WorldWideScience

Sample records for human autoantigen ku

  1. CRALBP is a Highly Prevalent Autoantigen for Human Autoimmune Uveitis

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    Cornelia A. Deeg

    2007-01-01

    uveitis patient's sera was first evaluated in two-dimensional (2D Western blot analysis. Subsequent identification of the immunoreactive proteins by mass spectrometry resulted in the identification of CRALBP as a putative autoantigen. Additionally, sera from human uveitis and control patients were by Western blot using purified human recombinant CRALBP. Anti-CRALBP autoantibodies occur more frequently (P<.01 in human uveitis patients than in normal controls. Thirty out of 56 tested uveitis patient's sera contained autoantibodies reactive against CRALBP, compared to only four out of 23 normal control subjects. The presence of CRALBP autoantibodies in 54% of tested uveitis patients supports CRALBP as a possible autoantigen in human autoimmune uveitis.

  2. Expression of pemphigus-autoantigen desmoglein 1 in human thymus.

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    Mouquet, H; Berrih-Aknin, S; Bismuth, J; Joly, P; Gilbert, D; Tron, F

    2008-05-01

    Desmoglein (Dsg) 1 is a transmembrane glycoprotein of the desmosome allowing cell-cell adhesion between keratinocytes, whose expression is restricted to stratified squamous epithelia-like epidermis. Dsg1 is the target autoantigen of pathogenic autoantibodies produced by pemphigus foliaceus and 50% of pemphigus vulgaris patients in a Dsg1-specific T-cell-dependent pathway. Herewith, we show that mRNA of the DSG1 gene is present in normal human thymus and show by quantitative real-time polymerase chain reaction analysis that the expression of DSG1 transcript increases with age. Although immunoblot analysis on human thymus extracts using different anti-Dsg1 antibodies did not allow to detect the protein, we show by double-immunofluorescence assay that Dsg1 is expressed at protein level by CD19+ CD63+ cells located in the medulla. These data provide another illustration of the thymic expression of a tissue-specific autoantigen involved in an organ-specific autoimmune disease, which may participate in the tolerance acquisition and/or regulation of Dsg1-specific T cells.

  3. Ku80 binds to human replication origins prior to the assembly of the ORC complex.

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    Sibani, Sahar; Price, Gerald B; Zannis-Hadjopoulos, Maria

    2005-05-31

    The Ku heterodimer, an abundant nuclear protein, binds DNA replication origins in a sequence-specific manner and promotes initiation. In this study, using HCT116 Ku80+/- haplo-insufficient and Orc2(delta/-) hypomorphic cells, the order of binding of Ku and the human origin recognition complex (HsORC) was determined. The nuclear expression of Ku80 was found to be decreased by 60% in Ku80+/- cells, while its general association with chromatin was decreased by 33%. Coimmunoprecipitation studies indicated that the Ku heterodimer associates specifically with the human HsOrc-2, -3, -4, and -6 subunits. Chromatin immunoprecipitation (ChIP) experiments, using cells synchronized to late G1, showed that the association of Ku80 with the lamin B2, beta-globin, and c-myc origins in vivo was decreased by 1.5-, 2.3-, and 2.5-fold, respectively, in Ku80+/- cells. The association of HsOrc-3, -4, and -6 was consistently decreased in all three origins examined in Ku80+/- cells, while that of HsOrc-2 showed no significant variation, indicating that the HsOrc-3, -4, and -6 subunits bind to the origins after Ku80. In Orc2(delta/-) cells, the association of HsOrc-2 with the lamin B2, beta-globin, and c-myc origins was decreased by 2.8-, 4.9-, and 2.8-fold, respectively, relative to wild-type HCT116 cells. Furthermore, nascent strand abundance at these three origins was decreased by 4.5-, 2.3-, and 2.6-fold in Orc2(delta/-) relative to HCT116 cells, respectively. Interestingly, the association of Ku80 with these origins was not affected in this hypomorphic cell line, indicating that Ku and HsOrc-2 bind to origins independently of each other.

  4. Shuttling of the autoantigen La between nucleus and cell surface after uv irradiation of human keratinocytes

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    Bachmann, M.; Chang, S.; Slor, H.; Kukulies, J.; Mueller, W.E. (Universitaet, Mainz (Germany, F.R.))

    1990-12-01

    During the past years we have established that the nuclear autoantigen La shuttles between the nucleus and the cytoplasm in tumor cells after inhibition of transcription or virus infection. We reinvestigated this shuttling using primary human keratinocytes from both healthy donors and patients with xeroderma pigmentosum. Ultraviolet irradiation resulted in both an inhibition of transcription and a translocation of La protein from the nucleus to the cytoplasm. After a prolonged inhibition of transcription La protein relocated into the nucleus and assembled with nuclear storage regions. The uv-induced shuttling included a translocation to the cell surface, where La protein colocalized with epidermal growth factor receptors.

  5. A sensitive method for detecting proliferation of rare autoantigen-specific human T cells.

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    Mannering, Stuart I; Morris, Jessica S; Jensen, Kent P; Purcell, Anthony W; Honeyman, Margo C; van Endert, Peter M; Harrison, Leonard C

    2003-12-01

    The ability to measure proliferation of rare antigen-specific T cells among many bystanders is critical for the evaluation of cellular immune function in health and disease. T-cell proliferation in response to antigen has been measured almost exclusively by 3H-thymidine incorporation. This method does not directly identify the phenotype of the proliferating cells and is frequently not sufficiently sensitive to detect rare autoantigen-specific T cells. To overcome these problems, we developed a novel assay for antigen-specific human T-cell proliferation. Peripheral blood mononuclear cells (PBMC) were labelled with the fluorescent dye 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) and cells that proliferated in response to antigen, with resultant reduction in CFSE intensity, were measured directly by flow cytometry. This assay was more sensitive than 3H-thymidine incorporation and detected the proliferation of rare antigen-specific CD4(+) T cells at 10-fold lower antigen concentrations. It also allowed the phenotype of the proliferating cells to be directly determined. Using the CFSE assay we were able to measure directly the proliferation of human CD4(+) T cells from healthy donors in response to the type 1 diabetes autoantigens glutamic acid decarboxylase (GAD) and proinsulin (PI).

  6. Changes in the expression of human cell division autoantigen-1 influence Toxoplasma gondii growth and development.

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    Jay R Radke

    2006-10-01

    Full Text Available Toxoplasma is a significant opportunistic pathogen in AIDS, and bradyzoite differentiation is the critical step in the pathogenesis of chronic infection. Bradyzoite development has an apparent tropism for cells and tissues of the central nervous system, suggesting the need for a specific molecular environment in the host cell, but it is unknown whether this environment is parasite directed or the result of molecular features specific to the host cell itself. We have determined that a trisubstituted pyrrole acts directly on human and murine host cells to slow tachyzoite replication and induce bradyzoite-specific gene expression in type II and III strain parasites but not type I strains. New mRNA synthesis in the host cell was required and indicates that novel host transcripts encode signals that were able to induce parasite development. We have applied multivariate microarray analyses to identify and correlate host gene expression with specific parasite phenotypes. Human cell division autoantigen-1 (CDA1 was identified in this analysis, and small interfering RNA knockdown of this gene demonstrated that CDA1 expression causes the inhibition of parasite replication that leads subsequently to the induction of bradyzoite differentiation. Overexpression of CDA1 alone was able to slow parasite growth and induce the expression of bradyzoite-specific proteins, and thus these results demonstrate that changes in host cell transcription can directly influence the molecular environment to enable bradyzoite development. Investigation of host biochemical pathways with respect to variation in strain type response will help provide an understanding of the link(s between the molecular environment in the host cell and parasite development.

  7. Human islets and dendritic cells generate post-translationally modified islet auto-antigens

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    McLaughlin, Rene J; de Haan, Anne; Zaldumbide, Arnaud; de Koning, Eelco J; de Ru, Arnoud H; van Veelen, Peter A; van Lummel, Menno; Roep, Bart O

    2016-01-01

    Initiation of type 1 diabetes (T1D) requires a break in peripheral tolerance. New insights into neo-epitope formation indicate that post-translational modification of islet auto-antigens, for example via deamidation, may be an important component of disease initiation or exacerbation. Indeed, deamid

  8. DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor

    Institute of Scientific and Technical Information of China (English)

    Paola Mazzarelli; Carolina Gravina; Marco Caricato; Maria Luana Poeta; Monica Rinaldi; Sergio Valeri; Roberto Coppola; Vito Michele Fazio; Paola Parrella; Davide Seripa; Emanuela Signori; Giuseppe Perrone; Carla Rabitti; Domenico Borzomati; Armando Gabbrielli; Maria Giovanna Matera

    2005-01-01

    AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis.METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis.RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P<0.00). However,changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86nuclear expression, as determined by Western blot and immunohistochemical analyses (P<0.001). Cytoplasmic protein expression was found in pathological samples,but not in normal tissues either from tumor patients or from healthy subjects.CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.

  9. A Highly Expressed Human Protein, Apolipoprotein B-100, Serves as an Autoantigen in a Subgroup of Patients With Lyme Disease.

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    Crowley, Jameson T; Drouin, Elise E; Pianta, Annalisa; Strle, Klemen; Wang, Qi; Costello, Catherine E; Steere, Allen C

    2015-12-01

    To discover novel autoantigens associated with Lyme arthritis (LA), we identified T-cell epitopes presented in vivo by human leukocyte antigen (HLA)-DR molecules in patients' inflamed synovial tissue or joint fluid and tested each epitope for autoreactivity. Using this approach, we identified the highly expressed human protein, apolipoprotein B-100 (apoB-100), as a target of T- and B-cell responses in a subgroup of LA patients. Additionally, the joint fluid of these patients had markedly elevated levels of apoB-100 protein, which may contribute to its autoantigenicity. In patients with antibiotic-refractory LA, the magnitude of apoB-100 antibody responses correlated with increased numbers of plasma cells in synovial tissue, greater numbers and activation of endothelial cells, and more synovial fibroblast proliferation. Thus, a subset of LA patients have high levels of apoB-100 in their joints and autoreactive T- and B-cell responses to the protein, which likely contributes to pathogenic autoimmunity in patients with antibiotic-refractory LA.

  10. Construction and expression of a humanized M2 autoantigen trimer and its application in the diagnosis of primary biliary cirrhosis

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    Xiao-Hua Jiang; Ren-Qian Zhong; Sheng-Qian Yu; Yin Hu; Weng-Weng Li; Xian-Tao Kong

    2003-01-01

    AIM: To construct and express a humanized M2 autoantigen trimer designated as BPO and to apply it in the diagnosis of primary biliary cirrhosis (PBC). METHODS: cDNA fragments encoding M2-reactive epitopes of pyruvate dehydrogenase complex Ez (PDCE2), branched chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) and 2-oxo-glutarate dehydrogenase complex E2 (OGDC-E2) were amplified with PCR using total RNA extracted from human peripheral mononuclear blood cells. The fragments were cloned into the plasmid vector pQE-30 and then transferred into E. coliM15 (pREP4) for expression, which was induced by isopropylthio-β-Dgalactoside. The expressed recombinant BPO protein was demonstrated by SDS-PAGE, Western-blotting and Immunoabsorption test, its antigenic reactivity and specificity were identified with seven M2-positive sera confirmed at Euroimmun Research Center (Germany).Using the purified BPO, M2 antibodies in sera from patients with PBC and other liver related diseases were detected with ELISA. RESULTS: The expressed BPO was observed with both antigenic reactivity and specificity of M2 autoantigens. The determination of M2 antibodies by BPO with ELISA was more sensitive than using the Euroimmun's kit with the coefficients of variation less than 10 % in both interassay and intraassay.With the newly established method, M2 antibodies were found in 100 % (20/20) of patients with PBC. Six cases of liver disease with unknown etiology and 1 patient with drug induced liver injury had detectable levels of serum M2antibodies. There were also 2 patients with autoimmune cholangitis and 1 with autoimmune hepatitis showing M2-antibody positive. CONCLUSION: Compared with the routine immunofluorescenoe assay and commercially available assay kit using porcine heart mitochondrial protein as the antigen, the detection system established in the present study shows higher sensitivity and specificity and may be used as a powerful tool for the diagnosis of PBC.

  11. Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse,fish,fly,and worm

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    Chun-Xia Wang; Andreas Teufel; Uta Cheruti; Joachim Gr(o)tzinger; Peter R Galle; Ansgar W Lohse; Johannes Herkel

    2006-01-01

    AIM: To approach the elusive function of the SLA/LP molecule, we have characterized genomic organization and conservation of the major antigenic and functional properties of the SLA/LP molecule in various species.METHODS: By means of computational biology, we have characterized the complete SLA/LP gene, mRNA and deduced protein sequences in man, mouse,zebrafish, fly, and worm.RESULTS: The human SLA/LP gene sequence of approximately 39 kb, which maps to chromosome 4p15.2, is organized in 11 exons, of which 10 or 11 are translated, depending on the splice variant. Homologous molecules were identified in several biological model organisms. The various homologous protein sequences showed a high degree of similarity or homology, notably at those residues that are of functional importance. The only domain of the human protein sequence that lacks significant homology with homologous sequences is the major antigenic epitope recognized by autoantibodies from autoimmune hepatitis (AIH) patients.CONCLUSION: The SLA/LP molecule and its functionally relevant residues have been highly conserved throughout the evoluti n, suggesting an indispensable function of the molecule. The finding that the only non-conserved domain is the dominant antigenic epitope of the human SLA/LP sequence, suggests that SLA/LP autoimmunity is autoantigen-driven rather than being driven by molecular mimicry.

  12. Human RECQ1 interacts with Ku70/80 and modulates DNA end-joining of double-strand breaks.

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    Swetha Parvathaneni

    Full Text Available Genomic instability is a known precursor to cancer and aging. The RecQ helicases are a highly conserved family of DNA-unwinding enzymes that play key roles in maintaining genome stability in all living organisms. Human RecQ homologs include RECQ1, BLM, WRN, RECQ4, and RECQ5β, three of which have been linked to diseases with elevated risk of cancer and growth defects (Bloom Syndrome and Rothmund-Thomson Syndrome or premature aging (Werner Syndrome. RECQ1, the first RecQ helicase discovered and the most abundant in human cells, is the least well understood of the five human RecQ homologs. We have previously described that knockout of RECQ1 in mice or knockdown of its expression in human cells results in elevated frequency of spontaneous sister chromatid exchanges, chromosomal instability, increased load of DNA damage and heightened sensitivity to ionizing radiation. We have now obtained evidence implicating RECQ1 in the nonhomologous end-joining pathway of DNA double-strand break repair. We show that RECQ1 interacts directly with the Ku70/80 subunit of the DNA-PK complex, and depletion of RECQ1 results in reduced end-joining in cell free extracts. In vitro, RECQ1 binds and unwinds the Ku70/80-bound partial duplex DNA substrate efficiently. Linear DNA is co-bound by RECQ1 and Ku70/80, and DNA binding by Ku70/80 is modulated by RECQ1. Collectively, these results provide the first evidence for an interaction of RECQ1 with Ku70/80 and a role of the human RecQ helicase in double-strand break repair through nonhomologous end-joining.

  13. Transfection, overexpression and clinical application of human 60 kDa Ro/SSA autoantigens in HEp-2 cells

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    吕良敬; 陈顺乐; 顾越英; 沈南; 鲍春德; 王元; 薛峰; 叶萍; 俞翀曌

    2003-01-01

    Objective To develop an improved substrate for indirect immunofluorescence test (IIF) for detecting anti-Ro60/Sjogren's syndrome A (Ro/SSA) autoantibodies.Methods 60-kDa Ro/SSA autoantigens (Ro60) cDNAs were obtained from human placental cDNA library using polymerase chain reaction (PCR) and were cloned into the mammalian expression vector-pEGFP-C1. Then, the recombinant plasmids were transfected into HEp-2 cells. We confirmed the overexpression, localization and antigenicity of fusion proteins in transfected cells by means of immunoblotting, confocal fluorescence microscopy and IIF. HEp-2 and HEp-Ro60 were analyzed by IIF using a panel of 10 precipitin-positive anti-Ro human sera simultaneously.Results Stable expression of Ro60-green fluorescent protein (Ro60-GFP) fusion proteins were maintained ten more generations. Ro60-GFP kept the antigenicity of Ro while demonstrating its own characteristic immunofluorescent pattern in HEp-Ro60 cells. The transfectants dramatically increased the sensitivity of IIF testing (a mean increase of 6.7-fold in endpoint titer). Eight overten (8/10) positive anti-Ro sera showed characteristic immunofluorescent patterns for HEp-Ro60, including two sera that were anti-nuclear antibodies (ANA) negative for untransfected HEp-2. IIF-ANA in all healthy sera was negative for HEp-Ro60. Conclusions As a new substrate for IIF, the Ro60 transfectants can be used to detect anti-Ro antibodies. In addition, transfected HEp-2 cells keep the immunofluorescent properties of HEp-2 cells in IIF-ANA tests and can be employed as a substrate for routine IIF-ANA detection.

  14. The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone

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    Schmidt, E; Reimer, S; Kruse, N; Bröcker, E-B; Zillikens, D

    2001-01-01

    Bullous pemphigoid (BP) is a subepidermal blistering disease associated with autoantibodies to the hemidesmosomal 180 kD BP autoantigen (BP180). However, the binding of autoantibodies to BP180 alone is not sufficient for blister formation in this disease and the infiltration of neutrophils into the skin is required. Dapsone and nicotinamide inhibit neutrophil chemotaxis and are used effectively in treating BP. IL-8 is a known chemoattractant for neutrophils and has been implicated in the inflammatory process of both human and experimental murine BP. We have recently shown that antibodies to BP180 mediate a dose and time-dependent release of IL-6 and IL-8 from cultured normal human epidermal keratinocytes (NHEK). In the present study, we addressed the question whether dapsone or nicotinamide influence this cytokine release. We demonstrate that dapsone, but not nicotinamide, in its pharmacological range, inhibits the IL-8, but not the IL-6 release from NHEK, induced by anti-BP180 IgG, in a dose-dependent fashion as detected by ELISA. IL-8 mRNA levels, as determined by RT-PCR, were the same in cells treated with BP IgG alone compared to cells treated with BP IgG plus dapsone. This observation suggests that dapsone inhibits the BP IgG-induced IL-8 release from cultured NHEK by mechanisms at the post-transcriptional level. Our findings contribute to the understanding how dapsone leads to a reduced influx of neutrophils into BP lesions and, finally, to the cessation of blister formation in this disease. PMID:11359455

  15. KU-32, a Novel Drug for Diabetic Neuropathy, Is Safe for Human Islets and Improves In Vitro Insulin Secretion and Viability

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    Kevin Farmer

    2012-01-01

    Full Text Available KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.

  16. KU-32, a novel drug for diabetic neuropathy, is safe for human islets and improves in vitro insulin secretion and viability.

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    Farmer, Kevin; Williams, S Janette; Novikova, Lesya; Ramachandran, Karthik; Rawal, Sonia; Blagg, Brian S J; Dobrowsky, Rick; Stehno-Bittel, Lisa

    2012-01-01

    KU-32 is a novel, novobiocin-based Hsp90 inhibitor that protects against neuronal glucotoxicity and reverses multiple clinical indices of diabetic peripheral neuropathy in a rodent model. However, any drug with potential for treating diabetic complications must also have no adverse effects on the function of pancreatic islets. Thus, the goal of the current study was to assess the effect of KU-32 on the in vitro viability and function of human islets. Treating human islets with KU-32 for 24 hours showed no toxicity as assessed using the alamarBlue assay. Confocal microscopy confirmed that with a minimum of 2-day exposure, KU-32 improved cellular viability by blocking apoptosis. Functionally, isolated human islets released more glucose-stimulated insulin when preincubated in KU-32. However, diabetic BKS-db/db mice, a model for type 2 diabetes, administered KU-32 for 10 weeks did not show any significant changes in blood glucose and insulin levels, despite having greater insulin staining/beta cell in the pancreas compared to untreated BKS db/db mice. In summary, KU-32 did not harm isolated human islets and may even be protective. However, the effect does not appear significant enough to alter the in vivo metabolic parameters of diabetic mice.

  17. Design of Chemical Conjugate for Targeted Therapy of Multiple Sclerosis Based of Constant Fragment of Human Antibody Heavy Chain and Peptoid Analog of Autoantigen MOG35-55.

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    Lomakin, Y A; Stepanov, A V; Balabashin, D S; Ponomarenko, N A; Smirnov, I V; Belogurov, A A

    2017-04-01

    Elimination of B cells producing autoantibodies to neuroantigens is considered as beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by pathological lymphocytes. We propose a structure of an innovative drug for targeted elimination of the pool of autoreactive B cells responsible for multiple sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc fragment of human immunoglobulin. The obtained Fc-PEG-AMogP3 conjugate effectively interact with autoreactive antibodies, which attests to their high therapeutic potential.

  18. Molecular cloning of a cDNA encoding the human Sm-D autoantigen

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    Rokeach, L.A.; Haselby, J.A.; Hoch, S.O. (Agouron Institute, La Jolla, CA (USA))

    1988-07-01

    Antibodies to the Sm-D polypeptide antigen are closely associated with the rheumatic disease systemic lupus erythematosus. Sm-D exists in the cell as one of the core proteins of the small nuclear ribonucleoprotein complexes implicated in RNA processing. The authors have isolated a cDNA clone, D45-2, coding for the Sm-D human nuclear antigen by screening a human B-lymphocyte cDNA library with synthetic oligonucleotide probes. The 1633-base-pair clone contains an open reading frame (ORF) 357 nucleotides long, capable of encoding a 13,282-dalton polypeptide. The Sm-D coding region is initiated at an AUG codon downstream from a sequence with excellent match to the consensus for the eukaryotic ribosome-binding site. The Sm-D ORF is preceded by a 150-nucleotide-long untranslated leader and followed by a 1126-nucleotide-long untranslated region containing four putative poly(A) signals. The predicted amino acid sequence reveals a (Gly-Arg){sub 9} repeated motif at the C terminus, which may constitute one of the Sm-D immunoreactive determinants. Moreover, this C terminus shows interesting features: (i) a good homology to protamines as expected for a nucleic acid binding protein and (ii) a striking similarity to a region in the Epstein-Barr nuclear antigen.

  19. KU004 induces G1 cell cycle arrest in human breast cancer SKBR-3 cells by modulating PI3K/Akt pathway.

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    Fu, Jing; Tian, Chongchong; Xing, Mengtao; Wang, Xinzhi; Guo, Hongli; Sun, Lixin; Sun, Lan; Jiang, Zhenzhou; Zhang, Luyong

    2014-06-01

    KU004 is a newly synthesized compound which has been demonstrated possessing potent anti-cancer activities through targeting the highly-expressed protein HER2 on the surface of the cells. In this study, we investigated the potential roles of KU004 in the induced-cell cycle arrest in human breast cancer SK-BR-3 cells. KU004 could not only inhibit the proliferation of SK-BR-3 in a concentration-dependent manner but also induce G1 phase arrest in SK-BR-3 cells. The western blot results showed KU004 decreased the expression of cyclin D, CDK-4, p-Rb708/780, and up-regulated the p21. In order to verify whether KU004 takes the anti-tumor effect thought the regulation of PI3K/Akt pathway, we used western blot to detect the expression of protein Akt, Her2, p-Akt and p-Her2. Our results shown that after KU004 treatment, the amount of p-Akt and p-Her2 decreased but the total amount of Akt and Her2 remained unchanged. In conclusion, these results provide a framework for further exploration of KU004 as a novel chemotherapeutic for human breast tumors by modulating PI3K/Akt pathway.

  20. Characterization of Ku-deficient cells derived from Ku70-/- and Ku80-/- mice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ To determine the physiological roles of Ku70 and Ku80, we generated Ku70-/- and Ku80-/- knockout mice via targeted gene disruption (Nussenzweig et al. Nature 382, 1996; Ouyang et al. J Exp Med 186, 1997).

  1. Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells.

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    Farjana Fattah

    2010-02-01

    Full Text Available The repair of DNA double-strand breaks (DSBs is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR and non-homologous end joining (NHEJ. In mammalian cells, most DSBs are preferentially repaired by NHEJ. Recent work has demonstrated that NHEJ consists of at least two sub-pathways-the main Ku heterodimer-dependent or "classic" NHEJ (C-NHEJ pathway and an "alternative" NHEJ (A-NHEJ pathway, which usually generates microhomology-mediated signatures at repair junctions. In our study, recombinant adeno-associated virus knockout vectors were utilized to construct a series of isogenic human somatic cell lines deficient in the core C-NHEJ factors (Ku, DNA-PK(cs, XLF, and LIGIV, and the resulting cell lines were characterized for their ability to carry out DNA DSB repair. The absence of DNA-PK(cs, XLF, or LIGIV resulted in cell lines that were profoundly impaired in DNA DSB repair activity. Unexpectedly, Ku86-null cells showed wild-type levels of DNA DSB repair activity that was dominated by microhomology joining events indicative of A-NHEJ. Importantly, A-NHEJ DNA DSB repair activity could also be efficiently de-repressed in LIGIV-null and DNA-PK(cs-null cells by subsequently reducing the level of Ku70. These studies demonstrate that in human cells C-NHEJ is the major DNA DSB repair pathway and they show that Ku is the critical C-NHEJ factor that regulates DNA NHEJ DSB pathway choice.

  2. Ku regulates the non-homologous end joining pathway choice of DNA double-strand break repair in human somatic cells.

    Directory of Open Access Journals (Sweden)

    Farjana Fattah

    2010-02-01

    Full Text Available The repair of DNA double-strand breaks (DSBs is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR and non-homologous end joining (NHEJ. In mammalian cells, most DSBs are preferentially repaired by NHEJ. Recent work has demonstrated that NHEJ consists of at least two sub-pathways-the main Ku heterodimer-dependent or "classic" NHEJ (C-NHEJ pathway and an "alternative" NHEJ (A-NHEJ pathway, which usually generates microhomology-mediated signatures at repair junctions. In our study, recombinant adeno-associated virus knockout vectors were utilized to construct a series of isogenic human somatic cell lines deficient in the core C-NHEJ factors (Ku, DNA-PK(cs, XLF, and LIGIV, and the resulting cell lines were characterized for their ability to carry out DNA DSB repair. The absence of DNA-PK(cs, XLF, or LIGIV resulted in cell lines that were profoundly impaired in DNA DSB repair activity. Unexpectedly, Ku86-null cells showed wild-type levels of DNA DSB repair activity that was dominated by microhomology joining events indicative of A-NHEJ. Importantly, A-NHEJ DNA DSB repair activity could also be efficiently de-repressed in LIGIV-null and DNA-PK(cs-null cells by subsequently reducing the level of Ku70. These studies demonstrate that in human cells C-NHEJ is the major DNA DSB repair pathway and they show that Ku is the critical C-NHEJ factor that regulates DNA NHEJ DSB pathway choice.

  3. Molecular analysis of Ku redox regulation

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    Shatilla Andrea

    2009-08-01

    Full Text Available Abstract Background DNA double-strand breaks (DSBs can occur in response to ionizing radiation (IR, radiomimetic agents and from endogenous DNA-damaging reactive oxygen metabolites. Unrepaired or improperly repaired DSBs are potentially the most lethal form of DNA damage and can result in chromosomal translocations and contribute to the development of cancer. The principal mechanism for the repair of DSBs in humans is non-homologous end-joining (NHEJ. Ku is a key member of the NHEJ pathway and plays an important role in the recognition step when it binds to free DNA termini. Ku then stimulates the assembly and activation of other NHEJ components. DNA binding of Ku is regulated by redox conditions and evidence from our laboratory has demonstrated that Ku undergoes structural changes when oxidized that results in a reduction in DNA binding activity. The C-terminal domain and cysteine 493 of Ku80 were investigated for their contribution to redox regulation of Ku. Results We effectively removed the C-terminal domain of Ku80 generating a truncation mutant and co-expressed this variant with wild type Ku70 in an insect cell system to create a Ku70/80ΔC heterodimer. We also generated two single amino acid variants of Cys493, replacing this amino acid with either an alanine (C493A or a serine (C493S, and over-expressed the variant proteins in SF9 insect cells in complex with wild type Ku70. Neither the truncation nor the amino acid substitutions alters protein expression or stability as determined by SDS-PAGE and Western blot analysis. We show that the C493 mutations do not alter the ability of Ku to bind duplex DNA in vitro under reduced conditions while truncation of the Ku80 C-terminus slightly reduced DNA binding affinity. Diamide oxidation of cysteines was shown to inhibit DNA binding similarly for both the wild-type and all variant proteins. Interestingly, differential DNA binding activity following re-reduction was observed for the Ku70/80

  4. Autoantigenic targets of B-cell receptors derived from chronic lymphocytic leukemias bind to and induce proliferation of leukemic cells.

    Science.gov (United States)

    Zwick, Carsten; Fadle, Natalie; Regitz, Evi; Kemele, Maria; Stilgenbauer, Stephan; Bühler, Andreas; Pfreundschuh, Michael; Preuss, Klaus-Dieter

    2013-06-06

    Antigenic targets of the B-cell receptor (BCR) derived from malignant cells in chronic lymphocytic leukemia (CLL) might play a role in the pathogenesis of this neoplasm. We screened human tissue-derived protein macroarrays with antigen-binding fragments derived from 47 consecutive cases of CLL. An autoantigenic target was identified for 12/47 (25.5%) of the cases, with 3 autoantigens being the target of the BCRs from 2 patients each. Recombinantly expressed autoantigens bound specifically to the CLL cells from which the BCR used for the identification of the respective autoantigen was derived. Moreover, binding of the autoantigen to the respective leukemic cells induced a specific activation and proliferation of these cells. In conclusion, autoantigens are frequent targets of CLL-BCRs. Their specific binding to and induction of proliferation in the respective leukemic cells provide the most convincing evidence to date for the long-time hypothesized role of autoantigens in the pathogenesis of CLL.

  5. Specific interaction of IP6 with human Ku70/80, the DNA-binding subunit of DNA-PK.

    Science.gov (United States)

    Hanakahi, Les A; West, Stephen C

    2002-04-15

    In eukaryotic cells, DNA double-strand breaks can be repaired by non-homologous end-joining, a process dependent upon Ku70/80, XRCC4 and DNA ligase IV. In mammals, this process also requires DNA-PK(cs), the catalytic subunit of the DNA-dependent protein kinase DNA-PK. Previously, inositol hexakisphosphate (IP6) was shown to be bound by DNA-PK and to stimulate DNA-PK-dependent end-joining in vitro. Here, we localize IP6 binding to the Ku70/80 subunits of DNA- PK, and show that DNA-PK(cs) alone exhibits no detectable affinity for IP6. Moreover, proteolysis mapping of Ku70/80 in the presence and absence of IP6 indicates that binding alters the conformation of the Ku70/80 heterodimer. The yeast homologue of Ku70/80, yKu70/80, fails to bind IP6, indicating that the function of IP6 in non-homologous end-joining, like that of DNA-PK(cs), is unique to the mammalian end-joining process.

  6. Immunogenicity of autoantigens

    Directory of Open Access Journals (Sweden)

    Keller Andreas

    2011-07-01

    Full Text Available Abstract Background Autoantibodies against self-antigens have been associated not only with autoimmune diseases, but also with cancer and are even found in healthy individuals. The mechanism causing the autoantibody response remains elusive for the majority of the immunogenic antigens. To deepen the understanding of autoantibody responses, we ask whether natural-occurring, autoimmunity-associated and tumor-associated antigens have structural or biological features related to the immune response. To this end, we have carried out the most comprehensive in-silicio study of different groups of autoantigens including large antigen sets identified by our groups combined with publicly available antigen sets. Results We found evidence for an enrichment of genes with a larger exon length increasing the probability of the occurrence of potential immunogenic features such as mutations, SNPs, immunogenic sequence patterns and structural epitopes, or alternative splicing events. While SNPs seem to play a more central role in autoimmunity, somatic mutations seem to be stronger enriched in tumor-associated antigens. In addition, antigens of autoimmune diseases are different from other antigen sets in that they appear preferentially secreted, have frequently an extracellular location, and they are enriched in pathways associated with the immune system. Furthermore, for autoantibodies in general, we found enrichment of sequence-based properties including coiled-coils motifs, ELR motifs, and Zinc finger DNA-binding motifs. Moreover, we found enrichment of proteins binding to proteins or nucleic acids including RNA and enrichment of proteins that are part of ribosome or spliceosome. Both, homologies to proteins of other species and an enrichment of ancient protein domains indicate that immunogenic proteins are evolutionary conserved and that mimicry might play a central role. Conclusions Our results provide evidence that proteins which i are evolutionary conserved

  7. TRF2 Interaction with Ku Heterotetramerization Interface Gives Insight into c-NHEJ Prevention at Human Telomeres

    Directory of Open Access Journals (Sweden)

    Albert Ribes-Zamora

    2013-10-01

    Full Text Available Telomeres are protected from nonhomologous end-joining (NHEJ to avoid deleterious chromosome fusions, yet they associate with the Ku heterodimer that is principal in the classical NHEJ (c-NHEJ pathway. T-loops have been proposed to inhibit Ku’s association with telomeric ends, thus inhibiting c-NHEJ; however, deficiencies in the t-loop model suggest additional mechanisms are in effect. We demonstrate that TRF2 interacts with Ku at telomeres and via residues in Ku70 helix 5 (α5, which are vital for NHEJ. We show that Ku’s interaction with a TRF2 mutant that induces telomeric fusions is significantly impaired. Additionally, we demonstrate that Ku70 α5 is required for Ku self-association in live cells, which can bridge DNA ends. Together, these findings lead us to propose a model in which telomeres are directly protected from c-NHEJ via TRF2 impeding Ku’s ability to synapse telomere ends.

  8. Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-κB in human KU812 cells

    Institute of Scientific and Technical Information of China (English)

    LI Li; ZHANG Xiao-Hui; LIU Guang-Rong; LIU Chang; DONG Yin-Mao

    2016-01-01

    Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm.Both cell types are involved in a variety of inflammatory and immune events,producing an array of inflammatory mediators,such as cytokines.The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation.The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187 (PMACI).The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent (ELISA) assays.Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels.Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines,such as interleukin (IL)-6,IL-8,IL-1β,and tumor necrosis factor (TNF)-α.The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase (ERK),revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition.Furthermore,isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells.In conclusion,the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.

  9. Isoquercitrin suppresses the expression of histamine and pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-κB in human KU812 cells.

    Science.gov (United States)

    Li, Li; Zhang, Xiao-Hui; Liu, Guang-Rong; Liu, Chang; Dong, Yin-Mao

    2016-06-01

    Mast cells and basophils are multifunctional effector cells that contain abundant secretory granules in their cytoplasm. Both cell types are involved in a variety of inflammatory and immune events, producing an array of inflammatory mediators, such as cytokines. The aim of the study was to examine whether isoquercitrin modulates allergic and inflammatory reactions in the human basophilic KU812 cells and to elucidate its influence on the phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB activation. The KU812 cells were stimulated with phorbol-12-myristate 13-acetate plus the calcium ionophore A23187 (PMACI). The inhibitory effects of isoquercitrin on the productions of histamine and pro-inflammatory cytokines in the stimulated KU812 cells were measured using cytokine-specific enzyme-linked immunosorbent (ELISA) assays. Western blotting analysis was used to assess the effects of isoquercitrin on the MAPKs and NF-κB protein levels. Our results indicated that the isoquercitrin treatment of PMACI-stimulated KU812 cells significantly reduced the production of histamine and the pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, IL-1β, and tumor necrosis factor (TNF)-α. The treated cells exhibited decreased phosphorylation of extracellular signal-regulated kinase (ERK), revealing the role of ERK MAPK in isoquercitrin-mediated allergy inhibition. Furthermore, isoquercitrin suppressed the PMACI-mediated activation of NF-κB in the human basophil cells. In conclusion, the results from the present study provide insights into the potential therapeutic use of isoquercitrin for the treatment of inflammatory and allergic reactions.

  10. Localization of two human autoantigen genes by PCR screening and in situ hybridization-glycyl-tRNA synthetase locates to 7p15 and Alanyl-tRNA synthetase locates to 16q22

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, R.C.; Pai, S.I.; Liu, P. [National Inst. of Health, Bethesda, MD (United States); Ge, Q.; Targoff, I.N. [Oklahoma Medical Research Foundation, Oklahoma City, OK (United States)

    1995-11-01

    Aminoacyl-tRNA synthetases (aminoacyl-RS) catalyze the attachment of an amino acid to its cognate tRNA. Five of 20 human aminoacyl-RS (histidyl-RS, threonyl-RS, isoleucyl-RS, glycyl-RS, and alanyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis (PM/DM; 9). A sixth autoantigenic amino-acyl-RS, lysyl-RS, was recently reported. The genes for histidyl-RS and threonyl-RS have been assigned to chromosome 5, as have the genes for leucyl-RS and arginyl-RS. Six other aminoacyl-RS (glutamyl-prolyl-RS, valyl-RS, cysteinyl-RS, methionyl-RS, tryptophanyl-RS, and asparaginyl-RS) were assigned to chromosomes 1, 6, 11, 12, 14, and 18, respectively. The reason for a preponderance of aminoacyl-RS genes on chromosome 5 is unknown, but it has been suggested that regulatory relatedness might be a factor. Recently the entire or partial cDNA sequences for two autoantigenic aminoacyl-RS genes, glycyl-RS (gene symbol GARS; 4) and alanyl-RS (gene symbol AARS; 1), were reported. To understand further the genesis of autoimmune responses to aminoacyl-RS and to determine whether genes for autoantigenic aminoacyl-RS colocalize to chromosome 5, we have determined the chromosomal site of the GARS and AARS genes by PCR-based screening of somatic cell hybrid panels and by fluorescence in situ hybridization (FISH) analysis. 10 refs., 1 fig.

  11. Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, R.C.; Blinder, J.; Pai, S.I. [National Inst. of Health, Bethesda, MD (United States)] [and others

    1996-08-15

    Protein synthesis is initiated by the attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (aaRS). Five of twenty human aaRS (histidyl-RS, threonyl-RS, alanyl-RS, glycyl-RS, and isoleucyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Autoantibodies to human lysyl-RS, a sixth autoantigenic aminoacyl-RS, were recently identified. The genes for histidyl-RS and threonyl-RS have been localized to chromosome 5, and we recently reported that the genes for alanyl-RS and glycyl-RS localize to chromosomes 16 and 7, respectively. To understand the genesis of autoimmune responses to aaRS better, we have used PCR-based screening of somatic cell hybrid panels and fluorescence in situ hybridization (FISH) to assign the genes for isoleucyl-RS and lysyl-RS. 19 refs., 1 fig.

  12. JNK-dependent NFATc1 pathway positively regulates IL-13 gene expression induced by (-)-epigallocatechin-3-gallate in human basophilic KU812 cells.

    Science.gov (United States)

    Wu, Haitao; Qi, Hang; Iwasaki, Dai; Zhu, Beiwei; Shimoishi, Yasuaki; Murata, Yoshiyuki; Nakamura, Yoshimasa

    2009-10-01

    (-)-Epigallocatechin-3-gallate (EGCG) has been reported to possess a wide range of biological and pharmacological properties. In this study, we investigated the effects of EGCG on IL-13 gene expression in human basophilic KU812 cells. The IL-13 mRNA expression level was dose-dependently increased by treatment with EGCG (5-20 microM) for 1 h and additional incubation in a medium for 23 h. EGCG significantly increased the intracellular peroxide level as detected by the peroxide-sensitive probe 2',7'-dichlorodihydrofluorescein diacetate. A pharmacological experiment using catalase and a structure-activity relationship study revealed that the exogenously produced H(2)O(2) significantly, but partially, contributed to the IL-13 expression as well as the intracellular oxidative status. Furthermore, EGCG at the concentration required for IL-13 up-regulation activated c-Jun NH(2)-terminal kinase (JNK), but not extracellular signal-regulated protein kinase or p38 mitogen-activated protein kinase in KU812 cells. Transfection of a JNK-specific siRNA as well as treatment with a JNK-specific inhibitor, SP600125, significantly reduced the EGCG-induced IL-13 mRNA expression, by 47.1 and 44.6%, respectively. In addition, we observed the nuclear translocation, mRNA up-regulation, and activation of DNA binding with the IL-13 promoter of nuclear factor of activated T cells (NFATc1) in the EGCG-treated cells. These data provide biological evidence that EGCG induces IL-13 mRNA expression via the JNK-dependent NFATc1 pathway in KU812 cells.

  13. Antiallergic tea catechin, (-)-epigallocatechin-3-O-(3-O-methyl)-gallate, suppresses FcepsilonRI expression in human basophilic KU812 cells.

    Science.gov (United States)

    Fujimura, Yoshinori; Tachibana, Hirofumi; Maeda-Yamamoto, Mari; Miyase, Toshio; Sano, Mitsuaki; Yamada, Koji

    2002-09-25

    We previously found that the O-methylated derivative of (-)-epigallocatechin-3-O-gallate (EGCg), (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG' '3Me), has potent antiallergic activity. The high-affinity IgE receptor, FcepsilonRI, is found at high levels on basophils and mast cells and plays a key role in a series of acute and chronic human allergic reactions. To understand the mechanism of action for the antiallergic EGCG' '3Me, the effect of EGCG' '3Me on the cell surface expression of FcepsilonRI in human basophilic KU812 cells was examined. Flow cytometric analysis showed that EGCG' '3Me was able to decrease the cell surface expression of FcepsilonRI. Moreover, immunoblot analysis revealed that total cellular expression of the FcepsilonRI alpha chain decreased upon treatment with EGCG' '3Me. FcepsilonRI is a tetrameric structure comprising one alpha chain, one beta chain, and two gamma chains. The level of mRNA production of each subunit in KU812 cells was investigated. EGCG' '3Me reduced FcepsilonRI alpha and gamma mRNA levels. The cross-linkage of FcepsilonRI causes the activation of basophils, which leads to the secretion of inflammatory mediators including histamine. EGCG' '3Me treatment inhibited the FcepsilonRI cross-linking-induced histamine release. These results suggested that EGCG' '3Me can negatively regulate basophil activation through the suppression of FcepsilonRI expression.

  14. 人嗜碱性粒细胞肿瘤细胞系KU812F检灏牛乳及其替代品致敏性方法的建立%Construction of an in vitro Allergy Reaction Evaluation Method for Cow Milk and Its Substitutes Using Human Leukemia Cell Line KU812F

    Institute of Scientific and Technical Information of China (English)

    丛艳君; 任发政

    2011-01-01

    比较牛乳及其替代品释放组胺的能力,以建立体外细胞检测牛乳及替代品疑似过敏原组分致敏性的检测方法。以嗜碱性粒细胞KU812F为研究对象,通过牛乳过敏患者血清的孵育,使细胞处于致敏状态,再以牛乳及其替代品过敏原作为激发物,使细胞脱颗粒释放组胺。结果表明:利用嗜碱性粒细胞KU812F检测牛乳及替代制品组胺释放量的方法具有较高的可靠性及重现性,细胞释放组胺的量与过敏原的剂量相关,在一定的剂量范围内,组胺的释放率与过敏原的剂量呈正比,组胺释放率达到最大之后,组胺释放率与剂量呈负相关。%This study aimed to construct an in vitro cellular assay for suspected allergenic components of cow milk and its substitutes using human leukemia cell line KU812F, an immature prebasophillic cell line based on their histamine release ability. KU812F was differentiated into basophils by incubation with serum from cow milk allergic people. The release of histamine from differentiated KU812F cells was monitored after sensitization with either cow milk or its substitutes. The results showed that this in vitro assay was highly reliable and reproducible in determining histamine release from KU812F cells after respective sensitization with cow milk and its products. Cow milk and its substitutes differed in their histamine release ability. Cow milk allergen induced histamine release in a dose-dependent manner. Specifically, a positive relationship was observed in a defmed range of allergen dose, followed by a negative relationship after maximum histamine release.

  15. Extraction of Ku antigen and anti-Ku antibody assay in various autoimmune connective tissue diseases

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To extract Ku antigen and to detect anti-Ku antibody in connective tissue diseases (CTDs). Methods: Ku antigen was prepared from rabbit thymus acetone powder. Anti-Ku antibodies were tested in 50 normal controls and 438 patients

  16. The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome II, and its polymorphisms

    Energy Technology Data Exchange (ETDEWEB)

    Frank, M.B.; Itoh, Kazuko (Oklahoma Medical Research Foundation, Oklahoma City (United States)); Fujisaku, Atsushi (Hokkaido Univ., Sapporo (Japan)); Pontarotti, P. (Centre de Recherches sur le Polymorphisme Genetique des Populations Humaines, Toulouse (France)); Mattei, M.G. (INSERM U 242, Marseille (France)); Neas, B.R. (Oklahoma Medical Research Foundation, Oklahoma City (United States) Univ. of Oklahoma, Oklahoma City (United States))

    1993-01-01

    Autoantibodies to the ribonucleoprotein Ro/SSA occur in nearly half of the patients with systemic lupus erythematosus and are associated with lymphopenia, photosensitive dermatitis, and pulmonary and renal disease, which suggests that they have an immunopathologic role. The majority of Ro/SSA precipitin-positive patients produce serum antibodies that bind to the 60-kD and 52-kD Ro/SSA proteins. The authors previously isolated and determined the nucleotide sequence of a cDNA clone that encodes the 52-kD form of the human Ro/SSA protein. In the present study, they have determined the chromosomal location of the gene by in situ hybridization to the end of the short arm of chromosome 11. Hybridization of portions of the cDNA probe to restriction enzyme-digested DNA indicated the gene is composed of at least three exons. The exon encoding the putative zinc fingers of this protein was found to be distinct from that which encodes the leucine zipper. An RFLP of this gene was identified and is associated with the presence of lupus, primarily in black Americans. 60 refs., 3 figs., 3 tabs.

  17. Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis.

    Science.gov (United States)

    Swadzba, Margarete E; Hauck, Stefanie M; Naim, Hassan Y; Amann, Barbara; Deeg, Cornelia A

    2012-01-01

    Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like equine recurrent uveitis (ERU), a spontaneous model for human autoimmune uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role in ERU pathology.

  18. Deletion of ku homologs increases gene targeting frequency in Streptomyces avermitilis.

    Science.gov (United States)

    Zhang, Xiaojuan; Chen, Wei; Zhang, Yang; Jiang, Libin; Chen, Zhi; Wen, Ying; Li, Jilun

    2012-06-01

    Streptomyces avermitilis is an industrially important soil bacterium known for production of avermectins, which are antiparasitic agents useful in animal health care, agriculture, and treatment of human infections. ku genes play a key role in the non-homologous end-joining pathway for repair of DNA double strand breaks. We identified homologs of eukaryotic ku70 and ku80 genes, termed ku1 and ku2, in S. avermitilis. Mutants with deletion of ku1, ku2, and both genes were constructed and their phenotypic changes were characterized. Deletion of ku genes had no apparent adverse effects on growth, spore formation, or avermectin production. The ku mutants, in comparison to wild-type strain, were slightly more sensitive to the DNA-damaging agent ethyl methanesulfonate, but not to UV exposure or to bleomycin. Gene targeting frequencies by homologous recombination were higher in the ku mutants than in wild-type strain. We conclude that ku-deleted strains will be useful hosts for efficient gene targeting and will facilitate functional analysis of genes in S. avermitilis and other industrially important bacterial strains.

  19. Ku70 Senses HTLV-1 DNA and Modulates HTLV-1 Replication.

    Science.gov (United States)

    Wang, Jie; Kang, Lixia; Song, Di; Liu, Lu; Yang, Shuai; Ma, Lingling; Guo, Zhixiang; Ding, Huaxia; Wang, Hui; Yang, Bo

    2017-10-01

    Human T lymphotropic virus type 1 (HTLV-1) belongs to the deltaretrovirus family and has been linked to multiple diseases. However, the innate host defense against HTLV-1 is unclear. In this study, we report that the expression of Ku70, a known DNA sensor against DNA viruses, could be induced by HTLV-1 infection in HeLa, PMA-differentiated THP1 cells, primary human monocytes, and human monocyte-derived macrophages. In these cells, the overexpression of Ku70 inhibited the HTLV-1 protein expression, whereas the knockdown of Ku70 promoted the HTLV-1 protein expression. Furthermore, the overexpression of Ku70 enhanced the cellular response to HTLV-1 infection, whereas Ku70 knockdown yielded the opposite effect. Additionally, Ku70 was found to interact with HTLV-1 reverse transcription intermediate ssDNA90. ssDNA90 stimulation induced Ku70 expression and Ku70 promoted ssDNA90-triggered innate immune responses. Finally, HTLV-1 infection enhanced the association between Ku70 and stimulator of IFN genes, suggesting that stimulator of IFN genes was involved in Ku70-mediated host defenses against HTLV-1 infection. Taken together, our findings suggest a new sensor that detects HTLV-1 reverse transcription intermediate and controls HTLV-1 replication. These findings may provide new angles to understand host defenses against HTLV-1 infection and HTLV-1-associated diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  20. "Paper Cut Lady" Ku Shulan

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    WHEN the people in Xunyi County of Shaanxi Province talk about the traditional paper cut, they always speak of a "paper cut lady" Ku Shulan. Her works have been shown at the Xi’an Artists’ Gallery, Beijing China Art Gallery and Exhibition Hall of Central Academy of Fine Arts. Almost seventy years old, Ku Shulan is an ordinary country lady, and her artistic achievements were closely linked with her mother countryside. The traditional paper cut created and developed in Xunyi County, has a simple and bold style of Northern Shaanxi, and an exquisitely

  1. Impact of the Ku complex on HIV-1 expression and latency.

    Directory of Open Access Journals (Sweden)

    Gwenola Manic

    Full Text Available Ku, a cellular complex required for human cell survival and involved in double strand break DNA repair and multiple other cellular processes, may modulate retroviral multiplication, although the precise mechanism through which it acts is still controversial. Recently, Ku was identified as a possible anti-human immunodeficiency virus type 1 (HIV-1 target in human cells, in two global approaches. Here we investigated the role of Ku on the HIV-1 replication cycle by analyzing the expression level of a panel of non-replicative lentiviral vectors expressing the green fluorescent protein in human colorectal carcinoma HCT 116 cells, stably or transiently depleted of Ku. We found that in this cellular model the depletion of Ku did not affect the efficiency of (pre-integrative steps but decreased the early HIV-1 expression by acting at the transcriptional level. This negative effect was specific of the HIV-1 promoter, required the obligatory step of viral DNA integration and was reversed by transient depletion of p53. We also provided evidence on a direct binding of Ku to HIV-1 LTR in transduced cells. Ku not only promotes the early transcription from the HIV-1 promoter, but also limits the constitution of viral latency. Moreover, in the presence of a normal level of Ku, HIV-1 expression was gradually lost over time, likely due to the counter-selection of HIV-1-expressing cells. On the contrary, the reactivation of transgene expression from HIV-1 by means of trichostatin A- or tumor necrosis factor α-administration was enhanced under condition of Ku haplodepletion, suggesting a phenomenon of provirus latency. These observations plead in favor of the hypothesis that Ku has an impact on HIV-1 expression and latency at early- and mid-time after integration.

  2. Suppression of OsKu80 results in defects in developmental growth and increased telomere length in rice (Oryza sativa L.).

    Science.gov (United States)

    Byun, Mi Young; Cui, Li Hua; Kim, Woo Taek

    2015-12-25

    The Ku70-Ku80 heterodimer plays a critical role in the maintenance of genomic stability in humans and yeasts. In this report, we identified and characterized OsKu80 in rice, a model monocot crop. OsKu80 forms a heterodimer with OsKu70 in yeast and plant cells, as demonstrated by yeast two-hybrid, in vivo co-immunoprecipitation, and bimolecular fluorescence complementation assays. RNAi-mediated knock-down T3 transgenic rice plants (Ubi:RNAi-OsKu80) displayed a retarded growth phenotype at the post-germination stage. In addition, the Ubi:RNAi-OsKu80 knock-down progeny exhibited noticeably increased telomere length as compared to wild-type rice. These results are discussed with the idea that OsKu80 plays a role in developmental growth and telomere length regulation in rice plants.

  3. Purification of pituitary autoantigen by column liquid chromatography and chromatofocusing

    OpenAIRE

    Gut, Paweł; Fischbach, Jakub; Ziemnicka, Katarzyna; Bączyk, Maciej; Baszko-Błaszyk, Daria; Wrotkowska, Elżbieta; Ruchała, Marek

    2014-01-01

    Introduction Pituitary autoantibodies can be determined both in patients with pituitary disease as well as patients with autoimmune endocrine diseases. The purpose of the study was to isolate and purify pituitary autoantigen using sera of patients and the microsomal fraction of the pituitary. Material and methods To isolate a pituitary autoantigen, patient sera were used, which showed a strong immune response to pituitary antigens. Pituitary microsomal fractions were prepared from pituitary t...

  4. Identification of the novel autoantigen candidate Rab GDP dissociation inhibitor alpha in isolated adrenocorticotropin deficiency.

    Science.gov (United States)

    Kiyota, Atsushi; Iwama, Shintaro; Sugimura, Yoshihisa; Takeuchi, Seiji; Takagi, Hiroshi; Iwata, Naoko; Nakashima, Kohtaro; Suzuki, Haruyuki; Nishioka, Tomoki; Kato, Takuya; Enomoto, Atsushi; Arima, Hiroshi; Kaibuchi, Kozo; Oiso, Yutaka

    2015-01-01

    Isolated adrenocorticotropin deficiency (IAD) is characterized by low or absent adrenocorticotropic hormone (ACTH) production. IAD is presumed to be caused in part by an autoimmune mechanism, and several lines of evidence have suggested the presence of anti-pituitary antibodies in IAD. However, the exact autoantigens remain unknown. The present study was designed to identify the autoantigen(s) in IAD using chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Rat anterior pituitary lysate was subjected to SDS-PAGE, and immunoblotting was performed using the sera from two patients with IAD and from a healthy subject. The bands detected by the patient serum samples, but not by the healthy subject sample, were excised, in-gel digested using trypsin, and subjected to LC-MS/MS analysis. On immunoblots, a 51-kDa band in the insoluble pellet was detected by the sera from the IAD patients but not from the healthy subject. Mass spectrometric analysis revealed the 51-kDa band contained Rab guanine nucleotide dissociation inhibitor (GDI) alpha. Consistent with the mass spectrometric analysis, a recombinant full-length human Rab GDI alpha was recognized by the two IAD patient samples but not by the healthy subject sample using immunoblotting. In total, anti-Rab GDI alpha antibodies were detected in serum samples from three of five patients with IAD (60%) but were absent in 5 healthy subjects. In addition, Rab GDI alpha was expressed in the anterior pituitary. In conclusion, it appears that Rab GDI alpha is a candidate autoantigen involved in IAD, and that anti-Rab GDI alpha antibodies are present predominantly in patients with IAD.

  5. Cytosolic Ku70 regulates Bax-mediated cell death.

    Science.gov (United States)

    Hada, Manila; Subramanian, Chitra; Andrews, Phillip C; Kwok, Roland P S

    2016-10-01

    The first known function of Ku70 is as a DNA repair factor in the nucleus. Using neuronal neuroblastoma cells as a model, we have established that cytosolic Ku70 binds to the pro-apoptotic protein Bax in the cytosol and blocks Bax's cell death activity. Ku70-Bax binding is regulated by Ku70 acetylation in that when Ku70 is acetylated Bax dissociates from Ku70, triggering cell death. We propose that Ku70 may act as a survival factor in these cells such that Ku70 depletion triggers Bax-dependent cell death. Here, we addressed two fundamental questions about this model: (1) Does all Bax, which is a cytosolic protein, bind to all cytosolic Ku70? and (2) Is Ku70 a survival factor in cells types other than neuronal neuroblastoma cells? We show here that, in neuronal neuroblastoma cells, only a small fraction of Ku70 binds to a small fraction of Bax; most Bax is monomeric. Interestingly, there is no free or monomeric Ku70 in the cytosol; most cytosolic Ku70 is in complex with other factors forming several high molecular weight complexes. A fraction of cytosolic Ku70 also binds to cytosolic Ku80, Ku70's binding partner in the nucleus. Ku70 may not be a survival factor in some cell types (Ku70-depletion less sensitive) because Ku70 depletion does not affect survival of these cells. These results indicate that, in addition to Ku70 acetylation, other factors may be involved in regulating Ku70-Bax binding in the Ku70-depletion less sensitive cells because Ku70 acetylation in these cells is not sufficient to dissociate Bax from Ku70 or to activate Bax.

  6. Downregulated Ku70 and ATM associated to poor prognosis in colorectal cancer among Chinese patients

    Directory of Open Access Journals (Sweden)

    Lu YF

    2014-10-01

    Full Text Available Yuanfang Lu,1,2 Jingyan Gao,1,3 Yuanming Lu,1 1Department of Toxicology, School of Public Health, Guilin Medical University, Guangxi, People's Republic of China; 2Department of Clinical Research Center, Affiliated 2nd Hospital of Nanjing Medical University, Nanjing, People's Republic of China; 3Department of Human Anatomy and Histo-Embryology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Background: Double-strand DNA breaks (DSBs are a key factor in carcinogenesis. The necessary repair of DSBs is pivotal in maintaining normal cell division. To address the relationship between altered expression of DSB repair of proteins Ku70 and ataxia-telangiectasia mutated (ATM in colorectal cancer (CRC, we examined the expression levels and patterns of Ku70 and ATM in CRC samples. Methods: Expression and coexpression of Ku70 and ATM were investigated by using real-time quantitative polymerase chain reaction assays and confirmed further with fluorescent immunohistochemistry in CRC and pericancerous samples from 112 Chinese patients. Results: Downexpression patterns for both Ku70 and ATM were found in the CRC samples and were significantly associated with advanced tumor node metastasis stage and decreased 5-year overall survival rate. Conclusion: Downregulated Ku70 and ATM were associated with poor disease-free survival. Loss of Ku70 and ATM expression might act as a biomarker to predict poor prognosis in patients with CRC. Keywords: DNA double-strand breaks, ataxia-telangiectasia mutated, Ku70, colorectal cancer

  7. Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis.

    Science.gov (United States)

    Ma, Jiali; Hui, Pingping; Meng, Wenying; Wang, Na; Xiang, Shihao

    2017-03-18

    The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown. On the other hand, exogenous overexpression of Ku70 in Mia-PaCa-2 cells suppressed gemcitabine-induced DNA damage and subsequent cell apoptosis. In a severe combined immune deficient (SCID) mice Mia-PaCa-2 xenograft model, gemcitabine-induced anti-tumor activity was remarkably pontificated when combined with Ku70 shRNA knockdown in the xenografts. The results of this preclinical study imply that Ku70 might be a primary resistance factor of gemcitabine, and Ku70 silence could significantly chemo-sensitize gemcitabine in pancreatic cancer cells.

  8. Electron microscopy visualization of DNA-protein complexes formed by Ku and DNA ligase IV.

    Science.gov (United States)

    Grob, Patricia; Zhang, Teri T; Hannah, Ryan; Yang, Hui; Hefferin, Melissa L; Tomkinson, Alan E; Nogales, Eva

    2012-01-02

    The repair of DNA double-stranded breaks (DSBs) is essential for cell viability and genome stability. Aberrant repair of DSBs has been linked with cancer predisposition and aging. During the repair of DSBs by non-homologous end joining (NHEJ), DNA ends are brought together, processed and then joined. In eukaryotes, this repair pathway is initiated by the binding of the ring-shaped Ku heterodimer and completed by DNA ligase IV. The DNA ligase IV complex, DNA ligase IV/XRRC4 in humans and Dnl4/Lif1 in yeast, is recruited to DNA ends in vitro and in vivo by an interaction with Ku and, in yeast, Dnl4/Lif1 stabilizes the binding of yKu to in vivo DSBs. Here we have analyzed the interactions of these functionally conserved eukaryotic NHEJ factors with DNA by electron microscopy. As expected, the ring-shaped Ku complex bound stably and specifically to DNA ends at physiological salt concentrations. At a ratio of 1 Ku molecule per DNA end, the majority of DNA ends were occupied by a single Ku complex with no significant formation of linear DNA multimers or circular loops. Both Dnl4/Lif1 and DNA ligase IV/XRCC4 formed complexes with Ku-bound DNA ends, resulting in intra- and intermolecular DNA end bridging, even with non-ligatable DNA ends. Together, these studies, which provide the first visualization of the conserved complex formed by Ku and DNA ligase IV at juxtaposed DNA ends by electron microscopy, suggest that the DNA ligase IV complex mediates end-bridging by engaging two Ku-bound DNA ends.

  9. Ku80 interaction with apurinic/apyrimidinic sites depends on the structure of DNA ends

    Directory of Open Access Journals (Sweden)

    Kosova A. A.

    2014-01-01

    Full Text Available Aim. The identification of a protein from human cell extract which specifically interacts with the apurinic/apyrimidinic (AP site in the partial DNA duplex containing 5'and 3'-dangling ends (DDE-AP DNA and mimicking clustered DNA damage. Methods. The Schiff base-dependent cross-linking of a protein to AP DNA (borohydride trapping, MALDI-TOF-MS, chromatography, and gel electrophoresis. Results. A human cell extract protein which forms a major covalent adduct with the AP DNA duplex with dangling ends was identified as the Ku80 subunit of Ku antigen by peptide mass mapping based on MALDI-TOF-MS data. The Ku antigen purified from the HeLa cell extract was shown to form the covalent adducts with the same mobility as observed in cell extracts. Conclusions. The Ku80 subunit of Ku antigen can specifically interact with AP DNA forming the Schiff base-mediated adducts which electrophoretic mobility depends on the structure of DNA ends. The difference in electrophoretic mobility can be caused by the cross-linking of AP DNA to distinct target amino acids that appears to reflect unequal positioning of AP DNAs in the complex with Ku antigen.

  10. Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.

    Science.gov (United States)

    Evans-Axelsson, Susan; Vilhelmsson Timmermand, Oskar; Welinder, Charlotte; Borrebaeck, Carl Ak; Strand, Sven-Erik; Tran, Thuy A; Jansson, Bo; Bjartell, Anders

    2014-01-01

    The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer.

  11. Preclinical evaluation of 111In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer

    Science.gov (United States)

    Evans-Axelsson, Susan; Vilhelmsson Timmermand, Oskar; Welinder, Charlotte; Borrebaeck, Carl AK; Strand, Sven-Erik; Tran, Thuy A; Jansson, Bo; Bjartell, Anders

    2014-01-01

    The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the 111In-labeled human internalizing antibody, INCA-X (111In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of 111In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of 111In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the 111In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the 111In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer. PMID:24982817

  12. Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

    Science.gov (United States)

    Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

    2016-01-01

    Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role.

  13. Increased polyamines alter chromatin and stabilize autoantigens in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wesley H. Brooks

    2013-04-01

    Full Text Available Polyamines are small cations with unique combinations of charge and length that give them many putative interactions in cells. Polyamines are essential since they are involved in replication, transcription, translation, and stabilization of macro-molecular complexes. However, polyamine synthesis competes with cellular methylation for S-adenosylmethionine, the methyl donor. Also, polyamine degradation can generate reactive molecules like acrolein. Therefore, polyamine levels are tightly controlled. This control may be compromised in autoimmune diseases since elevated polyamine levels are seen in autoimmune diseases. Here a hypothesis is presented explaining how polyamines can stabilize autoantigens. In addition, the hypothesis explains how polyamines can inappropriately activate enzymes involved in NETosis, a process in which chromatin is modified and extruded from cells as extracellular traps that bind pathogens during an immune response. This polyamine-induced enzymatic activity can lead to an increase in NETosis resulting in release of autoantigenic material and tissue damage.

  14. Psychodynamics of the Ku Klux Klan.

    Science.gov (United States)

    Salmony, Steven E.; Smoke, Richard

    The Ku Klux Klan (KKK), characterized by disguises, secrecy, bigotry, and terror, came into power in the South after the Civil War. In some parts of the country the KKK, an extreme example of pathological group process, appears as strong and violent today as ever. Fromm (1941) noted that the basis of group psychology is the individual personality…

  15. Bax-induced apoptosis shortens the life span of DNA repair defect Ku70-knockout mice by inducing emphysema.

    Science.gov (United States)

    Matsuyama, Shigemi; Palmer, James; Bates, Adam; Poventud-Fuentes, Izmarie; Wong, Kelvin; Ngo, Justine; Matsuyama, Mieko

    2016-06-01

    Cells with DNA damage undergo apoptosis or cellular senescence if the damage cannot be repaired. Recent studies highlight that cellular senescence plays a major role in aging. However, age-associated diseases, including emphysema and neurodegenerative disorders, are caused by apoptosis of lung alveolar epithelial cells and neurons, respectively. Therefore, enhanced apoptosis also promotes aging and shortens the life span depending on the cell type. Recently, we reported that ku70(-) (/) (-)bax(-) (/) (-) and ku70(-) (/) (-)bax(+/) (-) mice showed significantly extended life span in comparison with ku70(-) (/) (-)bax(+/+) mice. Ku70 is essential for non-homologous end joining pathway for DNA double strand break repair, and Bax plays an important role in apoptosis. Our study suggests that Bax-induced apoptosis has a significant impact on shortening the life span of ku70(-) (/) (-) mice, which are defective in one of DNA repair pathways. The lung alveolar space gradually enlarges during aging, both in mouse and human, and this age-dependent change results in the decrease of respiration capacity during aging that can lead to emphysema in more severe cases. We found that emphysema occurred in ku70(-) (/) (-) mice at the age of three-months old, and that Bax deficiency was able to suppress it. These results suggest that Bax-mediated apoptosis induces emphysema in ku70(-) (/) (-) mice. We also found that the number of cells, including bronchiolar epithelial cells and type 2 alveolar epithelial cells, shows a higher DNA double strand break damage response in ku70 KO mouse lung than in wild type. Recent studies suggest that non-homologous end joining activity decreases with increased age in mouse and rat model. Together, we hypothesize that the decline of Ku70-dependent DNA repair activity in lung alveolar epithelial cells is one of the causes of age-dependent decline of lung function resulting from excess Bax-mediated apoptosis of lung alveolar epithelial cells (and their

  16. Ku80-deleted cells are defective at base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

    2013-05-15

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  17. Purification of pituitary autoantigen by column liquid chromatography and chromatofocusing.

    Science.gov (United States)

    Gut, Paweł; Fischbach, Jakub; Ziemnicka, Katarzyna; Bączyk, Maciej; Baszko-Błaszyk, Daria; Wrotkowska, Elżbieta; Ruchała, Marek

    2014-01-01

    Pituitary autoantibodies can be determined both in patients with pituitary disease as well as patients with autoimmune endocrine diseases. The purpose of the study was to isolate and purify pituitary autoantigen using sera of patients and the microsomal fraction of the pituitary. To isolate a pituitary autoantigen, patient sera were used, which showed a strong immune response to pituitary antigens. Pituitary microsomal fractions were prepared from pituitary tissue homogenates. In the study, sera of patients with pituitary disease, Addison and Graves' disease were used. The initial stages were carried out by affinity chromatography on CN -Br sepharose column whereas purification was continued by column liquid chromatography on AcA54 Ultrogel. Chromatofocusing was performed by Polybuffer exchanger PBE 94. (125)I-labeled pituitary antigens after isolation appeared in column chromatography in three peaks. The first peak contained 50-70 kDa proteins, the second peak - 17 to 22 kDa proteins and the third peak contains (125)-iodides. Three fractions obtained from filtration on Ultrogel were separated in a polyacrylamide gel. In the first peak two bands 67 and 55 kDa appeared. The second peak contained low molecular weight substances, and the third peak contained (125)I. The first peak from Ultrogel was isolated by chromatofocusing - the first peak with pH 5.9 and the second one with pH 4.9. Isolation and purification of pituitary autoantigen with the use of column liquid chromatography and chromatofocusing resulted in obtainment of two antigenic proteins of specific gravity of 67 and 55 kDa.

  18. Peroxiredoxin 2 is a novel autoantigen for anti-endothelial cell antibodies in systemic vasculitis

    Science.gov (United States)

    Karasawa, R; Kurokawa, M S; Yudoh, K; Masuko, K; Ozaki, S; Kato, T

    2010-01-01

    Anti-endothelial cell antibodies (AECA) have been frequently detected in systemic vasculitis, which affects blood vessels of various sizes. To understand the pathogenic roles of AECA in systemic vasculitis, we attempted to identify target antigens for AECA comprehensively by a proteomic approach. Proteins extracted from human umbilical vein endothelial cells (HUVEC) were separated by two-dimensional electrophoresis, and Western blotting was subsequently conducted using sera from patients with systemic vasculitis. As a result, 53 autoantigenic protein spots for AECA were detected, nine of which were identified by mass spectrometry. One of the identified proteins was peroxiredoxin 2 (Prx2), an anti-oxidant enzyme. Frequency of anti-Prx2 autoantibodies, measured by enzyme-linked immunosorbent assay (ELISA), was significantly higher in systemic vasculitis (60%) compared to those in collagen diseases without clinical vasculitis (7%, P vasculitis and would be involved in the inflammatory processes of systemic vasculitis. PMID:20646000

  19. Ku70 and ku80 null mutants improve the gene targeting frequency in Monascus ruber M7.

    Science.gov (United States)

    He, Yi; Liu, Qingpei; Shao, Yanchun; Chen, Fusheng

    2013-06-01

    Normally, gene targeting by homologous recombination occurs rarely during a transformation process since non-homologous recombination is predominant in filamentous fungi. In our previous researches, the average gene replacement frequency (GRF) in Monascus ruber M7 was as low as 15 %. To develop a highly efficient gene targeting system for M. ruber M7, two M. ruber M7 null mutants of ku70 (MrΔku70) and ku80 (MrΔku80) were constructed which had no apparent defects in the development including vegetative growth, colony phenotype, microscopic morphology and spore yield compared with M. ruber M7. In addition, the production of some significant secondary metabolites such as pigments and citrinin had no differences between the two disruptants and the wild-type strain. Further results revealed that the GRFs of triA (encoding a putative acetyltransferase) were 42.2 % and 61.5 % in the MrΔku70 and MrΔku80 strains, respectively, while it was only about 20 % in M. ruber M7. Furthermore, GRFs of these two disruptants at other loci (the pigE, fmdS genes in MrΔku70 and the ku70 gene in MrΔku80) were investigated, and the results indicated that GRFs in the MrΔku70 strain and the MrΔku80 strain were doubled and tripled compared with that in M. ruber M7, respectively. Therefore, the ku70 and ku80 null mutants of M. ruber M7, especially the ku80-deleted strain, will be excellent hosts for efficient gene targeting.

  20. Ku-Band Data-Communication Adapter

    Science.gov (United States)

    Schadelbauer, Steve

    1995-01-01

    Data-communication adapter circuit on single printed-circuit board serves as general-purpose interface between personal computer and satellite communication system. Designed as direct interface with Ku-band data-communication system for payloads on space shuttle, also used with any radio-frequency transmission systems. Readily installed in almost any personal computer via widely used Industry Standard Architecture (ISA) bus.

  1. RNA recognition by the DNA end-binding Ku heterodimer.

    Science.gov (United States)

    Dalby, Andrew B; Goodrich, Karen J; Pfingsten, Jennifer S; Cech, Thomas R

    2013-06-01

    Most nucleic acid-binding proteins selectively bind either DNA or RNA, but not both nucleic acids. The Saccharomyces cerevisiae Ku heterodimer is unusual in that it has two very different biologically relevant binding modes: (1) Ku is a sequence-nonspecific double-stranded DNA end-binding protein with prominent roles in nonhomologous end-joining and telomeric capping, and (2) Ku associates with a specific stem-loop of TLC1, the RNA subunit of budding yeast telomerase, and is necessary for proper nuclear localization of this ribonucleoprotein enzyme. TLC1 RNA-binding and dsDNA-binding are mutually exclusive, so they may be mediated by the same site on Ku. Although dsDNA binding by Ku is well studied, much less is known about what features of an RNA hairpin enable specific recognition by Ku. To address this question, we localized the Ku-binding site of the TLC1 hairpin with single-nucleotide resolution using phosphorothioate footprinting, used chemical modification to identify an unpredicted motif within the hairpin secondary structure, and carried out mutagenesis of the stem-loop to ascertain the critical elements within the RNA that permit Ku binding. Finally, we provide evidence that the Ku-binding site is present in additional budding yeast telomerase RNAs and discuss the possibility that RNA binding is a conserved function of the Ku heterodimer.

  2. An Innovative Method to Identify Autoantigens Expressed on the Endothelial Cell Surface: Serological Identification System for Autoantigens Using a Retroviral Vector and Flow Cytometry (SARF

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Shirai

    2013-01-01

    Full Text Available Autoantibodies against integral membrane proteins are usually pathogenic. Although anti-endothelial cell antibodies (AECAs are considered to be critical, especially for vascular lesions in collagen diseases, most molecules identified as autoantigens for AECAs are localized within the cell and not expressed on the cell surface. For identification of autoantigens, proteomics and expression library analyses have been performed for many years with some success. To specifically target cell-surface molecules in identification of autoantigens, we constructed a serological identification system for autoantigens using a retroviral vector and flow cytometry (SARF. Here, we present an overview of recent research in AECAs and their target molecules and discuss the principle and the application of SARF. Using SARF, we successfully identified three different membrane proteins: fibronectin leucine-rich transmembrane protein 2 (FLRT2 from patients with systemic lupus erythematosus (SLE, intercellular adhesion molecule 1 (ICAM-1 from a patient with rheumatoid arthritis, and Pk (Gb3/CD77 from an SLE patient with hemolytic anemia, as targets for AECAs. SARF is useful for specific identification of autoantigens expressed on the cell surface, and identification of such interactions of the cell-surface autoantigens and pathogenic autoantibodies may enable the development of more specific intervention strategies in autoimmune diseases.

  3. The HTLV-1 Tax Oncoprotein Represses Ku80 Gene Expression

    OpenAIRE

    Ducu, Razvan I.; Dayaram, Tajhal; Marriott, Susan J

    2011-01-01

    The HTLV-I oncoprotein Tax interferes with DNA double strand break repair. Since non-homologous end joining (NHEJ) is a major pathway used to repair DNA double strand breaks we examined the effect of Tax on this pathway, with particular interest in the expression and function of Ku80, a critical component of the NHEJ pathway. Tax expression decreased Ku80 mRNA and protein levels, and repressed transcription from the Ku80 promoter. Conversely, Ku80 mRNA increased following siRNA knockdown of T...

  4. An Intrinsically Disordered APLF Links Ku, DNA-PKcs, and XRCC4-DNA Ligase IV in an Extended Flexible Non-homologous End Joining Complex.

    Science.gov (United States)

    Hammel, Michal; Yu, Yaping; Radhakrishnan, Sarvan K; Chokshi, Chirayu; Tsai, Miaw-Sheue; Matsumoto, Yoshihiro; Kuzdovich, Monica; Remesh, Soumya G; Fang, Shujuan; Tomkinson, Alan E; Lees-Miller, Susan P; Tainer, John A

    2016-12-30

    DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4). Ku also interacts with accessory factors such as aprataxin and polynucleotide kinase/phosphatase-like factor (APLF). Yet, how these factors interact to tether, process, and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic. Here, small angle X-ray scattering (SAXS) and mutational analyses show APLF is largely an intrinsically disordered protein that binds Ku, Ku/DNA-PKcs (DNA-PK), and X4L4 within an extended flexible NHEJ core complex. X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C-terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with Ku, DNA-PK, and X4L4. Collective results unveil the solution architecture of the six-protein complex and suggest cooperative assembly of an extended flexible NHEJ core complex that supports APLF accessibility while possibly providing flexible attachment of the core complex to chromatin. The resulting dynamic tethering furthermore, provides geometric access of L4 catalytic domains to the DNA ends during ligation and of DNA-PKcs for targeted phosphorylation of other NHEJ proteins as well as trans-phosphorylation of DNA-PKcs on the opposing DSB without disrupting the core ligation complex. Overall the results shed light on evolutionary conservation of Ku, X4, and L4 activities, while explaining the observation that Ku80CTR and DNA-PKcs only occur in a subset of higher eukaryotes.

  5. A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen.

    Science.gov (United States)

    Xue, Dahai; Shi, Hong; Smith, James D; Chen, Xinguo; Noe, Dennis A; Cedervall, Tommy; Yang, Derek D; Eynon, Elizabeth; Brash, Douglas E; Kashgarian, Michael; Flavell, Richard A; Wolin, Sandra L

    2003-06-24

    Antibodies against a conserved RNA-binding protein, the Ro 60-kDa autoantigen, occur in 24-60% of all patients with systemic lupus erythematosus. Anti-Ro antibodies are correlated with photosensitivity and cutaneous lesions in these patients and with neonatal lupus, a syndrome in which mothers with anti-Ro antibodies give birth to children with complete congenital heart block and photosensitive skin lesions. In higher eukaryotes, the Ro protein binds small RNAs of unknown function known as Y RNAs. Because the Ro protein also binds misfolded 5S rRNA precursors, it is proposed to function in a quality-control pathway for ribosome biogenesis. Consistent with a role in the recognition or repair of intracellular damage, an orthologue of Ro in the radiation-resistant eubacterium Deinococcus radiodurans contributes to survival of this bacterium after UV irradiation. Here, we show that mice lacking the Ro protein develop an autoimmune syndrome characterized by anti-ribosome antibodies, anti-chromatin antibodies, and glomerulonephritis. Moreover, in one strain background, Ro-/- mice display increased sensitivity to irradiation with UV light. Thus, one function of this major human autoantigen may be to protect against autoantibody development, possibly by sequestering defective ribonucleoproteins from immune surveillance. Furthermore, the finding that mice lacking the Ro protein are photosensitive suggests that loss of Ro function could contribute to the photosensitivity associated with anti-Ro antibodies in humans.

  6. Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

    National Research Council Canada - National Science Library

    Kostianets, Olga; Antoniuk, Stepan; Filonenko, Valeriy; Kiyamova, Ramziya

    2012-01-01

    ... and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile...

  7. Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Fumio, E-mail: fnomura@faculty.chiba-u.jp [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Sogawa, Kazuyuki; Noda, Kenta; Seimiya, Masanori; Matsushita, Kazuyuki; Miura, Toshihide [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Tomonaga, Takeshi [Laboratory of Proteome Research, National Institute of Biomedical Innovation, Ibaraki (Japan); Yoshitomi, Hideyuki [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Imazeki, Fumio [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan); Takizawa, Hirotaka [Kashiwado Clinic in Port-Square of the Kashiwado Memorial Foundation, Chiba (Japan); Mogushi, Kaoru [Information Center for Medical Sciences, Tokyo Dental and Medical University, Tokyo (Japan); Miyazaki, Masaru [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Yokosuka, Osamu [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Overexpression of Ku86 in human liver cancer was shown by immunohistochemistry. Black-Right-Pointing-Pointer Serum anti-Ku86 was significantly elevated in early hepatocellular carcinoma. Black-Right-Pointing-Pointer Anti-Ku86 may be more sensitive than the conventional markers for early detection. Black-Right-Pointing-Pointer Serum anti-Ku86 significantly decreased after surgical resection of liver tumors. Black-Right-Pointing-Pointer Elevation of serum anti-Ku86 in other non-liver solid tumors was minimal. -- Abstract: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is one of the most common cancers worldwide and the third most common cause of cancer-related death. Imaging studies including ultrasound and computed tomography are recommended for early detection of HCC, but they are operator dependent, costly and involve radiation. Therefore, there is a need for simple and sensitive serum markers for the early detection of hepatocellular carcinoma (HCC). In our recent proteomic studies, a number of proteins overexpressed in HCC tissues were identified. We thought if the serum autoantibodies to these overexpressed proteins were detectable in HCC patients. Of these proteins, we focused on Ku86, a nuclear protein involved in multiple biological processes and aimed to assess the diagnostic value of serum anti-Ku86 in the early detection of HCC. Serum samples were obtained prior to treatment from 58 consecutive patients with early or relatively early hepatitis C virus (HCV)-related HCC and 137 patients with HCV-related liver cirrhosis without evidence of HCC. Enzyme immunoassays were used to measure serum levels of autoantibodies. Serum levels of anti-Ku86 antibodies were significantly elevated in HCC patients compared to those in liver cirrhosis patients (0.41 {+-} 0.28 vs. 0.18 {+-} 0.08 Abs at 450 nm, P < 0001). Setting the cut-off level to give 90% specificity, anti-Ku86 was positive in 60.7% of

  8. Combinations of siRNAs against La Autoantigen with NS5B or hVAP-A Have Additive Effect on Inhibition of HCV Replication

    Science.gov (United States)

    Mandal, Anirban; Ganta, Krishna Kumar

    2016-01-01

    Hepatitis C virus is major cause of chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Presently available direct-acting antiviral drugs have improved success rate; however, high cost limits their utilization, especially in developing countries like India. In the present study, we evaluated anti-HCV potential of several siRNAs targeted against the HCV RNA-dependent RNA polymerase NS5B and cellular factors, La autoantigen, PSMA7, and human VAMP-associated protein to intercept different steps of viral life cycle. The target genes were downregulated individually as well as in combinations and their impact on viral replication was evaluated. Individual downregulation of La autoantigen, PSMA7, hVAP-A, and NS5B resulted in inhibition of HCV replication by about 67.2%, 50.7%, 39%, and 52%, respectively. However, antiviral effect was more pronounced when multiple genes were downregulated simultaneously. Combinations of siRNAs against La autoantigen with NS5B or hVAP-A resulted in greater inhibition in HCV replication. Our findings indicate that siRNA is a potential therapeutic tool for inhibiting HCV replication and simultaneously targeting multiple viral steps with the combination of siRNAs is more effective than silencing a single target. PMID:27446609

  9. Role of Ku80-dependent end-joining in delayed genomic instability in mammalian cells surviving ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Keiji, E-mail: kzsuzuki@nagasaki-u.ac.jp [Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Kodama, Seiji [Research Institute for Advanced Science and Technology, Osaka Prefecture University, 1-2 Gakuen-machi, Sakai 599-8570 (Japan); Watanabe, Masami [Kyoto University Research Reactor Institute, Kumatori-cho Sennan-gun, Osaka 590-0494 (Japan)

    2010-01-05

    Ionizing radiation induces delayed destabilization of the genome in the progenies of surviving cells. This phenomenon, which is called radiation-induced genomic instability, is manifested by delayed induction of radiation effects, such as cell death, chromosome aberration, and mutation in the progeny of cells surviving radiation exposure. Previously, there was a report showing that delayed cell death was absent in Ku80-deficient Chinese hamster ovary (CHO) cells, however, the mechanism of their defect has not been determined. We found that delayed induction of DNA double strand breaks and chromosomal breaks were intact in Ku80-deficient cells surviving X-irradiation, whereas there was no sign for the production of chromosome bridges between divided daughter cells. Moreover, delayed induction of dicentric chromosomes was significantly compromised in those cells compared to the wild-type CHO cells. Reintroduction of the human Ku86 gene complimented the defective DNA repair and recovered delayed induction of dicentric chromosomes and delayed cell death, indicating that defective Ku80-dependent dicentric induction was the cause of the absence of delayed cell death. Since DNA-PKcs-defective cells showed delayed phenotypes, Ku80-dependent illegitimate rejoining is involved in delayed impairment of the integrity of the genome in radiation-survived cells.

  10. Identification of novel autoantigens by a triangulation approach.

    Science.gov (United States)

    Cottrell, Tricia R; Hall, John C; Rosen, Antony; Casciola-Rosen, Livia

    2012-11-30

    High titer autoantibodies, which are often associated with specific clinical phenotypes, are useful diagnostically and prognostically in systemic autoimmune diseases. In several autoimmune rheumatic diseases (e.g. myositis and Sjogren's syndrome), 20-40% of patients are autoantibody negative as assessed by conventional assays. The recent discovery of new specificities (e.g., anti-MDA5) in a subset of these autoantibody-negative subjects demonstrates that additional specificities await identification. In this manuscript, we describe a rapid multidimensional method to identify new autoantigens. A central foundation of this rapid approach is the use of an antigen source in which a pathogenic pathway active in the disease is recapitulated. Additionally, the method involves a modified serological proteome analysis strategy which allows confirmation that the correct gel plug has been removed prior to sending for sequencing. Lastly, the approach uses multiple sources of information to enable rapid triangulation and identification of protein candidates. Possible permutations and underlying principles of this triangulation strategy are elaborated to demonstrate the broad utility of this approach for antigen discovery.

  11. Aberrant accumulation of the diabetes autoantigen GAD65 in Golgi membranes in conditions of ER stress and autoimmunity

    DEFF Research Database (Denmark)

    Phelps, Edward A; Cianciaruso, Chiara; Michael, Iacovos P

    2016-01-01

    Pancreatic islet beta cells are particularly susceptible to endoplasmic reticulum (ER) stress, which is implicated in beta cell dysfunction and loss during the pathogenesis of type 1 diabetes (T1D). The peripheral membrane protein GAD65 is an autoantigen in human T1D. GAD65 synthesizes GABA......, an important autocrine and paracrine signaling molecule and a survival factor in islets. We show that ER stress in primary beta cells perturbs the palmitoylation cycle controlling GAD65 endomembrane distribution, resulting in aberrant accumulation of the palmitoylated form in trans-Golgi membranes....... The palmitoylated form has heightened immunogenicity, exhibiting increased uptake by antigen presenting cells and T cell stimulation compared to the non-palmitoylated form. Similar accumulation of GAD65 in Golgi membranes is observed in human beta cells in pancreatic sections from GAD65 autoantibody positive...

  12. β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome.

    Science.gov (United States)

    Tanimura, Kenji; Jin, Hui; Suenaga, Tadahiro; Morikami, Satoko; Arase, Noriko; Kishida, Kazuki; Hirayasu, Kouyuki; Kohyama, Masako; Ebina, Yasuhiko; Yasuda, Shinsuke; Horita, Tetsuya; Takasugi, Kiyoshi; Ohmura, Koichiro; Yamamoto, Ken; Katayama, Ichiro; Sasazuki, Takehiko; Lanier, Lewis L; Atsumi, Tatsuya; Yamada, Hideto; Arase, Hisashi

    2015-04-30

    Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy complications. β2-glycoprotein I (β2GPI) complexed with phospholipid is recognized as a major target for autoantibodies in APS; however, less than half the patients with clinical manifestations of APS possess autoantibodies against the complexes. Therefore, the range of autoantigens involved in APS remains unclear. Recently, we found that human leukocyte antigen (HLA) class II molecules transport misfolded cellular proteins to the cell surface via association with their peptide-binding grooves. Furthermore, immunoglobulin G heavy chain/HLA class II complexes were specific targets for autoantibodies in rheumatoid arthritis. Here, we demonstrate that intact β2GPI, not peptide, forms a complex with HLA class II molecules. Strikingly, 100 (83.3%) of the 120 APS patients analyzed, including those whose antiphospholipid antibody titers were within normal range, possessed autoantibodies that recognize β2GPI/HLA class II complexes in the absence of phospholipids. In situ association between β2GPI and HLA class II was observed in placental tissues of APS patients but not in healthy controls. Furthermore, autoantibodies against β2GPI/HLA class II complexes mediated complement-dependent cytotoxicity against cells expressing the complexes. These data suggest that β2GPI/HLA class II complexes are a target in APS that might be involved in the pathogenesis.

  13. MHC Class II Auto-antigen Processing and Presentation is Unconventional

    Directory of Open Access Journals (Sweden)

    Scheherazade eSadegh-Nasseri

    2015-07-01

    Full Text Available Antigen presentation is highly critical in adoptive immunity. Only by interacting with antigens presented by MHC Class II molecules, can helper T cells be stimulated to fight infections or diseases. The degradation of a full protein into small peptide fragments bound to class II molecules is a dynamic, lengthy process consisting of many steps and chaperons. Deregulation in any step of antigen processing could lead to the development of self-reactive T cells or defective immune response to pathogens. Indeed Human Leucocyte Antigens (HLA Class II genes are the predominant contributors to susceptibility to autoimmune diseases. Conventional antigen processing calls for internalization of extracellular antigens followed by processing and epitope selection within antigen processing subcellular compartments, enriched with all necessary accessory molecules, processing enzymes, and proper pH and denaturing conditions. However, recent data examining the temporal relationship between antigen uptakes, processing and epitope selection revealed unexpected characteristics for autoantigenic epitopes, which was not shared with antigenic epitopes from pathogens. This review provides a discussion of the relevance of these findings to the mechanisms of autoimmunity.

  14. Uudised : Jamaika reggae-laulja KuKu klubis. Moskva Patriarhaadi koor Tartus. Barry White vilistati välja. Wolfgang Flur süüdistab Kraftwerki

    Index Scriptorium Estoniae

    2000-01-01

    Natural Pretty esineb 16. dets. KuKu klubis. Moskva koor esineb jõulukontserdiga 21. dets. Tartus. B.White'i ebaõnnestunud kontserdist Sydneys. W.Fluri mälestusteraamatust "Kraftwerk ئ ma olin robot"

  15. Uudised : Jamaika reggae-laulja KuKu klubis. Moskva Patriarhaadi koor Tartus. Barry White vilistati välja. Wolfgang Flur süüdistab Kraftwerki

    Index Scriptorium Estoniae

    2000-01-01

    Natural Pretty esineb 16. dets. KuKu klubis. Moskva koor esineb jõulukontserdiga 21. dets. Tartus. B.White'i ebaõnnestunud kontserdist Sydneys. W.Fluri mälestusteraamatust "Kraftwerk ئ ma olin robot"

  16. The Ku-band Polarization Identifier

    CERN Document Server

    Gundersen, J O

    2003-01-01

    The Ku-band Polarization Identifier (KUPID) will integrate a very low noise 12-18 GHz, correlation polarimeter onto the Crawford Hill seven meter, millimeter-wave antenna. The primary components of the polarimeter will be built at the University of Miami and other key components, including the microwave horn and data acquisition system will be built at the University of Chicago and Princeton University. This project will measure the Q and U Stokes parameters in regions near the north celestial pole, in regions of low galactic contamination, and in regions near the galactic plane. The KUPID survey experiment makes use of many of the techniques employed in the Princeton IQU Experiment (PIQUE) that was developed by the members of this collaboration to detect CMB polarization at shorter wavelengths. The KUPID experiment will be constructed in parallel and on the same timescale as the CAPMAP experiment (see Barkats, this volume) which is the follow-on experiment to PIQUE. KUPID will observe on the Crawford Hill an...

  17. Renewal of KU-FEL Facility

    CERN Document Server

    Kii, Toshiteru; Masuda, Kai; Murakami, Shio; Ohgaki, Hideaki; Yamazaki, Tetsuo; Yoshikawa, Kiyoshi; Zen, Heishun

    2004-01-01

    Users demands to a high power tunable IR laser are increasing in Japan in energy-related science, such as basic study of high-efficiency solar cells, generation of new energy source of alcohol and/or H2 from polluted gas, and separation of DNA and/or RNA. To satisfy these demands, we decided to renew our FEL facility more user friendly and to operate more flexibly. Construction and fundamental studies on the KU-FEL have been carried out at a building of Institute of Chemical Research where few other accelerators are operating. Therefore, available machine time for our experiments is quite limited. We are now modifying the room by adding concrete walls of 2-m thickness and some space for users will be available. The present FEL system will be moved to the room A photocathode RF-gun system will be nearly added to the system and the present thermionic RF-gun will be used ternatively according to the demands of users. The photocathode material will be Cs2Te. The room with the shielding will be completed in June, ...

  18. Autoantigens produced in plants for oral tolerance therapy of autoimmune diseases.

    Science.gov (United States)

    Ma, S; Jevnikar, A M

    1999-01-01

    Oral administration of protein antigens can induce antigen-specific immune hyporesponsiveness and may be useful in treating autoimmune diseases or preventing transplant rejection. However, the therapeutic value of oral tolerance may be limited when candidate autoantigens cannot be produced by conventional system in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can produce hugh quantities of functional mammalian proteins at extremely competitive cost. Furthermore, transgenic food plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Here we show that the diabetes-associated autoantigen glutamic acid decarboxylase (GAD) is efficiently expressed in both tobacco and potato plants, and that mice, when fed with fresh transgenic potato tubers, are fully protected from diabetes.

  19. Major retinal autoantigens remain stably expressed during all stages of spontaneous uveitis.

    Science.gov (United States)

    Deeg, Cornelia A; Hauck, Stefanie M; Amann, Barbara; Kremmer, Elisabeth; Stangassinger, Manfred; Ueffing, Marius

    2007-07-01

    Equine recurrent uveitis (ERU) is a valuable model for autoimmune diseases, since it develops frequently and occurs spontaneously. We investigated the overall expression level of three major retinal autoantigens in normal retinas and various ERU stages. Analysis of retinal proteomes of both, healthy and diseased retinas revealed an almost unaffected expression of IRBP, S-antigen and cRALBP in ERU cases. Validation of these findings with western blots and immunohistochemistry confirmed constant to increased expression of these autoantigens, although loss of their physiological expression sites within retina is evident. In contrast to stable expression of autoantigens, rhodopsin, the major component of phototransduction in photoreceptors, disappeared from destructed retinas. These results explain persistent uveitic attacks even in severely damaged eyes and draw the attention to further investigations of biological pathways and regulations in autoimmune target tissues.

  20. KU32 Prevents 5-Fluorouracil Induced Cognitive Impairment.

    Science.gov (United States)

    Sofis, Michael J; Jarmolowicz, David P; Kaplan, Sam V; Gehringer, Rachel C; Lemley, Shea M; Blagg, Brian S; Johnson, Michael A

    2017-03-27

    Chemotherapy induced cognitive impairment (i.e. Chemobrain) involves acute and long-term deficits in memory, executive function, and processing speed. Animal studies investigating these cognitive deficits have had mixed results, potentially due to variability in the complexity of behavioral tasks across experiments. Further, common chemotherapy treatments such as 5-Fluorouracil (5-FU) break down myelin integrity corresponding to hippocampal neurodegenerative deficits and mitochondrial dysfunction. There is little evidence, however, of pharmacological treatments that may target mitochondrial dysfunction. Using a differential reinforcement of low rates (DRL) task combining spatial and temporal components, the current study evaluated the preventative effects of the pharmacological agent KU32 on the behavior of rats treated with 5-FU (5-FU+Saline vs. 5FU+KU32). DRL performance was analyzed the day after the first set of injections (D1), the day after the second set of injections (D7) and the last day of the experiment (D14). The 5FU+KU32 group earned significantly more reinforcers on the DRL task at D7 and D14 than the 5FU+Saline group. Further, the 5FU+KU32 group showed significantly better temporal discrimination. The 5FU+KU32 showed within-group improvement in temporal discrimination from D7 to D14. No significant differences were observed in spatial discrimination, however, those in the 5FU+Saline group responded more frequently on T3 compared to the 5FU+KU32 group, highlighting temporal discrimination differences between groups. The current data suggest that KU32 shows promise in the prevention of chemotherapy induced impairments in temporal discrimination.

  1. Accumulation of Ku70 at DNA double-strand breaks in living epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Koike, Manabu, E-mail: m_koike@nirs.go.jp [DNA Repair Gene Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Yutoku, Yasutomo [DNA Repair Gene Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan); Graduate School of Science, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522 (Japan); Koike, Aki [DNA Repair Gene Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

    2011-10-15

    Ku70 and Ku80 play an essential role in the DNA double-strand break (DSB) repair pathway, i.e., nonhomologous DNA-end-joining (NHEJ). No accumulation mechanisms of Ku70 at DSBs have been clarified in detail, although the accumulation mechanism of Ku70 at DSBs plays key roles in regulating the NHEJ activity. Here, we show the essential domains for the accumulation and function of Ku70 at DSBs in living lung epithelial cells. Our results showed that EGFP-Ku70 accumulation at DSBs began immediately after irradiation. Our findings demonstrate that three domains of Ku70, i.e., the {alpha}/{beta}, DNA-binding, and Ku80-binding domains, but not the SAP domain, are necessary for the accumulation at or recognition of DSBs in the early stage after irradiation. Moreover, our findings demonstrate that the leucine at amino acid 385 of Ku70 in the Ku80-binding domain, but not the three target amino acids for acetylation in the DNA-binding domain, is involved in the localization and accumulation of Ku70 at DSBs. Furthermore, accumulations of XRCC4 and XLF, but not that of Artemis, at DSBs are dependent on the presence of Ku70. These findings suggest that Artemis can work in not only the Ku-dependent repair process, but also the Ku-independent process at DSBs in living epithelial cells.

  2. Changes in the level and distribution of Ku proteins during cellular senescence

    Science.gov (United States)

    Seluanov, Andrei; Danek, Jacquelynn; Hause, Nola; Gorbunova, Vera

    2009-01-01

    Aging is associated with accumulation of genomic rearrangements consistent with aberrant repair of DNA breaks. We have shown previously that DNA repair by nonhomologous end joining (NHEJ) becomes less efficient and more error-prone in senescent cells. Here we show that the levels of Ku70 and Ku80 drop approximately two fold in replicatively senescent cells. Intracellular distribution of Ku also changes. In the young cells roughly half of Ku is located in the nucleus and half in the cytoplasm. In senescent cells the nuclear levels of Ku do not change, while the cytoplasmic Ku fraction disappears. Upon treatment with gamma-irradiation, in the young cells cytoplasmic Ku moved into the nuclear and membrane fractions, while no change in the Ku distribution occurred in senescent cells. Upon treatment with UVC Ku moved out of the nucleus in the young cells, while most Ku remained nuclear in senescent cells. This suggests that the nuclear Ku in senescent cells is unable to respond to DNA damage. We hypothesize that overall decline in Ku levels, changes in Ku intracellular distribution, and the loss of appropriate response of Ku to DNA damage in senescent cells contribute to the decline of NHEJ and to age-related genomic instability. PMID:17686666

  3. KARP-1 works as a heterodimer with Ku70, but the function of KARP-1 cannot perfectly replace that of Ku80 in DSB repair.

    Science.gov (United States)

    Koike, Manabu; Yutoku, Yasutomo; Koike, Aki

    2011-10-01

    Ku, the heterodimer of Ku70 and Ku80, plays an essential role in the DNA double-strand break (DSB) repair pathway, i.e., non-homologous end-joining (NHEJ). Two isoforms of Ku80 encoded by the same genes, namely, Ku80 and KARP-1 are expressed and function in primate cells, but not in rodent cells. Ku80 works as a heterodimer with Ku70. However, it is not yet clear whether KARP-1 forms a heterodimer with Ku70 and works as a heterodimer. Although KARP-1 appears to work in NHEJ, its physiological role remains unclear. In this study, we established and characterized EGFP-KARP-1-expressing xrs-6 cell lines, EGFP-KARP-1/xrs-6. We found that nuclear localization signal (NLS) of KARP-1 is localized in the C-terminal region. Our data showed that KARP-1 localizes within the nucleus in NLS-dependent and NLS-independent manner and forms a heterodimer with Ku70, and stabilizes Ku70. On the other hand, EGFP-KARP-1 could not perfectly complement the radiosensitivity and DSB repair activity of Ku80-deficient xrs-6 cells. Furthermore, KARP-1 could not accumulate at DSBs faster than Ku80, although EGFP-KARP-1 accumulates at DSBs. Our data demonstrate that the function of KARP-1 could not perfectly replace that of Ku80 in DSB repair, although KARP-1 has some biochemical properties, which resemble those of Ku80, and works as a heterodimer with Ku70. On the other hand, the number of EGFP-KARP-1-expressing xrs-6 cells showing pan-nuclear γ-H2AX staining significantly increases following X-irradiation, suggesting that KARP-1 may have a novel role in DSB response. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Identification of immunodominant autoantigens in rat autoimmune orchitis.

    Science.gov (United States)

    Fijak, Monika; Iosub, Radu; Schneider, Eva; Linder, Monika; Respondek, Kathrin; Klug, Jörg; Meinhardt, Andreas

    2005-10-01

    Infection and inflammation of the genital tract are amongst the leading causes of male infertility. Experimental autoimmune orchitis (EAO) in the rat serves as a model for the investigation of inflammatory testicular impairment. In this study, experiments were conducted to identify the molecules that are responsible for eliciting the autoimmune attack on the testis. EAO was induced in in-bred Wistar rats by active immunization with testis homogenates (EAO group I). Development of disease was observed using histological techniques and a new non-invasive three-dimensional (3D) imaging technology for in vivo monitoring, termed flat-panel volumetric computed tomography (fpvCT). Examination of control and EAO testes demonstrated the superior image quality of high-resolution fpvCT. A proteomics approach using 2D SDS-PAGE and immunoblotting analysis with EAO sera identified 12 spots. Seven were subsequently identified by mass spectrometry as heat shock proteins 60 (Hsp60) and 70 (Hsp70), disulphide isomerase ER-60, alpha-1-anti-trypsin, heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1), sperm outer dense fibre major protein 2 (ODF-2), and phosphoglycerate kinase 1. Hsp70, ODF-2, hnRNP H1, and ER-60 were identified by all EAO sera studied. To test the capacity of the identified proteins to elicit testicular autoimmune disease, recombinant proteins were used either individually or in combination to immunize rats (EAO group II). In all groups, the incidence of EAO was 25%. Inflammatory-type (ED1+) and resident (ED2+) macrophages, lymphocytes (CD45RA+), and dendritic cells (Ox-62+) were strongly increased in EAO group II animals, comparable to the testes of EAO I rats. Pre-immunization with a low dose of recombinant Hsp 70, hnRNP H1 or ODF-2 before induction of EAO with testis homogenate significantly delayed the onset of EAO but could not prevent disease. The identification of testicular autoantigens will allow a better understanding of disease pathogenesis and could

  5. A Ku-band satellite system for the cable television industry

    Science.gov (United States)

    Napoli, Joseph

    This paper describes the satellite requirements for the Ku-band used for satellite delivery of television programming. The case for using the Ku-band is reviewed, including the business benefits to the cable industry, the superior protection against failure, the pace of technical advances, and the channel capacity. The characteristics of the satellites carrying the Ku-band are described, and a protection plan for the satellites is considered. The technical characteristics of the Ku-band and related systems considerations are addressed. Signal outage at the Ku-band is discussed, and Ku-band receiving system design is examined, including system installation and operations.

  6. Ku-pa-ro en las tablillas de Cnoso

    Directory of Open Access Journals (Sweden)

    José L. Melena

    1974-12-01

    Full Text Available This paper is intended to be a comprehensive analysis of the evidence of ku-pa-ro in the Knossos Linear B tablets. Its main purpose is to set up the importance of such aromatic plant in the Mycenaean economy at Knossos and to identify what kind of sedge was concealed under the name ku-pa-ro and what part of the plant was used and for what purposes. What it is stressed is the usage of the Cyperus rotundus L. (i. e. the ku-pa-ro in the industry of perfumes and as a food additive as well. What is inferred from the discussion on the evidence of ku-pa-ro issues a series of valuable data concerning the localization of certain place-names in the map of Crete, and concerning the explanation of ideogram *171. The high qualities of ku-pa-ro preserved in the tablets lead the author to assume that such a plant was cultivated in Crete and was one of the main aromatic plants used by the Mycenaeans in the making of perfumes.

  7. Glucocorticoid Receptor Transcriptional Activation via the BRG1-Dependent Recruitment of TOP2β and Ku70/86.

    Science.gov (United States)

    Trotter, Kevin W; King, Heather A; Archer, Trevor K

    2015-08-01

    BRG1, the central ATPase of the human SWI/SNF complex, is critical for biological functions, including nuclear receptor (NR)-regulated transcription. Analysis of BRG1 mutants demonstrated that functional motifs outside the ATPase domain are important for transcriptional activity. In the course of experiments examining protein interactions mediated through these domains, Ku70 (XRCC6) was found to associate with a BRG1 fragment encompassing the conserved helicase-SANT-associated (HSA) and BRK domains of BRG1. Subsequent transcriptional activation assays and chromatin immunoprecipitation studies showed that Ku70/86 and components of the topoisomerase IIβ (TOP2β)/poly(ADP ribose) polymerase 1 (PARP1) complex are necessary for NR-mediated SWI/SNF-dependent transcriptional activation from endogenous promoters. In addition to establishing Ku-BRG1 binding and TOP2β/PARP1 recruitment by nuclear receptor transactivation, we demonstrate that the transient appearance of glucocorticoid receptor (GR)/BRG1-dependent, TOP2β-mediated double-strand DNA breaks is required for efficient GR-stimulated transcription. Taken together, these results suggest that a direct interaction between Ku70/86 and BRG1 brings together SWI/SNF remodeling capabilities and TOP2β activity to enhance the transcriptional response to hormone stimulation.

  8. Epiplakin Is a Paraneoplastic Pemphigus Autoantigen and Related to Bronchiolitis Obliterans in Japanese Patients

    NARCIS (Netherlands)

    Tsuchisaka, Atsunari; Numata, Sanae; Teye, Kwesi; Natsuaki, Yohei; Kawakami, Tamihiro; Takeda, Yoshito; Wang, Wenqing; Ishikawa, Kazushi; Goto, Mizuki; Koga, Hiroshi; Sogame, Ryosuke; Ishii, Norito; Takamori, Shinzo; Hoshino, Tomoaki; Brandt, Oliver; Pas, Hendri H.; Fujiwara, Sakuhei; Hashimoto, Takashi

    All plakin family proteins are known to be autoantigens in paraneoplastic pemphigus (PNP). In this study, we first examined whether PNP sera also react with epiplakin, another plakin protein, by various immunological methods using 48 Japanese PNP sera. Immunofluorescence confirmed that cultured

  9. Satellite communications application to Pacific countries above Ku band

    Science.gov (United States)

    Iida, Takashi

    1992-01-01

    An application of satellite communications above the Ku band to the Pacific region is described, focusing on: (1) Lightsat system and (2) a high capacity satellite system. A small geostationary satellite system using Ku band for the Federated States of Micronesia is shown as an example. A concept of multi-gigabits/second high capacity communications system using two satellites in the Ka band is described. The onboard bit-by-bit processing is very useful in the low link margin environment due to rain attenuation. These topics were obtained by the Asia Pacific Telecommunications Study granted by NASA conducted by the University of Colorado at Boulder.

  10. Selective inhibition of class switching to IgG and IgE by recruitment of the HoxC4 and Oct-1 homeodomain proteins and Ku70/Ku86 to newly identified ATTT cis-elements.

    Science.gov (United States)

    Schaffer, András; Kim, Edmund C; Wu, Xiaoping; Zan, Hong; Testoni, Lucia; Salamon, Szilvia; Cerutti, Andrea; Casali, Paolo

    2003-06-20

    Immunoglobulin (Ig) class switching is central to the maturation of the antibody response as IgG, IgA, and IgE are endowed with more diverse biological effector functions than IgM. It is induced upon engagement of CD40 on B lymphocytes by CD40L expressed by activated CD4+ T cells and exposure of B cells to T cell-secreted cytokines including interleukin-4 and transforming growth factor-beta. It begins with germ line IH-CH transcription and unfolds through class switch DNA recombination (CSR). We show here that the HoxC4 and Oct-1 homeodomain proteins together with the Ku70/Ku86 heterodimer bind as a complex to newly identified switch (S) regulatory ATTT elements (SREs) in the Igamma and Iepsilon promoters and downstream regions to dampen basal germ line Igamma-Cgamma and Iepsilon-Cepsilon transcriptions and repress CSR to Cgamma and Cepsilon. This mechanism is inactive in the Calpha1/Calpha2 loci because of the lack of SREs in the Ialpha1/Ialpha2 promoters. Accordingly, in resting human IgM+IgD+ B cells, HoxC4, Oct-1, and Ku70/Ku86 can be readily identified as bound to the Igamma and Iepsilon promoters but not the Ialpha1/Ialpha2 promoters. CD40 signaling dissociates the HoxC4.Oct-1. Ku complex from the Igamma and Iepsilon promoter SREs, thereby relieving the IH-CH transcriptional repression and allowing CSR to unfold. Dissociation of HoxC4.Oct-1. Ku from DNA is hampered by CD153 engagement, a CD40-signaling inhibitor. Thus, these findings outline a HoxC4.Oct-1. Ku-dependent mechanism of selective regulation of class switching to IgG and IgE and further suggest distinct co-evolution and shared CSR activation pathways in the Cgamma and Cepsilon as opposed to the Calpha1/Calpha2 loci.

  11. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination

    Science.gov (United States)

    Zan, Hong; Tat, Connie; Qiu, Zhifang; Taylor, Julia R.; Guerrero, Justin A.; Shen, Tian; Casali, Paolo

    2017-01-01

    Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S–S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR. Compared with their Rad52+/+ counterparts, which display normal CSR, Rad52−/− B cells show increased CSR, fewer intra-Sμ region recombinations, no/minimal microhomologies in S–S junctions, decreased c-Myc/IgH translocations and increased Ku70/Ku86 recruitment to S-region DSB ends. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends. It also facilitates a Ku-independent DSB repair, which favours intra-S region recombination and mediates, particularly in Ku absence, inter-S–S recombination, as emphasized by the significantly greater CSR reduction in Rad52−/− versus Rad52+/+ B cells on Ku86 knockdown. PMID:28176781

  12. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends to modulate antibody class-switch DNA recombination.

    Science.gov (United States)

    Zan, Hong; Tat, Connie; Qiu, Zhifang; Taylor, Julia R; Guerrero, Justin A; Shen, Tian; Casali, Paolo

    2017-02-08

    Antibody class-switch DNA recombination (CSR) is initiated by AID-introduced DSBs in the switch (S) regions targeted for recombination, as effected by Ku70/Ku86-mediated NHEJ. Ku-deficient B cells, however, undergo (reduced) CSR through an alternative(A)-NHEJ pathway, which introduces microhomologies in S-S junctions. As microhomology-mediated end-joining requires annealing of single-strand DNA ends, we addressed the contribution of single-strand annealing factors HR Rad52 and translesion DNA polymerase θ to CSR. Compared with their Rad52(+/+) counterparts, which display normal CSR, Rad52(-/-) B cells show increased CSR, fewer intra-Sμ region recombinations, no/minimal microhomologies in S-S junctions, decreased c-Myc/IgH translocations and increased Ku70/Ku86 recruitment to S-region DSB ends. Rad52 competes with Ku70/Ku86 for binding to S-region DSB ends. It also facilitates a Ku-independent DSB repair, which favours intra-S region recombination and mediates, particularly in Ku absence, inter-S-S recombination, as emphasized by the significantly greater CSR reduction in Rad52(-/-) versus Rad52(+/+) B cells on Ku86 knockdown.

  13. Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis.

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    Eun Young Yu

    2015-10-01

    Full Text Available A subset of human cancer cells uses a specialized, aberrant recombination pathway known as ALT to maintain telomeres, which in these cells are characterized by complex aberrations including length heterogeneity, high levels of unpaired C-strand, and accumulation of extra-chromosomal telomere repeats (ECTR. These phenotypes have not been recapitulated in any standard budding or fission yeast mutant. We found that eliminating Ku70 or Ku80 in the yeast-like fungus Ustilago maydis results initially in all the characteristic telomere aberrations of ALT cancer cells, including C-circles, a highly specific marker of ALT. Subsequently the ku mutants experience permanent G2 cell cycle arrest, accompanied by loss of telomere repeats from chromosome ends and even more drastic accumulation of very short ECTRs (vsECTRs. The deletion of atr1 or chk1 rescued the lethality of the ku mutant, and "trapped" the telomere aberrations in the early ALT-like stage. Telomere abnormalities are telomerase-independent, but dramatically suppressed by deletion of mre11 or blm, suggesting major roles for these factors in the induction of the ALT pathway. In contrast, removal of other DNA damage response and repair factors such as Rad51 has disparate effects on the ALT phenotypes, suggesting that these factors process ALT intermediates or products. Notably, the antagonism of Ku and Mre11 in the induction of ALT is reminiscent of their roles in DSB resection, in which Blm is also known to play a key role. We suggest that an aberrant resection reaction may constitute an early trigger for ALT telomeres, and that the outcomes of ALT are distinct from DSB because of the unique telomere nucleoprotein structure.

  14. Mre11 and Blm-Dependent Formation of ALT-Like Telomeres in Ku-Deficient Ustilago maydis.

    Science.gov (United States)

    Yu, Eun Young; Pérez-Martín, José; Holloman, William K; Lue, Neal F

    2015-10-01

    A subset of human cancer cells uses a specialized, aberrant recombination pathway known as ALT to maintain telomeres, which in these cells are characterized by complex aberrations including length heterogeneity, high levels of unpaired C-strand, and accumulation of extra-chromosomal telomere repeats (ECTR). These phenotypes have not been recapitulated in any standard budding or fission yeast mutant. We found that eliminating Ku70 or Ku80 in the yeast-like fungus Ustilago maydis results initially in all the characteristic telomere aberrations of ALT cancer cells, including C-circles, a highly specific marker of ALT. Subsequently the ku mutants experience permanent G2 cell cycle arrest, accompanied by loss of telomere repeats from chromosome ends and even more drastic accumulation of very short ECTRs (vsECTRs). The deletion of atr1 or chk1 rescued the lethality of the ku mutant, and "trapped" the telomere aberrations in the early ALT-like stage. Telomere abnormalities are telomerase-independent, but dramatically suppressed by deletion of mre11 or blm, suggesting major roles for these factors in the induction of the ALT pathway. In contrast, removal of other DNA damage response and repair factors such as Rad51 has disparate effects on the ALT phenotypes, suggesting that these factors process ALT intermediates or products. Notably, the antagonism of Ku and Mre11 in the induction of ALT is reminiscent of their roles in DSB resection, in which Blm is also known to play a key role. We suggest that an aberrant resection reaction may constitute an early trigger for ALT telomeres, and that the outcomes of ALT are distinct from DSB because of the unique telomere nucleoprotein structure.

  15. A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models.

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    Full Text Available Rapamycin analogs, temsirolimus and everolimus, are approved for the treatment of advance renal cell carcinoma (RCC. Currently approved agents inhibit mechanistic target of rapamycin (mTOR complex 1 (mTORC1. However, the mTOR kinase exists in two distinct multiprotein complexes, mTORC1 and mTORC2, and both complexes may be critical regulators of cell metabolism, growth and proliferation. Furthermore, it has been proposed that drug resistance develops due to compensatory activation of mTORC2 signaling during treatment with temsirolimus or everolimus. We evaluated Ku0063794, which is a small molecule that inhibits both mTOR complexes. Ku0063794 was compared to temsirolimus in preclinical models for renal cell carcinoma. Ku0063794 was effective in inhibiting the phosphorylation of signaling proteins downstream of both mTORC1 and mTORC2, including p70 S6K, 4E-BP1 and Akt. Ku0063794 was more effective than temsirolimus in decreasing the viability and growth of RCC cell lines, Caki-1 and 786-O, in vitro by inducing cell cycle arrest and autophagy, but not apoptosis. However, in a xenograft model there was no difference in the inhibition of tumor growth by Ku0063794 or temsirolimus. A potential explanation is that temsirolimus has additional effects on the tumor microenvironment. Consistent with this possibility, temsirolimus, but not Ku0063794, decreased tumor angiogenesis in vivo, and decreased the viability of HUVEC (Human Umbilical Vein Endothelial Cells cells in vitro at pharmacologically relevant concentrations. Furthermore, expression levels of VEGF and PDGF were lower in Caki-1 and 786-O cells treated with temsirolimus than cells treated with Ku0063794.

  16. Towards structural integration of airborne Ku-band SatCom antenna

    NARCIS (Netherlands)

    Schippers, Harmen; Verpoorte, Jaco; Hulzinga, Adriaan; Roeloffzen, C.G.H.; Baggen, Rens

    2013-01-01

    The paper describes research towards a fully structurally integrated Ku-band SatCom antenna. This antenna covers the complete receive band for aeronautical earth stations and DVB-S broadcast in Ku band (10.7 - 12.75 GHz). The antenna front-end consists of 32 tiles where each tile has 8×8 Ku-band

  17. Ku stabilizes replication forks in the absence of Brc1.

    Directory of Open Access Journals (Sweden)

    Arancha Sánchez

    Full Text Available DNA replication errors are a major source of genome instability in all organisms. In the fission yeast Schizosaccharomyces pombe, the DNA damage response protein Brc1 binds phospho-histone H2A (γH2A-marked chromatin during S-phase, but how Brc1 protects genome integrity remains unclear. Here we report that the non-homologous end-joining (NHEJ protein Ku becomes critical for survival of replication stress in brc1∆ cells. Ku's protective activity in brc1∆ cells does not involve its canonical NHEJ function or its roles in protecting telomeres or shielding DNA ends from Exo1 exonuclease. In brc1∆ pku80∆ cells, nuclear foci of Rad52 homologous recombination (HR protein increase and Mus81-Eme1 Holliday junction resolvase becomes critical, indicating increased replication fork instability. Ku's localization at a ribosomal DNA replication fork barrier associated with frequent replisome-transcriptosome collisions increases in brc1∆ cells and increased collisions correlate with an enhanced requirement for Brc1. These data indicate that Ku stabilizes replication forks in the absence of Brc1.

  18. Violence, The Ku Klux Klan and the Struggle for Equality.

    Science.gov (United States)

    Council on Interracial Books for Children, Inc., New York, NY.

    This paper provides teachers with information about the Ku Klux Klan (KKK) and makes available instructional procedures and resources for teaching about the Klan. First, some ideas are presented for dealing with the unusual emotional climate that can arise when the KKK is discussed in a classroom. Next, a brief history of the KKK is provided,…

  19. Architectures for ku-band broadband airborne satellite communication antennas

    NARCIS (Netherlands)

    Verpoorte, Jaco; Schippers, Harmen; Jorna, Pieter; Roeloffzen, Chris G.H.; Marpaung, David A.I.; Baggen, Rens; Sanadgol, Bahram

    2010-01-01

    This paper describes different architectures for a broadband antenna for satellite communication on aircraft. The antenna is a steerable (conformal) phased array antenna in Ku-band (receive-only). First the requirements for such a system are addressed. Subsequently a number of potential architecture

  20. Production of the main celiac disease autoantigen by transient expression in Nicotiana benthamiana

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    Vanesa Soledad Marin Viegas

    2015-12-01

    Full Text Available Celiac Disease (CD is a gluten sensitive enteropathy that remains widely undiagnosed and implementation of massive screening tests is needed to reduce the long term complications associated to untreated CD. The main CD autoantigen, human tissue transglutaminase (TG2, is a challenge for the different expression systems available since its cross-linking activity affects cellular processes. Plant-based transient expression systems can be an alternative for the production of this protein. In this work, a transient expression system for the production of human TG2 in Nicotiana benthamiana leaves was optimized and reactivity of plant-produced TG2 in CD screening test was evaluated. First, a subcellular targeting strategy was tested. Cytosolic, secretory, endoplasmic reticulum (C-terminal SEKDEL fusion and vacuolar (C-terminal KISIA fusion TG2 versions were transiently expressed in leaves and recombinant protein yields were measured. ER-TG2 and vac-TG2 levels were 9 to 16 fold higher than their cytosolic and secretory counterparts. As second strategy, TG2 variants were co-expressed with a hydrophobic elastin-like polymer (ELP construct encoding for 36 repeats of the pentapeptide VPGXG in which the guest residue X were V and F in ratio 8:1. Protein bodies (PB were induced by the ELP, with a consequent 2 fold-increase in accumulation of both ER-TG2 and vac-TG2. Subsequently, ER-TG2 and vac-TG2 were produced and purified using immobilized metal ion affinity chromatography. Plant purified ER-TG2 and vac-TG2 were recognized by three anti-TG2 monoclonal antibodies that bind different epitopes proving that plant-produced antigen has immunochemical characteristics similar to those of human TG2. Lastly, an ELISA was performed with sera of CD patients and healthy controls. Both vac-TG2 and ER-TG2 were positively recognized by IgA of CD patients while they were not recognized by serum from non-celiac controls. These results confirmed the usefulness of plant

  1. Regulation of Nuclear Positioning and Dynamics of the Silent Mating Type Loci by the Yeast Ku70/Ku80 Complex▿

    Science.gov (United States)

    Bystricky, Kerstin; Van Attikum, Haico; Montiel, Maria-Dolores; Dion, Vincent; Gehlen, Lutz; Gasser, Susan M.

    2009-01-01

    We have examined the hypothesis that the highly selective recombination of an active mating type locus (MAT) with either HMLα or HMRa is facilitated by the spatial positioning of relevant sequences within the budding yeast (Saccharomyces cerevisiae) nucleus. However, both position relative to the nuclear envelope (NE) and the subnuclear mobility of fluorescently tagged MAT, HML, or HMR loci are largely identical in haploid a and α cells. Irrespective of mating type, the expressed MAT locus is highly mobile within the nuclear lumen, while silent loci move less and are found preferentially near the NE. The perinuclear positions of HMR and HML are strongly compromised in strains lacking the Silent information regulator, Sir4. However, HMLα, unlike HMRa and most telomeres, shows increased NE association in a strain lacking yeast Ku70 (yKu70). Intriguingly, we find that the yKu complex is associated with HML and HMR sequences in a mating-type-specific manner. Its abundance decreases at the HMLα donor locus and increases transiently at MATa following DSB induction. Our data suggest that mating-type-specific binding of yKu to HMLα creates a local chromatin structure competent for recombination, which cooperates with the recombination enhancer to direct donor choice for gene conversion of the MATa locus. PMID:19047366

  2. The radiosensitizing effect of Ku70/80 knockdown in MCF10A cells irradiated with X-rays and p(66+Be(40 neutrons

    Directory of Open Access Journals (Sweden)

    Thierens Hubert

    2010-04-01

    Full Text Available Abstract Background A better understanding of the underlying mechanisms of DNA repair after low- and high-LET radiations represents a research priority aimed at improving the outcome of clinical radiotherapy. To date however, our knowledge regarding the importance of DNA DSB repair proteins and mechanisms in the response of human cells to high-LET radiation, is far from being complete. Methods We investigated the radiosensitizing effect after interfering with the DNA repair capacity in a human mammary epithelial cell line (MCF10A by lentiviral-mediated RNA interference (RNAi of the Ku70 protein, a key-element of the nonhomologous end-joining (NHEJ pathway. Following irradiation of control and Ku-deficient cell lines with either 6 MV X-rays or p(66+Be(40 neutrons, cellular radiosensitivity testing was performed using a crystal violet cell proliferation assay. Chromosomal radiosensitivity was evaluated using the micronucleus (MN assay. Results RNAi of Ku70 caused downregulation of both the Ku70 and the Ku80 proteins. This downregulation sensitized cells to both X-rays and neutrons. Comparable dose modifying factors (DMFs for X-rays and neutrons of 1.62 and 1.52 respectively were obtained with the cell proliferation assay, which points to the similar involvement of the Ku heterodimer in the cellular response to both types of radiation beams. After using the MN assay to evaluate chromosomal radiosensitivity, the obtained DMFs for X-ray doses of 2 and 4 Gy were 2.95 and 2.66 respectively. After neutron irradiation, the DMFs for doses of 1 and 2 Gy were 3.36 and 2.82 respectively. The fact that DMFs are in the same range for X-rays and neutrons confirms a similar importance of the NHEJ pathway and the Ku heterodimer for repairing DNA damage induced by both X-rays and p(66+Be(40 neutrons. Conclusions Interfering with the NHEJ pathway enhanced the radiosensitivity of human MCF10A cells to low-LET X-rays and high-LET neutrons, pointing to the importance

  3. Enhanced gene replacements in Ku80 disruption mutants of the dermatophyte, Trichophyton mentagrophytes.

    Science.gov (United States)

    Yamada, Tsuyoshi; Makimura, Koichi; Hisajima, Tatsuya; Ishihara, Yumiko; Umeda, Yoshiko; Abe, Shigeru

    2009-09-01

    The frequency of targeted gene disruption via homologous recombination is low in the clinically important dermatophyte, Trichophyton mentagrophytes. The Ku genes, Ku70 and Ku80, encode key components of the nonhomologous end-joining pathway involved in DNA double-strand break repair. Their deletion increases the homologous recombination frequency, facilitating targeted gene disruption. To improve the homologous recombination frequency in T. mentagrophytes, the Ku80 ortholog was inactivated. The nucleotide sequence of the Ku80 locus containing a 2788-bp ORF encoding a predicted product of 728 amino acids was identified, and designated as TmKu80. The predicted TmKu80 product showed a high degree of amino acid sequence similarity to known fungal Ku80 proteins. Ku80 disruption mutant strains of T. mentagrophytes were constructed by Agrobacterium tumefaciens-mediated genetic transformation. The average homologous recombination frequency was 73.3 +/- 25.2% for the areA/nit-2-like nitrogen regulatory gene (tnr) in Ku80(-) mutants, about 33-fold higher than that in wild-type controls. A high frequency (c. 67%) was also obtained for the Tri m4 gene encoding a putative serine protease. Ku80(-) mutant strains will be useful for large-scale reverse genetics studies of dermatophytes, including T. mentagrophytes, providing valuable information on the basic mechanisms of host invasion.

  4. Phosphorylation of Ku dictates DNA double-strand break (DSB) repair pathway choice in S phase.

    Science.gov (United States)

    Lee, Kyung-Jong; Saha, Janapriya; Sun, Jingxin; Fattah, Kazi R; Wang, Shu-Chi; Jakob, Burkhard; Chi, Linfeng; Wang, Shih-Ya; Taucher-Scholz, Gisela; Davis, Anthony J; Chen, David J

    2016-02-29

    Multiple DNA double-strand break (DSB) repair pathways are active in S phase of the cell cycle; however, DSBs are primarily repaired by homologous recombination (HR) in this cell cycle phase. As the non-homologous end-joining (NHEJ) factor, Ku70/80 (Ku), is quickly recruited to DSBs in S phase, we hypothesized that an orchestrated mechanism modulates pathway choice between HR and NHEJ via displacement of the Ku heterodimer from DSBs to allow HR. Here, we provide evidence that phosphorylation at a cluster of sites in the junction of the pillar and bridge regions of Ku70 mediates the dissociation of Ku from DSBs. Mimicking phosphorylation at these sites reduces Ku's affinity for DSB ends, suggesting that phosphorylation of Ku70 induces a conformational change responsible for the dissociation of the Ku heterodimer from DNA ends. Ablating phosphorylation of Ku70 leads to the sustained retention of Ku at DSBs, resulting in a significant decrease in DNA end resection and HR, specifically in S phase. This decrease in HR is specific as these phosphorylation sites are not required for NHEJ. Our results demonstrate that the phosphorylation-mediated dissociation of Ku70/80 from DSBs frees DNA ends, allowing the initiation of HR in S phase and providing a mechanism of DSB repair pathway choice in mammalian cells.

  5. Structural Basis for Recognition and Sequestration of UUUOH 3 ' Temini of Nascent RNA Polymerase III Transcripts by La, a Rheumatic Disease Autoantigen

    Energy Technology Data Exchange (ETDEWEB)

    Teplova,M.; Yuan, Y.; Phan, A.; Malinina, L.; Ilin, S.; Teplov, A.; Patel, D.

    2006-01-01

    The nuclear phosphoprotein La was identified as an autoantigen in patients with systemic lupus erythematosus and Sjogren's syndrome. La binds to and protects the UUUOH 3' terminii of nascent RNA polymerase III transcripts from exonuclease digestion. We report the 1.85 Angstroms crystal structure of the N-terminal domain of human La, consisting of La and RRM1 motifs, bound to r(U1-G2-C3-U4-G5-U6-U7-U8-U9OH). The U7-U8-U9OH 3' end, in a splayed-apart orientation, is sequestered within a basic and aromatic amino acid-lined cleft between the La and RRM1 motifs. The specificity-determining U8 residue bridges both motifs, in part through unprecedented targeting of the {beta} sheet edge, rather than the anticipated face, of the RRM1 motif. Our structural observations, supported by mutation studies of both La and RNA components, illustrate the principles behind RNA sequestration by a rheumatic disease autoantigen, whereby the UUUOH 3' ends of nascent RNA transcripts are protected during downstream processing and maturation events.

  6. Autoantigenic proteins that bind recombinogenic sequences in Epstein-Barr virus and cellular DNA.

    OpenAIRE

    1994-01-01

    We have identified conserved autoantigenic cellular proteins that bind to G-rich sequence motifs in recombinogenic regions of Epstein-Barr virus (EBV) DNA. This binding activity, called TRBP, recognizes the EBV terminal repeats, a locus responsible for interconversion of linear and circular EBV DNA. We found that TRBP also binds to EBV DNA sequences involved in deletion of EBNA2, a gene product required for immortalization. We show that TRBP binds sequences present in repetitive cellular DNA,...

  7. Heterogeneous nuclear ribonucleoproteins C1/C2 identified as autoantigens by biochemical and mass spectrometric methods

    DEFF Research Database (Denmark)

    Heegaard, N H; Larsen, Martin Røssel; Muncrief, T

    2000-01-01

    The antigenic specificity of an unusual antinuclear antibody pattern in three patient sera was identified after separating HeLa-cell nuclear extracts by two-dimensional (2D) gel electrophoresis and localizing the antigens by immunoblotting with patient serum. Protein spots were excised from the 2......-separation methods and mass-spectrometric peptide mapping in combination with database searches are powerful tools in the identification of novel autoantigen specificities....

  8. Aberrant Accumulation of the Diabetes Autoantigen GAD65 in Golgi Membranes in Conditions of ER Stress and Autoimmunity.

    Science.gov (United States)

    Phelps, Edward A; Cianciaruso, Chiara; Michael, Iacovos P; Pasquier, Miriella; Kanaani, Jamil; Nano, Rita; Lavallard, Vanessa; Billestrup, Nils; Hubbell, Jeffrey A; Baekkeskov, Steinunn

    2016-09-01

    Pancreatic islet β-cells are particularly susceptible to endoplasmic reticulum (ER) stress, which is implicated in β-cell dysfunction and loss during the pathogenesis of type 1 diabetes (T1D). The peripheral membrane protein GAD65 is an autoantigen in human T1D. GAD65 synthesizes γ-aminobutyric acid, an important autocrine and paracrine signaling molecule and a survival factor in islets. We show that ER stress in primary β-cells perturbs the palmitoylation cycle controlling GAD65 endomembrane distribution, resulting in aberrant accumulation of the palmitoylated form in trans-Golgi membranes. The palmitoylated form has heightened immunogenicity, exhibiting increased uptake by antigen-presenting cells and T-cell stimulation compared with the nonpalmitoylated form. Similar accumulation of GAD65 in Golgi membranes is observed in human β-cells in pancreatic sections from GAD65 autoantibody-positive individuals who have not yet progressed to clinical onset of T1D and from patients with T1D with residual β-cell mass and ongoing T-cell infiltration of islets. We propose that aberrant accumulation of immunogenic GAD65 in Golgi membranes facilitates inappropriate presentation to the immune system after release from stressed and/or damaged β-cells, triggering autoimmunity.

  9. Design of a Ku band miniature multiple beam klystron

    Energy Technology Data Exchange (ETDEWEB)

    Bandyopadhyay, Ayan Kumar, E-mail: ayan.bandyopadhyay@gmail.com; Pal, Debasish; Kant, Deepender [Microwave Tubes Division, CSIR-CEERI, Pilani, Rajasthan-333031 (India); Saini, Anil; Saha, Sukalyan; Joshi, Lalit Mohan

    2016-03-09

    The design of a miniature multiple beam klystron (MBK) working in the Ku-band frequency range is presented in this article. Starting from the main design parameters, design of the electron gun, the input and output couplers and radio frequency section (RF-section) are presented. The design methodology using state of the art commercial electromagnetic design tools, analytical formulae as well as noncommercial design tools are briefly presented in this article.

  10. Analysis of Fade Dynamic at Ku-Band in Malaysia

    OpenAIRE

    2014-01-01

    This work investigates fade dynamics of satellite communication systems in equatorial heavy rain region based on a one year of Ku-band propagation measurement campaign carried out in Universiti Teknologi Malaysia (UTM), Johor, Malaysia. First order statistics of rain attenuation are deduced and the results are found to be in good agreement with those obtained from other beacon measurements gathered within the same area (Kuala Lumpur). Moreover, the fade duration and slope statistics of the sa...

  11. Paradoxical effect of pertussis toxin on the delayed hypersensitivity response to autoantigens in mice.

    Directory of Open Access Journals (Sweden)

    Rajwahrdhan Yadav

    Full Text Available BACKGROUND: Pertussis toxin (PTX, an exotoxin of Bordetella pertussis, enhances the development of experimental autoimmune diseases such as experimental autoimmune uveitis (EAU and experimental autoimmune encephalomyelitis (EAE in rodent models. The mechanisms of the promotion of experimental autoimmune diseases by PTX may be based upon PTX-induced disruption of the blood eye/brain barriers facilitating the infiltration of inflammatory cells, the modulation of inflammatory cell migration and the enhancement of the activation of inflammatory cells. We hypothesized that the facilitation of experimental autoimmunity by PTX suggests that its influence on the in vivo immune response to auto-antigen may differ from its influence on non-self antigens. METHODOLOGY/PRINCIPAL FINDINGS: We have evaluated the effect of PTX on the simultaneous generation of delayed type hypersensitivity (DTH responses and autoimmune responses to uveitogenic interphotoreceptor retinoid binding protein peptide (IRBP161-180, encephalitogenic myelin oligodendrocyte glycoprotein peptide (MOG35-55 or ovalbumin (OVA. PTX injection of mice immunized to IRBP peptide161-180 led to (i the development of EAU as shown by histopathology of the retina, (ii pro-inflammatory cytokine production by splenocytes in response to IRBP peptide161-180, and (iii symptomatic EAE in mice immunized with encephalitogenic MOG peptide35-55. However, mice that received PTX had a reduced DTH response to IRBP161-180 peptide or MOG peptide35-55 when challenged distal to the site affected by autoreactive T cells. Moreover, footpad challenge with MOG35-55 peptide reduced EAE in mice immunized with MOG peptide. In contrast, the use of PTX when immunizing with OVA protein or an OVA immunogenic peptide did not affect the DTH response to OVA. CONCLUSIONS/SIGNIFICANCE: The results suggest that that the reduced DTH response in mice receiving PTX may be specific for autoantigens and autoantigen-reactive T cells are

  12. Interaction of caveolin-1 with Ku70 inhibits Bax-mediated apoptosis.

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    Huafei Zou

    Full Text Available Caveolin-1, the structural protein component of caveolae, acts as a scaffolding protein that functionally regulates signaling molecules. We show that knockdown of caveolin-1 protein expression enhances chemotherapeutic drug-induced apoptosis and inhibits long-term survival of colon cancer cells. In vitro studies demonstrate that caveolin-1 is a novel Ku70-binding protein, as shown by the binding of the scaffolding domain of caveolin-1 (amino acids 82-101 to the caveolin-binding domain (CBD of Ku70 (amino acids 471-478. Cell culture data show that caveolin-1 binds Ku70 after treatment with chemotherapeutic drugs. Mechanistically, we found that binding of caveolin-1 to Ku70 inhibits the chemotherapeutic drug-induced release of Bax from Ku70, activation of Bax, translocation of Bax to mitochondria and apoptosis. Potentiation of apoptosis by knockdown of caveolin-1 protein expression is greatly reduced in the absence of Bax expression. Finally, we found that overexpression of wild type Ku70, but not a mutant form of Ku70 that cannot bind to caveolin-1 (Ku70 Φ→A, limits the chemotherapeutic drug-induced Ku70/Bax dissociation and apoptosis. Thus, caveolin-1 acts as an anti-apoptotic protein in colon cancer cells by binding to Ku70 and inhibiting Bax-dependent cell death.

  13. Molecular and biochemical characterization of xrs mutants defective in Ku80.

    Science.gov (United States)

    Singleton, B K; Priestley, A; Steingrimsdottir, H; Gell, D; Blunt, T; Jackson, S P; Lehmann, A R; Jeggo, P A

    1997-01-01

    The gene product defective in radiosensitive CHO mutants belonging to ionizing radiation complementation group 5, which includes the extensively studied xrs mutants, has recently been identified as Ku80, a subunit of the Ku protein and a component of DNA-dependent protein kinase (DNA-PK). Several group 5 mutants, including xrs-5 and -6, lack double-stranded DNA end-binding and DNA-PK activities. In this study, we examined additional xrs mutants at the molecular and biochemical levels. All mutants examined have low or undetectable levels of Ku70 and Ku80 protein, end-binding, and DNA-PK activities. Only one mutant, xrs-6, has Ku80 transcript levels detectable by Northern hybridization, but Ku80 mRNA was detectable by reverse transcription-PCR in most other mutants. Two mutants, xrs-4 and -6, have altered Ku80 transcripts resulting from mutational changes in the genomic Ku80 sequence affecting RNA splicing, indicating that the defects in these mutants lie in the Ku80 gene rather than a gene controlling its expression. Neither of these two mutants has detectable wild-type Ku80 transcript. Since the mutation in both xrs-4 and xrs-6 cells results in severely truncated Ku80 protein, both are likely candidates to be null mutants. Azacytidine-induced revertants of xrs-4 and -6 carried both wild-type and mutant transcripts. The results with these revertants strongly support our model proposed earlier, that CHO-K1 cells carry a copy of the Ku80 gene (XRCC5) silenced by hypermethylation. Site-directed mutagenesis studies indicate that previously proposed ATP-binding and phosphorylation sites are not required for Ku80 activity, whereas N-terminal deletions of more than the first seven amino acids result in severe loss of activities. PMID:9032253

  14. CD8+ T cells specific for the islet autoantigen IGRP are restricted in their T cell receptor chain usage

    Science.gov (United States)

    Fuchs, Yannick F.; Eugster, Anne; Dietz, Sevina; Sebelefsky, Christian; Kühn, Denise; Wilhelm, Carmen; Lindner, Annett; Gavrisan, Anita; Knoop, Jan; Dahl, Andreas; Ziegler, Anette-G.; Bonifacio, Ezio

    2017-01-01

    CD8+ T cells directed against beta cell autoantigens are considered relevant for the pathogenesis of type 1 diabetes. Using single cell T cell receptor sequencing of CD8+ T cells specific for the IGRP265-273 epitope, we examined whether there was expansion of clonotypes and sharing of T cell receptor chains in autoreactive CD8+ T cell repertoires. HLA-A*0201 positive type 1 diabetes patients (n = 19) and controls (n = 18) were analysed. TCR α- and β-chain sequences of 418 patient-derived IGRP265-273-multimer+ CD8+ T cells representing 48 clonotypes were obtained. Expanded populations of IGRP265-273-specific CD8+ T cells with dominant clonotypes that had TCR α-chains shared across patients were observed. The SGGSNYKLTF motif corresponding to TRAJ53 was contained in 384 (91.9%) cells, and in 20 (41.7%) patient-derived clonotypes. TRAJ53 together with TRAV29/DV5 was found in 15 (31.3%) clonotypes. Using next generation TCR α-chain sequencing, we found enrichment of one of these TCR α-chains in the memory CD8+ T cells of patients as compared to healthy controls. CD8+ T cell clones bearing the enriched motifs mediated antigen-specific target cell lysis. We provide the first evidence for restriction of T cell receptor motifs in the alpha chain of human CD8+ T cells with specificity to a beta cell antigen. PMID:28300170

  15. A La autoantigen homologue is required for the internal ribosome entry site mediated translation of giardiavirus.

    Directory of Open Access Journals (Sweden)

    Srinivas Garlapati

    Full Text Available Translation of Giardiavirus (GLV mRNA is initiated at an internal ribosome entry site (IRES in the viral transcript. The IRES localizes to a downstream portion of 5' untranslated region (UTR and a part of the early downstream coding region of the transcript. Recent studies indicated that the IRES does not require a pre-initiation complex to initiate translation but may directly recruit the small ribosome subunit with the help of a number of trans-activating protein factors. A La autoantigen homologue in the viral host Giardia lamblia, GlLa, was proposed as one of the potential trans-activating factors based on its specific binding to GLV-IRES in vitro. In this study, we further elucidated the functional role of GlLa in GLV-IRES mediated translation in Giardia by knocking down GlLa with antisense morpholino oligo, which resulted in a reduction of GLV-IRES activity by 40%. An over-expression of GlLa in Giardia moderately stimulated GLV-IRES activity by 20%. A yeast inhibitory RNA (IRNA, known to bind mammalian and yeast La autoantigen and inhibit Poliovirus and Hepatitis C virus IRES activities in vitro and in vivo, was also found to bind to GlLa protein in vitro and inhibited GLV-IRES function in vivo. The C-terminal domain of La autoantigen interferes with the dimerization of La and inhibits its function. An over-expression of the C-terminal domain (200-348aa of GlLa in Giardia showed a dominant-negative effect on GLV-IRES activity, suggesting a potential inhibition of GlLa dimerization. HA tagged GlLa protein was detected mainly in the cytoplasm of Giardia, thus supporting a primary role of GlLa in translation initiation in Giardiavirus.

  16. Identification of novel autoantigen in the synovial fluid of rheumatoid arthritis patients using an immunoproteomics approach.

    Directory of Open Access Journals (Sweden)

    Sagarika Biswas

    Full Text Available Rheumatoid arthritis (RA is a chronic, autoimmune and inflammatory joint disease with a poorly understood etiology. Despite widespread diagnostic use of anti-citrullinated protein antibodies and rheumatoid factor proteins there is a strong demand for novel serological biomarkers to improve the diagnosis this disease. The present study was aimed to identify novel autoantigens involved in rheumatoid arthritis (RA pathogenesis through immune-proteomic strategy. Synovial fluid samples from clinically diagnosed RA patients were separated on two-dimensional gel electrophoresis (2-DE. Samples from patients with non-RA rheumatisms (osteoarthritis and trauma were used as controls. Immunoreactive proteins were spotted by Western blotting followed by identification through Q-TOF mass spectrometer analysis. Forty Western blots were generated using plasma from ten individual RA patients and 33 reactive spots were identified, 20 from the high molecular weight (HMW gel and 13 from the low molecular weight (LMW gel. Among the 33 common immunogenic spots, 18 distinct autoantigens were identified, out of which 14 are novel proteins in this context. Expression analysis of five important proteins, vimentin, gelsolin, alpha 2 HS glycoprotein (AHSG, glial fibrillary acidic protein (GFAP, and α1B-glycoprotein (A1BG by Western blot analysis using their specific antibodies revealed their higher expression in RA synovial fluid as compared to non-RA samples. Recombinantly expressed GFAP and A1BG protein were used to develop an in-house ELISA to quantify the amount of autoantibodies in the RA patients. RA patients revealed an increase in the expression of GFAP and A1BG in the plasma as compared to osteoarthritis patients. Therefore, GFAP and A1BG can be proposed as potential new autoantigens of diagnostic importance for RA subjects. Further characterization of these proteins in rheumatoid arthritis will be helpful in understanding the role of these proteins in the disease

  17. Posttranslational modification of HLA-DQ binding islet autoantigens in type 1 diabetes.

    Science.gov (United States)

    van Lummel, Menno; Duinkerken, Gaby; van Veelen, Peter A; de Ru, Arnoud; Cordfunke, Robert; Zaldumbide, Arnaud; Gomez-Touriño, Iria; Arif, Sefina; Peakman, Mark; Drijfhout, Jan W; Roep, Bart O

    2014-01-01

    Posttranslational modification (PTM) of islet autoantigens can cause lack of central tolerance in type 1 diabetes (T1D). Tissue transglutaminase (tTG), involved in PTM of gluten antigens in celiac disease, creates negatively charged peptides favored by T1D-predisposing HLA-DQ molecules, offering an attractive candidate modifying islet autoantigens in T1D. The highly predisposing HLA-DQ8cis/trans molecules share preferences for negatively charged peptides, as well as distinct peptide-binding characteristics that distinguish their peptide-binding repertoire. We screened islet autoantigens with the tTG substrate motif for candidate-modified epitopes binding to HLA-DQ8cis/trans and identified 31 candidate islet epitopes. Deamidation was confirmed for 28 peptides (90%). Two of these epitopes preferentially bound to HLA-DQ8cis and six to HLA-DQ8trans upon deamidation, whereas all other peptides bound equally to HLA-DQ8cis/trans. HLA-DQ8cis-restricted T cells from a new-onset T1D patient could only be generated against a deamidated proinsulin peptide, but cross-reacted with native proinsulin peptide upon restimulation. The rate of T-cell autoreactivity in recent-onset T1D patients extended from 42% to native insulin to 68% adding responses to modified proinsulin, versus 20% and 37% respectively, in healthy donors. Most patients responded by interferon-γ, whereas most healthy donors produced interleukin-10 only. Thus, T-cell autoreactivity exists to modified islet epitopes that differs in quality and quantity between patients and healthy donors.

  18. Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus.

    Science.gov (United States)

    Haddon, D James; Diep, Vivian K; Price, Jordan V; Limb, Cindy; Utz, Paul J; Balboni, Imelda

    2015-06-17

    Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early-stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n = 45) to healthy controls (n = 17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n = 23) and without significant renal involvement (n = 18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n = 23) and longitudinal samples (88 patient visits) to test its accuracy. Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B cell-activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV and X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative

  19. Induction of tolerance with intranasal administration of human cartilage gp-39 in DBA/1 mice - Amelioration of clinical, histologic, and radiologic signs of type II collagen-induced arthritis

    NARCIS (Netherlands)

    Joosten, LAB; Coenen-de Roo, CJJ; Helsen, MMA; Lubberts, E; Boots, AMH; van den Berg, WB; Miltenburg, AMM

    2000-01-01

    Objective. Human cartilage glycoprotein 39 (HC gp-39) was recently identified as a candidate autoantigen in the pathogenesis of rheumatoid arthritis, In the present studies, we investigated the capacity of HC gp-39 to interfere in clinical disease induced by an unrelated autoantigen, type II collage

  20. Design of a Ku band Instrumentation Synthetic Aperture Radar System

    Science.gov (United States)

    2015-10-14

    small form-factor Ku band Synthetic Aperture Radar (SAR) for use on aerial drones . Group 105 have also been using this radar as an instrumentation...frequency of the LFM chirp would be over the Nyquist frequency. To solve this problem , the bandwidth of the LFM chirp was halved to 275 MHz. The...to 40 m/s based off of the speed of a predator drone . Parameter Value Speed of Light 299720000 m/s Center Frequency 16.75 GHz Wavelength 0.0179 m

  1. Identification of Autoantigen Epitopes in Alopecia Areata.

    Science.gov (United States)

    Wang, Eddy H C; Yu, Mei; Breitkopf, Trisia; Akhoundsadegh, Noushin; Wang, Xiaojie; Shi, Feng-Tao; Leung, Gigi; Dutz, Jan P; Shapiro, Jerry; McElwee, Kevin J

    2016-08-01

    Alopecia areata (AA) is believed to be a cell-mediated autoimmune hair loss disease. Both CD4 and cytotoxic CD8 T cells (CTLs) are important for the onset and progression of AA. Hair follicle (HF) keratinocyte and/or melanocyte antigen epitopes are suspected potential targets of autoreactive CTLs, but the specific epitopes have not yet been identified. We investigated the potential for a panel of known epitopes, expressed by HF keratinocytes and melanocytes, to induce activation of CTL populations in peripheral blood mononuclear cells. Specific synthetic epitopes derived from HF antigens trichohyalin and tyrosinase-related protein-2 induced significantly higher frequencies of response in AA CTLs compared with healthy controls (IFN-gamma secretion). Apoptosis assays revealed conditioned media from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides elevated the expression of apoptosis markers in primary HF keratinocytes. A cytokine array revealed higher expression of IL-13 and chemokine ligand 5 (CCL5, RANTES) from AA peripheral blood mononuclear cells stimulated with trichohyalin peptides compared with controls. The data indicate that AA affected subjects present with an increased frequency of CTLs responsive to epitopes originating from keratinocytes and melanocytes; the activated CTLs secreted soluble factors that induced apoptosis in HF keratinocytes. Potentially, CTL response to self-antigen epitopes, particularly trichohyalin epitopes, could be a prognostic marker for human AA.

  2. 葡萄膜炎自身抗原表位的研究%Studies on autoantigenic epitopes involving in the development of uveitis

    Institute of Scientific and Technical Information of China (English)

    赵长霖; 杨培增

    2008-01-01

    It has been proposed that a few kinds of autoantigens imitate the development of autoimmune uveitis while the immunodominant epitopes of these antigens have not been identified.Researches on retinal S-antigen and interphotoreceptor retinoid-binding protein as well as tyrosinase-related protein epitopes mapping have shown that each autoantigen contains several immunopathogenic epitopes and immunogenic epitopes and that the immunopathogenic sites ale not coincident with the immunogenic epitopes.The reactivity of peripheral blood mononucleal cells from uveitis patients against each autoantigenic epitopes displays high heterogeneity.Epitopes spreading phenomenon has been disclosed in human uveifis study and reinforced in animal experiments.Study on this epitope spreading may contribute to our understanding of immune tolerance induced by different epitopes in the treatment of autoimmune disease including uveifis.%多种抗原参与自身免疫性葡萄膜炎的发生发展,但是这些抗原的免疫优势表位尚不明确.针对视网膜S抗原等葡萄膜炎自身抗原免疫表位的研究显示,每种抗原蛋白均存在多个可诱导易感动物葡萄膜炎发作的致病位点,每种抗原均存在多个可诱导葡萄膜炎患者产生体外细胞免疫反应的免疫原性表位,同种抗原的致病表位和免疫原性表位不完全一致.葡萄膜炎患者对于各抗原表位肽的反应性显示出高度异质性,表现为不同患者对不同肽发生反应和同一例患者在不同时期对不同肽发生反应.由此,提出了葡萄膜炎表位扩展现象,并利用动物实验得以证实.表位扩展可能是自身免疫反应的防御现象,但是自身免疫反应的多样化同时又对抗原特异性耐受疗法提出了挑战.

  3. The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency.

    Directory of Open Access Journals (Sweden)

    Erwin Reiling

    Full Text Available Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs-/- mice. However, these observations are based on independent studies with varying genetic backgrounds. Here, we generated ku80-/-, dna-pkcs-/- and double knock out mice in a C57Bl6/J*FVB F1 hybrid background and compared their lifespan, end of life pathology and mutation frequency in liver and spleen using a lacZ reporter. Our data confirm that inactivation of Ku80 and DNA-PKCS causes reduced lifespan and bodyweights, which is most severe in ku80-/- mice. All mutant mice exhibited a strong increase in lymphoma incidence as well as other aging-related pathology (skin epidermal and adnexal atrophy, trabacular bone reduction, kidney tubular anisokaryosis, and cortical and medullar atrophy and severe lymphoid depletion. LacZ mutation frequency analysis did not show strong differences in mutation frequencies between knock out and wild type mice. The ku80-/- mice had the most severe phenotype and the Ku80-mutation was dominant over the DNA-PKCS-mutation. Presumably, the more severe degenerative effect of Ku80 inactivation on lifespan compared to DNA-PKCS inactivation is caused by additional functions of Ku80 or activity of free Ku70 since both Ku80 and DNA-PKCS are essential for NHEJ.

  4. The clinical significance of posttranslational modification of autoantigens.

    Science.gov (United States)

    Zavala-Cerna, Maria G; Martínez-García, Erika A; Torres-Bugarín, Olivia; Rubio-Jurado, Benjamín; Riebeling, Carlos; Nava, Arnulfo

    2014-08-01

    Posttranslational modifications (PTMs) are defined as covalent modifications occurring in a specific protein amino acid in a time- and signal-dependent manner. Under physiological conditions, proteins are posttranslationally modified to carry out a large number of cellular events from cell signaling to DNA replication. However, an absence, deficiency, or excess in PTMs of a given protein can evolve into a target to trigger autoimmunity, since PTMs arise in the periphery and may not occur in the thymus; hence, proteins with PTMs never tolerize developing thymocytes. Consequently, when PTMs arise during cellular responses, such as inflammation, these modified self-antigens can be taken up and processed by the antigen-presenting cells (APCs). Autoreactive T cells, which recognize peptides presented by APCs, can then infiltrate into host tissue where the modified antigen serves to amplify the autoimmune response, eventually leading to autoimmune pathology. Furthermore, a PTM occurring in an amino acid residue can induce changes in the net charge of the protein, leading to conformational modifications in the tertiary and quaternary structure of the protein, especially interaction with human leukocyte antigen (HLA) molecules. Molecular mimicry (MM) was until now the prevailing hypothesis explaining generation of autoimmunity; nevertheless, experimental animal models need inflammation via infection or other immunogens to ensure autoimmunity; MM alone is not sufficient to develop autoimmunity. PTMs could arise as an additive factor to MM, which is required to start an autoimmune response. PTMs have been found to be present in different pathologic conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, and primary biliary cirrhosis. The aim of the present review is to expose protein posttranslational modifications and the evidence suggesting their role in the generation of autoimmunity.

  5. Enhanced International Space Station Ku-Band Telemetry Service

    Science.gov (United States)

    Cecil, Andrew J.; Pitts, R. Lee; Welch, Steven J.; Bryan, Jason D.

    2014-01-01

    The International Space Station (ISS) is in an operational configuration. To fully utilize the ISS and take advantage of the modern protocols and updated Ku-band access, the Huntsville Operations Support Center (HOSC) has designed an approach to extend the Kuband forward link access for payload investigators to their on-orbit payloads. This dramatically increases the ground to ISS communications for those users. This access also enables the ISS flight controllers operating in the Payload Operations and Integration Center to have more direct control over the systems they are responsible for managing and operating. To extend the Ku-band forward link to the payload user community the development of a new command server is necessary. The HOSC subsystems were updated to process the Internet Protocol Encapsulated packets, enable users to use the service based on their approved services, and perform network address translation to insure that the packets are forwarded from the user to the correct payload repeating that process in reverse from ISS to the payload user. This paper presents the architecture, implementation, and lessons learned. This will include the integration of COTS hardware and software as well as how the device is incorporated into the operational mission of the ISS. Thus, this paper also discusses how this technology can be applicable to payload users of the ISS.

  6. T2Ku: Building a Semantic Wiki of Mathematics

    CERN Document Server

    Pan, Minqi

    2012-01-01

    We introduce T2Ku, an open source project that aims at building a semantic wiki of mathematics featuring automated reasoning(AR) techniques. We want to utilize AR techniques in a way that truly helps mathematical researchers solve problems in the real world, instead of building another ambitious yet useless system. By setting this as our objective, we exploit pragmatic design decisions that have proven feasible in other projects, while still employs a loosely coupled architecture to allow better inference programs to be integrated in the future. In this paper, we state the motivations and examine state-of-the-art systems, why we are not satisfied with those systems and how we are going to improve. We then describe our architecture and the way we implemented the system. We present examples showing how to use its facilities. T2Ku is an on-going project. We conclude this paper by summarizing the development progress and encouraging the reader to join the project.

  7. Deacetylation of Ku70 by SIRT6 attenuates Bax-mediated apoptosis in hepatocellular carcinoma.

    Science.gov (United States)

    Tao, Na-Na; Ren, Ji-Hua; Tang, Hua; Ran, Long-Kuan; Zhou, Hong-Zhong; Liu, Bo; Huang, Ai-Long; Chen, Juan

    2017-04-15

    SIRT6 is a class III histone deacetylase that has been implicated in HCC development. We previously reported that SIRT6 potentiated apoptosis evasion in hepatocellular carcinoma by inhibiting both Bax expression and mitochondrial translocalization. However, the mechanism underlying SIRT6-mediated inhibition of Bax mitochondrial localization remains elusive. In this study, we found that although SIRT6 had no effect on the expression level of Ku70, SIRT6 could interact with Ku70 and deacetylate it. The increased acetylation of Ku70 in SIRT6-depleted cells disrupt its interaction with Bax, which finally resulted in Bax mitochondrial translocalization. Furthermore, lysine K542 on Ku70 was the target for deacetylation by SIRT6. Ku70(K542Q) mutation abolished suppression of association between Ku70 and Bax and caused redistribution of Bax to the cytosol in SIRT6-depleted cells. Finally, Ku70(K542Q) mutation could reversed the inhibition of growth and apoptosis promotion mediated by SIRT6 silencing. Together, our findings revealed SIRT6 could block the mitochondrial translocation of Bax and decrease the apoptotic ratio of HCC cells by deacetylation of Ku70. SIRT6 may serve as a promising target for developing targeted therapies for HCC in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Lethality in PARP-1/Ku80 double mutant mice reveals physiologicalsynergy during early embryogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Henrie, Melinda S.; Kurimasa, Akihiro; Burma, Sandeep; Menissier-de Murcia, Josiane; de Murcia, Gilbert; Li, Gloria C.; Chen,David J.

    2002-09-24

    Ku is an abundant heterodimeric nuclear protein, consisting of 70-kDa and 86-kDa tightly associated subunits that comprise the DNA binding component of DNA-dependent protein kinase. Poly(ADP)ribose polymerase-1 (PARP-1) is a 113-kDa protein that catalyzes the synthesis of poly(ADP-ribose) on target proteins. Both Ku and PARP-1 recognize and bind to DNA ends. Ku functions in the non-homologous end joining (NHEJ) repair pathway whereas PARP-1 functions in the single strand break repair and base excision repair (BER) pathways. Recent studies have revealed that PARP-1 and Ku80 interact in vitro. To determine whether the association of PARP-1 and Ku80 has any physiological significance or synergistic function in vivo, mice lacking both PARP-1 and Ku80 were generated. The resulting offspring died during embryonic development displaying abnormalities around the gastrulation stage. In addition, PARP-1-/-Ku80-/- cultured blastocysts had an increased level of apoptosis. These data suggest that the functions of both Ku80 and PARP-1 are essential for normal embryogenesis and that a loss of genomic integrity leading to cell death through apoptosis is likely the cause of the embryonic lethality observed in these mice.

  9. The progeroid phenotype of Ku80 deficiency is dominant over DNA-PKCS deficiency

    NARCIS (Netherlands)

    Reiling, Erwin; Dollé, Martijn E T; Youssef, Sameh A; Lee, Moonsook; Nagarajah, Bhawani; Roodbergen, Marianne; de With, Piet; de Bruin, Alain; Hoeijmakers, Jan H; Vijg, Jan; van Steeg, Harry; Hasty, Paul

    2014-01-01

    Ku80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs-/- mice. However, these observations are based on independent

  10. The progeroid phenotype of Ku80 deficiency Is dominant over DNA-PK CS deficiency

    NARCIS (Netherlands)

    E. Reiling (Erwin); M.E.T. Dollé (Martijn); A.R. Youssef; M. Lee (Moonsook); B. Nagarajah (Bhawani); M. Roodbergen (Marianne); P. de With (Piet); A. de Bruin (Alain); J.H.J. Hoeijmakers (Jan); J. Vijg (Jan); H. van Steeg (Harry); P. Hasty (Paul)

    2014-01-01

    textabstractKu80 and DNA-PKCS are both involved in the repair of double strand DNA breaks via the nonhomologous end joining (NHEJ) pathway. While ku80-/- mice exhibit a severely reduced lifespan and size, this phenotype is less pronounced in dna-pkcs -/- mice. However, these observations are based

  11. Memories of the Ku Klux Klan Honorary Society at the University of Wisconsin.

    Science.gov (United States)

    Messer-Kruse, Timothy

    1999-01-01

    Recounts the history of the Ku Klux Klan Honorary Junior Society at the University of Wisconsin from 1919 to 1926. Although not tied to the national Ku Klux Klan, this honorary group became a powerful intrafraternity society that served as a barometer of the cultural and ideological climate of the university. (SLD)

  12. Jauno vecāku apmierinātības ar attiecībām saistība ar vecāku stresu.

    OpenAIRE

    Strangate, Ilze

    2011-01-01

    Bakalaura darba mērķis ir izpētīt apmierinātības ar pāra attiecībām saistību ar vecāku stresu, un atbildēt uz jautājumiem - Vai pastāv saistība starp jauno vecāku apmierinātību ar attiecībām un vecāku stresu? Vai pastāv apmierinātības ar attiecībām un vecāku stresa saistības atšķirības jaunajām mātēm un tēviem? Vai atšķiras apmierinātība ar attiecībām un vecāku stress jaunajiem vecākiem ar dažādu kopdzīves veidu? Vai kopdzīves ilgums ir saistīts ar apmierinātību ar attiecībām un vecāku stresu...

  13. Transient systemic inflammation does not alter the induction of tolerance to gastric autoantigens by migratory dendritic cells.

    Science.gov (United States)

    Bourges, Dorothée; Ross, Ellen M; Allen, Stacey; Read, Simon; Houghton, Fiona J; Bedoui, Sammy; Boon, Louis; Gleeson, Paul A; van Driel, Ian R

    2014-06-01

    It has been proposed that activation of dendritic cells (DCs) presenting self-antigens during inflammation may lead to activation of autoreactive T cells and the development of autoimmunity. To test this hypothesis, we examined the presentation of the autoantigen recognized in autoimmune gastritis, gastric H(+)/K(+) ATPase, which is naturally expressed in the stomach and is constitutively presented in the stomach-draining lymph nodes. Systemic administration to mice of the TLR9 agonist CpG DNA, agonist anti-CD40 Ab, or TLR4 agonist LPS all failed to abrogate the process of peripheral clonal deletion of H(+)/K(+) ATPase-specific CD4 T cells or promote the development of autoimmune gastritis. We demonstrated that migratory DCs from the stomach-draining lymph nodes are the only DC subset capable of constitutively presenting the endogenous gastric H(+)/K(+) ATPase autoantigen in its normal physiological context. Analysis of costimulatory molecules indicated that, relative to resident DCs, migratory DCs displayed a partially activated phenotype in the steady state. Furthermore, migratory DCs were refractory to stimulation by transient exposure to TLR agonists, as they failed to upregulate costimulatory molecules, secrete significant amounts of inflammatory cytokines, or induce differentiation of effector T cells. Together, these data show that transient systemic inflammation failed to break tolerance to the gastric autoantigen, as migratory DCs presenting the gastric autoantigen remain tolerogenic under such conditions, demonstrating the robust nature of peripheral tolerance.

  14. The orthologue of Sjogren's syndrome nuclear autoantigen 1 (SSNA1 in Trypanosoma brucei is an immunogenic self-assembling molecule.

    Directory of Open Access Journals (Sweden)

    Helen P Price

    Full Text Available Primary Sjögren's Syndrome (PSS is a highly prevalent autoimmune disease, typically manifesting as lymphocytic infiltration of the exocrine glands leading to chronically impaired lacrimal and salivary secretion. Sjögren's Syndrome nuclear autoantigen 1 (SSNA1 or NA14 is a major specific target for autoantibodies in PSS but the precise function and clinical relevance of this protein are largely unknown. Orthologues of the gene are absent from many of the commonly used model organisms but are present in Chlamyodomonas reinhardtii (in which it has been termed DIP13 and most protozoa. We report the functional characterisation of the orthologue of SSNA1 in the kinetoplastid parasite, Trypanosoma brucei. Both TbDIP13 and human SSNA1 are small coiled-coil proteins which are predicted to be remote homologues of the actin-binding protein tropomyosin. We use comparative proteomic methods to identify potential interacting partners of TbDIP13. We also show evidence that TbDIP13 is able to self-assemble into fibril-like structures both in vitro and in vivo, a property which may contribute to its immunogenicity. Endogenous TbDIP13 partially co-localises with acetylated α-tubulin in the insect procyclic stage of the parasite. However, deletion of the DIP13 gene in cultured bloodstream and procyclic stages of T. brucei has little effect on parasite growth or morphology, indicating either a degree of functional redundancy or a function in an alternative stage of the parasite life cycle.

  15. KuDGR- Dual Gridded Carbon Fiber Reinforced Plastic Reflector

    Science.gov (United States)

    Ihle, Alexander; Reichmann, O.; Lori, M.; Nathrath, N.; Pereira, C.; Linke, S.; Rinous, P.

    2014-06-01

    In the frame of an ESA-funded TRP activity HPS GmbH, together with INVENT GmbH and INEGI, has developed an advanced concept for dual gridded reflectors. The target frequency band is the Ku-band requiring high in-orbit thermo-elastic stability. It is a follow-on of the previous KaDGR [1] activity. The concept concerns the polarisation grid of the front and rear reflector. The grids are connected by a full CFRP monolithic peripheral ring. The demonstrator has an overall diameter of 1.4 x 1.2 m and a weight of only 4.23 kg. The design of this concept allows for smaller and larger reflectors.In the following we will present the results of the different development steps and current status of the TRP activity.

  16. Ku Band Rotary Joint Design for SNG Vehicles

    Directory of Open Access Journals (Sweden)

    H. Torpi

    2015-12-01

    Full Text Available A wideband I-type rectangular waveguide rotary joint (RJ is designed, simulated and built. It has an excellent performance over the whole Ku Band (10.7-14.5 GHz where the return loss is less than -23 dB at its highest and the insertion loss is below 0.4 dB. The rotary joint is specifically designed for satellite news gathering (SNG vehicles providing elevation and azimuthal movement to the antenna and matching polarization when it is needed at the feed. It can also be used in other high power microwave applications,where rotation ability of the antenna is a must during the transmission such as radars.

  17. Novel Ku Band Reflectarray Antenna for Satellite Communication

    Directory of Open Access Journals (Sweden)

    Sridhar Bilvam

    2014-04-01

    Full Text Available This study focuses on the design and analysis of Ku band reflectarray antenna using a novel crossed dumbbell (clover patch unit cell. The reflectarray is proposed for application in satellite communication more specifically for Satellite newsgathering (12.5-13.75 GHz. The clover shaped unit cell is designed for 13.07 GHz and the suitability of the unit cell is validated using the phase characteristics analysis. The effect of the elements on the performance represented by the range of the reflection phase is of prime importance. From the observation, Clover unit cell has large phase variation compared to minkowski and koch unit cells. Therefore, the main purpose of this study is to investigate and validate the novel unit cell with a wide phase characteristics and the reflectarray constructed.

  18. Initial assessment of an airborne Ku-band polarimetric SAR.

    Energy Technology Data Exchange (ETDEWEB)

    Raynal, Ann Marie; Doerry, Armin Walter

    2013-02-01

    Polarimetric synthetic aperture radar (SAR) has been used for a variety of dual-use research applications since the 1940s. By measuring the direction of the electric field vector from radar echoes, polarimetry may enhance an analysts understanding of scattering effects for both earth monitoring and tactical surveillance missions. Polarimetry may provide insight into surface types, materials, or orientations for natural and man-made targets. Polarimetric measurements may also be used to enhance the contrast between scattering surfaces such as man-made objects and their surroundings. This report represents an initial assessment of the utility of, and applications for, polarimetric SAR at Ku-band for airborne or unmanned aerial systems.

  19. [The effect of long-term exposure to low doses of endocrine disruptor ddt on serum levels of thyroid protein autoantigenes and antithyroid autoantibodies].

    Science.gov (United States)

    Yaglova, N V; Yaglov, V V

    2016-01-01

    Changes in secretion of thyroid autoantigenes and production of antithyroid autoantibodies after long-term exposure to low doses of DDT were studied. Changes in serum levels of antithyroid peroxidase antibodies and thyroid peroxidase, attributed to disruption of thyroxine production by DDT were found. Long-term exposure of rats to low doses of DDT revealed no specific impact on serum autoantibodies to all thyroid autoantigenes studied. The increase of the ratio of autoantibody/autoantigen for thyroid peroxidase and thyroglobulin was rather small and thus could not be considered as a significant symptom of thyroid autoimmunity.

  20. Asialoglycoprotein receptor (ASGPR) as target autoantigen in liver autoimmunity: lost and found.

    Science.gov (United States)

    Rigopoulou, Eirini I; Roggenbuck, Dirk; Smyk, Daniel S; Liaskos, Christos; Mytilinaiou, Maria G; Feist, Eugen; Conrad, Karsten; Bogdanos, Dimitrios P

    2012-12-01

    Asialoglycoprotein receptor (ASGPR) has attracted the attention of liver immunologists for many years. This liver-specific lectin was found to be a major B and T cell autoantigenic target in patients with autoimmune liver diseases, and in particular in autoimmune hepatitis (AIH). This review discusses the biological significance of ASGPR and its relevance to the pathogenesis of autoimmune and virus-triggered liver diseases. We also discuss emerging data on the diagnostic and clinical relevance of anti-ASGPR antibodies in light of recent reports based on commercially available anti-ASGPR enzyme-linked immunosorbent assays. Finally, we critically revisit the data reporting on disease-specific cellular immune responses against ASGPR and their relevance in relation to the pathogenesis of AIH.

  1. Structural and Biochemical Basis for Misfolded RNA Recognition by the Ro Autoantigen

    Energy Technology Data Exchange (ETDEWEB)

    Fuchs,G.; Stein, A.; Fu, C.; Reinisch, K.; Wolin, S.

    2006-01-01

    The Ro autoantigen is ring-shaped, binds misfolded noncoding RNAs and is proposed to function in quality control. Here we determine how Ro interacts with misfolded RNAs. Binding of Ro to misfolded precursor (pre)-5S ribosomal RNA requires a single-stranded 3 end and helical elements. As mutating most sequences of the helices and tail results in modest decreases in binding, Ro may be able to associate with a range of RNAs. Ro binds several other RNAs that contain single-stranded tails. A crystal structure of Ro bound to a misfolded pre-5S rRNA fragment reveals that the tail inserts into the cavity, while a helix binds on the surface. Most contacts of Ro with the helix are to the backbone. Mutagenesis reveals that Ro has an extensive RNA-binding surface. We propose that Ro uses this surface to scavenge RNAs that fail to bind their specific RNA-binding proteins.

  2. Multiple sclerosis autoantigen myelin basic protein escapes control by ubiquitination during proteasomal degradation.

    Science.gov (United States)

    Belogurov, Alexey; Kudriaeva, Anna; Kuzina, Ekaterina; Smirnov, Ivan; Bobik, Tatyana; Ponomarenko, Natalia; Kravtsova-Ivantsiv, Yelena; Ciechanover, Aaron; Gabibov, Alexander

    2014-06-20

    The vast majority of cellular proteins are degraded by the 26S proteasome after their ubiquitination. Here, we report that the major component of the myelin multilayered membrane sheath, myelin basic protein (MBP), is hydrolyzed by the 26S proteasome in a ubiquitin-independent manner both in vitro and in mammalian cells. As a proteasomal substrate, MBP reveals a distinct and physiologically relevant concentration range for ubiquitin-independent proteolysis. Enzymatic deimination prevents hydrolysis of MBP by the proteasome, suggesting that an abnormally basic charge contributes to its susceptibility toward proteasome-mediated degradation. To our knowledge, our data reveal the first case of a pathophysiologically important autoantigen as a ubiquitin-independent substrate of the 26S proteasome.

  3. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Honglin Zhu

    2015-08-01

    Full Text Available Systemic lupus erythematosus (SLE is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins, cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.

  4. Re-exposure to beta cell autoantigens in pancreatic allograft recipients with preexisting beta cell autoantibodies.

    Science.gov (United States)

    Mujtaba, Muhammad Ahmad; Fridell, Jonathan; Book, Benita; Faiz, Sara; Sharfuddin, Asif; Wiebke, Eric; Rigby, Mark; Taber, Tim

    2015-11-01

    Re-exposure to beta cell autoantigens and its relevance in the presence of donor-specific antibodies (DSA) in pancreatic allograft recipients is not well known. Thirty-three patients requiring a pancreas transplant were enrolled in an IRB approved study. They underwent prospective monitoring for DSA and beta cell autoantibody (BCAA) levels to GAD65, insulinoma-associated antigen 2 (IA-2), insulin (micro-IAA [mIAA]), and islet-specific zinc transporter isoform-8 (ZnT8). Twenty-five (75.7%) had pre-transplant BCAA. Twenty had a single antibody (mIAA n = 15, GAD65 n = 5); five had two or more BCAA (GAD65 + mIAA n = 2, GAD65 + mIAA+IA-2 n = 2, GA65 + mIAA+IA-2 + ZnT8 = 1). No changes in GAD65 (p > 0.29), IA-2 (>0.16), and ZnT8 (p > 0.07) were observed between pre-transplant and post-transplant at 6 or 12 months. A decrease in mIAA from pre- to post-6 months (p BCAA was observed at one yr. Seven (21.0%) developed de novo DSA. The incidence of DSA was 24% in patients with BCAA vs. 25% in patients without BCAA (p = 0.69). Pancreatic allograft function of patients with vs. without BCAA, and with and without BCAA + DSA was comparable until last follow-up (three yr). Re-exposure to beta cell autoantigens by pancreas transplant may not lead to increased levels or development of new BCAA or pancreatic allograft dysfunction.

  5. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Zhu, Honglin; Luo, Hui; Yan, Mei; Zuo, Xiaoxia; Li, Quan-Zhen

    2015-08-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.

  6. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer.

    Science.gov (United States)

    Shukla, Sanjeev; Fu, Pingfu; Gupta, Sanjay

    2014-05-01

    Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70-Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy.

  7. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70–Bax interaction in prostate cancer

    Science.gov (United States)

    Shukla, Sanjeev; Fu, Pingfu; Gupta, Sanjay

    2014-01-01

    Dysfunction of the apoptotic pathway in prostate cancer cells confers apoptosis resistance towards various therapies. A novel strategy to overcome resistance is to directly target the apoptotic pathway in cancer cells. Apigenin, an anticancer agent, selectively toxic to cancer cells induces cell cycle arrest and apoptosis through mechanisms which are not fully explored. In the present study we provide novel insight into the mechanisms of apoptosis induction by apigenin. Treatment of androgen-refractory human prostate cancer PC-3 and DU145 cells with apigenin resulted in dose-dependent suppression of XIAP, c-IAP1, c-IAP2 and survivin protein levels. Apigenin treatment resulted in significant decrease in cell viability and apoptosis induction with the increase of cytochrome C in time-dependent manner. These effects of apigenin were accompanied by decrease in Bcl-xL and Bcl-2 and increase in the active form of Bax protein. The apigenin-mediated increase in Bax was due to dissociation of Bax from Ku70 which is essential for apoptotic activity of Bax. Apigenin treatment resulted in the inhibition of class I histone deacetylases and HDAC1 protein expression, thereby increasing the acetylation of Ku70 and the dissociation of Bax resulting in apoptosis of cancer cells. Furthermore, apigenin significantly reduced HDAC1 occupancy at the XIAP promoter, suggesting that histone deacetylation might be critical for XIAP downregulation. These results suggest that apigenin targets inhibitor of apoptosis proteins and Ku70–Bax interaction in the induction of apoptosis in prostate cancer cells and in athymic nude mouse xenograft model endorsing its in vivo efficacy. PMID:24563225

  8. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Science.gov (United States)

    Shawi, May; Chu, Tsz Wai; Martinez-Marignac, Veronica; Yu, Y; Gryaznov, Sergei M; Johnston, James B; Lees-Miller, Susan P; Assouline, Sarit E; Autexier, Chantal; Aloyz, Raquel

    2013-01-01

    We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR), can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1) if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2) the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo) on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku) to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  9. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Directory of Open Access Journals (Sweden)

    May Shawi

    Full Text Available We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR, can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1 if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2 the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  10. Ku/Ka/W-band Antenna for Electronically-Scanned Cloud and Precipitation Radar Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Development of the key antenna technologies for Tri-band (Ku/Ka/W), scanning precipitation and cloud radar is a required milestone in preparation for one or more...

  11. 50 ku keratin-like protein and β-microtublin coexist in higher plant cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    IF-like proteins have been obtained from suspension cells of Nicotiana tabacum by selective extraction. Western blot analysis shows that the major components of IF-like proteins are 6 keratin-like proteins of 64, 58, 55, 54, 50 and 45 ku. Specially the 50 ku protein also reacts with polyantibody against microtublin. Two-dimensional gel electrophoresis shows that the 50 ku protein is composed of two different proteins and their amino acid sequences have been determined. Part of the sequence of one protein is identical to that of -microtublin and the other protein's sequence has no significant homologue, which should be a new sequence-unknown protein. These results suggest that 50 ku keratin-like protein and -microtublin coexist in higher plant cells, and that may lead to the phenomenon of co-distribution of IF and microtuble in plant cells.

  12. Unstabilized DNA breaks in HTLV-1 Tax expressing cells correlate with functional targeting of Ku80, not PKcs, XRCC4, or H2AX

    Directory of Open Access Journals (Sweden)

    Majone Franca

    2012-04-01

    Full Text Available Abstract Background Expression of the human T-cell leukemia virus type 1 (HTLV-1 Tax oncoprotein rapidily induces a significant increase of micronuclei (MN and unstabilized DNA breaks in cells. Unstabilized DNA breaks can have free 3′-OH ends accessible to in situ addition of digoxygenin (DIG-labeled dUTP using terminal deoxynucleotidyl transferase. In the present work, we used a GFP-Tax (green fluorescent protein plasmid, which produces a functionally active GFP-tagged Tax protein, to detect the cellular target(s for Tax which might mechanistically explain the clastogenic phenomenon. We examined the induction of MN and unstabilized DNA breaks in wild type cells and cells individually knocked out for Ku80, PKcs, XRCC4, and H2AX proteins. We also assessed in the same cells, the signal strengths produced by DIG-dUTP incorporation at the unstable DNA breaks in the presence and absence of Tax. Results Cells mutated for PKcs, XRCC4 and H2AX showed increased frequency of MN and unstabilized DNA breaks in response to the expression of Tax, while cells genetically mutated for Ku80 were refractory to Tax’s induction of these cytogenetic effects. Moreover, by measuring the size of DIG-dUTP incorporation signal, which indicates the extent of unstable DNA ends, we found that Tax induces larger signals than those in control cells. However, in xrs-6 cells deficient for Ku80, this Tax effect was not seen. Conclusions The data here demonstrate that clastogenic DNA damage in Tax expressing cells is explained by Tax targeting of Ku80, but not PKcs, XRCC4 or H2AX, which are all proteins directly or indirectly related to the non-homologous end-joining (NHEJ repair system. Of note, the Ku80 protein plays an important role at the initial stage of the NHEJ repair system, protecting and stabilizing DNA-breaks. Accordingly, HTLV-1 Tax is shown to interfere with a normal cellular protective mechanism for stabilizing DNA breaks. These DNA breaks, unprotected by Ku80

  13. Desain dan Implementasi Antena Mikrostrip VSAT Bergerak pada Frekuensi Downlink Ku Band

    Directory of Open Access Journals (Sweden)

    HANNY MADIAWATI

    2016-08-01

    Full Text Available ABSTRAK Kebutuhan sistem komunikasi satelit bergerak pada pita Ku sekarang ini mulai berkembang di Indonesia. Ku-band memiliki ketersediaan lebar pita yang besar dan memilikipanjang gelombang yang lebih pendek. Panjang gelombang yang pendek berpengaruh pada dimensi perangkat yang lebih kecil.Pada umumnya antena satelit untuk sistem yang bergerak menggunakan parabola namun penggunaannya pada kendaraanterkendalaberatnya masa keseluruhan sistem sehingga diperlukan sistem kendali motor dengan harga mahal. Oleh karena itu, penggunaan antena mikrostrip dengan metode antena susun (array menjadi solusi yang dapat memungkinkan kendaraan tetap bergerak dengan baikdengan tetap menjaga kelangsungan hubungan telekomunikasi selama bergerak.Pada penilitian ini, suatu antena mikrostrip penerima dengan menggunakan metode array dengan jumlah patch2x16 yang mampu bekerja pada pita Ku-Band telah dirancang dan direalisasikan. Antena ini bekerja pada frekuensi 11,9 GHz dengan gain sebesar18,69 dB. Kata kunci: komunikasi satelit, Ku-Band, antena mikrostrip, antena mikrostrip array. ABSTRACT Needs of mobile satellite communication system at Ku Band are currently being widely grown in Indonesia. Ku-band has a large bandwidth availability and has a shorter wavelengt. The short wavelength effect on the smaller device dimensions. In general, satellite antennas for mobile system uses parabolic antenna but if its use on vehicles the obstacle is weighing of the whole system so it takes motor control system with an expensive price. Therefor, the use of microstrip antenna by using antenna array is a solution that can allow the vehicle to keep moving well while maintaining the continuity of telecommunication links during the move. In this research, a microstrip antenna array receiver using the patch number 2x16 are able to work in the Ku-band has been design dan realized. The antenna work at 11.9GHz with a gain 18,69dB.   Keywords: satellite communication, Ku-Band, microstrip

  14. Comparison of the Accuracy of Canon KU-1 IOL Measurer and VPLUS A/B Scanner in Axial Length Measurement

    Institute of Scientific and Technical Information of China (English)

    Chuyin Chen; Zhende Lin; Bo Feng; Yonghua Li

    2003-01-01

    Purpose: To evaluate the accuracy of Canon KU-1 IOL measurer (Japanese Canon Company) and VPLUS A/B scanner (French Quantel Company) in axial length (AL)measurement.Methods:Canon KU-1 IOL measurer and VPLUS A/B scanner were used to measure axial length of human cataractous eyes before cataract surgery. Two hundred and twentytwo cases (433 eyes) were involved. The results were compared and the postoperative visual acuity, refractive results were recorded during the follow-ups to evaluate the accuracy of the two instruments.Results:In the 222 cases (433 eyes), the absolute value of the measurement differences was 0.4 mm or above in 35 eyes, 0.8 mm or above in 17 eyes, 1.2 mm or above in 12 eyes,2.0mm or above in 5 eyes. The refractive error was less than 2.0D in all patients. The mean values of ocular axial length by the two methods were 23.82 mm and 23.83 mm respectively and the difference had no statistic significance with compared t test ( P=0.902, two tail, or=0.01).Conclusion:The accurate AL measurements can be obtained with the two instruments and the measurement results should be analyzed comprehensively to obtain accurate values in the complicated cases.

  15. Binding of inositol hexakisphosphate (IP6) to Ku but not to DNA-PKcs.

    Science.gov (United States)

    Ma, Yunmei; Lieber, Michael R

    2002-03-29

    The nonhomologous DNA end joining (NHEJ) pathway is responsible for repairing a major fraction of double strand DNA breaks in somatic cells of all multicellular eukaryotes. As an indispensable protein in the NHEJ pathway, Ku has been hypothesized to be the first protein to bind at the DNA ends generated at a double strand break being repaired by this pathway. When bound to a DNA end, Ku improves the affinity of another DNA end-binding protein, DNA-PK(cs), to that end. The Ku.DNA-PK(cs) complex is often termed the DNA-PK holoenzyme. It was recently shown that myo-inositol hexakisphosphate (IP(6)) stimulates the joining of complementary DNA ends in a cell free system. Moreover, the binding data suggested that IP(6) bound to DNA-PK(cs) (not to Ku). Here we clearly show that, in fact, IP(6) associates not with DNA-PK(cs), but rather with Ku. Furthermore, the binding of DNA ends and IP(6) to Ku are independent of each other. The possible relationship between inositol phosphate metabolism and DNA repair is discussed in light of these findings.

  16. The Ku80 carboxy terminus stimulates joining and artemis-mediated processing of DNA ends

    DEFF Research Database (Denmark)

    Weterings, Eric; Verkaik, Nicole S; Keijzers, Guido

    2008-01-01

    Repair of DNA double-strand breaks (DSBs) is predominantly mediated by nonhomologous end joining (NHEJ) in mammalian cells. NHEJ requires binding of the Ku70-Ku80 heterodimer (Ku70/80) to the DNA ends and subsequent recruitment of the DNA-dependent protein kinase catalytic subunit (DNA......-PK(CS)) and the XRCC4/ligase IV complex. Activation of the DNA-PK(CS) serine/threonine kinase requires an interaction with Ku70/80 and is essential for NHEJ-mediated DSB repair. In contrast to previous models, we found that the carboxy terminus of Ku80 is not absolutely required for the recruitment and activation...... of DNA-PK(CS) at DSBs, although cells that harbored a carboxy-terminal deletion in the Ku80 gene were sensitive to ionizing radiation and showed reduced end-joining capacity. More detailed analysis of this repair defect showed that DNA-PK(CS) autophosphorylation at Thr2647 was diminished, while Ser2056...

  17. Neddylation Promotes Ubiquitylation and Release of Ku from DNA-Damage Sites

    Directory of Open Access Journals (Sweden)

    Jessica S. Brown

    2015-05-01

    Full Text Available The activities of many DNA-repair proteins are controlled through reversible covalent modification by ubiquitin and ubiquitin-like molecules. Nonhomologous end-joining (NHEJ is the predominant DNA double-strand break (DSB repair pathway in mammalian cells and is initiated by DSB ends being recognized by the Ku70/Ku80 (Ku heterodimer. By using MLN4924, an anti-cancer drug in clinical trials that specifically inhibits conjugation of the ubiquitin-like protein, NEDD8, to target proteins, we demonstrate that NEDD8 accumulation at DNA-damage sites is a highly dynamic process. In addition, we show that depleting cells of the NEDD8 E2-conjugating enzyme, UBE2M, yields ionizing radiation hypersensitivity and reduced cell survival following NHEJ. Finally, we demonstrate that neddylation promotes Ku ubiquitylation after DNA damage and release of Ku and Ku-associated proteins from damage sites following repair. These studies provide insights into how the NHEJ core complex dissociates from repair sites and highlight its importance for cell survival following DSB induction.

  18. Pancreatic beta cells express two autoantigenic forms of glutamic acid decarboxylase, a 65-kDa hydrophilic form and a 64-kDa amphiphilic form which can be both membrane-bound and soluble

    DEFF Research Database (Denmark)

    Christgau, S; Schierbeck, H; Aanstoot, H J

    1991-01-01

    The 64-kDa pancreatic beta-cell autoantigen, which is a target of autoantibodies associated with early as well as progressive stages of beta-cell destruction, resulting in insulin-dependent diabetes (IDDM) in humans, has been identified as the gamma-aminobutyric acid-synthesizing enzyme glutamic...... acid decarboxylase. We have identified two autoantigenic forms of this protein in rat pancreatic beta-cells, a Mr 65,000 (GAD65) hydrophilic and soluble form of pI 6.9-7.1 and a Mr 64,000 (GAD64) component of pI 6.7. GAD64 is more abundant than GAD65 and has three distinct forms with regard to cellular...... compartment and hydrophobicity. A major portion of GAD64 is hydrophobic and firmly membrane-anchored and can only be released from membrane fractions by detergent. A second portion is hydrophobic but soluble or of a low membrane avidity, and a third minor portion is soluble and hydrophilic. All the GAD64...

  19. Analysis of Fade Dynamic at Ku-Band in Malaysia

    Directory of Open Access Journals (Sweden)

    Siat Ling Jong

    2014-01-01

    Full Text Available This work investigates fade dynamics of satellite communication systems in equatorial heavy rain region based on a one year of Ku-band propagation measurement campaign carried out in Universiti Teknologi Malaysia (UTM, Johor, Malaysia. First order statistics of rain attenuation are deduced and the results are found to be in good agreement with those obtained from other beacon measurements gathered within the same area (Kuala Lumpur. Moreover, the fade duration and slope statistics of the satellite signal variations are also carefully derived and subsequently compared with the ITU-R recommendation model. Such information is useful for the system operator and radio communication engineer for the design of appropriate fade mitigation techniques as well as the quality of service that could be offered to the user (according to the time interval for a typical day. Further evaluation on the performances of several ITU-R models in the heavy rain region are needed based on the measurement database available of this climatic region.

  20. Electronic Power Conditioner for Ku-band Travelling Wave Tube

    Science.gov (United States)

    Kowstubha, Palle; Krishnaveni, K.; Ramesh Reddy, K.

    2017-04-01

    A highly sophisticated regulated power supply is known as electronic power conditioner (EPC) is required to energise travelling wave tubes (TWTs), which are used as RF signal amplifiers in satellite payloads. The assembly consisting of TWT and EPC together is known as travelling wave tube amplifier (TWTA). EPC is used to provide isolated and conditioned voltage rails with tight regulation to various electrodes of TWT and makes its RF performance independent of solar bus variations which are caused due to varying conditions of eclipse and sunlit. The payload mass and their power consumption is mainly due to the existence of TWTAs that represent about 35 % of total mass and about 70-90 % (based on the type of satellite application) of overall dc power consumption. This situation ensures a continuous improvement in the design of TWTAs and their associated EPCs to realize more efficient and light products. Critical technologies involved in EPCs are design and configuration, closed loop regulation, component and material selection, energy limiting of high voltage (HV) outputs and potting of HV card etc. This work addresses some of these critical technologies evolved in realizing and testing the state of art of EPC and it focuses on the design of HV supply with a HV and high power capability, up to 6 kV and 170 WRF, respectively required for a space TWTA. Finally, an experimental prototype of EPC with a dc power of 320 W provides different voltages required by Ku-band TWT in open loop configuration.

  1. Electronic Power Conditioner for Ku-band Travelling Wave Tube

    Science.gov (United States)

    Kowstubha, Palle; Krishnaveni, K.; Ramesh Reddy, K.

    2016-07-01

    A highly sophisticated regulated power supply is known as electronic power conditioner (EPC) is required to energise travelling wave tubes (TWTs), which are used as RF signal amplifiers in satellite payloads. The assembly consisting of TWT and EPC together is known as travelling wave tube amplifier (TWTA). EPC is used to provide isolated and conditioned voltage rails with tight regulation to various electrodes of TWT and makes its RF performance independent of solar bus variations which are caused due to varying conditions of eclipse and sunlit. The payload mass and their power consumption is mainly due to the existence of TWTAs that represent about 35 % of total mass and about 70-90 % (based on the type of satellite application) of overall dc power consumption. This situation ensures a continuous improvement in the design of TWTAs and their associated EPCs to realize more efficient and light products. Critical technologies involved in EPCs are design and configuration, closed loop regulation, component and material selection, energy limiting of high voltage (HV) outputs and potting of HV card etc. This work addresses some of these critical technologies evolved in realizing and testing the state of art of EPC and it focuses on the design of HV supply with a HV and high power capability, up to 6 kV and 170 WRF, respectively required for a space TWTA. Finally, an experimental prototype of EPC with a dc power of 320 W provides different voltages required by Ku-band TWT in open loop configuration.

  2. 1型糖尿病自身抗原研究进展%Autoantigens in type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    翟双

    2015-01-01

    自身免疫是1型糖尿病发病的重要机制.1型糖尿病自身抗原的发现为疾病的发病机制及临床诊治开拓了视野.胰岛素、谷氨酸脱羧酶65、胰岛细胞瘤相关抗原2等是已发现的1型糖尿病主要的自身抗原.近年来,1型糖尿病自身抗原如嗜铬粒蛋白A、胰岛淀粉样多肽、锌转运体8、胰-十二指肠同源盒因子1备受重视.该文就1型糖尿病自身抗原的研究进展进行综述.%Autoimmunity is the main mechanism of type 1 diabetes.The discovery of autoantigens has broadened our understanding of pathogenesis and clinical diagnosis of type 1 diabetes.Insulin,glutamic acid decarboxylase 65,and insulinoma-associated protein 2 have been found to be major autoantigens of type 1 diabetes.In recent years,some autoantigens in type 1 diabetes,such as chromogranin A,islet amyloid polypeptide,zinc transporter 8,and pancreatic duodenal homeobox factor-1,have received some attention in the literature.The purpose of this article is to review the progress of novel autoantigens in type 1 diabetes.

  3. Apoptosis and Redistribution of the Ro Autoantigen in Balb/c Mouse Like in Subacute Cutaneous Lupus Erythematosus

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    Rafael Herrera-Esparza

    2006-01-01

    Full Text Available In subacute cutaneous lupus eryhematosus (SCLE the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5–30 mJ/cm2 equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti-Ro antibodies from SCLE patients. Apoptosis was also induced by anti-Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT-PCR. Major findings of present studies were: 1. UVB irradiation and anti-Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac-DEVD-CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti-Ro. In conclusion, the caspase pathway would be blocked to avoid anti-Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.

  4. Efficient gene replacements in ku70 disruption strain of Aspergillus chevalieri var. intermedius

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    Qingqing Huang

    2017-01-01

    Full Text Available Aspergillus chevalieri var. intermedius is a dominant filamentous fungal species in Fuzhuan tea and is associated with the quality and health benefits of this tea. The sexual or asexual reproduction of this fungus depends on the osmotic pressure of the tea. Efforts to enhance the beneficial effects of A. chevalieri var. intermedius are hampered by difficulties in disrupting its genes. To address this issue, we identified the A. chevalieri var. intermedius homolog (Acku70 of human Ku70 and generated an Acku70 disruption strain (ΔAcku70, aiming to improve the gene replacement efficiency. ΔAcku70 grew at a slightly lower rate in vitro than the wild-type strain; however, the two strains exhibited similar sensitivity to temperature, osmotic pressure and the effects of ethyl methane sulphonate and H2O2. The replacement efficiency of veA and flbA dramatically increased in ΔAcku70 compared to that in the wild type. The efficiency of flbA replacement increased from 2.6% to 80%, whereas the frequency of veA disruption increased from 15.2% to 83.9% and from 30.8% to 86.8%. Thus, ΔAcku70 is suitable for use as a type strain for large-scale functional genomic analysis of A. chevalieri var. intermedius.

  5. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus

    Institute of Scientific and Technical Information of China (English)

    Honglin Zhu; Hui Luo; Mei Yan; Xiaoxia Zuo; Quan-Zhen Li

    2015-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplas-mic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epi-topes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection.

  6. Autoantigen TRIM21/Ro52 as a Possible Target for Treatment of Systemic Lupus Erythematosus

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    Ryusuke Yoshimi

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a chronic, systemic, and autoimmune disease, whose etiology is still unknown. Although there has been progress in the treatment of SLE through the use of glucocorticoid and immunosuppressive drugs, these drugs have limited efficacy and pose significant risks of toxicity. Moreover, prognosis of patients with SLE has remained difficult to assess. TRIM21/Ro52/SS-A1, a 52-kDa protein, is an autoantigen recognized by antibodies in sera of patients with SLE and Sjögren's syndrome (SS, another systemic autoimmune disease, and anti-TRIM21 antibodies have been used as a diagnostic marker for decades. TRIM21 belongs to the tripartite motif-containing (TRIM super family, which has been found to play important roles in innate and acquired immunity. Recently, TRIM21 has been shown to be involved in both physiological immune responses and pathological autoimmune processes. For example, TRIM21 ubiquitylates proteins of the interferon-regulatory factor (IRF family and regulates type I interferon and proinflammatory cytokines. In this paper, we summarize molecular features of TRIM21 revealed so far and discuss its potential as an attractive therapeutic target for SLE.

  7. Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

    Science.gov (United States)

    Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

    2016-07-01

    Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease.

  8. Flat Array Antennas for Ku-Band Mobile Satellite Terminals

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    Roberto Vincenti Gatti

    2009-01-01

    Full Text Available This work presents the advances in the development of two innovative flat array antennas for Ku-band mobile satellite terminals. The first antenna is specifically conceived for double-deck trains to allow a bi-directional high data rate satellite link. The available circular surface (diameter 80 cm integrates both a transmitting and a receiving section, operating in orthogonal linear polarizations. The TX frequency range is fully covered while the RX bandwidth is around 1 GHz arbitrarily allocated on the DVB range depending on requirements. The beam is steered in elevation through a phased array architecture not employing costly phase shifters, while the steering in azimuth is mechanical. Active BFNs allow excellent performance in terms of EIRP and G/T, maintaining extremely low profile. High antenna efficiency and low fabrication cost are ensured by the employment of innovative SIW (Substrate Integrated Waveguide structures. The second antenna, receiving-only, is designed for radio/video streaming services in mobile environment. Full DVB coverage is achieved thanks to cavity-backed patches operating in double linear polarization. Two independent broadband active BFNs allow simultaneous reception of both polarizations with full tracking capabilities and a squintless beam steering from 20∘ to 60∘ in elevation. A minimum gain of 20 dBi and G/T >−3 dB/∘K are achieved, while maintaining extremely compact size and flat profile. In the design of both antennas fabrication cost is considered as a driving factor, yet providing high performance with a flat profile and thus resulting in a great commercial potentiality.

  9. Low-cost Ku band interferometer for educational purposes

    Science.gov (United States)

    Herrera, Daniel E.; Saez, Alejandro F.; Dauvin, Louise

    2016-07-01

    Latest discoveries in the field of astronomy have been associated to the development of extremely sophisticated instruments. With regards to radio-astronomy, instrumentation has evolved to higher processing data rates and a continuous performance improvement, in the analog and digital domain. Developing, maintaining, and using such kinds of instruments - especially in radio-astronomy - requires understanding complex processes which involve plenty of subtle details. The above has inspired the engineering and astronomical communities to design low-cost instruments, which can be easily replicated by the non-specialist or highly skilled personnel who possess a basic technical background. The final goal of this work is to provide the means to build an affordable tool for teaching radiometry sciences. In order to take a step further this way, a design of a basic interferometer (two elements) is here below introduced, intended to turn into a handy tool for learning the basic principles behind the interferometry technique and radiometry sciences. One of the pedagogical experiences using this tool will be the measurement of the sun's angular diameter. Using these two Ku band receptors, we aim to capture the solar radiation in the 11-12GHz frequency range, the power variations at the earth spin, with a proper phase-lock of the receptors will generate a cross-correlation power oscillation where we can obtain an approximation of the angular sun's diameter. Variables of interest in this calculation are the declination of the sun (which depends on the capture date and location) and the relation between maximal and minimal power within a fringe cycle.

  10. The principal role of Ku in telomere length maintenance is promotion of Est1 association with telomeres.

    Science.gov (United States)

    Williams, Jaime M; Ouenzar, Faissal; Lemon, Laramie D; Chartrand, Pascal; Bertuch, Alison A

    2014-08-01

    Telomere length is tightly regulated in cells that express telomerase. The Saccharomyces cerevisiae Ku heterodimer, a DNA end-binding complex, positively regulates telomere length in a telomerase-dependent manner. Ku associates with the telomerase RNA subunit TLC1, and this association is required for TLC1 nuclear retention. Ku-TLC1 interaction also impacts the cell-cycle-regulated association of the telomerase catalytic subunit Est2 to telomeres. The promotion of TLC1 nuclear localization and Est2 recruitment have been proposed to be the principal role of Ku in telomere length maintenance, but neither model has been directly tested. Here we study the impact of forced recruitment of Est2 to telomeres on telomere length in the absence of Ku's ability to bind TLC1 or DNA ends. We show that tethering Est2 to telomeres does not promote efficient telomere elongation in the absence of Ku-TLC1 interaction or DNA end binding. Moreover, restoration of TLC1 nuclear localization, even when combined with Est2 recruitment, does not bypass the role of Ku. In contrast, forced recruitment of Est1, which has roles in telomerase recruitment and activation, to telomeres promotes efficient and progressive telomere elongation in the absence of Ku-TLC1 interaction, Ku DNA end binding, or Ku altogether. Ku associates with Est1 and Est2 in a TLC1-dependent manner and enhances Est1 recruitment to telomeres independently of Est2. Together, our results unexpectedly demonstrate that the principal role of Ku in telomere length maintenance is to promote the association of Est1 with telomeres, which may in turn allow for efficient recruitment and activation of the telomerase holoenzyme.

  11. Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair.

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    Yong Jun Choi

    Full Text Available Ku70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS to repair DNA double strand breaks (DSBs through the nonhomologous end joining (NHEJ pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70(-/- cells and ku80(-/- cells also appeared to have a defect in base excision repair (BER. BER corrects base lesions, apurinic/apyrimidinic (AP sites and single stand breaks (SSBs utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1 and DNA Polymerase β (Pol β. In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80 and/or free Ku80 (not bound to Ku70 possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80(-/- mice had a shorter life span than dna-pkcs(-/- mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol β. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT, an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER.

  12. Expression of Ku70 predicts results of radiotherapy in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Tomokazu; Someya, Masanori; Hori, Masakazu; Nakata, Kensei; Kitagawa, Mio; Tsuchiya, Takaaki; Sakata, Koh-ichi [Sapporo Medical University School of medicine, Department of Radiology, Chuo-ku, Sapporo, Hokkaido (Japan); Matsumoto, Yoshihisa [Research Laboratory for Nuclear Reactors, Tokyo Institute of Technology, Meguro-ku, Tokyo (Japan); Nojima, Masanori [The University of Tokyo, The Institute of Medical Science Hospital, Minatoku, Tokyo (Japan); Masumori, Naoya [Sapporo Medical University School of medicine, Department of Urology, Chuo-ku, Sapporo, Hokkaido (Japan); Hasegawa, Tadashi [Sapporo Medical University School of medicine, Department of Surgical Pathology, Chuo-ku, Sapporo, Hokkaido (Japan)

    2017-01-15

    Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse. We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens. Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained. Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches. (orig.) [German] Die Behandlung beim Prostatakarzinom ist abhaengig von T-Stadium, Gleason-Score und prostataspezifischem Antigen (PSA). Diese klinischen Faktoren sind jedoch zu ungenau, um das individuelle Lokalrezidivrisiko beim Prostatakarzinom nach

  13. 系统性红斑狼疮中内皮细胞相关自身抗原的鉴定%Identification of autoantigens associated with systemic lupus erythematosus from endothelial cells

    Institute of Scientific and Technical Information of China (English)

    曹毅; 吴乔; 牟芝蓉

    2012-01-01

    We aimed to identify new potential autoantigens associated with systemic lupus erythematosus (SLE) in human umbilical vein endothelial cells (HUVEC). Serum samples were collected from 27 SLE patients and 24 health donors. And IgG from serum was captured by Protein G Beads. Then the beads were washed and incubated with HUVEC lysate. The proteins which reacted with IgG-Beads were separated by immobilized pH gradient two -dimensional (2 -D) gel electrophoresis, and the unique protein spots in SLE patients group were identified by LC -MS -MS. We identified several proteins including known SLE autoantigen GAPDH, in which calcium/calmodulin-dependent serine protein kinase (CASK) was the first find to be involved in SLE. Furthermore, we also found that CASK antibody expression in SLE was significantly higher than that in health donor. From all the results, we presumed that CASK in HUVEC may be a new potential autoantigen in SLE. Systemic lupus erythematosus; Human umbilical vein endothelial cells; Calcium/calmodulin-%目的 在内皮细胞中筛选与系统性红斑狼疮(systemic lupus erythematosus,SLE)疾病相关的自身抗原.方法 用免疫沉淀法以SLE病人血清中自身抗体捕获人脐带内皮细胞(human umbilical vein endothelial cell,HUVEC)相关抗原,并用双向电泳法分离免疫沉淀产物,然后用LC-MS-MS串联质谱鉴定与SLE病人血清反应的蛋白点.最后用Western blot法验证部分鉴定蛋白.结果 相对于正常人血清对照,SLE病人血清捕获了多个内皮细胞相关蛋白,质谱鉴定结果 显示:通过免疫沉淀与双向电泳结合的方法 成功鉴定了包括GAPDH等已知SLE自身抗原在内的一系列蛋白,其中钙/钙调蛋白依赖性丝氨酸蛋白激酶(calcium/calmodulin-dependent serine protein kinase,CASK)为新发现SLE候选自身抗原.并以重组人CASK蛋白证实SLE病人血清中CASK抗体水平显著高于正常人对照.结论 内皮细胞蛋白CASK可能作为一个新的SLE相关自身抗原.

  14. Efficient processing of abasic sites by bacterial nonhomologous end-joining Ku proteins.

    Science.gov (United States)

    de Ory, Ana; Zafra, Olga; de Vega, Miguel

    2014-12-01

    Intracellular reactive oxygen species as well as the exposure to harsh environmental conditions can cause, in the single chromosome of Bacillus subtilis spores, the formation of apurinic/apyrimidinic (AP) sites and strand breaks whose repair during outgrowth is crucial to guarantee cell viability. Whereas double-stranded breaks are mended by the nonhomologous end joining (NHEJ) system composed of an ATP-dependent DNA Ligase D (LigD) and the DNA-end-binding protein Ku, repair of AP sites would rely on an AP endonuclease or an AP-lyase, a polymerase and a ligase. Here we show that B. subtilis Ku (BsuKu), along with its pivotal role in allowing joining of two broken ends by B. subtilis LigD (BsuLigD), is endowed with an AP/deoxyribose 5'-phosphate (5'-dRP)-lyase activity that can act on ssDNA, nicked molecules and DNA molecules without ends, suggesting a potential role in BER during spore outgrowth. Coordination with BsuLigD makes possible the efficient joining of DNA ends with near terminal abasic sites. The role of this new enzymatic activity of Ku and its potential importance in the NHEJ pathway is discussed. The presence of an AP-lyase activity also in the homolog protein from the distantly related bacterium Pseudomonas aeruginosa allows us to expand our results to other bacterial Ku proteins. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Cloning and molecular characterization of cDNA encoding a mouse male-enhanced antigen-2 (Mea-2): a putative family of the Golgi autoantigen.

    Science.gov (United States)

    Kondo, M; Sutou, S

    1997-01-01

    The male-enhanced antigen-2 (Mea-2) gene was originally identified with a monoclonal histocompatibility Y (H-Y) antibody (mAb4VII). There is no report of the full length cDNA encode for Mea-2 product until this report. In this study, we isolated the full length mouse Mea-2 cDNA by screening a testis cDNA library with a PCR-amplified Mea-2 product, and direct PCR amplification of its upstream sequences from the cDNA library. The primary structure of the Mea-2 peptide, deduced from this nucleotide sequence, shows that it encode a 150 kDa protein, of 1325 amino acid residues, which contained five putative N-glycosylation sites and four leucine zipper motifs. A data bank search indicated that it has high homology with a human Golgi autoantigen (golgin-160) both in its nucleotides (78%) and amino acids sequence (83%). This suggests that Mea-2 gene product may encode a golgi structural protein. In situ hybridization analysis suggested that the Mea-2 gene is expressed in spermatids during spermatogenesis as already shown by Mea-1, suggesting that Mea-2 gene product as well as Mea-1 have also some role for spermatogenesis.

  16. La Autoantigen Induces Ribosome Binding Protein 1 (RRBP1) Expression through Internal Ribosome Entry Site (IRES)-Mediated Translation during Cellular Stress Condition.

    Science.gov (United States)

    Gao, Wenqing; Li, Qi; Zhu, Ruiyu; Jin, Jian

    2016-07-20

    The function of ribosome binding protein 1 (RRBP1) is regulating the transportation and secretion of some intracellular proteins in mammalian cells. Transcription of RRBP1 is induced by various cytokines. However, few studies focused on the process of RRPB1 mRNA translation. The RRBP1 mRNA has a long 5' untranslated region that potentially formed a stable secondary structure. In this study, we show that the 5' UTR of RRBP1 mRNA contains an internal ribosome entry site (IRES). Moreover, the RRBP1 expression is induced by chemotherapeutic drug paclitaxel or adriamycin in human hepatocellular carcinoma cells and accompanied with the increased expression of La autoantigen (La), which binds to RRBP1 IRES element and facilitates translation initiation. Interestingly, we found IRES-mediated RRBP1 translation is also activated during serum-starvation condition which can induce cytoplasmic localization of La. After mapping the entire RRBP1 5' UTR, we determine the core IRES activity is located between nt-237 and -58. Furthermore, two apical GARR loops within the functional RRBP1 IRES elements may be important for La binding. These results strongly suggest an important role for IRES-dependent translation of RRBP1 mRNA in hepatocellular carcinoma cells during cellular stress conditions.

  17. Genetics and pathophysiology of granulomatosis with polyangiitis (GPA) and its main autoantigen proteinase 3.

    Science.gov (United States)

    Relle, Manfred; Föhr, Bernd; Fasola, Federica; Schwarting, Andreas

    2016-12-01

    Granulomatosis with polyangiitis (GPA) is a severe autoimmune disease and one of the small vessel anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although its etiology and pathophysiology are still widely unknown, it is accepted that infections, environmental factors, epigenetic modifications, and a genetic predisposition provide the basis for this systemic disorder. GPA typically evolves into two phases: an initial phase characterized by ear, nose and throat (ENT) manifestations, such as chronic sinusitis and otitis, ulceration of the oral cavity and pharynx, as well as pulmonary nodules and a severe generalized phase, defined by the occurrence of rapidly progressive glomerulonephritis, pulmonary hemorrhage, and arthritis. ANCAs, directed against the neutrophilic enzymes proteinase 3 and myeloperoxidase, are present in up to 90% of the affected patients in the systemic phase. As the humoral immunity is predominantly directed against neutrophilic antigens, it is apparent that neutrophils play a critical role in GPA both as target and effector cells. Although GPA pathogenesis is not well known, some susceptibility genes and loci have been identified by candidate gene approaches, genome-wide association studies, and meta-analyses, as well as familial association studies. Such genes are CTLA4, PTPN22, COL11A2, SERPINA1, and the MHC class II gene cluster. This review highlights the clinical, pathophysiological, and genetic background of GPA and aims to give an overview of recent efforts to identify GPA susceptibility genes. We point out the genetic basis of the main autoantigen PR3 and why it is so difficult to establish a murine GPA model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Identification of critical residues of linear B cell epitope on Goodpasture autoantigen.

    Directory of Open Access Journals (Sweden)

    Xiao-yu Jia

    Full Text Available The autoantigen of anti-glomerular basement membrane (GBM disease has been identified as the non-collagenous domain 1 of α3 chain of type IV collagen, α3(IVNC1. Our previous study revealed a peptide on α3(IVNC1 as a major linear epitope for B cells and potentially nephrogenic, designated as P14 (α3129-150. This peptide has also been proven to be the epitope of auto-reactive T cells in anti-GBM patients. This study was aimed to further characterize the critical motif of P14.16 patients with anti-GBM disease and positive anti-P14 antibodies were enrolled. A set of truncated and alanine substituted peptides derived from P14 were synthesized. Circulating antibodies against the peptides were detected by enzyme linked immunosorbent assay (ELISA.We found that all sera with anti-P14 antibodies reacted with the 13-mer sequence in the C-terminus of P14 (P14c exclusively. The level of antibodies against P14 was highly correlated with the level of antibodies against P14c (r=0.970, P<0.001. P14c was the core immunogenic region and the amino acid sequence (ISLWKGFSFIMFT was highly hydrophobic. Each amino acid residue in P14c was sequentially replaced by alanine. Three residues of glycine142, phenylalanine143, and phenylalanine145 were identified crucial for antibody binding based on the remarkable decline (P<0.001 of antibody reaction after each residue replacement.We defined GFxF (α3142, 143,145 as the critical motif of P14. It may provide some clues for understanding the etiology of anti-GBM disease.

  19. Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity.

    Science.gov (United States)

    Le, Sarah N; Porebski, Benjamin T; McCoey, Julia; Fodor, James; Riley, Blake; Godlewska, Marlena; Góra, Monika; Czarnocka, Barbara; Banga, J Paul; Hoke, David E; Kass, Itamar; Buckle, Ashley M

    2015-01-01

    Thyroid peroxidase (TPO) catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto's disease--the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B). TPO has been a major target for structural studies for over 20 years; however, to date, the structure of TPO remains to be determined. We have used a molecular modelling approach to investigate plausible modes of TPO structure and dimer organisation. Sequence features of the C-terminus are consistent with a coiled-coil dimerization motif that most likely anchors the TPO dimer in the apical membrane of thyroid follicular cells. Two contrasting models of TPO were produced, differing in the orientation and exposure of their active sites relative to the membrane. Both models are equally plausible based upon the known enzymatic function of TPO. The "trans" model places IDR-B on the membrane-facing side of the myeloperoxidase (MPO)-like domain, potentially hindering access of autoantibodies, necessitating considerable conformational change, and perhaps even dissociation of the dimer into monomers. IDR-A spans MPO- and CCP-like domains and is relatively fragmented compared to IDR-B, therefore most likely requiring domain rearrangements in order to coalesce into one compact epitope. Less epitope fragmentation and higher solvent accessibility of the "cis" model favours it slightly over the "trans" model. Here, IDR-B clusters towards the surface of the MPO-like domain facing the thyroid follicular lumen preventing steric hindrance of autoantibodies. However, conformational rearrangements may still be necessary to allow full engagement with autoantibodies, with IDR-B on both models being close to the dimer interface. Taken together, the modelling highlights the need to consider the oligomeric state of TPO, its conformational

  20. A novel Ku70 function in colorectal homeostasis separate from nonhomologous end joining.

    Science.gov (United States)

    Puebla-Osorio, N; Kim, J; Ojeda, S; Zhang, H; Tavana, O; Li, S; Wang, Y; Ma, Q; Schluns, K S; Zhu, C

    2014-05-22

    Ku70, a known nonhomologous end-joining (NHEJ) factor, also functions in tumor suppression, although this molecular mechanism remains uncharacterized. Previously, we showed that mice deficient for DNA ligase IV (Lig4), another key NHEJ factor, succumbed to aggressive lymphoma in the absence of tumor suppressor p53. However, the tumor phenotype is abrogated by the introduction of a hypomorphic mutant p53(R172P), which impaired p53-mediated apoptosis but not cell-cycle arrest. However, Lig4(-/-)p53(R172P) mice succumbed to severe diabetes. To further elucidate the role of NHEJ and p53-mediated apoptosis in vivo, we bred Ku70(-/-) p53(R172P) mice. Unexpectedly, these mice were free of diabetes, although 80% of the mutant mice had abnormally enlarged colons with pronounced inflammation. Remarkably, most of these mutant mice progressed to dysplasia, adenoma and adenocarcinoma; this is in contrast to the Lig4(-/-)p53(R172P) phenotype, strongly suggesting an NHEJ-independent function of Ku70. Significantly, our analyses of Ku70(-/-)p53(R172P) colonic epithelial cells show nuclear stabilization of β-catenin accompanied by higher expression of cyclin D1 and c-Myc in affected colon sections than in control samples. This is not due to the p53 mutation, as Ku70(-/-) mice share this phenotype. Our results not only unravel a novel function of Ku70 essential for colon homeostasis, but also establish an excellent in vivo model in which to study how chronic inflammation and abnormal cellular proliferation underlie tumorigenesis and tumor progression in the colon.

  1. Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

    Science.gov (United States)

    Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

    2015-01-01

    Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

  2. The Ku70/80 ring in Non-Homologous End-Joining

    DEFF Research Database (Denmark)

    Kragelund, Birthe Brandt; Weterings, Eric; Hartmann-Petersen, Rasmus;

    2016-01-01

    Non-homologous end-joining (NHEJ) is an essential DNA double strand break repair pathway during all cell cycle stages. Deficiency in NHEJ factors can lead to accumulation of unrepaired DNA breaks or faulty DNA repair, which may ultimately result in cell death, senescence or carcinogenesis. The Ku70....../80 heterodimer is a key-player in the NHEJ pathway and binds to DNA termini with high affinity, where it helps to protect DNA ends from degradation and to recruit other NHEJ factors required for repair. The mechanism of Ku70/80 detachment from the DNA helix after completion of DNA repair is incompletely...

  3. Rain fade in Ku-band VSAT networks - A design consideration

    Science.gov (United States)

    Raust, Eric H.

    The components of a Very Small Aperture Terminal (VSAT) network are shown to determine the effect that rainfall has on Ku-band satellite communications. This paper considers the effect of the signal attenuation caused by rain as predicted by a well known rain fade model. The result, of considering the highest rain attenuations experienced is related to both transmission availabilities and signal margins. The results of link calculations are tabulated for typical network designs. These results show that proper selection of the VSAT's components and the satellite transponder power can all but eliminate rain outages while maintaining the economics of a Ku-band VSAT network.

  4. Building Spiritual Care in Nursing: An Overview of Ku's Spiritual Studies in Taiwan.

    Science.gov (United States)

    Ku, Ya-Lie

    This paper describes the overview of Ku's spiritual literature on nursing through five stages in Taiwan: the development of a spiritual framework, a scale of spiritual distress, a spiritual care model, a spiritual nursing course, and a spiritual care book in nursing. The article demonstrates the process of building spiritual care in nursing from constructing theoretical frameworks, measurements, and applying to education. The integrative overview of Ku's spiritual studies developed in this article could be an example in clinical and education fields for nurse administrators to develop spiritual capabilities.

  5. Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

    Science.gov (United States)

    Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

    2015-11-01

    Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

  6. 75 FR 28095 - Culturally Significant Object Imported for Exhibition Determinations: “E Ku Ana Ka Paia...

    Science.gov (United States)

    2010-05-19

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF STATE Culturally Significant Object Imported for Exhibition Determinations: ``E Ku Ana Ka Paia: Unification... 15, 2003 , I hereby determine that the object to be included in the exhibition ``E Ku Ana Ka...

  7. Analysis of metals in asphaltenes of KU-46 by PIXE analysis; Analisis de metales en asfaltenos de crudo mexicano KU-46 por PIXE

    Energy Technology Data Exchange (ETDEWEB)

    Navidad G, P.; Pina L, L.I.; Lopez M, J.; Ramirez T, J.J.; Aspiazu F, J.A.; Romero G, E.T. [Gerencia de Ciencias Basicas, Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2002-07-01

    The content of metals of the asphaltenes obtained from the KU-46 mexican crude with n-heptane was evaluated. The found metals in higher concentration are transition metals as well as the vanadium, nickel, copper and zinc. Moreover the sulfur in high concentrations was quantified. The metallic content of the asphaltenes revealed that the crude contains a lower quantity of metals unlike the vacuum residue previously analysed. (Author)

  8. 33 ku protein associated several polypeptides with nearly the same molecular weight but not the same isoelectric point

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The 33 ku protein,prepared from NaCl-treated PSⅡ particles,has shown an single band by SDS-PAGE.After being dialyzed against the low-osmotic medium at 4℃,it has been found that the 33 ku protein degraded into several small fragments.This result suggests that the preparations of 33 ku protein probably contain some latent proteinases.It has also been found,by the 2-D electrophoresis and IEF,that the preparations of 33 ku protein not dialyzed against the low-osmotic medium contain several polypeptides with nearly the same molecular weight but not the same isoelectric point as the 33 ku protein.

  9. Serum anti-Ku86: a potential biomarker for early detection of hepatocellular carcinoma%抗Ku86抗体在肝细胞癌早期诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    储磊; 张霞军; 王国忠; 周文俊; 杜忠祥; 刘安定; 赵宏

    2014-01-01

    Objective To investigate the clinical value of serum anti-Ku86 in early detection of hepatocellular carcinoma (HCC).Methods Expression levels of Ku86 protein in HCC and adjacent normal liver tissues were detected by Western blotting.Serum anti-Ku86 level in 83 patients with early HCC and 124 patients with liver cirrhosis were detected by enzyme-linked immunosorbent assay (ELISA).Chemiluminescence was used to measure the serum level of α-fetoprotein (AFP).Results Expression of Ku86 protein in HCC was increased when compared with the adjacent normal liver tissues (0.21 ±0.05 vs.0.08 ±0.02,P <0.01).Serum anti-Ku86 level was significantly elevated in HCC patients compared with that in liver cirrhosis patients (0.47 ±0.22 vs.0.22 ±0.06 Abs at 450 nm,P <0.01),but there was no significant difference between HBV infection and HCV infection in HCC patients (0.51 ±0.19 vs.0.47 ±0.24,P =0.267).Of note,serum anti-Ku86 level was significantly decreased after surgical resection of the tumors in the 30 HCC cases tested (P < 0.01).The results of ROC analysis indicated a better performance of anti-Ku86 (0.857) than AFP (0.739) for early detection of HCC.In 83 HCC patients,the positive rate of anti-Ku86 was 61.4% (51/83),significantly higher than that of the AFP positive rate (27.7%,23/83).The anti-Ku86 level was positive in 37 of 60 HCC cases with negative AFP.Combination assay of AFP and anti-Ku86 could detect 60 of 83 HCC cases (72.3%,60/83).There was no significant correlation of antiKu86 and AFP (r =0.156,P =0.161).Conclusions Serum anti-Ku86 level is significantly elevated and is not related to HBV and HCV infection in HCC patients.Serum anti-Ku86 antibody may be a potential biomarker for early detection of HCC,and can be used in combination with AFP in clinics.%目的 探讨Ku86蛋白在肝细胞癌(HCC)组织中的表达及血清抗Ku86抗体在HCC早期诊断中的临床价值.方法 采用Western blot法检测HCC和癌旁正常组织中Ku86蛋白的表

  10. Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells.

    Science.gov (United States)

    Katsiougiannis, S; Tenta, R; Skopouli, F N

    2015-08-01

    The aim of this study was to examine the levels of endoplasmic reticulum (ER) stress in minor salivary glands, to investigate the interplay between ER stress-induced autophagy and apoptosis in human salivary gland (HSG) cells and to test the effect of ER stress-induced apoptosis on the cellular redistribution of the two major Sjögren's syndrome (SS) autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/Sjögren's syndrome-related antigen B (SSB). Minor salivary gland biopsies from SS patients and sicca controls were examined by immunohistochemistry for the expression of 78 kDa glucose-regulated protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell viability, autophagy and apoptosis were assessed. Immunoblot was applied to detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and X-box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal epithelial cells in salivary glands of patients and sicca controls. TG treatment induced autophagy, as indicated by enhanced protein expression of LC3II. The protein levels of UPR marker XBP-1 were increased after TG treatment, while GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the cytoplasm in resting cells, while they were redistributed to cell membrane and blebs in the apoptotic cells. In conclusion, ER stress is activated in minor salivary gland epithelial cells from SS patients and controls. ER stress-induced apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization of Ro/SSA and La/SSB autoantigens.

  11. Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair

    NARCIS (Netherlands)

    Y.J. Choi (Yong Jun); H. Li (Han); M.Y. Son (Mi Young); X.-H. Wang (Xiao-Hong); J.L. Fornsaglio (Jamie L.); R.W. Sobol (Robert W.); M. Lee (Moonsook); J. Vijg (Jan); S. Imholz (Sandra); M.E.T. Dollé (Martijn); H. van Steeg (Harry); E. Reiling (Erwin); P. Hasty (Paul)

    2014-01-01

    textabstractKu70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB

  12. Development of intense terahertz coherent synchrotron radiation at KU-FEL

    Energy Technology Data Exchange (ETDEWEB)

    Sei, Norihiro, E-mail: sei.n@aist.go.jp [Research Institute for Measurement and Analytical Instrumentation, National Institute of Advanced Industrial Science and Technology, 1-1-1 Umezono, Umezono, Tsukuba, Ibaraki 305-8568 (Japan); Zen, Heishun; Ohgaki, Hideaki [Institute for Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan)

    2016-10-01

    We produced intense coherent synchrotron radiation (CSR) in the terahertz (THz) region using an S-band linac at the Kyoto University Free Electron Laser (KU-FEL), which is a mid-infrared free-electron laser facility. The CSR beam was emitted from short-pulse electron bunches compressed by a 180° arc, and was transferred to air at a large solid angle of 0.10 rad. The measured CSR energy was 55 μJ per 7 μs macropulse, and KU-FEL was one of the most powerful CSR sources in normal conducting linear accelerator facilities. The CSR spectra were measured using an uncooled pyroelectric detector and a Michelson-type interferometer designed specifically for the KU-FEL electron beam, and had a maximum at a frequency of 0.11 THz. We found that adjusting the energy slit enhanced the CSR energy and shortened the electron beam bunch length in the CSR spectra measurements. Our results demonstrated that the efficient use of the energy slit can help improve the characteristics of CSR. - Highlights: • We have developed intense coherent synchrotron radiation (CSR) at KU-FEL. • The elevation angle of the CSR was correctly measured by a new technique. • The CSR power extracted to the air was 55 μJ per 7 μs macropulse. • It was demonstrated that an energy slit was effective to improve the CSR properties.

  13. Expression of Recombinant Baculovirus Carrying Schistosoma japonicum 26 ku GST in Mammalian Cells

    Institute of Scientific and Technical Information of China (English)

    YU Guangqing; SONG Jianhua; LIU Wenqi; LONG Xiaochun; MO Hongmei; LI Yonglong; CHEN Xinwen

    2006-01-01

    In order to construct recombinant baculovirus carrying Schistosoma japonicum 26 ku glutathione S-transferase gene (Sj26), and observe the expression of Sj26 in mammalian cells, the Sj26 gene was amplified with plasmid pGEX-3X as template by PCR, and then recombined into Tvector for sequencing. Sj26 gene was inserted into the downstream of CMV promoter of donor plasmid pFBDGC, and the recombinant donor plasmid pFBDGC-Sj26 transformed into DH10Bac,then the recombinant bacmid AcCMVSj26 was isolated and transfected into Sf9 cells. The recombinant baculovirus was harvested and final titer of vAcCMVSj26 was measured. BHK cells were transducted with recombinant baculovirus in vitro. By using Western blot, the expression of 26 ku glutathione S-transferase (GST) was detected. The results showed that after enzyme digestion and sequencing, the donor plasmid was successfully constructed. PCR confirmed that pFBDGC-Sj26 and Bacmid homologous recombination occurred in E. coli. After transfection of Sf9 cells with recombinant Bacmid, recombinant baculovirus was replicated in Sf9 cells and expressed green fluorescent protein. PCR further revealed recombinant baculovirus contained Sj26. The titer of the harvested baculovirus was 1.24 × 108. Western blot demonstrated that recombinant baculovirus could express 26 ku GST in BHK cells. It was concluded that Sj26 recombinant baculovirus was successfully constructed, and the 26 ku GST was expressed in mammalian cells.

  14. A Ku-band magnetically insulated transmission line oscillator with overmoded slow-wave-structure

    Science.gov (United States)

    Jiang, Tao; He, Jun-Tao; Zhang, Jian-De; Li, Zhi-Qiang; Ling, Jun-Pu

    2016-12-01

    In order to enhance the power capacity, an improved Ku-band magnetically insulated transmission line oscillator (MILO) with overmoded slow-wave-structure (SWS) is proposed and investigated numerically and experimentally. The analysis of the dispersion relationship and the resonant curve of the cold test indicate that the device can operate at the near π mode of the TM01 mode, which is useful for mode selection and control. In the particle simulation, the improved Ku-band MILO generates a microwave with a power of 1.5 GW and a frequency of 12.3 GHz under an input voltage of 480 kV and input current of 42 kA. Finally, experimental investigation of the improved Ku-band MILO is carried out. A high-power microwave (HPM) with an average power of 800 MW, a frequency of 12.35 GHz, and pulse width of 35 ns is generated under a diode voltage of 500 kV and beam current of 43 kA. The consistency between the experimental and simulated far-field radiation pattern confirms that the operating mode of the improved Ku-band MILO is well controlled in π mode of the TM01 mode. Project supported partly by the National Natural Science Foundation of China (Grant No. 61171021).

  15. A 1-Watt Ku-Band Power Amplifier MMIC Using Cost-Effective Organic SMD Package

    NARCIS (Netherlands)

    Bessemoulin, A.; Parisot, M.; Quentin, P.; Saboureau, C.; Heijningen, M. van; Priday, J.

    2004-01-01

    This paper presents the design and performance of a compact 1-Watt Ku-band power amplifier MMIC implemented in a novel microwave organic power package, compatible with SMD assembly lines. Due to the use of simple materials, like RO4003 substrate and copper, it allows significant cost reduction for

  16. An integrated Ka/Ku-band payload for personal, mobile and private business communications

    Science.gov (United States)

    Hayes, Edward J.; Keelty, J. Malcolm

    1991-01-01

    The Canadian Department of Communications has been studying options for a government-sponsored demonstration payload to be launched before the end of the century. A summary of the proposed system concepts and network architectures for providing an advanced private business network service at Ku-band and personal and mobile communications at Ka-band is presented. The system aspects addressed include coverage patterns, traffic capacity, and grade of service, multiple access options as well as special problems, such as Doppler in mobile applications. Earth terminal types and the advanced payload concept proposed in a feasibility study for the demonstration mission are described. This concept is a combined Ka-band/Ku-band payload which incorporates a number of advanced satellite technologies including a group demodulator to convert single-channel-per-carrier frequency division multiple access uplink signals to a time division multiplex downlink, on-board signal regeneration, and baseband switching to support packet switched data operation. The on-board processing capability of the payload provides a hubless VSAT architecture which permits single-hop full mesh interconnectivity. The Ka-band and Ku-band portions of the payload are fully integrated through an on-board switch, thereby providing the capability for fully integrated services, such as using the Ku-band VSAT terminals as gateway stations for the Ka-band personal and mobile communications services.

  17. A 1-Watt Ku-Band Power Amplifier MMIC Using Cost-Effective Organic SMD Package

    NARCIS (Netherlands)

    Bessemoulin, A.; Parisot, M.; Quentin, P.; Saboureau, C.; Heijningen, M. van; Priday, J.

    2004-01-01

    This paper presents the design and performance of a compact 1-Watt Ku-band power amplifier MMIC implemented in a novel microwave organic power package, compatible with SMD assembly lines. Due to the use of simple materials, like RO4003 substrate and copper, it allows significant cost reduction for R

  18. Ku80 gene G-1401T promoter polymorphism and risk of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Jia-Qi Li; Jie Chen; Nan-Nan Liu; Li Yang; Ying Zeng; Bin Wang; Xue-Rong Wang

    2011-01-01

    AIM: To evaluate the possible relationship between the Ku80 gene polymorphism and the risk of gastric cancer in China. METHODS: In this hospital-based case-control study of gastric cancer in Jiangsu Province, China, we investigated the association of the Ku80 G-1401T (rs828907) polymorphism with gastric cancer risk. A total of 241 patients with gastric cancer and 273 age- and sexmatched control subjects were genotyped and analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of genotypes GG, GT and TT were 65.6%, 22.8% and 11.6% in gastric cancer cases, respectively, and 75.8%, 17.6% and 6.6% in controls, respectively. There were significant differences between gastric cancer and control groups in the distribution of their genotypes (P = 0.03) and allelic requencies (P = 0.002) in the Ku80 promoter G-1401T polymorphism. CONCLUSION: The T allele of Ku80 G-1401T may be associated with the development of gastric cancer.

  19. Red Schoolhouse, Burning Cross: The Ku Klux Klan of the 1920s and Educational Reform

    Science.gov (United States)

    Laats, Adam

    2012-01-01

    In this article, the author focuses on the Ku Klux Klan of the 1920s and educational reform. The Klan's meteoric rise to national prominence in the 1920s has attracted a great deal of attention from historians, yet the group and its popularity during this time frame remain poorly understood. This is due in part to the fact that Klan symbols such…

  20. Development of an integrated photonic beamformer for electronically-steered Ku-band phased array antenna

    NARCIS (Netherlands)

    Zhuang, L.; Marpaung, D.A.I.; Burla, M.; Boot, R.; Hulzinga, A.; Beeker, W.P.; Beeker, Willem; van Dijk, P.; Roeloffzen, C.G.H.

    2011-01-01

    Currently an integrated photonic beamformer for electronically-steered Ku-band phased array antenna (PAA) system for satellite communications is being developed within a Dutch Point One R&D Innovation Project “Broadband Satellite Communication Services on High-Speed Transport Vehicles‿, targeting

  1. Development of a broadband integrated optical beamformer for Ku-Band Phased Array Antennas

    NARCIS (Netherlands)

    Roeloffzen, C.G.H.; van Dijk, Paul; Marpaung, D.A.I.; Burla, M.; Zhuang, L.

    2012-01-01

    Currently an integrated photonic beamformer for electronically-steered Ku-band phased array antenna (PAA) systems for satellite communications is being developed, targeting continuous reception of the full DVB-S band (10.7- 12.75 GHz), squint-free and seamless beam steering, and polarization

  2. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways

    Science.gov (United States)

    Wang, Minli; Wu, Weizhong; Wu, Wenqi; Rosidi, Bustanur; Zhang, Lihua; Wang, Huichen; Iliakis, George

    2006-01-01

    Poly(ADP-ribose)polymerase 1 (PARP-1) recognizes DNA strand interruptions in vivo and triggers its own modification as well as that of other proteins by the sequential addition of ADP-ribose to form polymers. This modification causes a release of PARP-1 from DNA ends and initiates a variety of responses including DNA repair. While PARP-1 has been firmly implicated in base excision and single strand break repair, its role in the repair of DNA double strand breaks (DSBs) remains unclear. Here, we show that PARP-1, probably together with DNA ligase III, operates in an alternative pathway of non-homologous end joining (NHEJ) that functions as backup to the classical pathway of NHEJ that utilizes DNA-PKcs, Ku, DNA ligase IV, XRCC4, XLF/Cernunnos and Artemis. PARP-1 binds to DNA ends in direct competition with Ku. However, in irradiated cells the higher affinity of Ku for DSBs and an excessive number of other forms of competing DNA lesions limit its contribution to DSB repair. When essential components of the classical pathway of NHEJ are absent, PARP-1 is recruited for DSB repair, particularly in the absence of Ku and non-DSB lesions. This form of DSB repair is sensitive to PARP-1 inhibitors. The results define the function of PARP-1 in DSB repair and characterize a candidate pathway responsible for joining errors causing genomic instability and cancer. PMID:17088286

  3. Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity.

    Directory of Open Access Journals (Sweden)

    Sarah N Le

    Full Text Available Thyroid peroxidase (TPO catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto's disease--the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B. TPO has been a major target for structural studies for over 20 years; however, to date, the structure of TPO remains to be determined. We have used a molecular modelling approach to investigate plausible modes of TPO structure and dimer organisation. Sequence features of the C-terminus are consistent with a coiled-coil dimerization motif that most likely anchors the TPO dimer in the apical membrane of thyroid follicular cells. Two contrasting models of TPO were produced, differing in the orientation and exposure of their active sites relative to the membrane. Both models are equally plausible based upon the known enzymatic function of TPO. The "trans" model places IDR-B on the membrane-facing side of the myeloperoxidase (MPO-like domain, potentially hindering access of autoantibodies, necessitating considerable conformational change, and perhaps even dissociation of the dimer into monomers. IDR-A spans MPO- and CCP-like domains and is relatively fragmented compared to IDR-B, therefore most likely requiring domain rearrangements in order to coalesce into one compact epitope. Less epitope fragmentation and higher solvent accessibility of the "cis" model favours it slightly over the "trans" model. Here, IDR-B clusters towards the surface of the MPO-like domain facing the thyroid follicular lumen preventing steric hindrance of autoantibodies. However, conformational rearrangements may still be necessary to allow full engagement with autoantibodies, with IDR-B on both models being close to the dimer interface. Taken together, the modelling highlights the need to consider the oligomeric state of TPO, its

  4. Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis.

    Science.gov (United States)

    Pedchenko, Vadim; Bondar, Olga; Fogo, Agnes B; Vanacore, Roberto; Voziyan, Paul; Kitching, A Richard; Wieslander, Jörgen; Kashtan, Clifford; Borza, Dorin-Bogdan; Neilson, Eric G; Wilson, Curtis B; Hudson, Billy G

    2010-07-22

    In Goodpasture's disease, circulating autoantibodies bind to the noncollagenous-1 (NC1) domain of type IV collagen in the glomerular basement membrane (GBM). The specificity and molecular architecture of epitopes of tissue-bound autoantibodies are unknown. Alport's post-transplantation nephritis, which is mediated by alloantibodies against the GBM, occurs after kidney transplantation in some patients with Alport's syndrome. We compared the conformations of the antibody epitopes in Goodpasture's disease and Alport's post-transplantation nephritis with the intention of finding clues to the pathogenesis of anti-GBM glomerulonephritis. We used an enzyme-linked immunosorbent assay to determine the specificity of circulating autoantibodies and kidney-bound antibodies to NC1 domains. Circulating antibodies were analyzed in 57 patients with Goodpasture's disease, and kidney-bound antibodies were analyzed in 14 patients with Goodpasture's disease and 2 patients with Alport's post-transplantation nephritis. The molecular architecture of key epitope regions was deduced with the use of chimeric molecules and a three-dimensional model of the alpha345NC1 hexamer. In patients with Goodpasture's disease, both autoantibodies to the alpha3NC1 monomer and antibodies to the alpha5NC1 monomer (and fewer to the alpha4NC1 monomer) were bound in the kidneys and lungs, indicating roles for the alpha3NC1 and alpha5NC1 monomers as autoantigens. High antibody titers at diagnosis of anti-GBM disease were associated with ultimate loss of renal function. The antibodies bound to distinct epitopes encompassing region E(A) in the alpha5NC1 monomer and regions E(A) and E(B) in the alpha3NC1 monomer, but they did not bind to the native cross-linked alpha345NC1 hexamer. In contrast, in patients with Alport's post-transplantation nephritis, alloantibodies bound to the E(A) region of the alpha5NC1 subunit in the intact hexamer, and binding decreased on dissociation. The development of Goodpasture

  5. Dėl lie. kúopa ir kaũpas etimologinio siejimo

    Directory of Open Access Journals (Sweden)

    Simas Karaliūnas

    2011-05-01

    Full Text Available ON THE ETYMOLOGICAL IDENTIFICATION OF LITH. kúopa AND kaũpas SummaryThe paper deals with an etymological analysis of Lith. kúopa „crowd, throng, multitude; heap, pile etc.”, Latv. kuõpa „heap, pile; crowd etc.” and Lith. kaũpas „heap, pile”, which are supposed to stem from one and the same root. A thorough examination of these examples shows that they most likely belong to quite different roots from the etymological point of view, thus there is no basis to assume an apophony uo : au in Baltic. The vocalism uo of Lith. kúopa, Latv. kuõpa derived from Baltic ō represents e / o apophonic series. Lith. kúopa, Latv. kuõpa may be etymologically identified with the verbs Lith. kuõpti „clean; harvest, gather in; snatch, seize, grasp, grab, plunder”, Latv. kùopt „clean; apply, wait etc.”. The last two are the morphonological con­tinuants of the Baltic root *kep- (or *kap- „take, snatch, seize, grasp” represented by Lith. kė̃p­ti, Latv. ķept, ķêpît, Lith. kàptelėti, kàpterti, kàpalioti, kapaliúoti, kópti. The vocalism au of Lith. kaũpas belongs to и apophonic series. Lith. kaũpas, OPr. Caupe- (in the river name Caupeaps may be etymologically identified with the verb kaũpti „hill, earth up, hoe” (which in all probabi­lity is a denominative and derived from the Baltic root *keu-p-/*ku-p- „bend, turn out(wards, become convex (while growing sour, thriving, getting in heap” which is represented in Lith. kùpti, kupė́ti, Latv. kupt, kupêt, Lith. prisi-kiaupti, Latv. ķaũpêtiês.

  6. [The management of nurses' training school of PO KU NYO KWAN (1903~1933)].

    Science.gov (United States)

    Lee, Bang-weon

    2011-12-31

    This paper aims to examine the establishing background, curriculum and organization of personnel of Nurses' Training School of PO KU NYO KWAN(Caring For and Saving Woman's Hospital), the first nurses' training school in Korea. It is attempt to richen Korean medical history by the historical approach to modern nurses' training institution in Korea. PO KU NYO KWAN, the first women's hospital in Korea was established in 1887 by Metta Howard, who was sent by the Woman's Foreign Missionary Society of Northern Methodist Episcopal Church. Women doctors who were responsible for PO KU NYO KWAN felt the necessity of the professional nurses' training institution during performing medical activity with the help of Korean assistants and asked the Woman's Foreign Missionary Society to establish the nurses' training institution consistently. Margaret J. Edmunds was sent with the mission to establish nurses' training school in PO KU NYO KWAN. She made regulations for establishing nurses' training school, translated 'nurse' into "Gan-ho-won" in Korean language, made nurses' uniforms and prepared textbooks. Nurses' Training School of PO KU NYO KWAN was opened late December in 1903 officially. It had various subjects relating nursing in curriculum. The faculty of it was mainly comprised of medical missionaries of Methodist Episcopal Church and Presbyterian Church. Also the graduates of Severance Medical School and the graduates and students of Nurses' Training School of PO KU NYO KWAN participated its curriculum as teaching staff. In late 1920, Joseon Nurses Association (Joseon ganhobuhoe) discussed about the requirements for admission and the course of study for missionary nurses training school. After this process, students who were qualified for high-level class could have admission for Nurses' Training School of PO KU NYO KWAN. Medical staff belonged to East Gate Hospital and the graduates of Ewha College taught classes in it. First capping ceremony was held on January 25, 1906

  7. Renesansna kuća Moise u Cresu - rezultati konzervatorskih istraživanja 2011. godne

    Directory of Open Access Journals (Sweden)

    Tea Sušanj Protić

    2014-12-01

    Full Text Available Renesansnu stambenu arhitekturu grada Cresa obilježava manji broj očuvanih kuća (palazzetta creskog plemstva koje su atribuirane udomaćenoj kameno-klesarskoj radionici okupljenoj oko majstora Francesca Marangonicha, lombardskog kamenoklesara koji s venecijanskih gradilišta dolazi u Cres uvodeći stilske elemente renesanse na kvarnerske otoke. Najpoznatija renesansna stambena građevina u Cresu je kuća Marcello-Petris, izgrađena u prvom desetljeću 16. stoljeća prema narudžbi franjevačkog provincijala i biskupa fra Antuna Marcella-Petrisa. Patricijske renesansne kuće Cresa obilježavaju nešto veći gabariti, građa zida od pravilno klesanog kamena i stroži ritam ukrašenih otvora reprezentativnih pročelja. Jedna od tih građevina je kuća Moise, smještena u srednjovjekovnoj jezgri grada, na istaknutoj poziciji križanja onodobnih glavnih ulica. Dokumenti iz arhiva franjevačkog samostana u Cresu svjedoče da je 1441. godine „Ser Andrea Moisenich“ mijenjao vrt za kuću s „Nobilis Ser Stefano de Petris“ koji je palaču Petris izgradio prije 1405. godine, prema čemu bi današnja kuća Moise mogla biti starija palača Petris. Građevina nosi grbove obije obitelji iz istog razdoblja pa je mogla funckionirati kao dvo-obiteljska, što je čest slučaj i u Veneciji na primjerima većih palača s dva rezidencijalna kata i dva dvorišta, elementima koje posjeduje i kuća Moise. Kuća Moise najveća je stambena građevina renesansnog Cresa, u gabaritima usporediva s istaknutim primjerima većih palača u dalmatinskim gradovima. Zbog velikih preinaka, slabije očuvanosti izvornih značajki i umanjene reprezentativnosti nije bila predmetnom znanstvenih i stručnih istraživanja te nisu bile poznate njezine osnovne karakteristike. Konzervatorskim istraživanjima razjašnjena je tlocrtna organizacija i ustanovljen tlocrt koncipiran prema venecijanskom modelu središnje dvorane i četiri bočne prostorije, čime se građevina izdvojila

  8. Multifrequency Two-Dimensional Fourier Transform ESR: An X/Ku Band Spectrometer

    Science.gov (United States)

    Borbat, Petr P.; Crepeau, Richard H.; Freed, Jack H.

    1997-08-01

    A two-dimensional Fourier Transform ESR (2D FT ESR) spectrometer operating at 9.25 and 17.35 GHz is described. The Ku-band bridge uses an efficient heterodyne technique wherein 9.25 GHz is the intermediate frequency. At Ku-band the sensitivity is increased by almost an order of magnitude. One may routinely collect a full 2D ELDOR spectrum in less than 20 min for a sample containing 0.5-5 nmol of nitroxide spin-probe in the slow-motional regime. Broad spectral coverage at Ku-band is obtained by use of a bridged loop-gap resonator (BLGR) and of a dielectric ring resonator (DR). It is shown that an even more uniform spectral excitation is obtained by using shorter microwave pulses of about 3 ns duration. The dead-time at Ku-band is just 30-40 ns, yielding an improved SNR in 2D ELDOR spectra of nitroxide spin-probes withT2as short as 20-30 ns. A comparison of 2D ELDOR spectra obtained at 9.25 and 17.35 GHz for spin-labeled phospholipid probes (16PC) in 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) membrane vesicles showed that both spectra could be satisfactorily simulated using the same set of model parameters even though they are markedly different in appearance. The improved sensitivity and shorter dead-time at Ku-band made it possible to obtain orientation-dependent 2D ELDOR spectra of the Cholestane (CSL) spin-probe in macroscopically aligned lipid bilayers of egg yolk PC using samples containing only 1 mg of lipid and just 5 nmol of spin-probe.

  9. Künstlerische Irritationen in Unternehmen: Einsatzmöglichkeiten, Wirkungsvielfältigkeiten und Anregungspotenziale

    Directory of Open Access Journals (Sweden)

    Susanne Fenkart

    2014-06-01

    Full Text Available Der Artikel befasst sich im Sinne des Fortschrittsgedankens mit den Einsatz- und Wirkungsmöglichkeiten künstlerischer Irritationen in Unternehmen. Denn die Kunst ermöglicht es, bestehende Konstruktionen zu überprüfen und sich mit Alternativen auseinanderzusetzen, die dem System ansonsten selbst nicht zugänglich wären. Exemplarisch werden drei Fallgeschichten erzählt: Das erste Beispiel widmet sich dem Kunstkonzept der Unternehmensberatung Droege Group. Dabei wird die wirtschaftseigene Umgangsweise mit Kunst herausgearbeitet, gleichzeitig wird aber auch versucht, ausgelösten Irritationen im Unternehmen auf die Spur zu kommen. In der zweiten Fallgeschichte wird hingegen ein dezidiert künstlerischer Blickwinkel aufgezeigt: Hierbei wird das Projekt „8 x 5 x 363 + 1“ der Künstlerin Raphaëlle De Groot – es geht dabei um die Reflexion des Arbeitsalltages der Mitarbeiter_innen einer Tuchfabrik – vorgestellt und der künstlerische Beitrag zur Weiterentwicklung im Unternehmen thematisiert. Im dritten Fallbeispiel begegnet die künstlerische Irritation in Unternehmen dann als reines Kunstwerk: Die Arbeit „The Trainee“ der Künstlerin Pilvi Takala setzt sich mit den Rahmenbedingungen des Nachdenkens in Unternehmen sowie auch mit den Gepflogenheiten und Grenzen sozialer Gemeinschaften auseinander. Anhand dieser drei Beispiele wird also versucht, die Wirkungsvielfältigkeiten künstlerischer Irritationen aufzuzeigen und ein Nachdenken über mögliche Anregungspotenziale zu initiieren.

  10. Ku80蛋白在前列腺癌中表达的临床研究%The clinical study of Ku80 protein expression in the prostatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    黄锦坤; 吴文启; 梁叶萍; 欧莉莉; 罗金泰; 钟东亮; 雷鸣

    2012-01-01

    Objectives Discuss the relationship of Ku80 protein expression and the gleason score in prostatic carcinoma and serum PSA.Methods To Observae the histological pattern by HE staining in prostate carcinoma and detect the expression of Ku70 protein in the prostate carcinoma by immunohistochemical SP method.Then divide the 58 cases of prostate carcinoma specimens into two groups by according to the Gleason score of prostate cancer and divide into three groups by according to the PSA,compare the levels of Ku80 protein expression in each group.The datas were analyzed by Fisher's exact test and WILCOXON rank test.Furthermore,by SPEARMAN rank correlation analysis to compare the correlation in the intensity of Ku80 protein and the Gleason score,serum PSA in prostatic carcinoma.Results The positive expression of Ku80 protein in 58 cases of prostate carcinoma specimens,The expression intensity of Ku80 protein is positive correlation with Gleason score and serum PSA in the prostate carcinoma.According to Gleason grade prostate cancer.There have 27 cases in the 4 ~ 6 grade group,The strong positive expression of Ku80 protein levels were 11.11% ( 3/27 ),40.74% ( 11/27 ),48.15% ( 13/27 ).There have 31 cases in the 7 ~ 10 group,The strong positive expression of Ku80 protein levels were 3.23% ( 1/31 ),16.13% (5/31),80.65%(25/31).According to PSA value,the 58 cases of prostate carcinoma divide into the < 10ng/L group,the 10 ~20ng/L group and the > 20ng/L group.The strong positive expression of Ku80 protein levels in the three groups were 50.00% ( 6/12 ),62.68 % ( 18/29 ) and 82.35 % ( 14/17 ).The expression intensity of Ku70 protein is negative correlation with Gleason score and serum PSA in the prostate carcinoma.Conclusions The level of Ku80 protein expression is a valuable prognostic factor in the prostate carcinoma.%目的 探讨Ku80蛋白表达与前列腺癌血清PSA和前列腺癌Gleason分级之间的关系.方法 采用HE染色观察前列腺癌

  11. Autophagy inhibition sensitizes KU-0063794-mediated anti-HepG2 hepatocellular carcinoma cell activity in vitro and in vivo.

    Science.gov (United States)

    Yongxi, Tong; Haijun, Huang; Jiaping, Zheng; Guoliang, Shao; Hongying, Pan

    2015-09-25

    Recent studies have indicated that mammalian target of rapamycin (mTOR) signaling has a critical role in the pathogenesis of hepatocellular carcinoma (HCC). In the current study, we investigated the activity of KU-0063794, a novel mTOR kinase inhibitor, against HepG2 HCC cells. Our results demonstrated that KU-0063794 blocked mTOR complex 1/2 (mTORC1/2) activation, and downregulated mTOR-regulated genes (Cyclin D1 and hypoxia-inducible factor 1α) in HepG2 cells. Consequently, KU-0063794 induced significant anti-survival and pro-apoptotic activities against HepG2 cells. When analyzing the possible KU-0063794-resistance factors, we showed that KU-0063794 induced cyto-protective autophagy activation in HepG2 cells, evidenced by GFP-light chain 3B (LC3B) puncta formation, p62 degradation, Beclin-1 expression and LC3B-I to LC3B-II conversion. Correspondingly, autophagy inhibitors, including bafliomycin A1, 3-methyladenine (3-MA) and chloroquine, dramatically enhanced KU-0063794-induced cytotoxicity against HepG2 cells. Further, RNAi knockdown of Beclin-1 also increased KU-0063794 sensitivity in HepG2 cells. In vivo, oral administration of KU-0063794 repressed HepG2 xenograft growth in severe combined immunodeficient (SCID) mice, and its activity was further enhanced with co-administration of the autophagy inhibitor 3-MA. In summary, KU-0063794 inhibits HepG2 cell growth in vitro and in vivo, its activity could be further enhanced with autophagy inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. DNA-PKcs-OBA/Ku associate in the absence of DNA, as revealed by two-dimensional capillary gel electromobility shift assay.

    Science.gov (United States)

    Ruiz, Marcia T; Nichols, Amanda; Price, Gerald B; Zannis-Hadjopoulos, Maria

    2002-08-01

    Ors-binding activity (OBA) has been previously purified by its ability to specifically interact with A3/4, a 36-bp mammalian origin consensus sequence [1]. Peptide sequence analyses identified OBA as Ku86, the largest subunit of Ku antigen, a heterodimeric protein (Ku70/Ku86) involved in several autoimmune disorders [2-5]. The affinity-purified fraction containing OBA/Ku is also enriched for DNA-dependent protein kinase DNA-PKcs, the catalytic subunit of the DNA-PK holoenzyme, of which Ku antigen is the DNA-binding subunit [6-8]. Glycerol-gradient sedimentation analyses have demonstrated the presence of OBA/Ku in a high-molecular-weight complex. In order to investigate whether OBA/Ku and DNA-PKcs are associated in this fraction, we have used a modification of the two-dimensional gel electrophoresis technique originally described [9]. Electromobility shift assays were developed in native capillary gels, which were subsequently used for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the second dimension. The gels were then processed for Western blotting using the Ku70, Ku86 and DNA-PKcs antibodies. This approach has revealed the association of OBA/Ku and DNA-PKcs to give rise to the DNA-PK holoenzyme irrespective of the presence, or the absence of DNA. Altogether, we have proven the utility of this technique for the study of protein-protein and protein-DNA interactions.

  13. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Seho [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Lim, Chunghun [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Lee, Jae Young [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of); Song, Yoon-Jae [Department of Life Science, Kyungwon University, Seongnam-Si, Kyeonggi-Do 461-701 (Korea, Republic of); Park, Junsoo [Division of Biological Science and Technology, Yonsei University, Wonju 220-100 (Korea, Republic of); Choe, Joonho [Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701 (Korea, Republic of); Seo, Taegun, E-mail: tseo@dongguk.edu [Department of Life Science, Dongguk Univ-Seoul, Seoul 100-715 (Korea, Republic of)

    2010-04-16

    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  14. Renal cell apoptosis in human lupus nephritis: a histological study

    DEFF Research Database (Denmark)

    Faurschou, M; Penkowa, Milena; Andersen, C B

    2009-01-01

    Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney...... biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any...... cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis....

  15. Ku-mediated coupling of DNA cleavage and repair during programmed genome rearrangements in the ciliate Paramecium tetraurelia.

    Directory of Open Access Journals (Sweden)

    Antoine Marmignon

    2014-08-01

    Full Text Available During somatic differentiation, physiological DNA double-strand breaks (DSB can drive programmed genome rearrangements (PGR, during which DSB repair pathways are mobilized to safeguard genome integrity. Because of their unique nuclear dimorphism, ciliates are powerful unicellular eukaryotic models to study the mechanisms involved in PGR. At each sexual cycle, the germline nucleus is transmitted to the progeny, but the somatic nucleus, essential for gene expression, is destroyed and a new somatic nucleus differentiates from a copy of the germline nucleus. In Paramecium tetraurelia, the development of the somatic nucleus involves massive PGR, including the precise elimination of at least 45,000 germline sequences (Internal Eliminated Sequences, IES. IES excision proceeds through a cut-and-close mechanism: a domesticated transposase, PiggyMac, is essential for DNA cleavage, and DSB repair at excision sites involves the Ligase IV, a specific component of the non-homologous end-joining (NHEJ pathway. At the genome-wide level, a huge number of programmed DSBs must be repaired during this process to allow the assembly of functional somatic chromosomes. To understand how DNA cleavage and DSB repair are coordinated during PGR, we have focused on Ku, the earliest actor of NHEJ-mediated repair. Two Ku70 and three Ku80 paralogs are encoded in the genome of P. tetraurelia: Ku70a and Ku80c are produced during sexual processes and localize specifically in the developing new somatic nucleus. Using RNA interference, we show that the development-specific Ku70/Ku80c heterodimer is essential for the recovery of a functional somatic nucleus. Strikingly, at the molecular level, PiggyMac-dependent DNA cleavage is abolished at IES boundaries in cells depleted for Ku80c, resulting in IES retention in the somatic genome. PiggyMac and Ku70a/Ku80c co-purify as a complex when overproduced in a heterologous system. We conclude that Ku has been integrated in the Paramecium

  16. Ku-mediated coupling of DNA cleavage and repair during programmed genome rearrangements in the ciliate Paramecium tetraurelia.

    Science.gov (United States)

    Marmignon, Antoine; Bischerour, Julien; Silve, Aude; Fojcik, Clémentine; Dubois, Emeline; Arnaiz, Olivier; Kapusta, Aurélie; Malinsky, Sophie; Bétermier, Mireille

    2014-08-01

    During somatic differentiation, physiological DNA double-strand breaks (DSB) can drive programmed genome rearrangements (PGR), during which DSB repair pathways are mobilized to safeguard genome integrity. Because of their unique nuclear dimorphism, ciliates are powerful unicellular eukaryotic models to study the mechanisms involved in PGR. At each sexual cycle, the germline nucleus is transmitted to the progeny, but the somatic nucleus, essential for gene expression, is destroyed and a new somatic nucleus differentiates from a copy of the germline nucleus. In Paramecium tetraurelia, the development of the somatic nucleus involves massive PGR, including the precise elimination of at least 45,000 germline sequences (Internal Eliminated Sequences, IES). IES excision proceeds through a cut-and-close mechanism: a domesticated transposase, PiggyMac, is essential for DNA cleavage, and DSB repair at excision sites involves the Ligase IV, a specific component of the non-homologous end-joining (NHEJ) pathway. At the genome-wide level, a huge number of programmed DSBs must be repaired during this process to allow the assembly of functional somatic chromosomes. To understand how DNA cleavage and DSB repair are coordinated during PGR, we have focused on Ku, the earliest actor of NHEJ-mediated repair. Two Ku70 and three Ku80 paralogs are encoded in the genome of P. tetraurelia: Ku70a and Ku80c are produced during sexual processes and localize specifically in the developing new somatic nucleus. Using RNA interference, we show that the development-specific Ku70/Ku80c heterodimer is essential for the recovery of a functional somatic nucleus. Strikingly, at the molecular level, PiggyMac-dependent DNA cleavage is abolished at IES boundaries in cells depleted for Ku80c, resulting in IES retention in the somatic genome. PiggyMac and Ku70a/Ku80c co-purify as a complex when overproduced in a heterologous system. We conclude that Ku has been integrated in the Paramecium DNA cleavage

  17. Experimental research on Ku-band magnetically insulated transmission line oscillator

    Science.gov (United States)

    Jiang, Tao; Zhang, Jiande; He, Juntao; Li, Zhiqiang; Ling, Junpu

    2015-10-01

    An improved Ku-band magnetically insulated transmission line oscillator is proposed and investigated experimentally. In the particle-in-cell simulation, the Ku-band MILO generates the microwave with a power of 1.62 GW and a frequency of 13 GHz at the input voltage of 474 kV. The device is fabricated based on the simulation results, and an experiment system is designed. In the preliminary experiments, output microwave with frequency of 13.02 GHz, power of 150 MW, and pulse width of 17 ns is generated, under the diode voltage of 450 kV. Analysis on the experiment results shows that plasma produced due to the large current hitting to the outside of the collection tank is the essential cause for the low amplitude of the microwave power and short pulse width.

  18. Experimental research on Ku-band magnetically insulated transmission line oscillator

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Tao; Zhang, Jiande; He, Juntao; Li, Zhiqiang; Ling, Junpu [College of Optoelectric Science and Engineering, National University of Defense Technology, Hunan 410073 (China)

    2015-10-15

    An improved Ku-band magnetically insulated transmission line oscillator is proposed and investigated experimentally. In the particle-in-cell simulation, the Ku-band MILO generates the microwave with a power of 1.62 GW and a frequency of 13 GHz at the input voltage of 474 kV. The device is fabricated based on the simulation results, and an experiment system is designed. In the preliminary experiments, output microwave with frequency of 13.02 GHz, power of 150 MW, and pulse width of 17 ns is generated, under the diode voltage of 450 kV. Analysis on the experiment results shows that plasma produced due to the large current hitting to the outside of the collection tank is the essential cause for the low amplitude of the microwave power and short pulse width.

  19. Deletion of a KU80 homolog enhances homologous recombination in the thermotolerant yeast Kluyveromyces marxianus.

    Science.gov (United States)

    Choo, Jin Ho; Han, Changpyo; Kim, Jae-Young; Kang, Hyun Ah

    2014-10-01

    Targeted gene replacement in the thermotolerant yeast Kluyveromyces marxianus KCTC 17555 has been hampered by its propensity to non-homologous end joining (NHEJ). To enhance homologous recombination (HR) by blocking NHEJ, we identified and disrupted the K. marxianus KU80 gene. The ku80 deletion mutant strain (Kmku80∆) of K. marxianus KCTC 17555 did not show apparent growth defects under several conditions with the exception of exposure to tunicamycin. The targeted disruption of the three model genes, KmLEU2, KmPDC1, and KmPDC5, was increased by 13-70 % in Kmku80∆, although the efficiency was greatly affected by the length of the homologous flanking fragments. In contrast, the double HR frequency was 0-13.7 % in the wild-type strain even with flanking fragments 1 kb long. Therefore, Kmku80∆ promises to be a useful recipient strain for targeted gene manipulation.

  20. Design, fabrication and characterising of 100 W GaN HEMT for Ku-band application

    Science.gov (United States)

    Chunjiang, Ren; Shichang, Zhong; Yuchao, Li; Zhonghui, Li; Yuechan, Kong; Tangsheng, Chen

    2016-08-01

    Ku-band GaN power transistor with output power over 100 W under the pulsed operation mode is presented. A high temperature A1N nucleation together with an Fe doped GaN buffer was introduced for the developed GaN HEMT. The AlGaN/GaN hetero-structure deposited on 3 inch SiC substrate exhibited a 2DEG hall mobility and density of ˜2100 cm2/(V·s) and 1.0 × 1013 cm-2, respectively, at room temperature. Dual field plates were introduced to the designed 0.25 μm GaN HEMT and the source connected field plate was optimized for minimizing the peak field plate near the drain side of the gate, while maintaining excellent power gain performance for Ku-band application. The load-pull measurement at 14 GHz showed a power density of 5.2 W/mm for the fabricated 400 μm gate periphery GaN HEMT operated at a drain bias of 28 V. A Ku-band internally matched GaN power transistor was developed with two 10.8 mm gate periphery GaN HEMT chips combined. The GaN power transistor exhibited an output power of 102 W at 13.3 GHz and 32 V operating voltage under pulsed operation mode with a pulse width of 100 μs and duty cycle of 10%. The associated power gain and power added efficiency were 9.2 dB and 48%, respectively. To the best of the authors' knowledge, the PAE is the highest for Ku-band GaN power transistor with over 100 W output power.

  1. Utjecaj dodatka alkoholnog ekstrakta propolisa na fizikalno-kemljsku i mikrobiološku kvalitetu "MILPIA"

    OpenAIRE

    Mišanović, Đ.; N. Kezić; Capan, N.

    1993-01-01

    Svrha ovog rada bila je da se utvrdi utjecaj dodatka alkoholnog ekstrakta propolisa na fizikalno-kemijsku i mikrobiološku kvalitetu proizvoda Milpi. Određivani su slijedeći parametri: aktivna i titracijska kiselost, elektroprovodljivost i ukupan broj mikroorganizama. Rezultati istraživanja ukazuju na velik utjecaj dodatka alkoholnog ekstrakta propolisa na trajnost proizvoda "Milpi“ i ukupan broj mikroorganizama.

  2. Elaine Frantz Parsons, Ku-Klux: The Birth of the Klan during Reconstruction

    OpenAIRE

    Grandi, Elisa

    2017-01-01

    Il libro di Elaine Frantz Parsons, professoressa associata della Duquesne University (Pittsburgh, Pennsylvania) fornisce il primo resoconto dettagliato delle origini e dell’affermazione del Ku Klux Klan all’indomani della Guerra Civile. A differenza di altri episodi di violenza razziale che caratterizzarono gli anni immediatamente successivi alla sconfitta degli Stati del Sud, il Klan si affermò come un fenomeno radicalmente diverso, poggiando allo stesso tempo su di un forte radicamento loca...

  3. Development of intense terahertz coherent synchrotron radiation at KU-FEL

    Science.gov (United States)

    Sei, Norihiro; Zen, Heishun; Ohgaki, Hideaki

    2016-10-01

    We produced intense coherent synchrotron radiation (CSR) in the terahertz (THz) region using an S-band linac at the Kyoto University Free Electron Laser (KU-FEL), which is a mid-infrared free-electron laser facility. The CSR beam was emitted from short-pulse electron bunches compressed by a 180° arc, and was transferred to air at a large solid angle of 0.10 rad. The measured CSR energy was 55 μJ per 7 μs macropulse, and KU-FEL was one of the most powerful CSR sources in normal conducting linear accelerator facilities. The CSR spectra were measured using an uncooled pyroelectric detector and a Michelson-type interferometer designed specifically for the KU-FEL electron beam, and had a maximum at a frequency of 0.11 THz. We found that adjusting the energy slit enhanced the CSR energy and shortened the electron beam bunch length in the CSR spectra measurements. Our results demonstrated that the efficient use of the energy slit can help improve the characteristics of CSR.

  4. Oxidative DNA Damage in Neurons: Implication of Ku in Neuronal Homeostasis and Survival

    Directory of Open Access Journals (Sweden)

    Daniela De Zio

    2012-01-01

    Full Text Available Oxidative DNA damage is produced by reactive oxygen species (ROS which are generated by exogenous and endogenous sources and continuously challenge the cell. One of the most severe DNA lesions is the double-strand break (DSB, which is mainly repaired by nonhomologous end joining (NHEJ pathway in mammals. NHEJ directly joins the broken ends, without using the homologous template. Ku70/86 heterodimer, also known as Ku, is the first component of NHEJ as it directly binds DNA and recruits other NHEJ factors to promote the repair of the broken ends. Neurons are particularly metabolically active, displaying high rates of transcription and translation, which are associated with high metabolic and mitochondrial activity as well as oxygen consumption. In such a way, excessive oxygen radicals can be generated and constantly attack DNA, thereby producing several lesions. This condition, together with defective DNA repair systems, can lead to a high accumulation of DNA damage resulting in neurodegenerative processes and defects in neurodevelopment. In light of recent findings, in this paper, we will discuss the possible implication of Ku in neurodevelopment and in mediating the DNA repair dysfunction observed in certain neurodegenerations.

  5. Alterations in cellular energy metabolism associated with the antiproliferative effects of the ATM inhibitor KU-55933 and with metformin.

    Directory of Open Access Journals (Sweden)

    Mahvash Zakikhani

    Full Text Available KU-55933 is a specific inhibitor of the kinase activity of the protein encoded by Ataxia telangiectasia mutated (ATM, an important tumor suppressor gene with key roles in DNA repair. Unexpectedly for an inhibitor of a tumor suppressor gene, KU-55933 reduces proliferation. In view of prior preliminary evidence suggesting defective mitochondrial function in cells of patients with Ataxia Telangiectasia (AT, we examined energy metabolism of cells treated with KU-55933. The compound increased AMPK activation, glucose uptake and lactate production while reducing mitochondrial membrane potential and coupled respiration. The stimulation of glycolysis by KU-55933 did not fully compensate for the reduction in mitochondrial functions, leading to decreased cellular ATP levels and energy stress. These actions are similar to those previously described for the biguanide metformin, a partial inhibitor of respiratory complex I. Both compounds decreased mitochondrial coupled respiration and reduced cellular concentrations of fumarate, malate, citrate, and alpha-ketogluterate. Succinate levels were increased by KU-55933 levels and decreased by metformin, indicating that the effects of ATM inhibition and metformin are not identical. These observations suggest a role for ATM in mitochondrial function and show that both KU-55933 and metformin perturb the TCA cycle as well as oxidative phosphorylation.

  6. Evidence for an inositol hexakisphosphate-dependent role for Ku in mammalian nonhomologous end joining that is independent of its role in the DNA-dependent protein kinase

    Science.gov (United States)

    Cheung, Joyce C.Y.; Salerno, Brenda; Hanakahi, Les A.

    2008-01-01

    Nonhomologous end-joining (NHEJ) is an important pathway for the repair of DNA double-strand breaks (DSBs) and plays a critical role in maintaining genomic stability in mammalian cells. While Ku70/80 (Ku) functions in NHEJ as part of the DNA-dependent protein kinase (DNA-PK), genetic evidence indicates that the role of Ku in NHEJ goes beyond its participation in DNA-PK. Inositol hexakisphosphate (IP6) was previously found to stimulate NHEJ in vitro and Ku was identified as an IP6-binding factor. Through mutational analysis, we identified a bipartite IP6-binding site in Ku and generated IP6-binding mutants that ranged from 1.22% to 58.48% of wild-type binding. Significantly, these Ku IP6-binding mutants were impaired for participation in NHEJ in vitro and we observed a positive correlation between IP6 binding and NHEJ. Ku IP6-binding mutants were separation-of-function mutants that bound DNA and activated DNA-PK as well as wild-type Ku. Our observations identify a hitherto undefined IP6-binding site in Ku and show that this interaction is important for DSB repair by NHEJ in vitro. Moreover, these data indicate that in addition to binding of exposed DNA termini and activation of DNA-PK, the Ku heterodimer plays a role in mammalian NHEJ that is regulated by binding of IP6. PMID:18776215

  7. Deformed epidermal autoregulatory factor-1 (DEAF1 interacts with the Ku70 subunit of the DNA-dependent protein kinase complex.

    Directory of Open Access Journals (Sweden)

    Philip J Jensik

    Full Text Available Deformed Epidermal Autoregulatory Factor 1 (DEAF1 is a transcription factor linked to suicide, cancer, autoimmune disorders and neural tube defects. To better understand the role of DEAF1 in protein interaction networks, a GST-DEAF1 fusion protein was used to isolate interacting proteins in mammalian cell lysates, and the XRCC6 (Ku70 and the XRCC5 (Ku80 subunits of DNA dependent protein kinase (DNA-PK complex were identified by mass spectrometry, and the DNA-PK catalytic subunit was identified by immunoblotting. Interaction of DEAF1 with Ku70 and Ku80 was confirmed to occur within cells by co-immunoprecipitation of epitope-tagged proteins, and was mediated through interaction with the Ku70 subunit. Using in vitro GST-pulldowns, interaction between DEAF1 and the Ku70 subunit was mapped to the DEAF1 DNA binding domain and the C-terminal Bax-binding region of Ku70. In transfected cells, DEAF1 and Ku70 colocalized to the nucleus, but Ku70 could not relocalize a mutant cytoplasmic form of DEAF1 to the nucleus. Using an in vitro kinase assay, DEAF1 was phosphorylated by DNA-PK in a DNA-independent manner. Electrophoretic mobility shift assays showed that DEAF1 or Ku70/Ku80 did not interfere with the DNA binding of each other, but DNA containing DEAF1 binding sites inhibited the DEAF1-Ku70 interaction. The data demonstrates that DEAF1 can interact with the DNA-PK complex through interactions of its DNA binding domain with the carboxy-terminal region of Ku70 that contains the Bax binding domain, and that DEAF1 is a potential substrate for DNA-PK.

  8. Identification of ku70 as a Novel Transcriptional Coactivator of AP-2α%一类新的AP-2α转录共激活物Ku 70蛋白的鉴定

    Institute of Scientific and Technical Information of China (English)

    黄前川; 曹军皓; 季蒙

    2009-01-01

    目的 鉴定新的AP-2α转录共激活物,为乳腺癌的防治寻找新的靶点.方法 以AP-2α为诱饵采用酵母双杂交技术寻找新的AP-2α结合蛋白,免疫共沉淀证实AP-2α与其结合蛋白的相互作用,免疫荧光技术检测AP-2α与其结合蛋白的亚细胞共定位.荧光素酶报导基因检测AP-2α结合蛋白对AP-2α转录活性的影响.结果 酵母双杂交技术鉴定出Ku 70蛋白为新的AP-2α结合蛋白.免疫共沉淀证实了AP-2α和Ku 70蛋白在细胞内的相互作用.亚细胞共定位研究显示AP-2α和Ku 70蛋白都定位于细胞核内.在功能上发现Ku70可以增强AP-2α的转录活性.结论 本研究首次揭示Ku70可以结合AP-2α并促进其转录活性,证明Ku70是一类新的AB-2α的转录共激活物,提示Ku70有望成为治疗AP-2α高表达乳腺癌的新靶点.

  9. Differential expression of glutamic acid decarboxylase in rat and human islets

    DEFF Research Database (Denmark)

    Petersen, J S; Russel, S; Marshall, M O;

    1993-01-01

    The GABA synthesizing enzyme GAD is a prominent islet cell autoantigen in type I diabetes. The two forms of GAD (GAD64 and GAD67) are encoded by different genes in both rats and humans. By in situ hybridization analysis of rat and human pancreases, expression of both genes was detected in rat isl...

  10. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents.

    OpenAIRE

    Honeyman, M C; Stone, N. L.; Harrison, L. C.

    1998-01-01

    The tyrosine phosphatase IA-2 is a molecular target of pancreatic islet autoimmunity in type 1 diabetes. T-cell epitope peptides in autoantigens have potential diagnostic and therapeutic applications, and they may hold clues to environmental agents with similar sequences that could trigger or exacerbate autoimmune disease. We identified 13 epitope peptides in IA-2 by measuring peripheral blood T-cell proliferation to 68 overlapping, synthetic peptides encompassing the intracytoplasmic domain ...

  11. Comparison of in vivo efficacy of hypoxic cytotoxin tirapazamine and hypoxic cell radiosensitizer KU-2285 in combination with single and fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Shibata, Toru; Shibamoto, Yuta; Sasai, Keisuke; Oya, Natsuo; Murata, Rumi; Takagi, Takehisa; Hiraoka, Masahiro [Kyoto Univ. (Japan). Chest Disease Research Inst.; Abe, Mitsuyuki

    1996-01-01

    Development of strategies to eradicate radioresistant hypoxic cells would be of great benefit for clinical radiotherapy. In the present study, the in vivo effects of promising hypoxic cytotoxin, tirapazamine (3-amino-1,2,4-benzotriazine 1,4-di-N-oxide), were examined in comparison with those of KU-2285, one of the best hypoxic cell radiosensitizers, in combination with both single and fractionated irradiation. The tumor response was assessed by the standard in vivo-in vitro clonogenic assay using SCCVII tumors in C3H mice and EMT-6/KU tumors in Balb/c mice with different characteristics of tumor hypoxia. With single-dose irradiation (18 Gy), both tirapazamine and KU-2285 showed significant enhancement of cell killing in a dose-dependent manner, but tirapazamine was more effective for SCCVII tumors with acutely hypoxic cells, while KU-2285 was more effective for EMT-6/KU tumors predominantly with chronically hypoxic cells. In fractionated irradiation regimens (4 fractions of 5 Gy at 12 h intervals), tirapazamine showed more marked combined effects at 10 and 20 mg/kg than KU-2285 at 100-200 mg/kg in both SCCVII and EMT-6/KU tumors. We concluded that the effectiveness of KU-2285 and tirapazamine was correlated with the nature of tumor hypoxia with single-dose irradiation, whereas tirapazamine appeared more potent than KU-2285 with fractionated irradiation. These findings suggest the potential usefulness of tirapazamine in clinical fractionated radiotherapy. (author).

  12. Simulation of radar backscattering from snowpack at X-band and Ku-band

    Science.gov (United States)

    Gay, Michel; Phan, Xuan-Vu; Ferro-Famil, Laurent

    2016-04-01

    This paper presents a multilayer snowpack electromagnetic backscattering model, based on Dense Media Radiative Transfer (DMRT). This model is capable of simulating the interaction of electromagnetic wave (EMW) at X-band and Ku-band frequencies with multilayer snowpack. The air-snow interface and snow-ground backscattering components are calculated using the Integral Equation Model (IEM) by [1], whereas the volume backscattering component is calculated based on the solution of Vector Radiative Transfer (VRT) equation at order 1. Case study has been carried out using measurement data from NoSREx project [2], which include SnowScat data in X-band and Ku-band, TerraSAR-X acquisitions and snowpack stratigraphic in-situ measurements. The results of model simulations show good agreement with the radar observations, and therefore allow the DMRT model to be used in various applications, such as data assimilation [3]. [1] A.K. Fung and K.S. Chen, "An update on the iem surface backscattering model," Geoscience and Remote Sensing Letters, IEEE, vol. 1, no. 2, pp. 75 - 77, april 2004. [2] J. Lemmetyinen, A. Kontu, J. Pulliainen, A. Wiesmann, C. Werner, T. Nagler, H. Rott, and M. Heidinger, "Technical assistance for the deployment of an x- to ku-band scatterometer during the nosrex ii experiment," Final Report, ESA ESTEC Contract No. 22671/09/NL/JA., 2011. [3] X. V. Phan, L. Ferro-Famil, M. Gay, Y. Durand, M. Dumont, S. Morin, S. Allain, G. D'Urso, and A. Girard, "3d-var multilayer assimilation of x-band sar data into a detailed snowpack model," The Cryosphere Discussions, vol. 7, no. 5, pp. 4881-4912, 2013.

  13. Ku80高表达对肝癌SMMC7721细胞凋亡的影响%Effect of Ku80 re-expression on cell apoptosis in hepatocellular carcinoma SMMC7721 cells

    Institute of Scientific and Technical Information of China (English)

    魏双; 黄志勇; 王洋洋; 纪桂宝; 占大钱

    2011-01-01

    目的 观察Ku80高表达对SMMC7721肝癌细胞凋亡的影响。方法 将Ku80基因转染到SMMC7721细胞;流式细胞术和TUNEL法检测细胞凋亡;Western blot检测凋亡相关蛋白表达。结果 筛选获得稳定高表达Ku80的克隆细胞;流式检测显示,Ku80高表达克隆的凋亡率(9.44±1.52)%和(9.26±1.72)%与对照组(1.81±0.15)%和(1.83±0.25%)比较轻度增高,差异有统计学意义(P <0.05);TUNEL实验显示,Ku80高表达克隆形成裸鼠皮下瘤的凋亡率(9.3±2.0)%和(10.0±2.1)%与对照组(3.5±1.0)%和(3.6±1.1)%比较轻度增高,差异有统计学意义(P<0.05);Western blot检测显示,Ku80高表达克隆cleaved PARP-1、active Caspase-3和cleaved Caspase-9的表达与对照组比较明显增高,bcl-2的表达减低,而bax无变化。结论 体内外实验均证实Ku80高表达可引起SMMC7721细胞凋亡轻度增加。%Objective To investigate the effect of Ku80 re-expression on cell apoptosis in hepatocellular carcinoma (HCC) SMMC7721 cells. Methods PcDNA3. 1 ( + )-myc-his-Ku80 and pcDNA3. 1( + )-myc-his expressive plasmids were transfected into Ku80 deficient SMMC7721 HCC cells. The cell apoptotic rates were analyzed by facial action coding system (FACS). The expression of cell apoptosis related regulators were analyzed by Western blotting. Cell apoptotic levels in xenograft tumor tissue were detected by TUNEL assay. Results The Western blotting analysis confirmed that Ku80-transfected cells expressed high protein levels of Ku80,whereas the vector-transfected and the parental SMMC7721 cells lacked Ku80 expression. FACS analysis indicated that, the apoptotic rates in SMMC7721, vector-transfected cells and the two Ku80-expressing clones were (9.44 ±1.52)%, (9.26 ±1.72)% ; (1.81 ±0. 15)% and (1.83 ±0. 25) %, respectively. There was a significant difference in cell apoptotic rate between Ku80-expressing clones group and SMMC7721 or vector-transfected cells group ( P < 0. 05 ). TUNEL

  14. Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome.

    Science.gov (United States)

    Kalluri, R; Wilson, C B; Weber, M; Gunwar, S; Chonko, A M; Neilson, E G; Hudson, B G

    1995-10-01

    Antiglomerular basement membrane (GBM) antibodies can cause glomerulonephritis or pulmonary hemorrhage by themselves or Goodpasture syndrome when they occur together. It is unknown if variations in antibody reactivity contribute to the different patterns of organ involvement seen in this disease. This study examines the reactivity of the alpha 1-alpha 6 NC1 domains of Type IV collagen, the putative autoantigen, in sera from patients with anti-GBM antibodies after various clinical presentations of lung hemorrhage and renal injury. Serum or plasma containing anti-GBM antibodies from 35 patients with combined glomerulonephritis and pulmonary hemorrhage, 19 with glomerulonephritis alone, and 4 with pulmonary hemorrhage alone were compared with samples from 19 normal controls and 32 patients with other kidney diseases. Four different immunologic assays were performed with bovine alpha 1-alpha 6(IV) and recombinant human type alpha 1-alpha 5(IV) collagen NC1 domains. The study found that the anti-GBM antibodies from all patients reacted with the alpha 3(IV) NC1 (85% exclusively). Additional limited reactivity with the alpha 1(IV) NC1 and alpha 4(IV) NC1 was found in 15 and 3%, respectively. This non-alpha 3(IV) NC1 reactivity was most frequent in the patients with anti-GBM antibodies and glomerulonephritis alone. None of the patients had reactivity to other basement membrane components like laminin, fibronectin, heparan sulfate proteoglycan, entactin, or the 7S and triple helical fragments of Type IV collagen. The observed alpha-chain NC1 reactivity was confined to patients with anti-GBM antibodies with no additional reactivities detected among a large number of other kidney diseases controls. The correlation of alpha 1-alpha 6(IV) NC1 reactivity in a large number of patients with anti-GBM antibodies defined by classic assays definitively establishes that reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary for the expression of autoimmune disease

  15. Shuttle Ku-band bent-pipe implementation considerations. [for Space Shuttle digital communication systems

    Science.gov (United States)

    Batson, B. H.; Seyl, J. W.; Huth, G. K.

    1977-01-01

    This paper describes an approach for relay of data-modulated subcarriers from Shuttle payloads through the Shuttle Ku-band communications subsystem (and subsequently through a tracking and data relay satellite system to a ground terminal). The novelty is that a channel originally provided for baseband digital data is shown to be suitable for this purpose; the resulting transmission scheme is referred to as a narrowband bent-pipe scheme. Test results demonstrating the validity of the narrowband bent-pipe mode are presented, and limitations on system performance are described.

  16. Analysis of Standards Efficiency in Digital Television Via Satellite at Ku and Ka Bands

    Directory of Open Access Journals (Sweden)

    Landeros-Ayala Salvador

    2013-06-01

    Full Text Available In this paper, an analysis on the main technical features of digital television standards for satellite transmission is carried out. Based on simulations and link budgets, the standard with the best operational performance is defined, based on simulations and link budget analysis, as well as a comparative efficiency analysis is conducted for the Ku and Ka bands for both transparent and regenerative transponders in terms of power, bandwidth, information rate and link margin, including clear sky, uplink rain, downlink rain and rain in both.

  17. Ku Klux Rising : toward an understanding of American right wing terrorist campaigns

    OpenAIRE

    Brister, Paul D.

    2011-01-01

    Since 1866, the Ku Klux Klan has been able to muster three distinctive and sustained campaigns of terrorism, commonly referred to as the three "waves" of Klan violence. The first occurred between 1866 and 1871, the second between 1915 and 1928, and the third from roughly 1954 to the mid-1960s. Subsequent to the third wave, the Klan unsuccessfully attempted another resurgence in the mid-1970s/early 1980s but was snuffed out before a campaign could be triggered. By studying the three most s...

  18. Hatred and Profits: Getting Under the Hood of the Ku Klux Klan

    OpenAIRE

    Roland G. Fryer, Jr; Steven D. Levitt

    2007-01-01

    The Ku Klux Klan reached its heyday in the mid-1920s, claiming millions of members. In this paper, we analyze the 1920s Klan, those who joined it, and the social and political impact that it had. We utilize a wide range of newly discovered data sources including information from Klan membership roles, applications, robe-order forms, an internal audit of the Klan by Ernst and Ernst, and a census that the Klan conducted after an internal scandal. Combining these sources with data from the 1920 ...

  19. Chemical compatibility study of Cooley L18KU, Herculite, and Elephant Mat with Hanford tank waste

    Energy Technology Data Exchange (ETDEWEB)

    Mercado, J.E.

    1998-06-23

    An independent chemical compatibility review of various wrapping and absorbent/padding materials was conducted to evaluate resistance to chemicals and constituents present in liquid waste from the Hanford underground tanks. These materials will be used to wrap long-length contaminated equipment when such equipment is removed from the tanks and prepared for transportation and subsequent disposal or storage. The materials studied were Cooley L18KU, Herculite, and Elephant Mat. The study concludes that these materials are appropriate for use in this application.

  20. Ku-band radar penetration into snow cover Arctic sea ice using airborne data

    OpenAIRE

    Willatt, R.; Laxon, S.; Giles, K.; R. Cullen; Haas, C.; V. Helm

    2011-01-01

    Satellite radar altimetry provides data to monitor winter Arctic sea-ice thickness variability on interannual, basin-wide scales. When using this technique an assumption is made that the peak of the radar return originates from the snow/ice interface. This has been shown to be true in the laboratory for cold, dry snow as is the case on Arctic sea ice during winter. However, this assumption has not been tested in the field. We use data from an airborne normal-incidence Ku-band radar altimeter ...

  1. Izrada 3D modela kućišta centrifugalne pumpe

    OpenAIRE

    Hršak, Božidar; Golubić, Stjepan; Carek, Dalibor

    2012-01-01

    Prikazana je izrada 3D modela kućišta centrifugalne pumpe na temelju postojećeg 2D nacrta gotovog proizvoda primjenom sinkrone tehnologije 3D modeliranja, i reverzibilnog inženjeringa. Na temelju kreiranog 3D modela, predložene su moguće modifikacije postojeće izvedbe proizvoda. Provedene su analize zakrivljenosti površina, Bézierove krivulje modela i 3D geometrije. Prikazana je i mogućnost vizualizacije gotovog 3D modela na Web stranicama u cilju prezentiranja proizvoda budućim kupcima primj...

  2. Izrada 3D modela kućišta ravnog ventila DN 50

    OpenAIRE

    Hršak, Božidar; Golubić, Stjepan; Bošnjak, Matej

    2012-01-01

    Prikazana je izrada 3D modela kućišta centrifugalne pumpe na temelju postojećeg 2D nacrta gotovog proizvoda primjenom sinkrone tehnologije 3D modeliranja, i reverzibilnog inženjeringa. Na temelju kreiranog 3D modela, predložene su moguće modifikacije postojeće izvedbe proizvoda. Provedene su analize zakrivljenosti površina, Bézierove krivulje modela i 3D geometrije. Prikazana je i mogućnost vizualizacije gotovog 3D modela na Web stranicama u cilju prezentiranja proizvoda budućim kupcima primj...

  3. 6株旋毛虫49ku ES抗原基因克隆及序列分析%Cloning and sequence analysis of 49 ku ES antigen gene of six Trichinella spp.strains

    Institute of Scientific and Technical Information of China (English)

    路义鑫; 韩彩霞; 李晓云; 董晓波; 宋铭忻

    2011-01-01

    49 ku ES antigen gene of six different strains of Trichinella spp. Were cloned by RT-PCR, then the cloned sequences and the corresponding sequence of T. Spiralis in GenBank were aligned and compared. The results showed that 49 ku ES gene of Trichinella spp. Were highly conserved, shared high similarities on the levels of nucleotides and amino acids, more than 97.2% and 94.0%, respectively. Therefore, the gene could not well identify different species of Trichinella spp. Encoded protein analysis showed the identity in antigenicity of the six strains, suggesting just one strain the recombinant antigen could be used to detect antiserum against P49 protein of different Trichinella spp.%应用RT-PCR方法从不同来源的6株旋毛虫肌幼虫总RNA中克隆49 ku ES抗原基因序列,与GenBank中T.spiralis相应序列进行比对分析.结果表明,旋毛虫49 ku ES基因具有相当强的保守性,不同虫株核苷酸和氨基酸序列的同源性分别达97.2%和94.0%以上,序列间差异很小,不能较好地区分各旋毛虫种;该基因编码蛋白的抗原性很稳定,不同旋毛虫49 ku ES抗原性几乎没有差别,只要获得一个虫株的重组49 ku ES蛋白,即可用于其他不同种株旋毛虫病的免疫诊断及预防.

  4. Ku70 acetylation and modulation of c-Myc/ATF4/CHOP signaling axis by SIRT1 inhibition lead to sensitization of HepG2 cells to TRAIL through induction of DR5 and down-regulation of c-FLIP

    DEFF Research Database (Denmark)

    Kim, Mi-Ju; Hong, Kyung-Soo; Kim, Hak-Bong

    2013-01-01

    In this study, we investigated the role of c-Myc/ATF4/CHOP signaling pathway in sensitization of human hepatoma HepG2 cells to TRAIL. Knockdown of SIRT1 or treatment with SIRT1 inhibitor caused the up-regulation of DR5 and down-regulation of c-FLIP through modulation of c-Myc/ATF4/CHOP pathway......, and subsequently enhanced the cytotoxic and apoptotic effects of TRAIL on HepG2 cells. Interestingly, SIRT1 interacted directly with c-FLIP(L) and Ku70, and treatment with SIRT1 inhibitor enhanced acetylation of Ku70 and subsequently decreased its binding to c-FLIP. And this was followed by degradation of c....... These findings reveal for the first time that SIRT1 inhibition increases Ku70 acetylation, and the acetylated Ku70 with a decreased function mediates the induction of DR5 and the down-regulation of c-FLIP by up-regulating c-Myc/ATF4/CHOP pathway, and consequently promotes the TRAIL-induced apoptosis of HepG2...

  5. KU-55933 depresses temozolomide-induced autophagy in U87 glioma cell%KU-55933抑制替莫唑胺诱导的U87胶质瘤细胞自噬

    Institute of Scientific and Technical Information of China (English)

    邹宇辉; 王伟民

    2015-01-01

    目的 研究KU-55933对替莫唑胺(TMZ)诱导的U87细胞自噬及TMZ毒性的影响及机制.方法 U87细胞分别给予5、10、15、20 μmol/L KU-55933作用72 h,或10 μmol/L KU-55933作用24、48、72、96 h,MTT法检测细胞增殖.U87细胞分别给予DMSO、100 μmol/L TMZ、10 μmol/L KU-55933、100 μmol/L TMZ+ 10 μmol/L KU-55933作用72 h,流式细胞术检测自噬小体,Western blot检测相关蛋白的表达.结果 KU-55933抑制U87细胞的增殖,并呈剂量及时间依赖性;KU-55933抑制TMZ诱导的共济失调突变蛋白(ataxia-telangiectasia mutated,ATM)、自噬激活激酶(unc-51 like autophagy activating kinase 1,ULK1)、P53蛋白磷酸化,降低微管相关蛋白(microtubule-associated protein 1 light chain 3 beta,LC3B)裂解,减少自噬小体的生成,增加TMZ敏感细胞组蛋白亚型γH2AX的形成,但对细胞周期检测点激酶1(checkpoint kinase 1,Chk1)、细胞周期检测点激酶2 (checkpoint kinase 2,Chk2)蛋白磷酸化无影响.结论 KU-55933可抑制TMZ诱导的胶质瘤细胞自噬,并且增强TMZ对敏感胶质瘤的细胞毒性.

  6. Analysis of a Compact Wideband Slotted Antenna for Ku Band Applications

    Directory of Open Access Journals (Sweden)

    M. R. Ahsan

    2014-01-01

    Full Text Available The design procedure and physical module of a compact wideband patch antenna for Ku band application are presented in this paper. Finite element method based on 3D electromagnetic field solver has been utilized for the designing and analyzing process of proposed microstrip line fed modified E-H shaped electrically small patch antenna. After successful completion of the design process through various simulations, the proposed antenna has been fabricated on printed circuit board (PCB and its characteristics have been studied. The parameters of the proposed antenna prototype have been measured in standard far-field rectangular shape anechoic measurement compartment. It is apparent from the measured antenna parameters that the proposed antenna achieved almost stable variation of radiation pattern over the entire operational band with 1380 MHz of -10 dB return loss bandwidth. The maximum gain of 7.8 dBi and 89.97% average efficiency within the operating band from 17.15 GHz to 18.53 GHz ensure the suitability of the proposed antenna for Ku band applications.

  7. Shuttle Ku-band and S-band communications implementation study

    Science.gov (United States)

    Dodds, J. G.; Huth, G. K.; Nilsen, P. W.; Polydoros, A.; Simon, M. K.; Weber, C. L.

    1980-05-01

    Various aspects of the shuttle orbiter S-band network communication system, the S-band payload communication system, and the Ku-band communication system are considered. A method is proposed for obtaining more accurate S-band antenna patterns of the actual shuttle orbiter vehicle during flight because the preliminary antenna patterns using mock-ups are not realistic that they do not include the effects of additional appendages such as wings and tail structures. The Ku-band communication system is discussed especially the TDRS antenna pointing accuracy with respect to the orbiter and the modifications required and resulting performance characteristics of the convolutionally encoded high data rate return link to maintain bit synchronizer lock on the ground. The TDRS user constraints on data bit clock jitter and data asymmetry on unbalanced QPSK with noisy phase references are included. The S-band payload communication system study is outlined including the advantages and experimental results of a peak regulator design built and evaluated by Axiomatrix for the bent-pipe link versus the existing RMS-type regulator. The nominal sweep rate for the deep-space transponder of 250 Hz/s, and effects of phase noise on the performance of a communication system are analyzed.

  8. Rainfall measurement from opportunistic use of earth-space link in Ku Band

    Directory of Open Access Journals (Sweden)

    L. Barthès

    2013-02-01

    Full Text Available The present study deals with the development of a low cost microwave device devoted to measure average rain rate observed along earth – satellite links. The principle is to use rain atmospheric attenuation along Earth – space links in Ku-band to deduce the path averaged rain rate. These links are characterized by a path length of a few km through the troposphere. Ground based power measurements are carried out by receiving TV channels from different geostationary satellites in Ku-band.

    The major difficulty in this study is to retrieve rain characteristics among many fluctuations of the received signal which are due to atmospheric scintillations, changes in the composition of the atmosphere (water vapour concentration, cloud water content or satellite features (variation of the emitted power, satellite motions. In order to perform a feasibility study of such a device, a measurement campaign has been performed for five months near Paris. This paper proposes an algorithm based on an artificial neural network to identify drought and rainy periods and to suppress the variability of the received signal due to no-rain effects. Taking into account the height of the rain layer, rain attenuation is then inverted to obtain path averaged rain rate. Obtained rainfall rates are compared with co-located rain gauges and radar measurements on the whole experiment period, then the most significant rainy events are analyzed.

  9. Abnormal DNA-PKcs and Ku 70/80 expression may promote malignant pathological processes in gastric carcinoma.

    Science.gov (United States)

    Li, Wei; Xie, Chuan; Yang, Zhen; Chen, Jiang; Lu, Nong-Hua

    2013-10-28

    To determine the expression of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and the Ku70/Ku80 heterodimer (Ku 70/80) in gastric carcinoma. Gastric biopsies were obtained from 146 gastric carcinoma patients [Helicobacter pylori (H. pylori)-negative: 89 and H. pylori-positive: 57] and 34 from normal subjects (H. pylori-negative: 16 and H. pylori-positive: 18) via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University. Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system. An ''in-house'' rapid urease test and modified Giemsa staining were employed to detect H. pylori infection. The expression of DNA-PKcs and the Ku 70/80 protein was detected by immunohistochemistry. Overall, the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer (χ(2) = 133.04, P gastric mucosa. There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa, and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0% (0/34), whereas the rate in gastric cancer (GC) was 93.8% (137/146). The difference between the two groups was statistically significant. Additionally, the positive rate of Ku 70/80 was 79.4% (27/34) in normal gastric mucosa and 96.6% (141/146) in gastric cancer. The DNA-PKcs protein level was significantly increased in gastric cancer (Mann-Whitney U = 39.00, P gastric mucosa. In addition, there was a significant difference in the expression of Ku 70/80 (Mann-Whitney U = 1117.00, P gastric cancer and normal gastric mucosa. There was also a significant difference in Ku70/80 protein expression between GC patients with and without H. pylori infection (P gastric carcinoma.

  10. Microwave absorption in X and Ku band frequency of cotton fabric coated with Ni-Zn ferrite and carbon formulation in polyurethane matrix

    Science.gov (United States)

    Gupta, K. K.; Abbas, S. M.; Goswami, T. H.; Abhyankar, A. C.

    2014-08-01

    The present study highlights various microwave properties, i.e. reflection, transmission, absorption and reflection loss, of the coated cotton fabric [formulation: Ni-Zn ferrite (Ni 0.5Zn0.5Fe2O4) and carbon black (acetylene black) at concentrations of 30, 40, 50, 60 and70 g of ferrite and 5 g carbon in each 100 ml polyurethane] evaluated at 8-18 GHz frequency. The uniform density of filling materials in coated fabrics (dotted marks in SEM micrograph) indicates homogeneous dispersion of conducting fillers in polyurethane and the density of filling material cluster increases with increase in ferrite concentration. SEM images also show uniform coating of conducting fillers/resin system over individual fibers and interweave spaces. The important parameters governing the microwave properties of coated fabrics i.e. permittivity and permeability, S-parameters, reflection loss, etc. were studied in a HVS free space microwave measurement system. The lossy character of coated fabric is found to increase with increase of ferrite content; the ferrite content decreases the impedance and increases the permittivity and permeability values. The 1.6-1.8 mm thick coated fabric sample (40 wt% ferrite, 3 wt% carbon and 57 wt% PU) has shown about 40% absorption, 20% transmission and 40% reflectance in X (8.2-12.4 GHz) and Ku (12-18 GHz) frequency bands. The reflection loss at 13.5 GHz has shown the highest peak value (22.5 dB) due to coated sample optical thickness equal to λ/4 and more than 7.5 dB in entire Ku band. Owing to its thin and flexible nature, the coated fabric can be used as apparel in protecting human being from hazardous microwaves and also as radar camouflage covering screen in defense.

  11. High diversity in the TCR repertoire of GAD65 autoantigen-specific human CD4+ T cells.

    Science.gov (United States)

    Eugster, Anne; Lindner, Annett; Catani, Mara; Heninger, Anne-Kristin; Dahl, Andreas; Klemroth, Sylvia; Kühn, Denise; Dietz, Sevina; Bickle, Marc; Ziegler, Anette-Gabrielle; Bonifacio, Ezio

    2015-03-15

    Autoreactive CD4(+) T cells are an essential feature of type 1 diabetes mellitus. We applied single-cell TCR α- and β-chain sequencing to peripheral blood GAD65-specific CD4(+) T cells, and TCR α-chain next-generation sequencing to bulk memory CD4(+) T cells to provide insight into TCR diversity in autoimmune diabetes mellitus. TCRs obtained for 1650 GAD65-specific CD4(+) T cells isolated from GAD65 proliferation assays and/or GAD65 557I tetramer staining in 6 patients and 10 islet autoantibody-positive children showed large diversity with 1003 different TCRs identified. TRAV and TRBV gene usage was broad, and the TRBV5.1 gene was most prominent within the GAD65 557I tetramer(+) cells. Limited overlap (<5%) was observed between TCRs of GAD65-proliferating and GAD65 557I tetramer(+) CD4(+) T cells. Few TCRs were repeatedly found in GAD65-specific cells at different time points from individual patients, and none was seen in more than one subject. However, single chains were often shared between patients and used in combination with different second chains. Next-generation sequencing revealed a wide frequency range (<0.00001-1.62%) of TCR α-chains corresponding to GAD65-specific T cells. The findings support minor selection of genes and TCRs for GAD65-specific T cells, but fail to provide strong support for TCR-targeted therapies. Copyright © 2015 by The American Association of Immunologists, Inc.

  12. Literatura jest sprawą ludu. Recenzja Kafki. Ku literaturze mniejszej Gillesa Deleuze’a i Feliksa Guttariego

    Directory of Open Access Journals (Sweden)

    Joanna Bednarek

    2016-12-01

    Full Text Available Artykuł jest recenzją polskiego przekładu pracy Deleuze’a i Guattariego Kafka. Ku literaturze mniejszej. Autorka szczególny nacisk kładzie na zagadnienia eksperymentu literackiego i polityki/polityczności literatury.

  13. Dicentric chromosome stretching during anaphase reveals roles of Sir2/Ku in chromatin compaction in budding yeast.

    Science.gov (United States)

    Thrower, D A; Bloom, K

    2001-09-01

    We have used mitotic spindle forces to examine the role of Sir2 and Ku in chromatin compaction. Escherichia coli lac operator DNA was placed between two centromeres on a conditional dicentric chromosome in budding yeast cells and made visible by expression of a lac repressor-green fluorescent fusion protein. Centromeres on the same chromatid of a dicentric chromosome attach to opposite poles approximately 50% of the time, resulting in chromosome bridges during anaphase. In cells deleted for yKU70, yKU80, or SIR2, a 10-kb region of the dicentric chromosome stretched along the spindle axis to a length of 6 microm during anaphase. On spindle disassembly, stretched chromatin recoiled to the bud neck and was partitioned to mother and daughter cells after cytokinesis and cell separation. Chromatin immunoprecipitation revealed that Sir2 localizes to the lacO region in response to activation of the dicentric chromosome. These findings indicate that Ku and Sir proteins are required for proper chromatin compaction within regions of a chromosome experiencing tension or DNA damage. The association of Sir2 with the affected region suggests a direct role in this process, which may include the formation of heterochromatic DNA.

  14. Robust AlGaN/GaN low noise amplifier MMICs for C-, Ku- and Ka-band space applications

    NARCIS (Netherlands)

    Suijker, E.M.; Rodenburg, M.; Hoogland, J.A.; Heijningen, M. van; Seelmann-Eggebert, M.; Quay, R.; Brückner, P.; Vliet, F.E. van

    2009-01-01

    The high power capabilities in combination with the low noise performance of Gallium Nitride (GaN) makes this technology an excellent choice for robust receivers. This paper presents the design and measured results of three different LNAs, which operate in C-, Ku-, and Ka-band. The designs are reali

  15. The Hoosier Newsman and the Hooded Order: Indiana Press Reaction to the Ku Klux Klan in the 1920s.

    Science.gov (United States)

    Scharlott, Bradford W.

    Coverage in a sample of ten Indiana daily newspapers was analyzed, documentary evidence was gathered, and interviews with surviving newswriters were conducted to determine how the Indiana press reported the Ku Klux Klan during the 1920s. The study found that Indiana papers gave the Klan, while it was powerful, more favorable coverage than…

  16. Thermodynamic description of the ion exchange and superequivalent sorption of phenylalanine by KU-2-8 cationite

    Science.gov (United States)

    Khokhlova, O. N.; Khokhlov, V. Yu.; Trunaeva, E. S.

    2015-02-01

    The coefficients and thermodynamic equilibrium constants, activity coefficients of the sorbent phase, and integral and differential Gibbs energies of the ion-exchange and superequivalent sorption of phenylalanine by strongly acidic KU-2-8 cationites in the H form are calculated using a new thermodynamic approach that allows us to describe the simultaneous exchange and superequivalent sorption of substances by ionites.

  17. Increase of sulphur-containing amino acids in transgenic potato with 10 ku zein gene from maize

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The 10 k zein gene of maize was under control of patatin class ⅠPromoter of potato and transferred into potato genome by the leaf-disc method.The expression of 10 ku zein was determined in the tuber of transgenic plants by RT-PCR.Furthermore,the sulphur-containing amino acids in transgenic tuber increase remarkably.

  18. Investigation on the performance of an optically generated RF local oscillator signal in Ku-band DVB-S systems

    NARCIS (Netherlands)

    Khan, M.R.H.; Marpaung, D.A.I.; Burla, M.; Roeloffzen, C.G.H.; Bernhardi, E.H.; Ridder, de R.M.

    2011-01-01

    We investigate a way to externally generate the local oscillator (LO) signal used for downconversion of the Ku-band (10.7 − 12.75 GHz) RF signal received from a phased array antenna (PAA). The signal is then translated to an intermediate frequency (950 − 2150 MHz) at the output of the mixer of stand

  19. Radar altimetry backscattering signatures at Ka, Ku, C, and S bands over West Africa

    Science.gov (United States)

    Frappart, F.; Fatras, C.; Mougin, E.; Marieu, V.; Diepkilé, A. T.; Blarel, F.; Borderies, P.

    This study presents a comprehensive comparison of radar altimetry signatures at Ka-, Ku-, C-, and S-bands using SARAL, ENVISAT and Jason-2 data over the major bioclimatic zones, soil and vegetation types encountered in West-Africa, with an emphasis on the new information at Ka-band provided by the recently launched SARAL-Altika mission. Spatio-temporal variations of the radar altimetry responses were related to changes in surface roughness, land cover and soil wetness. Analysis of time series of backscattering coefficients along the West African bioclimatic gradient shows that radar echoes at nadir incidence are well correlated to soil moisture in semi-arid savannah environments. Radar altimeters are able to detect the presence of water even under a dense canopy cover at all frequencies. But only measurements at Ka-band are able to penetrate underneath the canopy of non-inundated tropical evergreen forests.

  20. A technical writing programme implemented in a first-year engineering course at KU Leuven

    Science.gov (United States)

    Heylen, Christel; Vander Sloten, Jos

    2013-12-01

    Technical communication and technical writing are important skills for the daily work-life of every engineer. In the first-year engineering programme at KU Leuven, a technical writing programme is implemented within the project-based course 'Problem Solving and Engineering Design'. This paper describes a case study for implementing a writing programme based on active learning methods and situated learning in large classes. The programme consists of subsequent cycles of instructions, learning by doing and reflection on received feedback. In addition, a peer-review assignment, together with an interactive lecture using clicking devices, is incorporated within the assignments of the second semester. A checklist of desired writing abilities makes it easier to grade the large number of papers. Furthermore, this ensures that all staff involved in the evaluation process uses the same criteria to grade and for providing feedback.

  1. CCD Astrometric Measurements of Double Stars BAL 746, BPM 342, KU 92, and STF 897

    Science.gov (United States)

    Smith, Schuyler

    2017-07-01

    Double stars WDS 06589-0106 (BAL 746), WDS 06579+1430 (BPM 342), WDS 07006+0921 (KU 92), and WDS 06224+2640 (STF 897) were measured as part of a science fair project for the 2016 Greater San Diego Science and Engineering Fair. The goal was to measure the separation and position angles of stars by using a telescope with a charge-coupled device (CCD) on the iTelescope network. Five images were taken of each of the stars. These images were plate solved with Visual PinPoint and measured using Aladin Sky Atlas. Measurements for all five doubles compare well to the more recent values in the Washington Double Star Catalog.

  2. Ku Band Hemispherical Fully Electronic Antenna for Aircraft in Flight Entertainment

    Directory of Open Access Journals (Sweden)

    Alfredo Catalani

    2009-01-01

    Full Text Available The results obtained in the frame of the ESA activity “Advanced Antenna Concepts For Aircraft In Flight Entertainment” are presented. The aim of the activity consists in designing an active antenna able to guarantee the Ku band link between an aircraft and a geostationary satellite in order to provide in flight entertainment services. The transmit-receive antenna generates a single narrow beam to be steered electronically in a half sphere remaining compliant with respect to stringent requirements in terms of pattern shape, polarization alignment, EIRP, G/T, and using customized electronic devices. At the same time, the proposed solution should be competitive in terms of cost and complexity.

  3. Rewizje historii i dyskursu kryminologicznego: Kuśniewicz, Terlecki, Rymkiewicz

    Directory of Open Access Journals (Sweden)

    Dorota Wojda

    2011-01-01

    Full Text Available The article concerns texts which problematize such figures of criminological discourse as crime, perpetrator, victim, interrogator, or the penitentiary system. The works of A. Kuśniewicz, W.L. Terlecki and J.M. Rymkiewicz perform multidimensional revisions: they question traditional thinking about historical truth and the means of reaching it; they trespass the border between literature and fiction; they resist criminological discourse. The writers discussed formulate a diagnosis in many aspects close to that of M. Foucault’s and the new victimology, proving that representations of history as well as mechanisms of social control are discourses of restrictive authority. Korupcja [Corruption], Odpocznij po biegu [Rest after The Race], and Wielki książę [The Grand Duke] respond to such violence with revisions of history as well as the present, thanks to which literature becomes a form of radical hermeneuti

  4. Low-loss negative index metamaterials for X, Ku, and K microwave bands

    Directory of Open Access Journals (Sweden)

    David A. Lee

    2015-04-01

    Full Text Available Low-loss, negative-index of refraction metamaterials were designed and tested for X, Ku, and K microwave frequency bands. An S-shaped, split-ring resonator was used as a unit cell to design homogeneous slabs of negative-index metamaterials. Then, the slabs of metamaterials were cut unto prisms to measure experimentally the negative index of refraction of a plane electromagnetic wave. Theoretical simulations using High-Frequency Structural Simulator, a finite element equation solver, were in good agreement with experimental measurements. The negative index of refraction was retrieved from the angle- and frequency-dependence of the transmitted intensity of the microwave beam through the metamaterial prism and compared well to simulations; in addition, near-field electromagnetic intensity mapping was conducted with an infrared camera, and there was also a good match with the simulations for expected frequency ranges for the negative index of refraction.

  5. Ku-band satellite data networks using very small aperture terminals. II - System design

    Science.gov (United States)

    Raychaudhuri, D.

    1987-12-01

    An overview is presented of system design for Ku-band star networks intended for interactive data applications. The component elements of such a network are discussed, and the critical items for performance, capacity, and cost are identified. A systematic design procedure combining delay-throughput characterization of the multiaccess inbound and TDM outbound channels with satellite link analysis is provided by which system components and their parameters are selected once the network response time and availability objectives are specified. The results are presented in the form of charts and tables which may serve as the basis for star network design over a range of typical traffic models, component parameters, and performance objectives. The methodology is potentially useful for evaluating alternative network architectures and traffic scenarios which may become important as VSAT technology evolves.

  6. A Cryogenic GaAs PHEMT/ Ferroelectric Ku-Band Tunable Oscillator

    Science.gov (United States)

    Romanofsky, Robert R.; Miranda, Felix A.; VanKeuls, Fred W.

    1998-01-01

    A Ku-band tunable oscillator operated at and below 77 K is described. The oscillator is based on two separate technologies: a 0.25 mm GaAs pseudomorphic high electron mobility transistor (PHEMT) circuit optimized for cryogenic operation, and a gold microstrip ring resonator patterned on a thin ferroelectric (SrTiO3) film which was laser ablated onto a LaAlO3 substrate. A tuning range of up to 3% of the center frequency was achieved by applying dc bias between the ring resonator and ground plane. To the best of our knowledge, this is the first tunable oscillator based on a thin film ferroelectric structure demonstrated in the microwave frequency range. The design methodology of the oscillator and the performance characteristics of the tunable resonator are described.

  7. Subdominant positive solutions of the discrete equation Δu(k+n=−p(ku(k

    Directory of Open Access Journals (Sweden)

    Jaromír Baštinec

    2004-01-01

    Full Text Available A delayed discrete equation Δu(k+n=−p(ku(k with positive coefficient p is considered. Sufficient conditions with respect to p are formulated in order to guarantee the existence of positive solutions if k→∞. As a tool of the proof of corresponding result, the method described in the author's previous papers is used. Except for the fact of the existence of positive solutions, their upper estimation is given. The analysis shows that every positive solution of the indicated family of positive solutions tends to zero (if k→∞ with the speednot smaller than the speed characterized by the function k·(n/(n+1k. A comparison with the known results is given and some open questions are discussed.

  8. Pulzní generování vodíku

    OpenAIRE

    Poláčik, Ján

    2015-01-01

    Diplomová práca sa zaoberá elektrolýzou vody so zameraním na pulzovú elektrolýzu. V teoretickej časti venuje pozornosť najprv vodíku, jeho vlastnostiam, využitiu a skladovaniu. Ďalej podáva analýzu rôznych spôsobov generovania vodíka. Podrobne rozoberá elektrolýzu vody, jej energetickú a chemickú bilanciu, účinnosť elektrolýzy a možnosti zvyšovania jej účinnosti. Následne popisuje pulzovú elektrolýzu. Navrhuje laboratórne zariadenie na jednosmernú a pulzovú výrobu vodíka. Experimentálne overu...

  9. Tunable Microwave Components for Ku- and K-Band Satellite Communications

    Science.gov (United States)

    Miranada, F. A.; VanKeuls, F. W.; Romanofsky, R. R.; Subramanyam, G.

    1998-01-01

    The use of conductor/ferroelectric/dielectric thin film multilayer structures for frequency and phase agile components at frequencies at and above the Ku-band will be discussed. Among these components are edge coupled filters, microstripline ring resonators, and phase shifters. These structures were implemented using SrTiO3 (STO) ferroelectric thin films, with gold or YBa2Cu3O7-d (YBCO) high temperature superconducting (HTS) microstrip fines deposited by laser ablation on LaAlO3 (LAO) substrates. The performance of these structures in terms of tunability, operating temperature, frequency, and dc bias will be presented. Because of their small size, light weight, and low loss, these tunable microwave components are being studied very intensely at NASA as well as the commercial communication industry. An assessment of the progress made so far, and the issues yet to be solved for the successful integration of these components into the aforementioned communication systems will be presented.

  10. Bioproduction of hydrogen by Rhodobacter capsulatus KU002 isolated from leather industry effluents

    Energy Technology Data Exchange (ETDEWEB)

    Merugu, Ramchander; Girisham, S.; Reddy, S.M. [Department of Biochemistry and Microbiology, Kakatiya University, Warangal (India)

    2010-09-15

    A preliminary study on photoproduction of hydrogen by Rhodobacter capsulatus KU002 isolated from leather industry effluents under different cultural conditions with various carbon and nitrogen sources was investigated. Hydrogen production was measured using a Gas chromatograph. Lactate promoted more amounts of hydrogen production under anaerobic light conditions and aerobic light conditions. Cumulative hydrogen production by the organism was recorded at various time intervals. Incubation period of 120 h was optimum for production of hydrogen. pH 7.0 {+-} 0.2 was optimum for production of hydrogen by growing cells, while pH 7.5 {+-} 0.26 for resting cells. L-cystine was a good nitrogen source for production of hydrogen. Growing cells produced more amount of hydrogen than resting cells. Glutamine was a poor nitrogen source for hydrogen production by Rb. capsulatus. Significance of the above results in the presence of existing literature is discussed. (author)

  11. Wideband Array for C, X, and Ku-Band Applications with 5.3:1 Bandwidth

    Science.gov (United States)

    Novak, Markus H.; Volakis, John L.; Miranda, Felix A.

    2015-01-01

    Planar arrays that exploit strong intentional coupling between elements have allowed for very wide bandwidths in low-profile configurations. However, such designs also require complex impedance matching networks that must also be very compact. For many space applications, typically occurring at C-, X-, Ku-, and most recently at Ka-band, such designs require specialized and expensive fabrication techniques. To address this issue, a novel ultra-wideband array is presented, using a simplified feed network to reduce fabrication cost. The array operates from 3.5-18.5 GHz with VSWR less than 2.4 at broadside, and is of very low profile, having a total height of lambda/10 at the lowest frequency of operation. Validation is provided using a 64-element prototype array, fabricated using common Printed Circuit Board (PCB) technology. The low size, weight, and cost of this array make it attractive for space-borne applications.

  12. Thermal stability of neutron irradiation effects on KU1 fused silica

    Energy Technology Data Exchange (ETDEWEB)

    Leon, M. [Materiales Para Fusion, CIEMAT, Avenida Complutense 22, Madrid (Spain)], E-mail: monica.leon@ciemat.es; Martin, P. [Materiales Para Fusion, CIEMAT, Avenida Complutense 22, Madrid (Spain); Bravo, D.; Lopez, F.J. [Departamento Fisica de Materiales, Universidad Autonoma, Cantoblanco, Madrid (Spain); Ibarra, A. [Materiales Para Fusion, CIEMAT, Avenida Complutense 22, Madrid (Spain); Rascon, A. [Metrologia Radiaciones Ionizantes, CIEMAT, Avenida Complutense 22, Madrid (Spain); Mota, F. [Instituto de Fusion Nuclear, DENIM, Universidad Politecnica, Madrid (Spain)

    2008-03-15

    Optical absorption spectra of neutron irradiated (10{sup 21} n/m{sup 2} and 10{sup 22} n/m{sup 2}) KU1 quartz glass samples have been measured. The effects of post-irradiation isochronal thermal annealing, up to 850 deg. C, have been investigated. The general effect of the isochronal annealing is a decrease in the optical absorption bands as the temperature increases. Optical absorption bands have been identified with known defects from the literature, and their concentration temperature dependence has been analyzed. While the annealing curves of the E' and non-bridging oxygen hole centres (NBOHC) are similar, that corresponding to oxygen deficiency centres (ODC(II)) is quite different suggesting that the recombination of E' and NBOHC is part of the same process whereas the recombination of ODC is controlled by the presence of another undetected defect.

  13. Genome stability of Arabidopsis atm, ku80 and rad51b mutants: somatic and transgenerational responses to stress.

    Science.gov (United States)

    Yao, Youli; Bilichak, Andriy; Titov, Viktor; Golubov, Andrey; Kovalchuk, Igor

    2013-06-01

    DNA double-strand breaks (DSBs) can be repaired via two main mechanisms: non-homologous end joining (NHEJ) and homologous recombination (HR). Our previous work showed that exposure to abiotic stresses resulted in an increase in point mutation frequency (PMF) and homologous recombination frequency (HRF), and these changes were heritable. We hypothesized that mutants impaired in DSB recognition and repair would also be deficient in somatic and transgenerational changes in PMF and HRF. To test this hypothesis, we analyzed the genome stability of the Arabidopsis thaliana mutants deficient in ATM (communication between DNA strand break recognition and the repair machinery), KU80 (deficient in NHEJ) and RAD51B (deficient in HR repair) genes. We found that all three mutants exhibited higher levels of DSBs. Plants impaired in ATM had a lower spontaneous PMF and HRF, whereas ku80 plants had higher frequencies. Plants impaired in RAD51B had a lower HRF. HRF in wild-type, atm and rad51b plants increased in response to several abiotic stressors, whereas it did not increase in ku80 plants. The progeny of stressed wild-type and ku80 plants exhibited an increase in HRF in response to all stresses, and the increase was higher in ku80 plants. The progeny of atm plants showed an increase in HRF only when the parental generation was exposed to cold or flood, whereas the progeny of rad51b plants completely lacked a transgenerational increase in HRF. Our experiments showed that mutants impaired in the recognition and repair of DSBs exhibited changes in the efficiency of DNA repair as reflected by changes in strand breaks, point mutation and HRF. They also showed that the HR RAD51B protein and the protein ATM that recognized damaged DNA might play an important role in transgenerational changes in HRF.

  14. The pretreatment of corn stover with Gloeophyllum trabeum KU-41 for enzymatic hydrolysis

    Directory of Open Access Journals (Sweden)

    Gao Ziqing

    2012-05-01

    Full Text Available Abstract Background Pretreatment is an essential step in the enzymatic hydrolysis of biomass for bio-ethanol production. The dominant concern in this step is how to decrease the high cost of pretreatment while achieving a high sugar yield. Fungal pretreatment of biomass was previously reported to be effective, with the advantage of having a low energy requirement and requiring no application of additional chemicals. In this work, Gloeophyllum trabeum KU-41 was chosen for corn stover pretreatment through screening with 40 strains of wood-rot fungi. The objective of the current work is to find out which characteristics of corn stover pretreated with G. trabeum KU-41 determine the pretreatment method to be successful and worthwhile to apply. This will be done by determining the lignin content, structural carbohydrate, cellulose crystallinity, initial adsorption capacity of cellulase and specific surface area of pretreated corn stover. Results The content of xylan in pretreated corn stover was decreased by 43% in comparison to the untreated corn stover. The initial cellulase adsorption capacity and the specific surface area of corn stover pretreated with G. trabeum were increased by 7.0- and 2.5-fold, respectively. Also there was little increase in the cellulose crystallinity of pretreated corn stover. Conclusion G. trabeum has an efficient degradation system, and the results indicated that the conversion of cellulose to glucose increases as the accessibility of cellulose increases due to the partial removal of xylan and the structure breakage of the cell wall. This pretreatment method can be further explored as an alternative to the thermochemical pretreatment method.

  15. Serological proteome analysis of dogs with breast cancer unveils common serum biomarkers with human counterparts.

    Science.gov (United States)

    Zamani-Ahmadmahmudi, Mohamad; Nassiri, Seyed Mahdi; Rahbarghazi, Reza

    2014-03-01

    Canine mammary tumor is being touted as a model for investigating the human breast cancer. Breast cancer of the both species has similar biological behavior, histopathologic characteristics, and metastatic pattern. In this study, we used the serological proteome analysis to detect autoantigens that elicit a humoral response in dogs with mammary tumor in order to identify serum biomarkers with potential usefulness as diagnostic markers and to better understand molecular mechanisms underlying canine breast cancer development. Protein extract from a cell line was subject to 2DE followed by Western blotting using sera from 15 dogs with mammary tumor and sera from 15 healthy control dogs. Immunoreactive autoantigens were subsequently identified by the MALDI-TOF MS. Four autoantigens, including manganese-superoxide dismutase, triose phosphate isomerase, alpha-enolase, and phosphoglycerate mutase1, with significantly higher immunoreactivity in the tumor samples than in the normal samples were identified as biomarker candidates. Immunohistochemistry and Western blotting revealed higher expression of these biomarkers in the malignant tumors than in the normal or benign tumors. The autoantigens found in this study have been reported to elicit autoantibody response in the human breast cancer, indicating the similarity of breast cancer proteome profile in dogs with that in human beings.

  16. Homing of GAD65 specific autoimmunity and development of insulitis requires expression of both DQ8 and human GAD65 in transgenic mice

    Science.gov (United States)

    Elagin, Raya B.; Balijepalli, Sadguna; Diacovo, Maria J.; Baekkeskov, Steinunn; Jaume, Juan C.

    2009-01-01

    MHC-class II genes determine susceptibility in human type-1 diabetes. In their context, presentation of target antigen(s) results in autoimmunity and β-cell destruction. An animal model, in which human β-cell autoantigen(s) are presented to effector-cells in the context of human MHC-class II diabetes susceptibility genes, would be desirable for studying molecular mechanisms of disease and developing antigen-specific immune-interventions. We report the development of antigen-specific insulitis in double-transgenic mice carrying the HLA-DQ8 diabetes susceptibility haplotype and expressing the human autoantigen GAD65 in pancreatic β-cells. Immunization with human GAD65 cDNA resulted in severe insulitis and low antibody levels in double-transgenic mice while control mice were mostly insulitis free. CFA/protein immunization resulted in high antibody levels and modest insulitis. Pancreatic lymphocytic infiltration progressed through stages (exocrine pancreas followed by peri and intra-insulitis). Adoptive transfer of splenocytes from DNA-immunized mice resulted in development of insulitis in recipient transgenics. Our results show that immunization with a clinically relevant, type-1 diabetes human autoantigen, in a humanized genetic setting, results in the development of an immune response that homes to islets of Langerhans. This animal model will facilitate studies of autoimmunity to GAD65 in the context of HLA-DQ8, and development of methods to induce tolerance and prevent insulitis. PMID:19289270

  17. Kuguacin J, a triterpeniod from Momordica charantia leaf, modulates the progression of androgen-independent human prostate cancer cell line, PC3.

    Science.gov (United States)

    Pitchakarn, Pornsiri; Suzuki, Shugo; Ogawa, Kumiko; Pompimon, Wilart; Takahashi, Satoru; Asamoto, Makoto; Limtrakul, Pornngarm; Shirai, Tomoyuki

    2012-03-01

    In this study, we focused on the in vitro effects of Kuguacin J (KuJ), a purified component of bitter melon (Momordica charantia) leaf extract (BMLE), on the androgen-independent human prostate cancer cell line PC3 and the in vivo effect of dietary BMLE on prostate carcinogenesis using a PC3-xenograph model. KuJ exerted a strong growth-inhibitory effect on PC3 cells. Growth inhibition was mainly through G1-arrest: KuJ markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (Cdk2 and Cdk4) and proliferating cell nuclear antigen. Interestingly, KuJ also dramatically decreased the levels of survivin expressed by PC3 cells. In addition, KuJ exerted anti-invasive effects on PC3 cells, significantly inhibiting migration and invasion: KuJ inhibited secretion of the active forms of MMP-2, MMP-9 and uPA by PC3 cells. In addition, KuJ treatment significantly decreased the expression of membrane type 1-MMP (MT1-MMP) by PC3 cells. In vivo, 1% and 5% BMLE in the diet resulted in 63% and 57% inhibition of PC3 xenograft growth without adverse effect on host body weight. Our results suggest that KuJ is a promising new candidate chemopreventive and chemotherapeutic agent for prostate cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Expression and identification of type 1 diabetes associated autoantigen IA-2

    Institute of Scientific and Technical Information of China (English)

    贾秀娟; 李果; 陈战; 许光武; 谢超; 张迪; 周文中; 郑升; 谢晓雁; 杨键; 李纪平; 罗敏

    2003-01-01

    Objectives To obtain prokaryotic expressed IA-2 recombinant protein and to identify its immunological activity.Methods The complimentary DNA (cDNA) coding for the intracytoplasmic part of IA-2 (IA-2ic) was amplified from human fetal brain RNA, and was subcloned into the PinPoint Xa-1 T vector to construct recombinant expression plasmid, and was then expressed in E.coli JM109 cells as a fusion protein with a biotinylated peptide sequence at the aminoterminus. The biotinylated fusion protein was then purified by affinity chromatography and was subsequently dialyzed. Finally, its immunogenicity was evaluated by enzyme linked immunosorbent assay (ELISA).Results The purified IA-2ic fusion protein resolved on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a single Coomassie brilliant blue stained band with a molecular weight of 59 kDa and its immunogenicity was confirmed by ELISA. Conclusions E.coli expressed IA-2ic fusion protein has immunological activity. It can be used for detection of IA-2 autoantibodies (IA-2A) and for further studies on type 1 diabetes in future.

  19. Specific autoantigens identified by sera obtained from mice that are immunized with testicular germ cells alone

    Science.gov (United States)

    Terayama, Hayato; Hirai, Shuichi; Naito, Munekazu; Qu, Ning; Katagiri, Chiaki; Nagahori, Kenta; Hayashi, Shogo; Sasaki, Hiraku; Moriya, Shota; Hiramoto, Masaki; Miyazawa, Keisuke; Hatayama, Naoyuki; Li, Zhong-Lian; Sakabe, Kou; Matsushita, Masayuki; Itoh, Masahiro

    2016-01-01

    There are various autoimmunogenic antigens (AIs) in testicular germ cells (TGCs) recognized as foreign by the body’s immune system. However, there is little information of TGC-specific AIs being available. The aim of this study is to identify TGC-specific AIs. We have previously established that immunization using viable syngeneic TGC can also induce murine experimental autoimmune orchitis (EAO) without using any adjuvant. This study is to identify TGC-specific AIs by TGC liquid chromatography–tandem mass spectrometry analysis, followed by two-dimensional gel electrophoresis that reacted with serum IgG from EAO mice. In this study, we identified 11 TGC-specific AIs that reacted with serum from EAO mice. Real-time RT-PCR analysis showed that the mRNA expressions of seven TGC-specific AIs were significantly higher in only mature testis compared to other organs. Moreover, the recombinant proteins of identified 10 (except unnamed protein) TGC-specific AIs were created by using human embryonic kidney 293 (HEK293) cells and these antigencities were reconfirmed by Western blot using EAO serum reaction. These results indicated Atp6v1a, Hsc70t, Fbp1 and Dazap1 were candidates for TGC-specific AIs. Identification of these AIs will facilitate new approaches for understanding infertility and cancer pathogenesis and may provide a basis for the development of novel therapies. PMID:27752123

  20. Interaction of the Ku heterodimer with the DNA ligase IV/Xrcc4 complex and its regulation by DNA-PK.

    Science.gov (United States)

    Costantini, Silvia; Woodbine, Lisa; Andreoli, Lucia; Jeggo, Penny A; Vindigni, Alessandro

    2007-06-01

    DNA non-homologous end-joining (NHEJ) is a major mechanism for repairing DNA double-stranded (ds) breaks in mammalian cells. Here, we characterize the interaction between two key components of the NHEJ machinery, the Ku heterodimer and the DNA ligase IV/Xrcc4 complex. Our results demonstrate that Ku interacts with DNA ligase IV via its tandem BRCT domain and that this interaction is enhanced in the presence of Xrcc4 and dsDNA. Moreover, residues 644-748 of DNA ligase IV encompassing the first BRCT motif are necessary for binding. We show that Ku needs to be in its heterodimeric form to bind DNA ligase IV and that the C-terminal tail of Ku80, which mediates binding to DNA-PKcs, is dispensable for DNA ligase IV recognition. Although the interaction between Ku and DNA ligase IV/Xrcc4 occurs in the absence of DNA-PKcs, the presence of the catalytic subunit of DNA-PK kinase enhances complex formation. Previous studies have shown that DNA-PK kinase activity causes disassembly of DNA-PKcs from Ku at the DNA end. Here, we show that DNA-PK kinase activity also results in disassembly of the Ku/DNA ligase IV/Xrcc4 complex. Collectively, our findings provide novel information on the protein-protein interactions that regulate NHEJ in cells.

  1. A new phosphorylated form of Ku70 identified in resistant leukemic cells confers fast but unfaithful dna repair in cancer cell lines

    Science.gov (United States)

    Schellenbauer, Amelie; Biard, Denis; Paget, Vincent; Morel-Altmeyer, Sandrine; Guipaud, Olivier; Chambon, Christophe; Salles, Bernard; Maloum, Karim; Merle-Béral, Hélène; Chevillard, Sylvie; Delic, Jozo

    2015-01-01

    Ku70-dependent canonical nonhomologous end-joining (c-NHEJ) DNA repair system is fundamental to the genome maintenance and B-cell lineage. c-NHEJ is upregulated and error-prone in incurable forms of chronic lymphocytic leukemia which also displays telomere dysfunction, multiple chromosomal aberrations and the resistance to DNA damage-induced apoptosis. We identify in these cells a novel DNA damage inducible form of phospho-Ku70. In vitro in different cancer cell lines, Ku70 phosphorylation occurs in a heterodimer Ku70/Ku80 complex within minutes of genotoxic stress, necessitating its interaction with DNA damage-induced kinase pS2056-DNA-PKcs and/or pS1981-ATM. The mutagenic effects of phospho-Ku70 are documented by a defective S/G2 checkpoint, accelerated disappearance of γ-H2AX foci and kinetics of DNA repair resulting in an increased level of genotoxic stress-induced chromosomal aberrations. Together, these data unveil an involvement of phospho-Ku70 in fast but inaccurate DNA repair; a new paradigm linked to both the deregulation of c-NHEJ and the resistance of malignant cells. PMID:26337656

  2. Cloning and expression of the Chinese wheat mosaic virus RNA2 coat protein read- through and 19 ku cysteine- rich domains and localization of these proteins

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 5′-terminal (RTn) and 3′-terminal (RTc) halves of the coat protein readthrough domain and the 19 ku cysteine-rich protein of Chinese wheat mosaic virus (CWMV) were amplified by RT-PCR, cloned and expressed in E. coli. Antisera and monoclonal antibodies against these proteins were prepared by immunising these purified proteins to mice. Detection of RTn, RTc and 19 ku proteins in CWMV infected wheat sap and leaf tissue indicated that the RTn and RTc proteins were distributed on the surface of virus particles whereas the 19 ku protein was in the cytoplasm of the infected wheat cells.

  3. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils

    DEFF Research Database (Denmark)

    Volck, B; Price, P A; Johansen, J S;

    1998-01-01

    YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function ...

  4. Melanoma inhibitor of apoptosis protein (ML-IAP) specific cytotoxic T lymphocytes cross-react with an epitope from the auto-antigen SS56

    DEFF Research Database (Denmark)

    Baek Sørensen, Rikke; Faurschou, Mikkel; Troelsen, Lone;

    2009-01-01

    A large proportion of melanoma patients host a spontaneous T-cell response specifically against ML-IAP-derived peptides. In this study, we describe that some ML-IAP-specific cytotoxic T cells isolated from melanoma patients cross react with an epitope from the auto-antigen SS56. SS56 is a recently...... described target of autoantibody responses in Sjögren's syndrome (SS) as well as systemic lupus erythematosus (SLE). Here, we describe that SS56 is also an auto-antigen for T cells in SS and SLE. Hence, SS56-specific T cells could readily be detected in circulation and among the infiltrating cells of SLE...... skin lesions. SS56-specific T cells were able to lyse target cells presenting the peptide epitope on the surface. Notably, SS56-specific CD8 T cells isolated from an SS patient cross reacted with the ML-IAP epitope. This early evidence of a target for auto-reactive CTL in SS and SLE patients...

  5. Pathogen and autoantigen homologous regions within the cystic fibrosis transmembrane conductance regulator (CFTR) protein suggest an autoimmune treatable component of cystic fibrosis.

    Science.gov (United States)

    Carter, Chris J

    2011-07-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel provides the glutathione and hypochlorous acid necessary for bactericidal/viricidal actions. CFTR mutations block these effects, diminishing pathogen defence and allowing extracellular pathogen accumulation, where antibody encounter is likely. KEGG pathway analysis of the CFTR interactome shows that CFTR is involved in pathogen entry pathways and immune defence as well as in pathways relevant to comorbid conditions (diabetes, cardiomyopathies and sexual organ development). Pseudomonas aeruginosa and Staphylococcus aureus infections decrease the lifespan of cystic fibrosis patients and Stenotrophomonas maltophilia colonization is increased. Autoantibodies, targeting myeloperoxidase, the bactericidal/permeability-increasing protein and calgranulin may further compromise pathogen defence. Short consensus sequences, within immunogenic extracellular regions of the CFTR protein, are homologous to proteins expressed by P. aeruginosa, S. aureus and S. maltophilia, and to several autoantigens, with a universal overlap between autoantigen/pathogen/CFTR consensi. Antibodies to pathogens are thus likely responsible for the creation of these autoantibodies, which, with pathogen antibodies, may target the CFTR protein acting as antagonists, further compromising its function. This creates a feedforward cycle, diminishing the function of the CFTR protein and increasing the probability of pathogen accumulation and antibody production at every turn. Interruption of this cycle by antibody adsorption or immunosuppressant therapy may be beneficial in cystic fibrosis.

  6. In type 1 diabetes a subset of anti-coxsackievirus B4 antibodies recognize autoantigens and induce apoptosis of pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    Caterina Bason

    Full Text Available Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients'sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients' sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.

  7. Histone deacetylase inhibitors sensitize lung cancer cells to hyperthermia: involvement of Ku70/SirT-1 in thermo-protection.

    Directory of Open Access Journals (Sweden)

    Mohamed K Hassan

    Full Text Available This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs. Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings showed that, pre-treating lung cancer cells with HDACIs, nicotinamide (NM or Trichostatin A (TsA or both significantly enhanced hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3, therefore transfection with dominant negative SirT-1 (Y/H also eliminated the protection and resulted in more cell death by hyperthermia, in H1299 cells through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was dissociated. Although hyperthermia did not affect total Ku70 expression level, it stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10 cells. These findings suggest an escape mechanism from hyperthermia-induced Bax activation. To verify the role of Ku70 in this protection mechanism, Ku70 was silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase-dependant apoptosis when compared to scrambled transfectants which showed only G2/M cytostatic arrest in the cell lines investigated, suggesting an additional cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken together, our data show a Ku70-dependent protection mechanism from hyperthermia. Targeting Ku70 and/or its acetylation during hyperthermia may represent a promising therapeutic approach for lung cancer.

  8. Histone deacetylase inhibitors sensitize lung cancer cells to hyperthermia: involvement of Ku70/SirT-1 in thermo-protection.

    Science.gov (United States)

    Hassan, Mohamed K; Watari, Hidemichi; Salah-Eldin, Alaa-Eldin; Sultan, Ahmed S; Mohamed, Zainab; Fujioka, Yoichiro; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs) in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs). Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings showed that, pre-treating lung cancer cells with HDACIs, nicotinamide (NM) or Trichostatin A (TsA) or both significantly enhanced hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3, therefore transfection with dominant negative SirT-1 (Y/H) also eliminated the protection and resulted in more cell death by hyperthermia, in H1299 cells through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was dissociated. Although hyperthermia did not affect total Ku70 expression level, it stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10 cells. These findings suggest an escape mechanism from hyperthermia-induced Bax activation. To verify the role of Ku70 in this protection mechanism, Ku70 was silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase-dependant apoptosis when compared to scrambled transfectants which showed only G2/M cytostatic arrest in the cell lines investigated, suggesting an additional cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken together, our data show a Ku70-dependent protection mechanism from hyperthermia. Targeting Ku70 and/or its acetylation during hyperthermia may represent a promising therapeutic approach for lung cancer.

  9. EPR study of gamma and neutron irradiation effects on KU1, KS-4V and Infrasil 301 silica glasses

    Energy Technology Data Exchange (ETDEWEB)

    Lagomacini, Juan C., E-mail: jc.lagomacini@uam.es [Dept. Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Bravo, David [Dept. Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Leon, Monica; Martin, Piedad; Ibarra, Angel [Materiales para Fusion, CIEMAT, Avda. Complutense 22, E-28040 Madrid (Spain); Martin, Agustin [Dept. Fisica e Instalaciones, ETS Arquitectura UPM, E-28040 Madrid (Spain); Lopez, Fernando J. [Dept. Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain)

    2011-10-01

    Electron paramagnetic resonance (EPR) studies have been carried out on KU1 and KS-4V high purity quartz glasses and commercial silica Infrasil 301, irradiated with gamma rays up to a dose of 11.6 MGy and neutron fluences of 10{sup 21} and 10{sup 22} n/m{sup 2}. Gamma irradiations produce a much higher concentration of defect centres (mainly E', POR and NBOHC) for KU1 and I301 than for KS-4V silica. In contrast, neutron irradiation at the highest fluence produces similar concentrations in all silica types. These results agree to a good extent with those obtained in previous optical absorption measurements. Moreover, oxygen-related centres (POR and NBOHC) have been well characterized by means of electron paramagnetic resonance.

  10. Analysis of Dual-Frequency Ocean Backscatter Measurements at Ku- and Ka-Bands Using Near-Nadir Incidence GPM Radar Data

    OpenAIRE

    NOUGUIER, Frederic; Mouche, Alexis; Rascle, Nicolas; Chapron, Bertrand; Vandemark, Douglas

    2016-01-01

    Global colocalized ocean surface measurements using the Global Precipitation Measurement near-nadir dual-frequency Ku- and Ka-band microwave measurements are analyzed and compared. Focusing on the Ka and Ku cross-sections fall-off with incidence angles, the contemporaneous measurements enable to more precisely document differing ocean scattering characteristics for both microwave frequencies. Sensitivity with wind speed and significant wave height is further reported using global comparisons ...

  11. KuMu KUMUs, ili Tshto nas zhdjot v novom Dome iskusstva XXI veka? / Natalja Saveljeva-Sikkemäe

    Index Scriptorium Estoniae

    Saveljeva-Sikkemäe, Natalja

    2006-01-01

    Eesti Interpreetide Liidu etendustesarjast "KuMu KUMUs". 2. märtsil kontsert-etendus "Mäng" ansambel U: esituses (Taavi Kerkimäe ja Mart Kangro idee). 23. märtsil Jüri Reinvere multimeediaetendus "Taevas" Monika Mattiiseni ja Küberstuudio esituses, 6. aprillil esinevad Jaan Toomiku videote foonil Ursula Saal ja Anne-Liis Poll ning 11. mail toimub kontsert-installatsioon ReVISIOON ansambel Resonabilise osavõtul

  12. PAXX Is an Accessory c-NHEJ Factor that Associates with Ku70 and Has Overlapping Functions with XLF

    Directory of Open Access Journals (Sweden)

    Satish K. Tadi

    2016-10-01

    Full Text Available In mammalian cells, classical non-homologous end joining (c-NHEJ is critical for DNA double-strand break repair induced by ionizing radiation and during V(DJ recombination in developing B and T lymphocytes. Recently, PAXX was identified as a c-NHEJ core component. We report here that PAXX-deficient cells exhibit a cellular phenotype uncharacteristic of a deficiency in c-NHEJ core components. PAXX-deficient cells display normal sensitivity to radiomimetic drugs, are proficient in transient V(DJ recombination assays, and do not shift toward higher micro-homology usage in plasmid repair assays. Although PAXX-deficient cells lack c-NHEJ phenotypes, PAXX forms a stable ternary complex with Ku bound to DNA. Formation of this complex involves an interaction with Ku70 and requires a bare DNA extension for stability. Moreover, the relatively weak Ku-dependent stimulation of LIG4/XRCC4 activity by PAXX is unmasked by XLF ablation. Thus, PAXX plays an accessory role during c-NHEJ that is largely overlapped by XLF’s function.

  13. Heat shock protein 70 is necessary to improve mitochondrial bioenergetics and reverse diabetic sensory neuropathy following KU-32 therapy.

    Science.gov (United States)

    Ma, Jiacheng; Farmer, Kevin L; Pan, Pan; Urban, Michael J; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T

    2014-02-01

    Impaired neuronal mitochondrial bioenergetics contributes to the pathophysiologic progression of diabetic peripheral neuropathy (DPN) and may be a focal point for disease management. We have demonstrated that modulating heat shock protein (Hsp) 90 and Hsp70 with the small-molecule drug KU-32 ameliorates psychosensory, electrophysiologic, morphologic, and bioenergetic deficits of DPN in animal models of type 1 diabetes. The current study used mouse models of type 1 and type 2 diabetes to determine the relationship of changes in sensory neuron mitochondrial bioenergetics to the onset of and recovery from DPN. The onset of DPN showed a tight temporal correlation with a decrease in mitochondrial bioenergetics in a genetic model of type 2 diabetes. In contrast, sensory hypoalgesia developed 10 weeks before the occurrence of significant declines in sensory neuron mitochondrial bioenergetics in the type 1 model. KU-32 therapy improved mitochondrial bioenergetics in both the type 1 and type 2 models, and this tightly correlated with a decrease in DPN. Mechanistically, improved mitochondrial function following KU-32 therapy required Hsp70, since the drug was ineffective in diabetic Hsp70 knockout mice. Our data indicate that changes in mitochondrial bioenergetics may rapidly contribute to nerve dysfunction in type 2 diabetes, but not type 1 diabetes, and that modulating Hsp70 offers an effective approach toward correcting sensory neuron bioenergetic deficits and DPN in both type 1 and type 2 diabetes.

  14. [Professor Wacław Kuśnierczyk (1908-1997)--Pro Memoria in the century of birthday].

    Science.gov (United States)

    Brozek, Krzysztof; Kozakiewicz, Jacek; Kierzek, Andrzej

    2009-01-01

    Wacław Kuśnierczyk was born in 1908 in Sniatyń. He received the degree in medicine at Jan Kazimierz University in Lwów in 1932. He did his PhD degree under Professor Zaleski supervision in 1938 at Jan Kazimierz University. At that time he concentrated his scientific activity on research on tuberculosis. In 1953 he obtained the title of second degree specialist in ear, nose and throat diseases. He became a chief of Otolaryngology at Urban Hospital No 4 in Katowice in 1960. Since then this eminent physician was working on tumours located in upper respiratory tract and the possibility of its endoscopic diagnosis at Silesian Academy of Medicine in Katowice. As one of the first he pointed out the negative influence of smoking cigarettes on cancer of larynx. It was Wacław Kuśnierczyk who implemented new priorities for integrated programs in patient care, research, education and cancer prevention. He has published widely in peer reviewed journals and has edited or contributed to many books. He has given many major lectures and is the recipient of numerous prestigious awards for his scientific accomplishments. The achievement of Professor Kuśnierczyk were the valuable source of information for the physicians. In 1997, on the 31st of January he died in Katowice.

  15. Differential Role of Rapamycin and Torin/KU63794 in Inflammatory Response of 264.7 RAW Macrophages Stimulated by CA-MRSA

    Directory of Open Access Journals (Sweden)

    Rebekah K. H. Shappley

    2014-01-01

    Full Text Available Background. Rapamycin suppresses the RAW264.7 macrophage mediated inflammatory response but in lower doses induces it. In the present study, we tested the suppression of the inflammatory response in the presence of mTOR 1 and 2 inhibitors, Torin and KU63794. Methods. RAW264.7 cells were stimulated for 18 hrs with 106 to 107 CFU/mL inocula of community-acquired- (CA- MRSA isolate, USA400 strain MW2, in the presence of Vancomycin. Then, in sequential experiments, we added Torin, KU63794, and Rapamycin alone and in various combinations. Supernatants were collected and assayed for TNF, IL-1, IL-6, INF, and NO. Results. Rapamycin induces 10–20% of the inflammatory cascade at dose of 0.1 ng/mL and suppresses it by 60% at dose of 10 ng/mL. The induction is abolished in the presence of Torin KU63794. Torin and KU63794 are consistently suppressing cytokine production 50–60%. Conclusions. There is a differential response between Rapamycin (mTOR-1 inhibitor and Torin KU63794 (mTOR 1 and 2 inhibitors. Torin and KU63794 exhibit a dose related suppression. Rapamycin exhibits a significant induction-suppression biphasic response. Knowledge of such response may allow manipulation of the septic inflammatory cascade for clinical advantages.

  16. Understanding community receptivity to water re-use: Ku-ring-gai Council case study.

    Science.gov (United States)

    Brown, R R; Davies, P

    2007-01-01

    This social research project investigated community receptivity to using rainwater and greywater as alternative domestic water sources. It was focused in the Ku-ring-gai local government area in northern Sydney, and involved a household questionnaire followed by community leader interviews and resident focus groups. Trends, such as a prolonged drought and increasing population, compound the current crisis and concern facing Sydney's available water supply. Substitution of domestic potable water has been promoted as part of the solution. The research results revealed that community receptivity was highest for external uses, such as watering gardens and flushing toilets, and progressively decreased with increasing personal contact. Receptivity to greywater reuse fell more rapidly with the community believing there was a higher health risk associated with its use. Gender and cultural background were revealed as significant variables and give insight into the design of strategies to target these demographic groups. This evidence provides a reliable stocktake of current receptivity revealing that the community has good awareness and positive association with water reuse for many household activities. This now needs to be harnessed through programs targeted at developing skills, resources and motivation for new water reuse practices and technologies across diverse social groupings.

  17. Invariant sets techniques for Youla-Kučera parameter synthesis

    Science.gov (United States)

    Luca, Anamaria; Rodriguez-Ayerbe, Pedro; Dumur, Didier

    2011-09-01

    This article addresses an invariant sets approach for Youla-Kučera parameter synthesis using linear matrix inequality (LMI) techniques. Given a linear discrete-time observer-based system affected by bounded disturbances and constraints, the proposed technique furnishes the best Youla parameter in terms of finding an invariant ellipsoidal set satisfying the constraints and having the maximal ellipsoidal projection on the state space. Compared with the results obtained for an observer-based design, the synthesis of a Youla parameter provides a larger ellipsoidal projection and an improved sensitivity function. The price to pay for these achievements in terms of robustness is usually a slow closed-loop performance with degraded complementary sensitivity function. In order to obtain a compromise between robustness and performance two methods are proposed: the first method imposes a new bound on the Lyapunov function decreasing speed and the second refers to the pole placement concept. The aforementioned approaches are finally validated in simulation considering position control of an induction motor.

  18. Analysis and comparison model for measuring tropospheric scintillation intensity for Ku-band frequency in Malaysia

    Directory of Open Access Journals (Sweden)

    Mandeep JS

    2011-06-01

    Full Text Available This study has been based on understanding local propagation signal data distribution characteristics and identifying and predicting the overall impact of significant attenuating factors regarding the propagation path such as impaired propagation for a signal being transmitted. Predicting propagation impairment is important for accurate link budgeting, thereby leading to better communication network system designation. This study has thus used sample data for one year concerning beacon satellite operation in Malaysia from April 2008 to April 2009. Data concerning 12GHz frequency (Ku-band and 40° elevation angle was collected and analysed, obtaining average signal amplitude value, ÷ and also standard deviation ó which is normally measured in dB to obtain long-term scintillation intensity distribution. This analysis showed that scintillation intensity distribution followed Gaussian distribution for long-term data distribution. A prediction model was then selected based on the above; Karasawa,
    ITU-R, Van de Kamp and Otung models were compared to obtain the best prediction model performance for selected data regarding specific meteorological conditions. This study showed that the Karasawa model had the best performance for predicting scintillation intensity for the selected da ta.

  19. Design studies of the Ku-band, wide-band Gyro-TWT amplifier

    Science.gov (United States)

    Jung, Sang Wook; Lee, Han Seul; Jang, Kwong Ho; Choi, Jin Joo; Hong, Yong Jun; Shin, Jin Woo; So, Jun Ho; Won, Jong Hyo

    2014-02-01

    This paper reports a Ku-band, wide band Gyrotron-Traveling-wave-tube(Gyro-TWT) that is currently being developed at Kwangwoon University. The Gyro-TWT has a two stage linear tapered interaction circuit to obtain a wide operating bandwidth. The linearly-tapered interaction circuit and nonlinearly-tapered magnetic field gives the Gyro-TWT a wide operating bandwidth. The Gyro-TWT bandwidth is 23%. The 2d-Particle-in-cell(PIC) and MAGIC2d code simulation results are 17.3 dB and 24.34 kW, respectively for the maximum saturated output power. A double anode MIG was simulated with E-Gun code. The results were 0.7 for the transvers to the axial beam velocity ratio (=alpha) and a 2.3% axial velocity spread at 50 kV and 4 A. A magnetic field profile simulation was performed by using the Poisson code to obtain the grazing magnetic field of the entire interaction circuit with Poisson code.

  20. Optimization of Enterobacter cloacae (KU923381) for diesel oil degradation using response surface methodology (RSM).

    Science.gov (United States)

    Ramasamy, Sugumar; Arumugam, Arumugam; Chandran, Preethy

    2017-02-01

    Efficiency of Enterobacter cloacae KU923381 isolated from petroleum hydrocarbon contaminated soil was evaluated in batch culture and bioreactor mode. The isolate were screened for biofilm formation using qualitative and quantitative assays. Response surface methodology (RSM) was used to study the effect of pH, temperature, glucose concentration, and sodium chloride on diesel degradation. The predicted values for diesel oil degradation efficiency by the statistical designs are in a close agreement with experimental data (R (2) = 99.66%). Degradation efficiency is increased by 36.78% at pH = 7, temperature = 35°C, glucose = 5%, and sodium chloride concentration = 5%. Under the optimized conditions, the experiments were performed for diesel oil degradation by gas chromatographic mass spectrometric analysis (GC-MS). GC-MS analysis confirmed that E. cloacae had highly degrade hexadecane, heptadecane, tridecane, and docosane by 99.71%, 99.23%, 99.66%, and 98.34% respectively. This study shows that rapid bioremoval of hydrocarbons in diesel oil is acheived by E. cloacae with abet of biofilm formation. The potential use of the biofilms for preparing trickling filters (gravel particles) for the degradation of hydrocarbons from petroleum wastes before their disposal in the open environment is highly suggested. This is the first successful attempt for artificially establishing petroleum hydrocarbon degrading bacterial biofilm on solid substrates in bioreactor.

  1. Electrical and dielectric properties of irradiated KU1 quartz glass from DC to 145 GHz

    CERN Document Server

    Vila, R; Heidinger, R; Morono, A; Hodgson, E R

    2002-01-01

    To characterize and examine the possible use of the KU1 quartz glass for both diagnostic and remote handling applications, the radiation induced conductivity and electrical degradation (RIC and RIED), together with dielectric loss and permittivity (10 mHz-145 GHz) have been determined for as-received, electron and neutron irradiated material. Results show that the RIC is extremely low (<10 sup - sup 8 S/m compared with about 10 sup - sup 7 S/m) for candidate oxide materials at the same dose rate, but markedly increases for doses up to about 3x10 sup - sup 5 dpa while the conductivity without radiation is reduced with dose. Dielectric measurements from 1 kHz to 20 GHz during electron irradiation show that prompt effects are only observed at very low frequencies, consistent with the low RIC results. For neutron irradiation to 10 sup - sup 4 dpa, post-irradiation measurements indicate a permanent increase in loss by up to a factor of 2 below 60 MHz. No effect is observed in the GHz range.

  2. Endogenous HLA-DR-restricted presentation of the cartilage antigens human cartilage gp-39 and melanoma inhibitory activity in the inflamed rheumatoid joint

    NARCIS (Netherlands)

    van Lierop, M. J. C.; den Hoed, L.; Houbiers, J.; Vencovsky, J.; Ruzickova, S.; Krystufkova, O.; van Schaardenburg, M.; van den Hoogen, F.; Vandooren, B.; Baeten, D.; De Keyser, F.; Sonderstrup, G.; Bos, E.; Boots, A. M.

    2007-01-01

    Objective. The cartilage proteins melanoma inhibitory activity (MIA) and human cartilage gp-39 (HC gp-39) are candidate autoantigens in rheumatoid arthritis (RA). The present study was undertaken to investigate the endogenous HLA-DR4-restricted presentation of these self proteins, in order to seek i

  3. DNA ligase III and DNA ligase IV carry out genetically distinct forms of end joining in human somatic cells.

    Science.gov (United States)

    Oh, Sehyun; Harvey, Adam; Zimbric, Jacob; Wang, Yongbao; Nguyen, Thanh; Jackson, Pauline J; Hendrickson, Eric A

    2014-09-01

    Ku-dependent C-NHEJ (classic non-homologous end joining) is the primary DNA EJing (end joining) repair pathway in mammals. Recently, an additional EJing repair pathway (A-NHEJ; alternative-NHEJ) has been described. Currently, the mechanism of A-NHEJ is obscure although a dependency on LIGIII (DNA ligase III) is often implicated. To test the requirement for LIGIII in A-NHEJ we constructed a LIGIII conditionally-null human cell line using gene targeting. Nuclear EJing activity appeared unaffected by a deficiency in LIGIII as, surprisingly, so were random gene targeting integration events. In contrast, LIGIII was required for mitochondrial function and this defined the gene's essential activity. Human Ku:LIGIII and Ku:LIGIV (DNA ligase IV) double knockout cell lines, however, demonstrated that LIGIII is required for the enhanced A-NHEJ activity that is observed in Ku-deficient cells. Most unexpectedly, however, the majority of EJing events remained LIGIV-dependent. In conclusion, although human LIGIII has an essential function in mitochondrial maintenance, it is dispensable for most types of nuclear DSB repair, except for the A-NHEJ events that are normally suppressed by Ku. Moreover, we describe that a robust Ku-independent, LIGIV-dependent repair pathway exists in human somatic cells.

  4. Microwave absorption in X and Ku band frequency of cotton fabric coated with Ni–Zn ferrite and carbon formulation in polyurethane matrix

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, K.K., E-mail: krishna62@rediffmail.com [Defence Materials and Stores Research and Development Establishment, Kanpur PO, GT Road, Kanpur 208013 (India); Abbas, S.M.; Goswami, T.H. [Defence Materials and Stores Research and Development Establishment, Kanpur PO, GT Road, Kanpur 208013 (India); Abhyankar, A.C. [Defence Institute of Advanced Technology( DIAT), Giri Nagar, Pune 411025 (India)

    2014-08-01

    The present study highlights various microwave properties, i.e. reflection, transmission, absorption and reflection loss, of the coated cotton fabric [formulation: Ni–Zn ferrite (Ni {sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4}) and carbon black (acetylene black) at concentrations of 30, 40, 50, 60 and70 g of ferrite and 5 g carbon in each 100 ml polyurethane] evaluated at 8–18 GHz frequency. The uniform density of filling materials in coated fabrics (dotted marks in SEM micrograph) indicates homogeneous dispersion of conducting fillers in polyurethane and the density of filling material cluster increases with increase in ferrite concentration. SEM images also show uniform coating of conducting fillers/resin system over individual fibers and interweave spaces. The important parameters governing the microwave properties of coated fabrics i.e. permittivity and permeability, S-parameters, reflection loss, etc. were studied in a HVS free space microwave measurement system. The lossy character of coated fabric is found to increase with increase of ferrite content; the ferrite content decreases the impedance and increases the permittivity and permeability values. The 1.6–1.8 mm thick coated fabric sample (40 wt% ferrite, 3 wt% carbon and 57 wt% PU) has shown about 40% absorption, 20% transmission and 40% reflectance in X (8.2–12.4 GHz) and Ku (12–18 GHz) frequency bands. The reflection loss at 13.5 GHz has shown the highest peak value (22.5 dB) due to coated sample optical thickness equal to λ/4 and more than 7.5 dB in entire Ku band. Owing to its thin and flexible nature, the coated fabric can be used as apparel in protecting human being from hazardous microwaves and also as radar camouflage covering screen in defense. - Highlights: • Ni–Zn ferrite (Ni{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4}) with acetylene black found effective coating for microwave absorption. • Coating formulation containing 40 wt% ferrite, 3 wt% carbon and 57 wt% PU offered 40% absorption, 20

  5. Virus and autoantigen-specific CD4+ T cells are key effectors in a SCID mouse model of EBV-associated post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Linnerbauer, Stefanie; Behrends, Uta; Adhikary, Dinesh; Witter, Klaus; Bornkamm, Georg W; Mautner, Josef

    2014-05-01

    Polyclonal Epstein-Barr virus (EBV)-infected B cell line (lymphoblastoid cell lines; LCL)-stimulated T-cell preparations have been successfully used to treat EBV-positive post-transplant lymphoproliferative disorders (PTLD) in transplant recipients, but function and specificity of the CD4+ component are still poorly defined. Here, we assessed the tumor-protective potential of different CD4+ T-cell specificities in a PTLD-SCID mouse model. Injection of different virus-specific CD4+ T-cell clones showed that single specificities were capable of prolonging mouse survival and that the degree of tumor protection directly correlated with recognition of target cells in vitro. Surprisingly, some CD4+ T-cell clones promoted tumor development, suggesting that besides antigen recognition, still elusive functional differences exist among virus-specific T cells. Of several EBV-specific CD4+ T-cell clones tested, those directed against virion antigens proved most tumor-protective. However, enriching these specificities in LCL-stimulated preparations conferred no additional survival benefit. Instead, CD4+ T cells specific for unknown, probably self-antigens were identified as principal antitumoral effectors in LCL-stimulated T-cell lines. These results indicate that virion and still unidentified cellular antigens are crucial targets of the CD4+ T-cell response in this preclinical PTLD-model and that enriching the corresponding T-cell specificities in therapeutic preparations may enhance their clinical efficacy. Moreover, the expression in several EBV-negative B-cell lymphoma cell lines implies that these putative autoantigen(s) might also qualify as targets for T-cell-based immunotherapy of virus-negative B cell malignancies.

  6. Collagen induced arthritis (CIA) in mice features regulatory transcriptional network connecting major histocompatibility complex (MHC H2) with autoantigen genes in the thymus.

    Science.gov (United States)

    Donate, Paula B; Fornari, Thaís A; Junta, Cristina M; Magalhães, Danielle A; Macedo, Cláudia; Cunha, Thiago M; Nguyen, Catherine; Cunha, Fernando Q; Passos, Geraldo A

    2011-05-01

    Considering that imbalance of central tolerance in the thymus contributes to aggressive autoimmunity, we compared the expression of peripheral tissue autoantigens (PTA) genes, which are involved in self-representation in the thymic stroma, of two mouse strains; DBA-1/J (MHC-H2(q)) susceptible and DBA-2/J (MHC-H2(d)) resistant to collagen induced arthritis (CIA). We evaluate whether these strains differ in their thymic gene expression, allowing identification of genes that might play a role in susceptibility/resistance to CIA. Microarray profiling showed that 1093 PTA genes were differentially modulated between collagen immunized DBA-1/J and DBA-2/J mice. These genes were assigned to 17 different tissues/organs, including joints/bone, characterizing the promiscuous gene expression (PGE), which is implicated in self-representation. Hierarchical clustering of microarray data and quantitative RT-PCR analysis showed that Aire (autoimmune regulator), an important regulator of the PGE process, Aire-dependent (insulin), Aire-independent (Col2A1 and Gad67), and other 22 joint/bone autoantigen genes were down-regulated in DBA-1/J compared with DBA-2/J in the thymus. Considering the importance of MHC-H2 in peptide-self presentation and autoimmunity susceptibility, we reconstructed transcriptional networks of both strains based on actual microarray data. The networks clearly demonstrated different MHC-H2 transcriptional interactions with PTAs genes. DBA-1/J strain featured MHC-H2 as a node influencing downstream genes. Differently, in DBA-2/J strain network MHC-H2 was exclusively self-regulated and does not control other genes. These findings provide evidence that CIA susceptibility in mice may be a reflex of a cascade-like transcriptional control connecting different genes to MHC-H2 in the thymus.

  7. The effect of DN (dominant-negative) Ku70 and reoxygenation on hypoxia cell-kill: evidence of hypoxia-induced potentially lethal damage.

    Science.gov (United States)

    Urano, Muneyasu; Li, Gloria C; He, Fuqiu; Minami, Akiko; Burgman, Paul; Ling, C Clifton

    2012-07-01

    To study the effect of DN (dominant-negative) Ku70 and reoxygenation on the hypoxia-induced cell-kill. Cell lines were human colorectal carcinoma HCT8 and HT29 cells and their respective derivatives, v-HCT8 and v-HT29 infected with DNKu70-containing adenovirus. Cells were plated in glass tubes and made hypoxic by flushing N(2) gas containing 0, 0.1 or 0.5% O(2). Cell survival was determined by colony formation assay immediately after 0-96 h hypoxia. To reoxygenate medium were replaced fresh following 48 or 72 h in hypoxia and cells were incubated in aerobic environment for 2-24 h before survival assay. When incubated in hypoxia, cells lost reproductive capability ∼ exponentially as a function of time in hypoxia, and depending on the O(2) concentration. DNKu70 rendered cells more prone to hypoxia-induced cell-kill. Following reoxygenation cell survival increased rapidly but without detectable cell proliferation during first 24 hours. This evinced hypoxia-induced potentially lethal damage (PLD) that was repairable upon reoxygenation. DNKu70 did not significantly inhibit this repair. Hypoxia-induced cell lethality was facilitated by DNKu70, but substantially repaired upon reoxygenation. This may have negative impact on the effect of reoxygenation in cancer therapy.

  8. Estimating Snow Water Equivalent with Backscattering at X and Ku Band Based on Absorption Loss

    Directory of Open Access Journals (Sweden)

    Yurong Cui

    2016-06-01

    Full Text Available Snow water equivalent (SWE is a key parameter in the Earth’s energy budget and water cycle. It has been demonstrated that SWE can be retrieved using active microwave remote sensing from space. This necessitates the development of forward models that are capable of simulating the interactions of microwaves and the snow medium. Several proposed models have described snow as a collection of sphere- or ellipsoid-shaped ice particles embedded in air, while the microstructure of snow is, in reality, more complex. Natural snow usually forms a sintered structure following mechanical and thermal metamorphism processes. In this research, the bi-continuous vector radiative transfer (bi-continuous-VRT model, which firstly constructs snow microstructure more similar to real snow and then simulates the snow backscattering signal, is used as the forward model for SWE estimation. Based on this forward model, a parameterization scheme of snow volume backscattering is proposed. A relationship between snow optical thickness and single scattering albedo at X and Ku bands is established by analyzing the database generated from the bi-continuous-VRT model. A cost function with constraints is used to solve effective albedo and optical thickness, while the absorption part of optical thickness is obtained from these two parameters. SWE is estimated after a correction for physical temperature. The estimated SWE is correlated with the measured SWE with an acceptable accuracy. Validation against two-year measurements, using the SnowScat instrument from the Nordic Snow Radar Experiment (NoSREx, shows that the estimated SWE using the presented algorithm has a root mean square error (RMSE of 16.59 mm for the winter of 2009–2010 and 19.70 mm for the winter of 2010–2011.

  9. Wideband electromagnetic wave absorber using doped barium hexaferrite in Ku-band

    Energy Technology Data Exchange (ETDEWEB)

    Tehrani, Masoud Kavosh, E-mail: m_kavosh@mut-es.ac.ir [Department of Physics, Malek-ashtar University of Technology, Shahin Shahr (Iran, Islamic Republic of); Ghasemi, Ali [Department of Material Engineering, Malek-ashtar University of Technology, Shahin Shahr (Iran, Islamic Republic of); Moradi, Mahmood; Alam, Reza Shams [Department of Physics, Shiraz University, Shiraz (Iran, Islamic Republic of)

    2011-08-18

    Highlights: > Substituted barium hexaferrite BaMg{sub 0.25}Mn{sub 0.25}Co{sub 0.5}Ti{sub 1.0}Fe{sub 10}O{sub 19} was prepared in powder configuration by solid state reaction. > The results exhibit a wideband single-layer microwave absorber with a satisfactory reflection loss throughout Ku-band. > The composite specimens for measurement of microwave absorber properties were prepared by mixing doped barium ferrite and PVC with a concentration of 70:30 by weight. > The bandwidth that can be achieved by utilization of this sample is 4.5 GHz. Minimum reflection loss of -34 dB can be obtained by sample '(e)'. - Abstract: Substituted barium hexaferrite BaMg{sub 0.25}Mn{sub 0.25}Co{sub 0.5}Ti{sub 1.0}Fe{sub 10}O{sub 19} was prepared in powder configuration by solid state reaction. The ferrite powders were mixed with polyvinylcloride (PVC) plasticizer to fabricate a microwave absorbing composite. X-ray diffraction (XRD), scanning electron microscope (SEM), vibrating sample magnetometer (VSM), and vector network analyzer were employed to characterize phase identification coupled with size and morphology of powder and microwave absorption properties of synthesized composites. It was found that the maximum reflection loss of -40 dB was appeared at frequency range of 12-18 GHz. In the present work, new cation substitutions in iron sites in the crystal lattice of barium ferrite, which can easily tune the bandwidth of the reflection loss, were used. To the best of our knowledge, this is the first study which displays the wideband absorber by employing single layer hexaferrite backed on the surface of copper.

  10. Rainfall measurement from the opportunistic use of an Earth–space link in the Ku band

    Directory of Open Access Journals (Sweden)

    L. Barthès

    2013-08-01

    Full Text Available The present study deals with the development of a low-cost microwave device devoted to the measurement of average rain rates observed along Earth–satellite links, the latter being characterized by a tropospheric path length of a few kilometres. The ground-based power measurements, which are made using the Ku-band television transmissions from several different geostationary satellites, are based on the principle that the atmospheric attenuation produced by rain encountered along each transmission path can be used to determine the path-averaged rain rate. This kind of device could be very useful in hilly areas where radar data are not available or in urban areas where such devices could be directly placed in homes by using residential TV antenna. The major difficulty encountered with this technique is that of retrieving rainfall characteristics in the presence of many other causes of received signal fluctuation, produced by atmospheric scintillation, variations in atmospheric composition (water vapour concentration, cloud water content or satellite transmission parameters (variations in emitted power, satellite pointing. In order to conduct a feasibility study with such a device, a measurement campaign was carried out over a period of five months close to Paris. The present paper proposes an algorithm based on an artificial neural network, used to identify dry and rainy periods and to model received signal variability resulting from effects not related to rain. When the altitude of the rain layer is taken into account, the rain attenuation can be inverted to obtain the path-averaged rain rate. The rainfall rates obtained from this process are compared with co-located rain gauges and radar measurements taken throughout the full duration of the campaign, and the most significant rainfall events are analysed.

  11. [Anaphylaxis caused by human seminal fluid].

    Science.gov (United States)

    Rubira, N; Roger, A; Nogueiras, C; Server, T; Guspi, R; Cadahia, A

    1995-01-01

    Anaphylaxis to human seminal fluid (HSF) is rare. We present an atopic woman with postcoital cutaneous and respiratory symptoms. Prick by prick to HSF was positive. CAP to FSH was also positive (4 KU/l). The clinical findings, differential diagnosis and different treatments are discussed.

  12. Design and study on the dual-band radome with FSS operation at Ku-/Ka-band%Ku/Ka波段双通带频率选择表面雷达罩设计研究

    Institute of Scientific and Technical Information of China (English)

    王秀芝; 高劲松; 徐念喜

    2013-01-01

    In order to meet the multi-band and integration requirements of the communication apparatus, the coupling and resonance mecha-nism can be exploited to design a frequency selective surface (FSS), with two pass-bands at Ku-band and Ka-band, which is composed of three metallic layers and fabricated on a flat substrate equivalent to a solid wall radome or an A-sandwiched radome. According to the physical structure of the FSS, an equivalent circuit model is established to analyze the filtering mechanism, and the transmission characteristics of the radomes with FSS are obtained by using a full-wave analysis software. The first pass-band at Ku-band with miniaturization property can be achieved by coupling the electric and magnetic field of the three surfaces, while the second pass-band at Ka-band can be achieved by the resonance of the square loop slots embedded in the capacitive surfaces. The transmissions of the solid wall radome and A-sandwiched radome with FSS are 89%and 94.7%at Ku-band, and 88.2%and 93.7%at Ka-band, respectively. When the incident angle is varied from normal to 60◦, the frequency response characteristics of the two pass-bands are stable. Finally, the experimental results of the prototype with a solid substrate measured in free-space environment are in good agreement with the simulated values. The proposed radome structure with FSS, which is based on the coupling and resonance mechanism, can achieve two stable pass-bands at Ku-/Ka-band. This may provide some theoretical and experimental assistance for the study of the multi-band and wide band spacing FSS.%为了满足现代通信设备多频带及集成化要求,基于耦合机理和谐振机理,在实心半波壁雷达罩和A夹层雷达罩等效平板基底上设计了一种由容性表面(内嵌谐振单元)-感性表面-容性表面(内嵌谐振单元)-等效基底级联而成的Ku/Ka波段双通带频率选择表面结构.根据FSS的物理结构建立了等效电路模型,分析了滤波机

  13. Study on the Expression and Clinical Significance of SIRT-1 and Ku70 in Pancreatic Carcinoma%SIRT-1和Ku70在胰腺癌中的表达及其临床病理意义

    Institute of Scientific and Technical Information of China (English)

    徐超; 金政锡; 刘大伟; 金英朝; 李小东

    2013-01-01

    目的:研究胰腺癌中S IRT-1和Ku70的表达及其临床病理意义,为胰腺癌患者的预后及生物治疗提供理论依据.方法:采用免疫组织化学技术(S-P)法检测46例胰腺癌及20例非肿瘤性胰腺组织中SIRT-1和Ku70表达情况,并分析其与胰腺癌临床病理参数的关系.结果:胰腺癌组织中SIRT-1的表达明显升高,其表达强度与临床分期、淋巴结有无转移、年龄和肿瘤大小呈正相关(P<0.05),与组织学分级呈负相关(P<0.05),与患者的性别和肿瘤部位均无关.胰腺癌组织中Ku70表达明显升高,其表达强度与临床分期、淋巴结有无转移及呈正相关(P<0.05),与组织学分级呈负相关(P<0.05),与患者的性别、年龄、肿瘤部位和大小均无关.结论:SIRT-1和Ku70在胰腺癌组织中的表达显著高于非肿瘤胰腺组织,且与胰腺癌的临床病理及预后相关,在胰腺癌的发展中也起一定作用,存在协同关系.

  14. Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    Directory of Open Access Journals (Sweden)

    Yan Ting-Ting

    2010-12-01

    Full Text Available Abstract Background The association of rs1044925 polymorphism in the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1 gene and serum lipid profiles is not well known in different ethnic groups. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was carried out to clarify the association of rs1044925 polymorphism in the ACAT-1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 626 subjects of Bai Ku Yao and 624 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of rs1044925 polymorphism in the ACAT-1 gene was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, apolipoprotein (Apo AI and ApoB were lower in Bai Ku Yao than in Han (P P P P P P Conclusions These results suggest that the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum TC, LDL-C and ApoB levels in the Bai Ku Yao population. The C allele carriers had lower serum TC, LDL-C and ApoB levels than the C allele noncarriers.

  15. Novel approach for designing a thin and broadband microwave absorber in Ku band based on substituted M-hexaferrites

    Energy Technology Data Exchange (ETDEWEB)

    Afghahi, Seyyed Salman Seyyed [Department of Materials Engineering, Imam Hossein University, Tehran (Iran, Islamic Republic of); Jafarian, Mojtaba, E-mail: m.jafarian@srbiau.ac.ir [Young Researchers and Elite Club, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Atassi, Yomen [Department of Applied Physics, Higher Institute for Applied Sciences and Technology, Damascus (Syrian Arab Republic)

    2016-12-01

    The design of novel microwave absorbers in the Ku band is still challenging. The aim of this work is to report the design of a new Ku absorber based on the combination of three M-hexaferrites with the formula of BaX{sub 0.3}Y{sub 0.3}Cr{sub 0.3}Fe{sub 11.1}O{sub 19} (XY=Co{sup 2+}Zr{sup 4+}, Zn{sup 2+}Ti{sup 4+}, Mn{sup 2+}Ce{sup 4+}), 15 wt% of each in epoxy matrix. The results indicate the formation of a broadband absorber with a reflection loss (RL) lower than −10 dB over the whole bandwidth 13.75–18 GHz. It has three matching frequencies (14.2, 15.3 and 16.8 GHz) with RL (−29.2, −21.5 and −24.7 dB, respectively) at a matching thickness of only 2.5 mm. This is to be compared with the RL of the absorbers based on 45 wt% of each ferrite alone in epoxy matrix are (−15, −28.8 and −20 dB, respectively) at matching frequency of (14.15, 13.55 and 16.5 GHz) and a matching thickness of 4 mm. This favorable performance resulting from combining the three ferrites within the absorber may be attributed to the enhanced exchange coupling interactions between the three powders of distinct magnetic characteristics. - Highlights: • Design a novel microwave absorber in the Ku band. • Proper combination of the 3 types of substituted M-hexaferrites in one layer. • Making broad band absorber with a maximum RL of −29.2 dB at 14.2 GHz. • The sample had 4.2 GHz bandwidth at a matching thickness of only 2.5 mm.

  16. Study of the Effect of Simulated Rain on the Offset Parabolic Antenna at Ku-Band with Different Elevation Angles

    Directory of Open Access Journals (Sweden)

    H. Mostafa

    2007-01-01

    Full Text Available Effect of rain on the receiver antenna is a major factor to degrade the system performance in a frequency above 10 GHz. This paper deals with the wet antenna attenuation at Ku-band with three different frequencies at different rain rates. During the Ku-band propagation experiment, it was discovered that rain water on the antenna caused a significant attenuation. It is necessary to estimate the losses caused by water on the antenna in order to separate these losses from the atmospheric propagation losses. The experiment was done at USM Engineering Campus to study the attenuation for these physical parameters. A Ku-band RF signal was generated by a signal generator and transmitted via horn antenna. The signal was received using a smooth offset antenna of 60 cm by 54 cm (Astro dish and measured using spectrum analyzer. In order to simulate a rain, pipes with bores of a same distance were implemented. Three cases were considered: in the first case one pipe was used to simulate low rain rate, the second case two pipes were used to simulate medium rain rate, and the third case three pipes were used to simulate heavy rain rate. In addition, the tap was used to control the flow of water in order to get more values of rain rate. The total attenuation of RF signals due to water layer on the feed and on the reflector feed was found to be 3.1 dB at worst case. On the other hand, the attenuation of RF signal due to the feed only was 2.83 dB, so the major attenuation occur was due to feed.

  17. Search for molecular bremsstrahlung radiation signals in Ku band with coincidental operations of radio telescopes with air shower detectors

    Directory of Open Access Journals (Sweden)

    Fukushima Masaki

    2013-06-01

    Full Text Available Microwave radiation from extensive air showers is expected to provide a new technique to observe UHECR. We insatlled and operate radio telescopes in Osaka and at Telescope Array site in Utah, USA. In Osaka, we are coincidentally operating two Ku band radio telescopes with an air shower array which consists of nine plastic scintillators with about 10 m separation. In Utah, we installed two telescopes just beside the Black Rock Mesa fluorescence detector (FD station of the Telescope Array experiment, and we operated the radio telescopes coincidentally with FD event triggers. We report the experimental setups and the results of these measurements.

  18. Ku Klux Klan activism in the 1960s is linked to the South’s swing to the Republican Party

    OpenAIRE

    McVeigh, Rory

    2014-01-01

    After the midterm elections, the Democratic Party is now very nearly unrepresented in the Southern states of the U.S., the culmination of a political realignment that began in the 1960s. In new research, Rory McVeigh finds that those counties that experienced greater levels of activism by the racist Ku Klux Klan experienced a five percent greater swing to the Republican Party. He argues that these results show that social movement activism can be effective in bringing about change, as people’...

  19. Forma sinistra de americanismo : o puritanismo na ética e na retórica do Ku Klux Klan

    OpenAIRE

    Sousa, Luísa Maria Vilhena Ribeiro de

    2006-01-01

    Dissertação de Mestrado em Estudos Americanos apresentada à Universidade Aberta RESUMO - Nas últimas décadas, os estudos sobre a proeminência sinistra dos grupos de supremacia branca nos Estados Unidos da América, nomeadamente do Ku Klux Klan, têm-se intensificado a nível internacional, embora concentrados na sua trajectória política, social e económica, no perfil psicológico e social dos seus membros ou nos seus motivos e intuitos pessoais. Neste contexto, afigurou-se-nos necessária e per...

  20. Određivanje alergena grinja u kućnoj prašini enzim-imunokemijskom metodom

    OpenAIRE

    Prester, Ljerka; Brčić Karačonji, Irena; Macan, Jelena

    2007-01-01

    Cilj ovoga rada bio je odrediti razine alergena grinja Dermatophagoides pteronyssinus (Der p 1) i Dermatophagoides farinae (Der f 1) u 30 uzoraka kućne prašine uzorkovane u gradskim stanovima u Zagrebu enzim-imunokemijskom metodom (ELISA, Indoor Biotechnologies Ltd, Carfiff, UK). Metoda se koristi tehnikom dvaju monoklonskih protutijela, a primjenjuje se kao standardna metoda za određivanje alergena grinja u prašini. Uzorci prašine skupljeni su usisavanjem prašine s tepiha u celulozne filtre....

  1. Pirmsskolas vecuma bērnu vecāku emocionālais intelekts un stresa līmenis saistībā ar vecāku audzināšanas pieejām

    OpenAIRE

    Pastare, Ilze

    2007-01-01

    Rezumējums Pētījuma mērķis bija noskaidrot pirmsskolas vecuma bērnu vecāku emocionālā intelekta un stresa līmeņa rādītāju saistību ar audzināšanas pieejām. Kopā pētījumā piedalījās 41 māte. Vidējais vecums mātēm – 33 gadi, bērnu vidējais vecums – 5 gadi. Pētījumā tika izmantotas šādas metodes: “ Bar-On Emocionālā intelekta aptauja”, “Vecāku stresa indekss”, “ Alabamas audzināšanas aptaujas pirmsskolas versija”. Pētījumā tika noskaidrots, ka pastāv statistiski nozīmīga po...

  2. Over-expression of 72 ku protein of wheat yellow mosaic virus in E.coli and preparation of its antiserum

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    By reverse transcription-polymerase chain reaction (RT-PCR),cDNA fragment of wheat yellow mosaic virus (WYMV) RNA2 encoding 72 ku protein has been synthesized and cloned into plasmid pET30a(+) for overexpression in prokaryotic cells.BL21(DE3) pLys S of E.coli transformed with the recombinant plasmid pETP72 containing the fragment has been induced to express the 72 ku protein on high level.The produced protein has been purified from sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE) for its antiserum preparation.In Western-blotting analysis,the antibodies reacted with the 72 ku protein expressed in E.coli.

  3. Triple Band Parasitic Array Antenna for C-X-Ku-Band Application Using Out-of-Phase Coupling Approach

    Directory of Open Access Journals (Sweden)

    Anubhuti Khare

    2014-01-01

    Full Text Available Triple band parasitic array antenna for C-X-Ku-band application is presented. The proposed antenna is designed using the concept of parasitic array and out-of-phase coupling approach. The objects of research are to optimize total inductance of geometry by using out-of-phase inductance approach. The out of phase inductance of geometry consists of using two U-patches novel director on the left side of geometry, appropriate dimension of ground plan, and gap coupling between parasitic and active patches. The dimension of the ground plan geometry is 0.5λ mil × 0.5154λ mil. The usable impedance bandwidth of design antenna is “5.8 GHz to 18 GHz” (102% impedance bandwidth and gain enhancement is up to 11.8 dBi. The proposed antenna can be used for X-Ku band and C-band applications. Both simulated and measured results are presented, which are in good agreement. The proposed antenna was fabricated with a thin copper layer printed on a thin lossy FR4 substrate for low-cost production.

  4. A unified C-band and Ku-band geophysical model function determined by neural network approach

    Institute of Scientific and Technical Information of China (English)

    ZOU Juhong; LIN Mingsen; PAN Delu; CHEN Zhenghua; YANG Le

    2008-01-01

    The geophysical model function (GMF) describes the relationship between backscattering and sea surface wind,so that wind vec-tors can be retrieved from backscattering measurement.The GMF plays an important role in ocean wind vector retrievals,its per-formance will directly influence the accuracy of the retrieved wind vector.Neural network (NN) approach is used to develop a unified GMF for C-band and Ku-band (NN-GMF).Empirical GMF CMOD4 and QSCAT-1 are used to generate the simulated training data-set,and Gaussian noise at a signal noise ratio of 30 dB is added to the data-set to simulate the noise in the backscat-tering measurement.The NN-GMF employs radio frequency as an additional parameter,so it can be applied for both C-hand and Ku-band.Analyses show that the σ0 predicted by the NN-GMF is comparable with the σ0predicted by CMOD4 and QSCAT-1.Al-so the wind vectors retrieved from the NN-GMF and empirical GMF CMOD4 and QSCAT-1 are comparable,indicating that the NN-GMF is as effective as the empirical GMF,and has the advantages of the universal form.

  5. Cytoplasm-translocated Ku70/80 complex sensing of HBV DNA induces hepatitis-associated chemokine secretion

    Directory of Open Access Journals (Sweden)

    Haiming Wei

    2016-12-01

    Full Text Available Chronic hepatitis B remains a serious disease, mainly owing to the severe pathological consequences of persistent hepatitis B virus (HBV infection of carriers, which is difficult to cure using current therapies. When the immune system responds to hepatocytes experiencing rapid HBV replication, effector cells (such as HBV-specific CD8+ T cells, NK cells, NKT cells and other subtypes of immune cells infiltrate the liver and cause hepatitis. However, precisely how these cells are recruited remains unclear. In the present study, we found that the cytoplasm-translocated Ku70/80 complex in liver-derived cells sensed cytosolic HBV DNA and promoted hepatitis-associated chemokine secretion. Upon sensing HBV DNA, DNA-dependent protein kinase catalytic subunit (DNA-PKcs and PARP1 were assembled. Then IRF1 was activated and translocated into the nucleus, which upregulated CCL3 and CCL5 expression. Because CCR5, a major chemokine receptor for CCL3 and CCL5, is known to be critical in hepatitis B, Ku70/80 sensing of HBV DNA likely plays a critical role in immune cell recruitment in response to HBV infection.

  6. Cytoplasm-Translocated Ku70/80 Complex Sensing of HBV DNA Induces Hepatitis-Associated Chemokine Secretion

    Science.gov (United States)

    Li, Young; Wu, Yang; Zheng, Xiaohu; Cong, Jingjing; Liu, Yanyan; Li, Jiabin; Sun, Rui; Tian, Zhigang G.; Wei, Haiming M.

    2016-01-01

    Chronic hepatitis B virus (HBV) infection remains a serious disease, mainly due to its severe pathological consequences, which are difficult to cure using current therapies. When the immune system responds to hepatocytes experiencing rapid HBV replication, effector cells (such as HBV-specific CD8+ T cells, NK cells, NKT cells, and other subtypes of immune cells) infiltrate the liver and cause hepatitis. However, the precise recruitment of these cells remains unclear. In the present study, we found that the cytoplasm-translocated Ku70/80 complex in liver-derived cells sensed cytosolic HBV DNA and promoted hepatitis-associated chemokine secretion. Upon sensing HBV DNA, DNA-dependent protein kinase catalytic subunit and PARP1 were assembled. Then, IRF1 was activated and translocated into the nucleus, which upregulated CCL3 and CCL5 expression. Because CCR5, a major chemokine receptor for CCL3 and CCL5, is known to be critical in hepatitis B, Ku70/80 sensing of HBV DNA likely plays a critical role in immune cell recruitment in response to HBV infection. PMID:27994596

  7. COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.

    Science.gov (United States)

    Lemmens, Bennie B L G; Johnson, Nicholas M; Tijsterman, Marcel

    2013-01-01

    Successful completion of meiosis requires the induction and faithful repair of DNA double-strand breaks (DSBs). DSBs can be repaired via homologous recombination (HR) or non-homologous end joining (NHEJ), yet only repair via HR can generate the interhomolog crossovers (COs) needed for meiotic chromosome segregation. Here we identify COM-1, the homolog of CtIP/Sae2/Ctp1, as a crucial regulator of DSB repair pathway choice during Caenorhabditis elegans gametogenesis. COM-1-deficient germ cells repair meiotic DSBs via the error-prone pathway NHEJ, resulting in a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. In contrast to its yeast counterparts, COM-1 is not required for Spo11 removal and initiation of meiotic DSB repair, but instead promotes meiotic recombination by counteracting the NHEJ complex Ku. In fact, animals defective for both COM-1 and Ku are viable and proficient in CO formation. Further genetic dissection revealed that COM-1 acts parallel to the nuclease EXO-1 to promote interhomolog HR at early pachytene stage of meiotic prophase and thereby safeguards timely CO formation. Both of these nucleases, however, are dispensable for RAD-51 recruitment at late pachytene stage, when homolog-independent repair pathways predominate, suggesting further redundancy and/or temporal regulation of DNA end resection during meiotic prophase. Collectively, our results uncover the potentially lethal properties of NHEJ during meiosis and identify a critical role for COM-1 in NHEJ inhibition and CO assurance in germ cells.

  8. COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.

    Directory of Open Access Journals (Sweden)

    Bennie B L G Lemmens

    Full Text Available Successful completion of meiosis requires the induction and faithful repair of DNA double-strand breaks (DSBs. DSBs can be repaired via homologous recombination (HR or non-homologous end joining (NHEJ, yet only repair via HR can generate the interhomolog crossovers (COs needed for meiotic chromosome segregation. Here we identify COM-1, the homolog of CtIP/Sae2/Ctp1, as a crucial regulator of DSB repair pathway choice during Caenorhabditis elegans gametogenesis. COM-1-deficient germ cells repair meiotic DSBs via the error-prone pathway NHEJ, resulting in a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. In contrast to its yeast counterparts, COM-1 is not required for Spo11 removal and initiation of meiotic DSB repair, but instead promotes meiotic recombination by counteracting the NHEJ complex Ku. In fact, animals defective for both COM-1 and Ku are viable and proficient in CO formation. Further genetic dissection revealed that COM-1 acts parallel to the nuclease EXO-1 to promote interhomolog HR at early pachytene stage of meiotic prophase and thereby safeguards timely CO formation. Both of these nucleases, however, are dispensable for RAD-51 recruitment at late pachytene stage, when homolog-independent repair pathways predominate, suggesting further redundancy and/or temporal regulation of DNA end resection during meiotic prophase. Collectively, our results uncover the potentially lethal properties of NHEJ during meiosis and identify a critical role for COM-1 in NHEJ inhibition and CO assurance in germ cells.

  9. Reduction of reactive red 241 by oxygen insensitive azoreductase purified from a novel strain Staphylococcus KU898286.

    Science.gov (United States)

    Nisar, Numrah; Aleem, Amber; Saleem, Faiza; Aslam, Fakhra; Shahid, Ammara; Chaudhry, Hina; Malik, Kausar; Albaser, Abdulhadi; Iqbal, Amjad; Qadri, Rashad; Yang, Yaodong

    2017-01-01

    An oxygen insensitive azoreductase was purified from a novel bacterial strain (Staphylococcus sp. KU898286) that was isolated from an abandoned site of the textile waste discharge unit. The isolated enzyme had efficiently cleaved the azo-bonds through reductive transformation under aerobic conditions. Initial phenotypic characterization and final construction of phylogenetic tree on the basis of 16s rDNA demonstrated 99% resemblance of the isolate to Staphylococcus aureus. The purified azoreductase was found to have a broad spectrum activity that reduced RR241 at a concentration of 50mg/L with pH between 6-8 and 30°C temperature). Besides, the reactive red 241 (RR241) was reduced at extracellular level as well as NADH dependent intracellular level. Complete reduction/ decolourization of RR241 were achieved after 18 hrs of exposure. The final degradation product observed to be 2-nephthol was purified by High Pressure Liquid Chromatography (HPLC) and the molecular mass was computed by Gas Chromatography-Mass spectroscopy (GC-MS). The study revealed a cost effective and eco-friendly approach to degrade the toxic dyes into less toxic products by Staphylococcus sp. KU898286.

  10. Inhibition of DNA double-strand break repair by the Ku heterodimer in mrx mutants of Saccharomyces cerevisiae

    Science.gov (United States)

    Wasko, Brian M.; Holland, Cory L.; Resnick, Michael A.; Lewis, L. Kevin

    2009-01-01

    Yeast rad50 and mre11 nuclease mutants are hypersensitive to physical and chemical agents that induce DNA double-strand breaks (DSBs). This sensitivity was suppressed by elevating intracellular levels of TLC1, the RNA subunit of telomerase. Suppression required proteins linked to homologous recombination, including Rad51, Rad52, Rad59 and Exo1, but not genes of the nonhomologous end-joining (NHEJ) repair pathway. Deletion mutagenesis experiments demonstrated that the 5′ end of TLC1 RNA was essential and a segment containing a binding site for the Yku70/Yku80 complex was sufficient for suppression. A mutant TLC1 RNA unable to associate with Yku80 protein did not increase resistance. These and other genetic studies indicated that association of the Ku heterodimer with broken DNA ends inhibits recombination in mrx mutants, but not in repair-proficient cells or in other DNA repair single mutants. In support of this model, DNA damage resistance of mrx cells was enhanced when YKU70 was co-inactivated. Defective recombinational repair of DSBs in mrx cells thus arises from at least two separate processes: loss of Mrx nuclease-associated DNA end-processing and inhibition of the Exo1-mediated secondary recombination pathway by Ku. PMID:18992851

  11. Expression of DNA-dependent protein kinase in human granulocytes

    Institute of Scientific and Technical Information of China (English)

    Annahita SALLMYR; Anna MILLER; Aida GABDOULKHAKOVA; Valentina SAFRONOVA; Gunnel HENRIKSSON; Anders BREDBERG

    2004-01-01

    Human polymorphonuclear leukocytes (PMN) have been reported to completely lack of DNA-dependent protein kinase (DNA-PK) which is composed of Ku protein and the catalytic subunit DNA-PKcs, needed for nonhomologous end-joining (NHEJ) of DNA double-strand breaks. Promyelocytic HL-60 cells express a variant form of Ku resulting in enhanced radiation sensitivity. This raises the question if low efficiency of NHEJ, instrumental for the cellular repair of oxidative damage, is a normal characteristic of myeloid differentiation. Here we confirmed the complete lack of DNAPK in P MN protein extracts, and the expression of the truncated Ku86 variant form in HL-60. However, this degradation of DNA-PK was shown to be due to a DNA-PK-degrading protease in PMN and HL-60. In addition, by using a protease-resistant whole cell assay, both Ku86 and DNA-PKcs could be demonstrated in PMN, suggesting the previously reported absence in PMN of DNA-PK to be an artefact. The levels of Ku86 and DNA-PKcs were much reduced in PMN, as compared with that of the lymphocytes, whereas HL-60 displayed a markedly elevated DNA-PK concentration.In conclusion, our findings provide evidence of reduced, not depleted expression of DNA-PK during the mature stages of myeloid differentiation.

  12. Relationships between values of antibodies to several connective tissue disease autoantigens and pulmonary function in a Japanese general population: the Takahata study.

    Directory of Open Access Journals (Sweden)

    Hiroshi Nakano

    Full Text Available BACKGROUND: Accumulating evidence suggests the involvement of an autoimmune mechanism in the pathogenesis of respiratory dysfunction. The aim of this study was to investigate the relationship between pulmonary function and serum antibodies to several connective tissue disease autoantigens (ACTDA levels, which has not been investigated in a general population. METHODS: Blood sampling and spirometry were performed for subjects (n = 3,257 aged ≥40 years who participated in a community-based annual health check in Takahata, Japan, from 2004 to 2006. ACTDA was measured by enzyme immunoassay, and subjects with ACTDA values ≥20 were defined as positive. RESULTS: In males, there were significant inverse relationships between logarithmically transformed ACTDA values and spirometric parameters, including % predicted values for forced expiratory volume in 1 s (FEV1 and maximal midexpiratory flow (MMF as well as FEV1/forced vital capacity (FVC. Multiple linear regression analysis revealed that except for the relationship between ACTDA and FEV1/FVC, these relationships were still significant after adjustment for Brinkman index (a measure of inhaled cigarette consumption. The prevalence of positive ACTDA was greater in male never-smokers with mixed ventilation disorders and relatively severe airflow obstruction (% predicted FEV1 below the median value. CONCLUSIONS: Autoimmunity may be involved in the mechanism of impaired pulmonary function in the general population.

  13. Aire-dependent thymic expression of desmoglein 3, the autoantigen in pemphigus vulgaris, and its role in T-cell tolerance.

    Science.gov (United States)

    Wada, Naoko; Nishifuji, Koji; Yamada, Taketo; Kudoh, Jun; Shimizu, Nobuyoshi; Matsumoto, Mitsuru; Peltonen, Leena; Nagafuchi, Seiho; Amagai, Masayuki

    2011-02-01

    In the mechanism of thymus-induced central tolerance, the transcription factor Aire has been demonstrated to promote the expression of a wide range of peripheral organ-specific antigens (Ags) in the medullary thymic epithelial cells (mTECs), which serve as self-Ags in negative selection. We examined the expression of desmoglein 3 (Dsg3), the autoantigen in pemphigus vulgaris (PV), in mouse thymus and the involvement of Aire in tolerance to Dsg3. Immunofluorescence and in situ hybridization revealed Dsg3 in single cells or in clusters in ∼3% of mTECs near the cortico-medullary junction of the thymus in C57BL/6 mice. Dsg3-expressing mTECs also expressed some Ags of skin-unrelated peripheral organs simultaneously. In contrast, Dsg3-positive mTECs were not detected in the Aire(-/-) thymus. Adoptive transfer of splenocytes from Aire(-/-) mice immunized with Dsg3 did not induce anti-Dsg3 IgG production or PV phenotype in Rag2(-/-) recipient mice. However, Aire(-/-) CD4(+) T cells, but not Aire(+/+) CD4(+) T cells, induced low levels of anti-Dsg3 IgG production when transferred with Dsg3(-/-) B cells. These findings indicate that Aire has an important role in Dsg3 expression as well as in selection of T cells that help B cells to produce anti-Dsg3 IgG in thymus.

  14. DNA double-strand break induction in Ku80-deficient CHO cells following Boron Neutron Capture Reaction

    Directory of Open Access Journals (Sweden)

    Masunaga Shinichiro

    2011-09-01

    Full Text Available Abstract Background Boron neutron capture reaction (BNCR is based on irradiation of tumors after accumulation of boron compound. 10B captures neutrons and produces an alpha (4He particle and a recoiled lithium nucleus (7Li. These particles have the characteristics of high linear energy transfer (LET radiation and have marked biological effects. The purpose of this study is to verify that BNCR will increase cell killing and slow disappearance of repair protein-related foci to a greater extent in DNA repair-deficient cells than in wild-type cells. Methods Chinese hamster ovary (CHO-K1 cells and a DNA double-strand break (DSB repair deficient mutant derivative, xrs-5 (Ku80 deficient CHO mutant cells, were irradiated by thermal neutrons. The quantity of DNA-DSBs following BNCR was evaluated by measuring the phosphorylation of histone protein H2AX (gamma-H2AX and 53BP1 foci using immunofluorescence intensity. Results Two hours after neutron irradiation, the number of gamma-H2AX and 53BP1 foci in the CHO-K1 cells was decreased to 36.5-42.8% of the levels seen 30 min after irradiation. In contrast, two hours after irradiation, foci levels in the xrs-5 cells were 58.4-69.5% of those observed 30 min after irradiation. The number of gamma-H2AX foci in xrs-5 cells at 60-120 min after BNCT correlated with the cell killing effect of BNCR. However, in CHO-K1 cells, the RBE (relative biological effectiveness estimated by the number of foci following BNCR was increased depending on the repair time and was not always correlated with the RBE of cytotoxicity. Conclusion Mutant xrs-5 cells show extreme sensitivity to ionizing radiation, because xrs-5 cells lack functional Ku-protein. Our results suggest that the DNA-DSBs induced by BNCR were not well repaired in the Ku80 deficient cells. The RBE following BNCR of radio-sensitive mutant cells was not increased but was lower than that of radio-resistant cells. These results suggest that gamma-ray resistant cells have

  15. Multiple Ku orthologues mediate DNA non-homologous end-joining in the free-living form and during chronic infection of Sinorhizobium meliloti.

    Science.gov (United States)

    Kobayashi, Hajime; Simmons, Lyle A; Yuan, Daniel S; Broughton, William J; Walker, Graham C

    2008-01-01

    The bacterial non-homologous end-joining (NHEJ) apparatus is a two-component system that uses Ku and LigD to repair DNA double-strand breaks. Although the reaction mechanism has been extensively studied, much less is known about the physiological role of bacterial NHEJ. Recent studies suggest that NHEJ acts under conditions where DNA replication is reduced or absent (such as in a spore or stationary phase). Interestingly, genes encoding Ku and LigD have been identified in a wide range of bacteria that can chronically infect eukaryotic hosts. Strikingly, Sinohizobium meliloti, an intracellular symbiont of legume plants, carries four genes encoding Ku homologues (sku1 to sku4). Deletion analysis of the sku genes indicated that all Ku homologues are functional. One of these genes, sku2, is strongly expressed in free-living cells, as well as in bacteroid cells residing inside of the host plant. To visualize the NHEJ apparatus in vivo, SKu2 protein was fused to yellow fluorescent protein (YFP). Ionizing radiation (IR) induced focus formation of SKu2-YFP in free-living cells in a dosage-dependent manner. Moreover, SKu2-YFP foci formed in response to IR in non-dividing bacteroids, indicating that NHEJ system is functional even during the chronic infection phase of symbiosis.

  16. Impact of tropospheric scintillation in the Ku/K bands on the communications between two LEO satellites in a radio occultation geometry

    DEFF Research Database (Denmark)

    Martini, Enrica; Freni, A.; Facheris, L.

    2006-01-01

    A theoretical analysis of the impact of clear-air tropospheric scintillation on a radio occultation link between two low Earth orbit satellites in K- and Ku-bands is presented, with particular reference to differential approaches for the measure of the total content of water vapor. The troposphere...

  17. Association of methylenetetrahydrofolate reductase C677T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    Directory of Open Access Journals (Sweden)

    Cao Xiao-Li

    2010-10-01

    Full Text Available Abstract Background The association of methylenetetrahydrofolate reductase (MTHFR gene polymorphism and serum lipid profiles is still controversial in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. The aim of the present study was to eveluate the association of MTHFR C677T polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 780 subjects of Bai Ku Yao and 686 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the MTHFR C677T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum total cholesterol (TC, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C, apolipoprotein (Apo AI and ApoB were lower in Bai Ku Yao than in Han (P P P P P P P Conclusions The differences in serum TC, TG, LDL-C and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of the MTHFR C677T or different MTHFR gene-enviromental interactions.

  18. Lenka Procházková, Slunce v ùplňku (Přiběh Jana Palacha

    Directory of Open Access Journals (Sweden)

    Richard Vacula

    2009-02-01

    Full Text Available Lorsque Lenka Procházková publia son roman Slunce v úplňku (Plein soleil en 2008, le thème n’était pas nouveau pour elle. En effet, en 1988 elle avait rédigé un texte sur le sacrifice de Jan Palach, l’étudiant tchèque qui, en janvier 1969, s’immola à Prague pour protester contre l’occupation de la Tchécoslovaquie par les armées du Pacte de Varsovie. Ce texte ne vit alors le jour que sous la forme d’un samizdat. L’auteur a décidé de reprendre et de modifier son texte.Dans son roman, Procházko...

  19. Rain Rate-Radar Reflectivity Relationship for Drop Size Distribution and Rain Attenuation Calculation of Ku Band Signals

    Directory of Open Access Journals (Sweden)

    Govardhani.Immadi

    2014-05-01

    Full Text Available With the increased demand for long distance Tele communication day by day, satellite communication system was developed. Satellite communications utilize L, C, Ku and Ka bands of frequency to fulfil all the requirements. Utilization of higher frequencies causes severe attenuation due to rain. Rain attenuation is noticeable for frequencies above 10ghz. Amount of attenuation depends on whether the operating wave length is comparable with rain drop diameter or not. In this paper the main focus is on drop size distribution using empirical methods, especially Marshall and Palmer distributions. Empirical methods deal with power law relation between the rain rate(mm/h and radar reflectivity(dBz. Finally it is discussed about the rain rate variation, radar reflectivity, drop size distribution, that is made for two rain events at K L University, Vijayawada on 4th September 2013 and on 18 th August 2013.

  20. Vinac Marijana Jaića Molitvenik ili dio kućne baštine

    OpenAIRE

    Blažević, Krešimir

    2006-01-01

    U ovom članku želio sam pokazati kako se mnoge stvari mogu i moraju redefinirati i nanovo razjasniti u recentno vrijeme. Marijan Jaić, vjerojatno najtiražniji hrvatski pisac, dugo godina je bio u zapećku proučavanja hrvatske književnosti. Iako je zanimanje za Jaića u posljednjih desetak ili petnaest godina naraslo (napisano je puno knjiga o njemu i njegovu radu), još uvijek nije njegov rad do kraja obrađen i prostora za istraživanje o Jaićevu radu još uvijek ima. Jaić možda i nije književnik ...

  1. Effects of surface roughness on sea ice freeboard retrieval with an Airborne Ku-Band SAR radar altimeter

    DEFF Research Database (Denmark)

    Hendricks, Stefan; Stenseng, Lars; Helm, Veit

    2010-01-01

    Results from two years of the CryoSat Validation Experiment (CryoVEx) over sea ice in the western Arctic Ocean are presented. The estimation of freeboard, the height of sea ice floating above the water level, is one the main goals of the CryoSat-2 mission of the European Space Agency (ESA) in order...... to investigate sea ice volume changes on an Arctic wide scale. Freeboard retrieval requires precise radar range measurements to the ice surface, therefore we investigate the penetration of the Ku-Band radar waves into the overlying snow cover as well as the effects of sub-footprint-scale surface roughness using...... of the airborne validation dataset, since the radar overestimates the amount of open water and thin ice as well the freeboard of heavy ice deformation zones....

  2. A Ku-band high power density AlGaN/GaN HEMT monolithic power amplifier

    Institute of Scientific and Technical Information of China (English)

    Ge Qin; Chen Xiaojuan; Luo Weijun; Yuan Tingting; Pang Lei; Liu Xinyu

    2011-01-01

    A high power density monolithic power amplifier operated at Ku band is presented utilizing a 0.3 μm AlGaN/GaN HEMT production process on a 2-inch diameter semi-insulating (SI) 4H-SiC substrate by MOCVD.Over the 12-14 GHz frequency range,the single chip amplifier demonstrates a maximum power of 38 dBm (6.3 W),a peak power added efficiency (PAE) of 24.2% and linear gain of 6.4 to 7.5 dB under a 10% duty pulse conditionwhen operated at Vds =25 V and Vgs =-4 V.At these power levels,the amplifier exhibits a power density in excess of 5 W/mm.

  3. Significant Delay of Lethal Outcome in Cancer Patients Due to Peroral Administration of Bacillus oligonitrophilus KU-1

    Directory of Open Access Journals (Sweden)

    Sergey V. Malkov

    2006-01-01

    Full Text Available Treatment of cancer patients remains a serious medical problem and the development of alternative treatment strategies is therefore of great importance. In this connection, we developed a new bacterial-based, anticancer method. Ten cancer patients (three males, seven females were involved in this study. Bacterial suspension of stationary phase Bacillus oligonitrophilus KU-1 was used as a remedy for peroral administration. In five patients, side effects (sicchasia, slight blood, and intracranial pressure gain were detected, but all patients showed significant delay of lethal outcome without serious side effects. In conclusion, the suggested method was, in our opinion, a good alternative to conventional chemo- and radiotherapy techniques. In order to evaluate its efficiency for various tumors, a double-blind, placebo-controlled, multicenter study is needed.

  4. Effect of Ku80 deficiency on mutation frequencies and spectra at a LacZ reporter locus in mouse tissues and cells.

    Directory of Open Access Journals (Sweden)

    Rita A Busuttil

    Full Text Available Non-homologous end joining (NHEJ is thought to be an important mechanism for preventing the adverse effects of DNA double strand breaks (DSBs and its absence has been associated with premature aging. To investigate the effect of inactivated NHEJ on spontaneous mutation frequencies and spectra in vivo and in cultured cells, we crossed a Ku80-deficient mouse with mice harboring a lacZ-plasmid-based mutation reporter. We analyzed various organs and tissues, as well as cultured embryonic fibroblasts, for mutations at the lacZ locus. When comparing mutant with wild-type mice, we observed a significantly higher number of genome rearrangements in liver and spleen and a significantly lower number of point mutations in liver and brain. The reduced point mutation frequency was not due to a decrease in small deletion mutations thought to be a hallmark of NHEJ, but could be a consequence of increased cellular responses to unrepaired DSBs. Indeed, we found a substantial increase in persistent 53BP1 and gammaH2AX DNA damage foci in Ku80-/- as compared to wild-type liver. Treatment of cultured Ku80-deficient or wild-type embryonic fibroblasts, either proliferating or quiescent, with hydrogen peroxide or bleomycin showed no differences in the number or type of induced genome rearrangements. However, after such treatment, Ku80-deficient cells did show an increased number of persistent DNA damage foci. These results indicate that Ku80-dependent repair of DNA damage is predominantly error-free with the effect of alternative more error-prone pathways creating genome rearrangements only detectable after extended periods of time, i.e., in young adult animals. The observed premature aging likely results from a combination of increased cellular senescence and an increased load of stable, genome rearrangements.

  5. Resistance to Sri Lankan Cassava Mosaic Virus (SLCMV) in Genetically Engineered Cassava cv. KU50 through RNA Silencing

    KAUST Repository

    Ntui, Valentine Otang

    2015-04-22

    Cassava ranks fifth among the starch producing crops of the world, its annual bioethanol yield is higher than for any other crop. Cassava cultivar KU50, the most widely grown cultivar for non-food purposes is susceptible to Sri Lankan cassava mosaic virus (SLCMV). The objective of this work was to engineer resistance to SLCMV by RNA interference (RNAi) in order to increase biomass yield, an important aspect for bioethanol production. Here, we produced transgenic KU50 lines expressing dsRNA homologous to the region between the AV2 and AV1 of DNA A of SLCMV. High level expression of dsRNA of SLCMV did not induce any growth abnormality in the transgenic plants. Transgenic lines displayed high levels of resistance to SLCMV compared to the wild-type plants and no virus load could be detected in uninoculated new leaves of the infected resistant lines after PCR amplification and RT-PCR analysis. The agronomic performance of the transgenic lines was unimpaired after inoculation with the virus as the plants presented similar growth when compared to the mock inoculated control plants and revealed no apparent reduction in the amount and weight of tubers produced. We show that the resistance is correlated with post-transcriptional gene silencing because of the production of transgene specific siRNA. The results demonstrate that transgenic lines exhibited high levels of resistance to SLCMV. This resistance coupled with the desirable yield components in the transgenic lines makes them better candidates for exploitation in the production of biomass as well as bioethanol.

  6. Microwave-assisted synthesis of graphene–Ni composites with enhanced microwave absorption properties in Ku-band

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zetao [College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, 210016 Nanjing (China); Sun, Xin [Science and Technology on Electromagnetic Scattering Laboratory, 100854 Beijing (China); Li, Guoxian [Shenyang National Laboratory for Materials Science Institute of Metal Research, Chinese Academy of Sciences, 110016 Shenyang (China); Xue, Hairong; Guo, Hu; Fan, Xiaoli; Pan, Xuchen [College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, 210016 Nanjing (China); He, Jianping, E-mail: jianph@nuaa.edu.cn [College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, 210016 Nanjing (China)

    2015-03-01

    Recently, graphene has been applied as a new microwave absorber because of its high dielectric loss and low density. Nevertheless, the high dielectric constant of pristine graphene has caused unbalanced electromagnetic parameters and results in a bad impedance matching characteristic. In this study, we report a facile microwave-assisted heating approach to produce reduced graphene oxide–nickel (RGO–Ni) composites. The phase and morphology of as-synthesized RGO–Ni composites are characterized by XRD, Raman, FESEM and TEM. The results show that Ni nanoparticles with a diameter around 20 nm are grown densely and uniformly on the RGO sheets. In addition, enhanced microwave absorption properties in Ku-band of RGO–Ni composites is mainly due to the synergistic effect of dielectric loss and magnetic loss and the dramatically electron polarizations caused by the formation of large conductive network. The minimum reflection loss of RGO–Ni-2 composite with the thickness of 2 mm can reaches −42 dB at 17.6 GHz. The RGO–Ni composite is an attractive candidate for the new type of high performance microwave absorbing material. - Highlights: • Ni nanoparticles are grown densely and uniformly on the RGO sheets via microwave-assisted heating approach. • Ni resistance effect is proposed to explain the mechanism to decrease the permittivity with the rising combination of Ni and RGO. • The microwave absorption properties in Ku-band of RGO–Ni composites are effectively enhanced. • The mechanism to improve the microwave absorption properties is discussed.

  7. Resistance to Sri Lankan cassava mosaic virus (SLCMV in genetically engineered cassava cv. KU50 through RNA silencing.

    Directory of Open Access Journals (Sweden)

    Valentine Otang Ntui

    Full Text Available Cassava ranks fifth among the starch producing crops of the world, its annual bioethanol yield is higher than for any other crop. Cassava cultivar KU50, the most widely grown cultivar for non-food purposes is susceptible to Sri Lankan cassava mosaic virus (SLCMV. The objective of this work was to engineer resistance to SLCMV by RNA interference (RNAi in order to increase biomass yield, an important aspect for bioethanol production. Here, we produced transgenic KU50 lines expressing dsRNA homologous to the region between the AV2 and AV1 of DNA A of SLCMV. High level expression of dsRNA of SLCMV did not induce any growth abnormality in the transgenic plants. Transgenic lines displayed high levels of resistance to SLCMV compared to the wild-type plants and no virus load could be detected in uninoculated new leaves of the infected resistant lines after PCR amplification and RT-PCR analysis. The agronomic performance of the transgenic lines was unimpaired after inoculation with the virus as the plants presented similar growth when compared to the mock inoculated control plants and revealed no apparent reduction in the amount and weight of tubers produced. We show that the resistance is correlated with post-transcriptional gene silencing because of the production of transgene specific siRNA. The results demonstrate that transgenic lines exhibited high levels of resistance to SLCMV. This resistance coupled with the desirable yield components in the transgenic lines makes them better candidates for exploitation in the production of biomass as well as bioethanol.

  8. Resistance to Sri Lankan cassava mosaic virus (SLCMV) in genetically engineered cassava cv. KU50 through RNA silencing.

    Science.gov (United States)

    Ntui, Valentine Otang; Kong, Kynet; Khan, Raham Sher; Igawa, Tomoko; Janavi, Gnanaguru Janaky; Rabindran, Ramalingam; Nakamura, Ikuo; Mii, Masahiro

    2015-01-01

    Cassava ranks fifth among the starch producing crops of the world, its annual bioethanol yield is higher than for any other crop. Cassava cultivar KU50, the most widely grown cultivar for non-food purposes is susceptible to Sri Lankan cassava mosaic virus (SLCMV). The objective of this work was to engineer resistance to SLCMV by RNA interference (RNAi) in order to increase biomass yield, an important aspect for bioethanol production. Here, we produced transgenic KU50 lines expressing dsRNA homologous to the region between the AV2 and AV1 of DNA A of SLCMV. High level expression of dsRNA of SLCMV did not induce any growth abnormality in the transgenic plants. Transgenic lines displayed high levels of resistance to SLCMV compared to the wild-type plants and no virus load could be detected in uninoculated new leaves of the infected resistant lines after PCR amplification and RT-PCR analysis. The agronomic performance of the transgenic lines was unimpaired after inoculation with the virus as the plants presented similar growth when compared to the mock inoculated control plants and revealed no apparent reduction in the amount and weight of tubers produced. We show that the resistance is correlated with post-transcriptional gene silencing because of the production of transgene specific siRNA. The results demonstrate that transgenic lines exhibited high levels of resistance to SLCMV. This resistance coupled with the desirable yield components in the transgenic lines makes them better candidates for exploitation in the production of biomass as well as bioethanol.

  9. Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis.

    Science.gov (United States)

    Xiong, Yi-Song; Cheng, Yue; Lin, Qiu-Shui; Wu, Ai-Lin; Yu, Juan; Li, Chang; Sun, Yi; Zhong, Ren-Qian; Wu, Li-Juan

    2014-02-01

    Elevated expression of Siglec-1 on circulating monocytes has been reported in some inflammatory and autoimmune diseases, but its expression and role in RA has not been elucidated. The aims of this study were to determine the expression of Siglec-1 in peripheral blood and to explore its role in mononuclear cell reactivity to autoantigen in RA. Siglec-1 protein and mRNA levels in 42 RA patients, 39 OA patients, 28 SLE patients and 42 normal controls were determined by flow cytometry and quantitative RT-PCR, respectively. In addition, 10 patients with active RA received DMARDs for 12 weeks and the frequencies of Siglec-1-positive cells and the 28-joint DAS (DAS28) were assessed before and after therapy. Furthermore, TNF-α, IFN-γ and type II collagen were used to up-regulate Siglec-1. Peripheral blood mononuclear cells (PBMCs) from different groups were stimulated with mitogens or antigens and cell proliferation and cytokine production were determined. The protein and mRNA levels of Siglec-1 on PBMCs and monocytes in RA patients were significantly higher than those in OA patients and healthy controls. Moreover, the expression of Siglec-1 protein on PBMCs was positively correlated with DAS28, ESR, high-sensitivity CRP and IgM-RF, but not with anti-CCP antibody. Interestingly, Siglec-1 expression was decreased in parallel with the decrease in the DAS28 after 12 weeks of anti-rheumatic treatment. Furthermore, TNF-α, IFN-γ and type II collagen can up-regulate Siglec-1 in PBMCs. Elevated PBMC proliferation and proinflammatory cytokine production to collagen stimulation in RA patients decreased when Siglec-1 was inhibited by anti-Siglec-1 antibodies. Elevated Siglec-1 expression in PBMCs and monocytes can potentially serve as a biomarker for monitoring disease activity in RA. Siglec-1 may also play a proinflammatory role in stimulating lymphocyte proliferation and activation in RA.

  10. Ku80 as a novel receptor for thymosin beta4 that mediates its intracellular activity different from G-actin sequestering.

    Science.gov (United States)

    Bednarek, Radoslaw; Boncela, Joanna; Smolarczyk, Katarzyna; Cierniewska-Cieslak, Aleksandra; Wyroba, Elzbieta; Cierniewski, Czeslaw S

    2008-01-18

    Our data demonstrate that increased intracellular expression of thymosin beta4(Tbeta4) is necessary and sufficient to induce plasminogen activator inhibitor type 1 (PAI-1) gene expression in endothelial cells. To describe the mechanism of this effect, we produced Tbeta4 mutants with impaired functional motifs and tested their intracellular location and activity. Cytoplasmic distributions of Tbeta4((AcSDKPT/4A)), Tbeta4((KLKKTET/7A)), and Tbeta4((K16A)) mutants fused with green fluorescent protein did not differ significantly from those of wild-type Tbeta4. Overexpression of Tbeta4, Tbeta4((AcSDKPT/4A)), and Tbeta4((K16A)) affected intracellular formation of actin filaments. As expected, Tbeta4((K16A)) uptake by nuclei was impaired. On the other hand, overexpression of Tbeta4((KLKKTET/7A)) resulted in developing the actin filament network typical of adhering cells, indicating that the mutant lacked the actin binding site. The mechanism by which intracellular Tbeta4 induced the PAI-1 gene did not depend upon the N-terminal tetrapeptide AcSDKP and depended only partially on its ability to bind G-actin or enter the nucleus. Both Tbeta4 and Tbeta4((AcSDKPT/4A)) induced the PAI-1 gene to the same extent, whereas mutants Tbeta4((KLKKTET/7A)) and Tbeta4((K16A)) retained about 60% of the original activity. By proteomic analysis, the Ku80 subunit of ATP-dependent DNA helicase II was found to be associated with Tbeta4. Ku80 and Tbeta4 consistently co-immunoprecipitated in a complex from endothelial cells. Co-transfection of endothelial cells with the Ku80 deletion mutants and Tbeta4 showed that the C-terminal arm domain of Ku80 is directly involved in this interaction. Furthermore, down-regulation of Ku80 by specific short interference RNA resulted in dramatic reduction in PAI-1 expression at the level of both mRNA and protein synthesis. These data suggest that Ku80 functions as a novel receptor for Tbeta4 and mediates its intracellular activity.

  11. Three-year study on feasibility of Snow Water Equivalent retrieval using X- to Ku band SAR

    Science.gov (United States)

    Lemmetyinen, Juha; Pulliainen, Jouni; Kontu, Anna; Wiesmann, Andreas; Mätzler, Christian; Rott, Helmut; Nagler, Thomas; Meta, Adriano; Schneebeli, Martin; Proksch, Martin; Davidson, Malcolm; Schüttemeyer, Dirk; Kern, Michael

    2013-04-01

    The possibility of high-resolution SAR imagery to derive information on the Snow Water Equivalent (SWE) of seasonal snow cover is one of the main goals of the proposed CoReH2O (Cold Regions Hydrology High-Resolution Observatory) mission. CoReH2O is a candidate 7th Earth Explorer Core mission by the European Space Agency (ESA), currently in Phase A. The NoSREx (Nordic Snow Radar Experiment) campaign was initiated in 2009 to provide data for development of the CoReH2O geophysical retrieval algorithm. The campaign provides a time-series of backscatter observations at X to Ku bands, the dual frequency bands proposed for CoReH2O, from snow covered terrain in the boreal forest/taiga region. The campaign was designed to cover entire winter periods from snow free conditions to eventual snow melt-off. Backscatter measurements of snow cover are complemented by microwave emission (radiometer) observations and numerous in situ observations of snow, soil and atmospheric properties. The campaign thus provides a unique, near-continuous dataset of coinciding microwave observations of snow cover and diverse measurements of snow characteristics over several winter seasons. The main instrument of the campaign is the ESA SnowScat scatterometer, installed for the entire campaign at a fixed location. The instrument provides a consistent time series of observations, allowing relating the backscatter signature to small scale changes in the snowpack at a high temporal resolution. During the second and third seasons of the campaign, SnowScat measurements were complemented by extensive airborne data acquisitions using the ESA X/Ku band SnowSAR instrument. The airborne data provide additional information on spatial variability of the backscattering signal, and allow demonstration of the CoReH2O SWE retrieval concept. As a reference to backscatter observations, the campaign provides routinely both manual and automated measurements of snow properties throughout the season. In addition, several

  12. The construction and expression of chimeric urokinase-type plasminogen activator genes containing kringle domains of human plasminogen.

    Science.gov (United States)

    Boutaud, A; Castellino, F J

    1993-06-01

    A series of chimeric urokinase-type plasminogen activator (uPA) genes, which contain combinations of kringle domains of human plasminogen (HPg) in place of the uPA kringle (KuPA), has been constructed and expressed. Some of the resulting recombinant (r) variant uPA chimeras contain modules that potentially mediate the macroscopic binding of HPg to its activation effectors, fibrin(ogen) and 6-aminohexanoic acid (EACA). Such binding sites are not possessed by KuPA, but are present in certain of the HPg kringles, viz., kringle 1 (K1HPg), kringle 4 (K4HPg), and kringle 5 (K5HPg). The recombinant (r) chimeras constructed included molecules with replacements of KuPA with K1HPg (r-[KuPA-->K1HPg]uPA), and with KuPA replaced by double kringle combinations of K1HPgK4HPg (r-[KuPA-->K1HPgK4HPg]uPA), K2HPgK3HPg (r-[KuPA-->K2HPgK3HPg]uPA), and K4HPgK5HPg (r-[KuPA-->K4HPgK5HPg]uPA). All of these variant genes, along with their wild-type (wt) r-uPA counterparts, were expressed in human kidney 293 cells. In cases wherein EACA-binding kringles from HPg have been placed in uPA, this property has been retained in the chimeric molecule and employed as an essential part of the purification procedures for the variants. The steady state amidolytic activity of two-chain (tc) wtr-uPA toward the chromogenic substrate, H-D-pyroglutamyl-Gly-L-Arg-p-nitroanilide (S2444), is characterized by a kcat/KM (pH 7.4, 37 degrees C) of 120 s-1 mM-1. This value ranges from 92 s-1 mM-1 (tcr-[KuPA-->K1HPg]uPA) to 166 s-1 mM-1 (tcr-[KuPA-->K1HPgK4HPg]uPA) for each of the variants, demonstrating that the catalytic efficiency of the active site is altered only in a small way by changes in the noncatalytic domain of uPA. Small differences are also observed in the abilities of these tcr variants to interact with the fast-acting plasma inhibitor of uPA, viz., plasminogen activator inhibitor-1 (PAI-1). The second-order rate constant for the interaction of PAI-1 with tcr-uPA, 0.46 x 10(7) M-1s-1 (pH 7.4, 10 degrees

  13. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.

    Directory of Open Access Journals (Sweden)

    Chaojun Hu

    Full Text Available Autoantibodies in cerebrospinal fluid (CSF from patients with neuropsychiatric systemic lupus erythematosus (NPSLE may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosuspatients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43.Anti-proliferating cell nuclear antigen (PCNA was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A. The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045.Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009. Analysis with Spearman's rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE.

  14. Melanocyte antigen triggers autoimmunity in human psoriasis.

    Science.gov (United States)

    Arakawa, Akiko; Siewert, Katherina; Stöhr, Julia; Besgen, Petra; Kim, Song-Min; Rühl, Geraldine; Nickel, Jens; Vollmer, Sigrid; Thomas, Peter; Krebs, Stefan; Pinkert, Stefan; Spannagl, Michael; Held, Kathrin; Kammerbauer, Claudia; Besch, Robert; Dornmair, Klaus; Prinz, Jörg C

    2015-12-14

    Psoriasis vulgaris is a common T cell-mediated inflammatory skin disease with a suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8(+) T cells are essential for psoriasis development. Functional implications of HLA-C*06:02 and mechanisms of lesional T cell activation in psoriasis, however, remained elusive. Here we identify melanocytes as skin-specific target cells of an HLA-C*06:02-restricted psoriatic T cell response. We found that a Vα3S1/Vβ13S1 T cell receptor (TCR), which we had reconstituted from an epidermal CD8(+) T cell clone of an HLA-C*06:02-positive psoriasis patient specifically recognizes HLA-C*06:02-positive melanocytes. Through peptide library screening, we identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02-presented melanocytic autoantigen of the Vα3S1/Vβ13S1 TCR. Consistent with the Vα3S1/Vβ13S1-TCR reactivity, we observed numerous CD8(+) T cells in psoriasis lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, IL-17A, in CD8(+) T cells from psoriasis patients only, supporting a role as psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from tissue-infiltrating CD8(+) T cells reveals that in psoriasis HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation. We propose that HLA-C*06:02 may predispose to psoriasis via this newly identified autoimmune pathway.

  15. Cloning and prokaryotic expression of 49 Ku ES protein structural gene for Trichinella nativa%本地毛形线虫49 Ku ES蛋白结构基因的分子克隆及原核表达

    Institute of Scientific and Technical Information of China (English)

    郑宝亮; 王秀荣; 路义鑫; 李冬梅; 闫清波; 宋铭忻

    2007-01-01

    提取Trichinella nativa(T.nativa)肌幼虫的总RNA,用RT-PCR方法扩增出了编码T.nativa 49 Ku ES蛋白的结构基因.基因克隆后测序,序列测定结果表明:目的基因TNPG长度为951 bp,核苷酸序列同已发表的Trichinella spiralis(T.spiralis)相应的序列P49同源性为97.68%,所推导的氨基酸序列同源性为95.24%.将目的基因TNPG插入到原核表达栽体pET-30a的BamH I酶切位点处,并转化到感受态表达菌中进行诱导表达.结果显示TNPG在原核表达茵BL-21中获得了高效表达,表达产物为40.8 Ku的融合蛋白,表达量达到菌体总蛋白的22.8%.通过Western blot分析,表达产物可以被小鼠T.nativa和T.spiralis阳性血清以及它们的中国地理株的小鼠血清特异性识别.

  16. Time-series Doppler images and surface differential rotation of the effectively-single rapidly-rotating K-giant KU Pegasi

    CERN Document Server

    Kővári, Zs; Strassmeier, K G; Carroll, T A; Weber, M; Kriskovics, L; Oláh, K; Vida, K; Granzer, T

    2016-01-01

    According to most stellar dynamo theories, differential rotation (DR) plays a crucial role for the generation of toroidal magnetic fields. Numerical models predict surface differential rotation to be anti-solar for rapidly-rotating giant stars, i.e., their surface angular velocity could increase with stellar latitude. However, surface differential rotation has been derived only for a handful of individual giant stars to date. The spotted surface of the K-giant KU Pegasi is investigated in order to detect its time evolution and quantify surface differential rotation. We present altogether 11 Doppler images from spectroscopic data collected with the robotic telescope STELLA between 2006--2011. All maps are obtained with the surface reconstruction code iMap. Differential rotation is extracted from these images by detecting systematic (latitude-dependent) spot displacements. We apply a cross-correlation technique to find the best differential rotation law. The surface of KU Peg shows cool spots at all latitudes a...

  17. Tüketici Etnosentrizmi ve Tüketici Husumetinin X,Y,Z Kuşakları Açısından İncelenmesi

    OpenAIRE

    FETTAHLIOĞLU, H.Seçil; SÜNBÜL, Mehri Banu

    2015-01-01

    Bu çalışmada temel olarak tüketici etnosentrizmi ile tüketici husumetinin X, Y ve Z kuşakları açısından incelenmesi amaçlanmıştır. Bunun yanında ikincil amacımız tüketici etnosentrizmi ile tüketici husumeti arasındaki ilişkinin incelenmesidir. Çalışmada betimsel analizler, güvenilirlik analizi, faktör analizi, korelasyon ve One Way ANOVA analizleri gibi tekniklerden yararlanılmıştır. Bu analizlerden elde edilen bulgulara göre Türk tüketicilerin etnosentrik eğilimleri dahil oldukları kuşakla...

  18. The Goodpasture autoantigen. Structural delineation of two immunologically privileged epitopes on alpha3(IV) chain of type IV collagen.

    Science.gov (United States)

    Kalluri, R; Sun, M J; Hudson, B G; Neilson, E G

    1996-04-12

    The family of type IV collagen comprises six chains numbered alpha1 through alpha6. The alpha3(IV) NC1 domain is the primary target antigen for autoantibodies from patients with anti-basement membrane disease and Goodpasture syndrome. Earlier peptide studies suggested that the last 36 amino acids of the alpha3 NC1 domain probably contains one recognition site for Goodpasture autoantibodies, and an algorithm analysis of secondary structure from a later study predicted a second possible upstream epitope near the triple helix junction. We have used several analytic approaches to evaluate the likelihood of two immunologic epitopes for the Goodpasture antigen. In our first set of studies, peptide antibodies directed against these two putative regions co-inhibited Goodpasture autoantibodies binding to denatured human alpha3(IV) NC1 monomer by nearly 80%, with the helix-junction region of the alpha3 NC1 domain contributing 26% of the binding sites and the C-terminal region contributing the remaining 50%. Second, both of these candidate regions are normally sequestered within the associated alpha3(IV) NC1 hexamer but become more visible for binding by anti-peptide antibodies upon their dissociation, a property that is shared by the Goodpasture autoantibodies. Third, segment deletions of recombinant alpha3 NC1 domain further confirmed the presence of two serologic binding sites. Finally, we looked more closely at the C-terminal binding region of the alpha3(IV) NC1 domain. Since the lysines in that region have been previously advanced as possible contact sites, we created several substitutions within the C-terminal epitope of the alpha3 NC1 domain. Substitution of lysines to alanines revealed lysines 219 and 229 as essential for antibody binding to this distal site; no lysines were present in the NC1 part of the helix-NC1 junction region. Substitutions involving arginine and cysteines to alanines in the same C-terminal region did not produce significant reductions in

  19. A creative approach to the development of an agenda for knowledge utilization: outputs from the 11th international knowledge utilization colloquium (KU 11).

    Science.gov (United States)

    Wilkinson, Joyce E; Rycroft-Malone, Jo; Davies, Huw T O; McCormack, Brendan

    2012-12-01

    A group of researchers and practitioners interested in advancing knowledge utilization met as a colloquium in Belfast (KU 11) and used a "world café" approach to exploit the social capital and shared understanding built up over previous events to consider the research and practice agenda. We considered three key areas of relevance to knowledge use: (1) understanding the nature of research use, influence and impact; (2) blended and collaborative approaches to knowledge production and use; and (3) supporting sustainability and spread of evidence-informed innovations. The approach enabled the development of artifacts that reflected the three areas and these were analyzed using a creative hermeneutic approach. The themes that emerged and which are outlined in this commentary are not mutually exclusive. There was much overlap in the discussions and therefore of the themes, reflecting the complex nature of knowledge translation work. The agenda that has emerged from KU 11 also reflects the participatory and creative approach in which the meeting was structured and focused, and therefore emphasizes the processual, relational and contingent nature of some of the challenges we face. The past 20 years has seen an explosion in activity around understanding KU, and we have learned much about the difficulties. Whilst the agenda for the next decade may be becoming clearer, colloquia such as KU 11, using creative and engaging approaches, have a key role to play in dissecting, articulating and sharing that agenda. In this way, we also build an ever-expanding international community that is dedicated to working towards increasing the chances of success for better patient care. © 2012 Sigma Theta Tau International.

  20. Only Ku-band microwave absorption by Fe{sub 3}O{sub 4}/ferrocenyl-CuPc hybrid nanospheres

    Energy Technology Data Exchange (ETDEWEB)

    Wei Junji; Zhao Rui [Research Branch of Functional Materials, Institute of Microelectronic and Solid State Electronic, High-Temperature Resistant Polymers and Composites Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu 610054 (China); Liu Xiaobo, E-mail: liuxb@uestc.edu.cn [Research Branch of Functional Materials, Institute of Microelectronic and Solid State Electronic, High-Temperature Resistant Polymers and Composites Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu 610054 (China)

    2012-10-15

    A novel kind of hybrid nanospheres made of Fe{sub 3}O{sub 4} and ferrocenyl-CuPc (FCP) was prepared via effective solvothermal method and performed microwave absorptivity only in Ku-band with minimum reflection loss of -25 dB at 16.0 GHz corresponding to absorbing about 99.7% content of microwave. Scanning electron microscopy images indicated that the nanospheres with uniform particle size distribution have the average diameter of 135 nm. Due to the synergistic reaction between magnetic ferrocenyl-CuPc and Fe{sub 3}O{sub 4}, the hybrid nanospheres showed novel electromagnetic properties. The real part of complex permittivity of hybrid nanospheres remains stable in the range of 0.5-12.0 GHz and has a large fluctuation at 16.5 GHz. Moreover, the dielectric loss of hybrid nanospheres also appeared a sharp peak at 16.3 GHz with the value of 2.7. The specific gravity of hybrid nanospheres is about 2.08. On the basis of these results, the novel hybrids are believed to have potential applications in the microwave absorbing area in Ku-band. - Highlights: Black-Right-Pointing-Pointer A novel kind of ferrocenyl-CuPc/Fe{sub 3}O{sub 4} hybrid nanospheres was prepared. Black-Right-Pointing-Pointer The hybrids performed microwave absorptivity only in Ku-band. Black-Right-Pointing-Pointer The minimum absorbtion of hybrid nanospheres achieved -25 dB. Black-Right-Pointing-Pointer The material is believed to have broad application in notch filter in Ku-band.

  1. 抗细胞核自身抗原精子蛋白的抗体具有抗生育效果%The antibody against a nuclear autoantigenic sperm protein can result in reproductive failure

    Institute of Scientific and Technical Information of China (English)

    Min Wang; Jian-Li Shi; Guo-Yan Cheng; Yan-Qing Hu; Chen Xu

    2009-01-01

    为了研究抗睾丸型细胞核自身抗原精子蛋白(tNASP)的抗体是否会影响生育,我们成功克隆表达了一段339 bp小鼠睾丸型细胞核自身抗原精子蛋白(mtNASP)的cDNA.本实验以小鼠为动物模型,着重研究重组mtNASP蛋白和合成肽htNASP393-408(人睾丸型细胞核自身抗原精子蛋白第393-408氨基酸序列)的抗生育效果.用mtNASP和htNASP393-408分别主动免疫小鼠,二者都能在小鼠体内产生高效价的抗体.然后用8-10周龄的小鼠进行精卵结合和精卵融合实验.结果显示在不同浓度的抗mtNASP抗体存在下,小鼠卵子与获能精子的精卵结合能力以及去透明带小鼠卵子和获能精子的精卵融合能力都有明显下降.分别免疫重组mtNASP蛋白和htNASP393-408合成肽的小鼠也都能产生明显的抗生育效果,而且用合成肽免疫的小鼠其抗生育效果是可逆的.我们的实验数据表明,用重组的mtNASP蛋白进行免疫可以产生很强的抗体反应并且抑制小鼠生育.%To study whether the antibody against the testis form of the nuclear autoantigenic sperm protein (tNASP) could result in reproductive failure, we successfully cloned and expressed a 339-bp cDNA fragment of mouse tNASP (mtNASP). Using mouse as a model, recombinant mtNASP (rmtNASP) and a synthetic peptide, human tNASP393-408 (htNASP393-408), were investigated for their antifertility effect. Active immunization with rmtNASP or the synthesized peptide raised high antibody titers in the immunized mice. Sperm-egg binding and fusion assay were carried out in 8-10-week-old BALB/c mice. Sperm-egg binding and in vitro fertilization of mouse oocytes were inhibited by co-incubation of zona-free mouse oocytes with capacitated mouse spermatozoa in the presence of varying concentrations of the antisera against rmtNASP. There was a significant antifertility effect in animals immunized with rmtNASP or the synthesized peptide. The effect on fertility in the mice immunized

  2. Cloning and Sequencing of cDNA Encoding Islet Cell Autoantigen 69kD Protein from Chinese%国人 ICA69 基因 cDNA 的克隆及序列分析

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: It is reported that cDNA encoding human islet cell autoantigen 69kD protein (hiICA69) has been cloned, so to confirm the nucleotide sequences from the insulinoma cells of Chinese. Methods: cDNA encoding hiICA69 has been amplificated by PCR, from the cDNA library of Chinese insulinoma cells. The PCR product was inserted into the pSPORT 1 vector, and was subcloned into the pUC18 plasmid. After the positive colony was screened by the blue/white colony and the restriction analysis, the nucleotide sequences of the full - length cDNA were analysed by means of the dideoxy chain termination method. Resalts: The results showed that the amplified fragment contained 1449bp, encoded 483 - amino acids. For the sequencing analysis of ICA69 gene from the insulinoma in Mongolian race, the nucleotide sequence of the recombinant was coincident with that reported by Miyazaki and that from EMBL data's bank in addition to one difference of only base on the codon. The change located in the 416th base (A→T), which led to the change of one amino acid (Gln→Leu) . Conclusion: The gene obtained by the method of gene engineering and identified by means of sequence analysis would be able to lay a foundation for follow - up research.%目的:克隆国人胰岛细胞自身抗原 69kD 蛋白基因 ( hiICA69 ) 并经序列分析予以确证。方法:采用聚合酶链式反应技术,从中国人胰岛细胞瘤 cDNA 文库中扩增出 hiICA69 编码序列cDNA,将基因片段插入 pSPORT 1 质粒,进一步亚克隆到 pUCl8 载体中,经蓝白斑和限制性酶谱分析得以初步筛选后,双脱氧末端终止法对其全部核苷酸序列予以确定。结果:证实了 hiICA69 基因全长为 1449bp、编码 483 个氨基酸。与 pietropaolo 等报道的序列比较,仅在编码第 139 位氨基酸的密码子由 CAA→CTA,即由谷氨酰胺→亮氨酸,其余均与文献报道和 EMBL 核酸数据库提供的序列相同。结论:这一基因的获得和

  3. Ku teoretycznej wielości (w sprawie teorii słabych)

    OpenAIRE

    Januszkiewicz, Michał

    2005-01-01

    This article refers to the problems of disputes over the concept of a literary character and theory (in humanities). The reference to the historical perspective becomes an occasion for the presentation of an attitude which stems from post-modern reflection: the metaphysical (essential) claims are put forward both to the subject and to the manner of studies, they are lifted for the sake of pragmatic and hermeneutic interpretations within this which the author calls weak theories (a...

  4. Ku Klux Rising: Toward an Understanding of American Right Wing Terrorist Campaigns

    Science.gov (United States)

    2011-09-01

    Chomsky and Herman , for instance, claimed that “Washington has become the torture and political murder capital of the world.”125 This line was...32. 125 Noam Chomsky and Edward S. Herman , The Washington Connection and Third World Fascism, 1st ed., Their the Political Economy of Human Rights V...Context. Gregory Hess S. Brock Blomberg, Akila Weerapana, “Economic Conditions and Terrorism,” European Journal of Political Economy 20(April 2004). 534

  5. Gigawatt-class microwave generation from a novel Ku-band coaxial transit-time oscillator with low guiding magnetic field

    Science.gov (United States)

    Ling, Junpu; Zhang, Jiande; He, Juntao; Jiang, Tao; Song, Lili

    2016-10-01

    A non-uniform buncher and a depth-tunable collector have been proposed to improve the power capacity and conversion efficiency of the coaxial foilless transit-time oscillator (TTO) in our previous work. Recently, our Ku-band coaxial TTO with low guiding magnetic field is improved by employing them, and the related experimental investigations are carried out on the TORCH-01 accelerator. It is shown that the non-uniform buncher plays a key role in the enhancement of microwave pulse duration. The influences of the collector's depth on characteristics of the device indicate that the conversion efficiency can be improved by optimizing the collector's depth in the experiments. With the diode voltage 460 kV, the beam current 8.7 kA, and the guiding magnetic field of 0.6 T, a radiation power of 1 GW with the conversion efficiency of 25% at 14.3 GHz is generated by our improved TTO. The output pulse duration is 26 ns and no obvious pulse shortening is observed. The experimental results demonstrate the abilities of this improved Ku-band device to generate gigawatt-class Ku-band microwave with low guiding magnetic field.

  6. Electrochemical characteristics of pipeline-steel with planar-defect epoxy-coating in simulated solutions of Ku'erle soil

    Institute of Scientific and Technical Information of China (English)

    Cui-wei DU; Xiao-gang LI; Wei WANG; Yi-quan SONG

    2008-01-01

    An X70 pipeline steel and a low-carbon steel with different types of coating defects were studied using corrosion tests in Ku'erle simulated soil solution contain-ing 0.6000 mol/L Cl-. Electrochemical characteristics of the X70 pipeline steel with planar-defect epoxy-coating in simulated solutions of Ku'erle soil were tested. The results show that in 0.6000 mol/L Cl- simulated solution, for low-carbon steel with coating defects (the area ratio is 4.91%), at free corrosion potential and with immersion time, the corrosion with disbond was more severe than that with a break or with break and disbond. In Ku'erle soil simulated solution, when the coating defect area ratio was increased gradually (0.39% → 1.57% → 6.28%), the corrosion of the X70 steel under coating with break was promoted gradually, and the influence of immersion time on the corrosion decreased. The influence of the immer-sion time on the corrosion was weakened when the defect area ratio increased to a certain degree.

  7. Autoimmunity against INS-IGF2 protein expressed in human pancreatic islets.

    Science.gov (United States)

    Kanatsuna, Norio; Taneera, Jalal; Vaziri-Sani, Fariba; Wierup, Nils; Larsson, Helena Elding; Delli, Ahmed; Skärstrand, Hanna; Balhuizen, Alexander; Bennet, Hedvig; Steiner, Donald F; Törn, Carina; Fex, Malin; Lernmark, Åke

    2013-10-04

    Insulin is a major autoantigen in islet autoimmunity and progression to type 1 diabetes. It has been suggested that the insulin B-chain may be critical to insulin autoimmunity in type 1 diabetes. INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain, and eight amino acids of the C-peptide in addition to 138 amino acids from the IGF2 gene. We aimed to determine the expression of INS-IGF2 in human pancreatic islets and autoantibodies in newly diagnosed children with type 1 diabetes and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared with donors with either type 2 diabetes (p = 0.006) or high HbA1c levels (p INS-IGF2 autoantibody levels were increased in newly diagnosed patients with type 1 diabetes (n = 304) compared with healthy controls (n = 355; p INS-IGF2 revealed that more patients than controls had doubly reactive insulin-INS-IGF2 autoantibodies. These data suggest that INS-IGF2, which contains the preproinsulin signal peptide, the B-chain, and eight amino acids of the C-peptide may be an autoantigen in type 1 diabetes. INS-IGF2 and insulin may share autoantibody-binding sites, thus complicating the notion that insulin is the primary autoantigen in type 1 diabetes.

  8. Produkce vodíku s využitím bakterií rodu Clostridium

    OpenAIRE

    2013-01-01

    Bakalárska práca sa zaoberá produkciou vodíka baktériami rodu Clostridium – konkrétne C. butyricum a C. tyrobutyricum. V teoretickej časti sú rozobrané spôsoby výroby vodíka, rozdelené na biologické a nebiologické metódy. Práca sa ďalej zameriava na praktické využitie vyššie uvedených mikroorganizmov na účely výroby vodíku. Ako jedno z možných rastových médií pre vyššie uvedené baktérie predstavuje srvátku z mliekarenských výrob. V experimentálnej časti práce bola použitá polymerázová reťazov...

  9. A Ku band internally matched high power GaN HEMT amplifier with over 30% of PAE

    Science.gov (United States)

    Qin, Ge; Xiaojuan, Chen; Weijun, Luo; Tingting, Yuan; Yan, Pu; Xinyu, Liu

    2012-01-01

    We report a high power Ku band internally matched power amplifier (IMPA) with high power added efficiency (PAE) using 0.3 μm AlGaN/GaN high electron mobility transistors (HEMTs) on 6H-SiC substrate. The internal matching circuit is designed to achieve high power output for the developed devices with a gate width of 4 mm. To improve the bandwidth of the amplifier, a T type pre-matching network is used at the input and output circuits, respectively. After optimization by a three-dimensional electromagnetic (3D-EM) simulator, the amplifier demonstrates a maximum output power of 42.5 dBm (17.8 W), PAE of 30% to 36.4% and linear gain of 7 to 9.3 dB over 13.8-14.3 GHz under a 10% duty cycle pulse condition when operated at Vds = 30 V and Vgs = -4 V. At such a power level and PAE, the amplifier exhibits a power density of 4.45 W/mm.

  10. Comparison of neutron and gamma irradiation effects on KU1 fused silica monitored by electron paramagnetic resonance

    Energy Technology Data Exchange (ETDEWEB)

    Bravo, D. [Department Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain)], E-mail: david.bravo@uam.es; Lagomacini, J.C. [Department Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Leon, M.; Martin, P. [Materiales para Fusion, CIEMAT, Avda. Complutense 22, E-28040 Madrid (Spain); Martin, A. [Department Fisica e Instalaciones, ETS Arquitectura UPM, E-28040 Madrid (Spain); Lopez, F.J. [Department Fisica de Materiales, Universidad Autonoma de Madrid, E-28049 Madrid (Spain); Ibarra, A. [Materiales para Fusion, CIEMAT, Avda. Complutense 22, E-28040 Madrid (Spain)

    2009-06-15

    Electron paramagnetic resonance (EPR) studies have been carried out on KU1 fused silica irradiated with neutrons at fluences 10{sup 21} and 10{sup 22} n/m{sup 2}, and gamma-ray doses up to 12 MGy. The effects of post-irradiation thermal annealing treatments, up to 850 deg. C, have also been investigated. Paramagnetic oxygen-related defects (POR and NBOHC) and E'-type defects have been identified and their concentration has been measured as a function of neutron fluence, gamma dose and post-irradiation annealing temperature. It is found that neutrons at the highest fluence generate a much higher concentration of defects (mainly E' and POR, both at concentrations about 5 x 10{sup 18} spins/cm{sup 3}) than gamma irradiations at the highest dose (mainly E' at a concentration about 4 x 10{sup 17} spins/cm{sup 3}). Moreover, for gamma-irradiated samples a lower treatment temperature (about 400 deg. C) is required to annihilate most of the observed defects than for neutron-irradiated ones (about 600 deg. C)

  11. A Ku band internally matched high power GaN HEMT amplifier with over 30%of PAE

    Institute of Scientific and Technical Information of China (English)

    Ge Qin; Chen Xiaoiuan; Luo Weijun; Yuan Tingting; Pu Yan; Liu Xinyu

    2012-01-01

    We report a high power Ku band internally matched power amplifier (IMPA) with high power added efficiency (PAE) using 0.3 μm AlGaN/GaN high electron mobility transistors (HEMTs) on 6H-SiC substrate.The internal matching circuit is designed to achieve high power output for the developed devices with a gate width of 4 mm.To improve the bandwidth of the amplifier,a T type pre-matching network is used at the input and output circuits,respectively.After optimization by a three-dimensional electromagnetic (3D-EM) simulator,the amplifier demonstrates a maximum output power of 42.5 dBm (17.8 W),PAE of 30% to 36.4% and linear gain of 7 to 9.3 dB over 13.8-14.3 GHz under a 10% duty cycle pulse condition when operated at Vds =30 V and Vgs =-4 V.At such a power level and PAE,the amplifier exhibits a power density of 4.45 W/mm.

  12. Conduction mechanism in Polyaniline-flyash composite material for shielding against electromagnetic radiation in X-band & Ku band

    Science.gov (United States)

    Singh, Avanish Pratap; Anoop Kumar, S.; Chandra, Amita; Dhawan, S. K.

    2011-06-01

    β-Naphthalene sulphonic acid (β-NSA) doped polyaniline (PANI)-flyash (FA) composites have been prepared by chemical oxidative polymerization route whose conductivity lies in the range 2.37-21.49 S/cm. The temperature dependence of electrical conductivity has also been recorded which shows that composites follow Mott's 3D-VRH model. SEM images demonstrate that β-NSA leads to the formation of the tubular structure with incorporated flyash phase. TGA studies show the improvement in thermal stability of composites with increase in loading level of flyash. Complex parameters i.e. permittivity (ɛ* = ɛ'- iɛ″) and permeability (μ*=μ'- iμ″) of PANI-FA composites have been calculated from experimental scattering parameters (S11 & S21) using theoretical calculations given in Nicholson-Ross and Weir algorithms. The microwave absorption properties of the composites have been studied in X-band (8.2 - 12.4 GHz) & Ku-Band (12.4 - 18 GHz) frequency range. The maximum shielding effectiveness observed was 32dB, which strongly depends on dielectric loss and volume fraction of flyash in PANI matrix.

  13. SwissProt search result: AK070248 [KOME

    Lifescience Database Archive (English)

    Full Text Available igen 2) (Autoantigen PM/Scl 2) (Polymyositis/scleroderma autoantigen 100 kDa) (PM/Scl-100) (P100 polymyositis-scleroderma overlap syndrome associated autoantigen) EXOSX_HUMAN 5e-28 ...

  14. SwissProt search result: AK066936 [KOME

    Lifescience Database Archive (English)

    Full Text Available igen 2) (Autoantigen PM/Scl 2) (Polymyositis/scleroderma autoantigen 100 kDa) (PM/Scl-100) (P100 polymyositis-scleroderma overlap syndrome associated autoantigen) EXOSX_HUMAN 7e-46 ...

  15. SwissProt search result: AK067375 [KOME

    Lifescience Database Archive (English)

    Full Text Available igen 2) (Autoantigen PM/Scl 2) (Polymyositis/scleroderma autoantigen 100 kDa) (PM/Scl-100) (P100 polymyositis-scleroderma overlap syndrome associated autoantigen) EXOSX_HUMAN 4e-69 ...

  16. 在口腔鳞状细胞癌中Pokemon、Ku70的表达及临床病理学意义的研究%Expression and Clinical Significance of Pokemon, Ku70 in Oral Squamous Cell Carcinoma

    Institute of Scientific and Technical Information of China (English)

    赵凌冰; 古丽那尔·阿布拉江; 李晓梅; 王烨; 蒲红伟

    2011-01-01

    目的:研究口腔鳞状细胞癌组织中Pokemon、Ku70的表达及其临床病理学意义.方法:采用免疫组化En-vision二步法检测Pokemon、Ku70在47例口腔鳞状细胞癌组、20例正常口腔黏膜组中的表达.结果:1)Pokemon在口腔鳞状细胞癌组及正常口腔黏膜组中阳性表达率分别为:68.1%(32/47)、25.0%(5/20),P<0.05.高分化组与中低分化组Pokemon的阳性表达率分别为45.0%、85.2% (P<0.05).不同TNM的口腔鳞状细胞癌组织中,Ⅰ期+Ⅱ期组、Ⅲ期+Ⅳ期组Pokemon的阳性表达率分别为88.0%、45.5% (P<0.05).有淋巴结转移组、无淋巴结转移组Pokemon的阳性表达率分别为86.7%、35.5%(P<0.05).2)Ku70在口腔鳞状细胞癌组及正常口腔黏膜组中阳性表达率分别为:61.7%(29/47)、30.0%(6/20),P<0.05.高分化组与中低分化组Ku70的阳性表达率分别为55.0%、66.7% (P>0.05).不同TNM分期的口腔鳞状细胞癌组织中,Ⅰ期+Ⅱ期组、Ⅲ期+Ⅳ期组Ku70的阳性表达率分别为72.0%、50.0% (P>0.05).有淋巴结转移组、无淋巴结转移组Ku70的阳性表达率分别为73.3%、35.5% (P<0.05).结论:提示Pokemon及Ku70在口腔鳞状细胞癌发生发展中起重要作用;Pokemon与Ku70可能成为判定口腔鳞状细胞癌预后的生物标志物.%Objective: To study the expression and significance of Pokemon, Ku70 in oral squamous cell carcinoma (OSCC). Methods: Immunohistochemical Envision method was used to detect the expression of Pokemon and Ku70 in 47 cases of nasopharyngeal carcinoma and 20 cases of nasal polyp, and to retrospectively analyze their correlations to the clinicopathologic characteristics of OSCC. Results: Positive rates of Pokemon in OSCC group and normal oral mucosa group are 68. 1% (32/47) and 25. 0% (5/20) respectively(P0. 05). In different TNM of OSCC, I stage + Ⅱ stage group, and Ⅲ stage + Ⅳ stage group, positive rates of Ku70 are 72. 0% and 50. 0% respectively(P>0. 05

  17. Comparison of airborne radar altimeter and ground-based Ku-band radar measurements on the ice cap Austfonna, Svalbard

    Directory of Open Access Journals (Sweden)

    O. Brandt

    2008-11-01

    Full Text Available We compare coincident data from the European Space Agency's Airborne SAR/Interferometric Radar Altimeter System (ASIRAS with ground-based Very High Bandwidth (VHB stepped-frequency radar measurements in the Ku-band. The ASIRAS instrument obtained data from ~700 m above the surface, using a 13.5 GHz center frequency and a 1 GHz bandwidth. The ground-based VHB radar measurements were acquired using the same center frequency, but with a variable bandwidth of either 1 or 8 GHz. Four sites were visited with the VHB radar; two sites within the transition region from superimposed ice to firn, and two sites in the long-term firn area (wet-snow zone. The greater bandwidth VHB measurements show that the first peak in the airborne data is a composite of the return from the surface (i.e. air-snow interface and returns of similar or stronger amplitude from reflectors in the upper ~30 cm of the subsurface. The peak position in the airborne data is thus not necessarily a good proxy for the surface since the maximum and width of the first return depend on the degree of interference between surface and subsurface reflectors. The major response from the winter snowpack was found to be caused by units of thin crust/ice layers (0.5–2 mm surrounded by large crystals (>3 mm. In the airborne data, it is possible to track such layers for tens of kilometers. The winter snowpack lacked thicker ice layers. The last year's summer surface, characterized by a low density large crystal layer overlaying a harder denser layer, gives a strong radar response, frequently the strongest. The clear relationship observed between the VHB and ASIRAS waveforms, justifies the use of ground-based radar measurements in the validation of air- or spaceborne radars.

  18. 风湿性心脏病自身抗原RHDAG1的获得与鉴定%Screening and identification of auto-antigen RHDAG1 of rheumatic heart disease

    Institute of Scientific and Technical Information of China (English)

    孟锦绣; 李运雄; 朱平; 李玲; 卢聪; 郑少忆; 李广华; 余细勇

    2011-01-01

    目的 探索用风湿性心脏病患者噬菌体表达文库构建和免疫筛选方法来研究风湿性心脏病的自身抗原候选分子.方法 提取风湿性瓣膜性心脏病患者心肌组织总RNA,分离纯化mRNA并逆转录合成长链cDNA,用噬菌体载体构建表达文库,用风湿热患者血清免疫筛选该库,对筛选获得的自身抗原基因进行鉴定、生物信息学分析、体外表达、Western blotting鉴定和免疫反应结合性分析.结果 成功构建了风湿性心脏病患者心脏组织噬菌体表达文库,原始文库滴度为3.3×106pfu/ml,重组率为99%,81%外源片段大于1 kb.通过免疫筛选方法获得了自身抗原RHDAG1,该自身抗原与人类角蛋白18同源,能与活动性风湿热患者血清和风湿性心脏病患者血清结合,而与体检健康人血清无结合.结论 构建噬菌体展示文库方法可以有效地用于筛选和获得风湿性心脏病患者自身抗原;本研究提示自身抗原RHDAG1可成为风湿热和威风心病的候选分子标志物.%Objective To identify the candidate auto-antigen of rheumatic heart disease as a molecular marker for this disease. Methods The total RNA of the heart tissue of patients with rheumatic heart disease was extracted and reverse-transcribed into long cDNA to construct the phage expression library. The library was screened using the serum from patients with active rheumatic fever, and the positive clone was identified and analyzed by bioinformatics and expressed in vitro. The expressed products were evaluated with Western blotting and its cross-reactivity was assessed. Results The phage expression library of the heart tissue of patients with rheumatic heart disease was constructed, with the titer of the primary library of 3.3x106 pfu/ml, recombinant rate of 99%, and 81% of the inserted segments were larger than 1 kb. An auto-antigen RHDAG1 was identified by screening, which was homologous to keratin 18. RHDAG1 was detected in the serum of

  19. Cilvēku tirdzniecība un tās apkarošanas iespējas un īpatnības Latvijā

    OpenAIRE

    Ozoliņš, Aivars

    2011-01-01

    Darba nosaukums: „Cilvēku tirdzniecība un tās apkarošanas iespējas un īpatnības Latvijā”; Darba autors: Aivars Ozoliņš; Darba saturs: Cilvēku tirdzniecība ir mūsdienu problēma, kuras vēsture stiepjas daudzu gadsimtu garumā. Mūsdienu globalizētajā pasaulē cilvēku tirdzniecība ir sāpīga problēma, kas visiem spēkiem ir jācenšas novērst. Darbā kopumā ir veikts ieskats cilvēku tirdzniecības vēsturē un jēdzienā, kā arī atbildības par cilvēku tirdzniecību tiesiskajā regulējumā. ...

  20. Female Perspective: Progress in the Ku Klux Klan Studies in the United States%女性视角:美国三K党研究的新进展

    Institute of Scientific and Technical Information of China (English)

    李国庆

    2012-01-01

    The Ku Klux Klan in the United States as a research focus has always been a subject of academic attention. The traditional research in the Ku Klux Klan Movement focuses mainly on political and economic fields, and mainly from male perspective. The rise of the Feminist Movement and women's history urged the academia to begin to pay attention to the Ku Klux Klan women members. The female perspective expanded the horizon of the Ku Klux Klan research and has made new progress. It helps further expose the harm the Ku Klux Klan has made.%美国三K党作为研究的热点,一直受到美国学术界的广泛关注。传统的三K党运动研究主要侧重于政治、经济领域和男性视角。美国女权运动和妇女史的兴起促使学术界开始关注三K党妇女成员,以女性为视角的研究拓展了三K党研究的视野,取得了新的进展,有助于进一步揭露三K党的危害。

  1. Neogene basin development around Söke-Kuşadası (western Anatolia) and its bearing on tectonic development of the Aegean region

    Science.gov (United States)

    Gürer, Ömer Feyzi; Bozcu, Mustafa; Yılmaz, Kamil; Yılmaz, Yücel

    There is a N-S lying narrow strip of Neogene outcrop between the towns of Kuşadası and Söke in western Anatolia. It contains remnants of successive Neogene graben basins. The first graben began to form under the control of a N40-70°E-trending oblique fault system during the Early Miocene. At the initial phase of the opening coarse clastic rocks were deposited in front of the fault-elevated blocks as scree deposits and fanglomerates. Later the graben advanced into a large lake basin. Towards the end of the Middle Miocene the lacustrine sediments of the Early-Middle Miocene age underwent an approximately N-S compressional deformation and elevated above the lake level, and were partly eroded. During the Late Miocene a new graben basin began to form as a consequence of the development of E-W-trending normal faults, formed under the N-S extensional regime. This graben also turned later into a lake environment. The lake extended far beyond the limits of the fault zones, and covered the entire regions stretching from the south of Bafa Lake in the south to Kuşadası and beyond in the north. Micritic clayey limestones were predominantly deposited in the lake. A severe erosional phase followed the termination of the lake basin. This corresponds to the cessation of the N-S extension. When the N-S extension regenerated during the Pliocene(?)-Pleistocene, the Büyük Menderes graben system began to form. In the western part of the graben, a conjugated pair of oblique faults, the Priene-Sazlı fault and the Kuşadası fault, have formed. The faults having important strike-slip components, bounded a tectonic wedge, which began to move westward into the Aegean Sea region. Major morphological features of the region were formed under the effective control of these fault zones.

  2. Wpływ wysiłku fizycznego na funkcję układu oddechowego w twardzinie układowej

    Directory of Open Access Journals (Sweden)

    Stanisław Sierakowski

    2010-12-01

    Full Text Available Cel: Powikłania ze strony układu oddechowego stanowią główną przyczynę zgonów pacjentów z twardziną układową (TU. Tętniczenadciśnienie płucne i śródmiąższowa choroba płuc stanowią najistotniejszez nich. Pacjenci są jednak często zdiagnozowani dopierow późnym okresie choroby, dlatego też istotne jest opracowaniemetody diagnostycznej do wczesnego wykrywania tych powikłań.Celem pracy była ocena wpływu wysiłku fizycznego na zmiany parametrówoddechowych. Materiały i metody: Badania przeprowadzono wśród 32 pacjentów zezdiagnozowaną TU; 72% pacjentów miało postać ograniczoną TU,28% postać uogólnioną. Wykonywano pomiar zdolności dyfuzyjnejpłuc dla tlenku węgla (DLCO, natężonej pojemności życiowej (FVC,natężonej objętości wydechowej pierwszosekundowej (FEV1 orazcałkowitej pojemności płuc (TLC w spoczynku oraz bezpośrednio pozakończeniu wysiłku fizycznego. Wyniki: Pod wpływem wysiłku fizycznego obserwowano wzrostDLCO od 59,7% do 68,1% wartości należnej (p < 0,005. Nie stwierdzononatomiast istotnych statystycznie zmian wartości FVC, FEV1oraz TLC. Wnioski: U chorych na TU zdolność dyfuzyjna płuc dla tlenku węglapo wysiłku fizycznym uległa istotnej statystycznie poprawiew porównaniu z wartościami spoczynkowymi. Związane jest toz koniecznością zapewnienia właściwego utlenowania krwi tętniczeji wynika m.in. ze zwiększenia pojemności łożyska naczyniowego.W klinicznej interpretacji wartości DLCO należy uwzględniać opróczstężenia hemoglobiny i objętości pęcherzykowej także wpływ wysiłkuoraz związane z nim zmiany wielkości objętości rzutu serca.

  3. VISOKO GOSPODARSKO UČILIŠTE U KRIŽEVCIMA PRILOG OBRAZOVANJU ZA ODRŽIVU I EKOLOŠKU POLJOPRIVREDU

    OpenAIRE

    2009-01-01

    Rad daje pregled uloge koju ima Visoko gospodarsko učilište u Križevcima u području stručnih studija za poljoprivredu u Hrvatskoj i doprinos visokoškolskom obrazovanju za održivu i ekološku poljoprivredu. U radu se također donosi kratki opis povijesnoga razvoja križevačkoga Učilišta i opis suvremenih studijskih programa na razini stručnog i specijalističkog diplomskog studija te specijalističkih seminara u sklopu cjeloživotnoga učenja.

  4. Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks.

    Directory of Open Access Journals (Sweden)

    Petra Langerak

    2011-09-01

    Full Text Available The multifunctional Mre11-Rad50-Nbs1 (MRN protein complex recruits ATM/Tel1 checkpoint kinase and CtIP/Ctp1 homologous recombination (HR repair factor to double-strand breaks (DSBs. HR repair commences with the 5'-to-3' resection of DNA ends, generating 3' single-strand DNA (ssDNA overhangs that bind Replication Protein A (RPA complex, followed by Rad51 recombinase. In Saccharomyces cerevisiae, the Mre11-Rad50-Xrs2 (MRX complex is critical for DSB resection, although the enigmatic ssDNA endonuclease activity of Mre11 and the DNA-end processing factor Sae2 (CtIP/Ctp1 ortholog are largely unnecessary unless the resection activities of Exo1 and Sgs1-Dna2 are also eliminated. Mre11 nuclease activity and Ctp1/CtIP are essential for DSB repair in Schizosaccharomyces pombe and mammals. To investigate DNA end resection in Schizo. pombe, we adapted an assay that directly measures ssDNA formation at a defined DSB. We found that Mre11 and Ctp1 are essential for the efficient initiation of resection, consistent with their equally crucial roles in DSB repair. Exo1 is largely responsible for extended resection up to 3.1 kb from a DSB, with an activity dependent on Rqh1 (Sgs1 DNA helicase having a minor role. Despite its critical function in DSB repair, Mre11 nuclease activity is not required for resection in fission yeast. However, Mre11 nuclease and Ctp1 are required to disassociate the MRN complex and the Ku70-Ku80 nonhomologous end-joining (NHEJ complex from DSBs, which is required for efficient RPA localization. Eliminating Ku makes Mre11 nuclease activity dispensable for MRN disassociation and RPA localization, while improving repair of a one-ended DSB formed by replication fork collapse. From these data we propose that release of the MRN complex and Ku from DNA ends by Mre11 nuclease activity and Ctp1 is a critical step required to expose ssDNA for RPA localization and ensuing HR repair.

  5. Analysis of Chemical Constituents of Volatile Oils from Small Leaves Ku-Ding-Cha%小叶苦丁茶挥发油成分分析

    Institute of Scientific and Technical Information of China (English)

    武宏伟; 赵丽元; 郑宜婷; 相婷; 李银

    2012-01-01

    [ Objective ] To compare the chemical components of volatile oil from small leaves Ku-Ding-Cha which belonged to the family Oleaceae. [Method] Volatile oils of small leaves Ku-Ding-Cha in different production areas were extracted hy the technique of steam distillation; then,the components of volatile oils were analyzed by gas chromalography mass spectrometry (GC-MS). [Result] A total of 55 compounds were identified. There was great similarity in the old leaves and buds of Ku-Ding-Cha in different batches. Linalool had the highest content (48.34% -79.25% ) ; α-terpineol, geraniol and nerol had relatively high content. [Conclusion] This research provided scientific references for the quality control and reasonable utilization of the small leaves Ku-Ding-Cha.%[目的]分析比较不同品种或产地木犀科小叶苦丁茶老叶及芽中挥发油成分的异同.[方法]采用水蒸气蒸馏法分别对不同品种或产地的小叶苦丁茶中的挥发油进行提取,利用气质联用技术分析所提取的挥发油成分.[结果]共鉴定55个化合物,7个不同批次小叶苦丁茶老叶及芽中的成分具有较大的相似性,相对含量最高的均为以芳樟醇(48.34%~79.25%)为主的单萜类成分,其他含量较高的成分有α-松油醇、香叶醇何橙花醇等.[结论]该方法为小叶苦丁茶的质量控制和资源合理开发利用提供了科学依据.

  6. Origin of absorption peaks in reflection loss spectrum in Ku- frequency band of Co-Zr substituted strontium hexaferrites prepared using sucrose precursor

    Science.gov (United States)

    Narang, Sukhleen Bindra; Pubby, Kunal; Chawla, S. K.; Kaur, Prabhjyot

    2017-03-01

    This study presents the detailed explanation of the factors, contributing towards the absorption peaks in reflection loss spectrum of hexaferrites. Cobalt-Zirconium substituted strontium hexaferrites, synthesized using sucrose precursor sol-gel technique, were analyzed in 12.4-18 GHz frequency range. The concepts of impedance matching through quarter wavelength condition, complex thickness, dielectric phase angle and attenuation constant have been used to determine the location as well as intensity of absorption peaks. This study also demonstrates the potential application of three compositions of this series with doping content (x)==0.0, 0.6 and 0.8 as an effective microwave absorbers in Ku-frequency band.

  7. Subcarrier phase recovery performance in bent-pipe mode of Shuttle data transmission. [on Tracking and Data Relay Satellite System Ku-band return link

    Science.gov (United States)

    Mckenzie, T. M.; Braun, W. R.

    1978-01-01

    The subcarrier phase recovery is analyzed for the bent-pipe mode of Space Shuttle detached-payload data transmission on the Tracking and Data Relay Satellite System (TDRSS) Ku-band return link. The high-power component of the subcarrier modulation is unrestored payload data, either at baseband or modulating another subcarrier. At the receiver a Costas loop recovers the subcarrier phase. To analyze its performance in the baseband case, we obtain the loop S-curve, the power spectral density of the equivalent noise process, and the loop phase error variance.

  8. A comparative study of the FcepsilonRI molecule on human mast cell and basophil cell lines

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Dissing, S; Skov, P S;

    2005-01-01

    Mast cells and basophils express the high-affinity IgE receptor FcepsilonRI. We have analysed the human mast cell line LAD2 and four subclones of the basophil cell line KU812 in order to reveal possible differences concerning the FcepsilonRI surface regulation, anti-IgE-triggered activation...

  9. A comparative study of the FcepsilonRI molecule on human mast cell and basophil cell lines

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Dissing, S; Skov, P S

    2005-01-01

    Mast cells and basophils express the high-affinity IgE receptor FcepsilonRI. We have analysed the human mast cell line LAD2 and four subclones of the basophil cell line KU812 in order to reveal possible differences concerning the FcepsilonRI surface regulation, anti-IgE-triggered activation, Fcep...

  10. Involvement of 90-kuD ribosomal S6 kinase in collagen type Ⅰ expression in rat hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Miao-Fang Yang; Jun Xie; Xiao-Yi Gu; Xiao-Hua Zhang; Andrew K Davey; Shuang-Jie Zhang; Ji-Ping Wang; Ren-Min Zhu

    2009-01-01

    AIM: To investigate the relationship between 90-kuD ribosomal S6 kinase (p90RSK) and collagen type Ⅰ expression during the development of hepatic fibrosis in vivo and in vitro. METHODS: Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type Ⅰ were determined by co-immunofluoresence and confocal microscopy. Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell (HSC) line. The expression of collagen type Ⅰ in HSC-T6 cells was assessed by Western blotting and real-time polymerase chain reaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, then collagen type Ⅰ promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated with or without platelet-derived growth factor (PDGF)-BB at a final concentration of 20 μg/L and the cell growth was determined by MTS conversion. RESULTS: In fibrotic liver tissues, p90RSK was overexpressed in activated HSCs and had a significant positive correlation with collagen type Ⅰ levels. In HSC-T6 cells transfected with RNAi targeted to p90RSK, the expression of collagen type Ⅰ was downregulated (61.8% in mRNA, P < 0.01, 89.1% in protein, P < 0.01). However, collagen type Ⅰ promoter activity was not increased with over-expression of p90RSK and not decreased with low expression either, compared with controls in the same cell line ( P = 0.076). Furthermore, p90RSK siRNA exerted the inhibition of HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation. CONCLUSION: p90RSK is over-expressed in activated HSCs and involved in regulating the abnormal expression of collagen type Ⅰ through initiating the proliferation of HSCs.

  11. Ku dydaktyce afirmatywnej

    Directory of Open Access Journals (Sweden)

    Monika Rogowska-Stangret

    2016-11-01

    Full Text Available "Towards affirmative didactics" The article “Towards affirmative didactics” is a description of a project reflecting on the experience of teaching and learning in a systematic and complex manner. It is also an effort to define the conditions that could encourage values such as inclusiveness, tolerance, mindfulness, joint responsibility, as well as engagement in and support for actions undertaken to strengthen the above-mentioned values. The project is a work in progress and it consists of two parts. The first one is critical and it describes the given situation by pointing the main threats involved. The second – affirmative one – was created with the effort to develop positive guidelines that would encourage transformations in the approach to didactics.

  12. Ku-Band Interferometry.

    Science.gov (United States)

    mapping some discrete radio sources: the Crab Nebula , Cas A, and Cyg A. The system contains two 8 ft parabolic antennas and receives radiation at...degrees over a period of 2 hours. Consistent fringe components were obtained from the Crab Nebula with the baseline set at 8 m. (Author)

  13. KU24 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  14. KU31 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  15. Eiropas un starptautiskie standarti cilvēku tirdzniecības apkarošanai un to ietekme uz Gruzijas likumdošanu un praksi

    OpenAIRE

    Kukhianidze, Ketevan

    2010-01-01

    Katru dienu vairāki tūkstoši cilvēku dodas uz dažādām valstīm labākas dzīves meklējumos. Mūsdienās verdzība un cilvēku tirdzniecība atspoguļo nopietnus cilvēktiesību pārkāpumus. Tā ir problēma, kas ietver sociālos, politiskos un demogrāfiskos aspektus, dzimumu un etnisko noslāņošanos, organizēto transnacionālo noziedzību un cilvēktiesību pārkāpumus, un iesaista valsts un supranacionālas institūcijas, lai tās efektīvi cīnītos ar šīm problēmām. Maģistra darbā „Eiropas un starptautiskie stand...

  16. Terminal deoxynucleotidyl transferase requires KU80 and XRCC4 to promote N-addition at non-V(D)J chromosomal breaks in non-lymphoid cells.

    Science.gov (United States)

    Boubakour-Azzouz, Imenne; Bertrand, Pascale; Claes, Aurélie; Lopez, Bernard S; Rougeon, François

    2012-09-01

    Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase that increases the repertoire of antigen receptors by adding non-templated nucleotides (N-addition) to V(D)J recombination junctions. Despite extensive in vitro studies on TdT catalytic activity, the partners of TdT that enable N-addition remain to be defined. Using an intrachromosomal substrate, we show here that, in Chinese hamter ovary (CHO) cells, ectopic expression of TdT efficiently promotes N-additions at the junction of chromosomal double-strand breaks (DSBs) generated by the meganuclease I-SceI and that the size of the N-additions is comparable with that at V(D)J junctions. Importantly, no N-addition was observed in KU80- or XRCC4-deficient cells. These data show that, in a chromosomal context of non-lymphoid cells, TdT is actually able to promote N-addition at non-V(D)J DSBs, through a process that strictly requires the components of the canonical non-homologous end-joining pathway, KU80 and XRCC4.

  17. Focusing electrode and coaxial reflector used for reducing the guiding magnetic field of the Ku-band foilless transit-time oscillator.

    Science.gov (United States)

    Ling, Junpu; Zhang, Jiande; He, Juntao; Wang, Lei; Deng, Bingfang

    2014-08-01

    Based on the theoretical analysis of the intense relativistic electron beam propagation in the coaxial drift-tube, a focusing electrode and a coaxial reflector is proposed to lessen the demand of the coaxial Ku-band foilless transit-time oscillator (TTO) for the guiding magnetic field. Moreover, a Ku-band TTO with the focusing electrode and the coaxial reflector is designed and studied by particle in cell simulation. When the diode voltage is 390 kV, the beam current 7.8 kA, and the guiding magnetic field is only 0.3 T, the device can output 820 MW microwave pulse at 14.25 GHz by means of the simulation. However, for the device without them, the output power is only 320 MW. The primary experiments are also carried out. When the guiding magnetic field is 0.3 T, the output power of the device with the focusing electrode and the coaxial reflector is double that of the one without them. The simulation and experimental results prove that the focusing electrode and the coaxial reflector are effective on reducing the guiding magnetic field of the device.

  18. Interneta mārketinga rīku izmantošana Latvijas mazos un vidējos uzņēmumos

    OpenAIRE

    Škutāns, Mārtiņš

    2013-01-01

    Uzņēmumu konkurētspējas palielināšana ir tieši saistīta ar efektīvu resursu sadali kā arī izmantošanu un 21. gadsimtā efektīva interneta mārketinga rīku resursu izmantošana pozitīvi ietekmē gan apgrozījuma rādītājus, gan komunikāciju ar klientiem. Darbā pētāmā problēma un piedāvātie tās risinājumi ir saistīti ar to, kā Latvijas mazie un vidējie uzņēmumi izmanto šos rīkus. Darbā tika izvirzīti divi mērķi. Pirmais-izpētīt interneta mārketinga rīku izmantošanu Latvijas mazos un vidējos uzņēm...

  19. Recognition of DNA Termini by the C-Terminal Region of the Ku80 and the DNA-Dependent Protein Kinase Catalytic Subunit.

    Directory of Open Access Journals (Sweden)

    Derek S Woods

    Full Text Available DNA double strand breaks (DSBs can be generated by endogenous cellular processes or exogenous agents in mammalian cells. These breaks are highly variable with respect to DNA sequence and structure and all are recognized in some context by the DNA-dependent protein kinase (DNA-PK. DNA-PK is a critical component necessary for the recognition and repair of DSBs via non-homologous end joining (NHEJ. Previously studies have shown that DNA-PK responds differentially to variations in DSB structure, but how DNA-PK senses differences in DNA substrate sequence and structure is unknown. Here we explore the enzymatic mechanisms by which DNA-PK is activated by various DNA substrates and provide evidence that the DNA-PK is differentially activated by DNA structural variations as a function of the C-terminal region of Ku80. Discrimination based on terminal DNA sequence variations, on the other hand, is independent of the Ku80 C-terminal interactions and likely results exclusively from DNA-dependent protein kinase catalytic subunit interactions with the DNA. We also show that sequence differences in DNA termini can drastically influence DNA repair through altered DNA-PK activation. These results indicate that even subtle differences in DNA substrates influence DNA-PK activation and ultimately the efficiency of DSB repair.

  20. USP22 Induces Cisplatin Resistance in Lung Adenocarcinoma by Regulating γH2AX-Mediated DNA Damage Repair and Ku70/Bax-Mediated Apoptosis

    Directory of Open Access Journals (Sweden)

    Aman Wang

    2017-05-01

    Full Text Available Resistance to platinum-based chemotherapy is one of the most important reasons for treatment failure in advanced non-small cell lung cancer, but the underlying mechanism is extremely complex and unclear. The present study aimed to investigate the correlation of ubiquitin-specific peptidase 22 (USP22 with acquired resistance to cisplatin in lung adenocarcinoma. In this study, we found that overexpression of USP22 could lead to cisplatin resistance in A549 cells. USP22 and its downstream proteins γH2AX and Sirt1 levels are upregulated in the cisplatin- resistant A549/CDDP cell line. USP22 enhances DNA damage repair and induce cisplatin resistance by promoting the phosphorylation of histone H2AX via deubiquitinating histone H2A. In addition, USP22 decreases the acetylation of Ku70 by stabilizing Sirt1, thus inhibiting Bax-mediated apoptosis and inducing cisplatin resistance. The cisplatin sensitivity in cisplatin-resistant A549/CDDP cells was restored by USP22 inhibition in vivo and vitro. In summary, our findings reveal the dual mechanism of USP22 involvement in cisplatin resistance that USP22 can regulate γH2AX-mediated DNA damage repair and Ku70/Bax-mediated apoptosis. USP22 is a potential target in cisplatin-resistant lung adenocarcinoma and should be considered in future therapeutic practice.

  1. Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1

    Science.gov (United States)

    Yamauchi, Motohiro; Shibata, Atsushi; Suzuki, Keiji; Suzuki, Masatoshi; Niimi, Atsuko; Kondo, Hisayoshi; Miura, Miwa; Hirakawa, Miyako; Tsujita, Keiko; Yamashita, Shunichi; Matsuda, Naoki

    2017-01-01

    Chromosome rearrangement is clinically and physiologically important because it can produce oncogenic fusion genes. Chromosome rearrangement requires DNA double-strand breaks (DSBs) at two genomic locations and misrejoining between the DSBs. Before DSB misrejoining, two DSB-containing chromatin regions move and pair with each other; however, the molecular mechanism underlying this process is largely unknown. We performed a spatiotemporal analysis of ionizing radiation-induced foci of p53-binding protein 1 (53BP1), a marker for DSB-containing chromatin. We found that some 53BP1 foci were paired, indicating that the two damaged chromatin regions neighboured one another. We searched for factors regulating the foci pairing and found that the number of paired foci increased when Ku80, DNA-PKcs, or ATM was absent. In contrast, 53BP1 depletion reduced the number of paired foci and dicentric chromosomes—an interchromosomal rearrangement. Foci were paired more frequently in heterochromatin than in euchromatin in control cells. Additionally, the reduced foci pairing in 53BP1-depleted cells was rescued by concomitant depletion of a heterochromatin building factor such as Krüppel-associated box-associated protein 1 or chromodomain helicase DNA-binding protein 3. These findings indicate that pairing between DSB-containing chromatin regions was suppressed by Ku80, DNA-PKcs, and ATM, and this pairing was promoted by 53BP1 through chromatin relaxation. PMID:28155885

  2. Prokaryotic Homologs of the Eukaryotic 3-Hydroxyanthranilate 3,4-Dioxygenase and 2-Amino-3-Carboxymuconate-6-Semialdehyde Decarboxylase in the 2-Nitrobenzoate Degradation Pathway of Pseudomonas fluorescens Strain KU-7†

    OpenAIRE

    Muraki, Takamichi; Taki, Masami; Hasegawa, Yoshie; Iwaki, Hiroaki; Lau, Peter C. K.

    2003-01-01

    The 2-nitrobenzoic acid degradation pathway of Pseudomonas fluorescens strain KU-7 proceeds via a novel 3-hydroxyanthranilate intermediate. In this study, we cloned and sequenced a 19-kb DNA locus of strain KU-7 that encompasses the 3-hydroxyanthranilate meta-cleavage pathway genes. The gene cluster, designated nbaEXHJIGFCDR, is organized tightly and in the same direction. The nbaC and nbaD gene products were found to be novel homologs of the eukaryotic 3-hydroxyanthranilate 3,4-dioxygenase a...

  3. In vitro binding kinetics of DNA double strand break repair proteins Ku70/80 and DNA-PKcs quantified by fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy

    Science.gov (United States)

    Abdisalaam, Salim; Chen, David J.; Alexandrakis, George

    2012-02-01

    DNA double-strand breaks (DSBs) are one of the most lethal types of DNA damage that occurs in eukaryotic cells. There are two distinct pathways of repairing DSBs, homologous recombination (HR) and non-homologous end joining (NHEJ). In the NHEJ repairing pathway, DSB recognition and repair initiation is directed by the interaction of DNAbinding subunit Ku70/80 heterodimer with the DNA-PK protein catalytic subunit (DNA-PKcs). Mutations in these proteins result in repair stalling and eventual DNA misrepair that may lead to genomic instability. Studying the binding kinetics of these repair proteins is therefore important for understanding the conditions under which DSB repair stalls. Currently open questions are, what is the minimum DNA length that this complex needs to get a foothold onto a DSB and how tightly does DNA-PKcs bind onto the DNA-Ku70/80 complex. Fluorescence Correlation Spectroscopy (FCS) and Fluorescence Cross-Correlation Spectroscopy (FCCS) techniques have the potential to give information about the binding kinetics of DNA-protein and protein-protein interactions at the single-molecule level. In this work, FCS/FCCS measurements were performed to explore the minimum DNA base-pair (bp) length that Ku70/80 needed as a foothold to bind effectively onto the tips of different lengths of double-stranded DNA (dsDNA) fragments that mimic DSBs. 25 bp, 33 bp and 50 bp of dsDNA were used for these experiments and binding was studied as a function of salt concentration in solution. It was found that the 25 bp binding was weak even at physiological salt concentrations while the dissociation constant (Kd) remained constant for 33 and 50 bp dsDNA strand lengths. These studies indicated that the minimum binding length for the Ku70/8 is in the vicinity of 25 bp. The specificity of binding of Ku70/80 was proven by competitive binding FCCS experiments between Cy5-labeled DNA, GFP-Ku70/80 and titrations of unlabeled Ku70/80. Finally, using FCCS it was possible to estimate

  4. Anaerococcus nagyae sp. nov., isolated from human clinical specimens.

    Science.gov (United States)

    Veloo, A C M; de Vries, E D; Jean-Pierre, H; van Winkelhoff, A J

    2016-04-01

    We describe a new Anaerococcus species isolated from human clinical specimens. Analyses of 16S rRNA gene sequences of three strains showed octavius. Phylogenetically the isolated strains form a cluster and can be differentiated from other species of the genus Anaerococcus based on its phenotypic characteristics and its MALDI-TOF MS profile. We propose the name Anaerococcus nagyae, with A. nagyae DSM101193 (accession number KU043522) as the type strain. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Human chromosome pellicle antibody recognizing centromere protein—C (CENP0C),the main component of the kinetochore

    Institute of Scientific and Technical Information of China (English)

    XIEYONG; ZUMEINI; 等

    1997-01-01

    Recently the antichromosome antisera from several sclerogerma patients have been found to recognize the pellicle of metaphase and anaphase chromosomes.In order to identify the pellicle components,we used these antichromosome antisera to screen a human embryonic cDNA library.The sequences of the positive clones are identical to the cDNA gene sequence of CENP-C (centromere protein C),a human centromere autoantigen.This result suggusts that CENP-C is a component of the pellicle of human metaphase and anaphase chromosomes.

  6. A Cultural Anthropology Exploration of Bai KU Yao's Maternal Worship in Guangxi and Guizhou%桂黔白裤瑶母性崇拜的文化人类学考察

    Institute of Scientific and Technical Information of China (English)

    雷文彪

    2012-01-01

    在人类历史漫长的发展过程中,母性崇拜是一种普遍存在的民俗现象,母性崇拜意识一直是人类社会挥之不去共通性情节。广西与贵州边界的白裤瑶族群的母性崇拜意识有其自身独特的文化表征形态,其主要表现在供奉生殖图腾石的习俗"、姑女还舅门"婚俗、婚前盛行"玩婊"、妇女夏天身着"挂衣"、服饰图案的"卍"符号等方面。%Maternal worship has always been common fork-custom in the long history of human development, and the consciousness of maternal worship is regarded as a common and indispensable plot. This consciousness of Bai Ku Yao (It's a branch of Yao in which adult man has knee-length white trouser) in Nandan county of Guangxi province, has its own unique cultural expression, especially the birth custom that people consecrate the stone Guangxi and Guizhou hroder reproductive totem, the marriage custom that a young man should have priority to marriage to his aunt's daughter, the social convention that young men and women may keep an intimate relationship with others before marriage, the dress custom that women have Gua Yi(This kind of coat is made of two pieces of cloth) in summer, and the dress is decorated with the symbol 卍.

  7. Simulation of Ku-band magnetically insulated transmission line oscillator%Ku波段磁绝缘线振荡器的数值模拟

    Institute of Scientific and Technical Information of China (English)

    文杰; 田扬超; 范植开; 陈代兵; 王冬; 秦奋

    2011-01-01

    A Ku-band magnetically insulated transmission line oscillator(MILO) is put forward with the theoretical analysis according to dispersion characteristics of slow wave structure. Compared with common MILOs, the Ku-band MILO designed has a choke cavity whose outer radius is increased to avoid the breakdown between cathode and anode. The resonant frequency of 13. 536 GHz and loaded quality factor of 43 are obtained through numerical calculation of the open cavity model of MILO. Then the structure parameters are further optimized and the impact of diode voltage on output power and efficiency is investigated with 2. 5 dimensional particle-in-cell simulation. High power microwave is generated from the optimized Ku-band MILO with the average output power of 3. 69 GW, central frequency of 13. 62 GHz and efficiency of 12. 6% , when the beam voltage is 600 kV and current is 47. 4 kA.%根据现有的慢波结构色散特性的理论分析,提出了一种Ku波段的磁绝缘线振荡器(MILO).与常见MILO的慢波结构不同,该MILO的慢波结构通过增大扼流腔的外半径来实现扼流作用,以防止阴阳极击穿.利用3维电磁场模拟软件对Ku波段MILO的开放腔模型进行了分析,得到其谐振频率为13.536GHz以及有载品质因数为43.同时利用2.5维全电磁粒子模拟软件对其进行数值模拟,进一步优化了MILO结构,研究了输出微波的功率效率与输入电压的关系,得到的最优工作电压为600 kV.在外加电压600 kV、束流47.4 kA的情况下,模拟得到的平均功率为3.69 GW,中心频率为13.62 GHz,功率转换效率为12.6%.

  8. Generation, Transformation and Place in Inga Iwasiów’s Novels Bambino (2008 and Ku słońcu (2010

    Directory of Open Access Journals (Sweden)

    Ursula PHILLIPS

    2012-06-01

    Full Text Available This chapter will discuss two novels by contemporary writer Inga Iwasiów (b. 1963, Bambino (2008 and Ku słońcu [Towards the Sun] (2010, in the context of geopolitical, ideological, social and psycho-cultural transformations as they specifically affect different generations of inhabitants of the Polish city of Szczecin (pre-1945 German Stettin from 1945 until the first decade of the 21st century. Bambino covers the years 1945–1981, but also contains flashbacksto pre-war memory of Stettin and to the suppressed experiences of the new post-war inhabitants, as well as ‘flash-forwards’ to post-1989, post-communist reality; Ku słońcu covers 1981 to the first decade of 2000s. It will show how the novels portray these transformations through the experience primarily of women (but not only — in Bambino, through the main protagonists: Ula (formerly Ulrike, Anna and Marysia, and through that of the hidden narrator Magda (Marysia’s daughter born in the same year as the author, Iwasiów, 1963; and in Ku słońcu, primarily through the experience of Magda herself, as well as through that of two generations of ‘feminist’ academics: Małgorzata and Sylwia (in which it is hard not to perceive the personal experience of the author, though she is at pains to emphasize elsewhere that her work is a collective biography of the city, not so much of herself. The analysis follows KatarzynaChmielewska’s supposition that contemporary Polish fiction dealing with the past ‘constantly oscillates between memory and genealogy’, and that it raises raw issues not yet addressed by historians; it also derives inspiration from the new ‘postdependency’ studiesproposed by Hanna Gosk and Ryszard Nycz. It also attempts to capture the specific nature of Iwasiów’s use of language, her style of feminism, her method of portraying place, and the connections in her prose between place and memory.

  9. Human basophils express interleukin-4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Valent, P.; Besemer, J.; Kishi, K.; Di Padova, F.; Geissler, K.; Lechner, K.; Bettelheim, P. (Univ. of Vienna (Austria))

    1990-11-01

    Interleukin-4 (IL-4), a multipotential lymphokine reputed to play an important role in the regulation of immune responses, interacts with a variety of hemopoietic target cells through specific cell surface membrane receptors. The present study was designed to investigate whether human basophils express IL-4 binding sites. For this purpose, basophils were enriched to homogeneity (93% and 98% purity, respectively) from the peripheral blood of two chronic granulocytic leukemia (CGL) donors using a cocktail of monoclonal antibodies (MoAbs) and complement. Purified basophils bound 125I-radiolabeled recombinant human (rh) IL-4 in a specific manner. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high affinity IL-4 binding sites (280 +/- 40 sites per cell in donor 1 and 640 +/- 45 sites per cell in donor 2) with an apparent dissociation constant, kd, of 7.12 x 10(-11) +/- 2.29 x 10(-11) and 9.55 +/- 3.5 x 10(-11) mol/L, respectively. KU812-F, a human basophil precursor cell line, was found to express a single class of 810 to 1,500 high affinity IL-4 binding sites with a kd of 2.63 to 5.54 x 10(-10) mol/L. No change in the numbers or binding constants of IL-4 receptors was found after exposure of KU812-F cells to rhIL-3 (a potent activator of basophils) for 60 minutes. No effect of rhIL-4 on 3H-thymidine uptake, release or synthesis of histamine, or expression of basophil differentiation antigens (Bsp-1, CD11b, CD25, CD40, CD54) on primary human CGL basophils or KU812-F cells was observed.

  10. A Novel Ku-Band/Ka-Band and Ka-Band/E-Band Multimode Waveguide Couplers for Power Measurement of Traveling-Wave Tube Amplifier Harmonic Frequencies

    Science.gov (United States)

    Wintucky, Edwin G.; Simons, Rainee N.

    2015-01-01

    This paper presents the design, fabrication and test results for a novel waveguide multimode directional coupler (MDC). The coupler, fabricated from two dissimilar frequency band waveguides, is capable of isolating power at the second harmonic frequency from the fundamental power at the output port of a traveling-wave tube (TWT) amplifier. Test results from proof-of-concept demonstrations are presented for a Ku-band/Ka-band MDC and a Ka-band/E-band MDC. In addition to power measurements at harmonic frequencies, a potential application of the MDC is in the design of a satellite borne beacon source for atmospheric propagation studies at millimeter-wave (mm-wave) frequencies (Ka-band and E-band).

  11. Late Barremian-Early Aptian Urgonian Limestones from the south-eastern Kučaj Mountains (Carpatho-Balkanides, Eastern Serbia

    Directory of Open Access Journals (Sweden)

    Sudar Milan

    2008-01-01

    Full Text Available The newest results of sedimentological and paleontological investigations of part of the Urgonian Limestones studied in the surrounding of Boljevac on the SE slopes of the Kučaj Mts. (Carpatho-Balkanides, eastern Serbia are presented. On two localities, near the village Faca Vajali, four types of microfacies and one subtype within the bioclastic limestones were separated. The characteristics of the depositional environments of the investigated Urgonian Limestones were studied and are discussed. At the base of the established rich microassociations of foraminifera and algae, the vertical distribution of foraminiferal species was precisely defined which enabled the determination the the age of this part of the Urgonian Limestones as Late Barremian-Early Aptian.

  12. Vecāku audzināšanas stilu saistība ar pašcieņu pusaudžu vecumā

    OpenAIRE

    Miķelsone-Ježaka, Dace

    2008-01-01

    Darba mērķis ir izpētīt pašcieņas saistību ar mātes un tēvu audzināšanas stilu bērnībā. Pētījumā piedalījās 105 pusaudži no dažādām skolām vecumā no 16 līdz 18 gadiem, kas dzīvo pilnās ģimenēs. Tika izmantotas 2 aptaujas: 1. Vecāku autoritātes novērtējuma aptauja (The Parental Authority Questionnaire, Buri, 1991; Griškina, 2002). 2. Rozenberga pašcieņas aptauja (The Rosenberg Self – esteem Scale, Rosenberg, 1965).

  13. Vecāku audzināšanas stila saistība ar pusaudžu vientulības izjūtu

    OpenAIRE

    Vlasova, Iveta

    2013-01-01

    Pētījuma jautājums: Vai starp mātes audzināšanas stilu un vientulības līmeni pusaudžiem pastāv saistība? Pētījuma dalībnieki. Viena izlase, pēc pieejamības principa. Dalībnieku vecums: 12-16 gadi, 31 meitene, 23 zēni. Dzīvojoši pilnās ģimenēs. Pētījuma metode. 1.Lieto, lai noteiktu kopējo vientulības izjūtas līmeni, tika izmantota Vientulības skala (UCLA Loneliness Scale/UCLA LS/, VERSION 3; Russel, D.W. 1996).– visu jautājumu summa. 2.Vecāku audzināšanas stila aptauja (Parental...

  14. Návrh převodníku DA pro nízkonapěťové aplikace v technologii CMOS

    OpenAIRE

    Dušek, Petr

    2015-01-01

    Tato práce se zabývá návrhem přesného digitálně analogového převodníku, dále jen DAC. Práce poskytuje podklady pro pochopení principu převodu digitálního signálu na signál analogový. V práci je popsáno několik možností vytvoření topologie DAC. Vybraná konstrukce je použita k návrhu DAC v technologii CMOS 07. Simulacemi v programu PSPICE je ověřena funkčnost navrženého DAC. This thesis focuses on design of an accurate digital to analog converter (DAC). The thesis provides material to unders...

  15. Ku波段高效率脉冲行波管的研制%The Development and Manufacture for Ku-Band High Efficiency Pulse TWT

    Institute of Scientific and Technical Information of China (English)

    陈彩云; 李晓峰; 张超

    2012-01-01

    The Ku-band high efficiency pulse TWT(Travel Wave Tube)had been manufactured and its design,CAD simulation and test results were also presented. On the basic of CAD software the election gun, magnetic focus system,helical slow wave circuit beam wave intersection and electrion beam collector,of which this TWT consists, have been optimazed that the pulse TWT is continually improved in the period manufacture processing. The manufectured travel wave tubes meet the technical specifications for their proper use in the developing rada system. The high efficiency, high output are realized in this TWT, that the pulse output power is more than 2. 2 kW and officieney oves 30% at the condition of the same driven power and 2 GHz frequency range of Ku-band.%简要介绍了Ku波段高效率脉冲行渡管的设计、CAD计算和测试结果.通过对电子枪、聚焦系统、慢波电路、电子注和慢波线高频场大信号互作用的计算、收集极的设计,获得了符合新雷达系统技术指标要求的整管.实测结果为:在Ku波段2 GHz频带范围内,等激励、脉冲输出功率大于2.2 kW、效率大于30%.

  16. SIRT1 inhibition impairs non-homologous end joining DNA damage repair by increasing Ku70 acetylation in chronic myeloid leukemia cells.

    Science.gov (United States)

    Zhang, Wenjun; Wu, Haixia; Yang, Meng; Ye, Shiguang; Li, Liang; Zhang, Hong; Hu, Jiong; Wang, Xuguang; Xu, Jun; Liang, Aibin

    2016-03-22

    Most chemotherapeutic agents for leukemia are DNA damaging agents. However, DNA lesions can be repaired by activities of DNA repair systems. Increasing evidence have shown that enhanced DNA damage repair capacity contributes to chemotherapy resistance in leukemia cells. Thus, targeting DNA repair mechanisms is a promising strategy for novel leukemia treatment. SIRT1 expressions were downregulated by lentivirus-delivered SIRT1 shRNA in myeloid leukemia cells. SIRT1 mRNA and protein levels were analyzed by real-time PCR and Western blot, respectively. Flow cytometry was carried out to analyze cell cycle progression, apoptosis and DNA damage repair efficiency. DNA damage levels were assessed by alkaline comet assay, and H2AX phosphorylation was analyzed by immunoblotting and immunofluorescence. A mouse leukemia model was established by transplanting lentivirus-infected K562 cells containing SIRT1 shRNA into sublethally irradiated NOD/SCID mice, and tumorigenesis was evaluated by detecting tumor weights and mice survival. SIRT1 expressions were upregulated in myeloid leukemic patients. Downregulation of SIRT1 by RNAi promoted etoposide-induced DNA damage in myeloid leukemia cells accompanied by reduced NHEJ activity, and increased Ku70 acetylation. Furthermore, SIRT1 knockdown resulted in cell cycle arrest, induction of apoptosis and reduction of K562 cell proliferation accompanied by enhanced p53 and FOXO1 acetylation in K562 cells after etoposide treatment. Importantly, SIRT1 downregulation reduced the tumorigenesis ability of K562 cells in mouse xenografts following chemotherapy treatment. These results revealed that SIRT1 promotes the NHEJ repair pathway by deacetylating Ku70 in K562 cells, suggesting that SIRT1 is a novel therapeutic target for treating myeloid leukemia.

  17. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils

    DEFF Research Database (Denmark)

    Volck, B; Price, P A; Johansen, J S;

    1998-01-01

    YKL-40, also called human cartilage glycoprotein-39 (HC gp-39), is a member of family 18 glycosyl hydrolases. YKL-40 is secreted by chondrocytes, synovial cells, and macrophages, and recently it has been reported that YKL-40 has a role as an autoantigen in rheumatoid arthritis (RA). The function...... of YKL-40 is unknown, but the pattern of its expression in normal and disease states suggests that it could function in remodeling or degradation of the extracellular matrix. High levels of YKL-40 are found in synovial fluid from patients with active RA. Neutrophils are abundant in synovial fluid...

  18. Mapping of epitopes for autoantibodies to the Type 1 diabetes autoantigen IA-2 by peptide phage display and molecular modelling: Overlap of antibody and T-cell determinants

    DEFF Research Database (Denmark)

    A. Dromey, James; Weenink, Sarah M.; Peters, Günther H.J.

    2004-01-01

    phage display and homology modeling to characterize the epitope of a monoclonal IA-2 Ab (96/3) from a human type 1 diabetic patient. This Ab competes for IA-2 binding with Abs from the majority of patients with type 1 diabetes and therefore binds a region close to common autoantibody epitopes. Alignment...

  19. Batı Akdeniz Sahil Kuşağından Toplanan Yonca (Medicago sativa L. Populasyonlarının Moleküler Karakterizasyonu

    Directory of Open Access Journals (Sweden)

    Mehmet ÖTEN

    2016-06-01

    Full Text Available Medicago tür ve populasyonlarında moleküler markırlar kullanılarak genotipik varyasyon seviyesini belirlemek yaygın olarak kullanılmaktadır. Bu çalışmada; Batı Akdeniz sahil kuşağında yer alan, Antalya iline ait 13 ilçede, 26 farklı lokasyonda, doğal vejetasyondan toplanan üstün yonca genotipleri klon yöntemi ile çoğaltılmıştır. Elde edilen 26 genotip ve 2 standart çeşidin aralarındaki benzerlikler, Basit Tekrarlı Sekanslar (SSR moleküler analiz tekniğiyle, 15 adet primer kullanılarak belirlenmiştir. SSR primerlerinin % 99,7’si polimorfik bant vermiştir. Araştırma sonucunda; kümeleme analizi sonucu oluşan dendograma göre yonca genotipleri 2 ana ve 4 alt gruba ayrılmıştır. Birinci ana grup % 60, ikinci ana grup ise % 65 seviyesinde kendi içerisinde iki alt gruba ayrılmıştır. Benzerlik katsayıları 0.58-0.88 değerleri arasında değişim göstermiştir. En yakın genetik benzerlik Kaş-2 ve Çeşit-1 arasında bulunurken, en uzak ise Gazipaşa-1-Kumluca-2 genotipleri arasında bulunmuştur. Elde edilen bu sonuca göre Batı Akdeniz sahil kuşağından toplanan yonca genotipleri arasında genetik olarak önemli bir varyasyonun olduğu tespit edilmiştir.

  20. Bazı kafes kuşu yemlerinde doğal olumsuzluk faktörlerinin (Aflatoksinler, Nitrit, Nitrat, Tanen ve Sodyum Klorür) belirlenmesi

    OpenAIRE

    GÜRELİ, Hakan

    2010-01-01

    Bu çalışmada bazı kafes kuşu yemlerinde doğal olarak bulunan ya da sonradan oluşabilen doğal olumsuzluk faktörlerinden aflatoksinler, nitrat-nitrit, tanen ve tuz miktarları araştırıldı. Bu amaçla Ankara ili sınırları içerisindeki satılan muhabbet kuşu, kanarya ve papağan yemlerinin her birinden 20'şer adet olmak üzere toplam 60 örnek analiz edildi. Aflatoksin analizlerinde yüksek basınçlı sıvı kromatografi cihazı (HPLC) kullanıldı. Nitrat, nitrit ve tanen analizleri spekt...

  1. Room Temperature Thin Film Ba(x)Sr(1-x)TiO3 Ku-Band Coupled MicrostripPhase Shifters: Effects of Film Thickness, Doping, Annealing and Substrate Choice

    Science.gov (United States)

    VanKeuls, F. W.; Mueller, C. H.; Miranda, F. A.; Romanofsky, R. R.; Canedy, C. L.; Aggarwal, S.; Venkatesan, T.; Ramesh, R.; Horwitz, S.; Chang, W.

    1999-01-01

    We report on measurements taken on over twenty Ku-band coupled microstrip phase shifters (CMPS) using thin ferroelectric films of Ba(x)Sr(1-x)TiO3. This CMPS design is a recent innovation designed to take advantage of the high tunability and tolerate the high dielectric constant of ferroelectric films at Ku- and K-band frequencies. These devices are envisioned as a component in low-cost steerable beam phased area antennas, Comparisons are made between devices with differing film thickness, annealed vs unannealed, Mn-doped vs. undoped, and also substrates of LaAlO3 and MgO. A comparison between the CMPS structure and a CPW phase shifter was also made oil the same ferroelectric film.

  2. A comprehensive two-dimensional gel protein database of noncultured unfractionated normal human epidermal keratinocytes: towards an integrated approach to the study of cell proliferation, differentiation and skin diseases

    DEFF Research Database (Denmark)

    Celis, J E; Madsen, Peder; Rasmussen, H H

    1991-01-01

    proteins in alphabetical order), "basal cell markers", "differentiation markers", "proteins highly up-regulated in psoriatic skin", "microsequenced proteins" and "human autoantigens". For reference, we have also included 2-D gel (isoelectric focusing) patterns of cultured normal and psoriatic keratinocytes......A two-dimensional (2-D) gel database of cellular proteins from noncultured, unfractionated normal human epidermal keratinocytes has been established. A total of 2651 [35S]methionine-labeled cellular proteins (1868 isoelectric focusing, 783 nonequilibrium pH gradient electrophoresis) were resolved...

  3. Extraction of essential oil from Ku-shui rose and component analysis by GC/MS%苦水玫瑰精油提取及其成分的GC/MS分析

    Institute of Scientific and Technical Information of China (English)

    周学森; 蒋玉梅; 毕阳; 李霁昕; 齐治国; 张顺花

    2009-01-01

    The production process of Ku-shui rose essential oil was optimized.Some main affecting factors were analyzed about yield of extraction.The results showed.the optimum extraction conditions of Ku-shui rose essential oil:the rose-water ratio was 1:4,the time of distillation was 3h,distillation rate:distillate materials was 10% of the volume of liquid per hour. Under the best conditions of the extracted, Ku- shui rose essential oil yield reached 3.982 x 10 -4.Ku-shui rose essential oil from the optimum technology was analyzed by GC/MS,the main ingredients for the fragrance was citronellol 54.58%, nerol 0.09%, geraniol 10.55%, linalool 2.90%.%对苦水玫瑰精油的生产工艺进行了优化研究,探讨了影响玫瑰精油得率的主要因素,结果显示:苦水玫瑰精油提取的最佳工艺务件为:料液比1:4、蒸馏时间3h、蒸馏速率每小时馏出液为原料液体体积的10%,在最佳的提取工艺条件下苦水玫瑰精油得率达到了3.982 × 10-4.最佳工艺所得苦水玫瑰精油气相-质谱(GC/MS)分析显示:主要香气成分含量为香茅醇54.58%、橙花醇0.09%、香叶醇10.55%、芳樟醇2.90%.

  4. Characterization and expression of multiple alternatively spliced transcripts of the Goodpasture antigen gene region. Goodpasture antibodies recognize recombinant proteins representing the autoantigen and one of its alternative forms.

    Science.gov (United States)

    Penadés, J R; Bernal, D; Revert, F; Johansson, C; Fresquet, V J; Cervera, J; Wieslander, J; Quinones, S; Saus, J

    1995-05-01

    Collagen IV, the major component of basement membranes, is composed of six distinct alpha chains (alpha 1-alpha 6). Atypically among the collagen IV genes, the exons encoding the carboxyl-terminal region of the human alpha 3(IV) chain undergo alternative splicing. This region has been designated as the Goodpasture antigen because of its reactivity in the kidney and lung with the pathogenic autoantibodies causing Goodpasture syndrome. The data presented in this report demonstrate that, in human kidney, the gene region encompassing the Goodpasture antigen generates at least six alternatively spliced transcripts predicting five distinct proteins that differ in their carboxyl-terminus and retain, except in one case, the exon that harbors the characteristic amino-terminus of the antigen. Goodpasture antibodies specifically recognize recombinant proteins representing the antigen and the alternative form that retains the amino-half of the antigen, suggesting that this moiety could be involved in the in vivo binding of the pathogenic antibodies. Furthermore, the sera of control individuals contain autoantibodies against the antigen that can be differentiated from those causing the syndrome based on their specific reactivities, suggesting that the binding of the pathogenic autoantibodies to a specific determinant likely trigger a distinct and unique cascade of events causing the disease.

  5. SLA/LP/tRNP((Ser)Sec) antigen in autoimmune hepatitis: identification of the native protein in human hepatic cell extract.

    Science.gov (United States)

    Volkmann, Martin; Luithle, Daniel; Zentgraf, Hanswalter; Schnölzer, Martina; Fiedler, Sabine; Heid, Hans; Schulze-Bergkamen, Andrea; Strassburg, Christian P; Gehrke, Sven G; Manns, Michael P

    2010-02-01

    A diagnostic subgroup of AIH type 1 is characterized by specific serum antibodies against soluble liver protein. The respective autoantigen was named SLA/LP/tRNP((Ser)Sec), after three homologous recombinant polypeptides were isolated from expression gene libraries. We analyzed human cultured liver cells for the human homologue of recombinant SLA/LP/tRNP((Ser)Sec) by antigen purification. In addition, a monoclonal antibody was generated against recombinant SLA-p35, a truncated recombinant SLA-reactive polypeptide. With a positive patient serum, immune affinity chromatography was performed on the 52 kD-SLA main antigenic determinant pre-enriched by ion exchange chromatography. By mass spectrometry, the 52 kD-SLA/LP/tRNP ((Ser)Sec) autoantigen was unambiguously identified in the purification product. The identity of the recombinant SLA-p35 and its human homologue was further confirmed by a specific signal of the anti SLA-p35 monoclonal antibody with purified human SLA/LP/tRNP((Ser)Sec). The 48 kD-SLA species frequently comigrating in SLA-immunoblotting however was not identified by either approach. We conclude that the native counterpart of recombinant tRNP((Ser)(Sec)) indeed is detectable with a molecular weight of 52 kD in soluble liver extract of human cells as the major antigenic component of SLA/LP/tRNP((Ser)Sec). Copyright 2009 Elsevier Ltd. All rights reserved.

  6. Sociālo zinību mērķis un sasniedzamie rezultāti vecāku vērtējumā

    OpenAIRE

    Janmere, Lana

    2011-01-01

    Lanas Janmeres diplomdarbs „Sociālo zinību mērķis un sasniedzamie rezultāti vecāku vērtējumā”. Darba vadītāja ir profesore Dr.paed. Zanda Rubene. Diplomdarba mērķis ir noskaidrot vecāku viedokļus par sociālo zinību mērķi un sasniedzamajiem rezultātiem. Tā sasniegšanai analizēta teorētiskā literatūra par vecāku iesaistīšanos izglītības satura veidošanā un raksturots mācību priekšmets „Sociālās zinības”. Sociālo zinību sasniedzamie rezultāti, kas atspoguļoti Sociālo zinību mācību priekšmeta ...

  7. Cloning and Sequencing Analysis of 49 ku ES Protein Gene for Trichinella Nativa%本地毛形线虫49 ku排泄分泌蛋白基因的克隆及序列分析

    Institute of Scientific and Technical Information of China (English)

    郑宝亮; 边传周; 王秀荣; 宋铭忻

    2010-01-01

    为了获得本地毛形线虫(Trichinella nativa) 49 ku ES蛋白的结构基因,用Trizol提取T.nativa肌幼虫的总RNA,用RT-PCR方法扩增出了编码T. nativa 49 ku 排泄分泌蛋白的结构基因.将PCR产物与T载体连接并经过大肠埃希菌增殖后送检测序.序列测定表明,目的基因TNPG长度为951 bp,核苷酸序列同已发表的T. spiralis相应的序列P49同源性为98.63%,所推导的氨基酸序列同源性为99.05%.为T. nativa49 ku ES蛋白结构基因的进一步研究打下基础.

  8. Genetyczna analiza polimorfizmów genów naprawy DNA przez rekombinację niehomologiczną Ku70 i Ligazy IV u kobiet z rakiem piersi w wieku pomenopauzalnym

    Directory of Open Access Journals (Sweden)

    Marek Zadrożny

    2010-10-01

    Full Text Available Aim: Breast cancer is one of the major killers worldwide. Aberrant double-stranded break (DSB repair leads to genomic instability, which is a hallmark of malignant cells. Double-stranded breaks are repaired by two pathways: homologous recombination (HR and nonhomologous DNA end joining (NHEJ. It is not known whether these repair pathways are affected in sporadic breast tumours. Material and methods: In the present work the distribution of genotypes and frequency of alleles of the Ku70 gene, A46922G polymorphism and Ligase IV, A6008G (Ile591Val polymorphism in breast cancer women were investigated. The genetic polymorphisms analysis was performed using a PCR-RFLP method in 135 sporadic breast cancer cases. Results: The distribution of the genotypes of the A46922G polymorphism of the Ku70 gene in patients differed significantly (p 0.05 from those predicted by the Hardy-Weinberg distribution. Conclusion: The results support the hypothesis that the A46922G polymorphism of the Ku70 gene may be associated with the incidence of breast cancer in postmenopausal women from the Łódź region of Poland.

  9. A Ku-band wide-tuning-range high-output-power VCO in InGaP/GaAs HBT technology

    Science.gov (United States)

    Jincan, Zhang; Yuming, Zhang; Hongliang, Lü; Yimen, Zhang; Bo, Liu; Leiming, Zhang; Fei, Xiang

    2015-06-01

    A fully integrated Ku-band voltage controlled oscillator (VCO) is presented in an InGaP/GaAs heterojunction bipolar transistor (HBT) technology. To achieve the wide tuning range (TR), the VCO employs a Colpitts configuration, and the VCO simultaneously achieves high output power. The implemented VCO demonstrates an oscillation frequency range from 12.82 to 14.97 GHz, a frequency TR of 15.47%, an output power from 0.31 to 6.46 dBm, and a phase noise of -94.9 dBc/Hz at 1 MHz offset from 13.9 GHz center frequency. The VCO consumes 52.75 mW from 5 V supply and occupies an area of 0.81 × 0.78 mm2. Finally, the figures-of-merit for VCOs is discussed. Project supported by the National Basic Research Program of China (No. 2010CBxxxx05), the Advance Research Project of China (No. 51308xxxx06), the Advance Research Foundation of China (No. 9140A08xxxx11DZ111), and Doctoral Scientific Research Foundation of Henan University of Science and Technology (No. 400613480011), and the Foundation of He'nan Educational Commettee (No. 15A510001).

  10. Review of the Airborne Ku and Ka-band Satellite Communication System%机载Ku、Ka频段卫星通信系统综述

    Institute of Scientific and Technical Information of China (English)

    艾文光; 赵大勇; 邓军

    2011-01-01

    叙述了Ku频段和Ka频段机载卫星通信系统的国内外发展现状,列举了几个典型的卫星通信系统技术指标,并简述了研制机载卫星通信系统应注意的事项和技术途径,其中包括选择天线系统形式,合理分配系统指标,消除多普勒效应的影响等。%This paper reviews the Ku-band and Ka-band airborne satellite communication system both at home and abroad,cites a few typical satellite communication system specifications,and outlines matters that deserve our attention and some technical approaches in the development of airborne satellite communications systems,including choosing the form of antenna system,reasonably allocating system indicators,and eliminating the impact of the Doppler effect.

  11. Blockage of Autophagy in C6 Glioma Cells Enhanced Radiosensitivity Possibly by Attenuating DNA-PK-Dependent DSB Due to Limited Ku Nuclear Translocation and DNA Binding.

    Science.gov (United States)

    Liu, C; He, W; Jin, M; Li, H; Xu, H; Liu, H; Yang, K; Zhang, T; Wu, G; Ren, J

    2015-01-01

    Glioblastoma multiforme (GBM) is the most lethal brain tumor and notorious for its resistance to ionizing radiation (IR). Recent evidence suggests that one possible mechanism that enables resistance to IR and protects cells against therapeutic stress is cellular autophagy. The molecular basis for this pro-survival function, however, remains elusive. Herein, we report a molecular mechanism by which IR-induced autophagy accelerates the repair of DNA double-strand breaks (DSB). We demonstrate that IR induces the accumulation of autophagosomes, which is accompanied by elevated expression of autophagyrelated genes beclin-1, atg5, atg7, and atg12. Beclin-1 knockdown impaired the induction of IR-mediated autophagy and significantly sensitized glioma cells to radiation therapy in vitro and in vivo. Furthermore, our data is the first to demonstrate that the radiosensitizing effect of beclin-1 knockdown may result from the disruption of nuclear translocation and DNA binding activity of Ku proteins and consequent attenuation of DSB repair. Our findings help advance our understanding of the molecular mechanisms underlying IR-induced autophagy and provide a promising adjunctive therapeutic strategy for the radiosensitization of malignant glioma.

  12. Monomeric immunoglobulin E stabilizes FcepsilonRIalpha from the human basophil cell line KU812 by protecting it from natural turnover

    DEFF Research Database (Denmark)

    Jensen, Bettina Margrethe; Hansen, Jens Bo; Dissing, S;

    2003-01-01

    The high affinity IgE receptor (FcepsilonRI) on mast cells and basophils is up-regulated by its own ligand IgE; however, the mechanism is unknown.......The high affinity IgE receptor (FcepsilonRI) on mast cells and basophils is up-regulated by its own ligand IgE; however, the mechanism is unknown....

  13. Construction, expression, purification and functional analysis of recombinant 6C6 immunotoxin to human breast-tumor cells

    Institute of Scientific and Technical Information of China (English)

    刘晖; 朱玉贤; 李■秋

    1999-01-01

    The 28 ku membrane protein is usually over-expressl m human bnasl bmast cancer and other tumor cells. licould be a larget for tumor therapy . By using genetie engineermg teehmgues.a 606 immunotoxin (sefv606-PE40) was construeted by joining the 606 single-chain antibdy (SeFv606) with the truncll Pseudonwnas exotoxin A (PE40), SeFv606 contains both the heavy and light-chnia variable domams of 606 monoelonal antibody. Which speeifieally ree-ognizes the 28 ku protein. The bacterial expression level og 606 imnmmotoxin is 3.3%. about 5.5 mg ml baeterial lysate.lsing singlc-step llisTrap (Nr2 chelating) column chronnetogaphy, the reeombinant peptide was obtained with a purit of 33.2%.This baeterial espressed 606 immunotosin binuls to MDA-231 human breast-tumer ccll surfaee and kill these cells with a median lethal dosage of 92 ngnd.

  14. RECQ HELICASE RECQL4 PARTICIPATES IN NON-HOMOLOGOUS END JOINING AND INTERACTS WITH THE KU COMPLEX

    DEFF Research Database (Denmark)

    Shamanna, Raghavendra A; Singh, Dharmendra Kumar; Lu, Huiming

    2014-01-01

    RECQL4, a member of the RecQ helicase family, is a multifunctional participant in DNA metabolism. RECQL4 protein participates in several functions both in the nucleus and in the cytoplasm of the cell, and mutations in human RECQL4 are associated with three genetic disorders: Rothmund......-Thomson, RAPADILINO and Baller-Gerold syndromes. We previously reported that RECQL4 is recruited to laser-induced DNA double-strand breaks (DSB). Here, we have characterized the functional roles of RECQL4 in the non-homologous end joining (NHEJ) pathway of DSB repair. In an in vitro NHEJ assay that depends...... on the activity of DNA-PK, extracts from RECQL4 knockdown cells display reduced end-joining activity on DNA substrates with cohesive and non-cohesive ends. Depletion of RECQL4 also reduced the end joining activity on a GFP reporter plasmid in vivo. Knockdown of RECQL4 increased the sensitivity of cells to γ...

  15. In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

    DEFF Research Database (Denmark)

    Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

    2008-01-01

    BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...... in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar...

  16. Yearly variation of spontaneous somatic mutation frequency in the stamen hairs of Tradescantia clone KU 9 grown outdoors, which showed a significant increase after the Chernobyl accident.

    Science.gov (United States)

    Ichikawa, S; Nakano, A; Kenmochi, M; Yamamoto, I; Murai, M; Takahashi, E; Yamaguchi, A; Watanabe, K; Tomiyama, M; Sugiyama, K; Yogo, A; Yazaki, T; Okumura, M; Shima, N; Satoh, M; Yoshimoto, M; Xiao, L Z

    1996-02-01

    Scoring of spontaneous somatic pink mutation frequency in the stamen hairs of Tradescantia clone KU 9, a heterozygote for flower color (blue/pink; the blue color being dominant), was carried out for 11 years on plants grown outdoors, during the period of May 11-31 (for 3 weeks) in every year from 1982 to 1992. Weekly and yearly variations of the spontaneous mutation frequency were observed, and such variations could mostly be correlated to the difference in temperature. That is, the mutation frequency was generally higher in the weeks and years when the temperature was relatively low, showing the strongest negative correlation with the average minimum temperature. The variations were also correlated to the diurnal temperature difference, the mutation frequency being higher with larger diurnal temperature difference in general. However, the mutation frequency observed in 1986 was exceptionally higher than that expected from the temperature for this year, and was very significantly higher than for other years. The scoring of mutation frequency was thus continued in 1986 for an additional 4 weeks (June 1-28), and it was confirmed that such higher mutation frequencies lasted for 6 weeks in total. The exceptionally high mutation frequency seemed to be related to the radioactive fallout which occurred in early to mid May of 1986, even in Japan, after the serious nuclear reactor accident at Chernobyl, and also to the biological concentrations of radioactive nuclides which subsequently occurred, although it was difficult to conclude this definitely. The mutation frequency in 1987 was second highest, and was also significantly higher than the lowest mutation frequency observed in 1990.

  17. Bacterial flagellin induces IL-6 expression in human basophils.

    Science.gov (United States)

    Jeon, Jun Ho; Ahn, Ki Bum; Kim, Sun Kyung; Im, Jintaek; Yun, Cheol-Heui; Han, Seung Hyun

    2015-05-01

    Binding of allergen to IgE on basophils positively affects allergic inflammation by releasing inflammatory mediators. Recently, basophils were shown to express pattern-recognition receptors, such as toll-like receptors (TLRs), for recognizing microbe-associated molecular patterns (MAMPs) that are independent of allergen-IgE binding. In this study, we investigated whether MAMP alone can induce IL-6 production in a human basophil cell line, KU812. Stimulation with flagellin in the absence of allergen-IgE association induced IL-6 expression in KU812 cells, while stimulation with lipoteichoic acid, peptidoglycan, or poly I:C did not under the same condition. Flagellin-induced IL-6 expression was also observed in human primary basophils. Flow cytometric analysis showed that KU812 cells expressed flagellin-recognizing TLR5 both on the cell surface and in the cytoplasm while TLR2 and TLR3 were observed only in the cytoplasm. We further demonstrated that although flagellin augmented the phosphorylation of mitogen-activated protein kinases including p38 kinase, ERK, and JNK, flagellin-induced IL-6 production was attenuated by inhibitors for p38 kinase and ERK, but not by JNK inhibitors. In addition, flagellin enhanced phosphorylation of signaling molecules including CREB, PKCδ, and AKT. The inhibitors for PKA and PKC also showed inhibitory effects. Interestingly, flagellin-induced IL-6 production was further enhanced by pretreatment with inhibitors for PI3K, implying that PI3K negatively affects the flagellin-induced IL-6 production. Furthermore, DNA binding activities of NF-κB, AP-1, and CREB, which play pivotal roles in the induction of IL-6 gene expression, were increased by flagellin. These results suggest that flagellin alone is sufficient to induce IL-6 gene expression via TLR5 signaling pathways in human basophils.

  18. Role of Autophagy in the Radiosensitivity of Human Lung Adenocarcinoma A549 Cells

    Directory of Open Access Journals (Sweden)

    Liyao XU

    2016-12-01

    Full Text Available Background and objective Radiotherapy is an important treatment for lung cancer. The poor prognosis of lung cancer is largely caused by the high recurrence rate and metastasis of the tumor. Autophagy, which can be induced by radiotherapy, might be associated with DNA repair. The aim of this study is to investigate whether activating autophagy using rapamycin can enhance the radiosensitivity of lung cancer cells and clarify the association of autophagy with DNA repair. Methods The human adenocarcinoma A549 cell line was selected as the experimental subject. The specimens were divided into three groups: control (N, radiation (R, and Rapamycin and radiation (R+RAPA. The protein levels of γ-H2AX, Rad51, Ku70/Ku80, p62, and LC3 were determined by Western blot. Autophagosome was observed under a transmission electron microscope, and SF was determined by colony formation assay. Results Compared with group R, the activity of autophagy and the protein expression levels of Rad51 and Ku70/80 were remarkably increased in group R+RAPA. Conclusion The radiosensitivity of lung cancer can be promoted by activating autophagy via treatment with Rapamycin, and the process may be associated with DNA repair.

  19. Detection of expression level of 43 ku excretory-secretory antigen gene of Trichinella spiralis by RQ-PCR%旋毛虫43 ku ES抗原基因表达水平的实时荧光定量PCR检测

    Institute of Scientific and Technical Information of China (English)

    王守育; 路义鑫; 张子群; 韩彩霞; 宋铭忻

    2009-01-01

    根据GenBank中旋毛虫43 ku ES抗原基因(Ts43)序列设计引物和探针.以管家基因18 SrRNA为内参基因,对旋毛虫总RNA进行归一化处理,根据循环阈值(Ct值)的变化计算Ts43基因的表达量,建立检测旋毛虫Ts43表达量的实时荧光定量PCR方法,并用该方法测定旋毛虫不同寄生时期Ts43基因的表达水平.结果显示,旋毛虫Ts43基因在各寄生时期均有表达,成虫和新生幼虫Ts43基因的表达水平相对于其他寄生时期的虫体低,该基因表达量在感染后第18 d开始逐渐上升,于感染后第30 d达到高峰,而后开始逐渐下降,但感染后第58 d的虫体Ts43基因表达水平仍高于成虫和新生幼虫.结果表明,Ts43基因的表达与保姆细胞的形成有较大关系.

  20. Y Kuşağı Turistlerin Destinasyon İmaj Algıları Üzerine Bir Araştırma A Research On Generation Y Tourists Perceptions Of Destination Image

    Directory of Open Access Journals (Sweden)

    Aslı ALBAYRAK

    2013-07-01

    Full Text Available This study has been performed on the purposed of determiningeffects of the destination image composing factors on deciding tovacation resort of Y Generation tourists who show differentcharacterists in comparison to the previous and the next generation,and making recommendations related to destination marketing for thegeneration by examining the relationship between destinationperception and structural features of Y Generation tourist.In this study, questionnaire technique which is one thequantitative research method, were used and questionnaire study weremade face to face with 384 people who were determined by quotasampling method and represent the generation in Istanbul. On analysisobtained from data were used descriptive statistics, t-test, and Anovaanalysis.According to results of research, destination image differs fromdepending on gender, level of educaiton, also income levels ofparticipants. On the other other hand, it can be said that Y Generationtourists act at the request of seeing new places, leisure, andentertainment and are the individuals who look for quality and luxuryholiday with affordable price.Touristic purchase process is shaped by many factors. One of thefactors affecting this process is image of destination. The mostgenerational definition about destination image is as an individual’soverall perception and these perceptions ınfluenced by many factorssuch as age, education, income and culture. There are several studieshave been conducted about tourists’ perceptions of destination image inpast and generally these studies about effects of tourists’ characteristicssuch as age, education, culture income to perception of destinationimage but there are no studies about different generations’ destinationimage perceptions. Therefore ıt’s thought that the results obtained fromthis study could contribute to the tourism marketers. Bu çalışma, kendinden önceki ve sonraki kuşaklardan farklı özellikler gösteren Y ku

  1. Uztvertās vecāku pārraudzības un uztvertās iesaistīšanās bērna izglītībā saistībā ar alkohola lietošanas biežumu pusaudžiem.

    OpenAIRE

    Zotova, Darja

    2014-01-01

    Pētījuma mērķis bija noskaidrot, kādas saistības pastāv starp uztverto vecāku pārraudzību, iesaistīšanos bērna izglītībā un pusaudža alkohola lietošanas biežumu. Tika izvirzīti divi pētījuma jautājumi – kāda saistība pastāv starp uztverto vecāku pārraudzību un alkohola lietošanas biežumu un kāda saistība pastāv starp vecāku iesaistīšanos bērnu izglītībā un alkohola lietošanas biežumu? Darba teorētiskajā daļā ir raksturota vecāku pārraudzība un iesaistīšanās bērnu dzīvē, kā arī raksturota pusa...

  2. 由《别录》到《四库全书总目》看目录学的发展流变%To See the Development of Bibliography From Bie Lu To Si Ku Quan Shu

    Institute of Scientific and Technical Information of China (English)

    王茜

    2013-01-01

    This thesis briefly introduces and contrasts the famous literatures in the bibliography history ,for example ,BIe Lu,Qi Lue,Han Shu·Yi Wen Zhi,Sui Shu·Jing JI Zhi,and Si Ku Quan Shu Zong Mu .etc,thus to summarize the thread of development of the Chinese bibliography after the Han dynasties.%本文对《别录》《七略》《汉书·艺文志》《隋书·经籍志》《四库全书总目》等我国目录学史上重要著作进行介绍对比,以此理清汉代以来我国目录学在内容、体例、分类、结构上的发展脉络。

  3. Study and Application Prospect of Ku-band Automatic Tracking System of Double Satellites’ Antenna%双卫星Ku波段自动对星系统研究及应用展望

    Institute of Scientific and Technical Information of China (English)

    郑学东; 高云勇

    2015-01-01

    The invention is a set of equipment for Ku-band antenna’s switch of two communication modes, including satellite-tracking controller of two communication systems, man-machine operation unit, antenna, duplexer, LNB(Low Noise Block), power divider, downlink frequency adapter, ordinary satellite modem, IP-STAR satellite modem, ordinary satellite BUC(Block Up-Converter), IP-STAR satellite BUC(Block Up-Converter) and uplink waveguide switch. This invention also disclosed application methods based on the said equipment. The invention added downlink frequency adapter and uplink waveguide switch to the existing satellite communication system and merged the original two discrete Ku-band communication systems into one system, which reduced the costs by a large margin, and was beneifcial to the popularization application of satellite communication technology.%本文介绍了一套Ku波段天线切换两种通信模式的装置,包括双通信系统寻星控制器、人机操作单元、天线、双工器、LNB、功分器、下行频率适配器、普通卫星调制解调器、IP-STAR卫星调制解调器、普通卫星BUC、IP-STAR卫星BUC及上行波导转换器。它在现有卫星通信系统上增加了下行频率适配器和上行波导转换器,将原来分立的两套Ku波段通信系统融合为一套系统,大幅度减少成本,有利于卫星通信技术的推广应用。

  4. Kuş Gölü (Bandırma Makrobentik Omurgasız Faunası Hakkında Bir Ön Araştırma.

    Directory of Open Access Journals (Sweden)

    Süleyman Balık

    2015-12-01

    Full Text Available Kuş Gölü’nün makrobentik omurgasız faunasını belirlemek amacıyla 1987 ve 1988 yılları arasında aylık periyotlar halinde, bir yıl süre ile 5 istasyonda arazi çalışması yapılmıştır. Ekman grab ile alınan çamur örnekleri 500 μm göz açıklığındaki elekten geçirilmiş ve örnekler %4’lük formaldehit solüsyonunda tespit edilmiştir. Araştırma sonucunda, Oligochaeta sınıfından 10, Chironomidae familyasından 5 ve Ceratopogonidae familyasından 1 olmak üzere toplam 16 takson tespit edilmiştir. Kuş gölü’nde metrekarede ortalama 6759 birey tespit edilmiş, grupların oransal dağılımında %81,94 ile Oligochaeta bireylerinin en baskın grubu oluşturduğu, bu grubu Chironomidae (%17,90 ve Ceratopogonidae (%0,16 larvalarının takip ettiği saptanmıştır. Tespit edilen grupların istasyonlara göre oransal dağılımlarında ise, 1. istasyonun en zengin (%28,71, 4. istasyonun en fakir (%12,77 istasyon olduğu gözlenmiştir

  5. Uticaj povećanja dometa na dinamičku stabilnost artiljerijskih raketa sa olučastim krilima / Influence of range extension on dynamic stability for artillery rockets with wrap around fins

    Directory of Open Access Journals (Sweden)

    Danilo Ćuk

    2007-07-01

    Full Text Available U radu su prikazani efekti povećanja dometa artiljerijske rakete sa olučastim krilima na njenu dinamičku stabilnost. Totalni impuls raketnog motora, uvećan za 50% i let rakete kroz slojeve atmosfere sa malom gustinom vazduha povećavaju domet rakete za više od 75% od nominalnog dometa. Međutim, let rakete kroz razređeni vazduh proizvodi teškoće koje se odnose na dinamičku stabilnost. Male promene bočnog momenta indukovanog napadnim uglom i Magnusovog momenta mogu proizvesti nestabilnost kretanja i nedozvoljeni rast napadnog ugla. Određene su tolerancije bočnog momenta za osnovnu i poboljšanu varijantu rakete radi sprečavanja nestabilnog leta. Analiziran je, takođe uticaj povećanja dometa na verovatna odstupanja rakete po dometu i pravcu. / This paper presents the effects of the range extension of an artillery rocket with wrap around fins on its dynamic stability. The increased total impulse of the rocket engine for 50% and flight through the atmosphere layers with low air density extend the range for more than 75% of the nominal range. However, the flight of the unguided rocket through the rarefied air produces difficulties related to the dynamic stability. The small changes in the side moment which is induced by the angle of attack and Magnus moment of the improved rocket can produce instabilities in flight and increasement the angle of attack. The tolerances of the side moment were determined for both basic and improved type of the rocket in order to prevent instable flight. The influence of the range extension on the probable errors in range and cross-range was analyzed as well.

  6. Simian-Human immunodeficiency viruses expressing chimeric subtype B/C Vpu proteins demonstrate the importance of the amino terminal and transmembrane domains in the rate of CD4(+) T cell loss in macaques.

    Science.gov (United States)

    Ruiz, Autumn; Schmitt, Kimberly; Culley, Nathan; Stephens, Edward B

    2013-01-20

    Previously, we reported that simian-human immunodeficiency viruses expressing either the lab adapted subtype B (SHIV(KU-1bMC33)) or subtype C (SHIV(SCVpu)) Vpu proteins of human immunodeficiency virus type 1 (HIV-1) had different rates of CD4(+) T cell loss following inoculation into macaques. In this study, we have generated SHIVs that express either the subtype B or subtype C N-terminal (NTD) and transmembrane (TMD) domains and the opposing cytoplasmic domain (SHIV(VpuBC), SHIV(VpuCB)). In culture systems, SHIV(VpuBC) replicated faster than SHIV(VpuCB) while both proteins exhibited similar ability to down-modulate CD4 surface expression. Following inoculation into macaques, SHIV(VpuBC) resulted in rapid CD4(+) T cell loss similar to the parental SHIV(KU-1bMC33), while the rate of CD4(+) T cell loss in those inoculated with SHIV(VpuCB) was intermediate of SHIV(SCVpu) and SHIV(KU-1bMC33). These results emphasize the importance of the Vpu NTD/TMD region in the rate of CD4(+) T cell loss in the pathogenic X4 SHIV/macaque model.

  7. A Comparison of Epitope Repertoires Associated with Myasthenia Gravis in Humans and Nonhuman Hosts

    Directory of Open Access Journals (Sweden)

    Kerrie Vaughan

    2012-01-01

    Full Text Available Here we analyzed the molecular targets associated with myasthenia gravis (MG immune responses, enabled by an immune epitope database (IEDB inventory of approximately 600 MG-related epitopes derived from 175 references. The vast majority of epitopes were derived from the α-subunit of human AChR suggesting that other MG-associated autoantigens should be investigated further. Human α-AChR was mostly characterized in humans, whereas reactivity primarily to T. californica AChR was examined in animal models. While the fine specificity of T-cell response was similar in the two systems, substantial antibody reactivity to the C-terminus was detected in the nonhuman system, but not in humans. Further analysis showed that the reactivity of nonhuman hosts to the C-terminus was eliminated when data were restricted to hosts tested in the context of autoimmune disease (spontaneous or induced, demonstrating that the epitopes recognized in humans and animals were shared when disease was present. Finally, we provided data subsets relevant to particular applications, including those associated with HLA typing or restriction, sets of epitopes recognized by monoclonal antibodies, and epitopes associated with modulation of immunity or disease. In conclusion, this analysis highlights gaps, differences, and similarities in the epitope repertoires of humans and animal models.

  8. Farklı Test Sistemleri ile Somatik Hücrelerde Profenofos Genotoksisitesine Karşı Kuşburnu (Rosa canina L. Ekstrelerinin Doğal Bir Antigenotoksik Ajan Olarak Kullanılması

    Directory of Open Access Journals (Sweden)

    Caner KASIMOĞLU

    2016-04-01

    Full Text Available Bu çalışmada, profenofos insektisitinin genotoksik etkileri, Drosophila melanogaster’de somatik mutasyon ve rekombinasyon testi (SMART ve insan periferal lenfosit hücrelerinde mikronükleus (MN testi ile araştırılmıştır. Bu maddenin olası genotoksik etkilerinin giderilebilmesi için de kuşburnu (Rosa canina bitkisine ait su ve etanol ekstreleri kullanılmıştır. SMART için D.melanogaster’in kanat preparatları incelendiği zaman, profenofosun artan konsantrasyonuna (0,025, 0,05, 0,075 ve 0,1ppm bağlı olarak normal kanat fenotipinde mutasyon frekansının arttığı özellikle en yüksek uygulama grubunda (0,1 ppm bu artışın pozitif etkili (+ olduğu gözlenmiştir (P0,05. Kuşburnu bitkisinin su (RCsu ve etanol (RCeta ekstreleri, profenofosun en yüksek konsantrasyonu (0,1 ppm ile birlikte uygulandığı zaman (profenofos+ RCsu/RCeta mutasyon frekansındaki artışın azaldığı ve bunun da istatistiksel olarak önemli olduğu gözlenmiştir (P<0,05. Bu çalışmada, farklı konsantrasyonlarda in vitro profenofos uygulaması (0,25, 0,5, 0,75 ve 1ppm ile insan periferal lenfosit hücrelerinde mikronükleus frekansının arttığı ve nükleer bölünme indeksinin (NBİ azaldığı da görülmüştür (P<0,05. Ancak profenofos+RCsu ve RCeta uygulamaları ile mikronükleus frekansı düşerken NBİ değeri de kontrol grubuna yaklaşmıştır (P<0,05.

  9. Nonhomologous DNA end joining and chromosome aberrations in human embryonic lung fibroblasts treated with environmental pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Rossner, Pavel, E-mail: prossner@biomed.cas.cz; Rossnerova, Andrea; Beskid, Olena; Tabashidze, Nana; Libalova, Helena; Uhlirova, Katerina; Topinka, Jan; Sram, Radim J.

    2014-05-15

    Highlights: • We analyzed the effect of air pollutants on NHEJ and chromosome aberrations. • In HEL12469 cells B[a]P and extractable organic matter induced DSBs. • The compounds induced XRCC4 expression and a weak Ku70/80 response. • We found increased frequency of aberrations of chromosomes 1, 2, 4, 5, 7 and 17. • The tested compounds preferentially affected chromosome 7. - Abstract: In order to evaluate the ability of a representative polycyclic aromatic hydrocarbon (PAH) and PAH-containing complex mixtures to induce double strand DNA breaks (DSBs) and repair of damaged DNA in human embryonic lung fibroblasts (HEL12469 cells), we investigated the effect of benzo[a]pyrene (B[a]P) and extractable organic matter (EOM) from ambient air particles <2.5 μm (PM2.5) on nonhomologous DNA end joining (NHEJ) and induction of stable chromosome aberrations (CAs). PM2.5 was collected in winter and summer 2011 in two Czech cities differing in levels and sources of air pollutants. The cells were treated for 24 h with the following concentrations of tested chemicals: B[a]P: 1 μM, 10 μM, 25 μM; EOMs: 1 μg/ml, 10 μg/ml, 25 μg/ml. We tested several endpoints representing key steps leading from DSBs to the formation of CAs including histone H2AX phosphorylation, levels of proteins Ku70, Ku80 and XRCC4 participating in NHEJ, in vitro ligation activity of nuclear extracts of the HEL12469 cells and the frequency of stable CAs assessed by whole chromosome painting of chromosomes 1, 2, 4, 5, 7 and 17 using fluorescence in situ hybridization. Our results show that 25 μM of B[a]P and most of the tested doses of EOMs induced DSBs as indicated by H2AX phosphorylation. DNA damage was accompanied by induction of XRCC4 expression and an increased frequency of CAs. Translocations most frequently affected chromosome 7. We observed only a weak induction of Ku70/80 expression as well as ligation activity of nuclear extracts. In summary, our data suggest the induction of DSBs and

  10. Pusaudžu - hokeja spēlētāju sasniegumu stratēģijas un apmierinātības izjūta, spēlējot hokeju, saistībā ar vecāku audzināšanas stiliem.

    OpenAIRE

    Stālmane, Liene

    2014-01-01

    Maģistra darba mērķis bija izpētīt saistības starp pusaudžu, kuri trenējas hokejā jau no agrīna vecuma, sasniegumu stratēģijām, apmierinātības izjūtu, spēlējot hokeju, un viņu vecāku audzināšanas stilus. Pētījumā tika iekļauti 53 respondenti latviešu tautības zēni, vecumā no 9 – 14 gadiem, kuri trenējas hokejā. Par pētījuma instrumentāriju izmantotas: 1)Vecāku audzināšanas stila aptauja. (Parental Authority Questionnaire (PAQ), Buri, 1991); 2) Sasniegumu stratēģiju aptauja....

  11. Střevní paraziti v archeologickém materiálu ze středověku

    OpenAIRE

    Bruzlová, Pavlína

    2015-01-01

    The aim of this thesis was to search for and identify human and/or animal intestinal parasite eggs in archeological material from medieval period in Brno and Prague. Concentration methods - sedimentation and flotation were used for parasite identification. Polymerase chain reaction (PCR) was used for the detection of parasite DNA. The results were put into context with other data published in similar studies and research.

  12. Recognition of lyso-phospholipids by human natural killer T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Lisa M Fox

    2009-10-01

    Full Text Available Natural killer T (NKT cells are a subset of T lymphocytes with potent immunoregulatory properties. Recognition of self-antigens presented by CD1d molecules is an important route of NKT cell activation; however, the molecular identity of specific autoantigens that stimulate human NKT cells remains unclear. Here, we have analyzed human NKT cell recognition of CD1d cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC. Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in the chemistry of the head group stimulated only weak responses from human NKT cells. However, lyso-sphingomyelin, which shares the phosphocholine head group of LPC, also activated NKT cells. Antigen-presenting cells pulsed with LPC were capable of stimulating increased cytokine responses by NKT cell clones and by freshly isolated peripheral blood lymphocytes. These results demonstrate that human NKT cells recognize cholinated lyso-phospholipids as antigens presented by CD1d. Since these lyso-phospholipids serve as lipid messengers in normal physiological processes and are present at elevated levels during inflammatory responses, these findings point to a novel link between NKT cells and cellular signaling pathways that are associated with human disease pathophysiology.

  13. Využití singulárních funkcí k výpočtu průhybu nosníku.

    OpenAIRE

    Fiala, Petr

    2008-01-01

    Účelem práce je porovnání dvou metod výpočtu ohybové čáry nosníku, řešení diferenciální rovnice ohybové čáry a metody založené na singulárních funkcích. Nosník je zatěžovám v pružné oblasti různými typy zatížení. Singulární funkce umožní stanovit jednotný postup řešení, nezávislý na kombinaci aplikovaného zatížení a je pro velmi výhodný pro další počítačové zpracování. The aim of this work is to compare two methods of calculation deflection curve of the beam, by means of the solution of di...

  14. Uztura paradumu, fiziskās aktivitātes un miera vielmaiņas intensitātes izvērtējums jaunu cilvēku grupā

    OpenAIRE

    2016-01-01

    Liekais svars un aptaukošanās pazemina dzīves kvalitāti un ir par iemeslu daudzām saslimšanām: diabētam, koronārajām sirds slimībām, onkoloģiskajām saslimšanām, metabolajam sindromam. Pētījuma mērķis ir izvērtēt uztura, fiziskās aktivitātes (FA) un miera vielmaiņas intensitātes (RMR) korelāciju ar ķermeņa tauku masu jaunu, pieaugušu, klīniski veselu cilvēku grupā. Pētījuma gaitā tika analizēta izmeklējamo personu 3 dienu uztura dienasgrāmata, fiziskā aktivitāte noteikta ar anketēšanas metodi...

  15. 广西白裤瑶族40岁以上人群的血脂水平调查%Serum lipids levels in subjects aged 40 years and over in the Guangxi Bai Ku Yao population

    Institute of Scientific and Technical Information of China (English)

    李牡艳; 尹瑞兴; 潘尚领; 林伟雄; 杨德寨; 李树全

    2008-01-01

    目的 了解广西白裤瑶族40岁及以上人群的血脂水平. 方法 采用分层随机整群抽样方法对485例白裤瑶族40岁及以上人群的饮食摄入量、生活习惯等进行流行病学调查,对血压、身高、体质量、体质指数(BMI)、腰围、血脂及载脂蛋白(apo)进行测定,并将结果与501例当地的汉族人群进行比较. 结果 白裤瑶族的文化程度、身高、体质量、腰围、血压、高脂血症患病率以及总能量、总脂肪、总蛋白质、食物胆固醇和食盐的摄入量明显低于汉族(P0. 05). Conclusions There are significant differences in lipids levels and the risk factors between Bai Ku Yao and Han populations, which might result from different dietary habits, life styles, and physical activities.

  16. Organizacija tehnološkog procesa remonta složenih tehničkih sistema u tehničkom remontnom zavodu u Čačku

    Directory of Open Access Journals (Sweden)

    Vojkan M. Radonjić

    2014-04-01

    Full Text Available Složeni tehnički sistemi (STS od ostalih tehničkih sistema (TS razlikuju se po konstrukciji i nameni, koja može biti: zaštita ljudi, materijalnih bogatstava i teritorije. Ako želimo da STS budu ispravni i imaju zadovoljavajući nivo pouzdanosti i gotovosti,  sistem remonta mora biti u stanju da podrži zahteve koji proističu iz njihove specifičnosti. Sistem njihovog remonta mora biti programiran, a upravljanje njime zasnovano na konceptu QMS (Quality management system. Organizacija remonta STS za potrebe sistema odbrane Republike Srbije, u Tehničkom remontnom zavodu u Čačku (TRZ, primer je organizacije u koju je implementiran  procesni model sistema upravljanja kvalitetom (QMS. Ovaj članak opisuje proces remonta STS u TRZ sa njegovim procesnim sistemom upravljanja kvalitetom (QMS, koji je preduslov za efikasan i efektivan proces remonta. Proces remonta prikazan je na primeru remonta guseničnog borbenog vozila. 

  17. Meðferð við félagsfælni. Áhrif endurgjafar með upptöku á misræmi í mati á eigin frammistöðu

    OpenAIRE

    Helena Jónsdóttir 1985

    2010-01-01

    Rannsókn þessi fór fram á meðal þátttakenda á námskeiði við félagsfælni og meðal háskólanema. Þátttakendur voru 33. Í rannsókninni voru áhrif endurgjafar með upptöku og hugræns undirbúnings könnuð með tilliti til breytinga á væntingum félagsfælinna til eigin frammistöðu, mats þeirra á frammistöðu sinni og kvíða fyrir ræðuhöldum auk þess sem áhrif endurgjafar og hugræns undirbúnings á sjálfmiðaða athygli og bakþanka voru könnuð. Þátttakendur, sem allir uppfylltu greiningarskilmerki fyrir félag...

  18. Účinek aplikace vybraných forem selenu na výnos a kvalitu máku (Papaver somniferum L)

    OpenAIRE

    Hajátková, Iveta

    2015-01-01

    Selenium belongs to important mineral nutrients in terms of animal and human diet. Insufficient amount of this element in diet has been a worldwide problem. The study objective was to determine the effect of its foliar application on the poppy yield (Papaver somniferum L) and its content within the seed. The test was based on a pot experiment. Selenium was applied as a foliar feeding in minerals form of selenate and selenite in dosages of 20 and 40 g Se/ha. Foliar applications with selenium h...

  19. Breaking tolerance in transgenic mice expressing the human TSH receptor A-subunit: thyroiditis, epitope spreading and adjuvant as a 'double edged sword'.

    Science.gov (United States)

    McLachlan, Sandra M; Aliesky, Holly A; Chen, Chun-Rong; Chong, Gao; Rapoport, Basil

    2012-01-01

    Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a "double-edged sword". On the one hand, priming with CFA (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens (like the

  20. Breaking tolerance in transgenic mice expressing the human TSH receptor A-subunit: thyroiditis, epitope spreading and adjuvant as a 'double edged sword'.

    Directory of Open Access Journals (Sweden)

    Sandra M McLachlan

    Full Text Available Transgenic mice with the human thyrotropin-receptor (TSHR A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors, regulatory T cell (Treg depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a "double-edged sword". On the one hand, priming with CFA (mycobacteria emulsified in oil plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens

  1. Epitopes of microbial and human heat shock protein 60 and their recognition in myalgic encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Amal Elfaitouri

    Full Text Available Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome, a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60 occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM immune response was studied in 69 ME patients and 76 blood donors (BD (the Training set with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients, a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24% of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001. IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

  2. 《游仙窟》与《双女坟》的比较研究%Comparative study of"You Xian Ku"and"Shuang Nv Fen"

    Institute of Scientific and Technical Information of China (English)

    安顺男

    2013-01-01

    Chinese literature has a long and far-reaching influence on Korean literature. Since ancient Korea (11th century B.C.), ancestors of the Chinese and Korean people had very frequent and close communications in culture, especially after the unification of the Three Kingdoms when the two countries experienced a much further development in cultural communication. Xinluo Shuyi Zhuan was one literary work from the influence of mystery novels in Wei and Jin Dynasties that had a great influence on Korean literature. This paper made a comparison between Chinese legendary novel You Xian Ku and Korean mystery prose Shuang Nv Fen to study the influence of Chinese mystery novels on the Korean mystery prose style during the period of unification.%中国文学与朝鲜文学的渊源颇为深远,早在公元前11世纪古朝鲜之始,中国与朝鲜的先民之间就有着非常频繁而密切的文化交流。特别是到了统一三国时期,两国之间的文化交流更是有了猛进的发展。《新罗殊异传》就是在魏晋志怪小说的直接影响下产生的,并对朝鲜文学产生了深远的影响。本文主要以中国的传奇小说《游仙窟》和朝鲜的殊异传体散文《双女坟》为中心通过比较文学研究方法中影响研究方法分析中国志怪小说对朝鲜新罗统一时期的殊异传体散文的影响。

  3. Analysis of Constituents of Ku-Shui Rose Oil Extracted with Subcritical 4# Solvent by GC/MS%GC/MS分析亚临界四号溶剂萃取苦水玫瑰油的化学成分

    Institute of Scientific and Technical Information of China (English)

    常进文; 曹珊; 常进艳; 阳辉文; 赵彩贵; 李旭亮; 徐晶

    2013-01-01

    The Ku-Shui rose oil obtained from extraction with subcritical 4# solvent and purification with molecular distillation was analyzed by GC/MS.Eighty-two volatile constituents were detected,where 46 constituents among them were identified with the standard spectrum data,the main constituents included citronellol (35.90%),geraniol (11.27%) and ylangene (5.10%).The constituents that formed the top note of this rose oil were terpenes accounting to 23.21%.The rose oil obtained by this way showed more natural feeling,and the content of geraniol was close to that of Bulgaria Damascus rose oil.%应用GC/MS联用技术对以亚临界四号溶剂萃取和分子蒸馏纯化的苦水玫瑰油进行分析,检测出82种挥发性成分,利用计算机标准谱库匹配检索鉴定了46种化合物,其中主要成分有香茅醇(35.90%)、香叶醇(11.27%)、依兰烯(5.10%)等,构成玫瑰油头香的萜烯类物质占23.21%,使玫瑰油更具有天然感,其中香茅醇的含量与保加利亚大马士革玫瑰油接近.

  4. Izbor faktora rotacije vektora potiska za balističku raketu sa Lambertovim vođenjem / Choice of the rotational factor of the thrust vector for the ballistic missile with Lambert guidance

    Directory of Open Access Journals (Sweden)

    Danilo V. Ćuk

    2008-04-01

    Full Text Available Predmet rada jeste primena Lambertovog vođenja na balističku raketu. Koristeći fundamentalnu jednačinu za upravljački vektor brzine razvijena je formula za određivanje ugla orijentacije vektora potiska u zavisnosti od faktora rotacije njegovog pravca. Izvedena formula zahteva Q-matricu koja povezuje diferencijalnu promenu vektora položaja rakete sa odgovarajućom diferencijalnom promenom korelisane brzine za fiksnu poziciju cilja i konstantno vreme slobodnog leta rakete. Izborom parametra rotacije vektora potiska dobijaju se različiti profili ugaonog položaja rakete i ugla njene brzine u zavisnosti od vremena. Podešavanjem parametra rotacije vektora potiska moguće je ostvariti prekid rada raketnog motora pri nultom napadnom uglu i, na taj način, smanjiti početne poremećaje slobodnog leta rakete. / This paper deals with the application of the Lambert guidance to the ballistic missile. By using the fundamental equation for the velocity-to-be-gained, the demanded command for the thrust angle is developed in terms of the rotational factor of its direction. The developed formula requires the Q-matrix which links a differential change in the missile position vector to the corresponding differential change in the correlated velocity for the fixed target position and the constant time of free flight. The choice of the rotational parameter provides different profiles of the missile attitude and flight path angle with time. By adjusting the rotational parameter for the thrust vector, the cut-off of the rocket engine can occur at zero angle of attack and the initial perturbations during free flight may be thus reduced.

  5. Funkční a dynamická asymetrie u mládeže ve věku 14 a 16 let (komparativní výzkum Functional and dynamic asymmetry in youth aged 14 and 16 years (comparative research

    Directory of Open Access Journals (Sweden)

    Artur Hradzki

    2007-02-01

    Full Text Available Cílem tohoto výzkumu je vyhodnocení stupně lateralizace u mládeže ve věku 14 let a srovnání získaných výsledků s výsledky výzkumu provedeného u stejné skupiny mladých lidí o dva roky později (16 let. Úspěšná identifikace úrovně lateralizace je pro didaktickou a vzdělávací práci mimořádně významná a stává se jednou z priorit v boji proti poruchám učení a při odstraňování vývojových dysfunkcí. Vzhledem k tomu, že lateralizace je pro vývoj člověka charakteristická, může být poznání jejího stavu a určujících faktorů jednou ze základních podmínek účinného vlivu pedagoga. Výzkum byl prováděn v jednom z náhodně zvolených měst v Dolním Slezsku. Za účelem provedení výzkumu byli vybráni studenti prvního ročníku (60 studentů, z nich 30 dívek a 30 chlapců. Pro vyhodnocení funkční a dynamické asymetrie byly použity ověřené testy Koszczyce a Sekity (Osiński, 2003. Výzkumný projekt umožnil autorům naplnit cíl této práce. V průběhu dvou let se jak u funkční, tak i u dynamické asymetrie projevily změny. Zvýšilo se procento osob s vyhraněným profilem a vyhraněnou stranou funkční asymetrie. Vzrostl rovněž stupeň dynamické asymetrie u zkoumaných motorických schopností. Výše popsané změny se vztahují jak na skupinu dívek, tak i na skupinu chlapců, přestože u druhé skupiny byla jejich intenzita vyšší. This research purpose is an evaluation of the degree of lateralization in 14 year old youth and a comparison of the obtained results with the results of the research carried out in the same group of youth two years later (16 year olds. Effective identification of the level of lateralization is extremely significant for the practice of didactic and educational work, and it is becoming one of the priorities in the fight against difficulties in learning and eliminating developmental dysfunctions. Knowing that lateralization is a

  6. Rozbor morfologie nohy u chlapců a dívek ve věku Infans 2 a Juvenis Analysis of morphology of foot in Moravian male and female students in the age Infans 2 and Juvenis

    Directory of Open Access Journals (Sweden)

    Michaela Peštuková

    2005-02-01

    Full Text Available U 106 studentů a 162 studentek z Gymnázia ve Šternberku a Střední integrované školy v Ostravě ve věku 12–18 let byl sledován morfologický typ nohy, index nohy pro hodnocení podélné klenby nožní, vyosení palce a malíku, úhel paty a stav svalstva dolních končetin. U chlapců i dívek byla nalezena výrazně vyšší frekvence výskytu nohy egyptské (71,69 % a 70,99 %. Noha kvadratická se vyskytovala u chlapců ve velmi nízkém procentu (2,83 % s určitou individuální asymetrií, u dívek nalezena nebyla. Diagnostika plochonoží metodou Chippauxe–Šmiřáka poskytla velmi příznivé výsledky (4,94–10,38 % výskytu ploché nohy, metoda podle Szritera–Godunova naopak nález podstatně horší (38,2–43,21 % výskytu ploché nohy. S nulovým stavem vyosení palce jsme se setkali u necelé čtvrtiny souborů. U souboru chlapců byla četnost projevu valgozity a varozity palce téměř vyrovnána, věcně převažovalo varózní postavení palce vpravo. U souboru dívek dominovalo signifikantně valgózní postavení. Průměrné hodnoty se pohybovaly v rozmezí 4 až 7 stupňů. Průměrná hodnota úhlu malíku, charakterizující vbočený malík, byla vysoká (17,73 až 21,90 stupně. Průměrný úhel paty byl diagnostikován v rozmezí 15 až 18 stupňů. Při hodnocení vztahů mezi zkrácením svalů dolní končetiny a poruchami funkčního stavu klenby nožní (pouze u mužů jsme nalezli potvrzení statistické významnosti závislosti u vyosení paty a zkrácení m. triceps surae sin. a signifikantní závislost mezi úhlem paty a zkrácením flexorů kolen sin. Morphological foot type, foot index for longitudinal foot vault, misalignment of the big and little toes, heel angle and lower limb muscles condition were monitored in 106 male students and 162 female students from the Gymnasium school in Šternberk and the Integrated secondary school in Ostrava ranging in age from 12 to 18 years. A considerably

  7. Increased chemosensitivity and radiosensitivity of human breast cancer cell lines treated with novel functionalized single-walled carbon nanotubes

    Science.gov (United States)

    Jia, Yijun; Weng, Ziyi; Wang, Chuanying; Zhu, Mingjie; Lu, Yunshu; Ding, Longlong; Wang, Yongkun; Cheng, Xianhua; Lin, Qing; Wu, Kejin

    2017-01-01

    Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O2-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay. The cell surviving fractions were determined by colony forming assay. Cell apoptosis induction was monitored by flow cytometry. Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting. The novel synthesized R-O2-FA-CHI-SWCNTs were able to significantly enhance the chemosensitivity and radiosensitivity of human breast cancer cell lines and the material exhibited its expected function by downregulating the expression of Bcl-2, survivin, HIF-1α, P-gp, MRP-1, RAD51 and Ku80.

  8. RNA sensors enable human mast cell anti-viral chemokine production and IFN-mediated protection in response to antibody-enhanced dengue virus infection.

    Directory of Open Access Journals (Sweden)

    Michael G Brown

    Full Text Available Dengue hemorrhagic fever and/or dengue shock syndrome represent the most serious pathophysiological manifestations of human dengue virus infection. Despite intensive research, the mechanisms and important cellular players that contribute to dengue disease are unclear. Mast cells are tissue-resident innate immune cells that play a sentinel cell role in host protection against infectious agents via pathogen-recognition receptors by producing potent mediators that modulate inflammation, cell recruitment and normal vascular homeostasis. Most importantly, mast cells are susceptible to antibody-enhanced dengue virus infection and respond with selective cytokine and chemokine responses. In order to obtain a global view of dengue virus-induced gene regulation in mast cells, primary human cord blood-derived mast cells (CBMCs and the KU812 and HMC-1 mast cell lines were infected with dengue virus in the presence of dengue-immune sera and their responses were evaluated at the mRNA and protein levels. Mast cells responded to antibody-enhanced dengue virus infection or polyinosiniċpolycytidylic acid treatment with the production of type I interferons and the rapid and potent production of chemokines including CCL4, CCL5 and CXCL10. Multiple interferon-stimulated genes were also upregulated as well as mRNA and protein for the RNA sensors PKR, RIG-I and MDA5. Dengue virus-induced chemokine production by KU812 cells was significantly modulated by siRNA knockdown of RIG-I and PKR, in a negative and positive manner, respectively. Pretreatment of fresh KU812 cells with supernatants from dengue virus-infected mast cells provided protection from subsequent infection with dengue virus in a type I interferon-dependent manner. These findings support a role for tissue-resident mast cells in the early detection of antibody-enhanced dengue virus infection via RNA sensors, the protection of neighbouring cells through interferon production and the potential recruitment of

  9. Are humans prone to autoimmunity? Implications from evolutionary changes in hominin sialic acid biology.

    Science.gov (United States)

    Varki, Ajit

    2017-09-01

    Given varied intrinsic and extrinsic challenges to the immune system, it is unsurprising that each evolutionary lineage evolves distinctive features of immunoreactivity, and that tolerance mechanisms fail, allowing autoimmunity. Humans appear prone to many autoimmune diseases, with mechanisms both genetic and environmental. Another rapidly evolving biological system involves sialic acids, a family of monosaccharides that are terminal caps on cell surface and secreted molecules of vertebrates, and play multifarious roles in immunity. We have explored multiple genomic changes in sialic acid biology that occurred in human ancestors (hominins), some with implications for enhanced immunoreactivity, and hence for autoimmunity. Human ancestors lost the enzyme synthesizing the common mammalian sialic acid Neu5Gc, with an accumulation of the precursor sialic acid Neu5Ac. Resulting changes include an enhanced reactivity by some immune cells and increased ability of macrophages to kill bacteria, at the cost of increased endotoxin sensitivity. There are also multiple human-specific evolutionary changes in inhibitory and activating Siglecs, immune cell receptors that recognize sialic acids as "self-associated molecular patterns" (SAMPs) to modulate immunity, but can also be hijacked by pathogen molecular mimicry of SAMPs. Altered expression patterns and fixed or polymorphic SIGLEC pseudogenization in humans has modulated both innate and adaptive immunity, sometimes favoring over-reactivity. Meanwhile, dietary intake of Neu5Gc (derived primarily from red meats) allows metabolic incorporation of this non-human molecule into human cells--apparently the first example of "xeno-autoimmunity" involving "xeno-autoantigen" interactions with circulating "xeno-autoantibodies". Taken together, some of these factors may contribute to the apparent human propensity for autoimmunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Immunology of membranous nephropathy: from animal models to humans.

    Science.gov (United States)

    Sinico, R A; Mezzina, N; Trezzi, B; Ghiggeri, G M; Radice, A

    2016-02-01

    Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement-mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti-PLA2R. Some evidence suggests that IgG4 anti-PLA2R autoantibodies can bind mannan-binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome-wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)-DQA1 loci with iMN. In addition to their diagnostic value, anti-PLA2R antibodies may be useful to monitor disease activity and predict response to treatment.

  11. A Predistortion Linearizer for Ku-band Traveling Wave Tube Amplifier%一种适用于Ku波段行波管放大器的预失真线性化器

    Institute of Scientific and Technical Information of China (English)

    刘洁; 胡波雄; 王刚; 苏小保

    2014-01-01

    随着通信技术的发展,功率放大器线性度要求日益提高。该文提出一种两支路预失真电路,在单支路预失真电路基础上加入可调衰减器和非线性发生器级联成的辅助支路,改善了单个非线性发生器增益曲线斜率不足的问题,并在ADS中代入行波管模型仿真分析。在此基础上,加工Ku波段实际预失真电路并与行波管联合实验,线性化后的行波管放大器三阶载波交调比在输入功率回退3 dB时达到12.92 dB,回退6 dB时达到22.8 dB,线性度有了明显的改善。%With the development of communication technology, the requirements of power amplifier linearity are increasing. This paper presents a kind of two-branch predistortion circuit which contains the main branch and the auxiliary branch. The main branch is a diode based nonlinear generator and the auxiliary branch consists of variable attenuator and nonlinear generator. Compared with single nonlinear generator, this two-branch predistortion circuit increases the slope of amplitude characteristic. The ADS co-simulation of Traveling Wave Tube Amplifier (TWTA) and new predistorion circuit show the improvement of linearity. Based on the analysis and simulation, a Ku-band practically predistortion cuicuit is designed and tested with the TWTA. The results of experiments show that, the Carrier to Intermodulation (C/IM3) at TWTA Input Power Back Off (IPBO) of 3 dB can reach 12.92 dB, C/IM3 at TWTA IPBO of 6 dB can reach 22.8 dB. With the linearizer, the linearity of TWTA is clearly improved.

  12. 云南猪株旋毛虫43ku抗原基因的原核表达%Prokaryotic expression and purification of the 43 ku excretory-secretory antigen gene of Trichinella spiralis from swine in Yunnan Province

    Institute of Scientific and Technical Information of China (English)

    王丽娜; 赵蕾; 邴玉艳; 高杨; 刘金霞; 刘芳馨; 陈晓宁

    2015-01-01

    目的 构建云南猪株旋毛虫43 ku抗原基因原核表达载体,诱导其表达目的蛋白,为研究其功能奠定基础.方法 收集云南株旋毛虫成虫,提取总RNA,采用RT-PCR获得43 ku抗原基因.将PCR产物插入克隆载体pMD18-T中,重组质粒经酶切、PCR及测序鉴定正确后,将目的片段插入原核表达载体pET20b中并转化大肠埃希菌BL21,通过IPTG诱导表达目的蛋白,经镍柱亲和层析纯化后进行SDS-PAGE鉴定. 结果 RT-PCR扩增出云南猪株旋毛虫43ku抗原基因,其基因序列全长1 134 bp,与GenBank中注册的序列同源性最高为98.8%.重组表达质粒pET20b-Ts43经双酶切得到1 000 bp和3 700 bp左右两条片段,与预期结果相符.表达产物经SDS-PAGE鉴定,其分子质量单位为43 ku.纯化蛋白经SDS-PAGE分析为单一43 ku蛋白带. 结论 成功构建了云南猪株旋毛虫43 ku抗原基因的原核表达载体,表达并纯化了43 ku蛋白,为其功能研究奠定了基础.

  13. UTJECAJ GMO NA EKOLOŠKU POLJOPRIVREDU

    OpenAIRE

    Fagan, John

    2008-01-01

    Gotovo svi znanstvenici se slažu da su danas uobičajene metode za ugradnju novog gena u genom biljke putem genetičkog inženjerstva (genetičke modifikacije): (1) neprecizne i slučajne, (2) pa je njihov utjecaj na biološke funkcije biljke nepredvidiv, (3) a neželjeni učinci GMO na zdravlje konzumenta i na okoliš mogući. Korištenje GMO u ekološkoj poljoprivredi je zabranjeno, stoga potrošač vjeruje da oznaka “ekološki” zakonski štiti od prisustva GMO u hrani. Međutim, povećano korištenje GMO u k...

  14. Research in textile composites at KU, Leuven

    Science.gov (United States)

    Verpoest, Ignaas; Ivens, Jan; Willemvanvuure, Aart; Efstratiou, Vassilios

    1993-01-01

    An overview is presented of the research on textile composites at Katholieke Universiteit Leuven. Three dimensionally woven sandwich fabric preforms are investigated for delamination resistant sandwich structures, velvet woven 2.5 dimensional fabrics for delamination resistant laminates, and knitted fabrics with good drapability for laminates of complex shape.

  15. Alberti et le haïku

    OpenAIRE

    Flepp, Catherine

    2017-01-01

    La amante es el libro de Alberti en que más representado está el haiku. Se funden con frecuencia la sensación olfativa y la sensación visual en poemas concisos y a menudo impregnados de una estética surrealista. La poesía, arrastrada hacia la utopía de un lenguaje transparente, encuentra los límites de la expresión en esta forma que recuerda en ocasiones a la greguería. A diferencia de Machado, Alberti se aparta en estos breves poemas de cualquier tradición folclórica

  16. Kub5-Hera, the human Rtt103 homolog, plays dual functional roles in transcription termination and DNA repair.

    Science.gov (United States)

    Morales, Julio C; Richard, Patricia; Rommel, Amy; Fattah, Farjana J; Motea, Edward A; Patidar, Praveen L; Xiao, Ling; Leskov, Konstantin; Wu, Shwu-Yuan; Hittelman, Walter N; Chiang, Cheng-Ming; Manley, James L; Boothman, David A

    2014-04-01

    Functions of Kub5-Hera (In Greek Mythology Hera controlled Artemis) (K-H), the human homolog of the yeast transcription termination factor Rtt103, remain undefined. Here, we show that K-H has functions in both transcription termination and DNA double-strand break (DSB) repair. K-H forms distinct protein complexes with factors that repair DSBs (e.g. Ku70, Ku86, Artemis) and terminate transcription (e.g. RNA polymerase II). K-H loss resulted in increased basal R-loop levels, DSBs, activated DNA-damage responses and enhanced genomic instability. Significantly lowered Artemis protein levels were detected in K-H knockdown cells, which were restored with specific K-H cDNA re-expression. K-H deficient cells were hypersensitive to cytotoxic agents that induce DSBs, unable to reseal complex DSB ends, and showed significantly delayed γ-H2AX and 53BP1 repair-related foci regression. Artemis re-expression in K-H-deficient cells restored DNA-repair function and resistance to DSB-inducing agents. However, R loops persisted consistent with dual roles of K-H in transcription termination and DSB repair.

  17. Targeting inflammation with autoantigen-specific T cells

    NARCIS (Netherlands)

    Guichelaar, T.

    2008-01-01

    Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not res

  18. Autoimmune polyendocrine syndrome type 1 and NALP5, parathyroid autoantigen

    NARCIS (Netherlands)

    Alimohammadi, Mohammad; Bjorklund, Peyman; Hallgren, Asa; Pontynen, Nora; Szinnai, Gabor; Shikama, Noriko; Keller, Marcel P.; Ekwall, Olov; Kinkel, Sarah A.; Husebye, Eystein S.; Gustafsson, Jan; Rorsman, Fredrik; Peltonen, Leena; Betterle, Corrado; Perheentupa, Jaakko; Akerstrom, Goran; Westin, Gunnar; Scott, Hamish S.; Hollaender, Georg A.; Kampe, Olle

    2008-01-01

    Background: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene. Though recent studies concerning AIRE deficiency have begun to elucidate the molecular pathogenesis of organ-specific autoimmunity in patients

  19. Targeting inflammation with autoantigen-specific T cells

    NARCIS (Netherlands)

    Guichelaar, T.

    2008-01-01

    Chronic autoimmune diseases are driven by cells that respond to tissue components of the body. Inflammation in diseases like rheumatoid arthritis, diabetes or multiple sclerosis, can be suppressed by drug therapy. However, the broad range of immunosuppressive action of these drugs often does not

  20. Seismotectonics and Neotectonics of the Gulfs of Gökova-Kuşadasi-Siǧacik and Surrounding Regions (SW Turkey): Earthquake Mechanisms, Source Rupture Modeling, Tsunami Hazard and Geodynamic Implications

    Science.gov (United States)

    Yolsal-Cevikbilen, Seda; Karaoglu, Özgür; Taymaz, Tuncay; Helvaci, Cahit

    2013-04-01

    The mechanical behavior of the continental lithosphere for the Aegean region is one of the foremost interesting geological disputes in earth sciences. The Aegean region provides complex tectonic events which produced a strong heterogeneity in the crust (i.e. large thrusts and exhumation shear zones or extensional detachments) as such in among most continental regions. In order to investigate mechanical reasons of the ongoing lithospheric-scale extension within the region, we must tackle all of the existing kinematic and dynamic agents: (1) roll back of the subduction slab and back arc extension; (2) westward extrusion of the Anatolian micro-plate; (3) block rotations of the Aegean region and western Anatolia; and (4) transtensional transform faults. Furthermore, seismological studies, particularly earthquake source mechanisms and rupture modeling, play important roles on deciphering the ongoing deformation and seismotectonic characteristics of the region. Recently, many moderate earthquakes occurred in the Gulfs of Gökova, Kuşadası, Sıǧacık and surroundings. In the present study, we examined source mechanisms and rupture histories of those earthquakes with Mw > 5.0 in order to retrieve the geometry of active faulting, source characteristics, kinematic and dynamic source parameters and current deformations of the region by using teleseismic body-waveform inversion of long-period P- and SH-waves, and broad-band P-waveforms recorded by GDSN and FDSN stations. We also checked first motion polarities of P- waveforms recorded at regional and teleseismic stations and applied several uncertainty tests to find the error limits of minimum misfit solutions. Inversion results revealed E-W directed normal faulting mechanisms with small amount of left lateral strike slip components in the Gulf of Gökova and NE-SW oriented right lateral strike slip faulting mechanisms in the Gulf of Sıǧacık. Earthquakes mostly have N-S and NW-SE directed T- axes directions which are

  1. cDNA cloning, chromosome mapping and expression characterization of human geranylgeranyl pyrophosphate synthase

    Institute of Scientific and Technical Information of China (English)

    赵勇[1; 余龙[2; 高洁[3; 付强[4; 华益民[5; 张宏来[6; 赵寿元[7

    2000-01-01

    Geranylgeranyl pyrophosphate (GGPP) mainly participates in post-translational modification for various proteins including Rho/Rac, Rap and Rab families, as well as in regulation for cell apoptosis. Geranylgeranyl pyrophosphate synthase (GGPPS), which catalyzes the condensation reaction between farnesyl diphosphate and isopentenyl diphosphate, is the key enzyme for synthesizing GGPP. We report the isolation of a gene transcript showing high homology with Drosophila GGPPS cDNA. The transcript is 1 466 bp in length and contains an intact open reading frame (ORF) ranging from nt 239 to 1 138. This ORF encodes a deduced protein of 300 residues with calculated molecular weight of 35 ku. The deduced protein shows 57.5% identity and 75% similarity with Drosophila GGPPS, and contains five characteristic domains of prenyltransferases. Northern hybridization revealed that human GGPPS was expressed highest in heart, and moderately in spleen, testis, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas

  2. Zebrafish to humans: evolution of the alpha3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome.

    Science.gov (United States)

    MacDonald, Brian A; Sund, Malin; Grant, Marianne A; Pfaff, Kathleen L; Holthaus, Kathryn; Zon, Leonard I; Kalluri, Raghu

    2006-03-01

    Goodpasture syndrome is an autoimmune vascular disease associated with kidney and lung failure, with pathogenic circulating autoantibodies targeted to a set of discontinuous epitope sequences within the noncollagenous domain-1 (NC1) of the alpha3 chain of type IV collagen (alpha3(IV)NC1), the Goodpasture autoantigen. We demonstrate that basement membrane extracted NC1 domain preparations from Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio do not bind Goodpasture autoantibodies, while Xenopus laevis, chicken, mouse and human alpha3(IV)NC1 domains bind autoantibodies. The alpha3(IV) chain is not present in C elegans and Drosophila melanogaster, but is first detected in the Danio rerio. Interestingly, native Danio rerio alpha3(IV)NC1 does not bind Goodpasture autoantibodies. Next, we cloned, sequenced, and generated recombinant Danio rerio alpha3(IV)NC1 domain. In contrast to recombinant human alpha3(IV)NC1 domain, there was complete absence of autoantibody binding to recombinant Danio rerio alpha3(IV)NC1. Three-dimensional molecular modeling from existing x-ray coordinates of human NC1 domain suggest that evolutionary alteration of electrostatic charge and polarity due to the emergence of critical serine, aspartic acid, and lysine residues, accompanied by the loss of asparagine and glutamine, contributes to the emergence of the 2 major Goodpasture epitopes on the human alpha3(IV)NC1 domain, as it evolved from the Danio rerio over 450 million years.

  3. Zebrafish to humans: evolution of the α3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome

    Science.gov (United States)

    MacDonald, Brian A.; Sund, Malin; Grant, Marianne A.; Pfaff, Kathleen L.; Holthaus, Kathryn; Zon, Leonard I.; Kalluri, Raghu

    2006-01-01

    Goodpasture syndrome is an autoimmune vascular disease associated with kidney and lung failure, with pathogenic circulating autoantibodies targeted to a set of discontinuous epitope sequences within the noncollagenous domain-1 (NC1) of the α3 chain of type IV collagen (α3(IV)NC1), the Goodpasture autoantigen. We demonstrate that basement membrane extracted NC1 domain preparations from Caenorhabditis elegans, Drosophila melanogaster, and Danio rerio do not bind Goodpasture autoantibodies, while Xenopus laevis, chicken, mouse and human α3(IV)NC1 domains bind autoantibodies. The α3(IV) chain is not present in C elegans and Drosophila melanogaster, but is first detected in the Danio rerio. Interestingly, native Danio rerio α3(IV)NC1 does not bind Goodpasture autoantibodies. Next, we cloned, sequenced, and generated recombinant Danio rerio α3(IV)NC1 domain. In contrast to recombinant human α3(IV)NC1 domain, there was complete absence of autoantibody binding to recombinant Danio rerio α3(IV)NC1. Three-dimensional molecular modeling from existing x-ray coordinates of human NC1 domain suggest that evolutionary alteration of electrostatic charge and polarity due to the emergence of critical serine, aspartic acid, and lysine residues, accompanied by the loss of asparagine and glutamine, contributes to the emergence of the 2 major Goodpasture epitopes on the human α3(IV)NC1 domain, as it evolved from the Danio rerio over 450 million years. PMID:16254142

  4. Amsacrine suppresses matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia cells.

    Science.gov (United States)

    Liu, Wen-Hsin; Chen, Ying-Jung; Chien, Jen-Hung; Chang, Long-Sen

    2014-05-01

    This study explores the suppression mechanism of amsacrine (4-(9-Acridinylamino)-N-(methanesulfonyl)-m-anisidine hydrochloride) on matrix metalloproteinase-2 (MMP-2) and MMP-9 expression in human leukemia cells. Amsacrine attenuated cell invasion with decreased MMP-2/MMP-9 protein expression and mRNA levels in U937, Jurkat, HL-60, K562, KU812, and MEG-01 cells. Moreover, amsacrine reduced both MMP-2/MMP-9 promoter luciferase activity and MMP-2/MMP-9 mRNA stability in leukemia cells. Studies on amsacrine-treated U937 cells revealed that amsacrine-elicited ROS generation induced JNK and p38 MAPK activation but reduced the phospho-ERK level. Amsacrine-induced ERK inactivation and p38 MAPK/JNK activation were demonstrated to suppress MMP-2/MMP-9 promoter luciferase activity and promote MMP-2/MMP-9 mRNA decay, respectively. p38 MAPK/JNK activation led to up-regulation of protein phosphatase 2A catalytic subunit α (PP2Acα) in amsacrine-treated U937 cells. Okadaic acid (PP2A inhibitor) treatment increased MMP-2/MMP-9 mRNA stability in amsacrine-treated cells, whereas PP2Acα over-expression increased MMP-2/MMP-9 mRNA decay. Amsacrine-induced MMP-2/MMP-9 down-regulation was also related to PP2Acα up-regulation on Jurkat, HL-60, K562, KU812, and MEG-01 cells. Collectively, our data indicate that amsacrine induces MMP-2/MMP-9 down-regulation via simultaneous suppression of genetic transcription and mRNA stability in human leukemia cells.

  5. Effects of inhibition of ubiquitin-proteasome pathway on human primary leukemic cells

    Institute of Scientific and Technical Information of China (English)

    兰雨; 张学敏; 杨平地; 胡美茹; 于鸣; 杨怡; 沈倍奋

    2002-01-01

    Though there were a lot of reports about the totally different responses to the inhibition of ubiquitin-proteasome pathway in different kinds of cell lines, much less has been known about the responses in primary human leukemic cells. In this study, the effects of inhibition of ubiquitin-proteasome pathway on human bone marrow (BM) mononuclear cells (MNCs) obtained from 10 normal persons and 8 leukemia patients were examined. The results showed that the responses obviously varied individually. Among them, BM MNCs in 3 cases of leukemic patients were extremely sensitive, demonstrated by that >90% cells were induced to undergo apoptosis within 24 h, but MNCs in 10 cases of normal persons showed resistance to the inhibition and no apoptosis was observed. Furthermore, Western blots revealed that the Bcl-2 expression was relatively high in the sensitive primary leukemia cells, and especially the cleavage of 26 ku Bcl-2 into a 22 ku fragment occurred during the induction of apoptosis. In contrast, the Bcl-2 expression was either undetectable or detectable but no cleavage of that above was observed in the cells insensitive to the inhibition of the pathway (including BM MNCs in normal persons). Together with the observations on the leukemic cell lines, these findings suggested the correlation of the specific cleavage of Bcl-2 into a shortened fragment with the sensitivity of cells to the inhibition of ubiquitin-proteasome pathway, which provides clues to the further understanding of the mechanisms of that dramatically different responses existing in different kinds of cells to the inhibition of ubiquitin-proteasome pathway.

  6. The human histone chaperone sNASP interacts with linker and core histones through distinct mechanisms.

    Science.gov (United States)

    Wang, Huanyu; Ge, Zhongqi; Walsh, Scott T R; Parthun, Mark R

    2012-01-01

    Somatic nuclear autoantigenic sperm protein (sNASP) is a human homolog of the N1/N2 family of histone chaperones. sNASP contains the domain structure characteristic of this family, which includes a large acidic patch flanked by several tetratricopeptide repeat (TPR) motifs. sNASP possesses a unique binding specificity in that it forms specific complexes with both histone H1 and histones H3/H4. Based on the binding affinities of sNASP variants to histones H1, H3.3, H4 and H3.3/H4 complexes, sNASP uses distinct structural domains to interact with linker and core histones. For example, one of the acidic patches of sNASP was essential for linker histone binding but not for core histone interactions. The fourth TPR of sNASP played a critical role in interactions with histone H3/H4 complexes, but did not influence histone H1 binding. Finally, analysis of cellular proteins demonstrated that sNASP existed in distinct complexes that contained either linker or core histones.

  7. Possible Role of Human Herpesvirus 6 as a Trigger of Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Francesco Broccolo

    2013-01-01

    Full Text Available Human herpesvirus 6 (HHV-6 infection is common and has a worldwide distribution. Recently, HHV-6A and HHV-6B have been reclassified into two distinct species based on different biological features (genetic, antigenic, and cell tropism and disease associations. A role for HHV-6A/B has been proposed in several autoimmune disorders (AD, including multiple sclerosis (MS, autoimmune connective tissue diseases, and Hashimoto's thyroiditis. The focus of this review is to discuss the above-mentioned AD associated with HHV-6 and the mechanisms proposed for HHV-6A/B-induced autoimmunity. HHV-6A/B could trigger autoimmunity by exposing high amounts of normally sequestered cell antigens, through lysis of infected cells. Another potential trigger is represented by molecular mimicry, with the synthesis of viral proteins that resemble cellular molecules, as a mechanism of immune escape. The virus could also induce aberrant expression of histocompatibility molecules thereby promoting the presentation of autoantigens. CD46-HHV-6A/B interaction is a new attractive mechanism proposed: HHV-6A/B (especially HHV-6A could participate in neuroinflammation in the context of MS by promoting inflammatory processes through CD46 binding. Although HHV-6A/B has the ability to trigger all the above-mentioned mechanisms, more studies are required to fully elucidate the possible role of HHV-6A/B as a trigger of AD.

  8. Human See, Human Do.

    Science.gov (United States)

    Tomasello, Michael

    1997-01-01

    A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

  9. Metropolis Resepsiyon Salonu Mozaikleri Üzerindeki Balık ve Kuş Figürleri Üzerine Bir Değerlendirme / Analysis of Bird and Fish Figures on the Reception Hall Mosaics of Metropolis Theatre

    Directory of Open Access Journals (Sweden)

    Yaşar Serkal YILDIRIM

    2017-01-01

    Full Text Available Abstract 7.00 x 8.25 m. measured place which is located between housing ruins in the eastern part of the Metropolis Theatre is called reception hall. This place decorated with colorful mosaics and wall paintings also having a good handcrafted floor is dated back to Roman Empire period. Besides Dionysos, Ariadne, Meinad, and Eros holding a wineglass figures related with Dionysos cult on the mosaic; theatre masks, fish and bird figures all together demonstrate that it could be used as a banquet hall for official invitations during theatre plays.  These fish and bird figures have great importance to analyze the nutrition habits of antique cities, especially metropolis, which has few materials that could be read. The various fish and bird figures on the reception hall were examined by expert zoologists to try to identify the factors such as, this fish and birds’ species, their habitats and if they were eatable or not. The paper also tries to find out the nutrition habits of Metropolis community using the found data from ancient sources and obtained from this research. Öz Metropolis tiyatrosunun doğusunda konut kalıntıları arasında 7.00 x 8.25 m. Ölçülerindeki mekân Resepsiyon Salonu olarak adlandırılmaktadır.  Tabanı oldukça iyi bir işçilik gösteren renkli mozaiklerle ve duvar resimleri ile bezenmiş mekân Roma Dönemine tarihlenmektedir. Mozaik üzerinde Dionysos, Ariadne, Meinad ve elinde içki kadehi tutan (kantharos Eros figürleri gibi Dionysos kültü ile ilişkili figürlerinin yanı sıra tiyatro masklarının, balık ve kuş figürlerinin yer alması, buranın tiyatro gösterileri sırasında resmi davetlerin verildiği ziyafet salonu olarak kullanıldığını düşündürtmektedir. Bu balık ve kuş figürlerinin, özellikle okunabilir maddi kalıntıların az olduğu Metropolis gibi antik kentlerdeki toplumların beslenme anlayışının çözümlenmesinde büyük öneme sahiptir. Resepsiyon Salonu mozaiklerindeki

  10. Klima učitelského sboru: úprava dotazníku OCDQ-RS pro podmínky českých škol/ Organizational climate of schools: Adaptation of questionnaire OCDQ-RS for condition of Czech schools

    Directory of Open Access Journals (Sweden)

    Martin Chvál

    2014-05-01

    Full Text Available Cílem metodologické studie je představení psychometrických vlastností dotazníku KUS, a to i v porovnání s vlastnostmi originální verze OCDQ-RS a jeho slovenskou adaptací. V úvodní teoretické části je představen dotazník organizačního klimatu škol OCDQ-RS, jeho vznik a slovenská standardizace. Po upřesnění cíle studie následuje představení vzniku a výsledné verze dotazníku KUS, který je úpravou OCDQ-RS. Protože jsou některé výsledky porovnávány se známými psychometrickými vlastnostmi OCDQ-RS z USA, ze slovenské adaptace i nestandardizované české verze, jsou dále charakterizovány odpovídající datové soubory. Následují výsledky psychometrických analýz, diskuse zdůvodňující opuštění souhrnného indexu otevřenosti klimatu v dotazníku KUS oproti OCDQ-RS a orientační normy a odhadované chyby měření jednotlivých indexů KUSu. Po shrnujících závěrech jsou pojmenována i hlavní omezení studie. Výzkumný vzorek tvořilo 1823 učitelů ze 77 převážně základních škol. Návratnost dotazníků za školu byla minimálně 70 %. Data byla analyzována položkovou analýzou podle klasické teorie testů, exploratorní faktorovou analýzou, doplňkově i konfirmatorní faktorovou analýzou. Vnitřní konsistence indexů byla zjišťována pomocí Cronbachova alfa, ANOVA a standardní chyby měření indexů KUSu. Některé analýzy jsou s jednotkou učitel i škola. U dotazníku KUS byly zachovány čtyři indexy: podpora sboru vedením školy, angažovanost učitelů, frustrace učitelů, přátelské vztahy ve sboru. Pátý index direktivity ředitele byl nahrazen konotativně neutrálním pevnost vedení školy. Všechny indexy vykazují dostatečné hodnoty Cronbachova alfa v rozpětí od 0,84 do 0,96. Počet položek byl oproti OCDQ-RS navýšen z 34 na 40.

  11. Mehmet Harmancı’nın Küçürek Öykülerindegündelik Kuşatma Altındaki İnsanın Varoluş Görüngüleri Existence Perspectives Of An Individual Under Daily Blockage In The Short Short Stories Of Mehmet Harmancı

    Directory of Open Access Journals (Sweden)

    Mutlu DEVECİ

    2013-03-01

    Full Text Available Individual existing together with the others is carried into future bypreserving his/her own values / essence in his/her process ofindividualism. Being as everyone others is to die away in the world ofthings. Mehmet Harmancı, articulating truth of human being with itshistorical dimension, makes reference to existence of the individual. Fromthis viewpoint, existence states of human being, such as death, love andloneliness are evaluated in the context of pursuit of meaning.The characters in Probable Mangabats question the meaning of life.Interspecies transitivity attracts attention in this work and author prefersan expression method particular to short short story type by going beyondthe means of mangabat type. In the stories, values bringing now intoexistence are constructed in the projection of the past and they areexpressed in the form of existence perspectives of an individual under dailyblockage.Mehmet Harmancı considers traditions as the dominant value inProbable Mangabats that is written out in the projection of traditions,whereas he does not miss the modernity. Author regards traditions as thephenomenological foundation of modern world against those trying tocreate a civilization by ignoring their values. From this viewpoint, hewants a modern world based on traditions instead of the world/ life that isimposed on as modernity. Most of the stories in Probable Mangabatsbelong to such a spiritual world.Author benefits from the experiential, cultural and objects memory ofthe traditions in the stories of Probable Mangabats, and guiding function isbrought forward by means of the queries of life about the pursuit ofmeaning.In the study, stories in the work of Mehmet Harmancı namedProbable Mangabats are analyzed, and attention is drawn to the relationbetween the mangabat and short short story types, perspectives individualbetween traditions and modernity are given in the existential context. Başkalarıyla birlikte varlık olan insan, bireyle

  12. Glycosylation of recombinant human thyroid peroxidase ectodomain of insect cell origin has little effect on recognition by serum thyroid peroxidase antibody

    Institute of Scientific and Technical Information of China (English)

    LIU Ming-ming; LI Qing; ZHAO Lan-lan; GAO Ying; HUANG You-yuan; LU Gui-zhi; GAO Yan-ming

    2013-01-01

    Background Thyroid peroxidase (TPO) is an important autoantigen in Hashimoto's thyroiditis (HT),and almost all epitopes are located in TPO ectodomain.The glycosylation of TPO might contribute to breaking self-tolerance,therefore,purified glycosylated recombinant TPO ectodomain is prerequisite of elucidating its role in the pathogenesis of HT.The aim of our study was to investigate whether the glycosylation has influence on the antigenic determinants of recombinant TPO.Methods Bac-to-Bac baculovirus expression system was used to generate recombinant human TPO ectodomain.The antigenicity was analyzed by antigen specific enzyme-linked immunosorbant assays (ELISAs).The glycosylation of recombinant human TPO ectodomain of High Five insect cell origin was detected by lectin-ELISAs.Results TPO ectodomain was recovered from the culture media as a soluble protein,and it was fused with a hexahistidine tag which allowed purification by nickel-affinity chromatography.The recombinant TPO ectodomain could be recognized by all the 54 HT patients and three TPO monoclonal antibodies.Fucose,sialic acid and galactose were all detected on the recombinant TPO ectodomain.Sera TPOAb binding decreased slightly after non-specific deglycosylation of TPO by periodic acid.Conclusions High Five insect cells derived recombinant human TPO ectodomain had N-glycosylation sites,which might have little effect on recognition by serum TPOAb.

  13. Faktorová analýza antropometrických charakteristik u mladých plavců ve věku 11 a 12 let Factor analysis of anthropometric characteristics in young swimmers aged 11 and 12

    Directory of Open Access Journals (Sweden)

    Zofia Ignasiak

    2006-02-01

    Full Text Available Cílem této práce bylo popsat vybrané somatické charakteristiky typické pro mladé plavce. Faktorová analýza umožnila úměrné snížení somatických ukazatelů a umožnila vypočítat hlavní strukturální faktory typické pro mladé plavce. Do výzkumného souboru bylo zařazeno 80 žáků (11 a 12letých přijatých ke studiu na základní sportovní škole ve Wroclawi. Sledovaní probandi trénovali po dobu 2–3 let a jejich průměrný tréninkový čas byl 12 až 18 hodin týdně. Byly měřeny následující parametry: tělesná výška a hmotnost, délka horních a dolních končetin, obvod stehen, lýtka, paží, předloktí, hrudníku v klidu, hrudníku po nádechu a po výdechu, obvod pasu a boků, šířka ramen, šířka boků, šířka hrudníku, hloubka hrudníku a Rohrerův index. K dosažení cíle této studie byla použita metoda faktorové analýzy. Analýza výsledků ukázala, že pouze některé zvláštnosti mezi sledovanými parametry jsou pro mladé plavce charakteristické. Jsou spojeny do 2 trsů somatických charakteristik: kubický obsah (zahrnuje tělesnou hmotnost, svalstvo, trup a obvod horních a dolních končetin a vertikální rozměr (zahrnuje tělesnou výšku a délku horních a dolních končetin. Tyto parametry signalizují formování postavy typické pro plavce, charakteristické specifickými proporcemi tělesné hmotnosti a výšky, hrudníku a boků a obvykle delšími končetinami. Výsledky naznačují, že antropometrické charakteristiky lze použít pro optimalizaci tréninkového procesu mladých plavců. The aim of this study was to describe the set of somatic characteristics, which significantly discriminate young swimmers. The factor analysis let us reduce the number of somatic traits mostly correlated and to calculate the main structural factors typical for young swimmers. There were 80 pupils (11 and 12 years old from the primary sport school in Wroclaw recruited for the study

  14. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  15. Adherence to the aerobics exercise program in women aged 40 to 65 [Adherence ke cvičebnímu programu aerobiku u žen ve věku 40 až 65 let

    Directory of Open Access Journals (Sweden)

    Milan Elfmark

    2011-06-01

    Full Text Available BACKGROUND: The analysis of exercise adherence belongs among the basic criteria for evaluation of the efficiency of intervention exercise programs. OBJECTIVE: The aim of this study was to analyze the adherence of participants to the half-year dance and step aerobics program. METHODS: The experimental group consisted of 47 women aged 40 to 65 years old who exercised three times per week for a period of six months. The participant’s attendance sheets and their answers to two questions from the checklist were used for the evaluation of their adherence to the workouts. RESULTS: The mean value of the adherence of the whole group to the intervention exercise program was 70.43%. Mean values of the group gradually decreased from 85.39% to 68.35% during the first four months of the intervention exercise program. In the last two months of the intervention, the adherence continued to decrease when the average values of their attendance were slightly under 60%. Compared to other months, these differences were statistically and logically significant. CONCLUSIONS: Reasons for different or possibly decreasing degrees of adherence to long-lasting intervention exercise programs are mostly objective, e.g. health (55.17%, family (13.70% and work (22.41%. Other reasons (8.62% are based on psychological factors (motivational and personal characteristics, the offerings and attractiveness of the activities, which are closely associated to the current health status and movement experience of the individual. Even the group form of exercise does not guarantee a high rate of the participant’s adherence.[VÝCHODISKA: Jedním ze základních kritérií hodnocení efektivity dlouhodobých intervenčních pohybových programů je analýza adherence účastníků ke cvičení. CÍLE: Cílem této studie bylo analyzovat adherenci souboru žen k šestiměsíčnímu programu dance aerobiku a step aerobiku. METODIKA: Skupinu tvořilo 47 žen ve věku od 40 do 65 let (47,32

  16. Structure of a Questionnaire on Children's Attitudes towards Inclusive Physical Education (CAIPE-CZ [Struktura českého překladu dotazníku "Children's Attitudes toward Inclusive Physical Education" (CAIPE-CZ

    Directory of Open Access Journals (Sweden)

    Julie Wittmannová

    2011-12-01

    education.[VÝCHODISKA: Společné vzdělávání žáků se zdravotním postižením a žáků intaktních mělo v minulosti vice názvů. V češtině v současnosti převládá termín integrace a v angličtině termín inkluze (inclusion. Většina výzkumu se prozatím orientovala na postoje učitelů tělesné výchovy, ale úspěšná integrace je podmíněná porozuměním také postojům intaktních žáků. Z tohoto důvodu je třeba kvalitních a standardizovaných metodologických nástrojů. CÍLE: Cílem této studie je přeložit modifikovaný dotazník CAIPE-R, popsat jeho strukturu a porovnat strukturu českého překladu s originálním dotazníkem. METODIKA: Dotazník CAIPE-R (Block, 1995 byl modifikován a přeložen s využitím standardní procedury zpětného překladu. Výzkumný vzorek tvořilo 140 dívek (průměrný věk = 13,12 roků a 146 chlapců (průměrný věk = 13,26 roků. Analýza byla provedena s využitím softwaru SPSS PC 19.0. VÝSLEDKY: Výsledky faktorové analýzy prokázali strukturu dotazníku o dvou škálách, které byly nazvány: "Obecné tvrzení k integraci ve školní TV" a "Přesvědčení o vlastním jednání". Český dotazník prokázal podobnou strukturu s výjimkou počtu tvrzení, která se stala součástí první škály. ZÁVĚRY: CAIPE-CZ prokazuje vysokou hladinu vnitřní konzistence (α = 0.84 a je schopen také rozlišit postoje žáků, kteří mají osobní zkušenosti s dětmi s tělesným postižením a těch kteří takovéto zkušenosti nemají. CAIPE-CZ je tedy vhodný dotazníkem pro budoucí studie zaměřené na postoje dětí k integraci v tělesné výchově.

  17. Kunstnike Liidu volikogu koosolek toimus 20. X Ku-Ku klubis

    Index Scriptorium Estoniae

    2003-01-01

    Kinnitati EKLi 2004. a. eelarve, selle toetustest. Harry Liivrand tutvustas Kunstihoone ja selle galerii, Reet Varblane Linnagalerii, Elin Kard Hobusepea ja Draakoni galerii 2004. a. näituseplaane. Ateljee Vabaduse väljak 6-35 otsustati anda rendile Ülle Marksile, ateljee Ristiku 27 müüa Rafael Arutjunjanile. EKLi uued liikmed: Andrus Joonas, Alice Kask, Hermes Sarapuu, Epp Viires, Kristel Sibul

  18. Eesti Kunstnike Liidu volikogu kogunes 19. XII 2005 Ku-Ku klubis

    Index Scriptorium Estoniae

    2006-01-01

    Vastuvõetud EKL-i 2006. a. eelarvest, Tallinna Linnagalerii tulevikust, tarbekunstinäituste vähesusest. SA Tallinna Kunstihoone nõukogu uueks liikmeks valiti Leonhard Lapin. EKL-i auliikmeteks valiti Edgar Valter, Lea Walter, Jaan Klõsheiko, Lembit Sarapuu, Heinz Valk ja Helge Pihelga

  19. Kunstnike Liidu volikogu koosolek toimus 20. X Ku-Ku klubis

    Index Scriptorium Estoniae

    2003-01-01

    Kinnitati EKLi 2004. a. eelarve, selle toetustest. Harry Liivrand tutvustas Kunstihoone ja selle galerii, Reet Varblane Linnagalerii, Elin Kard Hobusepea ja Draakoni galerii 2004. a. näituseplaane. Ateljee Vabaduse väljak 6-35 otsustati anda rendile Ülle Marksile, ateljee Ristiku 27 müüa Rafael Arutjunjanile. EKLi uued liikmed: Andrus Joonas, Alice Kask, Hermes Sarapuu, Epp Viires, Kristel Sibul

  20. Serologic analysis of human rotavirus serotypes P1A and P2 by using monoclonal antibodies.

    Science.gov (United States)

    Padilla-Noriega, L; Werner-Eckert, R; Mackow, E R; Gorziglia, M; Larralde, G; Taniguchi, K; Greenberg, H B

    1993-01-01

    Three human rotavirus (HRV) VP4 serotypes and one subtype have been described on the basis of a fourfold or an eightfold-or-greater difference in neutralization titer when tested with hyperimmune antisera to recombinant VP4 or VP8* (serotypes P1A, P1B, P2, and P3). To start to analyze the antigenic basis underlying serotype specificity, we produced a library of 13 VP4-specific neutralizing monoclonal antibodies (NMAbs) to two HRVs, the serotype P1A strain Wa and the serotype P2 strain ST3, and characterized the reactivity of these NMAbs with a panel of serotypically diverse HRV strains by neutralization assay and enzyme-linked immunosorbent assay (ELISA). We characterized the serotypic specificity of the NMAbs by using a fourfold or an eightfold-or-greater difference in titer against the homologous (i.e., immunogen) and heterologous strains as a criterion for serotype. Some ST3-derived NMAbs reacted specifically with serotype P2 HRVs by ELISA and/or neutralization assay, while some Wa-derived NMAbs reacted specifically by ELISA and/or neutralization assay with some or all serotype P1A HRVs. Other Wa- and ST3-derived NMAbs reacted with some or all serotype P1A and P2 HRV strains by neutralization assay and ELISA. Most NMAbs did not react with serotype P1B or P3 strains. In previous studies, three distinct operationally defined epitopes have been identified on VP4 by examining the reactivity patterns of selected antigenic variants of HRV strain KU. At least one of the NMAbs described here recognizes an epitope unrelated to these previously identified epitopes, since it neutralized both KU and its variants. Images PMID:7681440