Sample records for systemic exposureto interferon-alpha

  1. Molecular stress response in the CNS of mice after systemic exposureto interferon-alpha, ionizing radiation and ketamine

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    Lowe, Xiu R.; Marchetti, Francesco; Lu, Xiaochen; Wyrobek, Andrew J.


    We previously showed that the expression of troponin T1 (Tnnt 1) was induced in the central nervous system (CNS) of adultmice 30 min after treatment with ketamine, a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist. We hypothesized that Tnnt 1 expression may be an early molecular biomarker of stress response in the CNS of mice. To further evaluate this hypothesis, we investigated the regional expression of Tnnt 1 in the mouse brain using RNA in situ hybridization 4 h after systemic exposure to interferon-a (IFN-a) and gamma ionizing radiation, both of which have be associated with wide ranges of neuropsychiatric complications. Adult B6C3F1 male mice were treated with either human IFN-a (a single i.p. injection at 1 x 105 IU/kg) or whole body gamma-radiation (10 cGy or 2 Gy). Patterns of Tnnt 1 transcript expression were compared in various CNS regions after IFN-a, radiation and ketamine treatments (previous study). Tnnt 1 expression was consistently induced in pyramidal neurons of cerebral cortex and hippocampus after all treatment regimens including 10 cGy of ionizing radiation. Regional expression of Tnnt 1 was induced in Purkinje cells of cerebellum after ionizing radiation and ketamine treatment; but not after IFN-a treatment. None of the three treatments induced Tnnt 1 expression in glial cells. The patterns of Tnnt 1 expression in pyramidal neurons of cerebral cortex andhippocampus, which are both known to play important roles in cognitive function, memory and emotion, suggest that the expression of Tnnt 1 may be an early molecular biomarker of induced CNS stress.

  2. Interferon Alpha in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Timothy B. Niewold


    Full Text Available The pleiotropic cytokine interferon alpha is involved in multiple aspects of lupus etiology and pathogenesis. Interferon alpha is important under normal circumstances for antiviral responses and immune activation. However, heightened levels of serum interferon alpha and expression of interferon response genes are common in lupus patients. Lupus-associated autoantibodies can drive the production of interferon alpha and heightened levels of interferon interfere with immune regulation. Several genes in the pathways leading to interferon production or signaling are associated with risk for lupus. Clinical and cellular manifestations of excess interferon alpha in lupus combined with the genetic risk factors associated with interferon make this cytokine a rare bridge between genetic risk and phenotypic effects. Interferon alpha influences the clinical picture of lupus and may represent a therapeutic target. This paper provides an overview of the cellular, genetic, and clinical aspects of interferon alpha in lupus.

  3. DMPD: The interferon-alpha/beta system in antiviral responses: a multimodal machineryof gene regulation by the IRF family of transcription factors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11790540 The interferon-alpha/beta system in antiviral responses: a multimodal mach...l. 2002 Feb;14(1):111-6. (.png) (.svg) (.html) (.csml) Show The interferon-alpha/beta system in antiviral responses: a multimoda...ion factors. PubmedID 11790540 Title The interferon-alpha/beta system in antiviral responses: a multimodal m

  4. Intrahepatic expression of interferon alpha & interferon alpha ...

    African Journals Online (AJOL)


    Alpha m-RNA while 30% only expressed Interferon Alpha Receptor m-RNA. Responders and non-responders to Interferon therapy ... expression of IFN Alpha Receptor mRNA. Regardless of the response to interferon, histological .... generation reverse hybridisation, line probe assay. (Inno-LiPA HCV II; Innogenetics, Ghent,.

  5. Genetic Analysis of the Pathogenic Molecular Sub-phenotype Interferon Alpha Identifies Multiple Novel Loci Involved in Systemic Lupus Erythematosus (United States)

    Kariuki, Silvia N.; Ghodke-Puranik, Yogita; Dorschner, Jessica M.; Chrabot, Beverly S.; Kelly, Jennifer A.; Tsao, Betty P.; Kimberly, Robert P.; Alarcón-Riquelme, Marta E.; Jacob, Chaim O.; Criswell, Lindsey A.; Sivils, Kathy L.; Langefeld, Carl D.; Harley, John B.; Skol, Andrew D.; Niewold, Timothy B.


    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of multiple organ systems and dysregulated interferon responses. SLE is both genetically and phenotypically heterogeneous, greatly reducing the power of case-control studies in SLE. Elevated circulating interferon alpha (IFN-α) is a stable, heritable trait in SLE, which has been implicated in primary disease pathogenesis. 40–50% of patients have high IFN-α, and high levels correspond with clinical differences. To study genetic heterogeneity in SLE, we performed a case-case study comparing patients with high vs. low IFN-α in over 1550 SLE cases, including GWAS and replication cohorts. In meta-analysis, the top associations in European ancestry were PRKG1 rs7897633 (PMeta=2.75 × 10−8) and PNP rs1049564 (PMeta=1.24 × 10−7). We also found evidence for cross-ancestral background associations with the ANKRD44 and PLEKHF2 loci. These loci have not been previously identified in case-control SLE genetic studies. Bioinformatic analyses implicated these loci functionally in dendritic cells and natural killer cells, both of which are involved in IFN-α production in SLE. As case-control studies of heterogeneous diseases reach a limit of feasibility with respect to subject number and detectable effect size, the study of informative pathogenic subphenotypes becomes an attractive strategy for genetic discovery in complex disease. PMID:25338677

  6. Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. (United States)

    Kariuki, S N; Ghodke-Puranik, Y; Dorschner, J M; Chrabot, B S; Kelly, J A; Tsao, B P; Kimberly, R P; Alarcón-Riquelme, M E; Jacob, C O; Criswell, L A; Sivils, K L; Langefeld, C D; Harley, J B; Skol, A D; Niewold, T B


    Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by inflammation of multiple organ systems and dysregulated interferon responses. SLE is both genetically and phenotypically heterogeneous, greatly reducing the power of case-control studies in SLE. Elevated circulating interferon-alpha (IFN-α) is a stable, heritable trait in SLE, which has been implicated in primary disease pathogenesis. About 40-50% of patients have high IFN-α, and high levels correspond with clinical differences. To study genetic heterogeneity in SLE, we performed a case-case study comparing patients with high vs low IFN-α in over 1550 SLE cases, including genome-wide association study and replication cohorts. In meta-analysis, the top associations in European ancestry were protein kinase, cyclic GMP-dependent, type I (PRKG1) rs7897633 (P(Meta) = 2.75 × 10(-8)) and purine nucleoside phosphorylase (PNP) rs1049564 (P(Meta) = 1.24 × 10(-7)). We also found evidence for cross-ancestral background associations with the ankyrin repeat domain 44 (ANKRD44) and pleckstrin homology domain containing, family F member 2 gene (PLEKHF2) loci. These loci have not been previously identified in case-control SLE genetic studies. Bioinformatic analyses implicated these loci functionally in dendritic cells and natural killer cells, both of which are involved in IFN-α production in SLE. As case-control studies of heterogeneous diseases reach a limit of feasibility with respect to subject number and detectable effect size, the study of informative pathogenic sub-phenotypes becomes an attractive strategy for genetic discovery in complex disease.

  7. Neuropsychiatric Complications Associated with Interferon - Alpha ...

    African Journals Online (AJOL)

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant ...

  8. Detection of Interferon Alpha Receptor 2 in Interferon Resistant HCV Patients. (United States)

    Trali, Gulshan A; Naveed, Abdul Khaliq; Rasheed, Amir; Bashir, Qudsia; Khan, Rao Saad Ali; Majeed, Asifa; Razak, Suhail


    Hepatitis C virus infects more than 3% of the world's population and 4% of Pakistan's population. The virus multiplies in the host using novel methods, defending itself from the host's immune response, ultimately leading to liver cirrhosis and hepatocellular carcinoma. The approved therapy for the disease is interferon alpha combined with ribavirin. The disease is incurable, and often resistant, due to multiple viral and cellular factors. However, a strong host system can minimize the viral count to zero. This study was designed to detect the functional interferon alpha receptor 2 in liver biopsies of interferon resistant hepatitis C virus patients. Total messenger ribonucleic acid was isolated from the liver biopsies of the interferon resistant hepatitis C virus patients and subjected to complementary deoxyribonucleic acid synthesis. Primers specific to interferon alpha receptor 2 were designed and used in polymerase chain reaction to detect interferon alpha receptor 2. Interferon alpha receptor 2 was detected in 90% of interferon resistant hepatitis C virus patients. Lack of expression of functional Interferon Alpha Receptor 2 does not seem to be the major cause of interferon resistance in hepatitis C virus patients receiving standard interferon therapy.

  9. Interferon alpha for chronic hepatitis D. (United States)

    Abbas, Zaigham; Khan, Muhammad Arsalan; Salih, Mohammad; Jafri, Wasim


    Hepatitis D virus is a small defective RNA virus that requires the presence of hepatitis B virus infection to infect a person. Hepatitis D is a difficult-to-treat infection. Several clinical trials have been published on the efficacy of interferon alpha for hepatitis D virus (HDV) infection. However, there are few randomised trials evaluating the effects of interferon alpha, and it is difficult to judge any benefit of this intervention from the individual trials. To evaluate the beneficial and harmful effects of interferon alpha for patients with chronic hepatitis D. We identified relevant for the review randomised clinical trials by electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until May 2011. We also checked the bibliographic references of identified randomised trials, textbooks, and review articles in order to find randomised trials not identified by the electronic searches. Randomised clinical trials evaluating interferon alpha versus placebo or no intervention for patients with chronic hepatitis D infection. Two authors assessed the trials and extracted data on mortality, virologic, biochemical, and histological response as well as adverse events at end of treatment and six months or more after completing treatment. The analyses were performed using the intention-to-treat principle including all randomised participants irrespective of follow-up. Drop-outs, withdrawals, and non-compliance were considered as treatment failures. Data were analysed with fixed- and random-effects models. Reported results were based on fixed-effect model except in cases where statistical significance varied between the two models. Six randomised trials fulfilled the inclusion criteria. Two hundred and one randomised participants (male = 174) were included. The risk of bias in all the included trials was high

  10. Generalized lichen nitidus with involvement of the palms following interferon alpha treatment. (United States)

    Scheler, Marina; Proelss, Julia; Bräuninger, Wolfgang; Bieber, Thomas; Wenzel, Joerg


    Lichen nitidus is an uncommon dermatosis of unknown etiology. Here we present the case of a generalized lichen nitidus with involvement of the palms in a patient with hepatitis C after systemic treatment with interferon alpha and ribavirin. Furthermore in our patient we could show a strong lesional expression of MxA, a protein specifically induced by type I interferon. It is tempting to speculate that interferon alpha may be involved in the pathogenesis of lichen nitidus. Copyright 2007 S. Karger AG, Basel.

  11. Expression of biologically active human interferon alpha 2 in aloe vera (United States)

    We have developed a system for transgenic expression of proteins in Aloe Vera. Using this approach we have generated plants expressing the human gene interferon alpha 2, IFNa2. IFNa2 is a small secreted cytokine that plays a vital role in regulating the body’s immune response to viral infections a...

  12. Interferon-alpha induced depressive-like behavior in rats

    DEFF Research Database (Denmark)

    Fischer, C. W.; Liebenberg, N.; Elfving, B.


    Background: A subpopulation of individuals with major depressive disorder (MDD) show increased levels of peripheral inflammatory biomarkers, indicating an association of MDD with a chronically activated immune system. Administration of the immune stimulating cytokine, interferon-alpha (IFN-(alpha...... of an inflammation-induced model of depression will be pivotal for our understanding of the underlying pathophysiological immune mechanisms in MDD and may lead to the design of better and more effective treatment options in the near future....... to link inflammation and depression, such as increased levels of the neurotoxic tryptophan metabolite, quinolinic acid (QUIN), and decreased brain-derived neurotrophic factor (BDNF), a protein that plays an important role in survival, differentiation and growth of neurons. The successful development...

  13. Interferon Alpha Association with Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Nasrin Asgari


    Full Text Available Interferon-alpha (IFN-α has immunoregulatory functions in autoimmune inflammatory diseases. The goal of this study was to determine occurrence and clinical consequences of IFN-α in neuromyelitis optica (NMO patients. Thirty-six NMO and 41 multiple sclerosis (MS patients from a population-based retrospective case series were included. Expanded Disability Status Scale (EDSS score and MRI findings determined disease activity. Linear regression was used to assess the effects of the level of IFN-α on disability (EDSS. IFN-α was determined by sensitive ELISA assays. IFN-α was detectable in sera from 9/36 NMO patients, significantly more often than in the MS group (2/41 (P=0.0197. A higher frequency of IFN-α was observed in NMO patients with acute relapse compared to NMO patients in remission (P<0.001 and compared to the MS patients with relapse (P=0.010. In NMO patients, the levels of IFN-α were significantly associated with EDSS (P=0.0062. It may be concluded that IFN-α was detectable in a subgroup of NMO patients. Association of IFN-α levels with clinical disease activity and severity suggests a role for IFN-α in disease perpetuation and may provide a plausible explanation for a negative effect of IFN-1 treatment in NMO patients.

  14. Hybrid (BDBB) interferon-alpha: preformulation studies. (United States)

    Allen, J D; Bentley, D; Stringer, R A; Lowther, N


    A number of techniques, including RP-HPLC, HP-SEC and SDS-PAGE have been used in the delineation of degradative mechanisms of recombinant hybrid (BDBB) interferon-alpha (IFN-alpha) in the solution phase. Different degradation profiles are found according to medium pH. At pH 4.0 the major routes of degradation are via chemical transformation of the monomeric protein to a species which retains antiviral activity, and by self-proteolytic hydrolysis. At pH 7.6, methionine-oxidation is the major chemical degradative process. Protein aggregation is also a significant route of degradation at the higher pH. The results have assisted in a targeted preformulation screen of potentially stabilising excipients and possible parenteral solution dosage forms have been identified. Preliminary 'real-time' storage data confirm excellent chemical and physical stability of IFN-alpha in vehicles formulated at pH 7.6 or, especially, pH 4.0 under the proposed shelf conditions.

  15. Therapeutic use of interferon-alpha for lymphomatoid papulosis. (United States)

    Schmuth, M; Topar, G; Illersperger, B; Kowald, E; Fritsch, P O; Sepp, N T


    Lymphomatoid papulosis is a primary cutaneous, CD30 positive lymphoproliferative disorder with the potential to transform into systemic, malignant lymphoma. Therapeutic strategies for patients with lymphomatoid papulosis have been designed to prevent transformation but have proved to be either inefficacious or limited by side effects. The authors compared the clinical, histologic, and immunohistochemical features from a group of five patients receiving interferon-alpha (IFN-alpha) subcutaneously three times per week with the same features from a group of six patients receiving conventional therapy, including photochemotherapy, antibiotics, topical corticosteroids, or surgery, in an open trial. In the IFN-alpha group, four patients showed a complete remission, and one patient showed a partial remission within a time period of 6 weeks. Two patients developed disease recurrences after discontinuation of short term IFN-alpha therapy (5-7 months). Thereof, one patient went into stable remission after long term IFN-alpha therapy (17 months), and one patient remains in partial remission. In the control group, one patient went into spontaneous remission, two patients showed partial remission, of which one patient developed progressive disease at a later time point, whereas three patients have recurrent disease despite of treatment. The current results indicate that the treatment with IFN-alpha of patients with lymphomatoid papulosis alters the clinical course of the disease with fewer side effects than previous regimens; however, short term treatment does not induce stable remission. Therefore, prolonged treatment appears to be warranted for these patients.

  16. Osteopontin as a marker for response to pegylated interferon Alpha ...

    African Journals Online (AJOL)

    Osteopontin as a marker for response to pegylated interferon Alpha-2b treatment in Chronic HCV Saudi patients. Yousri Mostafa Hussein1,2, Ayman Alhazmi1, Saad Alzahrani3, Ahmad El-Askary1,4,. Abdulrahman Alghamdy5, Eman Bayomy4, Assmaa Selim6, Mohammed Alghamdy1. 1. Medical Laboratories Department ...

  17. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis


    Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-a) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-a compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions...

  18. Polymorphism in the interferon-{alpha} gene family

    Energy Technology Data Exchange (ETDEWEB)

    Golovleva, I.; Lundgren, E.; Beckman, L. [Univ. of Umea (Sweden); Kandefer-Szerszen, M. [Maria Curie-Sklodowska Univ., Lublin (Poland)


    A pronounced genetic polymorphism of the interferon type I gene family has been assumed on the basis of RFLP analysis of the genomic region as well as the large number of sequences published compared to the number of loci. However, IFNA2 is the only locus that has been carefully analyzed concerning gene frequency, and only naturally occurring rare alleles have been found. We have extended the studies on a variation of expressed sequences by studying the IFNA1, IFNA2, IFNA10, IFNA13, IFNA14, and IFNA17 genes. Genomic white-blood-cell DNA from a population sample of blood donors and from a family material were screened by single-nucleotide primer extension (allele-specific primer extension) of PCR fragments. Because of sequence similarities, in some cases {open_quotes}nested{close_quotes} PCR was used, and, when applicable, restriction analysis or control sequencing was performed. All individuals carried the interferon-{alpha} 1 and interferon-{alpha} 13 variants but not the LeIF D variant. At the IFNA2 and IFNA14 loci only one sequence variant was found, while in the IFNA10 and IFNA17 groups two alleles were detected in each group. The IFNA10 and IFNA17 alleles segregated in families and showed a close fit to the Hardy-Weinberg equilibrium. There was a significant linkage disequilibrium between IFNA10 and IFNA17 alleles. The fact that the extent of genetic polymorphism was lower than expected suggests that a majority of the previously described gene sequences represent nonpolymorphic rare mutants that may have arisen in tumor cell lines. 44 refs., 4 figs., 4 tabs.

  19. Pegylated interferon-alpha2b: pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data. Hepatitis C Intervention Therapy Group. (United States)

    Glue, P; Fang, J W; Rouzier-Panis, R; Raffanel, C; Sabo, R; Gupta, S K; Salfi, M; Jacobs, S


    The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon-alpha2b monotherapy in patients with chronic hepatitis C. Fifty-eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open-label, randomized, active controlled study. Patients received 0.035 to 2.0 microg/kg pegylated interferon-alpha2b subcutaneously weekly or the active control, interferon-alpha2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4-week follow-up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. Pegylated interferon-alpha2b produced dose-related reductions in white blood cells, neutrophils, and platelets, and dose-related increases in oral temperature, serum neopterin, and serum 2'5'-oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon-alpha2b. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in pegylated interferon-alpha2b- and nonpegylated interferon-alpha2b-treated groups. Dose-related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (safety and pharmacodynamic profiles were comparable. Pegylated interferon-alpha2b demonstrated delayed clearance compared with nonpegylated interferon-alpha2b, consistent with once-weekly administration.

  20. An Assay in Microtitre Plates for Absolute Abundance of Chicken Interferon Alpha Transcripts

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    Renata Novak Kujundžić


    Full Text Available Immunosuppression of commercial chickens is a serious animal health and economic problem in the poultry industry. The major causes of the immunosuppression are viruses that suppress transcription of interferon genes, especially interferon alpha. There is a need for monitoring immunosuppression in commercially bred chickens. For this purpose, the absolute abundance of interferon alpha transcripts can be measured in blood of chickens by a suitable assay. Such an assay was used to estimate abundance of chicken interferon alpha in a sample of splenic cells induced with polyinosinic polycytidylic acid. The abundance measured was 29 ± 2 attomoles/µg total RNA. This assay can be performed in microtitre plates using samples collected from chickens in poultry houses.

  1. Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Bjerrum, O W; Pallisgaard, N


    Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia...... chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses...

  2. Targeting Jurkat T Lymphocyte Leukemia Cells by an Engineered Interferon-Alpha Hybrid Molecule. (United States)

    Yu, Dehai; Du, Zhonghua; Li, Wei; Chen, Huaqiu; Ye, Songgen; Hoffman, Andrew R; Cui, Jiuwei; Hu, Ji-Fan


    Adult T-cell leukemia/lymphoma (ATL) is a very aggressive T cell malignancy that carries a poor prognosis, primarily due to its resistance to chemotherapy and to life-threatening infectious complications. Interferon-alpha (IFNα) has been used in combination with the anti-retroviral drug zidovudine to treat patients with ATL. However, the efficacy of long-term therapy is significantly limited due to the systemic toxicity of IFNα. We utilized phage display library screening to identify short peptides that specifically bind to Jurkat T lymphocyte leukemia cells. By fusing the Jurkat-binding peptide to the C-terminus of IFNα, we constructed an engineered chimeric IFNα molecule (IFNP) for the treatment of ATL. We found that IFNP exhibited significantly higher activity than wild type IFNα in inhibiting the growth of leukemia cells and inducing cell blockage at the G0/G1 phase. The synthetic IFNP molecule exerted its antitumor activity by upregulating the downstream genes involved in the STAT1 pathway and in apoptosis. Using a cell receptor binding assay, we showed that this Jurkat-binding peptide facilitated the binding affinity of IFNα to the cell surface type I IFN receptor. The isolated Jurkat-binding peptide significantly potentiates the therapeutic activity of IFNα in T lymphocyte leukemia cells. The engineered IFNP molecule may prove to a novel antitumor approach in the treatment of patients with ATL. © 2017 The Author(s). Published by S. Karger AG, Basel.

  3. The use of interferon-alpha in the treatment of cutaneous melanoma: a review

    NARCIS (Netherlands)

    Punt, C. J.


    During the past few years significant progress has been made in the treatment of cutaneous melanoma. These developments often involve the use of interferon-alpha (IFNalpha). Promising results have been reported in high risk patients using adjuvant treatment with high dose IFNalpha. A confirmatory

  4. Aggressive giant cell granuloma of the jaws treated with interferon alpha: a report of two cases. (United States)

    O'Connell, J E; Kearns, G J


    Giant cell granulomas (GCGs) are benign tumours of the jaws of unknown aetiology. Aggressive lesions are difficult to manage and demonstrate a tendency to recur after surgical curettage. In the early 1980s, interferon alpha-2a was found to inhibit angiogenesis through a series of laboratory experiments and was subsequently used to treat a child with pulmonary haemangiomatosis. It has been hypothesised that GCGs are proliferative vascular lesions and would, therefor, be expected to respond to antiangiogenic therapy. The purpose of this study is to report a treatment protocol consisting of enucleation, followed by subcutaneous interferon alpha. Patients with a biopsy-confirmed giant cell lesion satisfying criteria for "aggressive" giant cell tumours were included. All lesions were enucleated, and the patients commenced interferon alpha-2a (3,000,000 units/m(2)) 48-72 h post-operatively. Two patients satisfied the criteria for aggressive giant cell lesions. All tumours were enucleated. There were no post-operative complications, and all patients tolerated the interferon therapy well. To date, there has been no evidence of tumour recurrence. The follow-up periods were 144 and 81 months, respectively. Antiangiogenic therapy, in combination with curettage, has proven to be a useful strategy for the management of these tumours. The use of interferon alpha-2a, following enucleation of these lesions, resulted in complete remission of all lesions, and decreased operative morbidity compared with conventional treatment.

  5. Combined zidovudine and interferon-alpha treatment in patients with AIDS-associated Kaposi's sarcoma

    NARCIS (Netherlands)

    de Wit, R.; Danner, S. A.; Bakker, P. J.; Lange, J. M.; Eeftinck Schattenkerk, J. K.; Veenhof, C. H.


    The effectiveness of addition of interferon-alpha (IFN-alpha) to zidovudine in patients with AIDS-associated Kaposi's sarcoma was assessed in a non-randomized, phase II clinical trial. Twenty-one patients were treated with oral zidovudine (600 mg daily) and IFN-alpha was increased to 18 MU daily for

  6. Liver-targeting of interferon-alpha with tissue-specific domain antibodies.

    Directory of Open Access Journals (Sweden)

    Edward Coulstock

    Full Text Available Interferon alpha (IFNα is used for the treatment of hepatitis C infection and whilst efficacious it is associated with multiple adverse events including reduced leukocyte, erythrocyte, and platelet counts, fatigue, and depression. These events are most likely caused by systemic exposure to interferon. We therefore hypothesise that targeting the therapeutic directly to the intended site of action in the liver would reduce exposure in blood and peripheral tissue and hence improve the safety and tolerability of IFNα therapy. We genetically fused IFN to a domain antibody (dAb specific to a hepatocyte restricted antigen, asialoglycoprotein receptor (ASGPR. Our results show that the murine IFNα2 homolog (mIFNα2 fused to an ASGPR specific dAb, termed DOM26h-196-61, could be expressed in mammalian tissue culture systems and retains the desirable biophysical properties and activity of both fusion partners when measured in vitro. Furthermore a clear increase in in vivo targeting of the liver by mIFNα2-ASGPR dAb fusion protein, compared to that observed with either unfused mIFNα2 or mIFNα2 fused to an isotype control dAb VHD2 (which does not bind ASGPR was demonstrated using microSPECT imaging. We suggest that these findings may be applicable in the development of a liver-targeted human IFN molecule with improved safety and patient compliance in comparison to the current standard of care, which could ultimately be used as a treatment for human hepatitis virus infections.

  7. Minocycline treatment ameliorates interferon-alpha-induced neurogenic defects and depression-like behaviors in mice

    Directory of Open Access Journals (Sweden)

    Lian-Shun eZheng


    Full Text Available Interferon-alpha (IFN-α is a proinflammatory cytokine that is widely used for the treatment of chronic viral hepatitis and malignancy, because of its immune-activating, antiviral, and antiproliferative properties. However, long-term IFN-α treatment frequently causes depression, which limits its clinical utility. The precise molecular and cellular mechanisms of IFN-α-induced depression are not currently understood. Neural stem cells (NSCs in the hippocampus continuously generate new neurons, and some evidence suggests that decreased neurogenesis plays a role in the neuropathology of depression. We previously reported that IFN-α treatment suppressed hippocampal neurogenesis and induced depression-like behaviors via its receptors in the brain in adult mice. However, it is unclear how systemic IFN-α administration induces IFN-α signaling in the hippocampus. In this study, we analyzed the role of microglia, immune cells in the brain, in mediating the IFN-α-induced neurogenic defects and depressive behaviors. In vitro studies demonstrated that IFN-α treatment induced the secretion of endogenous IFN-α from microglia, which suppressed NSC proliferation. In vivo treatment of adult mice with IFN-α for five weeks increased the production of proinflammatory cytokines, including IFN-α, and reduced neurogenesis in the hippocampus. Both effects were prevented by simultaneous treatment with minocycline, an inhibitor of microglial activation. Furthermore, minocycline treatment significantly suppressed IFN-α-induced depressive behaviors in mice. These results suggest that microglial activation plays a critical role in the development of IFN-α-induced depression, and that minocycline is a promising drug for the treatment of IFN-α-induced depression in patients, especially those who are low responders to conventional antidepressant treatments.

  8. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W


    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  9. [Antiviral activity of recombinant interferon-alpha-2b in combination with certain antioxidant]. (United States)

    Vasil'ev, A N; Deriabin, P G; Galegov, G A


    In vitro activity of interferon-alpha-2b in combination with various antioxidants against the influenza virus and Herpes simplex was studied. The standard strains and a clinical strain of Herpes simplex isolated from a patient with resistance to acyclovir were used. The in vitro studie showed that antioxidants, such as alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes simplex variants. They protected up to 100% of the cell monolayer from the virus cytopathic effect. The taurin solutions had no antiviral activity irrespective of the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic effect: the antiviral activity of interferon increased several times. The antiinfluenza activity of interferon-a-2b in the presence of various concentrations of taurin did not change.

  10. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W


    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  11. Interferon-alpha treatment of children with chronic hepatitis D virus infection: the Greek experience. (United States)

    Dalekos, G N; Galanakis, E; Zervou, E; Tzoufi, M; Lapatsanis, P D; Tsianos, E V


    The therapeutic experience of interferon-alpha therapy against hepatitis D virus infection in affected children is rather limited. For this reason, we conducted a retrospective study (duration: 1991-1995) in order to evaluate the efficacy and the safety of interferon-alpha in children suffering from chronic hepatitis D in Northwestern Greece. Seven children who were found to be infected with HDV in a total of 324 children seropositive for hepatitis B virus infection during the 5-year period of the study were treated with interferon-alpha, 3 x 10(6) U/m2 body surface area, intramuscularly or subcutaneously, 3 times weekly for 1 year (after an informed consent obtained from their parents). Patients were assessed monthly by hematological serological and biochemical tests. Clinical progress, levels of serum alanine aminotransferase, hepatitis D ribonucleic acid (HDV-RNA) and hepatitis B deoxyribonucleic acid (HBV-DNA), seroconversion of hepatitis B surface antigen (HBsAg) and Hepatitis Be Antigen (HBeAg) and liver histology were used as response criteria. Posttreatment alanine transferase levels were significantly reduced (P < 0.05) but Immunoglobulin M and total anti-hepatitis D virus (anti-HDV) antibodies remained positive in all, while hepatitis D ribonucleic acid persisted positive in 4 cases. In addition, no seroconversion of HBsAg or HBeAg was noted and the liver histology progress was disappointing. Side effects including mild fever, arthralgias and malaise and reversible neutropenia and thrombocytopenia were common, but not particularly disturbing. Nevertheless, the children remained fully active on treatment, felt well and attended school. Initially 4 children had been below the 10th percentile for weight and height. All thrived during treatment and two crossed above the 10th percentile indicating height velocity and body mass index increase. The administration of regular interferon-alpha doses for treating children with chronic hepatitis D was safe as


    Ene, Corina-Daniela; Nicolae, Ilinca


    The authors' interest was focused on prolactin status in patients with melanocytic lesions and on changes induced by interferon treatment in melanoma patients. The study lasted 5 years and included 128 melanoma patients, 48 dysplastic nevi patients and 48 healthy volunteers. Sixty melanoma cases were selected after surgical removal of tumor and divided into 2 groups: 30 patients with 10 MUmp(-1) interferon alpha2b treatment, three times a week, one year and 30 patients without interferon treatment. Prolactin assessment was made at inclusion in the study, after surgical removal of tumor, when patients started the treatment, after 1, 6, 12 months of treatment and 6 months after treatment end. In melanoma patients, high values of prolactin (10.55 ± 5.94 ng/ml) were detected when compared with dysplastic nevi group (5.94 ± 2.87 ng/ml) and control group (5.74 ± 3.66 Prolactin levels decreased after surgical removal of melanoma, significantly increased during interferon treatment and returned to baseline few months after the immunomodulatory treatment. The treatment with interferon alpha2b stimulated reversible and non-cumulative prolactin production. Evaluating prolactin in melanoma patients could become necessary in the future, both for finding a possible pituitary disorder, but also for a new pharmacological intervention.

  13. [Expression of interferon alpha family gene of Chinese marmot in eukaryotic and prokaryotic cells]. (United States)

    Lu, Yin-ping; Wang, Bao-ju; Huang, Hong-ping; Tian, Yong-jun; Yang, Yan; Dong, Ji-hua; Lu, Meng-ji; Yang, Dong-liang


    To investigate the function of interferon alpha (IFNalpha) in a Chinese marmot model of hepatitis B, we expressed the Chinese marmot (Marmota himalayana) IFNalpha family gene (IFNA) in eukaryotic cells and prokaryotic cells. Eukaryotic and prokaryotic expression plasmids harboring Chinese marmot interferon alpha gene with different genotypes were generated using molecular cloning technology. We detected the biological activity of all expression products by viral protection assay, and analyzed their differences and species restriction of the biological activity. The Chinese marmot functional genotype IFNalpha was expressed in the baby hamster kidney (BHK) cell line, and these products protected WH12/6 cells challenged by encephalomyocarditis virus (EMCV). The Chinese marmot IFN-alpha5 also expressed in E. Coli induced by IPTG, and purified fusion protein had antiviral biological activity. The biologic activity displayed differences among different subtype IFNalpha, and it had strict species restriction. The IFNalpha family gene of the Chinese marmot can be expressed in both eukaryotic and prokaryotic cells, and the expression products show antiviral activity in a protection assay. This study provides, for the first time, evidence that IFNalpha from the Chinese marmot has an antiviral function in vitro and can be used to improve the efficacy of current therapies for HBV infection in our Chinese marmot model.

  14. Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

    International Nuclear Information System (INIS)

    Andersson, G.; Lundgren, E.; Ekre, H.P.


    Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition of the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity

  15. Antitumor potential of a synthetic interferon-alpha/PLGF-2 positive charge peptide hybrid molecule in pancreatic cancer cells. (United States)

    Yin, Hongmei; Chen, Naifei; Guo, Rui; Wang, Hong; Li, Wei; Wang, Guanjun; Cui, Jiuwei; Jin, Haofan; Hu, Ji-Fan


    Pancreatic cancer is the most aggressive malignant disease, ranking as the fourth leading cause of cancer-related death among men and women in the United States. Interferon alpha (IFNα) has been used to treat pancreatic cancer, but its clinical application has been significantly hindered due to the low antitumor activity. We used a "cDNA in-frame fragment library" screening approach to identify short peptides that potentiate the antitumor activity of interferons. A short positively charged peptide derived from the C-terminus of placental growth factor-2 (PLGF-2) was selected to enhance the activity of IFNα. For this, we constructed a synthetic interferon hybrid molecule (SIFα) by fusing the positively charged PLGF-2 peptide to the C-terminus of the human IFNα. Using human pancreatic cell lines (ASPC and CFPAC1) as a model system, we found that SIFα exhibited a significantly higher activity than did the wild-type IFNα in inhibiting the tumor cell growth. The enhanced activity of the synthetic SIFα was associated with the activation of interferon pathway target genes and the increased binding of cell membrane receptor. This study demonstrates the potential of a synthetic SIFα as a novel antitumor agent.

  16. Sodium dodecyl sulfate-capillary gel electrophoresis of polyethylene glycolylated interferon alpha. (United States)

    Na, Dong H; Park, Eun J; Youn, Yu S; Moon, Byung W; Jo, Yeong W; Lee, Sung H; Kim, Won-Bae; Sohn, Yeowon; Lee, Kang C


    Sodium dodecyl sulfate-capillary gel electrophoresis (SDS-CGE) using a hydrophilic replaceable polymer network matrix was applied to characterize the polyethylene glycol(PEG)ylated interferon alpha (PEG-IFN). The SDS-CGE method resulted in a clearer resolution in both the PEG-IFN species and the native IFN species. The distribution profile of PEGylation determined by SDS-CGE was consistent with that obtained by SDS-polyacrylamide gel electrophoresis (PAGE) with Coomassie blue or barium iodide staining. The result was also compared using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. SDS-CGE was also useful for monitoring the PEGylation reaction to optimize the reaction conditions, such as reaction molar ratio. This study shows the potential of SDS-CGE as a new method for characterizing the PEGylated proteins with advantages of speed, minimal sample consumption and high resolution.

  17. Effects of adenoviral delivered interferon-alpha on porcine reproductive and respiratory syndrome virus infection in swine. (United States)

    Type I interferons, such as interferon alpha (IFN-alpha), contribute to innate antiviral immunity by promoting production of antiviral mediators and also play a role in the adaptive immune response. Porcine reproductive and respiratory syndrome (PRRS) is one of the most devastating and costly diseas...

  18. Comparative therapeutic response to pegylated interferon plus ribavirin versus interferon alpha-2b in chronic hepatitis C patients

    International Nuclear Information System (INIS)

    Ali, S.; Nazir, G.; Khan, S.A.; Fatima, F.; Iram, S.


    Background: Hepatitis C is an epidemic worldwide since discovery in 1989. Conventional interferon alpha-2b plus Ribavirin therapy was started in 1998 but over all sustained viral response (SVR) rates are much below the desired rates to eradicate the diseases and stopping its epidemic. This study was conducted to access the therapeutic and cost-effectiveness of long acting pegylated interferon alpha-2b plus Ribavirin therapy verses conventional interferon alpha-2b plus Ribavirin. Methods: This comparative study was done at PAF Hospital Shorkot Cantt from July 2005 to July 2008. One hundred anti-HCV positive patients were selected randomly for the study according to willingness due to cost afford ability of the patients for conventional interferon. Group-A was labelled as pegylated interferon alpha-2b plus Ribavirin group, and Group-B interferon alpha-2b plus Ribavirin group. Both groups were given treatment for 24 weeks. Early virological response (EVR) was accessed at 12 weeks of the treatment. Sustained virological response (SVR) in both the groups was done at 24 week during the treatment and 6 monthly after treatment for 2 years. Initially non-responders and relapsed patients within 2 years of treatment were re-treated for 24 weeks with the same treatment. In both groups non-responders and relapsed patients were labelled as resistant patients. Both groups were followed with same protocol for 2 years. Results: Out of 100 patients included in the study, 34% were females and 66% were males. Group-A patients over all showed 94% SVR as compare to 80% in Group-B in 2 year follow-up. Group-A showed 6% resistant patients as compare to Group-B (20%). Conventional interferons were better tolerated. Higher incidence of side-effects was seen in Group-A. Conclusion: Pegylated interferon plus Ribavirin showed 94% SVR in 2 years. Pegylated interferon plus Ribavirin is the treatment of choice.

  19. Comparative effectiveness and adverse effects of interferon alpha-2b plus ribavirin therapy in hepatitis 'C' for 26 weeks

    International Nuclear Information System (INIS)

    Ali, S.


    Hepatitis C is major emerging challenge for pathologists and treating physicians all over the world. Already 10 million Pakistani population has become anti-HCV positive. It is not only affecting hepatobiliary system but with passage of time research is revealing that Hepatitis C is going to involve almost every organ of the body. With timely diagnosis and treatment, millions of patients can be saved from morbidity and mortality. The nation has to sacrifice initial economic allocations to avoid later millions of mortalities and greater economic losses on affected patients and to support their families. The objective of this study was to evaluate effectiveness of combine therapy of Hepatitis C in local population of Pakistan. This case series study was done at CMH Okara, Kohat, Abbottabad, and PAF Hospital, Shorkot from August 2000 to August 2009. All 1,000 patients from 10 to 60 years of age, confirmed anti-HCV Positive by ELISA and PCR Positive for HCV RNA, were subjected to Interferon alpha-2b and Ribavirin therapy for similar period of time. Response and adverse affects were observed by clinical examination, blood complete picture including platelet count and ALT fortnightly. PCR for HCV RNA and ultrasound abdomen (hepatobiliary system) was done quarterly during treatment and 6 monthly for 2 years after treatment to review the sustained response and relapse. Over all cure rate after 2 years was 855 (85.5%) excluding the 50 (5%) of initial resistant to one year treatment and 95 (9.5%) re-treated relapse cases. One hundred and forty-five (14.5%) patients were found to be resistant to treatment. Hepatitis C must be treated timely after proper diagnosis. Interferon and Ribavirin combination have shown high 'cure' rate in Hepatitis C. In spite of high cure rate of 85.5% with timely and proper treatment, low socio-economic status is a major problem for poor individuals to get treatment. Preventive aspect must be strictly followed and implemented. (author)

  20. Evaluation criteria of rat hepatocytes transcriptome analysis under the influence of interferon alpha by DNA microarray

    Directory of Open Access Journals (Sweden)

    Kuklin A. V.


    Full Text Available The changes induced in transcriptome of rat hepatocytes treated with interferon alpha (IFN during three and six hours were analyzed by DNA microarray. Aim. To conduct a stepwise analysis of the results of microarray experiment and to determine whether they meet/fail to the conventional requirements. Methods. The files obtained after scanning microarrays were subjected to the analysis in statistical environment R by Bioconductor’s packages «affy», «simpleaffy», «affyPLM» and BRB Array Tools software for paired T-test. Results. All microarrays had quality metrics lying within recommended ranges, passed quality control, were normalized and are comparable with each other. The T-test revealed 28 and 124 differentially expressed genes after three and six hours of cells cultivation with IFNα , respectively. Conclusions. The obtained data meet the conventional criteria of quality and are applicable for further evaluation of their biological significance. The R-codes used in this study can be used for the analysis of the microarrays data.

  1. Reconstituted coronavirus TGEV virosomes lose the virus ability to induce porcine interferon-alpha production. (United States)

    Riffault, S; Grosclaude, J; Vayssier, M; Laude, H; Charley, B


    The transmissible gastroenteritis virus (TGEV) is a coronavirus which induces a strong interferon-alpha (IFN-alpha) production in vivo and in vitro. Previous studies have shown that the TGEV external protein M plays a major role in IFN-alpha induction by a non-infectious virus, whereas protein S is not involved. The present study extended these results by showing that monoclonal antibodies (MAbs) directed at the external viral protein sM could not block IFN-alpha induction, which argues against a direct role for this protein. In the same type of blocking experiment, MAbs to the TGEV receptor aminopeptidase N did not inhibit IFN-alpha induction, which strongly indicates that viral replication or entry through the receptor is not needed for TGEV induction of IFN-alpha in leukocytes. In an attempt to isolate functional envelope proteins, TGEV virions were detergent-solubilized and reconstituted in virosomes. Although BIAcore antigenic analysis revealed that the three external viral proteins were present on the virosomes, these proteins were unable to induce IFN-alpha in porcine leukocytes, and seemed to compete with the native virus for IFN-alpha induction. These data indicated that IFN-alpha inducing interactions between TGEV external proteins and leukocytes required a complex native envelope protein structure which has been lost in the virosomes.

  2. In-vitro antiviral efficacy of ribavirin and interferon-alpha against canine distemper virus. (United States)

    Carvalho, Otávio V; Saraiva, Giuliana L; Ferreira, Caroline G T; Felix, Daniele M; Fietto, Juliana L R; Bressan, Gustavo C; Almeida, Márcia R; Silva Júnior, Abelardo


    Canine distemper is a highly contagious disease with high incidence and lethality in the canine population. The objective of this study was to evaluate the efficacy of antiviral action with ribavirin (RBV), interferon-alpha (IFNα), and combinations of RBV and IFNα against canine distemper virus (CDV). Vero cells inoculated with CDV were treated with RBV, IFNα, and combinations of these drugs. The efficacy to inhibit viral replication was evaluated by adding the compounds at different times to determine which step of the viral replicative process was affected. Both drugs were effective against CDV in vitro. The IFNα was the most active compound, with an average IC50 (50% inhibitory concentration) value lower than the IC50 of the RBV. Ribavirin (RBV) was more selective than IFNα, however, and neither drug showed extracellular antiviral activity. The combination of RBV and IFNα exhibited antiviral activity for the intra- and extracellular stages of the replicative cycle of CDV, although the intracellular viral inhibition was higher. Both RBV and IFNα showed high antiviral efficacy against CDV, and furthermore, RBV + IFNα combinations have shown greater interference range in viral infectivity. These compounds could potentially be used to treat clinical disease associated with CDV infection.

  3. MR imaging of hepatic hemangiomas of infancy and changes seen with interferon alpha-2a treatment

    International Nuclear Information System (INIS)

    Chung, T.; Hoffer, F.A.; Burrows, P.E.; Paltiel, H.J.


    The purpose of this study was to describe the appearance on magnetic resonance (MR) imaging of hepatic hemangioma, and how the appearance changes in infants who have received interferon alpha-2a (IFN) treatment. We retrospectively studied 16 MR examinations in seven infants (mean age 3.2 months; range 5 days to 13 months) who were symptomatic with hepatic hemangiomas. Five of these seven patients had MR examinations both before and after treatment with IFN. In six of the seven patients, the hepatic hemangiomas were multicentric; they were usually discrete, well-defined nodules, best seen on T2-weighted images as high intensity lesions. One patient had a large solitary heterogeneous lesion. They all exhibited fast flow (seen as flow voids on spin-echo images and high signal intensity structures on gradient-recalled echo images) and enlarged hepatic arteries and veins. There was enlargement of the proximal abdominal aorta with distal tapering. Treatment was followed by accelerated regression of the hemangiomas in size and number and variable shrinkage of the enlarged vessels. As the tumor nodules regressed, they were replaced by normal-appearing hepatic parenchyma; neither fat nor fibrosis was detected by MR imaging. (orig.). With 4 figs., 1 tab

  4. Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients.

    Directory of Open Access Journals (Sweden)

    Clara Lehmann


    Full Text Available Circulating plasmacytoid dendritic cells (pDC decline during HIV-1 infection, but at the same time they express markedly higher levels of interferon alpha (IFNalpha, which is associated with HIV-1 disease progression. Here we show an accumulation of pDC in lymph nodes (LN of treatment-naïve HIV-1 patients. This phenomenon was associated with elevated expression of the LN homing marker, CCR7, on pDC in peripheral blood of HIV-1 patients, which conferred increased migratory capacity in response to CCR7 ligands in ex vivo functional assays. LN-homed pDC of HIV-1 patients presented higher CD40 and lower BDCA2 levels, but unchanged CD83 and CD86 expression. In addition, these cells expressed markedly higher amounts of IFNalpha compared to uninfected individuals, and were undergoing faster rates of cell death. These results demonstrate for the first time that in asymptomatic, untreated HIV-1 patients circulating pDC up-regulate CCR7 expression, accumulate in lymph nodes, and express high amounts of IFNalpha before undergoing cell death. Since IFNalpha inhibits cell proliferation and modulates immune responses, chronically high levels of this cytokine in LN of HIV-1 patients may impair differentiation and immune function of bystander CD4(+ T cells, thus playing into the mechanisms of AIDS immunopathogenesis.

  5. Human Interferon Alpha2a as Anti Hepatitis B and C

    Directory of Open Access Journals (Sweden)

    Ratih A. Ningrum


    Full Text Available Hepatitis is an inflammation of the liver mainly caused by hepatitis viruses. There are 5 different types of hepatitis based on the infecting virus; A, B, C, D and E. Hepatitis B and C are chronic diseases that potentially develop into hepatocarcinoma and cirrhosis on unappropriate treatments. World Health Organization (WHO stated that currently 350 million people worldwide are living with chronic hepatitis B and 150 million people are living with Hepatitis C. The mortality rate in the world due to hepatitis is about 1.5 million people per year. The human interferon alpha2a (hIFNα2a is a therapeutic protein used as therapeutic protein for hepatitis B and C. This review discusses the hepatitis B (HBV and C (HCV viruses, mechanisms of hIFNα2a as antivirus through signal transduction pathway and improvement of hIFNα2a properties by protein modification. The application of recombinant hIFNα2a (rhIFNα2a in the treatment of hepatitis B and C that recommended by European Association for The Study of Liver (EASL and the viral resistance mechanism are also included. The status of hepatitis B and C and the development of rhIFNα2a is also described as well.

  6. Total chemical synthesis of human interferon alpha-2b via native chemical ligation. (United States)

    Li, Jing; Lehmann, Clara; Chen, Xishan; Romerio, Fabio; Lu, Wuyuan


    Interferon-alpha (IFNα) is a cytokine that orchestrates innate and adaptive immune responses and potently inhibits proliferation of normal and tumor cells. These properties have warranted the use of IFNα in clinical practice for the treatment of several viral infections and malignancies. However, overexpression of IFNα leads to immunopathology observed in the context of chronic viral infections and autoimmune conditions. Thus, it is desirable to develop therapeutic approaches that aim at suppressing excessive IFNα production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFNα and its cell surface receptor and thus inhibit the ensuing biological effects. Mirror-image phage display that screens peptide libraries against the D-enantiomer is particularly attractive because it allows for identification of proteolysis-resistant D-peptide inhibitors. This approach, however, relies on the availability of chemically synthesized D-IFNα composed entirely of D-amino acids. Here, we describe the synthesis and biological properties of IFNα2b of 165 amino acid residues produced by native chemical ligation, which represents an important first step toward the discovery of D-peptide antagonists with potential therapeutic applications. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  7. Recombinant human interferon alpha 2b prevents and reverses experimental pulmonary hypertension.

    Directory of Open Access Journals (Sweden)

    Eileen M Bauer

    Full Text Available Pulmonary hypertension (PH is a progressive and fatal disease with no cure. Vascular remodeling in PH involves intraluminal growth of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Cell growth in these lesions is quasi-neoplastic, with evidence of monoclonality, apoptosis resistance and cancer-like metabolic derangements. Herein we tested the effect of human interferon alpha 2b (IFNα, a pleiotropic cytokine and anti-cancer therapeutic, on the development and progression of PH in the rat SU5416/hypoxia (SUH model and mouse hypoxia model of the disease. In both models IFNα attenuated the development of PH and reversed established PH as assessed by measuring right ventricular systolic pressure and right ventricular hypertrophy. The effect of IFNα was dependent on the type I interferon receptor (IFNAR since mice lacking a subunit of the IFNAR were not protected by IFNα. Morphometric analysis of pulmonary aterioles from hypoxic mice or SUH rats showed that IFNα inhibited pulmonary vascular remodeling in both models and that IFNα reversed remodeling in SUH rats with established disease. Immunohistochemical staining revealed that IFNα decreased the number of PCNA and Tunel positive cells in the wall of pulmonary arterioles. In vitro, IFNα inhibited proliferation of human pulmonary artery smooth muscle cells and as well as human pulmonary artery endothelial cell proliferation and apoptosis. Together these findings demonstrate that IFNα reverses established experimental PH and provide a rationale for further exploration of the use of IFNα and other immunotherpies in PH.

  8. Immunological Enhancement of Interferon Alpha Treatment to Allogeneic Bone Marrow Transplantation in Irradiated Rats

    International Nuclear Information System (INIS)

    Hussein, E.M.; Abd El-Naby, Y.H.


    The Influence of the biological response modifiers: interferon alpha (IFN-α) and bone marrow transplantation (BMT) on stimulation of blood cell recovery and boosting the immunological response were investigated in this work. Male rats received BMT 3 h post total body ?-irradiation of 5 Gy and were injected with 10 units of IFN-α weekly for 5 weeks. Irradiation induced a significant decrease in blood parameters, reduced glutathione (GSH) as well as bone marrow lymphocyte count and viability. Immunological data revealed that tumour necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) recorded a significant depression while lipid peroxidation (MDA) was conversely elevated. White blood cells (WBC), erythrocytes (RBC), haemoglobin (Hb), haematocrit (Hct), lymphocytes and GSH in irradiated animals receiving BMT and IFN-α, were significantly elevated, while MDA was significantly depressed as compared to the irradiated group. Bone marrow lymphocytic count and viability percentage were significantly increased while IL-2 and TNF-α were normalized. The curative action of IFN-α enforcing significant innate response could trigger and augment adaptive immune response by bone marrow transplantation. Such therapies boosting both components of immunity would be considered a potential strategy for irradiation treatment

  9. Frequency of depression and somatic symptoms in patients on interferon alpha/ribavirin for chronic hepatitis C

    International Nuclear Information System (INIS)

    Shakoor, A.; Shafqat, F.; Mehmud, T.H.; Akram, M.; Riaz, S.; Iqbal, Z.; Khan, A.A.


    Large numbers of patients suffering from Chronic Hepatitis C (HCV) are seeking treatment with interferon alpha (IFN) because of significant advances in overall improvement in the course of HCV and its complications. Objectives were to estimate the frequency of depression and somatic symptoms in patients on interferon alpha/ribavirin treatment for chronic hepatitis C. Methods: It was an observational study conducted in the out-patient Department of Gastroenterology Shaikh Zayed Hospital, Lahore during a period of three months, i.e., from September to November 2008. One hundred consecutive patients undergoing interferon alpha/ ribavirin treatment for chronic HCV were included in the study. All patients, irrespective of age, sex or duration of treatment were administered with a check list of common physical complaints and DSM-IV symptoms for Major Depressive Episode. Results: Out of a total of 100 subjects 37 were male and 63 were female. In all, 39 (39%) patients fulfilled the diagnostic criteria of DSM-IV for Major Depressive Episode. Major Depression was more common in female 28 (44.4%) as compared to male 11 (28.7%) patients. Somatic symptoms were common in all the patients but they were reported more frequently by patients with Major Depression compared to those without Major Depression. Myalgias, headache, joint pain, nausea/vomiting, abdominal pain and palpitation were the most common physical symptoms. Conclusion: Major Depression and somatic complaints are a common consequence of interferon alpha/ribavirin treatment for chronic hepatitis C. All patients receiving this treatment should be periodically assessed for the detection of these side effects to promptly address relevant treatment options. (author)

  10. Treatment profile of hepatitis C patients - a comparison of interferon alpha 2a and 2b treatment regimes

    International Nuclear Information System (INIS)

    Aziz, S.; Rajper, J.; Nafay, S.; Imran, K.; Khan, M.H.


    To compare the side effects, cost, end treatment response (ETR) and Sustained viral response (SVR) with combination therapy of either interferon alpha 2a or 2b in combination with Ribavarin. Study Design: Randomized Control Clinical Trial (RCCT). Place and Duration of Study: The study was conducted at Sarwar Zuberi Liver Centre (SZLC), Civil Hospital Karachi (CHK), from May 2004 to July 2009. Methodology: Patients positive for qualitative HCV ribonucleic acid (RNA) by Polymerase chain reaction (PCR) and genotype 3 were included. Patients with decompensated cirrhosis, severe depressive illness, autoimmune hepatitis, hyperthyroidism, pregnancy, heart failure, uncontrolled diabetes, obstructive pulmonary disease, children less than three years and patients who had previously received treatment were excluded. Single blind randomization using computerized randomization list was done and patients divided into groups A and B, those requiring treatment were given injection Interferon 3 million units (MU) subcutaneously (SC) three times/week and Ribavarin 1000 mg per day (weight greater or equal to 75kg) and 1200 mg/day (weight > 75kg) orally with either interferon alpha 2a (group A; FDA approved products) or alpha 2b (group B; non FDA approved product). Demographics, side effects, ETR and SVR were noted. ETR was defined as absence of virus at the end of treatment and SVR was taken as absence of HCV RNA at 6 months after completion of treatment. Results: There were a total 310 patients with mean age of 34.07 +- 9.38 years including 52.4% males, (n=162). Majority of the patients were from North Pakistan. There were 155 patients each in group A and group B respectively. The cost of treatment for interferon alpha for a single patient for 6 months was Rs 60,000, while for Interferon alpha 2b was Rs 30,000. Side effects (fever initially, followed by fatigue, headache, musculoskeletal pain, depression, alopecia, insomnia, and anorexia) were more prominent in group B when compared

  11. Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability. (United States)

    Moghadam, Shadi H; Saliaj, Evi; Wettig, Shawn D; Dong, Chilbert; Ivanova, Marina V; Huzil, J Torin; Foldvari, Marianna


    The outermost layer of the skin, known as the stratum corneum (SC), is composed of dead corneocytes embedded in an intercellular lipid matrix consisting of ceramides, free fatty acids, and cholesterol. The high level of organization within this matrix protects the body by limiting the permeation of most compounds through the skin. While essential for its protective functions, the SC poses a significant barrier for the delivery of topically applied pharmaceutical agents. Chemical permeation enhancers (CPEs) can increase delivery of small drug compounds into the skin by interacting with the intercellular lipids through physical processes including extraction, fluidization, increased disorder, and phase separation. However, it is not clear whether these same mechanisms are involved in delivery of biotherapeutic macromolecules, such as proteins. Here we describe the effect of three categories of CPEs {solvents [ethanol, propylene glycol, diethylene glycol monoethyl ether (transcutol), oleic acid], terpenes [menthol, nerol, camphor, methyl salicylate], and surfactants [Tween 80, SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (Cremophor RH40), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB)]} on the lipid organizational structure of human SC as determined by X-ray scattering studies. Small- and wide-angle X-ray scattering studies were conducted to correlate the degree of structural changes and hydrocarbon chain packing in SC lipids caused by these various classes of CPEs to the extent of permeation of interferon alpha-2b (IFNα), a 19 kDa protein drug, into human skin. With the exception of solvents, propylene glycol and ethanol, all classes of CPEs caused increased disordering of lamellar and lateral packing of lipids. We observed that the highest degree of SC lipid disordering was caused by surfactants (especially SDS, DDAB, and DTAB) followed by terpenes, such as nerol. Interestingly, in vitro skin permeation studies

  12. Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN. (United States)

    Kilday, John-Paul; Caldarelli, Massimo; Massimi, Luca; Chen, Robert Hsin-Hung; Lee, Yi Yen; Liang, Muh-Lii; Parkes, Jeanette; Naiker, Thuran; van Veelen, Marie-Lise; Michiels, Erna; Mallucci, Conor; Pettorini, Benedetta; Meijer, Lisethe; Dorfer, Christian; Czech, Thomas; Diezi, Manuel; Schouten-van Meeteren, Antoinette Y N; Holm, Stefan; Gustavsson, Bengt; Benesch, Martin; Müller, Hermann L; Hoffmann, Anika; Rutkowski, Stefan; Flitsch, Joerg; Escherich, Gabriele; Grotzer, Michael; Spoudeas, Helen A; Azquikina, Kristian; Capra, Michael; Jiménez-Guerra, Rolando; MacDonald, Patrick; Johnston, Donna L; Dvir, Rina; Constantini, Shlomi; Kuo, Meng-Fai; Yang, Shih-Hung; Bartels, Ute


    Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha. European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth). Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years. Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted. © The Author(s) 2017. Published by Oxford University Press on behalf of

  13. Molecular responses and chromosomal aberrations in patients with polycythemia vera treated with peg-proline-interferon alpha-2b (United States)

    Them, Nicole CC; Bagienski, Klaudia; Berg, Tiina; Gisslinger, Bettina; Schalling, Martin; Chen, Doris; Buxhofer-Ausch, Veronika; Thaler, Josef; Schloegl, Ernst; Gastl, Guenther A; Wolf, Dominik; Strecker, Karin; Egle, Alexander; Melchardt, Thomas; Burgstaller, Sonja; Willenbacher, Ella; Zagrijtschuk, Oleh; Klade, Christoph; Greil, Richard; Gisslinger, Heinz; Kralovics, Robert


    Fifty-one polycythemia vera (PV) patients were enrolled in the phase I/II clinical study PEGINVERA to receive a new formulation of pegylated interferon alpha (peg-proline-IFNα-2b, AOP2014/P1101). Peg-proline-IFNα-2b treatment led to high response rates on both hematologic and molecular levels. Hematologic and molecular responses were achieved for 46 and 18 patients (90 and 35% of the whole cohort), respectively. Although interferon alpha (IFNα) is known to be an effective antineoplastic therapy for a long time, it is currently not well understood which genetic alterations influence therapeutic outcomes. Apart from somatic changes in specific genes, large chromosomal aberrations could impact responses to IFNα. Therefore, we evaluated the interplay of cytogenetic changes and IFNα responses in the PEGINVERA cohort. We performed high-resolution SNP microarrays to analyze chromosomal aberrations prior and during peg-proline-IFNα-2b therapy. Similar numbers and types of chromosomal aberrations in responding and non-responding patients were observed, suggesting that peg-proline-IFNα-2b responses are achieved independently of chromosomal aberrations. Furthermore, complete cytogenetic remissions were accomplished in three patients, of which two showed more than one chromosomal aberration. These results imply that peg-proline-IFNα-2b therapy is an effective drug for PV patients, possibly including patients with complex cytogenetic changes. Am. J. Hematol. 90:288–294, 2015. © 2014 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc. PMID:25545244

  14. Clinico-pathogenetic substantiation and experience of the use of interferon alpha 2b in children with acute respiratory viral infections

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    Marushko Yu.V.


    Full Text Available Objective. To evaluate the efficacy and safety of interferon preparations in children under three years with acute respiratory viral infections. Patients and methods. A total of 97 observed children with a diagnosis ARVI has been consulted by doctor at 152 days after the onset of the disease. In the main group in the complex treatment additionally was prescribed nasal interferon alpha 2b «Nazoferon» in the age dosages. Children of the control group had received conventional treatment only. Results. Due to the application of Nazoferon was observed a decrease in the duration as of the main symptoms of the disease (catarrhal phenomena and temperature reaction, so the effects of intoxication. On the fifth day of treatment the difference between clinical parameters was more pronounced. It is found that Nazoferon well tolerated, does not cause discomfort on the part of the respiratory system. Conclusions. The good clinical efficacy and lack of adverse reactions allow recommending Nazoferon for use in pediatric patients. Application of Nazoferon is important to start from the early 152 days of the disease. Allow it to use as a prophylactic measure.

  15. A serial ¹⁸FDG-PET study of a patient with SSPE who had good prognosis by combination therapy with interferon alpha and ribavirin. (United States)

    Ohya, Takashi; Yamashita, Yushiro; Shibuya, Ikuhiko; Hara, Munetsugu; Nagamitsu, Shinichiro; Kaida, Hayato; Kurata, Seiji; Ishibashi, Masatoshi; Matsuishi, Toyojiro


    We describe a 15-year-old girl with subacute sclerosing panencephalitis (SSPE) in stage II who was treated with isoprinosine, intraventricular interferon alpha (IFN-α), and ribavirin for 3 years. She is alive at three years from onset and studies at school with the assistance of a special educational teacher. To assess residual brain function, serial (18)FDG-positron emission tomography (PET) was performed three times to measure cortical metabolism: at onset, a year later, and three years later. At onset, PET study revealed preserved glucose metabolism of the cerebral cortex. In serial PET study, glucose metabolism of the cerebral cortex was also preserved even after three years. Although SSPE is a progressive disease of the neuronal system, and typically leads to death in approximately 2-3 years, the neurological prognosis of our case was good. We consider that combination therapy in the very early stage without hypometabolism in the cerebral cortex may be effective for SSPE. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  16. Interferon alpha inhibits viral replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine (United States)

    Type I interferons, such as interferon alpha (IFNa), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and c...

  17. Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose interferon-alpha 2b for chronic myeloid leukemia

    NARCIS (Netherlands)

    Kluin-Nelemans, JC; Delannoy, A; Louwagie, A; Le Cessie, S; Hermans, J; van der Burgh, JF; Hagemeijer, AM; Van den Berghe, H


    Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha 2b (3 MIU, 5

  18. High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study

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    Tsai Jung-Fa


    Full Text Available Abstract Background Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues. Methods We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80 or 6-MU (n = 134 thrice weekly for 24 weeks, in Taiwan between 1992 and 2001. Results There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%. The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR were significantly higher in 6-MU regimen (37.1% than in 3-MU regimen (23.7%, p Conclusion We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis.

  19. [Reflections on the treatment of EDM in hepatitis C virus patients treated with interferon alpha from a retrospective survey concerning 29 patients]. (United States)

    Lang, J-Ph; Halleguen, O; Vecchionacci, V; Doffoel, M


    At this moment of new therapeutic protocols and the possibility of curing HCV infections, it is of utmost importance to widen antiviral treatment in many indications, to upgrade compliance, and to limit therapeutic discontinuations. Depressive disorders are probably the main reason for failure of this treatment. The lack of knowledge about depressive disorders and the little specialized psychiatric accompaniment in this field are obviously not beneficial for the patient and his disease (no access to interferon alpha therapy, poor compliance, frequent discontinuations of treatment.); 24 patients (15 men and 9 women) treated by interferon alpha and having a major depressive episode (MDE) (according to the DSM IV) and who were about to discontinue their treatment, had a emergency consultation with the psychiatrist of the network who took them immediately in charge in the most adapted way (psychotropic therapy, psychotherapy, hospitalization.) as well as a long term specialized follow up (up to several months after the treatment was discontinued). From this follow up and based on a retrospective questionnaire proposed to the patients, we have thought about the existence and the relevance of the risk factors of the appearance of MDE under interferon alpha (personal antecedents of depression, of suicide attempts, of antiviral treatment discontinuations, of the drug addiction-induced contamination.) and about the major interest of a psychiatric accompaniment within an organized network. Among the 29 patients regularly followed during and after the antiviral therapy, 23 (79.3%) received a psychotropic treatment adapted to the clinical situation (82.6% of initially prescribed antidepressants have not been modified) associated the the psychotherapy, 4 (13.7%) were hospitalized in the psychiatric ward where the network psychiatrist works, one attempted to commit suicide without associated depression disorders (hospitalization, no discontinuation of antiviral therapy). More

  20. Activity of interferon alpha, interleukin 6 and insulin in the regulation of differentiation in A549 alveolar carcinoma cells. (United States)

    McCormick, C; Freshney, R I; Speirs, V


    The differentiation of A549, a human tumour cell line from type II pneumocytes, can be induced by a crude fibroblast-derived factor (FDF) isolated from the conditioned medium of glucocorticoid-treated lung fibroblasts. In the present report, we have used alkaline phosphatase as a differentiation marker to investigate the activity of a number of growth factors as potential candidates for this paracrine activity. This showed that insulin, interleukin 6 (IL-6), and interferon alpha (IFN-alpha) could simulate the activity of conditioned medium. Their effects were dexamethasone (DX) dependent, additive and reversible with a half-life of 1 week. Transforming growth factor alpha and beta, IL-1 alpha and epidermal growth factor, were all inhibitory, and inhibition was opposed, partially or completely, by DX. The most potent inducer was IL-6, but as DX was shown to decrease the concentration of IL-6 in lung fibroblast-conditioned medium it seems an unlikely candidate for FDF. Unlike FDF, all of the positive-acting factors were shown to induce plasminogen activator. FDF has also been shown to be active in the absence of DX. This suggests that differentiation-inducing activity may be present in several paracrine factors, but that so far a candidate for FDF has not been identified.

  1. B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon Alpha

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    Yusuke Kajiyama


    Full Text Available Chronic hepatitis C (CHC patients frequently suffer from thyroid disorders during interferon therapy. However, the mechanism remains unclear. In this study, we investigated the association between serum B-cell-activating factor belonging to the TNF family (BAFF levels and the presence of antithyroid peroxidase antibody (anti-TPO in CHC patients treated with pegylated interferon alpha and ribavirin combination therapy. Six months after the therapy, anti-TPO antibody was detected in 10 (males, 1; females, 9 of 50 patients. The mean age of these patients was higher than that of the anti-TPO-negative patients (61 yr versus 55 yr. Before treatment, the serum BAFF levels of the anti-TPO-positive patients were higher than those of the anti-TPO-negative patients. After starting therapy, the serum BAFF levels of both the anti-TPO-positive and -negative patient groups were elevated. Our findings suggest that the serum BAFF concentration before therapy can predict the risk of thyroid autoimmunity in elderly female patients with CHC.

  2. Temozolomide and interferon-alpha in metastatic melanoma: a phase II study of the Italian Melanoma Intergroup. (United States)

    Ridolfi, Ruggero; Romanini, Antonella; Sileni, Vanna Chiarion; Michiara, Maria; Guida, Michele; Biasco, Guido; Poletti, Paola; Amaducci, Laura; Leoni, Maurizio; Ravaioli, Alessandra


    Temozolomide (TMZ) is a new oral alkylating agent which has proven to be as active as dacarbazine (DTIC) in the treatment of melanoma, but with a lower toxicity. A multicentric phase II trial was conducted in an out-patient setting to determine the therapeutic activity and safety of TMZ in combination with interferon-alpha (IFN-alpha). From June 2000 to July 2001, 41 patients were recruited to receive TMZ 200 mg/m orally on days 1-5 every 28 days and with 5 MU IFN-alpha subcutaneously three times a week, continuously for eight cycles or until disease progression occurred. Of the 40 treated patients, two complete responses (5%) and three partial responses (7.5%) were observed, with a median duration of 4 months (range, 1.5-13.5 months). Thirteen patients (32.5%) had stable disease for a median of 2.5 months. Time to progression was 2.6 months and the median overall survival was 11.8 months. Nine patients (22.5%) developed brain metastases. The grade 4 toxicity observed in seven patients was of a transient haematological nature. This combination therapy is well tolerated but does not appear to increase the response rate or overall survival with respect to TMZ alone or to chemotherapeutic regimens. Further and more complex associations of these two drugs could be investigated in specific subsets of patients, in particular to evaluate its real efficacy in preventing brain metastases. Copyright 2004 Lippincott Williams & Wilkins

  3. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: Successful treatment with repeated TIPS and interferon alpha

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    Akoum Riad


    Full Text Available Polycythemia vera (PV is a common cause of Budd-Chiari syndrome (BCS and portal vein thrombosis (PVT. The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years′ follow-up.

  4. The acute hepatic flare in a patient with chronic hepatitis C infection receiving pegylated interferon alpha 2b and ribavirin

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    Hayati Demiraslan


    Full Text Available The pegylated interferon alpha and ribavirin treatment is well established therapy for hepatitis C virus (HCV infection.During the treatment alanine aminotransferase (ALT flare may be observed rarely.A 51-year-old female receiving pegylated interferon and ribavirin therapy for HCV infection, complained nausea, vomitingin seventh week of the therapy, and her ALT level was detected over 20 times above the normal level. Hepatitis B surfaceantigen, anti-nuclear antibody, anti-mitochondrial antibody, anti-double stranded DNA antibody and anti-hepatitisA virus IgM antibody were negative, and thyroid stimulating hormone was normal. HCV RNA level was 424 IU/ml. PEGIFN and ribavirin therapy was interrupted for three weeks, after liver enzyme level was detected less than 100U/L, thetreatment was resumed. The patient was followed up for 2 months, ALT flare was not observed.In conclusion, we present a rare case with ALT flare, while receiving pegylated interferon and ribavirin therapy forchronic HCV infection. J Microbiol Infect Dis 2012; 2(3: 121-123Key words: Pegylated interferon, ribavirin, ALT flare, hepatitis C virus

  5. Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells.


    Pfeffer, L M; Eisenkraft, B L; Reich, N C; Improta, T; Baxter, G; Daniel-Issakani, S; Strulovici, B


    The early events that occur after treatment of the highly interferon alpha (IFN-alpha)-sensitive human lymphoblastoid Daudi cell line with human leukocyte IFN-alpha have been examined. IFN-alpha treatment of Daudi cells results in a rapid and transient increase in the cellular content of diacylglycerol, which occurs in the absence of inositol phospholipid turnover, or an increase in intracellular calcium concentration. Furthermore, IFN-alpha treatment results in a selective, time-dependent ac...

  6. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment.

    LENUS (Irish Health Repository)

    Bull, S J


    Depression and fatigue are frequent side effects of interferon-alpha (IFN-alpha) treatment, and there is compelling evidence that the inflammatory response system (including interleukin-6, IL-6) and the serotonergic system is important in the pathophysiology of such symptoms. Functional polymorphisms in the promoter region of the IL-6 gene (rs1800795) and serotonin transporter gene (5-HTTLPR) have been identified as regulating these systems. The present study aimed to determine if these polymorphisms were associated with the development of depression and fatigue during IFN-alpha and ribavirin treatment. Ninety-eight Caucasian patients receiving pegylated IFN-alpha and ribavirin treatment for chronic hepatitis C virus at King\\'s College Hospital, London, and Emory University Hospital, Atlanta, participated in this prospective cohort study. Symptoms of depression and fatigue were measured before treatment and at weeks 4, 8, 12 and 24 during treatment. The \\'low IL-6\\' synthesizing genotype (CC) was associated with significantly fewer symptoms of depression (effect size = 0.7 at week 24; F = 9.4, d.f. = 436, P = 0.002). The \\'high transcription\\' serotonin transporter (5-HTT) genotype (LL) was also associated with significantly fewer symptoms of depression, but with a much smaller effect (effect size = 0.2 at week 24; F = 4.5, d.f. = 436, P = 0.03). Neither polymorphisms were associated with symptoms of fatigue (IL-6: F = 1.2, d.f. = 430, P = 0.2; 5-HTT: F = 0.5, d.f. = 430, P = 0.5). The smaller effects of the 5-HTT polymorphism on depression may be explained by an interaction between the genes (F = 5.0, d.f. = 434, P = 0.02): the \\'protective\\' effect of the 5-HTTLPR polymorphism was evident only in the presence of the \\'low IL-6\\' genotype (F = 5.4, d.f. = 64, P = 0.02), not in the presence of the \\'high IL-6\\' genotype (F = 2.2, d.f. = 369, P = 0.1). The association between the IL-6 polymorphism and reduced risk of depressive symptoms confirms the role

  7. Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

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    Mariana Postal


    Full Text Available OBJECTIVE: To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features. METHODS: We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI. Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay. RESULTS: We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50, 64 firstdegree relatives (mean age 39.95±5.66, and 57 healthy (mean age 19.30±4.97 controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their firstdegree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels. CONCLUSION: Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in

  8. [Enhanced porcine interferon-alpha production by Pichia pastoris by methanol/sorbitol co-feeding and energy metabolism shift]. (United States)

    Wang, Huihui; Jin, Hu; Gao, Minjie; Dai, Keke; Dong, Shijuan; Yu, Ruisong; Li, Zhen; Shi, Zhongping


    Porcine interferon-alpha (pIFN-alpha) fermentative production by recombinant Pichia pastoris was carried out in a 10-L bioreactor to study its metabolism changes and effects on fermentation under different inducing strategies, by analyzing the change patterns of the corresponding metabolism and energy regeneration. The results show that the specific activities of alcohol oxidase (AOX), formaldehyde dehydrogenase (FLD) and formate dehydrogenase (FDH) largely increased when reducing temperature from 30 degrees C to 20 degrees C under pure methanol induction, leading significant enhancements in methanol metabolism, formaldehyde dissimilatory energy metabolism and pIFN-alpha antiviral activity. The highest pIFN-alpha antiviral activity reached 1.4 x 10(6) IU/mL, which was about 10-folds of that obtained under 30 degrees C induction. Using methanol/sorbitol co-feeding strategy at 30 degrees C, the major energy metabolism energizing pIFN-alpha synthesis shifted from formaldehyde dissimilatory energy metabolism pathway to TCA cycle, formaldehyde dissimilatory pathway was weakened and accumulation of toxic intermediate metabolite-formaldehyde was relieved, and methanol flux distribution towards to pIFN-alpha synthesis was enhanced. Under this condition, the highest pIFN-alpha antiviral activity reached 1.8 x 10(7) IU/mL which was about 100-folds of that obtained under pure methanol induction at 30 degrees C. More important, enhanced pIFN-alpha production with methanol/sorbitol co-feeding strategy could be implemented under mild conditions, which greatly reduced the fermentation costs and improved the entire fermentation performance.

  9. In vivo study of interferon-alpha-secreting cells in pig foetal lymphohaematopoietic organs following in utero TGEV coronavirus injection. (United States)

    Splíchal, I; Reháková, Z; Sinkora, M; Sinkora, J; Trebichavský, I; Laude, H; Charley, B


    Non-infectious UV-inactivated transmissible gastroenteritis virus (TGEV) was previously shown to induce interferon alpha (IFN alpha) secretion following in vitro incubation with blood mononuclear cells. In this study, pig foetuses at different stages of gestation were injected in utero with (a) partially UV-inactivated wild TGEV or (b) fully UV-inactivated wild or dm49-4 mutant TGEV coronavirus. Nucleated cells from foetal liver, bone marrow, spleen and blood were isolated 10 or 20 h after injection and assayed ex vivo for IFN alpha secretion by ELISPOT and ELISA techniques. The administration of TGEV induced IFN alpha-secreting cells in foetal lymphohaematopoietic organs at mid-gestation. In contrast, IFN alpha was not detected in control sham-operated foetuses. A specific point mutation in the amino acid sequence of the viral membrane glycoprotein M of TGEV mutant dm49-4 was associated with lower or absent IFN alpha in utero inducibility by mutant virus as compared with wild virus. Flow cytometry analysis did not show differences in leukocyte surface marker expression between control and TGEV- or between dm49-4 and wild virus-treated foetus cells, with the exception of a reduction in percentages of polymorphonuclear cells in TGEV-treated lymphohaematopoietic tissues, which is probably due to IFN alpha secretion. The present data provided in vivo evidence of IFN alpha secretion at the cell level in foetal lymphohaematopoietic organs. Such IFN alpha-secreting cells in lymphohaematopoietic tissues may be the source of IFN alpha detected during foetal infections.

  10. Interferon alpha therapy for hepatitis C: treatment completion and response rates among patients with substance use disorders

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    Loftis Jennifer M


    Full Text Available Abstract Background Individuals with substance use disorders (SUDs are at increased risk for hepatitis C viral infection (HCV, and few studies have explored their treatment responses empirically. The objective of this study was to assess interferon alpha therapy (IFN completion and response rates among patients with HCV who had a history of comorbid SUDs. More data is needed to inform treatment strategies and guidelines for these patients. Using a medical record database, information was retrospectively collected on 307,437 veterans seen in the Veterans Integrated Service Network 20 (VISN 20 of the Veterans Healthcare Administration (VHA between 1998 and 2003. For patients treated with any type of IFN (including regular or pegylated IFN or combination therapy (IFN and ribavirin who had a known HCV genotype, IFN completion and response rates were compared among patients with a history of SUD (SUD+ Group and patients without a history of SUD (SUD- Group. Results Odds ratio analyses revealed that compared with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if they had genotypes 2 and 3 (73.1% vs. 68.0%, and if they had genotypes 1 and 4 (39.5% vs. 39.9%. Within the sample of all patients who began IFN therapy, the SUD- and SUD+ groups were similarly likely to achieve an end of treatment response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8% and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1 and 4: 16.0% vs. 22.3%. Conclusion Individuals with and without a history of SUD responded to antiviral therapy for HCV at similar rates. Collectively, these findings suggest that patients who have co-morbid SUD and HCV diagnoses can successfully complete a course of antiviral therapy.

  11. Interferon-alpha suppressed granulocyte colony stimulating factor production is reversed by CL097, a TLR7/8 agonist.

    LENUS (Irish Health Repository)

    Tajuddin, Tariq


    BACKGROUND AND AIM: Neutropenia, a major side-effect of interferon-alpha (IFN-alpha) therapy can be effectively treated by the recombinant form of granulocyte colony stimulating factor (G-CSF), an important growth factor for neutrophils. We hypothesized that IFN-alpha might suppress G-CSF production by peripheral blood mononuclear cells (PBMCs), contributing to the development of neutropenia, and that a toll-like receptor (TLR) agonist might overcome this suppression. METHODS: Fifty-five patients who were receiving IFN-alpha\\/ribavirin combination therapy for chronic hepatitis C virus (HCV) infection were recruited. Absolute neutrophil counts (ANC), monocyte counts and treatment outcome data were recorded. G-CSF levels in the supernatants of PBMCs isolated from the patients and healthy controls were assessed by enzyme-linked immunosorbent assay following 18 h of culture in the absence or presence of IFN- alpha or the TLR7\\/8 agonist, CL097. RESULTS: Therapeutic IFN-alpha caused a significant reduction in neutrophil counts in all patients, with 15 patients requiring therapeutic G-CSF. The reduction in ANC over the course of IFN-alpha treatment was paralleled by a decrease in the ability of PBMCs to produce G-CSF. In vitro G-CSF production by PBMCs was suppressed in the presence of IFN-alpha; however, co-incubation with a TLR7\\/8 agonist significantly enhanced G-CSF secretion by cells obtained both from HCV patients and healthy controls. CONCLUSIONS: Suppressed G-CSF production in the presence of IFN-alpha may contribute to IFN-alpha-induced neutropenia. However, a TLR7\\/8 agonist elicits G-CSF secretion even in the presence of IFN-alpha, suggesting a possible therapeutic role for TLR agonists in treatment of IFN-alpha-induced neutropenia.

  12. Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

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    Gunduz Feyza


    Full Text Available Abstract Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC patients. The mechanism of response to interferon-alpha (IFN-α therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN

  13. Relative resistance of HIV-1 founder viruses to control by interferon-alpha. (United States)

    Fenton-May, Angharad E; Dibben, Oliver; Emmerich, Tanja; Ding, Haitao; Pfafferott, Katja; Aasa-Chapman, Marlen M; Pellegrino, Pierre; Williams, Ian; Cohen, Myron S; Gao, Feng; Shaw, George M; Hahn, Beatrice H; Ochsenbauer, Christina; Kappes, John C; Borrow, Persephone


    Following mucosal human immunodeficiency virus type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed. The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFNα2 (22 U/ml) was lower than that for IFNβ (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFNα2 and IFNβ, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFNα than virus isolates generated from the same individuals during chronic, asymptomatic infection. Viral IFN resistance declined rapidly after the acute phase of infection: in five subjects, viruses derived from six-month consensus molecular clones were significantly more sensitive to the antiviral effects of IFNs than the corresponding founder viruses. The establishment of systemic HIV-1 infection by relatively IFN

  14. Interferon-alpha administration enhances CD8+ T cell activation in HIV infection.

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    Maura Manion

    Full Text Available Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation.To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment.The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006. These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy. As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001.Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

  15. Poly-ε-caprolactone microspheres containing interferon alpha as alternative formulations for the treatment of chronic hepatitis C

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    Cristiane da Silva Melo


    Full Text Available Interferon-alpha (IFN-alpha is one of the main drugs used in the treatment of hepatitis C. Use of IFN-alpha has some limitations that result in poor treatment efficacy and low patient compliance. Therefore, the aim of this study was to develop poly-ε-caprolactone (PCL microspheres containing IFN-alpha as an alternative for the treatment of chronic hepatitis C. Microspheres were prepared using the multiple emulsion followed by solvent evaporation technique. Particle size, surface morphology, drug content and encapsulation efficiency of the microspheres produced were evaluated. The stability of the formulation was assessed after 90 days at -20ºC. An in vitro release study was performed in PBS. In vitro cytotoxicity of the formulation was studied using hepatic cell line. The freeze-dried microspheres had mean particle size, IFN-alpha content, and encapsulation efficiency of 38.52 ± 4.64 µm, 15.52 ± 3.28% and 83.93 ± 5.76%, respectively. There were no significant changes during storage and the structural integrity of the protein was not compromised by the preparation technique. A total of 82% of the IFN-alpha was released after 28 days and the developed microspheres did not present cytotoxicity to the hepatic cell line. In vivo studies are currently underway to evaluate the biological activity of IFN-alpha encapsulated into microspheres.O interferon alfa (IFN-alfa é um dos principais fármacos utilizados no tratamento de hepatite C, mas o seu uso apresenta limitações que resultam em baixa eficácia do tratamento e não adesão do paciente. Diante disso, este estudo objetiva o desenvolvimento de microesferas de poli-ε-caprolactona (PCL contendo IFN-alfa como alternativa ao tratamento de hepatite C crônica. As microesferas foram preparadas pelo método de emulsão múltipla seguido de evaporação do solvente e caracterizadas quanto ao diâmetro médio das partículas, morfologia da superfície, taxa e eficiência de encapsulamento. A

  16. The 2-5A/RNase L/RNase L inhibitor (RLI) [correction of (RNI)] pathway regulates mitochondrial mRNAs stability in interferon alpha-treated H9 cells. (United States)

    Le Roy, F; Bisbal, C; Silhol, M; Martinand, C; Lebleu, B; Salehzada, T


    Interferon alpha (IFNalpha) belongs to a cytokine family that exhibits antiviral properties, immuno-modulating effects, and antiproliferative activity on normal and neoplasic cells in vitro and in vivo. IFNalpha exerts antitumor action by inducing direct cytotoxicity against tumor cells. This toxicity is at least partly due to induction of apoptosis. Although the molecular basis of the inhibition of cell growth by IFNalpha is only partially understood, there is a direct correlation between the sensitivity of cells to the antiproliferative action of IFNalpha and the down-regulation of their mitochondrial mRNAs. Here, we studied the role of the 2-5A/RNase L system and its inhibitor RLI in this regulation of the mitochondrial mRNAs by IFNalpha. We found that a fraction of cellular RNase L and RLI is localized in the mitochondria. Thus, we down-regulated RNase L activity in human H9 cells by stably transfecting (i) RNase L antisense cDNA or (ii) RLI sense cDNA constructions. In contrast to control cells, no post-transcriptional down-regulation of mitochondrial mRNAs and no cell growth inhibition were observed after IFNalpha treatment in these transfectants. These results demonstrate that IFNalpha exerts its antiproliferative effect on H9 cells at least in part via the degradation of mitochondrial mRNAs by RNase L.

  17. Reversible, PET-positive, generalized lymphadenopathy and splenomegaly during high-dose interferon-alpha-2b adjuvant therapy for melanoma. (United States)

    Ridolfi, Laura; Cangini, Delia; Galassi, Riccardo; Passardi, Alessandro; Marzullo, Annamaria; Moretti, Andrea; Framarini, Massimo; Tauceri, Francesca; Serra, Luigi; Chiarion-Sileni, Vanna; Ridolfi, Ruggero


    A patient with resected stage III nodular melanoma treated with high-dose interferon-alpha-b2 adjuvant therapy went on to develop generalized lymphadenopathy and splenomegaly. The total body positron emission tomography showed a high F-fluorodeoxyglucose uptake (standardized uptake values >9), indicating possible lymph node and spleen malignancies. Histologic examinations of an axillary lymph node biopsy and an osteomedullar biopsy were negative, excluding both melanoma metastases and hematopoietic tumors. The symptoms completely regressed after suspension of treatment and a follow-up positron emission tomography was negative. It remains to be seen whether this unusual event can be ascribed to an autoimmune phenomenon linked to potential treatment efficacy and survival.

  18. Vitamin D in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C virus infection: ANRS-HC25-VITAVIC study. (United States)

    Terrier, Benjamin; Lapidus, Nathanael; Pol, Stanislas; Serfaty, Lawrence; Ratziu, Vlad; Asselah, Tarik; Thibault, Vincent; Souberbielle, Jean-Claude; Carrat, Fabrice; Cacoub, Patrice


    To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin (PegIFN/RBV) therapy could improve the efficacy of PegIFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus (HCV) infection. Genotype 1 or 4 HCV-infected patients with null response to previous PegIFN/RBV treatment and with hypovitaminosis D (vitamin D level was 15 ng/mL (range: 7-28). In modified intention-to-treat analysis, 29 patients who received at least one dose of PegIFN/RBV were included in the analysis. All patients except one normalized their vitamin D serum levels. The rate of early virologic response was 0/29 (0%). The rate of HCV RNA vitamin D to PegIFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1 or 4 HCV infection.

  19. MicroRNA Expression Profiling by Bead Array Technology in Human Tumor Cell Lines Treated with Interferon-Alpha-2a

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    Siegrist Fredy


    Full Text Available Abstract MicroRNAs are positive and negative regulators of eukaryotic gene expression that modulate transcript abundance by specific binding to sequence motifs located prevalently in the 3' untranslated regions of target messenger RNAs (mRNA. Interferon-alpha-2a (IFNα induces a large set of protein coding genes mediating antiproliferative and antiviral responses. Here we use a global microarray-based microRNA detection platform to identify genes that are induced by IFNα in hepatoma- or melanoma-derived human tumor cell lines. Despite the enormous differences in expression levels between these models, we were able to identify microRNAs that are upregulated by IFNα in both lines suggesting the possibility that interferon-regulated microRNAs are involved in the transcriptional repression of mRNA relevant to cytokine responses.

  20. Pegylated interferon alpha-2a combined with ribavirin for chronic hepatitis C: a clinical analysis of 160 patients of Uygur nationality or Han nationality

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    LIN Wei


    Full Text Available ObjectiveTo investigate the influencing factors for achieving sustained virological response (SVR to pegylated interferon alpha-2a combined with ribavirin in Uygur and Han patients with chronic hepatitis C, and to provide a reference for predicting the treatment of chronic hepatitis C in Uygur and Han patients. MethodsA retrospective analysis was performed on the clinical data of 160 patients (80 cases of Uygur nationality and 80 cases of Han nationality with chronic hepatitis C who received pegylated interferon alpha-2a combined with ribavirin in the Infectious Disease Hospital in Hetian from January 2012 to March 2014. All patients were followed up for 24 weeks after 48 weeks of treatment. The two groups were compared in terms of the ratios of rapid virological response (RVR, early virological response (EVR, end treated virus response (ETVR, SVR, and no response (NR. The factors which might influence achieving SVR to interferon therapy in the two groups were subjected to univariate analysis and multivariate analysis (conditional logistic regression. For normally distributed continuous data, the comparison was made by t test, and Wilcoxon rank-sum test was made for abnormally distributed continuous data. The comparison of categorical data was made by chi-square test. And univariate analysis and multivariate analysis (conditional logistic regression were carried out. ResultsThere were no significant differences in the rates of RVR (48.8% vs 60.0%, P>0.05, EVR (53.8% vs 63.8%, P>0.05, ETVR (72.5% vs 78.7%, P>0.05, SVR (63.8% vs 72.5%, P>0.05, and NR (27.5% vs 213%, P>0.05 between Uygur group and Han group. The univariate analysis showed that age and age>40 years were the influencing factors for all patients′ SVR (P<0.05. Age>40 years and HCV RNA level>1×106 copies/ml were the influencing factors for Uygur patients′ SVR (P<0.05. Male sex, age, and age>50 years were the influencing factors for Han patients′ SVR (P

  1. Seguridad de la terapia de interferón alfa 2b recombinante más ribavirina en la hepatitis crónica C Safety of recombinant interferon alpha 2b plus ribavirin in chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Yoan Antonio Sánchez Rodríguez


    main cause of chronic hepatitis, hepatic cirrhosis, hepatocarcinoma and liver transplantation worldwide. OBJECTIVE: to identify the side effects of a combined therapy of recombinant interpheron alpha 2b plus ribavirin during the treatment and up to 8 weeks afterwards, as well as the main effects related to temporary or definitive withdrawal. METHODS: a pharmacological surveillance study was performed in which 122 patients with chronic hepatitis C, who had been seen at the Institute of Gastroenterology from May 2001 to May 2006, were included. Recombinant interferon alpha 2b (3 million units administered 3 times a week plus ribavirin (1 000 or 1 200 mg daily depending on the body weight was the therapy used for 48 weeks. RESULTS: of the total number of cases, 88.5 % had side effects; 79.5 % of which corresponded to pseudocold syndrome followed by hematological, neuropsychiatric and gastrointestinal manifestations, and other less frequent ailments. In the studied group, 6.6% had to interrupt their treatment temporarily due to some side effect different from anemia whereas 4 patients gave up the study, three affected by severe hemolytic anemia and one with uncontrollable hyperthyroidism. CONCLUSIONS: the combined therapy of recombinant interferon alpha 2b plus ribavirin proved to be safe; the most frequent side effect was pseudocold syndrome in the majority of cases. The hematological manifestations that made the patients to give up the study led to recommend a strict follow-up of hemoglobin levels and thorough diagnosis and treatment of the main side effects found in other systems and associated to this combined therapy.

  2. Phase 2 Randomized Controlled Trial of Radiation Therapy Plus Concurrent Interferon-Alpha and Retinoic Acid Versus Cisplatin for Stage III Cervical Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Partha, E-mail: [Screening Group, Early Detection and Prevention Section, International Agency for Research on Cancer, Lyon (France); Jenson, Alfred Bennett [James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky (United States); Majhi, Tapas; Choudhury, Prabir [Department of Radiation Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Mandal, Ranajit; Banerjee, Dipanwita [Department of Gynecological Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Biswas, Jaydip [Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata (India); Pan, Jianmin; Rai, Shesh Nath; Ghim, Shin je; Miller, Donald [James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky (United States)


    Purpose: Because a combination of retinoic acid, interferon-alpha, and radiation therapy demonstrated synergistic action and effectiveness to treat advanced cervical cancers in earlier studies, we designed this randomized phase 2 open-label trial to assess efficacy and safety of interferon alpha-2b (IFN) and 13-cis-retinoic acid (RA) administered concomitantly with radiation therapy (IFN-RA-radiation) to treat stage III cervical cancer. Methods and Materials: Stage III cervical cancer patients were randomized to study and control groups in a 1:1 ratio. All patients were treated with radiation therapy; study arm patients received IFN (3 × 10{sup 6} IU subcutaneously) 3 times a week for 4 weeks and daily RA (40 mg orally) for 30 days starting on day 1 of radiation, whereas control arm patients received weekly cisplatinum (40 mg/m{sup 2}) for 5 weeks during radiation. Patients were followed for 3 years. The primary endpoint was overall survival at 3 years. Results: Patients in the study (n=104) and control (n=105) groups were comparable for clinicopathological characteristics, radiation therapy–related variables and treatment response. Proportions of disease-free patients in the study and control groups were 38.5% and 44.8%, respectively, after median follow-up of 29.2 months. Hazard ratios were 0.67 (95% confidence interval [CI]: 0.44-1.01) and 0.69 (95% CI: 0.44-1.06) for overall and disease-fee survival, respectively, comparing the study group to control, and demonstrated an inferior outcome with RA-IFN-radiation, although differences were statistically nonsignificant. Kaplan-Meier curves of disease-free and overall survival probabilities also showed inferior survival in the study group compared to those in the control. Acute toxicities of chemoradiation were significantly higher with 2 acute toxicity-related deaths. Conclusions: Treatment with RA-IFN-radiation did not demonstrate survival advantage over chemoradiation despite being less toxic. The

  3. Polyunsaturated fatty acids levels and initial presentation of somatic symptoms induced by interferon-alpha therapy in patients with chronic hepatitis C viral infection. (United States)

    Chang, Jane Pei-Chen; Lai, Hsueh-Chou; Yang, Hui-Ting; Su, Wen-Pang; Peng, Cheng-Yuan; Gałecki, Piotr; Walczewska, Anna; Pariante, Carmine M; Su, Kuan-Pin


    Somatic symptoms are common in depressive disorder and are similar to sickness behaviors due to inflammatory activation after cytokine administration. Omega-3 polyunsaturated fatty acids (PUFAs) are natural anti-inflammatory agents and may reduce inflammation-induced behavioral changes. The aim of this study was to investigate the role of PUFAs on the development of somatic symptoms and depression in patients of hepatitis C virus infection (HCV) receiving interferon-alpha therapy (IFN-α) in a prospective manner. In this 24-week, prospective cohort study, 43 patients with chronic HCV ongoing IFN-α therapy were assessed with the mini-international neuropsychiatric interview for major depressive episodes and neurotoxicity rating scale (NRS) for somatic symptoms. One-third later developed IFN-α-induced depression (depression (DEP) group). As compared to subjects without depression, DEP group had higher NRS scores (P < 0.001), lower eicosapentaenoic acid (EPA) levels (P = 0.038) at week 2. Somatic symptoms, regardless of painful/non-painful characteristics, had positive association with arachidonic acid (P < 0.05), and negative association with EPA (P < 0.05). This study implies that early intervention with omega-3 PUFAs might be a promising strategy to prevent depression and somatic symptoms in patients receiving cytokine therapy.

  4. First successful pregnancy outcome after intrauterine insemination in a woman with primary infertility and essential thrombocythemia treated with interferon-alpha and aspirin. (United States)

    Leković, Danijela; Gotić, Mirjana; Ljubić, Aleksandar


    The management of pregnancy in young women with essential thrombocythemia is complex and may present a difficult problem. An adverse pregnancy outcome due to thrombosis or bleeding is a common complication. in addition, little is known about fertility in these women prior to the disease. We present the first case of a young woman with primary infertility and essential thrombocythemia who had uneventfully delivered a healthy boy in the fortieth week of pregnancy. Her platelet count was normalized during treatment with interferon-alfa. The patient failed to become pregnant in the natural way and after three attempts of programmed intercourse. She conceived only following intrauterine insemination. During pregnancy, the patient was carefully controlled by a hematologist and gynecologist. Natural course and prognosis of essential thrombocythemia is not adversely affected by pregnancy. In these women, the pregnancy should be planned only after normalization of platelet count. The interferon-alpha should be administered before the pregnancy to regulate and maintain the platelet count within the normal range. Intrauterine insemination with minimal hormonal stimulation due to the risk of thrombosis could be recommended as the safest treatment option of infertility in women with essential thrombocythemia.

  5. Psychological changes in melanoma patients during ipilimumab treatment compared to low-dose interferon alpha therapy-a follow-up study of first experiences. (United States)

    Kovács, Péter; Pánczél, Gitta; Borbola, Kinga; Juhász, Gabriella; Liszkay, Gabriella


    Immuntherapies are frequently accompanied by psychological side effects. Our goals were to detect the changes of psychological factors (depression, anxiety) among melanoma patients during ipilimumab treatment. Ten ipilimumab treated melanoma patients (Group 1.) and 18 low-dose interferon-alpha treated patients (Group 2.) were compared. In our longitudinal study we measured depression (Zung Self-Rating Depression Scale) and anxiety (State-Trait Anxiety Inventory, STAI). Psychological status was tested four times: in every 3 week during ipilimumab treatment according to the relevant treatment protocol and at baseline, 1st, 3rd and 6th month of interferon therapy. No significant differences were detected at different timepoints in the level of depression or in the anxiety scale in Group 1. However significant increase of depression was found in Group 2 during the 6 months of the study. Increased levels of anxiety were found in the second timepoint in both treatment groups. This increase was only temporary and the level of anxiety returned to the baseline. In our sample no measurable psychological differences were detectable during the 12 weeks treatment period of ipilimumab. Ipilimumab seems to have fewer psychological side-effects compared to other immune therapies.

  6. The combination of arsenic, interferon-alpha, and zidovudine restores an “immunocompetent-like” cytokine expression profile in patients with adult T-cell leukemia lymphoma (United States)


    Background HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. Results Here we assessed Th1/Th2/Treg cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a Treg/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4+CD25+ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4+CD25+ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. Conclusions The observed shift from a Treg/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections. PMID:23962110

  7. The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma. (United States)

    Kchour, Ghada; Rezaee, Rahim; Farid, Reza; Ghantous, Akram; Rafatpanah, Houshang; Tarhini, Mahdi; Kooshyar, Mohamad-Mehdi; El Hajj, Hiba; Berry, Fadwa; Mortada, Mohamad; Nasser, Roudaina; Shirdel, Abbas; Dassouki, Zeina; Ezzedine, Mohamad; Rahimi, Hossein; Ghavamzadeh, Ardeshir; de Thé, Hugues; Hermine, Olivier; Mahmoudi, Mahmoud; Bazarbachi, Ali


    HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN. Here we assessed Th1/Th2/T(reg) cytokine gene expression profiles in 16 ATL patients before and 30 days after treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers and sero-negative blood donors. ATL patients at diagnosis displayed a T(reg)/Th2 cytokine profile with significantly elevated transcript levels of Foxp3, interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by decreased transcript levels of interferon-γ (IFN-γ) and IL-2. Most patients (15/16) responded, with CD4⁺CD25⁺ cells significantly decreasing after therapy, paralleled by decreases in Foxp3 transcript. Importantly, arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum levels concomittant with decrease in IL-4 and increases in IFN-γ and IL-2 mRNA, whether or not values were adjusted to the percentage of CD4⁺CD25⁺ cells. Finally, IL-10 transcript level negatively correlated with clinical response at Day 30. The observed shift from a T(reg)/Th2 phenotype before treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may play an important role in restoring an immuno-competent micro-environment, which enhances the eradication of ATL cells and the prevention of opportunistic infections.

  8. A strategy for high-level expression of soluble and functional human interferon alpha as a GST-fusion protein in E. coli. (United States)

    Rabhi-Essafi, Imen; Sadok, Amine; Khalaf, Noureddine; Fathallah, Dahmani M


    Escherichia coli is the most extensively used host for the production of recombinant proteins. However, most of the eukaryotic proteins are typically obtained as insoluble, misfolded inclusion bodies that need solubilization and refolding. To achieve high-level expression of soluble recombinant human interferon alpha (rhIFNalpha) in E. coli, we have first constructed a recombinant expression plasmid (pGEX-hIFNalpha2b), in which we merged the hIFNalpha2b cDNA with the glutathione S-transferase (GST) coding sequence downstream of the tac-inducible promoter. Using this plasmid, we have achieved 70% expression of soluble rhIFNalpha2b as a GST fusion protein using E. coli BL21 strain, under optimized environmental factors such as culture growth temperature and inducer (IPTG) concentration. However, release of the IFN moiety from the fusion protein by thrombin digestion was not optimal. Therefore, we have engineered the expression cassette to optimize the amino acid sequence at the GST-IFN junction and to introduce E. coli preferred codon within the thrombin cleavage site. We have used the engineered plasmid (pGEX-Delta-hIFNalpha2b) and the modified E. coli trxB(-)/gor(-) (Origami) strain to overcome the problem of removing the GST moiety while expressing soluble rhIFNalpha2b. Our results show the production of soluble and functional rhIFNalpha2b at a yield of 100 mg/l, without optimization of any step of the process. The specific biological activity of the purified soluble rhIFNalpha2b was equal to 2.0 x 10(8) IU/mg when compared with the WHO IFNalpha standard. Our data are the first to show that high yield production of soluble and functional rhIFNalpha2b tagged with GST can be achieved in E. coli.

  9. Overproduction, purification and characterization of human interferon alpha2a-human serum albumin fusion protein produced in methilotropic yeast Pichia pastoris (United States)

    Ningrum, R. A.; Santoso, A.; Herawati, N.


    Human interferon alpha2a (hIFNα2a) is a therapeutic protein that used in cancer and hepatitis B/C therapy. The main problem of using hIFNα-2a is its short elimination half life due to its low molecular weight. Development of higher molecular weight protein by albumin fusion technology is a rational strategy to solve the problem. In our previous research we constructed an open reading frame (ORF) encoding hIFNα2a-human serum albumin (HSA) fusion protein that expressed in Pichia pastoris (P. pastoris) protease deficient strain SMD1168. This research was performed to overproduce, purify and characterize the fusion protein. To overproduce the protein, cultivation was performed in buffered complex medium containing glyserol (BMGY) for 24 h and protein overproduction was applied in buffered complex medium containing methanol (BMMY) for 48 hours at 30°C. The fusion protein was purified by blue sepharose affinity chromatography. Molecular weight characterization by SDS PAGE corresponds with its theoretical size, 85 kDa. Western blot analysis demonstrated that the fusion protein was recognized by anti hIFNα2 and anti HSA monoclonal antibody as well. Amino acid sequence of the fusion protein was determined by LC MS/MS2 mass spectrometry with trypsin as proteolitic enzyme. There were three fragments that identified as hIFNα2a and seven fragments that identified as HSA. Total identified amino acids were 150 residues with 20% coverage from total residues. To conclude, hIFNα2a-HSA fusion protein was overproduced, purified and characterized. Characterization based on molecular weight, antibody recognition and amino acid sequence confirmed that the fusion protein has correct identity as theoretically thought.

  10. [The meaning of viral kinetics in the beginning of the pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C]. (United States)

    Husa, P; Slesinger, P; Stroblová, H; Svobodník, A


    Pegylated interferon alpha (PEG-IFN) and ribavirin combination therapy is the contemporary standard therapy of the patients chronically infected with hepatitis C virus (HCV). The study is monitoring the changes in viremy through the changes of HCV RNA in serum before and during antiviral therapy and it attempts to find a relationship between the viral kinetics in the beginning of the therapy and the sustained virologic response. SET OF THE PATIENTS AND THE METHODICS: The study involved 133 patients with chronic infection with HCV, of the average age of 38 years (ranged 18-68 years). 86 of them were men. There were 88 patients who had not been treated before (naive patients), 19 of them were relabing and 26 were non-responders to the previous therapy with conventional IFNalpha and ribavirin. 106 patients (80%) were infected with genotype (G) 1, 3 (2%) with G2, 18 (14%) with G3, 1 patient with G4 and 1 with G6 (under 1%), in 4 (3%) the genotype could not be determined. All of them were treated with the combination of PEG-IFNalpha-2a (180 microg once a week) and ribavirin (800 mg per day in the infection with G2 or G3, 1000 mg at the infection with G1 and the weight up to 74 kg, 1200 mg per day at the infection with G1 and the weight 75 kg and higher). Up to now, 122 patients completed the therapy and 93 of them (76%) had negative HCV RNA in serum at the time of completion of the therapy. Negative HCV RNA after 24 weeks (sustained virologic response SVR) after the completion of the therapy had 64/107 (60%) of the treated patients. In the course of 12 weeks of the therapy the viremy decreased by at least 2 decadic logarithms (early virologic response - EVR) in 87 patients (82%) and in 63 of them (72%) also SVR was noted. Only 19 patients had not EVR and just 1 one of them, nevertheless, achieved SVR (5%). The achievement of EVR is a prerequisite to the successful therapy for chronic infection with HCV with the combination of PEG-IFNalpha and ribavirin. Quantitative

  11. Enhanced expression in vivo of HLA-ABC antigens and beta 2-microglobulin on human lymphoid cells induced by human interferon-alpha in patients with lung cancer. Enhanced expression of class I major histocompatibility antigens prior to treatment

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Plesner, T; Larsen, J K


    than 0.5, respectively) by day-to-day analysis of an untreated healthy control group. An increased expression of both HLA-ABC (mean 55%, P less than 0.0005) and beta 2m (mean 23%, P less than 0.01) was also observed prior to treatment in the lung cancer patients when compared to a group of age matched......The effect of cloned human interferon-alpha (IFN-alpha) on the expression of HLA-ABC antigens (HLA-ABC) and beta 2-microglobulin (beta 2m) on human peripheral lymphoid cells in vivo was studied by cytofluorometry using monoclonal antibodies and fluorescein-labelled rabbit anti-mouse immunoglobulin....... A significant increase in the mean fluorescence intensity of HLA-ABC (median 59%, P less than 0.001) and beta 2m (median 57%, P less than 0.001) on small lymphoid cells was observed 24 h after initiation of IFN-alpha treatment (50 X 10(6) units IFN-alpha/m2 three times a week). The enhanced expression...

  12. Effects of Smoking on Pegylated Interferon alpha 2a and First Generation Protease Inhibitor-based Antiviral Therapy in Naïve Patients Infected with Hepatitis C Virus Genotype 1. (United States)

    Zimmermann, Tim; Hueppe, Dietrich; Mauss, Stefan; Buggisch, Peter; Pfeiffer-Vornkahl, Heike; Grimm, Daniel; Galle, Peter R; Alshuth, Ulrich


    Smoking has multiple effects on factors influencing hepatitis C and antiviral therapy, including lipid metabolism, fibrosis, platelet count and adherence aspects. The aim of this analysis was to determine the impact of smoking on hepatitis C virus antiviral therapy. Data of two cohorts of an observational multicenter study including therapy-naïve patients infected with genotype 1 hepatitis C virus (HCV) treated with dual antiviral therapy (n=7,796) with pegylated interferon alpha 2a in combination with ribavirin, or triple antiviral therapy (n=1,122) containing telaprevir or boceprevir, were analysed. In the univariate matched pair analysis of dual antiviral therapy patients (n=584), smoking was significantly associated with lower sustained viral response rates (p=0.026, OR 0.69 CI: 0.50 - 0.96). The effect of smoking on sustained viral response remained significant (p=0.028, OR 0.67 CI: 0.47 - 0.96) in the multivariate analysis when adjusting for all other baseline parameters with a significant association in the univariate analysis, i.e. diabetes, fibrosis, body mass index, transaminases and baseline viral load. Under protease inhibitors the influence of smoking on virological response did not arise. Smoking has a negative impact on antiviral therapy in naïve patients infected with HCV genotype 1 independently of age, gender, history of drug use or alcoholic liver disease. The effects of smoking might be overcome by the new antiviral agents.

  13. Evaluation of anticancer effects of a novel proteasome inhibitor (Velcade), interferon (alpha-interferon) and anti myeloma antibodies on the growth of myeloma cells

    International Nuclear Information System (INIS)

    El shershaby, H.M.M.


    Cancer is an abnormal growth of cells caused by multiple changes in gene expression leading to deregulated balance of cell proliferation and cell death and ultimately evolving into a population of cells that can invade tissues and metastasize to distant sites, causing significant morbidity. Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow leading to impaired hematopoiesis and bone diseases, which includes mainly lytic lesions, pathological fractures, hypercalcaemia and osteoporosis. Chemotherapy is the systemic treatment of cancer with anticancer drugs. Chemotherapy uses powerful drugs that work by slowing or stopping the cancer cells from growing, spreading or multiplying to other parts of the body. Extensive studies were run all over the world during the last years to discovery some new drugs which possess anticancer effect with less toxicity and have the ability to increase the survival time. In the current study Bortezomib was employed as chemotherapeutic drug for the treatment of myeloma cells where a variable dose of Bortezomib (5, 10,20,30,50 and 100 nM/ml) were used for treatment of myeloma cells in vitro. The results obtained indicated that the T.C/ml was decreased by increasing the drug conc. compared to that of control group. These results illustrated the effect of Bortezomib on the growth of myeloma cells, where the myeloma cell division was decreased while the older cells were deteriorated so that the T.C/ml were decreased. Also the viability of myeloma cells were significantly decreased after 72 hours of addition at drug concentration 20, 30, 50 and 100 nM/ml).

  14. Pharmacokinetic and pharmacodynamic characterization of a novel formulation containing co-formulated interferons alpha-2b and gamma in healthy male volunteers. (United States)

    García-García, Idrian; Hernández-González, Ignacio; Díaz-Machado, Alina; González-Delgado, Carlos A; Pérez-Rodríguez, Sonia; García-Vega, Yanelda; Campos-Mojena, Rosario; Tuero-Iglesias, Ángela D; Valenzuela-Silva, Carmen M; Cruz-Ramírez, Alieski; Martín-Trujillo, Alis; Santana-Milián, Héctor; López-Saura, Pedro A; Bello-Rivero, Iraldo


    More potent antitumor activity is desired in Interferon (IFN)-treated cancer patients. This could be achieved by combining IFN alpha and IFN gamma. The aim of this work was to characterize the pharmacokinetics and pharmacodynamics of a novel formulation containing a co-formulated combination of IFNs alpha-2b and gamma (CIGB-128-A). A group of nine healthy male subjects received intramuscularly 24.5 × 10 6 IU of CIGB-128-A. IFN concentrations were evaluated for 48 h. Serum neopterin, beta2-microglobulin (β 2 M) and 2'-5' oligoadenylate synthetase (2'-5' OAS), classical IFN-inducible serum markers, were measured during 192 h by enzyme immunoassay and body temperature was used as pharmacodynamic variable as well. Concerning pharmacokinetics, serum IFNs' profiles were better fitted to a mono-compartmental model with consecutive zero order and first order absorption, one bioavailability value. No interferences by simultaneous administered IFNs were observed in their typical similar systemic profiles. Neopterin and β 2 M time profiles showed a delay that was efficiently linked to pharmacokinetics by means of a zero order absorption rate constant. Neopterin level was nine-fold higher than initial values, 48 h post-administration, an increment not described before. At this time, mean serum β 2 M peaked around the double from baseline. Serum concentrations of the enzyme 2'-5' OAS was still elevated on the 8 day post-injection. The formulation was well tolerated. Most frequent adverse reactions were fever, headache, arthralgia and lymphopenia, mostly mild. The administration of co-formulated IFN alpha-2b and IFN gamma likely provides improved pharmacodynamic properties that may be beneficial to treat several malignancies. Cuban Public Registry of Clinical Trials RPCEC00000118 , May 24, 2011.

  15. Interferon-alpha signalling in bovine adrenal chromaffin cells: involvement of signal-transducer and activator of transcription 1 and 2, extracellular signal-regulated protein kinases 1/2 and serine 31 phosphorylation of tyrosine hydroxylase. (United States)

    Douglas, S A; Bunn, S J


    Adrenal medullary chromaffin cells are an integral part of the neuroendocrine system, playing an important role in the physiological adaptation to stress. In response to a wide variety of stimuli, including acetylcholine released from the splanchnic nerve, hormones such as angiotensin II or paracrine signals such as prostaglandins, chromaffin cells synthesise and secrete catecholamines and a number of biologically active peptides. This adrenal medullary output mediates a complex and diverse stress response. We report that chromaffin cells also respond both acutely and chronically to interferon (IFN)-alpha, thus providing a mechanism of interaction between the immune system and the stress response. Incubation of isolated bovine chromaffin cells maintained in culture, with IFN-alpha resulted in a rapid, transient activation of the extracellular signal-regulated protein kinase (ERK)1/2, which was maximal after 5 min. IFN-alpha mediated activation of ERK1/2 appeared to be responsible for the increased phosphorylation of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This tyrosine hydroxylase phosphorylation was exclusively on serine 31, with no change in the phosphorylation of serine 19 or 40. This increase in the serine 31 phosphorylation of tyrosine hydroxylase was prevented by inhibition of protein kinase C or ERK1/2 activation. Incubation with IFN-alpha also resulted in a time- and concentration-dependent phosphorylation and nuclear translocation of signal transducer and activator of transcription proteins (STAT)1 and 2. This response was maximal after approximately 60 min. Prolonged treatment with IFN-alpha (12-48 h) resulted in increased expression of STAT1 and, to a lesser extent, STAT2. Thus, these findings demonstrate that adrenal medullary chromaffin cells are responsive to IFN-alpha and provide a possible cellular mechanism by which this immune-derived signal can potentially influence and integrate with the stress response.

  16. Renal failure after treatment with interferon alpha 2b

    NARCIS (Netherlands)

    Roeloffzen, WWH; Hospers, GAP; De Vries, EGE; Navis, GJ


    Although there has been considerable experience with interferons in the treatment of malignancy and viral illnesses, acute renal failure as a side-effect of interferon treatment has rarely been reported. We present the case of a patient who developed acute on chronic renal failure 16 months after

  17. Interferon-alpha in the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Khoo, T.L.; Joshua, D.; Gibson, J.


    in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs" - thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment...

  18. Increased sensitivity to interferon-alpha in psoriatic T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Lovato, Paola; Skov, Lone


    Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important...... disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers...... and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT...

  19. Interferon alpha for treatment of chronic myeloid leukemia

    DEFF Research Database (Denmark)

    Simonsson, Bengt; Hjorth-Hansen, Henrik; Bjerrum, Ole Weis


    practice a maximally tolerated dose) compared with lower dose IFN-a. When IFN-a is combined with other drugs, we advice lower dose IFN to minimize toxicity and increase treatment adherence and duration. IFN-a combined with Ara-C moderately improves treatment outcome. Imatinib, a tyrosine kinase inhibitor......, is now first line treatment for CML, but two large randomized studies show improved outcome when pegylated IFN-a is added to the treatment with imatinib. One explanation for this might be that IFN-a, contrary to imatinib, stimulates the quiescent stem cells to proliferate and thereby potentially...... increases sensitivity to imatinib. Although imatinib and other tyrosine kinase inhibitors are very efficient, they are rarely curative. IFN-a could be included in curatively aimed combination treatment protocols and thus still be an important element in CML treatment....

  20. Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus (United States)

    Durcan, Laura; Petri, Michelle


    Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

  1. Safety and efficacy of combination therapy of interferon-alpha2 + JAK1-2 Inhibitor in the philadelphia-negative chronic myeloproliferative neoplasms. Preliminary results from the danish combi-trial-an open label, single arm, non-randomized multicenter phase II study

    DEFF Research Database (Denmark)

    Mikkelsen, S. U.; Kjaer, L.; Skov, V.


    Background: The Philadelphia-negative, chronic myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (MF) (PMF). Chronic inflammation and a deregulated immune system are considered important for clonal evolution and disease pro...


    Directory of Open Access Journals (Sweden)

    Кристина Владимировна Марочко


    Conclusion. Mono-infection was prevalent among HPV infected women HPV 16 is the most frequently detected hrHPV. The use of the drug interferon alfa-2b in the study group, contributed to viral load reduction.

  3. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, H.C.; Larsen, T.S.; Riley, C.H.


    The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F mu...... and potentially cure after long-term immune therapy with IFN-alpha2 is discussed and foreseen as an achievable goal in the future....

  4. Epidemiology, risk factors and prognosis of Interferon alpha induced thyroid disorders. A Prospective Clinical Study

    Directory of Open Access Journals (Sweden)

    Łukasz Obołończyk


    In conclusion: Thyroid disorders are common during IFN-α therapy. Previous epidemiological data seem to be underestimated. Important risk factors for IITD development are: female sex, elevated serum TSH concentration (≥2.5 μU/mL, positive TPO-Ab and increased blood velocity in thyroid arteries.

  5. Interferon alpha as monotherapy or combination therapy for chronic hepatitis B


    Zonneveld, Monika


    markdownabstract__Abstract__ The hepatitis B virus (HBV) is a DNA virus that belongs to the group ofhepadnaviridae. The partially double-stranded DNA contains 4 open reading frames, encoding for the envelope (pre-S/ S), core (precore/ core), polymerase and X proteins. The pre-S/S open reading frame encodes for the large, middle and small surface glycoproteins. The precore/ core region encodes for both the nucleocapsid protein (hepatitis B core antigen) and a soluble protein, the hepatitis B e...

  6. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Larsen, Thomas Stauffer; Riley, Caroline Hasselbalch


    The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F...

  7. Field production and functional evaluation of chloroplast-derived interferon-alpha2b. (United States)

    Arlen, Philip A; Falconer, Regina; Cherukumilli, Sri; Cole, Amy; Cole, Alexander M; Oishi, Karen K; Daniell, Henry


    Type I interferons (IFNs) inhibit viral replication and cell growth and enhance the immune response, and therefore have many clinical applications. IFN-alpha2b ranks third in world market use for a biopharmaceutical, behind only insulin and erythropoietin. The average annual cost of IFN-alpha2b for the treatment of hepatitis C infection is $26,000, and is therefore unavailable to the majority of patients in developing countries. Therefore, we expressed IFN-alpha2b in tobacco chloroplasts, and transgenic lines were grown in the field after obtaining United States Department of Agriculture Animal and Plant Health Inspection Service (USDA-APHIS) approval. Stable, site-specific integration of transgenes into chloroplast genomes and homoplasmy through several generations were confirmed. IFN-alpha2b levels reached up to 20% of total soluble protein, or 3 mg per gram of leaf (fresh weight). Transgenic IFN-alpha2b had similar in vitro biological activity to commercially produced PEG-Introntrade mark when tested for its ability to protect cells against cytopathic viral replication in the vesicular stomatitis virus cytopathic effect (VSV CPE) assay and to inhibit early-stage human immunodeficiency virus (HIV) infection. The antitumour and immunomodulating properties of IFN-alpha2b were also seen in vivo. Chloroplast-derived IFN-alpha2b increased the expression of major histocompatibility complex class I (MHC I) on splenocytes and the total number of natural killer (NK) cells. Finally, IFN-alpha2b purified from chloroplast transgenic lines (cpIFN-alpha2b) protected mice from a highly metastatic tumour line. This demonstration of high levels of expression of IFN-alpha2b, transgene containment and biological activity akin to that of commercial preparations of IFN-alpha2b facilitated the first field production of a plant-derived human blood protein, a critical step towards human clinical trials and commercialization.

  8. Suppression of saccharin-induced mutagenicity by interferon-alpha in human RSa cells. (United States)

    Suzuki, N; Suzuki, H


    Saccharin is an artificial sweetener commonly used in the formulation of foods and beverages. Sodium saccharin-induced mutagenicity is detectable in human RSa cells by estimation of cloning efficiency of ouabain-resistant mutant cells and determination of K-ras codon 12 mutation in genomic DNA, analyzed by PCR and differential dot-blot hybridization. However, in this study no phenotypic or genetic mutations were detected in RSa cells cultured with human IFN (HuIFN)-alpha before sodium saccharin treatment. The suppressive effect was lessened by transient treatment with antipain immediately after sodium saccharin treatment. Elevation of antipain-sensitive protease activity was found, furthermore, in RSa cells cultured with HuIFN-alpha and subsequently treated with sodium saccharin. Thus, antipain-sensitive protease induction in cells tested here may be involved in suppression of the mutagenicity of saccharin by HuIFN-alpha.

  9. Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma

    Directory of Open Access Journals (Sweden)

    Morris Cindy A


    Full Text Available Abstract Background Recent studies have shown that gamma interferon (IFN-γ synergizes with the innate IFNs (IFN-α and IFN-β to inhibit herpes simplex virus type 1 (HSV-1 replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV replication. Results We have found that as with HSV-1, IFN-γ synergizes with the innate IFNs (IFN-α/β to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs with IFN-α, IFN-β or IFN-γ alone inhibited HCMV plaque formation by ~30 to 40-fold, treatment with IFN-α and IFN-γ or IFN-β and IFN-γ inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-α/β and IFN-γ was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE genes (IE1 and IE2 revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-α/β and IFN-γ (~5-11-fold as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence. Conclusion These findings suggest that IFN-α/β and IFN-γ synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-γ produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo.

  10. 13 native human interferon-alpha species assessed for immunoregulatory properties

    DEFF Research Database (Denmark)

    Heron, I; Hokland, M; Berg, K


    weight-range of 16.6-23.5 kD. These stained IFN proteins were eluted individually from the gel slices and assessed for antiviral activity in human, monkey, and bovine cells, as well as for immunomodulatory effects (in vitro) on human lymphocytes. Based on equal amounts of (human) IFN units, as determined...

  11. Modulation of cell proliferation and differentiation of human lung carcinoma cells by the interferon-alpha

    Czech Academy of Sciences Publication Activity Database

    Krejčová, Daniela; Procházková, Jiřina; Kubala, Lukáš; Pacherník, J.


    Roč. 28, č. 3 (2009), s. 294-301 ISSN 0231-5882 R&D Projects: GA ČR(CZ) GA524/06/1197; GA ČR(CZ) GP524/06/P345 Grant - others:GA ČR(CZ) GA301/08/0717 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : ABC transporter proteins * cell cycle * interferons Subject RIV: BO - Biophysics Impact factor: 0.741, year: 2009

  12. Acute pericarditis due to pegylated interferon alpha therapy for chronic HCV hepatitis - Case report (United States)


    Background Cardio toxicity due to interferon therapy was reported only in small case series or case reports. The most frequent cardiac adverse effects related to interferon are arrhythmias and ischemic manifestations. The cardiomyopathy and pericarditis are rare but can be life threatening. The predisposing factors for interferon cardio toxicity were described only for ischemic manifestations and arrhythmias. Case presentation The authors report a case of pericarditis due to alpha interferon therapy for chronic hepatitis C, in a young woman without previous cardiac pathology. The clinical manifestations started during the 7-th month of interferon treatment. The cessation of interferon was necessary. After interferon discontinuation the patient recovered, with complete resolution of pericarditis. The patient scored 9 points on the Naranjo ADR probability scale, indicating a very probable association between pericarditis and interferon administration. Conclusion If a patient receiving interferon therapy complains of chest pain of sudden onset, a cardiac ultrasound should be performed in order to rule out pericarditis. We point out the possibility of an infrequent but severe adverse effect of interferon therapy. PMID:21453456

  13. Treatment with interferon-alpha delays disease in swine infected with a highly virulent CSFV strain (United States)

    Classical swine fever (CSF) is an economically significant, highly contagious swine disease. The etiological agent, CSF virus (CSFV), is an enveloped virus with a positive-sense, single-stranded RNA genome, classified as a member of the genus Pestivirus within the family Flaviviridae (Becher et al.,...

  14. Minimal residual disease after long-term interferon-alpha2 treatment

    DEFF Research Database (Denmark)

    Utke Rank, Cecilie; Weis Bjerrum, Ole; Larsen, Thomas Stauffer


    burden by a highly sensitive quantitative PCR (qPCR) assay appears to be a useful tool for monitoring minimal residual disease (MRD) and evaluating treatment efficacy. This report expands and substantiates existing data, showing that IFN-alpha2 is a highly potent immunomodulating agent capable...... of inducing MRD with low-burden JAK2 V617F, major molecular response (MMR), complete hematological remission (CHR) and complete histomorphological normalization of the bone marrow in a sub-set of patients with ET and PV after long-term treatment (≥ 3.5 years). Furthermore, long-lasting hematological...

  15. Interferon-alpha triggers B cell effector 1 (Be1 commitment.

    Directory of Open Access Journals (Sweden)

    Marie-Ghislaine de Goër de Herve

    Full Text Available B-cells can contribute to the pathogenesis of autoimmune diseases not only through auto-antibody secretion but also via cytokine production. Therapeutic depletion of B-cells influences the functions and maintenance of various T-cell subsets. The mechanisms governing the functional heterogeneity of B-cell subsets as cytokine-producing cells are poorly understood. B-cells can differentiate into two functionally polarized effectors, one (B-effector-1-cells producing a Th-1-like cytokine pattern and the other (Be2 producing a Th-2-like pattern. IL-12 and IFN-γ play a key role in Be1 polarization, but the initial trigger of Be1 commitment is unclear. Type-I-interferons are produced early in the immune response and prime several processes involved in innate and adaptive responses. Here, we report that IFN-α triggers a signaling cascade in resting human naive B-cells, involving STAT4 and T-bet, two key IFN-γ gene imprinting factors. IFN-α primed naive B-cells for IFN-γ production and increased IFN-γ gene responsiveness to IL-12. IFN-γ continues this polarization by re-inducing T-bet and up-regulating IL-12Rβ2 expression. IFN-α and IFN-γ therefore pave the way for the action of IL-12. These results point to a coordinated action of IFN-α, IFN-γ and IL-12 in Be1 polarization of naive B-cells, and may provide new insights into the mechanisms by which type-I-interferons favor autoimmunity.

  16. Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: role of CD81 and scavenger receptor class B type I and effect of antiviral drugs

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Scheel, Troels K H; Jensen, Tanja B


    -6 viruses had similar spread kinetics, intracellular Core, NS5A, and lipid amounts, and colocalization of Core and NS5A with lipids. Treatment with interferon-alpha2b but not ribavirin or amantadine showed a significant antiviral effect. Infection with all genotypes could be blocked by specific antibodies...... against the putative coreceptors CD81 and scavenger receptor class B type I in a dose-dependent manner. Finally, neutralizing antibodies in selected chronic phase HCV sera had differential effects against genotype 1-7 viruses. Conclusion: We completed and characterized a panel of JFH1-based cell culture...... systems of all seven major HCV genotypes and important subtypes and used these viruses in comparative studies of antivirals, HCV receptor interaction, and neutralizing antibodies....

  17. CRADA with Teledyne Electronic Technologies and Pacific Northwest National Laboratory (PNL-096): The Exposure-to-Risk monitoring system. Final letter report

    Energy Technology Data Exchange (ETDEWEB)

    Thrall, K.D.


    The purpose of this project was to demonstrate the ``Exposure-to- Risk`` monitoring system in an actual occupational environment. The system is a unique combination of existing hardware with proprietary software to create an integrated means of assessing occupational exposures to volatile organic compounds. One component of this system utilizes a portable mass spectrometer developed by Teledyne Electronic Technologies. Integration of the system was accomplished under Laboratory Directed Research and Development (LDRD) funding. Commercialization of the system will take place following demonstration in an actual occupational environment, and will include, in part, Teledyne Electronic Technologies. The Exposure-to-Risk monitoring system will benefit DOE by overcoming present-day limitations in worker health protection monitoring. There are numerous sites within the` DOE complex where many different hazardous chemicals are used on a routine basis. These chemicals range from paint stripers and cleaning solvents to chemical warfare agents, each having its own degree of potential adverse health risk to a worker. Thus, a real concern for DOE is to ensure that a worker is properly monitored to assess any adverse health risk from exposure to potentially hazardous chemicals. With current industrial hygiene technologies, this is an arduous task. The Exposure-to-Risk monitoring system integrates a patented breath-inlet device connecting a subject`s exhaled breath directly with a field-portable mass spectrometer with physiologically based pharmacokinetic (PBPK) modeling to estimate the target tissue dose following a chemical exposure. Estimation of the adverse health risk prediction follows from the exposure/dose calculation based on currently accepted methodologies. This new system can determine, in the field, the possible adverse health risks on a daily basis to an individual worker.

  18. HCN1 Channels Enhance Rod System Responsivity in the Retina under Conditions of Light Exposure.

    Directory of Open Access Journals (Sweden)

    Vithiyanjali Sothilingam

    Full Text Available Vision originates in rods and cones at the outer retina. Already at these early stages, diverse processing schemes shape and enhance image information to permit perception over a wide range of lighting conditions. In this work, we address the role of hyperpolarization-activated and cyclic nucleotide-gated channels 1 (HCN1 in rod photoreceptors for the enhancement of rod system responsivity under conditions of light exposure.To isolate HCN1 channel actions in rod system responses, we generated double mutant mice by crossbreeding Hcn1-/- mice with Cnga3-/- mice in which cones are non-functional. Retinal function in the resulting Hcn1-/- Cnga3-/- animals was followed by means of electroretinography (ERG up to the age of four month. Retinal imaging via scanning laser ophthalmoscopy (SLO and optical coherence tomography (OCT was also performed to exclude potential morphological alterations.This study on Hcn1-/- Cnga3-/- mutant mice complements our previous work on HCN1 channel function in the retina. We show here in a functional rod-only setting that rod responses following bright light exposure terminate without the counteraction of HCN channels much later than normal. The resulting sustained signal elevation does saturate the retinal network due to an intensity-dependent reduction in the dynamic range. In addition, the lack of rapid adaptational feedback modulation of rod photoreceptor output via HCN1 in this double mutant limits the ability to follow repetitive (flicker stimuli, particularly under mesopic conditions.This work corroborates the hypothesis that, in the absence of HCN1-mediated feedback, the amplitude of rod signals remains at high levels for a prolonged period of time, leading to saturation of the retinal pathways. Our results demonstrate the importance of HCN1 channels for regular vision.

  19. Intracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN

    NARCIS (Netherlands)

    Kilday, John-Paul; Caldarelli, Massimo; Massimi, Luca; Chen, Robert Hsin-Hung; Lee, Yi Yen; Liang, Muh-Lii; Parkes, Jeanette; Naiker, Thuran; van Veelen, Marie-Lise; Michiels, Erna; Mallucci, Conor; Pettorini, Benedetta; Meijer, Lisethe; Dorfer, Christian; Czech, Thomas; Diezi, Manuel; Schouten-van Meeteren, Antoinette Y. N.; Holm, Stefan; Gustavsson, Bengt; Benesch, Martin; Müller, Hermann L.; Hoffmann, Anika; Rutkowski, Stefan; Flitsch, Joerg; Escherich, Gabriele; Grotzer, Michael; Spoudeas, Helen A.; Azquikina, Kristian; Capra, Michael; Jiménez-Guerra, Rolando; MacDonald, Patrick; Johnston, Donna L.; Dvir, Rina; Constantini, Shlomi; Kuo, Meng-Fai; Yang, Shih-Hung; Bartels, Ute


    Background: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of

  20. Intracystic interferon-alpha in pediatric craniopharyngioma patients : An international multicenter assessment on behalf of SIOPE and ISPN

    NARCIS (Netherlands)

    Kilday, John-Paul; Caldarelli, Massimo; Massimi, Luca; Chen, Robert Hsin-Hung; Lee, Yi Yen; Liang, Muh-Lii; Parkes, Jeanette; Naiker, Thuran; van Veelen, Marie-Lise; Michiels, Erna; Mallucci, Conor; Pettorini, Benedetta; Meijer, Lisethe; Dorfer, Christian; Czech, Thomas; Diezi, Manuel; Schouten-van Meeteren, Antoinette Y. N.; Holm, Stefan; Gustavsson, Bengt; Benesch, Martin; Mueller, Hermann L.; Hoffmann, Anika; Rutkowski, Stefan; Flitsch, Joerg; Escherich, Gabriele; Grotzer, Michael; Spoudeas, Helen A.; Azquikina, Kristian; Capra, Michael; Jimenez-Guerra, Rolando; MacDonald, Patrick; Johnston, Donna L.; Dvir, Rina; Constantini, Shlomi; Kuo, Meng-Fai; Yang, Shih-Hung; Bartels, Ute


    Background: Craniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of

  1. Interferon-alpha-producing cells are localized in gut-associated lymphoid tissues in transmissible gastroenteritis virus (TGEV) infected piglets. (United States)

    Riffault, S; Carrat, C; van Reeth, K; Pensaert, M; Charley, B


    Transmissible gastroenteritis virus (TGEV) infection of piglets results in a very rapid and massive release of IFN-alpha in serum and secretions. The objective of this work was to characterize the IFN-alpha-producing cells (IPC) in tissues of TGEV-infected piglets. Caesarean-derived colostrum-deprived piglets were infected orally with the TGEV virulent Miller strain and IPC were characterized in situ by immunohistochemistry, using a rabbit anti-pig IFN-alpha antiserum. IPC were almost exclusively detected in intestinal tissues and mesenteric lymph nodes (MLN), as early as 6 h post inoculation (p.i.), with a peak at 12-18 h. They disappeared by 24 h. IPC were localized between enterocytes in the small intestine epithelial layer, in the lamina propria, around the Peyer's patches and, at highest frequency, in MLN. Very few IPC were present in the spleen and popliteal lymph nodes of infected piglets. Double immunohistochemical staining for IFN-alpha and leukocyte markers on MLN cryosections showed that IPC were mainly Swine Leukocyte Antigen (SLA) class II positive, and were not stained by an anti-macrophage (SWC3a) MAb. In addition, double staining with anti-TGEV and anti-IFN-alpha MAbs showed that viral antigens were present in MLN, close to IPC. These results show for the first time the presence of IPC in gut mucosa and gut-associated lymphoid tissues in response to an enteropathogenic virus. Moreover, this work shows that IFN-alpha released in serum is likely to originate almost exclusively from gut IPC triggered locally by viral antigens to produce IFN-alpha, since there were very few IPC in spleen or peripheral lymph nodes. MHC class II molecule expression by gut-associated IPC suggests that these cells may be the in vivo mucosal counterparts of the dendritic cells recently shown to produce IFN-alpha after in vitro viral induction.

  2. The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms

    DEFF Research Database (Denmark)

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads


    and II genes used by tumor cells to escape antitumor T-cell-mediated immune responses. Several genes encoding human leukocyte antigen (HLA) class I and II molecules have been shown to be significantly downregulated. Upregulation of HLA genes is considered one of the mechanisms of action of interferon...... (IFN)-alpha2, but regulation of these genes during IFN-alpha2 treatment in MPNs has never been studied. Our findings show a significant upregulation of several HLA genes of importance for tumor immune surveillance by IFN-alpha2 treatment in MPNs. This mechanism might enhance the cytotoxic potential...

  3. No development of neutralizing antibodies against recombinant interferon-alpha in Ph-negative myeloproliferative neoplasms-a prospective study

    DEFF Research Database (Denmark)

    Ocias, Lukas Frans; Lund Hansen, Dennis; Kielsgaard Kristensen, Thomas


    neutralizing antibodies (nAbs) against the drug leading to treatment failure. Most data on type 1 IFN immunogenicity are available from studies of patients with multiple sclerosis treated with rIFN-beta, and patients with hepatitis C treated with rIFN-alpha. A few reports have demonstrated nAbs in MPN patients......: ET: 67% CR, 29 % PR; PV: 64% CR, 31% PR (ELN 2009 criteria); PMF: 50% had at least a minor response (EUMNET). The median serum concentration of bioactive IFN-alpha at 12 months was 12,4 (range...

  4. Vaniprevir with pegylated interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Manns, Michael P; Gane, Edward; Rodriguez-Torres, Maribel


    mg once-daily [QD], or 800 mg QD) for 28 days, then open-label Peg-IFN-α-2a and RBV for an additional 44 weeks. The primary efficacy endpoint was rapid viral response (RVR), defined as undetectable plasma HCV RNA at week 4. Across all doses, vaniprevir was associated with a rapid two-phase decline...

  5. Inducibility of STAT 1/SOCS 3 transcripts and proteins by interferon-alpha/gamma in human melanoma cell lines

    Czech Academy of Sciences Publication Activity Database

    Kovařík, Aleš; Fojtová, Miloslava; Boudný, V.; Adamková, L.; Kovařík, J.


    Roč. 14, Suppl. 1 (2004), s. S87 ISSN 1107-3756. [World Congress on Advances in Oncology /9./ and International Symposium on Molecular Medicine /7./. 14.10.2004-16.10.2004, Hersonissos] R&D Projects: GA MZd NC7139; GA ČR GA301/03/0370; GA AV ČR IBS5004010 Keywords : melanoma cells * STAT 1 * SOCS 3 Subject RIV: BO - Biophysics

  6. Limited regression of central giant cell granuloma by interferon alpha after failed calcitonin therapy: a report of 2 cases

    NARCIS (Netherlands)

    de Lange, J.; van den Akker, H.P.; van den Berg, H.; Richel, D.J.; Gortzak, R.A.T.


    Central giant cell granuloma (CGCG) is a benign lesion of the jaws with a sometimes locally aggressive behaviour. The most common therapy is surgical curettage which has a high recurrence rate, especially in lesions with aggressive signs and symptoms (i.e. pain, paresthesia, root-resorption and

  7. The long-term effect of treatment with interferon-alpha 2a in chronic hepatitis B

    DEFF Research Database (Denmark)

    Krogsgaard, K


    published multicentre, randomized, controlled trials were analysed. Information about survival and response during long-term follow-up was available in 340 (73%) and 308 (66%) of 469 randomized patients respectively. Response to therapy (viral clearance) was defined as: loss of hepatitis B virus (HBV) DNA...

  8. Interferon-alpha treatment may negatively influence disease progression in melanoma patients by hyperactivation of STAT3 protein

    Czech Academy of Sciences Publication Activity Database

    Humpolíková Adámková, L.; Kovařík, J.; Dušek, L.; Lauerová, L.; Boudný, V.; Fait, V.; Fojtová, Miloslava; Krejčí, E.; Kovařík, Aleš


    Roč. 45, - (2009), s. 1315-1323 ISSN 0959-8049 Grant - others:GA ČR(CZ) GA301/06/0912 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : malignant melanoma * interferons * STAT3 activation Subject RIV: BO - Biophysics Impact factor: 4.121, year: 2009

  9. Exacerbated apoptosis of cells infected with infectious bursal disease virus (IBDV) upon exposure to Interferon alpha (IFN-α). (United States)

    Cubas-Gaona, Liliana L; Diaz-Beneitez, Elisabet; Ciscar, Marina; Rodríguez, José F; Rodríguez, Dolores


    Infectious bursal disease virus (IBDV) belongs to the Birnaviridae family and is the etiological agent of a highly contagious and immunosuppressive disease (IBD) that affects domestic chickens ( Gallus gallus ). IBD or Gumboro disease leads to high morbidity and mortality of infected animals, and is responsible for major economic losses to the poultry industry world-wide. IBD is characterized by a massive loss of IgM-bearing B lymphocytes and the destruction of the bursa of Fabricius. The molecular bases of the IBDV pathogenicity are still poorly understood, nonetheless, an exacerbated cytokine immune response and B cell depletion due to apoptosis are considered main factors contributing to the severity of the disease. Here we have studied the role of type I interferon (IFN) on IBDV infection. While IFN pre-treatment confers protection against subsequent IBDV infection, IFN addition to infected cell cultures early after infection drives to a massive apoptotic cell death. Downregulation of PKR, TNF-α or nuclear factor-κB (NF-κB) expression drastically reduces the extent of apoptosis, indicating that these are critical proteins in the apoptotic response induced by IBDV upon treatment with IFN-α. Our results indicate that IBDV genomic dsRNA is a major viral factor contributing to apoptosis triggering. These findings provide novel insights into the potential mechanisms of IBDV-induced immunosuppression and pathogenesis in chickens. IMPORTANCE IBDV infection represents an important threat to the poultry industry world-wide. IBDV-infected chickens develop a severe immunosuppression, which render them highly susceptible to secondary infections, and unresponsive to vaccination against other pathogens. The early dysregulation of the innate immune response lead by IBDV infection, and the exacerbated apoptosis of B cells, have been proposed as the main factors contributing to virus-induced immunopathogenesis. Our work contributes for the first time to elucidating a potential mechanism driving apoptotic death of IBDV infected cells upon exposure to type I IFN. We provide solid evidence about the critical importance of PKR, TNF-α and NF-κB in this phenomenon. The described mechanism could facilitate an early clearance of infected cells, thereby aiding to amelioration of IBDV-induced pathogenesis, but it could also contribute to B-cell depletion and immunosuppression. The balance between these two opposing effects might be dramatically affected by the genetic backgrounds of both the host and the infecting virus strain. Copyright © 2018 American Society for Microbiology.

  10. Monocyte-derived interferon-alpha primed dendritic cells in the pathogenesis of psoriasis: new pieces in the puzzle. (United States)

    Farkas, Arpád; Kemény, Lajos


    Psoriasis is a common chronic inflammatory skin disorder with serious clinical, psychosocial, and economic consequences. There is much evidence that different dendritic cell (DC) subsets, various proinflammatory cytokines and Toll-like receptors (TLRs) have a central role in the pathogenesis of the disease. One of the early events in psoriatic inflammation is the secretion of interferon (IFN)-α by activated plasmacytoid DCs, a special DC subset present in symptomless psoriatic skin. Secreted IFN-α along with other proinflammatory cytokines can lead to monocyte-derived DC (moDC) development, which might contribute to T-helper (Th)1 and Th17 lymphocyte differentiation/activation and to keratinocyte proliferation. Recently it was proven that interleukin (IL)-12 and IL-23 play a critical role in this process. Additionally in psoriatic lesions, Th1 and Th17 lympocytes can interact with monocytes and instruct these cells to differentiate into Th1- and Th17-promoting moDCs, further governing the formation and function of specialized moDC subsets. The concept we present here focuses on the initial and central role of IFN-α, on the importance of other proinflammatory cytokines, on TLR stimulation and on the effect of T lymphocytes in priming moDCs, which may play an important role in initiating and maintaining psoriasis. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Induction of interferon-alpha by glycoprotein D of herpes simplex virus : A possible role of chemokine receptors

    NARCIS (Netherlands)

    Ankel, H; Westra, DF; Welling-Wester, S; Lebon, P


    The induction of type I interferons by most RNA viruses is initiated by virus-derived double-stranded (ds)RNA. However, retro- and DNA-viruses, which do not synthesize dsRNA, must rely on different mechanisms of induction. For human immunodeficiency virus type 1 (HIV-1), recombinant glycoproteins

  12. Long-term effects of interferon-alpha in five HIV-positive patients with chronic hepatitis B. (United States)

    di Martino, V; Lunel, F; Cadranel, J F; Hoang, C; Parlier, Y; Le Charpentier, Y; Opolon, P


    Chronic hepatitis B viral infection is common in human immunodeficiency virus (HIV) carriers, but the effectiveness of interferon therapy is still unknown. We report the results of a long-term pilot study of five patients, who were infected with HIV and chronic hepatitis B, treated by interferon. Five males co-infected with HIV and hepatitis B virus (HBV) (mean age 27 years) were given a 6-month course of interferon (IFN)-alpha 2b 5 million units (MU) three times weekly. On initiating the treatment, their CD4 lymphocyte count was 340-553 mm-3, their CDC stage was IIa-III; all had histologically proven chronic hepatitis, with Knodell's score ranging from 6-10, and active HBV replication (HBV DNA and hepatitis B e antigen (HBeAg) were detectable). There was no associated hepatitis delta virus (H delta V) or hepatitis C virus (HCV) infection. Follow-up was for 53 months on average (24-74 months). After the treatment, hepatitis B e antibody (HBeAb) and hepatitis B s antibody (HBsAb) seroconversion was observed in one patient, HBeAb seroconversion alone in two patients, HBV DNA was absent from serum in three patients, and HBV DNA significantly decreased in one patient. The serum alanine aminotransferase (ALT) activity was normal in four patients. Histological improvement was obtained in four patients. The HIV stage remained unchanged in all patients during the whole follow-up. These preliminary results suggest that interferon can be successfully used in immunocompetent HIV carriers with chronic hepatitis B as well as in HIV-negative patients.

  13. Interleukin-6 concentrations in the serum of patients with AIDS-associated Kaposi's sarcoma during treatment with interferon-alpha

    NARCIS (Netherlands)

    de Wit, R.; Raasveld, M. H.; ten Berge, R. J.; van der Wouw, P. A.; Bakker, P. J.; Veenhof, C. H.


    Interleukin-6 (IL-6) levels were determined in the serum of 14 HIV-1-infected patients with Kaposi's sarcoma, 10 HIV-1-infected patients without symptoms, and 10 healthy male subjects. IL-6 levels were also determined in the serum of the 14 patients with Kaposi's sarcoma during treatment with

  14. Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations. (United States)

    Kozora, E; Filley, C M; Zhang, L; Brown, M S; Miller, D E; Arciniegas, D B; Pelzman, J L; West, S G


    This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations.

  15. Gene-Expression-Guided Selection of Candidate Loci and Molecular Phenotype Analyses Enhance Genetic Discovery in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Yelena Koldobskaya


    Full Text Available Systemic lupus erythematosus (SLE is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-α. In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs for validation. The top 200 GWAS SNPs were searched in a database which compares genome-wide expression data to genome-wide SNP genotype data in HapMap cell lines. SNPs were chosen for validation if they were associated with differential expression of 15 or more genes at a significance of P<9×10−5. This resulted in 11 SNPs which were genotyped in 453 SLE patients and 418 matched controls. Three SNPs were associated with SLE-associated autoantibodies, and one of these SNPs was also associated with serum IFN-α (P<4.5×10−3 for all. One additional SNP was associated exclusively with serum IFN-α. Case-control analysis was insensitive to these molecular subphenotype associations. This study illustrates the use of gene expression data to rationally select candidate loci in autoimmune disease, and the utility of stratification by molecular phenotypes in the discovery of additional genetic associations in SLE.

  16. Gene-expression-guided selection of candidate loci and molecular phenotype analyses enhance genetic discovery in systemic lupus erythematosus. (United States)

    Koldobskaya, Yelena; Ko, Kichul; Kumar, Akaash A; Agik, Sandra; Arrington, Jasmine; Kariuki, Silvia N; Franek, Beverly S; Kumabe, Marissa; Utset, Tammy O; Jolly, Meenakshi; Skol, Andrew D; Niewold, Timothy B


    Systemic lupus erythematosus (SLE) is a highly heterogeneous autoimmune disorder characterized by differences in autoantibody profiles, serum cytokines, and clinical manifestations. We have previously conducted a case-case genome-wide association study (GWAS) of SLE patients to detect associations with autoantibody profile and serum interferon alpha (IFN-α). In this study, we used public gene expression data sets to rationally select additional single nucleotide polymorphisms (SNPs) for validation. The top 200 GWAS SNPs were searched in a database which compares genome-wide expression data to genome-wide SNP genotype data in HapMap cell lines. SNPs were chosen for validation if they were associated with differential expression of 15 or more genes at a significance of P < 9 × 10(-5). This resulted in 11 SNPs which were genotyped in 453 SLE patients and 418 matched controls. Three SNPs were associated with SLE-associated autoantibodies, and one of these SNPs was also associated with serum IFN-α (P < 4.5 × 10(-3) for all). One additional SNP was associated exclusively with serum IFN-α. Case-control analysis was insensitive to these molecular subphenotype associations. This study illustrates the use of gene expression data to rationally select candidate loci in autoimmune disease, and the utility of stratification by molecular phenotypes in the discovery of additional genetic associations in SLE.

  17. Suppression of Angiogenesis and Therapy of Human Colon Cancer Liver Metastasis by Systemic Administration of Interferon-α

    Directory of Open Access Journals (Sweden)

    Shutaro Ozawa


    Full Text Available The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-α can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-α-sensitive or KM12L4 IFNR (IFN-α-resistant cells were injected into the spleen of nude mice. Seven days later, the mice were treated with subcutaneous (s.c. injections of IFN-α (70,000 units/week at different dosing schedules (1, 2, or 7 times/week. Significant inhibition of tumor growth, vascularization and expression of basic fibroblast growth factor (bFGF or matrix metal loproteinase9 (MMP-9 mRNA and protein occurred in mice given daily injections of IFN-α. Kinetic analysis of therapy showed that daily s.c. administrations of 10,000 units of IFN-α induced apoptosis in liver metastasis-associated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activity of IFN-α-2a depends on frequent administration of the optimal biologic dose.

  18. Effectiveness of mouse interferon alpha/beta compared to single-agent chemotherapy in increasing survival time of mice after intravenous inoculation of Friend erythroleukemia cells. (United States)

    Gresser, I; Maury, C; Belardelli, F; Maunoury, M T; Machover, D


    DBA/2 mice received an iv injection of 2 X 10(6) Friend erythroleukemia cells (FLCs; approximately equal to 4 X 10(5) lethal dose50), which multiplied rapidly in the liver and spleen and killed all untreated or control treated mice between 7 and 12 days. Daily interferon (IFN) treatment resulted in a very marked increase in survival time and apparent cure of 4 of 22 tumor-inoculated mice. In contrast, treatment of tumor-injected (iv) mice with cyclophosphamide, 5-fluorouracil, and methotrexate increased survival time by only a few days; and treatment of mice with cisplatin, vincristine, doxorubicin, bleomycin, or etoposide was ineffective. However, when FLCs were injected ip, both cytostatic drugs and IFN exerted an antitumor effect. We conclude that IFN alpha/beta was particularly effective in inhibiting the development of liver and spleen metastases and in increasing mouse survival time after iv inoculation of FLCs.

  19. Astrocyte-targeted expression of interleukin-3 and interferon-alpha causes region-specific changes in metallothionein expression in the brain

    DEFF Research Database (Denmark)

    Giralt, M; Carrasco, J; Penkowa, M


    Transgenic mice expressing IL-3 and IFN-alpha under the regulatory control of the GFAP gene promoter (GFAP-IL3 and GFAP-IFNalpha mice) exhibit a cytokine-specific, late-onset chronic-progressive neurological disorder which resemble many of the features of human diseases such as multiple sclerosis...... was confirmed by immunohistochemistry. MT-III immunoreactivity was present in cells that were mainly round or amoeboid monocytes/macrophages and in astrocytes. MT-I+II induction was more generalized in the GFAP-IFNalpha (GIFN12 and GIFN39 lines) mice, with significant increases in the cerebellum, thalamus...

  20. Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function

    DEFF Research Database (Denmark)

    Trepiakas, Redas; Pedersen, Anders Elm; Met, Ozcan


    and PGE(2) used for generating standard DCs (sDC). Several studies indicate that IFN-alpha might also be important for DC differentiation and maturation. In this study, we tested the effect of IFN-alpha alone or as addition to the gold standard sDC cocktail. We observed that maturation by IFN-alpha......Monocyte-derived dendritic cells (DCs) are used as adjuvant cells in cancer immunotherapy and have shown promising results. In order to obtain full functional capacity, these DCs need to be maturated, and the current "gold standard" for this process is maturation with TNF-alpha, IL-1beta, IL-6...... differs from sDC maturation: The major phenotypic change after IFN-alpha maturation was dose-dependent up-regulation of CD38 but not CD83, while sDCs expressed the opposite profile with low CD38 and high CD83 expression. Similarly, maturation by Poly I:C leads to CD38high, CD83low DCs indicating...

  1. The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin

    Directory of Open Access Journals (Sweden)

    Younossi Zobair M


    Full Text Available Abstract Background Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients. Methods Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56 and was correlated with IL28B genotype (IL28B C/C or non-C/C over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP. Pathways were ranked based on number of gene involved separately per each study cohort. Results The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype. Conclusions IL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV.

  2. Updated estimates of survival and cost effectiveness for imatinib versus interferon-alpha plus low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukaemia. (United States)

    Reed, Shelby D; Anstrom, Kevin J; Li, Yanhong; Schulman, Kevin A


    For trials in which participants are followed beyond the main study period to assess long-term outcomes, economic evaluations conducted using short-term data should be systematically updated to reflect new information. We used 60-month survival data from the IRIS (International Randomized study of Interferon vs STI571) trial to update previously published cost-effectiveness estimates, based on 19 months of follow-up, of imatinib versus interferon (IFN)-alpha plus low-dose cytarabine in patients with chronic-phase chronic myeloid leukaemia. For patients treated with imatinib, we used the 60-month data to calibrate the survival curves generated from the original cost-effectiveness model. We used historical data to model survival for patients randomized to IFNalpha. We updated costs for medical resources using 2006 Medicare reimbursement rates and applied average wholesale prices (AWPs) and wholesale acquisition costs (WACs) to study medications. Five-year survival for patients randomized to imatinib was better than predicted in the original model (89.4% vs 83.2%). We estimated remaining life expectancy with first-line imatinib to be 19.1 life-years (3.8 life-years over the original model) and 15.2 QALYs (3.1 QALYs over the original estimate). Estimates for IFNalpha remained at 9.1 life-years and 6.3 QALYs. When we applied AWPs to study medications, incremental cost-effectiveness ratios (ICERs) were $US 51,800-57,500 per QALY. When we applied WACs, ICERs were $US 42,000-46,200 per QALY. Although the analysis revealed that the original survival estimates were conservative, the updated cost-effectiveness ratios were consistent with, or slightly higher than, the original estimates, depending on the method for assigning costs to study medications.

  3. Pegylated-Interferon Alpha 2b and Ribavirin for Recurrent Hepatitis C after Liver Transplantation: From a Canadian Experience to Recommendations for Therapy

    Directory of Open Access Journals (Sweden)

    Mohamed Babatin


    Full Text Available BACKGROUND: Recurrent hepatitis C (HCV after liver transplantation (LT is often more aggressive and treatments tend to be less successful. Pegylated-interferon and ribavirin are the standard of care for the treatment of HCV; however, there is limited published experience of its use after LT.

  4. Differences in HCV viral decline between low and standard-dose pegylated-interferon-alpha-2a with ribavirin in HIV/HCV genotype 3 patients.

    Directory of Open Access Journals (Sweden)

    Antonio Rivero-Juárez

    Full Text Available BACKGROUND: The aim of the study was to analyze the different impact of standard and low-dose Peg-IFN-α2a/RBV therapies on HCV viral decline in HIV/HCV genotype 3 co-infected patients during the first weeks of treatment. METHODS: Plasma HCV viral decline was analyzed between baseline and weeks 1, 2 and 4 in two groups of treatment-naïve HCV genotype 3 patients with HIV co-infection. The Standard Dose Group (SDG included patients who received Peg-IFN at 180 µg/per week with a weight-adjusted dose of ribavirin; Low-Dose Group (LDG patients received Peg-IFN at 135 µg/per week with 800 mg/day ribavirin. The effect of IL28B genotype on HCV viral decline was evaluated in both groups. HCV viral decline was analyzed using a multivariate linear regression model. RESULTS: One hundred and six patients were included: 48 patients in the SDG and 58 in the LDG. HCV viral decline for patients in the LDG was less than for those in the SDG (week 1:1.72±0.74 log(10 IU/mL versus 1.78±0.67 log(10 IU/mL, p = 0.827; week 2:2.3±0.89 log(10 IU/mL versus 3.01±1.02 log(10 IU/mL, p = 0.013; week 4:3.52±1.2 log(10 IU/mL versus 4.09±1.1 log(10 IU/mL, p = 0.005. The linear regression model identified the Peg-IFN/RBV dose as an independent factor for HCV viral decline at week 4. CONCLUSIONS: Our results showed that HCV viral decline was less for patients in the low-dose group compared to those receiving the standard dose. Until a randomized clinical trial is conducted, clinicians should be cautious about using lower doses of Peg-IFN/RBV in HIV/HCV genotype 3 co-infected patients.

  5. Frequency of thyroid dysfunctions during interferon alpha treatment of single and combination therapy in hepatitis C virus-infected patients: a systematic review based analysis.

    Directory of Open Access Journals (Sweden)

    Chandrasekharan Nair Kesavachandran

    Full Text Available Thyroid dysfunction is the commonest endocrinopathy associated with HCV infection due to interferon-based treatment. This comprehensive and systematic review presents the available evidence for newly developed thyroid antibodies and dysfunctions during interferon treatment (both single and combination in HCV patients.This systematic review was conducted in accordance with the PRISMA guidelines. The data generated were used to analyze the risk for thyroid dysfunctions during interferon (IFN treatment in HCV patients. There was a wide range in the incidence of newly developed thyroid dysfunctions and thyroid antibodies in HCV patients during IFN treatment (both single and combination. The wide range of incidence also denoted the possibility of factors other than IFN treatment for thyroid-related abnormalities in HCV patients. These other factors include HCV viral factors, genetic predisposition, environmental factors, and patho-physiological factors. Variations in IFN dosage, treatment duration of IFN, definition/criteria followed in each study for thyroid dysfunction and irregular thyroid function testing during treatment in different studies influence the outcome of the single studies and jeopardise the validity of a pooled risk estimate of side effects of thyroid dysfunction. Importantly, reports differ as to whether the thyroid-related side effects disappear totally after withdrawal of the IFN treatment.The present review shows that there is a wide range in the incidence of newly developed thyroid dysfunctions and thyroid antibodies in IFN treated HCV patients. This is a comprehensive attempt to collate relevant data from 56 publications across several nations about IFN (both mono and combination therapy related thyroid dysfunction among HCV patients. The role of each factor in causing thyroid dysfunctions in HCV patients treated with IFN should be analyzed in detail in future studies, for a better understanding of the problem and sounder clinical management of the disease.

  6. De novo Cryoglobulinaemic Mononeuritis Multiplex during Treatment of Chronic Hepatitis C Infection: A Viral Effect or Induced by Pegylated Interferon Alpha

    Directory of Open Access Journals (Sweden)

    J.R. Potts


    Full Text Available Cryoglobulinaemic mononeuritis multiplex (MNM is an extrahepatic manifestation of chronic hepatitis C virus (HCV infection for which interferon-based antiviral therapy is currently the treatment of choice. Rarely MNM can be associated with HCV treatment though generally in the setting of pre-existing cryoglobulinaemia and detectable HCV viraemia. We report an unusual case of de novo MNM occurring late during the course of pegylated interferon and ribavirin therapy for chronic HCV infection, following a prolonged period of viral suppression. The patient had no evidence of cryoglobulinaemia prior to HCV treatment and undetectable HCV RNA levels at the time of presentation with MNM. The case raises the possibility that MNM could develop as an adverse immunomodulatory effect of pegylated interferon therapy.

  7. Long-term follow-up of conjunctival melanoma treated with topical interferon alpha-2b eye drops as adjunctive therapy following surgical resection. (United States)

    Kikuchi, Iku; Kase, Satoru; Ishijima, Kan; Ishida, Susumu


    The purpose of this study was to report the clinical outcomes of patients with conjunctival melanoma treated with interferon (IFN) α-2b eye drops following local tumor resection. Five eyes of five patients were enrolled in this study. All patients underwent the local resection of tumors, and topical IFNα-2b eye drops were subsequently administered 4 times/day until the complete disappearance of the pigmented lesions determined by slit-lamp examination. Ophthalmological findings, histopathological findings, and imaging modalities were retrospectively analyzed. The age of the patients ranged from 65 to 84 years (mean: 75.4 years). Locations of the tumor were the bulbar conjunctiva in three eyes, multiple palpebral conjunctivas in one eye, and palpebral conjunctiva and caruncle in one eye. All patients received topical IFNα-2b eye drop treatment for 6-10 months. Follow-up periods after resection ranged from 18 to 78 months. Histologically, all excised conjunctival tumors were diagnosed with malignant melanoma, where the surgical margins were completely negative in one patient. No patients had suffered from severe adverse effects related to IFNα-2b. Four out of five patients consequently achieved complete remission. Since one eye in one case showed resistance to the local chemotherapy containing IFNα-2b eye drops and the subconjunctival injection of IFN-β, orbital exenteration was eventually required 12 months after local resection. Topical IFNα-2b eye drops may be safe and one of the useful adjunctive treatments following surgical resection for patients with conjunctival melanoma.

  8. Expression of intracellular interferon-alpha confers antiviral properties in transfected bovine fetal fibroblasts and does not affect the full development of SCNT embryos. (United States)

    Yu, Dawei; Zhang, Shoufeng; Du, Weihua; Zhang, Jinxia; Fan, Zongxing; Hao, Haisheng; Liu, Yan; Zhao, Xueming; Qin, Tong; Zhu, Huabin


    Foot-and-mouth disease, one of the most significant diseases of dairy herds, has substantial effects on farm economics, and currently, disease control measures are limited. In this study, we constructed a vector with a human interferon-α (hIFN-α) (without secretory signal sequence) gene cassette containing the immediate early promoter of human cytomegalovirus. Stably transfected bovine fetal fibroblasts were obtained by G418 selection, and hIFN-α transgenic embryos were produced by somatic cell nuclear transfer (SCNT). Forty-six transgenic embryos were transplanted into surrogate cows, and five cows (10.9%) became pregnant. Two male cloned calves were born. Expression of hIFN-α was detected in transfected bovine fetal fibroblasts, transgenic SCNT embryos, and different tissues from a transgenic SCNT calf at two days old. In transfected bovine fetal fibroblasts, expression of intracellular IFN-α induced resistance to vesicular stomatitis virus infection, increased apoptosis, and induced the expression of double-stranded RNA-activated protein kinase gene (PKR) and the 2'-5'-oligoadenylate synthetase gene (2'-5' OAS), which are IFN-inducible genes with antiviral activity. Analysis by qRT-PCR showed that the mRNA expression levels of PKR, 2'-5' OAS, and P53 were significantly increased in wild-type bovine fetal fibroblasts stimulated with extracellular recombinant human IFN-α-2b, showing that intracellular IFN-α induces biological functions similar to extracellular IFN-α. In conclusion, expression of intracellular hIFN-α conferred antiviral properties in transfected bovine fetal fibroblasts and did not significantly affect the full development of SCNT embryos. Thus, IFN-α transgenic technology may provide a revolutionary way to achieve elite breeding of livestock.

  9. Understanding early serum hepatitis D virus and hepatitis B surface antigen kinetics during pegylated interferon-alpha therapy via mathematical modeling. (United States)

    Guedj, Jeremie; Rotman, Yaron; Cotler, Scott J; Koh, Christopher; Schmid, Peter; Albrecht, Jeff; Haynes-Williams, Vanessa; Liang, T Jake; Hoofnagle, Jay H; Heller, Theo; Dahari, Harel


    There is little information on the early kinetics of hepatitis delta virus (HDV) and hepatitis B surface antigen (HBsAg) during interferon-α therapy. Here a mathematical model was developed and fitted to frequent HDV and HBsAg kinetic data from 10 patients during the first 28 weeks of pegylated-interferon-α2a (peg-IFN) therapy. Three patients achieved a complete virological response (CVR), defined as undetectable HDV 6 months after treatment stopped with loss of HBsAg and anti-HBsAg seroconversion. After initiation of therapy, a median delay of 9 days (interquartile range [IQR]: 5-15) was observed with no significant changes in HDV level. Thereafter, HDV declined in a biphasic manner, where a rapid first phase lasting for 25 days (IQR: 23-58) was followed by a slower or plateau second phase. The model predicts that the main effect of peg-IFN is to reduce HDV production/release with a median effectiveness of 96% (IQR: 93-99.8). Median serum HDV half-life (t1/2 ) was estimated as 2.9 days (IQR: 1.5-5.3) corresponding to a pretreatment production and clearance of about 10(10) (IQR: 10(9.7) -10(10.7) ) virions/day. None of the patients with flat second phase in HDV achieved CVR. HBsAg kinetics of decline paralleled the second phase of HDV decline consistent with HBsAg-productive-infected cells being the main source of production of HDV, with a median t1/2 of 135 days (IQR: 20-460). The interferon lambda-3 polymorphism (rs12979860) was not associated with kinetic parameters. Modeling results provide insights into HDV-host dynamics, the relationship between serum HBsAg levels and HBsAg-infected cells, IFN's mode of action, and its effectiveness. The observation that a flat second phase in HDV and HBsAg kinetics was associated with failure to achieve CVR provides the basis to develop early stopping rules during peg-IFN treatment in HDV-infected patients. © 2014 by the American Association for the Study of Liver Diseases. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

  10. Interferon-alpha-induced changes in surface antigens in a hairy-cell leukemia (JOK-1), and a Burkitt's lymphoma cell line (Daudi) during in vitro culture

    DEFF Research Database (Denmark)

    Nielsen, B; Madsen, P S; Jensen, A W


    In further studying the mechanism of action of IFN-alpha in HCL, we cultured the HCL cell line JOK-1 and the IFN-sensitive Burkitt cell line Daudi with and without IFN-alpha and investigated the changes in density of a number of surface antigens by use of mAb and flow cytometry analyses. During...... culture with IFN-alpha, reproducible changes were induced in both cell lines, which were qualitatively similar but differed quantitatively with small and transient changes in JOK-1. Significant decreases in surface antigen expression were observed for CD 19, 23, 37, and for IgM on both cell lines...... of IFN-alpha in HCL was not paralleled by a specific direct effect on JOK-1 in vitro. Our findings therefore do not support the theory that IFN's mechanism of action in vivo is a direct effect on HC, but suggest that indirect effects are involved. Udgivelsesdato: 1992-Mar...

  11. Expression of intracellular interferon-alpha confers antiviral properties in transfected bovine fetal fibroblasts and does not affect the full development of SCNT embryos.

    Directory of Open Access Journals (Sweden)

    Dawei Yu

    Full Text Available Foot-and-mouth disease, one of the most significant diseases of dairy herds, has substantial effects on farm economics, and currently, disease control measures are limited. In this study, we constructed a vector with a human interferon-α (hIFN-α (without secretory signal sequence gene cassette containing the immediate early promoter of human cytomegalovirus. Stably transfected bovine fetal fibroblasts were obtained by G418 selection, and hIFN-α transgenic embryos were produced by somatic cell nuclear transfer (SCNT. Forty-six transgenic embryos were transplanted into surrogate cows, and five cows (10.9% became pregnant. Two male cloned calves were born. Expression of hIFN-α was detected in transfected bovine fetal fibroblasts, transgenic SCNT embryos, and different tissues from a transgenic SCNT calf at two days old. In transfected bovine fetal fibroblasts, expression of intracellular IFN-α induced resistance to vesicular stomatitis virus infection, increased apoptosis, and induced the expression of double-stranded RNA-activated protein kinase gene (PKR and the 2'-5'-oligoadenylate synthetase gene (2'-5' OAS, which are IFN-inducible genes with antiviral activity. Analysis by qRT-PCR showed that the mRNA expression levels of PKR, 2'-5' OAS, and P53 were significantly increased in wild-type bovine fetal fibroblasts stimulated with extracellular recombinant human IFN-α-2b, showing that intracellular IFN-α induces biological functions similar to extracellular IFN-α. In conclusion, expression of intracellular hIFN-α conferred antiviral properties in transfected bovine fetal fibroblasts and did not significantly affect the full development of SCNT embryos. Thus, IFN-α transgenic technology may provide a revolutionary way to achieve elite breeding of livestock.

  12. Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus. (United States)

    Miyaki, Eisuke; Hiraga, Nobuhiko; Imamura, Michio; Uchida, Takuro; Kan, Hiromi; Tsuge, Masataka; Abe-Chayama, Hiromi; Hayes, C Nelson; Makokha, Grace Naswa; Serikawa, Masahiro; Aikata, Hiroshi; Ochi, Hidenori; Ishida, Yuji; Tateno, Chise; Ohdan, Hideki; Chayama, Kazuaki


    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients.

  13. Development of a cultivation process for the enhancement of human interferon alpha 2b production in the oleaginous yeast, Yarrowia lipolytica

    Directory of Open Access Journals (Sweden)

    Gasmi Najla


    Full Text Available Abstract Background As an oleaginous yeast, Yarrowia lipolytica is able to assimilate hydrophobic substrates. This led to the isolation of several promoters of key enzymes of this catabolic pathway. Less is known about the behavior of Y. lipolytica in large bioreactors using these substrates. There is therefore a lack of established know-how concerning high cell density culture protocols of this yeast. Consequently, the establishment of suitable induction conditions is required, to maximize recombinant protein production under the control of these promoters. Results Human interferon α2b (huIFN α2b production in Yarrowia lipolytica was used as a model for the enhancement of recombinant protein production under the control of the oleic acid (OA-inducible promoter POX2. Cell viability and heterologous protein production were enhanced by exponential glucose feeding, to generate biomass before OA induction. The optimal biomass level before induction was determined (73 g L-1, and glucose was added with oleic acid during the induction phase. Several oleic acid feeding strategies were assessed. Continuous feeding with OA at a ratio of 0.02 g OA per g dry cell weight increased huIFNα2b production by a factor of 1.88 (425 mg L-1 and decreased the induction time (by a factor of 2.6, 21 h. huIFN α2b degradation by an aspartic protease secreted by Y. lipolytica was prevented by adding pepstatin (10 μM, leading to produce a 19-fold more active huIFN α2b (26.2 × 107 IU mg-1. Conclusion Y. lipolytica, a generally regarded as safe (GRAS microorganism is one of the most promising non conventional yeasts for the production of biologically active therapeutic proteins under the control of hydrophobic substrate-inducible promoter.

  14. Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis. (United States)

    Mogahed, Engy A; Abdelaziz, Hanan; Helmy, Heba; Ghita, Haytham; Abdel Mawla, Mohamed A; Hassanin, Fetouh; Fadel, Fatina I; El-Karaksy, Hanaa


    Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 μg/m 2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.

  15. Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication.

    Directory of Open Access Journals (Sweden)

    Kelly M Cheney


    Full Text Available Type I interferons (IFNα and β are induced directly in response to viral infection, resulting in an antiviral state for the cell. In vitro studies have shown that IFNα is a potent inhibitor of viral replication; however, its role in HIV-1 infection is incompletely understood. In this study we describe the ability of IFNα to restrict HIV-1 infection in primary human macrophages in contrast to peripheral blood mononuclear cells and monocyte-derived dendritic cells. Inhibition to HIV-1 replication in cells pretreated with IFNα occurred at an early stage in the virus life cycle. Late viral events such as budding and subsequent rounds of infection were not affected by IFNα treatment. Analysis of early and late HIV-1 reverse transcripts and integrated proviral DNA confirmed an early post entry role for IFNα. First strand cDNA synthesis was slightly reduced but late and integrated products were severely depleted, suggesting that initiation or the nucleic acid intermediates of reverse transcription are targeted. The depletion of integrated provirus is disproportionally greater than that of viral cDNA synthesis suggesting the possibility of a least an additional later target. A role for either cellular protein APOBEC3G or tetherin in this IFNα mediated restriction has been excluded. Vpu, previously shown by others to rescue a viral budding restriction by tetherin, could not overcome this IFNα induced effect. Determining both the viral determinants and cellular proteins involved may lead to novel therapeutic approaches. Our results add to the understanding of HIV-1 restriction by IFNα.

  16. Preliminary results of treatment with pegylated interferon alpha 2A for chronic hepatitis C virus in kidney transplant candidates on hemodialysis. (United States)

    Casanovas-Taltavull, T; Baliellas, C; Llobet, M; Cruzado, J M; Castellote, J; Casanova, A; Niubó, J; Valls, C; Serrano, T


    At present, there is little published information on the outcome of treatment with pegylated interferon (Peg-IF alpha 2a) in hepatitis C virus (HCV)-infected hemodialysis patients awaiting renal transplantation. The objective of this study was to assess the efficacy and tolerance of Peg-IF alpha 2a in this population. Twelve noncirrhotic HCV-infected patients (10 men, 50 +/- 8 years of age, genotype 1b 84%), were prescribed Peg-IF alpha 2a, at 135 microg/wk for 48 weeks. Liver biopsy was performed in 11 of 12 cases. Six patients completed 48 weeks of treatment, with one end of treatment response (ETR), two sustained viral responses (SVRs), and three HCV relapses. Treatment was shorter in the six remaining patients: two cases 24 weeks (one due to medical reasons with relapse, one due to nonresponse), one patient chose to discontinue at 14 weeks (with relapse), one patient died of stroke at 10 weeks, and in two additional patients interferon was withdrawn at 18 weeks because of severe anemia (SVR) and at 26 weeks due to prolonged fever (relapse). Other secondary treatment-related events included anemia (requiring transfusion in two patients and major erythropoietin administration in six), and fever in four patients. Peg-IF had limited efficacy in this group, with ETR in 83%, SVR in only 25%, and recurrence in 50%. Tolerance was moderate, with 4/12 (33%) discontinuing treatment due to adverse events, personal decision, or death. Large randomized controlled studies are needed to determine the role of Peg-IF treatment in this population.

  17. Effects of nasal or pulmonary delivered treatments with an adenovirus vectored interferon (mDEF201 on respiratory and systemic infections in mice caused by cowpox and vaccinia viruses.

    Directory of Open Access Journals (Sweden)

    Donald F Smee

    Full Text Available An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201 was evaluated for efficacy against lethal cowpox (Brighton strain and vaccinia (WR strain virus respiratory and systemic infections in mice. Two routes of mDEF201 administration were used, nasal sinus (5-µl and pulmonary (50-µl, to compare differences in efficacy, since the preferred treatment of humans would be in a relatively small volume delivered intranasally. Lower respiratory infections (LRI, upper respiratory infections (URI, and systemic infections were induced by 50-µl intranasal, 10-µl intranasal, and 100-µl intraperitoneal virus challenges, respectively. mDEF201 treatments were given prophylactically either 24 h (short term or 56d (long-term prior to virus challenge. Single nasal sinus treatments of 10(6 and 10(7 PFU/mouse of mDEF201 protected all mice from vaccinia-induced LRI mortality (comparable to published studies with pulmonary delivered mDEF201. Systemic vaccinia infections responded significantly better to nasal sinus delivered mDEF201 than to pulmonary treatments. Cowpox LRI infections responded to 10(7 mDEF201 treatments, but a 10(6 dose was only weakly protective. Cowpox URI infections were equally treatable by nasal sinus and pulmonary delivered mDEF201 at 10(7 PFU/mouse. Dose-responsive prophylaxis with mDEF201, given one time only 56 d prior to initiating a vaccinia virus LRI infection, was 100% protective from 10(5 to 10(7 PFU/mouse. Improvements in lung hemorrhage score and lung weight were evident, as were decreases in liver, lung, and spleen virus titers. Thus, mDEF201 was able to treat different vaccinia and cowpox virus infections using both nasal sinus and pulmonary treatment regimens, supporting its development for humans.


    African Journals Online (AJOL)


    May 25, 2009 ... or cryotherapy. Surgery is generally not recommended, as. Kaposi's sarcoma can appear in wound edges. More wide- spread disease, or disease affecting internal organs, is gener- ally treated with systemic therapy with interferon alpha and liposomal anthracyclines.7. Obstructive lymphoedema caused by ...

  19. Egyptian Journal of Medical Human Genetics - Vol 12, No 2 (2011)

    African Journals Online (AJOL)

    Egyptian Journal of Medical Human Genetics - Vol 12, No 2 (2011) ... Serum interferon-alpha level in first degree relatives of systemic lupus erythematosus patients: Correlation with autoantibodies titers · EMAIL FREE FULL TEXT EMAIL FREE FULL ... LB Salah, CB Salem, F B'Chir, K Bouraoui, F Broly, S Saguem, 183-186.

  20. Trait-stratified genome-wide association study identifies novel and diverse genetic associations with serologic and cytokine phenotypes in systemic lupus erythematosus. (United States)

    Kariuki, Silvia N; Franek, Beverly S; Kumar, Akaash A; Arrington, Jasmine; Mikolaitis, Rachel A; Utset, Tammy O; Jolly, Meenakshi; Crow, Mary K; Skol, Andrew D; Niewold, Timothy B


    Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder, characterized by differences in autoantibody profile, serum cytokines, and clinical manifestations. SLE-associated autoantibodies and high serum interferon alpha (IFN-α) are important heritable phenotypes in SLE which are correlated with each other, and play a role in disease pathogenesis. These two heritable risk factors are shared between ancestral backgrounds. The aim of the study was to detect genetic factors associated with autoantibody profiles and serum IFN-α in SLE. We undertook a case-case genome-wide association study of SLE patients stratified by ancestry and extremes of phenotype in serology and serum IFN-α. Single nucleotide polymorphisms (SNPs) in seven loci were selected for follow-up in a large independent cohort of 538 SLE patients and 522 controls using a multi-step screening approach based on novel metrics and expert database review. The seven loci were: leucine-rich repeat containing 20 (LRRC20); protein phosphatase 1 H (PPM1H); lysophosphatidic acid receptor 1 (LPAR1); ankyrin repeat and sterile alpha motif domain 1A (ANKS1A); protein tyrosine phosphatase, receptor type M (PTPRM); ephrin A5 (EFNA5); and V-set and immunoglobulin domain containing 2 (VSIG2). SNPs in the LRRC20, PPM1H, LPAR1, ANKS1A, and VSIG2 loci each demonstrated strong association with a particular serologic profile (all odds ratios > 2.2 and P < 3.5 × 10-4). Each of these serologic profiles was associated with increased serum IFN-α. SNPs in both PTPRM and LRRC20 were associated with increased serum IFN-α independent of serologic profile (P = 2.2 × 10-6 and P = 2.6 × 10-3 respectively). None of the SNPs were strongly associated with SLE in case-control analysis, suggesting that the major impact of these variants will be upon subphenotypes in SLE. This study demonstrates the power of using serologic and cytokine subphenotypes to elucidate genetic factors involved in complex autoimmune disease. The

  1. A Molecular Analysis of the Induction of Class II Major Histocompatibility Antigen Expression on Murine Macrophages by Interferon-Gamma and Its Down-Regulation by Interferon-Alpha/Beta and Dexamethasone (United States)


    y in the generation of murine lupus nephritis and have shown that treatment of (NZB x NZW)F 1 animals in vivo with purified anti-IFN-ymonoclonal... treatment of (NZB x NZW) F1 lupus -like nephritic with monoclonal antibody to yinterferon. J.Exp.Med. 166:798. Jacobi, A. 1877. Diphtherie. Hefte...Natl.Acad. Sci. USA 79: 1703. Wofsy, D. and W. E. Seaman. 1987. Reversal of advanced murine lupus in NZB/NZW F1 mice by treatment with monoclonal

  2. A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

    DEFF Research Database (Denmark)

    Vangsted, Annette J; Klausen, Tobias W; Gimsing, Peter


    Background: Maintenance therapy with interferon- after high-dose treatment with stem cell support in multiple myeloma has been intensively debated. In this study, we evaluated the response to treatment with interferon- in relation to genetic variation in genes related to inflammation. Design...... and Methods: In a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon- as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G...... homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-. Conclusions: Patients who are homozygous carriers...

  3. Systems

    International Nuclear Information System (INIS)



    Papers in this session describe the concept of mined geologic disposal system and methods for ensuring that the system, when developed, will meet all technical requirements. Also presented in the session are analyses of system parameters, such as cost and nuclear criticality potential, as well as a technical analysis of a requirement that the system permit retrieval of the waste for some period of time. The final paper discusses studies under way to investigate technical alternatives or complements to the mined geologic disposal system. Titles of the presented papers are: (1) Waste Isolation System; (2) Waste Isolation Economics; (3) BWIP Technical Baseline; (4) Criticality Considerations in Geologic Disposal of High-Level Waste; (5) Retrieving Nuclear Wastes from Repository; (6) NWTS Programs for the Evaluation of Technical Alternatives or Complements to Mined Geologic Repositories - Purpose and Objectives

  4. systems

    Directory of Open Access Journals (Sweden)

    Alexander Leonessa


    Full Text Available A nonlinear robust control-system design framework predicated on a hierarchical switching controller architecture parameterized over a set of moving nominal system equilibria is developed. Specifically, using equilibria-dependent Lyapunov functions, a hierarchical nonlinear robust control strategy is developed that robustly stabilizes a given nonlinear system over a prescribed range of system uncertainty by robustly stabilizing a collection of nonlinear controlled uncertain subsystems. The robust switching nonlinear controller architecture is designed based on a generalized (lower semicontinuous Lyapunov function obtained by minimizing a potential function over a given switching set induced by the parameterized nominal system equilibria. The proposed framework robustly stabilizes a compact positively invariant set of a given nonlinear uncertain dynamical system with structured parametric uncertainty. Finally, the efficacy of the proposed approach is demonstrated on a jet engine propulsion control problem with uncertain pressure-flow map data.

  5. T-Cell Gene Therapy to Eradicate Disseminated Breast Cancers (United States)


    9.12.2003, San Diego, USA 2. 9th Congress of the European Hematology Association, Amsterdam, The Netherlands 3. 8th International symposium on...diagnosis and possible pathogenesis. Leuk Lymphoma. 2003;44(12):2103-2108. 109. Ladoyanni E, Nambi R. Psoriasis exacerbated by interferon-alpha in a...aggravation of psoriasis 51,108-111 IFN-α Cutaneous T cell lymphoma Psoriasis 112 IFN-α Mid-gut carcinoid tumors Systemic lupus erythmatosis

  6. A Case of Pott’s Disease with Epidural Abscess and Probable Cerebral Tuberculoma following Bacillus Calmette-Guérin Therapy for Superficial Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Colin B Josephson


    Full Text Available Intravesical Bacillus Calmette-Guérin (BCG immunotherapy is an accepted treatment for transitional cell carcinoma of the bladder. Carcinoma in situ of the bladder progresses to invasive muscular disease in approximately 54% of untreated patients, mandating early initiation of therapy once the diagnosis is confirmed. Should BCG treatment fail, an additional course of BCG combined with interferon-alpha, both administered intravesically, is a promising second-line immunotherapy. In greater than 95% of patients, BCG is tolerated without significant morbidity or mortality. However, both early (within three months of the original treatment and late presentations of systemic infection resulting from intravesical BCG treatment have been described. The present study describes the course of a 75-year-old man with a late presentation of BCG vertebral osteomyelitis, discitis, epidural abscess, bilateral psoas abscesses and probable cerebral tuberculoma, following treatment regimens of intravesical BCG followed by intravesical BCG plus interferon-alpha 2b.

  7. systems

    Directory of Open Access Journals (Sweden)

    Patrick L. Brockett


    Full Text Available Suppose S={{Xnj,   j=1,2,…,kn}} is an infinitesimal system of random variables whose centered sums converge in law to a (necessarily infinitely divisible distribution with Levy representation determined by the triple (γ,σ2,M. If {Yj,   j=1,2,…} are independent indentically distributed random variables independent of S, then the system S′={{YjXnj,j=1,2,…,kn}} is obtained by randomizing the scale parameters in S according to the distribution of Y1. We give sufficient conditions on the distribution of Y in terms of an index of convergence of S, to insure that centered sums from S′ be convergent. If such sums converge to a distribution determined by (γ′,(σ′2,Λ, then the exact relationship between (γ,σ2,M and (γ′,(σ′2,Λ is established. Also investigated is when limit distributions from S and S′ are of the same type, and conditions insuring products of random variables belong to the domain of attraction of a stable law.


    Directory of Open Access Journals (Sweden)

    K. Swarnalatha


    Full Text Available Risk analysis of urban aquatic systems due to heavy metals turns significant due to their peculiar properties viz. persis tence, non-degradab ility, toxicity, and accumulation. Akkulam Veli (AV, an urba n tropical lake in south India is subjected to various environmental stresses due to multiple waste discharge, sand mining, developmental activities, tour ism related activitie s etc. Hence, a comprehensive approach is adopted for risk assessment using modified degree of contamination factor, toxicity units based on numerical sediment quality guidelines (SQGs, and potentialecological risk indices. The study revealed the presence of toxic metals such as Cr, C d, Pb and As and the lake is rated under ‘low ecological risk’ category.

  9. Interferon Induced Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Yusuf Kayar


    Full Text Available Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

  10. Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette–Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study

    Directory of Open Access Journals (Sweden)

    José Mordoh


    Full Text Available The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette–Guerin (BCG and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF is being tested against medium-dose IFN-α2b in stages IIB–III cutaneous melanoma (CM patients (pts after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study ( NCT01729663. Thirty-one pts were randomized to the CSF-470 vaccine (n = 20 or to the IFN-α2b arm (n = 11. During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 107 irradiated CSF-470 cells plus 106 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2–4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS for CSF-470 was observed (p = 0.022. Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1–2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs were grade 1. Pts in the IFN-α2b arm presented grades 2–3 hematological (7/11, hepatic (2/11, and cardiac (1/11 toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (p < 0.0001. Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.

  11. Cutaneous Sarcoidosis: An Uncommon Side Effect of Pegylated Interferon and Ribavirin Use for Chronic Hepatitis C (United States)

    Martins, Elson Vidal; Gaburri, Ana Karla; Gaburri, Debora; Sementilli, Angelo


    The treatment of chronic hepatitis C (CHC) has evolved in the past 15 years and combination of pegylated interferon plus ribavirin is its current standard therapy. However, several side effects are commonly observed and frequently lead to transient or definitive interruption of treatment. Although sarcoidosis in its systemic or cutaneous form is a very rare side effect in such circumstances, some cases have been reported even with conventional interferon. This brief review of the literature and description of a case of sarcoidosis occurring in a tattoo and a scar patient's face, during treatment with pegylated interferon alpha-2b plus ribavirin, is an educative report directed in special to dermatologists. The lesion improved after drug interruption and recurred after retreatment with pegylated interferon alpha-2a. We conclude that this side effect must call the attention of doctors to seek for the diagnosis and therapy as soon as possible in such circumstances. No differences were noticed neither with alpha-2a nor alpha-2b pegylated interferon employment. PMID:21103255

  12. Browse Title Index

    African Journals Online (AJOL)

    Items 51 - 100 of 139 ... Christopher Mafuva, Trayana Djarova, Hilda T Matarira. Vol 14, No 1 (2007), Intrahepatic expression of interferon alpha & interferon alpha receptor ... RB Duda, R Darko, J Seffah, RM Adanu, JK Anarfi, AG Hill. Vol 13, No 3 (2006), Prevalence of perceived pain and its impact on daily lives and activities ...

  13. Correlation between a single nucleotide polymorphism (G/T at nt ...

    African Journals Online (AJOL)



    Oct 12, 2011 ... correlated to achieving sustained virological response (SVR) after pegylated interferon alpha and ribavirin ... ribavirin. Key words: Hepatitis C virus (HCV), interferon (IFN), myxovirus resistance protein (Mx1 protein), myxovirus .... long injection of interferon alpha 2b plus daily oral dose of ribavirin). If SVR is ...

  14. System Budgets

    DEFF Research Database (Denmark)

    Jeppesen, Palle


    The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers.......The lecture note is aimed at introducing system budgets for optical communication systems. It treats optical fiber communication systems (six generations), system design, bandwidth effects, other system impairments and optical amplifiers....

  15. Ventilation systems

    International Nuclear Information System (INIS)



    The present paper deals with - controlled area ventilation systems - ventilation systems for switchgear-building and control-room - other ventilation systems for safety equipments - service systems for ventilation systems. (orig./RW)

  16. Cytokines: their pathogenic and therapeutic role in chronic viral hepatitis Citoquinas: papel patogénico y terapéutico de las hepatitis crónicas víricas

    Directory of Open Access Journals (Sweden)

    J. R. Larrubia


    Full Text Available Cytokines make up a network of molecules involved in the regulation of immune response and organ functional homeostasis. Cytokines coordinate both physiological and pathological processes occurring in the liver during viral infection, including infection control, inflammation, regeneration, and fibrosis. Hepatitis B and hepatitis C viruses interfere with the complex cytokine network brought about by the immune system and liver cells in order to prevent an effective immune response, capable of viral control. This situation leads to intrahepatic sequestration of nonspecific inflammatory infiltrates that release proinflammatory cytokines, which in turn favor chronic inflammation and fibrosis. The therapeutical administration of cytokines such as interferon alpha may result in viral clearance during persistent infection, and revert this process.


    Directory of Open Access Journals (Sweden)

    GIORGIO Selma


    Full Text Available In this study we investigated the effect of 8-Bromoguanosine, an immunostimulatory compound, on the cytotoxicity of macrophages against Leishmania amazonensis in an in vitro system. The results showed that macrophages treated with 8-Bromoguanosine before or after infection are capable to reduce parasite load, as monitored by the number of amastigotes per macrophage and the percentage of infected cells (i.e. phagocytic index. Since 8-Bromoguanosine was not directly toxic to the promastigotes, it was concluded that the ribonucleoside induced macrophage activation. Presumably, 8-Bromoguanosine primed macrophages by inducing interferon alpha and beta which ultimately led to L. amazonensis amastigote killing. The results suggest that guanine ribonucleosides may be useful to treat infections with intracellular pathogens.

  18. Time for change: conventional interferon regimes should not be the standard of care for management of Pakistani genotype-3 in chronic hepatitis C. (United States)

    Qureshi, Muhammad Saleem; Iqbal, Musarrat; Nomani, Ali Zohair; Rasheed, Kamran


    The aim of the present study was to determine the efficacy and side effect profile of conventional interferon alpha-2b plus ribavirin for treating chronic hepatitis C genotype-3 infections in Pakistan. The study was conducted on treating 220 treatment-naïve individuals at KRL Hospital with conventional interferon given for 6 months. Both the response and side effects were analyzed using simple descriptive statistics. Out of total cohort, 84.92% (169 out of 199) achieved end of treatment response (ETR) while 63.31% (126 out of 199) achieved sustained virological response (SVR). Leukopenia, gastrointestinal and miscellaneous systemic complaints were the most common adverse effects. In the context of a low ETR and SVR but a similar side effect profile as that of pegylated regimes, conventional therapy needs to be replaced with peg-interferon as the treatment of choice.

  19. Thermal systems; Systemes thermiques

    Energy Technology Data Exchange (ETDEWEB)

    Lalot, S. [Valenciennes Univ. et du Hainaut Cambresis, LME, 59 (France); Lecoeuche, S. [Ecole des Mines de Douai, Dept. GIP, 59 - Douai (France)]|[Lille Univ. des Sciences et Technologies, 59 - Villeneuve d' Ascq (France); Ahmad, M.; Sallee, H.; Quenard, D. [CSTB, 38 - Saint Martin d' Heres (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Gascoin, N.; Gillard, P.; Bernard, S. [Laboratoire d' Energetique, Explosion, Structure, 18 - Bourges (France); Gascoin, N.; Toure, Y. [Laboratoire Vision et Robotique, 18 - Bourges (France); Daniau, E.; Bouchez, M. [MBDA, 18 - Bourges (France); Dobrovicescu, A.; Stanciu, D. [Bucarest Univ. Polytechnique, Faculte de Genie Mecanique (Romania); Stoian, M. [Reims Univ. Champagne Ardenne, Faculte des Sciences, UTAP/LTM, 51 (France); Bruch, A.; Fourmigue, J.F.; Colasson, S. [CEA Grenoble, Lab. Greth, 38 (France); Bontemps, A. [Universite Joseph Fourier, LEGI/GRETh, 38 - Grenoble (France); Voicu, I.; Mare, T.; Miriel, J. [Institut National des Sciences Appliquees (INSA), LGCGM, IUT, 35 - Rennes (France); Galanis, N. [Sherbrooke Univ., Genie Mecanique, QC (Canada); Nemer, M.; Clodic, D. [Ecole des Mines de Paris, Centre Energetique et Procedes, 75 (France); Lasbet, Y.; Auvity, B.; Castelain, C.; Peerhossaini, H. [Nantes Univ., Ecole Polytechnique, Lab. de Thermocinetiquede Nantes, UMR-CNRS 6607, 44 (France)


    This session about thermal systems gathers 26 articles dealing with: neural model of a compact heat exchanger; experimental study and numerical simulation of the thermal behaviour of test-cells with walls made of a combination of phase change materials and super-insulating materials; hydraulic and thermal modeling of a supercritical fluid with pyrolysis inside a heated channel: pre-dimensioning of an experimental study; energy analysis of the heat recovery devices of a cryogenic system; numerical simulation of the thermo-hydraulic behaviour of a supercritical CO{sub 2} flow inside a vertical tube; mixed convection inside dual-tube exchangers; development of a nodal approach with homogenization for the simulation of the brazing cycle of a heat exchanger; chaotic exchanger for the cooling of low temperature fuel cells; structural optimization of the internal fins of a cylindrical generator; a new experimental approach for the study of the local boiling inside the channels of exchangers with plates and fins; experimental study of the flow regimes of boiling hydrocarbons on a bundle of staggered tubes; energy study of heat recovery exchangers used in Claude-type refrigerating systems; general model of Carnot engine submitted to various operating constraints; the free pistons Stirling cogeneration system; natural gas supplied cogeneration system with polymer membrane fuel cell; influence of the CRN coating on the heat flux inside the tool during the wood unrolling process; transport and mixture of a passive scalar injected inside the wake of a Ahmed body; control of a laser welding-brazing process by infrared thermography; 2D self-adaptative method for contours detection: application to the images of an aniso-thermal jet; exergy and exergy-economical study of an 'Ericsson' engine-based micro-cogeneration system; simplified air-conditioning of telephone switching equipments; parametric study of the 'low-energy' individual dwelling; brief synthesis of

  20. Data Systems vs. Information Systems


    Amatayakul, Margret K.


    This paper examines the current status of “hospital information systems” with respect to the distinction between data systems and information systems. It is proposed that the systems currently existing are incomplete data dystems resulting in ineffective information systems.



    Georgiana Marin; Mihai Catalin Andrei


    In recent decades IT and computer systems have evolved rapidly in economic informatics field. The goal is to create user friendly information systems that respond promptly and accurately to requests. Informatics systems evolved into decision assisted systems, and such systems are converted, based on gained experience, in expert systems for creative problem solving that an organization is facing. Expert systems are aimed at rebuilding human reasoning on the expertise obtained from experts, sto...

  2. Multibody Systems

    DEFF Research Database (Denmark)

    Wagner, Falko Jens


    Multibody Systems is one area, in which methods for solving DAEs are of special interst. This chapter is about multibody systems, why they result in DAE systems and what kind of problems that can arise when dealing with multibody systems and formulating their corresponding DAE system....

  3. Closure system

    International Nuclear Information System (INIS)

    Kube, L.J.


    This invention relates generally to gas-cooled nuclear reactor systems and, more particularly, to an improved closure system for a pressure vessel in such a system wherein a penetration is provided for accommodating a heat exchanger. (author)

  4. Lymph system (United States)

    Lymphatic system ... neck, under the arms, and groin. The lymph system includes the: Tonsils Adenoids Spleen Thymus ... JE, Flynn JA, Solomon BS, Stewart RW. Lymphatic system. In: Ball JW, Dains JE, Flynn JA, Solomon ...

  5. Detection of occult hepatitis B virus among chronic hepatitis C patients

    African Journals Online (AJOL)

    Ola Abd El Kader Mahmoud


    HBV) and hepatitis C virus ..... Table 2 Distribution of S, X, C and pol genes profile and liver enzymes among the 100 HCV positive patients. Gene profile. No ..... affect liver histology or response to therapy with interferon alpha.

  6. Dgroup: DG01750 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available tical recombination) (JAN) D02745 ... Interferon alfa-2b (USAN); Interferon alfa-2b (genetica... DG01750 Chemical ... DGroup Interferon alpha ... D00745 ... Interferon alfa-2a (USAN/INN); Interferon alfa-2a (gene

  7. The importance of animals in human schistosomiasis in South Africa ...

    African Journals Online (AJOL)

    The importance of animals in human schistosomiasis in South Africa is reviewed. The prevalence of animal schistosome species in humans, the role of animals as reservoir hosts of Schistosoma haematobium and S. mansoni, and the possibility of falsepositive serological reactions in humans following exposureto animal or ...

  8. INIS system

    International Nuclear Information System (INIS)

    Sokalski, A.


    History, organizational structure and operation principles of INIS system are presented. The preparation of input, checking and data processing as well as output production, computer forms of files and information retrieval systems are described in detail. The active participation of Poland in the system is emphasized. The possible ways of system development are presented. (author)

  9. Systems effectiveness

    CERN Document Server

    Habayeb, A R


    Highlights three principal applications of system effectiveness: hardware system evaluation, organizational development and evaluation, and conflict analysis. The text emphasizes the commonality of the system effectiveness discipline. The first part of the work presents a framework for system effectiveness, partitioning and hierarchy of hardware systems. The second part covers the structure, hierarchy, states, functions and activities of organizations. Contains an extended Appendix on mathematical concepts and also several project suggestions.

  10. Reactive Systems

    DEFF Research Database (Denmark)

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand

    A reactive system comprises networks of computing components, achieving their goals through interaction among themselves and their environment. Thus even relatively small systems may exhibit unexpectedly complex behaviours. As moreover reactive systems are often used in safety critical systems......, the need for mathematically based formal methodology is increasingly important. There are many books that look at particular methodologies for such systems. This book offers a more balanced introduction for graduate students and describes the various approaches, their strengths and weaknesses, and when...

  11. Bitcoin System

    Directory of Open Access Journals (Sweden)

    Jan Lánský


    Full Text Available Cryptocurrency systems are purely digital and decentralized systems that use cryptographic principles to confirm transactions. Bitcoin is the first and also the most widespread cryptocurrency. The aim of this article is to introduce Bitcoin system using a language understandable also to readers without computer science education. This article captures the Bitcoin system from three perspectives: internal structure, network and users. Emphasis is placed on brief and clear definitions (system components and their mutual relationships. A new system view of the stated terms constitutes author’s own contribution.

  12. Intelligent Systems (United States)

    National Aeronautics and Space Administration — The autonomous systems (AS) project, led by NASA Ames, is developing software for system operation automation. AS technology will help astronauts make more decisions...

  13. Crystal Systems. (United States)

    Schomaker, Verner; Lingafelter, E. C.


    Discusses characteristics of crystal systems, comparing (in table format) crystal systems with lattice types, number of restrictions, nature of the restrictions, and other lattices that can accidently show the same metrical symmetry. (JN)

  14. Filter systems

    International Nuclear Information System (INIS)

    Vanin, V.R.


    The multidetector systems for high resolution gamma spectroscopy are presented. The observable parameters for identifying nuclides produced simultaneously in the reaction are analysed discussing the efficiency of filter systems. (M.C.K.)

  15. Tear System (United States)

    ... and symptoms may result from the tear drainage system becoming obstructed at any point from the puncta ... specializes in the eyelids, orbit, and tear drain system. It’s also important that he or she is ...

  16. Biliary system (United States)

    The biliary system creates, moves, stores, and releases bile into the duodenum . This helps the body digest food. It also assists ... from the liver to the duodenum. The biliary system includes: The gallbladder Bile ducts and certain cells ...

  17. Expert systems

    International Nuclear Information System (INIS)

    Haldy, P.A.


    The definitions of the terms 'artificial intelligence' and 'expert systems', the methodology, areas of employment and limits of expert systems are discussed. The operation of an expert system is described, especially the presentation and organization of knowledge as well as interference and control. Methods and tools for expert system development are presented and their application in nuclear energy are briefly addressed. 7 figs., 2 tabs., 6 refs

  18. Watchdog System

    DEFF Research Database (Denmark)

    Madsen, Tanja Kidholm Osmann; Bahnsen, Chris Holmberg; Jensen, Morten Bornø

    This deliverable is part of WP4. Overall WP4 is motivated by the need for automatic systems that can ease the task of annotating massive amounts of traffic data. Concretely this deliverable is related to WP4.2 - the watchdog system. The idea with the watchdog is to develop a system that can remov...

  19. Embedded Systems

    Indian Academy of Sciences (India)

    system programmers should take into consideration all possi- bilities and write programs that do not fail. Responsiveness: Embedded systems should respond to events as soon as possible. For example, a patient monitoring system should process the patient'S heart signals quickly and immedi- ately notify if any abnormality ...

  20. Systems Engineering (United States)

    Pellerano, Fernando


    This short course provides information on what systems engineering is and how the systems engineer guides requirements, interfaces with the discipline leads, and resolves technical issues. There are many system-wide issues that either impact or are impacted by the thermal subsystem. This course will introduce these issues and illustrate them with real life examples.

  1. Creative Systems

    DEFF Research Database (Denmark)

    Manelius, Anne-Mette; Beim, Anne


    Opsamling af diskussioner på konferencen og udstillingen Creative Systems i september/oktober 2007. Konferencen og Udstillingen Creative Systems sætter fokus på systemer som en positiv drivkraft i den kreative skabelsesproces. CINARK inviterede fire internationale kapaciteter, som indenfor hver...

  2. Systems Biology

    Indian Academy of Sciences (India)

    IAS Admin

    Systems biology seeks to study biological systems as a whole, contrary to the reductionist approach that has dominated biology. Such a view of biological systems emanating from strong foundations of molecular level understanding of the individual components in terms of their form, function and interactions is promising to ...

  3. Digestive System (United States)

    ... Staying Safe Videos for Educators Search English Español Digestive System KidsHealth / For Parents / Digestive System What's in this ... the body can absorb and use. About the Digestive System Almost all animals have a tube-type digestive ...

  4. Embedded Systems

    Indian Academy of Sciences (India)

    sumer electronic systems, they are cost sensitive. Thus their cost must be low. Robustness: Embedded systems should be robust since they operate in a harsh environment. They should endure vibrations, power supply fluctuations and excessive heat. Due to limited power supply in an embedded system, the power ...

  5. Operating systems

    CERN Document Server

    Tsichritzis, Dionysios C; Rheinboldt, Werner


    Operating Systems deals with the fundamental concepts and principles that govern the behavior of operating systems. Many issues regarding the structure of operating systems, including the problems of managing processes, processors, and memory, are examined. Various aspects of operating systems are also discussed, from input-output and files to security, protection, reliability, design methods, performance evaluation, and implementation methods.Comprised of 10 chapters, this volume begins with an overview of what constitutes an operating system, followed by a discussion on the definition and pr

  6. Multifunction system

    International Nuclear Information System (INIS)

    Wauthier, J.; Fiori, R.


    The development, the characteristics and the applications of a multifunction system are presented. The system is used on the RBES laboratory pipes, at Marcoule. The system was developed in order to allow, without time loss, the modification of the circuit function by replacing only one component. The following elements form the multifunction system: a fixed base, which is part of the tube, a removable piece, which is inserted into the base, a cover plate and its locking system. The material, chosen among commercial trade marks, required small modifications in order to be used in the circuit [fr

  7. Cognitive Systems

    DEFF Research Database (Denmark)

    The tutorial will discuss the definition of cognitive systems as the possibilities to extend the current systems engineering paradigm in order to perceive, learn, reason and interact robustly in open-ended changing environments. I will also address cognitive systems in a historical perspective an...... in cognitive systems include e.g. personalized information systems, sensor network systems, social dynamics system and Web2.0, and cognitive components analysis. I will use example from our own research and link to other research activities.......The tutorial will discuss the definition of cognitive systems as the possibilities to extend the current systems engineering paradigm in order to perceive, learn, reason and interact robustly in open-ended changing environments. I will also address cognitive systems in a historical perspective...... to be modeled within a limited set of predefined specifications. There will inevitably be a need for robust decisions and behaviors in novel situations that include handling of conflicts and ambiguities based on the capability and knowledge of the artificial cognitive system. Further, there is a need...

  8. Expert System

    DEFF Research Database (Denmark)

    Hildebrandt, Thomas Troels; Cattani, Gian Luca


    An expert system is a computer system for inferring knowledge from a knowledge base, typically by using a set of inference rules. When the concept of expert systems was introduced at Stanford University in the early 1970s, the knowledge base was an unstructured set of facts. Today the knowledge...... base of expert systems is often given in terms of an ontology, extracted and built from various data sources by employing natural language-processing and statistics. To emphasize such capabilities, the term “expert” is now often replaced by “cognitive,” “knowledge,” “knowledge-based,” or “intelligent......” system. With very few exceptions, general-purpose expert systems have failed to emerge so far. However, expert systems are applied in specialized domains, particularly in healthcare. The increasing availability of large quantities of data to organizations today provides a valuable opportunity...

  9. Ternary systems

    International Nuclear Information System (INIS)

    Kagan, D.N.; Hubberstey, P.; Barker, M.G.


    The paper reviews the experimental and theoretical studies carried out on multicomponent alkali metal systems. Solid-liquid phase equilibria studies are mainly concerned with the systems Na-K-Rb and Na-K-Cs, and data on the liquidus temperatures in these systems are presented. The thermodynamic properties of the ternary Na-K-Cs eutectic system have been determined experimentally, and the enthalpy, heat capacity and excess functions of the alloy are given. An analysis of calculational methods used in determining thermodynamic functions of ternary liquid metals systems is described. Finally, data are tabulated for the density, compressibility, saturated vapour pressure, viscosity and thermal conductivity of the ternary Na-K-Cs eutectic system. (UK)

  10. Material Systems

    DEFF Research Database (Denmark)

    Jensen, Mads Brath; Mortensen, Henrik Rubæk; Mullins, Michael


    This paper describes and reflects upon the results of an investigative project which explores the setting up of a material system - a parametric and generative assembly consisting of and taking into consideration material properties, manufacturing constraints and geometric behavior. The project...... approaches the subject through the construction of a logic-driven system aiming to explore the possibilities of a material system that fulfills spatial, structural and performative requirements concurrently and how these are negotiated in situations where they might be conflicting....

  11. Recommender systems

    CERN Document Server

    Kembellec, Gérald; Saleh, Imad


    Acclaimed by various content platforms (books, music, movies) and auction sites online, recommendation systems are key elements of digital strategies. If development was originally intended for the performance of information systems, the issues are now massively moved on logical optimization of the customer relationship, with the main objective to maximize potential sales. On the transdisciplinary approach, engines and recommender systems brings together contributions linking information science and communications, marketing, sociology, mathematics and computing. It deals with the understan

  12. Energetic Systems (United States)

    Federal Laboratory Consortium — The Energetic Systems Division provides full-spectrum energetic engineering services (project management, design, analysis, production support, in-service support,...

  13. Intelligent systems

    CERN Document Server

    Irwin, J David


    Technology has now progressed to the point that intelligent systems are replacing humans in the decision making processes as well as aiding in the solution of very complex problems. In many cases intelligent systems are already outperforming human activities. Artificial neural networks are not only capable of learning how to classify patterns, such images or sequence of events, but they can also effectively model complex nonlinear systems. Their ability to classify sequences of events is probably more popular in industrial applications where there is an inherent need to model nonlinear system

  14. Reactive Systems

    DEFF Research Database (Denmark)

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand

    A reactive system comprises networks of computing components, achieving their goals through interaction among themselves and their environment. Thus even relatively small systems may exhibit unexpectedly complex behaviours. As moreover reactive systems are often used in safety critical systems...... they are best used. Milner's CCS and its operational semantics are introduced, together with the notions of behavioural equivalences based on bisimulation techniques and with recursive extensions of Hennessy-Milner logic. In the second part of the book, the presented theories are extended to take timing issues...

  15. Anticipatory systems as linguistic systems (United States)

    Ekdahl, Bertil


    The idea of system is well established although not well defined. What makes up a system depends on the observer. Thinking in terms of systems is only a convenient way to conceptualize organizations, natural or artificial, that show coherent properties. Among all properties, which can be ascribed to systems, one property seems to be more outstanding than others, namely that of being anticipatory. In nature, anticipatory properties are found only in living organizations. In this way it can be said to separate non-living systems from living because there is no indication that any natural phenomenon occurring in systems where there is no indication of life is anticipatory. The characteristic of living systems is that they are exposed to the evolution contrary to causal systems that do not undergo changes due to the influence of the environment. Causal systems are related to the past in such a way that subsequent situations can be calculated from knowledge of past situations. In causal systems the past is the cause of the present and there is no reference to the future as a determining agent, contrary to anticipatory systems where expectations are the cause of the present action. Since anticipatory properties are characteristic of living systems, this property, as all other properties in living systems, is a result of the evolution and can be found in plants as well as in animals. Thus, it is not only tied to consciousness but is found at a more basic level, i.e., in the interplay between genotype and phenotype. Anticipation is part of the genetic language in such a way that appropriate actions, for events in the anticipatory systems environment, are inscribed in the genes. Anticipatory behavior, as a result of the interpretation of the genetic language, has been selected by the evolution. In this paper anticipatory systems are regarded as linguistic systems and I argue that as such anticipation cannot be fragmented but must be holistically studied. This has the

  16. Vacuum system


    Gröbner, Oswald


    The vacuum system of a particle accelerator must provide the necessary conditions for the high energy beam to avoid loss of particles and deterioration of the beam quality. In this talk we will review basic design concepts, vacuum components and procedures required for an accelerator vacuum system.

  17. Immune System (United States)

    ... jobs to do: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses ... like the soldiers, destroying the invaders that the intelligence system has ... that invades the body is called an antigen (pronounced: AN-tih-jun). ...

  18. Retrofitting Systems

    DEFF Research Database (Denmark)

    Rose, Jørgen


    This report gives an overview of the different retrofitting possibilities that are available today. The report looks at both external and internal systems for external wall constructions, roof constructions, floor constructions and foundations. All systems are described in detail in respect to use...

  19. GEOMASS system

    International Nuclear Information System (INIS)

    Ohyama, Takuya; Saegusa, Hiromitsu


    As a part of the research and development regarding characterisation of deep geological environment, the GEOMASS (GEOLOGICAL MODELLING ANALYSIS AND SIMULATION SOFTWARE) system has been developed by the Japan Atomic Energy Agency in order to carry out geological and hydrogeological modelling and groundwater flow simulation and so on. The GEOMASS system integrates a commercial geological interpretation system (EarthVision), which is used for geological modelling and visualisation, with a proprietary code for groundwater flow (FracAffinity). This integrated system allows users to make rapid improvement of models as data increases. Also, it is possible to perform more realistic groundwater flow simulation due to the capability of modelling the rock mass as a continuum with discrete hydro-structural features in the rock mass. This paper consists of 'Overview of GEOMASS system', FracAffinity Theoretical Background' and 'FracAffinity User Guide' and is edited as a GEOMASS system manual. 'Overview of GEOMASS system' describes the outline of this system. 'FracAffinity Theoretical Background' describes the information of technical background of FracAffinity software. FracAffinity User Guide' describes the structure of the FracAffinity input files, the usage of FracAffinity Interface and flow-solver. Updating of the FracAffinity has been continued as needed and FracAffinity version3.3 is the latest version at present (July 2008). (author)

  20. Operating Systems

    Indian Academy of Sciences (India)

    M Suresh Babu is currently a fourth year undergraduate student in the Department of. Computer Science and. Engineering, Narayana. Engineering College,. Nellore, Andhra Pradesh. He would like to work in operating systems, computer networks and also in Internet security concepts. Keywords. Operating systems, file sys-.

  1. Operating Systems

    Indian Academy of Sciences (India)

    The process concept and concurrency are at the heart of modern operating systems (OS). A process is the unit of work in a computer system. A process must be in main memory during execution. To improve the utilization of central processing unit. (CPU) as well as the speed of its response to its users, the computer must ...

  2. Caste System


    Hoff, Karla


    In standard economics, individuals are rational actors and economic forces undermine institutions that impose large inefficiencies. The persistence of the caste system is evidence of the need for psychologically more realistic models of decision-making in economics. The caste system divides South Asian society into hereditary groups whose lowest ranks are represented as innately polluted. ...

  3. Energy System

    Energy Technology Data Exchange (ETDEWEB)

    Kaya, Yoichi


    In the wake of the oil shock in 1973, the need for developing more effective energy systems has been mounting. The dominant views and topics for power generation systems in terms of scale merit shifted from the advocacy of centralization/scaling-up of facilities to the soft energy path theory insisting on the efficiency of dispersed small-scale plants, followed by the recent holonic path theory which maintains that large and small scale plants should be centralized or dispersed in an optimum manner. At the same time, an autonomous-type system concept has emerged which points out that the energy systems can be operated efficiently through mutual coordination and cooperation between the suppliers and users to find a balance point that meets the market principle, while abolishing the conventional suppliers-governed system. As a result, the load management system based on time-of-use pricing or adaptive pricing is expected to be adopted widely in near future. All these new theories are aimed at developing flexible and reasonable system structures that can be adapted to the changing circumstances. (4 figs, 17 refs)

  4. Imaging system

    International Nuclear Information System (INIS)

    Froggatt, R.J.


    The invention provides a two dimensional imaging system in which a pattern of radiation falling on the system is detected to give electrical signals for each of a plurality of strips across the pattern. The detection is repeated for different orientations of the strips and the whole processed by compensated back projection. For a shadow x-ray system a plurality of strip x-ray detectors are rotated on a turntable. For lower frequencies the pattern may be rotated with a Dove prism and the strips condensed to suit smaller detectors with a cylindrical lens. (author)

  5. Dynamical systems

    CERN Document Server

    Sternberg, Shlomo


    Celebrated mathematician Shlomo Sternberg, a pioneer in the field of dynamical systems, created this modern one-semester introduction to the subject for his classes at Harvard University. Its wide-ranging treatment covers one-dimensional dynamics, differential equations, random walks, iterated function systems, symbolic dynamics, and Markov chains. Supplementary materials offer a variety of online components, including PowerPoint lecture slides for professors and MATLAB exercises.""Even though there are many dynamical systems books on the market, this book is bound to become a classic. The the

  6. Kaonic systems

    Directory of Open Access Journals (Sweden)

    Oset E.


    Full Text Available I make a short review of the situation of the kaonic systems, with novel information supporting the two Λ(1405 states from the K-d → nπΣ reaction. A review is made of the K¯$ar K$NN system with recent calculations converging to smaller bindings and larger widths. Novel systems involving two kaons and one nucleon or three kaons are also reported and finally a short discussion is made of the analogous state DNN for which recent studies find a large binding and a small width.

  7. Saturn Systems. (United States)

    U Rehman, Habib; McKee, Nida A; McKee, Michael L


    Several ring systems (Saturn systems) have been studied using DFT methods that include dispersion effects. Comparison with X-ray structures are made with three systems, and the agreement is quite good. Binding enthalpies and binding free energies in dichloromethane and toluene have been computed. The effect of an encapsulated lithium cation is accessed by comparing C60 @(C6 H4 )10 and [Li@C60 @(C6 H4 )10 ](+). The [Li@C60 ](+) cation is a much better acceptor than C60 which leads to greater donor-acceptor interactions and larger charge transfer from the ring to [Li@C60 ](+). © 2015 Wiley Periodicals, Inc.

  8. Bubble systems

    CERN Document Server

    Avdeev, Alexander A


    This monograph presents a systematic analysis of bubble system mathematics, using the mechanics of two-phase systems in non-equilibrium as the scope of analysis. The author introduces the thermodynamic foundations of bubble systems, ranging from the fundamental starting points to current research challenges. This book addresses a range of topics, including description methods of multi-phase systems, boundary and initial conditions as well as coupling requirements at the phase boundary. Moreover, it presents a detailed study of the basic problems of bubble dynamics in a liquid mass: growth (dynamically and thermally controlled), collapse, bubble pulsations, bubble rise and breakup. Special emphasis is placed on bubble dynamics in turbulent flows. The analysis results are used to write integral equations governing the rate of vapor generation (condensation) in non-equilibrium flows, thus creating a basis for solving a number of practical problems. This book is the first to present a comprehensive theory of boil...

  9. ring system

    African Journals Online (AJOL)

    1,3,2-DIAZABORACYCLOALKANE. RING SYSTEM. Negussie Retta" and Robert H. Neilson. 'Department of Chemistry, Addis Ababa University, P.O. Box 1176, Addis Ababa, Ethiopia. Department of Chemistry, Texas Christian University.

  10. Respiratory system (United States)

    Bartlett, R. G., Jr.


    The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.

  11. Dryland systems

    CSIR Research Space (South Africa)

    Wessels, Konrad J


    Full Text Available This chapter describes the current condition of dryland systems with respect to the services they provide and the drivers that determine trends in their provision. Within the context of the mounting global concern caused by land degradation...

  12. Nanorobotic Systems

    Directory of Open Access Journals (Sweden)

    Lixin Dong


    Full Text Available Two strategies towards the realization of nanotechnology have been presented, i.e., top-down and bottom up. The former one is mainly based on nanofabrication and includes technologies such as nano-lithography, nano-imprint, and etching. Presently, they are still 2D fabrication processes with low resolution. The later one is an assembly-based technique. At present, it includes such items as self-assembly, dip-pen lithography, and directed self-assembly. These techniques can generate regular nano patterns in large scales. To fabricate 3D complex nano devices there are still no effective ways by so far. Here we show our effort on the development of a nano laboratory, a prototype nanomanufacturing system, based on nanorobotic manipulations. In which, we take a hybrid strategy as shown in Fig. 1. In this system, nano fabrication and nano assembly can be performed in an arbitrary order to construct nano building blocks and finally nano devices. The most important feature in this system is that the products can be fed back into the system to shrink the system part by part leading to nanorobots. Property characterization can be performed in each intermediate process. Due to the nanorobotic manipulation system, dynamic measurement can be performed rather than conventional static observations.

  13. System-of-Systems Complexity

    Directory of Open Access Journals (Sweden)

    Hermann Kopetz


    Full Text Available The global availability of communication services makes it possible to interconnect independently developed systems, called constituent systems, to provide new synergistic services and more efficient economic processes. The characteristics of these new Systems-of-Systems are qualitatively different from the classic monolithic systems. In the first part of this presentation we elaborate on these differences, particularly with respect to the autonomy of the constituent systems, to dependability, continuous evolution, and emergence. In the second part we look at a SoS from the point of view of cognitive complexity. Cognitive complexity is seen as a relation between a model of an SoS and the observer. In order to understand the behavior of a large SoS we have to generate models of adequate simplicity, i.e, of a cognitive complexity that can be handled by the limited capabilities of the human mind. We will discuss the importance of properly specifying and placing the relied-upon message interfaces between the constituent systems that form an open SoS and discuss simplification strategies that help to reduce the cognitive complexity.

  14. Systems Studies

    Energy Technology Data Exchange (ETDEWEB)

    Graham, R.L.


    The Systems Studies Activity had two objectives: (1) to investigate nontechnical barriers to the deployment of biomass production and supply systems and (2) to enhance and extend existing systems models of bioenergy supply and use. For the first objective, the Activity focused on existing bioenergy markets. Four projects were undertaken: a comparative analysis of bioenergy in Sweden and Austria; a one-day workshop on nontechnical barriers jointly supported by the Production Systems Activity; the development and testing of a framework for analyzing barriers and drivers to bioenergy markets; and surveys of wood pellet users in Sweden, Austria and the US. For the second objective, two projects were undertaken. First, the Activity worked with the Integrated BioEnergy Systems (TBS) Activity of TEA Bioenergy Task XIII to enhance the BioEnergy Assessment Model (BEAM). This model is documented in the final report of the IBS Activity. The Systems Studies Activity contributed to enhancing the feedstock portion of the model by developing a coherent set of willow, poplar, and switchgrass production modules relevant to both the US and the UK. The Activity also developed a pretreatment module for switchgrass. Second, the Activity sponsored a three-day workshop on modeling bioenergy systems with the objectives of providing an overview of the types of models used to evaluate bioenergy and promoting communication among bioenergy modelers. There were nine guest speakers addressing different types of models used to evaluate different aspects of bioenergy, ranging from technoeconomic models based on the ASPEN software to linear programming models to develop feedstock supply curves for the US. The papers from this workshop have been submitted to Biomass and Bioenergy and are under editorial review.

  15. Fiscal system analysis - contractual systems

    International Nuclear Information System (INIS)

    Kaiser, M.J.


    Production sharing contracts are one of the most popular forms of contractual system used in petroleum agreements around the world, but the manner in which the fiscal terms and contract parameters impact system measures is complicated and not well understood. The purpose of this paper is to quantify the influence of private and market uncertainty in contractual fiscal systems. A meta-modelling approach is employed that couples the results of a simulation model with regression analysis to construct numerical functionals that quantify the fiscal regime. Relationships are derived that specify how the present value, rate of return, and take statistics vary as a function of the system parameters. The deepwater Girassol field development in Angola is taken as a case study. (author)

  16. Computer systems (United States)

    Olsen, Lola


    In addition to the discussions, Ocean Climate Data Workshop hosts gave participants an opportunity to hear about, see, and test for themselves some of the latest computer tools now available for those studying climate change and the oceans. Six speakers described computer systems and their functions. The introductory talks were followed by demonstrations to small groups of participants and some opportunities for participants to get hands-on experience. After this familiarization period, attendees were invited to return during the course of the Workshop and have one-on-one discussions and further hands-on experience with these systems. Brief summaries or abstracts of introductory presentations are addressed.

  17. Microbiology System (United States)


    Technology originating in a NASA-sponsored study of the measurement of microbial growth in zero gravity led to the development of Biomerieux Vitek, Inc.'s VITEK system. VITEK provides a physician with accurate diagnostic information and identifies the most effective medication. Test cards are employed to identify organisms and determine susceptibility to antibiotics. A photo-optical scanner scans the card and monitors changes in the growth of cells contained within the card. There are two configurations - VITEK and VITEK JR as well as VIDAS, a companion system that detects bacteria, viruses, etc. from patient specimens. The company was originally created by McDonnell Douglas, the NASA contractor.

  18. System Description:

    DEFF Research Database (Denmark)

    Schürmann, Carsten; Poswolsky, Adam


    Delphin is a functional programming language [Adam Poswolsky and Carsten Schürmann. Practical programming with higher-order encodings and dependent types. In European Symposium on Programming (ESOP), 2008] utilizing dependent higher-order datatypes. Delphin's two-level type-system cleanly separates...... data from computation, allowing for decidable type checking. The data level is LF [Robert Harper, Furio Honsell, and Gordon Plotkin. A framework for defining logics. Journal of the Association for Computing Machinery, 40(1):143-184, January 1993], which allows for the specification of deductive systems...

  19. Distributed systems

    CERN Document Server

    Van Steen, Maarten


    For this third edition of "Distributed Systems," the material has been thoroughly revised and extended, integrating principles and paradigms into nine chapters: 1. Introduction 2. Architectures 3. Processes 4. Communication 5. Naming 6. Coordination 7. Replication 8. Fault tolerance 9. Security A separation has been made between basic material and more specific subjects. The latter have been organized into boxed sections, which may be skipped on first reading. To assist in understanding the more algorithmic parts, example programs in Python have been included. The examples in the book leave out many details for readability, but the complete code is available through the book's Website, hosted at

  20. Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Wiley, H S.


    The biology revolution over the last 50 years has been driven by the ascendancy of molecular biology. This was enthusiastically embraced by most biologists because it took us into increasingly familiar territory. It took mysterious processes, such as the replication of genetic material and assigned them parts that could be readily understood by the human mind. When we think of ''molecular machines'' as being the underlying basis of life, we are using a paradigm derived from everyday experience. However, the price that we paid was a relentless drive towards reductionism and the attendant balkanization of biology. Now along comes ''systems biology'' that promises us a solution to the problem of ''knowing more and more about less and less''. Unlike molecular biology, systems biology appears to be taking us into unfamiliar intellectual territory, such as statistics, mathematics and computer modeling. Not surprisingly, systems biology has met with widespread skepticism and resistance. Why do we need systems biology anyway and how does this new area of research promise to change the face of biology in the next couple of decades?

  1. Operating Systems

    Indian Academy of Sciences (India)

    areas in which this type is useful are multimedia, virtual reality, and advanced scientific projects such as undersea exploration and planetary rovers. Because of the expanded uses for soft real-time functionality, it is finding its way into most current operating systems, including major versions of Unix and Windows NT OS.

  2. Solar system

    CERN Document Server

    Bell, Samantha


    "Using the new Next Generation Science Standards (NGSS), the My World of Science series provides the earliest readers with background on key STEM concepts. Solar System explores basic planetary astronomy in a simple, engaging way that will help readers develop word recognition and reading skills. Includes a glossary and index."-- Provided by publisher.

  3. Systems Science (United States)

    Christakis, Alexander; Hammond, Debora; Jackson, Michael; Laszlo, Alexander; Mitroff, Ian; Snowden, Dave; Troncale, Len; Carr-Chellman, Alison; Spector, J. Michael; Wilson, Brent


    Scholars representing the field of systems science were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Alexander Christakis, Debora Hammond, Michael Jackson, Alexander Laszlo, Ian Mitroff, Dave…

  4. Bioenergy systems

    International Nuclear Information System (INIS)

    Mitchell, C.P.


    The objective of this paper is to demonstrate that a bioenergy system has to be considered as an integrated process in which each stage or step interacts with other steps in the overall process. There are a number of stages in the supply and conversion of woody biomass for energy. Each step in the chain has implications for the next step and for overall system efficiency. The resource can take many forms and will have varying physical and chemical characteristics which will influence the efficiency and cost of conversion. The point in the supply chain at which size and moisture content is reduced and the manner in which it is done is influential in determining feedstock delivered cost and overall system costs. To illustrate the interactions within the overall system, the influence of the nature, size and moisture content of delivered feedstocks on costs of generating electricity via thermal conversion processes is examined using a model developed to investigate the inter-relationships between the stages in the supply chain. (author)

  5. Transport system

    NARCIS (Netherlands)

    Drenth, K.F.


    The transport system comprises at least one road surface (2) and at least one vehicle (4) on wheels (6). The road surface (2) has a substantially bowl-shaped cross section and the vehicle (4) is designed so that the wheels (6) run directly on the road surface (2) while the road surface (2) acts as a

  6. Barrier Systems

    NARCIS (Netherlands)

    Heteren, S. van


    Barrier-system dynamics are a function of antecedent topography and substrate lithology, Relative sea-level (RSL) changes, sediment availability and type, climate, vegetation type and cover, and various aero- and hydrodynamic processes during fair-weather conditions and extreme events. Global change

  7. Immune System (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  8. Fusion systems


    Aschbacher, Michael; Oliver, Bob


    This is a survey article on the theory of fusion systems, a relatively new area of mathematics with connections to local finite group theory, algebraic topology, and modular representation theory. We first describe the general theory and then look separately at these connections.

  9. Glymphatic system

    DEFF Research Database (Denmark)

    Benveniste, Helene; Nedergaard, Maiken


    a so-called glymphatic pathway which comprise the peri-vascular space and acuaporin-4 water channels on astroglial endfeet. As such the glymphatic pathway can be perceived as a hitherto overlooked compartment of the extracellular space of the central nervous system which is involved in clearance...

  10. Bricks / Systems

    DEFF Research Database (Denmark)

    At first glance, this book may appear eclectic. It contains writings from architectural practice in a language and structure based on subjective views and experiences, combined with research contributions based on systematic design investigations of discrete computational systems. Discussions range...... from an undulating masonry wall at the University of Virginia erected by then-U.S. President Thomas Jefferson to agile robotic manufacturing processes and computational solver strategies based on graph networks. Conversely, the focus of this anthology is expressed directly in the title: bricks...... and systems. The basis for this theme is the work conducted at the Utzon(x) Research Group at Aalborg University, in combination with the rich tradition and implementation of masonry work in Denmark, which has attracted increasing attention from architectural practitioners and researchers alike. How should...

  11. TUBO system

    International Nuclear Information System (INIS)

    Barbosa, H.J.C.; Guerreiro, J.N.C.; Toledo, E.M.


    Proceedings recently incorporated to TUBO system like the seismic analysis and the stress verification acccording to ASME-Boiler Rule and Pressure Vessel Code-section III are presented. The seismic analysis comprehend the consideration of uniform motion of the support, its multiple excitation, and the attainment of the spectral response for both cases. The module for stress verification uses stresses resulting fromthe combination of the loads specified by the user, in the automatic verification of permissible stresses for the pipings class 1 and 2, based on criteria NB-3650 and NC-3650 of ASME. The implementation of these proceedings in the TUBO system are discussed and a numerical example that covers the different phases of a stress analysis in a piping is presented [pt

  12. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational...... design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......-up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto...

  13. Bilateral system. The ABACC system

    International Nuclear Information System (INIS)

    Nicolas, Ruben O.


    After relating the antecedents of the creation of the Brazilian-Argentine Agency for the Accounting and Control of Nuclear Materials (ABACC), the paper describes the common system of accounting and control set up by Argentina and Brazil. The organization of ABACC is also outlined

  14. Physical system requirements: Overall system

    International Nuclear Information System (INIS)


    The Nuclear Waste Policy Act (NWPA) of 1982 assigned to the Department of Energy (DOE) the responsibility for managing the disposal of spent nuclear fuel and high-level radioactive waste and established the Office of Civilian Radioactive Waste Management (OCRWM) for that purpose. The Secretary of Energy, in his November 1989 report to Congress (DOE/RW-0247), announced three new initiatives for conduct of the Civilian Radioactive Waste Management (CRWM) program. One of these initiatives was to establish improved management structure and procedures. In response, OCRWM performed a management study and the Direct subsequently issued the Management Systems Improvement Strategy (MSIS) on August 10, 1990, calling for a rigorous implementation of systems engineering principles with a special emphasis on functional analysis. This approach establishes a framework for integrating the program management efforts with the technical requirements analysis into a single, unified, and consistent program. The functional analysis approach recognizes that just the facilities and equipment comprising the physical waste management system must perform certain functions, so must certain programmatic and management functions be performed within the program in order to successfully bring the physical system into being

  15. Cardiovascular system

    International Nuclear Information System (INIS)

    Soulen, R.L.; Grosh, J.


    Invasive cardiovascular diagnostic procedures involve a finite risk and therefore can be recommended only when the benefit appears to exceed the risk by a substantial margin. The risk/benefit ratio varies not only with the procedure concerned but with the status of the vascular system, concomitant diseases, and the risks of both the suspected illness and its treatment. The risks inherent in the procedures per se are detailed in the sections to follow

  16. Security system (United States)

    Baumann, Mark J.; Kuca, Michal; Aragon, Mona L.


    A security system includes a structure having a structural surface. The structure is sized to contain an asset therein and configured to provide a forceful breaching delay. The structure has an opening formed therein to permit predetermined access to the asset contained within the structure. The structure includes intrusion detection features within or associated with the structure that are activated in response to at least a partial breach of the structure.

  17. Systemic Assurance (United States)


    early lifecycle phases will have intended quality outcomes. Requirements and Quality Validation Develop requirements elicitation and management...gradients within a system. That is, there are attack surfaces at internal APIs and service interfaces. The complexity also arises from particular features...interoperation (compatibility and support for with SoS APIs and practices), as well as a diverse range of ilities (evolvability/extensibility

  18. CONTROL SYSTEM (United States)

    Shannon, R.H.; Williamson, H.E.


    A boiling water type nuclear reactor power system having improved means of control is described. These means include provisions for either heating the coolant-moderator prior to entry into the reactor or shunting the coolantmoderator around the heating means in response to the demand from the heat engine. These provisions are in addition to means for withdrawing the control rods from the reactor. (AEC)

  19. Complex Systems

    Directory of Open Access Journals (Sweden)

    Yi Zhao


    Full Text Available Quantum instanton (QI approximation is recently proposed for the evaluations of the chemical reaction rate constants with use of full dimensional potential energy surfaces. Its strategy is to use the instanton mechanism and to approximate time-dependent quantum dynamics to the imaginary time propagation of the quantities of partition function. It thus incorporates the properties of the instanton idea and the quantum effect of partition function and can be applied to chemical reactions of complex systems. In this paper, we present the QI approach and its applications to several complex systems mainly done by us. The concrete systems include, (1 the reaction of H+CH4→H2+CH3, (2 the reaction of H+SiH4→H2+SiH3, (3 H diffusion on Ni(100 surface; and (4 surface-subsurface transport and interior migration for H/Ni. Available experimental and other theoretical data are also presented for the purpose of comparison.

  20. Dynamical systems

    CERN Document Server

    Birkhoff, George D


    His research in dynamics constitutes the middle period of Birkhoff's scientific career, that of maturity and greatest power. -Yearbook of the American Philosophical Society The author's great book€¦is well known to all, and the diverse active modern developments in mathematics which have been inspired by this volume bear the most eloquent testimony to its quality and influence. -Zentralblatt MATH In 1927, G. D. Birkhoff wrote a remarkable treatise on the theory of dynamical systems that would inspire many later mathematicians to do great work. To a large extent, Birkhoff was writing about his o

  1. Videobasierte Systeme (United States)

    Knoll, Peter

    Videosensoren spielen für Fahrerassistenz systeme eine zentrale Rolle, da sie die Interpretation visueller Informationen (Objektklassifikation) gezielt unterstützen. Im Heckbereich kann die Video sensorik in der einfachsten Variante die ultraschallbasierte Einparkhilfe bei Einpark- und Rangiervorgängen unterstützen. Beim Nachtsichtsystem NightVision wird das mit Infrarotlicht angestrahlte Umfeld vor dem Fahrzeug mit einer Frontkamera aufgenommen und im Fahrzeugcockpit auf einem Display dem Fahrer angezeigt (s. Nachtsichtsysteme). Andere Fahrerassistenzsysteme verarbeiten die Videosignale und generieren daraus gezielt Informationen, die für eigenständige Funktionen (z. B. Spurverlassenswarner) oder aber als Zusatzinformation für andere Funktionen ausgewertet werden (Sensordatenfusion).

  2. Linear systems

    CERN Document Server

    Bourlès, Henri


    Linear systems have all the necessary elements (modeling, identification, analysis and control), from an educational point of view, to help us understand the discipline of automation and apply it efficiently. This book is progressive and organized in such a way that different levels of readership are possible. It is addressed both to beginners and those with a good understanding of automation wishing to enhance their knowledge on the subject. The theory is rigorously developed and illustrated by numerous examples which can be reproduced with the help of appropriate computation software. 60 exe

  3. Nuclear systems

    CERN Document Server

    Todreas, Neil E


    Principal Characteristics of Power ReactorsIntroductionPower CyclesPrimary Coolant SystemsReactor CoresFuel AssembliesAdvanced Water- and Gas-Cooled Reactors (Generation III And III+)Advanced Thermal and Fast Neutron Spectrum Reactors (Generation IV)ReferencesProblemsThermal Design Principles and ApplicationIntroductionOverall Plant Characteristics Influenced by Thermal Hydraulic ConsiderationsEnergy Production and Transfer ParametersThermal Design LimitsThermal Design MarginFigures of Merit for Core Thermal PerformanceThe Inverted Fuel ArrayThe Equivalent Annulus ApproximationReferencesProble

  4. Sterilization System (United States)


    Cox Sterile Products, Inc.'s Rapid Heat Transfer Sterilizer employs a heat exchange process that induces rapid air movement; the air becomes the heat transfer medium, maintaining a uniform temperature of 375 degrees Fahrenheit. It features pushbutton controls for three timing cycles for different instrument loads, a six-minute cycle for standard unpackaged instruments, eight minutes for certain specialized dental/medical instruments and 12 minutes for packaged instruments which can then be stored in a drawer in sterile condition. System will stay at 375 degrees all day. Continuous operation is not expensive because of the sterilizer's very low power requirements.

  5. Bearing system (United States)

    Kapich, Davorin D.


    A bearing system includes backup bearings for supporting a rotating shaft upon failure of primary bearings. In the preferred embodiment, the backup bearings are rolling element bearings having their rolling elements disposed out of contact with their associated respective inner races during normal functioning of the primary bearings. Displacement detection sensors are provided for detecting displacement of the shaft upon failure of the primary bearings. Upon detection of the failure of the primary bearings, the rolling elements and inner races of the backup bearings are brought into mutual contact by axial displacement of the shaft.

  6. Expert Systems: What Is an Expert System? (United States)

    Duval, Beverly K.; Main, Linda


    Describes expert systems and discusses their use in libraries. Highlights include parts of an expert system; expert system shells; an example of how to build an expert system; a bibliography of 34 sources of information on expert systems in libraries; and a list of 10 expert system shells used in libraries. (Contains five references.) (LRW)

  7. Booking System


    Jersák, Jan


    Cílem studie je definovat možné směry dalšího vývoje nové aplikace pro potřeby cestovního ruchu, online rezervačního systému Booking System. Tohoto cíle je dosaženo jednak zkoumáním dosavadního vývoje aplikace a zásadních inovací, které přináší, a dále analýzou socioekonomického prostředí a konkurenčních služeb.

  8. Posting system

    International Nuclear Information System (INIS)

    Hackney, S.


    A system for posting hazardous materials into and out of an enclosure, such as a glovebox, through a port in a wall of the enclosure. The port is normally closed by a door which cooperates with a removable end closure, on a container or the like when the latter is presented to and secured at the port. The container is secured in position at the port by means of a rotatable coupling ring. A single interlock ensures that the door cannot be opened in the absence of a container at the port and also that the container cannot be removed from the port when the door is open. In place of the container, a glove secured to a rigid sleeve may be used to enable the operator to perform a work function within the glovebox. (author)

  9. Systemic Planning

    DEFF Research Database (Denmark)

    Leleur, Steen

    This book presents principles and methodology for planning in a complex world. It sets out a so-called systemic approach to planning, among other things, by applying “hard” and “soft” methodologies and methods in combination. The book is written for Ph.D and graduate students in engineering......, business and other fields, and it is useful for all professionals, across a wide range of employment areas, who share an interest in renewing planning practice. Such an endeavour is seen as both important and timely, recognising that many complex planning tasks necessitate organisations – be they public...... or private – to engage in planning to prepare proactive decision-making....

  10. Nonlinear systems

    CERN Document Server

    Palmero, Faustino; Lemos, M; Sánchez-Rey, Bernardo; Casado-Pascual, Jesús


    This book presents an overview of the most recent advances in nonlinear science. It provides a unified view of nonlinear properties in many different systems and highlights many  new developments. While volume 1 concentrates on mathematical theory and computational techniques and challenges, which are essential for the study of nonlinear science, this second volume deals with nonlinear excitations in several fields. These excitations can be localized and transport energy and matter in the form of breathers, solitons, kinks or quodons with very different characteristics, which are discussed in the book. They can also transport electric charge, in which case they are known as polarobreathers or solectrons. Nonlinear excitations can influence function and structure in biology, as for example, protein folding. In crystals and other condensed matter, they can modify transport properties, reaction kinetics and interact with defects. There are also engineering applications in electric lattices, Josephson junction a...

  11. Posting system

    International Nuclear Information System (INIS)

    Jones, E.L.


    A posting system for the movement of equipment, such as a manipulator, into and out of an enclosure e.g. a cell or glovebox, for toxic or radioactive materials has the manipulator arranged within a collapsible bellows-like container with an end of the container cooperating with a port entry to the enclosure. The collapsible container isolates the manipulator from the environment outside the enclosure and allows the manipulator to enter and leave the contaminated enclosure without breach of the containment. A particular construction of cell for use with radioactive material is described, having a thick wall of shielding material such as concrete provided with a door normally closed by a Pb shutter and having a cylindrical gamma shield block located over the shutter on the exterior of the wall. (author)

  12. Systems engineering simplified

    CERN Document Server

    Cloutier, Robert; Bone, Mary Alice


    IntroductionOverviewDiscussion of Common TerminologyThe Case for Systems EngineeringA Brief History of Systems EngineeringSystem ExamplesSummaryThe System Life CycleManaging System Development-The Vee ModelSystem ProductionSystem Utilization and SupportSystem Retirement and DisposalOther Systems Engineering Development ModelsSpiral ModelAgile Model for Systems EngineeringSystem of InterestAbstraction and DecompositionIntegrationDeveloping and Managing RequirementsCyclone Requiremen

  13. Chem systems

    International Nuclear Information System (INIS)



    This paper reports that world styrene demand, paced by a near doubling of combined requirements in East Asia and Oceania, could reach 19.3 million metric tons by 2000, an average growth rate of 3.7%/year. So concludes Chem Systems Inc., Tarrytown, N.Y., in a study of world styrene markets through the end of the century. Pacific Rim styrene production and consumption throughout the 1990s are predicted to make up increasingly larger shares of world markets, while demand and production lag in the U.S. and western Europe. Demand and capacity in other parts of the world will grow in real terms, increasing combined market shares only slightly. Most of the increase will be driven by demand in East Asia and Oceania, where consumption by century's end is expected to increase 4.48 million metric tons from 2.25 million tons in 1991. Meantime, Japan's styrene demand in 2000 is projected at 2.64 million tons, a 500,000 ton increase from 1991 demand but a net market loss of 1.9%

  14. New Systems Produced by Systemic Change (United States)

    Battino, Wendy; Clem, Jo; Caine, Renate N.; Reigeluth, Charles M.; Chapman, Carrie; Flinders, David J.; Malopinsky, Larissa V.


    This article presents new systems produced by systemic change. First is Systemic Changes in the Chugach School District by Wendy Battino and Jo Clem. Second is Systemic Changes in Public Schools through Brain-Based Learning by Renate N. Caine. Third is A Vision of an Information-Age Educational System by Charles M. Reigeluth. Fourth is Systemic…

  15. Modulation of respiratory dendritic cells during Klebsiella pneumonia infection (United States)


    Background Klebsiella pneumoniae is a leading cause of severe hospital-acquired respiratory tract infections and death but little is known regarding the modulation of respiratory dendritic cell (DC) subsets. Plasmacytoid DC (pDC) are specialized type 1 interferon producing cells and considered to be classical mediators of antiviral immunity. Method By using multiparameter flow cytometry analysis we have analysed the modulation of respiratory DC subsets after intratracheal Klebsiella pneumonia infection. Results Data indicate that pDCs and MoDC were markedly elevated in the post acute pneumonia phase when compared to mock-infected controls. Analysis of draining mediastinal lymph nodes revealed a rapid increase of activated CD103+ DC, CD11b+ DC and MoDC within 48 h post infection. Lung pDC identification during bacterial pneumonia was confirmed by extended phenotyping for 120G8, mPDCA-1 and Siglec-H expression and by demonstration of high Interferon-alpha producing capacity after cell sorting. Cytokine expression analysis of ex vivo-sorted respiratory DC subpopulations from infected animals revealed elevated Interferon-alpha in pDC, elevated IFN-gamma, IL-4 and IL-13 in CD103+ DC and IL-19 and IL-12p35 in CD11b+ DC subsets in comparison to CD11c+ MHC-class IIlow cells indicating distinct functional roles. Antigen-specific naive CD4+ T cell stimulatory capacity of purified respiratory DC subsets was analysed in a model system with purified ovalbumin T cell receptor transgenic naive CD4+ responder T cells and respiratory DC subsets, pulsed with ovalbumin and matured with Klebsiella pneumoniae lysate. CD103+ DC and CD11b+ DC subsets represented the most potent naive CD4+ T helper cell activators. Conclusion These results provide novel insight into the activation of respiratory DC subsets during Klebsiella pneumonia infection. The detection of increased respiratory pDC numbers in bacterial pneumonia may indicate possible novel pDC functions with respect to lung repair

  16. System safety education focused on system management (United States)

    Grose, V. L.


    System safety is defined and characteristics of the system are outlined. Some of the principle characteristics include role of humans in hazard analysis, clear language for input and output, system interdependence, self containment, and parallel analysis of elements.

  17. Airport Information Retrieval System (AIRS) System Design (United States)


    This report presents the system design for a prototype air traffic flow control automation system developed for the FAA's Systems Command Center. The design was directed toward the immediate automation of airport data for use in traffic load predicti...

  18. Systems Biology and Health Systems Complexity in;

    NARCIS (Netherlands)

    Donald Combs, C.; Barham, S.R.; Sloot, P.M.A.


    Systems biology addresses interactions in biological systems at different scales of biological organization, from the molecular to the cellular, organ, organism, societal, and ecosystem levels. This chapter expands on the concept of systems biology, explores its implications for individual patients

  19. Variability and Evolution in Systems of Systems

    Directory of Open Access Journals (Sweden)

    Goetz Botterweck


    Full Text Available In this position paper (1 we discuss two particular aspects of Systems of Systems, i.e., variability and evolution. (2 We argue that concepts from Product Line Engineering and Software Evolution are relevant to Systems of Systems Engineering. (3 Conversely, concepts from Systems of Systems Engineering can be helpful in Product Line Engineering and Software Evolution. Hence, we argue that an exchange of concepts between the disciplines would be beneficial.

  20. System specifications for the NDS Dictionary System

    International Nuclear Information System (INIS)

    Attree, P.M.; Smith, P.M.


    The NDS Dictionary System is a computerized system for maintaining and distributing the EXFOR dictionaries and for preparing internal versions of these dictionaries for use in the NDS EXFOR System and other NDS systems. This document is an internal manual for the system specifications of the NDS Dictionary System. It includes flow charts, system and program summaries, input and output specifications and file and record descriptions. This manual is updated from time to time when system modifications are made; this is the version of January 1979

  1. Propriétés de luminescence et caractérisation structurale de films minces d'oxydes de silicium dopés au cérium et codopés cérium-ytterbium


    Weimmerskirch-Aubatin, Jennifer


    This thesis concerns the structural characterization and the photoluminescence propertiesof thin silicon oxide films doped with rare earths The films are doped with cerium. The codopingwith both cerium and ytterbium is also studied in the case of SiO 2 layers. It is shown thatin oxides with composition SiO1, cerium plays an important role in the structure and chemicalorganization of the oxide, in particular by promoting phase separation of the oxide. The exposureto a focused laser beam genera...

  2. Quality management system

    International Nuclear Information System (INIS)

    Lee, Mu Sung


    This book deals with ISO9001 quality management system which includes summary of this system such as classification of quality, principle of quality management, and definition, requirement and procedure of quality management system, introduction of ISO9001 system like model of ISO9001 quality management system, ISO certificate system, structure of ISO9001 standard, requirement of ISO9001 quality management system, process approach and documentation of system, propel cases of ISO9001 quality management system.

  3. Protecting Information in Systems of Systems

    NARCIS (Netherlands)

    Trivellato, Daniel; Zannone, Nicola; Etalle, Sandro


    Systems of Systems (SoS) are dynamic, distributed coalitions of autonomous and heterogeneous systems that collaborate to achieve a common goal. While offering several advantages in terms of scalability and flexibility, the SoS paradigm has a strong impact on system interoperability and on the

  4. Networked control of microgrid system of systems (United States)

    Mahmoud, Magdi S.; Rahman, Mohamed Saif Ur; AL-Sunni, Fouad M.


    The microgrid has made its mark in distributed generation and has attracted widespread research. However, microgrid is a complex system which needs to be viewed from an intelligent system of systems perspective. In this paper, a network control system of systems is designed for the islanded microgrid system consisting of three distributed generation units as three subsystems supplying a load. The controller stabilises the microgrid system in the presence of communication infractions such as packet dropouts and delays. Simulation results are included to elucidate the effectiveness of the proposed control strategy.

  5. System design specification Brayton Isotope Power System (BIPS) Flight System (FS), and Ground Demonstration System (GDS)

    International Nuclear Information System (INIS)


    The system design specification for ground demonstration, development, and flight qualification of a Brayton Isotope Power System (BIPS) is presented. The requirements for both a BIPS conceptual Flight System (FS) and a Ground Demonstration System (GDS) are defined

  6. Situation awareness with systems of systems

    CERN Document Server

    Tretmans, Jan; Borth, Michael


    This book discusses various aspects, challenges, and solutions for developing systems-of-systems for situation awareness, using applications in the domain of maritime safety and security.  Topics include advanced, multi-objective visualization methods for situation awareness, stochastic outlier selection, rule-based anomaly detection, an ontology-based event model for semantic reasoning, new methods for semi-automatic generation of adapters bridging communication gaps, security policies for systems-of-systems, trust assessment, and methods to deal with the dynamics of systems-of-systems in run-time monitoring, testing, and diagnosis. Architectural considerations for designing information-centric systems-of-systems such as situation awareness systems, and an integrated demonstrator implementing many of the investigated aspects, complete the book.

  7. Targeting Hepatitis B Virus With CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    Christoph Seeger


    Full Text Available Hepatitis B virus persistence in infected hepatocytes is due to the presence of covalently closed circular DNA (cccDNA, the template for the transcription of viral RNAs. Antiviral therapies with nucleoside analogues inhibit replication of HBV DNA in capsids present in the cytoplasm of infected cells, but do not reduce or destroy nuclear cccDNA. To investigate whether cccDNA derived from infectious HBV could be directly targeted for destruction, we used the CRISPR/Cas9 system in HepG2 cells expressing the HBV receptor sodium taurocholate cotransporting polypeptide (NTCP. We tested different HBV-specific guide RNAs and demonstrated that they could inhibit HBV infections up to eightfold. Inhibition was due to mutations and deletions in cccDNA similar to those observed with chromosomal DNA cleaved by Cas9 and repaired by nonhomologous end joining (NHEJ. Interferon alpha (IFN-α did not have a measurable effect on the antiviral activity of the CRISPR/Cas9 system, suggesting that Cas9 and NHEJ activities are not affected by induction of an innate immune response with the cytokine. Taken together, our results demonstrated that Cas9 can be recruited to cccDNA, opening the possibility for the development of future antiviral strategies aimed at targeting cccDNA for endonucleolytic cleavage with small molecules.

  8. Laser Photobiomodulation for a Complex Patient with Severe Hydroxyurea-Induced Oral Ulcerations. (United States)

    Cabras, Marco; Cafaro, Adriana; Gambino, Alessio; Broccoletti, Roberto; Romagnoli, Ercole; Marina, Davide; Arduino, Paolo G


    Patients affected by polycythemia vera (PV), a myeloproliferative neoplasm characterized by an elevated red blood cell mass, are at high risk of vascular and thrombotic complications. Conventional therapeutic options aim at reducing vascular and thrombotic risk; low-dose aspirin and phlebotomy are first-line recommendations, for patients at low risk of thrombotic events, whereas cytoreductive therapy, usually hydroxyurea (HU) or interferon alpha, is recommended for high-risk patients. In the present study, we report the case of a patient with persistent oral ulcerations, possibly related to long-lasting HU treatment, firstly treated with topic and systemic corticosteroids and then more effectively with the addition of low-level laser therapy. Laser photobiomodulation has achieved pain control and has contributed to the healing of oral ulcers without any adverse effect; this has permitted a reduction in the dose of systemic corticosteroids and the suspension of the use of the topic ones, due to the long-term stability of oral health, even after the interruption of low-level laser therapy sessions.

  9. Computer System Design System-on-Chip

    CERN Document Server

    Flynn, Michael J


    The next generation of computer system designers will be less concerned about details of processors and memories, and more concerned about the elements of a system tailored to particular applications. These designers will have a fundamental knowledge of processors and other elements in the system, but the success of their design will depend on the skills in making system-level tradeoffs that optimize the cost, performance and other attributes to meet application requirements. This book provides a new treatment of computer system design, particularly for System-on-Chip (SOC), which addresses th

  10. Immunotherapy of distant metastatic disease

    DEFF Research Database (Denmark)

    Schadendorf, D; Algarra, S M; Bastholt, L


    Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated with signif......Immunotherapy of metastatic melanoma consists of various approaches leading to specific or non-specific immunomodulation. The use of FDA-approved interleukin (IL)-2 alone, in combination with interferon alpha, and/or with various chemotherapeutic agents (biochemotherapy) is associated...

  11. Does Fasciola hepatica infection modify the response of acute hepatitis C virus infection to IFN-α treatment? (United States)

    Sahin, Mehmet; Isler, Mehmet; Senol, Altug; Demirci, Mustafa; Aydın, Zeynep Dilek


    Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response. Fasciola infection could theoretically interfere with the Th1 immune response, even when acquired after an initial response to interferon-alpha treatment for acute hepatitis C virus (HCV) infection. We report here the case of a male patient who acquired Fasciola hepatica infection after an initial response to IFN-alpha therapy with a favorable outcome PMID:16437701

  12. Smart electromechanical systems the central nervous system

    CERN Document Server

    Kurbanov, Vugar


    This book describes approaches to solving the problems of developing the central nervous system of robots (CNSR) based on smart electromechanical systems (SEMS) modules, principles of construction of the various modules of the central nervous system and variants of mathematical software CNSR in control systems for intelligent robots. It presents the latest advances in theory and practice at the Russian Academy of Sciences. Developers of intelligent robots to solve modern problems in robotics are increasingly addressing the use of the bionic approach to create robots that mimic the complexity and adaptability of biological systems. These have smart electromechanical system (SEMS), which are used in various cyber-physical systems (CPhS), and allow the functions of calculation, control, communications, information storage, monitoring, measurement and control of parameters and environmental parameters to be integrated. The behavior of such systems is based on the information received from the central nervous syst...

  13. Linking Political Systems and War Systems

    DEFF Research Database (Denmark)

    Harste, Gorm


    military coercion to be the appropriate mean. Using the system theory and the theory of systemic risks displayed by the German sociologist Niklas Luhmann the article demonstrates how military systems due to their own autonomy and autopoiesis do not fit into the idea of political government......Decisive parts of the Western political system have demonstrated a seemingly surprising misinterpretation of military might. As Madelaine Albright has suggested, the mighty perceived themselves as "almighty". Political power seems to have invested in instrumental coercive power relations and found....... The Clausewitzian ideal of a political system that could continue its power games by means of war was moderated by Clausewitz' own analysis of "friction". How can a political system be so blind towards the possibilities of another system? What are the risks of systemic blind spots? The argument of the paper...

  14. Situation Awareness with Systems of Systems

    NARCIS (Netherlands)

    Laar, P. van de; Tretmans, J.; Borth, M.


    This book discusses various aspects, challenges, and solutions for developing systems-of-systems for situation awareness, using applications in the domain of maritime safety and security. Topics include advanced, multi-objective visualization methods for situation awareness, stochastic outlier

  15. Designing information systems

    CERN Document Server

    Blethyn, Stanley G


    Designing Information Systems focuses on the processes, methodologies, and approaches involved in designing information systems. The book first describes systems, management and control, and how to design information systems. Discussions focus on documents produced from the functional construction function, users, operators, analysts, programmers and others, process management and control, levels of management, open systems, design of management information systems, and business system description, partitioning, and leveling. The text then takes a look at functional specification and functiona

  16. Triggering system innovation in agricultural innovation systems

    NARCIS (Netherlands)

    Turner, James A.; Williams, Tracy; Nicholas, Graeme; Foote, Jeff; Rijswijk, Kelly; Barnard, Tim; Beechener, Sam; Horita, Akiko


    This article describes a process for stimulating engagement among change agents to develop a shared understanding of systemic problems in the agricultural innovation system (AIS), challenge prevalent institutional logics and identify actions they might undertake to stimulate system innovation.

  17. Expert systems in process control systems

    International Nuclear Information System (INIS)

    Wittig, T.


    To illustrate where the fundamental difference between expert systems in classical diagnosis and in industrial control lie, the work of process control instrumentation is used as an example for the job of expert systems. Starting from the general process of problem-solving, two classes of expert systems can be defined accordingly. (orig.) [de

  18. System Design of the SWRL Financial System. (United States)

    Ikeda, Masumi

    To produce various management and accounting reports in order to maintain control of SWRL (Southwest Regional Laboratory) operational and financial activities, a computer-based SWRL financial system was developed. The system design is outlined, and various types of system inputs described. The kinds of management and accounting reports generated…

  19. Modeling learning technology systems as business systems

    NARCIS (Netherlands)

    Avgeriou, Paris; Retalis, Symeon; Papaspyrou, Nikolaos


    The design of Learning Technology Systems, and the Software Systems that support them, is largely conducted on an intuitive, ad hoc basis, thus resulting in inefficient systems that defectively support the learning process. There is now justifiable, increasing effort in formalizing the engineering

  20. Expert Systems for auditing management information systems

    Directory of Open Access Journals (Sweden)

    Gheroghe Popescu


    Full Text Available Expert systems are built with the help of: specialised programming languages or expert system generators (shell. But this structure was reached after tens of years of work and research, because expert systems are nothing but pragmatic capitalisation of the results of research carried out in artificial intelligence and theory of knowledge.

  1. General Systems Theory and Instructional Systems Design. (United States)

    Salisbury, David F.


    Describes basic concepts in the field of general systems theory (GST) and identifies commonalities that exist between GST and instructional systems design (ISD). Models and diagrams that depict system elements in ISD are presented, and two matrices that show how GST has been used in ISD literature are included. (11 references) (LRW)

  2. Optical system defect propagation in ABCD systems

    DEFF Research Database (Denmark)

    McKinley, W.G.; Yura, H.T.; Hanson, Steen Grüner


    We describe how optical system defects (tilt/jitter, decenter, and despace) propagate through an arbitrary paraxial optical system that can be described by an ABCD ray transfer matrix. A pedagogical example is given that demonstrates the effect of alignment errors on a typical optical system...

  3. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V


    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  4. Psychology of system design

    CERN Document Server

    Meister, D


    This is a book about systems, including: systems in which humans control machines; systems in which humans interact with humans and the machine component is relatively unimportant; systems which are heavily computerized and those that are not; and governmental, industrial, military and social systems. The book deals with both traditional systems like farming, fishing and the military, and with systems just now tentatively emerging, like the expert and the interactive computer system. The emphasis is on the system concept and its implications for analysis, design and evaluation of these many di

  5. Operating System Security

    CERN Document Server

    Jaeger, Trent


    Operating systems provide the fundamental mechanisms for securing computer processing. Since the 1960s, operating systems designers have explored how to build "secure" operating systems - operating systems whose mechanisms protect the system against a motivated adversary. Recently, the importance of ensuring such security has become a mainstream issue for all operating systems. In this book, we examine past research that outlines the requirements for a secure operating system and research that implements example systems that aim for such requirements. For system designs that aimed to

  6. Intrusion Detection Systems with Live Knowledge System (United States)


    AFRL-AFOSR-JP-TR-2016-0058 Intrusion Detection Systems with Live Knowledge System Byeong Ho Kang UNIVERSITY OF TASMANIA Final Report 05/31/2016...COVERED (From - To) 20 May 2015 to 19 May 2016 4. TITLE AND SUBTITLE Intrusion Detection Systems with Live Knowledge System 5a.  CONTRACT NUMBER 5b...298 10/26/2016 Final Report for AOARD Grant FA2386-15-1-4061 “ Intrusion Detection Systems with

  7. Systems Measures of Water Distribution System Resilience

    Energy Technology Data Exchange (ETDEWEB)

    Klise, Katherine A. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Murray, Regan [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Walker, La Tonya Nicole [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    Resilience is a concept that is being used increasingly to refer to the capacity of infrastructure systems to be prepared for and able to respond effectively and rapidly to hazardous events. In Section 2 of this report, drinking water hazards, resilience literature, and available resilience tools are presented. Broader definitions, attributes and methods for measuring resilience are presented in Section 3. In Section 4, quantitative systems performance measures for water distribution systems are presented. Finally, in Section 5, the performance measures and their relevance to measuring the resilience of water systems to hazards is discussed along with needed improvements to water distribution system modeling tools.

  8. Lighting system with thermal management system (United States)

    Arik, Mehmet; Weaver, Stanton; Stecher, Thomas; Seeley, Charles; Kuenzler, Glenn; Wolfe, Jr., Charles; Utturkar, Yogen; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc


    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  9. Automatic control systems engineering

    International Nuclear Information System (INIS)

    Shin, Yun Gi


    This book gives descriptions of automatic control for electrical electronics, which indicates history of automatic control, Laplace transform, block diagram and signal flow diagram, electrometer, linearization of system, space of situation, state space analysis of electric system, sensor, hydro controlling system, stability, time response of linear dynamic system, conception of root locus, procedure to draw root locus, frequency response, and design of control system.

  10. Root production method system (United States)

    Wayne Lovelace


    The RPM system (Root Production Method) is a multistep production system of container tree production that places primary emphasis on the root system because the root system ultimately determines the tree's survival and performance in its outplanted environment. This particular container production system has been developed to facilitate volume production, in a...

  11. Collaborative Systems Testing (United States)

    Pocatilu, Paul; Ciurea, Cristian


    Collaborative systems are widely used today in various activity fields. Their complexity is high and the development involves numerous resources and costs. Testing collaborative systems has a very important role for the systems' success. In this paper we present taxonomy of collaborative systems. The collaborative systems are classified in many…

  12. Systems Intelligence Inventory (United States)

    Törmänen, Juha; Hämäläinen, Raimo P.; Saarinen, Esa


    Purpose: Systems intelligence (SI) (Saarinen and Hämäläinen, 2004) is a construct defined as a person's ability to act intelligently within complex systems involving interaction and feedback. SI relates to our ability to act in systems and reason about systems to adaptively carry out productive actions within and with respect to systems such as…

  13. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena


    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  14. Hepatitis C-associated arthritis. (United States)

    Buskila, D


    Rheumatologic complications of hepatitis C virus (HCV) infection are common and include mixed cryoglobulinemia, vasculitis, sicca symptoms, myalgia, arthritis, and fibromyalgia. The prevalence of cryoglobulinemia in Sweden and Germany is much lower compared with data from southern Europe. Viral, genetic, or environmental factors may be responsible for such a difference in prevalence. There is no single clinical picture of arthritis in patients with HCV infection. There is a well-defined picture of arthritis associated with the presence of mixed cryoglobulinemia that consists of an intermittent mono- or oligoarticular, nondestructive arthritis affecting large and medium-size joints. Involvement of salivary and lacrimal glands is common in HCV-infected subjects, but HCV antigens are not detected in affected glands. HCV-infected subjects express a high prevalence of a variety of autoantibodies, usually in low titers. The clinical significance of most of these autoantibodies is not clear. The prevalence and titer of these autoantibodies are unaffected by interferon-alpha therapy. Several studies have attempted to assess whether HCV infection may be involved in the etiopathogenesis of rheumatic and autoimmune diseases. The results of most of these studies do not support the idea that HCV infection may play a pathogenic role in the development of systemic lupus erythematosus, antiphospholipid syndrome, or leukocytoclastic vasculitis. Experience treating patients with HCV-associated arthritis is limited and treatment remains controversial. No major therapeutic trials in HCV-associated arthritis were reported in the past 2 years.

  15. Hepatitis B, interferon, and acne fulminans in a young girl

    Directory of Open Access Journals (Sweden)

    Sandeep Arora


    Full Text Available Acne fulminans (AF is a very rare severe form of acne seen in young males, characterized by a sudden and explosive onset of hemorrhagic pustules and ulceration on the trunk, systemic features in the form of fever, polyarthropathy, malaise, erythema nodosum and painful osteolytic bone involvement with leukocytosis, and an elevated erythrocyte sedimentation rate. Conventional treatment of AF includes corticosteroids or immunosuppressive agents for the initial phase followed by isotretinoin. Active hepatitis B infection with a high viral load precludes the administration of any immunosuppressive drugs. We present the case of an 18-year-old girl with a history of occasional acne who presented with AF of sudden onset following administration of interferon-alpha-2a for her recently detected hepatitis B infection. Management of hepatitis B was withheld in view of her general condition. The patient was managed with low dose isotretinoin with subsidence of lesions. AF in a young female precipitated by interferon and its management with isotretinoin in the presence of active hepatitis B infection make the case unique.

  16. [Drug-induced autoimmune hemolytic anemia]. (United States)

    Homberg, J C


    AUTOANTIBODY PRODUCTION: The production of autoantibodies can only occur if immune tolerance is circumvented. Thus drug-induced autoimmune hemolytic anemia requires that the drug have an effect on both autoantigens and on the immune system. AN EXAMPLE, METHYLDOPA: Methyldopa is a hypotensive agent which induces major production of anti-Rh IgG anti-erythrocyte autoantibodies, anti-nuclear antibodies and anti-actin antibodies. These autoantibodies generally appear 6 months after treatment onset and are observed in 20% of treated patients. Hemolysis is however exceptional and is only clinically or biologically perceptible in 1 to 2% of the patients who become immunized. Induced lupus has been reported as have been several dozen cases of drug-induced hepatitis with anti-actin autoantibodies. DRUGS INDUCING HEMOLYTIC ANEMIA: Besides methyldopa, other drugs known to induce hemolytic anemia include levodopa used for Parkinson's disease, mefenamic acid, a nonsteroidal antiinflammatory drug, interferon-alpha, used in chronic viral hepatitis, cyclosporin used for the prevention of graft rejection and the treatment of certain autoimmune diseases, and fludarabin, used in chronic lymphoid leukemia. If there is no clinical or biological expression, the drug can be continued, excepting fludarabin where regular controls are needed. If hemolytic anemia is patent, the drug must be discontinued, transfusion and corticosteroid therapy should be envisaged.

  17. Construction of a Novel Liver-Targeting Fusion Interferon by Incorporation of a Plasmodium Region I-Plus Peptide

    Directory of Open Access Journals (Sweden)

    Xuemei Lu


    Full Text Available Interferon alpha (IFN α exerts a multiplicity of biological actions including antiviral, immunomodulatory, and antiproliferative effects. Administration of IFN α is the current treatment for chronic hepatitis B; however, therapy outcome has not been completely satisfactory. The systemic effects of IFN α may account for its low in vivo biological activity and multiple adverse events. The purpose of this study was to design a novel liver-targeting fusion interferon (IFN-CSP by fusing IFN α2b with a Plasmodium region I-plus peptide, thus targeting the drug specifically to the liver. The DNA sequence encoding IFN-CSP was constructed using improved splicing by overlapping extension-PCR method, and then cloned into the pET-21b vector for protein expression in E. coli BL21 (DE3. The recombinant protein was expressed as a His-tagged protein and purified using a combination of Ni affinity and HiTrap affinity chromatography at a purity of over 95%. The final yield of biologically active IFN-CSP was up to 270 mg/L culture. The purified recombinant protein showed anti-HBV activity and liver-targeting potentiality in vitro. These data suggests that the novel fusion interferon IFN-CSP may be an excellent candidate as a liver-targeting anti-HBV agent.

  18. Granulomatous slack skin - seven years follow-up of a case with features of "parapsoriasis en plaques", muscle involvement, granulomatous vasculitis, and necrobiotic changes. (United States)

    ChiriŢă, Aurel Doru; Mărgăritescu, Irina


    Granulomatous slack skin (GSS) represents an extremely rare variant of mycosis fungoides with only 70 cases reported in the literature to date. It is characterized clinically by the occurrence of bulky, pendulous skinfolds, usually located in flexural areas and histologically by an infiltrate composed of small neoplastic T-lymphocytes joined by granulomatous inflammation with scattered multinucleated giant cells containing nuclei arranged in a wreath-like fashion. Since its first description, very rare cases of GSS with muscle involvement, large vessels involvement, or necrobiotic changes have been reported. We present an extraordinary case of GSS with all these unusual features developing in the lesions of the same patient. The long follow-up of seven years allowed us to document the evolution of each lesion. Some lesions appeared and evolved in a manner very reminiscent of those of "parapsoriasis en plaques", others were classical GSS lesions, and still others developed large ulcerated lesions. These ulcerated lesions consistently failed to respond to conventional wound therapy, skin directed therapy [retinoids + psoralen combined with ultraviolet A (PUVA)-therapy], and interferon-alpha therapy. Remarkably, the ulcers completely healed when systemic corticosteroids were added. We hence postulate that the ulcers appeared because of large vessel vasculitis rather than tumoral direct destruction.

  19. Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin. (United States)

    Cuevas, José Manuel; Torres-Puente, Manuela; Jiménez-Hernández, Nuria; Bracho, María Alma; García-Robles, Inmaculada; Wrobel, Boris; Carnicer, Fernando; del Olmo, Juan; Ortega, Enrique; Moya, Andrés; González-Candelas, Fernando


    We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective pressures.

  20. Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin.

    Directory of Open Access Journals (Sweden)

    José Manuel Cuevas


    Full Text Available We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, to identify particular adaptation mechanisms and to analyze the patterns of evolutionary change in both genome regions. These analyses failed to detect a common adaptive mechanism for the lack of response to antiviral treatment in these patients. On the contrary, a wide range of situations were observed, from patients showing no positively selected sites to others with many, and with completely different topologies in the reconstructed phylogenetic trees. Altogether, these results suggest that viral strategies to evade selection pressure from the immune system and antiviral therapies do not result from a single mechanism and they are likely based on a range of different alternatives, in which several different changes, or their combination, along the HCV genome confer viruses the ability to overcome strong selective pressures.

  1. IgE in lupus pathogenesis: Friends or foes? (United States)

    Augusto, Jean-François; Truchetet, Marie-Elise; Charles, Nicolas; Blanco, Patrick; Richez, Christophe


    Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immunological pathways. Recently, several studies have suggested an implication of Immunoglobulin E (IgE) in the pathophysiology of SLE. In the Lyn -/- and FcγIIB -/- .Yaa lupus mouse models, autoreactive IgE activate basophils, and promote a Th2 environment with, subsequently, production of autoantibodies by plasma cells. Autoreactive IgE has been also shown to play a role in the activation of human plasmacytoid dendritic cells (pDCs), in synergy with IgG, which results in an increase of interferon-alpha (IFN-α) production. In contrast, a protective effect of total non-autoreactive IgE has also been suggested, through a decreased ability of FcεRI-triggered pDCs to secrete IFN-α. This review summarizes in a comprehensive manner the emerging recent literature in the field, and propose new concepts to reconcile the observations. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Promoter Variant of PIK3C3 Is Associated with Autoimmunity against Ro and Sm Epitopes in African-American Lupus Patients

    Directory of Open Access Journals (Sweden)

    Silvia N. Kariuki


    Full Text Available The PIK3C3 locus was implicated in case-case genome-wide association study of systemic lupus erythematosus (SLE which we had performed to detect genes associated with autoantibodies and serum interferon-alpha (IFN-α. Herein, we examine a PIK3C3 promoter variant (rs3813065/-442 C/T in an independent multiancestral cohort of 478 SLE cases and 522 controls. rs3813065 C was strongly associated with the simultaneous presence of both anti-Ro and anti-Sm antibodies in African-American patients [OR=2.24 (1.34–3.73, P=2.0×10−3]. This autoantibody profile was associated with higher serum IFN-α (P=7.6×10−6. In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (P=2.0×10−5, which encodes an enzyme involved in MHC class I peptide processing. Thus, rs3813065 C is associated with a particular autoantibody profile and altered expression of an MHC peptide processing enzyme, suggesting that this variant modulates serologic autoimmunity in African-American SLE patients.

  3. Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients. (United States)

    Kariuki, Silvia N; Franek, Beverly S; Mikolaitis, Rachel A; Utset, Tammy O; Jolly, Meenakshi; Skol, Andrew D; Niewold, Timothy B


    The PIK3C3 locus was implicated in case-case genome-wide association study of systemic lupus erythematosus (SLE) which we had performed to detect genes associated with autoantibodies and serum interferon-alpha (IFN-alpha). Herein, we examine a PIK3C3 promoter variant (rs3813065/-442 C/T) in an independent multiancestral cohort of 478 SLE cases and 522 controls. rs3813065 C was strongly associated with the simultaneous presence of both anti-Ro and anti-Sm antibodies in African-American patients [OR = 2.24 (1.34-3.73), P = 2.0 x 10(-3)]. This autoantibody profile was associated with higher serum IFN-alpha (P = 7.6 x 10(-6)). In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (P = 2.0 x 10(-5)), which encodes an enzyme involved in MHC class I peptide processing. Thus, rs3813065 C is associated with a particular autoantibody profile and altered expression of an MHC peptide processing enzyme, suggesting that this variant modulates serologic autoimmunity in African-American SLE patients.

  4. Retinal toxicities of cancer therapy drugs: biologics, small molecule inhibitors, and chemotherapies. (United States)

    Liu, Catherine Y; Francis, Jasmine H; Brodie, Scott E; Marr, Brian; Pulido, Jose S; Marmor, Michael F; Abramson, David H


    To review reported retinal side effects from current cancer therapy drugs. Retinal toxicities from ophthalmologic or oncologic case reports, case series, and clinical trials were identified by a systematic literature search using Lexicomp and PubMed. Four biologics, 8 small molecule inhibitors, and 17 traditional chemotherapy agents had reported retinal side effects. For biologics, interferon alpha 2b was associated with retinopathy, denileukin diftitiox with pigmentary retinopathy, ipilimumab with a Vogt-Koyanagi-Harada-like syndrome, and trastuzumab with retinal ischemia. For small molecule inhibitors, v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors were associated with uveitis, mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitors with pigment epithelium detachments, and tyrosine kinase inhibitors with macular edema. Steroid antagonists were associated with crystalline retinopathy and macular edema. Nitrosoureas, platinum analogs, and cytosine arabinoside were associated with retinal vascular occlusions. Antimicrotubular agents were associated with cystoid macular edema but without fluorescein leakage. Retinoic acid derivatives were associated with impaired night vision, and mitotane was associated with a pigmentary retinopathy and papilledema. Certain agents used in the treatment of systemic cancer are associated with ocular complications. Awareness of these complications will allow early detections and maybe reversal of some of the ocular problems.

  5. Hepatitis C Virus Evasion from RIG-I-Dependent Hepatic Innate Immunity

    Directory of Open Access Journals (Sweden)

    Helene Minyi Liu


    Full Text Available Exposure to hepatitis C virus (HCV usually results in persistent infection that often develops into chronic liver disease. Interferon-alpha (IFN treatment comprises the foundation of current approved therapy for chronic HCV infection but is limited in overall efficacy. IFN is a major effector of innate antiviral immunity and is naturally produced in response to viral infection when viral pathogen-associated molecular patterns (PAMPs are recognized as nonself and are bound by cellular pathogen recognition receptors (PRRs, including Toll-like receptors (TLRs and the RIG-I-like receptors (RLRs. Within hepatocytes, RIG-I is a major PRR of HCV infection wherein PAMP interactions serve to trigger intracellular signaling cascades in the infected hepatocyte to drive IFN production and the expression of interferon-stimulated genes (ISGs. ISGs function to limit virus replication, modulate the immune system, and to suppress virus spread. However, studies of HCV-host interactions have revealed several mechanisms of innate immune regulation and evasion that feature virus control of PRR signaling and regulation of hepatic innate immune programs that may provide a molecular basis for viral persistence.

  6. TWRSview system requirements specification

    International Nuclear Information System (INIS)

    Caldwell, J.A.; Lee, A.K.


    This document provides the system requirements specification for the TWRSview software system. The TWRSview software system is being developed to integrate electronic data supporting the development of the TWRS technical baseline

  7. Antiskid braking system (United States)

    Pazdera, J. S.


    Published report describes analytical development and simulation of braking system. System prevents wheels from skidding when brakes are applied, significantly reducing stopping distance. Report also presents computer simulation study on system as applied to aircraft.

  8. Calo trigger acquisition system

    CERN Multimedia

    Franchini, Matteo


    Calo trigger acquisition system - Evolution of the acquisition system from a multiple boards system (upper, orange cables) to a single board one (below, light blue cables) where all the channels are collected in a single board.

  9. The Trinity System

    Energy Technology Data Exchange (ETDEWEB)

    Archer, Billy Joe [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Vigil, Benny Manuel [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)


    This paper describes the Trinity system, the first ASC Advanced Technology System (ATS-1). We describe the Trinity procurement timeline, the ASC computing strategy, the Trinity specific mission needs, and the Trinity system specifications.

  10. Central Nervous System Vasculitis (United States)

    ... Forms of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... your Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

  11. What Are Expert Systems? (United States)

    d'Agapeyeff, A.


    Intended for potential business users, this paper describes the main characteristics of expert systems; discusses practical use considerations; presents a taxonomy of the systems; and reviews several expert system development projects in business and industry. (MBR)

  12. Connected motorcycle system performance. (United States)


    This project characterized the performance of Connected Vehicle Systems (CVS) on motorcycles based on two key components: global positioning and wireless communication systems. Considering that Global Positioning System (GPS) and 5.9 GHz Dedicated Sh...

  13. Pneumatic transfer systems

    International Nuclear Information System (INIS)

    Bichler, H.; Boeck, H.; Hammer, J.; Buchtela, K.


    A pneumatic transfer system for research reactors, including a sample changer system and to be used for neutron activation analysis, is described. The system can be obtained commercially from the Atominstitut. 2 figs. (qui)

  14. System Software 7 Macintosh

    CERN Multimedia


    System 7 is a single-user graphical user interface-based operating system for Macintosh computers and was part of the classic Mac OS line of operating systems. It was introduced on May 13, 1991, by Apple Computer. It succeeded System 6, and was the main Macintosh operating system until it was succeeded by Mac OS 8 in 1997. Features added with the System 7 release included virtual memory, personal file sharing, QuickTime, QuickDraw 3D, and an improved user interface. This is the first real major evolution of the Macintosh system, bringing a significant improvement in the user interface, improved stability and many new features such as the ability to use multiple applications at the same time. "System 7" is the last operating system name of the Macintosh that contains the word "system". Macintosh operating systems were later called "Mac OS" (for Macintosh Operating System).

  15. Immune System Quiz (United States)

    ... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! Partner Message ...

  16. Male Reproductive System (United States)

    ... Videos for Educators Search English Español Male Reproductive System KidsHealth / For Parents / Male Reproductive System What's in ... your son's reproductive health. About the Male Reproductive System Most species have two sexes: male and female. ...

  17. Autonomic Nervous System Disorders (United States)

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  18. Gas transfer system

    International Nuclear Information System (INIS)

    Oberlin, J.C.; Frick, G.; Kempfer, C.; North, C.


    The state of work on the Vivitron gas transfer system and the system functions are summarized. The system has to: evacuate the Vivitron reservoir; transfer gas from storage tanks to the Vivitron; recirculate gas during operation; transfer gas from the Vivitron to storage tanks; and assure air input. The system is now being installed. Leak alarms are given by SF6 detectors, which set off a system of forced ventilation. Another system continuously monitors the amount of SF6 in the tanks [fr

  19. Battery systems engineering

    CERN Document Server

    Rahn, Christopher D


    A complete all-in-one reference on the important interdisciplinary topic of Battery Systems Engineering Focusing on the interdisciplinary area of battery systems engineering, this book provides the background, models, solution techniques, and systems theory that are necessary for the development of advanced battery management systems. It covers the topic from the perspective of basic electrochemistry as well as systems engineering topics and provides a basis for battery modeling for system engineering of electric and hybrid electric vehicle platforms. This original

  20. Small test SDHW systems

    DEFF Research Database (Denmark)

    Vejen, Niels Kristian


    Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different.......Three small test SDHW systems was tested in a laboratory test facility.The three SDHW systems where all based on the low flow principe and a mantle tank but the design of the systems where different....

  1. Bridge Management Systems

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle

    In this paper bridge management systems are discussed with special emphasis on management systems for reinforced concrete bridges. Management systems for prestressed concrete bridges, steel bridges, or composite bridges can be developed in a similar way.......In this paper bridge management systems are discussed with special emphasis on management systems for reinforced concrete bridges. Management systems for prestressed concrete bridges, steel bridges, or composite bridges can be developed in a similar way....

  2. Geometric Fuzzy Logic Systems


    Coupland, Simon


    There has recently been a significant increase in academic interest in the field oftype-2 fuzzy sets and systems. Type-2 fuzzy systems offer the ability to model and reason with uncertain concepts. When faced with uncertainties type-2 fuzzy systems should, theoretically, give an increase in performance over type-l fuzzy systems. However, the computational complexity of generalised type-2 fuzzy systems is significantly higher than type-l systems. A direct consequence of this is that, prior to ...

  3. Marketing reporting system

    Directory of Open Access Journals (Sweden)

    Hanić Hasan M.


    Full Text Available The main components of a developed and good organized marketing information system are: internal reporting system, marketing reporting system, market research system and analytical marketing system. Marketing reporting system provides data and information about changes in business and micro marketing environment. This component of MIS ensures that marketing managers are up-to-date with what is going on, and to be informed about changes in company marketing environment.

  4. Avionics System Performance Management

    National Research Council Canada - National Science Library

    Damania, Bhavesh


    .... The reasons for improved performance management include advances in processor technology and architectures, increasingly integrated systems, and the requirement of reducing costs in developing and deploying the systems...

  5. Airports Geographic Information System - (United States)

    Department of Transportation — The Airports Geographic Information System maintains the airport and aeronautical data required to meet the demands of the Next Generation National Airspace System....

  6. Control system design method (United States)

    Wilson, David G [Tijeras, NM; Robinett, III, Rush D.


    A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.

  7. Neural Systems Laboratory (United States)

    Federal Laboratory Consortium — As part of the Electrical and Computer Engineering Department and The Institute for System Research, the Neural Systems Laboratory studies the functionality of the...

  8. Credit Management System (United States)

    US Agency for International Development — Credit Management System. Outsourced Internet-based application. CMS stores and processes data related to USAID credit programs. The system provides information...

  9. Aeronautical Information System - (United States)

    Department of Transportation — The Aeronautical Information System (AIS) is a leased weather automated system that provides a means of collecting and distributing aeronautical weather information...

  10. Cognitive Medical Multiagent Systems

    Directory of Open Access Journals (Sweden)

    Barna Iantovics


    Full Text Available The development of efficient and flexible agent-based medical diagnosis systems represents a recent research direction. Medical multiagent systems may improve the efficiency of traditionally developed medical computational systems, like the medical expert systems. In our previous researches, a novel cooperative medical diagnosis multiagent system called CMDS (Contract Net Based Medical Diagnosis System was proposed. CMDS system can solve flexibly a large variety of medical diagnosis problems. This paper analyses the increased intelligence of the CMDS system, which motivates its use for different medical problem’s solving.

  11. Systems engineering for very large systems (United States)

    Lewkowicz, Paul E.

    Very large integrated systems have always posed special problems for engineers. Whether they are power generation systems, computer networks or space vehicles, whenever there are multiple interfaces, complex technologies or just demanding customers, the challenges are unique. 'Systems engineering' has evolved as a discipline in order to meet these challenges by providing a structured, top-down design and development methodology for the engineer. This paper attempts to define the general class of problems requiring the complete systems engineering treatment and to show how systems engineering can be utilized to improve customer satisfaction and profit ability. Specifically, this work will focus on a design methodology for the largest of systems, not necessarily in terms of physical size, but in terms of complexity and interconnectivity.

  12. Integrated Systems Health Management for Intelligent Systems (United States)

    Figueroa, Fernando; Melcher, Kevin


    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. It is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this paper, concepts, procedures, and approaches are presented as a foundation for implementing an intelligent systems ]relevant ISHM capability. The capability stresses integration of DIaK from all elements of a system. Both ground-based (remote) and on-board ISHM capabilities are compared and contrasted. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  13. Systems analysis of a security alarm system

    International Nuclear Information System (INIS)

    Schiff, A.


    When the Lawrence Livermore Laboratory found that its security alarm system was causing more false alarms and maintenance costs than LLL felt was tolerable, a systems analysis was undertaken to determine what should be done about the situation. This report contains an analysis of security alarm systems in general and ends with a review of the existing Security Alarm Control Console (SACC) and recommendations for its improvement, growth and change. (U.S.)

  14. Formal System Verification for Trustworthy Embedded Systems (United States)


    step is for the first time formal and machine-checked. Contemporary OS verification projects include Verisoft, Verisoft XT, and Verve . The Verisoft...tens of thousands lines of code. The Verve kernel [22] shows that type and memory safety properties can be established on the assembly level via and therefore with much lower cost. Verve contains a formally verified runtime system, in particular a garbage collector that the type system

  15. L-system fractals

    CERN Document Server

    Mishra, Jibitesh


    The book covers all the fundamental aspects of generating fractals through L-system. Also it provides insight to various researches in this area for generating fractals through L-system approach & estimating dimensions. Also it discusses various applications of L-system fractals. Key Features: - Fractals generated from L-System including hybrid fractals - Dimension calculation for L-system fractals - Images & codes for L-system fractals - Research directions in the area of L-system fractals - Usage of various freely downloadable tools in this area - Fractals generated from L-System including hybrid fractals- Dimension calculation for L-system fractals- Images & codes for L-system fractals- Research directions in the area of L-system fractals- Usage of various freely downloadable tools in this area


    Directory of Open Access Journals (Sweden)

    Tadeja Jere Jakulin


    Full Text Available Systems approach represents thinking outside the box and is connected to the transformation of common linear approach and thinking. Western society followed rules of classical western science, which form many centuries took analysis as mainstream of thinking and researching. One can find perfect and logical explanation for this. In the past, classical science researched matter and reached optimal results with analysis and analytical thinking. Nowadays more and more scientists research intangible world around matter and cooperate with prevailed, fastest growing service industry such as tourism. Following paper presents systems approach in tourism, which defines wideness, co-dependency among tourism system elements, and "big picture" point of view. In a frame of systems methodology, we will show the importance of systems approach in order to understand complexity in the area of tourism. At once an excellent example of the analytical approach will be shown in so called "the tip of the iceberg" theory, where events represent analytical thinking and structure or base of the iceberg represents systems approach. Complexity of the tourism systems will be explained and a model of a common tourism system developed. We claim that the analysis, in the past, caused technological progress; it caused the development of western science, which we now know it. It led to the discoveries but for dealing with contemporary complex challenges is not sufficient. Today a systems approach is suitable enough for dealing with complex question in the area of tourism and of course in global society.

  17. Power system protection 2 systems and methods

    CERN Document Server


    The worldwide growth in demand for electricity has forced the pace of developments in electrical power system design to meet consumer needs for reliable, secure and cheap supplies. Power system protection, as a technology essential to high quality supply, is widely recognised as a specialism of growing and often critical importance, in which power system needs and technological progress have combined to result in rapid developments in policy and practice in recent years. In the United Kingdom, the need for appropriate training in power system protection was recognised in the early 1960s with t

  18. Automating System Assembly of Aerospace Systems (United States)

    Manolios, Panagiotis


    One of the major challenges in modern aerospace designs is the integration and assembly of independently developed components. We have formalized this as the system assembly problem: from a sea of available components, which should be selected and how should they be connected, integrated, and assembled so that the overall system requirements are satisfied in a certifiable way? We present a powerful framework for automatically solving the system assembly problem directly from system requirements by using formal verification technology. We also present a case study where we applied our work to large-scale industrial examples from the Boeing Dreamliner.

  19. Site systems engineering: Systems engineering management plan

    Energy Technology Data Exchange (ETDEWEB)

    Grygiel, M.L. [Westinghouse Hanford Co., Richland, WA (United States)


    The Site Systems Engineering Management Plan (SEMP) is the Westinghouse Hanford Company (WHC) implementation document for the Hanford Site Systems Engineering Policy, (RLPD 430.1) and Systems Engineering Criteria Document and Implementing Directive, (RLID 430.1). These documents define the US Department of Energy (DOE), Richland Operations Office (RL) processes and products to be used at Hanford to implement the systems engineering process at the site level. This SEMP describes the products being provided by the site systems engineering activity in fiscal year (FY) 1996 and the associated schedule. It also includes the procedural approach being taken by the site level systems engineering activity in the development of these products and the intended uses for the products in the integrated planning process in response to the DOE policy and implementing directives. The scope of the systems engineering process is to define a set of activities and products to be used at the site level during FY 1996 or until the successful Project Hanford Management Contractor (PHMC) is onsite as a result of contract award from Request For Proposal DE-RP06-96RL13200. Following installation of the new contractor, a long-term set of systems engineering procedures and products will be defined for management of the Hanford Project. The extent to which each project applies the systems engineering process and the specific tools used are determined by the project`s management.

  20. Hot Spot Removal System: System description

    International Nuclear Information System (INIS)


    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System''s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section

  1. Information Systems Security Audit


    Gheorghe Popescu; Veronica Adriana Popescu; Cristina Raluca Popescu


    The article covers:Defining an information system; benefits obtained by introducing new information technologies; IT management;Defining prerequisites, analysis, design, implementation of IS; Information security management system; aspects regarding IS security policy; Conceptual model of a security system; Auditing information security systems and network infrastructure security.

  2. Product Service Systems

    DEFF Research Database (Denmark)

    Departing from Product Development models based on physical artefacts. Moving towards integrated Product Development and System Operations models suited Product/Service-systems......Departing from Product Development models based on physical artefacts. Moving towards integrated Product Development and System Operations models suited Product/Service-systems...

  3. ERP–systems


    Shustova I.


    In this work, we analyzed the existing ERP–systems of foreign and domestic manufacturers. Popular ERP–systems in the Republic of Belarus were considered. The leading ERP-systems in the domestic market and their features were described in detail. Finally, we described the steps that must be taken to select the most suitable ERP-system for a particular company.

  4. Medical imaging systems (United States)

    Frangioni, John V


    A medical imaging system provides simultaneous rendering of visible light and diagnostic or functional images. The system may be portable, and may include adapters for connecting various light sources and cameras in open surgical environments or laparascopic or endoscopic environments. A user interface provides control over the functionality of the integrated imaging system. In one embodiment, the system provides a tool for surgical pathology.

  5. Expert Systems: An Overview. (United States)

    Adiga, Sadashiv


    Discusses: (1) the architecture of expert systems; (2) features that distinguish expert systems from conventional programs; (3) conditions necessary to select a particular application for the development of successful expert systems; (4) issues to be resolved when building expert systems; and (5) limitations. Examples of selected expert systems…

  6. CDMA systems capacity engineering

    CERN Document Server

    Kim, Kiseon


    This new hands-on resource tackles capacity planning and engineering issues that are crucial to optimizing wireless communication systems performance. Going beyond the system physical level and investigating CDMA system capacity at the service level, this volume is the single-source for engineering and analyzing systems capacity and resources.

  7. Combinatorial Hybrid Systems

    DEFF Research Database (Denmark)

    Larsen, Jesper Abildgaard; Wisniewski, Rafal; Grunnet, Jacob Deleuran


    As initially suggested by E. Sontag, it is possible to approximate an arbitrary nonlinear system by a set of piecewise linear systems. In this work we concentrate on how to control a system given by a set of piecewise linear systems defined on simplices. By using the results of L. Habets and J. v...


    NARCIS (Netherlands)

    Belikov, Andrey; Williams, Owen; Droge, Bob; Tsyganov, Andrey; Boxhoorn, Danny; McFarland, John; Verdoes Kleijn, Gijs; Valentijn, E; Altieri, Bruno; Dabin, Christophe; Pasian, F.; Osuna, Pedro; Soille, P.; Marchetti, P.G.


    The Euclid Archive System prototype is a functional information system which is used to address the numerous challenges in the development of fully functional data processing system for Euclid. The prototype must support the highly distributed nature of the Euclid Science Ground System, with Science

  9. System Performance and Testing

    NARCIS (Netherlands)

    Frei, U.; Oversloot, H.


    This chapter compares and contrasts the system performance of two widely used solar thermal systems using testing and simulation programs. Solar thermal systems are used in many countries for heating domestically used water. In addition to the simple thermosiphon systems, better designed pumped

  10. Hybrid intelligent engineering systems

    CERN Document Server

    Jain, L C; Adelaide, Australia University of


    This book on hybrid intelligent engineering systems is unique, in the sense that it presents the integration of expert systems, neural networks, fuzzy systems, genetic algorithms, and chaos engineering. It shows that these new techniques enhance the capabilities of one another. A number of hybrid systems for solving engineering problems are presented.

  11. Immune System (For Parents) (United States)

    ... Staying Safe Videos for Educators Search English Español Immune System KidsHealth / For Parents / Immune System What's in this ... can lead to illness and infection. About the Immune System The immune system is the body's defense against ...

  12. The Linux Operating System

    Indian Academy of Sciences (India)

    Linux Distributions. Linux per se refers only to the kernel of the operating system. A full fledged Unix system however requires a set of applications and support software that make the system user friendly. Hundreds of programmers around the world ,have contributed to bring the Linux system to its current state of robustness.

  13. A Multiagent System for Distributed Systems Management


    H. M. Kelash; H. M. Faheem; M. Amoon


    The demand for autonomous resource management for distributed systems has increased in recent years. Distributed systems require an efficient and powerful communication mechanism between applications running on different hosts and networks. The use of mobile agent technology to distribute and delegate management tasks promises to overcome the scalability and flexibility limitations of the currently used centralized management approach. This work proposes a multiagent s...


    Environmental Systems Management is the management of environmental problems at the systems level fully accounting for the multi-dimensional nature of the environment. This includes socio-economic dimensions as well as the usual physical and life science aspects. This is importa...

  15. Transdisciplinarity Needs Systemism

    Directory of Open Access Journals (Sweden)

    Wolfgang Hofkirchner


    Full Text Available The main message of this paper is that systemism is best suited for transdisciplinary studies. A description of disciplinary sciences, transdisciplinary sciences and systems sciences is given, along with their different definitions of aims, scope and tools. The rationale for transdisciplinarity is global challenges, which are complex. The rationale for systemism is the concretization of understanding complexity. Drawing upon Ludwig von Bertalanffy’s intention of a General System Theory, three items deserve attention—the world-view of a synergistic systems technology, the world picture of an emergentist systems theory, and the way of thinking of an integrationist systems method.

  16. What is systems engineering?

    Energy Technology Data Exchange (ETDEWEB)

    Bahill, A.T. [comp.] [Arizona Univ. (United States). Systems and Industrial Engineering


    Systems Engineering is an interdisciplinary process that ensures that the customers` needs are satisfied throughout a system`s entire life cycle. This process includes: understanding customer needs; stating the problem; specifying requirements; defining performance and cost measures, prescribing tests, validating requirements, conducting design reviews, exploring alternative concepts, sensitivity analyses, functional decomposition, system design, designing and managing interfaces, system integration, total system test, configuration management, risk management, reliability analysis; total quality management; project management; and documentation. Material for this paper was gathered from senior Systems Engineers at Sandia National Laboratories.

  17. Photovoltaic systems and applications

    Energy Technology Data Exchange (ETDEWEB)


    Abstracts are given of presentations given at a project review meeting held at Albuquerque, NM. The proceedings cover the past accomplishments and current activities of the Photovoltaic Systems Research, Balance-of-System Technology Development and System Application Experiments Projects at Sandia National Laboratories. The status of intermediate system application experiments and residential system analysis is emphasized. Some discussion of the future of the Photovoltaic Program in general, and the Sandia projects in particular is also presented.

  18. SQL injection detection system


    Vargonas, Vytautas


    SQL injection detection system Programmers do not always ensure security of developed systems. That is why it is important to look for solutions outside being reliant on developers. In this work SQL injection detection system is proposed. The system analyzes HTTP request parameters and detects intrusions. It is based on unsupervised machine learning. Trained by regular request data system detects outlier user parameters. Since training is not reliant on previous knowledge of SQL injections, t...

  19. Multiprocessor data acquisition system

    International Nuclear Information System (INIS)

    Haumann, J.R.; Crawford, R.K.


    A multiprocessor data acquisition system has been built to replace the single processor systems at the Intense Pulsed Neutron Source (IPNS) at Argonne National Laboratory. The multiprocessor system was needed to accommodate the higher data rates at IPNS brought about by improvements in the source and changes in instrument configurations. This paper describes the hardware configuration of the system and the method of task sharing and compares results to the single processor system

  20. Intrusion detection system elements

    International Nuclear Information System (INIS)

    Eaton, M.J.; Mangan, D.L.


    This report highlights elements required for an intrusion detection system and discusses problems which can be encountered in attempting to make the elements effective. Topics discussed include: sensors, both for exterior detection and interior detection; alarm assessment systems, with the discussion focused on video assessment; and alarm reporting systems, including alarm communication systems and dislay/console considerations. Guidance on careful planning and design of a new or to-be-improved system is presented

  1. Licensing open spectrum systems


    Vázquez, Miguel Angel; Pérez Neira, Ana Isabel; Lagunas Hernandez, Miguel A.


    This paper studies how the spectrum regulation could change in the future open spectrum communication systems. Due to their huge success in short-range communication systems (WiFi, Zigbee, ...), broader area telecommunication providers might mimic the open spectrum philosophy to their systems. Nevertheless, current wireless open spectrum systems are not designed for wide areas and they do not provide QoS to their users. This work proposes an alternative to the nowadays open spectrum systems i...

  2. The control system

    International Nuclear Information System (INIS)


    The present control system has matured both in terms of age and capacity. Thus a new system based on a local area network (LAN) is being developed. A pilot project has been started but, owing to difficulties encountered with the present operating system used with the microprocessors, it has become necessary to reconsider the choice of operating system. A recently-released multi-tasking operating system that runs on the existing hardware has been chosen. 1 fig

  3. Structures and semiotic systems


    Somov, Georgij Yu


    A model of interrelations between various types of mentation and semiotic systems is suggested. The relations of structures, forms, and signs in different mentation processes and their effect on semiotic systems are discussed. Major features of these systems are examined from the viewpoint of simulation of changes in physical objects and human environment. Most are multilateral and are clearly structures of various systems. Their organizing role in semiotic systemity are evinced through the a...

  4. Systems Theory and Systems Approach to Leadership

    Directory of Open Access Journals (Sweden)

    Dr.Sc. Berim Ramosaj


    Full Text Available Systems theory is product of the efforts of many researchers to create an intermediate field of coexistence of all sciences. If not for anything else, because of the magnitude that the use of systemic thinking and systemic approach has taken, it has become undisputed among the theories. Systems theory not only provides a glossary of terms with which researchers from different fields can be understood, but provides a framework for the presentation and interpretation of phenomena and realities. This paper addresses a systematic approach to leadership, as an attempt to dredge leadership and systems theory literature to find the meeting point. Systems approach is not an approach to leadership in terms of a manner of leader’s work, but it’s the leader's determination to factorize in his leadership the external environment and relationships with and among elements. Leader without followers is unable to exercise his leadership and to ensure their conviction he should provide a system, a structure, a purpose, despite the alternative chaos. Systems approach clarifies the thought on the complexity and dynamism of the environment and provides a framework for building ideas. If the general system theory is the skeleton of science (Boulding: 1956, this article aims to replenish it with leadership muscles by prominent authors who have written on systems theory and leadership, as well as through original ideas. In this work analytical methods were used (by analyzing approaches individually as well as synthetic methods (by assaying individual approaches in context of entirety. The work is a critical review of literature as well as a deductive analysis mingled with models proposed by authors through inductive analysis. Meta-analysis has been used to dissect the interaction and interdependence between leadership approaches.

  5. Modeling Power Systems as Complex Adaptive Systems

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.


    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  6. Design of combi systems

    DEFF Research Database (Denmark)

    Andersen, Elsa; Shah, Louise Jivan; Furbo, Simon


    Investigations have shown that the thermal performance of Danish combi systems is a subject of large variations from system to system. Some systems are well performing, however, more systems have a poor performance. [Ellehauge K et al (2000)]. Most of the combined systems that are installed...... is determined. The calculations are based on the simulation program TrnSys [Klein S.A et al. (1996)] and weather data from the Danish Design Reference Year, DRY. The paper will present and compare measured and calculated thermal performances and solar fractions of different combi systems and the main reasons...... in Denmark correspond to the system illustrated in Figure1. The control system operates the three-way valve in the solar collector circuit so solar heat is supplied either to the storage tank or to the heat exchanger between the collector loop and the space-heating loop. [Ellehauge K, ShahL.J. (2000...

  7. System performance optimization

    International Nuclear Information System (INIS)

    Bednarz, R.J.


    The System Performance Optimization has become an important and difficult field for large scientific computer centres. Important because the centres must satisfy increasing user demands at the lowest possible cost. Difficult because the System Performance Optimization requires a deep understanding of hardware, software and workload. The optimization is a dynamic process depending on the changes in hardware configuration, current level of the operating system and user generated workload. With the increasing complication of the computer system and software, the field for the optimization manoeuvres broadens. The hardware of two manufacturers IBM and CDC is discussed. Four IBM and two CDC operating systems are described. The description concentrates on the organization of the operating systems, the job scheduling and I/O handling. The performance definitions, workload specification and tools for the system stimulation are given. The measurement tools for the System Performance Optimization are described. The results of the measurement and various methods used for the operating system tuning are discussed. (Auth.)

  8. Rover waste assay system

    International Nuclear Information System (INIS)

    Akers, D.W.; Stoots, C.M.; Kraft, N.C.; Marts, D.J.


    The Rover Waste Assay System (RWAS) is a nondestructive assay system designed for the rapid assay of highly-enriched 235 U contaminated piping, tank sections, and debris from the Rover nuclear rocket fuel processing facility at the Idaho Chemical Processing Plant. A scanning system translates a NaI(Tl) detector/collimator system over the structural components where both relative and calibrated measurements for 137 Cs are made. Uranium-235 concentrations are in operation and is sufficiently automated that most functions are performed by the computer system. These functions include system calibration, problem identification, collimator control, data analysis, and reporting. Calibration of the system was done through a combination of measurements on calibration standards and benchmarked modeling. A description of the system is presented along with the methods and uncertainties associated with the calibration and analysis of the system for components from the Rover facility. 4 refs., 2 figs., 4 tabs

  9. ITER cooling systems

    International Nuclear Information System (INIS)

    Natalizio, A.; Hollies, R.E.; Sochaski, R.O.; Stubley, P.H.


    The ITER reference system uses low-temperature water for heat removal and high-temperature helium for bake-out. As these systems share common equipment, bake-out cannot be performed until the cooling system is drained and dried, and the reactor cannot be started until the helium has been purged from the cooling system. This study examines the feasibility of using a single high-temperature fluid to perform both heat removal and bake-out. The high temperature required for bake-out would also be in the range for power production. The study examines cost, operational benefits, and impact on reactor safety of two options: a high-pressure water system, and a low-pressure organic system. It was concluded that the cost savings and operational benefits are significant; there are no significant adverse safety impacts from operating either the water system or the organic system; and the capital costs of both systems are comparable

  10. Micro Information Systems

    DEFF Research Database (Denmark)

    Ulslev Pedersen, Rasmus; Kühn Pedersen, Mogens


    such as medical and manufacturing. These new sensor applications have implications for information systems (IS) and, the authors visualize this new class of information systems as fractals growing from an established class of systems; namely that of information systems (IS). The identified applications...... and implications are used as an empirical basis for creating a model for these small new information systems. Such sensor systems are called embedded systems in the technical sciences, and the authors want to couple it with general IS. They call the merger of these two important research areas (IS and embedded...... systems) for micro information systems (micro-IS). It is intended as a new research field within IS research. An initial framework model is established, which seeks to capture both the possibilities and constraints of this new paradigm, while looking simultaneously at the fundamental IS and ICT aspects...

  11. Nonlinearity of colloid systems oxyhydrate systems

    CERN Document Server

    Sucharev, Yuri I


    The present monograph is the first systematic study of the non-linear characteristic of gel oxy-hydrate systems involving d- and f- elements. These are the oxyhydrates of rare-earth elements and oxides - hydroxides of d- elements (zirconium, niobium, titanium, etc.) The non-linearity of these gel systems introduces fundamental peculiarities into their structure and, consequently, their properties. The polymer-conformational diversity of energetically congenial gel fragments, which continu-ously transform under the effect of, for instance, system dissipation heat, is central to the au-thor's hy

  12. Embedded systems handbook networked embedded systems

    CERN Document Server

    Zurawski, Richard


    Considered a standard industry resource, the Embedded Systems Handbook provided researchers and technicians with the authoritative information needed to launch a wealth of diverse applications, including those in automotive electronics, industrial automated systems, and building automation and control. Now a new resource is required to report on current developments and provide a technical reference for those looking to move the field forward yet again. Divided into two volumes to accommodate this growth, the Embedded Systems Handbook, Second Edition presents a comprehensive view on this area

  13. Photovoltaic systems engineering

    CERN Document Server

    Messenger, Roger A


    BackgroundPopulation and Energy DemandEnergy UnitsCurrent World Energy Use PatternsExponential GrowthHubbert's Gaussian ModelNet Energy, Btu Economics, and the Test for SustainabilityDirect Conversion of Sunlight to Electricity with PhotovoltaicsThe SunThe Solar SpectrumThe Effect of Atmosphere on SunlightSunlight SpecificsCapturing SunlightIntroduction to PV SystemsThe PV CellThe PV ModuleThe PV ArrayEnergy StoragePV System LoadsPV System AvailabilityAssociated System Electronic ComponentsGeneratorsBalance of System (BOS) ComponentsGrid-Connected Utility-Interactive PV SystemsApplicable Codes and StandardsDesign Considerations for Straight Grid-Connected PV SystemsDesign of a System Based on Desired Annual System PerformanceDesign of a System Based on Available Roof SpaceDesign of a Microinverter-Based SystemDesign of a Nominal 21 kW System that Feeds a Three-Phase Distribution PanelDesign of a Nominal 250 kW SystemSystem Performance MonitoringMechanical ConsiderationsImportant Properties of MaterialsEstabli...

  14. EPICS system: an overview

    International Nuclear Information System (INIS)

    Bartlett, J.F.; Bobbitt, J.S.; Kramper, B.J.; Lahey, T.E.; MacKinnon, B.A.; West, R.E.


    This paper presents an overview of the EPICS control system at FERMILAB. EPICS is a distributed, multi-user, interactive system for the control and monitoring of particle beamlines at a high-energy experimental physics laboratory. The overview discusses the operating environment of the control system, the requirements which determined the design decisions, the hardware and software configurations, and plans for the future growth and enhancement of the present system. This paper is the first of three related papers on the EPICS system. The other two cover (1) the system structure and user interface and (2) RSX implementation issues

  15. Adaptive intrusion data system

    International Nuclear Information System (INIS)

    Johnson, C.S.


    An Adaptive Intrusion Data System (AIDS) was developed to collect data from intrusion alarm sensors as part of an evaluation system to improve sensor performance. AIDS is a unique digital data compression, storage, and formatting system. It also incorporates capability for video selection and recording for assessment of the sensors monitored by the system. The system is software reprogrammable to numerous configurations that may be utilized for the collection of environmental, bi-level, analog and video data. The output of the system is digital tapes formatted for direct data reduction on a CDC 6400 computer, and video tapes containing timed tagged information that can be correlated with the digital data

  16. Cooperating systems: Layered MAS (United States)

    Rochowiak, Daniel


    Distributed intelligent systems can be distinguished by the models that they use. The model developed focuses on layered multiagent system conceived of as a bureaucracy in which a distributed data base serves as a central means of communication. The various generic bureaus of such a system is described and a basic vocabulary for such systems is presented. In presenting the bureaus and vocabularies, special attention is given to the sorts of reasonings that are appropriate. A bureaucratic model has a hierarchy of master system and work group that organizes E agents and B agents. The master system provides the administrative services and support facilities for the work groups.

  17. Hydraulic Yaw System

    DEFF Research Database (Denmark)

    Stubkier, Søren; Pedersen, Henrik C.; Mørkholt, M.

    system and rotor shaft when utilizing the soft yaw drive concept compared to the original stiff yaw system. The physical demands of the hydraulic yaw system are furthermore examined for a life time of 20 years. Based on the extrapolated loads, the duty cycles show that it is possible to construct...... a hydraulic soft yaw system, which is able to reduce the loads on the wind turbine significantly. A full scale hydraulic yaw test rig is available for experiments and tests. The test rig is presented as well as the system schematics of the hydraulic yaw system....

  18. Reliable computer systems. (United States)

    Wear, L L; Pinkert, J R


    In this article, we looked at some decisions that apply to the design of reliable computer systems. We began with a discussion of several terms such as testability, then described some systems that call for highly reliable hardware and software. The article concluded with a discussion of methods that can be used to achieve higher reliability in computer systems. Reliability and fault tolerance in computers probably will continue to grow in importance. As more and more systems are computerized, people will want assurances about the reliability of these systems, and their ability to work properly even when sub-systems fail.

  19. EPICS system: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Bartlett, J.F.; Bobbitt, J.S.; Kramper, B.J.; Lahey, T.E.; MacKinnon, B.A.; West, R.E.


    This paper presents an overview of the EPICS control system at FERMILAB. EPICS is a distributed, multi-user, interactive system for the control and monitoring of particle beamlines at a high-energy experimental physics laboratory. The overview discusses the operating environment of the control system, the requirements which determined the design decisions, the hardware and software configurations, and plans for the future growth and enhancement of the present system. This paper is the first of three related papers on the EPICS system. The other two cover (1) the system structure and user interface and (2) RSX implementation issues.

  20. Braking System Integration in Dual Mode Systems (United States)


    An optimal braking system for Dual Mode is a complex product of vast number of multivariate, interdependent parameters that encompass on-guideway and off-guideway operation as well as normal and emergency braking. : Details of, and interralations amo...

  1. System of Systems Technology Readiness Assessment

    National Research Council Canada - National Science Library

    Majumdar, WindyJoy S


    ...). In many cases, advanced technologies must be matured simultaneously by multiple systems to support the degree of interoperability and/or integration required Current DoD guidance with respect...

  2. Water Fluoridation Reporting System (Public Water Systems) (United States)

    U.S. Department of Health & Human Services — The Water Fluoridation Reporting System (WFRS) has been developed to provide tools to assist states in managing fluoridation programs. WFRS is designed to track all...

  3. Combat Systems Department Employee Recognition System

    National Research Council Canada - National Science Library


    This handbook contains two types of information: guidelines and instructions. The guidelines provide a foundation of purpose, assumptions, principles, expectations and attributes the Employee Recognition System is designed to reflect...

  4. Business System Planning Project System Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    NELSON, R.E.


    The purpose of the Business Systems Planning Project System Requirements Specification (SRS) is to provide the outline and contents of the requirements for the CH2M HILL Hanford Group, Inc. (CHG) integrated business and technical information systems. The SRS will translate proposed objectives into the statement of the functions that are to be performed and data and information flows that they require. The requirements gathering methodology will use (1) facilitated group requirement sessions; (2) individual interviews; (3) surveys; and (4) document reviews. The requirements will be verified and validated through coordination of the technical requirement team and CHG Managers. The SRS document used the content and format specified in Lockheed Martin Services, Inc. Organization Standard Software Practices in conjunction with the Institute of Electrical and Electronics Engineers Standard 8340-1984 for Systems Requirements Documents.

  5. Information system development activities and inquiring systems

    DEFF Research Database (Denmark)

    Carugati, Andrea


    This article presents a framework that maps information system development (ISD) activities on systems for the creation of knowledge. This work addresses the relevant and persisting problem of improving the chances of ISD success. The article builds upon previous research on knowledge aspects...... provides a new way to see the development of a system in terms of the knowledge created in the process. The main practical implication of the framework is that it improves the managers' ability to guide ISD activities as knowledge activities embedded in a knowledge process, a crucial element in development...... of ISD, abandoning the idea of a monolithic approach to knowledge and presenting a pluralistic approach based on the idea that different inquiring systems can support micro-level ISD activities. The article is divided into two parts. The first part presents the theoretical development of the framework...

  6. Test System Impact on System Availability

    DEFF Research Database (Denmark)

    Pau, L. F.


    The specifications are presented for an imperfect automatic test system (ATS) (test frequency distribution, reliability, false alarm rate, nondetection rate) in order to account for the availability, readiness, mean time between unscheduled repairs (MTBUR), reliability, and maintenance of the sys......The specifications are presented for an imperfect automatic test system (ATS) (test frequency distribution, reliability, false alarm rate, nondetection rate) in order to account for the availability, readiness, mean time between unscheduled repairs (MTBUR), reliability, and maintenance...... of the system subject to monitoring and test. A time-dependent Markov model is presented, and applied in three cases, with examples of numerical results provided for preventive maintenance decisions, design of an automatic test system, buffer testing in computers, and data communications....

  7. User Registration Systems for Distributed Systems (United States)

    Murphy, K. J.; Cechini, M.; Pilone, D.; Mitchell, A.


    As NASA’s Earth Observing System Data and Information System (EOSDIS) systems have evolved over the years, most of the EOSDIS data are now available to users via anonymous on-line access. Although the changes have improved the dissemination efficiency of earth science data, the anonymous access has made it difficult to characterize users, capture metrics on the value of EOSDIS and provide customized services that benefit users. As the number of web-based applications continues to grow, data centers and application providers have implemented their own user registration systems and provided new tools and interfaces for their registered users. This has led to the creation of independent registration systems for accessing data and interacting with online tools and services. The user profile information maintained at each of these registration systems is not consistent and the registration enforcement varies by system as well. This problem is in no way unique to EOSDIS and represents a general challenge to the distributed computing community. In a study done in 2007(, the average user has approximately 7 passwords for about 25 accounts and enters a password 8 times a day. These numbers have only increased in the last three years. To try and address this, a number of solutions have been offered including Single Sign-On solutions using a common backend like Microsoft Active Directory or an LDAP server, trust based identity providers like OpenID, and various forms of authorization delegation like OAuth or SAML/XACML. This talk discusses the differences between authentication and authorization, the state of the more popular user registration solutions available for distributed use, and some of the technical and policy drivers that need to be considered when incorporating a user registration system into your application.


    International Nuclear Information System (INIS)

    Wilson, T.; Novotny, R.


    The objective of this analysis is to identify issues and criteria that apply to the design of the Subsurface Emplacement Transportation System (SET). The SET consists of the track used by the waste package handling equipment, the conductors and related equipment used to supply electrical power to that equipment, and the instrumentation and controls used to monitor and operate those track and power supply systems. Major considerations of this analysis include: (1) Operational life of the SET; (2) Geometric constraints on the track layout; (3) Operating loads on the track; (4) Environmentally induced loads on the track; (5) Power supply (electrification) requirements; and (6) Instrumentation and control requirements. This analysis will provide the basis for development of the system description document (SDD) for the SET. This analysis also defines the interfaces that need to be considered in the design of the SET. These interfaces include, but are not limited to, the following: (1) Waste handling building; (2) Monitored Geologic Repository (MGR) surface site layout; (3) Waste Emplacement System (WES); (4) Waste Retrieval System (WRS); (5) Ground Control System (GCS); (6) Ex-Container System (XCS); (7) Subsurface Electrical Distribution System (SED); (8) MGR Operations Monitoring and Control System (OMC); (9) Subsurface Facility System (SFS); (10) Subsurface Fire Protection System (SFR); (11) Performance Confirmation Emplacement Drift Monitoring System (PCM); and (12) Backfill Emplacement System (BES)

  9. System and method for creating expert systems (United States)

    Hughes, Peter M. (Inventor); Luczak, Edward C. (Inventor)


    A system and method provides for the creation of a highly graphical expert system without the need for programming in code. An expert system is created by initially building a data interface, defining appropriate Mission, User-Defined, Inferred, and externally-generated GenSAA (EGG) data variables whose data values will be updated and input into the expert system. Next, rules of the expert system are created by building appropriate conditions of the rules which must be satisfied and then by building appropriate actions of rules which are to be executed upon corresponding conditions being satisfied. Finally, an appropriate user interface is built which can be highly graphical in nature and which can include appropriate message display and/or modification of display characteristics of a graphical display object, to visually alert a user of the expert system of varying data values, upon conditions of a created rule being satisfied. The data interface building, rule building, and user interface building are done in an efficient manner and can be created without the need for programming in code.

  10. Operating System for Runtime Reconfigurable Multiprocessor Systems

    Directory of Open Access Journals (Sweden)

    Diana Göhringer


    Full Text Available Operating systems traditionally handle the task scheduling of one or more application instances on processor-like hardware architectures. RAMPSoC, a novel runtime adaptive multiprocessor System-on-Chip, exploits the dynamic reconfiguration on FPGAs to generate, start and terminate hardware and software tasks. The hardware tasks have to be transferred to the reconfigurable hardware via a configuration access port. The software tasks can be loaded into the local memory of the respective IP core either via the configuration access port or via the on-chip communication infrastructure (e.g. a Network-on-Chip. Recent-series of Xilinx FPGAs, such as Virtex-5, provide two Internal Configuration Access Ports, which cannot be accessed simultaneously. To prevent conflicts, the access to these ports as well as the hardware resource management needs to be controlled, e.g. by a special-purpose operating system running on an embedded processor. For that purpose and to handle the relations between temporally and spatially scheduled operations, the novel approach of an operating system is of high importance. This special purpose operating system, called CAP-OS (Configuration Access Port-Operating System, which will be presented in this paper, supports the clients using the configuration port with the services of priority-based access scheduling, hardware task mapping and resource management.

  11. Business system: Sustainable development and anticipatory system

    Directory of Open Access Journals (Sweden)

    Vojko Potočan


    Full Text Available The existence and development of humankind depends mainly upon the co-ordinated operation of all areas and levels of human activity. However, in theory and in practice there is no model of operation, which would provide a harmonized and target oriented development. A partial solution is offered by sustainable development, which tries to define and carry out common goals of mankind with a harmonized implementation of human activities at all levels of its living and behaviour. Companies belong to central institutions of modern society which essentially co–create the sustainability of society. The company’s endeavour by simulation to prepare models of their goals concerning their internal and external environment. On the base of systemic treatment, we can define companies as business system, which can survive in a log-run only on the basis of sustainable development. The business system can also be supported by the application of the anticipatory systems. The anticipatory systems can be, in this sense, understood as an entity of the methodological approach, techniques and modes of work. Their characteristics have, a direct impact on the determination of goals, on the orientation of operation, and hence on the achievement of the business system results.

  12. Visitor Registration System (United States)

    US Agency for International Development — Visitor Registration System (VRS) streamlines visitor check-in and check-out process for expediting visitors into USAID. The system captures visitor information...

  13. Saturated Switching Systems

    CERN Document Server

    Benzaouia, Abdellah


    Saturated Switching Systems treats the problem of actuator saturation, inherent in all dynamical systems by using two approaches: positive invariance in which the controller is designed to work within a region of non-saturating linear behaviour; and saturation technique which allows saturation but guarantees asymptotic stability. The results obtained are extended from the linear systems in which they were first developed to switching systems with uncertainties, 2D switching systems, switching systems with Markovian jumping and switching systems of the Takagi-Sugeno type. The text represents a thoroughly referenced distillation of results obtained in this field during the last decade. The selected tool for analysis and design of stabilizing controllers is based on multiple Lyapunov functions and linear matrix inequalities. All the results are illustrated with numerical examples and figures many of them being modelled using MATLAB®. Saturated Switching Systems will be of interest to academic researchers in con...

  14. Voluntary Service System (VSS) (United States)

    Department of Veterans Affairs — Voluntary Service System (VSS) is a national-level application which replaced the site-based Voluntary Timekeeping System (VTK). VTK was used for many years at the...

  15. The remote control system

    International Nuclear Information System (INIS)

    Jansweijer, P.P.M.


    The remote-control system is applied in order to control various signals in the car of the spectrometer at distance. The construction (hardware and software) as well as the operation of the system is described. (author). 20 figs

  16. VT DSL Systems 2006 (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The VT DSL Broadband System dataset (DSL2006) includes polygons depicting the extent of Vermont's DSL broadband system as of 12/31/2006. This data...

  17. Drinking Water Distribution Systems (United States)

    Learn about an overview of drinking water distribution systems, the factors that degrade water quality in the distribution system, assessments of risk, future research about these risks, and how to reduce cross-connection control risk.

  18. Optical Airborne Tracker System (United States)

    National Aeronautics and Space Administration — The Optical Airborne Tracker System (OATS) is an airborne dual-axis optical tracking system capable of pointing at any sky location or ground target.  The objectives...

  19. Online data processing system

    International Nuclear Information System (INIS)

    Nakahara, Yoshinori; Yagi, Hideyuki; Yamada, Takayuki


    A pulse height analyzer terminal system PHATS has been developed for online data processing via JAERI-TOKAI computer network. The system is controled by using a micro-computer MICRO-8 which was developed for the JAERI-TOKAI network. The system program consists of two subprograms, online control system ONLCS and pulse height analyzer control system PHACS. ONLCS links the terminal with the conversational programming system of FACOM 230/75 through the JAERI-TOKAI network and controls data processing in TSS and remote batch modes. PHACS is used to control INPUT/OUTPUT of data between pulse height analyzer and cassette-MT or typewriter. This report describes the hardware configuration and the system program in detail. In the appendix, explained are real time monitor, type of message, PEX to PEX protocol and Host to Host protocol, required for the system programming. (author)

  20. Avian respiratory system disorders (United States)

    Olsen, Glenn H.


    Diagnosing and treating respiratory diseases in avian species requires a basic knowledge about the anatomy and physiology of this system in birds. Differences between mammalian and avian respiratory system function, diagnosis, and treatment are highlighted.

  1. Semiotic labelled deductive systems

    Energy Technology Data Exchange (ETDEWEB)

    Nossum, R.T. [Imperial College of Science, Technology and Medicine, London (United Kingdom)


    We review the class of Semiotic Models put forward by Pospelov, as well as the Labelled Deductive Systems developed by Gabbay, and construct an embedding of Semiotic Models into Labelled Deductive Systems.

  2. Cross Disciplinary Biometric Systems

    CERN Document Server

    Liu, Chengjun


    Cross disciplinary biometric systems help boost the performance of the conventional systems. Not only is the recognition accuracy significantly improved, but also the robustness of the systems is greatly enhanced in the challenging environments, such as varying illumination conditions. By leveraging the cross disciplinary technologies, face recognition systems, fingerprint recognition systems, iris recognition systems, as well as image search systems all benefit in terms of recognition performance.  Take face recognition for an example, which is not only the most natural way human beings recognize the identity of each other, but also the least privacy-intrusive means because people show their face publicly every day. Face recognition systems display superb performance when they capitalize on the innovative ideas across color science, mathematics, and computer science (e.g., pattern recognition, machine learning, and image processing). The novel ideas lead to the development of new color models and effective ...

  3. Health System Measurement Project (United States)

    U.S. Department of Health & Human Services — The Health System Measurement Project tracks government data on critical U.S. health system indicators. The website presents national trend data as well as detailed...

  4. Designing automatic resupply systems. (United States)

    Harding, M L


    This article outlines the process for designing and implementing autoresupply systems. The planning process includes determination of goals and appropriate participation. Different types of autoresupply mechanisms include kanban, breadman, consignment, systems contracts, and direct shipping from an MRP schedule.

  5. Handbook of systems toxicology

    National Research Council Canada - National Science Library

    Casciano, Daniel A; Sahu, Saura C


    "In the first handbook to comprehensively cover the emerging area of systems toxicology, the Handbook of Systems Toxicology provides an authoritative compilation of up-to-date developments presented...

  6. Organizing Systemic Innovation

    NARCIS (Netherlands)

    F.P.H. Jaspers (Ferdinand)


    textabstractSystemic innovation refers to product development activities that involve the change of multiple interdependent components. Unlike autonomous innovation, which refers to components that change independently, systemic innovation is for many firms the norm rather than the exception. This

  7. Renewable Energy Tracking Systems (United States)

    Renewable energy generation ownership can be accounted through tracking systems. Tracking systems are highly automated, contain specific information about each MWh, and are accessible over the internet to market participants.

  8. Inductive Monitoring System (IMS) (United States)

    National Aeronautics and Space Administration — IMS: Inductive Monitoring System The Inductive Monitoring System (IMS) is a tool that uses a data mining technique called clustering to extract models of normal...

  9. The Core Knowledge System

    National Research Council Canada - National Science Library

    Strat, Thomas M; Smith, Grahame B


    This document contains an in-depth description of the Core Knowledge System (CKS)-an integrative environment for the many functions that must be performed by sensor-based autonomous and semi-autonomous systems...

  10. Immune System and Disorders (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  11. Pneumonia - weakened immune system (United States)

    ... Pneumonia - weakened immune system To use the sharing features on this page, ... fighting off infection because of problems with the immune system. This type of disease is called "pneumonia in ...

  12. Geographical information systems

    DEFF Research Database (Denmark)

    Möller, Bernd


    The chapter gives an introduction to Geographical Information Systems (GIS) with particular focus on their application within environmental management.......The chapter gives an introduction to Geographical Information Systems (GIS) with particular focus on their application within environmental management....

  13. Systems engineering management plan

    International Nuclear Information System (INIS)

    Conner, C.W.


    The purpose of this Systems Engineering Management Plan (SEMP) is to prescribe the systems engineering procedures to be implemented at the Program level and the minimum requirements for systems engineering at the Program-element level. The Program level corresponds to the Director, OCRWM, or to the organizations within OCRWM to which the Director delegates responsibility for the development of the System and for coordinating and integrating the activities at the Program-element level. The Office of Policy and Outreach (OPO) and the Office of Resource Management (ORM) support the Director at the Program level. The Program-element level corresponds to the organizations within OCRWM (i.e., the Office of Geologic Repositories (OGR) and the Office of Storage and Transportation Systems (OSTS)) with overall responsibility for developing the System elements - that is, the mined geologic disposal system (MGDS), monitored retrievable storage (MRS) (if approved by Congress), and the transportation system

  14. Mobile intelligent autonomous systems

    National Research Council Canada - National Science Library

    Raol, J. R; Gopal, Ajith K


    "Written for systems, mechanical, aero, electrical, civil, industrial, and robotics engineers, this book covers robotics from a theoretical and systems point of view, with an emphasis on the sensor...

  15. BioSystems (United States)

    U.S. Department of Health & Human Services — The NCBI BioSystems Database provides integrated access to biological systems and their component genes, proteins, and small molecules, as well as literature...

  16. Multiuser MIMO Systems

    National Research Council Canada - National Science Library

    Poor, H. V


    .... This talk will discuss implications of using MIMO systems in multiple-access networks. The main focus of the talk will be on receiver signal processing for such systems and in particular on multiuser detection and related issues...

  17. Multiple System Atrophy (MSA) (United States)

    Multiple system atrophy (MSA) Overview Multiple system atrophy (MSA) is a rare, degenerative neurological disorder affecting your body's involuntary (autonomic) functions, including blood pressure, breathing, bladder function and muscle ...

  18. Cardiac conduction system (United States)

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals to the ... contract. The main components of the cardiac conduction system are the SA node, AV node, bundle of ...

  19. Gleason grading system (United States)

    ... Gleason grading system To use the sharing features on this page, ... score of between 5 and 7. Gleason Grading System Sometimes, it can be hard to predict how ...

  20. Central nervous system (United States)

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  1. Integrated Reporting Information System - (United States)

    Department of Transportation — The Integrated Reporting Information System (IRIS) is a flexible and scalable web-based system that supports post operational analysis and evaluation of the National...

  2. Pressurized water reactor systems

    International Nuclear Information System (INIS)

    Meyer, P.J.


    Design and mode of operation of the main PWR components are described: reactor core, pressure vessel and internals, cooling systems with pumps and steam generators, ancillary systems, and waste processing. (TK) [de

  3. Lithium battery management system (United States)

    Dougherty, Thomas J [Waukesha, WI


    Provided is a system for managing a lithium battery system having a plurality of cells. The battery system comprises a variable-resistance element electrically connected to a cell and located proximate a portion of the cell; and a device for determining, utilizing the variable-resistance element, whether the temperature of the cell has exceeded a predetermined threshold. A method of managing the temperature of a lithium battery system is also included.

  4. Systems of Innovation


    Soete, Luc; Verspagen, Bart; Weel, Bas ter


    We review the literature on national innovation systems. We first focus on the emergence of the concept of innovation systems, reviewing its historical origins and three main flavours (associated to three “founding fathers†of the concept). After this, we discuss how the notion of innovation systems filled a need for providing a broader basis for innovation policy. We conclude with some perspectives on the future of the innovation systems literature.

  5. Audit Management System

    CERN Document Server

    Alconada, Federico


    In the need of renewing their system, the Internal Audit department has given a proposal for building a new one. Taking into consideration the problems of their system they elaborated a requirement's list with the functionalities and features they were expecting from the new management system. This new system would be primarily for the use of the Internal Audit staff but it would also support the follow-up of internal audit recommendations by potentially all CERN staff members.

  6. Systemic Risk and Returns


    Boman, Arthur Lee


    I solve a consumption based model, with interfirm systemic risk, for a portfolio optimization with arbitrary return distributions and endogenous stochastic discount factor (sdf). The model highlights a new systemic risk: systemic allocation risk. In contrast to the case without systemic risk, the market and planner allocate capital differently. The externality causes the planner to reduce investment in the risky firm. The market, modeled as a representative agent, does not just ignore the ext...

  7. Wood Species Recognition System


    Bremananth R; Nithya B; Saipriya R


    The proposed system identifies the species of the wood using the textural features present in its barks. Each species of a wood has its own unique patterns in its bark, which enabled the proposed system to identify it accurately. Automatic wood recognition system has not yet been well established mainly due to lack of research in this area and the difficulty in obtaining the wood database. In our work, a wood recognition system has been designed based on pre-processing te...

  8. Market economic systems


    Pryor, Frederic L.


    The new comparative economics has focused on individual institutions, rather than the economic system as a whole. This essay argues that economic systems should be defined in terms of clusters of complementary or covarying institutions. A cluster analysis of OECD countries using data on forty different economic institutions shows that four economic systems characterize these nations. Further, these systems have no significant impact on economic growth or inflation, but they do have an importa...

  9. SSC Cryogenic System

    International Nuclear Information System (INIS)

    Brown, D.P.; Louttit, R.I.; Rode, C.; VanderArend, P.C.


    The design of the 4.5 K primary cooling system and higher temperature shield cooling systems for the SSC are described. Typical flow diagrams for the magnet piping systems are presented. Estimated heat loads are given. The systems have been designed to accomodate the great distances, 90 km and up, over which the load will be distributed. Provision has been made for cooldown, warmup, quench recovery and magnet replacement, as well as for steady-state operation

  10. IAEA safeguards information system

    International Nuclear Information System (INIS)

    Nardi, J.


    The basic concepts, structure, and operation of the Agency Safeguards Information System is discussed with respect to its role in accomplishing the overall objectives of safeguards. The basis and purposes of the Agency's information system, the structure and flow of information within the Agency's system, the relationship of the components is the Agency system, the requirements of Member States in respect of their reporting to the Agency, and the relationship of accounting data vis-a-vis facility and inspection data are described

  11. Operating system MINIX


    JIRKŮ, Radek


    This thesis introduces readers to the MINIX operating system, which was used in the creation of the Linux OS. It discusses the history and development of the system and explains its core and the file system. Also solves MINIX installation and configuration of the virtual machine at each step and deals with disputes that had a creator of Minix creator of Linux. In conclusion, compared with Linux MINIX and summarizes the advantages and disadvantages and the use of the operating system at present.

  12. Hybrid Action Systems

    DEFF Research Database (Denmark)

    Ronkko, Mauno; Ravn, Anders P.


    a differential action, which allows differential equations as primitive actions. The extension allows us to model hybrid systems with both continuous and discrete behaviour. The main result of this paper is an extension of such a hybrid action system with parallel composition. The extension does not change...... the original meaning of the parallel composition, and therefore also the ordinary action systems can be composed in parallel with the hybrid action systems....

  13. TMACS system description

    International Nuclear Information System (INIS)

    Scaief, C.C.


    This document provides a description of the Tank Monitor and Control System (TMACS). It is intended as an introduction for those persons unfamiliar with the system as well as a reference document for the users, maintenance personnel, and system designers. In addition to describing the system, the document outlines the associated drawing documentation, provides maintenance and spare parts information, and discusses other TMACS documents that provide additional detail

  14. Rainfed intensive crop systems

    DEFF Research Database (Denmark)

    Olesen, Jørgen E


    This chapter focuses on the importance of intensive cropping systems in contributing to the world supply of food and feed. The impact of climate change on intensive crop production systems is also discussed.......This chapter focuses on the importance of intensive cropping systems in contributing to the world supply of food and feed. The impact of climate change on intensive crop production systems is also discussed....

  15. System programming languages


    Šmit, Matej


    Most operating systems are written in the C programming language. Similar is with system software, for example, device drivers, compilers, debuggers, disk checkers, etc. Recently some new programming languages emerged, which are supposed to be suitable for system programming. In this thesis we present programming languages D, Go, Nim and Rust. We defined the criteria which are important for deciding whether programming language is suitable for system programming. We examine programming langua...

  16. Human Resource Management System


    Navaz, A. S. Syed; Fiaz, A. S. Syed; Prabhadevi, C.; Sangeetha, V.; Gopalakrishnan, S.


    The paper titled HUMAN RESOURCE MANAGEMENT SYSTEM is basically concerned with managing the Administrator of HUMAN RESOURCE Department in a company. A Human Resource Management System, refers to the systems and processes at the intersection between human resource management and information technology. It merges HRM as a discipline and in particular its basic HR activities and processes with the information technology field, whereas the programming of data processing systems evolved into standa...

  17. Vacuum system for ISABELLE

    International Nuclear Information System (INIS)

    Hobson, J.P.


    An analysis is presented of the proposed vacuum system for the planned ISABELLE storage rings with respect to acceptability and practicality from the vacuum viewport. A comparison is made between the proposed vacuum system and the vacuum system at the CERN ISR, and some comments on various design and operational parameters are made

  18. Flexible energy systems

    DEFF Research Database (Denmark)

    Lund, Henrik


    The paper discusses and analyses diffent national strategies and points out key changes in the energy system in order to achieve a system which can benefit from a high percentage of wind and CHP without having surplus production problems, introduced here as a flexible energy system....

  19. IDC System Specification Document.

    Energy Technology Data Exchange (ETDEWEB)

    Clifford, David J.


    This document contains the system specifications derived to satisfy the system requirements found in the IDC System Requirements Document for the IDC Reengineering Phase 2 project. Revisions Version Date Author/Team Revision Description Authorized by V1.0 12/2014 IDC Reengineering Project Team Initial delivery M. Harris

  20. Health Information Systems

    International Development Research Centre (IDRC) Digital Library (Canada)

    health information system can mean peoples' basic needs are unmet. Reducing silos and ensuring community input. Through its Governance and Equity in. Health Systems (GEHS) program, IDRC invests in research and training to help low- and middle-income countries strengthen their health information systems. The aim ...

  1. Lofar information system design

    NARCIS (Netherlands)

    Valentijn, E.; Belikov, A. N.


    The Lofar Information System is a solution for Lofar Long Term Archive that is capable to store and handle PBs of raw and processed data. The newly created information system is based on Astro-WISE - the information system for wide field astronomy. We review an adaptation of Astro-WISE for the new

  2. Central Dental Evacuation Systems. (United States)


    20 High-Vacuum Oral Evacuation System (HIVAC) for Oral Surgery, Periodontics, and Endodontics Treatment Rooms..................... steel rails. Rubber isolator pads between this frame and the structure floor absorb vibration and prevent its magnification . The inlet...System (HIVAC) for Oral Surgery, Periodontics, and Endodontics Treatment Rooms The HIVAC system is designed to build and sustain high vacuum pressures

  3. LOFAR Information System

    NARCIS (Netherlands)

    Begeman, K.; Belikov, A. N.; Boxhoorn, D. R.; Dijkstra, F.; Holties, H.; Meyer-Zhao, Z.; Renting, G. A.; Valentijn, E. A.; Vriend, W. -J.

    In this paper, we present a newly designed and implemented scientific information system for the LOFAR Long Term Archive. It is a distributed multi-tier storage and data processing system that allows a number of users to process Petabytes of data. The LOFAR Information System is designed on the base

  4. Automated System Marketplace 1994. (United States)

    Griffiths, Jose-Marie; Kertis, Kimberly


    Reports results of the 1994 Automated System Marketplace survey based on responses from 60 vendors. Highlights include changes in the library automation marketplace; estimated library systems revenues; minicomputer and microcomputer-based systems; marketplace trends; global markets and mergers; research needs; new purchase processes; and profiles…

  5. Maternal early warning systems. (United States)

    Friedman, Alexander M


    This article reviews evidence and recommendations for maternal early warning systems designed to reduce severe maternal morbidity and mortality. The clinical rationale for these systems is discussed as is research literature on early warning systems from other fields. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Personal Food System Mapping (United States)

    Wilsey, David; Dover, Sally


    Personal food system mapping is a practical means to engage community participants and educators in individualized and shared learning about food systems, decisions, and behaviors. Moreover, it is a useful approach for introducing the food system concept, which is somewhat abstract. We developed the approach to capture diversity of personal food…

  7. Polymerase chain reaction system (United States)

    Benett, William J.; Richards, James B.; Stratton, Paul L.; Hadley, Dean R.; Milanovich, Fred P.; Belgrader, Phil; Meyer, Peter L.


    A portable polymerase chain reaction DNA amplification and detection system includes one or more chamber modules. Each module supports a duplex assay of a biological sample. Each module has two parallel interrogation ports with a linear optical system. The system is capable of being handheld.

  8. Functional System Dynamics

    NARCIS (Netherlands)

    Ligterink, N.E.


    Functional system dynamics is the analysis, modelling, and simulation of continuous systems usually described by partial differential equations. From the infinite degrees of freedom of such systems only a finite number of relevant variables have to be chosen for a practical model description. The

  9. Operation auxiliary system (SAO)

    International Nuclear Information System (INIS)

    Lolich, J.; Santome, D.; Drexler, J.


    This work presents an auxiliary system for nuclear power plants operation (SAO). The development purpose consisted in a computing supervision system to be installed at different sites of a reactor, mainly in the control room. The inclusion of this system to a nuclear power plant minimizes the possibility of human error for the facility operation. (Author) [es

  10. Energy systems security

    CERN Document Server

    Voeller, John G


    Energy Systems Security features articles from the Wiley Handbook of Science and Technology for Homeland Security covering topics related to electricity transmission grids and their protection, risk assessment of energy systems, analysis of interdependent energy networks. Methods to manage electricity transmission disturbances so as to avoid blackouts are discussed, and self-healing energy system and a nano-enabled power source are presented.

  11. Information extraction system (United States)

    Lemmond, Tracy D; Hanley, William G; Guensche, Joseph Wendell; Perry, Nathan C; Nitao, John J; Kidwell, Paul Brandon; Boakye, Kofi Agyeman; Glaser, Ron E; Prenger, Ryan James


    An information extraction system and methods of operating the system are provided. In particular, an information extraction system for performing meta-extraction of named entities of people, organizations, and locations as well as relationships and events from text documents are described herein.

  12. Faculty Assignment Classification System. (United States)

    Whatcom Community Coll., Ferndale, WA.

    This document outlines the point-based faculty assignment classification system in effect at Whatcom Community College (Washington). The purpose of the point system is to provide an equitable and flexible means of compensating faculty members based on a system of assigning quantitative values to tasks. Teaching, which includes classroom…

  13. The Quality System

    DEFF Research Database (Denmark)

    Brogaard Buus, Daniel; Eland, Morten Vestergaard; Lystlund, Rasmus


    In this article, we present our efforts to try to increase cohesiveness and connectivity between quests generated by a recreation of an existing procedural quest generation system, with an addition of a progressive tier system called Quality System. A study gave strong indications that the Quality...

  14. Network SCADA System

    International Nuclear Information System (INIS)

    Milivojevic, Dragan R.; Tasic, Visa; Karabasevic, Dejan


    Copper Institute, Industrial Informatics department, is developing and applying network real time process monitoring and control systems. Some of these systems are already in use. The paper presents some hardware and software general remarks and performances, with special regard to communication sub-systems and network possibilities. (Author)

  15. Fusion systems engineering

    International Nuclear Information System (INIS)



    Summaries of research are included for each of the following topics: (1) fusion reactor systems studies, (2) development of blanket processing technology for fusion reactors, (3) safety studies of fusion concepts, (4) the MACK/MACKLIB system for nuclear response functions, and (5) energy storage and power supply systems for fusion reactors

  16. Digestive System (For Teens) (United States)

    ... Staying Safe Videos for Educators Search English Español Digestive System KidsHealth / For Teens / Digestive System What's in this ... out of the body as feces. About the Digestive System Every morsel of food we eat has to ...

  17. Automated Vehicle Monitoring System


    Wibowo, Agustinus Deddy Arief; Heriansyah, Rudi


    An automated vehicle monitoring system is proposed in this paper. The surveillance system is based on image processing techniques such as background subtraction, colour balancing, chain code based shape detection, and blob. The proposed system will detect any human's head as appeared at the side mirrors. The detected head will be tracked and recorded for further action.

  18. Solar tracking system (United States)

    Okandan, Murat; Nielson, Gregory N.


    Solar tracking systems, as well as methods of using such solar tracking systems, are disclosed. More particularly, embodiments of the solar tracking systems include lateral supports horizontally positioned between uprights to support photovoltaic modules. The lateral supports may be raised and lowered along the uprights or translated to cause the photovoltaic modules to track the moving sun.

  19. Radiology systems architecture. (United States)

    Deibel, S R; Greenes, R A


    This article focuses on the software requirements for enterprise integration in radiology. The needs of a future radiology systems architecture are examined, both at a concrete functional level and at an abstract system-properties level. A component-based approach to software development is described and is validated in the context of each of the abstract system requirements for future radiology computing environments.

  20. Expert Systems in Education. (United States)

    Hartschuh, Wayne

    This paper argues that the concepts and techniques used in the development of expert systems should be expanded and applied to the field of education, particularly in the area of intelligent tutoring systems. It is noted that expert systems are a well known area of artificial intelligence and have been proven effective in well-defined topic areas.…

  1. Knowledge systems in agroforestry (United States)

    Wieland Kunzel


    Pacific Islands agroforestry has evolved into sustainable, diverse and productive a land use systems in many areas. We marvel at these systems, and the scientific world is trying to catch up with the traditional knowledge. At the same time, Pacific Islands farmers are abandoning their agroforestry systems in great numbers. It is mainly intensified agriculture for cash...

  2. Interactions within wastewater systems

    NARCIS (Netherlands)

    Langeveld, J.G.


    Wastewater systems consist of sewer systems and wastewater treatment works. As the performance of a wastewater treatment plant is affected by the characteristics, i.e. operation and design, of the contributing sewer systems, knowledge of the interactions between sewers and wastewater treatment works

  3. NPOx Decontamination System

    Energy Technology Data Exchange (ETDEWEB)

    Archibald, K.; Demmer, R.; Argyle, M.; Ancho, M.; Hai-Pao, J.


    The nitric acid/potassium permanganate/oxalic acid (NPOx) Phase II system is being prepared for remote operation at the Idaho National Engineering and Environmental Laboratory (INEEL). Several tests have been conducted to prepare the system for remote operation. This system performs very well with high decontamination efficiencies and very low quantities of waste generated during decontamination.

  4. Dynamic Systems and Control Engineering

    International Nuclear Information System (INIS)

    Kim, Jong Seok


    This book deals with introduction of dynamic system and control engineering, frequency domain modeling of dynamic system, temporal modeling of dynamic system, typical dynamic system and automatic control device, performance and stability of control system, root locus analysis, analysis of frequency domain dynamic system, design of frequency domain dynamic system, design and analysis of space, space of control system and digital control system such as control system design of direct digital and digitalization of consecutive control system.

  5. Alpha -2b treatment of Malignant Melanoma

    African Journals Online (AJOL)

    Introduction. Interferon preparations such as interferon alpha are widely used in the treatment of a number of non malignant and malignant conditions including malignant melanoma where it used. Mania has been observed in patients undergoing interferon treatment especially after significant dose- reduction or treatment ...

  6. Status og perspektiver for behandling af de kroniske myeloproliferative neoplasier

    DEFF Research Database (Denmark)

    Ocias, Lukas Frans; Holmström, Morten Orebo; Riley, Caroline Hasselbalch


    of these malignancies has focused on lowering their inherent thromboembolic risk but with the discovery of the JAK2-V617F mutation and most recently the calreticulin mutations new therapeutic options such as interferon-alpha, JAK2-inhibitors and statins are being contemplated. This article reviews these new treatment...

  7. Role of IL-2 and interferon in the generation of natural cytotoxic activity in influenza virus-stimulated PBL cultures: analysis with the use of prednisolone

    NARCIS (Netherlands)

    Braakman, E.; Treep-van Leeuwen, P.; ten Berge, R. J.; Schellekens, P. T.; Lucas, C. J.


    We have examined the role of interleukin 2, interferon-gamma and interferon-alpha in the generation of natural cytotoxic (NC) activity and cytotoxic T-lymphocyte (CTL) activity in peripheral blood lymphocyte cultures stimulated with influenza virus, using the immunosuppressive effects of

  8. Hepatitis c virus antibodies in mother-infant blood pair in Zaria

    African Journals Online (AJOL)


    Jun 1, 2017 ... acute infection in children proceed to chronic infections at the same rate as in adults with vertically transmitted ... step 3rd generation indirect ELISA. The HCV antibody test for both mothers and babies .... duction of interferon (alpha. beta. gamma) as described in the placental environment. The finding in this ...

  9. Alpha interferon therapy in Danish haemophiliac patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Laursen, A L; Scheibel, E; Ingerslev, Jørgen


    Following a survey among all Danish haemophiliac patients 49 HIV-negative patients with chronic hepatitis C were offered enrollment in a randomized controlled open label study comparing two different maintenance regimens following standard interferon-alpha-2b treatment. Dose modifications and tre...

  10. Expression of recombinant interferon α-2a in tobacco chloroplasts ...

    African Journals Online (AJOL)



    Nov 23, 2011 ... Moreover, the interferon alpha-2a protein was purified by using Ni-NTA purification columns. The presence of a fragment of 20 kDa size on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and high performance liquid chromatography (HPLC) chromatogram confirms the expression ...

  11. Long-term follow-up of antiviral combination therapy in chronic hepatitis B

    NARCIS (Netherlands)

    de Man, R. A.; Schalm, S. W.; Heijtink, R. A.; Berk, L.; den Ouden, J.; ten Kate, F. J.; Chamuleau, R. A.; Reesink, H. W.


    For patients with chronic hepatitis B e (HBe)-positive hepatitis, long-term results of pilot studies with lymphoblastoid interferon-alpha, acyclovir, or a combination, and of a randomized controlled trial of interferon/desciclovir combination therapy are presented. HBe seroconversion was observed in


    Directory of Open Access Journals (Sweden)

    A.V. Gorelov


    Full Text Available The article presents an interim statistical analysis of the open multicenter randomized clinical trial, whose goal was to evaluate the efficiency and safety of immunomodulatory therapy of acute intestinal infections of viral etiology in children. Patients and methods: at this stage 28 children aged 6 months to 6 years with a clinically diagnosed viral diarrhea were included in the study. Children were randomly assigned to two groups: basic, where for the treatment was used the suppository preparation of recombinant human interferon alpha-2b in combination with taurine, and a control group, where the patients admitted the drug as the recombinant human interferon alpha-2b in combination with a complex immunoglobulin preparation. The dynamics of the relief of individual viral diarrhea symptoms was assessed within 5 days after the patient was included in the study. Results: the analysis of the data revealed no significant differences in the efficiency of the investigated drugs, this fact suggests the equivalence of the produced therapeutic effect. The use of the preparation containing recombinant human interferon alpha-2b in combination with taurine, reduces the level of a drug load on the child’s organism without loss of the treatment efficiency.Key words: recombinant human interferon alpha-2b, taurine, an acute intestinal infection of viral etiology, treatment, children.

  13. Immunotherapy with concurrent subcutaneous GM-CSF, low-dose IL-2 and IFN-alpha in patients with progressive metastatic renal cell carcinoma

    NARCIS (Netherlands)

    Verra, N.; Jansen, R.; Groenewegen, G.; Mallo, H.; Kersten, M. J.; Bex, A.; Vyth-Dreese, F. A.; Sein, J.; van de Kasteele, W.; Nooijen, W. J.; de Waal, M.; Horenblas, S.; de Gast, G. C.


    The purpose of the study was to determine toxicity, efficacy and immunologic effects of concurrent subcutaneous injections of low-dose interleukin-2 (LD-IL-2), granulocyte-monocyte colony-stimulating factor (GM-CSF) and interferon-alpha 2b (IFNalpha) in progressive metastatic renal cell carcinoma.

  14. Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model After Antibody Blockade of Type I Interferon (United States)


    46. Sheehan KC, Lazear HM, Diamond MS, Schreiber RD (2015) Selective Blockade of Interferon-alpha and -beta Reveals Their Non-Redundant Functions ...4: 229-237. 49. Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, et al. (1998) Microglia-specific 750 localisation of a novel calcium binding

  15. Study of toll-like receptor 7 expression and interferon α in Egyptian ...

    African Journals Online (AJOL)

    Tahany A. Abdel-Raouf


    com (H.M. Abdella). Peer review under responsibility of Ain Shams University. ..... interferon-alpha. Egypt J Immunol 2013;20(1):13–22. [28] Chang. Toll-like receptors: target of hepatitis c virus: A Disser- tation. University of ...

  16. Anti-hepatitis B viral activity of Phyllanthus niruri L (Phyllanthaceae ...

    African Journals Online (AJOL)

    obliteration, the infection can lead to HCC or cirrhosis [2]. More than 300 million individuals are infected with HBV, which is thus considered a pandemic [3]. Treatments for HBV infection include standard and pegylated interferon-alpha and nucleoside analogues such as entecavir, lamivudine and adefovir. However, current.

  17. African Health Sciences - Vol 17, No 2 (2017)

    African Journals Online (AJOL)

    Osteopontin as a marker for response to pegylated interferon Alpha-2b treatment in Chronic HCV Saudi patients · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Yousri Mostafa Hussein, Ayman Alhazmi, Saad Alzahrani, Ahmad El-Askary, Abdulrahman Alghamdy, ...

  18. Impact of occult hepatitis B virus infection on antiviral therapy in ...

    African Journals Online (AJOL)

    Gamal El Din Ahmed Elsawaf


    Jan 7, 2015 ... chronic hepatitis C; Peg-IFN o and RBV, pegylated interferon alpha and ribavirin; SVR, sustained virological response; RNA, ribonucleic acid. * Corresponding .... 2. Materials and methods. Fifty chronic HCV infected patients who were treated with. 180 μg Peg-IFNo-2a or 1.5 μg/kg Peg-IFNo-2b once a week.

  19. Case report

    African Journals Online (AJOL)



    Jun 4, 2012 ... Immunohistochemical staining revealed strong, diffuse positive S-100 protein and staining for the melanoma markers HMB45 and Milan A, was suggestive of malignant melanoma, and omentum?s lesion metastatic. Palliative Chemotherapy with. Interferon alpha 2b (IFN∞2b) was begun by the oncology ...

  20. Podophyllin induced urethral stricture in a young Nigerian male

    African Journals Online (AJOL)

    P.O. Areo

    acid and interferon alpha 2b. Others are cryotherapy, photodynamic therapy and electrocautery. They work by destroying affected tis- sue by cytotoxic or a physically ablative mode of action. None of these is uniformly successful in the treatment of this disease. [7]. Podophyllin resin is an antimitotic plant extract prepared as.