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Sample records for beta 1-integrin reverts

  1. Inhibiting Vimentin or beta 1-integrin Reverts Prostate Tumor Cells in IrECM and Reduces Tumor Growth

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xueping; Fournier, Marcia V.; Ware, Joy L.; Bissell, Mina J.; Zehner, Zendra E.

    2009-07-27

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphological changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional (3D) lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the parental prostate epithelial P69 cell line by selection in nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin or {alpha}6-, {beta}4- and {beta}1-integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via siRNA interference or {beta}1-integrin expression by the addition of the blocking antibody, AIIB2, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by subcutaneous injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in 3D lrECM gels. These studies suggest that the levels of vimentin and {beta}1-integrin play a key role in the homeostasis of the normal acini in prostate and that their dysregulation may lead to tumorigenesis.

  2. Genetic analysis of beta1 integrin "activation motifs" in mice

    DEFF Research Database (Denmark)

    Czuchra, Aleksandra; Meyer, Hannelore; Legate, Kyle R;

    2006-01-01

    /beta tails, leading to tail separation and integrin activation. We analyzed mice in which we mutated the tyrosines of the beta1 tail and the membrane-proximal aspartic acid required for the salt bridge. Tyrosine-to-alanine substitutions abolished beta1 integrin functions and led to a beta1 integrin...

  3. Beta 1 integrin is essential for teratoma growth and angiogenesis

    DEFF Research Database (Denmark)

    Bloch, W; Forsberg, E; Lentini, S;

    1997-01-01

    Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of beta 1 integrin during teratoma formation, we compared teratomas induced by normal and beta1-null ES cells. Injection of...... normal ES cells gave rise to large teratomas. In contrast, beta 1-null ES cells either did not grow or formed small teratomas with an average weight of <5% of that of normal teratomas. Histological analysis of beta 1-null teratomas revealed the presence of various differentiated cells, however, a much...... lower number of host-derived stromal cells than in normal teratomas. Fibronectin, collagen I, and nidogen were expressed but, in contrast to normal teratomas, diffusely deposited in beta1-null teratomas. Basement membranes were present but with irregular shape and detached from the cell surface. Normal...

  4. Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly; Zehner, Zendra E

    2008-06-12

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508].

  5. beta1-integrin-mediated signaling essentially contributes to cell survival after radiation-induced genotoxic injury

    DEFF Research Database (Denmark)

    Cordes, N; Seidler, J; Durzok, R; Geinitz, H; Brakebusch, C

    2006-01-01

    Integrin-mediated adhesion to extracellular matrix proteins confers resistance to radiation- or drug-induced genotoxic injury. To analyse the underlying mechanisms specific for beta1-integrins, wild-type beta1A-integrin-expressing GD25beta1A cells were compared to GD25beta1B cells, which express...... findings in tumor cells, human A-172 glioma cells were examined under the same conditions after siRNA-mediated silencing of beta1-integrins. We found that beta1A-integrin-mediated adhesion to fibronectin, collagen-III or beta1-IgG was essential for cell survival after radiation-induced genotoxic injury...... central role of beta1-integrins in Akt- and p130Cas/paxillin-mediated prosurvival signaling. These findings suggest beta1-integrins as critical regulators of cell survival after radiation-induced genotoxic injury. Elucidation of the molecular circuitry of prosurvival beta1-integrin-mediated signaling in...

  6. ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation

    DEFF Research Database (Denmark)

    Lafuste, Peggy; Sonnet, Corinne; Chazaud, Bénédicte; Dreyfus, Patrick A; Gherardi, Romain K; Wewer, Ulla M; Authier, François-Jérôme

    2005-01-01

    of alpha9 parallels that of ADAM12 and culminates at time of fusion. alpha9 and ADAM12 coimmunoprecipitate and participate to mpc adhesion. Inhibition of ADAM12/alpha9beta1 integrin interplay, by either ADAM12 antisense oligonucleotides or blocking antibody to alpha9beta1, inhibited overall mpc...

  7. Beta1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity

    DEFF Research Database (Denmark)

    Bauer, Martina; Brakebusch, Cord; Coisne, Caroline;

    2009-01-01

    )-integrin gene either in all hematopoietic cells or selectively in T lymphocytes. Our results show that T cells critically rely on beta(1) integrins to accumulate in the central nervous system (CNS) during EAE, whereas CNS infiltration of beta(1)-deficient myeloid cells remains unaffected, suggesting that T...

  8. Discoidin domain receptor 1 is activated independently of beta(1) integrin

    DEFF Research Database (Denmark)

    Vogel, W; Brakebusch, C; Fässler, R;

    2000-01-01

    Various types of collagen have been identified as potential ligands for the two mammalian discoidin domain receptor (DDR) tyrosine kinases, DDR1 and DDR2. It is presently unclear whether collagen-induced DDR receptor activation, which occurs with very slow kinetics, involves additional proteins...... blocking antibodies for alpha(2)beta(1) integrin or in cells with a targeted deletion of the beta(1) integrin gene. Finally, we show that overexpression of dominant negative DDR1 in the myoblast cell line C2C12 blocks cellular differentiation and the formation of myofibers....

  9. Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts

    DEFF Research Database (Denmark)

    Brakebusch, C; Wennerberg, K; Krell, H W; Weidle, U H; Sallmyr, A; Johansson, S; Fässler, R

    1999-01-01

    integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent beta1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgically removed. While average weights of GERM 11 and GERM 116 tumors were similar...

  10. CD46 and beta1 integrin relocation in the sperm head during capacitation and acrosome reaction

    Czech Academy of Sciences Publication Activity Database

    Šebková, N.; Frolíková, M.; Dvořáková-Hortová, Kateřina

    Madison: Society for the Study of Reproduction, 2015. s. 212. [48th Annual Meeting of the Society for the Study of reproduction. 18.06.2015-22.06.2015, San Juan] R&D Projects: GA ČR(CZ) GA14-05547S Institutional support: RVO:86652036 Keywords : CD46 * beta1 integrin * Proximity Ligation Assay * acrosome reaction Subject RIV: CE - Biochemistry

  11. Signaling through urokinase and urokinase receptor in lung cancer cells requires interactions with beta1 integrins.

    Science.gov (United States)

    Tang, Chi-Hui; Hill, Marla L; Brumwell, Alexis N; Chapman, Harold A; Wei, Ying

    2008-11-15

    The urokinase receptor (uPAR) is upregulated upon tumor cell invasion and correlates with poor lung cancer survival. Although a cis-interaction with integrins has been ascribed to uPAR, whether this interaction alone is critical to urokinase (uPA)- and uPAR-dependent signaling and tumor promotion is unclear. Here we report the functional consequences of point mutations of uPAR (H249A-D262A) that eliminate beta1 integrin interactions but maintain uPA binding, vitronectin attachment and association with alphaV integrins, caveolin and epidermal growth factor receptor. Disruption of uPAR interactions with beta1 integrins recapitulated previously reported findings with beta1-integrin-derived peptides that attenuated matrix-dependent ERK activation, MMP expression and in vitro migration by human lung adenocarcinoma cell lines. The uPAR mutant cells acquired enhanced capacity to adhere to vitronectin via uPAR-alphaVbeta5-integrin, rather than through the uPAR-alpha3beta1-integrin complex and they were unable to initiate uPA signaling to activate ERK, Akt or Stat1. In an orthotopic lung cancer model, uPAR mutant cells exhibited reduced tumor size compared with cells expressing wild-type uPAR. Taken together, the results indicate that uPAR-beta1-integrin interactions are essential to signals induced by integrin matrix ligands or uPA that support lung cancer cell invasion in vitro and progression in vivo. PMID:18940913

  12. Alpha9beta1 integrin in melanoma cells can signal different adhesion states for migration and anchorage

    DEFF Research Database (Denmark)

    Lydolph, Magnus C; Morgan-Fisher, Marie; Høye, Anette M;

    2009-01-01

    Cell surface integrins are the primary receptors for cell migration on extracellular matrix, and exist in several activation states regulated in part by ectodomain conformation. The alpha9 integrin subunit, which pairs only with beta1, has specific roles in the immune system and may regulate cell......beta1 integrin- and Rho kinase-dependent focal adhesion and stress fibre formation, suggesting that the activation status of alpha9beta1 integrin was altered. The effect of manganese ions in promoting focal adhesion formation was reproduced by beta1 integrin activating antibody. The alpha9beta1...

  13. Fetal and adult hematopoietic stem cells require beta1 integrin function for colonizing fetal liver, spleen, and bone marrow

    DEFF Research Database (Denmark)

    Potocnik, A J; Brakebusch, C; Fässler, R

    2000-01-01

    Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had hematoly......Homing of hematopoietic stem cells (HSCs) into hematopoietic organs is a prerequisite for the establishment of hematopoiesis during embryogenesis and after bone marrow transplantation. We show that beta1 integrin-deficient HSCs from the para-aortic splanchnopleura and the fetal blood had...... hematolymphoid differentiation potential in vitro and in fetal organ cultures but were unable to seed fetal and adult hematopoietic tissues. Adult beta1 integrin null HSCs isolated from mice carrying loxP-tagged beta1 integrin alleles and ablated for beta1 integrin expression by retroviral cre transduction...... failed to engraft irradiated recipient mice. Moreover, absence of beta1 integrin resulted in sequestration of HSCs in the circulation and their reduced adhesion to endothelioma cells. These findings define beta1 integrin as an essential adhesion receptor for the homing of HSCs....

  14. Conditional beta1-integrin gene deletion in neural crest cells causes severe developmental alterations of the peripheral nervous system

    DEFF Research Database (Denmark)

    Pietri, Thomas; Eder, Olivier; Breau, Marie Anne;

    2004-01-01

    Integrins are transmembrane receptors that are known to interact with the extracellular matrix and to be required for migration, proliferation, differentiation and apoptosis. We have generated mice with a neural crest cell-specific deletion of the beta1-integrin gene to analyse the role of beta1-...... almost complete absence of Schwann cells and sensory axon segregation and defective maturation in neuromuscular synaptogenesis. Thus, beta1-integrins are important for the control of embryonic and postnatal peripheral nervous system development....

  15. beta 1 integrin inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Catherine C.; Park, Catherine C.; Zhang, Hui J.; Yao, Evelyn S.; Park, Chong J.; Bissell, Mina J.

    2008-06-02

    {beta}1 integrin signaling has been shown to mediate cellular resistance to apoptosis after exposure to ionizing radiation (IR). Other signaling molecules that increase resistance include Akt, which promotes cell survival downstream of {beta}1 integrin signaling. We showed previously that {beta}1 integrin inhibitory antibodies, AIIB2, enhance apoptosis and decrease growth in human breast cancer cells in 3 dimensional laminin-rich extracellular matrix (3D lrECM) cultures and in vivo. Here we asked whether AIIB2 could synergize with IR to modify Akt-mediated IR resistance. We used 3D lrECM cultures to test the optimal combination of AIIB2 with IR treatment of two breast cancer cell lines, MCF-7 and HMT3522-T4-2, as well as T4-2 myr-Akt breast cancer colonies or HMT3522-S-1, which form normal organotypic structures in 3D lrECM. Colonies were assayed for apoptosis and {beta}1 integrin/Akt signaling pathways were evaluated using western blot. In addition, mice bearing MCF-7 xenografts were used to validate the findings in 3D lrECM. We report that AIIB2 increased apoptosis optimally post-IR by down regulating Akt in breast cancer colonies in 3D lrECM. In vivo, addition of AIIB2 after IR significantly enhanced tumor growth inhibition and apoptosis compared to either treatment alone. Remarkably, the degree of tumor growth inhibition using AIIB2 plus 2 Gy radiation was similar to that of 8 Gy alone. We showed previously that AIIB2 had no discernible toxicity in mice; here, its addition allowed for a significant reduction in the IR dose that was necessary to achieve comparable growth inhibition and apoptosis in breast cancer xenografts in vivo.

  16. alpha 11beta 1 integrin recognizes the GFOGER sequence in interstitial collagens.

    Science.gov (United States)

    Zhang, Wan-Ming; Kapyla, Jarmo; Puranen, J Santeri; Knight, C Graham; Tiger, Carl-Fredrik; Pentikainen, Olli T; Johnson, Mark S; Farndale, Richard W; Heino, Jyrki; Gullberg, Donald

    2003-02-28

    The integrins alpha(1)beta(1), alpha(2)beta(1), alpha(10)beta(1), and alpha(11)beta(1) are referred to as a collagen receptor subgroup of the integrin family. Recently, both alpha(1)beta(1) and alpha(2)beta(1) integrins have been shown to recognize triple-helical GFOGER (where single letter amino acid nomenclature is used, O = hydroxyproline) or GFOGER-like motifs found in collagens, despite their distinct binding specificity for various collagen subtypes. In the present study we have investigated the mechanism whereby the latest member in the integrin family, alpha(11)beta(1), recognizes collagens using C2C12 cells transfected with alpha(11) cDNA and the bacterially expressed recombinant alpha(11) I domain. The ligand binding properties of alpha(11)beta(1) were compared with those of alpha(2)beta(1). Mg(2+)-dependent alpha(11)beta(1) binding to type I collagen required micromolar Ca(2+) but was inhibited by 1 mm Ca(2+), whereas alpha(2)beta(1)-mediated binding was refractory to millimolar concentrations of Ca(2+). The bacterially expressed recombinant alpha(11) I domain preference for fibrillar collagens over collagens IV and VI was the same as the alpha(2) I domain. Despite the difference in Ca(2+) sensitivity, alpha(11)beta(1)-expressing cells and the alpha(11) I domain bound to helical GFOGER sequences in a manner similar to alpha(2)beta(1)-expressing cells and the alpha(2) I domain. Modeling of the alpha I domain-collagen peptide complexes could partially explain the observed preference of different I domains for certain GFOGER sequence variations. In summary, our data indicate that the GFOGER sequence in fibrillar collagens is a common recognition motif used by alpha(1)beta(1), alpha(2)beta(1), and also alpha(11)beta(1) integrins. Although alpha(10) and alpha(11) chains show the highest sequence identity, alpha(2) and alpha(11) are more similar with regard to collagen specificity. Future studies will reveal whether alpha(2)beta(1) and alpha(11)beta(1

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

    OpenAIRE

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

    1994-01-01

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

  18. Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes

    DEFF Research Database (Denmark)

    Brakebusch, C; Grose, R; Quondamatteo, F;

    2000-01-01

    developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression of......, the integrity of the basement membrane surrounding the beta 1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta 1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the...

  19. A preliminary optical and electron microscopic study of the beta(1) integrin distribution pattern of human osteosarcoma-derived cells.

    Science.gov (United States)

    Banai, Kiarash; Brady, Ken; McDonald, Fraser

    2004-07-01

    Immunogold labelling was used to study the organisation of the beta(1) integrins on osteosarcoma-derived osteoblasts (Saos-2 and MG-63). Monolayers of cells were prepared in multiwell culture plates on both uncovered and collagen-covered coverslips, and beta(1) integrins were primarily labelled using mouse monoclonal antibodies to beta(1) integrins. Indirect immunofluorescence labels using an anti-mouse fluorescein-conjugated goat antibody showed an even distribution of the beta(1) integrins on the cell membranes of all cell types used. A concentration of 2 microg/ml of the primary antibodies and a 1:100 dilution of the secondary antibodies were determined as the optimal concentration for labelling to use with indirect localisation of the primary antibodies gold conjugated to goat anti-mouse antibodies and viewed under an electron microscope. Ten nanometre gold particles were used for transmission electron microscopy (TEM) and 40 nm gold particles for scanning electron microscopy. TEM showed that beta(1) integrins were mainly clustered on the cell membrane processes with less labelling on the cell membranes themselves. The distribution of beta(1) integrins on osteosarcoma cells supports the concept that integrins may function by forming focal adhesions at the site of the cytoplasmic membrane processes. PMID:15241608

  20. Highly Potent, Water Soluble Benzimidazole Antagonist for Activated (alpha)4(beta)1 Integrin

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, R D; Andrei, M; Lau, E Y; Lightstone, F C; Liu, R; Lam, K S; Kurth, M J

    2007-08-29

    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC{sub 50} = 305 pM]. With exceptional solubility, this finding has potential for improving PK to help diagnose and treat lymphomas.

  1. Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression.

    LENUS (Irish Health Repository)

    Andrews, E J

    2012-02-03

    BACKGROUND: Recent studies have demonstrated that metastatic disease develops from tumor cells that adhere to endothelial cells and proliferate intravascularly. The beta-1 integrin family and its ligand laminin have been shown to be important in tumor-to-endothelial cell adhesion. Lipopolysaccharide (LPS) has been implicated in the increased metastatic tumor growth that is seen postoperatively. We postulated that LPS increases tumor cell expression of beta-1 integrins and that this leads to increased adhesion. METHODS: The human metastatic colon cancer cell line LS174T was labeled with an enhanced green fluorescent protein (eGFP) using retroviral transfection. Cell cultures were treated with LPS for 1, 2, and 4 h (n = 6 each) and were subsequently cocultured for 30 or 120 min with confluent human umbilical vein endothelial cells (HUVECs), to allow adherence. Adherent tumor cells were counted using fluorescence microscopy. These experiments were carried out in the presence or absence of a functional blocking beta-1 integrin monoclonal antibody (4B4). Expression of beta-1 integrin and laminin on tumor and HUVECs was assessed using flow cytometric analysis. Tumor cell NF-kappaB activation after incubation with LPS was measured. RESULTS: Tumor cell and HUVEC beta-1 integrin expression and HUVEC expression of laminin were significantly (P < 0.05) enhanced after incubation with LPS. Tumor cell adhesion to HUVECs was significantly increased. Addition of the beta-1 integrin blocking antibody reduced tumor cell adhesion to control levels. LPS increased tumor cell NF-kappaB activation. CONCLUSIONS: Exposure to LPS increases tumor cell adhesion to the endothelium through a beta-1 integrin-mediated pathway that is NF-kappaB dependent. This may provide a target for immunotherapy directed at reducing postoperative metastatic tumor growth.

  2. Lack of beta1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype

    DEFF Research Database (Denmark)

    Breau, Marie A; Pietri, Thomas; Eder, Olivier;

    2006-01-01

    The enteric nervous system arises mainly from vagal and sacral neural crest cells that colonise the gut between 9.5 and 14 days of development in mice. Using the Cre-LoxP system, we removed beta1 integrins in the neural crest cells when they emerge from the neural tube. beta1-null enteric neural...... integrins are required for the villi innervation in the small intestine. Our findings highlight the crucial roles played by beta1 integrins at various steps of enteric nervous system development....

  3. Beta1 integrin expression by podocytes is required to maintain glomerular structural integrity.

    Science.gov (United States)

    Pozzi, Ambra; Jarad, George; Moeckel, Gilbert W; Coffa, Sergio; Zhang, Xi; Gewin, Leslie; Eremina, Vera; Hudson, Billy G; Borza, Dorin-Bogdan; Harris, Raymond C; Holzman, Lawrence B; Phillips, Carrie L; Fassler, Reinhard; Quaggin, Susan E; Miner, Jeffrey H; Zent, Roy

    2008-04-15

    Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). beta1, the most abundantly expressed integrin subunit, binds at least 12 alpha subunits. beta1 containing integrins are highly expressed in the glomerulus of the kidney; however their role in glomerular morphogenesis and maintenance of glomerular filtration barrier integrity is poorly understood. To study these questions we selectively deleted beta1 integrin in the podocyte by crossing beta1(flox/flox) mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular capillary formation. We demonstrate that podocyte abnormalities are visualized during glomerulogenesis of the pod-Cre;beta1(flox/flox) mice and proteinuria is present at birth, despite a grossly normal glomerular basement membrane. Following the advent of glomerular filtration there is progressive podocyte loss and the mice develop capillary loop and mesangium degeneration with little evidence of glomerulosclerosis. By 3 weeks of age the mice develop severe end stage renal failure characterized by both tubulointerstitial and glomerular pathology. Thus, expression of beta1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus. PMID:18328474

  4. The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading

    DEFF Research Database (Denmark)

    Iba, K; Albrechtsen, R; Gilpin, B;

    2000-01-01

    spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn(2+) or the beta1 integrin-activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12-syndecan complex fails to modulate the function of beta1 integrin.......-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin beta1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and...... chondroblasts lacking beta1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain-mediated cell adhesion, and then the beta1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not...

  5. Rhodocytin (aggretin) activates platelets lacking alpha(2)beta(1) integrin, glycoprotein VI, and the ligand-binding domain of glycoprotein Ibalpha

    DEFF Research Database (Denmark)

    Bergmeier, W; Bouvard, D; Eble, J A;

    2001-01-01

    collagen may activate platelets by a similar mechanism. In contrast to these findings, we provided evidence that rhodocytin does not bind to alpha(2)beta(1) integrin. Here we show that the Cre/loxP-mediated loss of beta(1) integrin on mouse platelets has no effect on rhodocytin-induced platelet activation......Although alpha(2)beta(1) integrin (glycoprotein Ia/IIa) has been established as a platelet collagen receptor, its role in collagen-induced platelet activation has been controversial. Recently, it has been demonstrated that rhodocytin (also termed aggretin), a snake venom toxin purified from the......, excluding an essential role of alpha(2)beta(1) integrin in this process. Furthermore, proteolytic cleavage of the 45-kDa N-terminal domain of glycoprotein (GP) Ibalpha either on normal or on beta(1)-null platelets had no significant effect on rhodocytin-induced platelet activation. Moreover, mouse platelets...

  6. Mechanotransduction molecules in the plant gravisensory response: amyloplast/statolith membranes contain a beta 1 integrin-like protein

    Science.gov (United States)

    Lynch, T. M.; Lintilhac, P. M.; Domozych, D.

    1998-01-01

    It has been hypothesized that the sedimentation of amyloplasts within root cap cells is the primary event in the plant gravisensory-signal transduction cascade. Statolith sedimentation, with its ability to generate weighty mechanical signals, is a legitimate means for organisms to discriminate the direction of the gravity vector. However, it has been demonstrated that starchless mutants with reduced statolith densities maintain some ability to sense gravity, calling into question the statolith sedimentation hypothesis. Here we report on the presence of a beta 1 integrin-like protein localized inside amyloplasts of tobacco NT-1 suspension culture, callus cells, and whole-root caps. Two different antibodies to the beta 1 integrin, one to the cytoplasmic domain and one to the extracellular domain, localize in the vicinity of the starch grains within amyloplasts of NT-1. Biochemical data reveals a 110-kDa protein immunoprecipitated from membrane fractions of NT-1 suspension culture indicating size homology to known beta 1 integrin in animals. This study provides the first direct evidence for the possibility of integrin-mediated signal transduction in the perception of gravity by higher plants. An integrin-mediated pathway, initiated by starch grain sedimentation within the amyloplast, may provide the signal amplification necessary to explain the gravitropic response in starch-depleted cultivars.

  7. Beta 1 integrin predicts survival in breast cancer: a clinicopathological and immunohistochemical study

    Directory of Open Access Journals (Sweden)

    dos Santos Petra

    2012-08-01

    Full Text Available Abstract Background The main focus of several studies concerned with cancer progression and metastasis is to analyze the mechanisms that allow cancer cells to interact and quickly adapt with their environment. Integrins, a family of transmembrane glycoproteins, play a major role in invasive and metastatic processes. Integrins are involved in cell adhesion in both cell-extracellular matrix and cell-cell interactions, and particularly, β1 integrin is involved in proliferation and differentiation of cells in the development of epithelial tissues. This work aimed to investigate the putative role of β1 integrin expression on survival and metastasis in patients with breast invasive ductal carcinoma (IDC. In addition, we compared the expression of β1 integrin in patients with ductal carcinoma in situ (DCIS. Methods Through tissue microarray (TMA slides containing 225 samples of IDC and 67 samples of DCIS, β1 integrin expression was related with several immunohistochemical markers and clinicopathologic features of prognostic significance. Results β1 integrin was overexpressed in 32.8% of IDC. In IDC, β1 integrin was related with HER-2 (p = 0.019 and VEGF (p = 0.011 expression and it had a significant relationship with metastasis and death (p = 0.001 and p = 0.05, respectively. Kaplan-Meier survival analysis showed that the overexpression of this protein is very significant (p = 0.002 in specific survival (number of months between diagnosis and death caused by the disease. There were no correlation between IDC and DCIS (p = 0.559 regarding β1 integrin expression. Conclusions Considering that the expression of β1 integrin in breast cancer remains controversial, specially its relation with survival of patients, our findings provide further evidence that β1 integrin can be a marker of poor prognosis in breast cancer. Virtual slides The virtual slide(s for this article can be found here: http

  8. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    Directory of Open Access Journals (Sweden)

    Beecken Wolf-Dietrich

    2005-01-01

    Full Text Available Abstract Background Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Methods Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a, alpha2beta1 (CD49b, alpha3beta1 (CD49c, alpha4beta1 (CD49d, alpha5beta1 (CD49e, and alpha6beta1 (CD49f receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Results Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. Conclusion We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype.

  9. Mycophenolate mofetil modulates adhesion receptors of the beta1 integrin family on tumor cells: impact on tumor recurrence and malignancy

    International Nuclear Information System (INIS)

    Tumor development remains one of the major obstacles following organ transplantation. Immunosuppressive drugs such as cyclosporine and tacrolimus directly contribute to enhanced malignancy, whereas the influence of the novel compound mycophenolate mofetil (MMF) on tumor cell dissemination has not been explored. We therefore investigated the adhesion capacity of colon, pancreas, prostate and kidney carcinoma cell lines to endothelium, as well as their beta1 integrin expression profile before and after MMF treatment. Tumor cell adhesion to endothelial cell monolayers was evaluated in the presence of 0.1 and 1 μM MMF and compared to unstimulated controls. beta1 integrin analysis included alpha1beta1 (CD49a), alpha2beta1 (CD49b), alpha3beta1 (CD49c), alpha4beta1 (CD49d), alpha5beta1 (CD49e), and alpha6beta1 (CD49f) receptors, and was carried out by reverse transcriptase-polymerase chain reaction, confocal microscopy and flow cytometry. Adhesion of the colon carcinoma cell line HT-29 was strongly reduced in the presence of 0.1 μM MMF. This effect was accompanied by down-regulation of alpha3beta1 and alpha6beta1 surface expression and of alpha3beta1 and alpha6beta1 coding mRNA. Adhesion of the prostate tumor cell line DU-145 was blocked dose-dependently by MMF. In contrast to MMF's effects on HT-29 cells, MMF dose-dependently up-regulated alpha1beta1, alpha2beta1, alpha3beta1, and alpha5beta1 on DU-145 tumor cell membranes. We conclude that MMF possesses distinct anti-tumoral properties, particularly in colon and prostate carcinoma cells. Adhesion blockage of HT-29 cells was due to the loss of alpha3beta1 and alpha6beta1 surface expression, which might contribute to a reduced invasive behaviour of this tumor entity. The enhancement of integrin beta1 subtypes observed in DU-145 cells possibly causes re-differentiation towards a low-invasive phenotype

  10. Staged stromal extracellular 3D matrices differentially regulate breast cancer cell responses through PI3K and beta1-integrins

    International Nuclear Information System (INIS)

    Interactions between cancer cells and stroma are critical for growth and invasiveness of epithelial tumors. The biochemical mechanisms behind tumor-stromal interactions leading to increased invasiveness and metastasis are mostly unknown. The goal of this study was to analyze the direct effects of staged stroma-derived extracellular matrices on breast cancer cell behavior. Early and late three-dimensional matrices were produced by NIH-3T3 and tumor-associated murine fibroblasts, respectively. After removing fibroblasts, extracted matrices were re-cultured with breast epithelial cells of assorted characteristics: MCF-10A (non-tumorigenic), MCF-7 (tumorigenic, non-invasive), and MDA-MB-231 (tumorigenic, invasive). Effects prompted by staged matrices on epithelial cell's growth, morphology and invasion were determined. Also, matrix-induced velocity, directionality and relative track orientation of invasive cells were assessed in the presence or absence of inhibitors of phosphoinositide-3 kinase (PI3K) and/or beta-1 integrin. We observed that assorted breast epithelial cells reacted differently to two-dimensional vs. staged, control (early) and tumor-associated (late), three-dimensional matrices. MCF-10A had a proliferative advantage on two-dimensional substrates while MCF-7 and MDA-MB-231 showed no difference. MCF-10A and MCF-7 formed morphologically distinguishable aggregates within three-dimensional matrices, while MDA-MB-231 exhibited increased spindle-shape morphologies and directional movements within three-dimensional matrices. Furthermore, MDA-MB-231 acquired a pattern of parallel oriented organization within tumor-associated, but not control matrices. Moreover, tumor-associated matrices induced PI3K and beta1-integrin dependent Akt/PKB activity in MDA-MB-231 cells. Interestingly, beta1-integrin (but not PI3K) regulated tumor-associated matrix-induced mesenchymal invasion which, when inhibited, resulted in a change of invasive strategy rather than impeding

  11. Role of the beta1-integrin cytoplasmic tail in mediating invasin-promoted internalization of Yersinia

    DEFF Research Database (Denmark)

    Gustavsson, Anna; Armulik, Annika; Brakebusch, Cord;

    2002-01-01

    1B or different mutants of the beta1A subunit was used. Both beta1A and beta1B bound to invasin-expressing bacteria, but only beta1A was able to mediate internalization of the bacteria. The cytoplasmic region of beta1A, differing from beta1B, contains two NPXY motifs surrounding a double threonine...

  12. Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism.

    LENUS (Irish Health Repository)

    Wang, Jiang Huai

    2012-02-03

    Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin\\/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.

  13. Dystrophin Dp71f associates with the beta1-integrin adhesion complex to modulate PC12 cell adhesion

    Science.gov (United States)

    Cerna, Joel; Cerecedo, Doris; Ortega, Arturo; García-Sierra, Francisco; Centeno, Federico; Garrido, Efrain; Mornet, Dominique; Cisneros, Bulmaro

    2006-01-01

    Dystrophin Dp71 is the main product of the Duchenne muscular dystrophy gene in the brain; however, its function is unknown. To study the role of Dp71 in neuronal cells, we previously generated by antisense treatment PC12 neuronal cell clones with decreased Dp71 expression (antisense-Dp71 cells). PC12 cells express two different splicing isoforms of Dp71, a cytoplasmic variant called Dp71f and a nuclear isoform called Dp71d. We previously reported that antisense-Dp71 cells display deficient adhesion to substrate and reduced immunostaining of β1-integrin in the cell area contacting the substrate. In this study, we isolated additional antisenseDp71 clones to analyze in detail the potential involvement of Dp71f isoform with the β1-integrin adhesion system of PC12 cells. Immunofluorescence analyses as well as immunoprecipitation assays demonstrated that the PC12 cell β1-integrin adhesion complex is composed of β1-integrin, talin, paxillin, α-actinin, FAK and actin. In addition, our results showed that Dp71f associates with most of the β1-integrin complex components (β1-integrin, FAK, α-actinin, talin and actin). In the antisense-Dp71 cells, the deficiency of Dp71 provokes a significant reduction of the β1-integrin adhesion complex and, consequently, the deficient adhesion of these cells to laminin. In vitro binding experiments confirmed the interaction of Dp71f with FAK and β1-integrin. Our data indicate that Dp71f is a structural component of the β1-integrin adhesion complex of PC12 cells that modulates PC12 cell adhesion by conferring proper complex assembly and/or maintenance. PMID:16935300

  14. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    capacity to form colonies. Thus under our culture conditions breast acinar formation is at least a two-step process involving {beta}1-integrin-dependent cellular growth followed by polarization of the cells into organized structures. The regulation of this pathway appears to be impaired or lost in the tumor cells, suggesting that tumor colony formation occurs by independent mechanisms and that loss of proper integrinmediated cell-ECM interaction may be critical to breast tumor formation.

  15. Blood platelets contain and secrete laminin-8 (alpha4beta1gamma1) and adhere to laminin-8 via alpha6beta1 integrin.

    Science.gov (United States)

    Geberhiwot, T; Ingerpuu, S; Pedraza, C; Neira, M; Lehto, U; Virtanen, I; Kortesmaa, J; Tryggvason, K; Engvall, E; Patarroyo, M

    1999-12-15

    Laminins, a family of heterotrimeric proteins with cell adhesive/signaling properties, are characteristic components of basement membranes of vasculature and tissues. In the present study, permeabilized platelets were found to react with a monoclonal antibody to laminin gamma1 chain by immunofluorescence. In Western blot analysis of platelet lysates, several monoclonal antibodies to gamma1 and beta1 laminin chains recognized 220- to 230-kDa polypeptides, under reducing conditions, and a structure with much slower electrophoretic mobility under nonreducing conditions. Immunoaffinity purification on a laminin beta1 antibody-Sepharose column yielded polypeptides of 230, 220, 200, and 180 kDa from platelet lysates. In the purified material, mAbs to beta1 and gamma1 reacted with the two larger polypeptides, while affinity-purified rabbit antibodies to laminin alpha4 chain recognized the smallest polypeptide. Identity of the polypeptides was confirmed by microsequencing. One million platelets contained on average 1 ng of laminin (approximately 700 molecules per cell), of which 20-35% was secreted within minutes after stimulation with either thrombin or phorbol ester. Platelets adhered to plastic surfaces coated with the purified platelet laminin, and this process was largely inhibited by antibodies to beta1 and alpha6 integrin chains. We conclude that platelets contain and, following activation, secrete laminin-8 (alpha4beta1gamma1) and that the cells adhere to the protein by using alpha6beta1 integrin. PMID:10585296

  16. Treatment of marrow stroma with interferon-alpha restores normal beta 1 integrin-dependent adhesion of chronic myelogenous leukemia hematopoietic progenitors. Role of MIP-1 alpha.

    OpenAIRE

    R Bhatia; McGlave, P B; Verfaillie, C M

    1995-01-01

    The mechanisms by which interferon-alpha (IFN-alpha) restores normal hematopoiesis in chronic myelogenous leukemia (CML) are not well understood. We have recently demonstrated that IFN-alpha acts directly on CML hematopoietic progenitors to restore their adhesion to marrow stroma by modulating beta 1 integrin receptor function. In the present study we examined the effect of IFN-alpha treatment of marrow stroma on subsequent adhesion of CML progenitors. Stromal layers were preincubated with IF...

  17. Cellular partitioning of beta-1 integrins and their phosphorylated forms is altered after transformation by Rous sarcoma virus or treatment with cytochalasin D.

    OpenAIRE

    Haimovich, B; Aneskievich, B J; Boettiger, D

    1991-01-01

    A sequential extraction procedure of 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS) buffer followed by RIPA or Laemmli sample buffer was developed to define two distinct subpopulations of beta-1 integrins in primary chicken embryo fibroblasts. Extraction of cells in culture revealed an association of adhesion plaque-localized integrin with the CHAPS-insoluble fraction. Phosphorylated integrins were found in both fractions, but the specific phosphorylation was 12-fold high...

  18. Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Watanabe Takafumi

    2012-02-01

    Full Text Available Abstract Background A crucial step in the metastatic spread of ovarian cancer (OC is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3 from the non-metastatic FOC3 line. Methods Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.

  19. Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta1-integrin-mediated interaction with type I collagen.

    Science.gov (United States)

    Fishman, D A; Kearns, A; Chilukuri, K; Bafetti, L M; O'Toole, E A; Georgacopoulos, J; Ravosa, M J; Stack, M S

    1998-01-01

    Metastatic dissemination of epithelial ovarian carcinoma is thought to be mediated via tumor cell exfoliation into the peritoneal cavity, followed by adhesion to and invasion through the mesothelium which overlies the contents of the peritoneal cavity. In this study, we have utilized short-term primary cultures to analyze the effect of specific extracellular matrix proteins on properties of human ovarian epithelial carcinoma cells which contribute to the invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that ovarian carcinoma cells adhere preferentially to type I collagen. Immunoprecipitation analyses demonstrated the presence of the collagen-binding alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and cellular adhesion was inhibited by blocking antibodies directed against the alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu-Ala (DGEA) was also moderately effective at blocking adhesion to collagen relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma cells migrate preferentially on type I collagen coated surfaces. Type I collagen promoted migration in a concentration-dependent, saturable manner, with maximal migration observed at a collagen-coating concentration of 50 microg/ml. Migration on collagen was inhibited by antibodies directed against the alpha2 and beta1 integrin subunits and by DGEA peptide, providing evidence for the role of the alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian carcinoma cells on type I collagen gels led to a significant increase in conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form, suggesting that adhesion to collagen also influences matrix-degrading proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of ovarian carcinoma cells with type I collagen, a protein prevalent both in the

  20. Discovery, SAR, and Radiolabeling of Halogenated Benzimidazole Carboxamide Antagonists as Useful Tools for (alpha)4(beta)1 Integrin Expressed on T- and B-cell Lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, R D; Natarajan, A; Lau, E Y; Andrei, M; Solano, D M; Lightstone, F C; DeNardo, S J; Lam, K S; Kurth, M J

    2010-02-08

    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin is an attractive yet poorly understood target for selective diagnosis and treatment of T- and B-cell lymphomas. This report focuses on the rapid microwave preparation of medicinally pertinent benzimidazole heterocycles, structure-activity relationships (SAR) of novel halobenzimidazole carboxamide antagonists 3-6, and preliminary biological evaluation of radioiodinated agents 7, 8, and 18. The I-125 derivative 18 had good tumor uptake (12 {+-} 1% ID/g at 24 h; 4.5 {+-} 1% ID/g at 48 h) and tumor:kidney ratio ({approx}4:1 at 24 h; 2.5:1 at 48 h) in xenograft murine models of B-cell lymphoma. Molecular homology models of {alpha}{sub 4}{beta}{sub 1} integrin have predicted that docked halobenzimidazole carboxamides have the halogen atom in a suitable orientation for halogen-hydrogen bonding. These high affinity ({approx} pM binding) halogenated ligands are attractive tools for medicinal and biological use; the fluoro and iodo derivatives are potential radiodiagnostic ({sup 18}F) or radiotherapeutic ({sup 131}I) agents, whereas the chloro and bromo analogues could provide structural insight into integrin-ligand interactions through photoaffinity cross-linking/mass spectroscopy experiments, as well as co-crystallization X-ray studies.

  1. Induction of cell scattering by expression of beta1 integrins in beta1-deficient epithelial cells requires activation of members of the rho family of GTPases and downregulation of cadherin and catenin function

    DEFF Research Database (Denmark)

    Gimond, C; van Der Flier, A; van Delft, S;

    1999-01-01

    was required for a complete morphological transition towards the spindle-shaped fibroblast-like phenotype. The expression of an interleukin-2 receptor (IL2R)-beta1A chimera and its incorporation into focal adhesions also induced the disruption of cadherin-based adhesions and the reorganization of ECM......Adhesion receptors, which connect cells to each other and to the surrounding extracellular matrix (ECM), play a crucial role in the control of tissue structure and of morphogenesis. In this work, we have studied how intercellular adhesion molecules and beta1 integrins influence each other using two......-catenin protein levels accompanied by their redistribution from the cytoskeleton-associated fraction to the detergent-soluble fraction. Regulation of alpha-catenin protein levels by beta1 integrins is likely to play a role in the morphological transition, since overexpression of alpha-catenin in GE11 cells before...

  2. Irradiation and various cytotoxic drugs enhance tyrosine phosphorylation and {beta}{sub 1}-integrin clustering in human A549 lung cancer cells in a substratum-dependent manner in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Cordes, N.; Beinke, C.; Beuningen, D. van [Inst. of Radiobiology, German Armed Forces, Munich (Germany); Plasswilm, L. [Dept. of Radiation Oncology, Univ. Hospital Basel (Swaziland)

    2004-03-01

    Background and purpose: interactions of cells with a substratum, especially extracellular matrix proteins, initiate clustering of integrin receptors in the cell membrane. This process represents the initial step for the activation of signaling pathways regulating survival, proliferation, differentiation, adhesion, and migration, and could, furthermore, be important for cellular resistance-mediating mechanisms against radiation or cytotoxic drugs. The lack of data elucidating the impact of irradiation or cytotoxic drugs on this important phenomenon led to this study on human A549 lung cancer cells in vitro. Material and methods: the human lung carcinoma cell line A549 grown on polystyrene or fibronectin (FN) was irradiated with 0-8 Gy or treated with cisplatin (0.1-50 {mu}M), paclitaxel (0.1-50 nM), or mitomycin (0.1-50 {mu}M). Colony formation assays, immunofluorescence staining in combination with activation of integrin clustering using anti-{beta}{sub 1}-integrin antibodies (K20), and Western blotting for tyrosine phosphorylation under treatment of cells with the IC{sub 50} for irradiation (2 Gy; IC{sub 50} = 2.2 Gy), cisplatin (2 {mu}M), paclitaxel (5 nM), or mitomycin (7 {mu}M) were performed. Results: attachment of cells to FN resulted in a significantly reduced radio- and chemosensitivity compared to polystyrene. The clustering of {beta}{sub 1}-integrins examined by immunofluorescence staining was only stimulated by irradiation, cisplatin, paclitaxel, or mitomycin in case of cell attachment to FN. By contrast, tyrosine phosphorylation, as one of the major events following {beta}{sub 1}-integrin clustering, showed a 3.7-fold, FN-related enhancement, and treatment of cells with the IC{sub 50} of radiation, cisplatin, paclitaxel, or mitomycin showed a substratum-dependent induction. Conclusion: for the first time, a strong influence of irradiation and a variety of cytotoxic drugs on the clustering of {beta}{sub 1}-integrins could be shown. This event is a

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

  4. Simultaneous changes in the function and expression of beta 1 integrins during the growth arrest of poorly differentiated colorectal cells (LISP-1

    Directory of Open Access Journals (Sweden)

    R.A. Roela

    2003-08-01

    Full Text Available Cells usually lose adhesion and increase proliferation and migration during malignant transformation. Here, we studied how proliferation can affect the other two characteristics, which ultimately lead to invasion and metastasis. We determined the expression of ß1 integrins, as well as adhesion and migration towards laminin-1, fibronectin, collagens type I and type IV presented by LISP-1 colorectal cancer cells exposed to 2.5% dimethyl sulfoxide (DMSO, an agent capable of decreasing proliferation in this poorly differentiated colorectal cell line. Untreated cells (control, as shown by flow cytometry and monoclonal antibodies, expressed alpha2 (63.8 ± 11.3% positive cells, alpha3 (93.3 ± 7.0%, alpha5 (50.4 ± 12.0% and alpha6 (34.1 ± 4.9% integrins but not alpha1, alpha4, alphav or ß4. Cells adhered well to laminin-1 (73.4 ± 6.0% and fibronectin (40.0 ± 2.0% substrates but very little to collagens. By using blocking monoclonal antibodies, we showed that alpha2, alpha3 and alpha6 mediated laminin-1 adhesion, but neither alpha3 nor alpha5 contributed to fibronectin adherence. DMSO arrested cells at G0/G1 (control: 55.0 ± 2.4% vs DMSO: 70.7 ± 2.5% while simultaneously reducing alpha5 (24.2 ± 19% and alpha6 (14.3 ± 10.8% expression as well as c-myc mRNA (7-fold, the latter shown by Northern blotting. Although the adhesion rate did not change after exposure to DMSO, alpha3 and alpha5 played a major role in laminin-1 and fibronectin adhesion, respectively. Migration towards laminin-1, which was clearly increased upon exposure to DMSO (control: 6 ± 2 cells vs DMSO: 64 ± 6 cells, was blocked by an antibody against alpha6. We conclude that the effects of DMSO on LISP-1 proliferation were accompanied by concurrent changes in the expression and function of integrins, consequently modulating adhesion/migration, and revealing a complex interplay between function/expression and the proliferative state of cells.

  5. Complementary roles of glycoprotein VI and alpha2beta1 integrin in collagen-induced thrombus formation in flowing whole blood ex vivo

    DEFF Research Database (Denmark)

    Kuijpers, Marijke J E; Schulte, Valerie; Bergmeier, Wolfgang; Lindhout, Theo; Brakebusch, Cord; Offermanns, Stefan; Fässler, Reinhard; Heemskerk, Johan W M; Nieswandt, Bernhard

    2003-01-01

    function in ex vivo thrombus formation during perfusion of whole blood over collagen. With mice deficient in GPVI or blocking antibodies, we found that GPVI was indispensable for collagen-dependent Ca2+ mobilization, exposure of PS, and aggregation of platelets. Deficiency of integrin beta1 reduces the......Platelets interact vigorously with subendothelial collagens that are exposed by injury or pathological damage of a vessel wall. The collagen-bound platelets trap other platelets to form aggregates, and they expose phosphatidylserine (PS) required for coagulation. Both processes are implicated in...... the formation of vaso-occlusive thrombi. We previously demonstrated that the immunoglobulin receptor glycoprotein VI (GPVI), but not integrin alpha2beta1, is essential in priming platelet-collagen interaction and subsequent aggregation. Here, we report that these receptors have yet a complementary...

  6. Venom gland EST analysis of the saw-scaled viper, Echis ocellatus, reveals novel alpha9beta1 integrin-binding motifs in venom metalloproteinases and a new group of putative toxins, renin-like aspartic proteases.

    Science.gov (United States)

    Wagstaff, Simon C; Harrison, Robert A

    2006-08-01

    Echis ocellatus is the most medically important snake in West Africa. However, the composition of its venom and the differential contribution of these venom components to the severe haemorrhagic and coagulopathic pathology of envenoming are poorly understood. To address this situation we assembled a toxin transcriptome based upon 1000 expressed sequence tags (EST) from a cDNA library constructed from pooled venom glands of 10 individual E. ocellatus. We used a variety of bioinformatic tools to construct a fully annotated venom-toxin transcriptome that was interrogated with a combination of BLAST annotation, gene ontology cataloguing and disintegrin-motif searching. The results of these analyses revealed an unusually abundant and diverse expression of snake venom metalloproteinases (SVMP) and a broad toxin-expression profile including several distinct isoforms of bradykinin-potentiating peptides, phospholipase A(2), C-type lectins, serine proteinases and l-amino oxidases. Most significantly, we identified for the first time a conserved alpha(9)beta(1) integrin-binding motif in several SVMPs, and a new group of putative venom toxins, renin-like aspartic proteases. PMID:16713134

  7. β1 Integrins Mediate Mechanosensitive Signaling Pathways in Osteocytes

    OpenAIRE

    Litzenberger, Julie B.; Tummala, Padmaja; Kim, Jae-Beom; Jacobs, Christopher R.

    2010-01-01

    Integrins are cell-substrate adhesion proteins that initiate intracellular signaling and may serve as mechanosensors in bone. MLO-Y4 cells were stably transfected with a dominant negative form of the β1 integrin subunit (β1DN) containing the transmembrane domain and cytoplasmic tail of β1 integrin. Cells expressing β1DN had reduced vinculin localization to focal contacts but no change in intracellular actin organization. When exposed to oscillatory fluid flow, β1DN cells exhibited a significa...

  8. β1 Integrin Is Essential for Teratoma Growth and Angiogenesis

    OpenAIRE

    Bloch, Wilhelm; Forsberg, Erik; Lentini, Sylvia; Brakebusch, Cord; Martin, Karl; Krell, Hans W.; Weidle, Ulrich H.; Addicks, Klaus; Fässler, Reinhard

    1997-01-01

    Teratomas are benign tumors that form after ectopic injection of embryonic stem (ES) cells into mice and contain derivatives of all primitive germ layers. To study the role of β1 integrin during teratoma formation, we compared teratomas induced by normal and β1-null ES cells. Injection of normal ES cells gave rise to large teratomas. In contrast, β1-null ES cells either did not grow or formed small teratomas with an average weight of

  9. The involvement of Gab1 and PI 3-kinase in β1 integrin signaling in keratinocytes

    International Nuclear Information System (INIS)

    The control of the stem cell compartment in epidermis is closely linked to the regulation of keratinocyte proliferation and differentiation. β1 integrins are expressed 2-fold higher by stem cells than transit-amplifying cells. Signaling from these β1 integrins is critical for the regulation of the epidermal stem cell compartment. To clarify the functional relevance of this differential expression of β1 integrins, we established HaCaT cells with high β1integrin expression by repeated flow cytometric sorting of this population from the parental cell line. In these obtained cells expressing β1 integrins by 5-fold, MAPK activation was markedly increased. Regarding the upstream of MAPK, Gab1 phosphorylation was also higher with high β1 integrin expression, while Shc phosphorylation was not altered. In addition, enhanced phosphatidylinositol 3-kinase activation was also observed. These observations suggest that Gab1 and phosphatidylinositol 3-kinase play pivotal roles in the β1 integrin-mediated regulation of the epidermal stem cell compartment

  10. β1 integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli

    OpenAIRE

    Li, Na; Zhang, Yu; Naylor, Matthew J.; Schatzmann, Franziska; Maurer, Francisca; Wintermantel, Tim; Schuetz, Gunther; Mueller, Ulrich; Streuli, Charles H; Hynes, Nancy E.

    2005-01-01

    Integrin–extracellular matrix interactions play important roles in the coordinated integration of external and internal cues that are essential for proper development. To study the role of β1 integrin in the mammary gland, Itgβ1flox/flox mice were crossed with WAPiCre transgenic mice, which led to specific ablation of β1 integrin in luminal alveolar epithelial cells. In the β1 integrin mutant mammary gland, individual alveoli were disorganized resulting from alterations in cell–basement membr...

  11. Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen

    Directory of Open Access Journals (Sweden)

    Lisa A. Staudinger

    2013-09-01

    Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR, to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling.

  12. Revertant mosaicism in skin: natural gene therapy

    OpenAIRE

    Joey E Lai-Cheong; McGrath, John A; Uitto, Jouni

    2010-01-01

    Revertant mosaicism is a naturally occurring phenomenon involving spontaneous correction of a pathogenic mutation in a somatic cell. Recent studies suggest that it is not a rare event and that it could be clinically relevant to phenotypic expression and patient treatment. Indeed, revertant cell therapy represents a potential “natural gene therapy” because in vivo reversion obviates the need for further genetic correction. Revertant mosaicism has been observed in several inherited conditions, ...

  13. Modulation of radiation-induced oral mucositis (mouse) by selective inhibition of β1 integrin

    International Nuclear Information System (INIS)

    Introduction: Oral mucositis is a severe side effect of radio(chemo)therapy for head and neck tumors, for which β1 integrins have been proposed as potential therapeutic targets. The present study was initiated to determine the effect of selective inhibition of β1 integrin on the oral epithelial radiation response. Materials and methods: Daily fractionated irradiation was given with 5 × 3 Gy/week over 1 or 2 weeks with/without the β1 integrin-inhibiting monoclonal antibody AIIB2 or an IgG control. Each protocol was terminated by graded test doses to generate full dose–effect curves for mucosal ulceration. The same technique was used for single dose irradiation. Results: Combined single dose irradiation plus AIIB2 resulted in a significant decrease of the ED50 compared to irradiation alone or control IgG. No effect of AIIB2 was found with fractionated irradiation over 1 week. With 2 weeks of fractionation, AIIB2 induced a significant increase in the ED50 for the terminating test irradiation when administered in week 2. The time course of the response was largely unaffected by β1 integrin inhibition. Conclusions: A reduction of mucosal reactions by β1 integrin inhibition later in a course of fractionation was observed, i.e. when epithelial repopulation processes were active. Further mechanistic studies are required.

  14. IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

    Directory of Open Access Journals (Sweden)

    Aejaz Sayeed

    Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

  15. Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates myogenesis and β1 integrin expression in vitro

    International Nuclear Information System (INIS)

    Myogenesis in vitro involves myoblast cell cycle arrest, migration, and fusion to form multinucleated myotubes. Extracellular matrix (ECM) integrity during these processes is maintained by the opposing actions of matrix metalloproteinase (MMP) proteases and their inhibitors, the tissue inhibitor of metalloproteinases (TIMPs). Here, we report that TIMP-2, MMP-2, and MT1-MMP are differentially expressed during mouse myoblast differentiation in vitro. A specific role for TIMP-2 in myogenesis is demonstrated by altered TIMP-2-/- myotube formation. When differentiated in horse serum-containing medium, TIMP-2-/- myotubes are larger than wild-type myotubes. In contrast, when serum-free medium is used, TIMP-2-/- myotubes are smaller than wild-type myotubes. Regardless of culture condition, myotube size is directly correlated with MMP activity and inversely correlated with β1 integrin expression. Treatment with recombinant TIMP-2 rescues reduced TIMP-2-/- myotube size and induces increased MMP-9 activation and decreased β1 integrin expression. Treatment with either MMP-2 or MMP-9 similarly rescues reduced myotube size, but has no effect on β1 integrin expression. These data suggest a specific regulatory relationship between TIMP-2 and β1 integrin during myogenesis. Elucidating the role of TIMP-2 in myogenesis in vitro may lead to new therapeutic options for the use of TIMP-2 in myopathies and muscular dystrophies in vivo

  16. Interaction between fibronectin and β1 integrin is essential for tooth development.

    Directory of Open Access Journals (Sweden)

    Kan Saito

    Full Text Available The dental epithelium and extracellular matrix interact to ensure that cell growth and differentiation lead to the formation of teeth of appropriate size and quality. To determine the role of fibronectin in differentiation of the dental epithelium and tooth formation, we analyzed its expression in developing incisors. Fibronectin mRNA was expressed during the presecretory stage in developing dental epithelium, decreased in the secretory and early maturation stages, and then reappeared during the late maturation stage. The binding of dental epithelial cells derived from postnatal day-1 molars to a fibronectin-coated dish was inhibited by the RGD but not RAD peptide, and by a β1 integrin-neutralizing antibody, suggesting that fibronectin-β1 integrin interactions contribute to dental epithelial-cell binding. Because fibronectin and β1 integrin are highly expressed in the dental mesenchyme, it is difficult to determine precisely how their interactions influence dental epithelial differentiation in vivo. Therefore, we analyzed β1 integrin conditional knockout mice (Intβ1lox-/lox-/K14-Cre and found that they exhibited partial enamel hypoplasia, and delayed eruption of molars and differentiation of ameloblasts, but not of odontoblasts. Furthermore, a cyst-like structure was observed during late ameloblast maturation. Dental epithelial cells from knockout mice did not bind to fibronectin, and induction of ameloblastin expression in these cells by neurotrophic factor-4 was inhibited by treatment with RGD peptide or a fibronectin siRNA, suggesting that the epithelial interaction between fibronectin and β1 integrin is important for ameloblast differentiation and enamel formation.

  17. Essential function for PDLIM2 in cell polarization in three-dimensional cultures by feedback regulation of the β1-integrin-RhoA signaling axis.

    Science.gov (United States)

    Deevi, Ravi Kiran; Cox, Orla T; O'Connor, Rosemary

    2014-05-01

    PDLIM2 is a cytoskeletal and nuclear PDZ-LIM domain protein that regulates the stability of Nuclear Factor kappa-B (NFκB) and other transcription factors, and is required for polarized cell migration. PDLIM2 expression is suppressed by methylation in different cancers, but is strongly expressed in invasive breast cancer cells that have undergone an Epithelial Mesenchymal Transition (EMT). PDLIM2 is also expressed in non-transformed breast myoepithelial MCF10A cells and here we asked whether it is important for maintaining the polarized, epithelial phenotype of these cells. Suppression of PDLIM2 in MCF10A cells was sufficient to disrupt cell polarization and acini formation with increased proliferation and reduced apoptosis in the luminal space compared to control acini with hollow lumina. Spheroids with suppressed PDLIM2 exhibited increased expression of cell-cell and cell-matrix adhesion proteins including beta 1 (β1) integrin. Interestingly, levels of the Insulin-like growth factor 1 receptor (IGF-1 R) and Receptor of activated protein kinase C 1 (RACK1), which scaffolds IGF-1R to β1 integrin, were also increased, indicating a transformed phenotype. Focal Adhesion Kinase (FAK) and cofilin phosphorylation, and RhoA Guanosine Triphosphatase (GTPase) activity were all enhanced in these spheroids compared to control acini. Importantly, inhibition of either FAK or Rho Kinase (ROCK) was sufficient to rescue the polarity defect. We conclude that PDLIM2 expression is essential for feedback regulation of the β1-integrin-RhoA signalling axis and integration of cellular microenvironment signals with gene expression to control the polarity of breast epithelial acini structures. This is a mechanism by which PDLIM2 could mediate tumour suppression in breast epithelium. PMID:24863845

  18. Bidirectional remodeling of β1-integrin adhesions during chemotropic regulation of nerve growth

    Directory of Open Access Journals (Sweden)

    Carlstrom Lucas P

    2011-11-01

    Full Text Available Abstract Background Chemotropic factors in the extracellular microenvironment guide nerve growth by acting on the growth cone located at the tip of extending axons. Growth cone extension requires the coordination of cytoskeleton-dependent membrane protrusion and dynamic adhesion to the extracellular matrix, yet how chemotropic factors regulate these events remains an outstanding question. We demonstrated previously that the inhibitory factor myelin-associated glycoprotein (MAG triggers endocytic removal of the adhesion receptor β1-integrin from the growth cone surface membrane to negatively remodel substrate adhesions during chemorepulsion. Here, we tested how a neurotrophin might affect integrin adhesions. Results We report that brain-derived neurotropic factor (BDNF positively regulates the formation of substrate adhesions in axonal growth cones during stimulated outgrowth and prevents removal of β1-integrin adhesions by MAG. Treatment of Xenopus spinal neurons with BDNF rapidly triggered β1-integrin clustering and induced the dynamic formation of nascent vinculin-containing adhesion complexes in the growth cone periphery. Both the formation of nascent β1-integrin adhesions and the stimulation of axon extension by BDNF required cytoplasmic calcium ion signaling and integrin activation at the cell surface. Exposure to MAG decreased the number of β1-integrin adhesions in the growth cone during inhibition of axon extension. In contrast, the BDNF-induced adhesions were resistant to negative remodeling by MAG, correlating with the ability of BDNF pretreatment to counteract MAG-inhibition of axon extension. Pre-exposure to MAG prevented the BDNF-induced formation of β1-integrin adhesions and blocked the stimulation of axon extension by BDNF. Conclusions Altogether, these findings demonstrate the neurotrophin-dependent formation of integrin-based adhesions in the growth cone and reveal how a positive regulator of substrate adhesions can block

  19. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype

    OpenAIRE

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D.; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G.

    2013-01-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited dow...

  20. PRG-1 Regulates Synaptic Plasticity via Intracellular PP2A/β1-Integrin Signaling.

    Science.gov (United States)

    Liu, Xingfeng; Huai, Jisen; Endle, Heiko; Schlüter, Leslie; Fan, Wei; Li, Yunbo; Richers, Sebastian; Yurugi, Hajime; Rajalingam, Krishnaraj; Ji, Haichao; Cheng, Hong; Rister, Benjamin; Horta, Guilherme; Baumgart, Jan; Berger, Hendrik; Laube, Gregor; Schmitt, Ulrich; Schmeisser, Michael J; Boeckers, Tobias M; Tenzer, Stefan; Vlachos, Andreas; Deller, Thomas; Nitsch, Robert; Vogt, Johannes

    2016-08-01

    Alterations in dendritic spine numbers are linked to deficits in learning and memory. While we previously revealed that postsynaptic plasticity-related gene 1 (PRG-1) controls lysophosphatidic acid (LPA) signaling at glutamatergic synapses via presynaptic LPA receptors, we now show that PRG-1 also affects spine density and synaptic plasticity in a cell-autonomous fashion via protein phosphatase 2A (PP2A)/β1-integrin activation. PRG-1 deficiency reduces spine numbers and β1-integrin activation, alters long-term potentiation (LTP), and impairs spatial memory. The intracellular PRG-1 C terminus interacts in an LPA-dependent fashion with PP2A, thus modulating its phosphatase activity at the postsynaptic density. This results in recruitment of adhesome components src, paxillin, and talin to lipid rafts and ultimately in activation of β1-integrins. Consistent with these findings, activation of PP2A with FTY720 rescues defects in spine density and LTP of PRG-1-deficient animals. These results disclose a mechanism by which bioactive lipid signaling via PRG-1 could affect synaptic plasticity and memory formation. PMID:27453502

  1. Evaluation of β1-integrin expression on chondrogenically differentiating human adipose-derived stem cells using atomic force microscopy.

    Science.gov (United States)

    Quisenberry, Chrystal R; Nazempour, Arshan; Van Wie, Bernard J; Abu-Lail, Nehal I

    2016-06-01

    The expression of β1-integrin on human adipose-derived stem cells, differentiating toward a chondrogenic lineage, is hypothesized to decrease when cells are grown under in vivo-like environments due to sufficient extracellular matrix (ECM) buildup in the engineered tissues. The opposite is true when cells are grown in static cultures such as in pellet or micromass. To probe β1-integrin distribution on cellular surfaces, atomic force microscopy cantilevers modified with anti-β1-integrin antibodies were used. Specific antibody-antigen adhesion forces were identified and indicated the locations of β1-integrins on cells. ECM properties were assessed by estimating the Young's modulus of the matrix. Specific single antibody-antigen interactions averaged 78 ± 10 pN with multiple bindings occurring at approximate multiples of 78 pN. The author's results show that upregulated β1-integrin expression coincided with a less robust ECM as assessed by mechanical properties of tissues. In micromass and pellet cultures, transforming growth factor β3(TGF-β3) elicited a decrease in Young's modulus by 3.7- and 4.4-fold while eliciting an increase in β1-integrin count by 1.1- and 1.3-fold, respectively. β1-integrin counts on cells grown in the presence of TGF-β3 with oscillating hydrostatic pressure decreased by a 1.1-fold while the Young's modulus increased by a 1.9-fold. Collectively, our results suggest that cells in insufficiently robust ECM express more integrin perhaps to facilitate cell-ECM adhesion and compensate for a looser less robust ECM. PMID:27106564

  2. LFA-1 and Mac-1 integrins bind to the serine/threonine-rich domain of thrombomodulin.

    Science.gov (United States)

    Kawamoto, Eiji; Okamoto, Takayuki; Takagi, Yoshimi; Honda, Goichi; Suzuki, Koji; Imai, Hiroshi; Shimaoka, Motomu

    2016-05-13

    LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins regulate leukocyte trafficking in health and disease by binding primarily to IgSF ligand ICAM-1 and ICAM-2 on endothelial cells. Here we have shown that the anti-coagulant molecule thrombomodulin (TM), found on the surface of endothelial cells, functions as a potentially new ligand for leukocyte integrins. We generated a recombinant extracellular domain of human TM and Fc fusion protein (TM-domains 123-Fc), and showed that pheripheral blood mononuclear cells (PBMCs) bind to TM-domains 123-Fc dependent upon integrin activation. We then demonstrated that αL integrin-blocking mAb, αM integrin-blocking mAb, and β2 integrin-blocking mAb inhibited the binding of PBMCs to TM-domains 123-Fc. Furthermore, we show that the serine/threonine-rich domain (domain 3) of TM is required for the interaction with the LFA-1 (αLβ2) and Mac-1 (αMβ2) integrins to occur on PBMCs. These results demonstrate that the LFA-1 and Mac-1 integrins on leukocytes bind to TM, thereby establishing the molecular and structural basis underlying LFA-1 and Mac-1 integrin interaction with TM on endothelial cells. In fact, integrin-TM interactions might be involved in the dynamic regulation of leukocyte adhesion with endothelial cells. PMID:27055590

  3. Vesicle-associated membrane protein 2 mediates trafficking of α5β1 integrin to the plasma membrane

    International Nuclear Information System (INIS)

    Integrins are major receptors for cell adhesion to the extracellular matrix (ECM). As transmembrane proteins, the levels of integrins at the plasma membrane or the cell surface are ultimately determined by the balance between two vesicle trafficking events: endocytosis of integrins at the plasma membrane and exocytosis of the vesicles that transport integrins. Here, we report that vesicle-associated membrane protein 2 (VAMP2), a SNARE protein that mediates vesicle fusion with the plasma membrane, is involved in the trafficking of α5β1 integrin. VAMP2 was present on vesicles containing endocytosed β1 integrin. Small interfering RNA (siRNA) silencing of VAMP2 markedly reduced cell surface α5β1 and inhibited cell adhesion and chemotactic migration to fibronectin, the ECM ligand of α5β1, without altering cell surface expression of α2β1 integrin or α3β1 integrin. By contrast, silencing of VAMP8, another SNARE protein, had no effect on cell surface expression of the integrins or cell adhesion to fibronectin. In addition, VAMP2-mediated trafficking is involved in cell adhesion to collagen but not to laminin. Consistent with disruption of integrin functions in cell proliferation and survival, VAMP2 silencing diminished proliferation and triggered apoptosis. Collectively, these data indicate that VAMP2 mediates the trafficking of α5β1 integrin to the plasma membrane and VAMP2-dependent integrin trafficking is critical in cell adhesion, migration and survival.

  4. Interferon-induced revertants of ras-transformed cells: resistance to transformation by specific oncogenes and retransformation by 5-azacytidine.

    Science.gov (United States)

    Samid, D; Flessate, D M; Friedman, R M

    1987-01-01

    Prolonged alpha/beta interferon (IFN-alpha/beta) treatment of NIH 3T3 cells transformed by a long terminal repeat-activated Ha-ras proto-oncogene resulted in revertants that maintained a nontransformed phenotype long after IFN treatment had been discontinued. Cloned persistent revertants (PRs) produced large amounts of the ras-encoded p21 and were refractile to transformation by EJras DNA and by transforming retroviruses which carried the v-Ha-ras, v-Ki-ras, v-abl, or v-fes oncogene. Transient treatment either in vitro or in vivo with cytidine analogs that alter gene expression by inhibiting DNA methylation resulted in transformation of PR, but not of NIH 3T3, cells. The PR retransformants reverted again with IFN, suggesting that DNA methylation is involved in IFN-induced persistent reversion. Images PMID:2439904

  5. HGF Accelerates Wound Healing by Promoting the Dedifferentiation of Epidermal Cells through β1-Integrin/ILK Pathway

    Directory of Open Access Journals (Sweden)

    Jin-Feng Li

    2013-01-01

    Full Text Available Skin wound healing is a critical and complex biological process after trauma. This process is activated by signaling pathways of both epithelial and nonepithelial cells, which release a myriad of different cytokines and growth factors. Hepatocyte growth factor (HGF is a cytokine known to play multiple roles during the various stages of wound healing. This study evaluated the benefits of HGF on reepithelialization during wound healing and investigated its mechanisms of action. Gross and histological results showed that HGF significantly accelerated reepithelialization in diabetic (DB rats. HGF increased the expressions of the cell adhesion molecules β1-integrin and the cytoskeleton remodeling protein integrin-linked kinase (ILK in epidermal cells in vivo and in vitro. Silencing of ILK gene expression by RNA interference reduced expression of β1-integrin, ILK, and c-met in epidermal cells, concomitantly decreasing the proliferation and migration ability of epidermal cells. β1-Integrin can be an important maker of poorly differentiated epidermal cells. Therefore, these data demonstrate that epidermal cells become poorly differentiated state and regained some characteristics of epidermal stem cells under the role of HGF after wound. Taken together, the results provide evidence that HGF can accelerate reepithelialization in skin wound healing by dedifferentiation of epidermal cells in a manner related to the β1-integrin/ILK pathway.

  6. α-Hemolysin enhances Staphylococcus aureus internalization and survival within mast cells by modulating the expression of β1 integrin.

    Science.gov (United States)

    Goldmann, Oliver; Tuchscherr, Lorena; Rohde, Manfred; Medina, Eva

    2016-06-01

    Mast cells (MCs) are important sentinels of the host defence against invading pathogens. We previously reported that Staphylococcus aureus evaded the extracellular antimicrobial activities of MCs by promoting its internalization within these cells via β1 integrins. Here, we investigated the molecular mechanisms governing this process. We found that S. aureus responded to the antimicrobial mediators released by MCs by up-regulating the expression of α-hemolysin (Hla), fibronectin-binding protein A and several regulatory systems. We also found that S. aureus induced the up-regulation of β1 integrin expression on MCs and that this effect was mediated by Hla-ADAM10 (a disintegrin and metalloproteinase 10) interaction. Thus, deletion of Hla or inhibition of Hla-ADAM10 interaction significantly impaired S. aureus internalization within MCs. Furthermore, purified Hla but not the inactive HlaH35L induced up-regulation of β1 integrin expression in MCs in a dose-dependent manner. Our data support a model in which S. aureus counter-reacts the extracellular microbicidal mechanisms of MCs by increasing expression of fibronectin-binding proteins and by inducing Hla-ADAM10-mediated up-regulation of β1 integrin in MCs. The up-regulation of bacterial fibronectin-binding proteins, concomitantly with the increased expression of its receptor β1 integrin on the MCs, resulted in enhanced S. aureus internalization through the binding of fibronectin-binding proteins to integrin β1 via fibronectin. PMID:26595647

  7. Vipegitide: a folded peptidomimetic partial antagonist of α2β1 integrin with antiplatelet aggregation activity

    Directory of Open Access Journals (Sweden)

    Momic T

    2015-01-01

    Full Text Available Tatjana Momic,1 Jehoshua Katzhendler,1 Ela Shai,2 Efrat Noy,3 Hanoch Senderowitz,3 Johannes A Eble,4 Cezary Marcinkiewicz,5 David Varon,2 Philip Lazarovici11School of Pharmacy Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, 2Department of Hematology, Coagulation Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; 3Department of Chemistry, Bar-Ilan University, Ramat-Gan, Israel; 4Institute for Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; 5Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA, USAAbstract: Linear peptides containing the sequence WKTSRTSHY were used as lead compounds to synthesize a novel peptidomimetic antagonist of α2β1 integrin, with platelet aggregation-inhibiting activity, named Vipegitide. Vipegitide is a 13-amino acid, folded peptidomimetic molecule, containing two α-aminoisobutyric acid residues at positions 6 and 8 and not stable in human serum. Substitution of glycine and tryptophan residues at positions 1 and 2, respectively, with a unit of two polyethylene glycol (PEG molecules yielded peptidomimetic Vipegitide-PEG2, stable in human serum for over 3 hours. Vipegitide and Vipegitide-PEG2 showed high potency (7×10-10 M and 1.5×10-10 M, respectively and intermediate efficacy (40% and 35%, respectively as well as selectivity toward α2 integrin in inhibition of adhesion of α1/α2 integrin overexpressing cells toward respective collagens. Interaction of both peptidomimetics with extracellular active domain of α2 integrin was confirmed in cell-free binding assay with recombinant α2 A-domain. Integrin α2β1 receptor is found on the platelet membrane and triggers collagen-induced platelet aggregation. Vipegitide and Vipegitide-PEG2 inhibited α2β1 integrin-mediated adhesion of human and murine platelets under the flow condition, by 50%. They efficiently blocked adenosine diphosphate

  8. ADAM12-mediated focal adhesion formation is differently regulated by beta1 and beta3 integrins

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Frohlich, Camilla; Nielsen, Christian Kamp;

    2005-01-01

    ADAM12, adisintegrin and metalloprotease, has been demonstrated to be upregulated in human malignant tumors and to accelerate the malignant phenotype in a mouse model for breast cancer. ADAM12 is a substrate for beta1 integrins and may affect tumor and stromal cell behavior through its binding to...

  9. Cellular microenvironment controls the nuclear architecture of breast epithelia through β1-integrin.

    Science.gov (United States)

    Maya-Mendoza, Apolinar; Bartek, Jiri; Jackson, Dean A; Streuli, Charles H

    2016-02-01

    Defects in nuclear architecture occur in a variety of diseases, however the fundamental mechanisms that control the internal structure of nuclei are poorly defined. Here we reveal that the cellular microenvironment has a profound influence on the global internal organization of nuclei in breast epithelia. A 3D microenvironment induces a prolonged but reversible form of cell cycle arrest that features many of the classical markers of cell senescence. This unique form of arrest is dependent on signaling from the external microenvironment through β1-integrins. It is concomitant with alterations in nuclear architecture that characterize the withdrawal from cell proliferation. Unexpectedly, following prolonged cell cycle arrest in 3D, the senescence-like state and associated reprogramming of nuclear architecture are freely reversible on altering the dimensionality of the cellular microenvironment. Breast epithelia can therefore maintain a proliferative plasticity that correlates with nuclear remodelling. However, the changes in nuclear architecture are cell lineage-specific and do not occur in fibroblasts, and moreover they are overcome in breast cancer cells. PMID:26818565

  10. Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization

    Institute of Scientific and Technical Information of China (English)

    Wen-Liang Lei; Shi-Ge Xing; Cai-Yun Deng; Xiang-Chun Ju; Xing-Yu Jiang; Zhen-Ge Luo

    2012-01-01

    Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron,but how this increased microtubule stability is achieved is unclear.Here,we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1).Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices.Active Itgb1 was found to be concentrated in laminin-contacting neurites.Axon formation was promoted and abolished by enhancing and attenuating Itgbl signaling,respectively.Interestingly,laminin contact promoted plus-end microtubule assembly in a manner that required Itgbl.Moreover,stabilizing microtubules partially prevented polarization defects caused by ltgbl downregulation.Finally,genetic ablation of ltgbl in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons.Thus,laminin/Itgb1 signaling plays an instructive role in axon initiation and growth,both in vitro and in vivo,through the regulation of microtubule assembly.This study has established a linkage between an extrinsic factor and intrinsic cytoskeletai dynamics during neuronal polarization.

  11. Increasing α7β1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression

    OpenAIRE

    LIU, Jianming; Burkin, Dean J.; Kaufman, Stephen J.

    2007-01-01

    The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The α7β1-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of α7-integrin levels alleviates pathology in mdx/utrn−/− mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally...

  12. RECK-Mediated β1-Integrin Regulation by TGF-β1 Is Critical for Wound Contraction in Mice

    Science.gov (United States)

    Gutiérrez, Jaime; Droppelmann, Cristian A.; Contreras, Osvaldo; Takahashi, Chiaki; Brandan, Enrique

    2015-01-01

    Fibroblasts are critical for wound contraction; a pivotal step in wound healing. They produce and modify the extracellular matrix (ECM) required for the proper tissue remodeling. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) is a key regulator of ECM homeostasis and turnover. However, its role in wound contraction is presently unknown. Here we describe that Transforming growth factor type β1 (TGF-β1), one of the main pro-fibrotic wound-healing promoting factors, decreases RECK expression in fibroblasts through the Smad and JNK dependent pathways. This TGF-β1 dependent downregulation of RECK occurs with the concomitant increase of β1-integrin, which is required for fibroblasts adhesion and wound contraction through the activation of focal adhesion kinase (FAK). Loss and gain RECK expression experiments performed in different types of fibroblasts indicate that RECK downregulation mediates TGF-β1 dependent β1-integrin expression. Also, reduced levels of RECK potentiate TGF-β1 effects over fibroblasts FAK-dependent contraction, without affecting its cognate signaling. The above results were confirmed on fibroblasts derived from the Reck+/- mice compared to wild type-derived fibroblasts. We observed that Reck+/- mice heal dermal wounds more efficiently than wild type mice. Our results reveal a critical role for RECK in skin wound contraction as a key mediator in the axis: TGF-β1—RECK- β1-integrin. PMID:26247610

  13. Loss of β1-integrin from urothelium results in overactive bladder and incontinence in mice: a mechanosensory rather than structural phenotype.

    Science.gov (United States)

    Kanasaki, Keizo; Yu, Weiqun; von Bodungen, Maximilian; Larigakis, John D; Kanasaki, Megumi; Ayala de la Pena, Francisco; Kalluri, Raghu; Hill, Warren G

    2013-05-01

    Bladder urothelium senses and communicates information about bladder fullness. However, the mechanoreceptors that respond to tissue stretch are poorly defined. Integrins are mechanotransducers in other tissues. Therefore, we eliminated β1-integrin selectively in urothelium of mice using Cre-LoxP targeted gene deletion. β1-Integrin localized to basal/intermediate urothelial cells by confocal microscopy. β1-Integrin conditional-knockout (β1-cKO) mice lacking urothelial β1-integrin exhibited down-regulation and mislocalization of α3- and α5-integrins by immunohistochemistry but, surprisingly, had normal morphology, permeability, and transepithelial resistance when compared with Cre-negative littermate controls. β1-cKO mice were incontinent, as judged by random urine leakage on filter paper (4-fold higher spotting, Pbladder overfilling with 80% longer intercontractile intervals (Phyperactivity (3-fold more prevoid contractions, Pbladder due to abnormal mechanotransduction; more broadly, our findings indicate that urothelium itself directly modulates voiding. PMID:23395910

  14. ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function

    DEFF Research Database (Denmark)

    Kawaguchi, Nobuko; Sundberg, Christina; Kveiborg, Marie;

    2003-01-01

    Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We...... early adipocyte differentiation....

  15. Interactions of the integrin subunit beta1A with protein kinase B/Akt, p130Cas and paxillin contribute to regulation of radiation survival

    DEFF Research Database (Denmark)

    Seidler, Julia; Durzok, Rita; Brakebusch, Cord; Cordes, Nils

    2005-01-01

    BACKGROUND AND PURPOSE: Cell adhesion-mediated radioresistance is a common phenomenon particularly relevant in tumor cells, which might hamper anticancer therapies. To analyze the role of adhesion-mediating beta1-integrins, stably transfected functional beta1A-integrin-expressing GD25beta1A and G...

  16. Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom

    Energy Technology Data Exchange (ETDEWEB)

    Jakubowski, Piotr [Temple University, Department of Biology, Philadelphia, PA 19122 (United States); Calvete, Juan J. [Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Cientificas, 46010 Valencia (Spain); Eble, Johannes A. [Excellence Cluster Cardio-Pulmonary System, Center for Molecular Medicine, Vascular Matrix Biology, Frankfurt University Hospital, Frankfurt am Main 60590 (Germany); Lazarovici, Philip [The Hebrew University of Jerusalem, School of Pharmacy, Institute for Drug Research, Jerusalem 91120 (Israel); Marcinkiewicz, Cezary, E-mail: cmarcink@temple.edu [Temple University, Department of Biology, Philadelphia, PA 19122 (United States)

    2013-05-15

    Snake venom antagonists of α2β1 integrin have been identified as members of a C-lectin type family of proteins (CLP). In the present study, we characterized three new CLPs isolated from Echis sochureki venom, which interact with this integrin. These proteins were purified using a combination of gel filtration, ion exchange chromatography and reverse phase HPLC. Sochicetin-A and sochicetin-B potently inhibited adhesion of cells expressing α2β1 integrin and binding of isolated α2β1 ectodomain to collagen I, as well as bound to recombinant GST-α2A domain in ELISA, whereas activity of sochicetin-C in these assays was approximately two orders of magnitude lower. Structurally, sochicetin-B and sochicetin-C are typical heterodimeric αβ CLPs, whereas sochicetin-A exhibits a trimer of its subunits (αβ){sub 3} in the quaternary structure. Immobilized sochicetins supported adhesion of glioma cell lines, LN18 and LBC3, whereas in a soluble form they partially inhibited adhesion of these cells to collagen I. Glioma cells spread very poorly on sochicetin-A, showing no cytoskeleton rearrangement typical for adhesion to collagen I or fibronectin. Adhesion on CLP does not involve focal adhesion elements, such as vinculin. Sochicetin-A also inhibited collagen-induced platelet aggregation, similar to other CLPs' action on the blood coagulation system. - Highlights: • Isolation of three novel snake venom CLPs inhibiting α2β1 integrin • Reporting hexameric CLP, sochicetin-A with anti-collagen receptor activity • CLPs antagonize the interaction of glioma cells with collagen matrix. • Sochicetin-A does not support glioma cell spreading.

  17. The dermatan sulfate proteoglycan decorin modulates α2β1 integrin and the vimentin intermediate filament system during collagen synthesis.

    Directory of Open Access Journals (Sweden)

    Oliver Jungmann

    Full Text Available Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/- mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/- mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/- fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, we identified vimentin as one of the proteins that was differentially upregulated by the presence of decorin. We discovered that a decorin-deficient matrix leads to abnormal nuclear morphology in the Dcn(-/- fibroblasts. This phenotype could be rescued by the decorin proteoglycan but less efficiently by the decorin protein core. Decorin treatment led to a significant reduction of the α2β1 integrin at day 6 in Dcn(-/- fibroblasts, whereas the protein core had no effect on β1. Interestingly, only the decorin core induced mRNA synthesis, phosphorylation and de novo synthesis of vimentin indicating that the proteoglycan decorin in the extracellular matrix stabilizes the vimentin intermediate filament system. We could support these results in vivo, because the dermis of wild-type mice have more vimentin and less β1 integrin compared to Dcn(-/-. Furthermore, the α2β1 null fibroblasts also showed a reduced amount of vimentin compared to wild-type. These data show for the first time that decorin has an impact on the biology of α2β1 integrin and the vimentin intermediate filament system. Moreover, our findings provide a mechanistic explanation for the reported defects in wound healing associated with the Dcn(-/- phenotype.

  18. Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom

    International Nuclear Information System (INIS)

    Snake venom antagonists of α2β1 integrin have been identified as members of a C-lectin type family of proteins (CLP). In the present study, we characterized three new CLPs isolated from Echis sochureki venom, which interact with this integrin. These proteins were purified using a combination of gel filtration, ion exchange chromatography and reverse phase HPLC. Sochicetin-A and sochicetin-B potently inhibited adhesion of cells expressing α2β1 integrin and binding of isolated α2β1 ectodomain to collagen I, as well as bound to recombinant GST-α2A domain in ELISA, whereas activity of sochicetin-C in these assays was approximately two orders of magnitude lower. Structurally, sochicetin-B and sochicetin-C are typical heterodimeric αβ CLPs, whereas sochicetin-A exhibits a trimer of its subunits (αβ)3 in the quaternary structure. Immobilized sochicetins supported adhesion of glioma cell lines, LN18 and LBC3, whereas in a soluble form they partially inhibited adhesion of these cells to collagen I. Glioma cells spread very poorly on sochicetin-A, showing no cytoskeleton rearrangement typical for adhesion to collagen I or fibronectin. Adhesion on CLP does not involve focal adhesion elements, such as vinculin. Sochicetin-A also inhibited collagen-induced platelet aggregation, similar to other CLPs' action on the blood coagulation system. - Highlights: • Isolation of three novel snake venom CLPs inhibiting α2β1 integrin • Reporting hexameric CLP, sochicetin-A with anti-collagen receptor activity • CLPs antagonize the interaction of glioma cells with collagen matrix. • Sochicetin-A does not support glioma cell spreading

  19. Laminin isoforms differentially regulate adhesion, spreading, proliferation, and ERK activation of β1 integrin-null cells

    International Nuclear Information System (INIS)

    The presence of many laminin receptors of the β1 integrin family on most cells makes it difficult to define the biological functions of other major laminin receptors such as integrin α6β4 and dystroglycan. We therefore tested the binding of a β1 integrin-null cell line GD25 to four different laminin variants. The cells were shown to produce dystroglycan, which based on affinity chromatography bound to laminin-1, -2/4, and -10/11, but not to laminin-5. The cells also expressed the integrin α6Aβ4A variant. GD25 β1 integrin-null cells are known to bind poorly to laminin-1, but we demonstrate here that these cells bind avidly to laminin-2/4, -5, and -10/11. The initial binding at 20 min to each of these laminins could be inhibited by an integrin α6 antibody, but not by a dystroglycan antibody. Hence, integrin α6Aβ4A of GD25 cells was identified as a major receptor for initial GD25 cell adhesion to three out of four tested laminin isoforms. Remarkably, cell adhesion to laminin-5 failed to promote cell spreading, proliferation, and extracellular signal-regulated kinase (ERK) activation, whereas all these responses occurred in response to adhesion to laminin-2/4 or -10/11. The data establish GD25 cells as useful tools to define the role integrin α6Aβ4A and suggest that laminin isoforms have distinctly different capacities to promote cell adhesion and signaling via integrin α6Aβ4A

  20. Insulin-like Growth Factor I Controls Adhesion Strength Mediated by α5β1 Integrins in Motile Carcinoma Cells

    OpenAIRE

    Lynch, Laura; Vodyanik, Pavel I.; Boettiger, David; Guvakova, Marina A

    2005-01-01

    One of the intriguing questions regarding cell motility concerns the mechanism that makes stationary cells move. Here, we provide the first physical evidence that the onset of breast cancer cell motility in response to insulin-like growth factor I (IGF-I) correlates with lowering of adhesion strength from 2.52 ± 0.20 to 1.52 ± 0.13 μdynes/μm2 in cells attached to fibronectin via α5β1 integrin. The adhesion strength depends on the dose of IGF-I and time of IGF-I treatment. Weakening of cell-ma...

  1. Ofloxacin induces apoptosis via β1 integrin-EGFR-Rac1-Nox2 pathway in microencapsulated chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Sheng, Zhi-Guo [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing 100085 (China); Huang, Wei [Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 1000191 (China); Liu, Yu-Xiang [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing 100085 (China); Yuan, Ye [Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850 (China); Zhu, Ben-Zhan, E-mail: bzhu@rcees.ac.cn [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Science, Chinese Academy of Sciences, 18 Shuangqing Road, Beijing 100085 (China); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States)

    2013-02-15

    Quinolones (QNs)-induced arthropathy is an important toxic side-effect in immature animals leading to the restriction of their therapeutic use in pediatrics. Ofloxacin, a typical QN, was found to induce the chondrocytes apoptosis in the early phase (12–48 h) of arthropathy in our previous study. However, the exact mechanism(s) is unclear. Microencapsulated juvenile rabbit joint chondrocytes, a three-dimensional culture system, is utilized to perform the present study. Ofloxacin, at a therapeutically relevant concentration (10 μg/ml), disturbs the interaction between β1 integrin and activated intracellular signaling proteins at 12 h, which is inhibited when supplementing Mg{sup 2+}. Intracellular reactive oxygen species (ROS) significantly increases in a time-dependent manner after exposure to ofloxacin for 12–48 h. Furthermore, ofloxacin markedly enhances the level of activated Rac1 and epidermal growth factor receptor (EGFR) phosphorylation, and its inhibition in turn reduces the ROS production, apoptosis and Rac1 activation. Silencing Nox2, Rac1 or supplementing Mg{sup 2+} inhibits ROS accumulation, apoptosis occurrence and EGFR phosphorylation induced by ofloxacin. However, depletion of Nox2, Rac1 and inhibition of EGFR do not affect ofloxacin-mediated loss of interaction between β1 integrin and activated intracellular signaling proteins. In addition, ofloxacin also induces Vav2 phosphorylation, which is markedly suppressed after inactivating EGFR or supplementing Mg{sup 2+}. These results suggest that ofloxacin causes Nox2-mediated intracellular ROS production by disrupting the β1 integrin function and then activating the EGFR-Vav2-Rac1 pathway, finally resulting in apoptosis within 12–48 h exposure. The present study provides a novel insight regarding the potential role of Nox-driven ROS in QNs-induced arthropathy. - Highlights: ► Ofloxacin induces Nox2-driven ROS in encapsulated chondrocyte at 12–48 h. ► Ofloxacin stimulates ROS production via

  2. Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of β1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.

    Science.gov (United States)

    Álvarez-Santos, Mayra; Carbajal, Verónica; Tellez-Jiménez, Olivia; Martínez-Cordero, Erasmo; Ruiz, Victor; Hernández-Pando, Rogelio; Lascurain, Ricardo; Santibañez-Salgado, Alfredo; Bazan-Perkins, Blanca

    2016-10-01

    The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with β1 integrins (α1β1 and α2β1) in guinea pig. The putative role of β1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the β1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular β1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular β1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE-PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin-linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr(696) increased in asthma model. Our work suggests that β1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, β1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385-2396, 2016. © 2016 Wiley Periodicals, Inc. PMID:26969873

  3. The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive Entamoeba histolytica via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction.

    Directory of Open Access Journals (Sweden)

    Leanne Mortimer

    2015-05-01

    Full Text Available Entamoeba histolytica (Eh is an extracellular protozoan parasite of humans that invades the colon to cause life-threatening intestinal and extra-intestinal amebiasis. Colonized Eh is asymptomatic, however, when trophozoites adhere to host cells there is a considerable inflammatory response that is critical in the pathogenesis of amebiasis. The host and/or parasite factors that trigger the inflammatory response to invading Eh are not well understood. We recently identified that Eh adherence to macrophages induces inflammasome activation and in the present study we sought to determine the molecular events upon contact that coordinates this response. Here we report that Eh contact-dependent activation of α5β1 integrin is critical for activation of the NLRP3 inflammasome. Eh-macrophage contact triggered recruitment of α5β1 integrin and NLRP3 into the intercellular junction, where α5β1 integrin underwent activation by an integrin-binding cysteine protease on the parasite surface, termed EhCP5. As a result of its activation, α5β1 integrin induced ATP release into the extracellular space through opening of pannexin-1 channels that signalled through P2X7 receptors to deliver a critical co-stimulatory signal that activated the NLRP3 inflammasome. Both the cysteine protease activity and integrin-binding domain of EhCP5 were required to trigger α5β1 integrin that led to ATP release and NLRP3 inflammasome activation. These findings reveal engagement of α5β1 integrin across the parasite-host junction is a key regulatory step that initiates robust inflammatory responses to Eh. We propose that α5β1 integrin distinguishes Eh direct contact and functions with NLRP3 as pathogenicity sensor for invasive Eh infection.

  4. α2β1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis

    Directory of Open Access Journals (Sweden)

    Ackland Margaret

    2007-01-01

    Full Text Available Abstract Background Ovarian cancer is characterized by a wide-spread intra-abdominal metastases which represents a major clinical hurdle in the prognosis and management of the disease. A significant proportion of ovarian cancer cells in peritoneal ascites exist as multicellular aggregates or spheroids. We hypothesize that these cellular aggregates or spheroids are invasive with the capacity to survive and implant on the peritoneal surface. This study was designed to elucidate early inherent mechanism(s of spheroid survival, growth and disaggregation required for peritoneal metastases Methods In this study, we determined the growth pattern and adhesive capacity of ovarian cancer cell lines (HEY and OVHS1 grown as spheroids, using the well established liquid overlay technique, and compared them to a normal ovarian cell line (IOSE29 and cancer cells grown as a monolayer. The proteolytic capacity of these spheroids was compared with cells grown as a monolayer using a gelatin zymography assay to analyze secreted MMP-2/9 in conditioned serum-free medium. The disaggregation of cancer cell line spheroids was determined on extracellular matrices (ECM such as laminin (LM, fibronectin (FN and collagen (CI and the expression of α2, α3, αv, α6 and β1 interin was determined by flow cytometric analysis. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin was used to inhibit disaggregation as well as activation of MMPs in spheroids. Results We demonstrate that ovarian cancer cell lines grown as spheroids can sustain growth for 10 days while the normal ovarian cell line failed to grow beyond 2 days. Compared to cells grown as a monolayer, cancer cells grown as spheroids demonstrated no change in adhesion for up to 4 days, while IOSE29 cells had a 2–4-fold loss of adhesion within 2 days. Cancer cell spheroids disaggregated on extracellular matrices (ECM and demonstrated enhanced expression of secreted pro-MMP2 as well as activated MMP2

  5. THE α4β1 INTEGRIN AND THE EDA DOMAIN OF FIBRONECTIN REGULATE A PROFIBROTIC PHENOTYPE IN DERMAL FIBROBLASTS*

    Science.gov (United States)

    Shinde, Arti V.; Kelsh, Rhiannon; Peters, John H.; Sekiguchi, Kiyotoshi; Van De Water, Livingston; McKeown-Longo, Paula J.

    2015-01-01

    Prompt deposition of fibronectin-rich extracellular matrix is a critical feature of normal development and the host-response to injury. Fibronectin isoforms that include the EDA and EDB domains are prominent in these fibronectin matrices. We now report using human dermal fibroblast cultures that the EDA domain of fibronectin or EDA-derived peptides modeled after the C-C’ loop promote stress fiber formation and myosin-light chain phosphorylation. These changes are accompanied by an increase in fibronectin synthesis and fibrillogenesis. These effects are blocked by pretreating cells with either siRNA or blocking antibody to the α4 integrin. Our data indicate that the interaction between the α4β1 integrin and the EDA domain of fibronectin helps to drive tissue fibrosis by promoting a contractile phenotype and an increase in fibronectin synthesis and deposition. PMID:25433338

  6. The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts.

    Science.gov (United States)

    Shinde, Arti V; Kelsh, Rhiannon; Peters, John H; Sekiguchi, Kiyotoshi; Van De Water, Livingston; McKeown-Longo, Paula J

    2015-01-01

    Prompt deposition of fibronectin-rich extracellular matrix is a critical feature of normal development and the host-response to injury. Fibronectin isoforms that include the EDA and EDB domains are prominent in these fibronectin matrices. We now report using human dermal fibroblast cultures that the EDA domain of fibronectin or EDA-derived peptides modeled after the C-C' loop promote stress fiber formation and myosin-light chain phosphorylation. These changes are accompanied by an increase in fibronectin synthesis and fibrillogenesis. These effects are blocked by pretreating cells with either siRNA or blocking antibody to the α4 integrin. Our data indicate that the interaction between the α4β1 integrin and the EDA domain of fibronectin helps to drive tissue fibrosis by promoting a contractile phenotype and an increase in fibronectin synthesis and deposition. PMID:25433338

  7. The Activation of β1-integrin by Type I Collagen Coupling with the Hedgehog Pathway Promotes the Epithelial-Mesenchymal Transition in Pancreatic Cancer.

    Science.gov (United States)

    Duan, Wanxing; Ma, Jiguang; Ma, Qingyong; Xu, Qinhong; Lei, Jianjun; Han, Liang; Li, Xuqi; Wang, Zheng; Wu, Zheng; Lv, Shifang; Ma, Zhenhua; Liu, Mouzhu; Wang, Fengfei; Wu, Erxi

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by the excessive deposition of extracellular matrix (ECM), which is thought to contribute to this tumor's malignant behavior. However, the detailed mechanism and the contribution of excessive deposition of ECM in PDAC progression remain unclear. A better understanding of the mechanism involved in this process is essential for the design of new effective therapies. In this study, we demonstrated that pancreatic cancer cells exhibited increased proliferation and decreased apoptosis in response to type I collagen. In addition, PDAC cells exposed to type I collagen lost the expression of E-cadherin and increased expression of mesenchymal markers, including N-cadherin and vimentin. This epithelial- mesenchymal transition (EMT) was correlated with enhanced cell migration and invasiveness. Knockdown of β1-integrin abolished the effects induced by type I collagen, and further investigation revealed that type I collagen activates β1-integrin (marked by phosphorylation of β1 integrin downstream effectors, focal adhesion kinase [FAK], AKT, and ERK) accompanied by markedly up-regulation of Gli-1, a component of the Hedgehog (HH) pathway. Knockdown of Gli-1 reversed the effects of type I collagen on PDAC invasion and EMT. These results suggest that there is cross-talk between the β1-integrin signaling pathway and the HH pathway in pancreatic cancer and that activation of the HH pathway plays a key role in the type I collagen-induced effects on pancreatic cancer. PMID:24720337

  8. Unique DNA repair properties of a xeroderma pigmentosum revertant.

    OpenAIRE

    Cleaver, J.E.; Cortés, F; Lutze, L H; Morgan, W F; Player, A N; D. L. Mitchell

    1987-01-01

    A group A xeroderma pigmentosum revertant with normal sensitivity was created by chemical mutagenesis. It repaired (6-4) photoproducts normally but not pyrimidine dimers and had near normal levels of repair replication, sister chromatid exchange, and mutagenesis from UV light. The rate of UV-induced mutation in a shuttle vector, however, was as high as the rate in the parental xeroderma pigmentosum cell line.

  9. The Interaction of CD154 with the α5β1 Integrin Inhibits Fas-Induced T Cell Death.

    Science.gov (United States)

    Bachsais, Meriem; Naddaf, Nadim; Yacoub, Daniel; Salti, Suzanne; Alaaeddine, Nada; Aoudjit, Fawzi; Hassan, Ghada S; Mourad, Walid

    2016-01-01

    CD154, a critical regulator of the immune response, is usually associated with chronic inflammatory, autoimmune diseases as well as malignant disorders. In addition to its classical receptor CD40, CD154 is capable of binding other receptors, members of the integrin family, the αIIbβ3, αMβ2 and α5β1. Given the role attributed to integrins and particularly the β1 integrins in inhibiting apoptotic events in normal as well as malignant T cells, we were highly interested in investigating the role of the CD154/α5β1 interaction in promoting survival of malignant T cells contributing as such to tumor development and/or propagation. To support our hypothesis, we first show that soluble CD154 binds to the T-cell acute lymphoblastic leukemia cell line, Jurkat E6.1 in a α5β1-dependent manner. Binding of soluble CD154 to α5β1 integrin of Jurkat cells leads to the activation of key survival proteins, including the p38 and ERK1/2 mitogen-activated protein kinases (MAPKs), phosphoinositide 3 kinase (PI-3K), and Akt. Interestingly, soluble CD154 significantly inhibits Fas-mediated apoptosis in T cell leukemia-lymphoma cell lines, Jurkat E6.1 and HUT78 cells, an important hallmark of T cell survival during malignancy progression. These anti-apoptotic effects were mainly mediated by the activation of the PI-3K/Akt pathway but also involved the p38 and the ERK1/2 MAPKs cascades. Our data also demonstrated that the CD154-triggered inhibition of the Fas-mediated cell death response was dependent on a suppression of caspase-8 cleavage, but independent of de novo protein synthesis or alterations in Fas expression on cell surface. Together, our results highlight the impact of the CD154/α5β1 interaction in T cell function/survival and identify novel targets for the treatment of malignant disorders, particularly of T cell origin. PMID:27391025

  10. α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

    Science.gov (United States)

    Paul, Nikki R.; Allen, Jennifer L.; Chapman, Anna; Morlan-Mairal, Maria; Zindy, Egor; Jacquemet, Guillaume; Fernandez del Ama, Laura; Ferizovic, Nermina; Green, David M.; Howe, Jonathan D.; Ehler, Elisabeth; Hurlstone, Adam

    2015-01-01

    Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo. PMID:26370503

  11. SNARE-mediated trafficking of α5β1 integrin is required for spreading in CHO cells

    International Nuclear Information System (INIS)

    In this study, the role of SNARE-mediated membrane traffic in regulating integrin localization was examined and the requirement for SNARE function in cellular spreading was quantitatively assessed. Membrane traffic was inhibited with the VAMP-specific catalytic light chain from tetanus toxin (TeTx-LC), a dominant-negative form (E329Q) of N-ethylmaleimide-sensitive fusion protein (NSF), and brefeldin A (BfA). Inhibition of membrane traffic with either E329Q-NSF or TeTx-LC, but not BfA, significantly inhibited spreading of CHO cells on fibronectin. Spreading was rescued in TeTx-LC-expressing cells by co-transfection with a TeTx-resistant cellubrevin/VAMP3. E329Q-NSF, a general inhibitor of SNARE function, was a more potent inhibitor of cell spreading than TeTx-LC, suggesting that tetanus toxin-insensitive SNAREs contribute to adhesion. It was found that E329Q-NSF prevented trafficking of α5β1 integrins from a central Rab11-containing compartment to sites of protrusion during cell adhesion, while TeTx-LC delayed this trafficking. These results are consistent with a model of cellular adhesion that implicates SNARE function as an important component of integrin trafficking during the process of cell spreading

  12. Endorepellin, the C-terminal angiostatic module of perlecan, enhances collagen-platelet responses via the α2β1-integrin receptor

    OpenAIRE

    Bix, Gregory; Iozzo, Rex A.; Woodall, Ben; Burrows, Michelle; McQuillan, Angela; Campbell, Shelly; Fields, Gregg B.; Iozzo, Renato V.

    2007-01-01

    Endorepellin, a C-terminal fragment of the vascular basement membrane proteoglycan perlecan, inhibits angiogenesis via the α2β1-integrin receptor. Because this integrin is also implicated in platelet-collagen responses and because endorepellin or its fragments are generated in response to injury and inflammation, we hypothesized that endorepellin could also affect platelet biology. We discovered that endorepellin supported α2β1-dependent platelet adhesion, without appreciably activating or ag...

  13. Tauroursodeoxycholate Protects Rat Hepatocytes from Bile Acid-Induced Apoptosis via β1-Integrin- and Protein Kinase A-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Annika Sommerfeld

    2015-05-01

    Full Text Available Background/Aims: Ursodeoxycholic acid, which in vivo is rapidly converted into its taurine conjugate, is frequently used for the treatment of cholestatic liver disease. Apart from its choleretic effects, tauroursodeoxycholate (TUDC can protect hepatocytes from bile acid-induced apoptosis, but the mechanisms underlying its anti-apoptotic effects are poorly understood. Methods: These mechanisms were investigated in perfused rat liver and isolated rat hepatocytes. Results: It was found that TUDC inhibited the glycochenodeoxycholate (GCDC-induced activation of the CD95 death receptor at the level of association between CD95 and the epidermal growth factor receptor. This was due to a rapid TUDC-induced β1-integrin-dependent cyclic AMP (cAMP signal with induction of the dual specificity mitogen-activated protein (MAP kinase phosphatase 1 (MKP-1, which prevented GCDC-induced phosphorylation of mitogen-activated protein kinase kinase 4 (MKK4 and c-jun-NH2-terminal kinase (JNK activation. Furthermore, TUDC induced a protein kinase A (PKA-mediated serine/threonine phosphorylation of the CD95, which was recently identified as an internalization signal for CD95. Furthermore, TUDC inhibited GCDC-induced CD95 targeting to the plasma membrane in a β1-integrin-and PKA-dependent manner. In line with this, the β1-integrin siRNA knockdown in sodium taurocholate cotransporting polypeptide (Ntcp-transfected HepG2 cells abolished the protective effect of TUDC against GCDC-induced apoptosis. Conclusion: TUDC exerts its anti-apoptotic effect via a β1-integrin-mediated formation of cAMP, which prevents CD95 activation by hydrophobic bile acids at the levels of JNK activation and CD95 serine/threonine phosphorylation.

  14. Plumieribetin, a Fish Lectin Homologous to Mannose-binding B-type Lectins, Inhibits the Collagen-binding α1β1 Integrin*

    OpenAIRE

    de Santana Evangelista, Karla; Andrich, Filipe; Figueiredo de Rezende, Flávia; Niland, Stephan; Cordeiro, Marta N.; Horlacher, Tim; Castelli, Riccardo; Schmidt-Hederich, Alletta; Peter H. Seeberger; Sanchez, Eladio F.; Richardson, Michael; Gomes de Figueiredo, Suely; Eble, Johannes A.

    2009-01-01

    Recently, a few fish proteins have been described with a high homology to B-type lectins of monocotyledonous plants. Because of their mannose binding activity, they have been ascribed a role in innate immunity. By screening various fish venoms for their integrin inhibitory activity, we isolated a homologous protein from the fin stings and skin mucus of the scorpionfish (Scorpaena plumieri). This protein inhibits α1β1 integrin binding to basement membrane collagen IV. By protein chemical and s...

  15. Differential β3 and β1 Integrin Expression in Bone Marrow and Cortical Bone of Estrogen Deficient Rats.

    Science.gov (United States)

    Voisin, Muriel; McNamara, Laoise M

    2015-09-01

    Integrin-based (β3 ) attachments to the extracellular matrix (ECM) on osteocyte cell processes have recently been proposed to play an important role in facilitating osteocyte mechanosensation. However, it is not yet known whether integrin expression is altered in the mechanoregulatory osteocytes during osteoporosis. The objective of this study was to test the hypothesis that the expression of integrin-based mechanosensory complexes (β1 and β3 integrins) is altered as a direct response to estrogen deficiency, in an estrogen deficient animal model of osteoporosis. Four weeks post-operatively, immunohistochemistry was used to detect for β1 and β3 integrin subunits in bone tissue and marrow of ovariectomized (OVX; N = 4) and SHAM (N = 4) operated animals. A tartrate resistant acid phosphatase (TRAP) control stain was performed to quantify the presence of osteoclasts in the bone marrow and bone surfaces. Image analysis was performed to quantify expression patterns in different biological compartments, that is, bone marrow, endosteum, and cortical bone. Our results showed that β1 integrins were ubiquitously expressed throughout the bone and marrow, for both OVX and SHAM groups. β3 integrin subunit expression was lower in bone cells from osteoporotic animals compared to controls, whereas β3 expression in marrow cells did not differ significantly between groups. At the endosteum no difference was observed in β3 integrin subunit expression. As expected, the number of osteoclasts was higher in the OVX group validating an imbalance in bone remodeling. We propose that a reduction in β3 integrin expression in osteocytes might impair mechanosensation by bone cells during estrogen deficiency. PMID:25974241

  16. Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their α6β1 integrin receptor

    International Nuclear Information System (INIS)

    Bone marrow-derived mesenchymal stem cells (BMSCs) facilitate the angiogenic response of endothelial cells (ECs) within three-dimensional (3D) matrices in vivo and in engineered tissues in vitro in part through paracrine mediators and by acting as stabilizing pericytes. However, the molecular interactions between BMSCs and nascent tubules during the process of angiogenesis are not fully understood. In this study, we have used a tractable 3D co-culture model to explore the functional role of the α6β1 integrin adhesion receptor on BMSCs in sprouting angiogenesis. We report that knockdown of the α6 integrin subunit in BMSCs significantly reduces capillary sprouting, and causes their failure to associate with the nascent vessels. Furthermore, we demonstrate that the BMSCs with attenuated α6 integrin proliferate at a significantly lower rate relative to either control cells expressing non-targeting shRNA or wild type BMSCs; however, despite adding more cells to compensate for this deficit in proliferation, deficient sprouting persists. Collectively, our findings demonstrate that the α6 integrin subunit in BMSCs is important for their ability to stimulate vessel morphogenesis. This conclusion may have important implications in the optimization of cell-based strategies to promote angiogenesis. Highlights: • BMSCs stimulate angiogenesis, but the mechanisms remain unclear. • We silenced the expression of the α6 integrin subunit in BMSCs. • Silencing this receptor subunit significantly inhibited angiogenic sprouting. • Knocking down α6 integrin affected laminin and αSMA expression. • Silencing α6 integrin expression also reduced BMSC proliferation

  17. Bone marrow-derived mesenchymal stem cells enhance angiogenesis via their α6β1 integrin receptor

    Energy Technology Data Exchange (ETDEWEB)

    Carrion, Bita; Kong, Yen P. [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Kaigler, Darnell [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States); Department of Periodontics and Oral Medicine, University of Michigan, Ann Arbor, MI 48109 (United States); Putnam, Andrew J., E-mail: putnam@umich.edu [Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 (United States)

    2013-11-15

    Bone marrow-derived mesenchymal stem cells (BMSCs) facilitate the angiogenic response of endothelial cells (ECs) within three-dimensional (3D) matrices in vivo and in engineered tissues in vitro in part through paracrine mediators and by acting as stabilizing pericytes. However, the molecular interactions between BMSCs and nascent tubules during the process of angiogenesis are not fully understood. In this study, we have used a tractable 3D co-culture model to explore the functional role of the α6β1 integrin adhesion receptor on BMSCs in sprouting angiogenesis. We report that knockdown of the α6 integrin subunit in BMSCs significantly reduces capillary sprouting, and causes their failure to associate with the nascent vessels. Furthermore, we demonstrate that the BMSCs with attenuated α6 integrin proliferate at a significantly lower rate relative to either control cells expressing non-targeting shRNA or wild type BMSCs; however, despite adding more cells to compensate for this deficit in proliferation, deficient sprouting persists. Collectively, our findings demonstrate that the α6 integrin subunit in BMSCs is important for their ability to stimulate vessel morphogenesis. This conclusion may have important implications in the optimization of cell-based strategies to promote angiogenesis. Highlights: • BMSCs stimulate angiogenesis, but the mechanisms remain unclear. • We silenced the expression of the α6 integrin subunit in BMSCs. • Silencing this receptor subunit significantly inhibited angiogenic sprouting. • Knocking down α6 integrin affected laminin and αSMA expression. • Silencing α6 integrin expression also reduced BMSC proliferation.

  18. A vortex venturi for reverting antimisting fuel properties

    Science.gov (United States)

    Szetela, E. J.; Tevelde, J.

    1983-01-01

    The level of degradation of antimisting fuel polymers such as FM-9 which must be accomplished in order to use antimisting fuel in existing engines may require the use of cavitation. The hydrodynamic shear produced by the collapse of vapor bubbles is capable of producing more splitting of polymeric molecules than mechanically-induced shear. A program has been carried out to investigate the possibility of using a cavitating venturi with rotating flow as a fuel reverter. This investigation included the effects of a swirl-inducing twisted tape upstream of the throat, inlet pressure, recovery pressure ratio and a pintle for varying throat area. A correlation of the data was produced, system concepts for using the vortex venturi were investigated and problem areas were delineated.

  19. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    International Nuclear Information System (INIS)

    Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK). Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK). Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC) lines. Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway

  20. Recruitment of focal adhesion kinase and paxillin to β1 integrin promotes cancer cell migration via mitogen activated protein kinase activation

    Directory of Open Access Journals (Sweden)

    Ohannessian Arthur

    2004-05-01

    Full Text Available Abstract Background Integrin-extracellular matrix interactions activate signaling cascades such as mitogen activated protein kinases (MAPK. Integrin binding to extracellular matrix increases tyrosine phosphorylation of focal adhesion kinase (FAK. Inhibition of FAK activity by expression of its carboxyl terminus decreases cell motility, and cells from FAK deficient mice also show reduced migration. Paxillin is a focal adhesion protein which is also phosphorylated on tyrosine. FAK recruitment of paxillin to the cell membrane correlates with Shc phosphorylation and activation of MAPK. Decreased FAK expression inhibits papilloma formation in a mouse skin carcinogenesis model. We previously demonstrated that MAPK activation was required for growth factor induced in vitro migration and invasion by human squamous cell carcinoma (SCC lines. Methods Adapter protein recruitment to integrin subunits was examined by co-immunoprecipitation in SCC cells attached to type IV collagen or plastic. Stable clones overexpressing FAK or paxillin were created using the lipofection technique. Modified Boyden chambers were used for invasion assays. Results In the present study, we showed that FAK and paxillin but not Shc are recruited to the β1 integrin cytoplasmic domain following attachment of SCC cells to type IV collagen. Overexpression of either FAK or paxillin stimulated cancer cell migration on type IV collagen and invasion through reconstituted basement membrane which was dependent on MAPK activity. Conclusions We concluded that recruitment of focal adhesion kinase and paxillin to β1 integrin promoted cancer cell migration via the mitogen activated protein kinase pathway.

  1. ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Albrechtsen, Reidar; Grauslund, Morten;

    2002-01-01

    The ADAMs (a disintegrin and metalloprotease) comprise a large family of multidomain proteins with cell-binding and metalloprotease activities. The ADAM12 cysteine-rich domain (rADAM12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers bet...

  2. Glucocorticoid receptor antagonism reverts docetaxel resistance in human prostate cancer

    Science.gov (United States)

    Kroon, Jan; Puhr, Martin; Buijs, Jeroen T; van der Horst, Geertje; Hemmer, Daniëlle M; Marijt, Koen A; Hwang, Ming S; Masood, Motasim; Grimm, Stefan; Storm, Gert; Metselaar, Josbert M; Meijer, Onno C; Culig, Zoran; van der Pluijm, Gabri

    2016-01-01

    Resistance to docetaxel is a major clinical problem in advanced prostate cancer (PCa). Although glucocorticoids (GCs) are frequently used in combination with docetaxel, it is unclear to what extent GCs and their receptor, the glucocorticoid receptor (GR), contribute to the chemotherapy resistance. In this study, we aim to elucidate the role of the GR in docetaxel-resistant PCa in order to improve the current PCa therapies. GR expression was analyzed in a tissue microarray of primary PCa specimens from chemonaive and docetaxel-treated patients, and in cultured PCa cell lines with an acquired docetaxel resistance (PC3-DR, DU145-DR, and 22Rv1-DR). We found a robust overexpression of the GR in primary PCa from docetaxel-treated patients and enhanced GR levels in cultured docetaxel-resistant human PCa cells, indicating a key role of the GR in docetaxel resistance. The capability of the GR antagonists (RU-486 and cyproterone acetate) to revert docetaxel resistance was investigated and revealed significant resensitization of docetaxel-resistant PCa cells for docetaxel treatment in a dose- and time-dependent manner, in which a complete restoration of docetaxel sensitivity was achieved in both androgen receptor (AR)-negative and AR-positive cell lines. Mechanistically, we demonstrated down-regulation of Bcl-xL and Bcl-2 upon GR antagonism, thereby defining potential treatment targets. In conclusion, we describe the involvement of the GR in the acquisition of docetaxel resistance in human PCa. Therapeutic targeting of the GR effectively resensitizes docetaxel-resistant PCa cells. These findings warrant further investigation of the clinical utility of the GR antagonists in the management of patients with advanced and docetaxel-resistant PCa. PMID:26483423

  3. Stability of the tumor suppressor merlin depends on its ability to bind paxillin LD3 and associate with β1 integrin and actin at the plasma membrane

    Directory of Open Access Journals (Sweden)

    Maria Elisa Manetti

    2012-08-01

    The NF2 gene encodes a tumor suppressor protein known as merlin or schwannomin whose loss of function causes Neurofibromatosis Type 2 (NF2. NF2 is characterized by the development of benign tumors, predominantly schwannomas, in the peripheral nervous system. Merlin links plasma membrane receptors with the actin cytoskeleton and its targeting to the plasma membrane depends on direct binding to the paxillin scaffold protein. Exon 2 of NF2, an exon mutated in NF2 patients and deleted in a mouse model of NF2, encodes the merlin paxillin binding domain (PBD1. Here, we sought to determine the role of PBD1 in regulation of merlin stability and association with plasma membrane receptors and the actin cytoskeleton in Schwann cells. Using a fluorescence-based pulse-chase technique, we measured the half-life of Halo-tagged merlin variants carrying PBD1, exon 2, and exons 2 and 3 deletions in transiently transfected Schwann cells. We found that PBD1 alone was necessary and sufficient to increase merlin's half-life from approximately three to eleven hours. Merlin lacking PBD1 did not form a complex with surface β1 integrins or associate with the actin cytoskeleton. In addition, direct binding studies using purified merlin and paxillin domains revealed that merlin directly binds paxillin LD3 (leucine-aspartate 3 domain as well as the LD4 and LD5 domains. Together these results demonstrate that a direct interaction between merlin PBD1 and the paxillin LD3–5 domains targets merlin to the plasma membrane where it is stabilized by its association with surface β1 integrins and cortical actin.

  4. Gleditsia sinensis Thorn Attenuates the Collagen-Based Migration of PC3 Prostate Cancer Cells through the Suppression of α2β1 Integrin Expression

    Directory of Open Access Journals (Sweden)

    Sujin Ryu

    2016-03-01

    Full Text Available Gleditsia sinensis thorns (GST have been used as a traditional medicine for carbuncles and skin diseases. The purpose of this study was to decide whether non-toxicological levels of water extract of GST (WEGST are effective in inhibiting the progress of prostate cancer formation and to identify the target molecule involved in the WEGST-mediated inhibitory process of prostate cancer cell migration and in vivo tumor formation. Through the Boyden chamber migration assay, we found that non-toxic levels of WEGST could not attenuate the PC3 migration to the bottom area coated with serum but significantly inhibited PC3 cell migration to the collagen-coated bottom area. We also found that non-toxic levels of WEGST significantly attenuated collagen against adhesion. Interestingly, ectopic administration of WEGST could not affect the expression of α2β1 integrin, which is known as a receptor of collagen. However, when the PC3 cells adhered to a collagen-coated plate, the expression of α2 integrin but not that of β1 integrin was significantly inhibited by the administration of non-toxic levels of WEGST, leading to the inhibition of focal adhesion kinase (FAK phosphorylation. Furthermore, oral administration of WEGST (25 mg/kg/day significantly inhibited the size of a PC3 cell-xenografted tumor. Taken together, these results suggest a novel molecular mechanism for WEGST to inhibit prostate cancer progression at particular stages, such as collagen-mediated adhesion and migration, and it might provide further development for the therapeutic use of WEGST in the treatment of prostate cancer progression.

  5. Influence of reverted austenite on the texture and magnetic properties of 350 maraging steel

    Energy Technology Data Exchange (ETDEWEB)

    Abreu, Hamilton F.G., E-mail: hamilton@ufc.br [Universidade Federal do Ceará, Campus do Pici-Bloco 729, CEP 60440-554 Fortaleza, CE (Brazil); Silva, Jean J. [Universidade Federal do Ceará, Campus do Pici-Bloco 729, CEP 60440-554 Fortaleza, CE (Brazil); Silva, Manoel R. [Universidade Federal de Itajubá, Campus Sede Itajubá/IFQ- Instituto de Física e Química, Itajubá, MG (Brazil); Gomes da Silva, Marcelo J., E-mail: mgsilva@ufc.br [Universidade Federal do Ceará, Campus do Pici-Bloco 729, CEP 60440-554 Fortaleza, CE (Brazil)

    2015-11-01

    The aging temperature to improve magnetic properties in Maraging-350 steel (Mar-350) is limited by the onset of austenite reversion. The traditional process of cooling after aging is to remove the piece from the oven and then to air cool it. The purpose of this research was to characterize the reverted austenite and to investigate the effect of cooling below the martensite start temperature (M{sub s}) on the magnetic properties. The Mar350 samples aged at temperatures above 550 °C, and subsequently cooled in liquid nitrogen presented less austenite than samples cooled in air, resulting in higher magnetization saturation and a lower coercive force. A combination of optical microscopy (OM), X-ray diffraction (XRD) and electron backscatter diffraction (EBSD) techniques were used to characterize the presence of reverted austenite. The crystallographic texture of both martensite and reverted austenite were analyzed. The texture of the reverted austenite coincides with the texture of the parent austenite indicating that a phenomenon of texture memory is present. - Highlights: • Cooling maraging samples in liquid nitrogen reduces reverted austenite fraction. • Retained austenite increases coercive force and decreases saturation magnetization. • Reverted and parent austenites have the same crystallographic texture. • Memory effect found during reversion transformation.

  6. Influence of reverted austenite on the texture and magnetic properties of 350 maraging steel

    International Nuclear Information System (INIS)

    The aging temperature to improve magnetic properties in Maraging-350 steel (Mar-350) is limited by the onset of austenite reversion. The traditional process of cooling after aging is to remove the piece from the oven and then to air cool it. The purpose of this research was to characterize the reverted austenite and to investigate the effect of cooling below the martensite start temperature (Ms) on the magnetic properties. The Mar350 samples aged at temperatures above 550 °C, and subsequently cooled in liquid nitrogen presented less austenite than samples cooled in air, resulting in higher magnetization saturation and a lower coercive force. A combination of optical microscopy (OM), X-ray diffraction (XRD) and electron backscatter diffraction (EBSD) techniques were used to characterize the presence of reverted austenite. The crystallographic texture of both martensite and reverted austenite were analyzed. The texture of the reverted austenite coincides with the texture of the parent austenite indicating that a phenomenon of texture memory is present. - Highlights: • Cooling maraging samples in liquid nitrogen reduces reverted austenite fraction. • Retained austenite increases coercive force and decreases saturation magnetization. • Reverted and parent austenites have the same crystallographic texture. • Memory effect found during reversion transformation

  7. Isolation and genetic characterization of a fertility-restoring revertant induced from cytoplasmic male sterile rice

    International Nuclear Information System (INIS)

    A male fertile revertant was isolated from M1 of a cytoplasmic male sterile indica rice line II-32A, the dry seeds of which were treated with 60Co-γ rays at a dose of 290 Gy. The acquired revertant T24 was morphologically and agronomically similar to II-32B, the maintainer of II-32A. Testcrosses of the revertant with II-32A and Zhenshan 97A showed that the revertant was able to restore the fertility of CMS lines. Genetic analysis of the progenies between T24 and II-32A, Zhenshan 97A XieqingzaoA and DZhenshan 97A, which have different cytoplasms, showed that the fertility restoration of four CMS lines by T24 involved one nuclear gene, indicating that T24 was a result of the mutation of one nuclear gene. The mechanism of the restoration of CMS line by T24 was obviously different from other restorers such as Minghui 63 and 20964, which were shown to behave in two gene mode in fertility restoration. The discovery of the revertant T24 contributes to the understanding of CMS and fertility restoration of CMS in rice. The T24 and its parent II-32A may constitute a pair of near isogenic lines for the restoring gene, which should be valuable materials for molecular genetic analysis of CMS

  8. Revertants of a Transcription Termination Mutant of Yeast Contain Diverse Genetic Alterations

    OpenAIRE

    Kotval, Jeroo; Zaret, Kenneth S.; Consaul, Sandra; Sherman, Fred

    1983-01-01

    Revertants of the cyc1-512 transcription termination mutant of the yeast Saccharomyces cerevisiae were isolated and subjected to a detailed genetic analysis. The cyc1-512 mutation previously was shown to be a 38-base pair deletion that causes only 10% of the normal steady-state levels of CYC1 mRNA and of the CYC1 gene product, iso-1-cytochrome c. Forty-one cyc1-512 revertants were classified by their content of iso-1-cytochrome c and by their genetic properties in meiotic crosses. Many of the...

  9. Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes.

    Science.gov (United States)

    Ricardo, Elisabete; Costa-de-Oliveira, Sofia; Dias, Ana Silva; Guerra, José; Rodrigues, Acácio Gonçalves; Pina-Vaz, Cidália

    2009-06-01

    Several mechanisms may be associated with Candida albicans resistance to azoles. Ibuprofen was described as being able to revert resistance related to efflux activity in Candida. The aim of this study was to uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen. Sixty-two clinical isolates and five control strains of C. albicans were studied: the azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute, M27-A2 protocol and minimal inhibitory concentration values were recalculated with ibuprofen (100 microg mL(-1)); synergistic studies between fluconazole and FK506, a Cdr1p inhibitor, were performed using an agar disk diffusion assay and were compared with ibuprofen results. Gene expression was quantified by real-time PCR, with and without ibuprofen, regarding CDR1, CDR2, MDR1, encoding for efflux pumps, and ERG11, encoding for azole target protein. A correlation between susceptibility phenotype and resistance gene expression profiles was determined. Ibuprofen and FK506 showed a clear synergistic effect when combined with fluconazole. Resistant isolates reverting to susceptible after incubation with ibuprofen showed CDR1 and CDR2 overexpression especially of the latter. Conversely, strains that did not revert displayed a remarkable increase in ERG11 expression along with CDR genes. Ibuprofen did not alter resistance gene expression significantly (P>0.05), probably acting as a Cdrp blocker. PMID:19416368

  10. Adenovirus E1A gene autorepression: revertants of an E1A promoter mutation encode altered E1A proteins

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, P.L.; Tibbetts, C.

    1987-12-01

    Revertants have been isolated from Ad3hr15, a mutant of human adenovirus type 3 that carries a defective E1A promoter. Transcription of these revertant E1A genes is restored - from nil for Ad3hr15 mutant to levels exceeding that of the wild-type virus. The mutant Ad3hr15 virus and the revertants all have an aberrant E1A promoter that contains two short tandem duplications of viral DNA sequence. The E1A gene-coding region of the mutant is the same as that for wild-type adenovirus type 3, whereas the revertants are characterized by short in-frame deletions within the 5' exon region of their E1A genes. Location of these reverting, second-site deletions is discussed in relation to E1A gene autoregulation and the evolved diversity of E1A-related oncogenic potential among different human adenoviruses.

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

    OpenAIRE

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

    1991-01-01

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

  12. Beta Thalassemia

    Science.gov (United States)

    ... South Asian (Indian, Pakistani, etc.), Southeast Asian and Chinese descent. 1 Beta Thalassemia ßß Normal beta globin ... then there is a 25% chance with each pregnancy that their child will inherit two abnormal beta ...

  13. Evaluation of the Revertant Phenomenon in Patients with DMD by Immunostaining and Molecular Biology

    Institute of Scientific and Technical Information of China (English)

    Yu Wen; Wu Hua-Chen; Xie Jun; Fan Ji-Shi; Song Yong-Jian; Chen Sheng-Di

    2000-01-01

    Objective To evaluate the significance of revertant phenomenon in patients with Duchunnes muscular dystrophy(DMD). Methods In the present study, the muscles from the patients with DMD were detected by immunofluoresce staining and anti dystrophin antibody, and the 25 pairs of exons in the serum of patients were measured by repetitive PCR test. Results Fifty-one patients had progressive general weakness, especially in proximal and trunk, and hypertrophy calves. Four of them had absent reaction for sarcolemma, which was called as rcvertant phenomenon. The finding was unique and quite rare. The measurement of molecular biology showed no dystrophin deletion in these 4 cases. Conclusions The revertant phenomenon may involve the different mechanism from the conventional medical wisdom. The symptoms and signs of these patients might be improved by a newly therapeutic approach.

  14. ON THE SINGULARITY OF LEAST SQUARES ESTIMATOR FOR MEAN-REVERTING Α-STABLE MOTIONS

    Institute of Scientific and Technical Information of China (English)

    Hu Yaozhong; Long Hongwei

    2009-01-01

    We study the problem of parameter estimation for mean-reverting α-stable motion, dXt= (a0- θ0Xt)dt + dZt, observed at discrete time instants.A least squares estimator is obtained and its asymptotics is discussed in the singular case (a0, θ0)=(0,0).If a0=0, then the mean-reverting α-stable motion becomes Ornstein-Uhlenbeck process and is studied in [7] in the ergodie case θ0 > 0.For the Ornstein-Uhlenbeck process, asymptoties of the least squares estimators for the singular case (θ0 = 0) and for ergodic case (θ0 > 0) are completely different.

  15. Mutation types and aging differently affect revertant fiber expansion in dystrophic mdx and mdx52 mice.

    Directory of Open Access Journals (Sweden)

    Yusuke Echigoya

    Full Text Available Duchenne muscular dystrophy (DMD, one of the most common and lethal genetic disorders, and the mdx mouse myopathies are caused by a lack of dystrophin protein. These dystrophic muscles contain sporadic clusters of dystrophin-expressing revertant fibers (RFs, as detected by immunohistochemistry. RFs are known to arise from muscle precursor cells with spontaneous exon skipping (alternative splicing and clonally expand in size with increasing age through the process of muscle degeneration/regeneration. The expansion of revertant clusters is thought to represent the cumulative history of muscle regeneration and proliferation of such precursor cells. However, the precise mechanisms by which RFs arise and expand are poorly understood. Here, to test the effects of mutation types and aging on RF expansion and muscle regeneration, we examined the number of RFs in mdx mice (containing a nonsense mutation in exon 23 and mdx52 mice (containing deletion mutation of exon 52 with the same C57BL/6 background at 2, 6, 12, and 18months of age. Mdx mice displayed a significantly higher number of RFs compared to mdx52 mice in all age groups, suggesting that revertant fiber expansion largely depends on the type of mutation and/or location in the gene. A significant increase in the expression and clustering levels of RFs was found beginning at 6months of age in mdx mice compared with mdx52 mice. In contrast to the significant expansion of RFs with increasing age, the number of centrally nucleated fibers and embryonic myosin heavy chain-positive fibers (indicative of cumulative and current muscle regeneration, respectively decreased with age in both mouse strains. These results suggest that mutation types and aging differently affect revertant fiber expansion in mdx and mdx52 mice.

  16. Non-invasive Brain Stimulation, a Tool to Revert Maladaptive Plasticity in Neuropathic Pain.

    Science.gov (United States)

    Naro, Antonino; Milardi, Demetrio; Russo, Margherita; Terranova, Carmen; Rizzo, Vincenzo; Cacciola, Alberto; Marino, Silvia; Calabro, Rocco S; Quartarone, Angelo

    2016-01-01

    Neuromodulatory effects of non-invasive brain stimulation (NIBS) have been extensively studied in chronic pain. A hypothetic mechanism of action would be to prevent or revert the ongoing maladaptive plasticity within the pain matrix. In this review, the authors discuss the mechanisms underlying the development of maladaptive plasticity in patients with chronic pain and the putative mechanisms of NIBS in modulating synaptic plasticity in neuropathic pain conditions. PMID:27512368

  17. Has organic farming modernized itself out of business? - Reverting to conventional methods in Denmark

    OpenAIRE

    Kaltoft, Pernille; Risgaard, Marie-Louise

    2005-01-01

    This case study illustrates that reversion to conventional farming does not take place due to technical problems related to production but that farmers in general decided to stop farming organically due to economic problems – primarily marketing problems – and because of changes in regulations. Almost none of the reverters wished to start using pesticides again and most of them also considered organic farming to be a professional challenge. In general, however, organic and conventional produc...

  18. Has organic farming modernised itself out of business? An analysis of reverting organic farmers

    OpenAIRE

    Kaltoft, Pernille; Risgaard, Marie-Louise

    2004-01-01

    In Denmark organic farming presently experiences a recession with 500 organic farmers leaving the organic sector this year (out of a total of 3500 farmers) and a lot more are considering to revert. A range of earlier studies has reported on the process of modernisation of organic farming. Not at least in Denmark where a lot of conventional farmers have converted to the organic mode of production and where conventional/traditional production and distribution channels have adopted a line of org...

  19. User's guide to REVERT. A CDC 7600 program for converting Spent Fuel Test - Climax data to engineering units, with corrections

    International Nuclear Information System (INIS)

    A CDC 7600 computer program, REVERT, can revise Spent Fuel Test - Climax data files using one of several algorithms, depending on the type of data. The algorithms use coefficients from a separate file organized by data type identifiers. REVERT can also make that file of coefficients, using data from tapes made by Hewlett-Packard equipment employed for data acquisition on the spent Fuel Test - Climax at NTS. 12 references

  20. Isolation and characterization of revertants from four different classes of aryl hydrocarbon hydroxylase-deficient hepa-1 mutants.

    Science.gov (United States)

    Van Gurp, J R; Hankinson, O

    1984-01-01

    Revertants were selected from aryl hydrocarbon hydroxylase (AHH)-deficient recessive mutants belonging to three complementation groups and from a dominant mutant of the Hepa-1 cell line. The recessive mutants had low spontaneous reversion frequencies (less than 4 X 10(-7] that were increased by mutagenesis. The majority of these revertants also had reacquired only partial AHH activity. Revertants of group A mutants were identical to the wild type with respect to both in vivo and in vitro enzyme stability and the Km for the substrate, benzo [alpha]pyrene, and therefore failed to provide evidence that gene A is the AHH structural gene. Group B and group C mutants are defective in the functioning of the Ah receptor required for AHH induction. Revertants of these groups were normal with respect to in vivo temperature sensitivity for AHH induction and for the 50% effective dose for the inducer, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and thus provided no evidence that the B and C genes code for components of the receptor. Two rare group C revertants possessed AHH activity in the absence of induction. The phenotype of one of these was shown to be recessive to the wild type. Spontaneous revertants of the dominant mutant occurred at a frequency 300-fold greater than those of the recessive mutants, and this frequency was not increased by mutagenesis. These revertants all displayed complete restoration of AHH activity to wild type levels. These observations and the results from cell hybridization studies suggest that the dominant revertants arose by a high frequency event leading to functional elimination of the dominant mutation. PMID:6493230

  1. Is financial leverage mean-reverting? Unit root tests and corporate financing models

    OpenAIRE

    M. E. Bontempi; R. Golinelli

    2001-01-01

    In this paper we use the unit root test at both individual company (Dickey-Fuller) and panel (Im-Pesaran-Shin) level, in order to provide some quantitative evidence of the univariate behaviour of Italian companies’ debt-ratio. If it is mean-reverting, then at least a share of companies are going to behave according to the trade-off model, whereas if it is non-stationary, then companies may behave according to pecking order theory. Individual company test results support the pecking order theo...

  2. Revertant seedlings from crown gall tumors retain a portion of the bacterial Ti plasmid DNA sequences*

    OpenAIRE

    Yang, Funmei; Simpson, Robert B.

    1981-01-01

    BT37 is a crown gall teratoma incited on tobacco by Agrobacterium tumefaciens containing pTi-T37, a nopaline-type Ti plasmid. Treatment of this cloned tumor tissue with kinetin at 1 mg/liter results in the formation of relatively normal-appearing shoots. These shoots can be induced to root and set viable seed. In contrast to BT37 tissue, the derived tissues are not phytohormone independent and do not produce nopaline. The reverted plants, like normal tobacco plants, are susceptible to infecti...

  3. IL-10+ Innate-like B Cells Are Part of the Skin Immune System and Require α4β1 Integrin To Migrate between the Peritoneum and Inflamed Skin.

    Science.gov (United States)

    Geherin, Skye A; Gómez, Daniela; Glabman, Raisa A; Ruthel, Gordon; Hamann, Alf; Debes, Gudrun F

    2016-03-15

    The skin is an important barrier organ and frequent target of autoimmunity and allergy. In this study, we found innate-like B cells that expressed the anti-inflammatory cytokine IL-10 in the skin of humans and mice. Unexpectedly, innate-like B1 and conventional B2 cells showed differential homing capacities with peritoneal B1 cells preferentially migrating into the inflamed skin of mice. Importantly, the skin-homing B1 cells included IL-10-secreting cells. B1 cell homing into the skin was independent of typical skin-homing trafficking receptors and instead required α4β1-integrin. Moreover, B1 cells constitutively expressed activated β1 integrin and relocated from the peritoneum to the inflamed skin and intestine upon innate stimulation, indicating an inherent propensity to extravasate into inflamed and barrier sites. We conclude that innate-like B cells migrate from central reservoirs into skin, adding an important cell type with regulatory and protective functions to the skin immune system. PMID:26851219

  4. Patient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa.

    Science.gov (United States)

    Tolar, Jakub; McGrath, John A; Xia, Lily; Riddle, Megan J; Lees, Chris J; Eide, Cindy; Keene, Douglas R; Liu, Lu; Osborn, Mark J; Lund, Troy C; Blazar, Bruce R; Wagner, John E

    2014-05-01

    Spontaneous reversion of disease-causing mutations has been observed in some genetic disorders. In our clinical observations of severe generalized recessive dystrophic epidermolysis bullosa (RDEB), a currently incurable blistering genodermatosis caused by loss-of-function mutations in COL7A1 that results in a deficit of type VII collagen (C7), we have observed patches of healthy-appearing skin on some individuals. When biopsied, this skin revealed somatic mosaicism resulting in the self-correction of C7 deficiency. We believe this source of cells could represent an opportunity for translational 'natural' gene therapy. We show that revertant RDEB keratinocytes expressing functional C7 can be reprogrammed into induced pluripotent stem cells (iPSCs) and that self-corrected RDEB iPSCs can be induced to differentiate into either epidermal or hematopoietic cell populations. Our results give proof-of-principle that an inexhaustible supply of functional patient-specific revertant cells can be obtained--potentially relevant to local wound therapy and systemic hematopoietic cell transplantation. This technology may also avoid some of the major limitations of other cell therapy strategies, e.g., immune rejection and insertional mutagenesis, which are associated with viral- and nonviral-mediated gene therapy. We believe this approach should be the starting point for autologous cellular therapies using 'natural' gene therapy in RDEB and other diseases. PMID:24317394

  5. Sleep reverts changes in human gray and white matter caused by wake-dependent training.

    Science.gov (United States)

    Bernardi, Giulio; Cecchetti, Luca; Siclari, Francesca; Buchmann, Andreas; Yu, Xiaoqian; Handjaras, Giacomo; Bellesi, Michele; Ricciardi, Emiliano; Kecskemeti, Steven R; Riedner, Brady A; Alexander, Andrew L; Benca, Ruth M; Ghilardi, M Felice; Pietrini, Pietro; Cirelli, Chiara; Tononi, Giulio

    2016-04-01

    Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12h and 24h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites. PMID:26812659

  6. Investigation on the crystallography of the transformation products of reverted austenite in intercritically reheated coarse grained heat affected zone

    International Nuclear Information System (INIS)

    Highlights: ► Area of reverted austenite is traced out by crystallographic information. ► Bainite and martensite regions were confirmed within it. ► The martensite region is considered as the blocky MA particles. ► Martensite region has high deformation to initiate fracture. ► More uniform transformation of the reverted austenite is good for toughness. -- Abstract: In present study the intercritically reheated coarse grained heat affected zone (ICCGHAZ) showing the worst impact toughness in the heat affected zone of multi-pass welding was simulated by Gleeble-1500, and its microstructure was investigated in detail by means of scanning electron microscope (SEM) and electron backscattering diffraction (EBSD). With the crystallographic information from EBSD scanning the area of a single reverted austenite grain which formed during the thermal cycles of second pass simulation was traced out. Within it two regions with different characteristic both in morphology and crystallography were found out, showing an un-uniform transformation of the reverted austenite. The region I is a bainitic region containing larger bainitic ferrite grains, while the region II is made up of several clusters containing tiny grains. Based on the crystallographic information each cluster was determined as martensite island thereby should be considered as blocky Martensite/Austenite constituent (M/A), which is hard phase and harmful for toughness. Analysis on the level of deformation shows that the region II is much higher deformed than the region I, indicating there is high stress concentration within the region II. The possible influence of the region I and the region II on fracture is discussed under the early proposed M/A’s fracture-initiating mechanisms. It suggests that the main cause of the toughness reduction is the un-uniform transformation of the reverted austenite, and the toughness performance of the ICCGHAZ could be improved if the transformation of the reverted

  7. Nonlinear Filters for Hidden Markov Models of Regime Change with Fast Mean-Reverting States

    CERN Document Server

    Papanicolaou, Andrew

    2012-01-01

    We consider filtering for a hidden Markov model that evolves with multiple time scales in the hidden states. In particular, we consider the case where one of the states is a scaled Ornstein-Uhlenbeck process with fast reversion to a shifting-mean that is controlled by a continuous time Markov chain modeling regime change. We show that the nonlinear filter for such a process can be approximated by an averaged filter that asymptotically coincides with the true nonlinear filter of the regime-changing Markov chain as the rate of mean reversion approaches infinity. The asymptotics exploit weak converge of the state variables to an invariant distribution, which is significantly different from the strong convergence used to obtain asymptotic results in "Filtering for Fast Mean-Reverting Processes" (19).

  8. Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3

    OpenAIRE

    Pasmooij, Anna M. G.; Pas, Hendri H.; Bolling, Maria C.; Jonkman, Marcel F

    2007-01-01

    Revertant mosaicism due to in vivo reversion of an inherited mutation has been described in the genetic skin disease epidermolysis bullosa (EB) for the genes KRT14 and COL17A1. Here we demonstrate the presence of multiple second-site mutations, all correcting the germline mutation LAMB3:c.628G→A;p.E210K, in 2 unrelated non-Herlitz junctional EB patients with revertant mosaicism. Both probands had a severe reduction in laminin-332 expression in their affected skin. Remarkably, the skin on the ...

  9. Botanical Extracts from Rosehip (Rosa canina), Willow Bark (Salix alba), and Nettle Leaf (Urtica dioica) Suppress IL-1 beta-Induced NF-kappa B Activation in Canine Articular Chondrocytes

    OpenAIRE

    Shakibaei, Mehdi; Allaway, David; Nebrich, Simone; Mobasheri, Ali

    2012-01-01

    The aim of this study was to characterize the anti-inflammatory mode of action of botanical extracts from rosehip (Rosa canina), willow bark (Salix alba), and nettle leaf (Urtica dioica) in an in vitro model of primary canine articular chondrocytes. Methods. The biological effects of the botanical extracts were studied in chondrocytes treated with IL-1 beta for up to 72h. Expression of collagen type II, cartilage-specific proteoglycan (CSPG), beta 1-integrin, SOX-9, COX-2, and MMP-9 and MMP-1...

  10. Can the state of cancer chemotherapy resistance be reverted by epigenetic therapy?

    Directory of Open Access Journals (Sweden)

    Duenas-Gonzalez Alfonso

    2006-07-01

    Full Text Available Abstract Background Transcriptome analysis shows that the chemotherapy innate resistance state of tumors is characterized by: poorly dividing tumor cells; an increased DNA repair; an increased drug efflux potential by ABC-transporters; and a dysfunctional ECM. Because chemotherapy resistance involves multiple genes, epigenetic-mediated changes could be the main force responsible of this phenotype. Our hypothesis deals with the potential role of epigenetic therapy for affecting the chemotherapy resistant phenotype of malignant tumors. Presentation of the hypothesis Recent studies reveal the involvement of DNA methylation and histone modifications in the reprogramming of the genome of mammalian cells in cancer. In this sense, it can be hypothesized that epigenetic reprogramming can participate in the establishment of an epigenetic mark associated with the chemotherapy resistant phenotype. If this were correct, then it could be expected that agents targeting DNA methylation and histone deacetylation would by reverting the epigenetic mark induce a global expression profile that mirror the observed in untreated resistant cells. Testing the hypothesis It is proposed to perform a detailed analysis using all the available databases where the gene expression of primary tumors was analyzed and data correlated with the therapeutic outcome to determine whether a transcriptome profiling of "resistance" is observed. Assuming an epigenetic programming determines at some level the intrinsic resistant phenotype, then a similar pattern of gene expression dictated by an epigenetic mark should also be found in cell acquiring drug resistance. If these expectations are meet, then it should be further investigated at the genomic level whether these phenotypes are associated to certain patterns of DNA methylation and chromatin modification. Once confirmed the existence of an epigenetic mark associated to either the intrinsic or acquired chemotherapy resistant phenotype

  11. Energy-Saving Melting and Revert Reduction Technology (E-SMARRT): Final Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    White, Thornton C [SCRA Appiled R& D

    2014-03-31

    Energy-Saving Melting and Revert Reduction Technology (E-SMARRT) is a balanced portfolio of R&D tasks that address energy-saving opportunities in the metalcasting industry. E-SMARRT was created to: • Improve important capabilities of castings • Reduce carbon footprint of the foundry industry • Develop new job opportunities in manufacturing • Significantly reduce metalcasting process energy consumption and includes R&D in the areas of: • Improvements in Melting Efficiency • Innovative Casting Processes for Yield Improvement/Revert Reduction • Instrumentation and Control Improvement • Material properties for Casting or Tooling Design Improvement The energy savings and process improvements developed under E-SMARRT have been made possible through the unique collaborative structure of the E-SMARRT partnership. The E-SMARRT team consisted of DOE’s Office of Industrial Technology, the three leading metalcasting technical associations in the U.S: the American Foundry Society; the North American Die Casting Association; and the Steel Founders’ Society of America; and SCRA Applied R&D, doing business as the Advanced Technology Institute (ATI), a recognized leader in distributed technology management. This team provided collaborative leadership to a complex industry composed of approximately 2,000 companies, 80% of which employ less than 100 people, and only 4% of which employ more than 250 people. Without collaboration, these new processes and technologies that enable energy efficiencies and environment-friendly improvements would have been slow to develop and had trouble obtaining a broad application. The E-SMARRT R&D tasks featured low-threshold energy efficiency improvements that are attractive to the domestic industry because they do not require major capital investment. The results of this portfolio of projects are significantly reducing metalcasting process energy consumption while improving the important capabilities of metalcastings. Through June

  12. Activation of vanadium nitrogenase expression in Azotobacter vinelandii DJ54 revertant in the presence of molybdenum.

    Science.gov (United States)

    Lei, S; Pulakat, L; Gavini, N

    2000-09-29

    Azotobacter vinelandii carries three different and genetically distinct nitrogenase systems on its chromosome. Expression of all three nitrogenases is repressed by high concentrations of fixed nitrogen. Expression of individual nitrogenase systems is under the control of specific metal availability. We have isolated a novel type of A. vinelandii DJ54 revertant, designated A. vinelandii BG54, which carries a defined deletion in the nifH gene and is capable of diazotrophic growth in the presence of molybdenum. Inactivation of nifDK has no effect on growth of this mutant strain in nitrogen-free medium suggesting that products of the nif system are not involved in supporting diazotrophic growth of A. vinelandii BG54. Similar to the wild type, A. vinelandii BG54 is also sensitive to 1 mM tungsten. Tn5-B21 mutagenesis to inactivate the genes specific to individual systems revealed that the structural genes for vnf nitrogenase are required for diazotrophic growth of A. vinelandii BG54. Analysis of promoter activity of different nif systems revealed that the vnf promoter is activated in A. vinelandii BG54 in the presence of molybdenum. Based on these data we conclude that A. vinelandii BG54 strain utilizes vnf nitrogenase proteins to support its diazotrophic growth. PMID:11018539

  13. Co-expression of α9β1 integrin and VEGF-D confers lymphatic metastatic ability to a human breast cancer cell line MDA-MB-468LN.

    Directory of Open Access Journals (Sweden)

    Mousumi Majumder

    Full Text Available INTRODUCTION AND OBJECTIVES: Lymphatic metastasis is a common occurrence in human breast cancer, mechanisms remaining poorly understood. MDA-MB-468LN (468LN, a variant of the MDA-MB-468GFP (468GFP human breast cancer cell line, produces extensive lymphatic metastasis in nude mice. 468LN cells differentially express α9β1 integrin, a receptor for lymphangiogenic factors VEGF-C/-D. We explored whether (1 differential production of VEGF-C/-D by 468LN cells provides an autocrine stimulus for cellular motility by interacting with α9β1 and a paracrine stimulus for lymphangiogenesis in vitro as measured with capillary-like tube formation by human lymphatic endothelial cells (HMVEC-dLy; (2 differential expression of α9 also promotes cellular motility/invasiveness by interacting with macrophage derived factors; (3 stable knock-down of VEGF-D or α9 in 468LN cells abrogates lymphangiogenesis and lymphatic metastasis in vivo in nude mice. RESULTS: A comparison of expression of cyclo-oxygenase (COX-2 (a VEGF-C/-D inducer, VEGF-C/-D and their receptors revealed little COX-2 expression by either cells. However, 468LN cells showed differential VEGF-D and α9β1 expression, VEGF-D secretion, proliferative, migratory/invasive capacities, latter functions being stimulated further with VEGF-D. The requirement of α9β1 for native and VEGF-D-stimulated proliferation, migration and Erk activation was demonstrated by treating with α9β1 blocking antibody or knock-down of α9. An autocrine role of VEGF-D in migration was shown by its impairment by silencing VEGF-D and restoration with VEGF-D. 468LN cells and their soluble products stimulated tube formation, migration/invasiveness of HMVEC-dLy cell in a VEGF-D dependent manner as indicated by the loss of stimulation by silencing VEGF-D in 468LN cells. Furthermore, 468LN cells showed α9-dependent stimulation of migration/invasiveness by macrophage products. Finally, capacity for intra-tumoral lymphangiogenesis and

  14. Clinical and demographic features of vertigo: findings from the REVERT registry

    Directory of Open Access Journals (Sweden)

    Sam eAgus

    2013-05-01

    Full Text Available IntroductionDespite being a common disease, data on vertigo management in a real-world setting are scarce. AimsTo provide information on the vertigo and its management in a real-world setting.Materials and MethodsData were collected from 4,294 patients with vertigo in 13 countries over 28 months via a multi-national, non-interventional observational study (the so-called REVERT registry. Data included medical history and details of anti-vertigo therapy. ‘Clinical global impression’ (CGI of severity (CGI-S was assessed at baseline (V1 and then at 6 months follow-up (V2 along with CGI change (CGI-C. All variables were analysed descriptively. ResultsThe majority of patients were female, >40 years of age, and almost half had co-morbid cardiovascular disease. Diagnoses were split into 4 categories: 37.2% ‘other vertigo of peripheral vestibular origin’, 26.9% benign paroxysmal positional vertigo (BPPV, 20.5% ‘peripheral vestibular vertigo of unknown origin’ and 15.4% Menière’s disease (MD. Betahistine was the most commonly prescribed therapy prior to and after enrolment, and was followed by piracetam, ginkgo biloba and diuretics. MD had the highest proportion of betahistine treated patients. Almost half of patients were ‘moderately ill’ at V1 based on CGI-S. At V2, patient distribution moved towards ‘less severe illness’ (91.0% improved.The greatest improvements were in the more severely ill, and those with BPPV or ‘other vertigo of peripheral origin’. ConclusionsThere was a reduction in illness severity over the course of the study, some of which is likely to be due to pharmacological intervention. Further studies are needed to confirm these results.

  15. The burden and impact of vertigo: findings from the REVERT patient registry

    Directory of Open Access Journals (Sweden)

    Heike eBenecke

    2013-10-01

    Full Text Available Objective: Despite the high prevalence of vertigo globally and an acknowledged, but underreported, effect on an individual’s wellbeing, few studies have evaluated the burden on healthcare systems and society. This study was aimed to quantitatively determine the impact of vertigo on healthcare resource use and work productivity. Methods: The economic burden of vertigo was assessed through a multi-country, non-interventional, observational registry of vertigo patients: the Registry to Evaluate the Burden of Disease in Vertigo (REVERT. Patients included were those with a new diagnosis of Meniere’s disease (MD, benign paroxysmal positional vertigo (BPPV, other vertigo of peripheral vestibular origin or peripheral vestibular vertigo of unknown origin. Results: A total of 4,294 patients at 618 centers in 13 countries were included during the registry. Of the 4,105 patients analyzed, only half were in employment. Among this working patient population, 69.8% had reduced their workload, 63.3% had lost working days and 4.6% had changed and 5.7% had quit their jobs, due to vertigo symptoms. Use of healthcare services among patients was high. In the 3 months preceding Visit 1, patients used emergency services 0.4 ± 0.9 times, primary care consultations 1.6 ± 1.8 times and specialist consultations 1.4 ± 2.0 times (all mean ± SD. A mean of 2.0 ± 5.4 days/patient was also spent in hospital due to vertigo.Conclusions: In addition to the negative impact on the patient from a humanistic perspective, vertigo has considerable impact on work productivity and healthcare resource use.

  16. Promising genomic transfectant into Xeroderma pigmentosum group A with highly amplified mouse DNA and intermediate UV resistance turns revertant

    International Nuclear Information System (INIS)

    Following transfection of genomic mouse DNA into an SV40 transformed fibroblast cell line from a patient with Xeroderma pigmentosum (complementation group A, XPA), a single UV resistant cell clone was isolated out of a total of 10(4) independent transfectants. The recipient XPA cell line has as yet not produced spontaneous revertants among 2.2 x 10(8) cells. The isolated cell clone contains 50-70 kb of mouse sequences which are heavily amplified (500-fold), and has acquired both intermediate resistance to UV killing and intermediate unscheduled DNA synthesis (UDS) capacity. By continued passage without selective pressure, cells were generated, which had lost both the dominant marker gene and repetitive mouse sequences. Single colonies of these cells were still intermediately resistant to UV suggesting that either undetected unique mouse DNA had segregated from the bulk of repetitive DNA, or, more likely, that the initially isolated transfectant was a spontaneous revertant. This documents that a persuasive clone isolated can still be a false positive (spontaneous revertant) and that an extremely laborious approach may lead into a dead end

  17. THE DIALECTICS OF HUMANISM AND A POSTMODERN PLAY IN THE WORKS BY A.PEREZ-REVERTE ( THE SIEGE

    Directory of Open Access Journals (Sweden)

    Blinova M. P.

    2014-11-01

    Full Text Available The analysis of the philosophical and narrative structure’s features in the novels by modern Spanish writer A. Pérez-Reverte has been reviewed in this article. His works present an example of the postmodern double coding, that is the compound a mass and elite, playing and moral. It allows to avoid the text’s tendentiousness and to keep the content. In the novel “The Siege” A. Pérez-Reverte uses the detective story, but he deconstructs it: keeping the traditional plot’s scheme the writer changes the images’ interpretation, the meaning of the finale, adds the intertext and the conceptual metaphors (the chess, the net, the herbarium. They code some philosophical ideas about human life. At the same time A. Pérez-Reverte asks the traditional classic literature’s questions and shows how war influences the person, what is love and so on. He also makes a psychological analysis of actions’ reasons and reveal the feelings’ contradictory. As a result, the multilayer, nonlinear and metaphorical narrative has been viewed as a particular tool of the author’s opinion realization and the philosophical implication’s creation. And with it the postmodern polysemic text associates with a psychological analysis and humanism

  18. Marine bromophenol bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane inhibits the proliferation, migration, and invasion of hepatocellular carcinoma cells via modulating β1-integrin/FAK signaling.

    Science.gov (United States)

    Wu, Ning; Luo, Jiao; Jiang, Bo; Wang, Lijun; Wang, Shuaiyu; Wang, Changhui; Fu, Changqing; Li, Jian; Shi, Dayong

    2015-02-01

    Bis (2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL). Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM). Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL) significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL) completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9) is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK) is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents. PMID:25689564

  19. Marine Bromophenol Bis (2,3-Dibromo-4,5-dihydroxy-phenyl-methane Inhibits the Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells via Modulating β1-Integrin/FAK Signaling

    Directory of Open Access Journals (Sweden)

    Ning Wu

    2015-02-01

    Full Text Available Bis (2,3-dibromo-4,5-dihydroxy-phenyl-methane (BDDPM is a natural bromophenol compound derived from marine algae. Previous reports have shown that BDDPM possesses antimicrobial activity. In the present study, we found that BDDPM has cytotoxic activity on a wide range of tumor cells, including BEL-7402 cells (IC50 = 8.7 μg/mL. Further studies have shown that prior to the onset of apoptosis, the BDDPM induces BEL-7402 cell detachment by decreasing the adherence of cells to the extracellular matrix (ECM. Detachment experiments have shown that the treatment of BEL-7402 cells with low concentrations of BDDPM (5.0 μg/mL significantly inhibits cell adhesion to fibronectin and collagen IV as well as cell migration and invasion. High doses of BDDPM (10.0 μg/mL completely inhibit the migration of BEL-7402 cells, and the expression level of MMPs (MMP-2 and MMP-9 is significantly decreased. Moreover, the expression of β1-integrin and focal adhesion kinase (FAK is found to be down-regulated by BDDPM. This study suggests that BDDPM has a potential to be developed as a novel anticancer therapeutic agent due to its anti-metastatic activity and also indicates that BDDPM, which has a unique chemical structure, could serve as a lead compound for rational drug design and for future development of anticancer agents.

  20. [Levels of beta-endorphin in response to exercise and overtraining].

    Science.gov (United States)

    Cunha, Giovani S; Ribeiro, Jerri L; Oliveira, Alvaro R

    2008-06-01

    Overtraining (OT) is a complex and multifactorial sport phenomenon, and there is no independent marker that can diagnose OT. Interestingly, some symptoms of OT are related to beta-endorphin (beta-end(1-31)) effects. Some of its effects, such as analgesia, increasing lactate tolerance, and exercise-induced euphoria, are important for training. These effects can be reverted by detraining or OT, which may cause decrease in performance, reduced load tolerance, and depression. The main stimulus for beta-end(1-31) secretion is to exercise because its secretion is volume/intensity dependent for both aerobic and anaerobic exercise. Excess training, however, may reduce beta-end(1-31) concentrations, thus altering its beneficial effects. Therefore, beta-end(1-31) could be used as an additional OT marker, mainly because its effects are strongly related to OT symptoms. PMID:18604371

  1. El Club Dumas de Arturo Pérez-Reverte como paradigma de la narrativa posmoderna española

    Directory of Open Access Journals (Sweden)

    Isaac Gómez Laguna

    2015-06-01

    Full Text Available El presente artículo ofrece un análisis de los diferentes rasgos posmodernistas que aparecen de manera explícita en El Club Dumas, novela insignia de la narrativa posmoderna en España, en torno a tres ejes centrales: a género de la obra e intertextualidad, b indeterminación e irrealidad, y c individuo y sociedad. Mediante esta reflexión pretendemos evidenciar que su autor, Arturo Pérez-Reverte, no solo crea una novela puramente posmoderna, sino que su obra le sirve para teorizar acerca del posmodernismo.

  2. Recombinant laminin-8 (alpha(4)beta(1)gamma(1)). Production, purification,and interactions with integrins.

    Science.gov (United States)

    Kortesmaa, J; Yurchenco, P; Tryggvason, K

    2000-05-19

    Laminins are a large family of heterotrimeric extracellular matrix glycoproteins that, in addition to having structural roles, take part in the regulation of processes such as cell migration, differentiation, and proliferation. The laminin alpha(4) chain is widely distributed both in adults and during development in tissues such as cardiac, skeletal and smooth muscle fibers, vascular endothelia, lungs, and in peripheral nerves. It can associate with laminin beta(1)/gamma(1) chains to form laminin-8 and with the beta(2)/gamma(1) chains to form laminin-9. Functional studies on these laminins have been hampered by poor availability of the protein in pure and soluble forms. To facilitate studies on laminin-8, recombinant laminin-8 was produced in a mammalian expression system, purified and shown to form native Y-shaped molecules in rotary shadowing electron microscopy. Integrins mediating cell adhesion to laminin-8 were identified using function-blocking mAbs. The integrin specificities were found to differ somewhat from that of laminin-1. Integrin alpha(6)beta(1) was found to be a major mediator of adhesion of HT-1080 and cultured capillary endothelial cells to laminin-8. Considering the expression patterns of laminin-8 and integrin alpha(6)beta(1) it is likely that the former is a ligand for the latter in vivo as well. PMID:10809728

  3. The Lifestyle Carbon Dividend: Assessment of the Carbon Sequestration Potential of Grasslands and Pasturelands Reverted to Native Forests

    Science.gov (United States)

    Rao, S.; Jain, A. K.; Shu, S.

    2015-12-01

    What is the potential of a global transition to a vegan lifestyle to sequester carbon and mitigate climate change? To answer this question, we use an Earth System Model (ESM), the Integrated Science Assessment Model (ISAM). ISAM is a fully coupled biogeochemistry (carbon and nitrogen cycles) and biogeophysics (hydrology and thermal energy) ESM, which calculates carbon sources and sinks due to land cover and land use change activities, such as reforestation and afforestation. We calculate the carbon sequestration potential of grasslands and pasturelands that can be reverted to native forests as 265 GtC on 1.96E+7 km2 of land area, just 41% of the total area of such lands on Earth. The grasslands and pasturelands are assumed to revert back to native forests which existed prior to any human intervention and these include tropical, temperate and boreal forests. The results are validated with above ground regrowth measurements. Since this carbon sequestration potential is greater than the 240 GtC of that has been added to the atmosphere since the industrial era began, it shows that such global lifestyle transitions have tremendous potential to mitigate and even reverse climate change.

  4. Transforming growth factor beta receptor 2 (TGFBR2 changes sialylation in the microsatellite unstable (MSI Colorectal cancer cell line HCT116.

    Directory of Open Access Journals (Sweden)

    Jennifer Lee

    Full Text Available Aberrant glycosylation is a common feature of many malignancies including colorectal cancers (CRCs. About 15% of CRC show the microsatellite instability (MSI phenotype that is associated with a high frequency of biallelic frameshift mutations in the A10 coding mononucleotide microsatellite of the transforming growth factor beta receptor 2 (TGFBR2 gene. If and how impaired TGFBR2 signaling in MSI CRC cells affects cell surface glycan pattern is largely unexplored. Here, we used the TGFBR2-deficient MSI colon carcinoma cell line HCT116 as a model system. Stable clones conferring doxycycline (dox-inducible expression of a single copy wildtype TGFBR2 transgene were generated by recombinase-mediated cassette exchange (RMCE. In two independent clones, dox-inducible expression of wildtype TGFBR2 protein and reconstitution of its signaling function was shown. Metabolic labeling experiments using the tritiated sialic acid precursor N-acetyl-D-mannosamine (ManNAc revealed a significant decline (∼30% of its incorporation into newly synthesized sialoglycoproteins in a TGFBR2-dependent manner. In particular, we detected a significant decrease of sialylated ß1-integrin upon reconstituted TGFBR2 signaling which did not influence ß1-integrin protein turnover. Notably, TGFBR2 reconstitution did not affect the transcript levels of any of the known human sialyltransferases when examined by real-time RT- PCR analysis. These results suggest that reconstituted TGFBR2 signaling in an isogenic MSI cell line model system can modulate sialylation of cell surface proteins like ß1-integrin. Moreover, our model system will be suitable to uncover the underlying molecular mechanisms of altered MSI tumor glycobiology.

  5. Multidrug reverting activity toward leukemia cells in a group of new verapamil analogues with low cardiovascular activity

    DEFF Research Database (Denmark)

    Biscardi, Monica; Teodori, Elisabetta; Caporale, Roberto;

    2005-01-01

    designed and synthesized to improve their MDR-reverting activity and reduce cardiovascular effects. Cytotoxicity (WST-1 methods) and functional (calcein-acetoxymethyl (Calcein-AM)) assays were performed on a resistant cell line K-562/doxR and on the mononuclear cells (MNCs) of patients with AML...... strongest activity. Results obtained from the MNCs were superimposible to K-562/doxR. Further studies on pump functional analysis confirmed the cytotoxic test results: MM 36, CTS 27 and CTS 41 showed a striking inhibition of P-glycoprotein (Pgp) efflux in K-562/doxR and MNCs. Cardiovascular activity of MM...... 36, CTS 27 and CTS 41, that are the most interesting compounds as MDR inhibitors, followed this course: MM 36>CTS 27>CTS 41, the last one presenting no cardiovascular activity. Chemosensivity to IDA in K-562/doxR cells and AML blasts could be enhanced in vitro by the adjuvant use of the six new VRP...

  6. BETA-S, Multi-Group Beta-Ray Spectra

    International Nuclear Information System (INIS)

    1 - Description of program or function: BETA-S calculates beta-decay source terms and energy spectra in multigroup format for time-dependent radionuclide inventories of actinides, fission products, and activation products. Multigroup spectra may be calculated in any arbitrary energy-group structure. The code also calculates the total beta energy release rate from the sum of the average beta-ray energies as determined from the spectral distributions. BETA-S also provides users with an option to determine principal beta-decaying radionuclides contributing to each energy group. The CCC-545/SCALE 4.3 (or SCALE4.2) code system must be installed on the computer before installing BETA-S, which requires the SCALE subroutine library and nuclide-inventory generation from the ORIGEN-S code. 2 - Methods:Well-established models for beta-energy distributions are used to explicitly represent allowed, and 1., 2. - and 3. -forbidden transition types. Forbidden non-unique transitions are assumed to have a spectral shape of allowed transitions. The multigroup energy spectra are calculated by numerically integrating the energy distribution functions using an adaptive Simpson's Rule algorithm. Nuclide inventories are obtained from a binary interface produced by the ORIGEN-S code. BETA-S calculates the spectra for all isotopes on the binary interface that have associated beta-decay transition data in the ENSDF-95 library, developed for the BETA-S code. This library was generated from ENSDF data and contains 715 materials, representing approximately 8500 individual beta transition branches. 3 - Restrictions on the complexity of the problem: The algorithms do not treat positron decay transitions or internal conversion electrons. The neglect of positron transitions in inconsequential for most applications involving aggregate fission products, since most of the decay modes are via electrons. The neglect of internal conversion electrons may impact on the accuracy of the spectrum in the low

  7. Mutagenic activity of a fluorinated analog of the beta-adrenoceptor ligand carazolol in the Ames test

    International Nuclear Information System (INIS)

    S-1'[18F]-Fluorocarazolol (FCAR) is a fluorinated analog of the nonmutagenic beta-blocker carazolol (CAR). In former studies FCAR proved to be suitable for quantification of beta-adrenoceptors in vivo with positron emission tomography (PET). We report here that FCAR displays no acute toxicity in either rats or mice. However, FCAR induces a strong dose-related increase in the number of revertants in the Ames test. We conclude that FCAR yields mutagenic activity as measured by the Ames test

  8. Smaller is less stable: Size effects on twinning vs. transformation of reverted austenite in TRIP-maraging steels

    International Nuclear Information System (INIS)

    Steels containing reverted nanoscale austenite (γRN) islands or films dispersed in a martensitic matrix show excellent strength, ductility and toughness. The underlying microstructural mechanisms responsible for these improvements are not yet understood, but are observed to be strongly connected to the γRN island or film size. Two main micromechanical effects are conceivable in this context, namely: (i) interaction of γRN with microcracks from the matrix (crack blunting or arresting); and (ii) deformation-induced phase transformation of γRN to martensite (TRIP effect). The focus here is on the latter phenomenon. To investigate size effects on γRN transformation independent of other factors that can influence austenite stability (composition, crystallographic orientation, defect density, surrounding phase, etc.), a model (TRIP-maraging steel) microstructure is designed with support from diffusion simulations (using DICTRA software) to have the same, homogeneous chemical composition in all γRN grains. Characterization is conducted by in-situ tension and bending experiments in conjunction with high-resolution electron backscatter diffraction mapping and scanning electron microscopy imaging, as well as post-mortem transmission electron microscopy and synchrotron X-ray diffraction analysis. Results reveal an unexpected “smaller is less stable” effect due to the size-dependent competition between mechanical twinning and deformation-induced phase transformation

  9. Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism.

    Science.gov (United States)

    Kim, Kyung Eun; Jung, Youngae; Min, Soonki; Nam, Miso; Heo, Rok Won; Jeon, Byeong Tak; Song, Dae Hyun; Yi, Chin-Ok; Jeong, Eun Ae; Kim, Hwajin; Kim, Jeonghyun; Jeong, Seon-Yong; Kwak, Woori; Ryu, Do Hyun; Horvath, Tamas L; Roh, Gu Seob; Hwang, Geum-Sook

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. (1)H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications. PMID:27439777

  10. Energy Saving Melting and Revert Reduction Technology (Energy SMARRT): Manufacturing Advanced Engineered Components Using Lost Foam Casting Technology

    Energy Technology Data Exchange (ETDEWEB)

    Littleton, Harry; Griffin, John

    2011-07-31

    This project was a subtask of Energy Saving Melting and Revert Reduction Technology (Energy SMARRT) Program. Through this project, technologies, such as computer modeling, pattern quality control, casting quality control and marketing tools, were developed to advance the Lost Foam Casting process application and provide greater energy savings. These technologies have improved (1) production efficiency, (2) mechanical properties, and (3) marketability of lost foam castings. All three reduce energy consumption in the metals casting industry. This report summarizes the work done on all tasks in the period of January 1, 2004 through June 30, 2011. Current (2011) annual energy saving estimates based on commercial introduction in 2011 and a market penetration of 97% by 2020 is 5.02 trillion BTU's/year and 6.46 trillion BTU's/year with 100% market penetration by 2023. Along with these energy savings, reduction of scrap and improvement in casting yield will result in a reduction of the environmental emissions associated with the melting and pouring of the metal which will be saved as a result of this technology. The average annual estimate of CO2 reduction per year through 2020 is 0.03 Million Metric Tons of Carbon Equivalent (MM TCE).

  11. Levered and unlevered Beta

    OpenAIRE

    Fernandez, Pablo

    2003-01-01

    We prove that in a world without leverage cost the relationship between the levered beta ( L) and the unlevered beta ( u) is the No-costs-of-leverage formula: L = u + ( u - d) D (1 - T) / E. We also analyze 6 alternative valuation theories proposed in the literature to estimate the relationship between the levered beta and the unlevered beta (Harris and Pringle (1985), Modigliani and Miller (1963), Damodaran (1994), Myers (1974), Miles and Ezzell (1980), and practitioners) and prove that all ...

  12. Integrin alpha3beta1, a novel receptor for alpha3(IV) noncollagenous domain and a trans-dominant Inhibitor for integrin alphavbeta3.

    Science.gov (United States)

    Borza, Corina M; Pozzi, Ambra; Borza, Dorin-Bogdan; Pedchenko, Vadim; Hellmark, Thomas; Hudson, Billy G; Zent, Roy

    2006-07-28

    Exogenous soluble human alpha3 noncollagenous (NC1) domain of collagen IV inhibits angiogenesis and tumor growth. These biological functions are attributed to the binding of alpha3NC1 to integrin alphavbeta3. However, in some tumor cells that express integrin alphavbeta3, the alpha3NC1 domain does not inhibit proliferation, suggesting that integrin alphavbeta3 expression is not sufficient to mediate the anti-tumorigenic activity of this domain. Therefore, in the present study, we searched for novel binding receptors for the soluble alpha3NC1 domain in cells lacking alphavbeta3 integrin. In these cells, soluble alpha3NC1 bound integrin alpha3beta1; however, unlike alphavbeta3, alpha3beta1 integrin did not mediate cell adhesion to immobilized alpha3NC1 domain. Interestingly, in cells lacking integrin alpha3beta1, adhesion to the alpha3NC1 domain was enhanced due to activation of integrin alphavbeta3. These findings indicate that integrin alpha3beta1 is a receptor for the alpha3NC1 domain and transdominantly inhibits integrin alphavbeta3 activation. Thus integrin alpha3beta1, in conjunction with integrin alphavbeta3, modulates cellular responses to the alpha3NC1 domain, which may be pivotal in the mechanism underpinning its anti-angiogenic and anti-tumorigenic activities. PMID:16731529

  13. Betting Against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    .S. equities, 20 international equity markets, Treasury bonds, corporate bonds, and futures; (2) A betting-against-beta (BAB) factor, which is long leveraged low beta assets and short high-beta assets, produces significant positive risk-adjusted returns; (3) When funding constraints tighten, the return of the...

  14. Forward-Looking Betas

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Jacobs, Kris; Vainberg, Gregory

    Few issues are more important for finance practice than the computation of market betas. Existing approaches compute market betas using historical data. While these approaches differ in terms of statistical sophistication and the modeling of the time-variation in the betas, they are all backward-...

  15. Estudio de viabilidad de centro de estética con formación y distribución: Alejandra Revert-Pronails

    OpenAIRE

    Coterillo Ruisánchez, Rodolfo

    2016-01-01

    RESUMEN: En este trabajo se va a realizar un plan de viabilidad, en relación con la empresa “Alejandra Revert – Pronails” para la ampliación de su actividad tras la apertura de un nuevo centro en el municipio de Santa María de Cayón, más concretamente al pueblo de Sarón. La empresa “Alejandra Revert – Pronails” se dedica a la realización de trabajos de estética tales como manicura o maquillaje y a venta de productos cosméticos, para lo que trabaja con una de las mejores marcas actualmente ...

  16. An agent-based approach with collaboration among agents. Estimation of wholesale electricity price on PJM and artificial data generated by a mean reverting model

    International Nuclear Information System (INIS)

    This study examines the performance of MAIS (Multi-Agent Intelligent Simulator) equipped with various learning capabilities. In addition to the learning capabilities, the proposed MAIS incorporates collaboration among agents. The proposed MAIS is applied to estimate a dynamic change of wholesale electricity price in PJM (Pennsylvania-New Jersey-Mainland) and an artificial data set generated by a mean reverting model. Using such different types of data sets, the methodological validity of MAIS is confirmed by comparing it with other well-known alternatives in computer science. This study finds that the MAIS needs to incorporate both the mean reverting model and the collaboration behavior among agents in order to enhance its estimation capability. The MAIS discussed in this study will provide research on energy economics with a new numerical capability that can investigate a dynamic change of not only wholesale electricity price but also speculation and learning process of traders. (author)

  17. Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction.

    Science.gov (United States)

    López-Domínguez, José Alberto; Cánovas, Ángela; Medrano, Juan F; Islas-Trejo, Alma; Kim, Kyoungmi; Taylor, Sandra L; Villalba, José Manuel; López-Lluch, Guillermo; Navas, Plácido; Ramsey, Jon J

    2016-05-01

    Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in the liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-β) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid β-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil. PMID:26875793

  18. Chromosome 17p13.2 transfer reverts transformation phenotypes and Fas-mediated apoptosis in breast epithelial cells.

    Science.gov (United States)

    Lareef, Mohamed H; Tahin, Quivo; Song, Joon; Russo, Irma H; Mihaila, Dana; Slater, Carolyn M; Balsara, Binaifer; Testa, Joseph R; Broccoli, Dominique; Grobelny, Jennifer V; Mor, Gil; Cuthbert, Andrew; Russo, Jose

    2004-04-01

    Transformation of the human breast epithelial cells (HBEC) MCF-10F with the carcinogen benz(a)pyrene (BP) into BP1-E cells resulted in the loss of the chromosome 17 p13.2 locus (D17S796 marker) and formation of colonies in agar-methocel (colony efficiency (CE)), loss of ductulogenic capacity in collagen matrix, and resistance to anti-Fas monoclonal antibody (Mab)-induced apoptosis. For testing the role of that specific region of chromosome 17 in the expression of transformation phenotypes, we transferred chromosome 17 from mouse fibroblast donors to BP1-E cells. Chromosome 11 was used as negative control. After G418 selection, nine clones each were randomly selected from BP1-E-11neo and BP1-E-17neo hybrids, respectively, and tested for the presence of the donor chromosomes by fluorescent in situ hybridization and polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analyses. Sensitivity to Fas Mab-induced apoptosis and evaluation of transformation phenotype expression were tested in MCF-10F, BP1-E, and nine BP1-E-11neo and BP1-E-17neo clones each. Six BP1-E-17neo clones exhibited a reversion of transformation phenotypes and a dose dependent sensitivity to Fas Mab-induced apoptosis, behaving similarly to MCF-10F cells. All BP1-E-11neo, and three BP1-E-17neo cell clones, like BP1-E cells, retained a high CE, loss of ductulogenic capacity, and were resistant to all Fas Mab doses tested. Genomic analysis revealed that those six BP1-E-17neo clones that were Fas-sensitive and reverted their transformed phenotypes had retained the 17p13.2 (D17S796 marker) region, whereas it was absent in all resistant clones, indicating that the expression of transformation phenotypes and the sensitivity of the cells to Fas-mediated apoptosis were under the control of genes located in this region. PMID:15057875

  19. Koedam {beta} factors revisited

    Energy Technology Data Exchange (ETDEWEB)

    Lawler, J.E. [Physics Department, University of Wisconsin, Madison, WI (United States); Doughty, D.A. [Perkin-Elmer Optoelectronics, Santa Clara, CA (United States); Lister, G.G. [OSRAM SYLVANIA Inc., Beverly, MA (United States)

    2002-07-21

    A Koedam {beta} factor makes it possible to compute the total output power in line radiation from a positive column discharge using a single radiance measurement normal to an aperture in the wall. The results of analytic derivations of {beta} factors are presented for columns with uniform ({beta}=1.0) and parabolic ({beta}=0.75) excitation rates per unit volume and with negligible opacity. A Monte Carlo code for simulating radiation trapping with a spatially uniform density of absorbing atoms is then used to determine {beta} factors as a function of opacity. The code includes partial frequency redistribution and a Voigt line shape with radiative broadening, resonance collisional broadening, and Doppler broadening. The resulting {beta} factors are found to be nearly independent of opacity over a wide range of column radii for spectral line shapes dominated by Doppler broadening or by resonance collisional broadening. Additional Monte Carlo simulations are used to study {beta} factors as a function of a non-uniform density of absorbing atoms from radial cataphoresis with line shapes dominated by Doppler broadening, foreign gas broadening, and resonance collisional broadening. Radial cataphoresis is found to increase {beta} factors in all cases. Geometrical effects, refraction, and imperfect transmission at the glass wall are studied and found to decrease {beta} factors. (author)

  20. Beta-energy averaging and beta spectra

    International Nuclear Information System (INIS)

    A simple yet highly accurate method for approximately calculating spectrum-averaged beta energies and beta spectra for radioactive nuclei is presented. This method should prove useful for users who wish to obtain accurate answers without complicated calculations of Fermi functions, complex gamma functions, and time-consuming numerical integrations as required by the more exact theoretical expressions. Therefore, this method should be a good time-saving alternative for investigators who need to make calculations involving large numbers of nuclei (e.g., fission products) as well as for occasional users interested in restricted number of nuclides. The average beta-energy values calculated by this method differ from those calculated by ''exact'' methods by no more than 1 percent for nuclides with atomic numbers in the 20 to 100 range and which emit betas of energies up to approximately 8 MeV. These include all fission products and the actinides. The beta-energy spectra calculated by the present method are also of the same quality

  1. Double beta decay experiments

    OpenAIRE

    Barabash, A. S.

    2011-01-01

    The present status of double beta decay experiments is reviewed. The results of the most sensitive experiments are discussed. Proposals for future double beta decay experiments with a sensitivity to the $$ at the level of (0.01--0.1) eV are considered.

  2. Negative Beta Encoder

    CERN Document Server

    Kohda, Tohru; Aihara, Kazuyuki

    2008-01-01

    A new class of analog-digital (A/D), digital-analog (D/A) converters as an alternative to conventional ones, called $\\beta$-encoder, has been shown to have exponential accuracy in the bit rates while possessing self-correction property for fluctuations of amplifier factor $\\beta$ and quantizer threshold $\

  3. Betting against Beta

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Heje Pedersen, Lasse

    2014-01-01

    We present a model with leverage and margin constraints that vary across investors and time. We find evidence consistent with each of the model's five central predictions: (1) Because constrained investors bid up high-beta assets, high beta is associated with low alpha, as we find empirically for...

  4. Rapid synthesis of beta zeolites

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  5. Decreased expression of the amplified mdr1 gene in revertants of multidrug-resistant human myelogenous leukemia K562 occurs without loss of amplified DNA.

    OpenAIRE

    Sugimoto, Y.; Roninson, I B; Tsuruo, T.

    1987-01-01

    Amplification and increased expression of the mdr1 gene associated with multidrug resistance in human tumors were found in multidrug-resistant sublines of human myelogenous leukemia K562 selected with vincristine (K562/VCR) or adriamycin (K562/ADM). In two revertant cell lines of K562/ADM, amplification of the mdr1 gene was maintained at the same level as in K562/ADM, but expression of the 4.5-kilobase mdr1 mRNA was greatly decreased, indicating that amplified genes may be inactivated at the ...

  6. Beta-carotene

    Science.gov (United States)

    ... and deterioration of the lining of the mouth (oral mucositis). Taking beta-carotene by mouth doesn’t appear to prevent the development of oral mucositis during radiation therapy or chemotherapy. Pancreatic cancer. Taking ...

  7. Neutrinoless double beta decay

    International Nuclear Information System (INIS)

    The physics potential of neutrinoless double beta decay is discussed. Furthermore, experimental considerations as well as the current status of experiments are presented. Finally, an outlook towards the future, work on nuclear matrix elements and alternative processes is given. (author)

  8. Neutrinoless double beta decay

    Indian Academy of Sciences (India)

    Kai Zuber

    2012-10-01

    The physics potential of neutrinoless double beta decay is discussed. Furthermore, experimental considerations as well as the current status of experiments are presented. Finally, an outlook towards the future, work on nuclear matrix elements and alternative processes is given.

  9. [High beta tokamak research

    International Nuclear Information System (INIS)

    Our activities on High Beta Tokamak Research during the past 20 months of the present grant period can be divided into six areas: reconstruction and modeling of high beta equilibria in HBT; measurement and analysis of MHD instabilities observed in HBT; measurements of impurity transport; diagnostic development on HBT; numerical parameterization of the second stability regime; and conceptual design and assembly of HBT-EP. Each of these is described in some detail in the sections of this progress report

  10. High beta multipoles

    International Nuclear Information System (INIS)

    Multipoles are being employed as devices to study fusion issues and plasma phenomena at high values of beta (plasma pressure/magnetic pressure) in a controlled manner. Due to their large volume, low magnetic field (low synchrotron radiation) region, they are also under consideration as potential steady state advanced fuel (low neutron yield) reactors. Present experiments are investigating neoclassical (bootstrap and Pfirsch-Schlueter) currents and plasma stability at extremely high beta

  11. Autoregressive conditional beta

    OpenAIRE

    Yunmi Kim

    2012-01-01

    The capital asset pricing model provides various predictions about equilibrium expected returns on risky assets. One key prediction is that the risk premium on a risky asset is proportional to the nondiversifiable market risk measured by the asset's beta coefficient. This paper proposes a new method for estimating and drawing inferences from a time-varying capital asset pricing model. The proposed method, which can be considered a vector autoregressive model for multiple beta coefficients, is...

  12. Laminin-8 (alpha4beta1gamma1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation.

    Science.gov (United States)

    Geberhiwot, T; Assefa, D; Kortesmaa, J; Ingerpuu, S; Pedraza, C; Wondimu, Z; Charo, J; Kiessling, R; Virtanen, I; Tryggvason, K; Patarroyo, M

    2001-01-01

    Laminins are a growing family of large heterotrimeric proteins with cell adhesive and signalling functions. They are major components of basement membranes and are found in many organs, including the vasculature and other compartments of bone marrow, thymus, lymph nodes and spleen. However, expression, recognition and use of laminin isoforms by lymphoid cells are poorly understood. In the present study, lymphoid T cells (Jurkat) were found to synthesize laminin alpha4, beta1 and gamma1 mRNAs and polypeptides and to assemble the chains into laminin-8. Lymphoblastoid B (NAD-20) cells, lymphoid NK (NKL) cells and blood lymphocytes also contained laminin-8 and, after cell permeabilization, practically all blood lymphocytes reacted with mAbs to laminin beta1 and gamma1 chains. Following stimulation, blood lymphocytes secreted laminin-8, and this laminin isoform, but not laminin-10/11(alpha5beta1gamma1/alpha5beta2gamma1), promoted chemokine-induced migration of the cells. In an activation-dependent manner, purified blood CD4 T cells adhered to immobilized laminin-8 and laminin-10/11 by using alpha6beta1 integrin, but minimally to laminin-1 (alpha1beta1gamma1). Accordingly, laminin-8 and laminin-10/11, but not laminin-1, strongly costimulated proliferation of the T cells via the same integrin. Thus, lymphoid cells are able to synthesize and secrete complete laminin molecules. In addition, synthesis of laminin-8 and recognition of laminin-8 and -10/11 by lymphocytes indicate relevance of these laminin isoforms in lymphocyte physiology. PMID:11148143

  13. MST1: a promising therapeutic target to restore functional beta cell mass in diabetes.

    Science.gov (United States)

    Ardestani, Amin; Maedler, Kathrin

    2016-09-01

    The loss of insulin-producing beta cells by apoptosis is a hallmark of all forms of diabetes mellitus. Strategies to prevent beta cell apoptosis and dysfunction are urgently needed to restore the insulin-producing cells and to prevent severe diabetes progression. We recently identified the serine/threonine kinase known as mammalian sterile 20-like kinase 1 (MST1) as a critical regulator of apoptotic beta cell death and dysfunction. MST1 activates several apoptotic signalling pathways, which further stimulate its own cleavage, leading to a vicious cycle of cell death. This led us to hypothesise that MST1 signalling is central to the initiation of beta cell death in diabetes. We found that MST1 is strongly activated in a diabetic beta cell and induces not only its death but also directly impairs insulin secretion through promoting proteasomal degradation of key beta cell transcription factor, pancreatic and duodenal homeobox 1 (PDX1), which is critical for insulin production.Pre-clinical studies in various animal models of diabetes have reported that MST1 deficiency remarkably restores normoglycaemia and beta cell function and prevents the development of diabetes. Importantly, MST1 deficiency can revert fully diabetic beta cells to a non-diabetic state. MST1 may serve as a target for the development of novel therapies for diabetes that trigger the cause of the disease, namely, the destruction of the beta cells. The major current focus of our investigation is to identify and test the efficacy of potent inhibitors of this death signalling pathway to protect beta cells against the effects of autoimmune attack in type 1 diabetes and to preserve beta cell mass and function in type 2 diabetes. This review summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Heiko Lickert and colleagues, DOI: 10.1007/s00125-016-3949-9 , and by Harry

  14. INaP selective inhibition reverts precocious inter- and motorneurons hyperexcitability in the Sod1-G93R zebrafish ALS model

    Science.gov (United States)

    Benedetti, Lorena; Ghilardi, Anna; Rottoli, Elsa; De Maglie, Marcella; Prosperi, Laura; Perego, Carla; Baruscotti, Mirko; Bucchi, Annalisa; Del Giacco, Luca; Francolini, Maura

    2016-01-01

    The pathogenic role of SOD1 mutations in amyotrophic lateral sclerosis (ALS) was investigated using a zebrafish disease model stably expressing the ALS-linked G93R mutation. In addition to the main pathological features of ALS shown by adult fish, we found remarkably precocious alterations in the development of motor nerve circuitry and embryo behavior, and suggest that these alterations are prompted by interneuron and motor neuron hyperexcitability triggered by anomalies in the persistent pacemaker sodium current INaP. The riluzole-induced modulation of INaP reduced spinal neuron excitability, reverted the behavioral phenotypes and improved the deficits in motor nerve circuitry development, thus shedding new light on the use of riluzole in the management of ALS. Our findings provide a valid phenotype-based tool for unbiased in vivo drug screening that can be used to develop new therapies. PMID:27079797

  15. Double beta decay experiments

    International Nuclear Information System (INIS)

    The great sensitivity of double beta decay to neutrino mass and right handed currents has motivated many new and exciting attempts to observe this elusive nuclear phenomenon directly. Experiments in operation and other coming on line in the next one or two years are expected to result in order-of-magnitude improvements in detectable half lives for both the two-neutrino and no-neutrino modes. A brief history of double beta decay experiments is presented together with a discussion of current experimental efforts, including a gas filled time projection chamber being used to study selenium-82. (author)

  16. Plasma beta HCG determination

    International Nuclear Information System (INIS)

    There are three important indications for the early diagnosis of pregnancy through the determination of the beta sub-unit of chorionic gonadotrophin using radioimmunoassay: 1) some patient's or doctor's anxiety to discover the problem; 2) when it will be necessary to employ diagnostic or treatment procedures susceptible to affect the ovum; and 3) in the differential diagnosis of amenorrhoea, uterine hemorrhage and abdominal tumors. Other user's are the diagnosis of missed absortion, and the diagnosis and follow-up of chrorioncarcinoma. The AA. studied 200 determinations of plasma beta-HCG, considering the main difficulties occuring in the clinical use of this relevant laboratory tool in actual Obstetrics. (author)

  17. Beta and Gamma Gradients

    DEFF Research Database (Denmark)

    Løvborg, Leif; Gaffney, C. F.; Clark, P. A.;

    1985-01-01

    Experimental and/or theoretical estimates are presented concerning, (i) attenuation within the sample of beta and gamma radiation from the soil, (ii) the gamma dose within the sample due to its own radioactivity, and (iii) the soil gamma dose in the proximity of boundaries between regions of...... differing radioactivity. It is confirmed that removal of the outer 2 mm of sample is adequate to remove influence from soil beta dose and estimates are made of the error introduced by non-removal. Other evaluations include variation of the soil gamma dose near the ground surface and it appears that the...

  18. Evaluation of neutrino masses from $m_{\\beta\\beta}$ values

    CERN Document Server

    Khrushchov, V V

    2008-01-01

    A neutrino mass matrix is considered under conditions of the CP invariance and the negligible reactor mixing $\\theta_{13}$ angle. Absolute mass values for three neutrinos are evaluated in normal and inverted hierarchy spectra on the ground of data for oscillation mixing neutrino parameters and effective neutrino mass entering into a probability of neutrinoless two beta decay $m_{\\beta\\beta}$ values.

  19. Low-beta structures

    OpenAIRE

    M. Vretenar(CERN, Geneva, Switzerland)

    2012-01-01

    'Low-beta' radio-frequency accelerating structures are used in the sections of a linear accelerator where the velocity of the particle beam increases with energy. The requirement for space periodicity to match the increasing particle velocity led to the development of a large variety of structures, both normal and superconducting, which are described in this lecture.

  20. Applied Beta Dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Rich, B.L.

    1986-01-01

    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements.

  1. Roughing up Beta

    DEFF Research Database (Denmark)

    Bollerslev, Tim; Li, Sophia Zhengzi; Todorov, Viktor

    Motivated by the implications from a stylized equilibrium pricing framework, we investigate empirically how individual equity prices respond to continuous, or \\smooth," and jumpy, or \\rough," market price moves, and how these different market price risks, or betas, are priced in the cross-section...

  2. Neutrinoless Double Beta Decay

    CERN Document Server

    Päs, Heinrich

    2015-01-01

    We review the potential to probe new physics with neutrinoless double beta decay $(A,Z) \\to (A,Z+2) + 2 e^-$. Both the standard long-range light neutrino mechanism as well as short-range mechanisms mediated by heavy particles are discussed. We also stress aspects of the connection to lepton number violation at colliders and the implications for baryogenesis.

  3. Applied Beta Dosimetry

    International Nuclear Information System (INIS)

    Measurements of beta and/or nonpenetrating exposure results is complicated and past techniques and capabilities have resulted in significant inaccuracies in recorded results. Current developments have resulted in increased capabilities which make the results more accurate and should result in less total exposure to the work force. Continued development of works in progress should provide equivalent future improvements

  4. Interferon Beta-1b Injection

    Science.gov (United States)

    Interferon beta-1b injection is used to reduce episodes of symptoms in patients with relapsing-remitting (course ... and problems with vision, speech, and bladder control). Interferon beta-1b is in a class of medications ...

  5. Genetics Home Reference: beta thalassemia

    Science.gov (United States)

    ... for Disease Control and Prevention Centre for Genetics Education (Australia) Cold Spring Harbor Laboratory: Your Genes Your Health Disease InfoSearch: Beta Thalassemia Genomics Education Programme (UK) MalaCards: dominant beta-thalassemia Merck Manual ...

  6. Beta gets better with age

    OpenAIRE

    Tomunen, Tuomas

    2015-01-01

    The objective of my thesis is to study the cause for the low beta anomaly, which is an observation that the high beta stocks perform poorly relative to the low beta stocks. Based on earlier findings, I hypothesize that if a stock has high investor attention, its price overreacts to market-wide shocks, which results in a positive measurement error in its beta. Simultaneously, high attention causes overpricing, because the stock overreacts more often to positive shocks than to negat...

  7. Misleading Betas: An Educational Example

    Science.gov (United States)

    Chong, James; Halcoussis, Dennis; Phillips, G. Michael

    2012-01-01

    The dual-beta model is a generalization of the CAPM model. In the dual-beta model, separate beta estimates are provided for up-market and down-market days. This paper uses the historical "Anscombe quartet" results which illustrated how very different datasets can produce the same regression coefficients to motivate a discussion of the…

  8. Investigation of the algT operon sequence in mucoid and non-mucoid Pseudomonas aeruginosa isolates from 115 Scandinavian patients with cystic fibrosis and in 88 in vitro non-mucoid revertants

    DEFF Research Database (Denmark)

    Ciofu, Oana; Lee, Baoleri; Johannesson, Marie;

    2008-01-01

    are revertants. None of the non-mucoid isolates from intermittently colonized CF patients harboured mucA mutations. Although algT has been considered an important gene for secondary-site mutations responsible for reversion to non-mucoidy, only 30 % of the mucA-mutated non-mucoid CF isolates had mutations in alg...

  9. Beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Origa Raffaella

    2010-05-01

    Full Text Available Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands, dilated myocardiopathy, liver fibrosis and cirrhosis. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes, gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely

  10. Beta and muon decays

    International Nuclear Information System (INIS)

    These notes represent a series of lectures delivered by the authors in the Junta de Energia Nuclear, during the Spring term of 1965. They were devoted to graduate students interested in the Theory of Elementary Particles. Special emphasis was focussed into the computational problems. Chapter I is a review of basic principles (Dirac equation, transition probabilities, final state interactions.) which will be needed later. In Chapter II the four-fermion punctual Interaction is discussed, Chapter III is devoted to the study of beta-decay; the main emphasis is given to the deduction of the formulae corresponding to electron-antineutrino correlation, electron energy spectrum, lifetimes, asymmetry of electrons emitted from polarized nuclei, electron and neutrino polarization and time reversal invariance in beta decay. In Chapter IV we deal with the decay of polarized muons with radiative corrections. Chapter V is devoted to an introduction to C.V.C. theory. (Author)

  11. Integration of BETA with Eclipse

    DEFF Research Database (Denmark)

    Andersen, Peter; Madsen, Ole Lehrmann; Enevoldsen, Mads Brøgger

    2004-01-01

    This paper presents language interoperability issues appearing in order to implement support for the BETA language in the Java-based Eclipse integrated development environment. One of the challenges is to implement plug-ins in BETA and be able to load them in Eclipse. In order to do this, some form...... of language interoperability between Java and BETA is required. The first approach is to use the Java Native Interface and use C to bridge between Java and BETA. This results in a workable, but complicated solution. The second approach is to let the BETA compiler generate Java class files. With this...... approach it is possible to implement plug-ins in BETA and even inherit from Java classes. In the paper the two approaches are described together with part of the mapping from BETA to Java class files. http://www.sciencedirect.com/science/journal/15710661...

  12. COM Support in BETA

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    1999-01-01

    Component technologies based on binary units of independent production are some of the most important contributions to software architecture and reuse during recent years. Especially the COM technologies and the CORBA standard from the Object Management Group have contributed new and interesting ...... principles for software architecture, and proven to be useful in parctice. In this paper ongoing work with component support in the BETA language is described....

  13. Beta decay for pedestrians

    CERN Document Server

    Lipkin, Harry Jeannot

    1962-01-01

    The ""pedestrian approach"" was developed to describe some essentially simple experimental results and their theoretical implications in plain language. In this graduate-level text, Harry J. Lipkin presents simply, but without oversimplification, the aspects of beta decay that can be understood without reference to the formal theory; that is, the reactions that follow directly from conservation laws and elementary quantum mechanics.The pedestrian treatment is neither a substitute for a complete treatment nor a watered-down version.

  14. LHCb: $2\\beta_s$ measurement at LHCb

    CERN Multimedia

    Conti, G

    2009-01-01

    A measurement of $2\\beta_s$, the phase of the $B_s-\\bar{B_s}$ oscillation amplitude with respect to that of the ${\\rm b} \\rightarrow {\\rm c^{+}}{\\rm W^{-}}$ tree decay amplitude, is one of the key goals of the LHCb experiment with first data. In the Standard Model (SM), $2\\beta_s$ is predicted to be $0.0360^{+0.0020}_{-0.0016} \\rm rad$. The current constraints from the Tevatron are: $2\\beta_{s}\\in[0.32 ; 2.82]$ at 68$\\%$CL from the CDF experiment and $2\\beta_{s}=0.57^{+0.24}_{-0.30}$ from the D$\\oslash$ experiment. Although the statistical uncertainties are large, these results hint at the possible contribution of New Physics in the $B_s-\\bar{B_s}$ box diagram. After one year of data taking at LHCb at an average luminosity of $\\mathcal{L}\\sim2\\cdot10^{32}\\rm cm^{-2} \\rm s^{-1}$ (integrated luminosity $\\mathcal{L}_{\\rm int}\\sim 2 \\rm fb^{-1}$), the expected statistical uncertainty on the measurement is $\\sigma(2\\beta_s)\\simeq 0.03$. This uncertainty is similar to the $2\\beta_s$ value predicted by the SM.

  15. Xeroradiography in. beta. -thalassaemia

    Energy Technology Data Exchange (ETDEWEB)

    Scutellari, P.N.; Orzincolo, C.; Tamarozzi, R.

    1985-01-01

    Xeroradiographic investigations of the skull, hand, and elbow were performed on 27 patients with homozygous ..beta..-thalassaemia. The results were compared with plain radiographic examinations. Xeroradiography, because of its technical properties (i.e. edge contrast enhancement and wide latitude), was shown to demonstrate cortical thinning of long bones, swelling of the diploic space in the skull, and reticulated patterns in the elbow better than standard radiography. Moreover, the use of 'positive' mode imaging was shown to have advantages in the study of the skull and extremities.

  16. Realized Beta GARCH

    DEFF Research Database (Denmark)

    Hansen, Peter Reinhard; Lunde, Asger; Voev, Valeri Radkov

    2014-01-01

    particularly useful for modeling financial returns during periods of rapid changes in the underlying covariance structure. When applied to market returns in conjunction with returns on an individual asset, the model yields a dynamic model specification of the conditional regression coefficient that is known as...... conditional beta series during the financial crises.......We introduce a multivariate generalized autoregressive conditional heteroskedasticity (GARCH) model that incorporates realized measures of variances and covariances. Realized measures extract information about the current levels of volatilities and correlations from high-frequency data, which is...

  17. Double beta decay: present status

    OpenAIRE

    Barabash, A. S.

    2008-01-01

    The present status of double beta decay experiments (including the search for $2\\beta^{+}$, EC$\\beta^{+}$ and ECEC processes) are reviewed. The results of the most sensitive experiments are discussed. Average and recommended half-life values for two-neutrino double beta decay are presented. Conservative upper limits on effective Majorana neutrino mass and the coupling constant of the Majoron to the neutrino are established as $ < 0.75$ eV and $ < 1.9 \\cdot 10^{-4}$, respectively. Proposals fo...

  18. Simultaneous beta and gamma spectroscopy

    Science.gov (United States)

    Farsoni, Abdollah T.; Hamby, David M.

    2010-03-23

    A phoswich radiation detector for simultaneous spectroscopy of beta rays and gamma rays includes three scintillators with different decay time characteristics. Two of the three scintillators are used for beta detection and the third scintillator is used for gamma detection. A pulse induced by an interaction of radiation with the detector is digitally analyzed to classify the type of event as beta, gamma, or unknown. A pulse is classified as a beta event if the pulse originated from just the first scintillator alone or from just the first and the second scintillator. A pulse from just the third scintillator is recorded as gamma event. Other pulses are rejected as unknown events.

  19. Scintillator based beta batteries

    Science.gov (United States)

    Rensing, Noa M.; Tiernan, Timothy C.; Shirwadkar, Urmila; O'Dougherty, Patrick; Freed, Sara; Hawrami, Rastgo; Squillante, Michael R.

    2013-05-01

    Some long-term, remote applications do not have access to conventional harvestable energy in the form of solar radiation (or other ambient light), wind, environmental vibration, or wave motion. Radiation Monitoring Devices, Inc. (RMD) is carrying out research to address the most challenging applications that need power for many months or years and which have undependable or no access to environmental energy. Radioisotopes are an attractive candidate for this energy source, as they can offer a very high energy density combined with a long lifetime. Both large scale nuclear power plants and radiothermal generators are based on converting nuclear energy to heat, but do not scale well to small sizes. Furthermore, thermo-mechanical power plants depend on moving parts, and RTG's suffer from low efficiency. To address the need for compact nuclear power devices, RMD is developing a novel beta battery, in which the beta emissions from a radioisotope are converted to visible light in a scintillator and then the visible light is converted to electrical power in a photodiode. By incorporating 90Sr into the scintillator SrI2 and coupling the material to a wavelength-matched solar cell, we will create a scalable, compact power source capable of supplying milliwatts to several watts of power over a period of up to 30 years. We will present the latest results of radiation damage studies and materials processing development efforts, and discuss how these factors interact to set the operating life and energy density of the device.

  20. Drugs reverting multidrug resistance (chemosensitizers)

    Energy Technology Data Exchange (ETDEWEB)

    Gualtieri, F. [Florence Univ. (Italy). Dip. di Scienze Farmaceutiche

    1996-12-01

    Drug resistance is a phenomenon that frequently impairs proper treatment of cancer. Multidrug resistance (MDR) is a particular case of acquired drug resistance, resulting from overexpression of a protein (P-170) that functions as a pump, clearing cells from the chemotherapic. The P-170 protein functions can be inhibited by a variety of lipophilic drugs containing a hydrophilic nitrogen, protonated at physiological pH. A considerable effort is underway to identify new drugs able to reverse MDR. Few of these molecules are already undergoing clinical trials.

  1. Identifying Small Mean Reverting Portfolios

    OpenAIRE

    d'Aspremont, Alexandre

    2007-01-01

    Given multivariate time series, we study the problem of forming portfolios with maximum mean reversion while constraining the number of assets in these portfolios. We show that it can be formulated as a sparse canonical correlation analysis and study various algorithms to solve the corresponding sparse generalized eigenvalue problems. After discussing penalized parameter estimation procedures, we study the sparsity versus predictability tradeoff and the impact of predictability in various mar...

  2. Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion.

    Directory of Open Access Journals (Sweden)

    Ivona Pandrea

    2011-08-01

    Full Text Available Understanding the mechanism of infection control in elite controllers (EC may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4(+ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4(+ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This "functional cure" of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status.

  3. BETA SPECTRA. I. Negatrons spectra

    International Nuclear Information System (INIS)

    Using the Fermi theory of beta decay, the beta spectra for 62 negatrons emitters have been computed introducing a correction factor for unique forbidden transitions. These spectra are plotted vs. energy, once normal i sed, and tabulated with the related Fermi functions. The average and median energies are calculated. (Author)

  4. The best-beta CAPM

    NARCIS (Netherlands)

    L. Zou

    2006-01-01

    The issue of 'best-beta' arises as soon as potential errors in the Sharpe-Lintner-Black capital asset pricing model (CAPM) are acknowledged. By incorporating a target variable into the investor preferences, this study derives a best-beta CAPM (BCAPM) that maintains the CAPM's theoretical appeal and

  5. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-02-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  6. RAVEN Beta Release

    International Nuclear Information System (INIS)

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  7. Beta Beams Implementation at CERN

    CERN Document Server

    Hansen, Christian

    2011-01-01

    Beta Beam,the concept of generating a pure and intense (anti) neutrino beam by letting accelerated radioactive ions beta decay in a storage ring, called Decay Ring (DR), is the base of one of the proposed next generation neutrino oscillation facilities, necessary for a complete study of the neutrino oscillation parameter space. Sensitivities of the unknown neutrino oscillation parameters depend on the Decay Ring's ion intensity and of it's duty factor (the filled ratio of the ring). Therefore efficient ion production, stripping, bunching, acceleration and storing are crucial sub-projects under study and development within the Beta Beam collaboration. Specifically the feasibility of these tasks as parts of a Beta Beam implementation at CERN will be discussed in this report. The positive impact of the large {\\theta}13 indications from T2K on the Beta Beam performance will also be discussed.

  8. Intuitionistic Fuzzy Generalized Beta Closed Mappings

    OpenAIRE

    D. Jayanthi

    2014-01-01

    In this paper we introduce intuitionistic fuzzy generalized beta closed mappings and intuitionistic fuzzy generalized beta open mappings. We investigate some of their properties. We also introduce intuitionistic fuzzy M-generalized beta closed mappings as well as intuitionistic fuzzy M-generalized beta open mappings. We provide the relation between intuitionistic fuzzy M-generalized beta closed mappings and intuitionistic fuzzy generalized beta closed mappings.

  9. Derivatives of the Incomplete Beta Function

    Directory of Open Access Journals (Sweden)

    Robert J. Boik

    1998-03-01

    Full Text Available The incomplete beta function is defined as where Beta(p, q is the beta function. Dutka (1981 gave a history of the development and numerical evaluation of this function. In this article, an algorithm for computing first and second derivatives of Ix,p,q with respect to p and q is described. The algorithm is useful, for example, when fitting parameters to a censored beta, truncated beta, or a truncated beta-binomial model.

  10. Derivatives of the Incomplete Beta Function

    OpenAIRE

    Robison-Cox, James F.; Robert J. Boik

    1998-01-01

    The incomplete beta function is defined as where Beta(p, q) is the beta function. Dutka (1981) gave a history of the development and numerical evaluation of this function. In this article, an algorithm for computing first and second derivatives of Ix,p,q with respect to p and q is described. The algorithm is useful, for example, when fitting parameters to a censored beta, truncated beta, or a truncated beta-binomial model.

  11. High Temperature Stability of Potassium Beta Alumina

    Science.gov (United States)

    Williams, R. M.; Kisor, A.; Ryan, M. A.

    1996-01-01

    None. From Objectives section: Evaluate the stability of potassium beta alumina under potassium AMTEC operating conditions. Evaluate the stability regime in which potassium beta alumina can be fabricated.

  12. A semiconductor beta ray spectrometer

    International Nuclear Information System (INIS)

    Measurement of energy spectra of beta particles emitted from nuclei in beta-decay processes provides information concerning the mass difference of these nuclei between initial and final state. Moreover, experimental beta spectra yield information on the feeding of the levels in the daughter nucleus. Such data are valuable in the construction and checking of the level schemes. This thesis describes the design, construction, testing and usage of a detector for the accurate measurement of the mentioned spectra. In ch. 2 the design and construction of the beta spectrometer, which uses a hyper-pure germanium crystal for energy determination, is described. A simple wire chamber is used to discriminate beta particles from gamma radiation. Disadvantages arise from the large amounts of scattered beta particles deforming the continua. A method is described to minimize the scattering. In ch. 3 some theoretical aspects of data analysis are described and the results of Monte-Carlo simulations of the summation of annihilation radiation are compared with experiments. Ch. 4 comprises the results of the measurements of the beta decay energies of 103-108In. 87 refs.; 34 figs.; 7 tabs

  13. Effect of beta blockade and beta stimulation on stage fright.

    Science.gov (United States)

    Brantigan, C O; Brantigan, T A; Joseph, N

    1982-01-01

    Stage fright, physiologically the "fight or flight" reaction, is a disabling condition to the professional musician. Because it is mediated by the sympathetic nervous system, we have investigated the effects of beta blockade on musical performance with propranolol in a double blind fashion and the effects of beta stimulation using terbutaline. Stage fright symptoms were evaluated in two trials, which included a total of 29 subjects, by questionnaire and by the State Trai Anxiety Inventory. Quality of musical performance was evaluated by experienced music critics. Beta blockade eliminates the physical impediments to performance caused by stage fright and even eliminates the dry mouth so frequently encountered. The quality of musical performance as judged by experienced music critics is significantly improved. This effect is achieved without tranquilization. Beta stimulating drugs increase stage fright problems, and should be used in performing musicians only after consideration of the detrimental effects which they may have on musical performance. PMID:6120650

  14. Beta decay of 31Ar

    International Nuclear Information System (INIS)

    A complete study of 31Ar beta decay has been made by high-resolution charged-particle and gamma-ray spectroscopy. Beta-delayed radiation was detected by an array of three charged-particle detectors and a large-volume germanium detector. Fifteen new energy levels were discovered in 31Cl. The beta-strength distribution, measured to 14.5 MeV, is compared with a shell-model calculation in the full sd space. The quenching of the Gamow-Teller strength and the isospin impurity of the IAS in 31Cl are discussed. (orig.)

  15. The Age of Beta Pic

    OpenAIRE

    Navascues, D. Barrado y; Stauffer, J. R.; Song, I.; Caillault, J-P.

    1999-01-01

    We have reanalyzed data for the proposed moving group associated with beta Pic in order to determine if the group (or part of it) is real, and, if so, to derive an improved age estimate for beta Pic. By using new, more accurate proper motions from PPM and Hipparcos and a few new radial velocities, we conclude that on kinematic grounds, two M dwarfs have space motions that coincide with that of beta Pic to within 1 km/s with small error bars. Based on a CM diagram derived from accurate photome...

  16. Smart Beta or Smart Alpha

    DEFF Research Database (Denmark)

    Winther, Kenneth Lillelund; Steenstrup, Søren Resen

    2016-01-01

    that smart beta investing probably will do better than passive market capitalization investing over time, we believe many are coming to a conclusion too quickly regarding active managers. Institutional investors are able to guide managers through benchmarks and risk frameworks toward the same well...... only superior to the common capitalization weighted index but also to their smart beta benchmark, even after cost for value, size, and low volatility funds. We encourage investors to increase the use of smart beta as benchmarks while still obtaining extra performance through active management—a concept...

  17. Experiments on double beta decay

    Energy Technology Data Exchange (ETDEWEB)

    Busto, J. [Neuchatel Univ. (Switzerland). Inst. de Physique

    1996-11-01

    The Double Beta Decay, and especially ({beta}{beta}){sub 0{nu}} mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 10{sup 4} in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs.

  18. Dosimetry of {beta} extensive sources; Dosimetria de fuentes {beta} extensas

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E.L.; Lallena R, A.M. [Departamento de Fisica Moderna, Universidad de Granada, E-18071 Granada (Spain)

    2002-07-01

    In this work, we have been studied, making use of the Penelope Monte Carlo simulation code, the dosimetry of {beta} extensive sources in situations of spherical geometry including interfaces. These configurations are of interest in the treatment of the called cranealfaringyomes of some synovia leisure of knee and other problems of interest in medical physics. Therefore, its application can be extended toward problems of another areas with similar geometric situation and beta sources. (Author)

  19. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones

    OpenAIRE

    Hamid Arazi; Hadi Rohani; Ahmad Ghiasi; Nasrin Abdi Keikanloo

    2015-01-01

    RESUMOIntroduction:In recent years, there was an increased interest on the effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on skeletal muscle due to its anti-catabolic effects.Objectives:To investigate the effect of HMB supplementation on body composition, muscular strength and anabolic-catabolic hormones after resistance training.Methods:Twenty amateur male athletes were randomly assigned to supplement and control groups in a double-blind crossover design and participated i...

  20. Beta particle monitor for surfaces

    International Nuclear Information System (INIS)

    A beta radiation detector which is capable of reliably detecting beta radiation emitted from a surface. An electrically conductive signal collector is adjustably mounted inside an electrically conductive enclosure which may define a single large opening for placing against a surface. The adjustable mounting of the electrically conductive signal collector can be based on the distance from the surface or on the expected beta energy range. A voltage source is connected to the signal collector through an electrometer or other display means for creating an electric field between the signal collector and the enclosure. Air ions created by the beta radiation are collected and the current produced is indicated on the electrometer or other display means. 2 figs

  1. Peginterferon Beta-1a Injection

    Science.gov (United States)

    ... symptoms such as headaches, bone or muscle aches, fever, chills, and tiredness during your treatment with peginterferon beta- ... not go away: headache muscle or joint pain fever chills weakness Some side effects can be serious. If ...

  2. Beta-gamma discriminator circuit

    International Nuclear Information System (INIS)

    The major difficulty encountered in the determination of beta-ray dose in field conditions is generally the presence of a relatively high gamma-ray component. Conventional dosimetry instruments use a shield on the detector to estimate the gamma-ray component in comparison with the beta-ray component. More accurate dosimetry information can be obtained from the measured beta spectrum itself. At Los Alamos, a detector and discriminator circuit suitable for use in a portable spectrometer have been developed. This instrument will discriminate between gammas and betas in a mixed field. The portable package includes a 256-channel MCA which can be programmed to give a variety of outputs, including a spectral display, and may be programmed to read dose directly

  3. Recent double beta decay results

    Energy Technology Data Exchange (ETDEWEB)

    Balysh, A. (Kurchatov Institute, 123 182 Moscow (Russian Federation)); Beck, M. (Max-Planck-Institut fuer Kernphysik, W-6900 Heidelberg (Germany)); Belyaev, S.T. (Kurchatov Institute, 123 182 Moscow (Russian Federation)); Bensch, F.; Bockholt, J. (Max-Planck-Institut fuer Kernphysik, W-6900 Heidelberg (Germany)); Demehin, A.; Gurov, A. (Kurchatov Institute, 123 182 Moscow (Russian Federation)); Heusser, G.; Hirsch, M.; Klapdor-Kleingrothaus, H.V. (Max-Planck-Institut fuer Kernphysik, W-6900 Heidelberg (Germany)); Kondratenko, I.; Lebedev, V.I. (Kurchatov Institute, 123 182 Moscow (Russian Federation)); Maier, B. (Max-Planck-Institut fuer Kernphysik, W-6900 Heidelberg (Germany)); Mueller, A. (Istituto Nazionale di Fisica Nucleare LNGS, 67010 Assergi (Italy)); Petry, F.; Piepke, A.; Strecker, H.; Voellinger, M.; Zuber, K. (Max-Planck-Institut fuer Kernphysik, W-6900 Heidelberg (Germany))

    1992-02-01

    The status and recent results of second generation [beta][beta]-experiments using isotopically enriched source materials are described. These experiments are at present the most sensitive tools to distinguish Dirac from Majorana neutrinos. The at present most advanced experimental techniques, namely the use of high-resolution calorimetric detectors and of time projection chambers are compared. New limits on the Majorana neutrino mass as well as for the Majoron-neutrino coupling are presented.

  4. Apollo applications of beta fiber glass

    Science.gov (United States)

    Naimer, J.

    1971-01-01

    The physical characteristics of Beta fiber glass are discussed. The application of Beta fiber glass for fireproofing the interior of spacecraft compartments is described. Tests to determine the flammability of Beta fiber glass are presented. The application of Beta fiber glass for commercial purposes is examined.

  5. Synthesis of Beta Pyridyl Carbinol Tartrate

    Directory of Open Access Journals (Sweden)

    S. K. Shukla

    1968-04-01

    Full Text Available A process for the synthesis of Beta pyridine carboxylic acid ethy1 ester starting from quinoline has been developed. Beta-pyridine carboxylic acid ethy1 ester on reduction with lithium aluminium hydride gave Beta-pyridy1 carbinol which on treatment tartaric acid yielded Beta-pyridy1 carbinol tartrate, a vaso dilator known in trade as "Ronicoltartrate".

  6. Vasodilatory mechanisms of beta receptor blockade.

    OpenAIRE

    Rath, Géraldine; Balligand, Jean-Luc; Dessy, Chantal

    2012-01-01

    Beta-blockers are widely prescribed for the treatment of a variety of cardiovascular pathologies. Compared to traditional beta-adrenergic antagonists, beta-blockers of the new generation exhibit ancillary properties such as vasodilation through different mechanisms. This translates into a more favorable hemodynamic profile. The relative affinities of beta-adrenoreceptor antagonists towards the three beta-adrenoreceptor isotypes matter for predicting their functional impact on vasomotor contro...

  7. Tables of double beta decay data

    Energy Technology Data Exchange (ETDEWEB)

    Tretyak, V.I. [AN Ukrainskoj SSR, Kiev (Ukraine)]|[Strasbourg-1 Univ., 67 (France). Centre de Recherches Nucleaires; Zdesenko, Y.G. [AN Ukrainskoj SSR, Kiev (Ukraine)

    1995-12-31

    A compilation of experimental data on double beta decay is presented. The tables contain the most stringent known experimental limits or positive results of 2{beta} transitions of 69 natural nuclides to ground and excited states of daughter nuclei for different channels (2{beta}{sup -}; 2{beta}{sup +}; {epsilon}{beta}{sup +}; 2{epsilon}) and modes (0{nu}; 2{nu}; 0{nu}M) of decay. (authors). 189 refs., 9 figs., 3 tabs.

  8. A CAFEÍNA NÃO REVERTE O EFEITO DELETÉRIO DO EXERCÍCIO DE ENDURANCE SOBRE O SUBSEQUENTE DESEMPENHO DE FORÇA

    Directory of Open Access Journals (Sweden)

    Antônio Rubens dos Santos Filho

    2014-09-01

    Full Text Available Introdução: Diversos estudos demonstram que o exercício de endurance realizado previamente ao exercício de força exerce efeitos deletérios neste último. Contudo, nenhum desses estudos foi realizado com o uso da cafeína. Objetivo: Verificar se o consumo de cafeína pode atenuar os efeitos agudos do exercício de endurance sobre o desenvolvimento subsequente no número de Repetições Máximas (RMs e no Volume Total (VT. Metodologia:n=7 praticantes de musculação do sexo masculino (idade: 27±9.07 anos, massa corporal: 82±14.67 kg, estatura: 176±5.88 cm; Grupo Controle (GCRTL n=7, Grupo Placebo (GP n=7 e Grupo Cafeína (GC n=7. A 1ª sessão os voluntários realizaram um teste progressivo na esteira (Moviment ® , São Paulo, Brasil para a determinação do Limiar Anaeróbico Estimado de Conconi (Lane. Na 2ª sessão foi avaliada 1RM no Leg Press 45° (Moviment® , São Paulo, Brasil. A 3ª sessão o GCRTL realizou 4 séries (50%-1RM de RMs no Leg Press 45°, com 1’ de intervalo entre as séries sem a realização prévia do exercício de endurance. Na 4ª e 5ª sessões, os indivíduos ingeriram cápsulas de cafeína (6mg/kg ou placebo (35’ de absorção. Após os indivíduos correram em uma esteira por 20’ no Lane e em seguida (2’ de intervalo executaram protocolo de RMs do GCRTL. ANOVA-Two Way foi utilizada. Adotou-se um p0.05 entre o GP e GC nas RMs e no VT nas 4 séries. Conclusão: Conclui-se que uma sessão de exercício de endurance (limiar de conconi realizada previamente a um exercício de força afeta o desempenho nas RMs e no VT. Entretanto, o consumo de cafeína (6 mg/Kg antes do exercício de endurance não foi capaz de reverter o efeito prejudicial induzido pelo mesmo sobre a subsequente número de RMs e VT.

  9. Beta contamination monitor energy response

    International Nuclear Information System (INIS)

    Beta contamination is monitored at Los Alamos National Laboratory (LANL) with portable handheld probes and their associated counters, smear counters, air-breathing continuous air monitors (CAM), personnel contamination monitors (PCM), and hand and foot monitors (HFM). The response of these monitors was measured using a set of anodized-aluminum beta sources for the five isotopes: Carbon-14, Technetium-99, Cesium-137, Chlorine-36 and Strontium/Yttrium-90. The surface emission rates of the sources are traceable to the National Institute of Standards and Technology (NIST) with a precision of one relative standard deviation equal to 1.7%. All measurements were made in reproducible geometry, mostly using aluminum source holders. All counts, significantly above background, were collected to a precision of 1% or better. The study of the hand-held probes included measurements of six air gaps from 0.76 to 26.2 mm. The energy response of the detectors is well-parameterized as a function of the average beta energy of the isotopes (C14=50 keV, Tc99=85, Cs137=188, C136=246, and Sr/Y90=934). The authors conclude that Chlorine-36 is a suitable beta emitter for routine calibration. They recommend that a pancake Geiger-Mueller (GM) or gas-proportional counter be used for primarily beta contamination surveys with an air gap not to exceed 6 mm. Energy response varies about 30% from Tc99 to Sr/Y90 for the pancake GM detector. Dual alpha/beta probes have poor to negligible efficiency for low-energy betas. The rugged anodized sources represent partially imbedded contamination found in the field and they are provided with precise, NIST-traceable, emission rates for reliable calibration

  10. In-trap decay spectroscopy for {beta}{beta} decays

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Thomas

    2011-01-18

    The presented work describes the implementation of a new technique to measure electron-capture (EC) branching ratios (BRs) of intermediate nuclei in {beta}{beta} decays. This technique has been developed at TRIUMF in Vancouver, Canada. It facilitates one of TRIUMF's Ion Traps for Atomic and Nuclear science (TITAN), the Electron Beam Ion Trap (EBIT) that is used as a spectroscopy Penning trap. Radioactive ions, produced at the radioactive isotope facility ISAC, are injected and stored in the spectroscopy Penning trap while their decays are observed. A key feature of this technique is the use of a strong magnetic field, required for trapping. It radially confines electrons from {beta} decays along the trap axis while X-rays, following an EC, are emitted isotropically. This provides spatial separation of X-ray and {beta} detection with almost no {beta}-induced background at the X-ray detector, allowing weak EC branches to be measured. Furthermore, the combination of several traps allows one to isobarically clean the sample prior to the in-trap decay spectroscopy measurement. This technique has been developed to measure ECBRs of transition nuclei in {beta}{beta} decays. Detailed knowledge of these electron capture branches is crucial for a better understanding of the underlying nuclear physics in {beta}{beta} decays. These branches are typically of the order of 10{sup -5} and therefore difficult to measure. Conventional measurements suffer from isobaric contamination and a dominating {beta} background at theX-ray detector. Additionally, X-rays are attenuated by the material where the radioactive sample is implanted. To overcome these limitations, the technique of in-trap decay spectroscopy has been developed. In this work, the EBIT was connected to the TITAN beam line and has been commissioned. Using the developed beam diagnostics, ions were injected into the Penning trap and systematic studies on injection and storage optimization were performed. Furthermore, Ge

  11. Hierarchy of ADAM12 binding to integrins in tumor cells

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Fröhlich, Camilla; Nielsen, Christian Kamp;

    2005-01-01

    12. However, when alpha9beta1 integrin is not expressed--as in many carcinoma cells--other members of the beta1 integrin family can replace its ligand binding activity. In attachment assays, the recombinant disintegrin domain of ADAM12 only supported alpha9 integrin-dependent tumor cell attachment...... with a rounded morphology; attachment of cells with a spread morphology required further activation of the alpha9beta1 integrin. We demonstrated that phosphoinositide-3-kinase appears to be central in regulating alpha9beta1 integrin cell spreading activity in response to ADAM12....

  12. Cardiac glycoside-like structure and function of 5 beta,14 beta-pregnanes

    International Nuclear Information System (INIS)

    5 beta-Reduction and 14 beta-substitution convert the planar progesterone molecule to the cardiac glycoside configuration--A and D rings of the steroid moiety are bent toward the alpha-face relative to the B and C rings. Potency of the 5 beta,14 beta-derivative in a [3H]ouabain binding assay or its ability to inhibit the sodium pump in red blood cells is enhanced by 3 beta-hydroxylation, 20 beta-hydroxylation, and 3 beta-glycosidation. Synthesis of 14,20 beta-dihydroxy-3 beta-(beta-D-glucopyranosyloxy)- 5 beta,14 beta-pregnane from digitoxin is described. The glucoside is 1/20 as potent as ouabain and elicits prominent, sustained, positive inotropy in isolated cardiac muscle

  13. 50 years forward: beta cells.

    Science.gov (United States)

    Halban, Philippe A

    2015-08-01

    Our understanding of beta cell development and function has increased substantially these past 50 years but much remains to be learned before this knowledge can be put to clinical use. A comprehensive business plan will be necessary to develop a detailed molecular and functional blueprint of the beta cell in health and disease based on an integrated approach involving all necessary research disciplines. This blueprint will provide a platform for the development of novel therapeutic strategies for the treatment of both major forms of diabetes, foremost among them beta cell replacement therapy. This is one of a series of commentaries under the banner '50 years forward', giving personal opinions on future perspectives in diabetes, to celebrate the 50th anniversary of Diabetologia (1965-2015). PMID:25957776

  14. Predicting Neutrinoless Double Beta Decay

    CERN Document Server

    Hirsch, M; Valle, J W F; Moral, A V; Ma, Ernest

    2005-01-01

    We give predictions for the neutrinoless double beta decay rate in a simple variant of the A_4 family symmetry model. We show that there is a lower bound for the neutrinoless double beta decay amplitude even in the case of normal hierarchical neutrino masses, corresponding to an effective mass parameter |m_{ee}| >= 0.17 \\sqrt{\\Delta m^2_{ATM}}. This result holds both for the CP conserving and CP violating cases. In the latter case we show explicitly that the lower bound on |m_{ee}| is sensitive to the value of the Majorana phase. We conclude therefore that in our scheme, neutrinoless double beta decay may be accessible to the next generation of high sensitivity experiments.

  15. Mechanism of inactivation of alanine racemase by beta, beta, beta-trifluoroalanine

    International Nuclear Information System (INIS)

    The alanine racemases are a group of PLP-dependent bacterial enzymes that catalyze the racemization of alanine, providing D-alanine for cell wall synthesis. Inactivation of the alanine racemases from the Gram-negative organism Salmonella typhimurium and Gram-positive organism Bacillus stearothermophilus with beta, beta, beta-trifluoroalanine has been studied. The inactivation occurs with the same rate constant as that for formation of a broad 460-490-nm chromophore. Loss of two fluoride ions per mole of inactivated enzyme and retention of [1-14C]trifluoroalanine label accompany inhibition, suggesting a monofluoro enzyme adduct. Partial denaturation (1 M guanidine) leads to rapid return of the initial 420-nm chromophore, followed by a slower (t1/2 approximately 30 min-1 h) loss of the fluoride ion and 14CO2 release. At this point, reduction by NaB3H4 and tryptic digestion yield a single radiolabeled peptide. Purification and sequencing of the peptide reveals that lysine-38 is covalently attached to the PLP cofactor. A mechanism for enzyme inactivation by trifluoroalanine is proposed and contrasted with earlier results on monohaloalanines, in which nucleophilic attack of released aminoacrylate on the PLP aldimine leads to enzyme inactivation. For trifluoroalanine inactivation, nucleophilic attack of lysine-38 on the electrophilic beta-difluoro-alpha, beta-unsaturated imine provides an alternative mode of inhibition for these enzymes

  16. Constraining neutrinoless double beta decay

    International Nuclear Information System (INIS)

    A class of discrete flavor-symmetry-based models predicts constrained neutrino mass matrix schemes that lead to specific neutrino mass sum-rules (MSR). We show how these theories may constrain the absolute scale of neutrino mass, leading in most of the cases to a lower bound on the neutrinoless double beta decay effective amplitude.

  17. *608440 LACTAMASE, BETA; LACTB [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 608440 FIELD TI 608440 LACTAMASE, BETA; LACTB ;;MITOCHONDRIAL RIBOSOMAL PROTEIN L56; MR ... Chen et al. (2008) recorded weight, fat mass, and lean ... mass for Lpl heterozygous null mice, Lactb transge ... ifferent from those of controls, with the fat mass/lean ... mass ratio difference generally increasing over ti ...

  18. Monitor for alpha beta contamination of hands

    International Nuclear Information System (INIS)

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

  19. How Do Beta Blocker Drugs Affect Exercise?

    Science.gov (United States)

    ... Stroke More How do beta blocker drugs affect exercise? Updated:Aug 5,2015 Beta blockers are a ... about them: Do they affect your ability to exercise? The answer can vary a great deal, depending ...

  20. Interferon Beta-1a Intramuscular Injection

    Science.gov (United States)

    Interferon beta-1a intramuscular injection is used to reduce the number of episodes of symptoms and slow ... and problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications ...

  1. Interferon Beta-1a Subcutaneous Injection

    Science.gov (United States)

    Interferon beta-1a subcutaneous injection is used to reduce episodes of symptoms and slow the development of ... and problems with vision, speech, and bladder control). Interferon beta-1a is in a class of medications ...

  2. The beta subunit of casein kinase II

    DEFF Research Database (Denmark)

    Boldyreff, B; Piontek, K; Schmidt-Spaniol, I; Issinger, O G

    1991-01-01

    cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies.......cDNAs encoding the beta subunit of pig and mouse CKII were isolated. The porcine cDNA was expressed as a fusion protein in Escherichia coli and used for the production of anti-CKII-beta subunit specific antibodies....

  3. Beta adrenergic receptors in pigmented ciliary processes.

    OpenAIRE

    Trope, G. E.; Clark, B.

    1982-01-01

    Beta adrenergic receptors from membrane fragments of pigmented sheep eyes were studied and characterised by ligand binding techniques after the removal of melanin. In a representative experiment the beta max (total number of beta receptors) was 394.9 fmol/mg protein. The receptor affinity (Ka) was 440 pM. The potency series of drugs to displace 125I-HYP from the receptors was timolol = (-) propranolol greater than (+) propranolol greater than salbutamol greater than practolol. beta 1 Recepto...

  4. Theory of high-beta tokamaks

    International Nuclear Information System (INIS)

    The theoretical researches on high beta tokamak are reviewed. The ballooning mode instability is thought to be the most serious problem for the high beta tokamaks, and the theoretical results on the ballooning mode instability are discussed in detail. The experimental results in high beta belt pinch devices are also discussed. (author)

  5. Interferon Beta-1a Intramuscular Injection

    Science.gov (United States)

    Interferon beta-1a intramuscular injection is used to reduce the number of episodes of symptoms and slow the development of disability in patients ... Interferon beta-1a intramuscular injection comes as a powder in vials to be mixed into a solution for injection. Interferon beta-1a intramuscular ...

  6. Beta measurements at Department of Energy facilities

    International Nuclear Information System (INIS)

    Pacific Northwest Laboratory performed a two-step process to characterize the current beta measurement practices at DOE facilities. PNL issued a survey questionnaire on beta measurement practices to DOE facilities and reported the results. PNL measured beta doses and spectra at seven selected DOE facilities and compared selected measurement techniques in the facility environment. This report documents the results of the radiation field measurements and the comparison of measurement techniques at the seven facilities. Data collected included beta dose and spectral measurements at seven DOE facilities that had high beta-to-gamma ratios (using a silicon surface barrier spectrometer, a plastic scintillator spectrometer, and a multielement beta dosimeter). Other dosimeters and survey meters representative of those used at DOE facilities or under development were also used for comparison. Field spectra were obtained under two distinct conditions. Silicon- and scintillation-based spectrometer systems were used under laboratory conditions where high beta-to-gamma dose ratios made the beta spectra easier to observe and analyze. In the second case, beta spectrometers were taken into actual production and maintenance areas of DOE facilities. Analyses of beta and gamma spectra showed that 234Th- /sup 234m/Pa, 231Th, 137Cs, and 90Sr/90Y were the major nuclides contributing to beta doses at the facilities visited. Beta doses from other fission products and 60Co were also measured, but the potential for exposure was less significant. 21 refs., 64 figs., 18 tabs

  7. Measurement of the beta asymmetry in neutron beta decay

    International Nuclear Information System (INIS)

    Neutron beta decay is the simplest semi-leptonic weak decay and described accurately by the standard model using the first CKM-matrix element and the ratio of vector and axial vector couplings, λ. With more than a dozen observables it is a sensitive probe for investigating the nature of weak interaction and to search for physics beyond the standard model. In the past, measuring the beta asymmetry A in polarized neutron decay has been the most precise way of determining λ and nowadays it allows - together with other observables - to derive limits on non-standard model interactions, such as scalar and tensor couplings. The neutron decay spectrometer Perkeo III was installed at the PF1B cold neutron beam site at the Institut Laue-Langevin to measure the beta asymmetry. By using a pulsed beam combined with an improved detector design a significant reduction of several systematic uncertainties has been achieved compared to the predecessor, Perkeo II. In this talk recent results of the measurements with Perkeo III will be presented. In particular, we show the energy distribution of the electrons together with the calibration tools for the detectors.

  8. Beta thalassaemia mutations in Turkish Cypriots.

    OpenAIRE

    Sozuoz, A; Berkalp, A; A. Figus; Loi, A; Pirastu, M.; Cao, A

    1988-01-01

    Using oligonucleotide hybridisation or restriction endonuclease analysis, we have characterised the molecular defect in 94 patients with thalassaemia major and four with thalassaemia intermedia of Turkish Cypriot descent. We found that four mutations, namely beta+ IVS-1 nt 110, beta zero IVS-1 nt, beta+ IVS-1 nt 6, and beta+ IVS-2 nt 745 were prevalent, accounting for 69.9%, 11.7%, 8.7%, and 5.6% respectively of the beta thalassaemia chromosomes. This information may help in the organisation ...

  9. Plan beta: Core or Cusp?

    CERN Document Server

    Richardson, Thomas; Lehnert, Matt

    2013-01-01

    The inner profile of Dark Matter (DM) halos remains one of the central problems in small-scale cosmology. At present, the problem can not be resolved in dwarf spheroidal galaxies due to a degeneracy between the DM profile and the velocity anisotropy beta of the stellar population. We discuss a method which can break the degeneracy by exploiting 3D positions and 1D line-of-sight (LOS) velocities. With the full 3D spatial information, we can determine precisely what fraction of each stars LOS motion is in the radial and tangential direction. This enables us to infer the anisotropy parameter beta directly from the data. The method is particularly effective if the galaxy is highly anisotropic. Finally, we argue that such a test could be applied to Sagittarius and potentially other dwarfs with RR Lyrae providing the necessary depth information.

  10. Beta spectrum of 185W

    International Nuclear Information System (INIS)

    The measurement of the shape of the first forbidden beta transition of 185W is interesting from the point of view of the fact that this nucleus belongs to the deformed region 150185W is carried out employing an optimized Siegbahn-Slatis beta ray spectrometer and the result is compared with the theoretical shape factor incorporating Nilsson's wavefunctions using Simms formalism. The experimental shape factor is fitted to the correction factor C(W)=k(1+aW) with α=0.0026+-0.0432. The theoretical shape factor computed following the matrix elements due to Nilsson model is in good agreement with the present experimental shape factor. The value Λ(2.358) computed in the present measurement in the light of Nilsson model matrix elements of 185W is in agreement with the predicted value (2.4) of J.J. Fujita. (author)

  11. Abstraction Mechanisms in the BETA Programming Language

    DEFF Research Database (Denmark)

    Kristensen, Bent Bruun; Madsen, Ole Lehrmann; Møller-Pedersen, Birger;

    1983-01-01

    The BETA programming language is developed as part of the BETA project. The purpose of this project is to develop concepts, constructs and tools in the field of programming and programming languages. BETA has been developed from 1975 on and the various stages of the language are documented in [BETA...... a]. The application area of BETA is programming of embedded as well as distributed computing systems. For this reason a major goal has been to develop constructs that may be efficiently implemented. Furthermore the BETA language is intended to have a few number of basic but general constructs...... to SMALLTALK, BETA is a language in the ALGOL 60 ([ALGOL]) family. SIMULA 67 is a system description and a programming language. The DELTA language ([DELTA]) is a system description language only, allowing description of full concurrency, continuous change and component interaction, developed from a SIMULA...

  12. Beta emitters and radiation protection

    DEFF Research Database (Denmark)

    Jødal, Lars

    2009-01-01

    , and 90Y, using data from a freely available database. Bremsstrahlung yields were calculated for 90Y shielded by lead, aluminium, or perspex. Bremsstrahlung spectrum from 90Y shielded by perspex was measured, and attenuation of spectrum by lead was calculated. Whole-body and finger doses to persons...... the outside of the primary shielding material. If suitable shielding is used and larger numbers of handlings are divided among several persons, then handling of beta emitters can be a safe procedure....

  13. Review of double beta experiments

    OpenAIRE

    Sarazin, X.

    2012-01-01

    C13-10-22.1 International audience This paper gives a review of the double beta experimental techniques and projects, in the search for the Majorana neutrino. The purpose of this review is to detail, for each technique, the different origins of background, how they can be identified, and how they can be reduced. Advantages and limitations of the different techniques are discussed. 1. Introduction The neutrino is one of the most puzzling elementary particle with very unique properties. I...

  14. Electrolytic hydrogen in beta titanium

    International Nuclear Information System (INIS)

    Permeation of electrolytic hydrogen through beta titanium foils with palladium coated surfaces was studied using Ti--11.5 Mo--6 Zr--4.5 Sn. Ion bombardment etching followed by thin film vapor deposition of palladium were used to produce oxide-free titanium specimens for electrochemical hydrogen permeation and embrittlement studies. A thin metallic foil is cathodically charged with hydrogen on one side while the other side is maintained at a sufficiently anodic potential so that all the diffusing hydrogen is oxidized and turned into an equivalent current. The current is analyzed to determine diffusivity and solubility of hydrogen. X-ray diffraction was also used to determine the effects of hydrogen on the lattice parameter. Permeation experiments conducted with basic cyanide solutions exhibited simple diffusion behavior. The diffusivity at 210C for hydrogen through the beta alloy was 5.60 (+-1.92) x 10-7 cm2/s. Anomalous permeation occurred with hydrogen chemical potentials in acidic and basic solutions without cyanide during the later stages of the approach to steady state in the charging. This behavior is consistent with the trapping model of hydrogen in metals of McNabb and Foster. Plastic deformation and spontaneous cracking at the wetted portion of the specimen were observed under extreme conditions during this anomalous behavior. Part of the deformation is found to be reversible. In the mandrel bend experiments on the embrittlement phenomenon, the transgranular cleavage mode of fracture occurred. Interstitially dissolved hydrogen expanded the bcc lattice of the beta titanium with accompanying diffraction line broadening. The lattice contracted upon removal of the hydrogen. The satisfactory performance of the beta alloy Ti--11.5 Mo--6 Zr--4.5 Sn, in moderate electrochemical environments results principally from the protective oxide film

  15. Neutrinoless Double Beta Decay Experiments

    OpenAIRE

    Zuber, K.

    2014-01-01

    Neutrinoless double beta decay is the only process known so far able to test the neutrino intrinsic nature: its experimental observation would imply that the lepton number is violated by two units and prove that neutrinos have a Majorana mass components, being their own anti-particle. While several experiments searching for such a rare decay have been performed in the past, a new generation of experiments using different isotopes and techniques have recently released their results or are taki...

  16. Myokardinfarkt und Beta-Blocker

    Directory of Open Access Journals (Sweden)

    Stühlinger H-G

    2003-01-01

    Full Text Available Im Rahmen eines akuten koronaren Syndroms (akuter Herzinfarkt, Angina pectoris kommt es, aufgrund eines Ungleichgewichtes zwischen Angebot und Bedarf, zu einem akuten Mangel an Sauerstoff im Herzmuskel. Ursache ist eine reduzierte Sauerstoffzufuhr durch verengte bzw. verschlossene Gefäße. Bis zur Behebung der Ursache vergehen oft mehrere Stunden. In dieser Phase muß - durch Verminderung des Sauerstoffbedarfs im Herzmuskel - eine Verlangsamung der Nekroseentwicklung erreicht werden. Das Ausmaß der Nekrose wird reduziert, somit die für die Langzeitprognose wichtige Linksventrikelfunktion verbessert. Eine Verminderung des Sauerstoffbedarfs erreicht man durch kontrollierte Frequenzsenkung mittels intravenöser Beta-Blockade. In optimaler Weise wird diese Methode durch die Anwendung eines kardioselektiven Beta-Blockers mit kurzer Halbwertszeit durchgeführt. Beta-Blocker haben nicht nur auf die Nekroseentwicklung, sondern auch auf die Inzidenz von Rhythmusstörungen - besonders in der Akutphase - Auswirkungen. Vor allem die mit dieser therapeutischen Maßnahme verbundene Reduktion von Kammerflimmern ist von großer Bedeutung.

  17. Metalo-beta-lactamases Metallo-beta-lactamases

    Directory of Open Access Journals (Sweden)

    Rodrigo Elisandro Mendes

    2006-04-01

    Full Text Available Nos últimos anos tem sido observada maior incidência de bacilos Gram-negativos resistentes a cefalosporinas de espectro ampliado no ambiente hospitalar, ocasionando, assim, maior uso de betalactâmicos mais potentes, como os carbapenens. A utilização de carbapenens exerce maior pressão seletiva sobre a microbiota hospitalar, o que pode ocasionar aumento da resistência a esses agentes. Entre os mecanismos de resistência a carbapenens mais comumente identificados estão a produção de betalactamases, como, por exemplo, as pertencentes à classe D de Ambler e as que pertencem à classe B de Ambler, ou metalo-beta-lactamases (MbetaL. Essas últimas hidrolisam todos betalactâmicos comercialmente disponíveis, sendo a única exceção o monobactam aztreonam. Desde o início da década de 1990, novos genes que codificam MbetaLs têm sido descritos em microrganismos clinicamente importantes, como Pseudomonas spp., Acinetobacter spp. e membros da família Enterobacteriaceae. O encontro desses microrganismos não-sensíveis a carbapenens pode ser submetido a metodologias fenotípicas para detecção da produção de MbetaL com o intuito de auxiliar a Comissão de Controle de Infecção Hospitalar (CCIH e prevenir a disseminação desses determinantes de resistência, uma vez que genes que codificam MbetaLs estão contidos em estruturas genéticas que propiciam sua mobilidade de forma muito efetiva, sendo então facilmente disseminados.Increase isolation of Gram-negative bacilli resistant to broad-spectrum cephalosporin has been observed during the last few years, thus determining the use of more potent beta-lactams, such as carbapenems. The use of these antimicrobial agents may lead to the emergence of carbapenem resistant Gram-negative bacilli in the nosocomial environment. Carbapenem resistance may be due to the production of Ambler class D beta-lactamase or Ambler class B beta-lactamase, also called metallo-beta-lactamase (MbetaL. Apart from

  18. Beta-dosimetry studies at LLNL

    International Nuclear Information System (INIS)

    This paper summarizes three beta-dosimetry studies made recently at the Lawrence Livermore National Laboratory. The first study was to determine the beta-gamma exposure rates at the Los Alamos Godiva IV Critical Assembly. The beta spectra from the assembly were evaluated using absorption curves and the beta-gamma dose-rate ratios were determined at various distances from the assembly. A comparison was made of the doses determined using two types of TLD personnel dosimeters and a film badge. The readings of an Eberline RO-7 instrument and the dose rates determined by TLDs were compared. Shielding provided by various metals, gloves, and clothing were measured. The second study was to determine the beta energy response of the Eberline RO-7 instrument based on measurements made with the PTB beta sources. This study required additional calibration points for the PTB sources which were made using extrapolation chamber measurements. The third study resulted in two techniques to determine the beta energy (E/sub max/) from the readings of this-window portable survey instruments. Both techniques are based on the readings obtained using aluminium filters. One technique is for field application, requires one filter, and provides a quick estimate of the beta energy in three energy groups: 1.5 MeV. The second technique is more complex requiring measurements with two or three filters, but gives the beta energy and the approximate shape of the beta spectrum. 9 references, 6 figures

  19. On gaps in Rényi $\\beta$-expansions of unity for $\\beta > 1$ an algebraic number.

    OpenAIRE

    Verger-Gaugry, Jean-Louis

    2006-01-01

    Let $\\beta> 1$ be an algebraic number. We study the strings of zeros (“gaps”) in the Rényi $\\beta$ -expansion $d_{\\beta}(1)$ of unity which controls the set $\\mathbb{Z}_{\\beta}$ of $\\beta$-integers. Using a version of Liouville's inequality which extends Mahler's and Güting's approximation theorems, the strings of zeros in $d_{\\beta}(1)$ are shown to exhibit a “gappiness” asymptotically bounded above by $log(M(\\beta ))/ log(\\beta)$, where $M(\\beta)$ is the Mahler measure of $\\beta$ . The proo...

  20. Resistance training & beta-hydroxy-beta-methylbutyrate supplementation on hormones

    Directory of Open Access Journals (Sweden)

    Hamid Arazi

    2015-10-01

    Full Text Available RESUMOIntroduction:In recent years, there was an increased interest on the effects of beta-hydroxy-beta-methylbutyrate (HMB supplementation on skeletal muscle due to its anti-catabolic effects.Objectives:To investigate the effect of HMB supplementation on body composition, muscular strength and anabolic-catabolic hormones after resistance training.Methods:Twenty amateur male athletes were randomly assigned to supplement and control groups in a double-blind crossover design and participated in four weeks resistance training. Before and after the test period fasting blood samples were obtained to determine anabolic (the growth hormone and testosterone and catabolic (cortisol hormones, and fat mass, lean body mass (LBM and muscular strength were measured. Dependent and independent t-tests were used to analyze data.Results:After the training period, there were no significant differen-ces between the groups with respect to fat mass, LBM and anabolic-catabolic hormones. HMB supplementation resulted in a significantly greater strength gain (p≤0.05.Conclusion:Greater increase in strength for HMB group was not accompanied by body composition and basal circulating anabolic-catabolic hormonal changes. It seems that HMB supplementation may have beneficial effects on neurological adaptations of strength gain.

  1. GSK3beta is involved in JNK2-mediated beta-catenin inhibition.

    Directory of Open Access Journals (Sweden)

    Dong Hu

    Full Text Available BACKGROUND: We have recently reported that mitogen-activated protein kinase (MAPK JNK1 downregulates beta-catenin signaling and plays a critical role in regulating intestinal homeostasis and in suppressing tumor formation. This study was designed to determine whether JNK2, another MAPK, has similar and/or different functions in the regulation of beta-catenin signaling. METHODOLOGY AND PRINCIPAL FINDINGS: We used an in vitro system with manipulation of JNK2 and beta-catenin expression and found that activated JNK2 increased GSK3beta activity and inhibited beta-catenin expression and transcriptional activity. However, JNK2-mediated downregulation of beta-catenin was blocked by the proteasome inhibitor MG132 and GSK3beta inhibitor lithium chloride. Moreover, targeted mutations at GSK3beta phosphorylation sites (Ser33 and Ser37 of beta-catenin abrogated JNK2-mediated suppression of beta-catenin. In vivo studies further revealed that JNK2 deficiency led to upregulation of beta-catenin and increase of GSK3-beta phosphorylation in JNK2-/- mouse intestinal epithelial cells. Additionally, physical interaction and co-localization among JNK2, beta-catenin and GSK3beta were observed by immunoprecipitation, mammalian two-hybridization assay and confocal microscopy, respectively. CONCLUSION AND SIGNIFICANCE: In general, our data suggested that JNK2, like JNK1, interacts with and suppresses beta-catenin signaling in vitro and in vivo, in which GSK3beta plays a key role, although previous studies have shown distinct functions of JNK1 and JNK2. Our study also provides a novel insight into the crosstalk between Wnt/beta-catenin and MAPK JNKs signaling.

  2. Hyper-beta-alaninemia associated with beta-aminoaciduria and gamma-aminobutyricaciduaia, somnolence and seizures.

    Science.gov (United States)

    Scriver, C R; Pueschel, S; Davies, E

    1966-03-24

    Hyper-beta-alaninemia was found in a somnolent, convulsing infant. Hyper-beta-aminoaciduria (beta-ala, betaAIB and taurine) was also observed, varying directly with plasma beta-alanine concentration. The beta-aminoaciduria is explained by the interaction between beta-alanine and a specific cellular-transport system with preference for beta-amino compounds. Gamma-aminobutyricaciduria was also observed, its excretion being independent of beta-alanine levels. Dietary modifications, pyridoxine, pantothenic acid and antibiotic therapy were not beneficial. Post-mortem tissues had elevated levels of beta-alanine and carnosine; GABA levels in brain were probably elevated for the age of the patient. A proposed block in beta-alanine-alpha-ketoglutarate transaminase would expand the free beta-alanine pool, thus increasing tissue carnosine. beta-Alanine is a central-nervous-system depressant. Associated inhibition of GABA transaminase and displacement of GABA from central-nervous-system binding sites would produce GABAuria and convulsions. PMID:17926374

  3. Beta-2-mikroglobulin ved medicinske sygdomme

    DEFF Research Database (Denmark)

    Hansen, P B; Olsen, Niels Vidiendal

    1989-01-01

    Beta-2-microglobulin (beta 2M) is a low-molecular protein which is filtered freely over the glomeruli. Under normal circumstances, more than 99.9% is resorbed in the proximal tubuli of the kidneys and is metabolized there. In renal disease with damage to this segment of the nephron, eg acute tubulo......-interstitial nephropathy, increased quantities of beta 2M are excreted in the urine. If the rate of glomerular filtration is reduced, serum-beta 2M is increased and this is also the case in persons with increased cell division despite normal renal function. Serum-beta 2M is, therefore, raised in numerous malignant...... diseases and reflects the size of the tumour mass. During cytostatic treatment of myelomatosis and chronic lymphatic leukaemia, the serum-beta 2M levels decrease on remission and increase on relapse. In acute leukaemia and malignant lymphoma with infiltration of the CNS, similar conditions prevail for CSF...

  4. Experiments on double beta decay

    International Nuclear Information System (INIS)

    The Double Beta Decay, and especially (ββ)0ν mode, is an excellent test of Standard Model as well as of neutrino physics. From experimental point of view, a very large number of different techniques are or have been used increasing the sensitivity of this experiments quite a lot (the factor of 104 in the last 20 years). In future, in spite of several difficulties, the sensitivity would be increased further, keeping the interest of this very important process. (author) 4 figs., 5 tabs., 21 refs

  5. Beta blockers: A new role in chemotherapy

    OpenAIRE

    Nagaraja, Archana S; Sadaoui, Nouara C.; Lutgendorf, Susan K.; Ramondetta, Lois M.; Sood, Anil K

    2013-01-01

    Beta-blockers are a class of drugs widely used to treat cardiac, respiratory and other ailments. They act by blocking beta-adrenergic receptor–mediated signalling. Studies in various cancers have shown that patients taking a beta-blocker have higher survival and lower recurrence and metastasis rates. This is supported by several preclinical and in vitro studies showing that adrenergic activation modulates apoptosis, promotes angiogenesis and other cancer hallmarks, and these effects can be ab...

  6. The pancreatic beta cell surface proteome

    OpenAIRE

    Stützer, I.; Esterházy, D.; Stoffel, M.

    2012-01-01

    The pancreatic beta cell is responsible for maintaining normoglycaemia by secreting an appropriate amount of insulin according to blood glucose levels. The accurate sensing of the beta cell extracellular environment is therefore crucial to this endocrine function and is transmitted via its cell surface proteome. Various surface proteins that mediate or affect beta cell endocrine function have been identified, including growth factor and cytokine receptors, transporters, ion channels and prote...

  7. Constructions for a bivariate beta distribution

    OpenAIRE

    Olkin, Ingram; Trikalinos, Thomas A.

    2014-01-01

    The beta distribution is a basic distribution serving several purposes. It is used to model data, and also, as a more flexible version of the uniform distribution, it serves as a prior distribution for a binomial probability. The bivariate beta distribution plays a similar role for two probabilities that have a bivariate binomial distribution. We provide a new multivariate distribution with beta marginal distributions, positive probability over the unit square, and correlations over the full ...

  8. Theoretical aspects of double beta decay

    International Nuclear Information System (INIS)

    Considerable effort has been expended recently in theoretical studies of double beta decay. Much of this work has focussed on the constraints this process places on gauge theories of the weak interaction, in general, and on the neutrino mass matrix, in particular. In addition, interesting nuclear structure questions have arisen in studies of double beta decay matrix elements. After briefly reviewing the theory of double beta decay, some of the progress that has been made in these areas is summarized. 25 references

  9. First forbidden beta decay in light nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Millener, D.J.; Warburton, E.K.

    1984-01-01

    Beta decay matrix elements for the operators sigma dot del and sigma dot r are calculated for eight J/sup +/ ..-->.. J/sup -/ or J/sup -/ ..-->.. J/sup +/ beta transitions. Results using harmonic oscillator wave functions differ markedly from those using more realistic Woods-Saxon wave functions. A substantial contribution to the sigma dot del matrix elements from pion exchange currents is required to reproduce the experimental beta decay rates. 15 references.

  10. First forbidden beta decay in light nuclei

    International Nuclear Information System (INIS)

    Beta decay matrix elements for the operators sigma dot del and sigma dot r are calculated for eight J+ → J- or J- → J+ beta transitions. Results using harmonic oscillator wave functions differ markedly from those using more realistic Woods-Saxon wave functions. A substantial contribution to the sigma dot del matrix elements from pion exchange currents is required to reproduce the experimental beta decay rates. 15 references

  11. The Benchmark Beta, CAPM, and Pricing Anomalies.

    OpenAIRE

    Cheol S. Eun

    1994-01-01

    Recognizing that a part of the unobservable market portfolio is certainly observable, the author first reformulate the capital asset pricing model so that asset returns can be related to the 'benchmark' beta computed against a set of observable assets as well as the 'latent' beta computed against the remaining unobservable assets, and then shows that when the pricing effect of the latent beta is ignored, assets would appear to be systematically mispriced even if the capital asset pricing mode...

  12. C3 polymorphism in beta-thalassemia.

    Science.gov (United States)

    Germenis, A; Kalantzi, M; Karamerou, A; Politi, C; Fertakis, A

    1984-01-01

    The distribution of phenotypes and gene frequencies of the third component of complement (C3) were studied in 106 beta-thalassemic patients and in 112 carriers of the beta-thalassemia trait. A statistically significant association was found between the C3F gene and homozygous beta-thalassemia. It can be suggested that this association may be related with the high incidence of infections encountered in these patients. PMID:6419525

  13. Fabrication of beta particles detector for RMS

    International Nuclear Information System (INIS)

    The beta particles detector for RMS (radiation monitoring system) was fabricated to detect charged beta particles. The plastic scintillator was cutted, shaped, polished to make plastic disk for beta particles. The diameter of completed plastic scintillator disk is 40 mm and thickness is 1.5 mm. The mylar film and aluminium foil were used the front of plastic scintillator to intercept light and moisture. The completed plastic detector for RMS consist of the discriminator and counter were made by ULS (Co.). The absolute efficiency of plastic detector was 45.51% for beta particles (Sr/Y - 90)

  14. Sawtooth crashes at high beta on JET

    Energy Technology Data Exchange (ETDEWEB)

    Alper, B.; Huysmans, G.T.A.; Sips, A.C.C. [Commission of the European Communities, Abingdon (United Kingdom). JET Joint Undertaking; Nave, M.F.F. [Universidade Tecnica, Lisbon (Portugal). Inst. Superior Tecnico

    1994-07-01

    The sawtooth crashes on JET display features which depend on beta. The main observation is a transient bulging of flux surfaces (duration inferior to 30 microsec.), which is predominantly on the low field side and extends to larger radii as beta increases. This phenomenon reaches the plasma boundary when beta{sub N} exceeds 0.5 and in these cases is followed by an ELM within 50 microsec. These sawtooth/ELM events limit plasma performance. Modelling of mode coupling shows qualitative agreement between observations of the structure of the sawtooth precursor and the calculated internal kink mode at high beta. (authors). 6 refs., 5 figs.

  15. $\\beta$-decay study of $^{77}$Cu

    CERN Document Server

    Patronis, N; Górska, M; Huyse, M; Kruglov, K; Pauwels, D; Van de Vel, K; Van Duppen, P; Van Roosbroeck, J; Thomas, J-C; Franchoo, S; Cederkäll, J; Fedosseev, V; Fynbo, H; Georg, U; Jonsson, O; Köster, U; Materna, T; Mathieu, L; Serot, O; Weissman, L; Müller, W F; Mishin, V I; Fedorov, D

    2009-01-01

    A beta-decay study of Cu-77 has been performed at the ISOLDE mass separator with the aim to deduce its beta-decay properties and to obtain spectroscopic information on Zn-77. Neutron-rich copper isotopes were produced by means of proton- or neutron-induced fission reactions on U-238. After the production, Cu-77 was selectively laser ionized, mass separated and sent to different detection systems where beta-gamma and beta-n coincidence data were collected. We report on the deduced half-live, decay scheme, and possible spin assignment of 77Cu.

  16. Milk Intolerance, Beta-Casein and Lactose

    Directory of Open Access Journals (Sweden)

    Sebely Pal

    2015-08-01

    Full Text Available True lactose intolerance (symptoms stemming from lactose malabsorption is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows’ milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed.

  17. Milk Intolerance, Beta-Casein and Lactose

    OpenAIRE

    Sebely Pal; Keith Woodford; Sonja Kukuljan; Suleen Ho

    2015-01-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows’ milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows’ milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-...

  18. Milk Intolerance, Beta-Casein and Lactose.

    Science.gov (United States)

    Pal, Sebely; Woodford, Keith; Kukuljan, Sonja; Ho, Suleen

    2015-09-01

    True lactose intolerance (symptoms stemming from lactose malabsorption) is less common than is widely perceived, and should be viewed as just one potential cause of cows' milk intolerance. There is increasing evidence that A1 beta-casein, a protein produced by a major proportion of European-origin cattle but not purebred Asian or African cattle, is also associated with cows' milk intolerance. In humans, digestion of bovine A1 beta-casein, but not the alternative A2 beta-casein, releases beta-casomorphin-7, which activates μ-opioid receptors expressed throughout the gastrointestinal tract and body. Studies in rodents show that milk containing A1 beta-casein significantly increases gastrointestinal transit time, production of dipeptidyl peptidase-4 and the inflammatory marker myeloperoxidase compared with milk containing A2 beta-casein. Co-administration of the opioid receptor antagonist naloxone blocks the myeloperoxidase and gastrointestinal motility effects, indicating opioid signaling pathway involvement. In humans, a double-blind, randomized cross-over study showed that participants consuming A1 beta-casein type cows' milk experienced statistically significantly higher Bristol stool values compared with those receiving A2 beta-casein milk. Additionally, a statistically significant positive association between abdominal pain and stool consistency was observed when participants consumed the A1 but not the A2 diet. Further studies of the role of A1 beta-casein in milk intolerance are needed. PMID:26404362

  19. Beta attenuation transmission system (BATS)

    International Nuclear Information System (INIS)

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm2, of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A 90Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (μP) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined

  20. Beta attenuation transmission system (BATS)

    Energy Technology Data Exchange (ETDEWEB)

    Hagan, R.C.; Fullbright, H.J.

    1977-01-01

    The beta attenuation transmission system (BATS) is an automated radiation gauge designed for quantitative measurement of component thickness in explosive detonators. The BATS was designed and built by Group M-1, the Nondestructive Testing Group, of the Los Alamos Scientific Laboratory to measure the areal thickness, in mg/cm/sup 2/, of a cylinder of high explosive (HE) enclosed within a plastic holder. The problem is to determine the density of the HE. A /sup 90/Sr source is collimated by a 0.25 x 1.59-mm slit, and the transmitted beta-particle flux is detected by a plastic scintillator, coupled to a photomultiplier tube. The detonator is transported through the radiation beam by a leadscrew, ballnut, stepping-motor combination. Continuous analog position data are available, derived from the output from a linear-actuated potentiometer attached to the scanner. A linear electrometer amplifies the detected signal, which is then integrated for a preselected time, to obtain the desired statistical accuracy. A microprocessor (..mu..P) is used to control the scanner position and to make the data readings at the assigned positions. The data are stored, and, at the completion of the scan, are processed into the desired format. The final answer is displayed to the operator or output to a peripheral device for permanent record. The characteristics of the radiation source, the collimator, the signal detection and conditioning, and the final results are described in detail. The scanner and the microprocessor control system are briefly outlined.

  1. Pion beta decay at PILAC

    International Nuclear Information System (INIS)

    The proposal to build PILAC presents the possibility of making an improved measurement of the pion beta decay rate. The rate for the decay π+ → π0e+νe is predicted by the Standard Model (SM) to be R(π+ → π0e+νe) = 0.3999 ± 0.0005 s-1. The best experimental number, from LAMPF Experiment 32, using in-flight decays, is R(π+ → π0e+νe) = 0.394 ± 0.0015 s-1. A precise measurement would test the SM by testing the unitarity of the Cabibbo- Kobayashi-Maskawa matrix, for which one analysis of the nuclear beta decay data has shown a 0.4% discrepancy. Thus an experiment at the 0. 2% level would be a significant one. Detailed study of possible designs will be needed, as well as extensive testing of components. The reduction of systematic errors to the 0.1% level can only be done over a period of years with a highly stable apparatus and beam. At a minimum, three years of occupancy of a beam line, with 800 hours per year, would be required. 23 refs., 2 figs., 2 tabs

  2. Challenges in Double Beta Decay

    Directory of Open Access Journals (Sweden)

    Oliviero Cremonesi

    2014-01-01

    Full Text Available In the past ten years, neutrino oscillation experiments have provided the incontrovertible evidence that neutrinos mix and have finite masses. These results represent the strongest demonstration that the electroweak Standard Model is incomplete and that new Physics beyond it must exist. In this scenario, a unique role is played by the Neutrinoless Double Beta Decay searches which can probe lepton number conservation and investigate the Dirac/Majorana nature of the neutrinos and their absolute mass scale (hierarchy problem with unprecedented sensitivity. Today Neutrinoless Double Beta Decay faces a new era where large-scale experiments with a sensitivity approaching the so-called degenerate-hierarchy region are nearly ready to start and where the challenge for the next future is the construction of detectors characterized by a tonne-scale size and an incredibly low background. A number of new proposed projects took up this challenge. These are based either on large expansions of the present experiments or on new ideas to improve the technical performance and/or reduce the background contributions. In this paper, a review of the most relevant ongoing experiments is given. The most relevant parameters contributing to the experimental sensitivity are discussed and a critical comparison of the future projects is proposed.

  3. Association of heterocellular HPFH, beta(+)-thalassaemia, and delta beta(0)-thalassaemia: haematological and molecular aspects.

    OpenAIRE

    Cianetti, L; Care, A; Sposi, N M; Giampaolo, A; Calandrini, M; Petrini, M.; Massa, A.; Marinucci, M.; Mavilio, F; Ceccanti, M.

    1984-01-01

    An Italian family in which heterocellular hereditary persistence of fetal haemoglobin (HPFH) interacts with both beta(+)- and delta beta-thalassaemia is described. The index case was an 8 year old girl who was presumed to inherit both heterocellular HPFH and beta (+)-thalassaemia from her mother and delta beta-thalassaemia from her father. She was healthy and never needed blood transfusions. The possible contribution of heterocellular HPFH to the less severe expression of the compound delta b...

  4. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype.

    Directory of Open Access Journals (Sweden)

    Geert A Martens

    Full Text Available BACKGROUND AND METHODOLOGY: The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators. PRINCIPAL FINDINGS: A panel of 332 conserved beta cell biomarker genes was found to discriminate both isolated and laser capture microdissected beta cells from all other examined cell types. Of all conserved beta cell-markers, 15% were strongly beta cell-selective and functionally associated to hormone processing, 15% were shared with neuronal cells and associated to regulated synaptic vesicle transport and 30% with immune plus gut mucosal tissues reflecting active protein synthesis. Fasting specifically down-regulated the latter cluster, but preserved the neuronal and strongly beta cell-selective traits, indicating preserved differentiated state. Analysis of consensus binding site enrichment indicated major roles of CREB/ATF and various nutrient- or redox-regulated transcription factors in maintenance of differentiated beta cell phenotype. CONCLUSIONS: Conserved beta cell marker genes contain major gene clusters defined by their beta cell selectivity or by their additional abundance in either neural cells or in immune plus gut mucosal cells. This panel can be used as a template to identify changes in the differentiated state of beta cells.

  5. An imidazoline compound completely counteracts interleukin-1[beta] toxic effects to rat pancreatic islet [beta] cells

    DEFF Research Database (Denmark)

    Papaccio, Gianpaolo; Nicoletti, Ferdinando; Pisanti, Francesco A; Galdieri, Michela; Bendtzen, Klaus

    2002-01-01

    In vitro studies have demonstrated that interleukin (IL)-1beta decreases insulin and DNA contents in pancreatic islet beta cells, causing structural damage, that it is toxic to cultured human islet beta cells and that it is able to induce apoptosis in these cells....

  6. Expressions of GSK-3beta, Beta-Catenin and PPAR-Gamma in Medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiong Zhang; Lu Si; Yu Li; Can Mi

    2009-01-01

    Objective: To investigate the expressions of GSK-3beta, Beta-catenin and PPAR-gamma, and their relationship in medulloblastoma, and to explore their value in clinic application.Methods: Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta, Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues.Results: The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely, GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore, in medulloblastoma, beta-catenin and GSK-3beta showed a negative correlation, PPAR-gamma and beta-catenin had a positive correlation.Conclusion: Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile, PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

  7. Imperfect World of beta beta-decay Nuclear Data Sets

    Energy Technology Data Exchange (ETDEWEB)

    Pritychenko, B. [Brookhaven National Lab. (BNL), Upton, NY (United States). NNDC

    2015-01-03

    The precision of double-beta ββ-decay experimental half lives and their uncertainties is reanalyzed. The method of Benford's distributions has been applied to nuclear reaction, structure and decay data sets. First-digit distribution trend for ββ-decay T2v1/2 is consistent with large nuclear reaction and structure data sets and provides validation of experimental half-lives. A complementary analysis of the decay uncertainties indicates deficiencies due to small size of statistical samples, and incomplete collection of experimental information. Further experimental and theoretical efforts would lead toward more precise values of-decay half-lives and nuclear matrix elements.

  8. Dosimetry of low-energy beta radiation

    Energy Technology Data Exchange (ETDEWEB)

    Borg, J.

    1996-08-01

    Useful techniques and procedures for determination of absorbed doses from exposure in a low-energy {beta} radiation field were studied and evaluated in this project. The four different techniques included were {beta} spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical low-energy {beta} radiation field a moderated spectrum from a {sup 14}C source (E{sub {beta}},{sub max} =156 keV) was chosen for the study. The measured response of a Si(Li) detector to photons (bremsstrahlung) showed fine agreement with the MC calculated photon response, whereas the difference between measured and MC calculated responses to electrons indicates an additional dead layer thickness of about 12 {mu}m in the Si(Li) detector. The depth-dose profiles measured with extrapolation chambers at two laboratories agreed very well, and it was confirmed that the fitting procedure previously reported for {sup 147}Pm depth-dose profiles is also suitable for {beta} radiation from {sup 14}C. An increasing difference between measured and MC calculated dose rates for increasing absorber thickness was found, which is explained by limitations of the EGS4 code for transport of very low-energy electrons (below 10-20 keV). Finally a study of the thermally stimulated exoelectron emission (TSEE) response of BeO thin film dosemeters to {beta} radiation for radiation fields with maximum {beta} energies ranging from 67 keV to 2.27 MeV is reported. For maximum {beta} energies below approximately 500 keV, a decrease in the response amounting to about 20% was observed. It is thus concluded that a {beta} dose higher than about 10 {mu}Gy can be measured with these dosemeters to within 0 to -20% independently of the {beta}energy for E{sub {beta}},{sub max} values down to 67 keV. (au) 12 tabs., 38 ills., 71 refs.

  9. [Hemoglobin C -- beta-thalassemia disease and homozygous beta-thalassemia in a black African family (author's transl)].

    Science.gov (United States)

    Basset, P; Fall, M; Oudart, J L

    1975-01-01

    The study of a Malian family has allowed to prove existence of two types of beta-thalassemia genes: the beta0 gene which suppresses the synthesis of the beta chain into cis position and the beta+ gene which slows down only partially this synthesis. The difference between this two genes has been possible owing to the hemoglobin C found in this family and induced by the betaC mutated gene. The segregation of the four genes betaA, betaC, beta0 thal, and beta+ thal. has allowed to compare all the possible phenotypes deriving from the combinations by two of these allelic genes. PMID:128735

  10. Search for beta sup - and beta sup -beta sup - decays of sup 4 sup 8 Ca

    CERN Document Server

    Bakalyarov, A; Barabash, A; Briançon, C; Brudanin, V; Egorov, V; Hubert, F; Hubert, P; Kovalik, A; Lebedev, V I; Rukhadze, N I; Stekl, I; Umatov, V; Vylov, T D

    2002-01-01

    A sup 4 sup 8 CaCO sub 3 powder sample containing 20.18 g of sup 4 sup 8 Ca was measured for 797 h with a 400 cm sup 3 low-background HPGe detector. New limits on decays of sup 4 sup 8 Ca were obtained. For single beta transitions to sup 4 sup 8 Sc the limits are equal to 0.71x10 sup 2 sup 0 y, 1.1x10 sup 2 sup 0 y, and 0.82x10 sup 2 sup 0 y for transitions to the ground state, excited 5 sup + and 4 sup + states, respectively. The new limits on double beta decay to excited states of sup 4 sup 8 Ti are equal to 0.47x10 sup 2 sup 0 y, 1.1x10 sup 2 sup 0 y, and 0.90x10 sup 2 sup 0 y for transitions to the first 2 sup + , second 2 sup + and first 0 sup + excited states, respectively. All limits are given at the 90% CL.

  11. Signaling from beta1- and beta2-adrenergic receptors is defined by differential interactions with PDE4

    DEFF Research Database (Denmark)

    Richter, Wito; Day, Peter; Agrawal, Rani; Bruss, Matthew D; Granier, Sébastien; Wang, Yvonne L; Rasmussen, Søren Gøgsig Faarup; Horner, Kathleen; Wang, Ping; Lei, Tao; Patterson, Andrew J; Kobilka, Brian; Conti, Marco

    2008-01-01

    Beta1- and beta2-adrenergic receptors (betaARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by beta1AR but not beta2AR signaling, and chronic stimulation of the two receptors has opposing...

  12. Beta cell proliferation and growth factors

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis; Svensson, C; Møldrup, Annette;

    1999-01-01

    Formation of new beta cells can take place by two pathways: replication of already differentiated beta cells or neogenesis from putative islet stem cells. Under physiological conditions both processes are most pronounced during the fetal and neonatal development of the pancreas. In adulthood litt...

  13. Beta-agonists and animal welfare

    Science.gov (United States)

    The use of beta-agonists in animal feed is a high profile topic within the U.S. as consumers and activist groups continue to question its safety. The only beta-agonist currently available for use in swine is ractopamine hydrochloride (RAC). This is available as Paylean™ (Elanco Animal Health – FDA a...

  14. Dosimetry of Low-Energy Beta Radiation

    DEFF Research Database (Denmark)

    Borg, Jette

    Useful techniques and procedures for derermination of absorbed doses from exposure in a low-energy beta radiation were studied and evaluated. The four techniques included were beta spectrometry, extrapolation chamber dosimetry, Monte Carlo (MC) calculations, and exoelectron dosimetry. As a typical...

  15. Beta spectra. II-Positron spectra

    International Nuclear Information System (INIS)

    Using the Fermi theory of beta decay, the beta spectra for 30 positron emitters have been computed, introducing a correction factor for unique forbidden transitions. The spectra are ploted vs. energy, once normalised, and tabulated with the related Fermi functions. The average and median energies are calculated. (author)

  16. A proportional-scintillation counter beta spectrometer

    International Nuclear Information System (INIS)

    Using a proportional counter for coincidence gating of events in a plastic scintillator provides selective registration of beta interactions in the scintillator. This technique has been used to construct a field instrument that can selectively collect beta spectra (coincidence gating) or gamma spectra (anticoincidence gating). Associated dose rates are calculated from the spectra

  17. Broad resonances and beta-decay

    DEFF Research Database (Denmark)

    Riisager, K.; Fynbo, H. O. U.; Hyldegaard, S.;

    2015-01-01

    Beta-decay into broad resonances gives a distorted lineshape in the observed energy spectrum. Part of the distortion arises from the phase space factor, but we show that the beta-decay matrix element may also contribute. Based on a schematic model for p-wave continuum neutron states it is argued...

  18. Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy

    OpenAIRE

    Butler, A. E.; Cao-Minh, L.; Galasso, R; Rizza, R. A.; Corradin, A.; Cobelli, C; Butler, P C

    2010-01-01

    Aims/hypothesis We sought to establish the extent and basis for adaptive changes in beta cell numbers in human pregnancy. Methods Pancreas was obtained at autopsy from women who had died while pregnant (n = 18), post-partum (n = 6) or were not pregnant at or shortly before death (controls; n = 20). Pancreases were evaluated for fractional pancreatic beta cell area, islet size and islet fraction of beta cells, beta cell replication (Ki67) and apoptosis (TUNEL), and indirect markers of beta cel...

  19. Antibodies against chromosomal beta-lactamase

    DEFF Research Database (Denmark)

    Giwercman, B; Rasmussen, J W; Ciofu, Oana; Clemmentsen, I; Schumacher, H; Høiby, N

    1994-01-01

    A murine monoclonal anti-chromosomal beta-lactamase antibody was developed and an immunoblotting technique was used to study the presence of serum and sputum antibodies against Pseudomonas aeruginosa chromosomal group 1 beta-lactamase in patients with cystic fibrosis (CF). The serum antibody...... response was studied with serum samples collected in 1992 from 56 CF patients in a cross-sectional study and with serum samples from 18 CF patients in a longitudinal study. Anti-beta-lactamase immunoglobulin G antibodies were present in all of the serum samples from the patients with chronic...... bronchopulmonary P. aeruginosa infection (CF + P) but in none of the CF patients with no or intermittent P. aeruginosa infection. Anti-beta-lactamase antibodies were present in serum from CF + P patients after six antipseudomonal courses (median) and correlated with infection with a beta-lactam-resistant strain of...

  20. The search for neutrinoless double beta decay

    CERN Document Server

    Gomez-Cadenas, J J; Mezzetto, M; Monrabal, F; Sorel, M

    2011-01-01

    In the last few years the search for neutrinoless double beta decay has evolved from being almost a marginal activity in neutrino physics to one of the highest priorities for understanding neutrinos and the origin of mass. There are two main reasons for this paradigm shift: the discovery of neutrino oscillations, which clearly established the existence of massive neutrinos; and the existence of an unconfirmed, but not refuted, claim of evidence for neutrinoless double decay in 76Ge. As a consequence, a new generation of experiments, employing different detection techniques and {\\beta}{\\beta} isotopes, is being actively promoted by experimental groups across the world. In addition, nuclear theorists are making remarkable progress in the calculation of the neutrinoless double beta decay nuclear matrix elements, thus eliminating a substantial part of the theoretical uncertainties affecting the particle physics interpretation of this process. In this report, we review the main aspects of the double beta decay pro...

  1. Simultaneous beta/gamma digital spectroscopy

    Science.gov (United States)

    Farsoni, Abdollah T.

    A state-of-the-art radiation detection system for simultaneous spectroscopy of beta-particles and gamma-rays has been developed. The system utilizes a triple-layer phoswich detector and a customized Digital Pulse Processor (DPP) built in our laboratory. The DPP board was designed to digitally capture the analog signal pulses and, following several digital preprocessing steps, transfer valid pulses to the host computer for further digital processing. A MATLAB algorithm was developed to digitally discriminate beta and gamma events and reconstruct separate beta and gamma-ray energy spectra with minimum crosstalk. The spectrometer proved to be an effective tool for recording separate beta and gamma-ray spectra from mixed radiation fields. The system as a beta-gamma spectrometer will have broad-ranging applications in nuclear non-proliferation, radioactive waste management, worker safety, systems reliability, dose assessment, and risk analysis.

  2. Genetics Home Reference: dopamine beta-hydroxylase deficiency

    Science.gov (United States)

    ... Genetics Home Health Conditions dopamine beta-hydroxylase deficiency dopamine beta-hydroxylase deficiency Enable Javascript to view the ... boxes. Print All Open All Close All Description Dopamine beta (β)-hydroxylase deficiency is a condition that ...

  3. Clusters of conserved beta cell marker genes for assessment of beta cell phenotype

    DEFF Research Database (Denmark)

    Martens, Geert A; Jiang, Lei; Hellemans, Karine H;

    2011-01-01

    of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser......The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those...... capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators....

  4. Conformation, molecular packing and field effect mobility of regioregular beta,beta'-dihexylsexithiophiophene

    DEFF Research Database (Denmark)

    Kiriy, N.; Kiriy, A.; Bocharova, V.;

    2004-01-01

    (SEM), atomic force microscopy (AFM), and X-ray techniques. Absorption spectra of a beta,beta'-DH6T spin-cast film indicate the planar conformation of the aromatic backbone. SEM and AFM reveal the formation of an ordered lamellar phase. As a single-crystal X-ray study shows, beta,beta'-DH6T exhibits......Improved synthesis, charge carrier mobility, conformation, crystalline structure, and molecular packing of the regiochemically pure 4',3""-dihexyl-2,2';5',2";5",2 "';5"',2"";5"",2""'-sexithiophene (beta,beta'-DH6T) are reported. The sum of charge carrier mobilities of beta,beta'-DH6T measured...... by the pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) technique was found to be Sigmamu(min) = 3.9 x 10(-3) cm(2) V-1 s(-1), which is comparable with the PR-TRMC mobility found for alpha,omega-DH6T. The field-effect mobility (FEM) of beta,beta'-DH6T was found to be on the order of 10(-5) cm(2...

  5. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  6. Total synthesis of human beta-lipotropin.

    OpenAIRE

    Blake, J; Li, C. H.

    1983-01-01

    The total synthesis of human beta-lipotropin has been accomplished by the new segment-coupling method in aqueous solution. The peptides Ac-Arg-beta-lipotropin-(61-89) (I) and [GlyS60]-beta-lipotropin-(1-60) (II) were synthesized by the solid-phase method. Reaction of peptide I with citraconic anhydride followed by brief digestion with trypsin to remove the acetylarginyl group, gave Ia. Reaction of peptide II with citraconic anhydride gave the citraconyl peptide IIa. Ia and IIa were coupled to...

  7. Rotational beta expansion: Ergodicity and Soficness

    OpenAIRE

    Akiyama, Shigeki; Caalim, Jonathan

    2015-01-01

    We study a family of piecewise expanding maps on the plane, generated by composition of a rotation and an expansive similitude of expansion constant $\\beta$. We give two constants $B_1$ and $B_2$ depending only on the fundamental domain that if $\\beta>B_1$ then the expanding map has a unique absolutely continuous invariant probability measure, and if $\\beta>B_2$ then it is equivalent to $2$-dimensional Lebesgue measure. Restricting to a rotation generated by $q$-th root of unity $\\zeta$ with ...

  8. Falsifying Baryogenesis with Neutrinoless Double Beta Decay

    CERN Document Server

    Graf, Lukas

    2016-01-01

    We discuss the relation between lepton number violation at high and low energies, particularly, the constraints on baryogenesis models, which would be implied by an observation of neutrinoless double beta decay. The primordial baryon asymmetry can be washed out by effective lepton number violating operators triggering neutrinoless double beta decay in combination with sphaleron processes. A generic conclusion is that popular models of baryogenesis are excluded if a non-standard mechanism of neutrinoless double beta decay, i.e., other than the standard light neutrino exchange, is observed. Apart from the effective field approach, we also outline the possible extension of our arguments to a general UV-completed model.

  9. Beta-alanine synthesis in Escherichia coli.

    OpenAIRE

    Cronan, J. E.

    1980-01-01

    The enzyme, aspartate 1-decarboxylase (L-aspartate 1-carboxy-lyase; EC 4.1.1.15), that catalyzes the reaction aspartate leads to beta-alanine + CO2 was found in extracts of Escherichia coli. panD mutants of E. coli are defective in beta-alanine biosynthesis and lack aspartate 1-decarboxylase. Therefore, the enzyme functions in the biosynthesis of the beta-alanine moiety of pantothenate. The genetic lesion in these mutants is closely linked to the other pantothenate (pan) loci of E. coli K-12.

  10. Review of modern double beta decay experiments

    Science.gov (United States)

    Barabash, A. S.

    2015-10-01

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T1/2(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino ( at the level of ˜ 0.01-0.1 eV are discussed.

  11. Beta cell count instead of beta cell mass to assess and localize growth in beta cell population following pancreatic duct ligation in mice.

    Directory of Open Access Journals (Sweden)

    Marie Chintinne

    Full Text Available BACKGROUND: Pancreatic-tail duct ligation (PDL in adult rodents has been reported to induce beta cell generation and increase beta cell mass but increases in beta cell number have not been demonstrated. This study examines whether PDL increases beta cell number and whether this is caused by neogenesis of small clusters and/or their growth to larger aggregates. METHODOLOGY: Total beta cell number and its distribution over small (100 µm clusters was determined in pancreatic tails of 10-week-old mice, 2 weeks after PDL or sham. PRINCIPAL FINDINGS: PDL increased total beta cell mass but not total beta cell number. It induced neogenesis of small beta cell clusters (2.2-fold higher number which contained a higher percent proliferating beta cells (1.9% Ki67+cells than sham tails (<0.2%; their higher beta cell number represented <5% of total beta cell number and was associated with a similar increase in alpha cell number. It is unknown whether the regenerative process is causally related to the inflammatory infiltration in PDL-tails. Human pancreases with inflammatory infiltration also exhibited activation of proliferation in small beta cell clusters. CONCLUSIONS/SIGNIFICANCE: The PDL model illustrates the advantage of direct beta cell counts over beta cell mass measurements when assessing and localizing beta cell regeneration in the pancreas. It demonstrates the ability of the adult mouse pancreas for neogenesis of small beta cell clusters with activated beta cell proliferation. Further studies should investigate conditions under which neoformed small beta cell clusters grow to larger aggregates and hence to higher total beta cell numbers.

  12. Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

    Energy Technology Data Exchange (ETDEWEB)

    Caselli, E.; Powers, R.A.; Blaszczak, L.C.; Wu, C.Y.E.; Prati, F.; Shoichet, B.K. (NWU)

    2010-03-05

    Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well as four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly

  13. Bound beta-decay: BOB

    International Nuclear Information System (INIS)

    For many years exotic decay modes of the neutron have been investigated as possible doorways to the exploration of new physics. The bound beta-decay (BOB) of the neutron into a hydrogen atom and an anti-neutrino offers a very elegant method to study neutrino helicities. However, this rare decay has not yet been observed for the free neutron, owing to the challenge of measuring a decay involving only electrically neutral particles and with an estimated branching ratio of only a few 106 of the three-body decay mode. During the past few years scientists from the TUM E18 Group have developed a novel experimental scheme which addresses all necessary problems associated with the observation of this two-body neutron decay in a very coherent way. The BOB experiment shall be installed at a tangential beam tube of a powerful research reactor such as the SR6 at the FRMII in Garching or H6-H7 beam tube at ILL. This talk will provide insights and ideas on how such an experiment is to be performed.

  14. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  15. Neutron bound {beta}- decay- BOB

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, M.; Berger, M.; Emmerich, R.; Faestermann, T.; Gutsmiedl, E.; Hartmann, F.J.; Paul, S.; Ruschel, S.; Schoen, J.; Schott, W.; Schubert, U.; Trautner, A. [Physik-Department, TUM, 85748 Garching (Germany); Engels, R. [Institut fuer Kernphysik, Forschungszentrum Juelich, 52425 Juelich (Germany); Fierlinger, P. [Excellence Cluster Universe, TUM, 85748 Garching (Germany); Hertenberger, R. [Sektion Physik, LMU, 85748 Garching (Germany); Roehrmoser, R. [FRM2, TUM, 85748 Garching (Germany); Udem, T. [Max-Planck-Institut fuer Quantenphysik, 85748 Garching (Germany)

    2011-07-01

    The bound neutron {beta}-decay(BOB) into a hydrogen atom and an electron antineutrino is investigated.The hyper-fine-state population of the monoenergetic hydrogen atoms (326.3 eV) yields the neutrino left-handed-ness or a possible right-handed admixture and possible small scalar and tensor contributions to the weak force. Preexperiments to measure the BOB H(2s) atoms have been done or are being set up using ionizer and RF discharge proton sources, a Wien filter, Cs and Ar cells, a spin filter, electric counter and accelerating fields, a double focusing magnet and a solar blind PM for the Lyman-{alpha} photons. In a first experiment, the charge exchange of the H(2s) atoms into H{sup -}, offering a selective method to discriminate these states against background, is investigated. In a second step the number of background H(2s) resulting from protons interacting with the walls of the experimental setup are determined. For this a quenching E field and a solar blind PM are used.

  16. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Directory of Open Access Journals (Sweden)

    Murtadha Al-Khabori

    2013-03-01

    Full Text Available Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline, feeling unwell (2, severe diarrhea (1, pregnancy (1, death unrelated to chelator (2 and rise in serum transaminases (2. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013.Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

  17. Pressure phase lines and enthalpies for the. cap alpha. -. beta. and. beta. -liquid transitions in beryllium

    Energy Technology Data Exchange (ETDEWEB)

    Abey, A.

    1984-10-31

    The effect of hydrostatic pressure on the ..cap alpha..-..beta.. and ..beta..-liquid transition temperatures in Be was measured in a gas pressure system. Differential thermal analysis was used in the pressure range from 0.1 MPa to 0.7 GPa. For the ..cap alpha..-..beta.. transition, dT/dP = 43 +- 7 K/GPa; for the ..beta..-liquid transition, dT/dP = 35 +- 7 K/GPa. Although it is possible that large systematic errors may arise from experimental procedures, our results are seriously at odds with those of other investigators. Transition enthalpies for the ..cap alpha..-..beta.. and ..beta..-liquid transitions were 1.9 +- 0.2 and 2.2 +- 0.2 kcal/g.m., respectively, at a pressure of 0.1 MPa.

  18. A comparison of enzymatic phosphorylation and phosphatidylation of beta-L- and beta-D-nucleosides.

    Science.gov (United States)

    Birichevskaya, Larisa L; Kvach, Sergei V; Sivets, Grigorii G; Kalinichenko, Elena N; Zinchenko, Anatoly I; Mikhailopulo, Igor A

    2007-04-01

    Enzymatic 5'-monophosphorylation and 5'-phosphatidylation of a number of beta-L- and beta-D-nucleosides was investigated. The first reaction, catalyzed by nucleoside phosphotransferase (NPT) from Erwinia herbicola, consisted of the transfer of the phosphate residue from p-nitrophenylphosphate (p-NPP) to the 5'-hydroxyl group of nucleoside; the second was the phospholipase D (PLD)-catalyzed transphosphatidylation of L-alpha-lecithin with a series of beta-L- and beta-D-nucleosides as the phosphatidyl acceptor resulted in the formation of the respective phospholipid-nucleoside conjugates. Some beta-L-nucleosides displayed similar or even higher substrate activity compared to the beta-D-enantiomers. PMID:17206374

  19. Systematic Risk on Istanbul Stock Exchange: Traditional Beta Coefficient Versus Downside Beta Coefficient

    Directory of Open Access Journals (Sweden)

    Gülfen TUNA

    2013-03-01

    Full Text Available The aim of this study is to test the validity of Downside Capital Asset Pricing Model (D-CAPM on the ISE. At the same time, the explanatory power of CAPM's traditional beta and D-CAPM's downside beta on the changes in the average return values are examined comparatively. In this context, the monthly data for seventy three stocks that are continuously traded on the ISE for the period 1991-2009 is used. Regression analysis is applied in this study. The research results have shown that D-CAPM is valid on the ISE. In addition, it is obtained that the power of downside beta coefficient is higher than traditional beta coefficient on explaining the return changes. Therefore, it can be said that the downside beta is superior to traditional beta in the ISE for chosen period.

  20. Review of modern double beta decay experiments

    International Nuclear Information System (INIS)

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T1/2(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino (〈mν〉 < 0.46 eV) and a coupling constant of Majoron to neutrino (〈gee〉 < 1.3 · 10−5) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to 〈mν〉 at the level of ∼ 0.01-0.1 eV are discussed

  1. Neutrino potential for neutrinoless double beta decay

    CERN Document Server

    Iwata, Yoritaka

    2016-01-01

    Neutrino potential for neutrinoless double beta decay is studied with focusing on its statistical property. The statistics provide a gross view of understanding amplitude of constitutional components of the nuclear matrix element.

  2. Literature in Focus Beta Beams: Neutrino Beams

    CERN Document Server

    2009-01-01

    By Mats Lindroos (CERN) and Mauro Mezzetto (INFN Padova, Italy) Imperial Press, 2009 The beta-beam concept for the generation of electron neutrino beams was first proposed by Piero Zucchelli in 2002. The idea created quite a stir, challenging the idea that intense neutrino beams only could be produced from the decay of pions or muons in classical neutrino beams facilities or in future neutrino factories. The concept initially struggled to make an impact but the hard work by many machine physicists, phenomenologists and theoreticians over the last five years has won the beta-beam a well-earned position as one of the frontrunners for a possible future world laboratory for high intensity neutrino oscillation physics. This is the first complete monograph on the beta-beam concept. The book describes both technical aspects and experimental aspects of the beta-beam, providing students and scientists with an insight into the possibilities o...

  3. Genetics Home Reference: beta-mannosidosis

    Science.gov (United States)

    ... depression, or have behavioral problems such as hyperactivity, impulsivity or aggression. People with beta-mannosidosis may experience ... and management of various health conditions: Diagnostic Tests Drug Therapy Surgery and Rehabilitation Genetic Counseling Palliative Care ...

  4. Review of modern double beta decay experiments

    Energy Technology Data Exchange (ETDEWEB)

    Barabash, A. S., E-mail: barabash@itep.ru [Institute of Theoretical and Experimental Physics (NRC ”Kurchatov Institute”), B. Cheremushkinskaya 25, Moscow (Russian Federation)

    2015-10-28

    The review of modern experiments on search and studying of double beta decay processes is done. Results of the most sensitive current experiments are discussed. The main attention is paid to EXO-200, KamLAND-Zen, GERDA-I and CUORE-0 experiments. Modern values of T{sub 1/2}(2ν) and best present limits on neutrinoless double beta decay and double beta decay with Majoron emission are presented. Conservative limits on effective mass of a Majorana neutrino (〈m{sub ν}〉 < 0.46 eV) and a coupling constant of Majoron to neutrino (〈g{sub ee}〉 < 1.3 · 10{sup −5}) are obtained. Prospects of search for neutrinoless double beta decay in new experiments with sensitivity to 〈m{sub ν}〉 at the level of ∼ 0.01-0.1 eV are discussed.

  5. Beta decay of highly charged ions

    International Nuclear Information System (INIS)

    Ion storage rings and ion traps provide the very first opportunity to address nuclear beta decay under conditions prevailing in hot stellar plasmas during nucleosynthesis, i.e. at high atomic charge states. Experiments are summarized that were performed in this field during the last decade at the ion storage-cooler ring ESR in Darmstadt. Special emphasis is given to the first observation of bound-state beta decay, where the created electron remains bound in an inner orbital of the daughter atom. The impact of this specific 'stellar' decay mode for s-process nucleosynthesis as well as for nuclear 'eon clocks' is outlined. Finally, a new technique, single-ion decay spectroscopy, is presented, where one observes two-body beta decay characteristics (i.e. orbital electron capture or bound-state beta decay) of highly charged, single ions for well-defined nuclear and atomic quantum states of both the mother - and the daughter - ion.

  6. High-Beta and very high-beta optics studies for the LHC

    CERN Document Server

    Faus-Golfe, A

    2004-01-01

    New high-beta and very high-beta optics have been sought in order to find the best possible configuration for measuring elastic scattering at the LHC. They are based on the nominal powering scheme of the low-beta triplet. A list of the various possible solutions is given in this report. A particularly interesting solution has been found for a case where the phase advance in both planes at the detector are clore to pi/2.

  7. Ant parasite queens revert to mating singly

    DEFF Research Database (Denmark)

    Sumner, Seirian; Hughes, William Owen Hamar; Pedersen, Jes Søe;

    2004-01-01

    A parasitic ant has abandoned the multiple mating habit of the queens of its related host. Multiple mating (polyandry) is widespread among animal groups, particularly insects 1 . But the factors that maintain it and underlie its evolution are hard to verify because benefits and costs are not easily...... quantified and they tend to be similar in related species. Here we compare the mating strategies of the leaf-cutting ant Acromyrmex echinatior and its recently derived social parasite Acromyrmex insinuator, which is also its closest relative 2 (see Fig. 1 ). We find that although the host queens mate with up...... to a dozen different males, the social parasite mates only singly. This rapid and surprising reversion to single mating in a socially parasitic ant indicates that the costs of polyandry are probably specific to a free-living lifestyle....

  8. Sri Lanka's Trade Policy: Reverting to Dirigisme?

    OpenAIRE

    Prema-chandra Athukorala

    2012-01-01

    This paper surveys recent development in Sri Lankan trade policy, with an emphasis on emerging protectionist tendencies, using Sri Lanka’s Trade Policy Review (2010) by the World Trade Organization as a reference point. The Sri Lankan experience for over the three decades following the liberalization reforms started in 1977 has clearly demonstrated that an outward-oriented policy regime can yield a superior development outcome compared to a closed-economy regime, even under severe strains o...

  9. Genetic counselling in the beta-thalassaemias

    OpenAIRE

    Ioannides, Adonis S.

    2013-01-01

    The beta-thalassaemias are very important genetic disorders of haemoglobin synthesis and are amongst the commonest monogenic disorders. In view of the severity of beta-thalassaemia major, a number of screening programmes have been developed aimed at reducing the number of individuals born with the condition. Genetic counsellingplays a vital role in this process supporting the successful implementation of screening and delineating available options to at risk individuals. This review assesses ...

  10. Searches for neutrinoless double beta decay

    Science.gov (United States)

    Schwingenheuer, Bernhard

    2012-07-01

    Neutrinoless double beta decay is a lepton number violating process whose observation would also establish that neutrinos are their own anti-particles. There are many experimental efforts with a variety of techniques. Some (EXO, Kamland-Zen, GERDA phase I and CANDLES) started take data in 2011 and EXO has reported the first measurement of the half life for the double beta decay with two neutrinos of 136Xe. The sensitivities of the different proposals are reviewed.

  11. Searches for neutrinoless double beta decay

    CERN Document Server

    Schwingenheuer, B

    2012-01-01

    Neutrinoless double beta decay is a lepton number violating process whose observation would also establish that neutrinos are their own anti-particles. There are many experimental efforts with a variety of techniques. Some (EXO, Kamland-Zen, GERDA phase I and CANDLES) started take data in 2011 and EXO has reported the first measurement of the half life for the double beta decay with two neutrinos of $^{136}$Xe. The sensitivities of the different proposals are reviewed.

  12. Micro-battery Development using beta radioisotope

    International Nuclear Information System (INIS)

    Nuclear battery which use the beta radiation sources emitting the low penetration radiation energy from radioisotope can be applied as the long term (more than 10 years) micro power source in MEMS and nano components. This report describes the basic concept and principles of nuclear micro-battery and its fabrication in space and military field. In particular direct conversion method is described by investigating the electron-hole generation and recombination in p-n junction of silicon betavoltaics with beta radiation

  13. Conditionally parametric fits for CAPM betas

    OpenAIRE

    Abberger, Klaus

    2004-01-01

    The CAPM model assumes stock returns to be a linear function of the market return. However, there is considerable evidence that the beta stability assumption commonly used when estimating the model is invalid. Nonparametric regression methods are used to examine the stability of beta coefficients in German stock returns. Since local polynomial regression is used for estimation, known methods for testing the stability and for bandwidth choice can be used. For some returns the test indicates ti...

  14. Unexpected pattern of beta-globin mutations in beta-thalassaemia patients from northern Portugal

    OpenAIRE

    Cabeda, J.; Correia, C.; Estevinho, A.; Simões, C.; Amorim, M; L. Pinho; Justiça, B

    1999-01-01

    We characterized the genetic nature of beta-thalassaemia in northern Portugal. Of the 164 patients studied three were beta-thalassaemia major cases (one IVS-1-6/beta degrees 39 and two homozygous IVS-1-110). The analysis of the frequency of each mutation in the families revealed that the codon 6(-A) mutation was unexpectedly frequent (40%) and associated with the beta-globin haplotype E, and not with the usual European and North African CD6(-A) haplotypes. In contrast, the frequency of IVS-1-...

  15. The effect of physical therapy on beta-endorphin levels.

    Science.gov (United States)

    Bender, Tamás; Nagy, György; Barna, István; Tefner, Ildikó; Kádas, Eva; Géher, Pál

    2007-07-01

    Beta-endorphin (betaE) is an important reliever of pain. Various stressors and certain modalities of physiotherapy are potent inducers of the release of endogenous betaE to the blood stream. Most forms of exercise also increase blood betaE level, especially when exercise intensity involves reaching the anaerobic threshold and is associated with the elevation of serum lactate level. Age, gender, and mental activity during exercise also may influence betaE levels. Publications on the potential stimulating effect of manual therapy and massage on betaE release are controversial. Sauna, mud bath, and thermal water increase betaE levels through conveying heat to the tissues. The majority of the techniques for electrical stimulation have a similar effect, which is exerted both centrally and--to a lesser extent--peripherally. However, the parameters of electrotherapy have not yet been standardised. The efficacy of analgesia and the improvement of general well-being do not necessarily correlate with betaE level. Although in addition to blood, increased brain and cerebrospinal fluid betaE levels are also associated with pain, the majority of studies have concerned blood betaE levels. In general, various modalities of physical therapy might influence endorphin levels in the serum or in the cerebrospinal fluid--this is usually manifested by elevation with potential mitigation of pain. However, a causal relationship between the elevation of blood, cerebrospinal fluid or brain betaE levels and the onset of the analgesic action cannot be demonstrated with certainty. PMID:17483960

  16. Beta adrenergic receptors in human cavernous tissue

    International Nuclear Information System (INIS)

    Beta adrenergic receptor binding was performed with 125I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of 125iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype

  17. Beta adrenergic receptors in human cavernous tissue

    Energy Technology Data Exchange (ETDEWEB)

    Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

    1985-04-01

    Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptor density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.

  18. The beta-adrenoceptors mediating relaxation of rat oesophageal muscularis mucosae are predominantly of the beta 3-, but also of the beta 2-subtype.

    OpenAIRE

    de Boer, R. E.; Brouwer, F.; Zaagsma, J

    1993-01-01

    1. beta-Adrenoceptor-mediated relaxation of rat oesophageal smooth muscle was investigated by studying the effects of beta 1- and beta 2-selective antagonists on the relaxation induced by (-)-isoprenaline, the beta 2-selective agonists fenoterol and clenbuterol and the beta 3-agonist, BRL 37344. 2. The highly beta 1-selective antagonist CGP 20721A did not antagonize (-)-isoprenaline- or BRL 37344-induced relaxations in concentrations up to 10 microM. Only at 100 microM of CGP 20712A were clea...

  19. News on $\\beta$-delayed particle emission from $^{14}$Be

    CERN Document Server

    Jeppesen, H; Borge, M J G; Cederkäll, J; Fynbo, H O U; Fedoseyev, V N; Hansper, V Y; Jonson, B; Markenroth, K; Mishin, V I; Nilsson, T; Nyman, G; Riisager, K; Tengblad, O; Wilhelmsen Rolander, K

    2002-01-01

    $\\beta$-delayed charged particles from $^{14}$Be have been measured and give an upper limit on $\\beta$-delayed $\\alpha$-particles of B($\\beta\\alpha$) < $\\,6.7\\times\\!10^{-5}$ and a tentative branching ratio on $\\beta$-delayed tritons of $7.5\\times\\!10^{-5}$ < B($\\beta$t) < $\\,3.9\\times\\!10^{-4}$. We combine the knowledge on $\\beta$-delayed particles from $^{14}$Be to deduce information on the $\\beta$-strength distribution.

  20. Beta-Negative Binomial Process and Poisson Factor Analysis

    OpenAIRE

    Zhou, Mingyuan; Hannah, Lauren; Dunson, David; Carin, Lawrence

    2011-01-01

    A beta-negative binomial (BNB) process is proposed, leading to a beta-gamma-Poisson process, which may be viewed as a "multi-scoop" generalization of the beta-Bernoulli process. The BNB process is augmented into a beta-gamma-gamma-Poisson hierarchical structure, and applied as a nonparametric Bayesian prior for an infinite Poisson factor analysis model. A finite approximation for the beta process Levy random measure is constructed for convenient implementation. Efficient MCMC computations are...

  1. Oligomerization and toxicity of A{beta} fusion proteins

    Energy Technology Data Exchange (ETDEWEB)

    Caine, Joanne M., E-mail: Jo.Caine@csiro.au [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Bharadwaj, Prashant R. [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Centre for Excellence for Alzheimer' s Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Western Australia (Australia); Sankovich, Sonia E. [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Ciccotosto, Giuseppe D. [The Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010 (Australia); Streltsov, Victor A.; Varghese, Jose [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia)

    2011-06-10

    Highlights: {yields} We expressed amyloid-{beta} (A{beta}) peptide as a soluble maltose binding protein fusion (MBP-A{beta}42 and MBP-A{beta}16). {yields} The full length A{beta} peptide fusion, MBP-A{beta}42, forms oligomeric species as determined by SDS-PAGE gels, gel filtration and DLS. {yields} The MBP-A{beta}42, but not MBP-A{beta}16 or MBP alone, is toxic to both yeast and mammalian cells as determined by toxicity assays. -- Abstract: This study has found that the Maltose binding protein A{beta}42 fusion protein (MBP-A{beta}42) forms soluble oligomers while the shorter MBP-A{beta}16 fusion and control MBP did not. MBP-A{beta}42, but neither MBP-A{beta}16 nor control MBP, was toxic in a dose-dependent manner in both yeast and primary cortical neuronal cells. This study demonstrates the potential utility of MBP-A{beta}42 as a reagent for drug screening assays in yeast and neuronal cell cultures and as a candidate for further A{beta}42 characterization.

  2. Beta Gyres in Global Analysis Fields

    Institute of Scientific and Technical Information of China (English)

    Sun-Hee KIM; H.Joe KWON; R.L.ELSBERRY

    2009-01-01

    A three-component decomposition is applied to global analysis data to show the existence of a beta gyre,which causes Tropical Cyclone (TC) to drift from a large-scale environmental steering current.Analyses from the Global Data Assimilation and Prediction System (GDAPS) of the Korea Meteorological Administration (KMA),the Global Forecast System (GFS) of NCEP,and the Navy Operational Global Atmospheric Prediction System (NOGAPS) are used in this study.The structure of the beta gyre obtained in our analyses is in good agreement with the theoretical structure,with a cyclonic circulation to the southwest of the TC center,an anticyclonic circulation to the northeast,and a ventilation flow directed northwestward near the center.The circulation of the beta gyre is strongest at the 850-hPa level where the cyclonically swirling primary circulation is strongest,and decreases with height,in a pyramid shape similar to the primary circulation.The individual structure of the beta gyre is case- and model-dependent.At a certain analysis time,one model may clearly reveal a well-defined beta gyre,but the other models may not.Within one model,the beta gyre may be well defined at some analysis times,but not at other times.The structure of the beta gyre in the analysis field is determined by the nature of the vortex initialization scheme and the model behavior during the 6-h forecast in the operational data assimilation cycle.

  3. Detrimental effects of beta-blockers in COPD - A concern for nonselective beta-blockers

    NARCIS (Netherlands)

    van der Woude, HJ; Zaagsma, J; Postma, DS; Winter, TH; van Hulst, M; Aalbers, R

    2005-01-01

    Introduction: beta-Blockers are known to worsen FEV1 and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring beta-blocker treatment. Design: A double-blind, placebo-controlled, randomized,

  4. Mrp2 is essential for estradiol-17 beta(beta-D-glucuronide)-induced cholestasis in rats

    NARCIS (Netherlands)

    Huang, LY; Smit, JW; Meijer, DKF; Vore, M

    2000-01-01

    The present study evaluates the roles of the multidrug resistance-1 P-glycoprotein, Mdr1a/1b, the bile salt export pump (Bsep), and the multidrug resistance-associated protein-2 (Mrp2) in mediating cholestasis induced by estradiol-17 beta(beta-D-glucuronide) (E(2)17G). Administration of [H-3]E(2)17G

  5. Production of beta-xylanase and beta-xylosidase by the extremely halophilic archaeon Halorhabdus utahensis

    DEFF Research Database (Denmark)

    Wainø, M.; Ingvorsen, K.

    2003-01-01

    The extremely halophilic archaeon, Halorhabdus utahensis, isolated from the Great Salt Lake, Utah, produced beta-xylanase and beta-xylosidase activities. Both enzymes were active over a broad NaCl range from near zero to 30% NaCl when tested with culture broth. A broad NaCl optimum was observed f...

  6. On Gamow-Teller strength distributions for $\\beta\\beta$-decaying nuclei within continuum-QRPA

    CERN Document Server

    Igashov, S Yu; Faessler, Amand; Urin, M H

    2010-01-01

    An isospin-selfconsistent pn-continuum-QRPA approach is formulated and applied to describe the Gamow-Teller strength distributions for $\\beta\\beta$-decaying open-shell nuclei. The calculation results obtained for the pairs of nuclei $^{76}$Ge-Se, $^{100}$Mo-Ru, $^{116}$Cd-Sn, and $^{130}$Te-Xe are compared with available experimental data.

  7. Competition of $\\beta$-delayed protons and $\\beta$-delayed $\\gamma$ rays in $^{56}$Zn and the exotic $\\beta$-delayed $\\gamma$-proton decay

    CERN Document Server

    Orrigo, S E A; Fujita, Y; Blank, B; Gelletly, W; Agramunt, J; Algora, A; Ascher, P; Bilgier, B; Cáceres, L; Cakirli, R B; Fujita, H; Ganioglu, E; Gerbaux, M; Giovinazzo, J; Grévy, S; Kamalou, O; Kozer, H C; Kucuk, L; Kurtukian-Nieto, T; Molina, F; Popescu, L; Rogers, A M; Susoy, G; Stodel, C; Suzuki, T; Tamii, A; Thomas, J C

    2016-01-01

    Remarkable results have been published recently on the $\\beta$ decay of $^{56}$Zn. In particular, the rare and exotic $\\beta$-delayed $\\gamma$-proton emission has been detected for the first time in the $fp$ shell. Here we focus the discussion on this exotic decay mode and on the observed competition between $\\beta$-delayed protons and $\\beta$-delayed $\\gamma$ rays from the Isobaric Analogue State.

  8. Regulation of glycogen synthase kinase-3{beta} (GSK-3{beta}) after ionizing radiation; Regulation der Glykogen Synthase Kinase-3{beta} (GSK-3{beta}) nach ionisierender Strahlung

    Energy Technology Data Exchange (ETDEWEB)

    Boehme, K.A.

    2006-12-15

    Glycogen Synthase Kinase-3{beta} (GSK-3{beta}) phosphorylates the Mdm2 protein in the central domain. This phosphorylation is absolutely required for p53 degradation. Ionizing radiation inactivates GSK-3{beta} by phosphorylation at serine 9 and in consequence prevents Mdm2 mediated p53 degradation. During the work for my PhD I identified Akt/PKB as the kinase that phosphorylates GSK-3{beta} at serine 9 after ionizing radiation. Ionizing radiation leads to phosphorylation of Akt/PKB at threonine 308 and serine 473. The PI3 Kinase inhibitor LY294002 completely abolished Akt/PKB serine 473 phosphorylation and prevented the induction of GSK-3{beta} serine 9 phosphorylation after ionizing radiation. Interestingly, the most significant activation of Akt/PKB after ionizing radiation occurred in the nucleus while cytoplasmic Akt/PKB was only weakly activated after radiation. By using siRNA, I showed that Akt1/PKBa, but not Akt2/PKB{beta}, is required for phosphorylation of GSK- 3{beta} at serine 9 after ionizing radiation. Phosphorylation and activation of Akt/PKB after ionizing radiation depends on the DNA dependent protein kinase (DNA-PK), a member of the PI3 Kinase family, that is activated by free DNA ends. Both, in cells from SCID mice and after knockdown of the catalytic subunit of DNA-PK by siRNA in osteosarcoma cells, phosphorylation of Akt/PKB at serine 473 and of GSK-3{beta} at serine 9 was completely abolished. Consistent with the principle that phosphorylation of GSK-3 at serine 9 contributes to p53 stabilization after radiation, the accumulation of p53 in response to ionizing radiation was largely prevented by downregulation of DNA-PK. From these results I conclude, that ionizing radiation induces a signaling cascade that leads to Akt1/PKBa activation mediated by DNA-PK dependent phosphorylation of serine 473. After activation Akt1/PKBa phosphorylates and inhibits GSK-3{beta} in the nucleus. The resulting hypophosphorylated form of Mdm2 protein is no longer

  9. Closed-form expressions for moments of a class of beta generalized distributions

    OpenAIRE

    Cordeiro, Gauss M.; Nadarajah, Saralees

    2011-01-01

    For the first time, we derive explicit closed-form expressions for moments of some beta generalized distributions including the beta gamma, beta normal, beta beta, beta Student t and beta F distributions. These expressions are given as infinite weighted sums of well-known special functions for which numerical routines for computation are available.

  10. Neutrinoless double beta decay from lattice QCD

    CERN Document Server

    Nicholson, Amy; Chang, Chia Cheng; Clark, M A; Joo, Balint; Kurth, Thorsten; Rinaldi, Enrico; Tiburzi, Brian; Vranas, Pavlos; Walker-Loud, Andre

    2016-01-01

    While the discovery of non-zero neutrino masses is one of the most important accomplishments by physicists in the past century, it is still unknown how and in what form these masses arise. Lepton number-violating neutrinoless double beta decay is a natural consequence of Majorana neutrinos and many BSM theories, and many experimental efforts are involved in the search for these processes. Understanding how neutrinoless double beta decay would manifest in nuclear environments is key for understanding any observed signals. In these proceedings we present an overview of a set of one- and two-body matrix elements relevant for experimental searches for neutrinoless double beta decay, describe the role of lattice QCD calculations, and present preliminary lattice QCD results.

  11. Calibration of beta dosimeter and personal dosimeter

    International Nuclear Information System (INIS)

    This paper introduces ISO standard ISO 6980 which prepared especially for the calibration of beta dosimeter and personal dosimeter. The standard has three aspects including method of production of reference beta particle radiations, calibration fundamentals related to basic quantities characterizing the radiation field, and calibration of area and personal dosemters and the determination of their response as a function of beta radiation energy and angle of incidence. Here particular emphasis is placed on the determination of basic quantity of tissue absorbed dose at a depth of 0.07 mm in the tissue slab phantom and calibration procedure by mean of the calibration quantity of directional dose equivalent H'(0.07, Ω) and personal dose equivalent Hp (0.07, Ω). Finally, combined standard uncertainty for the determination of absorbed dose rate and component uncertainties of calibration is given as examples. (authors)

  12. Tevatron B0 low beta tuning report

    International Nuclear Information System (INIS)

    A detailed study of the low beta insertion for the B0 experimental area has been carried out and is described below. This insertion is similar to the Type C low beta previously report, anti p Note 169, although some changes have been made to the quadrupole lengths and positions. This insertion is designated Type E. The purpose of the study was to see if it is possible to turn the insertion on in a smooth and continuous manner and tune the insertion to a value of β* of less than one meter while maintaining the overall tune of the j Tevatron to a constant value. This was found to be possible. An examination of chromaticity corrections for the Tevatron with the low beta insertion on in various configurations was also undertaken

  13. BETASCAN: probable beta-amyloids identified by pairwise probabilistic analysis.

    Directory of Open Access Journals (Sweden)

    Allen W Bryan

    2009-03-01

    Full Text Available Amyloids and prion proteins are clinically and biologically important beta-structures, whose supersecondary structures are difficult to determine by standard experimental or computational means. In addition, significant conformational heterogeneity is known or suspected to exist in many amyloid fibrils. Recent work has indicated the utility of pairwise probabilistic statistics in beta-structure prediction. We develop here a new strategy for beta-structure prediction, emphasizing the determination of beta-strands and pairs of beta-strands as fundamental units of beta-structure. Our program, BETASCAN, calculates likelihood scores for potential beta-strands and strand-pairs based on correlations observed in parallel beta-sheets. The program then determines the strands and pairs with the greatest local likelihood for all of the sequence's potential beta-structures. BETASCAN suggests multiple alternate folding patterns and assigns relative a priori probabilities based solely on amino acid sequence, probability tables, and pre-chosen parameters. The algorithm compares favorably with the results of previous algorithms (BETAPRO, PASTA, SALSA, TANGO, and Zyggregator in beta-structure prediction and amyloid propensity prediction. Accurate prediction is demonstrated for experimentally determined amyloid beta-structures, for a set of known beta-aggregates, and for the parallel beta-strands of beta-helices, amyloid-like globular proteins. BETASCAN is able both to detect beta-strands with higher sensitivity and to detect the edges of beta-strands in a richly beta-like sequence. For two proteins (Abeta and Het-s, there exist multiple sets of experimental data implying contradictory structures; BETASCAN is able to detect each competing structure as a potential structure variant. The ability to correlate multiple alternate beta-structures to experiment opens the possibility of computational investigation of prion strains and structural heterogeneity of amyloid

  14. beta2-Agonists at the Olympic Games.

    Science.gov (United States)

    Fitch, Kenneth D

    2006-01-01

    The different approaches that the International Olympic Committee (IOC) had adopted to beta2-agonists and the implications for athletes are reviewed by a former Olympic team physician who later became a member of the Medical Commission of the IOC (IOC-MC). Steadily increasing knowledge of the effects of inhaled beta2-agonists on health, is concerned with the fact that oral beta2-agonists may be anabolic, and rapid increased use of inhaled beta2-agonists by elite athletes has contributed to the changes to the IOC rules. Since 2001, the necessity for athletes to meet IOC criteria (i.e., that they have asthma and/or exercise-induced asthma [EIA]) has resulted in improved management of athletes. The prevalence of beta2-agonist use by athletes mirrors the known prevalence of asthma symptoms in each country, although athletes in endurance events have the highest prevalence. The age-of-onset of asthma/EIA in elite winter athletes may be atypical. Of the 193 athletes at the 2006 Winter Olympics who met th IOC's criteria, only 32.1% had childhood asthma and 48.7% of athletes reported onset at age 20 yr or older. These findings lead to speculation that years of intense endurance training may be a causative factor in bronchial hyperreactivity. The distinction between oral (prohibited in sports) and inhaled salbutamol is possible, but athletes must be warned that excessive use of inhaled salbutamol can lead to urinary concentrations similar to those observed after oral administration. This article provides justification that athletes should provide evidence of asthma or EIA before being permitted to use inhaled beta2-agonists. PMID:17085798

  15. Beta/gamma test problems for ITS

    International Nuclear Information System (INIS)

    The Integrated Tiger Series of Coupled Electron/Photon Monte Carlo Transport Codes (ITS 3.0, PC Version) was used at Oak Ridge National Laboratory (ORNL) to compare with and extend the experimental findings of the beta/gamma response of selected health physics instruments. In order to assure that ITS gives correct results, several beta/gamma problems have been tested. ITS was used to simulate these problems numerically, and results for each were compared to the problem's experimental or analytical results. ITS successfully predicted the experimental or analytical results of all tested problems within the statistical uncertainty inherent in the Monte Carlo method

  16. Double-Beta Decay at TUNL

    Science.gov (United States)

    Kidd, Mary

    2007-10-01

    Studying double-beta decay at Triangle Universities Nuclear Laboratory (TUNL) is perhaps one of the most promising ways to pinpoint the neutrino mass. What they do not mention is that to study double-beta decay, you probably have to become a certified miner, and if you have a fear of goats, you should stay away. In this talk, I will tell you some of my experiences as a TUNL graduate student, and how I am now nearly qualified for a job in the mining industry.

  17. Microscopic calculations for rare beta decays

    OpenAIRE

    Mustonen, Mika

    2010-01-01

    In this thesis consisting of six publications and an overview part, three cases of rare beta decays are studied using microscopic nuclear models. Firstly, the half-lives and electron spectra of 113Cd and 115In fourth-forbidden nonunique ground-state-to-ground-state beta decays are studied using two closely related nuclear models: The microscopic quasiparticle-phonon model (MQPM) and the proton-neutron MQPM (pnMQPM), which has been developed as a part of this thesis work. Our...

  18. Nuclear beta decay after Les Houches

    International Nuclear Information System (INIS)

    Wilkinson's 1977 Les Houches lectures summarized in detail how nuclear beta decay can be used to investigate fundamental nuclear phenomena and the achievements of this utilization up to that time. In this short talk the subsequent activity is briefly summarized and one area of high activity, namely first-forbidden beta decay, is singled out for more lengthy discussion. Specifically, the subject of interest is the very large meson exchange contribution to the time-like component of the axial current and the efforts to isolate this enhancement by means of careful shell-model calculations. 19 refs., 4 figs., 2 tabs

  19. Survey instrument response to beta radiations

    International Nuclear Information System (INIS)

    Available survey instruments do not have the beta measurement characteristics needed for accurate dose rate assessments. Such instruments have severe angular and energy dependence. In addition, beta measurements often require corrections for the source geometry response of the detector to permit accurate assessments. Studies were performed to characterize present instruments and to determine optimum characteristics for a field instrument. Results of the studies were used to specify and procure an instrument with improved characteristics. The purpose of this paper is to describe the results of the studies and the design of the instrument

  20. Survey instrument response to beta radiations

    International Nuclear Information System (INIS)

    Available survey instruments do not have the beta measurement characteristics needed for accurate dose rate assessments. Such instruments have severe angular and energy dependence. In addition, beta measurements often require corrections for the source geometry response of the detector to permit accurate assessments. Studies were performed to characterize present instruments and to determine optimum characteristics for a field instrument. Results of the studies were used to specify and procure an instrument with improved characteristics. The purpose of this paper is to describe the results of the studies and the design of the instrument. 6 refs., 6 figs., 4 tabs

  1. Why search for double beta decay?

    International Nuclear Information System (INIS)

    Searching for neutrinoless double beta decay is the only known practical method for trying to determine whether neutrinos are their own antiparticles. The theoretical motivation for supposing that they may indeed be their own antiparticles is described. The reason that it is so difficult to ascertain experimentally whether they are or are not is explained, as is the special sensitivity of neutrinoless double beta decay. The potential implications of the observation of this reaction for neutrino mass and for the physics of neutrinos is discussed

  2. Helicity and nuclear $\\beta$ decay correlations

    CERN Document Server

    Hong, Ran; García, Alejandro

    2016-01-01

    We present simple derivations of nuclear $\\beta$-decay correlations with an emphasis on the special role of helicity. This provides a good opportunity to teach students about helicity and chirality in particle physics through exercises using simple aspects of quantum mechanics. In addition, this paper serves as an introduction to nuclear $\\beta$-decay correlations from both a theoretical and experimental vantage. This article can be used to introduce students to ongoing experiments searching for hints of new physics in the low-energy precision frontier.

  3. Card controlled beta backscatter thickness measuring instrument

    International Nuclear Information System (INIS)

    An improved beta backscatter instrument for the nondestructive measurement of the thickness of thin coatings on a substrate is described. Included therein is the utilization of a bank of memory stored data representative of isotope, substrate, coating material and thickness range characteristics in association with a control card having predetermined indicia thereon selectively representative of a particular isotope, substrate material, coating material and thickness range for conditioning electronic circuit means by memory stored data selected in accord with the predetermined indicia on a control card for converting backscattered beta particle counts into indicia of coating thickness

  4. Supermultiplet of $\\beta-$deformations from twistors

    CERN Document Server

    Milián, Segundo P

    2016-01-01

    We consider the supermultiplet of linearized beta-deformation of $\\mathcal{N}=4$ Super Yang-Mills(SYM). It was previously studied on the gravitational side. We study the supermultiplet of beta-deformations on the field theory side and we compare two finite-dimensional representations of $psl(4|4,\\bf{R})$ algebra. We show that they are related by an intertwining operator. We develop a twistor-based approach which could be useful for studying other finite-dimensional and nonunitary representations in AdS/CFT correspondence.

  5. Symmetry violations in nuclear and neutron $\\beta$ decay

    CERN Document Server

    Vos, K K; Timmermans, R G E

    2015-01-01

    The role of $\\beta$ decay as a low-energy probe of physics beyond the Standard Model is reviewed. Traditional searches for deviations from the Standard Model structure of the weak interaction in $\\beta$ decay are discussed in the light of constraints from the LHC and the neutrino mass. Limits on the violation of time-reversal symmetry in $\\beta$ decay are compared to the strong constraints from electric dipole moments. Novel searches for Lorentz symmetry breaking in the weak interaction in $\\beta$ decay are also included, where we discuss the unique sensitivity of $\\beta$ decay to test Lorentz invariance. We end with a roadmap for future $\\beta$-decay experiments.

  6. COBRA - Double beta decay searches using CdTe detectors

    OpenAIRE

    Zuber, K.

    2001-01-01

    A new approach (called COBRA) for investigating double beta decay using CdTe (CdZnTe) semiconductor detectors is proposed. It follows the idea that source and detector are identical. This will allow simultaneous measurements of 5 $\\beta^-\\beta^-$ - and 4 $\\beta^+\\beta^+$ - emitters at once. Half-life limits for neutrinoless double beta decay of Cd-116 and Te-130 can be improved by more than one order of magnitude with respect to current limits and sensitivities on the effective Majorana neutr...

  7. Molecular and chemical comparison of beta/sub 2/ and beta/sub 2/ adrenergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Shorr, R.G.L.; Gotlib, L.; Varrichio, A.; Strohsacker, M.; Minnich, M.; Crooke, S.T.

    1986-05-01

    Beta-adrenergic receptor proteins of 55,000M/sub r/ and 45,000M/sub r/ have been purified from rabbit lung, guinea pig lung, bovine lung and turkey red blood cell plasma membranes by affinity chromatography, size exclusion high performance liquid chromatography and preparative SDS polyacrylamide gel electrophoresis. Each purified receptor was characterized with agonists and selective antagonists in ligand binding competition experiments with (/sup 125/I) cyanopindolol as being of the ..beta../sub 1/ or ..beta../sub 2/ adrenergic receptor subclass. Purified rabbit lung, guinea pig lung and bovine lung were all found to be of the ..beta../sub 2/ receptor subclass. Purified turkey RBC receptor was of the ..beta../sub 1/ subclass. When compared by molecular weight, each of the receptor proteins was found to comigrate on SDS polyacylamide gels with its counterpart from the additional tissues. When the proteins were compared by amino acid composition similar results were obtained for each of the receptors. These results suggest significant levels of sequence homology between the avian ..beta../sub 1/ adrenergic receptor and the mammalian ..beta../sub 2/ adrenergic receptor preparations.

  8. Human liver alcohol dehydrogenase. 1. The primary structure of the beta 1 beta 1 isoenzyme.

    Science.gov (United States)

    Hempel, J; Bühler, R; Kaiser, R; Holmquist, B; de Zalenski, C; von Wartburg, J P; Vallee, B; Jörnvall, H

    1984-12-17

    Determination of the amino acid sequence of the beta 1 subunit from the class I (pyrazole-sensitive) human liver alcohol dehydrogenase isoenzyme beta 1 beta 1 revealed a 373-residue structure differing at 48 positions (including a gap) from that of the subunit of the well studied horse liver alcohol dehydrogenase EE isoenzyme. The structure deduced is compatible with known differences in composition, ultraviolet absorbance, electrophoretic mobility and catalytic properties between the horse and human enzymes. All zinc-liganding residues of the horse E subunit are strictly conserved in the human beta 1 subunit, despite an earlier report of a mutation involving Cys-46. This residue therefore remains conserved in all known alcohol dehydrogenase structures. However, the total cysteine content of the beta 1 structure is raised from 14 in the subunit of the horse enzyme to 15 by a Tyr----Cys exchange. Most exchanges are on the surface of the molecule and of a well conserved nature. Substitutions close to the catalytic centre are of interest to explain the altered substrate specificity and different catalytic activity of the beta 1 homodimer. Functionally, a Ser----Thr exchange at position 48 appears to be of special importance, since Thr-48 in beta 1 instead of Ser-48 in the horse enzyme can restrict available space. Four other substitutions also line the active-site pocket, and appear to constitute partly compensated exchanges. PMID:6391920

  9. Use of multi-element TL dosimeters for beta and mixed beta/gamma personnel monitoring

    International Nuclear Information System (INIS)

    Applied experience as well as theoretical considerations make it clear that traditional two-element TL dosimeters are not adequate for use in personnel dosimetry involving beta radiation fields. The principal shortcoming of such dosimeters is that the TL element measuring the beta dose normally under responds, and the readings of such elements must be multiplied by a correction factor, called the beta factor, to obtain the dose. The beta factor, however, is not a constant but varies with variations in the beta spectrum incident on the dosimeter. Experimental tests carried out using a number of multi-element TL dosimeter designs have shown that the element readouts can be used in conjunction with a suitable algorithm to determine a suitable beta factor for use under a variety of irradiation conditions. The precision attainable in calculating the beta factor in this manner depends on a number of dosimeter design parameters and is often quite poor unless special care is exercised both in the design of the dosimeter and also in the operation of the readout system

  10. Nuclear Matrix Elements for the $\\beta\\beta$ Decay of the $^{76}$Ge

    CERN Document Server

    Brown, B A; Horoi, M

    2015-01-01

    The nuclear matrix elements for two-neutrino double-beta (2 n$\\beta\\beta$ ) and zero-neutrino double-beta (0 n$\\beta\\beta$) decay of 76 Ge are evaluated in terms of the configuration interaction (CI), quasiparticle random phase approximation (QRPA) and interacting boson model (IBM) methods. We show that the decomposition of the matrix elements in terms of interemediate states in 74 Ge is dominated by ground state of this nucleus. We consider corrections to the CI results that arise from configurations admixtures involving orbitals out-side of the CI configuration space by using results from QRPA, many-body-perturbation theory, and the connections to related observables. The CI two-neutrino matrix element is reduced due to the inclusion of spin-orbit partners, and to many-body correlations connected with Gamow-Teller beta decay. The CI zero-neutrino matrix element for the heavy neutrino is enhanced due to particle-particle correlations that are connected with the odd-even oscillations in the nuclear masse...

  11. EMILIN1/α9β1 Integrin Interaction Is Crucial in Lymphatic Valve Formation and Maintenance

    OpenAIRE

    Danussi, Carla; Del Bel Belluz, Lisa; Pivetta, Eliana; Modica, Teresa Maria Elisa; Muro, Andres; Wassermann, Bruna; Doliana, Roberto; Sabatelli, Patrizia; Colombatti, Alfonso; Spessotto, Paola

    2013-01-01

    Lymphatic vasculature plays a crucial role in the maintenance of tissue interstitial fluid balance. The role of functional collecting lymphatic vessels in lymph transport has been recently highlighted in pathologies leading to lymphedema, for which treatments are currently unavailable. Intraluminal valves are of paramount importance in this process. However, valve formation and maturation have not been entirely elucidated yet, in particular, the role played by the extracellular matrix (ECM). ...

  12. Fibronectin increases the force production of mouse papillary muscles via α5β1 integrin

    OpenAIRE

    Wu, Xin; Chakraborty, Sanjukta; Heaps, Cristine L.; Davis, Michael J.; Meininger, Gerald A.; Muthuchamy, Mariappan

    2010-01-01

    The extracellular matrix (ECM) protein-integrin-cytoskeleton axis plays a central role as a mechanotransducing protein assemblage in many cell types. However, how the process of mechanotransduction and the mechanical generated signals arising from this axis affect myofilament function in cardiac muscle are not completely understood. We hypothesize that ECM proteins can regulate cardiac function through integrin binding, and thereby alter the intracellular calcium concentration ([Ca2+]i) and/o...

  13. Coalition of Oct4A and β1 integrins in facilitating metastasis in ovarian cancer

    OpenAIRE

    Samardzija, Chantel; Luwor, Rodney B.; Quinn, Michael A; Kannourakis, George; Jock K Findlay; Ahmed, Nuzhat

    2016-01-01

    Background Ovarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer meta...

  14. α8β1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism

    Science.gov (United States)

    Khalifeh-Soltani, Amin; Ha, Arnold; Podolsky, Michael J; McCarthy, Donald A; McKleroy, William; Azary, Saeedeh; Sakuma, Stephen; Tharp, Kevin M; Wu, Nanyan; Yokosaki, Yasuyuki; Hart, Daniel; Stahl, Andreas; Atabai, Kamran

    2016-01-01

    Coordinated gastrointestinal smooth muscle contraction is critical for proper nutrient absorption and is altered in a number of medical disorders. In this work, we demonstrate a critical role for the RGD-binding integrin α8β1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of α8 in mice result in enhanced gastric antral smooth muscle contraction, more rapid gastric emptying, and more rapid transit of food through the small intestine leading to malabsorption of dietary fats and carbohydrates as well as protection from weight gain in a diet-induced model of obesity. Mechanistically, ligation of α8β1 by the milk protein Mfge8 reduces antral smooth muscle contractile force by preventing RhoA activation through a PTEN-dependent mechanism. Collectively, our results identify a role for α8β1 in regulating gastrointestinal motility and identify α8 as a potential target for disorders characterized by hypo- or hyper-motility. DOI: http://dx.doi.org/10.7554/eLife.13063.001 PMID:27092791

  15. Massaspectrometrische analyse van enkele beta-agonisten

    OpenAIRE

    Traag, W.A.; Kienhuis, P.G.M.; Tuinstra, L.G.M.T.; Bennekom, van, C.A.M.; Huf, F.A.

    1990-01-01

    Zes beta-agonisten (isoproterenol, clenbuterol, cimaterol, terbutaline, salbutamol en fenoterol) zijn als TMS-derivaten onderzocht op hun GeMS-eigenschappen in zowel de Electron Impact (EI) als positieve Chemische Ionisatie mode (Cl). Tevens is clenbuterol-hexyl onderzocht. Deze component is geschikt om als interne standaard te fungeren.

  16. Association behavior of native beta-lactoglobulin

    DEFF Research Database (Denmark)

    Verheul, M.; Pedersen, J.S.; Roefs, S.P.F.M.; Kruif, K.G. de

    1999-01-01

    samples were obtained. These functions provided information on the maximum size, the weight-averaged molecular mass, and the z-averaged radius of gyration oo the the beta-lactoglobulin particles. Al room temperature and pH values below 4 and above IZ the protein consists predominantly of monomers and...

  17. Herwig++ 2.0beta Release Note

    OpenAIRE

    Gieseke, Stefan; Grellscheid, D.; Ribon, Alberto; Richardson, P.; Seymour, Michael H.; Stephens, Phil; Webber, Bryan R

    2006-01-01

    A new release of the Monte Carlo program Herwig++ (version 2.0beta) is now available. The main new feature is the extension of the program to include simple hadron-hadron processes including the initial-state parton shower.

  18. Characterization of a Commercial Silicon Beta Cell

    Energy Technology Data Exchange (ETDEWEB)

    Foxe, Michael P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hayes, James C. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mayer, Michael F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); McIntyre, Justin I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sivels, Ciara B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Suarez, Rey [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-03-31

    Silicon detectors are of interest for the verification of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) due to their enhanced energy resolution compared to plastic scintillators beta cells. Previous work developing a figure-of-merit (FOM) for comparison of beta cells suggests that the minimum detectable activity (MDA) could be reduced by a factor of two to three with the use of silicon detectors. Silicon beta cells have been developed by CEA (France) and Lares Ltd. (Russia), with the PIPSBox developed by CEA being commercially available from Canberra for approximately $35k, but there is still uncertainty about the reproducibility of the capabilities in the field. PNNL is developing a high-resolution beta-gamma detector system in the shallow underground laboratory, which will utilize and characterize the operation of the PIPSBox detector. Throughout this report, we examine the capabilities of the PIPSBox as developed by CEA. The lessons learned through the testing and use of the PIPSBox will allow PNNL to strategically develop a silicon detector optimized to better suit the communities needs in the future.

  19. Nuclear physics issues in double beta decay

    International Nuclear Information System (INIS)

    A number of issues in double beta decay are discussed: shell model estimates of 2nu matrix elements, a sum rule for the double Gamow-Teller operator, a comparison of shell model and quasiparticle RPA results, Pontecorvo's Te ratio argument, neutrinoless ββ decay mediated by heavy neutrinos, and the structure of O+ states in Ge isotopes. 24 refs., 3 figs

  20. Average beta measurement in EXTRAP T1

    International Nuclear Information System (INIS)

    Beginning with the ideal MHD pressure balance equation, an expression for the average poloidal beta, ΒΘ, is derived. A method for unobtrusively measuring the quantities used to evaluate ΒΘ in Extrap T1 is described. The results if a series of measurements yielding ΒΘ as a function of externally applied toroidal field are presented. (author)

  1. Topical beta-Blockers and Mortality

    NARCIS (Netherlands)

    Muskens, Rogier P. H. M.; Wolfs, Roger C. W.; Wittenian, Jacqueline C. M.; Hofman, Albert; de Jong, Paulus T. V. M.; Stricker, Bruno H. C.; Jansonius, Nomdo M.

    2008-01-01

    Purpose: To study the associations between long-term and short-term use of topical beta-blockers and mortality. Design: Prospective population-based cohort study. Participants: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484

  2. Redox Homeostasis in Pancreatic beta Cells

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Dlasková, Andrea; Plecitá-Hlavatá, Lydie

    2012-01-01

    Roč. 2012, č. 2012 (2012), s. 932838. ISSN 1942-0900 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204 Institutional support: RVO:67985823 Keywords : beta cells * reactive oxygen species homeostasis * mitochondria Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.393, year: 2012

  3. Semiconductor detectors and double beta decay

    International Nuclear Information System (INIS)

    The underlying theory of double beta decay is discussed as well as some experimental observations. A class of second generation 76Ge detector experiments is then discussed. The design and physics considerations involved in the system used by LBL are explained, particularly the means of rejecting background activity. 24 references, 18 figures, 3 tables

  4. Multiple nerve palsies in beta thalassaemia major.

    OpenAIRE

    Lamabadusuriya, S. P.

    1989-01-01

    A patient with beta thalassaemia major is described who developed a lower motor neurone facial nerve palsy on the left side, together with a phrenic nerve palsy on the same side, during the course of the illness. This complication has not been reported before in haemoglobinopathies.

  5. LHC dijet constraints on double beta decay

    CERN Document Server

    Helo, J C

    2015-01-01

    We use LHC dijet data to derive constraints on neutrinoless double beta decay. Upper limits on cross sections for the production of "exotic" resonances, such as a right-handed W boson or a diquark, can be converted into lower limits on the double beta decay half-life for fixed choices of other parameters. Constraints derived from run-I data are already surprisingly strong and complementary to results from searches using same-sign dileptons plus jets. For the case of the left-right symmetric model, in case no new resonance is found in future runs of the LHC and assuming $g_L=g_R$, we estimate a lower limit on the double beta decay half-live larger than $10^{27}$ ys can be derived from future dijet data, except in the window of relatively light right-handed neutrino masses in the range $0.5$ MeV to $50$ GeV. Part of this mass window will be tested in the upcoming SHiP experiment. We also discuss current and future limits on possible scalar diquark contributions to double beta decay that can be derived from dije...

  6. Double beta decay: A theoretical overview

    Energy Technology Data Exchange (ETDEWEB)

    Rosen, S.P.

    1988-01-01

    This paper reviews the theoretical possibility of double beta decay. The titles of the main sections of this paper are: Nuclear physics setting; Particle physics requirements; Kinematical features of the decay modes; Nuclear matrix elements; the Shell model and two-neutrino decay; Quasi-particle random phase approximation; and Future considerations. 18 refs., 7 tabs. (LSP)

  7. Frameshift mutation events in beta-glucosidases.

    Science.gov (United States)

    Rojas, Antonio; Garcia-Vallvé, Santiago; Montero, Miguel A; Arola, Lluís; Romeu, Antoni

    2003-09-18

    Compensated frameshift mutation is a modification of the reading frame of a gene that takes place by way of various molecular events. It appears to be a widespread event that is only observed when homologous amino acid and nucleodotide sequences are compared. To identify these mutation events, the sequence analysis rationale was based on the search for short regions that would have much lower degrees of conservation in protein, but not in DNA, in well-conserved beta-glucosidase families. We have restricted our study to a seed set of sequences of O-glycoside hydrolase families 1 and 3. We found compensated frameshift mutation in the family of 1 beta-glucosidases for the Erwinia herbicola, Cellulomonas fimi, and (non-cyanogenic) Trifolium repens gene sequences, and in the family of 3 beta-glucosidases for the Clostridium thermocellum and Clostridium stercorarium gene sequences. By computational treatment, the observed mutation events in the gene frameshifting sub-sequence have been neutralised. Each nucleotide insertion must be eliminated and each nucleotide deletion must be substituted by the symbol N (any nucleotide). When the frameshifting fragments of the amino acid sequences were substituted by the computationally neutralised subsequences, the beta-glucosidase alignments were improved. We also discuss the structural implications of the compensated frameshift mutations events. PMID:14527732

  8. Sources of beta cells inside the pancreas.

    Science.gov (United States)

    De Groef, Sofie; Staels, Willem; Van Gassen, Naomi; Lemper, Marie; Yuchi, Yixing; Sojoodi, Mozhdeh; Bussche, Leen; Heremans, Yves; Leuckx, Gunter; De Leu, Nico; Van de Casteele, Mark; Baeyens, Luc; Heimberg, Harry

    2016-09-01

    The generation of beta(-like) cells to compensate for their absolute or relative shortage in type 1 and type 2 diabetes is an obvious therapeutic strategy. Patients first received grafts of donor islet cells over 25 years ago, but this procedure has not become routine in clinical practice because of a donor cell shortage and (auto)immune problems. Transplantation of differentiated embryonic and induced pluripotent stem cells may overcome some but not all the current limitations. Reprogramming exocrine cells towards functional beta(-like) cells would offer an alternative abundant and autologous source of beta(-like) cells. This review focuses on work by our research group towards achieving such a source of cells. It summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Amin Ardestani and Kathrin Maedler, DOI: 10.1007/s00125-016-3892-9 , and by Heiko Lickert and colleagues, DOI: 10.1007/s00125-016-3949-9 ) and a commentary by the Session Chair, Shanta Persaud (DOI: 10.1007/s00125-016-3870-2 ). PMID:27053238

  9. Three loop QCD MOM beta-functions

    CERN Document Server

    Gracey, J A

    2011-01-01

    We present the full expressions for the QCD beta-function in the MOMggg, MOMq and MOMh renormalization schemes at three loops for an arbitrary colour group in the Landau gauge. The results for all three schemes are in very good agreement with the SU(3) numerical estimates provided by Chetyrkin and Seidensticker.

  10. Lepton nonconservation and double beta decay

    International Nuclear Information System (INIS)

    This paper reviews the status of double beta decay as a test of lepton number conservation. Present limits on the mass of a Majorana neutrino are in the range of 10 to 50 eV. Experiments now in progress should substantially improve these limits

  11. Association behavior of native beta-lactoglobulin

    DEFF Research Database (Denmark)

    Verheul, M.; Pedersen, J.S.; Roefs, S.P.F.M.;

    1999-01-01

    The association behavior of beta-lactoglobulin has been studied by small-angle neutron scattering as a function of protein concentration, temperature, pH, and NaCl concentration of the solution. By indirect Fourier transformation of the spectra, pair-distance distribution functions for the various...

  12. Long term prospects for double beta decay

    OpenAIRE

    Zuber, K.

    2010-01-01

    In rather general terms the long term perspective of double beta decay is discussed. All important experimental parameters are investigated as well as the status of nuclear matrix element issues. The link with other neutrino physics results and options to disentangle the underlying physics process are presented.

  13. Weak interaction studies from nuclear beta decay

    International Nuclear Information System (INIS)

    The studies performed at the theoretical nuclear physics division of the Laboratory of Nuclear Studies, Osaka University, are reported. Electron spin density and internal conversion process, nuclear excitation by electron transition, beta decay, weak charged current, and beta-ray angular distributions in oriented nuclei have been studied. The relative intensity of internal conversion electrons for the case in which the radial wave functions of orbital electrons are different for electron spin up and down was calculated. The calculated value was in good agreement with the experimental one. The nuclear excitation following the transition of orbital electrons was studied. The calculated probability of the nuclear excitation of Os189 was 1.4 x 10-7 in conformity with the experimental value 1.7 x 10-7. The second class current and other problems on beta-decay have been extensively studied, and described elsewhere. Concerning weak charged current, the effects of all induced terms, the time component of main axial vector, all partial waves of leptons, Coulomb correction for the electrons in finite size nuclei, and radiative correction were studied. The beta-ray angular distribution for the 1+ -- 0+ transition in oriented B12 and N12 was investigated. In this connection, investigation on the weak magnetism to include all higher order corrections for the evaluation of the spectral shape factors was performed. Other works carried out by the author and his collaborators are also explained. (Kato, T.)

  14. Plastic bronchitis in beta thalassemia minor

    OpenAIRE

    Makaresh Yadav; Sneha Tirpude; Joshi, Jyotsna M.

    2013-01-01

    Plastic bronchitis is a rare pulmonary disorder associated with various conditions like cystic fibrosis, asthma, pulmonary infection and characterized by formation and expectoration of cast which assumes the shape of the bronchial tree. We report a case of a 33-year-old woman with beta thalassemia minor who developed plastic bronchitis.

  15. Estimation error algorithm at analysis of beta-spectra

    International Nuclear Information System (INIS)

    This work describes the estimation error algorithm at the operations with beta-spectrums, as well as compares the theoretical and experimental errors by the processing of beta-channel's data. (authors)

  16. Binding capacity of a barley beta-D-glucan to the beta-glucan recognition molecule dectin-1.

    Science.gov (United States)

    Tada, Rui; Adachi, Yoshiyuki; Ishibashi, Ken-ichi; Tsubaki, Kazufumi; Ohno, Naohito

    2008-02-27

    To clarify whether barley beta-glucans exhibit their biological effects via binding to dectin-1, a pivotal receptor for beta-1,3-glucan, the structure of barley beta-glucan E70-S (BBG-70) was unambiguously investigated by NMR spectroscopy and studied for its binding capacity and specificity to dectin-1 by ELISA. NMR spectroscopy confirmed that BBG-70 contains two different linkage glucans, namely, alpha-glucan and beta-glucan, which are not covalently attached to one another. Beta-glucan within BBG-70 is a linear mixed-linkage beta-glucan composed of 1,3- and 1,4-beta-D-glucopyranose residues but does not contain the continuous 1,3-linkage. Competitive ELISA revealed that highly purified barley beta-glucan E70-S (pBBG-70) inhibits the binding of soluble dectin-1 to sonifilan (SPG), a beta-1,3-glucan, although at a concentration higher than that of SPG and laminarin. It was found that barley beta-glucan can be recognized by dectin-1, implying that barley beta-glucan might, at least in part, exhibit its biological effects via the recognition by dectin-1 of the ligand sugar structure, which may be formed by 1,3-beta- and 1,4-beta-glucosyl linkage. PMID:18205312

  17. RESEARCH OF BETA AS ADEQUATE RISK MEASURE-IS BETA STILL ALIVE?

    Directory of Open Access Journals (Sweden)

    Ante Perković

    2011-02-01

    Full Text Available The capital asset pricing model (CAPM is one of the most important models in financial economics and it has a long history of theoretical and empirical investigations. The main underlying concept of the CAPM model is that assets with a high risk (high beta should earn a higher return than assets with a low risk (low beta and vice versa. The implication which can be drawn out of this is that all assets with a beta above zero bear some risk and therefore their expected return is above the return of the risk-free rate. In this research observation on monthly stock prices on Croatian stock market from January 1st 2005 until December 31st 2009 is used to form our sample. CROBEX index is used as proxy of the market portfolio. The results demonstrate that beta can not be trusted in making investment decisions and rejects the validity of the whole CAPM model on Croatian stock market.

  18. Ordinary muon capture as a probe of virtual transitions of $\\beta\\beta$ decay

    CERN Document Server

    Kortelainen, M

    2002-01-01

    A reliable theoretical description of double-beta-decay processes needs a possibility to test the involved virtual transitions against experimental data. Unfortunately, only the lowest virtual transition can be probed by the traditional electron-capture or $\\beta^-$-decay experiments. In this article we propose that calculated amplitudes for many virtual transitions can be probed by experiments measuring rates of ordinary muon capture (OMC) to the relevant intermediate states. The first results from such experiments are expected to appear soon. As an example we discuss the $\\beta\\beta$ decays of $^{76}$Ge and $^{106}$Cd and the corresponding OMC for the $^{76}$Se and $^{106}$Cd nuclei in the framework of the proton-neutron QRPA with realistic interactions. It is found that the OMC observables, just like the $2\

  19. Parametrizing the exoplanet eccentricity distribution with the Beta distribution

    OpenAIRE

    Kipping, David M.

    2013-01-01

    It is suggested that the distribution of orbital eccentricities for extrasolar planets is well-described by the Beta distribution. Several properties of the Beta distribution make it a powerful tool for this purpose. For example, the Beta distribution can reproduce a diverse range of probability density functions (PDFs) using just two shape parameters (a and b). We argue that this makes it ideal for serving as a parametric model in Bayesian comparative population analysis. The Beta distributi...

  20. Isolation and characterization of chicken and turkey beta 2-microglobulin

    DEFF Research Database (Denmark)

    Skjødt, K; Welinder, K G; Crone, M;

    1986-01-01

    Chicken and turkey beta 2-m were isolated from citrated plasma in sequential use of three chromatographic steps: affinity chromatography, gel filtration chromatography and anion-exchange chromatography. The purified protein was identified as beta 2-m by reaction with a beta 2-m specific monoclonal...... incompatible with a previously published sequence also thought to be from turkey beta 2-m. Reasons for our opinion that the molecules isolated and sequenced in this paper are the correct ones are given. Udgivelsesdato: 1986-Dec...

  1. Extended Beta Regression in R: Shaken, Stirred, Mixed, and Partitioned

    OpenAIRE

    Bettina Grün; Ioannis Kosmidis; Achim Zeileis

    2012-01-01

    Beta regression - an increasingly popular approach for modeling rates and proportions - is extended in various directions: (a) bias correction/reduction of the maximum likelihood estimator, (b) beta regression tree models by means of recursive partitioning, (c) latent class beta regression by means of finite mixture models. All three extensions may be of importance for enhancing the beta regression toolbox in practice to provide more reliable inference and capture both observed and unobserved...

  2. Functional beta3-adrenoceptor in the human heart.

    OpenAIRE

    Gauthier, C.; Tavernier, G.; Charpentier, F.; Langin, D.; Le Marec, H

    1996-01-01

    Beta3-adrenoceptors are involved in metabolism, gut relaxation, and vascular vasodilation. However, their existence and role in the human heart have not been documented. We investigated the effects of several beta-adrenoceptor agonists and antagonists on the mechanical properties of ventricular endomyocardial biopsies. In the presence of nadolol, a beta1- and beta2-adrenoceptor antagonist, isoprenaline produced consistent negative inotropic effects. Similar negative inotropic effects also res...

  3. Milk composition and lactation of beta-casein-deficient mice.

    OpenAIRE

    Kumar, S.; Clarke, A R; Hooper, M L; Horne, D S; Law, A J; Leaver, J; Springbett, A; Stevenson, E.; Simons, J.P.

    1994-01-01

    beta-Casein is a major protein component of milk and, in conjunction with the other caseins, it is assembled into micelles. The casein micelles determine many of the physical characteristics of milk, which are important for stability during storage and for milk-processing properties. There is evidence that suggests that beta-casein may also possess other, nonnutritional functions. To address the function of beta-casein, the mouse beta-casein gene was disrupted by gene targeting in embryonic s...

  4. A guide to 17beta-hydroxysteroid dehydrogenases.

    Science.gov (United States)

    Adamski, J; Jakob, F J

    2001-01-22

    17beta-Hydroxysteroid dehydrogenases (17beta-HSD) are pivotal in controlling the biological potency of steroid hormones by catalyzing oxidation or reduction at position 17. Several 17beta-HSDs may as well metabolize further substrates including alcohols, bile acids, fatty acids and retinols. This review summarizes recent progress in the field of 17beta-HSD research provides an update of nomenclature. PMID:11165003

  5. International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

    OpenAIRE

    Wilson Jacob M; Fitschen Peter J; Campbell Bill; Wilson Gabriel J; Zanchi Nelo; Taylor Lem; Wilborn Colin; Kalman Douglas S; Stout Jeffrey R; Hoffman Jay R; Ziegenfuss Tim N; Lopez Hector L; Kreider Richard B; Smith-Ryan Abbie E; Antonio Jose

    2013-01-01

    Abstract Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close pro...

  6. Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: Possible implication of IL-6

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, H.; Ishibashi, T.; Shikama, Y.; Okano, A.; Akiyama, Y.; Uchida, T.; Maruyama, Y. (Fukushima Medical College (Japan))

    1990-12-15

    We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice.

  7. Interleukin-1 beta (IL-1 beta) induces thrombocytosis in mice: Possible implication of IL-6

    International Nuclear Information System (INIS)

    We administered recombinant human interleukin-1 beta (IL-1 beta), the common mediator of inflammation process, to C57B1/6 male mice (0.5 microgram, every 12 hours over five times) intraperitoneally and consequently induced a remarkable thrombocytosis. Day 1 was designated as the following day of the last injection in the morning. A significant thrombocytosis was observed on days 1 through 5 with a peak on day 2 (162 +/- 9 x 10(4)/mm3) compared with the control mice injected with heated IL-1 beta (101 +/- 11 x 10(4)/mm3). A striking increase in mean size of marrow megakaryocytes was noted on days 1 and 2. The incorporation of 75Se-selenomethionine into circulating platelets as a measure of platelet production was about 2.3 times higher in IL-1 beta-treated mice than in control mice. To determine which factor(s) is responsible for elicited thrombocytosis, the in vitro studies and bioassays for several hematopoietic factors were performed. IL-1 beta by itself did not stimulate megakaryocytopoiesis in vitro, suggesting that the thrombocytosis is attributed to other factor(s) via IL-1 beta stimulation. Serum colony-stimulating factor (CSF) activity after a single IL-1 beta (0.5 microgram) injection, monitored by colony assay with 10% tested serum, peaked at 3 hours. Formed colonies were mostly granulocyte (G) and granulocyte-macrophage (GM)-types, and studies using rabbit anti-mouse GM-CSF serum or using human marrow as target cells showed that the CSF activity of the tested serum consisted of, at least, GM-CSF and G-CSF. Addition of IL-3 concomitantly with the tested serum gave rise to a greater number of megakaryocytic colonies. Serum IL-3, monitored by IL-3-dependent cell line 32D clone 5, and erythropoietin activities were not detected at serum level in IL-1 beta-treated mice

  8. Inhibition of Akt activity induces the mesenchymal-to-epithelial reverting transition with restoring E-cadherin expression in KB and KOSCC-25B oral squamous cell carcinoma cells

    Directory of Open Access Journals (Sweden)

    Hong Sam-Pyo

    2009-02-01

    Full Text Available Abstract Background The Akt/PKB family of kinases is frequently activated in human cancers, including oral squamous cell carcinoma (OSCC. Akt-induced epithelial-to-mesenchymal transition (EMT involves downregulation of E-cadherin, which appears to result from upregulation of the transcription repressor Snail. Recently, it was proposed that carcinoma cells, especially in metastatic sites, could acquire the mesenchymal-to-epithelial reverting transition (MErT in order to adapt the microenvironments and re-expression of E-cadherin be a critical indicator of MErT. However, the precise mechanism and biologic or clinical importance of the MErT in cancers have been little known. This study aimed to investigate whether Akt inhibition would restore the expression of E-cadherin and β-catenin, reduce that of Vimentin, and induce the MErT in OSCC cells with low or negative expression of E-cadherin. We also investigate whether inhibition of Akt activity would affect the E-cadherin repressors and signaling molecules like NF-κB, ERK, and p38. Methods We screened several OSCC cell lines in order to select suitable cell line models for inducing MErT, using immunoblotting and methylation specific-PCR. We examined whether Akt inhibitor phosphatidylinositol ether lipid analogues (PIA treatment would restore the expression of E-cadherin and β-catenin, reduce that of Vimentin, and induce the MErT in KB and KOSCC-25B cells using RT-PCR, immunoblotting, immunofluorescence analysis, and in vitro migration assay. We also investigated whether inhibition of Akt activity would affect the E-cadherin repressors, including Snail, Twist, and SIP-1/ZEB-2 and signaling molecules like NF-κB, ERK, JNK, and p38 using RT-PCR, immunoblotting, and immunofluorescence analysis. Results Of the 7 OSCC cell lines, KB and KOSCC-25B showed constitutively activated phosphorylated Akt and low or negative expression of E-cadherin. Inhibition of Akt activity by PIA decreased NF-κB signaling

  9. Problems at the Development of personal Beta-particle dosemeters-Beta Particle dosemeters-

    International Nuclear Information System (INIS)

    Workplaces at which beta radiation might significantly contribute to the doses to the extremities are increasingly found in radiation therapy, radiation source production and nuclear plants. for the measurement of the individual beta-particle dose, personal dosemeters for fingers, arms and legs are needed. Intercomparison measurements organised from 1996 by the PTB have shown that some dosemeter types based on TLD are suitable for this purpose and can be used as legal dosemeters for both photon and beta radiation. Also, some electronic personal photon dosemeters are investigated in beta radiation fields. it turned out that a few types are also sensitive to beta radiation and measure the personal dose equivalent rate to the skin with a low energy dependence. Only their wearing position is by far not optimal foe extremity dosimetry because they are worn on the chest. Advantages and disadvantages are discussed. The characterisation of workplaces is carried out by measuring dose profiles using area dosemeters. Investigations performed with several commercial types of these dosemeters furnish information about the selection of the suitable measuring device and its correct practical use. the development of improved dosemeters has to towards smaller detectors and higher sensitivity. Personal dosemeters have to be robust and acceptable to the user, which generally is not achieved for beta extremity dosemeters. It is an additional problem that even such dosemeters cannot always be worn in the appropriate place. (Author)

  10. [beta]-Lactamases in the Biochemistry and Molecular Biology Laboratory

    Science.gov (United States)

    Amador, Paula; Prudencio, Cristina; Vieira, Monica; Ferraz, Ricardo; Fonte, Rosalia; Silva, Nuno; Coelho, Pedro; Fernandes, Ruben

    2009-01-01

    [beta]-lactamases are hydrolytic enzymes that inactivate the [beta]-lactam ring of antibiotics such as penicillins and cephalosporins. The major diversity of studies carried out until now have mainly focused on the characterization of [beta]-lactamases recovered among clinical isolates of Gram-positive staphylococci and Gram-negative…

  11. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

    NARCIS (Netherlands)

    Rudick, R.A.; Stuart, W.H.; Calabresi, P.A.; Confavreux, C.; Galetta, S.L.; Radue, E.W.; Lublin, F.D.; Weinstock-Guttman, B.; Wynn, D.R.; Lynn, F.; Panzara, M.A.; Sandrock, A.W.

    2006-01-01

    BACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. MET

  12. Why Downside Beta Is Better: An Educational Example

    Science.gov (United States)

    Chong, James T.; Jennings, William P.; Phillips, G. Michael

    2013-01-01

    An educational example is presented that is an effective teaching illustration to help students understand the difference between traditional CAPM beta and downside (or down-market) beta and why downside beta is a superior measure for use in personal financial planning investment policy statements.

  13. Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm

    DEFF Research Database (Denmark)

    Giwercman, B; Jensen, E T; Høiby, N;

    1991-01-01

    Imipenem induced high levels of beta-lactamase production in Pseudomonas aeruginosa biofilms. Piperacillin also induced beta-lactamase production in these biofilms but to a lesser degree. The combination of beta-lactamase production with other protective properties of the biofilm mode of growth...

  14. Mechanisms of beta-amyloid neurotoxicity : Perspectives of pharmacotherapy

    NARCIS (Netherlands)

    Harkany, T; Abraham, [No Value; Konya, C; Nyakas, C; Zarandi, M; Penke, B; Luiten, PGM

    2000-01-01

    One of the characteristic neuropathological hallmarks of Alzheimer's disease (AD) is the extracellular accumulation of beta -amyloid peptides (A beta) in neuritic plaques, Experimental data indicate that different molecular forms of A beta affect a wide array of neuronal and glial functions and ther

  15. 21 CFR 886.5100 - Ophthalmic beta radiation source.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ophthalmic beta radiation source. 886.5100 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5100 Ophthalmic beta radiation source. (a) Identification. An ophthalmic beta radiation source is a device intended to apply...

  16. Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia

    International Nuclear Information System (INIS)

    We have studied the consequences of introducing human recombinant transforming growth factor beta 1 (hrTGF-beta 1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1 microgram of hrTGF-beta 1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta 1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta 1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta 1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta 1 per 10(9) cells potentially available for secretion during degranulation of PMNs. [3H]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta 1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta 1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions

  17. Le livre au coeur du labyrinthe : Le Club Dumas ou l'ombre de Richelieu d'Arturo Pérez-Reverte El libro en el corazón mismo del laberinto : El Club Dumas o la sombra de Richelieu

    Directory of Open Access Journals (Sweden)

    Marie-Thérèse Garcia

    2002-11-01

    Full Text Available Dans le Club Dumas ou l’ombre de Richelieu, l’écrivain Arturo Pérez-Reverte, fervent lecteur, rend un hommage ludique au Livre. Deux manuscrits sont au cœur de sa construction labyrinthique, nouent l’intrigue et surtout dessinent, révèlent et déterminent les personnages. Héros d’Alexandre Dumas et créatures romanesques, filles de Conan Doyle et de Jacques Cazotte envahissent la fiction, poursuivent le protagoniste et l’amènent aux limites du fantastique. Mêlant les structures génériques du roman d’aventures et celles du roman policier, l’auteur entraîne le lecteur dans une quête herméneutique dont la fin est dans les livres. L’intertextualité y devient matière littéraire et facteur structurant du récit. Héritier de Borgès et de Cortazar, Arturo Pérez-Reverte. bouleverse les relations auteur-personnages, et redéfinit les liens qui unissent auteur et lecteur, attribuant à ce dernier un rôle prépondérant dans la genèse de l’oeuvre.En el Club Dumas o la sombra de Richelieu, el escritor Arturo Pérez-Reverte, ferviente lector, le rinde al Libro un homenaje lúdico. Dos manuscritos, en el centro de esta construcción laberíntica, manejan los hilos de la intriga y en particular dibujan, desvelan y determinan a los personajes. Héroes de Dumas y criaturas novelescas, hijas de Conan Doyle y de Jacques Cazotte invaden la ficción, acosan al protagonista empujándolo hasta el límite de lo fantástico. Mezclando las estructuras genéricas de la novela de aventuras con las de la novela policíaca, el autor arrastra al lector en una búsqueda hermenéutica cuyo término se halla en los libros. La intertextualidad se convierte aquí en materia literaria y en elemento estructurador del relato. Heredero de Borges y de Cortázar, Arturo Pérez-Reverte. altera las relaciones autor-personajes, y define nuevamente los vínculos que unen al autor con el lector, otorgándole a éste un papel relevante en la génesis de

  18. Beta-hypergeometric probability distribution on symmetric matrices

    OpenAIRE

    Hassairi, Abdelhamid; Masmoudi, Mouna

    2012-01-01

    Some remarkable properties of the beta distribution are based on relations involving independence between beta random variables such that a parameter of one among them is the sum of the parameters of an other (see (1.1) et (1.2) below). Asci, Letac and Piccioni \\cite{6} have used the real beta-hypergeometric distribution on $ \\reel$ to give a general version of these properties without the condition on the parameters. In the present paper, we extend the properties of the real beta to the beta...

  19. Double beta decay with large scale Yb-loaded scintillators

    OpenAIRE

    Zuber, K.

    2000-01-01

    The potential of large scale Yb-loaded liquid scintillators as proposed for solar neutrino spectroscopy are investigated with respect to double beta decay. The potential for beta-beta- - decay of 176Yb as well as the beta+/EC - decay for 168Yb is discussed. Not only getting for the first time an experimental half-life limit on 176Yb - decay, this will even be at least comparable or better than existing ones from other isotopes. Also for the first time a realistic chance to detect beta+/EC - d...

  20. 6 beta-Iodopenicillanic acid (UI-38,006), a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactam compounds: initial bacteriological characterization.

    OpenAIRE

    Moore, B A; Brammer, K W

    1981-01-01

    UK-38,006, 6 beta-iodopenicillanic acid, was shown to be a potent inhibitor of beta-lactamase enzymes. It potentiated the antibacterial action of ampicillin in vitro against beta-lactamase-producing strains of Staphylococcus aureus, Haemophilus influenzae, Bacteroides fragilis. Neisseria gonorrhoeae, and many Enterobacteriaceae. This ability to synergize with ampicillin was also demonstrated in vivo after oral administration of UK-38,006 to experimentally infected mice. UK-38,006 was also sho...

  1. Bactericidal interactions of a beta-lactam and beta-lactamase inhibitors in experimental Pseudomonas aeruginosa endocarditis caused by a constitutive overproducer of type Id beta-lactamase.

    OpenAIRE

    Bayer, A S; Selecky, M; Babel, K; Hirano, L; Yih, J; Parr, T R

    1987-01-01

    We investigated the in vitro and in vivo effects of a combination of a beta-lactam (ceftazidime) and a beta-lactamase inhibitor (dicloxacillin) to synergistically kill a ceftazidime-resistant variant, Pseudomonas aeruginosa PA-48, which overproduces type Id cephalosporinase constitutively. In vitro, dicloxacillin plus ceftazidime exerted bactericidal synergy at approximately 10(5) CFU/ml of inoculum (but not at approximately 10(7)-CFU inoculum), whereas other beta-lactamase inhibitors (sulbac...

  2. Search for $\\beta^+$EC and ECEC processes in $^{112}$Sn and $\\beta^-\\beta^-$ decay of $^{124}$Sn to the excited states of $^{124}$Te

    CERN Document Server

    Barabash, A S; Nachab, A; Konovalov, S I; Vanyushin, I A; Umatov, V I

    2008-01-01

    Limits on $\\beta^+$EC and ECEC processes in $^{112}$Sn and on $\\beta^-\\beta^-$ decay of $^{124}$Sn to the excited states of $^{124}$Te have been obtained using a 380 cm$^3$ HPGe detector and an external source consisting of natural tin. A limit with 90% C.L. on the $^{112}$Sn half-life of $0.92\\times 10^{20}$ y for the ECEC(0$\

  3. Comparative evaluation of a new beta-lactamase inhibitor, YTR 830, combined with different beta-lactam antibiotics against bacteria harboring known beta-lactamases.

    OpenAIRE

    Gutmann, L; Kitzis, M D; Yamabe, S; Acar, J F

    1986-01-01

    YTR 830, a new beta-lactamase inhibitor, combined with amoxicillin or carbenicillin, showed a synergistic effect similar to that observed with clavulanic acid, and generally better than that with sulbactam, against strains harboring chromosome-encoded penicillinases and broad-spectrum beta-lactamases or plasmid-determined beta-lactamases. With ampicillin, YTR 830 showed the best synergistic activity of the inhibitors against Proteus morganii, Citrobacter freundii, and Enterobacter cloacae and...

  4. Genetic counselling in the beta-thalassaemias

    Directory of Open Access Journals (Sweden)

    Adonis S. Ioannides

    2013-03-01

    Full Text Available The beta-thalassaemias are very important genetic disorders of haemoglobin synthesis and are amongst the commonest monogenic disorders. In view of the severity of beta-thalassaemia major, a number of screening programmes have been developed aimed at reducing the number of individuals born with the condition. Genetic counsellingplays a vital role in this process supporting the successful implementation of screening and delineating available options to at risk individuals. This review assesses the contribution of genetic counsellingat each stage of this process in the context of new diagnostic techniques and therapeutic options and discusses some of the more challenging aspects such as genotype/ phenotype correlation and coinheritance of other genetic conditions or genetic modifiers.

  5. JUNO and neutrinoless double beta decay

    Science.gov (United States)

    Ge, Shao-Feng; Rodejohann, Werner

    2015-11-01

    We study the impact of the precision determination of oscillation parameters in the JUNO experiment on half-life predictions for neutrinoless double beta decay. We show that the solar neutrino mixing angle can be measured by JUNO with below 1% uncertainty. This implies in particular that the minimal value of the effective mass in the inverted mass ordering will be known essentially without uncertainty. We demonstrate that this reduces the range of half-life predictions in order to test this value by a factor of 2. The remaining uncertainty is caused by nuclear matrix elements. This has important consequences for future double beta decay experiments that aim at ruling out the inverted mass ordering or the Majorana nature of neutrinos.

  6. JUNO and Neutrinoless Double Beta Decay

    CERN Document Server

    Ge, Shao-Feng

    2015-01-01

    We study the impact of the precision determination of oscillation parameters in the JUNO experiment on half-life predictions for neutrinoless double beta decay. We show that the solar neutrino mixing angle can be measured by JUNO with below 1% uncertainty. This implies in particular that the minimal value of the effective mass in the inverted mass ordering will be known essentially without uncertainty. We demonstrate that this reduces the range of half-life predictions in order to test this value by a factor of two. The remaining uncertainty is caused by nuclear matrix elements. This has important consequences for future double beta decay experiments that aim at ruling out the inverted mass ordering or the Majorana nature of neutrinos.

  7. Importance of neutrinoless double beta decay

    CERN Document Server

    Sarkar, Utpal

    2007-01-01

    A natural explanation for the smallness of the neutrino mass requires them to be Majorana particles violating lepton number by two units. Since lepton number violation can have several interesting consequences in particle physics and cosmology, it is of utmost importance to find out if there is lepton number violation in nature and what is its magnitude. The neutrinoless double beta decay experiment can answer these questions: if there is lepton number violation and if neutrinos are Majorana particles. In addition, the magnitude of neutrinoless double beta decay will constrain any other lepton number violating processes. This lepton number violation may also be relatd to the matter-antimatter asymmetry of the universe, dark matter and cosmological constant.

  8. Beta-plane turbulence: experiments with altimetry

    CERN Document Server

    Zhang, Y

    2013-01-01

    Results from a new series of experiments on flows generated by an electromagnetic method in a rotating tank with topographic beta-effect are presented. The velocity fields are measured by the Altimetric Imaging Velocimetry. The turbulent flows observed in the experiments develop zonal jets which are latent in a stationary forced-dissipative regime of the flow but become prominent in the decaying flow. The two-dimensional energy spectra of the flows exhibit the development of anisotropy towards zonal motions. The experiments demonstrate dual turbulent cascade with energy and enstrophy ranges. The frequency-wavenumber spectra reveal the presence of Rossby waves at low wavenumbers which are excited by the turbulent motions. The experimental results are compared with available theory of beta-plane turbulence.

  9. Search for Neutrinoless Double-Beta Decay

    CERN Document Server

    Tornow, Werner

    2014-01-01

    After the pioneering work of the Heidelberg-Moscow (HDM) and International Germanium Experiment (IGEX) groups, the second round of neutrinoless double-$\\beta$ decay searches currently underway has or will improve the life-time limits of double-$\\beta$ decay candidates by a factor of two to three, reaching in the near future the $T_{1/2} = 3 \\times 10^{25}$ yr level. This talk will focus on the large-scale experiments GERDA, EXO-200, and KamLAND-Zen, which have reported already lower half-life time limits in excess of $10^{25}$ yr. Special emphasis is given to KamLAND-Zen, which is expected to approach the inverted hierarchy regime before future 1-ton experiments probe completely this life-time or effective neutrino-mass regime, which starts at $\\approx 2 \\times 10^{26}$ yr or $\\approx 50$ meV.

  10. Numerical models for high beta magnetohydrodynamic flow

    International Nuclear Information System (INIS)

    The fundamentals of numerical magnetohydrodynamics for highly conducting, high-beta plasmas are outlined. The discussions emphasize the physical properties of the flow, and how elementary concepts in numerical analysis can be applied to the construction of finite difference approximations that capture these features. The linear and nonlinear stability of explicit and implicit differencing in time is examined, the origin and effect of numerical diffusion in the calculation of convective transport is described, and a technique for maintaining solenoidality in the magnetic field is developed. Many of the points are illustrated by numerical examples. The techniques described are applicable to the time-dependent, high-beta flows normally encountered in magnetically confined plasmas, plasma switches, and space and astrophysical plasmas. 40 refs

  11. Source preparations for alpha and beta measurements

    Energy Technology Data Exchange (ETDEWEB)

    Holm, E. [Risoe National Lab., Roskilde (Denmark)

    2001-01-01

    Regarding alpha particle emitters subject for environmental studies, electrodeposition or co-precipitation as fluorides are the most common methods. For electro deposition stainless steel is generally used as cathode material but also other metals such as Ni, Ag, and Cu showed promising results. The use of other anode material than platinum, such as graphite should be investigated. For other purposes such as optimal resolution other more sophisticated methods are used but often resulting in poorer recovery. For beta particle emitters the type of detection system will decide the source preparation. Similar methods as for alpha particle emitters, electrodeposition or precipitation techniques can be used. Due to the continuous energy distribution of the beta pulse height distribution a high resolution is not required. Thicker sources from the precipitates or a stable isotopic carrier can be accepted but correction for absorption in the source must be done. (au)

  12. Source preparations for alpha and beta measurements

    International Nuclear Information System (INIS)

    Regarding alpha particle emitters subject for environmental studies, electrodeposition or co-precipitation as fluorides are the most common methods. For electro deposition stainless steel is generally used as cathode material but also other metals such as Ni, Ag, and Cu showed promising results. The use of other anode material than platinum, such as graphite should be investigated. For other purposes such as optimal resolution other more sophisticated methods are used but often resulting in poorer recovery. For beta particle emitters the type of detection system will decide the source preparation. Similar methods as for alpha particle emitters, electrodeposition or precipitation techniques can be used. Due to the continuous energy distribution of the beta pulse height distribution a high resolution is not required. Thicker sources from the precipitates or a stable isotopic carrier can be accepted but correction for absorption in the source must be done. (au)

  13. Beta Beams for Precision Measurements of Neutrino Oscillation Parameters

    CERN Document Server

    Wildner, E; Hansen, C; De Melo Mendonca, T; Stora, T; Damjanovic, S; Payet, J; Chancé, A; Zorin, V; Izotov, I; Rasin, S; Sidorov, A; Skalyga, V; De Angelis, G; Prete, G; Cinausero, M; Kravchuk, V; Gramegna, F; Marchi, T; Collazuol, G; Mezzetto, M; Delbar, T; Loiselet, M; Keutgen, T; Mitrofanov, S; Burt, G; Dexter, A; Lamy, T; Latrasse, L; Marie-Jeanne, M; Sortais, P; Thuillier, T; Debray, F; Trophime, C; Hass, M; Hirsh, T; Berkovits, D; Stahl, A; Vardaci, E; Di Nitto, A; Brondi, A; La Rana, G; Moro, R; De Rosa, G; Palladino, V

    2012-01-01

    Neutrino oscillations have implications for the Standard Model of particle physics. The CERN Beta Beam has outstanding capabilities to contribute to precision measurements of the parameters governing neutrino oscillations. The FP7 collaboration EUROnu (2008-2012) is a design study that will review three facilities (Super-Beams, Beta Beams and Neutrino Factories) and perform a cost assessment that, coupled with the physics performance, will give means to the European research authorities to make decisions on future European neutrino oscillation facilities. ”Beta Beams” produce collimated pure electron (anti)neutrinos by accelerating beta active ions to high energies and having them decay in a storage ring. Using existing machines and infrastructure is an advantage for the cost evaluation; however, this choice is also constraining the Beta Beams. Recent work to make the Beta Beam facility a solid option will be described: production of Beta Beam isotopes, the 60 GHz pulsed ECR source development, integratio...

  14. Evaluation of cyclohexenoesculetin-beta-D-galactoside and 8-hydroxyquinoline-beta-D-galactoside as substrates for the detection of beta-galactosidase.

    OpenAIRE

    James, A.L.; Perry, J D; Ford, M.; Armstrong, L.; Gould, F K

    1996-01-01

    We describe the synthesis of two new substrates for the detection of beta-galactosidase and evaluate their performance in comparison with that of 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal). Of 171 Enterobacteriaceae strains that were able to hydrolyze X-Gal, 166 (97.1%) also hydrolyzed cyclohexenoesculetin-beta-D-galactoside whereas only 96 (56.1%) showed evidence of hydrolysis of 8-hydroxyquinoline-beta-D-galactoside. No false-positive results were observed with either subst...

  15. Antianginal Actions of Beta-Adrenoceptor Antagonists

    OpenAIRE

    O'Rourke, Stephen T.

    2007-01-01

    Angina pectoris is usually the first clinical sign of underlying myocardial ischemia, which results from an imbalance between oxygen supply and oxygen demand in the heart. This report describes the pharmacology of β-adrenoceptor antagonists as it relates to the treatment of angina. The β-adrenoceptor antagonists are widely used in long-term maintenance therapy to prevent acute ischemic episodes in patients with chronic stable angina. Beta-adrenoceptor antagonists competitively inhibit the bin...

  16. Beta-Blocking Agents and Electroconvulsive Therapy

    OpenAIRE

    Broek, Walter; Groenland, Theo; Kusuma, Ari; Birkenhäger, Tom; Pluijms, Esther; Bruijn, Jan; Mulder, Paul

    2007-01-01

    textabstractIn this review we want to summarize the results of the placebo-controlled randomized clinical trials with betablocking adrenergic agents during electroconvulsive therapy (ECT), and review the effect on seizure duration and cardiovascular variables. We searched for studies in the electronic databases Medline. Keywords combined in the search were: “beta-adrenergic blocking agents” and “electroconvulsive therapy”. The only limitation specified in the search was that the publications ...

  17. Tables of double beta decay data

    International Nuclear Information System (INIS)

    A compilation of experimental data on double beta decay is presented. The tables contain the most stringent known experimental limits or positive results of 2β transitions of 69 natural nuclides to ground and excited states of daughter nuclei for different channels (2β-; 2β+; εβ+; 2ε) and modes (0ν; 2ν; 0νM) of decay. (authors). 189 refs., 9 figs., 3 tabs

  18. JUNO and Neutrinoless Double Beta Decay

    OpenAIRE

    Ge, Shao-Feng; Rodejohann, Werner

    2015-01-01

    We study the impact of the precision determination of oscillation parameters in the JUNO experiment on half-life predictions for neutrinoless double beta decay. We show that the solar neutrino mixing angle can be measured by JUNO with below 1% uncertainty. This implies in particular that the minimal value of the effective mass in the inverted mass ordering will be known essentially without uncertainty. We demonstrate that this reduces the range of half-life predictions in order to test this v...

  19. Beta-Thalassaemia types in southern Sardinia.

    OpenAIRE

    Cao, A; Furbetta, M; Ximenes, A; Angius, A; Rosatelli, C; Tuveri, T; Scalas, M T; Falchi, A M; Maccioni, L; Melis, M A; R. Galanello

    1981-01-01

    In this study the prevalence of the different beta-thalassaemia types in southern Sardinia was investigated by cellulose acetate and agar gel electrophoresis or globin chain synthesis analysis on column chromatography or both in (1) all the patients (347) presenting with thalassaemia major or intermedia at our haematology service from 1976 to 1979, and (2) a group of 82 patients with transfusion-dependent thalassaemia major randomly chosen from 236 under our care. Apart from six subjects with...

  20. Risk adjusted equity valuation and accounting betas

    OpenAIRE

    Pope, P F; Wang, P.

    2000-01-01

    In this paper we develop a general equity valuation model where abnormal earnings, back value, the discount factor and interest rates evolve stochastically. Focusing on the dynamics of abnormal earnings, we demonstrate the back value, abnormal earnings, "other information" and two risk adjustment terms are sufficient for valuation when pricing kernel risk is attributable to a single market factor. The risk adjustment terms depend on accounting betas reflecting the covariances between abnormal...

  1. NEUTRINOLESS DOUBLE BETA DECAY: AN EXTREME CHALLENGE

    OpenAIRE

    Fernando Ferroni

    2013-01-01

    Neutrino-less Double Beta Decay is the only known way to possibly resolve the nature of neutrino mass. The chances to cover the mass region predicted by the inverted hierarchy require a step forward in detector capability. A possibility is to make use of scintillating bolometers. These devices shall have a great power in distinguishing signals from alfa particles from those induced by electrons. This feature might lead to an almost background-free experiment. Here the Lucifer concept will be ...

  2. Tensile creep of beta phase zircaloy-2

    International Nuclear Information System (INIS)

    The tensile creep and creep rupture properties of beta-phase zircaloy-2 are studied under vacuum in the temperature and stress range 1300-1550 K and 0.5-2 MN/m2. The new results are compared with previously reported uniaxial and biaxial data. A small but systematic difference is noted between the uniaxial and biaxial creep data and reasons for this discrepancy are discussed. (author)

  3. Precision mass measurements utilizing beta endpoints

    International Nuclear Information System (INIS)

    A technique for precise determination of beta endpoints with an intrinsic germanium detector has been developed. The energy calibration was derived from γ-ray photopeak measurements. This analysis procedure has been checked with a 27Si source produced in a (p,n) reaction on an 27Al target and subsequently applied to mass separated samples of 76Rb, 77Rb and 78Rb. Results indicate errors < 50 keV are obtainable. (orig.)

  4. Endopeptidase-Mediated Beta Lactam Tolerance

    OpenAIRE

    Dörr, Tobias; Davis, Brigid M.; Waldor, Matthew K.

    2015-01-01

    In many bacteria, inhibition of cell wall synthesis leads to cell death and lysis. The pathways and enzymes that mediate cell lysis after exposure to cell wall-acting antibiotics (e.g. beta lactams) are incompletely understood, but the activities of enzymes that degrade the cell wall (‘autolysins’) are thought to be critical. Here, we report that Vibrio cholerae, the cholera pathogen, is tolerant to antibiotics targeting cell wall synthesis. In response to a wide variety of cell wall- acting ...

  5. Nuclear Data Compilation for Beta Decay Isotope

    Science.gov (United States)

    Olmsted, Susan; Kelley, John; Sheu, Grace

    2015-10-01

    The Triangle Universities Nuclear Laboratory nuclear data group works with the Nuclear Structure and Decay Data network to compile and evaluate data for use in nuclear physics research and applied technologies. Teams of data evaluators search through the literature and examine the experimental values for various nuclear structure parameters. The present activity focused on reviewing all available literature to determine the most accurate half-life values for beta unstable isotopes in the A = 3-20 range. This analysis will eventually be folded into the ENSDF (Evaluated Nuclear Structure Data File). By surveying an accumulated compilation of reference articles, we gathered all of the experimental half-life values for the beta decay nuclides. We then used the Visual Averaging Library, a data evaluation software package, to find half-life values using several different averaging techniques. Ultimately, we found recommended half-life values for most of the mentioned beta decay isotopes, and updated web pages on the TUNL webpage to reflect these evaluations. To summarize, we compiled and evaluated literature reports on experimentally determined half-lives. Our findings have been used to update information given on the TUNL Nuclear Data Evaluation group website. This was an REU project with Triangle Universities Nuclear Laboratory.

  6. Thermal behaviour of beta-uranophane

    International Nuclear Information System (INIS)

    Beta-uranophane from Perus, SP, Brazil- has been heated progressively up to 1.3500C, and its thermal behaviour has been investigated thoroughly by several methods: thermo-gravimetry, differential thermal analysis, optical measurements, infra-red spectroscopy, and X-Ray diffraction. The mineral seems to be stable up to a temperature of 2000C, confirmed by the several experimental procedures. The differential thermal analysis gives a sharper point of transformation at 1650C, which should be ascribed to water evaporation (zeolitic water). The crystal structure of the mineral could be transformed into a random layer structure, due probably to loss of the structural water. This kind of crystal disorder induces, as a rule, in the X-ray powder diagrams, absences of the hkl reflections. This could explain the small number of observed lines in the powder photographs of the material heated above 2000C. A new phase transformation is reported in the temperature interval of 700 to 8000C. This transformation should be related to the beta-uranophane chemical breakdown into two or more new crystalline phases. The chemical composition of such products is discussed in the paper. As the temperature rises to a higher level, a phase transformation takes place between 1000 and 12000C and yet another one in the range of 1200 to 13500C. The latter transition could be ascribed to the formation of an alloy between the platinum holder and the breakdown products of beta-uranophane

  7. Beyond low beta-decay Q values

    Science.gov (United States)

    Mustonen, M. T.; Suhonen, J.

    2010-11-01

    Beta decays with low Q values can be utilized in the quest to determine the neutrino mass scale. This is being realized in two experiments, KATRIN and MARE, using tritium and 187Re, respectively. The beta-decay of 187Re had the lowest known Q value until 2005, when the beta decay of 115In to the first excited state of 115Sn was discovered in Gran Sasso underground laboratory. Last year two independent ion trap measurements confirmed that this decay breaks the former record by an order of magnitude. Our theoretical study on this tiny decay channel complemented the experimental effort by the JYFLTRAP group in Finland and HADES underground laboratory in Belgium. A significant discrepancy between the experimental and theoretical results was found. This might be explained by various atomic contributions known to grow larger as the Q value decreases. However, the traditional recipes for taking these effects into account break down on this new ultra-low Q value regime, providing new challenges for theorists on the borderline between nuclear and atomic physics.

  8. Beta decay properties from a statistical model

    International Nuclear Information System (INIS)

    The present work assumes that any intrinsic structure in the nuclei involved is not important. Only spin, parity, and energy are considered. Quantities such as half-life, average beta energy, or average gamma energy can be obtained by integrals over the beta strength function weighted by kinematic and other factors. The beta strength function is proportional to the level density multiplied by a reduced transition probability. Delayed neutron emission is calculated by assuming that the daughter is a compound nucleus which then statistically decays as in the Hauser-Feshbach approach. Using the ENDF/B-V fission product file which contains 877 nuclei, energy-dependent reduced transition probabilities were found for allowed 0+ → 1+ transitions (50 cases) and for other allowed transitions (over 600 cases), corresponding to log ft values of 4.3 and 5.6 respectively. No dependence on either transition energy or on mass was found. A reduced transition probability corresponding to log ft of 7.1 was used for first forbidden transitions. Some results are presented and discussed

  9. A low-noise beta-radiometer

    International Nuclear Information System (INIS)

    The two-channel detector for a low-noise (down to 0.06 sec-1) beta-radiometer for measuring the mass concentration of 90Sr in the environment after the chemical extraction of strontium by the oxalate-nitrate method was certified at the D.I. Mendeleev Institute of Metrology (certificate No. 137/93). A detector unit using two end-window self-quenching counters with thin input windows (8 μm thick and 60 mm in diameter) operating as a Geiger-Mueller counter and filled with a mixture of 90% helium (atomic gas) and 10% ethanol (organic molecules) can measure the beta-activity of two substrates concurrently. It is often used to detect the beta-radiation of 90Sr. This isotope produces particles with energies ranging from 180 to 1000 keV, and the detection efficiency is 50% at a level of 0.1 Bq after measuring for 20 min with an uncertainty of 25%

  10. Simulation in double-beta decay experiments

    International Nuclear Information System (INIS)

    A detailed understanding of background radiation sources is a key to interpretation and enhanced sensitivity of double-beta decay experiments. Improvement of several techniques will be discussed. An implementation of the EGS4 code was developed to improve the accuracy of detector simulations, in particular for a 100Mo double-beta decay experiment. The efficiency modification due to the angular dependence of the 539 keV - 590 keV gamma-ray coincidence was successfully determined. The success of the 100Mo effort led to the modeling of uranium-thorium backgrounds found in an electroformed copper shield built for a 76Ge experiment. The large copper mass increased our sensitivity to contaminants present in copper produced this way, and led to changes in our cryostat electroforming technique. The original goal was the determination of the 210Pb content of the 450 year old lead shield previously used in 71Ge two-neutrino double-beta decay measurements. The results pertaining to low background materials and fabrication techniques will also be discussed

  11. Neutrinoless beta-beta matrix element of 76Ge from spectroscopic data

    CERN Document Server

    Suhonen, J

    2008-01-01

    In this work we use the recently measured neutron pairing correlations in the 76Ge and 76Se nuclei as a guideline to adjust the single-particle energies in the 1p0f0g shell. The resulting BCS occupations reproduce the measured pairing data. The proton energies were inspected by using the odd-mass nuclei adjacent to 76Ge and 76Se as spectroscopic tools. The nuclear matrix element of the neutrinoless double beta (0-nu-beta-beta) decay of 76Ge is calculated in this fitted single-particle basis by using the proton-neutron quasiparticle random-phase approximation (pnQRPA) in a realistic model space and by adopting effective microscopic two-nucleon interactions. We include the nucleon-nucleon short-range correlations and other relevant corrections at the nucleon level. It is found that the resulting 0-nu-beta-beta matrix element is smaller than in the previous pnQRPA calculations, and closer to the recently reported shell-model results.

  12. Effects of calcium impurity on phase relationship, ionic conductivity and microstructure of Na$^{+}$-$\\beta/beta"$-alumina solid electrolyte

    Indian Academy of Sciences (India)

    SUNG-TAE LEE; DAE-HAN LEE; SANG-MIN LEE; SANG-SOO HAN; SANG-HYUNG LEE; SUNG-KI LIM

    2016-06-01

    Ca-doped Na$^{+}$-$\\beta/beta"$-alumina was synthesized using a solid-state reaction. The changes in the properties of Na$^{+}$-$\\beta/beta"$-alumina resulting from the presence of Ca impurity were studied. Ca (0–5 wt%) was added to the respective samples, which were then sintered. The specimens were characterized using X-ray diffraction, scanningelectron microscopy, densimetry and impedance analysis. In the sintered specimens, the $\\beta"$-alumina phase fraction decreased as Ca content increased, whereas the relative sintered density increased. The surface morphology of Cadoped Na$^{+}$-$\\beta/beta"$-alumina specimens showed a Ca-rich layer, which was the main cause of increase in the specificresistance.

  13. Beta-blockers and heart failure.

    Science.gov (United States)

    Cruickshank, John M

    2010-01-01

    The life-time risk of developing HF is about 20% (40% if hypertension present). With increasing longevity in the developed world the burden of HF (hospitalisation) is set to increase over the next 10-20 years. CAD and hypertension are the two main causes of HF; CAD (and obesity) in the case of systolic HF and hypertension in the case of diastolic HF (mainly in the elderly). BB have become the corner-stone (alongside ACE-inhibitors) in the treatment of systolic HF. Bisoprolol, metoprolol and carvedilol (on an ACE-inhibitor background) have reduced all-cause death by 34-5%. The presence of intrinsic sympathomemetic activity (xamoterol, bucindolol, nebivolol) diminishes efficacy in the treatment of systolic HF. First-line bisoprolol has proved "non-inferior" to first-line enalapril in reducing all-cause death and is probably superior in reducing sudden death. The main mode of action of BB in treating systolic HF is inhibition of chronic beta-1 stimulation-induced myocardial apoptosis/necrosis/inflammation. The combination of pure beta-1 blockade (low-dose bisoprolol) and pure beta-2 blockade (clenbuterol) may prove invaluable in the treatment of end-stage systolic HF (thus avoiding cardiac transplantation). The appropriate treatment of diastolic HF has yet to be determined. Beta-blockade is effective in the prevention of HF i) in the post-MI period and ii) as first-line agents in the treatment of young/middle-aged hypertension and as second-line agents (to first-line diuretics) in the treatment of elderly systolic hypertension. BB are highly effective in reversing LVH in young/middle-aged hypertensives (LVH pre-disposes to HF in young/middle-aged hypertension) and are (bisoprolol) at least as good as ACE-inhibitors. Choice of BB is important as benefit is not a class-effect. ISA (xamoterol, bucindolol, nebivolol) markedly diminishes efficacy. The choice is between bisoprolol, metoprolol succinate and carvedilol for optimal efficacy. Adverse reactions are associated

  14. A Novel Dimeric Inhibitor Targeting Beta2GPI in Beta2GPI/Antibody Complexes Implicated in Antiphospholipid Syndrome

    Energy Technology Data Exchange (ETDEWEB)

    A Kolyada; C Lee; A De Biasio; N Beglova

    2011-12-31

    {beta}2GPI is a major antigen for autoantibodies associated with antiphospholipid syndrome (APS), an autoimmune disease characterized by thrombosis and recurrent pregnancy loss. Only the dimeric form of {beta}2GPI generated by anti-{beta}2GPI antibodies is pathologically important, in contrast to monomeric {beta}2GPI which is abundant in plasma. We created a dimeric inhibitor, A1-A1, to selectively target {beta}2GPI in {beta}2GPI/antibody complexes. To make this inhibitor, we isolated the first ligand-binding module from ApoER2 (A1) and connected two A1 modules with a flexible linker. A1-A1 interferes with two pathologically important interactions in APS, the binding of {beta}2GPI/antibody complexes with anionic phospholipids and ApoER2. We compared the efficiency of A1-A1 to monomeric A1 for inhibition of the binding of {beta}2GPI/antibody complexes to anionic phospholipids. We tested the inhibition of {beta}2GPI present in human serum, {beta}2GPI purified from human plasma and the individual domain V of {beta}2GPI. We demonstrated that when {beta}2GPI/antibody complexes are formed, A1-A1 is much more effective than A1 in inhibition of the binding of {beta}2GPI to cardiolipin, regardless of the source of {beta}2GPI. Similarly, A1-A1 strongly inhibits the binding of dimerized domain V of {beta}2GPI to cardiolipin compared to the monomeric A1 inhibitor. In the absence of anti-{beta}2GPI antibodies, both A1-A1 and A1 only weakly inhibit the binding of pathologically inactive monomeric {beta}2GPI to cardiolipin. Our results suggest that the approach of using a dimeric inhibitor to block {beta}2GPI in the pathological multivalent {beta}2GPI/antibody complexes holds significant promise. The novel inhibitor A1-A1 may be a starting point in the development of an effective therapeutic for antiphospholipid syndrome.

  15. Search for beta plus/EC double beta decay of 120Te

    CERN Document Server

    Andreotti, E; Avignone, F T; Balata, M; Bandac, I; Barucci, M; Beeman, J W; Bellini, F; Brofferio, C; Bryant, A; Bucci, C; Canonica, L; Capelli, S; Carbone, L; Carrettoni, M; Clemenza, M; Cremonesi, O; Creswick, R J; Di Domizio, S; Dolinski, M J; Ejzak, L; Faccini, R; Farach, H A; Ferri, E; Fiorini, E; Foggetta, L; Giachero, A; Gironi, L; Giuliani, A; Gorla, P; Guardincerri, E; Haller, T D Gutierrez E E; Kazkaz, K; Kraft, S; Kogler, L; Maiano, C; Maruyama, R H; Martinez, C; Martinez, M; Mizouni, L; Newman, S; Nisi, S; Nones, C; Norman, E B; Nucciotti, A; Orio, F; Pallavicini, M; Palmieri, V; Pattavina, L; Pavan, M; Pedretti, M; Pessina, G; Pirro, S; Previtali, E; Risegari, L; Rosenfeld, C; Rusconi, C; Salvioni, C; Sangiorgio, S; Schaeffer, D; Scielzo, N D; Sisti, M; Smith, A R; Tomei, C; Ventura, G; Vignati, M

    2010-01-01

    We present a search for beta plus/EC double beta decay of 120Te performed with the CUORICINO experiment, an array of TeO2 cryogenic bolometers. After collecting 0.0573 kg y of 120Te, we see no evidence of a signal and therefore set the following limits on the half-life: T1/2 (0nu) > 1.9 10^{21} y at 90% C.L. for the 0 neutrino mode and T1/2 (2nu) > 7.6 10^{19} y at 90% C.L. for the two neutrino mode. These results improve the existing limits by almost three orders of magnitude (four in the case of 0 neutrino mode). Moreover the limit on zero neutrino beta plus/EC represents the most stringent half-life limit ever achieved for this decay mode for any isotope.

  16. Evaluation of thrombogenicity of beta-propiolactone/ultraviolet (beta-PL/UV) treated PPSB in chimpanzees

    Energy Technology Data Exchange (ETDEWEB)

    Kotitschke, R.; Stephan, W.; Prince, A.M.; Brotman, B.

    1983-05-01

    The thrombogenicity of beta-PL/UV-treated PPSB (factor IX concentrate) was evaluated in chimpanzees. PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma was injected into chimpanzees at a dose of approximately 100 units/kg body weight. An FDA licensed PPSB preparation served as the negative control, and a preparation containing activated as well as precursor clotting factors served as the positive control. 15 minutes, 1 h, 4 h, and 24 h after the PPSB application the following parameters were determined in the chimpanzee blood: factors II, VII, IX, X, VIII, fibrinogen, AT III, thrombin coagulase, Quick value, APTT and platelet count. Neither the untreated control preparation, nor the PPSB isolated from beta-propiolactone-treated and UV-irradiated plasma, showed signs of thrombogenicity in the chimpanzee model. The positive control indicated that the chimpanzee is a suitable model for the thrombogenicity testing of activated clotting factors.

  17. Beta-decay rate and beta-delayed neutron emission probability of improved gross theory

    Science.gov (United States)

    Koura, Hiroyuki

    2014-09-01

    A theoretical study has been carried out on beta-decay rate and beta-delayed neutron emission probability. The gross theory of the beta decay is based on an idea of the sum rule of the beta-decay strength function, and has succeeded in describing beta-decay half-lives of nuclei overall nuclear mass region. The gross theory includes not only the allowed transition as the Fermi and the Gamow-Teller, but also the first-forbidden transition. In this work, some improvements are introduced as the nuclear shell correction on nuclear level densities and the nuclear deformation for nuclear strength functions, those effects were not included in the original gross theory. The shell energy and the nuclear deformation for unmeasured nuclei are adopted from the KTUY nuclear mass formula, which is based on the spherical-basis method. Considering the properties of the integrated Fermi function, we can roughly categorized energy region of excited-state of a daughter nucleus into three regions: a highly-excited energy region, which fully affect a delayed neutron probability, a middle energy region, which is estimated to contribute the decay heat, and a region neighboring the ground-state, which determines the beta-decay rate. Some results will be given in the presentation. A theoretical study has been carried out on beta-decay rate and beta-delayed neutron emission probability. The gross theory of the beta decay is based on an idea of the sum rule of the beta-decay strength function, and has succeeded in describing beta-decay half-lives of nuclei overall nuclear mass region. The gross theory includes not only the allowed transition as the Fermi and the Gamow-Teller, but also the first-forbidden transition. In this work, some improvements are introduced as the nuclear shell correction on nuclear level densities and the nuclear deformation for nuclear strength functions, those effects were not included in the original gross theory. The shell energy and the nuclear deformation for

  18. The beta strength function structure in \\beta + decay of lutecium, thulium and cesium isotopes

    CERN Document Server

    Alkhazov, G D; Naumov, Yu V; Orlov, S Yu; Vitman, V D

    1981-01-01

    The spectra of total gamma -absorption in the decays of some lutetium, thulium and cesium isotopes have been measured. The probabilities for level population in the decay of the isotopes have been determined. The deduced beta strength functions reveal pronounced structure. Calculations of the strength functions using the Saxon-Woods potential and the residual Gamow-Teller interaction are presented. It is shown that in beta /sup +/ decay of light thulium and cesium isotopes the strength function comprises more than 70% of the Gamow-Teller excitations with mu /sub tau /=+1. This result is the first direct observation of the Gamov-Teller resonance in beta /sup +/ decay of nuclei with T/sub z/>0. (21 refs).

  19. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  20. Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    W. Theunissen

    2014-03-01

    Full Text Available Thymosin beta 4 (Tβ4 and thymosin beta 10 (Tβ10 are two members of the beta-thymosin family involved in many cellular processes such as cellular motility, angiogenesis, inflammation, cell survival and wound healing. Recently, a role for beta-thymosins has been proposed in the process of carcinogenesis as both peptides were detected in several types of cancer. The aim of the present study was to investigate the expression pattern of Tβ4 and Tβ10 in hepatocellular carcinoma (HCC. To this end, the expression pattern of both peptides was analyzed in liver samples obtained from 23 subjects diagnosed with HCC. Routinely formalin-fixed and paraffin-embedded liver samples were immunostained by indirect immunohistochemistry with polyclonal antibodies to Tβ4 and Tβ10. Immunoreactivity for Tβ4 and Tβ10 was detected in the liver parenchyma of the surrounding tumor area. Both peptides showed an increase in granular reactivity from the periportal to the periterminal hepatocytes. Regarding HCC, Tβ4 reactivity was detected in 7/23 cases (30% and Tβ10 reactivity in 22/23 (97% cases analyzed, adding HCC to human cancers that express these beta-thymosins. Intriguing finding was seen looking at the reactivity of both peptides in tumor cells infiltrating the surrounding liver. Where Tβ10 showed a strong homogeneous expression, was Tβ4 completely absent in cells undergoing stromal invasion. The current study shows expression of both beta-thymosins in HCC with marked differences in their degree of expression and frequency of immunoreactivity. The higher incidence of Tβ10 expression and its higher reactivity in tumor cells involved in stromal invasion indicate a possible major role for Tβ10 in HCC progression.

  1. BETA. A code for {beta}{sub eff} measurement and analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yuichi; Okajima, Shigeaki; Sakurai, Takeshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1999-03-01

    The code BETA has been developed to calculate the following reactor physics parameters which are used for the {beta}{sub eff} measurement and analysis; Diven factor, Spatial correction factor (g-factor) for neutron correlation experiment, Adjoint weighted g-factor, Fission rate integrated in whole reactor and Adjoint weighted fission rate integrated in whole reactor: The code also calculates the effective delayed neutron fraction with different evaluated delayed neutron data. These parameters are calculated with using the forward and adjoint fluxes given by SLAROM, POPLARS or TWOTRAN-II. This report describes the input data and job control statements instructions, file requirements and sample input output data. (author)

  2. Sizeable beta-strength in 31Ar (beta 3p) decay

    DEFF Research Database (Denmark)

    T. Koldste, G.; Blank, B.; J. G. Borge, M.;

    2014-01-01

    We present for the first time precise spectroscopic information on the recently discovered decay mode beta-delayed 3p-emission. The detection of the 3p events gives an increased sensitivity to the high energy part of the Gamow-Teller strength distribution from the decay of 31Ar revealing that as...... much as 30% of the strength resides in the beta-3p decay mode. A simplified description of how the main decay modes evolve as the excitation energy increases in 31Cl is provided....

  3. Sensitive behavior of 2{nu}{beta}{beta}-decay amplitude within QRPA and broken SU(4) symmetry in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Rodin, Vadim A. [Institut fuer Theoretische Physik der Universitaet Tuebingen, Auf der Morgenstelle 14, D-72076 Tuebingen (Germany)]. E-mail: vadim.rodin@uni-tuebingen.de; Urin, Michael H. [Department of Theoretical Nuclear Physics, Moscow State Engineering and Physics Institute, 115409 Moscow (Russian Federation); Kernfysisch Versneller Institute, NL-9747AA Groningen (Netherlands); Faessler, Amand [Institut fuer Theoretische Physik der Universitaet Tuebingen, Auf der Morgenstelle 14, D-72076 Tuebingen (Germany)

    2005-01-24

    Making use of an identity transformation independent of a nuclear model, we represent the 2{nu}{beta}{beta}-amplitude as a sum of two terms. One term accounts for most of the sensitivity of the original 2{nu}{beta}{beta}-amplitude to gpp' for realistic gpp'{approx}1 (with gpp' being the ratio of the triplet and singlet p-p interaction strengths) and is determined by a specific energy-weighted sum rule. The sum rule depends only on the particle-particle residual interaction (being linear function of gpp' in the QRPA) and passes through zero at the point gpp'=1 where the Wigner SU(4) symmetry is restored in the p-p sector of the Hamiltonian. The second term in the decomposition of the 2{nu}{beta}{beta}-amplitude is demonstrated within the QRPA to be a much smoother function for the realistic values of gpp' than the original 2{nu}{beta}{beta}-amplitude. This term is mainly determined by the intensity of the spin-orbit interaction of the nuclear mean field. Thus, the analysis of the present work reveals the reasons for the sensitivity of the 2{nu}{beta}{beta}-amplitude to different components of the nuclear Hamiltonian and thereby can help in constraining nuclear model uncertainties in calculations of the amplitude.

  4. Intrinsic, pro-apoptotic effects of IGFBP-3 on breast cancer cells are reversible: Involvement of PKA, Rho and ceramide.

    OpenAIRE

    Perks, Claire M.; Carla eBurrows; Holly, Jeff M P

    2011-01-01

    We established previously that IGFBP-3 could exert positive or negative effects on cell function depending upon the extracellular matrix composition and by interacting with integrin signaling. To elicit its pro-apoptotic effects IGFBP-3 bound to caveolin-1 and the beta 1 integrin receptor and increased their association culminating in MAPK activation. Disruption of these complexes or blocking the beta 1 integrin receptor reversed these intrinsic actions of IGFBP-3. In this study we have exami...

  5. The effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub

    2007-12-01

    Full Text Available BACKGROUND: Thalassemia is the most common hereditary disease in the world. Thalassemic erythrocytes are exposed to higher oxidative stress and lipid peroxidation. The aim of this study was to investigate the effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients.
    METHODS: A prospective double-blind, placebo-controlled study of the effect of beta-carotene and vitamin E on lipid peroxidation in erythrocytes membranes was performed on 120 beta-thalassemia major patients in four groups. The patients were supplemented for 4 weeks as follows: group 1 with beta-carotene (13 mg/day, group 2 with vitamin E (550 mg/day, group 3 with beta-carotene plus vitamin E and group 4 with placebo. We prepared all capsules for 4 roups in the same shape and color. Measurements of serum beta-carotene and vitamin E were performed by high performance
    liquid chromatography. After preparation of ghost cells from blood specimens, malondialdehyde (MDA was determined as index of lipid peroxidation in erythrocytes membranes before and after treatment. RESULTS: The levels of serum beta-carotene and vitamin E were significantly lower and MDA concentrations in erythrocytes membranes were significantly higher in beta-thalassemia patients compared to controls (P<0.001. In groups that treated with vitamin supplements for 4-weeks, lipid peroxidation rates were significantly reduced after treatment (P<0.001, but in placebo group there was not significant difference (P>0.05.
    CONCLUSIONS: Our findings provide evidence that an oral treatment with beta-carotene and vitamin E can significantly reduce lipid peroxidation of erythrocytes membranes and could be useful in management of beta-thalassemia major patients. KEYWORDS: Beta-thalassemia major, beta-carotene, vitamin E, malondialdehyde, lipid peroxidation.

  6. Coexistence of beta 1- and beta 2-adrenoceptors in the rabbit heart: quantitative analysis of the regional distribution by (-)-3H-dihydroalprenolol binding

    International Nuclear Information System (INIS)

    We determined the amount of beta 1- and beta 2-adrenoceptors in right and left atria and ventricles of rabbits. For this purpose inhibition of specific (-)-3H-dihydroalprenolol [(-)-3H-DHA] binding (5 nM) by beta 1-selective (practolol, metoprolol) and beta 2-selective (zinterol, IPS 339) adrenergic drugs was determined and analyzed by pseudo-Scatchard (Hofstee) plots. For both atria, inhibition of binding by the four selective beta-adrenergic drugs resulted in non-linear Hofstee plots, suggesting the coexistence of both beta-adrenoceptor subtypes. From these plots we calculated a beta 1:beta 2-adrenoceptor ratio of 72:28 for the right atrium and of 82:18 for the left. In contrast, only a very small amount of beta 2-adrenoceptors (approximately 5-7% of the total beta-adrenoceptor population) could be detected in the ventricles. For comparison we analyzed the inhibition of specific (-)-3H-DHA binding in tissues with homogeneous population of beta-adrenoceptors (beta 1:guinea pig left ventricle; beta 2: cerebellum of mature rats). For both tissues the four selective beta-adrenergic drugs showed linear Hofstee plots, demonstrating that in tissues with homogeneous beta-receptor population interaction of each drug with the receptor followed simple mass-action kinetics. We conclude that beta 1- and beta 2-adrenoceptors coexist in rabbit atria while the ventricles are predominantly endowed the beta 1-adrenoceptors

  7. Coexistence of beta 1- and beta 2-adrenoceptors in the rabbit heart: quantitative analysis of the regional distribution by (-)-/sup 3/H-dihydroalprenolol binding

    Energy Technology Data Exchange (ETDEWEB)

    Brodde, O.E.; Leifert, F.J.; Krehl, H.J.

    1982-01-01

    We determined the amount of beta 1- and beta 2-adrenoceptors in right and left atria and ventricles of rabbits. For this purpose inhibition of specific (-)-/sup 3/H-dihydroalprenolol ((-)-/sup 3/H-DHA) binding (5 nM) by beta 1-selective (practolol, metoprolol) and beta 2-selective (zinterol, IPS 339) adrenergic drugs was determined and analyzed by pseudo-Scatchard (Hofstee) plots. For both atria, inhibition of binding by the four selective beta-adrenergic drugs resulted in non-linear Hofstee plots, suggesting the coexistence of both beta-adrenoceptor subtypes. From these plots we calculated a beta 1:beta 2-adrenoceptor ratio of 72:28 for the right atrium and of 82:18 for the left. In contrast, only a very small amount of beta 2-adrenoceptors (approximately 5-7% of the total beta-adrenoceptor population) could be detected in the ventricles. For comparison we analyzed the inhibition of specific (-)-/sup 3/H-DHA binding in tissues with homogeneous population of beta-adrenoceptors (beta 1:guinea pig left ventricle; beta 2: cerebellum of mature rats). For both tissues the four selective beta-adrenergic drugs showed linear Hofstee plots, demonstrating that in tissues with homogeneous beta-receptor population interaction of each drug with the receptor followed simple mass-action kinetics. We conclude that beta 1- and beta 2-adrenoceptors coexist in rabbit atria while the ventricles are predominantly endowed the beta 1-adrenoceptors.

  8. Dopaminergic and beta-adrenergic effects on gastric antral motility

    DEFF Research Database (Denmark)

    Bech, K; Hovendal, C P; Gottrup, F;

    1984-01-01

    bethanechol or pentagastrin inducing motor activity patterns as in the phase III of the MMC and the digestive state respectively. The stimulated antral motility was dose-dependently inhibited by dopamine. The effect was significantly blocked by specifically acting dopaminergic blockers, while alpha- and beta......-adrenergic blockers were without any significant effects. Dose-response experiments with bethanechol and dopamine showed inhibition of a non-competitive type. Isoprenaline was used alone and in conjunction with selective blockade of beta 1- and beta 2-receptors during infusion of bethanechol which induces a pattern...... similar to phase III in the migrating myoelectric complex. The stimulated antral motility was dose-dependently inhibited by isoprenaline. The effect could be significantly blocked by propranolol (beta 1 + beta 2-adrenoceptor blocker) and by using in conjunction the beta 1-adrenoceptor blocker practolol...

  9. Fracture risk in perimenopausal women treated with beta-blockers

    DEFF Research Database (Denmark)

    Rejnmark, Lars; Vestergaard, Peter; Kassem, Moustapha;

    2004-01-01

    beta2-Adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with beta-adrenergic receptor antagonists (beta-blockers) on bone turnover, bone mineral density...... (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with beta-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study....... Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with beta-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with beta-blockers was associated with a threefold increased fracture...

  10. Distribution of beta-amyloid in the canine brain.

    Science.gov (United States)

    Hou, Y; White, R G; Bobik, M; Marks, J S; Russell, M J

    1997-03-01

    The distribution of amyloid-beta protein (A beta) in the canine brain was demonstrated by immunochemistry on serially sectioned tissues from 10 aged mixed breed dogs. Summation of quantitative data and relegation to anatomical sites for the 10 dogs showed A beta to be widely distributed in the cortex and hippocampus while completely absent in the brain stem and cerebellum. The highest density of A beta was in the dentate gyrus of the hippocampus. Cortical areas exhibiting the greatest A beta deposition were the posterior and medial suprasylvius gyrus and the proreus gyrus of the frontal lobe. Unlike humans the canine entorhinal cortex, amygdala, basal ganglia and olfactory bulbs were rarely affected. This suggested that the highly developed olfactory pathways of the canine are generally spared from A beta deposition. PMID:9141082

  11. Double-beta decay in gauge theories

    International Nuclear Information System (INIS)

    The double-beta decay in gauge theories is considered. The review of the 76Ge, 82Se, 96Zr, 100Cd, 128Te, 130Te, 136Xe and 150Nd experimental nuclear targets is presented. The mechanism of the Majorana intermediate neutrino is considered. The R-parity of the violation of the contribution to the 0νββ decay is studied. The effective nucleon currents in dependence on the momentum are discussed. The extraction of the lepton number, violating the double-β decay parameters is presented

  12. Double-beta decay in deformed nuclei

    International Nuclear Information System (INIS)

    A brief review of theoretical results for the double-beta decay and the double-electron capture in heavy deformed nuclei is presented. The ββ half life of 160Gd is evaluated using an extended version of the pseudo SU(3) model. While the 2ν mode is forbidden when the most probable occupations are considered, states with different occupation numbers can be mixed through the pairing interaction. The amount of this mixing is calculated using perturbation theory. The possibility of observing the ββ decay in 160Gd is discussed for both the 2ν and 0ν modes. (author)

  13. Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

    International Nuclear Information System (INIS)

    Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

  14. Neutrinoless double beta decay search with SNO+

    OpenAIRE

    Lozza V.

    2014-01-01

    The SNO+ experiment is the follow up of SNO. The detector is located 2 km underground in the Vale Canada Ltd.’s Creighton Mine near Sudbury, Ontario, Canada. The active volume of the detector consists of 780 tonnes of Linear Alkyl Benzene (LAB) in an acrylic vessel of 12 m diameter, surrounded by about 9500 PMTs. The main goal of the SNO+ experiment is the search for neutrinoless double beta decay of 130Te. With an initial loading of 0.3% of natural tellurium (nearly 800 kg of 130Te), it is e...

  15. The high sensitivity double beta spectrometer TGV

    Science.gov (United States)

    Briancon, Ch.; Brudanin, V. B.; Egorov, V. G.; Janout, Z.; Koníček, J.; Kovalík, A.; Kovalenko, V. E.; Kubašta, J.; Pospíšil, S.; Revenko, A. V.; Rukhadze, N. I.; Salamatin, A. V.; Sandukovsky, V. G.; Štekl, I.; Timkin, V. V.; Tsupko-Sitnikov, V. V.; Vorobel, V.; Vylov, Ts.

    1996-02-01

    A high sensitivity double beta spectrometer TGV (Telescope Germanium Vertical) has been developed. It is based on 16 HPGe detectors of volume 1200 × 6 mm 3 each in the same cryostat. The TGV spectrometer was proposed for the study of ultrarare nuclear processes (e.g. 2νββ, 0νββ, 2νEC/EC). Details of the TGV spectrometer construction are described, the principles of background suppression, the results of Monte Carlo simulations and the results of test background measurements (in Dubna and Modane underground laboratory) are provided.

  16. The high sensitivity double beta spectrometer TGV

    International Nuclear Information System (INIS)

    A high sensitivity double beta spectrometer TGV (Telescope Germanium Vertical) has been developed. It is based on 16 HPGe detectors of volume 1200 x 6 mm3 each in the same cryostat. The TGV spectrometer was proposed for the study of ultrarare nuclear processes (e.g. 2νββ, 0νββ, 2νEC/EC). Details of the TGV spectrometer construction are described, the principles of background suppression, the results of Monte Carlo simulations and the results of test background measurements (in Dubna and Modane underground laboratory) are provided. (orig.)

  17. MHD stable high beta spheromak equilibrium

    International Nuclear Information System (INIS)

    Recent observations of a pressure driven mode in CTX indicate that its performance is being limited by the low beta stability requirements typical of conventional spheromak designs. Improved designs with higher beat limits therefore have the potential to dramatically increase the temperature and lifetime of CTX and other spheromak experiments. This paper describes the results of an optimization study examining radically different geometries, but all with minimum energy current profiles which can easily be created experimentally and should be automatically stable to all ideal and resistive current drive modes. 2 refs., 3 figs

  18. NEUTRINOLESS DOUBLE BETA DECAY: AN EXTREME CHALLENGE

    Directory of Open Access Journals (Sweden)

    Fernando Ferroni

    2013-12-01

    Full Text Available Neutrino-less Double Beta Decay is the only known way to possibly resolve the nature of neutrino mass. The chances to cover the mass region predicted by the inverted hierarchy require a step forward in detector capability. A possibility is to make use of scintillating bolometers. These devices shall have a great power in distinguishing signals from alfa particles from those induced by electrons. This feature might lead to an almost background-free experiment. Here the Lucifer concept will be introduced and the prospects related to this project will be discussed.

  19. Perioperative Beta Blockade - A Case Report

    Directory of Open Access Journals (Sweden)

    Sunitha K. Zachariah

    2009-10-01

    Full Text Available Continuation of antihypertensives preoperatively and their influence on intraoperative hemodynamics is a big concern among anesthesiologists. The Peri Operative Ischaemia Study Evaluation (POISE trial showed a significant reduction of myocardial infarction, need for coronary revascularization and the incidence of atrial fibrillation with metoprolol started 2-4 hours prior to surgery but a significant increase in total mortality and clinically significant hypotension and bradycardia. This is a case report of intraoperative severe bradycardia in a young patient on recently started beta blocker.

  20. Mass spectrometric study of fluorinated. beta. -diketones

    Energy Technology Data Exchange (ETDEWEB)

    Lozinskii, M.O.; Fialkov, Yu.A.; Khomenko, V.S.; Krasovskaya, L.I.; Rasshinina, T.A.; Berenblit, V.V.

    1985-09-01

    Mass spectrometry has been applied in an investigation of fluorinated ..beta..-diketones and the decomposition of these compounds under electron impact. It has been shown that there is a possibility that intramolecular hydrogen bonds of the -H...O double bond and -H...F- types may exist in the fluorinated delta-diketones and the products of their decomposition in the gas phase, these bonds playing an important role in the mechanism fragmentation. The formation of cyclic structures in this process is postulated.

  1. Improved Synthesis Of Potassium Beta' '-Alumina

    Science.gov (United States)

    Williams, Roger M.; Jeffries-Nakamura, Barbara; Ryan, Margaret A.; O'Connor, Dennis E.; Kisor, Adam; Underwood, Mark

    1996-01-01

    Improved formulations of precursor materials synthesize nearly-phase-pure potassium beta' '-alumina solid electrolyte (K-BASE) powder. Materials are microhomogeneous powders (or, alternatively, gels) containing K(+,) Mg(2+), and Al(3+). K-BASE powder produced used in potassium-working-fluid alkali-metal thermal-to-electric conversion (K-AMTEC), in which heat-input and heat-rejection temperatures lower than sodium-working-fluid AMTEC (Na-AMTEC). Additional potential use lies in purification of pottassium by removal of sodium and calcium.

  2. The Beta-MANOVA Ensemble with General Covariance

    OpenAIRE

    Dubbs, Alexander; Edelman, Alan

    2013-01-01

    We find the joint generalized singular value distribution and largest generalized singular value distributions of the $\\beta$-MANOVA ensemble with positive diagonal covariance, which is general. This has been done for the continuous $\\beta > 0$ case for identity covariance (in eigenvalue form), and by setting the covariance to $I$ in our model we get another version. For the diagonal covariance case, it has only been done for $\\beta = 1,2,4$ cases (real, complex, and quaternion matrix entries...

  3. Reversion reactions of beta-galactosidase (Escherichia coli).

    Science.gov (United States)

    Huber, R E; Hurlburt, K L

    1986-04-01

    The reversion reactions of beta-galactosidase (Escherichia coli) produced beta-galactosyl-galactoses and beta-galactosyl-glucoses. About 10 beta-galactosyl-galactose and 10 beta-galactosyl-glucose gas-liquid chromatographic peaks were detected and it is thus very likely that every possible isomer of beta-galactosyl-galactose and beta-galactosyl-glucose was formed by the reversion reactions (taking into account both anomers for each isomer). The presence of lactose and allolactose among the beta-galactosyl-glucoses was confirmed with standards. An important finding relating to the role of allolactose as an inducer of the lac operon was that allolactose (beta-D-galactosyl-(1----6)-D-glucose) was the only disaccharide formed initially, and at equilibrium it was present in the largest amount (50%). Obviously the enzyme is specific in its ability to form allolactose, and allolactose is the most stable beta-galactosyl-glucose, both important inducer properties. The equilibrium constant (concentration of disaccharides divided by the concentration of reactants at equilibrium) of the reaction was about 9.5 mM-1. This is the first report of an equilibrium constant for the beta-galactosidase reaction. Of mechanistic significance is the fact that only three compounds were able to replace D-galactose as a reversion reactant. Two of these (L-arabinose and D-fucose) had alterations at carbon 6. The 6 position, therefore, is not essential for reactivity. The third compound was D-galactal. Any other sugars tested (even with very minor changes relative to D-galactose) did not react. Of special consequence is the 2 position. The results strongly suggest that there has to be either an equatorial hydroxyl at the 2 position of a sugar or a special reactivity (as with D-galactal) in order for the enzyme to catalyze the beta-galactosidase reaction. PMID:3083779

  4. Proceedings of the Department of Energy workshop on beta measurements

    Energy Technology Data Exchange (ETDEWEB)

    Swinth, K.L.; Vallario, E.J.

    1987-09-01

    Participants discussed current practices, efforts to upgrade the quality of beta measurements, and initiatives necessary to improve the measurement and control of beta doses. This proceedings includes papers presented at the workshop, transcripts of panel and open discussions, and documentation of question and answer sessions. The information exchange resulting from this meeting is expected to provide a clearer focus on the problems of beta measurements.

  5. Bootstrap transition to high beta equilibrium in helical system

    International Nuclear Information System (INIS)

    It is shown theoretically and computationally that helical magnetic field, produced by continuous winding helical coils and without the toroidal coil, can sustain MHD stable high beta plasma. Pressure driven toroidal current (bootstrap current) cancels the external magnetic field and reduces the MHD potential energy, depending on the plasma beta values. Ramp-up of heating power input induces bootstrap transition to higher beta plasmas with flat-top pressure profiles. Helical pitch parameter dependence of MHD stability is analyzed. (author)

  6. Proceedings of the Department of Energy workshop on beta measurements

    International Nuclear Information System (INIS)

    Participants discussed current practices, efforts to upgrade the quality of beta measurements, and initiatives necessary to improve the measurement and control of beta doses. This proceedings includes papers presented at the workshop, transcripts of panel and open discussions, and documentation of question and answer sessions. The information exchange resulting from this meeting is expected to provide a clearer focus on the problems of beta measurements

  7. Cyclic beta-glucans of members of the family Rhizobiaceae.

    OpenAIRE

    Breedveld, M. W.; Miller, K. J.

    1994-01-01

    Cyclic beta-glucans are low-molecular-weight cell surface carbohydrates that are found almost exclusively in bacteria of the Rhizobiaceae family. These glucans are major cellular constituents, and under certain culture conditions their levels may reach up to 20% of the total cellular dry weight. In Agrobacterium and Rhizobium species, these molecules contain between 17 and 40 glucose residues linked solely by beta-(1,2) glycosidic bonds. In Bradyrhizobium species, the cyclic beta-glucans are ...

  8. Beta adrenoreceptor subtype cross regulation in the human heart.

    OpenAIRE

    Hall, J. A.; Ferro, A; Dickerson, J. E.; Brown, M. J.

    1993-01-01

    OBJECTIVES--To find out in a prospective study whether beta 1 blocker treatment causes selective beta 2 adrenoreceptor sensitisation, and to find whether such sensitisation is confined to the heart. DESIGN--A placebo controlled cross over study of two weeks of selective beta 1 blocker treatment with 10 mg of bisoprolol daily. SUBJECTS--Six healthy volunteers. OUTCOME MEASURES--Three days after stopping the 10 mg of bisoprolol or placebo, subjects underwent treadmill exercise (to measure cardi...

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

    OpenAIRE

    Maccioni, L; Cao, A

    1985-01-01

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

  10. Pharmacokinetics of sex steroids in patients with beta thalassaemia major.

    OpenAIRE

    Katz, M; De Sanctis, V.; Vullo, C; Wonke, B; McGarrigle, H. H.; Bagni, B

    1993-01-01

    AIMS--To assess the pharmacokinetics of oral, intramuscular, or transdermal hormone replacement in patients with beta thalassaemia major. METHODS--Oral (testosterone undecanoate 40 mg) and intramuscular (testosterone propionate 15 mg, phenylpropionate 30 mg, isocaproate 30 mg and decanoate 50 mg) testosterone and transdermal (17 beta oestradiol 25 micrograms and 50 micrograms) oestradiol were evaluated in 21 male (16-29 years) and 11 female (19-26 years) patients with beta thalassaemia major ...

  11. Isospin and quarks in nuclear beta-decay

    International Nuclear Information System (INIS)

    This paper exposes in some detail the technical problems relating to the extraction of the vector coupling constant from the beta decay of complex nuclei. It also considers the extraction of the axial coupling constant from the beta-decay of the neutron. The internal consistency of all data relating to beta-decay, including that of the muon, is also examined, within the standard model, with a view to the possible intervention of WR. (Author) 52 refs., 4 figs., 2 tabs

  12. Time-Varying Beta: A Boundedly Rational Equilibrium Approach

    OpenAIRE

    Carl Chiarella; Roberto Dieci; Xue-Zhong He

    2010-01-01

    By taking into account conditional expectations and the dependence of the systematic risk of asset returns on micro- and macro-economic factors, the conditional CAPM with time-varying betas displays superiority in explaining the cross-section of returns and anomalies in a number of empirical studies. Most of the literature on time-varying beta is motivated by econometric estimation rather than explicit modelling of the stochastic behaviour of betas through agents' behaviour. Within the mean-v...

  13. Interactions between Polymyxa betae and plant systemic defense ways

    OpenAIRE

    Desoignies, Nicolas; Schramme, Florence; Legrève, Anne; Vienna Interntational Plant Conference Association - Plant Diseases and resistance mechanisms

    2013-01-01

    Polymyxa betae is the vector of Beet necrotic yellow vein virus (BNYVV), the causal agent of sugar beet rhizomania disease. Because of the widespread use of cultivars partially resistant to BNYVV, resistance breaking BNYVV isolates have been reported. In order to develop alternative control strategies, we investigated interactions between P. betae and plant defenses. A first set of bioassays was conducted in order to assess P. betae infection after the elicitation of inducible defenses in sug...

  14. Evaluation of the instrument correction factors need in beta dosimetry

    International Nuclear Information System (INIS)

    A wide variety of portable survey instruments using Geiger-Mueller (GM) detectors, ionization chambers, or scintillation detectors exists for the measurement of gamma dose rates. Generally, the same instruments are used for beta monitoring, but the beta response of these instruments has been secondary to their development, calibration, and use; information on the beta response is difficult to obtain and seldom provided by the manufacturer. This paper summarizes observations on energy, angular, and source-geometry response of survey instruments

  15. Phenotypic detection of beta-lactamases production in enterobacteriaceae

    OpenAIRE

    Ćirković Ivana; Pavlović Ljiljana; Konstantinović Neda; Kostić Katarina; Jovanović Snežana; Đukić Slobodanka

    2014-01-01

    Introduction. Beta-lactam antibiotics are the most commonly used antibacterial drugs. However, many bacteria have developed resistance to these antibiotics, and the most common form of resistance is the production of beta-lactamase enzymes. Many members of the Enterobacteriaceae family produce different types of these enzymes. Objective. The aim of this study was to perform phenotypic detection of production and identification of beta-lactamase type in Ente...

  16. Mitochondrial function in normal and diabetic beta-cells

    OpenAIRE

    Maechler, Pierre; Wollheim, Claes

    2001-01-01

    The aetiology of type 2, or non-insulin-dependent, diabetes mellitus has been characterized in only a limited number of cases. Among these, mitochondrial diabetes, a rare subform of the disease, is the consequence of pancreatic beta-cell dysfunction caused by mutations in mitochondrial DNA, which is distinct from the nuclear genome. The impact of such mutations on beta-cell function reflects the importance of mitochondria in the control of insulin secretion. The beta-cell mitochondria serve a...

  17. New Insights in the Amyloid-Beta Interaction with Mitochondria

    OpenAIRE

    Carlos Spuch; Saida Ortolano; Carmen Navarro

    2012-01-01

    Biochemical and morphological alterations of mitochondria may play an important role in the pathogenesis of Alzheimer’s disease (AD). Particularly, mitochondrial dysfunction is a hallmark of amyloid-beta-induced neuronal toxicity in Alzheimer’s disease. The recent emphasis on the intracellular biology of amyloid-beta and its precursor protein (APP) has led researchers to consider the possibility that mitochondria-associated and mitochondrial amyloid-beta may directly cause neurotoxicity. Both...

  18. Marginal versus average beta of equity under corporate taxation

    OpenAIRE

    Lund, Diderik

    2009-01-01

    Even for fully equity-financed firms there may be substantial effects of taxation on the after-tax cost of capital. Among the few studies of these effects, even fewer identify all effects correctly. When marginal investment is taxed together with inframarginal, marginal beta differs from average if there are investmentrelated deductions like depreciation. To calculate asset betas, one should not only "unlever" observed equity betas, but "untax" and "unaverage" them. Risky tax claims are value...

  19. Background capabilities of pixel detectors for double beta decay measurements

    Energy Technology Data Exchange (ETDEWEB)

    Cermak, Pavel, E-mail: pavel.cermak@utef.cvut.cz [Institute of Experimental and Applied Physics, CTU in Prague, 12800 Prague (Czech Republic); Stekl, Ivan; Bocarov, Viktor; Jose, Joshy M.; Jakubek, Jan; Pospisil, Stanislav [Institute of Experimental and Applied Physics, CTU in Prague, 12800 Prague (Czech Republic); Fiederle, Michael; Fauler, Alex [Freiburger Materialforschungszentrum, Albert-Ludwigs-Universitaet Freiburg, D-79104 Freiburg (Germany); Zuber, Kai [Institut fuer Kern- und Teilchenphysik, Technische Universitaet Dresden, 01069 Dresden (Germany); Loaiza, Pia [Laboratoire Souterrain de Modane, 73500 Modane (France); Shitov, Yuriy [Joint Institute for Nuclear Research, 141980 Dubna (Russian Federation)

    2011-05-15

    We discuss the possible use of a progressive detection technique based on pixel detectors for the study of double beta decay ({beta}{beta}) processes. A series of background measurements in various environments (surface laboratory, underground laboratory, with and without Pb shielding) was performed using the TimePix silicon hybrid pixel device. The pixel detector response to the natural background and intrinsic background properties measured by a low-background HPGe detector are presented.

  20. Neuroinflammation and Complexes of 17 beta-Hydroxysteroid Dehydrogenase type 10-Amyloid beta in Alzheimer's Disease

    Czech Academy of Sciences Publication Activity Database

    Krištofíková, Z.; Řípová, D.; Bartoš, A.; Bocková, Markéta; Hegnerová, Kateřina; Říčný, J.; Čechová, L.; Vrajová, M.; Homola, Jiří

    2013-01-01

    Roč. 10, č. 2 (2013), s. 165-173. ISSN 1567-2050 R&D Projects: GA MZd(CZ) NT11225 Institutional support: RVO:67985882 Keywords : Amyloid beta * mitochondrial enzyme * Alzheimer 's disease Subject RIV: JB - Sensors, Measurment, Regulation Impact factor: 3.796, year: 2013