Open Access Journals (Sweden)

    Bettina Schabschneider

    2015-12-01

    Full Text Available Ein aktueller von Sybille Krämer herausgegebener Sammelband beleuchtet die Bedeutung der Computertechnik-Pionierin Ada Lovelace. Bettina Schabschneider hat den Band einer detaillierten Lektüre unterzogen und für die MEDIENIMPULSE rezensiert …

  17. HPV16 E6-induced and E6AP-dependent inhibition of the transcriptional coactivator hADA3 in human cervical carcinoma cells.

    Science.gov (United States)

    Hu, Ying; Ye, Feng; Lu, Weiguo; Hong, Die; Wan, Xiaoyun; Xie, Xing

    2009-03-01

    To determine whether there exists an additional pathway of E6 that is independent of direct P53 degradation and whether hADA3, a transcriptional coactivator, is involved in this process. We investigated the association between E6 and hADA3, as well as E6-associated protein (E6AP) and hADA3, in SiHa cells via RNA interference technique. Our results showed that the expression of hADA3 protein was significantly increased, cellular proliferation was decreased and apoptotic rate was increased in SiHa cells treated by E6 siRNA and E6AP siRNA respectively. Our results suggested that oncoprotein E6 inhibits hADA3 in cervical cancer cells and this process is E6AP-dependent.

  18. Regulation of dCTP deaminase from Escherichia coli by nonallosteric dTTP binding to an inactive form of the enzyme

    DEFF Research Database (Denmark)

    Johansson, Eva; Thymark, Majbritt; Bynck, Julie H;

    2007-01-01

    the trimer. Also, the dCTP complex of the inactive H121A was found to have residues 120-125 in this new conformation, indicating that it renders the enzyme inactive. The C-terminal fold was found to be disordered for both new complexes. We suggest that the cooperative kinetics are imposed by a d......TTP-dependent lag of product formation observed in presteady-state kinetics. This lag may be derived from a slow equilibration between an inactive and an active conformation of dCTP deaminase represented by the dTTP complex and the dUTP/dCTP complex, respectively. The dCTP deaminase then resembles a simple...

  19. Concerted bifunctionality of the dCTP deaminase-dUTPase from Methanocaldococcus jannaschii: A structural and pre-steady state kinetic analysis

    DEFF Research Database (Denmark)

    Siggaard, Julie; Johansson, Eva; Vognsen, Tina Reinholdt;

    2009-01-01

    complexes and closed over the active site by interacting with the phosphate backbone of the nucleotide or with the diphosphate. A magnesium ion was readily observed to complex with all three phosphoryls in the nucleotide complex or with the diphosphate. A water molecule that is likely to be involved...... in the nucleotidyl diphosphorylase reaction was observed in the E145A:alpha,beta-imido-dUTP complex and positioned similarly as in the monofunctional trimeric dUTPase. A comparison of the active sites of the bifunctional enzyme and the monofunctional family members, dCTP deaminase and dUTPase, suggests similar...... reaction mechanisms. The similar side chain conformations in the deaminase site between the nucleotide and diphosphate complexes indicated a concerted re-arrangement, or induced fit, of the whole active site promoted by enzyme and nucleotide phosphoryl interactions. A pre-steady state kinetic analysis...

  20. The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Rongen, G.A.P.J.M.; Karemaker, J.M.; Wieling, W.; Marres, H.A.M.; Lenders, J.W.M.

    2004-01-01

    The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemorecepto

  1. Influence of the adenosine A1 receptor on blood pressure regulation and renin release

    DEFF Research Database (Denmark)

    Brown, Russell D.; Thorén, Peter; Steege, Andreas;

    2006-01-01

    The present study was performed to investigate the role of adenosine A1 receptors in regulating blood pressure in conscious mice. Adenosine A1-receptor knockout (A1R-/-) mice and their wild-type (A1R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS), or salt-deficient (SD...... in sodium excretion between the two genotypes on the HS diet. Even on the SD diet, A1R-/- mice had an increased sodium excretion compared with A1R+/+ mice. An abolished tubuloglomerular feedback response and reduced tubular reabsorption can account for the elevated salt excretion found in A1R-/- animals....... The elevated plasma renin concentrations found in the A1R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A1 receptor, plays an important role in regulating blood pressure, renin release, and sodium excretion....

  2. The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects

    DEFF Research Database (Denmark)

    Birk, S; Petersen, K.A.; Kruuse, Christina Rostrup;

    2005-01-01

    Adenosine is an endogenous neurotransmitter that is released from the brain during hypoxia and relaxes isolated human cerebral arteries. Many cerebral artery dilators cause migraine attacks. However, the effect of intravenous adenosine on headache and cerebral artery diameter has not previously...... been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 microg kg(-1) min(-1) and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design....... Headache was rated on a verbal scale (0-10). Regional cerebral blood flow (rCBF) with 133Xe inhalation and single-photon emission computed tomography (SPECT) and MCA flow velocity (V(MCA)) with transcranial Doppler, were measured in direct sequence. Six participants developed headache during 80 microg kg...

  3. Laboratory procedures manual for the firefly luciferase assay for adenosine triphosphate (ATP)

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.; Curtis, C. A.; Knust, E. A.; Nibley, D. A.; Vance, R. B.

    1975-01-01

    A manual on the procedures and instruments developed for the adenosine triphosphate (ATP) luciferase assay is presented. Data cover, laboratory maintenance, maintenance of bacterial cultures, bacteria measurement, reagents, luciferase procedures, and determination of microbal susceptibility to antibiotics.

  4. Actinides and rare earths complexation with adenosine phosphate nucleotides

    International Nuclear Information System (INIS)

    Organophosphorus compounds are important molecules in both nuclear industry and living systems fields. Indeed, several extractants of organophosphorus compounds (such as TBP, HDEHP) are used in the nuclear fuel cycle reprocessing and in the biological field. For instance, the nucleotides are organophosphates which play a very important role in various metabolic processes. Although the literature on the interactions of actinides with inorganic phosphate is abundant, published studies with organophosphate compounds are generally limited to macroscopic and / or physiological approaches. The objective of this thesis is to study the structure of several organophosphorus compounds with actinides to reach a better understanding and develop new specific buildings blocks. The family of the chosen molecules for this procedure consists of three adenine nucleotides mono, bi and triphosphate (AMP, adenosine monophosphate - ADP, adenosine diphosphate - ATP, adenosine triphosphate) and an amino-alkylphosphate (AEP O-phosphoryl-ethanolamine). Complexes synthesis was conducted in aqueous and weakly acidic medium (2.8-4) for several lanthanides (III) (Lu, Yb, Eu) and actinides (U (VI), Th (IV) and Am (III)). Several analytical and spectroscopic techniques have been used to describe the organization of the synthesized complexes: spectrometric analysis performed by FTIR and NMR were used to identify the functional groups involved in the complexation, analysis by ESI-MS and pH-metric titration were used to determine the solution speciation and EXAFS analyzes were performed on Mars beamline of the SOLEIL synchrotron, have described the local cation environment, for both solution and solid compounds. Some theoretical approaches of DFT were conducted to identify stable structures in purpose of completing the experimental studies. All solid complexes (AMP, ADP, ATP and AEP) have polynuclear structures, while soluble ATP complexes are mononuclear. For all synthesized complexes, it has been

  5. Novel Rhizosphere Soil Alleles for the Enzyme 1-Aminocyclopropane-1-Carboxylate Deaminase Queried for Function with an In Vivo Competition Assay.

    Science.gov (United States)

    Jin, Zhao; Di Rienzi, Sara C; Janzon, Anders; Werner, Jeff J; Angenent, Largus T; Dangl, Jeffrey L; Fowler, Douglas M; Ley, Ruth E

    2015-12-04

    Metagenomes derived from environmental microbiota encode a vast diversity of protein homologs. How this diversity impacts protein function can be explored through selection assays aimed to optimize function. While artificially generated gene sequence pools are typically used in selection assays, their usage may be limited because of technical or ethical reasons. Here, we investigate an alternative strategy, the use of soil microbial DNA as a starting point. We demonstrate this approach by optimizing the function of a widely occurring soil bacterial enzyme, 1-aminocyclopropane-1-carboxylate (ACC) deaminase. We identified a specific ACC deaminase domain region (ACCD-DR) that, when PCR amplified from the soil, produced a variant pool that we could swap into functional plasmids carrying ACC deaminase-encoding genes. Functional clones of ACC deaminase were selected for in a competition assay based on their capacity to provide nitrogen to Escherichia coli in vitro. The most successful ACCD-DR variants were identified after multiple rounds of selection by sequence analysis. We observed that previously identified essential active-site residues were fixed in the original unselected library and that additional residues went to fixation after selection. We identified a divergent essential residue whose presence hints at the possible use of alternative substrates and a cluster of neutral residues that did not influence ACCD performance. Using an artificial ACCD-DR variant library generated by DNA oligomer synthesis, we validated the same fixation patterns. Our study demonstrates that soil metagenomes are useful starting pools of protein-coding-gene diversity that can be utilized for protein optimization and functional characterization when synthetic libraries are not appropriate.

  6. Reduced striatal ecto-nucleotidase activity in schizophrenia patients supports the “adenosine hypothesis”

    OpenAIRE

    Aliagas, Elisabet; Villar-Menéndez, Izaskun; Sévigny, Jean; Roca, Mercedes; Romeu, Miriam; Ferrer, Isidre; Martín-Satué, Mireia; Barrachina, Marta

    2013-01-01

    Schizophrenia (SZ) is a major chronic neuropsychiatric disorder characterized by a hyperdopaminergic state. The hypoadenosinergic hypothesis proposes that reduced extracellular adenosine levels contribute to dopamine D2 receptor hyperactivity. ATP, through the action of ecto-nucleotidases, constitutes a main source of extracellular adenosine. In the present study, we examined the activity of ecto-nucleotidases (NTPDases, ecto-5′-nucleotidase, and alkaline phosphatase) in the postmortem putame...

  7. Severe hemorrhage attenuates cardiopulmonary chemoreflex control of regional sympathetic outputs via NTS adenosine receptors

    OpenAIRE

    Minic, Zeljka; Li, Cailian; O'Leary, Donal S.; Scislo, Tadeusz J.

    2014-01-01

    Selective stimulation of inhibitory A1 and facilitatory A2a adenosine receptor subtypes located in the nucleus of the solitary tract (NTS) powerfully inhibits cardiopulmonary chemoreflex (CCR) control of regional sympathetic outputs via different mechanisms: direct inhibition of glutamate release and facilitation of an inhibitory neurotransmitter release, respectively. However, it remains unknown whether adenosine naturally released into the NTS has similar inhibitory effects on the CCR as th...

  8. Cyclization of the phosphate side chain of adenosine triphosphate: formation of monoadenosine 5'-trimetaphosphate.

    Science.gov (United States)

    Glonek, T; Kleps, R A; Myers, T C

    1974-07-26

    Monoadenosine 5'-trimetaphosphate has been prepared from adeno-sine 5'-triphosphate by a carbodiimide-mediated condensation. The molecule was characterized by (3l)P nuclear magnetic resonance, and its (31)P spectrum was simulated through the assumption of a three-phosphorus spin system. The molecule is highly reactive and is rapidly converted to adenosine triphosphate upon contact with water. PMID:4834364

  9. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.

    OpenAIRE

    Cronstein, B. N.; Eberle, M A; Gruber, H E; Levin, R I

    1991-01-01

    Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, we determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts from 4 +/- 1% t...

  10. Regulation of aggregate size and pattern by adenosine and caffeine in cellular slime molds

    OpenAIRE

    Jaiswal Pundrik; Soldati Thierry; Thewes Sascha; Baskar Ramamurthy

    2012-01-01

    Abstract Background Multicellularity in cellular slime molds is achieved by aggregation of several hundreds to thousands of cells. In the model slime mold Dictyostelium discoideum, adenosine is known to increase the aggregate size and its antagonist caffeine reduces the aggregate size. However, it is not clear if the actions of adenosine and caffeine are evolutionarily conserved among other slime molds known to use structurally unrelated chemoattractants. We have examined how the known factor...

  11. Aptamer-based Electrochemical Biosensors for Highly Selective and Quantitative Detection of Adenosine

    Institute of Scientific and Technical Information of China (English)

    ZHENG Fan; WU Zai-sheng; ZHANG Song-bai; GUO Meng-meng; CHEN Chen-rui; SHEN Guo-li; YU Ru-qin

    2008-01-01

    A new adenosine biosensor based on aptamer probe is introduced in this article.An amino-labeled aptamer probe was immobilized on the gold electrode modified with an o-phenylenediamine electropolymerized film.When adenosine is bound specifically to the aptamer probe,the interface of the biosensor is changed,resulting in the decrement of the peak current.The response current is proportional to the amount of adenosine in sample.The used electrode can be easily regenerated in hot water.The proposed biosensor represents a linear response to adenosine over a concentration range of 1.0×10-7-1.0×10-4 mol/L with a detection limit of 1.0×10-8 mol/L.The presented biosensor exhibits a nice specificity towards adenosine.It offers a promising approach for adenosine assay due to its excellent electrochemical properties that are believed to be very attractive for electrochemical studies and electroanalytical applications.

  12. Label-Free Sensing of Adenosine Based on Force Variations Induced by Molecular Recognition

    Directory of Open Access Journals (Sweden)

    Jingfeng Li

    2015-03-01

    Full Text Available We demonstrate a simple force-based label-free strategy for the highly sensitive sensing of adenosine. An adenosine ssDNA aptamer was bound onto an atomic force microscopy (AFM probe by covalent modification, and the molecular-interface adsorption force between the aptamer and a flat graphite surface was measured by single-molecule force spectroscopy (SMFS. In the presence of adenosine, the molecular recognition between adenosine and the aptamer resulted in the formation of a folded, hairpin-like DNA structure and hence caused a variation of the adsorption force at the graphite/water interface. The sensitive force response to molecular recognition provided an adenosine detection limit in the range of 0.1 to 1 nM. The addition of guanosine, cytidine, and uridine had no significant interference with the sensing of adenosine, indicating a strong selectivity of this sensor architecture. In addition, operational parameters that may affect the sensor, such as loading rate and solution ionic strength, were investigated.

  13. Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells

    International Nuclear Information System (INIS)

    Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, the authors determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up [14C]adenine and released 14C-labeled purine (a measure of cell injury) in a manner identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils and stimulated neutrophils. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which has previously been shown to cause adenosine release from ischemic cardiac tissue. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs

  14. Suppression of adenosine-activated chloride transport by ethanol in airway epithelia.

    Directory of Open Access Journals (Sweden)

    Sammeta V Raju

    Full Text Available Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (I(SC in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR, a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A(2B adenosine receptor (A(2BAR, largely abolished the adenosine-stimulated chloride transport, suggesting that A(2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A(2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections.

  15. Functional proteomics of adenosine triphosphatase system in the rat striatum during aging

    Institute of Scientific and Technical Information of China (English)

    Roberto Federico Villa; Federica Ferrari; Antonella Gorini

    2012-01-01

    The maximum rates of adenosine triphosphatase (ATPase) systems related to energy consumption were systematically evaluated in synaptic plasma membranes isolated from the striata of male Wistar rats aged 2, 6, 12, 18, and 24 months, because of their key role in presynaptic nerve ending homeostasis. The following enzyme activities were evaluated: sodium-potassium-magnesium adenosine triphosphatase (Na+, K+, Mg2+-ATPase); ouabain-insensitive magnesium adenosine triphosphatase (Mg2+-ATPase); sodium-potassium adenosine triphosphatase (Na+, K+-ATPase); direct magnesium adenosine triphosphatase (Mg2+-ATPase); calcium-magnesium adenosine triphosphatase (Ca2+, Mg2+-ATPase); and acetylcholinesterase. The results showed that Na+, K+-ATPase decreased at 18 and 24 months, Ca2+, Mg2+-ATPase and acetylcholinesterase decreased from 6 months, while Mg2+-ATPase was unmodified. Therefore, ATPases vary independently during aging, suggesting that the ATPase enzyme systems are of neuropathological and pharmacological importance. This could be considered as an experimental model to study regeneration processes, because of the age-dependent modifications of specific synaptic plasma membranes. ATPases cause selective changes in some cerebral functions, especially bioenergetic systems. This could be of physiopathological significance, particularly in many central nervous system diseases, where, during regenerative processes, energy availability is essential.

  16. Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes

    DEFF Research Database (Denmark)

    Johansson, Eva; Fanø, Mathias; Bynck, Julie H;

    2005-01-01

    aid from a catalytic metal ion that facilitates preparation of a water molecule for nucleophilic attack on the substrate. Two active site amino acid residues, Arg(115) and Glu(138), were identified by mutational analysis as important for activity in E. coli dCTP deaminase. None of the mutant enzymes R......115A, E138A, or E138Q had any detectable activity but circular dichroism spectra for all mutant enzymes were similar to wild type suggesting that the overall structure was not changed. The crystal structures of wild-type E. coli dCTP deaminase and the E138A mutant enzyme have been determined...... in complex with dUTP and Mg(2+), and the mutant enzyme also with the substrate dCTP and Mg(2+). The enzyme is a third member of the family of the structurally related trimeric dUTPases and the bifunctional dCTP deaminase-dUTPase from Methanocaldococcus jannaschii. However, the C-terminal fold is completely...

  17. An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation.

    Science.gov (United States)

    Shang, Luqing; Wang, Yaxin; Qing, Jie; Shu, Bo; Cao, Lin; Lou, Zhiyong; Gong, Peng; Sun, Yuna; Yin, Zheng

    2014-12-01

    Enterovirus 71 (EV71), one of the major causative agents of Hand-Foot-Mouth Disease (HFMD), causes severe pandemics and hundreds of deaths in the Asia-Pacific region annually and is an enormous public health threat. However, effective therapeutic antiviral drugs against EV71 are rare. Nucleoside analogues have been successfully used in the clinic for the treatment of various viral infections. We evaluated a total of 27 nucleoside analogues and discovered that an adenosine nucleoside analogue NITD008, which has been reported to be an antiviral reagent that specifically inhibits flaviviruses, effectively suppressed the propagation of different strains of EV71 in RD, 293T and Vero cells with a relatively high selectivity index. Triphosphorylated NITD008 (ppp-NITD008) functions as a chain terminator to directly inhibit the RNA-dependent RNA polymerase activity of EV71, and it does not affect the EV71 VPg uridylylation process. A significant synergistic anti-EV71 effect of NITD008 with rupintrivir (AG7088) (a protease inhibitor) was documented, supporting the potential combination therapy of NITD008 with other inhibitors for the treatment of EV71 infections.

  18. Adenosine to Inosine editing frequency controlled by splicing efficiency.

    Science.gov (United States)

    Licht, Konstantin; Kapoor, Utkarsh; Mayrhofer, Elisa; Jantsch, Michael F

    2016-07-27

    Alternative splicing and adenosine to inosine (A to I) RNA-editing are major factors leading to co- and post-transcriptional modification of genetic information. Both, A to I editing and splicing occur in the nucleus. As editing sites are frequently defined by exon-intron basepairing, mRNA splicing efficiency should affect editing levels. Moreover, splicing rates affect nuclear retention and will therefore also influence the exposure of pre-mRNAs to the editing-competent nuclear environment. Here, we systematically test the influence of splice rates on RNA-editing using reporter genes but also endogenous substrates. We demonstrate for the first time that the extent of editing is controlled by splicing kinetics when editing is guided by intronic elements. In contrast, editing sites that are exclusively defined by exonic structures are almost unaffected by the splicing efficiency of nearby introns. In addition, we show that editing levels in pre- and mature mRNAs do not match. This phenomenon can in part be explained by the editing state of an RNA influencing its splicing rate but also by the binding of the editing enzyme ADAR that interferes with splicing. PMID:27112566

  19. Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption.

    Science.gov (United States)

    Welch, W J

    2015-01-01

    Adenosine type 1 receptor (A1 -AR) antagonists induce diuresis and natriuresis in experimental animals and humans. Much of this effect is due to inhibition of A1 -ARs in the proximal tubule, which is responsible for 60-70% of the reabsorption of filtered Na(+) and fluid. Intratubular application of receptor antagonists indicates that A1 -AR mediates a portion of Na(+) uptake in PT and PT cells, via multiple transport systems, including Na(+) /H(+) exchanger-3 (NHE3), Na(+) /PO4(-) co-transporter and Na(+) -dependent glucose transporter, SGLT. Renal microperfusion and recollection studies have shown that fluid reabsorption is reduced by A1 -AR antagonists and is lower in A1 -AR KO mice, compared to WT mice. Absolute proximal reabsorption (APR) measured by free-flow micropuncture is equivocal, with studies that show either lower APR or similar APR in A1 -AR KO mice, compared to WT mice. Inhibition of A1 -ARs lowers elevated blood pressure in models of salt-sensitive hypertension, partially due to their effects in the proximal tubule. PMID:25345761

  20. In Vitro Functional Study of Rice Adenosine 5'-Phosphosulfate Kinase

    Institute of Scientific and Technical Information of China (English)

    WANG De-zhen; CHEN Guo-guo; LU Lu-jia; JIANG Zhao-jun; RAO Yu-chun; SUN Mei-hao

    2016-01-01

    Sulfate can be activated by ATP sulfurylase and adenosine 5'-phosphosulfate kinase (APSK)in vivo. Recent studies suggested that APSK inArabidopsis thaliana regulated the partition between APS reduction and phosphorylation and its activity can be modulated by cellular redox status. In order to study regulation of APSK in rice (OsAPSK),OsAPSK1 gene was cloned and its activity was analyzed. OsAPSK1 C36 and C69 were found to be the conserved counterparts of C86 and C119, which involved in disulfide formation in AtAPSK.C36A/C69A OsAPSK1 double mutation was made by site directed mutagenesis. OsAPSK1 and its mutant were prokaryotically over-expressed and purified, and then assayed for APS phosphorylation activity. OsAPSK1 activity was depressed by oxidized glutathione, while the activity of its mutantwas not. Further studies in the case that oxidative stress will fluctuatein vivo3'-phosphoadenosine-5'-phosphosulfate content, and all APSK isoenzymes have similar regulation patterns are necessary to be performed.

  1. Cyclic adenosine monophosphate signal pathway in targeted therapy of lymphoma

    Institute of Scientific and Technical Information of China (English)

    DOU Ai-xia; WANG Xin

    2010-01-01

    Objective To review the role of cyclic adenosine monophosphate (cAMP) signal pathway in the pathogenesis oflymphoma and explore a potential lymphoma therapy targeted on this signaling pathway.Data sources The data cited in this review were mainly obtained from the articles listed in Medline and PubMed,published from January 1995 to June 2009. The search terms were "cAMP" and "lymphoma".Study selection Articles regarding the role of the cAMP pathway in apoptosis of lymphoma and associated cells and itspotential role in targeted therapy of lymphoma.Results In the transformation of lymphocytic malignancies, several signal pathways are involved. Among of them, thecAMP pathway has attracted increasing attention because of its apoptosis-inducing role in several lymphoma cells. cAMPpathway impairment is found to influence the prognosis of lymphoma. Targeted therapy to the cAMP pathway seems tobe a new direction for lymphoma treatment, aiming at restoring the cAMP function.Conclusions cAMP signal pathway has different effects on various lymphoma cells. cAMP analogues andphosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance. However, many challenges remain inunderstanding the various roles of such agents.

  2. Feasibility and safety of high-dose adenosine perfusion cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Holloway Cameron J

    2010-11-01

    Full Text Available Abstract Introduction Adenosine is the most widely used vasodilator stress agent for Cardiovascular Magnetic Resonance (CMR perfusion studies. With the standard dose of 140 mcg/kg/min some patients fail to demonstrate characteristic haemodynamic changes: a significant increase in heart rate (HR and mild decrease in systolic blood pressure (SBP. Whether an increase in the rate of adenosine infusion would improve peripheral and, likely, coronary vasodilatation in those patients is unknown. The aim of the present study was to assess the tolerance and safety of a high-dose adenosine protocol in patients with inadequate haemodynamic response to the standard adenosine protocol when undergoing CMR perfusion imaging. Methods 98 consecutive patients with known or suspected coronary artery disease (CAD underwent CMR perfusion imaging at 1.5 Tesla. Subjects were screened for contraindications to adenosine, and an electrocardiogram was performed prior to the scan. All patients initially received the standard adenosine protocol (140 mcg/kg/min for at least 3 minutes. If the haemodynamic response was inadequate (HR increase Results All patients successfully completed the CMR scan. Of a total of 98 patients, 18 (18% did not demonstrate evidence of a significant increase in HR or decrease in SBP under the standard adenosine infusion rate. Following the increase in the rate of infusion, 16 out of those 18 patients showed an adequate haemodynamic response. One patient of the standard infusion group and two patients of the high-dose group developed transient advanced AV block. Significantly more patients complained of chest pain in the high-dose group (61% vs. 29%, p = 0.009. On multivariate analysis, age > 65 years and ejection fraction Conclusions A substantial number of patients do not show adequate peripheral haemodynamic response to standard-dose adenosine stress during perfusion CMR imaging. Age and reduced ejection fraction are predictors of inadequate

  3. Adenosine preconditioning attenuates hepatic reperfusion injury in the rat by preventing the down-regulation of endothelial nitric oxide synthase

    Science.gov (United States)

    Serracino-Inglott, Ferdinand; Virlos, Ioannis T; Habib, Nagy A; Williamson, Robin CN; Mathie, Robert T

    2002-01-01

    Background Previous work has suggested that in the liver, adenosine preconditioning is mediated by nitric oxide. Whether the endothelial isoform of nitric oxide synthase plays a part in this mechanism has however not yet been investigated. Methods Wistar rats were used (6 in each group) – Groups: (1) sham, (2) ischemia-reperfusion, (3) adenosine + ischemia-reperfusion, (4) endothelial isoform inhibitor + adenosine + ischemia-reperfusion. Results Using immunohistochemistry, this study has revealed a decrease in the expression of endothelial nitric oxide synthase following hepatic ischemia-reperfusion. This was prevented by adenosine pre-treatment. When an inhibitor of endothelial nitric oxide synthase was administered prior to adenosine pre-treatment, pre-conditioning did not occur despite normal expression of endothelial nitric oxide synthase. Conclusions These findings suggest that adenosine attenuates hepatic injury by preventing the downregulation of endothelial nitric oxide synthase that occurs during ischemia-reperfusion. PMID:12241560

  4. Microevolution of the chromosomal region of acute disease antigen A (adaA in the query (Q fever agent Coxiella burnetii.

    Directory of Open Access Journals (Sweden)

    Dimitrios Frangoulidis

    Full Text Available The acute disease antigen A (adaA gene is believed to be associated with Coxiella burnetii strains causing acute Q fever. The detailed analysis of the adaA genomic region of 23 human- and 86 animal-derived C. burnetii isolates presented in this study reveals a much more polymorphic appearance and distribution of the adaA gene, resulting in a classification of C. burnetii strains of better differentiation than previously anticipated. Three different genomic variants of the adaA gene were identified which could be detected in isolates from acute and chronic patients, rendering the association of adaA positive strains with acute Q fever disease disputable. In addition, all adaA positive strains in humans and animals showed the occurrence of the QpH1 plasmid. All adaA positive isolates of acute human patients except one showed a distinct SNP variation at position 431, also predominant in sheep strains, which correlates well with the observation that sheep are a major source of human infection. Furthermore, the phylogenetic analysis of the adaA gene revealed three deletion events and supported the hypothesis that strain Dugway 5J108-111 might be the ancestor of all known C. burnetii strains. Based on our findings, we could confirm the QpDV group and we were able to define a new genotypic cluster. The adaA gene polymorphisms shown here improve molecular typing of Q fever, and give new insights into microevolutionary adaption processes in C. burnetii.

  5. Adenosine elicits an eNOS-independent reduction in arterial blood pressure in conscious mice that involves adenosine A(2A) receptors

    DEFF Research Database (Denmark)

    Andersen, Henrik; Jaff, Mohammad G; Høgh, Ditte;

    2011-01-01

    Aims:  Adenosine plays an important role in the regulation of heart rate and vascular reactivity. However, the mechanisms underlying the acute effect of adenosine on arterial blood pressure in conscious mice are unclear. Therefore, the present study investigated the effect of the nucleoside on mean...... arterial blood pressure (MAP) and heart rate (HR) in conscious mice. Methods:  Chronic indwelling catheters were placed in C57Bl/6J (WT) and endothelial nitric oxide synthase knock-out (eNOS(-/-) ) mice for continuous measurements of MAP and HR. Using PCR and myograph analysis involment of adenosine...... receptors was investigated in human and mouse renal blood vessels Results:  Bolus infusion of 0.5 mg/kg adenosine elicited significant transient decreases in MAP (99.3±2.3 to 70.4±4.5 mmHg) and HR (603.2±18.3 to 364.3±49.2 min(-1) ) which were inhibited by the A(2A) receptor antagonist ZM 241385. Activation...

  6. Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents: an in vitro study.

    Directory of Open Access Journals (Sweden)

    Robert Edward Sims

    Full Text Available Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K(+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.

  7. A2A adenosine receptor-mediated increase in coronary flow in hyperlipidemic APOE–knockout mice

    OpenAIRE

    Teng, Bunyen

    2011-01-01

    Bunyen Teng, S Jamal MustafaDepartment of Physiology and Pharmacology and Center for Cardiovascular and Respiratory Sciences, West Virginia University, Morgantown, WV, USAAbstract: Adenosine-induced coronary vasodilation is predominantly A2A adenosine receptor (AR)-mediated, whereas A1 AR is known to negatively modulate the coronary flow (CF). However, the coronary responses to adenosine in hyperlipidemia and atherosclerosis are not well understood. Using hyperlipidemic/atherosclerotic apolip...

  8. In vivo adenosine A(2B) receptor desensitization in guinea-pig airway smooth muscle: implications for asthma.

    Science.gov (United States)

    Breschi, Maria Cristina; Blandizzi, Corrado; Fogli, Stefano; Martinelli, Cinzia; Adinolfi, Barbara; Calderone, Vincenzo; Camici, Marcella; Martinotti, Enrica; Nieri, Paola

    2007-12-01

    This study was aimed at characterizing the role of adenosine receptor subtypes in the contractility modulation of guinea-pig airway smooth muscle in normal and pathological settings. In vitro and in vivo experiments were performed by testing selective agonists and antagonists on isolated tracheal smooth muscle preparations and pulmonary inflation pressure, respectively, under normal conditions or following ovalbumin-induced allergic sensitization. In normal and sensitized animals, the adenosine A(2A)/A(2B) receptor agonist, NECA, evoked relaxing responses of isolated tracheal preparations precontracted with histamine, and such an effect was reversed by the adenosine A(2B) antagonist, MRS 1706, in the presence or in the absence of epithelium. The expression of mRNA coding for adenosine A(2B) receptors was demonstrated in tracheal specimens. In vitro desensitization with 100 microM NECA markedly reduced the relaxing effect of the agonist. In vivo NECA or adenosine administration to normal animals inhibited histamine-mediated bronchoconstriction, while these inhibitory effects no longer occurred in sensitized guinea-pigs. Adenosine plasma levels were significantly higher in sensitized than normal animals. In conclusion, our data demonstrate that: (i) adenosine A(2B) receptors are responsible for the relaxing effects of adenosine on guinea-pig airways; (ii) these receptors can undergo rapid adaptive changes that may affect airway smooth muscle responsiveness to adenosine; (iii) ovalbumin-induced sensitization promotes a reversible inactivation of adenosine A(2B) receptors which can be ascribed to homologous desensitization. These findings can be relevant to better understand adenosine functions in airways as well as mechanisms of action of asthma therapies targeting the adenosine system.

  9. Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig Loci in activated B cells.

    Science.gov (United States)

    Staszewski, Ori; Baker, Richard E; Ucher, Anna J; Martier, Raygene; Stavnezer, Janet; Guikema, Jeroen E J

    2011-01-21

    After immunization or infection, activation-induced cytidine deaminase (AID) initiates diversification of immunoglobulin (Ig) genes in B cells, introducing mutations within the antigen-binding V regions (somatic hypermutation, SHM) and double-strand DNA breaks (DSBs) into switch (S) regions, leading to antibody class switch recombination (CSR). We asked if, during B cell activation, AID also induces DNA breaks at genes other than IgH genes. Using a nonbiased genome-wide approach, we have identified hundreds of reproducible, AID-dependent DSBs in mouse splenic B cells shortly after induction of CSR in culture. Most interestingly, AID induces DSBs at sites syntenic with sites of translocations, deletions, and amplifications found in human B cell lymphomas, including within the oncogene B cell lymphoma11a (bcl11a)/evi9. Unlike AID-induced DSBs in Ig genes, genome-wide AID-dependent DSBs are not restricted to transcribed regions and frequently occur within repeated sequence elements, including CA repeats, non-CA tandem repeats, and SINEs.

  10. S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase.

    Science.gov (United States)

    Wuerffel, Robert; Wang, Lili; Grigera, Fernando; Manis, John; Selsing, Erik; Perlot, Thomas; Alt, Frederick W; Cogne, Michel; Pinaud, Eric; Kenter, Amy L

    2007-11-01

    Molecular mechanisms underlying synapsis of activation-induced deaminase (AID)-targeted S regions during class switch recombination (CSR) are poorly understood. By using chromosome conformation capture techniques, we found that in B cells, the Emicro and 3'Ealpha enhancers were in close spatial proximity, forming a unique chromosomal loop configuration. B cell activation led to recruitment of the germline transcript (GLT) promoters to the Emicro:3'Ealpha complex in a cytokine-dependent fashion. This structure facilitated S-S synapsis because Smicro was proximal to Emicro and a downstream S region was corecruited with the targeted GLT promoter to Emicro:3'Ealpha. We propose that GLT promoter association with the Emicro:3'Ealpha complex creates an architectural scaffolding that promotes S-S synapsis during CSR and that these interactions are stabilized by AID. Thus, the S-S synaptosome is formed as a result of the self-organizing transcription system that regulates GLT expression and may serve to guard against spurious chromosomal translocations.

  11. Activation-induced cytidine deaminase targets DNA at sites of RNA polymerase II stalling by interaction with Spt5.

    Science.gov (United States)

    Pavri, Rushad; Gazumyan, Anna; Jankovic, Mila; Di Virgilio, Michela; Klein, Isaac; Ansarah-Sobrinho, Camilo; Resch, Wolfgang; Yamane, Arito; Reina San-Martin, Bernardo; Barreto, Vasco; Nieland, Thomas J; Root, David E; Casellas, Rafael; Nussenzweig, Michel C

    2010-10-01

    Activation-induced cytidine deaminase (AID) initiates antibody gene diversification by creating U:G mismatches. However, AID is not specific for antibody genes; Off-target lesions can activate oncogenes or cause chromosome translocations. Despite its importance in these transactions little is known about how AID finds its targets. We performed an shRNA screen to identify factors required for class switch recombination (CSR) of antibody loci. We found that Spt5, a factor associated with stalled RNA polymerase II (Pol II) and single stranded DNA (ssDNA), is required for CSR. Spt5 interacts with AID, it facilitates association between AID and Pol II, and AID recruitment to its Ig and non-Ig targets. ChIP-seq experiments reveal that Spt5 colocalizes with AID and stalled Pol II. Further, Spt5 accumulation at sites of Pol II stalling is predictive of AID-induced mutation. We propose that AID is targeted to sites of Pol II stalling in part via its association with Spt5. PMID:20887897

  12. SU-C-303-01: Activation-Induced Cytidine Deaminase Confers Cancer Resistance to Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To study the role of activation-induced cytidine deaminase (AID) in malignant cell resistance to radiation therapy. Methods: We first developed several small devices that could be used to adopt radiation beams from clinical high dose rate brachy therapy (HDR) or linac-based megavoltage machines to perform pre-clinical cell and mouse experiments. Then we used these devices to deliver radiation to AID-positive and AID-silenced cancer cells or tumors formed by these cells in mice. Cells and mice bearing tumors received the same dose under the same experimental conditions. For cells, we observed the apoptosis and the cell survival rate over time. For mice bearing tumors, we measured and recorded the tumor sizes every other day for 4 weeks. Results: For cell experiments, we found that the AID-positive cells underwent much less apoptosis compared with AID-silenced cells upon radiation. And for mouse experiments, we found that AID-positive tumors grew significantly faster than the AID-silenced tumors despite of receiving the same doses of radiation. Conclusion: Our study suggests that AID may confer cancer resistance to radiation therapy, and AID may be a significant biomarker predicting cancer resistance to radiation therapy for certain cancer types

  13. Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    De-Hua Wu; Li Liu; Long-Hua Chen

    2005-01-01

    AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells.METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (Tk) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fiuorocytosine (5FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay.RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystandereffect were markedly superior to a single prodrug (x2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.

  14. SU-C-303-01: Activation-Induced Cytidine Deaminase Confers Cancer Resistance to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yi, S [Sun Yat-Sen University, Guangzhou, Guangdong (China); La Count, S [Wittenberg University, Springfield, OH (United States); Liu, J; Bai, X; Lu, L [The Ohio State University, Columbus, OH (United States)

    2015-06-15

    Purpose: To study the role of activation-induced cytidine deaminase (AID) in malignant cell resistance to radiation therapy. Methods: We first developed several small devices that could be used to adopt radiation beams from clinical high dose rate brachy therapy (HDR) or linac-based megavoltage machines to perform pre-clinical cell and mouse experiments. Then we used these devices to deliver radiation to AID-positive and AID-silenced cancer cells or tumors formed by these cells in mice. Cells and mice bearing tumors received the same dose under the same experimental conditions. For cells, we observed the apoptosis and the cell survival rate over time. For mice bearing tumors, we measured and recorded the tumor sizes every other day for 4 weeks. Results: For cell experiments, we found that the AID-positive cells underwent much less apoptosis compared with AID-silenced cells upon radiation. And for mouse experiments, we found that AID-positive tumors grew significantly faster than the AID-silenced tumors despite of receiving the same doses of radiation. Conclusion: Our study suggests that AID may confer cancer resistance to radiation therapy, and AID may be a significant biomarker predicting cancer resistance to radiation therapy for certain cancer types.

  15. Isolation, characterization and colonization of 1-aminocyclopropane-1-carboxylate deaminase-producing bacteria XG32 and DP24.

    Science.gov (United States)

    Wang, Mei-Xia; Liu, Jia; Chen, Shuang-Lin; Yan, Shu-Zhen

    2012-03-01

    Two 1-aminocyclopropane-1-carboxylate deaminase-producing bacterial strains (DP24 and XG32) were isolated from surface-sterilized tomato roots and rizhospere soil. The strains were identified as Pseudomonas fluorescens biovar. IV (XG2) and Erwinia herbicola (DP24) by physiological and biochemical tests, and 16S rRNA gene analysis. Both strains showed positive plant growth-promoting activity when inoculated into cucumber (Cucumis sativus), tomato (Lycopersicon esculentum), pepper (Capsicum annuum) and rapeseed (Brassica napus L.). Colonization ability and behavior of these two strains were determined by treating mutant strains with rifampicin and fluorescence in situ hybridization (FISH) assay with rRNA targeted probes, respectively. Both strains were endophytic colonizers of pepper plants. The behavior of the two strains was not identical. Strain XG32 only colonized the root and reached the max level of 27.7 × 10(7) c.f.u./g (fresh weight), after 12 days postinoculation, while strain DP24 was able to colonize the roots, stems and leaves. The max level was reached at 40.87 × 10(7) c.f.u./g (fresh weight) in the roots, 17 × 10(7) c.f.u./g in the stems after 7 days postinoculation and 44.84 × 10(7) c.f.u./g in the leaves after 12 days postinoculation. PMID:22805836

  16. Haploinsufficiency of activation-induced deaminase for antibody diversification and chromosome translocations both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Isora V Sernández

    Full Text Available The humoral immune response critically relies on the secondary diversification of antibodies. This diversification takes places through somatic remodelling of the antibody genes by two molecular mechanisms, Class Switch Recombination (CSR and Somatic Hypermutation (SHM. The enzyme Activation Induced Cytidine Deaminase (AID initiates both SHM and CSR by deaminating cytosine residues on the DNA of immunoglobulin genes. While crucial for immunity, AID-catalysed deamination is also the triggering event for the generation of lymphomagenic chromosome translocations. To address whether restricting the levels of AID expression in vivo contributes to the regulation of its function, we analysed mice harbouring a single copy of the AID gene (AID(+/-. AID(+/- mice express roughly 50% of normal AID levels, and display a mild hyperplasia, reminiscent of AID deficient mice and humans. Moreover, we found that AID(+/- cells have an impaired competence for CSR and SHM, which indicates that AID gene dose is limiting for its physiologic function. We next evaluated the impact of AID reduction in AID(+/- mice on the generation of chromosome translocations. Our results show that the frequency of AID-promoted c-myc/IgH translocations is reduced in AID(+/- mice, both in vivo and in vitro. Therefore, AID is haploinsufficient for antibody diversification and chromosome translocations. These findings suggest that limiting the physiologic levels of AID expression can be a regulatory mechanism that ensures an optimal balance between immune proficiency and genome integrity.

  17. ATM increases activation-induced cytidine deaminase activity at downstream S regions during class-switch recombination.

    Science.gov (United States)

    Khair, Lyne; Guikema, Jeroen E J; Linehan, Erin K; Ucher, Anna J; Leus, Niek G J; Ogilvie, Colin; Lou, Zhenkun; Schrader, Carol E; Stavnezer, Janet

    2014-05-15

    Activation-induced cytidine deaminase (AID) initiates Ab class-switch recombination (CSR) in activated B cells resulting in exchanging the IgH C region and improved Ab effector function. During CSR, AID instigates DNA double-strand break (DSB) formation in switch (S) regions located upstream of C region genes. DSBs are necessary for CSR, but improper regulation of DSBs can lead to chromosomal translocations that can result in B cell lymphoma. The protein kinase ataxia telangiectasia mutated (ATM) is an important proximal regulator of the DNA damage response (DDR), and translocations involving S regions are increased in its absence. ATM phosphorylates H2AX, which recruits other DNA damage response (DDR) proteins, including mediator of DNA damage checkpoint 1 (Mdc1) and p53 binding protein 1 (53BP1), to sites of DNA damage. As these DDR proteins all function to promote repair and recombination of DSBs during CSR, we examined whether mouse splenic B cells deficient in these proteins would show alterations in S region DSBs when undergoing CSR. We find that in atm(-/-) cells Sμ DSBs are increased, whereas DSBs in downstream Sγ regions are decreased. We also find that mutations in the unrearranged Sγ3 segment are reduced in atm(-/-) cells. Our data suggest that ATM increases AID targeting and activity at downstream acceptor S regions during CSR and that in atm(-/-) cells Sμ DSBs accumulate as they lack a recombination partner. PMID:24729610

  18. 基于AdaBoost算法的人脸人眼分类器的设计与实现%Design and Implementation of Face and Eye Categorizer Based on AdaBoost Algorithm

    Institute of Scientific and Technical Information of China (English)

    汪仕才; 冯桑; 呙腾

    2015-01-01

    人脸检测和人眼定位是检测驾驶疲劳的首要工作,而人眼准确定位和检测速度直接影响后续疲劳检测的实时性和鲁棒性。基于AdaBoost算法检测速度快,泛化能力强等特点,通过建立针对驾驶环境下的人脸、人眼样本集,深入研究驾驶员的人脸人眼识别问题。实验证明,AdaBoost级联分类器不仅能够准确检测人的正脸,而且对于侧脸、戴眼睛和部分遮挡也有很高的识别率。%Face detection and eyes orientation are the primary task of detecting driver fatigue, and the real-time and robustness of the following fa-tigue detection is directly influenced by the accurate orientation of human eyes and the speed of detection. Studies the recognition prob-lem of driver's face and eyes further through establishing the sample database of face and eye under the driving environment, which is based on the features of fast detection speed and strong generalization ability of AdaBoost algorithm. Experimental results show that the AdaBoost cascade classifier can not only accurately detect frontal faces, but also have very high recognition rate for a face in profile or with glasses and the partially occluded face.

  19. Adenosine enhances sweet taste through A2B receptors in the taste bud.

    Science.gov (United States)

    Dando, Robin; Dvoryanchikov, Gennady; Pereira, Elizabeth; Chaudhari, Nirupa; Roper, Stephen D

    2012-01-01

    Mammalian taste buds use ATP as a neurotransmitter. Taste Receptor (type II) cells secrete ATP via gap junction hemichannels into the narrow extracellular spaces within a taste bud. This ATP excites primary sensory afferent fibers and also stimulates neighboring taste bud cells. Here we show that extracellular ATP is enzymatically degraded to adenosine within mouse vallate taste buds and that this nucleoside acts as an autocrine neuromodulator to selectively enhance sweet taste. In Receptor cells in a lingual slice preparation, Ca(2+) mobilization evoked by focally applied artificial sweeteners was significantly enhanced by adenosine (50 μM). Adenosine had no effect on bitter or umami taste responses, and the nucleoside did not affect Presynaptic (type III) taste cells. We also used biosensor cells to measure transmitter release from isolated taste buds. Adenosine (5 μM) enhanced ATP release evoked by sweet but not bitter taste stimuli. Using single-cell reverse transcriptase (RT)-PCR on isolated vallate taste cells, we show that many Receptor cells express the adenosine receptor, Adora2b, while Presynaptic (type III) and Glial-like (type I) cells seldom do. Furthermore, Adora2b receptors are significantly associated with expression of the sweet taste receptor subunit, Tas1r2. Adenosine is generated during taste stimulation mainly by the action of the ecto-5'-nucleotidase, NT5E, and to a lesser extent, prostatic acid phosphatase. Both these ecto-nucleotidases are expressed by Presynaptic cells, as shown by single-cell RT-PCR, enzyme histochemistry, and immunofluorescence. Our findings suggest that ATP released during taste reception is degraded to adenosine to exert positive modulation particularly on sweet taste.

  20. Three minute versus six minute adenosine infusion in myocardial perfusion scintigraphy

    International Nuclear Information System (INIS)

    Pharmacological stress imaging techniques are used widely in clinical nuclear cardiology for evaluation of ischemic heart disease. Adenosine is often used but is expensive and causes significant side effects .The aim of this retrospective review was to study the tolerance and efficacy, of adenosine infusion of a 3 minute (min) versus the conventional 6 min stress protocol and to assess the cost efficiency of the 3 min protocol. Three hundred thirty one patients had myocardial scintigraphy using adenosine as a stressing agent. Blood pressure, heart rate and ECG were recorded at baseline and during the test. Symptoms (flushing, headache, chest pain, dyspnoea, neck pain) were recorded throughout the adenosine infusion. All the patients had had either 6 min or 3 min adenosine infusion at 140 mg/kg per minute. 169 of them had side effects. Flushing (32% at 3 min vs 50 % at 6 min, p<0.05), headache (11.5% at 3 min vs 7 % at 6 min p-not significant-ns), chest pain (8% at 3 min vs 13 % at 6 min, ns), dyspnoea (7% at 3 min vs %10 at 6 min, ns), ECG changes (10% at 3 min vs 28% at 6 min, p<0.05), neck pain (4.5% at 3 min vs 9% at 6 min, ns), abdominal discomfort (3% at 3 min vs 3% at 6 min, ns) and fall in blood pressure (6% at 3 min vs 8.5% at 6 min, ns). The change in heart rate was not significant with either protocol. The 6 min and 3 min infusions of adenosine had similar accuracy (73% vs 70%) for the detection of coronary artery disease. The patients tolerated the 3 min protocol better with only 40% of the patients having minimal side effects compared with 60% for the 6 mon protocol. The 3 min protocol is also cost effective as it uses less adenosine and therefore reduces total costs by 40 US$ per patient. (author)

  1. Fusion of optimized indicators from Advanced Driver Assistance Systems (ADAS) for driver drowsiness detection.

    Science.gov (United States)

    Daza, Iván García; Bergasa, Luis Miguel; Bronte, Sebastián; Yebes, Jose Javier; Almazán, Javier; Arroyo, Roberto

    2014-01-09

    This paper presents a non-intrusive approach for monitoring driver drowsiness using the fusion of several optimized indicators based on driver physical and driving performance measures, obtained from ADAS (Advanced Driver Assistant Systems) in simulated conditions. The paper is focused on real-time drowsiness detection technology rather than on long-term sleep/awake regulation prediction technology. We have developed our own vision system in order to obtain robust and optimized driver indicators able to be used in simulators and future real environments. These indicators are principally based on driver physical and driving performance skills. The fusion of several indicators, proposed in the literature, is evaluated using a neural network and a stochastic optimization method to obtain the best combination. We propose a new method for ground-truth generation based on a supervised Karolinska Sleepiness Scale (KSS). An extensive evaluation of indicators, derived from trials over a third generation simulator with several test subjects during different driving sessions, was performed. The main conclusions about the performance of single indicators and the best combinations of them are included, as well as the future works derived from this study.

  2. Fusion of Optimized Indicators from Advanced Driver Assistance Systems (ADAS for Driver Drowsiness Detection

    Directory of Open Access Journals (Sweden)

    Iván G. Daza

    2014-01-01

    Full Text Available This paper presents a non-intrusive approach for monitoring driver drowsiness using the fusion of several optimized indicators based on driver physical and driving performance measures, obtained from ADAS (Advanced Driver Assistant Systems in simulated conditions. The paper is focused on real-time drowsiness detection technology rather than on long-term sleep/awake regulation prediction technology. We have developed our own vision system in order to obtain robust and optimized driver indicators able to be used in simulators and future real environments. These indicators are principally based on driver physical and driving performance skills. The fusion of several indicators, proposed in the literature, is evaluated using a neural network and a stochastic optimization method to obtain the best combination. We propose a new method for ground-truth generation based on a supervised Karolinska Sleepiness Scale (KSS. An extensive evaluation of indicators, derived from trials over a third generation simulator with several test subjects during different driving sessions, was performed. The main conclusions about the performance of single indicators and the best combinations of them are included, as well as the future works derived from this study.

  3. BASIC CRITERIA OF IRANIAN COMMERCIAL TOOTHPASTES AND AN ADA APPROVED BRAND (CREST

    Directory of Open Access Journals (Sweden)

    N NOUR BAKHSH

    2003-03-01

    Full Text Available Introduction: The effectiveness of fluorided toothpastes in reducing dental caries is well-documented, However not all fluorided toothpastes are equally effective. The objective of this study was to compare some essential criteria of six different toothpastes manufactured in Iran with one brand of ADA approved toothpaste (Crest. Methods. Six commercial toothpastes produced in Iran named as Paveh, Puneh, Nasim, Darugar, golpasand and saviz were compared with Crest in three subjects as follows: 1. Amount of fluoride concentration 2. Amount of releasing fluoride 3. Cleaning efficiency. Two first criteria were tested using the potentiometric method with F- Ion specific electrode, and Cleaning efficiency was done by O'Leary index on 60 volunteers (10 for each toothpaste. Results: Fluoride Concentration in Paveh, Puneh, Nasim toothpastes were nearly700PPM,while in three others were much lower. The highest amount of fluoride was seen in Crest (1450 PPM. Cleaning efficiency of Darugar was better than Crest, Paveh, Puneh. Cleaning efficiency of Nasim was the same as Crest and Golpasand and Saviz were weaker than Crest. Discussion: Since at the present time, the most effective, Cost-benefit method for preventive aspects of fluoride, especially in developing countries is obtained by fluoride toothpastes. Manufactures should improve quality of fluoride toothpastes, ensure that all pates maximize Fluoride bioavailability, develop active agents to help better cleaning efficiency and label products clearly with containig fluoride in PPM.

  4. Software architecture for a distributed real-time system in Ada, with application to telerobotics

    Science.gov (United States)

    Olsen, Douglas R.; Messiora, Steve; Leake, Stephen

    1992-01-01

    The architecture structure and software design methodology presented is described in the context of telerobotic application in Ada, specifically the Engineering Test Bed (ETB), which was developed to support the Flight Telerobotic Servicer (FTS) Program at GSFC. However, the nature of the architecture is such that it has applications to any multiprocessor distributed real-time system. The ETB architecture, which is a derivation of the NASA/NBS Standard Reference Model (NASREM), defines a hierarchy for representing a telerobot system. Within this hierarchy, a module is a logical entity consisting of the software associated with a set of related hardware components in the robot system. A module is comprised of submodules, which are cyclically executing processes that each perform a specific set of functions. The submodules in a module can run on separate processors. The submodules in the system communicate via command/status (C/S) interface channels, which are used to send commands down and relay status back up the system hierarchy. Submodules also communicate via setpoint data links, which are used to transfer control data from one submodule to another. A submodule invokes submodule algorithms (SMA's) to perform algorithmic operations. Data that describe or models a physical component of the system are stored as objects in the World Model (WM). The WM is a system-wide distributed database that is accessible to submodules in all modules of the system for creating, reading, and writing objects.

  5. Improvement of AdaBoost Face Detection Algorithm Based on Skin Color Detection%基于肤色检测的AdaBoost人脸检测算法改进

    Institute of Scientific and Technical Information of China (English)

    李明瑞; 傅明; 曹敦

    2012-01-01

    AdaBoost人脸检测算法用于嵌入式实时高清视频时检测速度缓慢.为此,提出一种改进的人脸检测算法.对图像做肤色检测,将检测到的区域进行形态学处理,并作为感兴趣区域,完成AdaBoost人脸检测,以得到检测结果.实验结果表明,该算法在嵌入式系统上运行稳定,能提高检测速度和检测正确率.%An improved face detection algorithm is proposed to solve the problem of slow speed in real-time HD video face detection. This paper does face detection on high color image, gets the morphology processing detection results, sets the Region of Interest(ROI), and does AdaBoost face detection on ROI to get the result. Experimental results show that the algorithm can steadily operate on embedded systems, and improve the detection accuracy and the detection speed.

  6. Rapid tolerance against focal cerebral ischemia induced by isoflurane anesthesia is attenuated by adenosine A1 receptor antagonist in rats

    Institute of Scientific and Technical Information of China (English)

    刘艳红; 熊利泽

    2003-01-01

    The brief anesthesia with isoflurane induces rapid tolerance against focal cerebral ischemia in rats and adenosine A1 receptor antagonist, DPCPX, attenuates the beneficial effect of isoflurane preconditioning.

  7. Disturbance of Antioxidant Enzymes and Purine Metabolism in the Ejaculate of Men Living in Disadvantaged Areas of Kyzylorda Region

    Directory of Open Access Journals (Sweden)

    Valentihna N. Kislitskaya

    2015-07-01

    CONCLUSIONS: According to the results of study, it was put the influence  of negative factors of the Aral Sea region in men’s sperm of reproductive  age gives to disability free-radical processes, that proves changing of ferments of ant oxidative protection Catalase and adenosine deaminase (ADA.  This disturbance in men’s sperm of reproductive age leading to increased level of oxidative stress and impaired activity of  antioxidant enzymes and purine metabolism, responsible for the abnormal transmembrane and intracellular processes, reflecting the degree of imbalance of enzymes.

  8. Adenosine triphosphate inhibits melatonin synthesis in the rat pineal gland.

    Science.gov (United States)

    Souza-Teodoro, Luis Henrique; Dargenio-Garcia, Letícia; Petrilli-Lapa, Camila Lopes; Souza, Ewerton da Silva; Fernandes, Pedro A C M; Markus, Regina P; Ferreira, Zulma S

    2016-03-01

    Adenosine triphosphate (ATP) is released onto the pinealocyte, along with noradrenaline, from sympathetic neurons and triggers P2Y1 receptors that enhance β-adrenergic-induced N-acetylserotonin (NAS) synthesis. Nevertheless, the biotransformation of NAS into melatonin, which occurs due to the subsequent methylation by acetylserotonin O-methyltransferase (ASMT; EC 2.1.1.4), has not yet been evaluated in the presence of purinergic stimulation. We therefore evaluated the effects of purinergic signaling on melatonin synthesis induced by β-adrenergic stimulation. ATP increased NAS levels, but, surprisingly, inhibited melatonin synthesis in an inverse, concentration-dependent manner. Our results demonstrate that enhanced NAS levels, which depend on phospholipase C (PLC) activity (but not the induction of gene transcription), are a post-translational effect. By contrast, melatonin reduction is related to an ASMT inhibition of expression at both the gene transcription and protein levels. These results were independent of nuclear factor-kappa B (NF-kB) translocation. Neither the P2Y1 receptor activation nor the PLC-mediated pathway was involved in the decrease in melatonin, indicating that ATP regulates pineal metabolism through different mechanisms. Taken together, our data demonstrate that purinergic signaling differentially modulates NAS and melatonin synthesis and point to a regulatory role for ATP as a cotransmitter in the control of ASMT, the rate-limiting enzyme in melatonin synthesis. The endogenous production of melatonin regulates defense responses; therefore, understanding the mechanisms involving ASMT regulation might provide novel insights into the development and progression of neurological disorders since melatonin presents anti-inflammatory, neuroprotective, and neurogenic effects. PMID:26732366

  9. Behavior and stability of adenosine triphosphate (ATP) during chlorine disinfection.

    Science.gov (United States)

    Nescerecka, Alina; Juhna, Talis; Hammes, Frederik

    2016-09-15

    Adenosine triphosphate (ATP) analysis is a cultivation-independent alternative method for the determination of bacterial viability in both chlorinated and non-chlorinated water. Here we investigated the behavior and stability of ATP during chlorination in detail. Different sodium hypochlorite doses (0-22.4 mg-Cl2 L(-1); 5 min exposure) were applied to an Escherichia coli pure culture suspended in filtered river water. We observed decreasing intracellular ATP with increasing chlorine concentrations, but extracellular ATP concentrations only increased when the chlorine dose exceeded 0.35 mg L(-1). The release of ATP from chlorine-damaged bacteria coincided with severe membrane damage detected with flow cytometry (FCM). The stability of extracellular ATP was subsequently studied in different water matrixes, and we found that extracellular ATP was stable in sterile deionized water and also in chlorinated water until extremely high chlorine doses (≤11.2 mg-Cl2 L(-1); 5 min exposure). In contrast, ATP decreased relatively slowly (k = 0.145 h(-1)) in 0.1 μm filtered river water, presumably due to degradation by either extracellular enzymes or the fraction of bacteria that were able to pass through the filter. Extracellular ATP decreased considerably faster (k = 0.368 h(-1)) during batch growth of a river water bacterial community. A series of growth potential tests showed that extracellular ATP molecules were utilized as a phosphorus source during bacteria proliferation. From the combined data we conclude that ATP released from bacteria at high chlorine doses could promote bacteria regrowth, contributing to biological instability in drinking water distribution systems. PMID:27295623

  10. Behavior and stability of adenosine triphosphate (ATP) during chlorine disinfection.

    Science.gov (United States)

    Nescerecka, Alina; Juhna, Talis; Hammes, Frederik

    2016-09-15

    Adenosine triphosphate (ATP) analysis is a cultivation-independent alternative method for the determination of bacterial viability in both chlorinated and non-chlorinated water. Here we investigated the behavior and stability of ATP during chlorination in detail. Different sodium hypochlorite doses (0-22.4 mg-Cl2 L(-1); 5 min exposure) were applied to an Escherichia coli pure culture suspended in filtered river water. We observed decreasing intracellular ATP with increasing chlorine concentrations, but extracellular ATP concentrations only increased when the chlorine dose exceeded 0.35 mg L(-1). The release of ATP from chlorine-damaged bacteria coincided with severe membrane damage detected with flow cytometry (FCM). The stability of extracellular ATP was subsequently studied in different water matrixes, and we found that extracellular ATP was stable in sterile deionized water and also in chlorinated water until extremely high chlorine doses (≤11.2 mg-Cl2 L(-1); 5 min exposure). In contrast, ATP decreased relatively slowly (k = 0.145 h(-1)) in 0.1 μm filtered river water, presumably due to degradation by either extracellular enzymes or the fraction of bacteria that were able to pass through the filter. Extracellular ATP decreased considerably faster (k = 0.368 h(-1)) during batch growth of a river water bacterial community. A series of growth potential tests showed that extracellular ATP molecules were utilized as a phosphorus source during bacteria proliferation. From the combined data we conclude that ATP released from bacteria at high chlorine doses could promote bacteria regrowth, contributing to biological instability in drinking water distribution systems.

  11. Aquifer Recharge Estimation through Atmospheric Chloride Mass Balance at Las Cañadas Caldera, Tenerife, Canary Islands, Spain

    OpenAIRE

    Rayco Marrero-Diaz; Alcalá, Francisco J.; Nemesio M. Pérez; Dina L. López; Gladys V. Melián; Eleazar Padrón; Germán D. Padilla

    2015-01-01

    The atmospheric chloride mass balance (CMB) method was used to estimate net aquifer recharge in Las Cañadas Caldera, an endorheic summit aquifer area about 2000 m a.s.l. with negligible surface runoff, which hosts the largest freshwater reserve in Tenerife Island, Canary Islands, Spain. The wet hydrological year 2005–2006 was selected to compare yearly atmospheric chloride bulk deposition and average chloride content in recharge water just above the water table, both deduced from periodical...

  12. 改进的AdaBoost检测算法在身份识别中的应用%Improved AdaBoost Detection Algorithm and Application in Identity Authentication

    Institute of Scientific and Technical Information of China (English)

    黄志威

    2015-01-01

    传统的AdaBoost人脸检测算法训练时间长对设备要求高,在复杂背景下存在漏检误检.提出一种基于小波重构和特征提取的AdaBoost人脸检测算法,并应用到身份验证中.采用小波重构方法,实现对人脸信息有用特征的重构,进行去噪处理提高人脸识别的准确性.采用人脸特征关联性方法将不同的人脸特征子集进行分类处理,采用特征提取算法实现对AdaBoost算法的改进.仿真结果表明,采用改进的人脸检测算法进行身份验证,能检测到一定范围内的非正脸图像特征,有效提取人脸的局部信息特征点,提高身份验证对象的检测精度和正确识别率.%The traditional face detection algorithm needs much training time, and has high requirements for equipment,and there are false detection in complex background. An AdaBoost face detection algorithm is proposed based on wavelet recon-struction and feature extraction, and it is applied in identity verification. By using the wavelet reconstruction method, the re-construction of useful face information features is obtained, denoising processing is used to improve the accuracy of face recognition. The facial feature relevance method is used, and the different features of face are classified in different sets. The feature extraction algorithm is used to improve the AdaBoost face detection algorithm. Simulation results show that,the new method can detect the non frontal face image features within a certain range, and the detection precision and accurate recognition rate are improved.

  13. Using vertical electrical soundings for characterizing hydrogeological and tectonic settings in Deir El-Adas area, Yarmouk Basin, Syria

    Science.gov (United States)

    Al-Fares, Walid

    2016-06-01

    The present study is aimed at characterizing the subsurface geological and tectonic structure in Deir El-Adas area, by using Vertical Electrical Sounding survey (VES) and hydrogeological investigations, in order to determine the causes of the failure for the majority of the wells drilled in the area. The survey data was treated in three different approaches including direct VES inversion, pseudo-2D method and horizontal profiling, in order to maximize the reliability of the data interpretation. The results revealed the presence of a local faulted anticline structure at the top of the Paleogene formation, underneath the basaltic outcrops where Deir El-Adas village is situated. The appearance of this subsurface anticline structure has complicated the local hydrogeological situation, and most likely led to limitation of the groundwater recharge in the area. Moreover, the performed piezometric and discharge maps indicated the presence of a notable groundwater watershed, in addition to feeble water productivity of the wells drilled adjacent to Deir El-Adas, mostly related to the subsurface geological and tectonic settings in the area.

  14. Biochemistry of an olfactory purinergic system: dephosphorylation of excitatory nucleotides and uptake of adenosine

    Energy Technology Data Exchange (ETDEWEB)

    Trapido-Rosenthal, H.G.; Carr, W.E.; Gleeson, R.A.

    1987-10-01

    The olfactory organ of the spiny lobster, Panulirus argus, is composed of chemosensory sensilla containing the dendrites of primary chemosensory neurons. Receptors on these dendrites are activated by the nucleotides AMP, ADP, and ATP but not by the nucleoside adenosine. It is shown here that the lobster chemosensory sensilla contain enzymes that dephosphorylate excitatory nucleotides and an uptake system that internalizes the nonexcitatory dephosphorylated product adenosine. The uptake of (/sup 3/H)-adenosine is saturable with increasing concentration, linear with time for up to 3 h, sodium dependent, insensitive to moderate pH changes and has a Km of 7.1 microM and a Vmax of 5.2 fmol/sensillum/min (573 fmol/micrograms of protein/min). Double-label experiments show that sensilla dephosphorylate nucleotides extracellularly; /sup 3/H from adenine-labeled AMP or ATP is internalized, whereas 32P from phosphate-labeled nucleotides is not. The dephosphorylation of AMP is very rapid; /sup 3/H from AMP is internalized at the same rate as /sup 3/H from adenosine. Sensillar 5'-ectonucleotidase activity is inhibited by ADP and the ADP analog alpha, beta-methylene ADP. Collectively, these results indicate that the enzymes and the uptake system whereby chemosensory sensilla of the lobster inactivate excitatory nucleotides and clear adenosine from extracellular spaces are very similar to those present in the internal tissues of vertebrates, where nucleotides have many neuroactive effects.

  15. Comparative transcriptome analysis of Bacillus subtilis responding to dissolved oxygen in adenosine fermentation.

    Directory of Open Access Journals (Sweden)

    Wen-Bang Yu

    Full Text Available Dissolved oxygen (DO is an important factor for adenosine fermentation. Our previous experiments have shown that low oxygen supply in the growth period was optimal for high adenosine yield. Herein, to better understand the link between oxygen supply and adenosine productivity in B. subtilis (ATCC21616, we sought to systematically explore the effect of DO on genetic regulation and metabolism through transcriptome analysis. The microarrays representing 4,106 genes were used to study temporal transcript profiles of B. subtilis fermentation in response to high oxygen supply (agitation 700 r/min and low oxygen supply (agitation 450 r/min. The transcriptome data analysis revealed that low oxygen supply has three major effects on metabolism: enhance carbon metabolism (glucose metabolism, pyruvate metabolism and carbon overflow, inhibit degradation of nitrogen sources (glutamate family amino acids and xanthine and purine synthesis. Inhibition of xanthine degradation was the reason that low oxygen supply enhanced adenosine production. These provide us with potential targets, which can be modified to achieve higher adenosine yield. Expression of genes involved in energy, cell type differentiation, protein synthesis was also influenced by oxygen supply. These results provided new insights into the relationship between oxygen supply and metabolism.

  16. Aberrant bone density in aging mice lacking the adenosine transporter ENT1.

    Directory of Open Access Journals (Sweden)

    David J Hinton

    Full Text Available Adenosine is known to regulate bone production and resorption in humans and mice. Type 1 equilibrative nucleoside transporter (ENT1 is responsible for the majority of adenosine transport across the plasma membrane and is ubiquitously expressed in both humans and mice. However, the contribution of ENT1-mediated adenosine levels has not been studied in bone remodeling. With the recent identification of the importance of adenosine signaling in bone homeostasis, it is essential to understand the role of ENT1 to develop novel therapeutic compounds for bone disorders. Here we examined the effect of ENT1 deletion on bone density using X-ray, dual energy X-ray absorptiometry and micro-computerized tomography analysis. Our results show that bone density and bone mineral density is reduced in the lower thoracic and lumbar spine as well as the femur of old ENT1 null mice (>7 months compared to wild-type littermates. Furthermore, we found increased mRNA expression of tartrate-resistant acid phosphatase (TRAP, an osteoclast marker, in isolated long bones from 10 month old ENT1 null mice compared to wild-type mice. In addition, aged ENT1 null mice displayed severe deficit in motor coordination and locomotor activity, which might be attributed to dysregulated bone density. Overall, our study suggests that ENT1-regulated adenosine signaling plays an essential role in lumbar spine and femur bone density.

  17. Parallel Ada implementation of a multiple-model Kalman-filter tracking system: a software engineering approach. Master's thesis

    Energy Technology Data Exchange (ETDEWEB)

    Lemanski, W.J.

    1989-03-01

    The success of the Strategic Defense Initiative depends directly on significant advances in both computer hardware and software development technologies. Parallel architectures and the Ada programming language have advantages that make them candidates for use in SDI command and control computer systems. This thesis examines those advantages in the context of an SDI-type application: implementation of a Kalman-filter tracking system. This research consists of three parts. The first is a set of software engineering guidelines developed for use in creating parallel designs suitable for implementation in Ada. These guidelines cover the design process from initial problem analysis to final detailed design. Methods of problem decomposition are discussed, as are language partitioning strategies. Justification is provided for using the Ada task construct for process boundaries, and Ada multitasking design issues are reviewed. A parallel software design methodology is also described.

  18. The adenosine A2B receptor is involved in anion secretion in human pancreatic duct Capan-1 epithelial cells.

    Science.gov (United States)

    Hayashi, M; Inagaki, A; Novak, I; Matsuda, H

    2016-07-01

    Adenosine modulates a wide variety of biological processes via adenosine receptors. In the exocrine pancreas, adenosine regulates transepithelial anion secretion in duct cells and is considered to play a role in acini-to-duct signaling. To identify the functional adenosine receptors and Cl(-) channels important for anion secretion, we herein performed experiments on Capan-1, a human pancreatic duct cell line, using open-circuit Ussing chamber and gramicidin-perforated patch-clamp techniques. The luminal addition of adenosine increased the negative transepithelial potential difference (V te) in Capan-1 monolayers with a half-maximal effective concentration value of approximately 10 μM, which corresponded to the value obtained on whole-cell Cl(-) currents in Capan-1 single cells. The effects of adenosine on V te, an equivalent short-circuit current (I sc), and whole-cell Cl(-) currents were inhibited by CFTRinh-172, a cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel inhibitor. The adenosine A2B receptor agonist, BAY 60-6583, increased I sc and whole-cell Cl(-) currents through CFTR Cl(-) channels, whereas the A2A receptor agonist, CGS 21680, had negligible effects. The A2B receptor antagonist, PSB 603, inhibited the response of I sc to adenosine. Immunohistochemical analysis showed that the A2A and A2B receptors colocalized with Ezrin in the luminal membranes of Capan-1 monolayers and in rat pancreatic ducts. Adenosine elicited the whole-cell Cl(-) currents in guinea pig duct cells. These results demonstrate that luminal adenosine regulates anion secretion by activating CFTR Cl(-) channels via adenosine A2B receptors on the luminal membranes of Capan-1 cells. The present study endorses that purinergic signaling is important in the regulation of pancreatic secretion. PMID:26965147

  19. InterProScan Result: CK494396 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available CK494396 CK494396_3_ORF1 69F05FB2EA4E0E07 PANTHER PTHR11409 ADENOSINE DEAMINASE 6.6...e-31 T IPR001365 Adenosine/AMP deaminase Biological Process: purine ribonucleoside monophosphate biosynthetic process (GO:0009168)|Molecular Function: deaminase activity (GO:0019239) ...

  20. InterProScan Result: CK494396 [KAIKOcDNA[Archive

    Lifescience Database Archive (English)

    Full Text Available CK494396 CK494396_3_ORF2 4F3F8EE1C8E79DF6 PANTHER PTHR11409 ADENOSINE DEAMINASE 2.6...e-28 T IPR001365 Adenosine/AMP deaminase Biological Process: purine ribonucleoside monophosphate biosynthetic process (GO:0009168)|Molecular Function: deaminase activity (GO:0019239) ...