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Sample records for double positive thymocytes

  1. Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte.

    PubMed

    Furmanski, Anna L; Saldana, Jose Ignacio; Rowbotham, Nicola J; Ross, Susan E; Crompton, Tessa

    2012-02-01

    In the thymus, developing T cells receive signals that determine lineage choice, specificity, MHC restriction and tolerance to self-antigen. One way in which thymocytes receive instruction is by secretion of Sonic hedgehog (Shh) from thymic epithelial cells. We have previously shown that Hedgehog (Hh) signalling in the thymus decreases the CD4:CD8 single-positive (SP) thymocyte ratio. Here, we present data indicating that double-positive (DP) thymocytes are Hh-responsive and that thymocyte-intrinsic Hh signalling plays a role in modulating the production of CD4(+) (SP4), CD8(+) (SP8) and unconventional T-cell subsets. Repression of physiological Hh signalling in thymocytes altered the proportions of DP and SP4 cells. Thymocyte-intrinsic Hh-dependent transcription also attenuated both the production of mature SP4 and SP8 cells, and the establishment of peripheral T-cell compartments in TCR-transgenic mice. Additionally, stimulation or withdrawal of Hh signals in the WT foetal thymus impaired or enhanced upregulation of the CD4 lineage-specific transcription factor Gata3 respectively. These data together suggest that Hh signalling may play a role in influencing the later stages of thymocyte development. PMID:22101858

  2. Activity of neutral endopeptidase and aminopeptidase N in mouse thymic stromal cells which bind double-positive thymocytes.

    PubMed

    Small, M; Kaiser, M; Tse, W; Heimfeld, S; Blumberg, S

    1996-04-01

    The activity of two peptidases was determined in immortalized lines of thymic stromal cells. A line of total stromal cells (T-TG-St) was grown from transgenic mouse expressing temperature-sensitive SV40 T antigen under the control of the regulatory elements of the mouse major histocompatibility complex class I gene. From these cells we isolated a subset (DP-TG-St) that binds thymocytes which are mainly CD4+8+. We also assayed a clone of fetal thymic epithelial cells (BA/10) that binds CD4+8+ thymocytes. Both lines of double -positive cell-binding stroma exhibited strong activity of two peptidases, neutral endopeptidase (NEP; EC 3.4.24.11) and aminopeptidase N (APN; EC 3.4.11.2). In contrast, the activity of both enzymes was very low in the total thymic stromal line. Use of the specific inhibitors confirmed that these two enzymes were responsible for the activity observed but also suggested the presence of additional unidentified aminopeptidase(s) in the same stromal cells. The high activity of the two peptidases on stromal cells that bind thymocytes at the double-positive stage raises the possibility that they might contribute to the microenvironment of the developing thymocytes. PMID:8625997

  3. β-Catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation

    PubMed Central

    Guo, Zhuyan; Dose, Marei; Kovalovsky, Damian; Chang, Rui; O'Neil, Jennifer; Look, A. Thomas; von Boehmer, Harald; Khazaie, Khashayarsha

    2007-01-01

    Activation of β-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T cells promotes thymocyte development without the requirement for pre-TCR signaling. We show here that activated β-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. β-Catenin–induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional up-regulation of c-Myc, whose activity is required for transformation because its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized β-catenin and remains low in the lymphomas, indicating that Notch activation is not required or selected for in β-catenin–induced lymphomas. Thus, β-catenin activation may provide a mechanism for the induction of T-cell–acute lymphoblastic leukemia (T-ALL) that does not depend on Notch activation. PMID:17317856

  4. c-Myb promotes the survival of CD4+CD8+ double positive thymocytes through up-regulation of Bcl-xL1

    PubMed Central

    Yuan, Joan; Crittenden, Rowena B.; Bender, Timothy P.

    2010-01-01

    Mechanisms that regulate the lifespan of CD4+CD8+ double positive (DP) thymocytes help shape the peripheral T cell repertoire. However, the molecular mechanisms that control DP thymocyte survival remain poorly understood. The Myb proto-oncogene encodes a transcription factor required during multiple stages of T cell development. We demonstrate that Myb mRNA expression is up-regulated in the small, pre-selection DP stage during T cell development. Using a conditional deletion mouse model, we demonstrate that Myb deficient DP thymocytes undergo premature apoptosis, resulting in a limited Tcrα repertoire biased towards 5’ Jα segment usage. Premature apoptosis occurs in the small pre-selection DP compartment in an αβTCR independent manner and is a consequence of decreased Bcl-xL expression. Forced Bcl-xL expression is able to rescue survival and re-introduction of c-Myb restores both Bcl-xL expression and the small pre-selection DP compartment. We further demonstrate that thymocytes become dependent on Bcl-xL for survival upon entering the quiescent, small pre-selection DP stage and c-Myb promotes transcription at the Bclx locus via a genetic pathway that is independent of the expression of TCF-1 or RORγt, two transcription factors that induce Bcl-xL expression in T cell development. Thus, Bcl-xL is a novel mediator of c-Myb activity during normal T cell development. PMID:20142358

  5. [Regulation of thymocyte apoptosis and positive selection].

    PubMed

    Iwata, M

    1996-07-01

    Developing T cells undergo thymic selection at the CD4+CD8+ stage. Only less than 5% of CD4+CD8+ thymocytes are positively selected to survive and differentiate into mature single positive CD4 or CD8 T cells. Positive selection requires signaling through the T cell receptors (TCR) with assistance of CD4 or CD8 coreceptor and LFA-1, but its molecular mechanism is poorly understood. By using glucocorticoids, anti-apoptotic activity was detected in CD4+CD8+ thymocytes upon proper cross-linking of TCR/CD3 complex with CD4, CD8, or LFA-1, and was mimicked by a combination of a calcium ionophore and a protein kinase C activator. Isolated CD4+CD8+ thymocytes underwent differentiation and commitment to the CD4 T cell lineage by moderate and transient stimulation with this combination of the drugs. PMID:8741662

  6. Alterations in the thymocyte phenotype of EphB-deficient mice largely affect the double negative cell compartment

    PubMed Central

    Alfaro, David; Muñoz, Juan José; García-Ceca, Javier; Cejalvo, Teresa; Jiménez, Eva; Zapata, Agustín

    2008-01-01

    In the present study, we have analysed the phenotype of EphB2 and/or EphB3 deficient thymocytes confirming and extending previous studies on the role of this family of molecules in T-cell differentiation. In all mutant thymuses statistically significant reduced cell contents were observed. This reduction of thymic cellularity correlated with increased proportions of apoptotic cells, largely both double negative (DN; CD4− CD8−) and double positive (CD4+ CD8+) cells, and decreased proportions of DN cycling cells. Adult deficient thymuses also showed increased proportions of DN cells but not significant variations in the percentages of other thymocyte subsets. In absolute terms, the thymocyte number decreased significantly in all thymocyte compartments from the DN3 (CD44− CD25+) cell stage onward, without variations in the numbers of both DN1 (CD44+ CD25−) and DN2 (CD44+ CD25+) cells. Remarkably, all these changes also occurred from the 15-day fetal EphB2 and/or EphB3 deficient mice, suggesting that adult phenotype results from the gradual accumulations of defects appearing early in the thymus ontogeny. As a reflection of thymus condition, a reduction in the number of T lymphocytes occurred in the peripheral blood and mesenteric lymph nodes, but not in spleen, maintaining the proportions of T-cell subsets defined by CD4/CD8 marker expression, in all cases. PMID:18397270

  7. TNF activation of NF-κB is essential for development of single-positive thymocytes.

    PubMed

    Webb, Louise V; Ley, Steven C; Seddon, Benedict

    2016-07-25

    NF-κB activation has been implicated at multiple stages of thymic development of T cells, during which it is thought to mediate developmental signals originating from the T cell receptor (TCR). However, the Card11-Bcl10-Malt1 (CBM) complex that is essential for TCR activation of NF-κB in peripheral T cells is not required for thymocyte development. It has remained unclear whether the TCR activates NF-κB independent of the CBM complex in thymocyte development or whether another NF-κB activating receptor is involved. In the present study, we generated mice in which T cells lacked expression of both catalytic subunits of the inhibitor of κB kinase (IKK) complex, IKK1 and IKK2, to investigate this question. Although early stages of T cell development were unperturbed, maturation of CD4 and CD8 single-positive (SP) thymocytes was blocked in mice lacking IKK1/2 in the T cell lineage. We found that IKK1/2-deficient thymocytes were specifically sensitized to TNF-induced cell death in vitro. Furthermore, the block in thymocyte development in IKK1/2-deficient mice could be rescued by blocking TNF with anti-TNF mAb or by ablation of TNFRI expression. These experiments reveal an essential role for TNF activation of NF-κB to promote the survival and development of single positive T cells in the thymus. PMID:27432943

  8. αPIX RhoGEF supports positive selection by restraining migration and promoting arrest of thymocytes.

    PubMed

    Korthals, Mark; Schilling, Kerstin; Reichardt, Peter; Mamula, Dejan; Schlüter, Thomas; Steiner, Michael; Langnäse, Kristina; Thomas, Ulrich; Gundelfinger, Eckart; Premont, Richard T; Tedford, Kerry; Fischer, Klaus-Dieter

    2014-04-01

    Thymocytes mature in a series of stages by migrating through specific areas of the thymus and interacting with other cells to receive the necessary developmental signals; however, little is known about the molecular mechanisms governing this migration. We report that murine thymocytes with a knockout mutation in α-PAK (p21-activated kinase)-interacting exchange factor (PIX; Arhgef6), an activator of Rho GTPases, showed greatly increased motility and altered morphology in two-dimensional migration on ICAM-1. αPIX was also required for efficient positive selection, but not negative selection, of thymocytes. TCR signaling was normal in αPix(-) thymocytes, indicating that the effects of αPIX on positive selection are largely independent of TCR signaling. αPix(-) thymocytes also paused less during migration in the thymic cortex, interacted less with ICAM-1 coated beads, and could overcome TCR stop signals, consistent with defective scanning behavior. These results identify αPIX as a regulator of thymocyte migration and subsequent arrest that is linked to positive selection. PMID:24591366

  9. HDAC3 Is Required for the Downregulation of RORγt during Thymocyte Positive Selection.

    PubMed

    Philips, Rachael L; Chen, Meibo W; McWilliams, Douglas C; Belmonte, Paul J; Constans, Megan M; Shapiro, Virginia Smith

    2016-07-15

    To generate functional peripheral T cells, proper gene regulation during T cell development is critical. In this study, we found that histone deacetylase (HDAC) 3 is required for T cell development. T cell development in CD2-icre HDAC3 conditional knockout (cKO) mice (HDAC3-cKO) was blocked at positive selection, resulting in few CD4 and CD8 T cells, and it could not be rescued by a TCR transgene. These single-positive thymocytes failed to upregulate Bcl-2, leading to increased apoptosis. HDAC3-cKO mice failed to downregulate retinoic acid-related orphan receptor (ROR) γt during positive selection, similar to the block in positive selection in RORγt transgenic mice. In the absence of HDAC3, the RORC promoter was hyperacetylated. In the periphery, the few CD4 T cells present were skewed toward RORγt(+) IL-17-producing Th17 cells, leading to inflammatory bowel disease. Positive selection of CD8 single-positive thymocytes was restored in RORγt-KO Bcl-xL transgenic HDAC3-cKO mice, demonstrating that HDAC3 is required at positive selection to downregulate RORγt. PMID:27279370

  10. Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53.

    PubMed

    Chen, Liang; Foreman, Daniel P; Sant'Angelo, Derek B; Krangel, Michael S

    2016-03-15

    Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used mouse models that depleted YY1 at two distinct stages of thymocyte development. When YY1 was depleted in CD4(-)CD8(-) double-negative thymocytes, development to the CD4(+)CD8(+) double-positive stage was impaired, due to increased apoptosis that prevented expansion of post-β-selection thymocytes. When YY1 was depleted in double-positive thymocytes, they underwent increased cell-autonomous apoptosis in vitro and displayed a shorter lifespan in vivo, as judged by their ability to undergo secondary Vα-to-Jα recombination. Mechanistically, we found that the increased apoptosis in YY1-deficient thymocytes was attributed to overexpression of p53, because concurrent loss of p53 completely rescued the developmental defects of YY1-deficient thymocytes. These results indicated that YY1 functions as a critical regulator of thymocyte survival and that it does so by suppressing the expression of p53. PMID:26843327

  11. Mesenchymal stromal cells support the viability and differentiation of thymocytes through direct contact in autologous co-cultures.

    PubMed

    Azghadi, Seyed Mohammad Reza; Suciu, Maria; Gruia, Alexandra Teodora; Barbu-Tudoran, Lucian; Cristea, Mirabela Iustina; Mic, Ani Aurora; Muntean, Danina; Nica, Dragos Vasile; Mic, Felix Aurel

    2016-08-01

    The development of thymocytes and generation of mature T cells is a complex process that requires spatio-temporal interactions of thymocytes with the other cells of the thymus microenvironment. Recently, mesenchymal stromal cells were isolated from the neonatal human thymus and differentiated into chondrogenic, osteogenic, and adipogenic lineages, just like their bone marrow counterparts. However, their function in thymocyte homeostasis is unknown. In our autologous co-cultures of rat mesenchymal stromal cells and thymocytes, the stromal cells preserve the viability of cultured thymocytes and stimulate the development of CD4-CD8- double-negative and the maturation of mainly CD4+ single-positive thymocytes. Thymocytes also influence the stemness of bone marrow mesenchymal stromal cells, as their expression of CD44, a marker associated with cellular proliferation and migration, is reduced in co-cultures. Mesenchymal stromal cells' influence on thymocyte development requires direct physical contact between the two cells and is not mediated by a soluble factor. When the two types of cells were physically separated, the stimulative effects of mesenchymal stromal cells on thymocytes did not occur. Electron microscopy confirmed the close contact between the membranes of thymocytes and mesenchymal stromal cells. Our experiments suggest that membrane exchanges could occur between mesenchymal stromal cells and thymocytes, such as the transfer of CD44 from mesenchymal stromal cells to the thymocytes, but its functional significance for thymocytes development remains to be established. These results suggest that mesenchymal stromal cells could normally be a part of the in vivo thymic microenvironment and form a niche that could sustain and guide the development of thymocytes. PMID:27085705

  12. Age-related synthesis of glucocorticoids in thymocytes

    SciTech Connect

    Qiao Shengjun Chen Liying; Okret, Sam; Jondal, Mikael

    2008-10-01

    Glucocorticoids (GCs) are primarily synthesized in the adrenal glands but an ectopic production has also been reported in the brain, the gastrointestinal tract and in thymic epithelial cells (TEC). Here we show that thymocytes express genes encoding for all enzymes required for de novo GC synthesis and produce the hormone as demonstrated by both a GC specific reporter assay and a corticosterone specific ELISA assay. Interestingly, GC synthesis is detectable in cells from young mice (4 weeks) and thereafter increases during aging (14-22 weeks) together with an increased gene expression of the rate-limiting enzymes StAR and CYP11A1. Hormone production occurred at a thymocyte differentiation stage characterized by being double positive for the CD4 and CD8 surface markers but was found to be unrelated to CD69 expression, a marker for thymocytes undergoing positive selection. No GC synthesis was found in resting or anti-CD3 activated CD4 and CD8 positive T cells isolated from the spleen. Thymocyte-derived GC had an anti-proliferative effect on a GR-transfected cell line and induced apoptosis in thymocytes. The age- and differentiation stage-related GC synthesis in thymocytes may play a role in the involution process that the thymus gland undergoes.

  13. Glucocorticoid (GC) sensitivity and GC receptor expression differ in thymocyte subpopulations.

    PubMed

    Berki, Timea; Pálinkás, László; Boldizsár, Ferenc; Németh, Péter

    2002-05-01

    Positive and negative selection steps in the thymus prevent non-functional or harmful T cells from reaching the periphery. To examine the role of glucocorticoid (GC) hormone and its intracellular receptor (GCR) in thymocyte development we measured the GCR expression in different thymocyte subpopulations of BALB/c mice with or without previous dexamethasone (DX), anti-CD3 mAb, RU-486 and RU-43044 treatment. Four-color labeling of thymocytes allowed detection of surface CD4/CD8/CD69 expression in parallel with intracellular GCR molecules by flow cytometry. Double-positive (DP) CD4+CD8+ thymocytes showed the lowest GCR expression compared to double-negative (DN) CD4-CD8- thymocytes and mature single-positive (SP) cells. DX treatment caused a concentration-dependent depletion of the DP cell population and increased appearance of mature SP cells with reduced GCR levels. GCR antagonists (RU-486 or RU-43044) did not influence the effect of DX on thymocyte composition; however, RU-43044 inhibited the high-dose GC-induced GCR down-regulation in SP and DN cells. GCR antagonists alone did not influence the maturation of thymocytes and receptor numbers. Combined low-dose anti-CD3 mAb and DX treatment caused an enhanced maturation (positive selection) of thymocytes followed by the elevation of CD69+ DP cells. The sensitivity of DP thymocytes with a GCRlow phenotype to GC action and the ineffectiveness of the GCR antagonist treatment may reflect a non-genomic GC action in the thymic selection steps. PMID:11978776

  14. Developmental regulation of p53-dependent radiation-induced thymocyte apoptosis in mice

    PubMed Central

    Gentil Dit Maurin, A; Lemercier, C; Collin-Faure, V; Marche, P N; Jouvin-Marche, E; Candéias, S M

    2015-01-01

    The production of T cell receptor αβ+ (TCRαβ+) T lymphocytes in the thymus is a tightly regulated process that can be monitored by the regulated expression of several surface molecules, including CD4, CD8, cKit, CD25 and the TCR itself, after TCR genes have been assembled from discrete V, D (for TCR-β) and J gene segments by a site-directed genetic recombination. Thymocyte differentiation is the result of a delicate balance between cell death and survival: developing thymocytes die unless they receive a positive signal to proceed to the next stage. This equilibrium is altered in response to various physiological or physical stresses such as ionizing radiation, which induces a massive p53-dependent apoptosis of CD4+CD8+ double-positive (DP) thymocytes. Interestingly, these cells are actively rearranging their TCR-α chain genes. To unravel an eventual link between V(D)J recombination activity and thymocyte radio-sensitivity, we analysed the dynamics of thymocyte apoptosis and regeneration following exposure of wild-type and p53-deficient mice to different doses of γ-radiation. p53-dependent radio-sensitivity was already found to be high in immature CD4−CD8− (double-negative, DN) cKit+CD25+ thymocytes, where TCR-β gene rearrangement is initiated. However, TCR-αβ−CD8+ immature single-positive thymocytes, an actively cycling intermediate population between the DN and DP stages, are the most radio-sensitive cells in the thymus, even though their apoptosis is only partially p53-dependent. Within the DP population, TCR-αβ+ thymocytes that completed TCR-α gene recombination are more radio-resistant than their TCR-αβ− progenitors. Finally, we found no correlation between p53 activation and thymocyte sensitivity to radiation-induced apoptosis. PMID:24635132

  15. Thymic education curtailed: defective immune responses in nude rats reconstituted with immature thymocyte subsets.

    PubMed

    Yang, C P; Bell, E B

    1994-04-01

    We have studied the ability of thymocyte subsets from allotype marked donors to populate athymic nude rats with T cells and to restore immune responsiveness. Following adoptive transfer, CD4-CD8- double-negative (DN) thymocytes (lymphoid precursor cells) or the CD4+CD8+ double-positive (DP) subset (intermediate thymocytes) or CD4+CD8- single-positive (CD4 SP) cells (mature thymocytes) each generated a permanent population of CD4+ progeny in syngeneic nude recipients. DN and DP thymocytes also produced small numbers of CD8+ cells; there was no evidence of a CD4-CD8- or CD4+CD8+ donor cell population. CD4 SP thymocytes conferred T cell functions [graft-versus-host (GVH) responses, allograft rejection and thymus-dependent antibody responses] on nude rats that were almost indistinguishable from those conferred by mature peripheral recirculating CD4 T cells. Transfer of DP thymocytes extended the life-span of the immunoincompetent nudes and produced CD4+ progeny with near normal GVH responsiveness. However, DP-derived CD4+ cells were deficient at inducing allograft rejection and provided little or no help for antibody synthesis. The CD4+ progeny of DN thymocytes did not prolong the survival of nude recipients, gave reduced GVH reactivity, showed almost no capacity to initiate skin allograft rejection and failed to help B cells produce antibody. The results suggest that intrathymic development proceeds stepwise; each stage is accompanied by acquisition of additional properties that are reflected by T cell responses in the periphery. Thymic education does not become complete until the SP stage is reached when thymocytes become fully independent of the thymic microenvironment. PMID:8018597

  16. A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development.

    PubMed

    Klein-Hessling, Stefan; Rudolf, Ronald; Muhammad, Khalid; Knobeloch, Klaus-Peter; Maqbool, Muhammad Ahmad; Cauchy, Pierre; Andrau, Jean-Christophe; Avots, Andris; Talora, Claudio; Ellenrieder, Volker; Screpanti, Isabella; Serfling, Edgar; Patra, Amiya Kumar

    2016-01-01

    NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are incompletely characterized. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibit only P2 promoter-derived Nfatc1β expression, preTCR-positive thymocytes express both Nfatc1β and P1 promoter-derived Nfatc1α transcripts. Inducing NFATc1α activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1β from P2 promoter impairs thymocyte development resulting in severe T-cell lymphopenia. In addition, we show that NFATc1 activity suppresses the B-lineage potential of immature thymocytes, and consolidates their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity is vital in facilitating T-cell differentiation and to prevent Notch3-induced T-acute lymphoblastic leukaemia. Altogether, our results show NFATc1 activity is crucial in determining the T-cell fate of thymocytes. PMID:27312418

  17. A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development

    PubMed Central

    Klein-Hessling, Stefan; Rudolf, Ronald; Muhammad, Khalid; Knobeloch, Klaus-Peter; Maqbool, Muhammad Ahmad; Cauchy, Pierre; Andrau, Jean-Christophe; Avots, Andris; Talora, Claudio; Ellenrieder, Volker; Screpanti, Isabella; Serfling, Edgar; Patra, Amiya Kumar

    2016-01-01

    NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are incompletely characterized. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibit only P2 promoter-derived Nfatc1β expression, preTCR-positive thymocytes express both Nfatc1β and P1 promoter-derived Nfatc1α transcripts. Inducing NFATc1α activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1β from P2 promoter impairs thymocyte development resulting in severe T-cell lymphopenia. In addition, we show that NFATc1 activity suppresses the B-lineage potential of immature thymocytes, and consolidates their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity is vital in facilitating T-cell differentiation and to prevent Notch3-induced T-acute lymphoblastic leukaemia. Altogether, our results show NFATc1 activity is crucial in determining the T-cell fate of thymocytes. PMID:27312418

  18. False Position, Double False Position and Cramer's Rule

    ERIC Educational Resources Information Center

    Boman, Eugene

    2009-01-01

    We state and prove the methods of False Position (Regula Falsa) and Double False Position (Regula Duorum Falsorum). The history of both is traced from ancient Egypt and China through the work of Fibonacci, ending with a connection between Double False Position and Cramer's Rule.

  19. Expression of ets genes in mouse thymocyte subsets and T cells.

    PubMed

    Bhat, N K; Komschlies, K L; Fujiwara, S; Fisher, R J; Mathieson, B J; Gregorio, T A; Young, H A; Kasik, J W; Ozato, K; Papas, T S

    1989-01-15

    The cellular ets genes (ets-1, ets-2, and erg) have been identified by their sequence similarity with the v-ets oncogene of the avian erythroblastosis virus, E26. Products of the ets-2 gene have been detected in a wide range of normal mouse tissues and their expression appears to be associated with cell proliferation in regenerating liver. In contrast, the ets-1 gene was previously shown to be more highly expressed in the mouse thymus than in other tissues. Because the thymic tissue contains various subsets of cells in different stages of proliferation and maturation, we have examined ets gene expression in fetal thymocytes from different stages of development, in isolated subsets of adult thymocytes, and in peripheral T lymphocytes. Expression of the ets-1 gene was first detected at day 18 in fetal thymocytes, corresponding to the first appearance of CD4+ (CD4+, CD8-) thymocytes, and reaches maximal/plateau levels of expression in the thymus at 1 to 2 days after birth. The ets-2 gene expression is detected at least 1 day earlier, coinciding with the presence of both double-positive (CD4+, CD8+) and double-negative (CD4-, CD8-) blast thymocytes and reaches maximal/plateau levels 1 day before birth. In the adult thymus, ets-1 and ets-2 mRNA expression is 10- to 8-fold higher respectively in the CD4+ subset than in the other subsets examined. Higher levels of p55 ets-1 protein were also shown to exist in the CD4+ subset. Because the CD4+ thymic subset is the pool from which the CD4+ peripheral, helper/inducer T cells are derived, the ets gene expression was examined in lymph node T cells. Both the CD4+ and the CD8+ T cells subsets had lower ets RNA levels than the CD4+ thymocytes. These results suggest that ets-2 and more particularly ets-1 gene products play an important role in T cell development and differentiation and are not simply associated with proliferating cells, which are observed at a higher frequency in fetal thymocytes, or dull Ly-1 (low CD5+), and

  20. Ternary complex factors SAP-1 and Elk-1, but not net, are functionally equivalent in thymocyte development.

    PubMed

    Costello, Patrick; Nicolas, Robert; Willoughby, Jane; Wasylyk, Bohdan; Nordheim, Alfred; Treisman, Richard

    2010-07-15

    The ternary complex factors (TCFs; SAP-1, Elk-1, and Net) are serum response factor cofactors that share many functional properties and are coexpressed in many tissues. SAP-1, the predominant thymus TCF, is required for thymocyte positive selection. In this study, we assessed whether the different TCFs are functionally equivalent. Elk-1 deletion, but not the hypomorphic Net(delta) mutation, exacerbated the SAP-1 positive selection phenotype, but triply deficient thymocytes were no more defective than SAP-1(-/-) Elk-1(-/-) cells. Inactivation of the other TCFs did not affect SAP-1-independent processes, including beta-selection, regulatory T cell selection, and negative selection, although reduced marginal zone B cells were observed in SAP-1(-/-) Elk-1(-/-) animals. Ectopic expression of Elk-1, but not Net, rescued positive selection of SAP-1(-/-) thymocytes; thus, SAP-1 and Elk-1 are functionally equivalent in this system, and the SAP-1 null selection phenotype reflects only its high expression in the thymus. Array analysis of TCR-stimulated double-positive cells identified SAP-1-dependent inducible genes whose transcription was further impaired in SAP-1(-/-) Elk-1(-/-) cells; thus, these genes, which include Egr-1 and Egr-2, represent candidate mediators of positive selection. Chromatin immunoprecipitation revealed subtly different promoter targeting between the different TCFs. Ectopic expression of Egr-1 restored positive selection in SAP-1 null thymocytes, establishing it (and possibly other Egr family members) as the major effector for ERK-SAP-1 signaling in thymocyte positive selection. PMID:20554967

  1. Hyperresponse to T-cell receptor signaling and apoptosis of Id1 transgenic thymocytes.

    PubMed

    Qi, Zengbiao; Sun, Xiao-Hong

    2004-09-01

    The basic helix-loop-helix transcription factors, E2A and HEB, play important roles in T-cell development at multiple checkpoints. Expression of their inhibitor, Id1, abolishes the function of both transcription factors in a dose-dependent manner. The Id1 transgenic thymus is characterized by an accumulation of CD4- CD8- CD44+ CD25- thymocytes, a dramatic reduction of CD4+ CD8+ thymocytes, and an abundance of apoptotic cells. Here we show that these apoptotic cells carry functional T-cell receptors (TCRs), suggesting that apoptosis occurs during T-cell maturation. In contrast, viable Id1 transgenic CD4 single positive T cells exhibit costimulation-independent proliferation upon treatment with anti-CD3 antibody, probably due to a hyperresponse to TCR signaling. Furthermore, Id1 expression causes apoptosis of CD4 and CD8 double- or single-positive thymocytes in HY- or AND-TCR transgenic mice under conditions that normally support positive selection. Collectively, these results suggest that E2A and HEB proteins are crucial for controlling the threshold for TCR signaling, and Id1 expression lowers the threshold, resulting in apoptosis of developing thymocytes. PMID:15314144

  2. A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

    PubMed

    Stevens, R B; Wrenshall, L E; Miles, C D; Farney, A C; Jie, T; Sandoz, J P; Rigley, T H; Osama Gaber, A

    2016-06-01

    A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.). PMID:26696251

  3. CD6 modulates thymocyte selection and peripheral T cell homeostasis.

    PubMed

    Orta-Mascaró, Marc; Consuegra-Fernández, Marta; Carreras, Esther; Roncagalli, Romain; Carreras-Sureda, Amado; Alvarez, Pilar; Girard, Laura; Simões, Inês; Martínez-Florensa, Mario; Aranda, Fernando; Merino, Ramón; Martínez, Vanesa-Gabriela; Vicente, Rubén; Merino, Jesús; Sarukhan, Adelaida; Malissen, Marie; Malissen, Bernard; Lozano, Francisco

    2016-07-25

    The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency. CD6(-/-) thymi showed a reduction in both CD4(+) and CD8(+) single-positive subsets, and double-positive thymocytes exhibited increased Ca(2+) mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell-autonomous selective disadvantage of CD6(-/-) T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T cell selection events occur in the absence of CD6. CD6(-/-) mice displayed increased frequencies of antigen-experienced peripheral T cells generated under certain levels of TCR signal strength or co-stimulation, such as effector/memory (CD4(+)TEM and CD8(+)TCM) and regulatory (T reg) T cells. The suppressive activity of CD6(-/-) T reg cells was diminished, and CD6(-/-) mice presented an exacerbated autoimmune response to collagen. Collectively, these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T cell subpopulations, including T reg cells. PMID:27377588

  4. Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter.

    PubMed

    Jang, J; Choi, Y I; Choi, J; Lee, K Y; Chung, H; Jeon, S H; Seong, R H

    2006-09-01

    One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation. PMID:16341126

  5. Process for immune defect and chromosomal translocation during early thymocyte development lacking ATM.

    PubMed

    Isoda, Takeshi; Takagi, Masatoshi; Piao, Jinhua; Nakagama, Shun; Sato, Masaki; Masuda, Kyoko; Ikawa, Tomokatsu; Azuma, Miyuki; Morio, Tomohiro; Kawamoto, Hiroshi; Mizutani, Shuki

    2012-07-26

    Immune defect in ataxia telangiectasia patients has been attributed to either the failure of V(D)J recombination or class-switch recombination, and the chromosomal translocation in their lymphoma often involves the TCR gene. The ATM-deficient mouse exhibits fewer CD4 and CD8 single-positive T cells because of a failure to develop from the CD4(+)CD8(+) double-positive phase to the single-positive phase. Although the occurrence of chromosome 14 translocations involving TCR-δ gene in ATM-deficient lymphomas suggests that these are early events in T-cell development, a thorough analysis focusing on early T-cell development has never been performed. Here we demonstrate that ATM-deficient mouse thymocytes are perturbed in passing through the β- or γδ-selection checkpoint, leading in part to the developmental failure of T cells. Detailed karyotype analysis using the in vitro thymocyte development system revealed that RAG-mediated TCR-α/δ locus breaks occur and are left unrepaired during the troublesome β- or γδ-selection checkpoints. By getting through these selection checkpoints, some of the clones with random or nonrandom chromosomal translocations involving TCR-α/δ locus are selected and accumulate. Thus, our study visualized the first step of multistep evolutions toward lymphomagenesis in ATM-deficient thymocytes associated with T-lymphopenia and immunodeficiency. PMID:22709691

  6. Preselection Thymocytes Are More Sensitive to T Cell Receptor Stimulation Than Mature T Cells

    PubMed Central

    Davey, Gayle M.; Schober, Sonya L.; Endrizzi, Bart T.; Dutcher, Angela K.; Jameson, Stephen C.; Hogquist, Kristin A.

    1998-01-01

    During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide–major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self-peptide–MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide–MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide–MHC complexes. PMID:9815264

  7. Regulation of RAG-2 protein expression in avian thymocytes.

    PubMed Central

    Ferguson, S E; Accavitti, M A; Wang, D D; Chen, C L; Thompson, C B

    1994-01-01

    The recombinase-activating genes, RAG-1 and RAG-2, have been shown to be necessary to initiate the process of V(D)J recombination during the ontogeny of lymphocytes. While much is known about the end products of this rearrangement process, little is known about the function or regulation of the components of the recombinase system. To this end, we have generated a monoclonal antibody to the chicken RAG-2 protein. Chicken thymocytes were found to express high levels of RAG-2, part of which is phosphorylated. Within thymocytes, RAG-2 is expressed primarily within the nucleus. RAG-2 protein levels are high in the CD4- CD8- and CD4+ CD8+ immature thymocytes but absent at the single-positive CD4+ CD8- or CD4- CD8+ stage of thymocyte development. Mitogenic stimulation of thymocytes with phorbol myristate acetate and ionomycin results in down-regulation of RAG-2 expression. Consistent with these data, in vivo levels of RAG-2 are markedly lower in proliferating thymocytes than in smaller, G0/G1 cells. Down-regulation of RAG-2 expression appears to occur before cells enter S phase, suggesting that RAG-2 function may be limited to noncycling cells. Images PMID:7935443

  8. Adenosine stimulates DNA fragmentation in human thymocytes by Ca(2+)-mediated mechanisms.

    PubMed

    Szondy, Z

    1994-12-15

    Incubation of human thymocytes with an optimum concentration of adenosine and its receptor site agonist, 2-chloroadenosine, induced increases in intracellular cyclic AMP (cAMP) (from a resting 0.6 +/- 0.1 to 4.1 +/- 0.2 pmol/10(7) cells within 5 min) and Ca2+ (from the resting 85 +/- 7 nM to a peak of 210 +/- 25 nM) levels and resulted in internucleosomal DNA fragmentation and cell death (apoptosis). Other adenosine analogues were also effective at inducing DNA fragmentation, the order of potency being 2-p-(carboxyethylphenylethylamino)-5'-carboxyamidoadenosine < 5'-(N-ethylcarboxamide)adenosine < or = cyclopentyladenosine < 2-chloroadenosine (2-CA). 2-CA treatment (with an optimum concentration of 40 microM) selectively depleted a thymocyte subpopulation (15-20% of the total cells) which expressed higher levels of the CD3 molecule and which was found mainly in the CD4+CD8+ double positive immature thymocyte population. DNA fragmentation was prevented by the addition of actinomycin D or cycloheximide to the thymocyte suspension, indicating that this process required both mRNA and protein synthesis. Endonuclease activation and cell killing were dependent on an early, sustained increase in cytosolic Ca2+ concentration, most of which was of extracellular origin and was a result of an adenosine-induced inositol trisphosphate release. Other agents known to elevate intracellular cAMP levels by different mechanisms failed to induce similar DNA fragmentation, but enhanced the effect of adenosine. This suggested a supporting role for cAMP in adenosine-induced DNA fragmentation. Phorbol dibutyrate, a protein kinase. C activator, previously shown to inhibit Ca(2+)-dependent DNA fragmentation and cell killing in human thymocytes [McConkey, Hartzell, Jondal and Orrenius (1989) J. Biol. Chem. 264, 13399-13402], at 60 ng/ml concentration also prevented adenosine-induced DNA fragmentation when added prior to adenosine. This suggested a complex cross-talk between the adenosine

  9. A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation.

    PubMed

    Sahni, Hemant; Ross, Susan; Barbarulo, Alessandro; Solanki, Anisha; Lau, Ching-In; Furmanski, Anna; Saldaña, José Ignacio; Ono, Masahiro; Hubank, Mike; Barenco, Martino; Crompton, Tessa

    2015-10-01

    Developing thymocytes require pre-TCR signalling to differentiate from CD4-CD8- double negative to CD4+CD8+ double positive cell. Here we followed the transcriptional response to pre-TCR signalling in a synchronised population of differentiating double negative thymocytes. This time series analysis revealed a complex transcriptional response, in which thousands of genes were up and down-regulated before changes in cell surface phenotype were detected. Genome-wide measurement of RNA degradation of individual genes showed great heterogeneity in the rate of degradation between different genes. We therefore used time course expression and degradation data and a genome wide transcriptional modelling (GWTM) strategy to model the transcriptional response of genes up-regulated on pre-TCR signal transduction. This analysis revealed five major temporally distinct transcriptional activities that up regulate transcription through time, whereas down-regulation of expression occurred in three waves. Our model thus placed known regulators in a temporal perspective, and in addition identified novel candidate regulators of thymocyte differentiation. PMID:26415229

  10. From pre-DP, post-DP, SP4, and SP8 Thymocyte Cell Counts to a Dynamical Model of Cortical and Medullary Selection

    PubMed Central

    Sawicka, Maria; Stritesky, Gretta L.; Reynolds, Joseph; Abourashchi, Niloufar; Lythe, Grant; Molina-París, Carmen; Hogquist, Kristin A.

    2014-01-01

    Cells of the mature αβ T cell repertoire arise from the development in the thymus of bone marrow precursors (thymocytes). αβ T cell maturation is characterized by the expression of thousands of copies of identical αβ T cell receptors and the CD4 and/or CD8 co-receptors on the surface of thymocytes. The maturation stages of a thymocyte are: (1) double negative (DN) (TCR−, CD4− and CD8−), (2) double positive (DP) (TCR+, CD4+ and CD8+), and (3) single positive (SP) (TCR+, CD4+ or CD8+). Thymic antigen presenting cells provide the appropriate micro-architecture for the maturation of thymocytes, which “sense” the signaling environment via their randomly generated TCRs. Thymic development is characterized by (i) an extremely low success rate, and (ii) the selection of a functional and self-tolerant T cell repertoire. In this paper, we combine recent experimental data and mathematical modeling to study the selection events that take place in the thymus after the DN stage. The stable steady state of the model for the pre-DP, post-DP, and SP populations is identified with the experimentally measured cell counts from 5.5- to 17-week-old mice. We make use of residence times in the cortex and the medulla for the different populations, as well as recently reported asymmetric death rates for CD4 and CD8 SP thymocytes. We estimate that 65.8% of pre-DP thymocytes undergo death by neglect. In the post-DP compartment, 91.7% undergo death by negative selection, 4.7% become CD4 SP, and 3.6% become CD8 SP. Death by negative selection in the medulla removes 8.6% of CD4 SP and 32.1% of CD8 SP thymocytes. Approximately 46.3% of CD4 SP and 27% of CD8 SP thymocytes divide before dying or exiting the thymus. PMID:24592261

  11. Investigation of the effect of mistletoe (Viscum album L.) extract Iscador on the proliferation and apoptosis of murine thymocytes.

    PubMed

    Hajtò, Tibor; Berki, Timea; Pàlinkàs, Làszlò; Boldizsàr, Ferenc; Németh, Péter

    2006-06-01

    Mistletoe (Viscum album L.) extracts (ME) have been shown to exhibit a bell-shaped curve of immunological efficacy and mistletoe lectins (MLs) were found to play an important role in this phenomenon. The aim of present in vivo study was to investigate the acute- and long-term effect of a standardized ME (Iscador M special) on thymocyte subpopulations and peripheral T cells using a murine (Balb/c) model. In thymus CD4-CD8- double negative (DN), CD4+CD8+ double positive (DP), CD4+ or CD8+ single positive T cells were determined 24 h after a single injection or following a long-term treatment (twice a week for 4 weeks) with three different dilutions of ME which are corresponding to 4.5 ng/ kg, 22.5 ng/kg and 112.5 ng/kg doses of MLs. The apoptosis of the thymocytes was also tested by flow cytometry using Annexin V and propidium iodide. 24 h after a single injection of ME only the lowest dose caused in the blood samples an elevated CD4+/CD8+ ratio and in thymus an enhanced proliferation of DN thymocytes indicating a similar bell-shaped curve of immunological efficacy. After a treatment for four weeks these responses were less intensive indicating that none of the three doses are immunologically optimal. Surprisingly, both in the acute and in the long-term trial only the lower doses induced significant enhancements in the ratio of apoptotic thymocytes. In addition, ME inhibited the dexamethasone (DX)-induced reduction of DN cell count in thymus, as well as the DX-induced decrease of CD4+/CD8+ ratio and CD4+ cell level in peripheral blood. These in vivo results suggest that investigation of thymocytes in vivo can be helpful in the immunological dose-finding since standardized ME is able to modulate the proliferation and apoptosis of thymocytes with a bell-shaped curve of efficacy. In addition, ME may act lymphoprotectively during DX treatment. PMID:16927524

  12. Choke position effects in double-choked circular waveguide antennas

    NASA Astrophysics Data System (ADS)

    Miyata, K.; Suzuki, M.

    1984-06-01

    A number of studies have been conducted regarding choke-loaded circular waveguide antennas. Aoki et al. (1970) have obtained improved results with respect to the beam circularity and the wide-angle radiation properties. Cowan (1973) suggested the employment of suitable compact, double choked feeds for frequency-reuse application. Further improvements can apparently be obtained by loading double chokes on a circular waveguide. The present investigation is concerned with the variation of the radiated fields for various choke positions in double-choked circular waveguide antennas. In the case of double-choked small circular waveguide antennas, it is found that the choke position has a pronounced effect on the radiation properties. Particularly sensitive to the choke position is the cross-polar level.

  13. An anti-silencer– and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development

    PubMed Central

    Hao, Bingtao; Naik, Abani Kanta; Watanabe, Akiko; Tanaka, Hirokazu; Chen, Liang; Richards, Hunter W.; Kondo, Motonari; Taniuchi, Ichiro; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

    2015-01-01

    Rag1 and Rag2 gene expression in CD4+CD8+ double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here, we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes. PMID:25847946

  14. Infection of human thymocytes by Epstein-Barr virus.

    PubMed

    Watry, D; Hedrick, J A; Siervo, S; Rhodes, G; Lamberti, J J; Lambris, J D; Tsoukas, C D

    1991-04-01

    The Epstein-Barr Virus (EBV) causes infectious mononucleosis, and has been strongly associated with certain human cancers. The virus is thought to exclusively bind to B lymphocytes and epithelial cells via receptors (CR2/CD21) that also interact with fragments of the third component of complement (C3). Recent evidence, however, has challenged this belief. We have used two-color immunofluorescence analysis using biotin-conjugated EBV and streptavidin-phycoerythrin along with fluorescein-conjugated anti-T cell antibodies and demonstrated that CD1-positive, CD3-dull (immature) human thymocytes express functional EBV receptors. In four replicate experiments, the binding of EBV to thymocytes ranged between 8 and 18%. This interaction is specific as evidenced by inhibition with nonconjugated virus, anti-CR2 antibodies, aggregated C3, and an antibody to the gp350 viral glycoprotein that the virus uses to bind to CR2. EBV can infect the thymocytes as evaluated by the presence of episomal EBV-DNA in thymocytes that had been incubated with the virus as short as 12 days or as long as 6 weeks. Episomal DNA analysis was performed by Southern blotting with a EBV-DNA probe that hybridizes to the first internal reiteration of the viral DNA. The presence of the EBV genome is also supported by the detection of EBV nuclear antigen 1 in infected thymocytes, assessed by Western blotting with EBV-immune sera. The EBV infection is specific as determined by blocking experiments using anti-CR2 and anti-gp350 antibodies. Finally, virus infection of thymocytes can act synergistically along with interleukin 2 and induce a lymphokine-dependent cellular proliferation. In view of previously reported cases of EBV-positive human T cell lymphomas, the possibility is raised that EBV may be involved in cancers of T lymphocytes that have not been previously appreciated. PMID:1706754

  15. Spontaneous apoptosis in human thymocytes.

    PubMed Central

    Tiso, M.; Gangemi, R.; Bargellesi Severi, A.; Pizzolitto, S.; Fabbi, M.; Risso, A.

    1995-01-01

    Apoptosis seems to be involved in different stages of immune cell development. In particular, experimental evidence suggests that it is a major form of cell death in the thymus. The present analysis of human thymocytes reveals that a fraction of these cells, cultured in vitro, undergoes spontaneous apoptosis. This observation is based both on molecular (DNA fragmentation) and morphological (electron microscopic) investigations of the cells. The apoptotic thymocytes are CD3- or CD3lo, CD4lo, and CD8lo and do not express Bcl-2 protein. Furthermore, thymocytes die by apoptosis when exposed to pharmacological stimuli, such as tumor necrosis factor-alpha, dexamethasone, ATP, or Ca++ ionophore. Thus the apoptotic machinery in thymocytes can be triggered by an imbalance in growth factors in the in vitro culture media and can be modulated by various biochemical signals. The process of spontaneous apoptosis is independent of mRNA or protein synthesis, as actinomycin D and cycloheximide fail to inhibit this phenomenon. Furthermore, apoptosis seems to require active oxidative phosphorylation, as it is prevented by incubation of the cells with inhibitors of the respiratory chain. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8 PMID:7639336

  16. Mushroom acidic glycosphingolipid induction of cytokine secretion from murine T cells and proliferation of NK1.1 {alpha}/{beta} TCR-double positive cells in vitro

    SciTech Connect

    Nozaki, Hirofumi; Itonori, Saki; Sugita, Mutsumi; Nakamura, Kimihide; Ohba, Kiyoshi; Suzuki, Akemi; Kushi, Yasunori

    2008-08-29

    Interferon (IFN)-{gamma} and interleukin (IL)-4 regulate many types of immune responses. Here we report that acidic glycosphingolipids (AGLs) of Hypsizigus marmoreus and Pleurotus eryngii induced secretion of IFN- {gamma} and IL-4 from T cells in a CD11c-positive cell-dependent manner similar to that of {alpha}-galactosylceramide ({alpha}-GalCer) and isoglobotriaosylceramide (iGb3), although activated T cells by AGLs showed less secretion of cytokine than those activated by {alpha}-GalCer. In addition, stimulation of these mushroom AGLs induced proliferation of NK1.1 {alpha}/{beta} TCR-double positive cells in splenocytes. Administration of a mixture of {alpha}-GalCer and AGLs affected the stimulation of {alpha}-GalCer and generally induced a subtle Th1 bias for splenocytes but induced an extreme Th2 bias for thymocytes. These results suggested that edible mushroom AGLs contribute to immunomodulation.

  17. 100 positive double-blind studies: enough or too little?

    NASA Astrophysics Data System (ADS)

    Tuner, Jan; Hode, Lars

    2000-06-01

    A major argument among the opponents of laser therapy has been the absence of scientific documentation. This was a valid position in the 80s and partly in the 90s. But today, is this still a sound argument. There are more than 2,000 published studies in the field, including meeting abstracts and anecdotal reports. The vast majority of these papers reports positive effects of LLLT in vitro and in vivo. It is fair to argue that negative results are less prone to be published, but certainly more than 80 percent of the published studies are positive. In the field of dentistry, for instance, the positive percentage is well above 90 percent. The present literature study will look at the heart of the positive documentation: the positive double blind studies. It may come as a surprise to many critics that there are more than 100 positive double blind studies in the field laser therapy. This is a god base for a further understanding of the effects of low level laser in the clinical setting. We must, however, be as critical as the sceptics themselves in order to obtain a constructive dialogue between 'attorneys' and sceptics. In this paper, a critical review of 100 positive double blind studies will be presented.

  18. Washington Double Star Catalog Cross Index (1950 position sort)

    NASA Technical Reports Server (NTRS)

    1993-01-01

    A machine-readable version of the Washington Catalog of Visual Double Stars (WDS) was prepared in 1984 on the basis of a data file that was collected and maintained for more than a century by a succession of double-star observers. Although this catalog is being continually updated, a new copy for distribution is not expected to be available for a few years. The WDS contains DM numbers, but many of these are listed only in the notes, which makes it difficult to search for double-star information, except by position. Hence, a cross index that provides complete DM identifications is desirable, and it appears useful to add HD numbers for systems in that catalog. Aitken Double Star (ADS) numbers were retained from the WDS, but no attempt was made to correct these except for obvious errors.

  19. Without peripheral interference, thymic deletion is mediated in a cohort of double-positive cells without classical activation

    PubMed Central

    Zhan, Yifan; Purton, Jared F.; Godfrey, Dale I.; Cole, Timothy J.; Heath, William R.; Lew, Andrew M.

    2003-01-01

    Peripheral activation can cause bystander thymocyte death by eliciting a “cytokine storm.” This event complicates in vivo studies using exogenous ligand-induced models of negative selection. A stable transgenic model that selectively eliminates peripheral CD4 cells has allowed us to analyze negative selection as direct cognate events in two T cell receptor transgenic mice, OT-II and DO11. Whereas cognate peptide induced a massive deletion in double-positive (DP) cells in mice with peripheral CD4 cells, this DP deletion was modest in mice lacking peripheral CD4 cells. Using BrdUrd and annexin V staining, we found that negative selection primarily occurs in a cohort of DP cells and the absence of single-positive (SP) cells is largely caused by reduction in the cohort of DP precursors. Moreover, the fates of DP cells and SP cells after antigen exposure were vastly different. Whereas SP cells up-regulated uniformly their CD69 and CD44 levels, increased their cell size, and survived after antigen exposure, DP cells had less CD69 and CD44 up-regulation, no size change, and promptly died. Thus, negative selection represents an “abortive” activation different from activation-induced cell death of mature T cells. PMID:12538873

  20. Clonally Expanding Thymocytes Having Lineage Capability in Gamma-Ray-Induced Mouse Atrophic Thymus

    SciTech Connect

    Yamamoto, Takashi; Morita, Shin-ichi; Go, Rieka; Obata, Miki; Katsuragi, Yoshinori; Fujita, Yukari; Maeda, Yoshitaka; Yokoyama, Minesuke; Aoyagi, Yutaka; Ichikawa, Hitoshi; Mishima, Yukio; Kominami, Ryo

    2010-05-01

    Purpose: To characterize, in the setting of gamma-ray-induced atrophic thymus, probable prelymphoma cells showing clonal growth and changes in signaling, including DNA damage checkpoint. Methods and Materials: A total of 111 and 45 mouse atrophic thymuses at 40 and 80 days, respectively, after gamma-irradiation were analyzed with polymerase chain reaction for D-J rearrangements at the TCRbeta locus, flow cytometry for cell cycle, and Western blotting for the activation of DNA damage checkpoints. Results: Limited D-J rearrangement patterns distinct from normal thymus were detected at high frequencies (43 of 111 for 40-day thymus and 21 of 45 for 80-day thymus). Those clonally expanded thymocytes mostly consisted of CD4{sup +}CD8{sup +} double-positive cells, indicating the retention of lineage capability. They exhibited pausing at a late G1 phase of cell cycle progression but did not show the activation of DNA damage checkpoints such as gammaH2AX, Chk1/2, or p53. Of interest is that 17 of the 52 thymuses showing normal D-J rearrangement patterns at 40 days after irradiation showed allelic loss at the Bcl11b tumor suppressor locus, also indicating clonal expansion. Conclusion: The thymocytes of clonal growth detected resemble human chronic myeloid leukemia in possessing self-renewal and lineage capability, and therefore they can be a candidate of the lymphoma-initiating cells.

  1. CCR4 promotes medullary entry and thymocyte-dendritic cell interactions required for central tolerance.

    PubMed

    Hu, Zicheng; Lancaster, Jessica N; Sasiponganan, Chayanit; Ehrlich, Lauren I R

    2015-10-19

    Autoimmunity results from a breakdown in central or peripheral tolerance. To establish central tolerance, developing T cells must enter the thymic medulla, where they scan antigen-presenting cells (APCs) displaying a diverse array of autoantigens. If a thymocyte is activated by a self-antigen, the cell undergoes either deletion or diversion into the regulatory T cell (T reg) lineage, thus maintaining self-tolerance. Mechanisms promoting thymocyte medullary entry and interactions with APCs are incompletely understood. CCR4 is poised to contribute to central tolerance due to its expression by post-positive selection thymocytes, and expression of its ligands by medullary thymic dendritic cells (DCs). Here, we use two-photon time-lapse microscopy to demonstrate that CCR4 promotes medullary entry of the earliest post-positive selection thymocytes, as well as efficient interactions between medullary thymocytes and DCs. In keeping with the contribution of thymic DCs to central tolerance, CCR4 is involved in regulating negative selection of polyclonal and T cell receptor (TCR) transgenic thymocytes. In the absence of CCR4, autoreactive T cells accumulate in secondary lymphoid organs and autoimmunity ensues. These studies reveal a previously unappreciated role for CCR4 in the establishment of central tolerance. PMID:26417005

  2. Krüppel-like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL-17 expression during Th17 differentiation

    PubMed Central

    An, Jie; Golech, Susanne; Klaewsongkram, Jettanong; Zhang, Yongqing; Subedi, Kalpana; Huston, Gail E.; Wood, William H.; Wersto, Robert P.; Becker, Kevin G.; Swain, Susan L.; Weng, Nanping

    2011-01-01

    Krüppel-like factor 4 (KLF4), a transcription factor, plays a key role in the pluripotency of stem cells. We sought to determine the function of KLF4 in T-cell development and differentiation by using T-cell-specific Klf4-knockout (KO) mice. We found that KLF4 was highly expressed in thymocytes and mature T cells and was rapidly down-regulated in mature T cells after activation. In Klf4-KO mice, we observed a modest reduction of thymocytes (27%) due to the reduced proliferation of double-negative (DN) thymocytes. We demonstrated that a direct repression of Cdkn1b by KLF4 was a cause of decreased DN proliferation. During in vitro T-cell differentiation, we observed significant reduction of IL-17-expressing CD4+ T cells (Th17; 24%) but not in other types of Th differentiation. The reduction of Th17 cells resulted in a significant attenuation of the severity (35%) of experimental autoimmune encephalomyelitis in vivo in Klf4-KO mice as compared with the Klf4 wild-type littermates. Finally, we demonstrated that KLF4 directly binds to the promoter of Il17a and positively regulates its expression. In summary, these findings identify KLF4 as a critical regulator in T-cell development and Th17 differentiation.—An, J., Golech, S., Klaewsongkram, J., Zhang, Y., Subedi, K., Huston, G. E., Wood, W. H., III, Wersto, R. P., Becker, K. G., Swain, S. L., Weng, N. Krüppel-like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL-17 expression during Th17 differentiation. PMID:21685331

  3. CD28 in thymocyte development and peripheral T cell activation in mice exposed to suspended particulate matter

    SciTech Connect

    Drela, Nadzieja . E-mail: ndrela@biol.uw.edu.pl; Zesko, Izabela; Jakubowska, Martyna; Biernacka, Marzena

    2006-09-01

    The CD28:B7 signaling pathway is very important for the activity of mature peripheral T lymphocytes and thymocyte development. The proper development of thymocytes into mature single positive CD4{sup +}and CD8{sup +} T cells is crucial for almost all immune functions. In naturally occurring conditions, T cells maturation in the thymus is influenced by environmental agents. The expression of CD28 and the distribution of CD28{sup low/high} thymocytes have been examined at various stages of thymocyte development in BALB/c mice exposed to air-suspended particulate matter (ASM). Acute exposure to ASM resulted in the decrease of CD28 expression in the total thymocyte population. The increase of the percentage of CD28{sup low} and the decrease of CD28{sup high} thymocytes were observed, which may account for the acceleration of thymocyte development under the conditions of elevated risk resulting from the exposure of animals to environmental xenobiotics. ASM exposure resulted in the increase of the level of proliferation of lymph node T cells induced by anti-CD3 and anti-CD28 monoclonal antibodies activation despite normal expression of CD28 molecule. In contrast, the level of proliferation of spleen T cells was lowered or normal dependently of the concentration of stimuli used for activation. Results of these studies demonstrate that acute exposure of mice to ASM can result in the progression of two contrasting processes in the immune system: upregulation of thymocyte development, which contributes to the maintenance of peripheral T cell pool, and over-activation of lymph node lymphocytes, which may lead to uncontrolled immunostimulation.

  4. RCAN 1 and 3 proteins regulate thymic positive selection.

    PubMed

    Serrano-Candelas, Eva; Alemán-Muench, Germán; Solé-Sánchez, Sònia; Aubareda, Anna; Martínez-Høyer, Sergio; Adán, Jaume; Aranguren-Ibáñez, Álvaro; Pritchard, Melanie A; Soldevila, Gloria; Pérez-Riba, Mercè

    2015-05-01

    Cooperation between calcineurin (CN)-NFATc and RAF-MEK-ERK signaling pathways is essential in thymocyte positive selection. It is known that the Regulators of Calcineurin (RCAN) proteins can act either facilitating or suppressing CN-dependent signaling events. Here, we show that RCAN genes are expressed in lymphoid tissues, and address the role of RCAN proteins in T cell development. Overexpression of human RCAN3 and RCAN1 can modulate T cell development by increasing positive selection-related surface markers, as well as the "Erk(hi) competence state" in double positive thymocytes, a characteristic molecular signature of positive selection, without affecting CN activity. We also found that RCAN1/3 interact with RAF kinases and CN in a non-exclusive manner. Our data suggests that the balance of RCAN interactions with CN and/or RAF kinases may influence T cell positive selection. PMID:25783055

  5. Differential role of NF-κB in selection and survival of CD4 and CD8 thymocytes

    PubMed Central

    Jimi, Eijiro; Voll, Reinhard E.; Strickland, Ian; Long, Meixiao; Ghosh, Sankar

    2008-01-01

    Summary Inhibition of NF-κB activity leads to a reduction in numbers of CD8+ single positive (SP) thymocytes suggesting a selective role for NF-κB in these cells. To further explore the role of NF-κB in SP thymocytes we utilized transgenic models that allow either inhibition or activation of NF-κB. We now show that activation of NF-κB plays an important role in the selection of MHC class I restricted, CD8 T-cells. Surprisingly NF-κB is not activated in positively selected CD4 thymocytes, and inhibition of NF-κB does not perturb positive or negative selection of CD4 cells. However, enforced activation of NF-κB using a constitutively active IκB kinase transgene leads to nearly complete deletion of CD4 cells by pushing positively selecting CD4 cells into negative selection. These studies therefore reveal a surprising difference of NF-κB activation in CD4 and CD8 thymocytes and suggest that NF-κB contributes to the establishment of thresholds of signaling that determine positive-negative selection of thymocytes. PMID:18957265

  6. An essential role for the transcription factor HEB in thymocyte survival, Tcra rearrangement and the development of natural killer T cells.

    PubMed

    D'Cruz, Louise M; Knell, Jamie; Fujimoto, Jessica K; Goldrath, Ananda W

    2010-03-01

    E proteins are basic helix-loop-helix transcription factors that regulate many key aspects of lymphocyte development. Thymocytes express multiple E proteins that are thought to provide cooperative and compensatory functions crucial for T cell differentiation. Contrary to that, we report here that the E protein HEB was uniquely required at the CD4(+)CD8(+) double-positive (DP) stage of T cell development. Thymocytes lacking HEB showed impaired survival, failed to make rearrangements of variable-alpha (V(alpha)) segments to distal joining-alpha (J(alpha)) segments in the gene encoding the T cell antigen receptor alpha-chain (Tcra) and had a profound, intrinsic block in the development of invariant natural killer T cells (iNKT cells) at their earliest progenitor stage. Thus, our results show that HEB is a specific and essential factor in T cell development and in the generation of the iNKT cell lineage, defining a unique role for HEB in the regulation of lymphocyte maturation. PMID:20154672

  7. Alterations during positive selection in the thymus of nackt CD4-deficient mice.

    PubMed

    Nepomnaschy, I; Lombardi, G; Bekinschtein, P; Berguer, P; Francisco, V; de Almeida, J; Buggiano, V; Pasqualini, C D; Piazzon, I

    2000-12-01

    The T-cell repertoire is shaped by the positive and negative selection of immature CD4(+) CD8(+) double positive (DP) thymocytes. Positive selection of DP T cells to the CD4(+) CD8(-) and CD4(-) CD8(+) simple positive (SP) lineages is a multistep process which involves cellular interactions between thymocytes and stromal cells. Mutant nackt (nkt/nkt) mice have been shown to have a deficiency in the CD4(+) CD8(-) T-cell subset both in the thymus and in the periphery. The present report suggests that nkt/nkt mice present alterations in early steps of positive selection because they show decreases in the percentages of CD69(+) and CD5(+) cells within the DP subset. Experiments involving bone marrow transfer and thymic chimeras demonstrate that the thymic epithelium of nkt/nkt mice is involved in the alterations registered during positive selection and dictates the ultimate fate of CD4(+) SP cells. PMID:11119260

  8. Effects of choke-load position on radiation properties in double-choked small horn antennas

    NASA Astrophysics Data System (ADS)

    Miyata, K.; Suzuki, M.

    1983-04-01

    Results of experiments conducted for the purpose of investigating the effects of the choke position on the beam circularity and the crosspolarisation properties in double-choked small horn antennas are presented. It is shown that the value of the maximum crosspolarisation can be suppressed below -37 dB by properly displacing the choke position from the circular waveguide aperture.

  9. The double universal joint wrist on a manipulator: Solution of inverse position kinematics and singularity analysis

    NASA Technical Reports Server (NTRS)

    Williams, Robert L., III

    1992-01-01

    This paper presents three methods to solve the inverse position kinematics position problem of the double universal joint attached to a manipulator: (1) an analytical solution for two specific cases; (2) an approximate closed form solution based on ignoring the wrist offset; and (3) an iterative method which repeats closed form position and orientation calculations until the solution is achieved. Several manipulators are used to demonstrate the solution methods: cartesian, cylindrical, spherical, and an anthropomorphic articulated arm, based on the Flight Telerobotic Servicer (FTS) arm. A singularity analysis is presented for the double universal joint wrist attached to the above manipulator arms. While the double universal joint wrist standing alone is singularity-free in orientation, the singularity analysis indicates the presence of coupled position/orientation singularities of the spherical and articulated manipulators with the wrist. The cartesian and cylindrical manipulators with the double universal joint wrist were found to be singularity-free. The methods of this paper can be implemented in a real-time controller for manipulators with the double universal joint wrist. Such mechanically dextrous systems could be used in telerobotic and industrial applications, but further work is required to avoid the singularities.

  10. Differential O-glycosylation in cortical and medullary thymocytes.

    PubMed

    Alvarez, Georgina; Lascurain, Ricardo; Hernández-Cruz, Pedro; Tetaert, Daniel; Degand, Pierre; Gorocica, Patricia; Espinosa, Blanca; Zenteno, Edgar; Chávez, Raúl

    2006-08-01

    Differentiation of T lymphocytes is characterized by variable expression of CD8/CD4 co-receptor molecules and changes in the glycosylation pattern. In this work, O-glycosylation was analyzed in microsomes from murine thymocytes purified with the PNA and Amaranthus leucocarpus (ALL) lectins, specific for the T antigen (Gal beta1,3GalNAc1,0 Ser/Thr) in cortical and medullary thymocytes, respectively. Three peptides were used as acceptors for UDP-N-acetylgalactosamine: polypeptide N-acetylgalactosaminyl-transferase (GalNAc transferase); the peptide motif TTSAPTTS was the best glycosylated one. Cortical ALL-PNA+ thymocytes showed two-fold higher GalNAc transferase activity than ALL+PNA- thymocytes; however, capillary electrophoresis showed a higher proportion of di- versus mono-glycosylated peptides for ALL+PNA- than for ALL-PNA+. We compared the GalNAc transferase activity of thymocytes from dexamethasone-treated mice versus control mice. GalNAc transferase activity was six-fold higher in thymocytes from control mice than from dexamethasone-treated mice; the rate of di-glycosylated peptides for dexamethosone-resistant ALL+ was two-fold higher than for ALL- thymocytes. Our results confirm an upregulated biosynthesis of O-glycosidically linked glycans on T cell surface glycoproteins, and suggest that the modification of GalNAc transferase activity plays a relevant role during the maturation process of thymic cells. PMID:16762509

  11. E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression.

    PubMed

    Wojciechowski, Jason; Lai, Anne; Kondo, Motonari; Zhuang, Yuan

    2007-05-01

    Thymocytes undergoing TCRbeta gene rearrangements are maintained in a low or nonproliferating state during early T cell development. This block in cell cycle progression is not released until the expression of a functional pre-TCR, which is composed of a successfully rearranged TCRbeta-chain and the Pre-Talpha-chain. The regulatory molecules responsible for the coordination of these differentiation and proliferation events are currently unknown. E2A and HEB are structurally and functionally related basic helix-loop-helix transcription factors involved in T cell development. To reveal the function of E2A and HEB through the stage of pre-TCR expression and alleviate functional compensation between E2A and HEB, we use a double-conditional knockout model. The simultaneous deletion of E2A and HEB in developing thymocytes leads to a severe developmental block before pre-TCR expression and a dramatic reduction of Pre-Talpha expression. These developmentally arrested thymocytes exhibit increased proliferation in vivo and dramatic expansion ex vivo in response to IL-7 signaling. These results suggest that E2A and HEB are not only critical for T cell differentiation but also necessary to retain developing thymocytes in cell cycle arrest before pre-TCR expression. PMID:17442955

  12. The role of ascorbic acid and monosodium glutamate in thymocyte apoptosis.

    PubMed

    Pavlovic, V; Sarac, M

    2010-01-01

    The studies on experimental animals have confirmed toxic effect of monosodium glutamate in different organs, mainly manifested by increased oxidative stress and cytotoxicity, strongly correlated with numerous diseases. Continuous intake of this flavor enhancer in modern nutrition also resulted with toxic effects on human health, known as Chinese restaurant syndrome. The reference data about influence of monosodium glutamate on the cells of the immune system or primary immune organs and possible protective effects of specific antioxidants are still largely unknown. This review summarizes recently known facts about the role of monosodium glutamate in the cells of the immune system, especially in thymocytes. Also, in this review many new data on positive effects of ascorbic acid on immune system and the mechanisms of its protective influence on thymocytes are discussed (Tab. 1, Ref. 52). PMID:20635684

  13. Inhibition of DNA fragmentation in thymocytes and isolated thymocyte nuclei by agents that stimulate protein kinase C.

    PubMed

    McConkey, D J; Hartzell, P; Jondal, M; Orrenius, S

    1989-08-15

    Glucocorticoid hormones and Ca2+ ionophores stimulate a suicide process in immature thymocytes, known as apoptosis or programmed cell death, that involves extensive DNA fragmentation. We have recently shown that a sustained increase in cytosolic Ca2+ concentration stimulates DNA fragmentation and cell killing in glucocorticoid- or ionophore-treated thymocytes. However, a sustained increase in the cytosolic Ca2+ level also mediates lymphocyte proliferation, suggesting that apoptosis is blocked in proliferating thymocytes. In this study we report that phorbol esters, which selectively stimulate protein kinase C (PKC), blocked DNA fragmentation and cell death in thymocytes exposed to Ca2+ ionophore or glucocorticoid hormone. The T cell mitogen, concanavalin A, which stimulates thymocytes by a mechanism that involves PKC activation, caused concentration-dependent increases in the cytosolic Ca2+ level that did not result in DNA fragmentation, but incubation with concanavalin A and the PKC inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) resulted in both DNA fragmentation and cell death. Phorbol ester directly inhibited Ca2+-dependent DNA fragmentation in isolated thymocyte nuclei. Our results strongly suggest that PKC activation blocks thymocyte apoptosis by preventing Ca2+-stimulated endonuclease activation. PMID:2503500

  14. Large acoustic solitons and double layers in plasmas with two positive ion species

    SciTech Connect

    Verheest, Frank; Hellberg, Manfred A.; Saini, Nareshpal Singh; Kourakis, Ioannis

    2011-04-15

    Large nonlinear acoustic waves are discussed in a plasma made up of cold supersonic and adiabatic subsonic positive ions, in the presence of hot isothermal electrons, with the help of Sagdeev pseudopotential theory. In this model, no solitons are found at the acoustic speed, and no compositional parameter ranges exist where solutions of opposite polarities can coexist. All nonlinear modes are thus super-acoustic, but polarity changes are possible. The upper limits on admissible structure velocities come from different physical arguments, in a strict order when the fractional cool ion density is increased: infinite cold ion compression, warm ion sonic point, positive double layers, negative double layers, and finally, positive double layers again. However, not all ranges exist for all mass and temperature ratios. Whereas the cold and warm ion sonic point limitations are always present over a wide range of mass and temperature ratios, and thus positive polarity solutions can easily be obtained, double layers have a more restricted existence range, specially if polarity changes are sought.

  15. THP-1 macrophage lipid accumulation unaffected by fatty acid double bond geometric or positional configuration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary fatty acid type alters atherosclerotic lesion progression and macrophage lipid accumulation. Incompletely elucidated are the mechanisms by which fatty acids differing in double-bond geometric or positional configuration alter arterial lipid accumulation. The objective of this study was to ev...

  16. Immunohistochemical Evidence of Active Thymocyte Proliferation in Thymoma

    PubMed Central

    Chilosi, Marco; Iannucci, Antonio; Menestrina, Fabio; Lestani, Maurizio; Scarpa, Aldo; Bonetti, Franco; Fiore-Donati, Luciano; Dipasquale, Bruno; Pizzolo, Giovanni; Palestro, Giorgio; Tridente, Giuseppe; Janossy, George

    1987-01-01

    Eight cases of human thymoma have been analyzed on cryostat sections with the monoclonal antibody Ki67, which reacts with cells in the proliferative phases of the cell cycle. The aim was to assess the proportion of proliferating thymocytes among lymphoid cells in the thymoma samples. In all cases a large number of cells (mean, 58.75%; range, 35-80%), recognized as thymocytes by morphology and lack of cytokeratin expression in a combined immunohistochemical assay, exhibited nuclear Ki67 staining. These findings differ from the reactivity pattern observed in age-matched nonneoplastic thymuses where lower growth activity of cortical thymocytes was observed (15-20% Ki67+ cells). Intensive thymocyte proliferation in thymomas may represent one of the factors which lead to autoimmunity in myasthenia gravis and thymomas. ImagesFigure 1Figure 2Figure 3 PMID:2443011

  17. TRIB2 regulates normal and stress-induced thymocyte proliferation

    PubMed Central

    Liang, Kai Ling; O’Connor, Caitriona; Veiga, J Pedro; McCarthy, Tommie V; Keeshan, Karen

    2016-01-01

    TRIB2, a serine/threonine pseudokinase identified as an oncogene, is expressed at high levels in the T-cell compartment of hematopoiesis. The proliferation of developing thymocytes is tightly controlled to prevent leukemic transformation of T cells. Here we examine Trib2 loss in murine hematopoiesis under steady state and proliferative stress conditions, including genotoxic and oncogenic stress. Trib2−/− developing thymocytes show increased proliferation, and Trib2−/− mice have significantly higher thymic cellularity at steady state. During stress hematopoiesis, Trib2−/− developing thymocytes undergo accelerated proliferation and demonstrate hypersensitivity to 5-fluorouracil (5-FU)-induced cell death. Despite the increased cell death post 5-FU-induced proliferative stress, Trib2−/− mice exhibit accelerated thymopoietic recovery post treatment due to increased cell division kinetics of developing thymocytes. The increased proliferation in Trib2−/− thymocytes was exacerbated under oncogenic stress. In an experimental murine T-cell acute lymphoblastic leukemia (T-ALL) model, Trib2−/− mice had reduced latency in vivo, which associated with impaired MAP kinase (MAPK) activation. High and low expression levels of Trib2 correlate with immature and mature subtypes of human T-ALL, respectively, and associate with MAPK. Thus, TRIB2 emerges as a novel regulator of thymocyte cellular proliferation, important for the thymopoietic response to genotoxic and oncogenic stress, and possessing tumor suppressor function. PMID:27462446

  18. Large amplitude double layers in a positively charged dusty plasma with nonthermal electrons

    SciTech Connect

    Djebli, M.; Marif, H.

    2009-06-15

    A pseudopotential approach is used to investigate large amplitude dust-acoustic solitary structures for a plasma composed of positively charged dust, cold electrons, and nonthermal hot electrons. Numerical investigation for an adiabatic situation is conducted to examine the existence region of the wave. The negative potential of the double layers is found to be dependent on nonthermal parameters, Mach number, and electrons temperature. A range of the nonthermal parameters values exists for which two possible double layers for the same plasma mix at different Mach numbers and with significant different amplitudes. The present model is used to investigate localized structures in the lower-altitude Earth's ionosphere.

  19. GRB2-Mediated Recruitment of THEMIS to LAT Is Essential for Thymocyte Development

    PubMed Central

    Paster, Wolfgang; Brockmeyer, Claudia; Fu, Guo; Simister, Philip C.; de Wet, Ben; Martinez-Riaño, Ana; Hoerter, John A. H.; Feller, Stephan M.; Wülfing, Christoph; Gascoigne, Nicholas R. J.

    2013-01-01

    Thymocyte-expressed molecule involved in selection (THEMIS) is a recently identified regulator of thymocyte positive selection. THEMIS’s mechanism of action is unknown, and whether it has a role in TCR-proximal signaling is controversial. In this article, we show that THEMIS and the adapter molecule growth factor receptor–bound protein 2 (GRB2) associate constitutively through binding of a conserved PxRPxK motif within the proline-rich region 1 of THEMIS to the C-terminal SH3-domain of GRB2. This association is indispensable for THEMIS recruitment to the immunological synapse via the transmembrane adapter linker for activation of T cells (LAT) and for THEMIS phosphorylation by Lck and ZAP-70. Two major sites of tyrosine phosphorylation were mapped to a YY-motif close to proline-rich region 1. The YY-motif was crucial for GRB2 binding, suggesting that this region of THEMIS might control local phosphorylation-dependent conformational changes important for THEMIS function. Finally, THEMIS binding to GRB2 was required for thymocyte development. Our data firmly assign THEMIS to the TCR-proximal signaling cascade as a participant in the LAT signalosome and suggest that the THEMIS–GRB2 complex might be involved in shaping the nature of Ras signaling, thereby governing thymic selection. PMID:23460737

  20. Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development

    SciTech Connect

    Hanson, Miranda L.; Brundage, Kathleen M.; Schafer, Rosana; Tou, Janet C.; Barnett, John B.

    2010-01-15

    Cadmium (Cd) is both an environmental pollutant and a component of cigarette smoke. Although evidence demonstrates that adult exposure to Cd causes changes in the immune system, there are limited reports in the literature of immunomodulatory effects of prenatal exposure to Cd. The sonic hedgehog (Shh) and Wnt/beta-catenin pathways are required for thymocyte maturation. Several studies have demonstrated that Cd exposure affects these pathways in different organ systems. This study was designed to investigate the effect of prenatal Cd exposure on thymocyte development, and to determine if these effects were linked to dysregulation of Shh and Wnt/beta-catenin pathways. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose (10 ppm) of Cd throughout pregnancy and effects on the thymus were assessed on the day of birth. Thymocyte phenotype was determined by flow cytometry. A Gli:luciferase reporter cell line was used to measure Shh signaling. Transcription of target genes and translation of key components of both signaling pathways were assessed using real-time RT-PCR and western blot, respectively. Prenatal Cd exposure increased the number of CD4{sup +} cells and a subpopulation of double-negative cells (DN; CD4{sup -}CD8{sup -}), DN4 (CD44{sup -}CD25{sup -}). Shh and Wnt/beta-catenin signaling were both decreased in the thymus. Target genes of Shh (Patched1 and Gli1) and Wnt/beta-catenin (c-fos, and c-myc) were affected differentially among thymocyte subpopulations. These findings suggest that prenatal exposure to Cd dysregulates two signaling pathways in the thymus, resulting in altered thymocyte development.

  1. Examination of Thymic Positive and Negative Selection by Flow Cytometry

    PubMed Central

    Baldwin, Troy A.

    2012-01-01

    A healthy immune system requires that T cells respond to foreign antigens while remaining tolerant to self-antigens. Random rearrangement of the T cell receptor (TCR) α and β loci generates a T cell repertoire with vast diversity in antigen specificity, both to self and foreign. Selection of the repertoire during development in the thymus is critical for generating safe and useful T cells. Defects in thymic selection contribute to the development of autoimmune and immunodeficiency disorders1-4. T cell progenitors enter the thymus as double negative (DN) thymocytes that do not express CD4 or CD8 co-receptors. Expression of the αβTCR and both co-receptors occurs at the double positive (DP) stage. Interaction of the αβTCR with self-peptide-MHC (pMHC) presented by thymic cells determines the fate of the DP thymocyte. High affinity interactions lead to negative selection and elimination of self-reactive thymocytes. Low affinity interactions result in positive selection and development of CD4 or CD8 single positive (SP) T cells capable of recognizing foreign antigens presented by self-MHC5. Positive selection can be studied in mice with a polyclonal (wildtype) TCR repertoire by observing the generation of mature T cells. However, they are not ideal for the study of negative selection, which involves deletion of small antigen-specific populations. Many model systems have been used to study negative selection but vary in their ability to recapitulate physiological events6. For example, in vitro stimulation of thymocytes lacks the thymic environment that is intimately involved in selection, while administration of exogenous antigen can lead to non-specific deletion of thymocytes7-9. Currently, the best tools for studying in vivo negative selection are mice that express a transgenic TCR specific for endogenous self-antigen. However, many classical TCR transgenic models are characterized by premature expression of the transgenic TCRα chain at the DN stage, resulting in

  2. Switching Algorithm for Maglev Train Double-Modular Redundant Positioning Sensors

    PubMed Central

    He, Ning; Long, Zhiqiang; Xue, Song

    2012-01-01

    High-resolution positioning for maglev trains is implemented by detecting the tooth-slot structure of the long stator installed along the rail, but there are large joint gaps between long stator sections. When a positioning sensor is below a large joint gap, its positioning signal is invalidated, thus double-modular redundant positioning sensors are introduced into the system. This paper studies switching algorithms for these redundant positioning sensors. At first, adaptive prediction is applied to the sensor signals. The prediction errors are used to trigger sensor switching. In order to enhance the reliability of the switching algorithm, wavelet analysis is introduced to suppress measuring disturbances without weakening the signal characteristics reflecting the stator joint gap based on the correlation between the wavelet coefficients of adjacent scales. The time delay characteristics of the method are analyzed to guide the algorithm simplification. Finally, the effectiveness of the simplified switching algorithm is verified through experiments. PMID:23112657

  3. Switching algorithm for maglev train double-modular redundant positioning sensors.

    PubMed

    He, Ning; Long, Zhiqiang; Xue, Song

    2012-01-01

    High-resolution positioning for maglev trains is implemented by detecting the tooth-slot structure of the long stator installed along the rail, but there are large joint gaps between long stator sections. When a positioning sensor is below a large joint gap, its positioning signal is invalidated, thus double-modular redundant positioning sensors are introduced into the system. This paper studies switching algorithms for these redundant positioning sensors. At first, adaptive prediction is applied to the sensor signals. The prediction errors are used to trigger sensor switching. In order to enhance the reliability of the switching algorithm, wavelet analysis is introduced to suppress measuring disturbances without weakening the signal characteristics reflecting the stator joint gap based on the correlation between the wavelet coefficients of adjacent scales. The time delay characteristics of the method are analyzed to guide the algorithm simplification. Finally, the effectiveness of the simplified switching algorithm is verified through experiments. PMID:23112657

  4. Determination of double bond position in conjugated dienes by chemical ionization mass spectrometry with isobutane

    SciTech Connect

    Doolittle, R.E.; Tumlinson, J.H.; Proveaux, A.

    1985-07-01

    The chemical ionization (CI) mass spectra of a series of functionalized conjugated dienes, including aldehydes, alcohols, formates, acetates, and hydrocarbons were investigated to determine whether fragmentations occur that are characteristic of the position of the conjugated system within the hydrocarbon chain. CI with isobutane as ionizing gas produces structure-specific fragment ions with m/z ratios that can be used to locate the positions of the double bonds in most of the cases studied. When the conjugated system is proximal to the functional group or conjugated with the functional group, other fragmentation processes take precedence. These patterns of fragmentations constitute a very useful analytical tool for the location of conjugated double bonds in a variety of natural products. 34 references, 3 tables, 3 figures.

  5. Test of local position invariance using a double-cavity laser system

    SciTech Connect

    Agachev, A. R.; Belov, I. Yu.; Bochkarev, V. V.; Daishev, R. A.; Mavrin, S. V.; Murzakhanov, Z. G.; Skochilov, A. F. Chugunov, Yu. P.; Shindyaev, O. P.

    2010-01-15

    The results of testing local position invariance, which is a constituent of the Einstein equivalence principle, in a 'null' gravitational redshift experiment are reported. The processing of the experimental data collected during the five-month operation of a double-c avity laser system, where one cavity operates in the free generation mode and the frequency of the second cavity is stabilized with the nonlinear ultranarrow absorption resonance of the methane molecule, has confirmed the universality of the gravitational redshift law at a level of 0.9%. This result almost doubly improves the best existing accuracy (1.7%) of testing local position invariance for clocks of different physical natures.

  6. Retinoids induce Nur77-dependent apoptosis in mouse thymocytes.

    PubMed

    Kiss, Beáta; Tóth, Katalin; Sarang, Zsolt; Garabuczi, Éva; Szondy, Zsuzsa

    2015-03-01

    Nur77 is a transcription factor, which plays a determinant role in mediating T cell receptor-induced cell death of thymocytes. In addition to regulation of transcription, Nur77 contributes to apoptosis induction by targeting mitochondria, where it can convert Bcl-2, an anti-apoptotic protein into a proapoptotic molecule. Previous studies have demonstrated that retinoids are actively produced in the mouse thymus and can induce a transcription-dependent apoptosis in mouse thymocytes. Here we show that retinoic acids induce the expression of Nur77, and retinoid-induced apoptosis is completely dependent on Nur77, as retinoids were unable to induce apoptosis in Nur77 null thymocytes. In wild-type thymocytes retinoids induced enhanced expression of the apoptosis-related genes FasL, TRAIL, NDG-1, Gpr65 and Bid, all of them in a Nur77-dependent manner. The combined action of these proteins led to Caspase 8-dependent Bid cleavage in the mitochondria. In addition, we could demonstrate the Nur77-dependent induction of STAT1 leading to enhanced Bim expression, and the mitochondrial translocation of Nur77 leading to the exposure of the Bcl-2/BH3 domain. The retinoid-induced apoptosis was dependent on both Caspase 8 and STAT1. Our data together indicate that retinoids induce a Nur77-dependent cell death program in thymocytes activating the mitochondrial pathway of apoptosis. PMID:25576519

  7. Double hysteresis loops and large negative and positive electrocaloric effects in tetragonal ferroelectrics.

    PubMed

    Wu, Hong-Hui; Zhu, Jiaming; Zhang, Tong-Yi

    2015-10-01

    Phase field modelling and thermodynamic analysis are employed to investigate depolarization and compression induced large negative and positive electrocaloric effects (ECEs) in ferroelectric tetragonal crystalline nanoparticles. The results show that double-hysteresis loops of polarization versus electric field dominate at temperatures below the Curie temperature of the ferroelectric material, when the mechanical compression exceeds a critical value. In addition to the mechanism of pseudo-first-order phase transition (PFOPT), the double-hysteresis loops are also caused by the abrupt rise of macroscopic polarization from the abc phase to the c phase or the sudden fall of macroscopic polarization from the c phase to the abc phase when the temperature increases. This phenomenon is called the electric-field-induced-pseudo-phase transition (EFIPPT) in the present study. Similar to the two types of PFOPTs, the two types of EFIPPTs cause large negative and positive ECEs, respectively, and give the maximum absolute values of negative and positive adiabatic temperature change (ATC ΔT). The temperature associated with the maximum absolute value of negative ATC ΔT is lower than that associated with the maximum positive ATC ΔT. Both maximum absolute values of ATC ΔTs change with the variation in the magnitude of an applied electric field and depend greatly on the compression intensity. PMID:26307461

  8. CHANGES IN POLARIZATION POSITION ANGLE ACROSS THE ECLIPSE IN THE DOUBLE PULSAR SYSTEM

    SciTech Connect

    Yuen, R.; Manchester, R. N.; Burgay, M.; Camilo, F.; Kramer, M.; Melrose, D. B.; Stairs, I. H.

    2012-06-20

    We investigate the changes in polarization position angle in radiation from pulsar A around the eclipse in the Double Pulsar system PSR J0737-3039A/B at the 20 cm and 50 cm wavelengths using the Parkes 64 m telescope. The changes are {approx}2{sigma} during and shortly after the eclipse at 20 cm but less significant at 50 cm. We show that the changes in position angle during the eclipse can be modeled by differential synchrotron absorption in the eclipse regions. Position angle changes after the eclipse are interpreted as Faraday rotation in the magnetotail of pulsar B. Implied charge densities are consistent with the Goldreich-Julian density, suggesting that the particle energies in the magnetotail are mildly relativistic.

  9. Increased CD4+/CD8+ Double-Positive T Cells in Chronic Chagasic Patients

    PubMed Central

    Giraldo, Nicolas A.; Bolaños, Natalia I.; Cuellar, Adriana; Guzman, Fanny; Uribe, Ana Maria; Bedoya, Astrid; Olaya, Natalia; Cucunubá, Zulma M.; Roa, Nubia; Rosas, Fernando; Velasco, Víctor; Puerta, Concepción J.; González, John M.

    2011-01-01

    Background CD4+/CD8+ double positive (DP) T cells have been described in healthy individuals as well as in patients with autoimmune and chronic infectious diseases. In chronic viral infections, this cell subset has effector memory phenotype and displays antigen specificity. No previous studies of double positive T cells in parasite infections have been carried out. Methodology/Principal Findings Seventeen chronic chagasic patients (7 asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T. cruzi K1 or influenza virus epitopes. Surface expression of CD107 and intracellular IFN-γ production were determined in K1-specific DP T cells from 11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies of DP T cells (2.1%±0.9) compared with healthy (1.1%±0.5) and non-chagasic cardiomyopathy (1.2%±0.4) donors. DP T cells from Chagasic patients also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T. cruzi K1-specific cells. IFN-γ production in K1-specific cells was higher in asymptomatic patients after polyclonal stimulation, while these cells tended to degranulate more in symptomatic donors. Immunochemistry revealed that double positive T cells infiltrate the cardiac tissue of a chagasic donor. Conclusions Chagasic patients have higher percentages of circulating double positive T cells expressing activation markers, potential effector molecules and greater class I antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell produced little IFN-γ, they displayed degranulation activity that was increased in symptomatic patients. Moreover, K1-specific DP T cells can

  10. ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis.

    PubMed

    Stefanelli, C; Bonavita, F; Stanic', I; Farruggia, G; Falcieri, E; Robuffo, I; Pignatti, C; Muscari, C; Rossoni, C; Guarnieri, C; Caldarera, C M

    1997-03-15

    In quiescent thymocytes, mitochondrial de-energization was not correlated to apoptotic death. In fact, thymocytes treated with oligomycin, a highly specific inhibitor of ATP synthase, alone or with atractyloside to block ATP translocation from the cytoplasm, were alive, even if their mitochondria were depolarized, as revealed by flow cytometry after Rhodamine 123 staining. Furthermore, oligomycin was a powerful inhibitor of apoptosis induced in rat thymocytes by dexamethasone and, to a lesser extent, by the calcium ionophore A23187 and etoposide, but was without effect when apoptosis was induced by staurosporine, and increased cell death in mitogen-treated thymocytes. The inhibition of apoptosis was confirmed by morphological criteria, inhibition of inter-nucleosomal DNA fragmentation and inhibition of the loss of membrane integrity. The anti-apoptotic effect of oligomycin in cells treated with A23187 or etoposide was correlated to the inhibition of protein synthesis, while inhibition of apoptosis induced by dexamethasone, already evident at an oligomycin concentration of 10 ng/ml, was instead strictly correlated to the effect exerted on the cellular ATP level. Thymocyte apoptosis triggered by dexamethasone was blocked or delayed by inhibitors of respiratory-chain uncouplers, inhibitors of ATP synthase and antioxidants: a lasting protection from dexamethasone-induced apoptosis was always correlated to a drastic and rapid reduction in ATP level (31-35% of control), while a delay in the death process was characterized by a moderate decrease in ATP (73-82% of control). Oligomycin inhibited the specific binding of radioactive corticosteroid to thymocyte nuclei, confirming the inhibitory effect of ATP depletion on glucocorticoid binding and suggesting that ATP depletion is a common mediator of the anti-apoptotic action of different effectors in glucocorticoid-induced apoptosis. In conclusion, the reported data indicate that ATP may act as a cellular modulator of some

  11. ATP depletion inhibits glucocorticoid-induced thymocyte apoptosis.

    PubMed Central

    Stefanelli, C; Bonavita, F; Stanic', I; Farruggia, G; Falcieri, E; Robuffo, I; Pignatti, C; Muscari, C; Rossoni, C; Guarnieri, C; Caldarera, C M

    1997-01-01

    In quiescent thymocytes, mitochondrial de-energization was not correlated to apoptotic death. In fact, thymocytes treated with oligomycin, a highly specific inhibitor of ATP synthase, alone or with atractyloside to block ATP translocation from the cytoplasm, were alive, even if their mitochondria were depolarized, as revealed by flow cytometry after Rhodamine 123 staining. Furthermore, oligomycin was a powerful inhibitor of apoptosis induced in rat thymocytes by dexamethasone and, to a lesser extent, by the calcium ionophore A23187 and etoposide, but was without effect when apoptosis was induced by staurosporine, and increased cell death in mitogen-treated thymocytes. The inhibition of apoptosis was confirmed by morphological criteria, inhibition of inter-nucleosomal DNA fragmentation and inhibition of the loss of membrane integrity. The anti-apoptotic effect of oligomycin in cells treated with A23187 or etoposide was correlated to the inhibition of protein synthesis, while inhibition of apoptosis induced by dexamethasone, already evident at an oligomycin concentration of 10 ng/ml, was instead strictly correlated to the effect exerted on the cellular ATP level. Thymocyte apoptosis triggered by dexamethasone was blocked or delayed by inhibitors of respiratory-chain uncouplers, inhibitors of ATP synthase and antioxidants: a lasting protection from dexamethasone-induced apoptosis was always correlated to a drastic and rapid reduction in ATP level (31-35% of control), while a delay in the death process was characterized by a moderate decrease in ATP (73-82% of control). Oligomycin inhibited the specific binding of radioactive corticosteroid to thymocyte nuclei, confirming the inhibitory effect of ATP depletion on glucocorticoid binding and suggesting that ATP depletion is a common mediator of the anti-apoptotic action of different effectors in glucocorticoid-induced apoptosis. In conclusion, the reported data indicate that ATP may act as a cellular modulator of some

  12. Negative and positive hysteresis in double-cavity optical bistability in a three-level atom

    SciTech Connect

    Babu, H. Aswath; Wanare, Harshawardhan

    2011-03-15

    We present dual hysteretic behavior of a three-level ladder system exhibiting optical bistability in a double-cavity configuration in the mean-field limit. The two fields coupling the atomic system experience competing cooperative effects along the two transitions. We observe a hump-like feature in the bistable curve arising due to cavity-induced inversion, which transforms into a negative-hysteresis loop. Apart from negative- and positive-hysteresis regions, the system offers a variety of controllable nonlinear dynamical features, ranging from switching, periodic self-pulsing to chaos.

  13. Themis1 enhances T cell receptor signaling during thymocyte development by promoting Vav1 activity and Grb2 stability.

    PubMed

    Zvezdova, Ekaterina; Mikolajczak, Judith; Garreau, Anne; Marcellin, Marlène; Rigal, Lise; Lee, Jan; Choi, Seeyoung; Blaize, Gaëtan; Argenty, Jérémy; Familiades, Julien; Li, Liqi; Gonzalez de Peredo, Anne; Burlet-Schiltz, Odile; Love, Paul E; Lesourne, Renaud

    2016-01-01

    The T cell signaling protein Themis1 is essential for the positive and negative selection of thymocytes in the thymus. Although the developmental defect that results from the loss of Themis1 suggests that it enhances T cell receptor (TCR) signaling, Themis1 also recruits Src homology 2 domain-containing phosphatase-1 (SHP-1) to the vicinity of TCR signaling complexes, suggesting that it has an inhibitory role in TCR signaling. We used TCR signaling reporter mice and quantitative proteomics to explore the role of Themis1 in developing T cells. We found that Themis1 acted mostly as a positive regulator of TCR signaling in vivo when receptors were activated by positively selecting ligands. Proteomic analysis of the Themis1 interactome identified SHP-1, the TCR-associated adaptor protein Grb2, and the guanine nucleotide exchange factor Vav1 as the principal interacting partners of Themis1 in isolated mouse thymocytes. Analysis of TCR signaling in Themis1-deficient and Themis1-overexpressing mouse thymocytes demonstrated that Themis1 promoted Vav1 activity both in vitro and in vivo. The reduced activity of Vav1 and the impaired T cell development in Themis1(-/-) mice were due in part to increased degradation of Grb2, which suggests that Themis1 is required to maintain the steady-state abundance of Grb2 in thymocytes. Together, these data suggest that Themis1 acts as a positive regulator of TCR signaling in developing T cells, and identify a mechanism by which Themis1 regulates thymic selection. PMID:27188442

  14. A dual-targeting triplebody mediates preferential redirected lysis of antigen double-positive over single-positive leukemic cells

    PubMed Central

    Schubert, Ingo; Saul, Domenica; Nowecki, Stefanie; Mackensen, Andreas; Fey, Georg H; Oduncu, Fuat S

    2014-01-01

    The single-chain triplebody HLA-ds16-hu19 consists of three single-chain Fv (scFv) antibody fragments connected in a single polypeptide chain. This protein with dual-targeting capacity mediated preferential lysis of antigen double-positive (dp) over single-positive (sp) leukemic cells by recruitment of natural killer (NK) cells as effectors. The two distal scFv modules were specific for the histocompatibility protein HLA-DR and the lymphoid antigen CD19, the central one for the Fc gamma receptor CD16. In antibody-dependent cellular cytotoxicity (ADCC) experiments with a mixture of leukemic target cells comprising both HLA-DR sp HuT-78 or Kasumi-1 cells and (HLA-DR plus CD19) dp SEM cells, the triplebody mediated preferential lysis of the dp cells even when the sp cells were present in ≤20-fold numerical excess. The triplebody promoted equal lysis of SEM cells at 2.5-fold and 19.5-fold lower concentrations than the parental antibodies specific for HLA-DR and CD19, respectively. Finally, the triplebody also eliminated primary leukemic cells at lower concentrations than an equimolar mixture of bispecific single-chain Fv fragments (bsscFvs) separately addressing each target antigen (hu19-ds16 and HLA-ds16). The increased selectivity of targeting and the preferential lysis of dp over sp cells achieved by dual-targeting open attractive new perspectives for the use of dual-targeting agents in cancer therapy. PMID:24135631

  15. Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes.

    PubMed

    Sándor, Katalin; Daniel, Bence; Kiss, Bea; Kovács, Fruzsina; Szondy, Zsuzsa

    2016-08-01

    Transglutaminase 2 (TGM2) is a ubiquitously expressed multifunctional protein, which participates in various biological processes including thymocyte apoptosis. As a result, the transcriptional regulation of the gene is complex and must depend on the cell type. Previous studies from our laboratory have shown that in dying thymocytes the expression of Tgm2 is induced by external signals derived from engulfing macrophages, such as retinoids, transforming growth factor (TGF)-β and adenosine, the latter triggering the adenylate cyclase signaling pathway. The existence of TGF-β and retinoid responsive elements in the promoter region of Tgm2 has already been reported, but the intergenic regulatory elements participating in the regulation of Tgm2 have not yet been identified. Here we used publicly available results from DNase I hypersensitivity analysis followed by deep sequencing and chromatin immunoprecipitation followed by deep sequencing against CCCTC-binding factor (CTCF), H3K4me3, H3K4me1 and H3K27ac to map a putative regulatory element set for Tgm2 in thymocytes. By measuring eRNA expressions of these putative enhancers in retinoid, rTGF-β or dibutiryl cAMP-exposed thymocytes we determined which of them are functional. By applying ChIP-qPCR against SMAD4, retinoic acid receptor, retinoid X receptor, cAMP response element binding protein, P300 and H3K27ac under the same conditions, we identified two enhancers of Tgm2, which seem to act as integrators of the TGF-β, retinoid and adenylate cyclase signaling pathways in dying thymocytes. Our study describes a novel strategy to identify and characterize the signal-specific functional enhancer set of a gene by integrating genome-wide datasets and measuring the production of enhancer specific RNA molecules. PMID:27262403

  16. Genomically imposed and somatically modified human thymocyte V sub. beta. gene repertoires

    SciTech Connect

    Baccala, R.; Kono, D.H.; Balderas, R.S.; Theofilopoulos, A.N. ); Walker, S. )

    1991-04-01

    The effect of thymic selection on the expressed human T-cell antigen receptor {beta}-chain variable region (V{sub {beta}}) gene repertoire was examined by using a multiprobe RNase protection assay. The relative abundance of transcripts for 22 V{sub {beta}} genes (encompassing 17 of the 20 human V{sub {beta}} gene subfamilies) within a thymus, and among 17 thymuses, was variable. On the basis of the presence of corresponding mRNAs, no genomic deletions were detected, but several coding region polymorphisms were identified. Analysis of mature T-cell subsets revealed the absence of complete superantigen-mediated V{sub {beta}} deletions, suggesting that this phenomenon, in contrast to mouse, is uncommon or absent in humans. However, several V{sub {beta}} genes were over- or underexpressed in one or both mature single-positive (CD4{sup +}8{sup {minus}} or CD8{sup +}4{sup {minus}}) thymocyte subsets compared to syngeneic total, mostly immature thymocytes. Whether these changes are induced by relatively weak superantigens or conventional antigens and whether the downshifts are caused by negative selection or lack of positive selection remains to be determined.

  17. Separation of human thymocytes at different stages of maturation by centrifugation on a discontinuous gradient of colloidal silica gel.

    PubMed

    Goust, J M; Perry, L R

    1981-06-01

    Separation of human intrathymic cells on a discontinuous gradient of colloidal silica gel (Percoll) yielded four layers. The first (density 1.054 +/- 0.002 g/ml) contained stromal cells and a few thymocytes positive for terminal deoxynucleotidyl transferase (Tdt), most of which were bound to large Tdt-negative non-T cells. The second layer (1.069+/- 0.003 g/ml) contained large Tdt-negative thymocytes. The third and forth layers (1.075 +/-0.004 and 1.085 +/- 0.003 g/ml, respectively) contained smaller T cells, more than 95% of which were Tdt-positive. Functional studies revealed that cells from the first layer had a high level of spontaneous [3H]thymidine uptake but did not respond to lectins; the second layer responded to PHA, ConA, and allogeneic stimuli; and the third and fourth layers did not respond to lectin stimulation. Addition of cells from the first layer to the other layers at a 1 : 10 ratio significantly increased the mitogenic responses of the cells from the second layer, but not of those from the third or fourth layer. These results suggest that, as in mice and rats, low-density intrathymic thymocytes in humans represent more mature T cells, the percentage of which increases with age. PMID:6973841

  18. Slant Wet Delays from GNSS observations - Precise Point Positioning vs. Double Difference Approach

    NASA Astrophysics Data System (ADS)

    Moeller, Gregor; Weber, Robert

    2015-04-01

    The tropospheric parameter SWD (Slant Wet Delay) is the path delay caused by the highly variable amount of humidity in the atmosphere at altitudes below 12 km. It can be derived from Numerical Weather Predication data or even more precisely from dual- or multi-frequency observations of a regional GNSS reference network. In order to find the most adequate processing strategy dual GNSS observations of a small network of reference stations were simulated and tropospheric parameters were estimated in Precise Point Positioning (PPP) and in Double Difference (DD) mode. In DD mode the integer character of the phase ambiguities remains which allows to fix them to their true values and to obtain the tropospheric zenith delay as well as north and east (N/E) gradients with highest precision over very short time periods. In PPP mode orbit and clock errors are not cancelled out which affects the quality of the tropospheric estimates. On the other hand it has the advantage that the GNSS observations are processed undifferenced. Latter is important because the Zero Difference Residuals (ZDR) contain the azimuthal-anisotropic part of the tropospheric delay which is not covered by the estimated parameters. From Double Difference Residuals (DDR) the ZDR can be recovered too but only conditionally since common tropospheric effects have been cancelled out in advance by differencing. In this presentation we show how good the anisotropic slant path delays can be obtained from GNSS observations processed using both concepts - the PPP and the DD approach. Therefore tropospheric zenith delays and N/E gradients were estimated and Pseudo-ZDR were reconstructed from DDR and afterwards compared with ZDR derived from the PPP solution. In addition it is shown how good both concepts are applicable for observations at very low elevation angles and under extreme weather conditions. The IGS final and ultra-rapid service products were taken into account to define the best strategy not only for post

  19. Thymocyte plasma membrane: the location of specific glucocorticoid binding sites

    SciTech Connect

    Sergeev, P.V.; Kalinin, G.V.; Dukhanin, A.S.

    1987-01-01

    In modern molecular endocrinology it is now possible to determine the localization of receptors for biologically active substances with the aid of ligands, with high affinity for the receptor, immobilized on polymers. The purpose of this paper is to study the ability of hydrocortisone (HC), immobilized on polyvinylpyrrolidone (PVP-HC), to reduce binding of tritium-HC by thymocytes of adrenalectomized rats. It is determined that specific binding sites for HC on rat thymocytes are also accessible for PVP-HC, which, due to the fact that this immobilized version of HC does not penetrate into the cell, leads to the conclusion that the binding sites for HC itself are located in the plasma membrane.

  20. Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells.

    PubMed

    Wang, Hong-Xia; Qiu, Yu-Rong; Zhong, Xiao-Ping

    2016-01-01

    Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is crucial for negative selection of self-reactive T cells to establish central tolerance. Intercellular transfer of self-peptide-MHC complexes from mTECs to thymic dendritic cells (DCs) allows DCs to acquire TRAs, which in turn contributes to negative selection and regulatory T cell generation. However, mTECs are unlikely to express all TRAs, such as immunoglobulins generated only in B cells after somatic recombination, hyper-mutation, or class-switches. We report here that both mTECs and cortical TECs can efficiently acquire not only cell surface but also intracellular proteins from thymocytes. This reveals a previously unappreciated intercellular sharing of molecules from thymocytes to TECs, which may broaden the TRA inventory in mTECs for establishing a full spectrum of central tolerance. PMID:27022746

  1. Intercellular Protein Transfer from Thymocytes to Thymic Epithelial Cells

    PubMed Central

    Wang, Hong-Xia; Qiu, Yu-Rong; Zhong, Xiao-Ping

    2016-01-01

    Promiscuous expression of tissue restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) is crucial for negative selection of self-reactive T cells to establish central tolerance. Intercellular transfer of self-peptide-MHC complexes from mTECs to thymic dendritic cells (DCs) allows DCs to acquire TRAs, which in turn contributes to negative selection and regulatory T cell generation. However, mTECs are unlikely to express all TRAs, such as immunoglobulins generated only in B cells after somatic recombination, hyper-mutation, or class-switches. We report here that both mTECs and cortical TECs can efficiently acquire not only cell surface but also intracellular proteins from thymocytes. This reveals a previously unappreciated intercellular sharing of molecules from thymocytes to TECs, which may broaden the TRA inventory in mTECs for establishing a full spectrum of central tolerance. PMID:27022746

  2. Multiparameter double hole contrast detail phantom: Ability to detect image displacement due to off position anode stem

    NASA Astrophysics Data System (ADS)

    Pauzi, Nur Farahana; Majid, Zafri Azran Abdul; Sapuan, Abdul Halim; Azemin, Mohd Zulfaezal Che; Junet, Laila Kalidah

    2015-04-01

    Contrast Detail phantom is a quality control tool to analyze the performance of imaging devices. Currently, its function is solely to evaluate the contrast detail characteristic of imaging system. It consists of drilled hole which gives effect to the penetration of x-ray beam divergence to pass through the base of each hole. This effect will lead to false appearance of image from its original location but it does not being visualized in the radiograph. In this study, a new design of Contrast Detail phantom's hole which consists of double hole construction has been developed. It can detect the image displacement which is due to off position of anode stem from its original location. The double hole differs from previous milled hole, whereby it consists of combination of different hole diameters. Small hole diameter (3 mm) is positioned on top of larger hole diameter (10 mm). The thickness of double hole acrylic blocks is 13 mm. Result revealed` that, Multiparameter Double Hole Contrast Detail phantom can visualize the shifted flaw image quality produced by x-ray machine due to improper position of the anode stem which is attached to rotor and stator. The effective focal spot of x-ray beam also has been shifted from the center of collimator as a result of off-position anode stem. As a conclusion, the new design of double hole Contrast Detail phantom able to measure those parameters in a well manner.

  3. Multiparameter double hole contrast detail phantom: Ability to detect image displacement due to off position anode stem

    SciTech Connect

    Pauzi, Nur Farahana; Majid, Zafri Azran Abdul; Sapuan, Abdul Halim; Junet, Laila Kalidah; Azemin, Mohd Zulfaezal Che

    2015-04-24

    Contrast Detail phantom is a quality control tool to analyze the performance of imaging devices. Currently, its function is solely to evaluate the contrast detail characteristic of imaging system. It consists of drilled hole which gives effect to the penetration of x-ray beam divergence to pass through the base of each hole. This effect will lead to false appearance of image from its original location but it does not being visualized in the radiograph. In this study, a new design of Contrast Detail phantom’s hole which consists of double hole construction has been developed. It can detect the image displacement which is due to off position of anode stem from its original location. The double hole differs from previous milled hole, whereby it consists of combination of different hole diameters. Small hole diameter (3 mm) is positioned on top of larger hole diameter (10 mm). The thickness of double hole acrylic blocks is 13 mm. Result revealed that Multiparameter Double Hole Contrast Detail phantom can visualize the shifted flaw image quality produced by x-ray machine due to improper position of the anode stem which is attached to rotor and stator. The effective focal spot of x-ray beam also has been shifted from the center of collimator as a result of off-position anode stem. As a conclusion, the new design of double hole Contrast Detail phantom able to measure those parameters in a well manner.

  4. Thymic medullary epithelium and thymocyte self tolerance require cooperation between CD28-CD80/86 and CD40-CD40L costimulatory pathways

    PubMed Central

    Williams, Joy A.; Zhang, Jingjing; Jeon, Hyein; Nitta, Takeshi; Ohigashi, Izumi; Klug, David; Kruhlak, Michael J.; Choudhury, Baishakhi; Sharrow, Susan O.; Granger, Larry; Adams, Anthony; Eckhaus, Michael A.; Jenkinson, S. Rhiannon; Richie, Ellen R.; Gress, Ronald E.; Takahama, Yousuke; Hodes, Richard J.

    2014-01-01

    A critical process during thymic development of the T cell repertoire is the induction of self-tolerance. Tolerance in developing T cells is highly dependent on medullary thymic epithelial cells (mTEC) and mTEC development in turn requires signals from mature single positive (SP) thymocytes, a bidirectional relationship termed thymus crosstalk. We show that CD28-CD80/86 and CD40-CD40L costimulatory interactions, which mediate negative selection and self-tolerance, upregulate expression of LTα, LTβ and RANK in the thymus and are necessary for medullary development. Combined absence of CD28-CD80/86 and CD40-CD40L results in profound deficiency in mTEC development comparable to that observed in the absence of SP thymocytes. This requirement for costimulatory signaling is maintained even in a TCR transgenic model of high affinity TCR-ligand interactions. CD4 thymocytes maturing in the altered thymic epithelial environment of CD40/CD80/86 KO mice are highly autoreactive in vitro and are lethal in congenic adoptive transfer in vivo, demonstrating a critical role for these costimulatory pathways in self-tolerance as well as thymic epithelial development. These findings demonstrate that cooperativity between CD28-CD80/86 and CD40-CD40L pathways is required for normal medullary epithelium and for maintenance of self-tolerance in thymocyte development. PMID:24337745

  5. Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice.

    PubMed

    Tateishi, Ryosuke; Akiyama, Nobuko; Miyauchi, Maki; Yoshinaga, Riko; Sasanuma, Hiroki; Kudo, Takashi; Shimbo, Miki; Shinohara, Masahiro; Obata, Koji; Inoue, Jun-Ichiro; Shirakawa, Masaki; Shiba, Dai; Asahara, Hiroshi; Yoshida, Nobuaki; Takahashi, Satoru; Morita, Hironobu; Akiyama, Taishin

    2015-01-01

    Gravity change affects many immunological systems. We investigated the effects of hypergravity (2G) on murine thymic cells. Exposure of mice to 2G for three days reduced the frequency of CD4+CD8+ thymocytes (DP) and mature medullary thymic epithelial cells (mTECs), accompanied by an increment of keratin-5 and keratin-8 double-positive (K5+K8+) TECs that reportedly contain TEC progenitors. Whereas the reduction of DP was recovered by a 14-day exposure to 2G, the reduction of mature mTECs and the increment of K5+K8+ TEC persisted. Interestingly, a surgical lesion of the inner ear's vestibular apparatus inhibited these hypergravity effects. Quantitative PCR analysis revealed that the gene expression of Aire and RANK that are critical for mTEC function and development were up-regulated by the 3-day exposure and subsequently down-regulated by the 14-day exposure to 2G. Unexpectedly, this dynamic change in mTEC gene expression was independent of the vestibular apparatus. Overall, data suggest that 2G causes a temporary reduction of DP and a persistent reduction of mature mTECs in a vestibular system-dependent manner, and also dysregulates mTEC gene expression without involving the vestibular system. These data might provide insight on the impact of gravity change on thymic functions during spaceflight and living. PMID:26513242

  6. Hypergravity Provokes a Temporary Reduction in CD4+CD8+ Thymocyte Number and a Persistent Decrease in Medullary Thymic Epithelial Cell Frequency in Mice

    PubMed Central

    Miyauchi, Maki; Yoshinaga, Riko; Sasanuma, Hiroki; Kudo, Takashi; Shimbo, Miki; Shinohara, Masahiro; Obata, Koji; Inoue, Jun-ichiro; Shirakawa, Masaki; Shiba, Dai; Asahara, Hiroshi; Yoshida, Nobuaki; Takahashi, Satoru; Morita, Hironobu; Akiyama, Taishin

    2015-01-01

    Gravity change affects many immunological systems. We investigated the effects of hypergravity (2G) on murine thymic cells. Exposure of mice to 2G for three days reduced the frequency of CD4+CD8+ thymocytes (DP) and mature medullary thymic epithelial cells (mTECs), accompanied by an increment of keratin-5 and keratin-8 double-positive (K5+K8+) TECs that reportedly contain TEC progenitors. Whereas the reduction of DP was recovered by a 14-day exposure to 2G, the reduction of mature mTECs and the increment of K5+K8+ TEC persisted. Interestingly, a surgical lesion of the inner ear’s vestibular apparatus inhibited these hypergravity effects. Quantitative PCR analysis revealed that the gene expression of Aire and RANK that are critical for mTEC function and development were up-regulated by the 3-day exposure and subsequently down-regulated by the 14-day exposure to 2G. Unexpectedly, this dynamic change in mTEC gene expression was independent of the vestibular apparatus. Overall, data suggest that 2G causes a temporary reduction of DP and a persistent reduction of mature mTECs in a vestibular system-dependent manner, and also dysregulates mTEC gene expression without involving the vestibular system. These data might provide insight on the impact of gravity change on thymic functions during spaceflight and living. PMID:26513242

  7. Multifrequency invisibility and masking of cylindrical dielectric objects using double-positive and double-negative metamaterials

    NASA Astrophysics Data System (ADS)

    Serebryannikov, A. E.; Ozbay, Ekmel

    2009-11-01

    We demonstrate that a circular dielectric cylinder can be nearly invisible at multiple frequencies when being coated with a ring shell, which is made of an isotropic material simultaneously showing large positive or large negative values of permittivity and permeability. The suggested cloaking mechanism is based on the use of radial resonances, which are similar to those in conventional Fabry-Perot resonators. It can be used for cylindrical objects for a wide range of variation of the diameter-to-wavelength ratio, which includes the values corresponding to subwavelength to resonant-sized objects. The presence of frequency dispersion of the shell material positively affects the possibility of multifrequency operation.

  8. Anchorage and lymphocyte function. Spreading-capacity distinguishes common thymocytes and peripheral T lymphocytes.

    PubMed Central

    Otteskog, P; Sundqvist, K G

    1983-01-01

    Contact of T-enriched human blood lymphocytes with an adhesive surface in the presence of Concanavalin A (Con A) almost immediately induced a sequence of motile changes in virtually all cells. The initial event in this spreading process was the formation of filopodia distinct from the microvilli of lymphocytes in suspension. The filopodia were accompanied by lamellipodia, ruffles and flattening of the nucleus. Contact with a nonadhesive substratum in the presence of Con A did not trigger this sequence of changes. Cytochalasin B and D or low temperature inhibited the contact-induced changes. With the exception of a small number of cells (5-15%), T-enriched lymphocytes that were allowed to settle in the absence of Con A showed a radius of action (area occupied by the cells/translational movement per hr) of 39 micrometers 2/ less than 1 micrometer. The small 'motile' population showed a radius of action of 74 micrometers 2/8 micrometers. The Con-A-mediated spreading-process yielded a radius of action of the lymphocytes of 117 micrometers 2/6 micrometers. This augmented radius of action markedly facilitated cell-cell interaction in a high frequency of the cells and appeared to be a prerequisite for such interactions at 'low' cell density. Thymocytes reactive with OKT 6 antibodies or belonging to the 'high-density' fraction of cells attached to a Con-A-coated surface to the same extent as peripheral OKT 3 positive lymphocytes, but did not exhibit the morphological changes characteristic of a spreading-process. In contrast, OKT 6 negative thymocytes or thymocytes with a relatively low density showed spreading indistinguishable from that of OKT 3 positive peripheral lymphocytes. These results characterize the spreading-process in human T lymphocytes and demonstrate its functional importance for interactions with the environment. Spreading-capacity appears to reflect the stage of maturation of T cells. Images Figure 1 Figure 2 Figure 3 Figure 4b Figure 4c Figure 7 PMID

  9. Functional characteristics of a double positive feedback loop coupled with autorepression

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhasis; Bose, Indrani

    2008-12-01

    We study the functional characteristics of a two-gene motif consisting of a double positive feedback loop and an autoregulatory negative feedback loop. The motif appears in the gene regulatory network controlling the functional activity of pancreatic β-cells. The model exhibits bistability and hysteresis in appropriate parameter regions. The two stable steady states correspond to low (OFF state) and high (ON state) protein levels, respectively. Using a deterministic approach, we show that the region of bistability increases in extent when the copy number of one of the genes is reduced from 2 to 1. The negative feedback loop has the effect of reducing the size of the bistable region. Loss of a gene copy, brought about by mutations, hampers the normal functioning of the β-cells giving rise to the genetic disorder, maturity-onset diabetes of the young (MODY). The diabetic phenotype makes its appearance when a sizable fraction of the β-cells is in the OFF state. Using stochastic simulation techniques we show that, on reduction of the gene copy number, there is a transition from the monostable ON to the ON state in the bistable region of the parameter space. Fluctuations in the protein levels, arising due to the stochastic nature of gene expression, can give rise to transitions between the ON and OFF states. We show that as the strength of autorepression increases, the ON → OFF state transitions become less probable whereas the reverse transitions are more probable. The implications of the results in the context of the occurrence of MODY are pointed out.

  10. Kinetic analysis of thymocyte attachment to thymus stromal cells in culture by using phase-contrast and scanning electron microscopy

    SciTech Connect

    LaRochelle, G.G.; Jones, K.H.

    1989-05-01

    Direct cellular contact between thymocytes and thymus stromal cells within the thymus appears to contribute to the maturation of thymocytes. Thymocyte-stromal cell complexes, formed in vivo, have been isolated by others and postulated to play a role in T-cell differentiation. These previous studies have been hampered, however, by a time-consuming isolation procedure from which only small numbers of these complexes are recovered. We have examined a model to study thymocyte-stromal cell complexes in vitro in which thymocytes are added to primary cultures of thymus stromal cells. In the present study, we found that thymocytes were histotypically selective in their attachment to thymus stromal cells. We also investigated the kinetics of thymocyte attachment to these thymus stromal cells. Cultures were examined at selected time intervals from 5 min through 3 days of incubation. Thymocyte attachment to stromal cells was a biphasic interaction, with maximum surface attachment at 15 min of cocultivation, followed by migration of thymocytes into the cultures. Morphological studies were confirmed by using /sup 3/H-leucine-labeled thymocytes and liquid scintigraphy. With increased time in culture, thymocytes became amoeboid and migrated between the layers of stromal cells where thymocyte mitotic figures were seen at 4 and 8 hr. In some cases it appeared that stromal cells, which often grew two to three cell layers deep, played an active role in enclosing thymocytes within the cultures. Large numbers of viable thymocytes were observed in the cultures at 24 hr. The number of thymocytes then decreased progressively on days 2 and 3, when relatively few were found within the layers of the culture.

  11. In Vivo Detection of Intracellular Signaling Pathways in Developing Thymocytes

    PubMed Central

    Zúñiga-Pflücker, Juan Carlos

    2000-01-01

    Information regarding the intracellular signaling processes that occur during the development of T cells has largely been obtained with the use of transgenic mouse models, which although providing invaluable information are time consuming and costly. To this end, we have developed a novel system that facilitates the In Vivo analysis of signal transduction pathways during T-lymphocyte development. This approach uses reporter-plasmids for the detection of intracellular signals mediated by the mitogen-activated protein kinase or cyclic AMP-dependent protein kinase. Reporter-plasmids are transfected into thymocytes in fetal thymic organ culture by accelerated DNA/particle bombardment (gene gun), and the activation of a signaling pathway is determined in the form of a standard luciferase assay. Importantly, this powerful technique preserves the structural integrity of the thymus, and will provide an invaluable tool to study how thymocytes respond to normal environmental stimuli encountered during differentiation within the thymic milieu. Thus, this method allows for the monitoring of signals that occur in a biological time frame, such as during differentiation, and within the natural environment of differentiating cells. PMID:11293810

  12. Activins and inhibins: Novel regulators of thymocyte development

    SciTech Connect

    Licona-Limon, Paula; Aleman-Muench, German; Macias-Silva, Marina; Garcia-Zepeda, Eduardo A.; Fortoul, Teresa I.; Soldevila, Gloria

    2009-04-03

    Activins and inhibins are members of the transforming growth factor-{beta} superfamily that act on different cell types and regulate a broad range of cellular processes including proliferation, differentiation, and apoptosis. Here, we provide the first evidence that activins and inhibins regulate specific checkpoints during thymocyte development. We demonstrate that both activin A and inhibin A promote the DN3-DN4 transition in vitro, although they differentially control the transition to the DP stage. Whereas activin A induces the accumulation of a CD8{sup +}CD24{sup hi}TCR{beta}{sup lo} intermediate subpopulation, inhibin A promotes the differentiation of DN4 to DP. In addition, both activin A and inhibin A appear to promote CD8{sup +}SP differentiation. Moreover, inhibin {alpha} null mice have delayed in vitro T cell development, showing both a decrease in the DN-DP transition and reduced thymocyte numbers, further supporting a role for inhibins in the control of developmental signals taking place during T cell differentiation in vivo.

  13. Multiyear measurements of Position Angle and Separation of selected binary stars from the Washington Double Star Catalog

    NASA Astrophysics Data System (ADS)

    Muller, Rafael J.; Cersosimo, Juan C.; Lopez, Andy J.; Vergara, Nelson; Torres, Brian; Mendoza, Lizyan; Ortiz, Deliris; Del Valle, Yashira; Espinosa, Gabriela; Reyes, Marjory

    2016-01-01

    We present here the multiyear data sets on separation and position angle of binary stars obtained at the NURO telescope, located east of Flagstaff Arizona at an elevation of 7200 feet. The data was analyzed at the Humacao University Observatory of the University of Puerto Rico and will be submitted for publication at the Journal of Double Star Observations. We describe the methodology for the analysis of the images we obtained.

  14. Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

    PubMed Central

    Singer, K H; Wolf, L S; Lobach, D F; Denning, S M; Tuck, D T; Robertson, A L; Haynes, B F

    1986-01-01

    The thymus plays a critical role in the generation of immunocompetent T lymphocytes. In the thymus, lymphocytes are in close contact with epithelial cells, and this contact is necessary for T-cell maturation. Using cultured human thymic epithelial (TE) cells, we have found that human thymocytes bind to human TE cells in vitro. Thymocytes bound to both allogeneic and autologous TE cells and to the epidermoid carcinoma cell line A431 but did not bind to epidermal keratinocytes or to thymic fibroblasts. Thymocyte binding to TE cells was trypsin- and cytochalasin B-sensitive. Indirect immunofluorescence assays showed that both mature (T6-, T3+) and immature (T6+, T3-) thymocytes bound TE cells. In our system, TE-thymocyte binding was not inhibited by antibodies to class I or class II major histocompatibility antigens. In vitro binding of thymocytes to TE cells may represent a correlate of in vivo TE-thymocyte interactions and provides a model system for the study of human intrathymic T-lymphocyte maturation and activation. Images PMID:3092215

  15. A timeline demarcating two waves of clonal deletion and Foxp3 upregulation during thymocyte development.

    PubMed

    Hu, Daniel Y; Yap, Jin Y; Wirasinha, Rushika C; Howard, Debbie R; Goodnow, Christopher C; Daley, Stephen R

    2016-04-01

    Thymocytes that bind strongly to self-antigens are prevented from becoming naive T cells by several mechanisms. They undergo clonal deletion at two stages of development; wave 1 in immature thymocytes lacking the medulla-homing chemokine receptor, CCR7, or wave 2 in more mature CCR7(+) thymocytes. Alternatively, self-reactive thymocytes upregulate Foxp3 to become T-regulatory cells. Here, we describe the differential timing of the two waves of deletion and Foxp3 upregulation relative to the immature proliferating stage. Proliferating thymocytes were pulse-labeled in normal C57BL/6 mice with 5-ethynyl-2'-deoxyuridine (EdU). Thymocytes progressed into wave 1 (CCR7(-)) and wave 2 (CCR7(+)) of clonal deletion ~2 and 5 days after proliferation, respectively. Foxp3 upregulation occurred between 4 and 8 days after proliferation, predominantly in thymocytes with a Helios(+) CCR7(+) phenotype. These findings establish a timeline that suggests that wave 1 of clonal deletion occurs in the thymic cortex, whereas wave 2 and Foxp3 upregulation both occur in the thymic medulla. PMID:26510893

  16. CD4+ T cells from MHC II-dependent thymocyte–thymocyte interaction provide efficient help for B cells

    PubMed Central

    Kim, Eun Ji; Choi, Bomi; Moon, Hana; Lee, You Jeong; Jeon, Yoon Kyeong; Park, Seong Hoe; Kim, Tae Jin; Jung, Kyeong Cheon

    2011-01-01

    Recently, a novel CD4+ T-cell developmental pathway was reported that generates thymocyte–thymocyte (T–T) CD4+ T cells. We established a mouse system (CIITAtgCIITApIV−/−) where thymic positive selection occurred only by major histocompatibility complex (MHC) class II+ thymocytes. T–T CD4+ T cells selected via MHC class II-dependent T–T interaction are comprised of PLZF-negative and innate PLZF-positive populations. Until recently, the functional role of the PLZF-negative population was unclear. In this study, we demonstrate that naïve T–T CD4+ T cells provide B-cell help to a level comparable with that of naïve conventional CD4+ T cells. Considering the absence of PLZF expression in naïve T–T CD4+ T cells, these results suggest that PLZF-negative naïve T–T CD4+ T cells are functionally equivalent to conventional naïve CD4+ T cells in terms of B-cell help. PMID:21358747

  17. The production of alpha/beta and gamma/delta double negative (DN) T-cells and their role in the maintenance of pregnancy.

    PubMed

    Chapman, John C; Chapman, Fae M; Michael, Sandra D

    2015-01-01

    The ability of the thymus gland to convert bone marrow-derived progenitor cells into single positive (SP) T-cells is well known. In this review we present evidence that the thymus, in addition to producing SP T-cells, also has a pathway for the production of double negative (DN) T-cells. The existence of this pathway was noted during our examination of relevant literature to determine the cause of sex steroid-induced thymocyte loss. In conducting this search our objective was to answer the question of whether thymocyte loss is the end product of a typical interaction between the reproductive and immune systems, or evidence that the two systems are incompatible. We can now report that "thymocyte loss" is a normal process that occurs during the production of DN T-cells. The DN T-cell pathway is unique in that it is mediated by thymic mast cells, and becomes functional following puberty. Sex steroids initiate the development of the pathway by binding to an estrogen receptor alpha located in the outer membrane of the mast cells, causing their activation. This results in their uptake of extracellular calcium, and the production and subsequent release of histamine and serotonin. Lymphatic vessels, located in the subcapsular region of the thymus, respond to the two vasodilators by undergoing a substantial and preferential uptake of gamma/delta and alpha/beta DN T- cells. These T- cells exit the thymus via efferent lymphatic vessels and enter the lymphatic system.The DN pathway is responsible for the production of three subsets of gamma/delta DN T-cells and one subset of alpha/beta DN T-cells. In postpubertal animals approximately 35 % of total thymocytes exit the thymus as DN T-cells, regardless of sex. In pregnant females, their levels undergo a dramatic increase. Gamma/delta DN T-cells produce cytokines that are essential for the maintenance of pregnancy. PMID:26164866

  18. Allocating More Experienced Teachers to Leadership Positions in Schools: A Double-Edged Sword?

    ERIC Educational Resources Information Center

    Camburn, Eric M.

    2009-01-01

    This article presents a critical discussion of the implications of allocating the most experienced and skilled teachers in schools to teacher leadership positions. Placing such teachers in leadership positions supports school improvement initiatives, but it can also pull valuable teaching resources from the classroom. The article examines this…

  19. Unconventional double bent-crystal diffractometer equipped by position-sensitive detector

    NASA Astrophysics Data System (ADS)

    Mikula, Pavel; Lukas, Petr; Kulda, Jiri; Strunz, Pavel; Saroun, Jan; Wagner, Volker; Scherm, Reinhard; Alefeld, Berthold; Reinartz, Richard

    1992-11-01

    Using Bragg diffraction optics, an unconventional DBC diffractometer was tested for medium resolution small-angle neutron scattering experiments. The diffraction geometry of the analyzer enables to transform the angular beam distribution into the positional distribution and, consequently, to analyze it by means of a one-dimensional position sensitive detector. First experimental results obtained with a sample of PE+graphite proves a compatibility and a higher speed of data collection compared to a standard DBC diffractometer.

  20. Glycoprotein biosynthesis in quiescent and stimulated thymocytes and a T-cell lymphoma.

    PubMed Central

    Rupar, C A; Cook, G M

    1982-01-01

    Quiescent thymocytes, mitogen-stimulated thymocytes and acute-leukaemic lymphoblasts provide a model for the study of protein glycosylation in quiescent cells, mitotically active non-malignant and malignant cells respectively. The biosynthesis of both complex and high-mannose-type oligosaccharides was monitored by metabolic labelling with [6-3]fucose and [2-3H]mannose. Bio-Gel P6 elution profiles of [6-3H]fucose-labelled glycopeptides showed that quiescent thymocytes and stimulated thymocytes synthesized qualitatively and quantitatively similar glycopeptides; however, higher-molecular-weight glycopeptides were synthesized by the acute-leukaemic lymphoblasts. The amount of [2(-3)H]mannose incorporated into glycopeptide by quiescent thymocytes was less than 10% of that incorporated by stimulated thymocytes. The Bio-Gel P6 elution profile of [2(-3)H]mannose-labelled glycopeptides from acute leukaemic lymphoblasts was qualitatively similar to that of stimulated thymocytes, with about 40% of the radioactivity incorporated into one glycopeptide peak. This glycopeptide was characterized by Bio-Gel P6 and concanavalin A affinity chromatography, radioactive-sugar analysis, sensitivity to alpha-mannosidase and endoglycosidase H and resistance to beta-glucosaminidase as containing a high-mannose oligosaccharide, possible of Man7-8GlcNAc2 structure. Pulse/chase experiments indicated that this high-mannose oligosaccharide was an end product and not a biosynthetic intermediate. It is concluded that higher-molecular-weight fucose-labelled glycopeptides are characteristic of the malignant cell type, and the synthesis of high-mannose oligosaccharide, Man7-8GlcNAc2, in stimulated thymocytes and acute-leukaemic lymphoblasts is associated with mitotically active cells. PMID:6979338

  1. Functional characterization of human thymocyte subpopulations separated by density gradient centrifugation.

    PubMed Central

    Lederman, H M; Lee, J W; Cohen, A; Gelfand, E W

    1984-01-01

    A bovine serum albumin gradient was used to separate two populations of human thymocytes--a minority population (8%) of large thymocytes (LT) and a majority population (92%) of small thymocytes (ST). Fifty per cent of LT cells were in the S, G2 or M phases of the cell cycle compared to 5% of ST cells and 15% of unfractionated thymocytes. LT cells proliferated in response to T cell mitogens and included all of the T colony precursor cells (TCPC). In contrast, ST cells proliferated with mitogens only in the presence of added T cell growth factors and contained none of the thymocyte TCPC. ST cells neither helped nor suppressed the function of LT cells in any assay. This separation technique has provided a rapid method for isolating functionally distinct thymic lymphocyte subpopulations and permitted a further definition of the TCPC in the human thymus. Furthermore it should prove useful in studies of thymocytes at different stages of the cell cycle. PMID:6607793

  2. A phase II multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction.

    PubMed

    Komrokji, Rami S; Mailloux, Adam W; Chen, Dung-Tsa; Sekeres, Mikkael A; Paquette, Ronald; Fulp, William J; Sugimori, Chiharu; Paleveda-Pena, Jennifer; Maciejewski, Jaroslaw P; List, Alan F; Epling-Burnette, Pearlie K

    2014-07-01

    Immune dysregulation is a mechanism contributing to ineffective hematopoiesis in a subset of myelodysplastic syndrome patients. We report the first US multicenter non-randomized, phase II trial examining the efficacy of rabbit(r)-anti-thymocyte globulin using 2.5 mg/kg/day administered daily for 4 doses. The primary end point was hematologic response; secondary end points included duration of response, time to response, time to progression, and tolerance. Nine (33%;95% confidence interval=17%-54%) of the 27 patients treated experienced durable hematologic improvement in an intent-to-treat analysis with a median time to response and median response duration of 75 and 245 days, respectively. While younger age is the most significant factor favoring equine(e)-anti-thymocyte globulin response, treatment outcome on this study was independent of age (P=0.499). A shorter duration between diagnosis and treatment showed a positive trend (P=0.18), but International Prognostic Scoring System score (P=0.150), karyotype (P=0.319), and age-adjusted bone marrow cellularity (P=0.369) were not associated with response classification. Since activated T-lymphocytes are the primary cellular target of anti-thymocyte globulin, a T-cell expression profiling was conducted in a cohort of 38 patients consisting of rabbit and equine-antithymocyte globulin-treated patients. A model containing disease duration, CD8 terminal memory T cells and T-cell proliferation-associated-antigen expression predicted response with the greatest accuracy using a leave-one-out cross validation approach. This profile categorized patients independent of other covariates, including treatment type and age using a leave-one-out-cross-validation approach (75.7%). Therefore, rabbit-anti-thymocyte globulin has hematologic remitting activity in myelodysplastic syndrome and a T-cell activation profile has potential utility classifying those who are more likely to respond (NCT00466843 clinicaltrials.gov). PMID:24488560

  3. Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial

    PubMed Central

    Jiang, Yan; Zhang, Zhen-Lin; Zhang, Zhong-Lan; Zhu, Han-Min; Wu, Yi-Yong; Cheng, Qun; Wu, Feng-Li; Xing, Xiao-Ping; Liu, Jian-Li; Yu, Wei; Meng, Xun-Wu

    2014-01-01

    Objective To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women. Method This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups. Results A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol. Conclusion Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women. PMID:24426779

  4. Vibrational stabilization of the upright statically unstable position of a double pendulum

    NASA Astrophysics Data System (ADS)

    Arkhipova, Inga M.; Luongo, Angelo; Seyranian, Alexander P.

    2012-01-01

    The phenomenon of stabilization by parametric excitation of an unstable, elastically restrained double inverted pendulum under its own weight is addressed. The solution is pursued by the Multiple Scale Method, as a perturbation of a critical Hamiltonian system, possessing a zero- and a real frequency. Several asymptotic expansions are carried out, which are able to capture the long-term behavior of the system, for generic (non-resonant) values of the excitation frequency, and some special (resonant) values of excitation-to-natural frequency ratio. It is shown that a proper ordering of the control parameters must be performed, and proper use of integer or fractional power expansions must be made, according to the resonance under study. In particular, a non-standard application of the Multiple Scale Method is illustrated for the 1:1 resonant case, requiring fractional powers and accounting for the 'arbitrary constants', generally omitted in regular cases. A comprehensive scenario of the stabilization regions is given in which lower-bound as well as upper-bound curves are evaluated, thus integrating results that recently appeared in the literature.

  5. Quantum dots-based double-color imaging of HER2 positive breast cancer invasion

    SciTech Connect

    Liu, Xiu-Li; Peng, Chun-Wei; Chen, Chuang; Yang, Xue-Qin; Hu, Ming-Bai; Xia, He-Shun; Liu, Shao-Ping; and others

    2011-06-10

    Highlights: {yields} HER2 level is closely related to the biologic behaviors of breast cancer cells. {yields} A new method to simultaneously image HER2 and type IV collagen was established. {yields} HER2 status and type IV collagen degradation predict breast cancer invasion. {yields} The complex interactions between tumor and its environment were revealed. -- Abstract: It has been well recognized that human epidermal growth factor receptor 2 (HER2) level in breast cancer (BC) is closely related to the malignant biologic behaviors of the tumor, including invasion and metastasis. Yet, there has been a lack of directly observable evidence to support such notion. Here we report a quantum dots (QDs)-based double-color imaging technique to simultaneously show the HER2 level on BC cells and the type IV collagen in the tumor matrix. In benign breast tumor, the type IV collagen was intact. With the increasing of HER2 expression level, there has been a progressive decrease in type IV collagen around the cancer nest. At HER2 (3+) expression level, there has virtually been a total destruction of type IV collagen. Moreover, HER2 (3+) BC cells also show direct invasion into the blood vessels. This novel imaging method provides direct observable evidence to support the theory that the HER2 expression level is directly related to BC invasion.

  6. Chromosome position determines the success of double-strand break repair

    PubMed Central

    Lee, Cheng-Sheng; Wang, Ruoxi W.; Chang, Hsiao-Han; Capurso, Daniel; Segal, Mark R.; Haber, James E.

    2016-01-01

    Repair of a chromosomal double-strand break (DSB) by gene conversion depends on the ability of the broken ends to encounter a donor sequence. To understand how chromosomal location of a target sequence affects DSB repair, we took advantage of genome-wide Hi-C analysis of yeast chromosomes to create a series of strains in which an induced site-specific DSB in budding yeast is repaired by a 2-kb donor sequence inserted at different locations. The efficiency of repair, measured by cell viability or competition between each donor and a reference site, showed a strong correlation (r = 0.85 and 0.79) with the contact frequencies of each donor with the DSB repair site. Repair efficiency depends on the distance between donor and recipient rather than any intrinsic limitation of a particular donor site. These results further demonstrate that the search for homology is the rate-limiting step in DSB repair and suggest that cells often fail to repair a DSB because they cannot locate a donor before other, apparently lethal, processes arise. The repair efficiency of a donor locus can be improved by four factors: slower 5′ to 3′ resection of the DSB ends, increased abundance of replication protein factor A (RPA), longer shared homology, or presence of a recombination enhancer element adjacent to a donor. PMID:26715752

  7. Post-selection thymocyte maturation and emigration are independent of IL-7 and ERK5

    PubMed Central

    Weinreich, Michael A.; Jameson, Stephen C.; Hogquist, Kristin A.

    2016-01-01

    The transcription factor Kruppel-Like Factor 2 (KLF2) controls the emigration of conventional T cells from the thymus through its regulation of the cell surface receptor, S1P1. Prior to KLF2 expression, developing T cells require a positive selection signal through the T cell receptor. However, following positive selection there are time, spatial and maturational events that occur before KLF2 is finally upregulated and emigration occurs. We are interested in determining the signals that upregulate KLF2 and allow thymocytes to emigrate into circulation, and if they are linked to functional maturation. In endothelial cells KLF2 expression has been shown to be dependent on the MAP kinase ERK5. Furthermore, it has been reported that IL-7 signaling leads to the phosphorylation of ERK5. Thus it was hypothesized that IL-7 receptor signaling through ERK5 could drive the expression of KLF2. In this study we provide evidence that this hypothesis is incorrect. We also found that CD8 lineage specification occurred normally in the absence of IL-7R signaling, in contrast to a recently proposed model. We showed that both CD4 and CD8 T cells complete maturation and express KLF2 independently of ERK5 and IL-7. PMID:21187442

  8. Accuracy of relative positioning by interferometry with GPS Double-blind test results

    NASA Technical Reports Server (NTRS)

    Counselman, C. C., III; Gourevitch, S. A.; Herring, T. A.; King, B. W.; Shapiro, I. I.; Cappallo, R. J.; Rogers, A. E. E.; Whitney, A. R.; Greenspan, R. L.; Snyder, R. E.

    1983-01-01

    MITES (Miniature Interferometer Terminals for Earth Surveying) observations conducted on December 17 and 29, 1980, are analyzed. It is noted that the time span of the observations used on each day was 78 minutes, during which five satellites were always above 20 deg elevation. The observations are analyzed to determine the intersite position vectors by means of the algorithm described by Couselman and Gourevitch (1981). The average of the MITES results from the two days is presented. The rms differences between the two determinations of the components of the three vectors, which were about 65, 92, and 124 m long, were 8 mm for the north, 3 mm for the east, and 6 mm for the vertical. It is concluded that, at least for short distances, relative positioning by interferometry with GPS can be done reliably with subcentimeter accuracy.

  9. Positioning.

    ERIC Educational Resources Information Center

    Conone, Ruth M.

    The key to positioning is the creation of a clear benefit image in the consumer's mind. One positioning strategy is creating in the prospect's mind a position that takes into consideration the company's or agency's strengths and weaknesses as well as those of its competitors. Another strategy is to gain entry into a position ladder owned by…

  10. Undergraduate Observations of Separation and Position Angle of Double Stars ARY 6 AD and ARY 6 AE at Manzanita Observatory

    NASA Astrophysics Data System (ADS)

    Hoffert, Michael J.; Weise, Eric; Clow, Jenna; Hirzel, Jacquelyn; Leeder, Brett; Molyneux, Scott; Scutti, Nicholas; Spartalis, Sarah; Tokuhara, Corey

    2014-05-01

    Six beginning astronomy students, part of an undergraduate stellar astronomy course, one advanced undergraduate student assistant, and a professor measured the position angles and separations of Washington Double Stars (WDS) 05460 + 2119 (also known as ARY 6 AD and ARY 6 AE). The measurements were made at the Manzanita Observatory (116° 20'42" W, 32° 44' 5" N) of the Tierra Astronomical Institute on 10 Blackwood Rd. in Boulevard, California (www.youtube.com/watch?v=BHVdcMGBGDU), at an elevation of 4,500 ft. A Celestron 11" HD Edge telescope was used to measure the position angles and separations of ARY 6 AD and ARY 6 AE. The averages of our measurements are as follows: separation AD: trial 1 124.1 arcseconds and trial 2 124.5 arcseconds. The average of separation for AE: trial 1 73.3 arcseconds and trial 2 73.8 arcseconds. The averages of position angle for AD: trial 1 159.9 degrees and trial 2 161.3 degrees. The averages of position angle for AE: trial 1 232.6 degrees and trial 2 233.7 degrees.

  11. High-intensity positive beams extracted from a compact double-chamber ion source

    SciTech Connect

    Huck, H.; Somacal, H.; Di Gregorio, D.E.; Fernandez Niello, J.O.; Igarzabal, M.; Di Paolo, H.; Reinoso, M.

    2005-06-15

    This work presents the design and development of a simple ion source, the associated ion extraction optics, and the beam transport of a low-energy and high-current proton accelerator. In its actual version, the ion source can deliver positive proton currents up to 100 mA. This rather high beam current is achieved by adding a small ionization chamber between the discharge chamber containing the filament and the extraction electrode of the ion source. Different parameters of the ion source and the injection beam line are evaluated by means of computer simulations to optimize the beam production and transmission.

  12. Strength of TCR signal from self-peptide modulates autoreactive thymocyte deletion and Foxp3(+) Treg-cell formation.

    PubMed

    Caton, Andrew J; Kropf, Elizabeth; Simons, Donald M; Aitken, Malinda; Weissler, Katherine A; Jordan, Martha S

    2014-03-01

    Autoreactive CD4(+) CD8(-) (CD4SP) thymocytes can be subjected to deletion when they encounter self-peptide during their development, but they can also undergo selection to become CD4SPFoxp3(+) Treg cells. We have analyzed the relationship between these distinct developmental fates using mice in which signals transmitted by the TCR have been attenuated by mutation of a critical tyrosine residue of the adapter protein SLP-76. In mice containing polyclonal TCR repertoires, the mutation caused increased frequencies of CD4SPFoxp3(+) thymocytes. CD4SP thymocytes expressing TCR Vβ-chains that are subjected to deletion by endogenous retroviral superantigens were also present at increased frequencies, particularly among Foxp3(+) thymocytes. In transgenic mice in which CD4SP thymocytes expressing an autoreactive TCR undergo both deletion and Treg-cell formation in response to a defined self-peptide, SLP-76 mutation abrogated deletion of autoreactive CD4SP thymocytes. Notably, Foxp3(+) Treg-cell formation still occurred, albeit with a reduced efficiency, and the mutation was also associated with decreased Nur77 expression by the autoreactive CD4SP thymocytes. These studies provide evidence that the strength of the TCR signal can play a direct role in directing the extent of both thymocyte deletion and Treg-cell differentiation, and suggest that distinct TCR signaling thresholds and/or pathways can promote CD4SP thymocyte deletion versus Treg-cell formation. PMID:24307208

  13. Optical signatures of valence-band mixing in positive trion recombination spectra of double quantum dots

    NASA Astrophysics Data System (ADS)

    Pasek, W. J.; Nowak, M. P.; Szafran, B.

    2014-06-01

    We consider optical signatures of valence band mixing in positive trion and exciton complexes in vertically stacked InGaAs quantum dots. We use the configuration interaction method and an axially symmetric four-band Luttinger-Kohn Hamiltonian (KL) that allows for heavy-hole and light-hole band mixing due to spin-orbit interaction. A scalar effective hole mass model is also included for comparison. We found essential differences (i.e., different recombination patterns) between the KL and separated-bands model spectra. In the weak-coupling regime for KL model, we obtained a good agreement with experimentally observed X patterns in contrast to the scalar effective mass model.

  14. Double-phase transition and giant positive magnetoresistance in the quasi-skutterudite Gd3Ir4Sn13

    NASA Astrophysics Data System (ADS)

    Nair, Harikrishnan S.; Ghosh, Sarit K.; Ramesh Kumar, K.; Strydom, André M.

    2016-03-01

    The magnetic, thermodynamic, and electrical/thermal transport properties of the caged-structure quasi-skutterudite Gd3Ir4Sn13 are re-investigated. The magnetization M(T), the specific heat C p ( T ) , and the resistivity ρ ( T ) reveal a double-phase transition—at TN1 ˜ 10 K and at TN2 ˜ 8.8 K—which was not observed in the previous report on this compound. The antiferromagnetic transition is also visible in the thermal transport data, thereby suggesting a close connection between the electronic and lattice degrees of freedom in this Sn-based quasi-skutterudite. The temperature dependence of ρ ( T ) is analyzed in terms of a power-law for resistivity pertinent to Fermi liquid picture. Giant, positive magnetoresistance (MR) ≈ 80% is observed in Gd3Ir4Sn13 at 2 K with the application of 9 T. The giant MR and the double magnetic transition can be attributed to the quasi-cages and layered antiferromagnetic structure of Gd3Ir4Sn13 vulnerable to structural distortions and/or dipolar or spin-reorientation effects. The giant value of MR observed in this class of 3:4:13 type alloys, especially in a Gd-compound, is the highlight of this work.

  15. Canine CD4(+)CD8(+) double-positive T cells can develop from CD4(+) and CD8(+) T cells.

    PubMed

    Bismarck, Doris; Moore, Peter F; Alber, Gottfried; von Buttlar, Heiner

    2014-12-15

    For a long time the expression of the CD4 and CD8 receptor on peripheral blood T cells was thought to be mutually exclusive. However, in canine peripheral blood, similar to other species as swine or human for example, mature CD4(+)CD8(+) double-positive (dp) T cells exist which simultaneously express both surface receptors and have features of activated T cells. Canine CD4(+)CD8(+)dp T cells are heterogeneous and can be divided into three subpopulations by their intensity of CD4 and CD8α expression: CD4(bright)CD8α(bright), CD4(dim)CD8α(bright) and CD4(dim)CD8α(dim). The number of CD4(+)CD8α(+)dp T cells increases after in vitro stimulation of canine peripheral blood mononuclear cells (PBMC) raising the question of their progenitor(s). Thus, the aim of our study was to characterize the progenitor(s) of canine CD4(+)CD8α(+)dp T cells. By cell tracing experiments we identified both CD4(+) single-positive (sp) and also CD8α(+)sp T cells as progenitors of canine CD4(+)CD8α(+)dp T cells after in vitro stimulation. CD4(+)sp T cells almost exclusively upregulate a CD8αα homodimer, whereas CD8α(+)sp T cells can become CD4(+)CD8αβ(+) or CD4(+)CD8αα(+). Even in the absence of other cells, highly purified CD4(+)sp T cells can become double-positive upon in vitro stimulation, whereas highly purified CD8α(+)sp T cells fail to do so. However, CD8α(+)sp T cells can additionally express CD4 when stimulated in the presence of CD4(-)CD8α(-) double-negative (dn) cells or more efficiently when stimulated in the presence of CD4(+)sp T cells. Soluble factors secreted by CD4(+)sp T cells are sufficient for the upregulation of CD4 on CD8α(+)sp T cells, but direct cell-cell contact between CD4(+)sp and CD8α(+)sp T cells is more efficient. mRNA analysis shows that additional CD4 expression on CD8α(+)sp T cells results from de novo synthesis. Thus, uptake of soluble CD4 or trogocytosis is less likely as mechanism for generation of canine double-positive T cells. CD4(+)CD

  16. Shaped electric fields for fast optimal manipulation of electron spin and position in a double quantum dot

    NASA Astrophysics Data System (ADS)

    Budagosky, J. A.; Khomitsky, D. V.; Sherman, E. Ya.; Castro, Alberto

    2016-01-01

    We use quantum optimal control theory algorithms to design external electric fields that drive the coupled spin and orbital dynamics of an electron in a double quantum dot, subject to the spin-orbit coupling and Zeeman magnetic fields. We obtain time profiles of multifrequency electric field pulses which increase the rate of spin-flip transitions by several orders of magnitude in comparison with monochromatic fields, where the spin Rabi oscillations were predicted to be very slow. This precise (with fidelity higher than 1 ×10-4 ) and fast (at the time scale of the order of 0.1 ns, comparable with the Zeeman spin rotation and the interdot tunneling time) simultaneous control of the spin and position is achieved while keeping the electron in the four lowest tunneling- and Zeeman-split levels through the duration of the pulse. The proposed algorithms suggest effective applications in spintronics and quantum information devices.

  17. Celiac Disease-Related Inflammation Is Marked by Reduction of Nkp44/Nkp46-Double Positive Natural Killer Cells

    PubMed Central

    Marafini, Irene; Monteleone, Ivan; Di Fusco, Davide; Sedda, Silvia; Cupi, Maria Laura; Fina, Daniele; Paoluzi, Alessandro Omero; Pallone, Francesco; Monteleone, Giovanni

    2016-01-01

    Introduction and Aim Natural killer (NK) cells are a first line of defence against viruses and down-regulation of NK cell cytotoxic receptors represents one of the strategies by which viruses escape the host’s immune system. Since onset of celiac disease (CD), a gluten-driven enteropathy, has been associated with viral infections, we examined whether CD-associated inflammation is characterized by abnormal distribution of NK cell receptors involved in recognition of viral-infected cells. Materials and Methods Intraepithelial mononuclear cells, isolated from duodenal biopsies of active and inactive CD patients and healthy controls (CTR) and jejunal specimens of obese subjects undergoing gastro-intestinal bypass, were analysed for NK cell markers by flow-cytometry. Expression of granzyme B, interleukin (IL)-22 and tumor necrosis factor (TNF)-α was as assessed in freshly isolated and toll-like receptor (TLR) ligand-stimulated cells. Results The percentages of total NK cells and NKT cells did not significantly differ between CD patients and CTR. In active CD, the fractions of NKp30+ NK cells, NKG2D+ NK cells and NKG2D+ NKT cells were significantly increased as compared to inactive CD patients and CTR. In contrast, CD-associated inflammation was marked by diminished presence of NKG2A+ NK cells and NKG2A+ NKT cells. The fractions of NK cells and NKT cells expressing either NKp44 or NKp46 did not differ between CD and controls, but in CD less NK cells and NKT cells co-expressed these receptors. NKp44/NKp46-double positive cells produced granzyme B and IL-22 but not TNF-α and responded to TLR ligands with enhanced expression of granzyme B. Conclusions These data indicate that active phase of CD associates with reduced presence of NKp44/NKp46-double positive NK cells and NKT cells in the epithelial compartment. PMID:27171408

  18. Curcumin attenuates Mancozeb-induced toxicity in rat thymocytes through mitochondrial survival pathway.

    PubMed

    Pavlovic, Voja; Cekic, Snezana; Ciric, Milan; Krtinic, Dane; Jovanovic, Jelena

    2016-02-01

    The widely used fungicide Mancozeb (Man) has been shown to cause genotoxic effects in rodents and toxicological manifestations in different cells, mainly by altering the antioxidant defense in cells. On the other hand, curcumin (Cur), a natural phenolic compound, is thought to possess anti-inflammatory and antioxidant properties. Here, we investigated the possible protective role of Cur on Man-induced toxicity in rat thymocytes and potential mechanism involved. Rat thymocytes were treated with Man(0.01 μg/ml) and/or increasing Cur(0.3, 1, 3 μM) concentrations and levels of cell viability, apoptosis, mitochondrial membrane potential (MMP),Bcl-2, Bax protein expression, caspase-3 and -9 activity and p38 MAPK signaling involvement were examined. Cells treated with Man displayed increased cell toxicity, hypodiploid cells, caspase-3 and -9 activity, Bax protein expression, followed with decreased MMP and Bcl-2 protein expression. Inhibition of p38 MAPK signaling pathway markedly reduced apoptosis rate and caspase-3 activity in thymocytes exposed to Man. Application of increasing Cur (1, 3 μM) concentrations resulted with significantly reduced cytotoxicity, apoptosis, caspase-3, -9 activity, Bax protein expression, together with increased MMP and Bcl-2 protein expression in rat thymocytes. These result suggest that certain Cur concentrations may mediate Man-induced rat thymocytes toxicity through mitochondrial survival pathway, which may be useful in preventing possible secondary immunological consequences induced by Man. PMID:26763609

  19. Inhibins Tune the Thymocyte Selection Process by Regulating Thymic Stromal Cell Differentiation

    PubMed Central

    Carbajal-Franco, Ebzadrel; de la Fuente-Granada, Marisol; Alemán-Muench, Germán R.; García-Zepeda, Eduardo A.; Soldevila, Gloria

    2015-01-01

    Inhibins and Activins are members of the TGF-β superfamily that regulate the differentiation of several cell types. These ligands were initially identified as hormones that regulate the hypothalamus-pituitary-gonadal axis; however, increasing evidence has demonstrated that they are key regulators in the immune system. We have previously demonstrated that Inhibins are the main Activin ligands expressed in the murine thymus and that they regulate thymocyte differentiation, promoting the DN3-DN4 transition and the selection of SP thymocytes. As Inhibins are mainly produced by thymic stromal cells, which also express Activin receptors and Smad proteins, we hypothesized that Inhibins might play a role in stromal cell differentiation and function. Here, we demonstrate that, in the absence of Inhibins, thymic conventional dendritic cells display reduced levels of MHC Class II (MHCII) and CD86. In addition, the ratio between cTECs and mTECs was affected, indicating that mTEC differentiation was favoured and cTEC diminished in the absence of Inhibins. These changes appeared to impact thymocyte selection leading to a decreased selection of CD4SP thymocytes and increased generation of natural regulatory T cells. These findings demonstrate that Inhibins tune the T cell selection process by regulating both thymocyte and stromal cell differentiation. PMID:25973437

  20. Association of malachite green-positive material with heparan sulfate proteoglycan double tracks in basement membrane of mouse kidney tubules.

    PubMed

    Inoue, S

    1995-03-01

    The presence of lipids in the basement membrane of the mouse kidney tubules was examined by histochemical staining with malachite green. Pieces of mouse kidney cortex were immersed in a fixative containing 3% glutaraldehyde and 0.1% malachite green in 0.067 M sodium cacodylate buffer, pH 6.8, for 18 hr at 4 degrees C. Control tissue was fixed in the same way except that no malachite green was added to the fixative. The tissue pieces were cryoprotected, frozen in Freon 22, and subjected to freeze-substitution in dry acetone containing 1% OsO4. Thin sections of Epon-embedded specimens were observed by electron microscopy at first without uranyl-lead counterstaining. The basement membrane of mouse kidney tubules was positively stained in a pattern composed of an irregular assembly of 5-8-nm wide strands. The nature of these malachite green-positive strands was further examined by counterstaining thin sections with uranyl-lead, and they were identified as 4.5-5-nm wide ribbon-like "double tracks" previously characterized as the form taken by heparan sulfate proteoglycan in basement membranes. It is concluded that lipids are present in the basement membrane of mouse kidney tubules in association with heparan sulfate proteoglycan. PMID:7868858

  1. Relationships among the positive strand and double-strand RNA viruses as viewed through their RNA-dependent RNA polymerases.

    PubMed Central

    Bruenn, J A

    1991-01-01

    The sequences of 50 RNA-dependent RNA polymerases (RDRPs) from 43 positive strand and 7 double strand RNA (dsRNA) viruses have been compared. The alignment permitted calculation of distances among the 50 viruses and a resultant dendrogram based on every amino acid, rather than just those amino acids in the conserved motifs. Remarkably, a large subgroup of these viruses, including vertebrate, plant, and insect viruses, forms a single cluster whose only common characteristic is exploitation of insect hosts or vectors. This similarity may be due to molecular constraints associated with a present and/or past ability to infect insects and/or to common descent from insect viruses. If common descent is important, as it appears to be, all the positive strand RNA viruses of eucaryotes except for the picornaviruses may have evolved from an ancestral dsRNA virus. Viral RDRPs appear to be inherited as modules rather than as portions of single RNA segments, implying that RNA recombination has played an important role in their dissemination. PMID:2014162

  2. HER2-positive double primary tumor of gastric and breast cancer occur synchronously in a patient: A case report

    PubMed Central

    OUYANG, QUCHANG; TIAN, CAN; GAO, JIANXIANG; HUANG, JIN; FU, HUA; HE, JINSONG; YANG, JIANBO

    2016-01-01

    The simultaneous occurrence of primary gastric cancer and breast cancer is rare, and the positive expression of human epidermal growth factor receptor (HER)2 in double primary carcinoma of gastric and breast cancer remains to be reported. The present study presented a 46-year-old woman complaining of irregular acid reflux and stomach discomfort. The stomach cancer was diagnosed by esophagogastroduodenoscopy examination of the pathological biopsies in 2010. The patient underwent a radical gastrectomy for gastric cancer, and postoperative pathological examination revealed moderately-poorly differentiated adenocarcinoma with HER2 positive expression. The tumor invaded into the entire thickness of the gastric wall and lymph nodes. The patient received five treatments of postoperative chemotherapy. In August 2011, the patient felt a lump in the right breast. Simple excision of the right breast mass was performed on September 2011, and postoperative pathological examination revealed the invasive ductal carcinoma of the right breast with HER2 amplification by fluorescent in situ hybridization assay. The patient was treated with postoperative chemotherapy and radiotherapy, and also Trastuzumab target therapy. The patient succumbed to aggressive disease progression in March 2012. PMID:27123269

  3. High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.

    PubMed Central

    Mari, B; Breittmayer, J P; Guerin, S; Belhacene, N; Peyron, J F; Deckert, M; Rossi, B; Auberger, P

    1994-01-01

    Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes. PMID:7959879

  4. Identifying the Spatial Relationships of Thymic Stromal and Thymocyte Subsets by Immunofluorescence Analysis.

    PubMed

    Bain, Virginia; Richie, Ellen R

    2016-01-01

    Immunofluorescence analysis of thymic tissue sections is an indispensable technique for visualizing spatial relationships among thymocyte and stromal cell subsets. The thymus is organized into distinct microenvironmental zones in which particular thymic epithelial cell (TEC) subsets support specific stages of thymocyte maturation. Conversely, thymocytes and lymphoid tissue inducer cells support functional maturation of TECs. The composition and organization of TECs change during ontogeny to generate a maximally functional organ in the young adult. Deterioration of thymic architecture and stromal organization occurs with age as the thymus undergoes involution. Such changes can be monitored by immunofluorescent staining of thymic sections obtained at different ages throughout the life-span. Here we describe methods to generate frozen or paraffin-embedded thymic tissue sections for multicolor immunofluorescence staining using antibodies to surface and/or cytoplasmic antigens. PMID:26294399

  5. Expression of CR2/EBV receptors on human thymocytes detected by monoclonal antibodies.

    PubMed

    Tsoukas, C D; Lambris, J D

    1988-08-01

    The biologic effects of the third component of complement, C3, are mediated via receptors which specifically bind the enzymatic degradation products resulting from the cleavage of C3. One of the products, C3d, has been associated with binding to the second complement receptor CR2 (CD21). This receptor, which is identical to the receptor for Epstein-Barr virus (EBV), has been primarily found on cells of the B lineage, but not on mature T cells or other cells of erythroid or myeloid lineages. In the present investigation, we report the presence of CR2 on human thymocytes. Indirect immunofluorescence analysis employing monoclonal anti-CR2 antibodies revealed a range of thymocyte reactivity from 15% to 63% in thirteen experiments using cells of different donors. Reactivity was always greater with the monoclonal anti-CR2 (CD21) antibody HB-5 than with two other antibodies which recognize distinct epitopes on the CR2 molecule. Two-color immunofluorescence analysis indicated that the brightest of the HB-5-stained thymocytes also reacted with the monoclonal anti-CD1 antibody T6 (immature thymocyte marker) while some of the duller HB-5-staining cells reacted with the monoclonal anti-CD3 antibody Leu-4 (mature thymocyte marker). Immunoprecipitation of CR2 on thymocytes with antibody HB-5 and polyacrylamide gel electrophoretic analysis revealed a protein of 145 kDa molecular mass which is consistent with the size of CR2 found on B lymphocytes. These findings raise several questions regarding the biologic role of CR2-EBV receptor on cells of the T lineage. PMID:2970972

  6. SCL, LMO1 and Notch1 Reprogram Thymocytes into Self-Renewing Cells

    PubMed Central

    Rojas-Sutterlin, Shanti; Herblot, Sabine; Hébert, Josée; Sauvageau, Guy; Lemieux, Sébastien; Lécuyer, Eric; Veiga, Diogo F. T.; Hoang, Trang

    2014-01-01

    The molecular determinants that render specific populations of normal cells susceptible to oncogenic reprogramming into self-renewing cancer stem cells are poorly understood. Here, we exploit T-cell acute lymphoblastic leukemia (T-ALL) as a model to define the critical initiating events in this disease. First, thymocytes that are reprogrammed by the SCL and LMO1 oncogenic transcription factors into self-renewing pre-leukemic stem cells (pre-LSCs) remain non-malignant, as evidenced by their capacities to generate functional T cells. Second, we provide strong genetic evidence that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1. Moreover, LYL1 can substitute for SCL to reprogram thymocytes in concert with LMO1. In contrast, inhibition of E2A was not sufficient to substitute for SCL, indicating that thymocyte reprogramming requires transcription activation by SCL-LMO1. Third, only a specific subset of normal thymic cells, known as DN3 thymocytes, is susceptible to reprogramming. This is because physiological NOTCH1 signals are highest in DN3 cells compared to other thymocyte subsets. Consistent with this, overexpression of a ligand-independent hyperactive NOTCH1 allele in all immature thymocytes is sufficient to sensitize them to SCL-LMO1, thereby increasing the pool of self-renewing cells. Surprisingly, hyperactive NOTCH1 cannot reprogram thymocytes on its own, despite the fact that NOTCH1 is activated by gain of function mutations in more than 55% of T-ALL cases. Rather, elevating NOTCH1 triggers a parallel pathway involving Hes1 and Myc that dramatically enhances the activity of SCL-LMO1 We conclude that the acquisition of self-renewal and the genesis of pre-LSCs from thymocytes with a finite lifespan represent a critical first event in T-ALL. Finally, LYL1 and LMO1 or LMO2 are co-expressed in most human T-ALL samples, except the cortical T subtype. We therefore anticipate that the self-renewal network

  7. SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.

    PubMed

    Gerby, Bastien; Tremblay, Cedric S; Tremblay, Mathieu; Rojas-Sutterlin, Shanti; Herblot, Sabine; Hébert, Josée; Sauvageau, Guy; Lemieux, Sébastien; Lécuyer, Eric; Veiga, Diogo F T; Hoang, Trang

    2014-12-01

    The molecular determinants that render specific populations of normal cells susceptible to oncogenic reprogramming into self-renewing cancer stem cells are poorly understood. Here, we exploit T-cell acute lymphoblastic leukemia (T-ALL) as a model to define the critical initiating events in this disease. First, thymocytes that are reprogrammed by the SCL and LMO1 oncogenic transcription factors into self-renewing pre-leukemic stem cells (pre-LSCs) remain non-malignant, as evidenced by their capacities to generate functional T cells. Second, we provide strong genetic evidence that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1. Moreover, LYL1 can substitute for SCL to reprogram thymocytes in concert with LMO1. In contrast, inhibition of E2A was not sufficient to substitute for SCL, indicating that thymocyte reprogramming requires transcription activation by SCL-LMO1. Third, only a specific subset of normal thymic cells, known as DN3 thymocytes, is susceptible to reprogramming. This is because physiological NOTCH1 signals are highest in DN3 cells compared to other thymocyte subsets. Consistent with this, overexpression of a ligand-independent hyperactive NOTCH1 allele in all immature thymocytes is sufficient to sensitize them to SCL-LMO1, thereby increasing the pool of self-renewing cells. Surprisingly, hyperactive NOTCH1 cannot reprogram thymocytes on its own, despite the fact that NOTCH1 is activated by gain of function mutations in more than 55% of T-ALL cases. Rather, elevating NOTCH1 triggers a parallel pathway involving Hes1 and Myc that dramatically enhances the activity of SCL-LMO1 We conclude that the acquisition of self-renewal and the genesis of pre-LSCs from thymocytes with a finite lifespan represent a critical first event in T-ALL. Finally, LYL1 and LMO1 or LMO2 are co-expressed in most human T-ALL samples, except the cortical T subtype. We therefore anticipate that the self-renewal network

  8. Radical formation in the FMN-photosensitized reactions of unsaturated fatty acids bearing double bonds at different positions.

    PubMed

    Nishihama, Nao; Iwahashi, Hideo

    2016-08-15

    Although the reaction mechanisms through which flavin mononucleotide works as an endogenous photosensitizer have been investigated (Baier et al., 2006; Edwards and Silva, 2001; Pajares et al., 2001; Criado et al., 2003; Massad et al., 2008) [23-27], few studies have been performed for the reactions of flavin mononucleotide with unsaturated fatty acids. To examine the reactions of flavin mononucleotide with unsaturated fatty acids bearing a double bond at different positions, an electron spin resonance, a high performance liquid chromatography-electron spin resonance and a high performance liquid chromatography-electron spin resonance-mass spectrometry were employed. The control reaction mixtures contained 25μmolL(-1) of flavin mononucleotide, 1.0mmolL(-1) of FeSO4(NH4)2SO4, 10mmolL(-1) of cholic acid, 30mmolL(-1) of phosphate buffer (pH 7.4) and 0.1molL(-1) of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone in deuterium oxide. In addition, it also contained 4.3mmolL(-1) of one of the following: (z)-11-octadecenoic acid, (z)-6-octadecenoic acid, (z)-9-octadecenoic acid or (z, z)-9, 12-octadecadienoic acid. The control reaction mixtures without FeSO4(NH4)2SO4 and α-(4-pyridyl-1-oxide)-N-tert-butylnitrone were exposed to the visible light at 436nm (7.8Jcm(-2)). After the irradiation, α-(4-pyridyl-1-oxide)-N-tert-butylnitrone was added. The reactions started from adding FeSO4(NH4)2SO4 and performed at 25°C for 1min. Electron spin resonance measurements of the control reaction mixtures showed prominent signals (α(N)=1.58mT and α(Hβ)=0.26mT). High performance liquid chromatography-electron spin resonance analyses of the control reaction mixtures showed prominent peaks at the retention times of 31.1min {(z)-6-octadecenoic acid}, 39.6min {(z)-9-octadecenoic acid}, 44.9min {(z)-11-octadecenoic acid} and 40.2min {(z, z)-9, 12-octadecadienoic acid}. High performance liquid chromatography-electron spin resonance-mass analyses of the control reaction mixtures showed that 4

  9. Requirement of mitoses for the reversal of X-inactivation in cell hybrids between murine embryonal carcinoma cells and normal female thymocytes

    SciTech Connect

    Takagi, N. )

    1988-04-01

    By means of a 5-bromodeoxyuridine (BrdU) incorporation and acridine orange fluorescence staining method the authors studied reactivation of the inactivated X chromosome (X{sub i}) in newly formed cell hybrids between the near-diploid HPRT-deficient OTF9-63 murine embryonal carcinoma cell (ECC) with an XO sex chromosome constitution and the normal female mouse thymocyte. Synchronization of the late replicating S chromosome in such hybrid cells, indicative of reactivation, was found for the first time on Day 3, and the frequency of reactivation was attained 90% on Day 5. Inhibition of cell cycle progression either by methylglyoxal bis(guanylhydrazone) dihydrochloride, an inhibitor of polyamine metabolism, or by isoleucine-deficient medium after cell fusion delayed reactivation of the X{sub i}, which implied that the number of cell division cycles traversed by individual cells rather than the length of time after cell fusion is critical for the reactivation. Double-labeling experiments using ({sup 3}H)thymidine and BrdU indicated that hybrid cells had undergone three or four mitoses before reactivation of the X{sub i}. Most probably reactivation of the X{sub i} is consequent to reversion of the thymocyte genome to an undifferentiated state under the influence of OTF9 genome. DNA demethylation or dilution of X{sub i}-specific factors by mitoses may be involved in this process.

  10. Standing striations as a series of double layers induced in a positive column by a transverse magnetic field

    SciTech Connect

    Toma, M.; Biborosch, L.; Curteanu, M.

    1995-12-31

    It was experimentally proved that the action of a static transverse magnetic field (TMF) on a cylindrical positive column (PC) can change its internal structure. As a result, a succession of luminous structures known as standing striations are observed. The excitation of striations in a PC (frequently in molecular gases) is usually explained taking into account the periodic changes in ionised rate. It is known that the ionization rate is a strong function of the electron temperature (more precisely, kinetic energy). Thus, the standing striations being the spatial periodic change in the ionization rate, are affected by electron velocity. It can easily observed that in a striated PC there is a periodic change in light intensity. This means that beside ionization processes there is also a periodic change in excitation processes. It was showed that standing striations are, in fact spatial sequences of space charge structures known as double layers (Dls). In the last time it was proved that there is a direct connection between the excitation processes and the ordered spatial arrangement of the electric charges inside the DLs. The aim of this paper is to emphasize that the appearance of standing striations can be adequately described by the model of DL generation in a collisional plasma, that takes into account the electron-neutral excitation processes.

  11. Canine CD4+CD8+ double positive T cells in peripheral blood have features of activated T cells.

    PubMed

    Bismarck, Doris; Schütze, Nicole; Moore, Peter; Büttner, Mathias; Alber, Gottfried; Buttlar, Heiner v

    2012-10-15

    In dogs a CD4(+)CD8(+) double positive T cell subpopulation exists that has not been phenotypically defined yet. We demonstrate that canine CD4(+)CD8(+) T cells are mature CD1a(-) and TCRαβ(+) T cells. To analyse the activation potential of CD4(+)CD8(+) T cells, PBMC from dogs vaccinated against canine distemper virus (CDV) were re-stimulated with CDV. Upon antigen-specific stimulation, the CD4(+)CD8(+) T cell fraction increases and consists nearly exclusively of proliferated cells. Similarly, other features of activated effector/memory T cells such as up-regulation of CD25 and MHC-II as well as down-regulation of CD62L (L-selectin) were observed in CD4(+)CD8(+) T cells after stimulation. Canine CD4(+)CD8(+) T cells are less abundant, but more heterogeneous than porcine ones, comprising a small proportion expressing the β chain of CD8 in addition to the CD8α chain, like human CD4(+)CD8(+) T cells. In summary, this analysis provides the basis for functional characterisation of the in vivo relevance of CD4(+)CD8(+) T cells in T-cell mediated immunity. PMID:22789871

  12. Double Positive CD4CD8 αβ T Cells: A New Tumor-Reactive Population in Human Melanomas

    PubMed Central

    Desfrançois, Juliette; Moreau-Aubry, Agnès; Vignard, Virginie; Godet, Yann; Khammari, Amir; Dréno, Brigitte; Jotereau, Francine; Gervois, Nadine

    2010-01-01

    Background Double positive (DP) CD4CD8 Tαβ cells have been reported in normal individuals as well as in different pathological conditions including inflammatory diseases, viral infections and cancer, but their function remains to be elucidated. We recently reported the increased frequency of DP Tαβ cells in human breast pleural effusions. This manuscript addresses the question of the existence and above all the role of this non-conventional DP sub-population among tumor associated lymphocytes in melanomas. Methodology/Principal Findings We analyzed the intratumoral cell infiltrate in solid metastasis (n = 6) and tumor invaded lymph nodes (n = 26) samples from melanomas patients by multiparametric cytometry. Here we documented for the first time significant increased frequency of DP T cells in about 60% of melanoma tumors compared to blood samples. Interestingly, a high proportion of these cells produced TNF-α in response to autologous melanoma cell lines. Besides, they are characterized by a unique cytokine profile corresponding to higher secretion of IL-13, IL-4 and IL-5 than simple positive T cells. In deep analysis, we derived a representative tumor-reactive DP T cell clone from a melanoma patient's invaded lymph node. This clone was restricted by HLA-A*2402 and recognized both autologous and allogeneic tumor cells of various origins as well as normal cells, suggesting that the target antigen was a ubiquitous self antigen. However, this DP T cell clone failed to kill HLA-A*2402 EBV-transformed B cells, probably due to the constitutive expression of immunoproteasome by these cells. Conclusions/Significance In conclusion, we can postulate that, according to their broad tumor reactivity and to their original cytokine profile, the tumor associated DP T cells could participate in immune responses to tumors in vivo. Therefore, the presence of these cells and their role will be crucial to address in cancer patients, especially in the context of

  13. Fish thymocyte viability, apoptosis and necrosis: In-vitro effects of organochlorine contaminants

    USGS Publications Warehouse

    Sweet, L.I.; Passino-Reader, D. R.; Meier, P.G.; Omann, G.M.

    1998-01-01

    The thymus is believed to be a central component of haematopoiesis and immune function in teleosts. Hence, chemically-elicited adverse effects to the thymus may result in immunomodulation and organ dysfunction. The objective of this research was to assess the levels of active (apoptotic) and passive (necrotic) cell death in untreated and organochlorine treated fish thymocytes. Lake trout (Salvelinus namaycush) thymocytes were challenged with Aroclor 1254 (concentration range 1.5-10.5??g ml-1) and alpha, beta, gamma, delta isomers of hexachlorocyclohexane (concentration range 10-100??M). The resulting maintenance or loss of viability was assessed by cytofluorometry (expression of phosphatidylserine and exclusion of propidium iodide) and confirmed with fluorescence microscopy. The results indicate that 20-60% of thymocytes in healthy fish undergo apoptosis, whereas thymocytes treated for 6-24 h with organochlorines exhibit increased levels of apoptotic cell death. This study demonstrates that given sufficient concentration, contact time and cellular receptors, organochlorines such as Aroclor 1254 and hexachlorocyclohexanes may induce direct or indirect toxicity, altered functionality, or cell death to an organ important for fish immunocompetence. ?? 1998 Academic Press Limited.

  14. CCX-CKR deficiency alters thymic stroma impairing thymocyte development and promoting autoimmunity.

    PubMed

    Bunting, Mark D; Comerford, Iain; Seach, Natalie; Hammett, Maree V; Asquith, Darren L; Körner, Heinrich; Boyd, Richard L; Nibbs, Robert J B; McColl, Shaun R

    2013-01-01

    The atypical chemokine receptor CCX-CKR regulates bioavailability of CCL19, CCL21, and CCL25, homeostatic chemokines that play crucial roles in thymic lymphopoiesis. Deletion of CCX-CKR results in accelerated experimental autoimmunity induced by immunization. Here we show that CCX-CKR deletion also increases incidence of a spontaneous Sjögren's syndrome-like pathology, characterized by lymphocytic infiltrates in salivary glands and liver of CCX-CKR(-/-) mice, suggestive of a defect in self-tolerance when CCX-CKR is deleted. This prompted detailed examination of the thymus in CCX-CKR(-/-) mice. Negatively selected mature SP cells were less abundant in CCX-CKR(-/-) thymi, yet expansion of both DP and immature SP cells was apparent. Deletion of CCX-CKR also profoundly reduced proportions of DN3 thymocyte precursors and caused DN2 cells to accumulate within the medulla. These effects are likely driven by alterations in thymic stroma as CCX-CKR(-/-) mice have fewer cTECs per thymocyte, and cTECs express the highest level of CCX-CKR in the thymus. A profound decrease in CCL25 within the thymic cortex was observed in CCX-CKR(-/-) thymi, likely accounting for their defects in thymocyte distribution and frequency. These findings identify a novel role for CCX-CKR in regulating cTEC biology, which promotes optimal thymocyte development and selection important for self-tolerant adaptive immunity. PMID:23152546

  15. BIM Deficiency Protects NOD Mice From Diabetes by Diverting Thymocytes to Regulatory T Cells.

    PubMed

    Krishnamurthy, Balasubramanian; Chee, Jonathan; Jhala, Gaurang; Trivedi, Prerak; Catterall, Tara; Selck, Claudia; Gurzov, Esteban N; Brodnicki, Thomas C; Graham, Kate L; Wali, Jibran A; Zhan, Yifan; Gray, Daniel; Strasser, Andreas; Allison, Janette; Thomas, Helen E; Kay, Thomas W H

    2015-09-01

    Because regulatory T-cell (Treg) development can be induced by the same agonist self-antigens that induce negative selection, perturbation of apoptosis will affect both negative selection and Treg development. But how the processes of thymocyte deletion versus Treg differentiation bifurcate and their relative importance for tolerance have not been studied in spontaneous organ-specific autoimmune disease. We addressed these questions by removing a critical mediator of thymocyte deletion, BIM, in the NOD mouse model of autoimmune diabetes. Despite substantial defects in the deletion of autoreactive thymocytes, BIM-deficient NOD (NODBim(-/-)) mice developed less insulitis and were protected from diabetes. BIM deficiency did not impair effector T-cell function; however, NODBim(-/-) mice had increased numbers of Tregs, including those specific for proinsulin, in the thymus and peripheral lymphoid tissues. Increased levels of Nur77, CD5, GITR, and phosphorylated IκB-α in thymocytes from NODBim(-/-) mice suggest that autoreactive cells receiving strong T-cell receptor signals that would normally delete them escape apoptosis and are diverted into the Treg pathway. Paradoxically, in the NOD model, reduced thymic deletion ameliorates autoimmune diabetes by increasing Tregs. Thus, modulating apoptosis may be one of the ways to increase antigen-specific Tregs and prevent autoimmune disease. PMID:25948683

  16. TRIBUTYLTIN AND DEXAMETHASONE INDUCE APOPTOSIS IN RAT THYMOCYTES BY MUTUALLY ANTAGONISTIC MECHANISMS

    EPA Science Inventory

    We observed that rat thymocyte cultures exposed to 1.O'- 2. 5 uM tri-n-butyltin methoxide (TBT) exhibiteda rapid time- and concentration-dependent induction of apoptosis, with > 85% of cells exhibiting reduced DNAcontent within 1 hr after ensure to 2.0 - 2,5 uM TBT. Moreover, wit...

  17. Early effects of carbon-ion irradiation on murine lymphocytes and thymocytes

    NASA Astrophysics Data System (ADS)

    Xie, Yi; Zhang, Hong; Dang, Bingrong; Bing, Tao; Hao, Jifang; Guo, Hongyun; Wang, Xiaohu

    To estimate the biological risks from space radiation encountered by cosmonauts in outer space, the effects from whole-body exposure to carbon ions or X-rays irradiations at 0, 0.39, 0.55 and 1 Gy at a dose rate of 0.2 Gy/min were investigated in BALB/c mice. The relative thymus and spleen weights were measured at 24 h after exposure, and the cell cycle distribution and percentage of apoptosis of thymocytes and spleen and peripheral blood lymphocytes were determined by flow cytometry. The data showed that exposure to carbon ions delayed cell progression of peripheral blood lymphocytes in S-phase, and delayed thymocytes and spleen lymphocytes in G 0/G 1-phase. Apoptosis of thymocytes and peripheral blood lymphocytes induced by carbon ions increased more rapidly with dose than was the case for X-rays. There were some differences between the relative weight loss of the thymus and the spleen with increasing dose of either carbon ions or X-rays. The results obtained provide evidence of dose- and organ-specific differences induced by carbon ions compared to X-rays, with increased apoptosis in peripheral blood lymphocytes and thymocytes, but not spleen lymphocytes. Our data may suggest that further work would be of interest to estimate risk of changes in immune function during particle radiation exposures in space travel.

  18. Increased Leptin Response and Inhibition of Apoptosis in Thymocytes of Young Rats Offspring from Protein Deprived Dams during Lactation

    PubMed Central

    da Silva, Simone Vargas; Salama, Carolina; Renovato-Martins, Mariana; Helal-Neto, Edward; Citelli, Marta; Savino, Wilson; Barja-Fidalgo, Christina

    2013-01-01

    We investigated the consequences of mild maternal malnutrition in rat dams, in terms of thymocyte responses and the putative role of leptin. The young progeny of dams submitted to protein deprivation (PD) during lactation showed at 30 days of age lower body and thymus weights, significant alterations in CD4/CD8-defined T cell subsets without modifications in total thymocyte number as well as in proliferative response. Despite, the rats from PD group did not present alterations in leptin circulating levels, the expression of leptin receptor ObRb was enhanced in their thymocytes. This change was accompanied by an increase in leptin signaling response of thymocytes from PD rats, with an increase in JAK2 and STAT3 phosphorylation after leptin stimulation. Thymocytes from PD rats also presented a decreased rate of spontaneous apoptosis when compared to controls. Accordingly, higher expression of anti-apoptotic protein Bcl-2, and lower of pro-apoptotic protein Bax, with no change of pro-apoptotic Bad, and higher pro-caspase 3 content were detected in PD thymocytes. Moreover, thymocytes from PD group exhibited a constitutive higher nuclear content of p65 NF-kB associated to a lower IkB content in the cytoplasm. Finally, although there was no change in ob gene expression in PD thymocytes, a higher mRNA expression for the Ob gene was observed in the thymic microenvironment from PD animals. Taken together, the results show that mild maternal protein deprivation during lactation affects thymic homeostasis, enhancing leptin activity, which in turn protects thymocytes from apoptosis in the young progeny, with possible consequences upon the immune response of these animals in adult life. PMID:23675529

  19. Analysis of crutch position in the horizontal plane to confirm the stability of the axillary pad for safe double-crutch walking

    PubMed Central

    Nagasaki, Takayuki; Katoh, Hiroshi; Arizono, Hisashi; Chijimatsu, Hikaru; Chijiwa, Naoki; Onda, Takaaki; Wada, Chikamune

    2016-01-01

    [Purpose] The aim of this study was to analyze the crutch position in the horizontal plane to confirm the stability of the axillary pad during double-crutch walking. [Subjects] Twelve healthy young subjects (6 males and 6 females). [Methods] The subjects were asked to walk in a straight line, using double crutches, for a distance of 5 m, 5 times. Crutch position data were obtained using four infrared reflective markers attached to both crutches (two markers each on both crutches). The crutch angles of each subject were compared across three time points during the crutch stance phase (crutch contact, mid stance, and crutch off). [Results] Crutch angles of each of the two crutches were significantly different across the crutch stance phase of 11 of the 12 subjects. Phasic differences were shown by 4 of the 12 subjects, and a strong correlation was observed between the left and right crutch angles of all subjects. [Conclusion] External rotation of the crutch throughout the stance phase was very important for keeping the axillary pad in the axilla, not only for single-crutch walking, but also for double-crutch walking. In addition, symmetry of the crutch positioning is one of the most important factors for safe double-crutch walking. PMID:27313346

  20. Evaluating the Safety of Retroviral Vectors Based on Insertional Oncogene Activation and Blocked Differentiation in Cultured Thymocytes

    PubMed Central

    Zhou, Sheng; Fatima, Soghra; Ma, Zhijun; Wang, Yong-Dong; Lu, Taihe; Janke, Laura J; Du, Yang; Sorrentino, Brian P

    2016-01-01

    Insertional oncogenesis due to retroviral (RV) vector integration has caused recurrent leukemia in multiple gene therapy trials, predominantly due to vector integration effects at the LMO2 locus. While currently available preclinical safety models have been used for evaluating vector safety, none have predicted or reproduced the recurrent LMO2 integrations seen in previous X-linked severe combined immunodeficiency (X-SCID) and Wiskott–Aldrich clinical gene therapy trials. We now describe a new assay for assessing vector safety that recapitulates naturally occurring insertions into Lmo2 and other T-cell proto-oncogenes leading to a preleukemic developmental arrest in primary murine thymocytes cultured in vitro. This assay was used to compare the relative oncogenic potential of a variety of gamma-RV and lentiviral vectors and to assess the risk conferred by various transcriptional elements contained in these genomes. Gamma-RV vectors that contained full viral long-terminal repeats were most prone to causing double negative 2 (DN2) arrest and led to repeated cases of Lmo2 pathway activation, while lentiviral vectors containing these same elements were significantly less prone to activate proto-oncogenes or cause DN2 arrest. This work provides a new preclinical assay that is especially relevant for assessing safety in SCID disorders and provides a new tool for designing safer RV vectors. PMID:26957223

  1. Effects of irradiation, glucocorticoid and FK506 on cell-surface antigen expression by rat thymocytes: a three-colour flow cytofluorometric analysis.

    PubMed Central

    Tsuchida, M; Konishi, M; Takai, K; Naito, K; Fujikura, Y; Fukumoto, T

    1994-01-01

    The expression of T-cell antigen receptor (TCR) alpha beta was investigated in rat CD4- CD8- thymocytes during thymic reconstitution after the exposure of animals to irradiation or glucocorticoid. The effect of the immunosuppressant FK506 on the expression of TCR alpha beta in rat CD4- CD8- thymocytes was also examined. The percentage of CD4- CD8- thymocytes constituted 2.6% of total thymocytes and that of CD4- CD8- TCR alpha beta high cells constituted 12.6% of CD4- CD8- thymocytes in normal adult Lewis rats. The percentage of CD4- CD8- TCR alpha beta high cells increased during thymic reconstitution after irradiation, and maximally constituted 28.6% of CD4- CD8- thymocytes on day 7. Similar results were obtained during thymic reconstitution after glucocorticoid treatment. In contrast, continuous treatment with FK506 for 7 days markedly decreased not only the percentages of CD4+ CD8- TCR alpha beta high and CD4- CD8+ TCR alpha beta high thymocytes, but also that of CD4- CD8- TCR alpha beta high thymocytes. These results indicate that rat CD4- CD8- thymocytes contain a subpopulation of mature (TCR alpha beta high) cells. The possible implications of the existence of this subpopulation with regard to thymocyte differentiation and maturation are discussed. PMID:7530693

  2. [Generation of active oxygen forms in rat thymocytes under action of hydrogen peroxide and fullerene C60].

    PubMed

    Hrebinyk, S M; Hryniuk, I I; Pryluts'ka, S V; Matyshevs'ka, O P

    2012-01-01

    The dynamics of active oxygen forms (AOF) generation in rat thymocytes 50 min after treatment with 0.1 and 0.5 mM H2O2 was estimated with the use of fluorescent probe DCFDA. Both enhanced AOF generation, which was dependent on H2O2 concentration, and glutathione peroxidase and superoxide dismutase activation, followed by a decrease of thymocytes viability were demonstrated. Preincubation of cells with 10(-5) M fullerene C60 was shown not only to prevent H2O2--induced AOF generation but to increase viability of H2O2-treated thymocytes at more prolonged time period. The data obtained indicate to fullerene C60 ability to prevent oxidative stress in thymocytes. PMID:22642121

  3. Peroxynitrite-induced thymocyte apoptosis: the role of caspases and poly (ADP-ribose) synthetase (PARS) activation.

    PubMed Central

    Virág, L; Scott, G S; Cuzzocrea, S; Marmer, D; Salzman, A L; Szabó, C

    1998-01-01

    The mechanisms by which immature thymocyte apoptosis is induced during negative selection are poorly defined. Reports demonstrated that cross-linking of T-cell receptor leads to stromal cell activation, expression of inducible nitric oxide synthase (iNOS) and, subsequently, to thymocyte apoptosis. Therefore we examined, whether NO directly or indirectly, through peroxynitrite formation, causes thymocyte apoptosis. Immuno-histochemical detection of nitrotyrosine revealed in vivo peroxynitrite formation in the thymi of naive mice. Nitrotyrosine, the footprint of peroxynitrite, was predominantly found in the corticomedullary junction and the medulla of naive mice. In the thymi of mice deficient in the inducible isoform of nitric oxide synthase, considerably less nitrotyrosine was found. Exposure of thymocytes in vitro to low concentrations (10 microM) of peroxynitrite led to apoptosis, whereas higher concentrations (50 microM) resulted in intense cell death with the characteristics of necrosis. We also investigated the effect of poly (ADP-ribose) synthetase (PARS) inhibition on thymocyte apoptosis. Using the PARS inhibitor 3-aminobenzamide (3-AB), or thymocytes from PARS-deficient animals, we established that PARS determines the fate of thymocyte death. Suppression of cellular ATP levels, and the cellular necrosis in response to peroxynitrite were prevented by PARS inhibition. Therefore, in the absence of PARS, cells are diverted towards the pathway of apoptotic cell death. Similar results were obtained with H2O2 treatment, while apoptosis induced by non-oxidative stimuli such as dexamethasone or anti-FAS antibody was unaffected by PARS inhibition. In conclusion, we propose that peroxynitrite-induced apoptosis may play a role in the process of thymocyte negative selection. Furthermore, we propose that the physiological role of PARS cleavage by apopain during apoptosis may serve as an energy-conserving step, enabling the cell to complete the process of apoptosis

  4. Comparison of cerebral glucose metabolic rates measured with fluorodeoxyglucose and glucose labeled in the 1, 2, 3-4, and 6 positions using double label quantitative digital autoradiography

    SciTech Connect

    Lear, J.L.; Ackermann, R.F.

    1988-08-01

    We compared local cerebral glucose metabolic rates (LCMRglu) that were determined with (/sup 18/F)fluorodeoxyglucose (FDG) and (/sup 14/C)glucose labeled in the 1, 2, 3-4, and 6 positions. Double label digital autoradiography was used with published kinetic models to determine LCMRglu for FDG and glucose in the same animals. Glucose showed metabolic rate dependent underestimation of LCMRglu compared to FDG, which worsened with increasing experimental times. The least underestimation occurred with glucose labeled in the 6 position at 6 min, reaching 10% in areas of high metabolism. Labeling in the 1 position, the 2 position and the 3-4 position caused progressively worse underestimation at all times. In addition, some structures showed differences not directly related to metabolic rate, indicating regional variations in relationships between individual kinetic constants of FDG and glucose.

  5. Simultaneous spatial and angular positioning of plane specular samples by a novel double beam triangulation probe with full auto-compensation

    NASA Astrophysics Data System (ADS)

    Makai, Janos P.

    2016-02-01

    The positioning of a plane specular sample to be measured or processed is an important requirement in many fields of research and industry. Where a sample is to be processed either by electromagnetic waves or a particle beam of higher numerical aperture the irradiance or the particle number over unit area is position and angle dependent. Where optical properties of a sample are to be measured, such as in spectrophotometry, these parameters can depend on the angle of incidence and on the value of the irradiance, i.e. on the angular and spatial position of the sample. In some cases parameters of many samples have to be compared among each other or to those of a standard, this also requires the highly accurate positioning of each sample to the same position. This paper describes a method that is suitable for high accuracy alignment of specular plane samples both angularly and spatially. It applies a double beam triangulation probe, where the second beam serves not only as a reference beam to compensate for any changes of the transmitting media and that of the laser but also doubles the sensitivity of the probe. The method does not compete with interferometric methods, it is required only in special applications, but provides an absolute uncertainty for spatial positioning in the sub-micrometer range and an angular one in the 0.0003° range. Furthermore, the accuracy is tunable by the parameters of the setup.

  6. Sequential appearance of thymocyte subpopulations and T cell antigen receptor gene messages in the mouse thymus after sublethal irradiation

    SciTech Connect

    Tomooka, S.; Matsuzaki, G.; Kishihara, K.; Tanaka, K.; Yoshikai, Y.; Taniguchi, K.; Himeno, K.; Nomoto, K.

    1987-12-15

    The sequential differentiation patterns of thymocyte were observed with cell surface phenotypes and the expression of T cell antigen receptor in 800 rad irradiated adult mice. Thymus was severely reduced in size and cell number by day 5 after whole body irradiation and rapidly recovered from day 7 to day 14. Surface marker analysis on day 5 after irradiation showed thymocytes with Thy-1low L3T4+/Lyt-2- dominantly existed and suggested that these cells were radioresistant-survived cells. On the other hand, thymocytes on day 7 were composed of a large number of Thy-1high L3T4+/Lyt-2+ blast-like cells and a relatively high proportion of Thy-1high L3T4-/Lyt-2- cells which expressed a large amount of gamma-chain gene messages but scarcely any alpha- and beta-chain gene messages similar to the fetal thymocytes. On day 14, thymocytes were composed mostly of Thy-1high H-2low L3T4+/Lyt-2+ subpopulation which expressed a remarkably low level of gamma-chain gene messages, and high levels of alpha- and beta-chain transcripts analogous to those of normal adult thymus. Taken together, intrathymic radioresistent stem cells for T thymocytes seem to proliferate and differentiate after irradiation with the same pattern as was seen in a fetal thymus development.

  7. Cytotoxic actions of FTY720, a novel immunosuppressant, on thymocytes and brain neurons dissociated from the rat.

    PubMed

    Oyama, Y; Chikahisa, L; Kanemaru, K; Nakata, M; Noguchi, S; Nagano, T; Okazaki, E; Hirata, A

    1998-04-01

    Effects of FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol HCl), a novel immunosuppressant, were examined on neurons and thymocytes respectively dissociated from rat brains and thymus glands using a flow cytometer to see if FTY720 exerts cytotoxic actions not only on spleen cells as previously reported but also on the other cells. FTY720 at a concentration of 10 microM deteriorated almost all of the thymocytes, while it was not the case for brain neurons. FTY720 increased the intracellular concentration of Ca2+ ([Ca2+]i) of thymocytes in both the presence and absence of external Ca2+, although the [Ca2+]i increased by FTY720 in the presence of external Ca2+ was much greater than that in the absence of external Ca2+. Thus, FTY720 may increase the membrane permeability of Ca2+ and release Ca2+ from intracellular Ca2+ stores in thymocytes. Furthermore, the number of thymocytes stained with ethidium, a dye impermeant to intact membranes, time-dependently increased after drug application. Therefore, FTY720 at concentrations of 3 - 10 microM non-specifically increases the membrane permeability of thymocytes, resulting in necrotic cell death, although FTY720 at micromolar concentrations was reported to induce apoptosis of spleen cells. PMID:9623716

  8. Haploidentical stem cell transplantation: anti-thymocyte globulin-based experience.

    PubMed

    Chang, Ying-Jun; Huang, Xiao-Jun

    2016-04-01

    Haploidentical stem cell transplantation (haplo-SCT) with an anti-thymocyte globulin (ATG) preparative regimen is associated with induced immune tolerance, rapid hematopoietic recovery, effective prevention of graft-versus-host disease (GVHD), and lower non-relapse mortality (NRM). This has become a common and successfully applied protocol in patients with hematological diseases undergoing haplo-SCT. Survival rates among patients who undergo unmanipulated haploidentical blood and marrow transplantation (HBMT) with anti-thymocyte globulin (ATG)-based regimens are comparable to those following human leukocyte antigen (HLA)-matched sibling transplantation or unrelated donor transplantation. Unmanipulated HBMT can also be successfully used as a post-remission treatment algorithm for acute lymphoblastic leukemia (ALL) and adult acute myeloid leukemia (AML) in cases with unfavorable cytogenetics. Future investigations should focus on further improving donor selection, optimizing allografts, dealing with primary graft failure, and relapse prophylaxis and treatment. PMID:27000731

  9. Immunomodulation with rabbit anti-thymocyte globulin in solid organ transplantation.

    PubMed

    Ippoliti, Giovanbattista; Lucioni, Marco; Leonardi, Giuseppe; Paulli, Marco

    2015-12-24

    Rabbit anti-thymocyte globulin's manifold mechanisms of action may be attribuited to its polyclonal nature. Its T-cell depleting effect on lymphoid cells is well established: Occurring in the blood and secondary lymphoid tissues, depletion proceeds through complement-dependent lysis, opsonization and apoptotic pathways. Clinical studies have shown that rabbit anti-thymocyte globulin's immunomodulatory effect extends beyond the initial T-cell depletion and up to the period during which lymphocyte populations begin to recover. The drug is able to mediate immunomodulation and graft tolerance by functionally inactivating cell surface receptors involved in antigen recognition, leukocyte trafficking and leukocyte endothelium adhesion. The complex and prolonged immunomodulation induced by this drug contributes to its efficacy in solid organ transplantation, mainly by reducing the incidence of acute graft rejection. PMID:26722653

  10. Immunomodulation with rabbit anti-thymocyte globulin in solid organ transplantation

    PubMed Central

    Ippoliti, Giovanbattista; Lucioni, Marco; Leonardi, Giuseppe; Paulli, Marco

    2015-01-01

    Rabbit anti-thymocyte globulin’s manifold mechanisms of action may be attribuited to its polyclonal nature. Its T-cell depleting effect on lymphoid cells is well established: Occurring in the blood and secondary lymphoid tissues, depletion proceeds through complement-dependent lysis, opsonization and apoptotic pathways. Clinical studies have shown that rabbit anti-thymocyte globulin’s immunomodulatory effect extends beyond the initial T-cell depletion and up to the period during which lymphocyte populations begin to recover. The drug is able to mediate immunomodulation and graft tolerance by functionally inactivating cell surface receptors involved in antigen recognition, leukocyte trafficking and leukocyte endothelium adhesion. The complex and prolonged immunomodulation induced by this drug contributes to its efficacy in solid organ transplantation, mainly by reducing the incidence of acute graft rejection. PMID:26722653

  11. Isolation of the receptor for Amaranthus leucocarpus lectin from murine naive thymocytes.

    PubMed

    Porras, F; Lascurain, R; Chávez, R; Ortiz, B; Hernández, P; Debray, H; Zenteno, E

    2000-05-01

    From murine medullary thymocytes we purified the receptor for the Amaranthus leucocarpus lectin (ALL) using a complex with the biotin-labeled lectin and avidin-agarose as the affinity matrix. Most ALL(+)thymocytes (83%) are naive cells with the CD4(+)CD8(-)CD45RB(+)phenotype. The receptor for this lectin is a 70 kDa glycoprotein that contains 20% of sugar by mass. It is constituted mainly by aspartic and glutamic acids, serine, proline, and glycine; its glycosidic portion contains mainly O-glycosidically linked glycans with Gal, GalNAc and NeuAc residues as well as one N-glycosidically linked glycan per molecule. Ionic strength chromatography revealed that the ALL-thymocyte receptor (ALLTr) is made up by three isoforms, which possess similar amino acid composition but show slight differences in their sugar composition. The N-terminal amino acid residues are blocked both in the receptor and its purified isoforms. Analyses of the receptor's peptides, obtained by trypsin digestion with MALDI-TOF (matrix assisted laser desorption ionization-time of flight), were compared with the relative values obtained from the NCBInr (Swiss-Prot 10/01/99) database. Our results indicate that the peptides of ALLTr show low homology (<17%) with the human KIIA protein, the Fas-associated death domain protein, and the transforming growth factor-beta type II receptor. Our results suggest that the ALL thymocyte receptor could be considered a novel phenotypic marker specific for naive T cells. PMID:10764834

  12. beta. -endorphin modulation of mitogen-stimulated calcium uptake by rat thymocytes

    SciTech Connect

    Hemmick, L.M.; Bidlack, J.M.

    1987-10-19

    Lymphocytes stimulated by mitogens or antigens exhibit an enhanced calcium uptake early in the proliferation or activation response. Modulation of this calcium uptake results in alterations of proliferation and immunocompetence. ..beta..-endorphin and other opioids affect several parameters of lymphocyte competence. Limited data are available concerning the mechanism(s) of these effects. This study examines whether a possible opioid mechanism is the modification of the early calcium influx into stimulated lymphocytes. The time course of both concanavalin A (Con A) and phytohemagglutinin (PHA)-stimulated /sup 45/Ca/sup 2 +/ uptake into thymocytes was characterized to determine the optimal time for testing the effects of opioids. BETA-Endorphin 1-31 significantly enhanced Con A-stimulated /sup 45/Ca/sup 2 +/ uptake into rat thymocytes. This peptide had no significant effect on PHA-simulated /sup 45/Ca/sup 2 +/ uptake or on basal thymocyte /sup 45/Ca/sup 2 +/ flux. The ..beta../sub h/-endorphin stimulatory effect was titratable in the range of 0.1 nM to 10 ..mu..M. Naloxone did not reverse the enhancement. Met-enkephalinamide and other opioid agonists did not duplicate the stimulatory effect. Thus, the ..beta../sub h/-endorphin 1-31 enhancement of Con A-stimulated /sup 45/Ca/sup 2 +/ uptake by rat thymocytes does not operate via classical opioid receptor mechanisms. ..beta../sub h/-endorphin 1-31 appears to be acting on a subset of T cells that are responsive to Con A but not to PHA. 30 references, 4 figures, 1 table.

  13. The preparation and immunosuppressive properties of equine antihuman thymocyte membrane immunoglobulin G.

    PubMed

    Diethelm, A G; Chambers, L; Sachs, G; Balch, C M; Phillips, S J; Thiry, C

    1979-02-01

    Human thymocytes separated by a Ficoll gradient produced a cell population that was 99% pure thymocytes and free of platelets, leukocytes, and epithelial cells. These cells, disrupted by a nitrogen bomb, produced a membrane-ribosome antigen fraction confirmed by enzyme analysis. Equine antithymocyte membrane-immunoglobulin G (ATM-IgC) prepared against this antigen in four of five horses contained immunosuppressive properties capable of prolonging monkey skin allograft survival longer than 21 days. No adverse effects were noted by the intramuscular and intravenous administration of this antisera to primates, and autopsy examination showed marked depletion of paracortical lymphocytes in the spleen and mesenteric lymph nodes. A moderate thrombocytopenia occurred during a 4 hour intravenous administration of ATM-IgG to primates with a marked decrease in the peripheral lymphocyte count. The deposition of ATM-IgG upon monkey glomerular basement membrane could not be demonstrated by immunofluorescent techniques. The specificity of this globulin to contain anti-T-cell antibody was confirmed by an immunofluorescent assay in that ATM-IgG reacted with both human thymocytes and peripheral blood thymus-dependent cells, but was nonreactive when tested against a panel of human cells free of thymus-dependent antigens. PMID:105416

  14. Mysm1 is required for interferon regulatory factor expression in maintaining HSC quiescence and thymocyte development.

    PubMed

    Huang, X F; Nandakumar, V; Tumurkhuu, G; Wang, T; Jiang, X; Hong, B; Jones, L; Won, H; Yoshii, H; Ozato, K; Masumi, A; Chen, S-Y

    2016-01-01

    Mysm1(-/-) mice have severely decreased cellularity in hematopoietic organs. We previously revealed that Mysm1 knockout impairs self-renewal and lineage reconstitution of HSCs by abolishing the recruitment of key transcriptional factors to the Gfi-1 locus, an intrinsic regulator of HSC function. The present study further defines a large LSKs in >8-week-old Mysm1(-/-) mice that exhibit increased proliferation and reduced cell lineage differentiation compared with those of WT LSKs. We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at lower levels in Mysm1(-/-) HSCs, and Mysm1 enhanced function of the IRF2 and IRF8 promoters, suggesting that Mysm1 governs the IRFs for HSC homeostasis. We further found that the lower expressions of IRF2 and IRF8 led to an enhanced transcription of p53 in Mysm1(-/-) HSCs, which was recently defined to have an important role in mediating Mysm1(-/-)-associated defects. The study also revealed that Mysm1(-/-) thymocytes exhibited lower IRF2 expression, but had higher Sca1 expression, which has a role in mediating thymocyte death. Furthermore, we found that the thymocytes from B16 melanoma-bearing mice, which display severe thymus atrophy at late tumor stages, exhibited reduced Mysm1 and IRF2 expression but enhanced Sca1 expression, suggesting that tumors may downregulate Mysm1 and IRF2 for thymic T-cell elimination. PMID:27277682

  15. Natural hidden antibodies reacting with DNA or cardiolipin bind to thymocytes and evoke their death.

    PubMed

    Zamulaeva, I A; Lekakh, I V; Kiseleva, V I; Gabai, V L; Saenko, A S; Shevchenko, A S; Poverenny, A M

    1997-08-18

    Both free and hidden natural antibodies to DNA or cardiolipin were obtained from immunoglobulins of a normal donor. The free antibodies reacting with DNA or cardiolipin were isolated by means of affinity chromatography. Antibodies occurring in an hidden state were disengaged from the depleted immunoglobulins by ion-exchange chromatography and were then affinity-isolated on DNA or cardiolipin sorbents. We used flow cytometry to study the ability of free and hidden antibodies to bind to rat thymocytes. Simultaneously, plasma membrane integrity was tested by propidium iodide (PI) exclusion. The hidden antibodies reacted with 65.2 +/- 10.9% of the thymocytes and caused a fast plasma membrane disruption. Cells (28.7 +/- 7.1%) were stained with PI after incubation with the hidden antibodies for 1 h. The free antibodies bound to a very small fraction of the thymocytes and did not evoke death as compared to control without antibodies. The possible reason for the observed effects is difference in reactivity of the free and hidden antibodies to phospholipids. While free antibodies reacted preferentially with phosphotidylcholine, hidden antibodies reacted with cardiolipin and phosphotidylserine. PMID:9280287

  16. Transcriptomics analysis of primary mouse thymocytes exposed to bis(tri-n-butyltin)dioxide (TBTO).

    PubMed

    van Kol, Sandra W M; Hendriksen, Peter J M; van Loveren, Henk; Peijnenburg, Ad

    2012-06-14

    The biocide bis(tri-n-butyltin)oxide (TBTO) causes thymus atrophy in rodents and is toxic to many cell types of which thymocytes are the most sensitive. To obtain insight in the mechanisms of action of TBTO, we exposed primary mouse thymocytes in vitro for 3, 6 and 11 h to 0.1, 0.5, 1 and 2 μM TBTO. Subsequently, the cells were subjected to whole-genome gene expression profiling. Biological interpretation of the gene expression data revealed that TBTO affects a wide range of processes. Cell proliferation related genes were downregulated by all treatments except for 3 and 6 h 0.5 μM TBTO which upregulated these genes. Treatment with TBTO resulted in upregulation of genes involved in endoplasmatic reticulum (ER) stress, NFkB and TNFα pathways, and genes involved in DNA damage, p53 signaling and apoptosis. Remarkably, TBTO also increased the expression of genes that are known to be upregulated during T cell activation or during negative selection of thymocytes. The effect of TBTO on expression of genes involved in ER stress and apoptosis was confirmed by qPCR. Induction of the T cell activation response was corroborated by demonstrating that TBTO exposure resulted in translocation of NFAT to the nucleus, which is an essential event for T cell activation. PMID:22434021

  17. Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation

    PubMed Central

    Lee, Jae Geun; Lee, Juhan; Lee, Jung Jun; Song, Seung Hwan; Ju, Man Ki; Choi, Gi Hong; Kim, Myoung Soo; Choi, Jin Sub; Kim, Soon Il; Joo, Dong Jin

    2016-01-01

    Abstract Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child–Turcotte–Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients’ median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver

  18. Efficacy of rabbit anti-thymocyte globulin for steroid-resistant acute rejection after liver transplantation.

    PubMed

    Lee, Jae Geun; Lee, Juhan; Lee, Jung Jun; Song, Seung Hwan; Ju, Man Ki; Choi, Gi Hong; Kim, Myoung Soo; Choi, Jin Sub; Kim, Soon Il; Joo, Dong Jin

    2016-06-01

    Acute cellular rejection after liver transplantation (LT) can be treated with steroid pulse therapy, but there is no ideal treatment for steroid-resistant acute rejection (SRAR). We aimed to determine the feasibility and potential complications of rabbit anti-thymocyte globulin (rATG) application to treat SRAR in liver transplant recipients. We retrospectively reviewed medical records of 429 recipients who underwent LT at Severance Hospital between January 2010 and March 2015. We compared clinical features and graft survival between patients with steroid-sensitive acute rejection (SSAR; n = 23) and SRAR (n = 11). We also analyzed complications and changes in laboratory findings after 2.5 mg/kg rATG treatment in patients with SRAR for 6 to 10 days. There were no significant differences in gender, age, model for end-stage liver disease score, Child-Turcotte-Pugh score, or original liver diseases between patients with SSAR and SRAR, although deceased donors were more frequently associated with the SRAR group (P = 0.004). All SRAR patients responded positively to rATG treatment; after treatment, the patients' median AST levels decreased from 138 to 63 IU/L, and their median ALT levels dropped from 327 to 70 IU/L 1 day after rATG treatment (P = 0.022 and 0.017, respectively). Median aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin levels significantly decreased 1 month post-treatment (P = 0.038, 0.004, and 0.041, respectively). Median survival after LT was 23 months, and median survival after rATG was 22 months in patients with SRAR. Adverse effects included hepatitis C virus (HCV) reactivation, fungemia, and cytomegalovirus (CMV) infection. Nine SRAR patients survived with healthy liver function, 1 died from a traffic accident during follow-up, and 1 died from graft-versus-host disease and fungemia. Administration of rATG is an effective therapeutic option for SRAR with acceptable complications in liver transplant recipients

  19. Double outlet right ventricle with L-position of the aorta, D-loop, subaortic VSD, and pulmonary stenosis.

    PubMed Central

    Caffarena, J M; Sanchez, F G; Concha, M; Gomez-Ullate, J M; Peris, J J; Frias, R; Otero, E; Ferrer, H; Montero, A

    1976-01-01

    We describe a case of double outlet right ventricle with subaortic ventricular septal defect and pulmonary stenosis treated successfully with cardiopulmonary bypass. We consider the clinical history and angiocardiographic and surgical findings of this rare anomaly. We stress the difficulties of reconstruction of the outflow tract of the right ventricle, because of the anomalous pathway of the right coronary artery, the posterior situation of the pulmonary artery, and the abnormal anatomy present in the outflow tract of the right ventricle. Images PMID:996822

  20. Localization of Fatty Acyl and Double Bond Positions in Phosphatidylcholines Using a Dual Stage CID Fragmentation Coupled with Ion Mobility Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Castro-Perez, Jose; Roddy, Thomas P.; Nibbering, Nico M. M.; Shah, Vinit; McLaren, David G.; Previs, Stephen; Attygalle, Athula B.; Herath, Kithsiri; Chen, Zhu; Wang, Sheng-Ping; Mitnaul, Lyndon; Hubbard, Brian K.; Vreeken, Rob J.; Johns, Douglas G.; Hankemeier, Thomas

    2011-09-01

    A high content molecular fragmentation for the analysis of phosphatidylcholines (PC) was achieved utilizing a two-stage [trap (first generation fragmentation) and transfer (second generation fragmentation)] collision-induced dissociation (CID) in combination with travelling-wave ion mobility spectrometry (TWIMS). The novel aspects of this work reside in the fact that a TWIMS arrangement was used to obtain a high level structural information including location of fatty acyl substituents and double bonds for PCs in plasma, and the presence of alkali metal adduct ions such as [M + Li]+ was not required to obtain double bond positions. Elemental compositions for fragment ions were confirmed by accurate mass measurements. A very specific first generation fragment ion m/z 577 (M-phosphoryl choline) from the PC [16:0/18:1 (9Z)] was produced, which by further CID generated acylium ions containing either the fatty acyl 16:0 (C15H31CO+, m/z 239) or 18:1 (9Z) (C17H33CO+, m/z 265) substituent. Subsequent water loss from these acylium ions was key in producing hydrocarbon fragment ions mainly from the α-proximal position of the carbonyl group such as the hydrocarbon ion m/z 67 (+H2C-HC = CH-CH = CH2). Formation of these ions was of important significance for determining double bonds in the fatty acyl chains. In addition to this, and with the aid of 13C labeled lyso-phosphatidylcholine (LPC) 18:1 (9Z) in the ω-position (methyl) TAP fragmentation produced the ion at m/z 57. And was proven to be derived from the α-proximal (carboxylate) or distant ω-position (methyl) in the LPC.

  1. Position and flux stabilization of X-ray beams produced by double-crystal monochromators for EXAFS scans at the titanium K-edge.

    PubMed

    van Silfhout, Roelof; Kachatkou, Anton; Groppo, Elena; Lamberti, Carlo; Bras, Wim

    2014-03-01

    The simultaneous and active feedback stabilization of X-ray beam position and monochromatic beam flux during EXAFS scans at the titanium K-edge as produced by a double-crystal monochromator beamline is reported. The feedback is generated using two independent feedback loops using separate beam flux and position measurements. The flux is stabilized using a fast extremum-searching algorithm that is insensitive to changes in the synchrotron ring current and energy-dependent monochromator output. Corrections of beam height are made using an innovative transmissive beam position monitor instrument. The efficacy of the feedback stabilization method is demonstrated by comparing the measurements of EXAFS spectra on inhomogeneous diluted Ti-containing samples with and without feedback applied. PMID:24562562

  2. Collision-Induced Dissociation of Fatty Acid [M - 2H + Na]- Ions: Charge-Directed Fragmentation and Assignment of Double Bond Position

    NASA Astrophysics Data System (ADS)

    Thomas, Michael C.; Altvater, Jens; Gallagher, Thomas J.; Nette, Geoffrey W.

    2014-08-01

    The collision-induced dissociation (CID) of cationic fatty acid-metal ion complexes has been extensively studied and, in general, provides rich structural information. In particular, charge-remote fragmentation processes are commonly observed allowing the assignment of double bond position. In a previous manuscript, we presented two methods to doubly deprotonate polyunsaturated fatty acids to form anionic fatty acid-sodium ion complexes, referred to as [M - 2H + Na] - ions. In the current manuscript, the CID behavior of these [M - 2H + Na] - ions is investigated for the first time. Significantly, we also present a deuterium-labeling experiment, which excludes the possibility that deprotonation occurs predominately at the α-carbon in the formation of fatty acid [M - H + NaF]- ions. This supports our original proposal where deprotonation occurs at the bis-allylic positions of polyunsaturated fatty acids. CID spectra of polyunsaturated fatty acid [M - 2H + Na]- ions display abundant product ions arising from acyl chain cleavages. Through the examination of fatty acid isomers, it is demonstrated that double bond position may be unequivocally determined for methylene-interrupted polyunsaturated fatty acids with three or more carbon-carbon double bonds. In addition, CID of [M - 2H + Na]- ions was applied to 18:3 isomers of Nannochloropsis oculata and three isomers were tentatively identified: ∆9,12,1518:3, ∆6,9,1218:3, and ∆5,8,1118:3. We propose that structurally-informative product ions are formed via charge-driven fragmentation processes at the site of the resonance-stabilized carbanion as opposed to charge-remote fragmentation processes, which could be inferred if deprotonation occurred predominately at the α-carbon.

  3. Carrier-mediated (/sup 125/I)-T3 uptake by mouse thymocytes

    SciTech Connect

    Centanni, M.; Mancini, G.; Andreoli, M.

    1989-05-01

    Thyroid hormone entry into the thymocyte, a thyroid hormone target, was investigated by incubating the cells with tracer amounts of (/sup 125/I)L-T3. At 37 C T3 uptake was linear with time up to 2 min, and then approached a plateau. The specific T3 uptake, obtained by subtracting the uptake in the presence of excess unlabeled T3, represented 48 +/- 6% of the total at equilibrium. Unlabeled L-T4, D-T3, and triiodothyroacetic acid were less effective than L-T3 in reducing (/sup 125/I)T3 uptake. Kinetic studies on the initial rate of T3 uptake indicated, for the saturable process, a maximum velocity of approximately 1 pmol/10(6) cells.min and a Km of approximately 0.8 nM. Lowering incubation temperature to 4 C resulted in a two thirds reduction of the total T3 uptake. Washout experiments indicated a different hormone release, being more rapid for cells incubated at 4 C than at 37 C; at 30 min 70% of labeled T3 was released when incubation was carried out at 4 C compared to only 35% after incubation at 37 C, indicating the major intracellular location of the hormone at the latter temperature. An energy requirement of T3 uptake in thymocytes was shown by sensitivity to oligomycin; the effect was dose dependent, showing a maximal decrease in specific uptake of 85%. The involvement of cation movement in the entry process of T3 was indicated by the sensitivity to ouabain. These results indicate the existence of a stereospecific, energy-dependent, saturable process for T3 entry in thymocytes.

  4. Cyclophilin A produced by thymocytes regulates the migration of murine bone marrow cells.

    PubMed

    Khromykh, Ludmila M; Kulikova, Natalia L; Anfalova, Tatiana V; Muranova, Tatiana A; Abramov, Vyacheslav M; Vasiliev, Anatoliy M; Khlebnikov, Valentin S; Kazansky, Dmitriy B

    2007-09-01

    Supernatant obtained from high dose hydrocortisone resistant thymocytes can induce migration of the bone marrow cell precursors to the periphery. This biological activity depends on the presence of the 18 kDa protein, whose amino acid sequence fits with the sequence of the secretory form of murine cyclophilin A (SP-18). Cyclophilin A isolated from the supernatant of the cortisone-resistant thymoma EL-4 shows its characteristic functional features as it demonstrates isomerase activity and binds with cyclosporine A. The cyclophilin A obtained manifests chemotactic activity that regulates migration of bone marrow cell precursors of neutrophils, T-, B- and dendritic cells. PMID:18082675

  5. Cholesterol interactions with tetracosenoic acid phospholipids in model cell membranes: role of the double-bond position.

    PubMed

    Ayanoglu, E; Chiche, B H; Beatty, M; Djerassi, C; Düzgüneş, N

    1990-04-10

    The synthesis and thermotropic properties of 1,2-di-(9Z)-9-tetracosenoylphosphatidylcholine [delta 9-PC(24:1,24:1), 1], 1,2-di-(5Z)-5-tetracosenoylphosphatidylcholine [delta 5-PC(24:1,24:1), 2], and 1,2-di-(15Z)-15- tetracosenoylphosphatidylcholine [delta 15-PC(24:1,24:1), 3] are reported. Liposomes prepared from these phospholipids differ from those of the natural sponge phospholipids, 1,2-di-(5Z,9Z)-5,9-hexacosadienoylphosphatidylcholine (4a) and the corresponding ethanolamine (4b), both of which virtually exclude cholesterol from their bilayers. The behavior of 1 and 2 is similar to that of 1,2-di-(6Z,9Z)-6,9-hexacosadienoylphosphatidylcholine (5), which exhibits a partial molecular interaction with cholesterol. In the case of 3, cholesterol appears to interact with the saturated acyl chain regions of this phospholipid in a manner similar to that of its interaction with DPPC acyl chains. This study delineates the effect of the double-bond location in long fatty acyl chains of phospholipids on their interactions with cholesterol. PMID:2354147

  6. Effects of selected polybrominated diphenyl ether flame retardants on lake trout (Salvelinus namaycush) thymocyte viability, apoptosis, and necrosis

    USGS Publications Warehouse

    Birchmeier, Kelly L.; Smith, Kimberly A.; Passino-Reader, Dora R.; Sweet, Leonard I.; Chernyak, Sergei M.; Adams, Jean V.; Omann, Geneva M.

    2005-01-01

    Polybrominated diphenyl ether (PBDE) flame-retardants have been identified as an emergent contaminants issue in many parts of the world. In vitro analyses were conducted to test the hypothesis that selected PBDEs congeners affect viability, apoptosis, and necrosis of thymocytes from laboratory-reared lake trout (Salvelinus namaycush). At current environmental levels (<1 mg/L), effects of the tested PBDEs on thymocytes were negligible. However, at 100 mg/L, major effects were seen for congener brominated diphenyl ether 47 (BDE-47) and minor effects were seen for congener BDE-99.

  7. T-cell reprogramming through targeted CD4-coreceptor and T-cell receptor expression on maturing thymocytes by latent Circoviridae family member porcine circovirus type 2 cell infections in the thymus

    PubMed Central

    Klausmann, Stefanie; Sydler, Titus; Summerfield, Artur; Lewis, Fraser I; Weilenmann, Roseline; Sidler, Xaver; Brugnera, Enrico

    2015-01-01

    Although porcine circovirus type 2 (PCV2)-associated diseases have been evaluated for known immune evasion strategies, the pathogenicity of these viruses remained concealed for decades. Surprisingly, the same viruses that cause panzootics in livestock are widespread in young, unaffected animals. Recently, evidence has emerged that circovirus-like viruses are also linked to complex diseases in humans, including children. We detected PCV2 genome-carrying cells in fetal pig thymi. To elucidate virus pathogenicity, we developed a new pig infection model by in vivo transfection of recombinant PCV2 and the immunosuppressant cofactor cyclosporine A. Using flow cytometry, immunofluorescence and fluorescence in situ hybridization, we found evidence that PCV2 dictates positive and negative selection of maturing T cells in the thymus. We show for the first time that PCV2-infected cells reside at the corticomedullary junction of the thymus. In diseased animals, we found polyclonal deletion of single positive cells (SPs) that may result from a loss of major histocompatibility complex class-II expression at the corticomedullary junction. The percentage of PCV2 antigen-presenting cells correlated with the degree of viremia and, in turn, the severity of the defect in thymocyte maturation. Moreover, the reversed T-cell receptor/CD4-coreceptor expression dichotomy on thymocytes at the CD4+CD8interm and CD4SP cell stage is viremia-dependent, resulting in a specific hypo-responsiveness of T-helper cells. We compare our results with the only other better-studied member of Circoviridae, chicken anemia virus. Our data show that PCV2 infection leads to thymocyte selection dysregulation, adding a valuable dimension to our understanding of virus pathogenicity. PMID:26038767

  8. Apoptosis induced by oxysterols in murine lymphoma cells and in normal thymocytes.

    PubMed Central

    Christ, M; Luu, B; Mejia, J E; Moosbrugger, I; Bischoff, P

    1993-01-01

    Oxygenated derivatives of cholesterol (oxysterols), a family of naturally occurring compounds, possess marked anti-proliferative and immunosuppressive activities, in particular they have been shown to inhibit T-cell responses to different stimuli. 25-Hydroxycholesterol (25-OHC) and 7 beta,25-dihydroxycholesterol (7.25-OHC) are able to kill not only RDM4 murine lymphoma in vitro, but also, surprisingly, mouse thymocytes after several hours of incubation. In this study, we report that the death of RDM4 and thymocytes induced by oxysterols exhibits the features of apoptosis. This phenomenon was identified by agarose gel electrophoresis of DNA fragments extracted from the cells and quantified by flow cytometric analysis of the DNA fluorescence of propidium iodide-stained cells. Cycloheximide and actinomycin D were found to decrease the number of apoptotic cells and to increase cell viability, indicating a requirement for the synthesis of macromolecules in oxysterol-induced programmed cell death. The pathway by which 25-OHC and 7.25-OHC are able to induce apoptosis in this type of cell and the possible contribution of these compounds to thymus involution during development are discussed. Images Figure 2 Figure 4 PMID:7682990

  9. The mitochondrial and death receptor pathways involved in the thymocytes apoptosis induced by aflatoxin B1.

    PubMed

    Peng, Xi; Yu, Zhengqiang; Liang, Na; Chi, Xiaofeng; Li, Xiaochong; Jiang, Min; Fang, Jing; Cui, Hengmin; Lai, Weimin; Zhou, Yi; Zhou, Shan

    2016-03-15

    Aflatoxin B1 (AFB1) is a potent immunosuppressive agent in endotherms, which can be related to the up-regulated apoptosis of immune organs. In this study, we investigated the roles of the mitochondrial, death receptor, and endoplasmic reticulum pathways in Aflatoxin B1 induced thymocytes apoptosis. Chickens were fed an aflatoxin B1 containing diet (0.6 mg/kg AFB1) for 3 weeks. Our results showed that (1) AFB1 diet induced the decrease of T-cell subsets, morphological changes, and excessive apoptosis of thymus. (2) The excessive apoptosis involved the mitochondrial pathway (up-regulation of Bax, Bak, cytC and down-regulation of Bcl-2 and Bcl-xL) and death receptor pathway (up-regulation of FasL, Fas and FADD). (3) Oxidative stress, an apoptosis inducer, was confirmed in the thymus. In conclusion, this is the first study to demonstrate that mitochondrial and death receptor pathways involved in AFB1 induced thymocytes apoptosis in broilers. PMID:26933817

  10. Susceptibility of neonatal T cells and adult thymocytes to peripheral tolerance to allogeneic stimuli

    PubMed Central

    do Canto, Fábio B; Lima, Celso; Teixeira, Ivan A; Bellio, Maria; Nóbrega, Alberto; Fucs, Rita

    2008-01-01

    We studied the tolerization of neonatal thymocytes (NT), neonatal splenocytes (NS) and adult thymocytes (AT), transferred to syngeneic nude (nu/nu) hosts previously injected with semi-allogeneic splenocytes, without any supportive immunosuppressive treatment. This protocol allows the study of peripheral tolerance in the absence of the thymus. BALB/c neonatal T cells and ATs were able to expand in syngeneic BALB/c nu/nu mice and functionally reconstituted an allogeneic response, rejecting (BALB/c × B6.Ba) F1 splenocytes transferred 3–4 weeks after injection of BALB/c cells. However, if (BALB/c × B6.Ba) F1 cells were injected into BALB/c nude hosts 30 days before transfer of NT, NS or AT cells, the F1 population was preserved and specific tolerance to B6 allografts was established. Furthermore, transfer to lymphopenic F1 nu/nu showed that tolerance could be established only for neonatal populations, showing that unique properties of neonatal T cells allow their tolerization in both lymphopenic and non-lymphopenic conditions, in the absence of suppressive immunotherapy. These results bring empirical support to the possibility of T-cell engraftment in immunodeficient patients showing partial identity with donor major histocompatibility complex (MHC) genes; the manipulation of immunological maturity of donor T cells may be the key for successful reconstitution of immunocompetence without induction of graft-versus-host disease. PMID:18462348

  11. PbCl2-induced hyperpolarization of rat thymocytes: involvement of charybdotoxin-sensitive K+ channels.

    PubMed

    Nishizaki, Yasutaka; Oyama, Yasuo; Sakai, Yoshiro; Hirama, Seigo; Tomita, Kazuyoshi; Nakao, Hiromi; Umebayashi, Chisato; Ishida, Shiro; Okano, Yoshiro; Carpenter, David O

    2003-10-01

    The effect of PbCl2 on membrane potential and intracellular divalent metal cation concentrations of rat thymocytes was examined by flow cytometry. PbCl2 at concentrations of 0.3 microM or higher (up to 10 microM) produced persistent, dose-dependent hyperpolarization (decrease in the intensity of di-BA-C4 fluorescence). Removal of external Ca2+ did not significantly affect the PbCl2-induced hyperpolarization. Charybdotoxin, a specific antagonist of Ca(2+)-dependent K+ conductance, greatly attenuated the PbCl2-induced hyperpolarization. PbCl2 increased the intensity of fluo-3 fluorescence under both normal Ca2+ and nominally Ca(2+)-free conditions. These results suggest that Pb2+ enters thymocytes, causing an increase in fluo-3 fluorescence, and activates Ca(2+)-dependent K+ channels, resulting in hyperpolarization. The persistent activation of K+ channels by Pb2+, leading to persistent hyperpolarization, may be one mechanism whereby Pb2+ alters immune function, as membrane potential changes influence physiological functions of lymphocytes. PMID:14502585

  12. The mitochondrial and death receptor pathways involved in the thymocytes apoptosis induced by aflatoxin B1

    PubMed Central

    Chi, Xiaofeng; Li, Xiaochong; Jiang, Min; Fang, Jing; Cui, Hengmin; Lai, Weimin; Zhou, Yi; Zhou, Shan

    2016-01-01

    Aflatoxin B1 (AFB1) is a potent immunosuppressive agent in endotherms, which can be related to the up-regulated apoptosis of immune organs. In this study, we investigated the roles of the mitochondrial, death receptor, and endoplasmic reticulum pathways in Aflatoxin B1 induced thymocytes apoptosis. Chickens were fed an aflatoxin B1 containing diet (0.6 mg/kg AFB1) for 3 weeks. Our results showed that (1) AFB1 diet induced the decrease of T-cell subsets, morphological changes, and excessive apoptosis of thymus. (2) The excessive apoptosis involved the mitochondrial pathway (up-regulation of Bax, Bak, cytC and down-regulation of Bcl-2 and Bcl-xL) and death receptor pathway (up-regulation of FasL, Fas and FADD). (3) Oxidative stress, an apoptosis inducer, was confirmed in the thymus. In conclusion, this is the first study to demonstrate that mitochondrial and death receptor pathways involved in AFB1 induced thymocytes apoptosis in broilers. PMID:26933817

  13. Comparison of a tube-holder (Rescuefix) versus tape-tying for minimizing double-lumen tube displacement during lateral positioning in thoracic surgery

    PubMed Central

    Byun, Sung Hye; Kang, Su Hwang; Kim, Jong Hae; Ryu, Taeha; Kim, Baek Jin; Jung, Jin Yong

    2016-01-01

    Abstract Background: Double-lumen endotracheal tubes (DLTs) are often displaced during change from the supine to the lateral decubitus position. The aim of this study was to determine whether Rescuefix, a recently developed tube-holder device, is more effective than the traditional tape-tying method for tube security during lateral positioning. Methods: Patients were randomly assigned to a Rescuefix (R) group (n = 22) or a tape (T) group (n = 22). After intubation with a left-sided DLT and adjustment of the appropriate DLT position using a fiberoptic bronchoscope, the DLT was fixed firmly at the side of the mouth by either Rescuefix or Durapore tape. “Tracheal depth” (from the tracheal carina to the elbow connector of the DLT) and “bronchial depth” (from the left bronchial carina to the elbow connector of the DLT) were measured in the supine position using the fiberoptic bronchoscope. After positional change, tracheal and bronchial depths were measured as described above. As the primary endpoint, displacement of the DLT during positional change was evaluated by obtaining the difference in depths measured when the patient was in the supine and lateral decubitus positions. In addition, after lateral positioning of the patient, any requirement for repositioning the DLT was recorded. Results: After lateral positioning, there were no significant differences in changes in tracheal and bronchial depths between the groups (tracheal depth 6.1 ± 4.4 mm [R group] and 9.1 ± 5.6 mm [T group], P = 0.058; bronchial depth 6.5 ± 4.4 mm [R group], and 8.5 ± 4.6 mm [T group], P = 0.132). Although the amount of change in tracheal and bronchial depths was not different between the groups, the need to reposition the DLT was significantly lower in the R group than in the T group (32% vs 68%, P = 0.016). Conclusion: This study demonstrated that use of Rescuefix did not reduce the amount of DLT displacement, but it did significantly

  14. Structure-specific nuclease activity of RAGs is modulated by sequence, length and phase position of flanking double-stranded DNA.

    PubMed

    Kumari, Rupa; Raghavan, Sathees C

    2015-01-01

    RAGs (recombination activating genes) are responsible for the generation of antigen receptor diversity through the process of combinatorial joining of different V (variable), D (diversity) and J (joining) gene segments. In addition to its physiological property, wherein RAG functions as a sequence-specific nuclease, it can also act as a structure-specific nuclease leading to genomic instability and cancer. In the present study, we investigate the factors that regulate RAG cleavage on non-B DNA structures. We find that RAG binding and cleavage on heteroduplex DNA is dependent on the length of the double-stranded flanking region. Besides, the immediate flanking double-stranded region regulates RAG activity in a sequence-dependent manner. Interestingly, the cleavage efficiency of RAGs at the heteroduplex region is influenced by the phasing of DNA. Thus, our results suggest that sequence, length and phase positions of the DNA can affect the efficiency of RAG cleavage when it acts as a structure-specific nuclease. These findings provide novel insights on the regulation of the pathological functions of RAGs. PMID:25327637

  15. The control in cis of the position and the amount of the ARG4 meiotic double-strand break of Saccharomyces cerevisiae.

    PubMed Central

    de Massy, B; Nicolas, A

    1993-01-01

    During meiosis, a transient DNA double-strand break (DSB) occurs in the promoter region (positions -200/-185) of the Saccharomyces cerevisiae ARG4 gene and is a likely intermediate in the initiation of meiotic gene conversion events in this region. We report here a functional analysis of the ARG4 DSB based on the study of various deletions in this chromosomal region. We have identified several cis-acting elements located within the -465/+3 region of the ARG4 promoter that control the formation of this DSB. The -465/-317 region includes a transcription terminator and is necessary for a normal amount of ARG4 DSB, but not for its positioning. The -316/-140 region can be replaced by an unrelated DNA sequence where a meiotic DSB then occurs, suggesting that the site of DSB is not sequence-specific, but is positioned at a fixed distance from the adjacent -139/+3 region. Also, in all strains constructed, the amount of meiotic DSB is correlated with the frequency of gene conversion in ARG4, which provides a strong argument for the initiation of gene conversion by a DSB in this region of the yeast genome. Images PMID:8467798

  16. Simian immunodeficiency virus infection in rhesus macaques induces selective tissue specific B cell defects in double positive CD21+CD27+ memory B cells

    PubMed Central

    Das, Arpita; Veazey, Ronald S.; Wang, Xiaolei; Lackner, Andrew A.; Xu, Huanbin; Pahar, Bapi

    2011-01-01

    B cell dysfunction represents a central feature in HIV infection and pathogenesis. Our recent studies have shown that peripheral and lymphoid double positive CD21+CD27+ B cells were able to become activated and proliferate at higher rates than other B cell subpopulations. Increased proliferation of tonsillar memory B cells were identified compared to other tissues examined. Here, we demonstrate the decreased proliferation of tonsillar memory (CD21+CD27+) B cells during acute SIV infection also suggests that these cells may play an important role in SIV pathogenesis. Our findings demonstrate that SIV infection may induce selective defective responses in specific tissues, by suppressing memory B cell proliferation in tissues. PMID:21622026

  17. T Cell Adolescence: Maturation Events Beyond Positive Selection.

    PubMed

    Hogquist, Kristin A; Xing, Yan; Hsu, Fan-Chi; Shapiro, Virginia Smith

    2015-08-15

    Single-positive thymocytes that successfully complete positive and negative selection must still undergo one final step, generally termed T cell maturation, before they gain functional competency and enter the long-lived T cell pool. Maturation initiates after positive selection in single-positive thymocytes and continues in the periphery in recent thymic emigrants, before these newly produced T cells gain functional competency and are ready to participate in the immune response as peripheral naive T cells. Recent work using genetically altered mice demonstrates that T cell maturation is not a single process, but a series of steps that occur independently and sequentially after positive selection. This review focuses on the changes that occur during T cell maturation, as well as the molecules and pathways that are critical at each step. PMID:26254267

  18. Molecular characterization of the mouse involuted thymus: aberrations in expression of transcription regulators in thymocyte and epithelial compartments.

    PubMed

    Ortman, Crystal L; Dittmar, Kimberly A; Witte, Pamela L; Le, Phong T

    2002-07-01

    Despite playing a critical role in the development of naive T cells, the thymus is involuted with age. Whether a single age-associated defect or multiple aberrations contribute to thymic involution remains controversial. Here, we determined molecular aberrations in the thymocyte and epithelium compartments of the aging thymus. We demonstrated that total thymocyte numbers declined with a stepwise kinetics; clear demarcations occurred at 1.5, 3, 12 and 22 months of age. By quantitative PCR, a 2.4-fold reduction in the copies of signal joint TCR-excised circle (sjTREC)/10(5) thymocytes was first detected at 3 months; no further reduction observed thereafter. Nevertheless, the combined reductions in thymocyte numbers and sjTREC/10(5) cells caused a 7-fold decrease in sjTREC/thymus by 3 months, 21-fold by 18 months and 72-fold by 22 months as compared to 1 month. We showed aberration in expression of E2A, a transcription regulator critical for TCR beta rearrangement. While E2A expression declined 3-fold by 3 months and 18-fold by 7 months, expression of LMO2, a negative regulator of E2A activities, increased 5-fold by 18 months. Interestingly, expression of pre-T alpha and its transcriptional regulator HEB were not reduced with age. Furthermore, keratin-8 expression, specific for cortical thymic epithelium, declined 3-fold by 7 months and remained stable thereafter. In contrast, Foxn1 expression was reduced 3-fold by 3 months, 16-fold by 12 months and 37-fold by 18 months. IL-7 expression was not reduced until 7 months and reached 15-fold reduction by 22 months. Thus, the data demonstrate that thymic involution results not from a single defect, but culminates from an array of molecular aberrations in both the developing thymocytes and thymic epithelials. PMID:12096041

  19. Evolution of Double Positive Autoregulatory Feedback Loops in CYCLOIDEA2 Clade Genes Is Associated with the Origin of Floral Zygomorphy[W

    PubMed Central

    Yang, Xia; Pang, Hong-Bo; Liu, Bo-Ling; Qiu, Zhi-Jing; Gao, Qiu; Wei, Lai; Dong, Yang; Wang, Yin-Zheng

    2012-01-01

    Members of the CYCLOIDEA2 (CYC2) clade of the TEOSINTE BRANCHED1, CYCLOIDEA, and PCF transcription factor genes are widely involved in controlling floral zygomorphy, a key innovation in angiosperm evolution, depending on their persistently asymmetric expression in the corresponding floral domains. However, it is unclear how this asymmetric expression is maintained throughout floral development. Selecting Primulina heterotricha as a model, we examined the expression and function of two CYC2 genes, CYC1C and CYC1D. We analyzed the role of their promoters in protein–DNA interactions and transcription activation using electrophoresis mobility shift assays, chromatin immunoprecipitation, and transient gene expression assays. We find that CYC1C and CYC1D positively autoregulate themselves and cross-regulate each other. Our results reveal a double positive autoregulatory feedback loop, evolved for a pair of CYC2 genes to maintain their expression in developing flowers. Further comparative genome analyses, together with the available expression and function data of CYC2 genes in the core eudicots, suggest that this mechanism might have led to the independent origins of floral zygomorphy, which are associated with plant–insect coevolution and the adaptive radiation of angiosperms. PMID:22649271

  20. Undergraduate Observations of Separation and Position Angle of Double Stars WDS J05460+2119AB (ARY 6AD and ARY 6 AE) at Manzanita Observatory (Abstract)

    NASA Astrophysics Data System (ADS)

    HOffert, M. J.; Weise, E.; Clow, J.; Hirzel, J.; Leeder, B.; Molyneux, S.; Scutti, N.; Spartalis, S.; Takuhara, C.

    2014-12-01

    (Abstract only) Six beginning astronomy students, part of an undergraduate stellar astronomy course, one advanced undergraduate student assistant, and a professor measured the position angles and separations of Washington Double Stars (WDS) J05460+2119 (= WDS J05460+2119AB; also known as ARY 6 AD and ARY 6 AE). The measurements were made at the Manzanita Observatory (116º 20' 42" W, 32º 44' 5" N) of the Tierra Astronomical Institute on 10 Blackwood Road in Boulevard, California (www.youtube.com/watch?v=BHVdeMGBGDU), at an elevation of 4,500 ft. A Celestron 11-inch HD Edge telescope was used to measure the position angles and separations of ARY 6 AD and ARY 6 AE. The averages of our measurements are as follows: separation AD: trial 1 124.1 arcseconds and trial 2 124.5 arcseconds; separation AE: trial 1 73.3 arcseconds and trial 2 73.8 arcseconds. The averages of positon angle for AD: trial 1 159.9 degrees and trial 2 161.3 degrees, for AE: trial 1 232.6 degrees and trial 2 233.7 degrees.

  1. Thymocyte development in the absence of matrix metalloproteinase-9/gelatinase B

    PubMed Central

    Gounko, Natalia V.; Martens, Erik; Opdenakker, Ghislain; Rybakin, Vasily

    2016-01-01

    Matrix metalloproteinases (MMP) play critical roles in a variety of immune reactions by facilitating cell migration, and affect cell communication by processing both cytokines and cell surface receptors. Based on published data indicating that MMP-9 is upregulated upon T cell activation and also in the thymus upon the induction of negative selection, we investigated the contribution of MMP-9 into mouse T cell development and differentiation in the thymus. Our data suggest that MMP-9 deficiency does not result in major abnormalities in the development of any conventionally selected or agonist selected subsets and does not interfere with thymocyte apoptosis and clearance, and that MMP-9 expression is not induced in immature T cells at any stage of their thymic development. PMID:27432536

  2. Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans.

    PubMed

    Vera, Gabriella; Rivera-Munoz, Paola; Abramowski, Vincent; Malivert, Laurent; Lim, Annick; Bole-Feysot, Christine; Martin, Christelle; Florkin, Benoit; Latour, Sylvain; Revy, Patrick; de Villartay, Jean-Pierre

    2013-02-01

    Cernunnos is a DNA repair factor of the nonhomologous end-joining machinery. Its deficiency in humans causes radiosensitive severe combined immune deficiency (SCID) with microcephaly, characterized in part by a profound lymphopenia. In contrast to the human condition, the immune system of Cernunnos knockout (KO) mice is not overwhelmingly affected. In particular, Cernunnos is dispensable during V(D)J recombination in lymphoid cells. Nevertheless, the viability of thymocytes is reduced in Cernunnos KO mice, owing to the chronic activation of a P53-dependent DNA damage response. This translates into a qualitative alteration of the T cell repertoire to one in which the most distal Vα and Jα segments are missing. This results in the contraction of discrete T cell populations, such as invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, in both humans and mice. PMID:23207905

  3. Methylprednisolone inhibits uptake of Ca2+ and Na+ ions into concanavalin A-stimulated thymocytes.

    PubMed Central

    Buttgereit, F; Krauss, S; Brand, M D

    1997-01-01

    The glucocorticoid drug methylprednisolone inhibits respiration in concanavalin A-stimulated rat thymocytes at concentrations that are relevant to its acute clinical efficacy against autoimmune diseases and spinal cord injury. Methylprednisolone affects several processes, including ion cycling, substrate oxidation reactions and RNA/DNA synthesis. The inhibition of respiration used to drive ATP-consuming cycles of Ca2+ and Na+ ions across the plasma membrane has been proposed to be either primary or secondary to restriction of cellular ATP supply. By comparing the effects of methylprednisolone with those of myxothiazol, an inhibitor of the mitochondrial electron transport chain, we show that the effects of methylprednisolone on Ca2+ and Na+ cycling are primary. We propose that methylprednisolone acts by affecting membrane properties to inhibit Ca2+ and Na+ uptake across the plasma membrane and to increase H+ uptake across the mitochondrial membrane, and that other effects are secondary. PMID:9291100

  4. Purification of the Thy-1 molecule, a major cell-surface glycoprotein of rat thymocytes.

    PubMed Central

    Letarte-Muirhead, M; Barclay, A N; Williams, A F

    1975-01-01

    The Thy-1-molecule, which was identified by its antigenic activities, has been purified from rat thymocytes. The purification involved preparation of crude membranes and solubilization in deoxycholate, followed by gel filtration and affinity chromatography on antibody or lectin columns. In all cases the purified molecule was a glycoprotein that did not form higher polymers and was not associated with other polypeptide chains. The Thy-1 glycoprotein could be found in two forms, one binding to lentil lectin, the other not. Both forms had the same detectable antigens and were of a similar but not identical size. After sodium dodecyl sulphate-polyacrylamide-gel electrophoresis the apparent molecular weight of Thy-1 binding to lentil lectin was 25 000, whereas that not binding to the lectin was 27 000, with heterogeneity towards forms of apparently higher molecular weight. Images PLATE 4 PLATE 1 PLATE 2 PLATE 3 PMID:56177

  5. Detecting contaminant-induced apoptosis and necrosis in lake trout thymocytes via flow cytometry.

    USGS Publications Warehouse

    Sweet, Leonard I.; Passino-Reader, Dora R.; Meier, Peter G.; Omann, Geneva M.

    1997-01-01

    This chapter details the cytofluorometric techniques employed to assess levels of active (apoptosis) and passive (necrotic) cell death in untreated and contaminant-treated fish thymocytes. The thymus is believed to be a central component of hematopoiesis and immune function in teleosts (Abelli et al., 1996). Hence, chemically-elicited adverse effects to the thymus may result in immunomodulation and organ dysfunction. However, it is not well documented that environmental contaminants induce apoptosis, or programmed cell death. There is some evidence suggesting that low level exposure to waterborne contaminants can specifically induce cell death in the olfactory epithelium of rainbow trout (Julliard et al., 1996). Presently, only limited information is available in the literature regarding apoptotic death in piscine immune cells (Alford et al., 1994; Greenlee et al., 1991).

  6. Bisabololoxide A, one of the main constituents in German chamomile extract, induces apoptosis in rat thymocytes.

    PubMed

    Ogata, Ikuko; Kawanai, Takuya; Hashimoto, Erika; Nishimura, Yumiko; Oyama, Yasuo; Seo, Hakaru

    2010-01-01

    German chamomile (Matricaria recutita L.), one of the popular ingredients in herbal teas, has been traditionally used for medicinal purposes. Bisabololoxide A (BSBO) is one of the main constituents in this herb. BSBO is supposed to be principle in some bioactivities of German chamomile such as anti-inflammatory, gastrointestinal, and antipruritic actions. Although the use of German chamomile has spread, the information related to toxicity of BSBO is very limited. In present study, the cytotoxic effect of micromolar BSBO was cytometrically examined on rat thymocytes by using appropriate fluorescent dyes. When the cells were incubated with BSBO for 24 h, BSBO at concentrations of 30 microM or more significantly increased populations of dead cells, shrunken cells, and cells with phosphatidylserine exposed on membrane surface. Both cell shrinkage and externalization of membrane phosphatidylserine are general features in an early stage of apoptosis. In addition, BSBO significantly increased population of cells containing hypodiploid DNA, and the increase was completely attenuated by Z-VAD-FMK, a pan-inhibitor for caspases, indicating an involvement of caspase activation. Thus, it is likely that the type of cell death induced by BSBO is apoptosis. The significant changes in cellular parameters of rat thymocytes by BSBO were not observed when the concentration was 10 microM or less. Furthermore, the short incubation (3 h) of cells even with 30-100 microM BSBO did not significantly affect the cells. Therefore, it may be suggested that BSBO is practically safe when German chamomile is conventionally used. PMID:19834689

  7. T cell adolescence: maturation events beyond positive selection1

    PubMed Central

    Hogquist, Kristin A.; Xing, Yan; Hsu, Fan-Chi; Shapiro, Virginia Smith

    2015-01-01

    Single positive (SP) thymocytes that successfully complete positive and negative selection must still undergo one final step, generally termed T cell maturation, before they gain functional competency and enter the long-lived T cell pool. Maturation initiates after positive selection in SP thymocytes, and continues in the periphery in recent thymic emigrants (RTEs), before these newly produced T cells gain functional competency and are ready to participate in the immune response as peripheral naïve T cells. Recent work using genetically altered mice demonstrates that T cell maturation is not a single process, but a series of steps that occur independently and sequentially after positive selection. This review will focus on the changes that occur during T maturation, and the molecules and pathways that are critical at each step. PMID:26254267

  8. [The characteristic of proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of females with experimental chronic liver diseases of various aetiology].

    PubMed

    Briukhin, G V; Fedosov, A A

    2006-01-01

    The aim of the study was a comparative analysis of the proliferative activity of thymocytes and peripheral blood lymphocytes in the offspring of female rats with chronic liver pathology of various genesis. In adult female Wistar rats toxic and autoimmune forms of liver lesions were modeled. The offspring of these experimental animals was studied at different time points of postnatal ontogenesis. Proliferative activity of thymocytes and lymphocytes was estimated by counting the proportion of cells with multiple nucleolar organizing regions (AgNORs) and using the cytofluorometric method with acridine orange. In the offspring of experimental animals, the depression of proliferative activity of thymocytes as well as the increase of the proliferative activity of peripheral blood lymphocytes were found at all the time points studied. This was indicated by a change in a relative number of AgNORs-activated cells and a decrease of nucleic acid content in cortical thymocytes. PMID:17201321

  9. RNA interference-mediated knockdown of CD49e (α5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

    PubMed Central

    2010-01-01

    Background The thymus is a central lymphoid organ, in which bone marrow-derived T cell precursors undergo a complex process of maturation. Developing thymocytes interact with thymic microenvironment in a defined spatial order. A component of thymic microenvironment, the thymic epithelial cells, is crucial for the maturation of T-lymphocytes through cell-cell contact, cell matrix interactions and secretory of cytokines/chemokines. There is evidence that extracellular matrix molecules play a fundamental role in guiding differentiating thymocytes in both cortical and medullary regions of the thymic lobules. The interaction between the integrin α5β1 (CD49e/CD29; VLA-5) and fibronectin is relevant for thymocyte adhesion and migration within the thymic tissue. Our previous results have shown that adhesion of thymocytes to cultured TEC line is enhanced in the presence of fibronectin, and can be blocked with anti-VLA-5 antibody. Results Herein, we studied the role of CD49e expressed by the human thymic epithelium. For this purpose we knocked down the CD49e by means of RNA interference. This procedure resulted in the modulation of more than 100 genes, some of them coding for other proteins also involved in adhesion of thymocytes; others related to signaling pathways triggered after integrin activation, or even involved in the control of F-actin stress fiber formation. Functionally, we demonstrated that disruption of VLA-5 in human TEC by CD49e-siRNA-induced gene knockdown decreased the ability of TEC to promote thymocyte adhesion. Such a decrease comprised all CD4/CD8-defined thymocyte subsets. Conclusion Conceptually, our findings unravel the complexity of gene regulation, as regards key genes involved in the heterocellular cell adhesion between developing thymocytes and the major component of the thymic microenvironment, an interaction that is a mandatory event for proper intrathymic T cell differentiation. PMID:21210968

  10. Double mutagenesis of a positive charge cluster in the ligand-binding site of the ferric enterobactin receptor, FepA.

    PubMed

    Newton, S M; Allen, J S; Cao, Z; Qi, Z; Jiang, X; Sprencel, C; Igo, J D; Foster, S B; Payne, M A; Klebba, P E

    1997-04-29

    Siderophores and colicins enter bacterial cells through TonB-dependent outer membrane proteins. Using site-directed substitution mutagenesis, we studied ligand recognition by a prototypic Escherichia coli siderophore receptor, FepA, that binds the iron chelate ferric enterobactin and colicins B and D. These genetic experiments identified a common binding site for two of the three ligands, containing multiple positive charges, within cell surface residues of FepA. Elimination of single residues in this region did not impair the adsorption or transport of ferric enterobactin, but double mutagenesis in the charge cluster identified amino acids (Arg-286 and Arg-316) that participate in siderophore binding and function in FepA-mediated killing by colicins B and D. Ferric enterobactin binding, furthermore, prevented covalent modification of FepA within this domain by either a fluorescent probe or an arginine-specific reagent, corroborating the involvement of this site in ligand recognition. These results identify, for the first time, residues in a TonB-dependent outer membrane protein that participate in ligand binding. They also explain the competition between ferric enterobactin and the colicins on the bacterial cell surface: all three ligands interact with the same arginine residues within FepA during their penetration through the outer membrane. PMID:9114029

  11. IL-9 promotes the survival and function of human melanoma-infiltrating CD4(+) CD8(+) double-positive T cells.

    PubMed

    Parrot, Tiphaine; Allard, Mathilde; Oger, Romain; Benlalam, Houssem; Raingeard de la Blétière, Diane; Coutolleau, Anne; Preisser, Laurence; Desfrançois, Juliette; Khammari, Amir; Dréno, Brigitte; Labarrière, Nathalie; Delneste, Yves; Guardiola, Philippe; Gervois, Nadine

    2016-07-01

    We previously demonstrated an accumulation of tumor-reactive CD4(+) CD8(+) double positive (DP) T cells within melanoma-infiltrating lymphocytes, supporting their role in the regulation of anti-tumor immune responses. Similarly to their CD8(+) counterparts, intra-tumor DP T cells are MHC class-I restricted but differed by a limited lytic activity against autologous melanoma cells. Based on these observations and to further characterize DP T cells, both populations were compared at the transcriptional level. Our results revealed the overexpression of the IL-9 receptor (IL-9R) by DP T cells and prompted us to investigate the impact of IL-9 on their biology. We show that IL-9 favors DP T-cell survival by protecting them from apoptosis and by promoting their proliferation. In addition, IL-9 enhances their ability to produce cytokines and increased their levels of granzyme B/perforin as well as degranulation capacity, leading to a strengthened cytotoxic activity against melanoma cells. Taken together, the IL-9R(high) DP T-cell population could be a new preferential target for IL-9, which could take part in their retention within the melanoma infiltrate while also favoring their anti-tumor activity. More generally, our results extend the pleiotropic effects of IL-9 to IL-9R-expressing intra-tumor T cells, which could further potentiate anti-tumor immune responses. PMID:27094152

  12. DNA double strand break repair defect and sensitivity to poly ADP-ribose polymerase (PARP) inhibition in human papillomavirus 16-positive head and neck squamous cell carcinoma

    PubMed Central

    Weaver, Alice N.; Cooper, Tiffiny S.; Rodriguez, Marcela; Trummell, Hoa Q.; Bonner, James A.; Rosenthal, Eben L.; Yang, Eddy S.

    2015-01-01

    Patients with human papillomavirus-positive (HPV+) head and neck squamous cell carcinomas (HNSCCs) have increased response to radio- and chemotherapy and improved overall survival, possibly due to an impaired DNA damage response. Here, we investigated the correlation between HPV status and repair of DNA damage in HNSCC cell lines. We also assessed in vitro and in vivo sensitivity to the PARP inhibitor veliparib (ABT-888) in HNSCC cell lines and an HPV+ patient xenograft. Repair of DNA double strand breaks (DSBs) was significantly delayed in HPV+ compared to HPV− HNSCCs, resulting in persistence of γH2AX foci. Although DNA repair activators 53BP1 and BRCA1 were functional in all HNSCCs, HPV+ cells showed downstream defects in both non-homologous end joining and homologous recombination repair. Specifically, HPV+ cells were deficient in protein recruitment and protein expression of DNA-Pk and BRCA2, key factors for non-homologous end joining and homologous recombination respectively. Importantly, the apparent DNA repair defect in HPV+ HNSCCs was associated with increased sensitivity to the PARP inhibitor veliparib, resulting in decreased cell survival in vitro and a 10–14 day tumor growth delay in vivo. These results support the testing of PARP inhibition in combination with DNA damaging agents as a novel therapeutic strategy for HPV+ HNSCC. PMID:26336991

  13. Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain A expressed in mouse small intestinal epithelium.

    PubMed

    Park, Eun Jeong; Takahashi, Ichiro; Ikeda, Junko; Kawahara, Kazuko; Okamoto, Tetsuji; Kweon, Mi-Na; Fukuyama, Satoshi; Groh, Veronika; Spies, Thomas; Obata, Yuichi; Miyazaki, Jun-Ichi; Kiyono, Hiroshi

    2003-10-15

    Expression of a distant homologue MHC class I molecule, MHC class I-related chain A (MICA), has been found to be stress inducible and limited to the intestinal epithelium. This nonclassical MHC molecule is associated with various carcinomas in humans. To understand the biological consequences of MICA expression in the gut, we generated transgenic (Tg) mice (T3(b)-MICA Tg) under the control of the T3(b) promoter. The T3(b)-MICA Tg mice expressed MICA selectively in the intestine and had an increased number of TCRalphabeta CD4CD8alphaalpha, double-positive (DP) intraepithelial lymphocytes (IELs) in the small bowel. These MICA-expanded DP IELs exhibited a bias to Vbeta8.2 and overlapped motifs of the complementarity-determining region 3 region among various Tg mice. Hence, the overexpression of MICA resulted in a clonal expansion of DP IELs. Studies in model of inflammatory bowel disease showed that transgenic MICA was able to attenuate the acute colitis induced by dextran sodium sulfate administration. Therefore, this unique in vivo model will enable investigation of possible influences of stress-inducible MICA on the gut immune surveillance. PMID:14530335

  14. Graves' disease TSHR-stimulating antibodies (TSAbs) induce the activation of immature thymocytes: a clue to the riddle of TSAbs generation?

    PubMed

    Giménez-Barcons, Mireia; Colobran, Roger; Gómez-Pau, Ana; Marín-Sánchez, Ana; Casteràs, Anna; Obiols, Gabriel; Abella, Raúl; Fernández-Doblas, Joaquín; Tonacchera, Massimo; Lucas-Martín, Ana; Pujol-Borrell, Ricardo

    2015-05-01

    Graves' disease (GD) is an autoimmune thyroid disease defined by the production of stimulating autoantibodies to the thyroid-stimulating hormone receptor (TSHR) (TSAbs) that induce a sustained state of hyperthyroidism in patients. We previously demonstrated that TSHR, the target of this autoimmune response, is also a key susceptibility gene for GD, probably acting through thymic-dependent central tolerance. We also showed that TSHR is, unexpectedly, expressed in thymocytes. In this report, we confirm the expression of TSHR in thymocytes by protein immunoblotting and quantitative PCR, and show that expression is confined to maturing thymocytes. Using functional assays, we show that thymic TSHR is functional and that TSAbs can stimulate thymocytes through this receptor. This new activity of TSAbs on thymocytes may: 1) explain GD-associated thymic enlargement (hyperplasia), and 2) suggest the provocative hypothesis that the continuous stimulation of thymocytes by TSAbs could lead to a vicious cycle of iterative improvement of the affinity and stimulating capability of initially low-affinity antibacterial (e.g., Yersinia) Abs cross-reactive with TSHR, eventually leading to TSAbs. This may help to fill one of the gaps in our present understanding of unusual characteristics of TSAbs. PMID:25801430

  15. Distinct kinetic responses in vivo of cortical thymocytes of ageing mice to primary as compared to secondary peripheral antigenic stimulation.

    PubMed Central

    Luscieti, P; Graff, P; Luethi, M; Cottier, H; Hess, M W; Kraft, R; Stoner, R D

    1983-01-01

    We have studied cellular kinetic changes in the thymic cortex of ageing mice as a function of time after primary and secondary stimulation with aluminum phosphate adsorbed tetanus toxoid via the hind leg footpads. Absolute numbers of DNA synthesizing cortical thymocytes per cross-section of the thymus were computed from combined data obtained by planimetry, counts of cell density (cellularity) and assessment of the labelling index, 1 h after injection of (methyl-3H)-thymidine. The proliferative activity of these cells in the outer fourth of the thymic cortex reached a peak exceeding significantly control values by 45% 14 days after primary, but not secondary, peripheral antigenic stimulation. We conclude that the cortical thymocyte population responded in a distinct manner to the first immunization as opposed to the booster injection of the same antigen. PMID:6602681

  16. Defective selection of thymic regulatory T cells accompanies autoimmunity and pulmonary infiltrates in Tcra-deficient mice double transgenic for human La/SS-B and human La-specific T cell receptor1

    PubMed Central

    Yaciuk, Jane C.; Pan, Yujun; Schwarz, Karen; Pan, Zi-jian; Maier-Moore, Jacen S.; Kosanke, Stanley D.; Lawrence, Christina; Farris, A. Darise

    2014-01-01

    A human La/SS-B (hLa)-specific TCR/hLa neo-self antigen double transgenic mouse model was developed and used to investigate cellular tolerance and autoimmunity to the ubiquitous RNA-binding La antigen often targeted in systemic lupus erythematosus and Sjögren's syndrome. Extensive thymic clonal deletion of CD4+ T cells occurred in H-2k/k double transgenic mice presenting high levels of the I-Ek-restricted hLa T cell epitope. In contrast, deletion was less extensive in H-2k/b double transgenic mice presenting lower levels of the epitope, and some surviving thymocytes were positively selected as thymic regulatory T cells (tTreg). These mice remained serologically tolerant to hLa and healthy. H-2k/b double transgenic mice deficient of all endogenous Tcra genes, a deficiency known to impair Treg development and function, produced IgG anti-hLa autoantibodies and displayed defective tTreg development. These autoimmune mice had interstitial lung disease characterized by lymphocytic aggregates containing transgenic T cells with an activated, effector memory phenotype. Salivary gland infiltrates were notably absent. Thus, expression of nuclear hLa antigen induces thymic clonal deletion and tTreg selection, and lymphocytic infiltration of the lung is a consequence of La-specific CD4+ T cell autoimmunity. PMID:25582858

  17. Identification of cDNA clones encoding HMG 2, a major protein of the mexican axolotl hydrocortisone-sensitive thymocytes.

    PubMed

    de Guerra, A; Guillet, F; Charlemagne, J; Fellah, J S

    1995-01-01

    We have identified and analyzed cDNA clones encoding a major 26 kDa protein of the HMG1-2 family which is abundant in the cytoplasm and nucleus of axolotl hydrocortisone-sensitive thymocytes. The axolotl HMG2 protein is very similar to proteins belonging to the HMG1-2 family, from teleost fish to mammals. All the molecular features of the HMG1-2 proteins are conserved, including the high proportion of basic and aromatic residues, and the characteristic acidic C-terminus tail. The 3'-untranslated region of the HMG2 axolotl cDNA is also similar to the avian and mammalian HMG2 3'-UT sequences, suggesting that some selective events have acted at the DNA level to conserve this region, which could be important in the differential expression of the HMG1 and HMG2 genes. The axolotl HMG2 protein contains the two well conserved HMG boxes which are thought to be the DNA-binding domains of the molecule. Axolotl thymocytes and spleen cells contain almost identical amounts of HMG2 mRNAs but HMG2 polypeptide is undetectable in spleen cells using anti-26 kDa antibodies. The reason for the accumulation of HMG1-2 molecules in vertebrate hydrocortisone-sensitive thymocytes is discussed, as well as their possible role in apoptosis. PMID:8654668

  18. UEA-I-binding to thymic medullary epithelial cells selectively reduces numbers of cortical TCRalphabeta+ thymocytes in FTOCs.

    PubMed

    Graziano, M; St-Pierre, Y; Potworowski, E F

    2001-07-01

    Thymic medullary epithelial cells (TMECs) constitute a major stromal cell type, the function of which is incompletely understood. Some TMECs express L-fucose-glycosylated proteins on their plasma membrane; these have been shown to specifically bind the lectin UEA-I. We exploited this observation to investigate the consequences of in situ blockage of TMECs in FTOCs by UEA-I. In UEA-I-treated FTOCs, we noted a decreased cellularity among TCRalphabeta+ but not TCRgammadelta+ cells. In fact, CD3- and CD3lo cortical cells were markedly depleted, while CD3hi cells were unaffected. Since the affected cell subsets are in a different compartment from that where UEA-I binding occurs, it is likely that the effect is mediated through a soluble factor. Two possible mechanisms are proposed: a reduced activation of either TMECs or of medullary thymocytes which normally bind to them, results in lowered production of soluble factors responsible for cortical thymocyte proliferation. Alternately, the binding of UEA-I to TMECs could activate the latter to produce signals inhibitory to cortical thymocytes. PMID:11410246

  19. Double-Positive CD21+CD27+ B Cells Are Highly Proliferating Memory Cells and Their Distribution Differs in Mucosal and Peripheral Tissues

    PubMed Central

    Das, Arpita; Xu, Huanbin; Wang, Xiaolei; Yau, Canddy L.; Veazey, Ronald S.; Pahar, Bapi

    2011-01-01

    Background Several B-cell defects arise in HIV infected patients, particularly in patients with chronic infection and high viral load. Loss of memory B cells (CD27+ B cells) in peripheral blood and lymphoid tissues is one of the major B cell dysfunctions in HIV and simian immunodeficiency virus (SIV) infection. Despite several studies, definitive identification of memory B cells based on CD27 surface expression has not been described. Similarly, the rates of cell turnover in different B cell subpopulation from lymphoid and mucosal tissues have not been well documented. In this study, we demonstrate the presence of memory B cell populations and define their distribution, frequency and immunophenotype with regards to activation, proliferation, maturation, and antibody production in normal rhesus macaques from different lymphoid tissues. Methodology/Principal Findings Thirteen healthy, uninfected rhesus macaques were selected for this study. CD20+ B cells were isolated from peripheral blood and sorted based on CD27 and CD21 surface markers to define memory B cell population. All the B cell subpopulation was further characterized phenotypically and their cell turnover rates were evaluated in vivo following bromodeoxyuridine (BrdU) inoculation. Double positive (DP) CD21+CD27+ B cells in both peripheral and lymphoid tissues are memory B cells, able to produce antibody by polyclonal activation, and without T cell help. Peripheral and lymphoid DP CD21+CD27+ B cells were also able to become activated and proliferate at higher rates than other B cell subpopulations. Increased turnover of tonsillar memory B cells were identified compared to other tissues examined. Conclusions/Significance We suggest that this DP memory B cells play a major role in the immune system and their function and proliferation might have an important role in HIV/SIV mediated B cell dysregulation and pathogenesis. PMID:21304587

  20. Anaplastic large cell lymphoma arises in thymocytes and requires transient TCR expression for thymic egress

    PubMed Central

    Malcolm, Tim I. M.; Villarese, Patrick; Fairbairn, Camilla J.; Lamant, Laurence; Trinquand, Amélie; Hook, C. Elizabeth; Burke, G. A. Amos; Brugières, Laurence; Hughes, Katherine; Payet, Dominique; Merkel, Olaf; Schiefer, Ana-Iris; Ashankyty, Ibraheem; Mian, Shahid; Wasik, Mariusz; Turner, Martin; Kenner, Lukas; Asnafi, Vahid; Macintyre, Elizabeth; Turner, Suzanne D.

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma presenting mostly in children and young adults. The natural progression of this disease is largely unknown as is the identity of its true cell of origin. Here we present a model of peripheral ALCL pathogenesis where the malignancy is initiated in early thymocytes, before T-cell receptor (TCR) β-rearrangement, which is bypassed in CD4/NPM–ALK transgenic mice following Notch1 expression. However, we find that a TCR is required for thymic egress and development of peripheral murine tumours, yet this TCR must be downregulated for T-cell lymphomagenesis. In keeping with this, clonal TCR rearrangements in human ALCL are predominantly in-frame, but often aberrant, with clonal TCRα but no comparable clonal TCRβ rearrangement, yielding events that would not normally be permissive for survival during thymic development. Children affected by ALCL may thus harbour thymic lymphoma-initiating cells capable of seeding relapse after chemotherapy. PMID:26753883

  1. Pre-TCR ligand binding impacts thymocyte development before αβTCR expression

    PubMed Central

    Mallis, Robert J.; Bai, Ke; Arthanari, Haribabu; Hussey, Rebecca E.; Handley, Maris; Li, Zhenhai; Chingozha, Loice; Duke-Cohan, Jonathan S.; Lu, Hang; Wang, Jia-Huai; Zhu, Cheng; Wagner, Gerhard; Reinherz, Ellis L.

    2015-01-01

    Adaptive cellular immunity requires accurate self- vs. nonself-discrimination to protect against infections and tumorous transformations while at the same time excluding autoimmunity. This vital capability is programmed in the thymus through selection of αβT-cell receptors (αβTCRs) recognizing peptides bound to MHC molecules (pMHC). Here, we show that the pre-TCR (preTCR), a pTα-β heterodimer appearing before αβTCR expression, directs a previously unappreciated initial phase of repertoire selection. Contrasting with the ligand-independent model of preTCR function, we reveal through NMR and bioforce-probe analyses that the β-subunit binds pMHC using Vβ complementarity-determining regions as well as an exposed hydrophobic Vβ patch characteristic of the preTCR. Force-regulated single bonds akin to those of αβTCRs but with more promiscuous ligand specificity trigger calcium flux. Thus, thymic development involves sequential β- and then, αβ-repertoire tuning, whereby preTCR interactions with self pMHC modulate early thymocyte expansion, with implications for β-selection, immunodominant peptide recognition, and germ line-encoded MHC interaction. PMID:26056289

  2. Pre-TCR ligand binding impacts thymocyte development before αβTCR expression.

    PubMed

    Mallis, Robert J; Bai, Ke; Arthanari, Haribabu; Hussey, Rebecca E; Handley, Maris; Li, Zhenhai; Chingozha, Loice; Duke-Cohan, Jonathan S; Lu, Hang; Wang, Jia-Huai; Zhu, Cheng; Wagner, Gerhard; Reinherz, Ellis L

    2015-07-01

    Adaptive cellular immunity requires accurate self- vs. nonself-discrimination to protect against infections and tumorous transformations while at the same time excluding autoimmunity. This vital capability is programmed in the thymus through selection of αβT-cell receptors (αβTCRs) recognizing peptides bound to MHC molecules (pMHC). Here, we show that the pre-TCR (preTCR), a pTα-β heterodimer appearing before αβTCR expression, directs a previously unappreciated initial phase of repertoire selection. Contrasting with the ligand-independent model of preTCR function, we reveal through NMR and bioforce-probe analyses that the β-subunit binds pMHC using Vβ complementarity-determining regions as well as an exposed hydrophobic Vβ patch characteristic of the preTCR. Force-regulated single bonds akin to those of αβTCRs but with more promiscuous ligand specificity trigger calcium flux. Thus, thymic development involves sequential β- and then, αβ-repertoire tuning, whereby preTCR interactions with self pMHC modulate early thymocyte expansion, with implications for β-selection, immunodominant peptide recognition, and germ line-encoded MHC interaction. PMID:26056289

  3. Anaplastic large cell lymphoma arises in thymocytes and requires transient TCR expression for thymic egress.

    PubMed

    Malcolm, Tim I M; Villarese, Patrick; Fairbairn, Camilla J; Lamant, Laurence; Trinquand, Amélie; Hook, C Elizabeth; Burke, G A Amos; Brugières, Laurence; Hughes, Katherine; Payet, Dominique; Merkel, Olaf; Schiefer, Ana-Iris; Ashankyty, Ibraheem; Mian, Shahid; Wasik, Mariusz; Turner, Martin; Kenner, Lukas; Asnafi, Vahid; Macintyre, Elizabeth; Turner, Suzanne D

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is a peripheral T-cell lymphoma presenting mostly in children and young adults. The natural progression of this disease is largely unknown as is the identity of its true cell of origin. Here we present a model of peripheral ALCL pathogenesis where the malignancy is initiated in early thymocytes, before T-cell receptor (TCR) β-rearrangement, which is bypassed in CD4/NPM-ALK transgenic mice following Notch1 expression. However, we find that a TCR is required for thymic egress and development of peripheral murine tumours, yet this TCR must be downregulated for T-cell lymphomagenesis. In keeping with this, clonal TCR rearrangements in human ALCL are predominantly in-frame, but often aberrant, with clonal TCRα but no comparable clonal TCRβ rearrangement, yielding events that would not normally be permissive for survival during thymic development. Children affected by ALCL may thus harbour thymic lymphoma-initiating cells capable of seeding relapse after chemotherapy. PMID:26753883

  4. Elevation of intracellular Zn2+ level by nanomolar concentrations of triclocarban in rat thymocytes.

    PubMed

    Morita, Junpei; Teramachi, Aoi; Sanagawa, Yosuke; Toyson, Saramaiti; Yamamoto, Hiroshi; Oyama, Yasuo

    2012-12-17

    It was recently reported that nanomolar concentrations of triclocarban, an antimicrobial agent, were detected in human blood after the use of soap containing triclocarban. Due to the widespread use of triclocarban in adult and infant personal care products, the report prompted us to study its cytotoxicity. The cytotoxicity of triclocarban was examined in rat thymocytes by using a cytometric technique with propidium iodide for examining cell lethality, FluoZin-3-AM for monitoring the intracellular Zn(2+) level, and 5-chloromethylfluorescencein diacetate for estimating the cellular content of non-protein thiol. The incubation with triclocarban at nanomolar concentrations (50-500nM) for 1h did not affect cell lethality but significantly elevated the intracellular Zn(2+) level. The elevation of the intracellular Zn(2+) level by triclocarban was not significantly dependent on external Zn(2+) level. There was a negative correlation (r=-0.9225) between the effect on the intracellular Zn(2+) level and that on the cellular content of non-protein thiol. These results suggest that nanomolar concentrations of triclocarban decrease the cellular content of non-protein thiol, leading to intracellular Zn(2+) release. Since zinc plays physiological roles in mammalian cells, the percutaneous absorption of triclocarban from soap may, therefore, affect some cellular functions. PMID:23099084

  5. Nanomolar concentration of triclocarban increases the vulnerability of rat thymocytes to oxidative stress.

    PubMed

    Kanbara, Yasuhiro; Murakane, Kazuyoshi; Nishimura, Yumiko; Satoh, Masaya; Oyama, Yasuo

    2013-02-01

    It was recently reported that triclocarban was absorbed significantly from soap used during showering in human subjects and that its C(max) in their whole blood ranged from 23 nM to 530 nM. We revealed that a nanomolar concentration (300 nM) of triclocarban potentiated the cytotoxicity of 300 µM H(2)O(2) in rat thymocytes by using cytometric techniques with appropriate fluorescent probes. Although 300 nM triclocarban did not itself increase the population of dead cells (cell lethality), it facilitated the process of cell death induced by H(2)O(2), resulting in a further increase in the population of dead cells. Nanomolar concentrations (300 nM or higher) of triclocarban significantly decreased the cellular content of nonprotein thiol (glutathione), which has a protective role against oxidative stress. Triclocarban at 300 nM or higher increased the cell vulnerability to oxidative stress. The results may suggest that nanomolar concentration (300 nM or higher) of triclocarban affects some cellular functions although there is no evidence for adverse effects of triclocarban in humans at present. PMID:23358139

  6. Augmentation of erythroid burst formation by the addition of thymocytes and other myelo-lymphoid cells.

    PubMed

    Kanamaru, A; Durban, E; Gallagher, M T; Miller, S C; Trentin, J J

    1980-08-01

    Bone marrow from barrier-sustained specific pathogen-free (SPF) CBA and C57BL/6 mice gave relatively low numbers of BFU-E colonies in methylcellulose culture, as compared to conventional mice. Addition of thymocytes to the marrow cultures increased the yield of BFU-E colonies more than fourfold in SPF mice but only 1.5-fold in conventional mice. Colony size was also increased. Increased yield of BFU-E colonies was also obtained by co-culture of bone marrow with lymph node cells or with bone marrow or spleen cells from 900R whole-body irradiated mice. The effect appeared to be cellular rather than humoral. It was not reproduced by conditioned medium from thymus or pokeweed mitogen stimulated spleen cells. The helper effect of thymus cells was eliminated or reduced by freezing and thawing, or by 48 hours of incubation after irradiation. Treatment of bone marrow cells in vitro with anti-theta serum and complement did not decrease the number of BFU-E colonies. The putative helper cells appear not to be T cells, were non-adherent to the plastic culture dish, and were cortisone resistant and radioresistant. The low BFU-E colony yield from SPF mouse marrow is presumed to be largely the result of deficiency of these non-T helper cells in SPF bone marrow, rather than of BFU-E progenitor cells. PMID:6447706

  7. [Successful double-lumen tube intubation with the Pentax-AWS Airwayscope and a tracheal tube introducer in the lateral position for a patient with a giant mediastinal tumor].

    PubMed

    Nakao, Kenta; Komasawa, Nobuyasu; Kuzukawa, Yosuke; Fujitate, Yasutaka; Minami, Toshiaki

    2014-06-01

    Anesthetic management of a patient with giant mediastinal tumors is challenging from the perspective of both cardiovascular and respiratory management. We report the successful use of the Pentax-AWS Airwayscope (AWS; Hoya, Japan) and a tracheal tube introducer in the left lateral position for a patient with a giant mediastinal tumor. An 18-year-old man weighing 62 kg was scheduled for resection of a giant mediastinal tumor. He suffered from slight dyspnea in the supine position, and slept in the left lateral position. Preoperative chest X-P and computed tomography revealed compression of the left bronchus, heart and aorta. To avoid cardiac and respiratory collapse, anesthesia was induced in the left lateral position without a muscle relaxant. The patient was administered fentanyl 200 microg and propofol 150 mg; mask ventilation with the two-hand technique in the lateral position was successful. Subsequently, the AWS was inserted into his mouth and a 10 Fr tracheal tube introducer was placed in the trachea under the guidance of the AWS monitor. The patient was then intubated with a 35 Fr right-sided double-lumen tracheal tube under the guidance of the tracheal tube introducer. The head of the double-lumen tube was placed in the right bronchus under the guidance of a bronchofiberscope. Following tracheal tube placement, posture was shifted from the left lateral position to supine position without affecting vital signs. After median sternotomy, a muscle relaxant was administered for immobilization. PMID:24979858

  8. Surface Oxidation under Ambient Air—Not Only a Fast and Economical Method to Identify Double Bond Positions in Unsaturated Lipids But Also a Reminder of Proper Lipid Processing

    PubMed Central

    2015-01-01

    A simple, fast approach elucidated carbon–carbon double bond positions in unsaturated lipids. Lipids were deposited onto various surfaces and the products from their oxidation in ambient air were observed by electrospray ionization (ESI) mass spectrometry (MS). The most common oxidative products, aldehydes, were detected as transformations at the cleaved double bond positions. Ozonides and carboxylic acids were generated in certain lipids. Investigations of the conditions controlling the appearance of these products indicated that the surface oxidation depends on light and ambient air. Since the lipid oxidation was slower in a high concentration of ozone, singlet oxygen appeared to be a parallel oxidant for unsaturated lipids. The 3-hydroxyl group in the sphingoid base of sulfatides offered some protection from oxidation for the Δ4,5-double bond, slowing its oxidation rate relative to that of the isolated double bond in the N-linked fatty acyl chain. Direct sampling by thin-layer chromatography (TLC)-ESI-MS provides a powerful approach to elucidate detailed structural information on biological samples. Co-localization of the starting lipids and their oxidation products after TLC separation allowed assignment of the native unsaturation sites. Phosphatidylserine and N,N-dimethyl phosphatidylethanolamine isomers in a bovine brain total lipid extract were distinguished on the basis of their oxidation products. Meanwhile, the findings reported herein reveal a potential pitfall in the assignment of structures to lipids extracted from TLC plates because of artifactual oxidation after the plate development. PMID:24832382

  9. Anti-Thymocyte Globulin Induces Neoangiogenesis and Preserves Cardiac Function after Experimental Myocardial Infarction

    PubMed Central

    Lichtenauer, Michael; Mildner, Michael; Werba, Gregor; Beer, Lucian; Hoetzenecker, Konrad; Baumgartner, Andrea; Hasun, Matthias; Nickl, Stefanie; Mitterbauer, Andreas; Zimmermann, Matthias; Gyöngyösi, Mariann; Podesser, Bruno Karl; Klepetko, Walter; Ankersmit, Hendrik Jan

    2012-01-01

    Rationale Acute myocardial infarction (AMI) followed by ventricular remodeling is the major cause of congestive heart failure and death in western world countries. Objective Of relevance are reports showing that infusion of apoptotic leucocytes or anti-lymphocyte serum after AMI reduces myocardial necrosis and preserves cardiac function. In order to corroborate this therapeutic mechanism, the utilization of an immunosuppressive agent with a comparable mechanism, such as anti-thymocyte globulin (ATG) was evaluated in this study. Methods and Results AMI was induced in rats by ligation of the left anterior descending artery. Initially after the onset of ischemia, rabbit ATG (10 mg/rat) was injected intravenously. In vitro and in vivo experiments showed that ATG induced a pronounced release of pro-angiogenic and chemotactic factors. Moreover, paracrine factors released from ATG co-incubated cell cultures conferred a down-regulation of p53 in cardiac myocytes. Rats that were injected with ATG evidenced higher numbers of CD68+ macrophages in the ischemic myocardium. Animals injected with ATG evidenced less myocardial necrosis, showed a significant reduction of infarct dimension and an improvement of post-AMI remodeling after six weeks (infarct dimension 24.9% vs. 11.4%, p<0.01). Moreover, a higher vessel density in the peri-infarct region indicated a better collateralization in rats that were injected with ATG. Conclusions These data indicate that ATG, a therapeutic agent successfully applied in clinical transplant immunology, triggered cardioprotective effects after AMI that salvaged ischemic myocardium by down-regulation of p53. This might have raised the resistance against apoptotic cell death during ischemia. The combination of these mechanisms seems to be causative for improved cardiac function and less ventricular remodeling after experimental AMI. PMID:23284885

  10. Immunomodulatory role of Emblica officinalis in arsenic induced oxidative damage and apoptosis in thymocytes of mice

    PubMed Central

    2013-01-01

    Background Arsenic is widely distributed in the environment and has been found to be associated with the various health related problems including skin lesions, cancer, cardiovascular and immunological disorders. The fruit extract of Emblica officinalis (amla) has been shown to have anti-oxidative and immunomodulatory properties. In view of increasing health risk of arsenic, the present study has been carried out to investigate the protective effect of amla against arsenic induced oxidative stress and apoptosis in thymocytes of mice. Methods Mice were exposed to arsenic (sodium arsenite 3 mg/kg body weight p.o.) or amla (500 mg/kg body weight p.o.) or simultaneously with arsenic and amla for 28 days. The antioxidant enzyme assays were carried out using spectrophotometer and generation of ROS, apoptotic parameters, change in cell cycle were carried out using flow cytometer following the standard protocols. Results Arsenic exposure to mice caused a significant increase in the lipid peroxidation, ROS production and decreased cell viability, levels of reduced glutathione, the activity of superoxide dismutase, catalase, cytochrome c oxidase and mitochondrial membrane potential in the thymus as compared to controls. Increased activity of caspase-3 linked with apoptosis assessed by the cell cycle analysis and annexin V/PI binding was also observed in mice exposed to arsenic as compared to controls. Co-treatment with arsenic and amla decreased the levels of lipid peroxidation, ROS production, activity of caspase-3, apoptosis and increased cell viability, levels of antioxidant enzymes, cytochrome c oxidase and mitochondrial membrane potential as compared to mice treated with arsenic alone. Conclusions The results of the present study exhibits that arsenic induced oxidative stress and apoptosis significantly protected by co-treatment with amla that could be due to its strong antioxidant potential. PMID:23889914

  11. Anti-thymocyte globulin-induced hyperbilirubinemia in patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation.

    PubMed

    Ecsedi, Matyas; Schmohl, Jörg; Zeiser, Robert; Drexler, Beatrice; Halter, Jörg; Medinger, Michael; Duyster, Justus; Kanz, Lothar; Passweg, Jakob; Finke, Jürgen; Bethge, Wolfgang; Lengerke, Claudia

    2016-10-01

    Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment option for myelofibrosis (MF) despite the emergence of novel targeted therapies. To reduce graft rejection and graft-versus-host disease (GvHD), current allo-HCT protocols often include in vivo T lymphocyte depletion using polyclonal anti-thymocyte globulin (ATG). Shortly after ATG administration, an immediate inflammatory response with fever, chills, and laboratory alterations such as cytopenias, elevation of serum C-reactive protein, bilirubin, and transaminases can develop. Here, we explore whether MF patients, who commonly exhibit extramedullary hematopoiesis in the liver, might be particularly susceptible to ATG-induced liver toxicity. To test this hypothesis, we analyzed 130 control and 94 MF patients from three transplant centers treated with or without ATG during the allo-HCT conditioning regimen. Indeed, hyperbilirubinemia was found in nearly every MF patient treated with ATG (MF-ATG 54/60 = 90 %) as compared to non-ATG treated MF (MF-noATG 15/34 = 44.1 %, p < 0.001) and respectively ATG-treated non-MF patients of the control group (control-ATG, 43/77 = 56 %, p < 0.001). In contrast, transaminases were only inconsistently elevated. Hyperbilirubinemia was in most cases self-limiting and not predictive of increased incidence of non-relapse mortality, hepatic sinusoidal obstruction syndrome (SOS) or liver GvHD. In sum, awareness of this stereotypic bilirubin elevation in MF patients treated with ATG provides a relatively benign explanation for hyperbilirubinemia occurring in these patients during the early transplant. However, attention to drug levels of biliary excreted drugs is warranted, since altered bile flow may influence their clearance and enhance toxicity (e.g., busulfan, antifungal agents). PMID:27480090

  12. Cell proliferation and thymocyte subset reconstitution in sublethally irradiated mice: Compared kinetics of endogenous and intrathymically transferred progenitors

    SciTech Connect

    Penit, C.; Ezine, S.

    1989-07-01

    After sublethal (6 Gy) whole-body irradiation, the C57BL/Ba (Thy-1.1) murine thymus regenerated in two waves, on days 3-10 and 25-32, separated by a severe relapse. The second phase of depletion-reconstitution reproduced the first one, in a less synchronous manner. The depletion affected all cell subsets, but CD4+ CD8- cells decreased later than immature cells. Cell proliferation, measured by BrdUrd incorporation, started on day 3 after irradiation and concerned CD4- CD8-, CD4- CD8+, and CD4+ CD8+ cells, sequentially. CD4+ CD8- cells never represented a significant percentage of cycling cells. When irradiation was immediately followed by an intrathymic injection of 10(5) C57BL/Ka (Thy-1.2) bone marrow cells, the relapse in thymus reconstitution was no longer observed. Detected with anti-Thy-1.2 antibodies, donor cells started cycling on day 14 and showed only one wave of proliferation. In these chimeras, recipient thymocytes behave exactly like thymocytes of solely irradiated mice. Intrathymically transferred CD4- CD8- thymocytes 10(5) showed the same proliferation kinetics as endogenous cells, with a peak in number on day 10 but completely disappeared from the thymus on days 14-21. These data reflect maturational differences between intrathymic and bone marrow precursor cells and suggest different radiosensitivities not linked to proliferative status. The resting state of the thymus immigrants was shown by the absence of Thy-1 acquisition by bone marrow cells continuously labeled for 10 days with BrdUrd in vivo before intrathymic transfer. When such labeled bone marrow cells were injected in the thymus, only the minor BrdUrd- subset gave rise to Thy-1+ cells.

  13. V(D)J recombination generates a high frequency of nonstandard TCR D[delta]-associated rearrangements in thymocytes

    SciTech Connect

    Carroll, A.M.; Slack, J.K.; Mu, Xiaochun )

    1993-03-15

    The standard products of V(D)J recombination are coding junctions, which encode Ag receptor polypeptide, and their commonly excised reciprocal products, signal junctions. Additional nonstandard products also have been detected, mostly in artificial recombination substrate studies. The occurrence of nonstandard products, including pseudonormal, hybrid, and open/shut junctions, indicates significant indeterminacy of the V(D)J recombinase. However, the incidence of nonstandard products of endogenous Ag receptor genes in vivo has not been specifically addressed. The data presented here show that for the TCR-[delta] locus, D element-associated recombination in mouse thymocytes results in a high incidence of nonstandard recombination products. D[delta]1-D[delta]2 rearrangements, both chromosome retained and excised episomal products, were studied by polymerase chain reaction amplification, cloning, and sequence analysis. The proximity of D[delta]1 and D[delta]2 elements, and the fact that both are flanked by 5[prime] and 3[prime] recombination signal sequences with 12-bp and 23-bp spacers, respectively, results in frequent pseudonormal joining. The resulting products are signal junctions retained on the chromosome. Excised episomal products include coding junctions, hybrid junctions formed in apparent violation of the 12/23 spacer rule, and standard signal junctions; some signal junctions show evidence of imprecise cleavage. Evidence for open/shut and/or oligonucleotide capture events was also seen. Similar rearrangements were detectable in thymocytes of mutant scid mice. These findings indicate a high degree of indeterminancy of V(D)J recombinase-mediated D[delta]1-D[delta]2 rearrangement in both wild-type and scid thymocytes. This indeterminacy affects the productive potential of TCR-[delta] loci. 45 refs., 4 figs.

  14. Negative selection of semimature CD4+8-HSA+ thymocytes requires the BH3-only protein Bim but is independent of death receptor signaling

    PubMed Central

    Villunger, Andreas; Marsden, Vanessa S.; Zhan, Yifan; Erlacher, Miriam; Lew, Andrew M.; Bouillet, Philippe; Berzins, Stuart; Godfrey, Dale I.; Heath, William R.; Strasser, Andreas

    2004-01-01

    T cell receptor/CD3 ligation induces apoptosis in semimature CD4+8-HSA+ thymocytes, and this helps establish immunological tolerance and constitutes one of the safeguards against autoimmune disease. We analyzed several knockout and transgenic mouse lines and found that T cell receptor/CD3-ligation-induced killing of semimature thymocytes occurred independently of Fas and “death receptor” signaling in general but required the proapoptotic BH3-only protein Bim and could be inhibited by Bcl-2. Loss of Apaf-1 or caspase-9, which act downstream of the Bcl-2 family protein family, provided only minor protection, indicating that the “apoptosome” functions as an amplifier rather than as an essential initiator of this death program. These results reveal the mechanisms of apoptosis in negative selection of semimature thymocytes and have implications for immunological tolerance and autoimmunity. PMID:15118096

  15. Position dependence of the particle density in a double-chain section of a linear network in a totally asymmetric simple exclusion process

    NASA Astrophysics Data System (ADS)

    Pesheva, N. C.; Brankov, J. G.

    2013-06-01

    We report here results on the study of the totally asymmetric simple exclusion process, defined on an open network, consisting of head and tail simple-chain segments with a double-chain section inserted in between. Results of numerical simulations for relatively short chains reveal an interesting feature of the network. When the current through the system takes its maximum value, a simple translation of the double-chain section forward or backward along the network leads to a sharp change in the shape of the density profiles in the parallel chains, thus affecting the total number of particles in that part of the network. In the symmetric case of equal injection and ejection rates α=β>1/2 and equal lengths of the head and tail sections, the density profiles in the two parallel chains are almost linear, characteristic of the coexistence line (shock phase). Upon moving the section forward (backward), their shape changes to the one typical for the high- (low-) density phases of a simple chain. The total bulk density of particles in a section with a large number of parallel chains is evaluated too. The observed effect might have interesting implications for the traffic flow control as well as for biological transport processes in living cells. An explanation of this phenomenon is offered in terms of a finite-size dependence of the effective injection and ejection rates at the ends of the double-chain section.

  16. Effect of 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) in vitro on RNA synthesis in rat thymocytes

    SciTech Connect

    Olnes, M.; Abraham, M.; Kurl, R.N. )

    1991-03-11

    TCDD, a potent inducer of cytochrome P-450, augments synthesis of specific liver constituents while simultaneously causing marked involution of the thymus. To elucidate the mechanism by which TCDD induces thymic atrophy, initial experiments were performed to establish the kinetics of uptake of TCDD in vitro by thymocytes. The latter were incubated with either {sup 3}H-TCDD or TCDD for various time intervals. Measurement of radio-activity and gel mobility shift assays using nuclear extracts and a dioxin-responsive element (DRE-3) of the cytochrome P-450 (Cyplal) gene revealed maximum uptake of TCDD by thymocyte nuclei at 30-60 min post incubation. RNA synthesis was increased as early as 30 min. The increase in RNA synthesis could be inhibited by actinomycin D. At these time points degradation of DNA was visible. Whether newly formed RNA is translated into a protein(s) which in turn is (are) responsible for degradation of DNA leading to cell death needs to be established.

  17. Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after {gamma}-irradiation

    SciTech Connect

    Maruyama, Masaki; Yamamoto, Takashi; Kohara, Yuki; Katsuragi, Yoshinori; Mishima, Yukio; Aoyagi, Yutaka; Kominami, Ryo; E-mail: rykomina@med.niigata-u.ac.jp

    2007-03-02

    Mouse strains exhibit different susceptibilities to {gamma}-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of {gamma}-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas.

  18. QUANTITATION OF ABERRANT INTERLOCUS T-CELL RECEPTOR REARRANGEMENTS IN MOUSE THYMOCYTES AND THE EFFECT OF THE HERBICIDE 2,4- DICHLOROPHENOXYACETIC ACID

    EPA Science Inventory

    Quantitation of aberrant interlocus T-cell receptor rearrangements in mouse thymocytes and the effect of the herbicide 2,4- Dichlorophenoxyacetic acid

    Small studies in human populations have suggested a correlation between the frequency of errors in antigen receptor gene a...

  19. Analyses of the radiation of birnaviruses from diverse host phyla and of their evolutionary affinities with other double-stranded RNA and positive strand RNA viruses using robust structure-based multiple sequence alignments and advanced phylogenetic methods

    PubMed Central

    2013-01-01

    Background Birnaviruses form a distinct family of double-stranded RNA viruses infecting animals as different as vertebrates, mollusks, insects and rotifers. With such a wide host range, they constitute a good model for studying the adaptation to the host. Additionally, several lines of evidence link birnaviruses to positive strand RNA viruses and suggest that phylogenetic analyses may provide clues about transition. Results We characterized the genome of a birnavirus from the rotifer Branchionus plicalitis. We used X-ray structures of RNA-dependent RNA polymerases and capsid proteins to obtain multiple structure alignments that allowed us to obtain reliable multiple sequence alignments and we employed “advanced” phylogenetic methods to study the evolutionary relationships between some positive strand and double-stranded RNA viruses. We showed that the rotifer birnavirus genome exhibited an organization remarkably similar to other birnaviruses. As this host was phylogenetically very distant from the other known species targeted by birnaviruses, we revisited the evolutionary pathways within the Birnaviridae family using phylogenetic reconstruction methods. We also applied a number of phylogenetic approaches based on structurally conserved domains/regions of the capsid and RNA-dependent RNA polymerase proteins to study the evolutionary relationships between birnaviruses, other double-stranded RNA viruses and positive strand RNA viruses. Conclusions We show that there is a good correlation between the phylogeny of the birnaviruses and that of their hosts at the phylum level using the RNA-dependent RNA polymerase (genomic segment B) on the one hand and a concatenation of the capsid protein, protease and ribonucleoprotein (genomic segment A) on the other hand. This correlation tends to vanish within phyla. The use of advanced phylogenetic methods and robust structure-based multiple sequence alignments allowed us to obtain a more accurate picture (in terms of

  20. In vitro suppression of thymocyte apoptosis by metal-rich complex environmental mixtures: potential role of zinc and cadmium excess.

    PubMed

    Chukhlovi, A B; Tokalov, S V; Yagunov, A S; Westendorf, J; Reincke, H; Karbe, L

    2001-12-17

    Excessive amounts of heavy metals (e.g. Zn, Cu, Mn, Cr) are accumulated in river bottom sediments (RBS), being available to humans and animals along food chains. Increased exposure of mammals to certain metals (Cr, Cu) induces immunosuppresion, due to DNA damage and decreased survival of lymphoid cells. By contrast, excess of Zn and Cd causes inhibition of apoptosis thus suggesting increased survival of genetically mutated cells and higher cancer risks in exposed populations. Rat thymic lymphocytes represent a well-established model for apoptosis testing. The primary goal of our study was to assess the degree of apoptosis modulation with a number of RBS extracts differing in their metal contents. A series of freshly deposited RBS was collected at nine sampling stations along the Elbe River. All sediments were rich in Fe, Mn and Zn. The contents of Cu, Cr, Ni, Cd, Hg, Pb and As were much lower and interrelated. The short-term cytotoxicity of aqueous sediment extracts was assessed, using the following criteria: total cell counts; incidence of apoptosis and necrosis (morphological detection by fluorescent microscopy); and nuclear chromatin decay (by DNA flow cytometry). RBS extracts produced both apoptosis and necrosis of thymocytes. High contents of zinc and other heavy metals in the samples correlated with decreased thymocyte apoptosis (r= -0.543 to -0.608, P <0.01). The rates of thymocyte damage showed a distinct dependence on the time and region of sampling. Apoptosis modulation was also tested with pure salts of Mn(II), Zn(II), Cu(II), Cr(III) and Cd(II), at the test concentrations of 1, 10 and 100 microM. Cu(II) and Cr(III) proved to induce marked dose-related apoptosis, whereas Zn(II) ions caused significant suppression of apoptosis. These effects were similar to those trends observed with metal-rich sediments. In the present study. DNA flow cytometry proved to be a less sensitive index of cell death than morphological assay of apoptosis and/or necrosis. In

  1. Effects of Systemic Administration of Dexmedetomidine on Intraocular Pressure and Ocular Perfusion Pressure during Laparoscopic Surgery in a Steep Trendelenburg Position: Prospective, Randomized, Double-Blinded Study

    PubMed Central

    2016-01-01

    Increased intraocular pressure (IOP) during surgery is a risk factor for postoperative ophthalmological complications. We assessed the efficacy of systemically infused dexmedetomidine in preventing the increase in IOP caused by a steep Trendelenburg position, and evaluated the influence of underlying hypertension on IOP during surgery. Sixty patients undergoing laparoscopic surgery in a steep Trendelenburg position were included. Patients in the dexmedetomidine group received a 1.0 µg/kg IV loading dose of dexmedetomidine before anesthesia, followed by an infusion of 0.5 µg/kg/hr throughout the operation. Patients in the saline group were infused with the same volume of normal saline. IOP and ocular perfusion pressure (OPP) were measured 16 times pre- and intraoperatively. In the saline group, IOP increased in the steep Trendelenburg position, and was 11.3 mmHg higher at the end of the time at the position compared with the baseline value (before anesthetic induction). This increase in IOP was attenuated in the dexmedetomidine group, for which IOP was only 4.2 mmHg higher (P < 0.001 vs. the saline group). The steep Trendelenburg position was associated with a decrease in OPP; the degree of decrease was comparable for both groups. In intragroup comparisons between patients with underlying hypertension and normotensive patients, the values of IOP at every time point were comparable. Dexmedetomidine infusion attenuated the increase in IOP during laparoscopic surgery in a steep Trendelenburg position, without further decreasing the OPP. Systemic hypertension did not seem to be associated with any additional increase in IOP during surgery. (Registration at the Clinical Research Information Service of Korea National Institute of Health ID: KCT0001482) PMID:27247511

  2. Determining the DUF55-domain structure of human thymocyte nuclear protein 1 from crystals partially twinned by tetartohedry

    SciTech Connect

    Yu, Feng; Song, Aixin; Xu, Chunyan; Sun, Lihua; Li, Jian; Tang, Lin; Yu, Minmin; Yeates, Todd O.; Hu, Hongyu; He, Jianhua

    2009-06-06

    Human thymocyte nuclear protein 1 (hTHYN1) contains a unique DUF55 domain of 167 residues (55-221), but its cellular function is unclear. Crystals of DUF55 belong to the trigonal space group P3{sub 1}, but twinning causes the data to approach an apparent 622 symmetry. Two datasets to 2.3 {angstrom} resolution were collected. Statistical analysis confirmed that both datasets were partially twinned by tetartohedry. Tetartohedral twin fractions were estimated. After the structure was determined, only one twofold axis of rotational pseudosymmetry was found in the crystal structure. Using the DALI program, a YTH domain, which is a potential RNA binding domain from human YTH domain-containing protein 2, was identified to have the most similar three-dimensional fold to DUF55. It is implied that DUF55 might be a potential RNA-related domain.

  3. In vitro toxicity and interactions of environmental contaminants (Arochlor 1254 and mercury) and immunomodulatory agents (lipopolysaccharide and cortisol) on thymocytes from lake trout (Salvelinus namaycush)

    USGS Publications Warehouse

    Miller, Gregory G.; Sweet, Leonard I.; Adams, Jean V.; Omann, Geneva M.; Passino-Reader, Dora R.; Meier, Peter G.

    2002-01-01

    The immunotoxicity of chemical combinations commonly encountered by the lake trout (Salvelinus namaycush) immune system was the focus of this study. It was hypothesised that combinations of an environmental contaminant (mercuric chloride or Aroclor 1254) and an immunomodulatory agent (bacterial endotoxin or cortisol) might interact to produce a greater toxicity than that of the environmental contaminant alone at concentrations typically encountered in piscine blood and other tissues. Thus lake trout thymocytes were isolated and treated with mercuric chloride or Aroclor 1254 in the presence and absence of cortisol or lipopolysaccharide. Incubations were performed for 6 or 20 h at 4° C or 10° C. Lipopolysaccharide did not affect the toxicity of either contaminant. In contrast, cortisol enhanced the toxicity of both environmental contaminants. Hence, stressors that lead to increased cortisol production, but not lipopolysaccharide directly, may increase the toxicity of mercury and Aroclor 1254 to lake trout thymocytes.

  4. Dissociation of peripheral T cell responses from thymocyte negative selection by weak agonists supports a spare receptor model of T cell activation

    PubMed Central

    McNeil, Lisa K.; Evavold, Brian D.

    2002-01-01

    We have focused on stability of the peptide-MHC complex as a determining factor of ligand potency for thymocytes and peripheral CD4+ T cell responses. MHC variant peptides that have low affinities and fast dissociation rates are different in that they stimulate proliferation and cytolysis of mature T cells (classifying the variant peptides as weak agonists) but do not induce thymocyte negative selection. The MHC variant weak agonists require significant receptor reserve, because decreasing the level of T cell receptor on mature T cells blocks the proliferative response. These results demonstrate that peripheral T cells are more sensitive to MHC variant ligands by virtue of increased T cell receptor expression; in addition, the data support a T cell model of the spare receptor theory. PMID:11904393

  5. Pharmacokinetic and pharmacodynamic characterisation of JNJ-40411813, a positive allosteric modulator of mGluR2, in two randomised, double-blind phase-I studies.

    PubMed

    Salih, Hiba; Anghelescu, Ion; Kezic, Iva; Sinha, Vikash; Hoeben, Eef; Van Nueten, Luc; De Smedt, Heidi; De Boer, Peter

    2015-04-01

    Metabotropic glutamate receptor-2 positive allosteric modulator, JNJ-40411813 (ADX71149), was characterised for clinical effects in healthy volunteers in two phase-1 studies. In study 1, healthy men received 50-, 100-, 150- or 225 mg and women received 100 mg JNJ-40411813 (n=6, each cohort) or placebo (n=2, each cohort) twice daily for seven days; smoking men (n=30) received placebo twice daily on days 1-7, 100 mg JNJ-40411813 (n=20) or placebo (n=10) on days 8-14. In study 2, healthy men received intravenous 0.005 mg/kg S(+) ketamine over 60 min at 3 (n=24; cohort 1), 12 h (n=8; cohort 3), and 24 h (n=8; cohort 2) after a single oral dose of 500 mg JNJ-40411813 or placebo. The pharmacokinetics and effects of JNJ-40411813 on cognition and subjective awareness were evaluated. Plasma JNJ-40411813 exposure was dose-dependent, t max ranged from 3-4 h and t 1/2 19.4-34.2 h across the dose levels. JNJ-40411813 significantly (p=0.02) reduced continuity of attention score (150 mg dose) and ameliorated smoking withdrawal-induced changes in power of attention and quality of episodic memory versus placebo. A modest reduction in alertness was observed at 150-225 mg doses, JNJ-40411813 (500 mg) reduced S(+) ketamine-induced negative symptoms by approximately 43% and 30% in cohorts 1 and 3, respectively. JNJ-40411813 was generally well-tolerated. PMID:25735992

  6. Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery

    SciTech Connect

    Brown, Nicole; Nagarkatti, Mitzi; Nagarkatti, Prakash S. . E-mail: pnagark@hsc.vcu.edu

    2006-04-15

    Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effects of DES on T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8{sup +} T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8{sup +} T cells. The density of expression of HY-TCR on CD8{sup +} cells was increased following DES exposure in both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery.

  7. Tracking The Double Eagle

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Last summer a trio of aeronauts made aviation history. Ben Abruzzo, Maxie Anderson and Larry Newman, all of Albuquerque, New Mexico, piloted their balloon Double Eagle I1 from Presque Isle, Maine to Miserey, France, some 50 miles from Paris. They were the first to negotiate a successful Atlantic crossing in a freeflying balloon after a score of attempts over a span of more than a century. A year earlier, Abruzzo and Anderson had made an unsuccessful try in their predecessor balloon Double Eagle. On that occasion, a NASA-developed satellite beacon helped save their lives. Carried aboard the balloon, the simple, seven-pound beacon continuously transmitted signals to NASA's Nimbus-6 satellite. Nimbus relayed the signals to monitors at Goddard Space Flight Center, enabling Goddard to compute the balloon's position. Position reports were then telephoned regularly to Double Eagle's control center at Bedford, Massachusetts. This monitoring system proved invaluable when the balloon encountered trouble several days after liftoff.

  8. Exuberant cortical thymocyte proliferation mimicking T-lymphoblastic lymphoma within recurrent large inguinal lymph node masses of localized Castleman disease.

    PubMed

    Kansal, Rina; Nathwani, Bharat N; Yiakoumis, Xanthi; Moschogiannis, Maria; Sachanas, Sotirios; Stefanaki, Kalliopi; Pangalis, Gerassimos A

    2015-07-01

    We report a 13-year-old adolescent girl, the youngest thus far, with "an indolent T-lymphoblastic" proliferation (~10%) that uniquely presented within recurrent, large inguinal lymph node masses in a predominating (90%) background of Castleman disease. These nodal masses were resected thrice; the patient is well 5 years after diagnosis without further treatment. Histologically, the features of Castleman disease, hyaline vascular type, were present. Importantly, the interfollicular T-lymphoblastic component occurred as multiple clusters and islands of variable shapes and sizes composed of small "lymphoblasts" indistinguishable from normal cortical thymocytes but without thymic epithelial cells. Immunohistochemically, these lymphoblasts were consistent with the intermediate stage of T-cell differentiation (TdT(+)CD34(-)CD99(+)CD1a(+)CD2(+)CD3(+)CD4(+)CD8(+)CD5(+)CD7(+)CD10(+) [subset]), with 80% Ki-67. Molecularly, the T cells were nonclonal. Our case provides evidence for the benign nature of this highly unusual and poorly understood entity; because the current terminology can be readily misinterpreted as an indolent lymphoblastic lymphoma, we suggest a new term accurately reflecting this entity. PMID:25953658

  9. Low-dose Anti-thymocyte Globulin Inhibits Human B-cell Differentiation into Antibody-Secreting Cells.

    PubMed

    Klaus, Pascal; Heine, Guido; Rasche, Claudia; Worm, Margitta

    2015-07-01

    Anti-thymocyte globulin (ATG) is used in the treatment of acute organ rejection. We studied in vitro the effect of low-dose ATG on B-cell activation and differentiation to antibody-secreting cells, as this may have an effect on B cell-driven autoimmune diseases, such as pemphigus vulgaris. Immunoglobulin production was analysed in the supernatants of peripheral blood mononuclear cells (PBMC) and CD19+ B cells from healthy donors and from patients with different autoimmune diseases. B-cell proliferation, viability and differentiation were analysed using flow cytometry. Differentiation of B cells to immunoglobulin G (IgG) secreting cells was significantly reduced by ATG, but not by control unspecific IgG from non-immunized rabbits (rIgG). B-cell viability was not altered by sub-depleting concentrations of ATG. In contrast, B-cell proliferation was enhanced by ATG. When PBMC from patients with autoimmune diseases were studied, specific autoantibodies could be detected in 1 out of 10 patients. In this patient, who had pemphigus vulgaris, ATG not only decreased total IgG, but decreased also specific anti-desmoglein-3. In conclusion, these data suggest that ATG at low concentrations inhibits B-cell differentiation and function. PMID:25587881

  10. A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors

    PubMed Central

    Buono, Mario; Facchini, Raffaella; Matsuoka, Sahoko; Thongjuea, Supat; Waithe, Dominique; Luis, Tiago C.; Giustacchini, Alice; Besmer, Peter; Mead, Adam J.; Jacobsen, Sten Eirik W.; Nerlov, Claus

    2016-01-01

    Thymic T-cell development is initiated from bone marrow-derived multi-potent thymus seeding progenitors (TSPs). During the early stages of thymocyte differentiation progenitors become T-cell restricted. However, the cellular environments supporting these critical initial stages of T-cell development within the thymic cortex are not known. We here use the dependence of early, c-Kit–expressing thymic progenitors on Kit ligand (KitL) to show that CD4–CD8–c-Kit+CD25– DN1-stage progenitors associate with, and depend on the membrane-bound form of KitL (mKitL) provided by, a cortex-specific KitL-expressing vascular endothelial cell (VEC) population. In contrast, the subsequent CD4–CD8–c-Kit+CD25+ DN2 stage progenitors associate selectively with cortical thymic epithelial cells (cTECs) and depend on cTEC-presented mKitL. These results show that the dynamic process of early thymic progenitor differentiation is paralleled by migration-dependent changes to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand. PMID:26780297

  11. Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes and mapping of Rapop1, a novel susceptibility gene

    SciTech Connect

    Mori, Nobuko; Okumoto, Masaaki; Esaki, Kozaburo

    1995-02-10

    Genetic dissection of susceptibility to radiation-induced apoptosis of thymocytes was performed by counting dead cells in histologically processed thymuses after 0.5 Gy of whole-body X-irradiation, using recombinant congenic (CcS/Dem) strains derived from inbred mouse strains BALB/cHeA (susceptible) and STS/A (resistant). A high (8/20) number of strains with lower dead cell scores than BALB/cHeA among CcS/Dem recombinant congenic strains (RCS), which contain 12.5% of STS/A genome in the genetic background of BALB/cHeA strain, indicates that the difference between BALB/cHeA and STS/A is caused by several genes and that susceptibility probably requires BALB/ cHeA alleles at more than one locus. Similar results were obtained with CXS/Hg recombinant inbred (CXS/ Hg) strains. Analysis of F{sub 2} hybrids between BALB/ cHeA and CcS-7, one of the CcS/Dem strains that showed lower dead cell scores than BALB/cHeA, demonstrated that a novel gene (Rapop1, radiation-induced apoptosis 1) controlling susceptibility to radiation-induced apoptosis in the thymus is located in the proximal region of mouse chromosome 16. 40 refs., 2 figs., 2 tabs.

  12. Effects of ultraviolet radiation on the production of epidermal derived thymocyte-activating factor/interleukin-1

    SciTech Connect

    Gahring, L.C.

    1986-01-01

    The effect of both a single exposure and multiple exposures to ultraviolet radiation (UVR) on the production and/or release of epidermal cell derived thymocyte activating factor/interleukin-1 (ETAF/IL-1) were investigated. A single exposure to UVR enhances the release of ETAF/IL-1 both in vitro and in vivo. This conclusion was based on the observation that: (1) in vitro UV-irradiation of the keratinocyte cell line elevated the release of ETAF/IL-1 on a per cell basis; (2) exposure of animals to UVR stimulated a number of in vivo biologic responses which are known to be mediated by ETAF/IL-1; and (3) ETAF/IL-1 could be detected in the serum of UVR exposed but not normal animals. Exposure of mice to UV-irradiation on a daily basis induced a desensitized state in which animals were found to be refractory to further stimulation with this inflammatory agent. A similar desensitization or tolerance was also shown to be induced by multiple intraperitoneal injections of bacterial lipopolysaccharide (LPS). Desensitization, induced by either LPS or UVR, was found to be regulated at the site of interaction between the cells capable of ETAF/IL-1 production and the exogenous inflammatory stimulus. The results indicate that the regulatory mechanisms for ETAF/IL-1 production which are employed by the keratinocyte are distinct from those regulating ETAF/Il-1 production by the macrophage.

  13. A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.

    PubMed

    Buono, Mario; Facchini, Raffaella; Matsuoka, Sahoko; Thongjuea, Supat; Waithe, Dominique; Luis, Tiago C; Giustacchini, Alice; Besmer, Peter; Mead, Adam J; Jacobsen, Sten Eirik W; Nerlov, Claus

    2016-02-01

    Thymic T cell development is initiated from bone-marrow-derived multi potent thymus-seeding progenitors. During the early stages of thymocyte differentiation, progenitors become T cell restricted. However, the cellular environments supporting these critical initial stages of T cell development within the thymic cortex are not known. Here we use the dependence of early, c-Kit-expressing thymic progenitors on Kit ligand (KitL) to show that CD4(-)CD8(-)c-Kit(+)CD25(-) DN1-stage progenitors associate with, and depend on, the membrane-bound form of KitL (mKitL) provided by a cortex-specific KitL-expressing vascular endothelial cell (VEC) population. In contrast, the subsequent CD4(-)CD8(-)c-Kit(+)CD25(+) DN2-stage progenitors associate selectively with cortical thymic epithelial cells (cTECs) and depend on cTEC-presented mKitL. These results show that the dynamic process of early thymic progenitor differentiation is paralleled by migration-dependent change to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand. PMID:26780297

  14. Clinical Comparison of Non-Myeloablative Conditioning with Anti-Thymocyte Globulin and Fludarabine for Patients with Hematologic Malignancies

    PubMed Central

    Li, Qingshan; Meng, Fanyi; Zhou, Ming; Yu, Bizhen; Mo, Wenjian; Du, Qinghua; Jiang, Xuejie; Wei, Yaming

    2015-01-01

    Background The influence of different non-myeloablative conditioning regimens on clinical outcome remains undefined. Material/Methods We retrospectively analyzed the hematopoietic reconstitution, graft-versus-host disease (GVHD), and quality of life (QOL) in 56 patients with hematologic malignancies who underwent non-myeloablative stem cell transplantation (NST) with a conditioning regimen based on anti-thymocyte globulin (ATG), followed by donor lymphocyte infusion (n=24), or Fludarabine (FLU) (n=32). Hematopoietic stem cells were derived from low-resolution HLA-matched identical sibling donors. Results The blood type transformation and platelet reconstitution presented significantly earlier in the FLU group than the ATG group (P<0.05). Within 100 days post-transplantation, the incidence of grade I–IV acute GVHD was significantly lower in the ATG group than the FLU group (P<0.05). After 100 days post-transplant, extensive chronic GVHD (cGVHD) was more prevalent in the ATG group than the FLU group (P<0.05). There were lower cumulative risk of relapse and higher non-relapse-related mortality in the ATG group, but better QOL in the FLU group within 24 months, and no difference in 3-year disease-free survival (DFS) or overall survival (OS) between the 2 groups (P>0.05). Conclusions The FLU-based conditioning regimen improved hematopoietic reconstitution and decreased extensive cGVHD, but there was no difference in 3-year DFS or OS between the 2 groups. PMID:26238068

  15. Nanomolar concentrations of zinc pyrithione increase cell susceptibility to oxidative stress induced by hydrogen peroxide in rat thymocytes.

    PubMed

    Oyama, Tomohiro M; Saito, Minoru; Yonezawa, Takayasu; Okano, Yoshiro; Oyama, Yasuo

    2012-06-01

    Zinc pyrithione is used as an antifouling agent. However, the environmental impacts of zinc pyrithione have recently been of concern. Zinc induces diverse actions during oxidative stress; therefore, we examined the effect of zinc pyrithione on rat thymocytes suffering from oxidative stress using appropriate fluorescent probes. The cytotoxicity of zinc pyrithione was not observed when the cells were incubated with 3 μM zinc pyrithione for 3 h. However, zinc pyrithione at nanomolar concentrations (10 nM or more) significantly increased the lethality of cells suffering from oxidative stress induced by 3 mM H(2)O(2). The application of zinc pyrithione alone at nanomolar concentrations increased intracellular Zn(2+) level and the cellular content of superoxide anions, and decreased the cellular content of nonprotein thiols. The simultaneous application of nanomolar zinc pyrithione and micromolar H(2)O(2) synergistically increased the intracellular Zn(2+) level. Therefore, zinc pyrithione at nanomolar concentrations may exert severe cytotoxic action on cells simultaneously exposed to chemicals that induce oxidative stress. If so, zinc pyrithione leaked from antifouling materials into surrounding environments would be a risk factor for aquatic ecosystems. Alternatively, zinc pyrithione under conditions of oxidative stress may become more potent antifouling ingredient. PMID:22356860

  16. Unfractionated human thymocytes have a lower proliferative capacity than CD3/sup -/4/sup -/8/sup -/ ones but have a similar capacity for expression of interleukin 2 receptors and production of interleukin 2

    SciTech Connect

    Vives, J.; Sole, J.; Suarez, B.

    1987-12-01

    CD3/sup -/4/sup -/8/sup -/ and unfractionated thymocytes were compared for their capacity to proliferate, to express interleukin 2 (IL-2) receptor, and to secrete IL-2. Phorbol ester and Ca/sup 2 +/ ionophore were used as mitogens. CD3/sup -/4/sup -/8/sup -/ thymocytes responded vigorously when stimulated with phorbol ester in the presence of IL-2 or in combination with Ca/sup 2 +/ ionophore. In contrast, unfractionated thymocytes responded weakly when stimulated with either of these mitogens. Surprisingly, however, the stimulation of these populations with either phorbol ester plus IL-2 or phorbol ester plus ionophore induced a high and similar level of IL-2 receptor expression in both thymocyte populations. A similar level of IL-2 secretion in both populations was also obtained when they were stimulated with a combination of phorbol ester plus ionophere. These results suggest that during the maturation process, the majority of thymocytes lose their capacity to be activated by some mitogens, although they maintain their capacity to secrete IL-2 and to express the IL-2 receptor.

  17. Apple Valley Double Star Workshop

    NASA Astrophysics Data System (ADS)

    Brewer, Mark

    2015-05-01

    The High Desert Astronomical Society hosts an annual double star workshop, where participants measure the position angles and separations of double stars. Following the New Generation Science Standards (NGSS), adopted by the California State Board of Education, participants are assigned to teams where they learn the process of telescope set-up and operation, the gathering of data, and the reduction of the data. Team results are compared to the latest epoch listed in the Washington Double Star Catalog (WDS) and papers are written for publication in the Journal of Double Star Observations (JDSO). Each team presents a PowerPoint presentation to their peers about actual hands-on astronomical research.

  18. Recognition of a CD4+ mouse medullary thymocyte subpopulation by Amaranthus leucocarpus lectin.

    PubMed

    Lascurain, R; Chávez, R; Gorocica, P; Pérez, A; Montaño, L F; Zenteno, E

    1994-11-01

    We have used the Gal beta(1-->3)GalNAc-specific Amaranthus leucocarpus lectin to isolate a thymus cell subpopulation which is different from that sorted with Arachis hypogaea lectin. The cells recognized by A. leucocarpus lectin were predominantly CD4+, whereas a minor proportion of CD8+ cells (approximately 11%) were also identified. The A. leucocarpus-positive cells were located in the thymus medulla and the cortico-medullary junction. The cortex was negative for A. leucocarpus cells. PMID:7835965

  19. Inhibition of CD25 (IL-2R alpha) expression and T-cell proliferation by polyclonal anti-thymocyte globulins.

    PubMed Central

    Bonnefoy-Berard, N; Verrier, B; Vincent, C; Revillard, J P

    1992-01-01

    Anti-lymphocyte and anti-thymocyte globulins (ATG) are currently used as immunosuppressive agents in organ transplantation. Their administration in vivo may induce not only lymphocyte depletion but also functional effects which were investigated in the present study. In vitro ATG inhibited T-cell proliferation induced by monocyte-dependent T-cell mitogens, like CD3 antibodies, phytohaemagglutinin (PHA) and concanavalin A (Con A), by monocyte-independent mitogens, like CD2 antibodies, or by protein kinase C activators (phorbol esters) associated with a calcium ionophore. The inhibitory effect of ATG was therefore not solely accounted for by a suppression of co-stimulatory signals delivered by monocytes, but rather implied a direct action on T cells. Addition of recombinant human interleukin-2 (rIL-2) did not overcome the inhibition. Suppression of T-cell proliferation by ATG was characterized by normal RNA synthesis and IL-2 secretion contrasting with markedly reduced expression of the CD25 protein [p55, the alpha-chain of interleukin-2 receptor (IL-2R)] both in cytoplasm and on T-cell membrane, as well as a decreased secretion of interferon-gamma (IFN-gamma). Northern blot analysis revealed increased levels of CD25 and IFN-gamma mRNA, suggesting a post-transcriptional inhibition of these molecules, whereas IL-2 mRNA levels were unchanged. These data demonstrate that inhibition of T-cell proliferation by ATG can be attributed primarily to a post-transcriptional defect of CD25 expression, implying a novel mechanism different from those described with other immunosuppressive agents. Blocking of T-cell proliferation in the late G1 phase of the cell cycle may contribute to the immunosuppressive activity of ATG in prophylactic treatment of allograft rejection. Images Figure 2 PMID:1398765

  20. Induction by anti-thymocyte globulins in kidney transplantation: a review of the literature and current usage

    PubMed Central

    Malvezzi, Paolo; Jouve, Thomas; Rostaing, Lionel

    2015-01-01

    Context: Preventing acute rejection (AR) after kidney transplantation is of utmost importance because an AR can have a negative impact on long-term allograft survival. Evidence Acquisition: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO, and Web of Science have been searched. Results: At the moment this can be done by using rabbit anti-thymocyte globulins (rATGs) as an induction therapy. However, because rATGs are associated with some deleterious side-effects, such as the opportunistic infections cytomegalovirus (CMV) and de novo post-transplant cancer, it is very important they are used optimally, i.e., at minimal doses that avoid many side-effects but still retain optimal treatment efficacy. Recent data show that the risk of CMV infection can be minimized using tacrolimus plus everolimus, and not tacrolimus plus mycophenolic acid, as the maintenance immunosuppression. The use of rATG is particularly valuable in; (a) sensitized patients; (b) in recipients from an expanded-criteria donor, thus enabling the introduction of calcineurin inhibitors at reduced doses; and (c) for patients where steroid avoidance is contemplated. However, we also need to consider that rATG may increase the risk of de novo cancer, even though recent data indicate this is unlikely and that any risk can be reduced by using mammalian target of rapamycin (mTOR) inhibitors instead of mycophenolic acid combined with low-dose calcineurin inhibitors. Conclusions: Even though rATGs do not improve long-term kidney-allograft survival, they may help reduce calcineurin-inhibitor dosage during the early post-transplant period and minimize the risk of AR. PMID:26457257

  1. Treatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA).

    PubMed

    Miles, David; Baselga, José; Amadori, Dino; Sunpaweravong, Patrapim; Semiglazov, Vladimir; Knott, Adam; Clark, Emma; Ross, Graham; Swain, Sandra M

    2013-11-01

    Although the incidence of cancer increases with age, older patients are under-represented in cancer treatment trials, resulting in limited data availability in this patient population. Here we present results from pre-defined subgroup analyses conducted by age group (<65 vs ≥ 65 years) from a randomized, double-blind, placebo-controlled phase III trial in patients with HER2-positive metastatic breast cancer. Patients who had not received previous chemotherapy or biological therapy for HER2-positive locally recurrent, unresectable or metastatic breast cancer were randomly assigned to treatment with placebo, trastuzumab, and docetaxel or with pertuzumab, trastuzumab, and docetaxel. Primary endpoint was independently assessed progression-free survival. We performed pre-specified subgroup analyses of progression-free survival according to age. The study is registered with ClinicalTrials.gov, NCT00567190. 808 patients were enrolled. Of those, 127 patients were 65 years of age or older (placebo arm: 67, pertuzumab arm: 60). Patients in both age groups experienced progression-free survival benefit with treatment in the pertuzumab arm (<65 years: HR: 0.65; 95 % CI 0.53-0.80; ≥65 years: HR: 0.52; 95 % CI 0.31-0.86). Diarrhoea, fatigue, asthenia, decreased appetite, vomiting, and dysgeusia were reported more frequently in patients 65 years of age or older compared with younger patients. Neutropenia and febrile neutropenia were reported less frequently in the older age group. The efficacy and safety data reported in CLEOPATRA suggest that the combined use of pertuzumab, trastuzumab, and docetaxel should not be limited by patient age. PMID:24129974

  2. Inhibition of CD26 enzyme activity with pro-boropro stimulates rat granulocyte/macrophage colony formation and thymocyte proliferation in vitro.

    PubMed

    Bristol, L A; Bachovchin, W; Takács, L

    1995-06-15

    CD26 dipeptidyl peptidase (DPPIV) is involved in the regulation of proliferation of some hematopoietic and T-lineage cells. Here, we show that Pro-boropro a potent inhibitor of DPP activity has a costimulating effect in hematopoietic colony assays for macrophage and, to a lesser extent, for granulocyte colonies and has a stimulating effect in organ cultures of immature thymocytes. Based on these and other evidences, we propose that the mechanism by which CD26 regulates proliferation is associated with its DPP activity. PMID:7780144

  3. Effect of Dexmedetomidine on Heart Rate-Corrected QT and Tpeak-Tend Intervals During Robot-Assisted Laparoscopic Prostatectomy With Steep Trendelenburg Position: A Prospective, Randomized, Double-Blinded, Controlled Study.

    PubMed

    Kim, Na Young; Han, Dong Woo; Koh, Jae Chul; Rha, Koon Ho; Hong, Jung Hwa; Park, Jong Min; Kim, So Yeon

    2016-05-01

    Intraperitoneal insufflation of carbon dioxide may affect the sympathetic activity that leads to changes in ventricular repolarization. This in turn can result in changes of heart rate-corrected QT (QTc) interval and Tpeak-Tend (Tp-e) interval. Dexmedetomidine is a highly selective α2-receptor agonist and has potential antiarrhythmic properties. This prospective, randomized, double-blinded, controlled study evaluated the effects of dexmedetomidine administration on QTc and Tp-e intervals during robot-assisted laparoscopic prostatectomy with steep Trendelenburg position.Fifty patients scheduled for robot-assisted laparoscopic prostatectomy randomly received either a continuous infusion of dexmedetomidine at a rate of 0.3 μg/kg/hour, from anesthetic induction until the end of the Trendelenburg position (dexmedetomidine group; n = 25), or the same volume of normal saline (control group; n = 25). Anesthesia was maintained with sevoflurane and remifentanil. The primary and secondary goals were to evaluate the effect of dexmedetomidine on the QTc and Tp-e interval changes. Mean arterial pressure, heart rate, end-tidal CO2, and end-tidal sevoflurane concentrations were assessed as well.Forty-seven patients (94%) completed the study. Dexmedetomidine significantly attenuated QTc interval prolongation and reduced the Tp-e interval, even though the baseline values of the QTc and Tp-e intervals were similar between the 2 groups (PGroup × Time = 0.001 and 0.014, respectively). Twenty-two patients (96%) in the control group and 13 (54%) in the dexmedetomidine group had QTc interval prolongation of >20 ms from the baseline value during surgery (P = 0.001). The maximum QTc interval prolongation from the baseline value during surgery was 46 ± 21 ms in the control group and 24 ± 21 ms in the dexmedetomidine group (mean ± SD, P = 0.001). Mean arterial pressure and heart rate were comparable between the groups.Continuous infusion of

  4. [Responses of thymocytes and splenocytes to low-intensity extremely high-frequency electromagnetic radiation in normal mice and in mice with systemic inflammation].

    PubMed

    Gapeev, A B; Sirota, N P; Kudriavtsev, A A; Chemeris, N K

    2010-01-01

    Changes in T cell subsets and expression of cytokine genes in thymocytes and splenocytes after exposure of BAL/c mice to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, exposure duration 20 min) under normal conditions and in systemic inflammation were studied using flow cytometry and the methods of reverse transcription and real-time polymerase chain reaction. It was found that the number of CD4+ and CD8+ T cells statistically significantly increased in the thymus and considerably decreased in the spleen of exposed animals. Apparently, the exposure of animals leads to an intensification of the host defense, by activating the T-cellular immunity. As for effector functions, the increased expression of IL-1beta and IFNgamma genes in thymocytes and essentially enhanced expression of IL-1beta, IL-10, and TNFalpha genes in splenocytes were observed in mice exposed against the background of a progressive inflammatory process. The experimental data obtained specify that the directed (anti-inflammatory) response of an organism to a specific combination of effective exposure parameters of electromagnetic radiation can be realized by the activation of particular immunocompetent cells and changes in the cytokine profile. PMID:20968076

  5. Double Layers in Astrophysics

    NASA Technical Reports Server (NTRS)

    Williams, Alton C. (Editor); Moorehead, Tauna W. (Editor)

    1987-01-01

    Topics addressed include: laboratory double layers; ion-acoustic double layers; pumping potential wells; ion phase-space vortices; weak double layers; electric fields and double layers in plasmas; auroral double layers; double layer formation in a plasma; beamed emission from gamma-ray burst source; double layers and extragalactic jets; and electric potential between plasma sheet clouds.

  6. Anti-thymocyte globulin/G-CSF treatment preserves β cell function in patients with established type 1 diabetes

    PubMed Central

    Haller, Michael J.; Gitelman, Stephen E.; Gottlieb, Peter A.; Michels, Aaron W.; Rosenthal, Stephen M.; Shuster, Jonathan J.; Zou, Baiming; Brusko, Todd M.; Hulme, Maigan A.; Wasserfall, Clive H.; Mathews, Clayton E.; Atkinson, Mark A.; Schatz, Desmond A.

    2014-01-01

    BACKGROUND. Previous efforts to preserve β cell function in individuals with type 1 diabetes (T1D) have focused largely on the use of single immunomodulatory agents administered within 100 days of diagnosis. Based on human and preclinical studies, we hypothesized that a combination of low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte CSF (G-CSF) would preserve β cell function in patients with established T1D (duration of T1D >4 months and <2 years). METHODS. A randomized, single-blinded, placebo-controlled trial was performed on 25 subjects: 17 subjects received ATG (2.5 mg/kg intravenously) followed by pegylated G-CSF (6 mg subcutaneously every 2 weeks for 6 doses) and 8 subjects received placebo. The primary outcome was the 1-year change in AUC C-peptide following a 2-hour mixed-meal tolerance test (MMTT). At baseline, the age (mean ± SD) was 24.6 ± 10 years; mean BMI was 25.4 ± 5.2 kg/m2; mean A1c was 6.5% ± 1.1%; insulin use was 0.31 ± 0.22 units/kg/d; and length of diagnosis was 1 ± 0.5 years. RESULTS. Combination ATG/G-CSF treatment tended to preserve β cell function in patients with established T1D. The mean difference in MMTT-stimulated AUC C-peptide between treated and placebo subjects was 0.28 nmol/l/min (95% CI 0.001–0.552, P = 0.050). A1c was lower in ATG/G-CSF–treated subjects at the 6-month study visit. ATG/G-CSF therapy was associated with relative preservation of Tregs. CONCLUSIONS. Patients with established T1D may benefit from combination immunotherapy approaches to preserve β cell function. Further studies are needed to determine whether such approaches may prevent or delay the onset of the disease. TRIAL REGISTRATION. Clinicaltrials.gov NCT01106157. FUNDING. The Leona M. and Harry B. Helmsley Charitable Trust and Sanofi. PMID:25500887

  7. Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis.

    PubMed

    Solti, Izabella; Kvell, Krisztian; Talaber, Gergely; Veto, Sara; Acs, Peter; Gallyas, Ferenc; Illes, Zsolt; Fekete, Katalin; Zalan, Petra; Szanto, Arpad; Bognar, Zita

    2015-01-01

    Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone's deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes. PMID:26053248

  8. Double screening

    NASA Astrophysics Data System (ADS)

    Gratia, Pierre; Hu, Wayne; Joyce, Austin; Ribeiro, Raquel H.

    2016-06-01

    Attempts to modify gravity in the infrared typically require a screening mechanism to ensure consistency with local tests of gravity. These screening mechanisms fit into three broad classes; we investigate theories which are capable of exhibiting more than one type of screening. Specifically, we focus on a simple model which exhibits both Vainshtein and kinetic screening. We point out that due to the two characteristic length scales in the problem, the type of screening that dominates depends on the mass of the sourcing object, allowing for different phenomenology at different scales. We consider embedding this double screening phenomenology in a broader cosmological scenario and show that the simplest examples that exhibit double screening are radiatively stable.

  9. Triclocarban-induced change in intracellular Ca²⁺ level in rat thymocytes: cytometric analysis with Fluo-3 under Zn²⁺-free conditions.

    PubMed

    Miura, Yukari; Chen, Xiaohui; Yamada, Saki; Sugihara, Aya; Enkhjargal, Molomjamts; Sun, Yuanzhi; Kuroda, Keiko; Satoh, Masaya; Oyama, Yasuo

    2014-03-01

    Triclocarban (TCC) is an antimicrobial used in personal hygiene products. Recent health concerns arose after TCC was detected in the blood of human subjects who showered with soap containing TCC. In this study, the effect of TCC on intracellular Ca(2+) concentration in rat thymocytes was examined using Fluo-3, an indicator of intracellular Ca(2+). TCC at concentrations ranging from 0.1 μM to 3 μM increased intracellular Ca(2+) concentration biphasically: first by releasing Ca(2+) from intracellular Ca(2+) stores and then inducing Ca(2+) influx through store-operated Ca(2+) channels. The threshold TCC concentration to increase intracellular Ca(2+) concentration in this study was lower than the maximum TCC concentrations reported in human blood samples. Therefore, we anticipate that TCC at concentrations reported in human blood samples might disturb intracellular Ca(2+) signaling in human lymphocytes. PMID:24562054

  10. Seeing Double

    NASA Astrophysics Data System (ADS)

    Pesic, Peter

    2003-10-01

    The separateness and connection of individuals is perhaps the central question of human life: What, exactly, is my individuality? To what degree is it unique? To what degree can it be shared, and how? To the many philosophical and literary speculations about these topics over time, modern science has added the curious twist of quantum theory, which requires that the elementary particles of which everything consists have no individuality at all. All aspects of chemistry depend on this lack of individuality, as do many branches of physics. From where, then, does our individuality come? In Seeing Double, Peter Pesic invites readers to explore this intriguing set of questions. He draws on literary and historical examples that open the mind (from Homer to Martin Guerre to Kafka), philosophical analyses that have helped to make our thinking and speech more precise, and scientific work that has enabled us to characterize the phenomena of nature. Though he does not try to be all-inclusive, Pesic presents a broad range of ideas, building toward a specific point of view: that the crux of modern quantum theory is its clash with our ordinary concept of individuality. This represents a departure from the usual understanding of quantum theory. Pesic argues that what is bizarre about quantum theory becomes more intelligible as we reconsider what we mean by individuality and identity in ordinary experience. In turn, quantum identity opens a new perspective on us. Peter Pesic is a Tutor and Musician-in-Residence at St. John's College, Santa Fe, New Mexico. He has a Ph.D. in physics from Stanford University.

  11. Double inflation

    SciTech Connect

    Silk, J.; Turner, M.S.

    1986-04-01

    The Zel'dovich spectrum of adiabatic density perturbations is a generic prediction of inflation. There is increasing evidence that when the spectrum is normalized by observational data on small scales, there is not enough power on large scales to account for the observed large-scale structure in the Universe. Decoupling the spectrum on large and small scales could solve this problem. As a means of decoupling the large and small scales we propose double inflation (i.e., two episodes of inflation). In this scenario the spectrum on large scales is determined by the first episode of inflation and those on small scales by a second episode of inflation. We present three models for such a scenario. By nearly saturating the large angular-scale cosmic microwave anisotropy bound, we can easily account for the observed large-scale structure. We take the perturbations on small scales to be very large, deltarho/rho approx. = 0.1 to 0.01, which results in the production of primordial black holes (PBHs), early formation of structure, reionization of the Universe, and a rich array of astrophysical events. The ..cap omega..-problem is also addressed by our scenario. Allowing the density perturbations produced by the second episode of inflation to be large also lessens the fine-tuning required in the scalar potential and makes reheating much easier. We briefly speculate on the possibility that the second episode of inflation proceeds through the nucleation of bubbles, which today manifest themselves as empty bubbles whose surfaces are covered with galaxies. 37 refs., 1 fig.

  12. Upregulation of cAMP-specific PDE-4 activity following ligation of the TCR complex on thymocytes is blocked by selective inhibitors of protein kinase C and tyrosyl kinases.

    PubMed

    Michie, A M; Rena, G; Harnett, M M; Houslay, M D

    1998-01-01

    We have previously shown that the major cAMP phosphodiesterase (PDE) isoforms present in murine thymocytes are the cGMP-stimulated PDE activity (PDE-2) and the cAMP-specific PDE activity (PDE-4), and that these isoforms are differentially regulated following ligation of the TCR (Michie, A.M., Lobban, M. D., Mueller, T., Harnett, M. M., and Houslay, M.D. [1996] Cell. Signalling 8, 97-110). We show here that the anti-CD3-stimulated elevation in PDE-4 activity in murine thymocytes is dependent on protein tyrosine kinase and protein kinase C (PKC)-mediated signals as the TCR-coupled increase in PDE-4 activity can be abrogated by both the tyrosine kinase inhibitor, genistein, and the PKC selective inhibitors chelerythrine and staurosporine. Moreover, the PKC-activating phorbol ester, phorbol-12-myristate, 13-acetate (PMA) caused an increase in PDE-4 activity, similar to that observed in cells challenged with anti-CD3 monoclonal antibodies and which was not additive with cochallenge using anti-CD3 antibodies. Both the PMA- and the anti-CD3 antibody-mediated increases in PDE-4 activity were blocked by treatment with either cycloheximide or actinomycin D. Despite the upregulation of PDE-4 activity consequent to TCR ligation, intracellular cAMP levels increased on challenge of thymocytes with anti-CD3 antibody, indicating that adenylate cyclase activity was also increased by TCR ligation. It is suggested that the anti-CD3-mediated increase in PDE-4 activity was owing to a rapid PKC-dependent induction of PDE-4 activity following crosslinking of the TCR complex. This identifies "crosstalk" occurring between the PKA and PKC signaling pathways initiated by ligation of the antigen receptor in murine thymocytes. That both adenylate cyclase and PDE-4 activities were increased may indicate the presence of compartmentalized cAMP responses present in these cells. PMID:9515165

  13. Thymocytes, Pre-B Cells, and Organ Changes in a Mouse Model of Chronic Ethanol Ingestion—Absence of Subset-Specific Glucocorticoid-Induced Immune Cell Loss

    PubMed Central

    Cook, Robert T.; Schlueter, Annette J.; Coleman, Ruth A.; Tygrett, Lorraine; Ballas, Zuhair K.; Jerrells, Thomas R.; Nashelsky, Marcus B.; Ray, Nancy B.; Haugen, Thomas H.; Waldschmidt, Thomas J.

    2008-01-01

    Background The well-known immune deficiency of the chronic alcoholic dictates the need for a long-term rodent ethanol administration model to evaluate the baseline immunologic effects of chronic ethanol abuse, and investigate the genetic determinants of those effects. Much published work with rodents has shown clearly that acute ethanol administration and short-term ethanol-containing liquid diets both cause elevated corticosterone and can cause significant thymocyte, pre-B cell and peripheral lymphocyte losses. Such losses may mask more subtle alterations in immune homeostasis, and in any case are generally short-lived compared with the span of chronic ethanol abuse. Thus, it is important to have a model in which long-term immune alterations can be studied free of corticosteroid-induced cell losses. Methods We have utilized chronic 20% (w / v) ethanol in water administration to several mouse strains for prolonged periods of time and evaluated serum corticosterone, immunologic stress parameters, and other organ changes by standard methods. Results We now confirm earlier reports that chronic ethanol in water administration to mice does not produce net elevations of corticosterone, although diurnal variation is altered. Importantly, there is neither selective loss of immune cell populations known to be corticosteroid sensitive, CD4+CD8+ thymocytes and pre-B cells, nor are changes observed in the histologic appearance of the thymus. Nonetheless, there are significant chronic ethanol effects in other tissues, including reduced heart weight, mild hepatic steatosis, alterations of gut flora, increased serum peptidoglycan, and as published elsewhere, immune system abnormalities. Conclusions This model of ethanol administration is convenient, sustainable for up to 1 year, demonstrably feasible in several mouse strains, permits good weight gains in most strains, and results in significant changes in a number of organs. The administration method also will permit modeling of

  14. Estimation of stress in child neglect from thymic involution.

    PubMed

    Tanegashima, A; Yamamoto, H; Yada, I; Fukunaga, T

    1999-04-12

    It is difficult to evaluate the extent of stress in cases of suspected child abuse/neglect in a medico-legal autopsy. We have previously reported that stress due to abuse/neglect was found to have led to thymic involution. To elucidate the influence upon thymocytes differentiation, we compared the proportion of the thymocyte subpopulation in the thymus of a neglected child with one in an age-matched control obtained from cardiac surgery. We found that the relative number of CD4+ CD8+ double positive (DP) thymocytes decreased in the neglected child. It was presumed that the selective decrease in the number of the immature DP thymocytes with CD3- to low bcl-2low caused the thymic involution in the neglected child. It was suggested that an alteration in the proportion of thymocytes subpopulation might be used as an index of stress in cases of child abuse/neglect. PMID:10376338

  15. Double pituitary adenomas.

    PubMed

    Iacovazzo, D; Bianchi, A; Lugli, F; Milardi, D; Giampietro, A; Lucci-Cordisco, E; Doglietto, F; Lauriola, L; De Marinis, L

    2013-04-01

    Double pituitary adenomas represent up to 2.6 % of pituitary adenomas in large surgical series and up to 3.3 % of patients with Cushing's disease have been found to have double or multiple pituitary adenomas. We report the case of a 60-year-old male patient whose medical history began in 2002 with erectile dysfunction; hyperprolactinemia was found and MRI showed a 6-mm area of delayed enhancement in the lateral portion of the right pituitary lobe. Treatment with cabergoline was started with normalization of prolactin levels; the following MRI, performed in 2005 and 2008, showed shrinkage of the pituitary lesion. In 2005, the patient began to manifest weight gain, hypertension, and facial plethora, but no further evaluations were done. In January 2010, the patient came to our attention and underwent multiple tests that suggested Cushing's disease. A new MRI was negative. Bilateral inferior petrosal sinus sampling showed significant pituitary-to-peripheral ratio and, in May 2010, the patient underwent exploratory pituitary surgery with evidence of a 1-2-mm white-coloured midline area compatible with pituitary adenoma that was surgically removed. Post-operatively, the patient's clinical conditions improved with onset of secondary hypoadrenalism. The histologic examination confirmed a pituitary adenoma (immunostaining was found to be positive for ACTH and negative for prolactin). We report the case of an ACTH-producing microadenoma metachronous to a prolactin secreting microadenoma although not confirmed histologically, shrunk by medical treatment. A review of data in the literature regarding double or multiple pituitary adenomas has also been done. PMID:23325364

  16. Rapid regulation of PDE-2 and PDE-4 cyclic AMP phosphodiesterase activity following ligation of the T cell antigen receptor on thymocytes: analysis using the selective inhibitors erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) and rolipram.

    PubMed

    Michie, A M; Lobban, M; Müller, T; Harnett, M M; Houslay, M D

    1996-02-01

    The PDE2, cyclic GMP-stimulated, and the PDE4, cyclic AMP-specific enzymes provide the major, detectable cyclic AMP phosphodiesterase activities in murine thymocytes. In the absence of the cyclic GMP, PDE4 activity predominated (approximately 80% total) but in the presence of low (10 microM) cyclic GMP concentrations, PDE2 activity constituted the major PDE activity in thymocytes (approximately 80% total). The PDE4 selective inhibitor rolipram dose-dependently inhibited thymocyte PDE4 activity (IC50 approximately 65 nM). PDE2 was dose-dependently activated (EC50 approximately 1 microM) by cyclic GMP and inhibited by erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) (IC50 approximately 4 microM). EHNA was shown to serve as a selective inhibitor of PDE-2 activity as assessed from studies using separated PDE1, PDE2, PDE3 and PDE4 species from hepatocytes as well as human PDE2 and PDE4 enzymes. EHNA completely ablated the ability of cyclic GMP to activate PDE2 activity, whilst having a much smaller inhibitory effect on the unstimulated PDE2 activity. EHNA exhibited normal Michaelian kinetics of inhibition for the cyclic GMP-stimulated PDE2 activity with Hill plots near unity. Apparent negative co-operative effect were seen in the absence of cyclic GMP with Hill coefficients of approximately 0.3 for inhibition of PDE2 activity. Within 5 min of challenge of thymocytes with the lectin phytohaemagglutinin (PHA) there was a transient decrease (approximately 83%) in PDE-4 activity and in PDE2 activity (approximately 40%). Both anti-TCR antibodies also caused an initial reduction in the PDE4 activity which was followed by a sustained and profound increase in activity. In contrast to that observed with PHA, anti-TCR/CD3 antisera had little effect on PDE2 activity. It is suggested that, dependent upon the intracellular concentrations of cyclic GMP, thymocyte cyclic AMP metabolism can be expected to switch from being under the predominant control of PDE4 activity to that determined

  17. Anti-thymocyte globulin for conditioning in matched unrelated donor hematopoietic cell transplantation provides comparable outcomes to matched related donor recipients

    PubMed Central

    Portier, DA; Sabo, RT; Roberts, CH; Fletcher, DS; Meier, J; Clark, WB; Neale, MC; Manjili, MH; McCarty, JM; Chung, HM; Toor, AA

    2016-01-01

    Rabbit anti-thymocyte globulin (ATG) is used as prophylaxis against GVHD following allogeneic hematopoietic cell transplantation (HCT). At our institution, ATG is exclusively used in the conditioning of matched unrelated donor (URD) transplant recipients. A total of 50 URD HCT recipients who received ATG (ATG group) were retrospectively compared with 48 matched related donor (MRD) HCT recipients who did not receive ATG (no ATG group). There were no significant differences between the groups in rates of day 100 mortality, acute GVHD or relapse. Chronic GVHD incidence was significantly lower in the ATG group (P = 0.007). At a median follow-up of 36 months in the entire cohort, 50% patients are alive in the ATG group and 63% of the patients are alive in the no ATG group (P = 0.13). We conclude that the administration of ATG to patients undergoing URD HCT preserves the anti-leukemia benefit of the transplant, while reducing the risk of developing GVHD, resulting in OS rates that are comparable to MRD HCT recipients. PMID:22580767

  18. Prenatal exposure to radiofrequencies: effects of WiFi signals on thymocyte development and peripheral T cell compartment in an animal model.

    PubMed

    Laudisi, Federica; Sambucci, Manolo; Nasta, Francesca; Pinto, Rosanna; Lodato, Rossella; Altavista, Pierluigi; Lovisolo, Giorgio Alfonso; Marino, Carmela; Pioli, Claudio

    2012-12-01

    Wireless local area networks are an increasing alternative to wired data networks in workplaces, homes, and public areas. Concerns about possible health effects of this type of signal, especially when exposure occurs early in life, have been raised. We examined the effects of prenatal (in utero) exposure to wireless fidelity (WiFi) signal-associated electromagnetic fields (2450 MHz center-frequency band) on T cell development and function. Pregnant mice were exposed whole body to a specific absorption rate of 4 W/kg, 2 h per day, starting 5 days after mating and ending 1 day before the expected delivery. Sham-exposed and cage control groups were used as controls. No effects on cell count, phenotype, and proliferation of thymocytes were observed. Also, spleen cell count, CD4/CD8 cell frequencies, T cell proliferation, and cytokine production were not affected by the exposure. These findings were consistently observed in the male and female offspring at early (5 weeks of age) and late (26 weeks of age) time points. Nevertheless, the expected differences associated with aging and/or gender were confirmed. In conclusion, our results do not support the hypothesis that the exposure to WiFi signals during prenatal life results in detrimental effects on the immune T cell compartment. PMID:22556007

  19. Treatment of acute graft-versus-host disease with prednisolone: significant survival advantage for day +5 responders and no advantage for nonresponders receiving anti-thymocyte globulin.

    PubMed

    Van Lint, Maria Teresa; Milone, Giuseppe; Leotta, Salvatore; Uderzo, Cornelio; Scimè, Rosanna; Dallorso, Sandro; Locasciulli, Anna; Guidi, Stefano; Mordini, Nicola; Sica, Simona; Cudillo, Laura; Fagioli, Franca; Selleri, Carmine; Bruno, Barbara; Arcese, William; Bacigalupo, Andrea

    2006-05-15

    Newly diagnosed patients with acute graft-versus-host disease (GvHD, grades I-IV; n = 211) were given 6-methylprednisolone (6MPred) 2 mg/kg per day for 5 consecutive days; 150 patients (71%) tapered 6MPred on day +5 and were considered responders; 61 patients (29%) could not taper their steroid dose and were considered nonresponders. The cumulative incidence of transplant-related mortality (TRM) for responders and nonresponders is, respectively, 27% and 49% (P = .009), and the 5-year survival is 53% and 35% (P = .007). Nonresponders on day +5 (n = 61) were randomized to receive 6MPred 5 mg/kg per day for 10 days alone (n = 34) or in combination with rabbit anti-thymocyte globulin (ATG, 6.25 mg/kg in 10 days; n = 27). The 2 groups were balanced for clinical and GvHD characteristics. One month after randomization, 26% had a complete response; 23%, a partial response; 33%, stable GvHD; 10%, worsened; and 8%, died. There was no significant difference in response, TRM, and survival between the non-ATG and ATG group. In conclusion, 5 days of prednisolone as first-line therapy of acute GvHD identifies patients with different risk of TRM, and second-line therapy with a combination of 6MPred + ATG does not improve patient outcome, compared with 6MPred alone. PMID:16449522

  20. Nursing Positions

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Nursing Positions KidsHealth > For Parents > Nursing Positions Print A ... and actually needs to feed. Getting Comfortable With Breastfeeding Nursing can be one of the most challenging ...

  1. Positive Psychology

    ERIC Educational Resources Information Center

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive…

  2. A double-double/double-single computation package

    SciTech Connect

    Bailey, David H.

    2004-12-01

    The DDFUNIDSFUN software permits a new or existing Fortran-90 program to utilize double-double precision (approx. 31 digits) or double-single precision (approx. 14 digits) arithmetic. Double-double precision is required by a rapidly expandirtg body of scientific computations in physics and mathematics, for which the conventional 64-bit IEEE computer arithmetic (about 16 decimal digit accuracy) is not sufficient. Double-single precision permits users of systems that do not have hardware 64-bit IEEE arithmetic (such as some game systems) to perform arithmetic at a precision nearly as high as that of systems that do. Both packages run significantly faster Than using multiple precision or arbitrary precision software for this purpose. The package includes an extensive set of low-level routines to perform high-precision arithmetic, including routines to calculate various algebraic and transcendental functions, such as square roots, sin, ccc, exp, log and others. In addition, the package includes high-level translation facilities, so that Fortran programs can utilize these facilities by making only a few changes to conventional Fortran programs. In most cases, the only changes that are required are to change the type statements of variables that one wishes to be treated as multiple precision, plus a few other minor changes. The DDFUN package is similar in functionality to the double-double part of the GD package, which was previously written at LBNL. However, the DDFUN package is written exclusively in Fortran-90, thus avoidIng difficulties that some users experience when using GD, which includes both Fortran-90 and C++ code.

  3. A double-double/double-single computation package

    Energy Science and Technology Software Center (ESTSC)

    2004-12-01

    The DDFUNIDSFUN software permits a new or existing Fortran-90 program to utilize double-double precision (approx. 31 digits) or double-single precision (approx. 14 digits) arithmetic. Double-double precision is required by a rapidly expandirtg body of scientific computations in physics and mathematics, for which the conventional 64-bit IEEE computer arithmetic (about 16 decimal digit accuracy) is not sufficient. Double-single precision permits users of systems that do not have hardware 64-bit IEEE arithmetic (such as some game systems)more » to perform arithmetic at a precision nearly as high as that of systems that do. Both packages run significantly faster Than using multiple precision or arbitrary precision software for this purpose. The package includes an extensive set of low-level routines to perform high-precision arithmetic, including routines to calculate various algebraic and transcendental functions, such as square roots, sin, ccc, exp, log and others. In addition, the package includes high-level translation facilities, so that Fortran programs can utilize these facilities by making only a few changes to conventional Fortran programs. In most cases, the only changes that are required are to change the type statements of variables that one wishes to be treated as multiple precision, plus a few other minor changes. The DDFUN package is similar in functionality to the double-double part of the GD package, which was previously written at LBNL. However, the DDFUN package is written exclusively in Fortran-90, thus avoidIng difficulties that some users experience when using GD, which includes both Fortran-90 and C++ code.« less

  4. Positional plagiocephaly

    PubMed Central

    Cummings, Carl

    2011-01-01

    Cranial asymmetry occurring as a result of forces that deform skull shape in the supine position is known as deformational plagiocephaly. The risk of plagiocephaly may be modified by positioning the baby on alternate days with the head to the right or the left side, and by increasing time spent in the prone position during awake periods. When deformational plagiocephaly is already present, physiotherapy (including positioning equivalent to the preventive positioning, and exercises as needed for torticollis and positional preference) has been shown to be superior to counselling about preventive positioning only. Helmet therapy (moulding therapy) to reduce skull asymmetry has some drawbacks: it is expensive, significantly inconvenient due to the long hours of use per day and associated with skin complications. There is evidence that helmet therapy may increase the initial rate of improvement of asymmetry, but there is no evidence that it improves the final outcome for patients with moderate or severe plagiocephaly. PMID:23024590

  5. The Cambridge Double Star Atlas

    NASA Astrophysics Data System (ADS)

    MacEvoy, Bruce; Tirion, Wil

    2015-12-01

    Preface; What are double stars?; The binary orbit; Double star dynamics; Stellar mass and the binary life cycle; The double star population; Detecting double stars; Double star catalogs; Telescope optics; Preparing to observe; Helpful accessories; Viewing challenges; Next steps; Appendices: target list; Useful formulas; Double star orbits; Double star catalogs; The Greek alphabet.

  6. Design, conduct, and analyses of Breast International Group (BIG) 1-98: A randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer

    PubMed Central

    Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

    2010-01-01

    Background Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. Purpose To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. Methods From 1998–2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. Results The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Limitations Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. Conclusions BIG 1-98 is an example of an enriched design, involving

  7. A randomized, double-blind, positive-controlled, 3-way cross-over human experimental pain study of a TRPV1 antagonist (V116517) in healthy volunteers and comparison with preclinical profile.

    PubMed

    Arendt-Nielsen, Lars; Harris, Steve; Whiteside, Garth T; Hummel, Michele; Knappenberger, Terri; OʼKeefe, Sarah; Kapil, Ram; Kyle, Don

    2016-09-01

    This experimental, translational, experimental pain, single-center, randomized, double-blind, single-dose, 3-treatment, 3-period cross-over proof-of-concept volunteer trial studied the efficacy of a novel TRPV1 antagonist (V116517) on capsaicin- and UV-B-induced hyperalgesia. Heat and pressure pain thresholds, von Frey stimulus-response functions, and neurogenic inflammation were assessed together with safety. Each treatment period was 4 days. The 3 single oral treatments were 300 mg V116517, 400 mg celecoxib (a COX-2 inhibitor), and placebo. The heat pain detection and tolerance thresholds were increased significantly (P < 0.0001) by V116517. Heat pain detection and tolerance thresholds showed significantly less capsaicin hyperalgesia after V116517 (P = 0.004 and P < 0.0001, respectively). Celecoxib reduced UV-B-provoked pressure pain sensitization (P = 0.01). Laser Doppler flowmetry and erythema index after UV-B were significantly (P < 0.0001) reduced by celecoxib. Stimulus-response function in capsaicin-treated areas showed significant differences between both celecoxib and placebo and between V116517 and placebo. The body temperature showed no change, and no side effects were reported for any of the treatments. The TRPV1 antagonists and the COX-2 inhibitor showed different antihyperalgesic profiles indicating different clinical targets. In addition, the preclinical profile of V116517 in rat models of UV-B and capsaicin-induced hypersensitivity was compared with the human experimental data and overall demonstrated an alignment between 2 of the 3 end points tested. The TRPV1 antagonist showed a potent antihyperalgesic action without changing the body temperature but heat analgesia may be a potential safety issue. PMID:27168361

  8. Double outlet right ventricle

    MedlinePlus

    ... medlineplus.gov/ency/article/007328.htm Double outlet right ventricle To use the sharing features on this page, please enable JavaScript. Double outlet right ventricle (DORV) is a heart disease that is ...

  9. Chromosome doubling method

    DOEpatents

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  10. Astrometric Measurements of Seven Double Stars, September 2011 Report

    NASA Astrophysics Data System (ADS)

    Carro, Joseph

    2012-01-01

    From my residence in Paso Robles, California, measurements of the separation and position angle of seven double stars were made. Listed in chronological order, the double stars were Zeta Ursae Majoris, Zeta Lyrae, Epsilon Delphini, SAO 105104 in Sagitta, STF 2840 in Cepheus, 61 Cygni, and 17 Cygni. The two goals of this project were to measure the position angle and separation of the aforementioned double stars, and to learn the necessary techniques to conduct this research.

  11. Lingmao Formula Combined with Entecavir for HBeAg-Positive Chronic Hepatitis B Patients with Mildly Elevated Alanine Aminotransferase: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Zhu, Xiao-Jun; Sun, Xue-Hua; Zhou, Zheng-Hua; Liu, Shun-Qing; Lv, Hua; Li, Man; Li, Lu; Gao, Yue-Qiu

    2013-01-01

    Objective. To determine the efficacy and safety of Lingmao Formula combined with entecavir for HBeAg-positive chronic hepatitis B patients with mildly elevated alanine aminotransferase (ALT). Methods. 301 patients were randomly assigned to receive Lingmao Formula combined with entecavir (treatment group) or placebo combined with entecavir (control group) for 52 weeks. The outcomes of interest included the reduction of serum HBV DNA level, HBeAg loss, HBeAg seroconversion, ALT normalization, and histological improvement. Results. The mean decrease of serum HBV DNA level from baseline and the percentage of patients who had reduction in serum HBV DNA level ≥2 lg copies/mL in treatment group were significantly greater than that in control group (5.5 versus 5.4 lg copies/mL, P = 0.010; 98.5% versus 92.6%, P = 0.019). The percentage of HBeAg loss in treatment group was 22.8%, which was much higher than a percentage of 12.6% in control group (P = 0.038). There was no significant difference between the two groups in histological improvement. Safety was similar in the two groups. Conclusions. The combination of Lingmao Formula with entecavir could result in significant decrease of serum HBV DNA and increase of HBeAg loss for HBeAg-positive chronic hepatitis B patients with mildly elevated ALT without any serious adverse events. Clinical trial registration number is ChiCTR-TRC-09000594. PMID:24058372

  12. Inverse solutions for tilting orthogonal double prisms.

    PubMed

    Li, Anhu; Ding, Ye; Bian, Yongming; Liu, Liren

    2014-06-10

    An analytical reverse solution and actual examples are given to show how to direct a laser beam from a pair of orthogonal prisms to given targets in free space. Considering the influences of double-prism structural parameters, a lookup table method to seek the numerical reverse solution of each prism's tilting angle is also proposed for steering the double-prism orientation to track a target position located in the near field. Some case studies, as well as a specified elliptical target trajectory scanned by the cam-based driving double prisms, exhibit the significant application values of the theoretical derivation. The analytic reverse and numerical solutions can be generalized to investigate the synthesis of scanning patterns and the controlling strategy of double-prism tilting motion, the potentials of which can be explored to perform the orientation and position tracking functions in applications of precision engineering fields. PMID:24921137

  13. A comparison of cell killing by heat and/or x rays in Chinese hamster V79 cells, Friend erythroleukemia mouse cells, and human thymocyte MOLT-4 cells

    SciTech Connect

    Raaphorst, G.P.; Szekely, J.; Lobreau, A.; Azzam, E.I.

    1983-05-01

    The radiation and/or heat sensitivity of Chinese hamster V79 cells, Friend erythroleukemia (FELC) mouse cells, and MOLT-4 human transformed thymocytes were compared. MOLT-4 cells were more radiosensitive (D/sub o/=0.50 Gy) than FELC (D/sub o/ = 0.65 Gy) and V79 cells (D/sub o/ = 1.43 Gy). Arrhenius analysis showed that MOLT-4 cells were more heat sensitive than FELC or V79 cells below 42.0/sup 0/C, but more heat resistant at higher temperatures. In addition, the MOLT-4 cells showed a single-heat inactivation energy between 41.0 and 45.0/sup 0/C, while FELC and V79 cells both showed a transition in the inactivation energy at about 43.0 and 43.5/sup 0/C, respectively. These differences may be related to the fact that the upper temperature limit for the development of thermal tolerance during continuous heating was lower for MOLT-4 cells than for FELC or V79 cells. Killing of FELC and V79 cells was dependent on the sequence in which heat and X rays were applied, but the greatest effect was obtained when both treatments were given simultaneously. Recovery occurred when treatments were separated by incubation at 37.0/sup 0/C. The MOLT-4 cells did not show a sequence dependence for heating and irradiation. Survival of MOLT-4 cells after heating and/or irradiation was compared using trypan blue dye exclusion or colony formation. Both assays showed similar qualitative responses, but survival levels measured by the trypan blue assay were much higher than those determined from the colony-forming assay.

  14. Recombinant anti-monkey CD3 immunotoxin depletes peripheral lymph node T lymphocytes more effectively than rabbit anti-thymocyte globulin in naïve baboons

    PubMed Central

    Wamala, Isaac; Matar, Abraham J.; Farkash, Evan; Wang, Zhirui; Huang, Christene A.; Sachs, David H.

    2014-01-01

    T cell depletion is an important procedure for both experimental and therapeutic immune modulation. Rabbit anti-thymocyte globulin (ATG), which is a commonly used T cell depletion antibody in clinical organ and cell transplantation protocols, is effective in temporarily depleting peripheral blood T lymphocytes but only moderately effective in depleting peripheral lymph node T cells which comprise the majority of T lymphocytes. A recombinant anti-CD3 immunotoxin, A-dmDT390-scfbDb (C207), has been developed and shown in an initial study to retain the lymph node depleting properties of conjugated CD3 immunotoxin. This agent could potentially be used synergistically with or as a replacement for rabbit ATG in preclinical primate models of transplantation. We directly compared the peripheral blood and lymph node depleting abilities of this recombinant anti-CD3 immunotoxin and rabbit ATG in naïve animals at clinically tolerated doses. Baboons were treated with a full course of either rabbit ATG (n = 2) or CD3 immunotoxin (n = 3). Peripheral blood and lymph node T lymphocytes were measured before and following treatment. Peripheral blood CD3+ cells fell below 100 cells/μL in every animal. In the two animals receiving ATG, CD3+ cells represented 53% and 68% of lymph node cells two days following a full course of rabbit ATG. In contrast, CD3+ cells represented 3%, 5%, and 38% in lymph nodes following a full course of CD3-IT. Thus, recombinant anti-monkey CD3 immunotoxin showed improved peripheral lymph node T lymphocyte depletion to rabbit ATG and spared other immune cells. PMID:24157659

  15. Does anti-thymocyte globulin have a place in busulfan/fludarabine conditioning for matched related donor hematopoietic stem cell transplantation?

    PubMed Central

    Ji, Young Sok; Lee, Min Sung; Min, Chang Wook; Park, Seong Kyu; Kim, Se Hyung; Yun, Jina; Kim, Hyun Jung; Kim, Kyoung Ha; Kim, Chan Kyu; Lee, Kyu-Taek; Won, Jong-Ho; Hong, Dae Sik

    2016-01-01

    Background/Aims: There is controversy about the prophylactic effect of anti-thymocyte globulin (ATG) on graft versus host disease (GVHD) in the setting of matched related-donor hematopoietic stem cell transplantation (HSCT). This study assessed the inf luences of ATG on the incidences of acute and chronic GVHD and other clinical outcomes in matched related-donor HSCT. Methods: Sixty-one patients received allogeneic HSCT from human leukocyte antigen-matched, related donors. Patients received busulfan/fludarabine conditioning regimens and standard GVHD prophylaxis with or without additional ATG. Results: There was no significant difference in the cumulative incidences of overall acute GVHD, grade II to IV acute GVHD at day 100, and chronic GVHD during the follow-up period between the ATG and non-ATG groups. Three-year overall survival rates were very similar, but three year disease-free survival of the non-ATG group was higher than that of the ATG group (56.2% for ATG vs. 63.1% for non-ATG, p = 0.597). Relapse rate at 3 years in the ATG group was slightly higher than that of the non-ATG group (37.5% vs. 20%, p = 0.29). Non-relapse mortality rate at 3 years was lower in the ATG group (6.25% vs. 15.6%, p = 0.668). Conclusions: Although the addition of ATG doesn’t guarantee a reduction in the incidences of acute and chronic GVHD, pre-transplantation ATG may result in lower non-relapse mortality in the context of matched related-donor HSCT with a busulfan/fludarabine conditioning regimen. However, caution is needed when using ATG because of a possibility to increase relapse rate. PMID:27017944

  16. Positive Psychotherapy

    ERIC Educational Resources Information Center

    Seligman, Martin E. P.; Rashid, Tayyab; Parks, Acacia C.

    2006-01-01

    Positive psychotherapy (PPT) contrasts with standard interventions for depression by increasing positive emotion, engagement, and meaning rather than directly targeting depressive symptoms. The authors have tested the effects of these interventions in a variety of settings. In informal student and clinical settings, people not uncommonly reported…

  17. Cardiac Tolerability of Pertuzumab Plus Trastuzumab Plus Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer in CLEOPATRA: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

    PubMed Central

    Ewer, Michael S.; Cortés, Javier; Amadori, Dino; Miles, David; Knott, Adam; Clark, Emma; Benyunes, Mark C.; Ross, Graham; Baselga, José

    2013-01-01

    Introduction. We report cardiac tolerability of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel observed in the phase III study CLEOPATRA in patients with HER2-positive first-line metastatic breast cancer (MBC). Patients and Methods. Left ventricular ejection fraction (LVEF) ≥50% and ECOG performance status of 0 or 1 were required for study entry. During the study, LVEF assessments took place every 9 weeks. Pertuzumab/placebo was given at 840 mg, then 420 mg q3w; trastuzumab was administered at 8 mg/kg, then 6 mg/kg q3w, and docetaxel was initiated at 75 mg/m2 q3w. Results. The incidence of cardiac adverse events (all grades) was 16.4% in the placebo arm and 14.5% in the pertuzumab arm, with left ventricular systolic dysfunction (LVSD, all grades) being the most frequently reported event (8.3% versus 4.4% in the placebo and pertuzumab arm). Declines in LVEF by ≥10% points from baseline and to <50% were reported in 6.6% and 3.8% of patients in the placebo and pertuzumab arm, respectively. Seventy-two percent (placebo arm) and 86.7% (pertuzumab arm) of those patients recovered to a value ≥50%. The incidence of symptomatic LVSD was low, occurring in 1.8% (n = 7) versus 1.0% (n = 4) of patients in the placebo and pertuzumab arm. In 8/11 patients, the symptomatic LVSD had resolved at data cutoff. Conclusion. The combination of pertuzumab plus trastuzumab plus docetaxel did not increase the incidence of cardiac adverse events, including LVSD, compared with the control arm in HER2-positive MBC. The majority of cardiac adverse events were reversible. PMID:23475636

  18. Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development.

    PubMed

    Jones, Mary Elizabeth; Zhuang, Yuan

    2011-04-01

    The E-protein transcription factors E2A and HEB function in a lineage- and stage-specific manner to orchestrate many critical events throughout lymphocyte development. The function of E-proteins in both B- and T-lymphocyte development has been extensively studied through the use of single-gene knockout animals. Unlike B cells, which rely primarily on E2A alone, T cells are regulated by the combinatorial expression of both E2A and HEB. Therefore, many of the roles of E-proteins during T-cell development may be masked in single-gene knockout studies due to the compensatory function of E2A and HEB. More recently, our laboratory has established double-conditional knockout models to eliminate both E2A and HEB in a stage-specific manner throughout T-cell development. These models, in combination with other complimentary genetic approaches, have identified new E-protein functions at each of the two major T-cell developmental checkpoints. Here, we will discuss how E-proteins function to regulate the expression of T-cell receptor components and cell cycle at the β-selection checkpoint, and how they control positive selection, survival, and lineage-specific gene expression at the subsequent T-cell receptor checkpoint. PMID:21128008

  19. Kinetics of mature T-cell development in the thymus

    SciTech Connect

    Egerton, M.; Scollay, R.; Shortman, K. )

    1990-04-01

    We have reexamined the balance between cell birth, cell maturation, and cell death in the thymus by labeling dividing thymocytes and their progeny in vivo with (3H)-thymidine, isolating clearly defined subpopulations by fluorescence-activated cell sorting, and determining the distribution of label by autoradiography. When mature thymocytes were precisely defined (as CD4+CD8- CD3+ or CD4-CD8+ CD3+) and separated from immature single positives (CD4+CD8- CD3- and CD4-CD8+ CD3-), a lag was observed in the rate of entry of (3H)thymidine into mature cells. Thus, many of the mature thymocytes appear to derive from a small nondividing cortical thymocyte pool, rather than originating directly from the earliest dividing CD4+CD8+ blasts. There was little evidence for cell division during or after mature thymocyte formation, suggesting a one-for-one differentiation from cortical cells rather than selective clonal expansion. The rate of production of mature single positive thymocytes agreed closely with estimates of the rate of export of mature T cells from the thymus and was only 3% of the rate of production of double-positive cortical thymocytes. This was compatible with a stringent selection process and extensive intrathymic cell death and suggested that no extensive negative selection occurred after the mature cells were formed.

  20. Nucleosome Positioning

    PubMed Central

    Nishida, Hiromi

    2012-01-01

    Nucleosome positioning is not only related to genomic DNA compaction but also to other biological functions. After the chromatin is digested by micrococcal nuclease, nucleosomal (nucleosome-bound) DNA fragments can be sequenced and mapped on the genomic DNA sequence. Due to the development of modern DNA sequencing technology, genome-wide nucleosome mapping has been performed in a wide range of eukaryotic species. Comparative analyses of the nucleosome positions have revealed that the nucleosome is more frequently formed in exonic than intronic regions, and that most of transcription start and translation (or transcription) end sites are located in nucleosome linker DNA regions, indicating that nucleosome positioning influences transcription initiation, transcription termination, and gene splicing. In addition, nucleosomal DNA contains guanine and cytosine (G + C)-rich sequences and a high level of cytosine methylation. Thus, the nucleosome positioning system has been conserved during eukaryotic evolution.

  1. Positive Proof.

    ERIC Educational Resources Information Center

    Auty, Geoffrey

    1988-01-01

    Presents experiments which show that in electrostatics there are logical reasons for describing charged materials as positive or negative. Indicates that static and current electricity are not separate areas of physics. Diagrams of experiments and circuits are included. (RT)

  2. Randomized Phase II, Double-Blind, Placebo-Controlled Study of Exemestane With or Without Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Treatment With a Nonsteroidal Aromatase Inhibitor

    PubMed Central

    Yardley, Denise A.; Ismail-Khan, Roohi R.; Melichar, Bohuslav; Lichinitser, Mikhail; Munster, Pamela N.; Klein, Pamela M.; Cruickshank, Scott; Miller, Kathy D.; Lee, Min J.; Trepel, Jane B

    2013-01-01

    Purpose Entinostat is an oral isoform selective histone deacetylase inhibitor that targets resistance to hormonal therapies in estrogen receptor–positive (ER+) breast cancer. This randomized, placebo-controlled, phase II study evaluated entinostat combined with the aromatase inhibitor exemestane versus exemestane alone. Patients and Methods Postmenopausal women with ER+ advanced breast cancer progressing on a nonsteroidal aromatase inhibitor were randomly assigned to exemestane 25 mg daily plus entinostat 5 mg once per week (EE) or exemestane plus placebo (EP). The primary end point was progression-free survival (PFS). Blood was collected in a subset of patients for evaluation of protein lysine acetylation as a biomarker of entinostat activity. Results One hundred thirty patients were randomly assigned (EE group, n = 64; EP group, n = 66). Based on intent-to-treat analysis, treatment with EE improved median PFS to 4.3 months versus 2.3 months with EP (hazard ratio [HR], 0.73; 95% CI, 0.50 to 1.07; one-sided P = .055; two-sided P = .11 [predefined significance level of .10, one-sided]). Median overall survival was an exploratory end point and improved to 28.1 months with EE versus 19.8 months with EP (HR, 0.59; 95% CI, 0.36 to 0.97; P = .036). Fatigue and neutropenia were the most frequent grade 3/4 toxicities. Treatment discontinuation because of adverse events was higher in the EE group versus the EP group (11% v 2%). Protein lysine hyperacetylation in the EE biomarker subset was associated with prolonged PFS. Conclusion Entinostat added to exemestane is generally well tolerated and demonstrated activity in patients with ER+ advanced breast cancer in this signal-finding phase II study. Acetylation changes may provide an opportunity to maximize clinical benefit with entinostat. Plans for a confirmatory study are underway. PMID:23650416

  3. Double acting bit holder

    DOEpatents

    Morrell, Roger J.; Larson, David A.; Ruzzi, Peter L.

    1994-01-01

    A double acting bit holder that permits bits held in it to be resharpened during cutting action to increase energy efficiency by reducing the amount of small chips produced. The holder consist of: a stationary base portion capable of being fixed to a cutter head of an excavation machine and having an integral extension therefrom with a bore hole therethrough to accommodate a pin shaft; a movable portion coextensive with the base having a pin shaft integrally extending therefrom that is insertable in the bore hole of the base member to permit the moveable portion to rotate about the axis of the pin shaft; a recess in the movable portion of the holder to accommodate a shank of a bit; and a biased spring disposed in adjoining openings in the base and moveable portions of the holder to permit the moveable portion to pivot around the pin shaft during cutting action of a bit fixed in a turret to allow front, mid and back positions of the bit during cutting to lessen creation of small chip amounts and resharpen the bit during excavation use.

  4. Position indicator

    DOEpatents

    Tanner, David E.

    1981-01-01

    A nuclear reactor system is described in which a position indicator is provided for detecting and indicating the position of a movable element inside a pressure vessel. The movable element may be a valve element or similar device which moves about an axis. Light from a light source is transmitted from a source outside the pressure vessel to a first region inside the pressure vessel in alignment with the axis of the movable element. The light is redirected by a reflector prism to a second region displaced radially from the first region. The reflector prism moves in response to movement of the movable element about its axis such that the second region moves arcuately with respect to the first region. Sensors are arrayed in an arc corresponding to the arc of movement of the second region and signals are transmitted from the sensors to the exterior of the reactor vessel to provide indication of the position of the movable element.

  5. Observing Double Stars

    NASA Astrophysics Data System (ADS)

    Genet, Russell M.; Fulton, B. J.; Bianco, Federica B.; Martinez, John; Baxter, John; Brewer, Mark; Carro, Joseph; Collins, Sarah; Estrada, Chris; Johnson, Jolyon; Salam, Akash; Wallen, Vera; Warren, Naomi; Smith, Thomas C.; Armstrong, James D.; McGaughey, Steve; Pye, John; Mohanan, Kakkala; Church, Rebecca

    2012-05-01

    Double stars have been systematically observed since William Herschel initiated his program in 1779. In 1803 he reported that, to his surprise, many of the systems he had been observing for a quarter century were gravitationally bound binary stars. In 1830 the first binary orbital solution was obtained, leading eventually to the determination of stellar masses. Double star observations have been a prolific field, with observations and discoveries - often made by students and amateurs - routinely published in a number of specialized journals such as the Journal of Double Star Observations. All published double star observations from Herschel's to the present have been incorporated in the Washington Double Star Catalog. In addition to reviewing the history of visual double stars, we discuss four observational technologies and illustrate these with our own observational results from both California and Hawaii on telescopes ranging from small SCTs to the 2-meter Faulkes Telescope North on Haleakala. Two of these technologies are visual observations aimed primarily at published "hands-on" student science education, and CCD observations of both bright and very faint doubles. The other two are recent technologies that have launched a double star renaissance. These are lucky imaging and speckle interferometry, both of which can use electron-multiplying CCD cameras to allow short (30 ms or less) exposures that are read out at high speed with very low noise. Analysis of thousands of high speed exposures allows normal seeing limitations to be overcome so very close doubles can be accurately measured.

  6. [Positive psychiatry].

    PubMed

    Timmerby, Nina; Austin, Stephen; Bech, Per

    2016-02-01

    Positive psychiatry (PP) is a field within psychiatry with a particular focus on promoting well-being in people who already have or are at high risk of developing mental or physical illness. PP should be considered a supplement to trad-tional psychiatry and a call for therapists in psychiatry to focus on the person as a whole rather than just as a patient. PP is in line with current national and international health policy focus on promoting positive mental health. PMID:26857411

  7. Positive psychotherapy.

    PubMed

    Seligman, Martin E P; Rashid, Tayyab; Parks, Acacia C

    2006-11-01

    Positive psychotherapy (PPT) contrasts with standard interventions for depression by increasing positive emotion, engagement, and meaning rather than directly targeting depressive symptoms. The authors have tested the effects of these interventions in a variety of settings. In informal student and clinical settings, people not uncommonly reported them to be "life-changing." Delivered on the Web, positive psychology exercises relieved depressive symptoms for at least 6 months compared with placebo interventions, the effects of which lasted less than a week. In severe depression, the effects of these Web exercises were particularly striking. This address reports two preliminary studies: In the first, PPT delivered to groups significantly decreased levels of mild-to-moderate depression through 1-year follow-up. In the second, PPT delivered to individuals produced higher remission rates than did treatment as usual and treatment as usual plus medication among outpatients with major depressive disorder. Together, these studies suggest that treatments for depression may usefully be supplemented by exercises that explicitly increase positive emotion, engagement, and meaning. ((c) 2006 APA, all rights reserved). PMID:17115810

  8. Induction of p53-mediated apoptosis in splenocytes and thymocytes of C57BL/6 mice exposed to perfluorooctane sulfonate (PFOS)

    SciTech Connect

    Dong, Guang-Hui; Wang, Jing; Zhang, Ying-Hua; Liu, Miao-Miao; Wang, Da; Zheng, Li; Jin, Yi-He

    2012-10-15

    Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333 mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50 mg PFOS/kg, respectively, over 60 days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50 mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host. -- Highlights: ► PFOS immunotoxicity is caused by induction of apoptosis via the p53 activation. ► PFOS exposure can induce down regulation of Bcl-xl. ► Mitochondria are involved in PFOS-induced apoptosis. ► PFOS exposure can cause the release of cytochrome c and activation of caspase-3.

  9. Position sensor

    NASA Technical Reports Server (NTRS)

    Auer, Siegfried (Inventor)

    1988-01-01

    A radiant energy angle sensor is provided wherein the sensitive portion thereof comprises a pair of linear array detectors with each detector mounted normal to the other to provide X and Y channels and a pair of slits spaced from the pair of linear arrays with each of the slits positioned normal to its associated linear array. There is also provided electrical circuit means connected to the pair of linear array detectors and to separate X and Y axes outputs.

  10. Positive Psychologists on Positive Constructs

    ERIC Educational Resources Information Center

    Lyubomirsky, Sonja

    2012-01-01

    Comments on the original article by McNulty and Fincham (see record 2011-15476-001). In their article, the authors offered compelling evidence that constructs such as forgiveness and optimism can have both beneficial and adverse consequences, depending on the context. Their caution about labeling particular psychological processes as "positive" is…

  11. Living positively as HIV positive.

    PubMed

    Garraty, Sarah J

    2011-01-01

    A nursing student records a brief biography of a Zambian nurse and certified midwife living with HIV/AIDS while shadowing the nurse during an undergraduate cross-cultural course in Macha, Zambia in January 2009. The nurse strives to live positively, educating, encouraging, and empowering others. PMID:21294466

  12. Lunar Occultation Observations of Double Stars – Report #5

    NASA Astrophysics Data System (ADS)

    Loader, Brian

    2016-02-01

    Reports are presented of lunar occultations of close double stars observed using video techniques. Included are cases where a determination of the position angle and separation of the pair can be made as well as instances where no duplicity has been observed of known or reported double stars. A number of double stars discovered as a result of an occultation are also included together with the light curves for the discovery event.

  13. Positioning apparatus

    DOEpatents

    Vogel, Max A.; Alter, Paul

    1986-05-06

    An apparatus for precisely positioning materials test specimens within the optimum neutron flux path emerging from a neutron source located in a housing. The test specimens are retained in a holder mounted on the free end of a support pivotably mounted and suspended from a movable base plate. The support is gravity biased to urge the holder in a direction longitudinally of the flux path against the housing. Means are provided for moving the base plate in two directions to effect movement of the holder in two mutually perpendicular directions normal to the axis of the flux path.

  14. Positioning apparatus

    DOEpatents

    Vogel, Max A.; Alter, Paul

    1986-01-01

    An apparatus for precisely positioning materials test specimens within the optimum neutron flux path emerging from a neutron source located in a housing. The test specimens are retained in a holder mounted on the free end of a support pivotably mounted and suspended from a movable base plate. The support is gravity biased to urge the holder in a direction longitudinally of the flux path against the housing. Means are provided for moving the base plate in two directions to effect movement of the holder in two mutually perpendicular directions normal to the axis of the flux path.

  15. POSITIONING DEVICE

    DOEpatents

    Wall, R.R.; Peterson, D.L.

    1959-09-15

    A positioner is described for a vertical reactor-control rod. The positioner comprises four grooved friction rotatable members that engage the control rod on all sides and shift it longitudinally. The four friction members are drivingly interconnected for conjoint rotation and comprise two pairs of coaxial members. The members of each pair are urged toward one another by hydraulic or pneumatic pressure and thus grip the control rod so as to hold it in any position or adjust it. Release of the by-draulic or pneumatic pressure permits springs between the friction members of each pair to force them apart, whereby the control rod moves quickly by gravity into the reactor.

  16. Positioning apparatus

    DOEpatents

    Vogel, M.A.; Alter, P.

    1983-07-07

    An apparatus is provided for precisely adjusting the position of an article relative to a beam emerging from a neutron source disposed in a housing. The apparatus includes a support pivotably mounted on a movable base plate and freely suspended therefrom. The support is gravity biased toward the housing and carries an article holder movable in a first direction longitudinally of the axis of said beam and normally urged into engagement against said housing. Means are provided for moving the base plate in two directions to effect movement of the suspended holder in two mutually perpendicular directions, respectively, normal to the axis of the beam.

  17. Topological Quantum Double

    NASA Astrophysics Data System (ADS)

    Bonneau, Philippe

    Following a preceding paper showing how the introduction of a t.v.s. topology on quantum groups led to a remarkable unification and rigidification of the different definitions, we adapt here, in the same way, the definition of quantum double. This topological double is dualizable and reflexive (even for infinite dimensional algebras). In a simple case we show, considering the double as the "zero class" of an extension theory, the uniqueness of the double structure as a quasi-Hopf algebra. A la suite d'un précédent article montrant comment l'introduction d'une topologie d'e.v.t. sur les groupes quantiques permet une unification et une rigidification remarquables des différentes définitions, on adapte ici de la même manière la définition du double quantique. Ce double topologique est alors dualisable et reflexif (même pour des algèbres de dimension infinie). Dans un cas simple on montre, en considérant le double comme la "classe zéro" d'une théorie d'extensions, l'unicité de cette structure comme algèbre quasi-Hopf.

  18. Emerging double helical nanostructures

    NASA Astrophysics Data System (ADS)

    Zhao, Meng-Qiang; Zhang, Qiang; Tian, Gui-Li; Wei, Fei

    2014-07-01

    As one of the most important and land-mark structures found in nature, a double helix consists of two congruent single helices with the same axis or a translation along the axis. This double helical structure renders the deoxyribonucleic acid (DNA) the crucial biomolecule in evolution and metabolism. DNA-like double helical nanostructures are probably the most fantastic yet ubiquitous geometry at the nanoscale level, which are expected to exhibit exceptional and even rather different properties due to the unique organization of the two single helices and their synergistic effect. The organization of nanomaterials into double helical structures is an emerging hot topic for nanomaterials science due to their promising exceptional unique properties and applications. This review focuses on the state-of-the-art research progress for the fabrication of double-helical nanostructures based on `bottom-up' and `top-down' strategies. The relevant nanoscale, mesoscale, and macroscopic scale fabrication methods, as well as the properties of the double helical nanostructures are included. Critical perspectives are devoted to the synthesis principles and potential applications in this emerging research area. A multidisciplinary approach from the scope of nanoscience, physics, chemistry, materials, engineering, and other application areas is still required to the well-controlled and large-scale synthesis, mechanism, property, and application exploration of double helical nanostructures.

  19. Double Jeopardy and University Students in Wisconsin.

    ERIC Educational Resources Information Center

    Witmer, David R.

    This document addresses the question of students being put into a position of double jeopardy--if they commit a civil offense, they are subject not only to trial by the public courts but are also subject to punishment by their educational institution. As a general rule, colleges and universities should not prosecute students for acts subject to…

  20. An Investigation of Double Bass Vibrato Characteristics

    ERIC Educational Resources Information Center

    Mick, James

    2015-01-01

    The purpose of this study was to investigate and describe various vibrato characteristics of university double bass students. The primary objectives were: (1) to describe vibrato rate and width for commonly used fingers in first, fourth, and thumb positions; (2) to investigate whether students initiate vibrato in an upward or downward direction;…

  1. Cellular cooperation during in vivo anti-hapten antibody responses. III. The helper cell activity of activated thymocytes, of spleen cells treated with anti-theta serum, and of spleen cells from anti-thymocyte serum-treated or adult thymectomized donors.

    PubMed

    Janeway, C A

    1975-04-01

    An adoptive secondary anti-2,4-dinitrophenyl (DNP) antibody response involving T-B cell collaboration has been studied. In particular, attempts have been made to affect the unexpectedly steep log dose-response curve obtained when graded numbers of helper cells are transferred to irradiated recipients given a fixed number of B cells (premium effect). A variety of means were used to alter helper cell activity, and this activity was then measured quantitatively, as was the ability of the helper cells present after these treatments to give a premium effect. It was shown that activated T cells are approximately twice as active as spleen cells in helper activity and give a comparable premium effect. Graded doses of anti-theta serum plus complement markedly reduce the helper activity of spleen cells without affecting the premium effect given by the residual cells. Treatment of primed cell donors with limited doses of heterologous anti-mouse thymocyte serum (ATS) before transfer does not affect B cell activity, but readily inactivates helper cells, again without affecting the premium effect given by the residual cells. Adult thymectomy (ATx) of helper cell donors before priming with carrier led initially to increased helper activity relative to age-matched control donors. This increase may reflect the loss of nonspecific suppressor T cells from spleens shortly after ATx. Late after ATx, there was about a 2-fold decrease in helper activity, probably reflecting a loss of helper cell precursors. At no time was there any change in the premium effect. In view of the failure of any of the techniques used to abolish the premium effect given by helper cells in this response, it seems likely that this premium effect is due to the cooperative interaction of two very similar types of mature T cell. Alternatively, the premium effect observed here may result from the interaction of two activities of a single type of T cell which is mediated by independent factors. PMID:1078836

  2. Developmentally regulated changes in glucosidase II association with, and carbohydrate content of, the protein tyrosine phosphatase CD45.

    PubMed

    Baldwin, T A; Ostergaard, H L

    2001-10-01

    Glucosidase II (GII) stably interacts with the external domain of CD45 in a carbohydrate-dependent manner. We have found that the association occurs in immature cells, but is significantly reduced in mature T cells. Using mannose-binding protein (MBP), in both FACS analysis and pull-down assays, we find that MBP can specifically recognize cell surface CD45 from immature, but not mature T cells. Analysis of thymocytes reveals increased MBP binding and GII association with CD45 in double-positive thymocytes compared with either double-negative or single-positive thymocytes. As well, the same pool of CD45 recognized by MBP can also associate with GII. Initial analysis of the basis of the interaction between CD45 and MBP suggests MBP binds two different glycoforms of CD45 based on the differential competition with glucose. Finally, inhibition of GII activity in cells that do not normally express MBP ligands results in significant increases in cell surface MBP ligands, including CD45. Taken together, these data suggest that the glucose content of the cell surface CD45 changes as thymocytes undergo maturation to mature T cells, and may be regulated by GII interactions. Such changes in the cell surface carbohydrate on CD45 may affect the development of thymocytes, perhaps via binding of CD45 on thymocytes to lectins on stromal cells. PMID:11564800

  3. Double Degenerate Binary Systems

    SciTech Connect

    Yakut, K.

    2011-09-21

    In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.

  4. Double aortic arch

    MedlinePlus

    ... double aortic arch may press on the windpipe (trachea) and esophagus, leading to trouble breathing and swallowing. ... to relieve pressure on the esophagus and windpipe (trachea). The surgeon ties off the smaller branch and ...

  5. Direct and Synergistic Interactions of 3,5,3′-Triiodothyronine and the Adrenergic System in Stimulating Sugar Transport by Rat Thymocytes

    PubMed Central

    Segal, Joseph; Ingbar, Sidney H.

    1980-01-01

    Isolated rat thymocytes were preincubated with various catecholamines, alone and together with 3,5,3′-triiodothyronine (T3), and the accumulation of the glucose analogues, 2-deoxy-d-glucose (2-DG) and 3-O-methylglucose (3-O-MG), was then measured. Epinephrine induced a time- and dose-dependent increase in the 15-min accumulation of 2-DG; at a concentration of 100 μM epinephrine, the effect was evident after a preincubation period of only 5 min. The lowest concentration of epinephrine at which a significant effect was evident was 1 μM. Epinephrine also produced a dose-dependent increase in the accumulation of 3-O-MG, and the lowest concentration at which a significant effect was evident was again 1 μM. Isoproterenol, a β-adrenergic agonist, like epinephrine, increased the accumulation of 2-DG, whereas the α-agonist, phenylephrine, had no effect. The response to epinephrine was inhibited by the β-antagonist, alprenolol, but the α-antagonist, phentolamine, had no effect. As previously demonstrated, T3 increased 2-DG accumulation, and like epinephrine, its effect was blocked by alprenolol. Neither T3 (0.1 nM) nor epinephrine (0.1 μM) had any effect when acting alone, but when added together at these concentrations, they significantly increased the accumulation of both 2-DG and 3-O-MG. Neither T3 with isoproterenol nor T3 with phenylephrine produced a comparable synergistic effect. But T3 (0.1 nM) acting with isoproterenol (0.1 μM) and phenylephrine (0.1 μM) together, synergistically increased 2-DG accumulation. In addition, the α-antagonist, phentolamine, which alone had no effect, inhibited the synergistic effect induced by T3 and epinephrine. The effects of epinephrine and T3 alone, as well as their combined synergistic effect on 2-DG accumulation, were not blocked by the inhibitor of protein synthesis, puromycin. From these results we conclude the following: (a) the stimulatory effect of the catecholamines on the accumulation of 2-DG and 3-O-MG reflects

  6. Biosynthesis of major histocompatibility complex molecules and generation of T cells in Ii TAP1 double-mutant mice.

    PubMed Central

    Tourne, S; van Santen, H M; van Roon, M; Berns, A; Benoist, C; Mathis, D; Ploegh, H

    1996-01-01

    Major histocompatibility complex (MHC) class I and II molecules are loaded with peptides in distinct subcellular compartments. The transporter associated with antigen processing (TAP) is responsible for delivering peptides derived from cytosolic proteins to the endoplasmic reticulum, where they bind to class I molecules, while the invariant chain (Ii) directs class II molecules to endosomal compartments, where they bind peptides originating mostly from exogenous sources. Mice carrying null mutations of the TAP1 or Ii genes (TAP10) or Ii0, respectively) have been useful tools for elucidating the two MHC/peptide loading pathways. To evaluate to what extent these pathways functionally intersect, we have studied the biosynthesis of MHC molecules and the generation of T cells in Ii0TAP10 double-mutant mice. We find that the assembly and expression of class II molecules in Ii0 and Ii0TAP10 animals are indistinguishable and that formation and display of class I molecules is the same in TAP10 and Ii0TAP10 animals. Thymic selection in the double mutants is as expected, with reduced numbers of both CD4+ CD8- and CD4- CD8+ thymocyte compartments. Surprisingly, lymph node T-cell populations look almost normal; we propose that population expansion of peripheral T cells normalizes the numbers of CD4+ and CD8+ cells in Ii0TAP10 mice. Images Fig. 1 Fig. 2 PMID:8643655

  7. Dynamics of Double Stochastic Operators

    NASA Astrophysics Data System (ADS)

    Saburov, Mansoor

    2016-03-01

    A double stochastic operator is a generalization of a double stochastic matrix. In this paper, we study the dynamics of double stochastic operators. We give a criterion for a regularity of a double stochastic operator in terms of absences of its periodic points. We provide some examples to insure that, in general, a trajectory of a double stochastic operator may converge to any interior point of the simplex.

  8. Close Double Stars from Occultation Video Recordings

    NASA Astrophysics Data System (ADS)

    Waring Dunham, David; George, Anthony; Loader, Brian; Herald, David Russell

    2015-08-01

    Astronomers around the world, both amateur and professional, have been recording lunar and asteroidal occultations of close double stars during the past several years using inexpensive but quite sensitive video cameras that are now available. Several new double stars have been discovered, and the parameters of many close systems have been determined. Besides rather good measurements of the relative magnitudes of the components, the actual separations and position angles can be measured if observations of the same event are made from two or more separate stations. These observations collected by the International Occultation Timing Association (IOTA) are published in the Journal of Double Star Observations. Recently, IOTA has encouraged the observation of occultations of stars in the Kepler 2 program, which is interested in data about close duplicity that affects their analyses for exoplanet transits.

  9. Double Emulsion Templated Celloidosomes

    NASA Astrophysics Data System (ADS)

    Arriaga, Laura R.; Marquez, Samantha M.; Kim, Shin-Hyun; Chang, Connie; Wilking, Jim; Monroy, Francisco; Marquez, Manuel; Weitz, David A.

    2012-02-01

    We present a novel approach for fabricating celloidosomes, which represent a hollow and spherical three-dimensional self-assembly of living cells encapsulating an aqueous core. Glass- capillary microfluidics is used to generate monodisperse water-in-oil-in-water double emulsion templates using lipids as stabilizers. Such templates allow for obtaining single but also double concentric celloidosomes. In addition, after a solvent removal step the double emulsion templates turn into monodisperse lipid vesicles, whose membrane spontaneously phase separates when choosing the adequate lipid composition, providing the adequate scaffold for fabricating Janus-celloidosomes. These structures may find applications in the development of bioreactors in which the synergistic effects of two different types of cells selectively adsorbed on one of the vesicle hemispheres may be exploited.

  10. Double face sealing device

    NASA Technical Reports Server (NTRS)

    Weddendorf, Bruce C. (Inventor)

    1991-01-01

    A double face sealing device for mounting between two surfaces to provide an airtight and fluid-tight seal between a closure member bearing one of the surfaces and a structure or housing bearing the other surface which extends around the opening or hatchway to be closed. The double face sealing device includes a plurality of sections or segments mounted to one of the surfaces, each having a main body portion, a pair of outwardly extending and diverging, cantilever, spring arms, and a pair of inwardly extending and diverging, cantilever, spring arms, an elastomeric cover on the distal, free, ends of the outwardly extending and diverging spring arms, and an elastomeric cover on the distal, free, ends of the inwardly extending and diverging spring arms. The double face sealing device has application or use in all environments requiring a seal, but is particularly useful to seal openings or hatchways between compartments of spacecraft or aircraft.

  11. Design friendly double patterning

    NASA Astrophysics Data System (ADS)

    Yesilada, Emek

    2012-03-01

    Double patterning using 193nm immersion has been adapted as the solution to enable 2x nm technology nodes until the arrival of EUV tools. As a result the past few years have seen a huge effort in creating double patterning friendly design flows. These flows have so far proposed a combination of decomposition rules at cell level and/or at placement level as well as sophisticated decomposition tools with varying density, design iteration and decomposition complexity penalties. What is more, designers have to familiarize themselves with double patterning challenges and decomposition tools. In this paper an alternative approach is presented that allows the development of dense standard cells with minimal impact on design flow due to double patterning. A real case study is done on 20nm node first metal layer where standard cells are designed without considering decomposition restrictions. The resulting layout is carefully studied in order to establish decomposition or color rules that can map the layout into two masks required for double patterning but without the need of complex coloring algorithms. Since the rules are derived from a decomposition unaware design they do not in return impose heavy restrictions on the design at the cell or placement level and show substantial density gains compared to previously proposed methods. Other key advantages are a simplified design flow without complex decomposition tools that can generate a faster time to market solution all at the same time keeping designers isolated from the challenges of the double patterning. The derived design rules highlight process development path required for design driven manufacturing.

  12. Double Bragg Interferometry.

    PubMed

    Ahlers, H; Müntinga, H; Wenzlawski, A; Krutzik, M; Tackmann, G; Abend, S; Gaaloul, N; Giese, E; Roura, A; Kuhl, R; Lämmerzahl, C; Peters, A; Windpassinger, P; Sengstock, K; Schleich, W P; Ertmer, W; Rasel, E M

    2016-04-29

    We employ light-induced double Bragg diffraction of delta-kick collimated Bose-Einstein condensates to create three symmetric Mach-Zehnder interferometers. They rely on (i) first-order, (ii) two successive first-order, and (iii) second-order processes which demonstrate the scalability of the corresponding momentum transfer. With respect to devices based on conventional Bragg scattering, these symmetric interferometers double the scale factor and feature a better suppression of noise and systematic uncertainties intrinsic to the diffraction process. Moreover, we utilize these interferometers as tiltmeters for monitoring their inclination with respect to gravity. PMID:27176520

  13. Double Bragg Interferometry

    NASA Astrophysics Data System (ADS)

    Ahlers, H.; Müntinga, H.; Wenzlawski, A.; Krutzik, M.; Tackmann, G.; Abend, S.; Gaaloul, N.; Giese, E.; Roura, A.; Kuhl, R.; Lämmerzahl, C.; Peters, A.; Windpassinger, P.; Sengstock, K.; Schleich, W. P.; Ertmer, W.; Rasel, E. M.

    2016-04-01

    We employ light-induced double Bragg diffraction of delta-kick collimated Bose-Einstein condensates to create three symmetric Mach-Zehnder interferometers. They rely on (i) first-order, (ii) two successive first-order, and (iii) second-order processes which demonstrate the scalability of the corresponding momentum transfer. With respect to devices based on conventional Bragg scattering, these symmetric interferometers double the scale factor and feature a better suppression of noise and systematic uncertainties intrinsic to the diffraction process. Moreover, we utilize these interferometers as tiltmeters for monitoring their inclination with respect to gravity.

  14. Double-helix stellarator

    SciTech Connect

    Moroz, P.E.

    1997-09-01

    A new stellarator configuration, the Double-Helix Stellarator (DHS), is introduced. This novel configuration features a double-helix center post as the only helical element of the stellarator coil system. The DHS configuration has many unique characteristics. One of them is the extreme low plasma aspect ratio, A {approx} 1--1.2. Other advantages include a high enclosed volume, appreciable rotational transform, and a possibility of extreme-high-{beta} MHD equilibria. Moreover, the DHS features improved transport characteristics caused by the absence of the magnetic field ripple on the outboard of the torus. Compactness, simplicity and modularity of the coil system add to the DHS advantages for fusion applications.

  15. Double arch mirror study

    NASA Technical Reports Server (NTRS)

    Vukobratovich, D.; Hillman, D.

    1983-01-01

    The development of a method of mounting light weight glass mirrors for astronomical telescopes compatible with the goals of the Shuttle Infrared Telescope Facility (SIRTF) was investigated. A 20 in. diameter double arch lightweight mirror previously fabricated was modified to use a new mount configuration. This mount concept was developed and fabricated. The mounting concept of the double mounting mirror is outlined. The modifications made to the mirror, fabrication of the mirror mount, and room temperature testing of the mirror and mount and the extension of the mirror and mount concept to a full size (40 in. diameter) primary mirror for SIRTF are discussed.

  16. Double-Glazing Interferometry

    ERIC Educational Resources Information Center

    Toal, Vincent; Mihaylova, Emilia M.

    2009-01-01

    This note describes how white light interference fringes can be seen by observing the Moon through a double-glazed window. White light interferometric fringes are normally observed only in a well-aligned interferometer whose optical path difference is less than the coherence length of the light source, which is approximately one micrometer for…

  17. Rosette (Double Blossom)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rosette, or double blossom, is a serious disease of erect blackberries that is limited to the genus Rubus. Rosette may occur on trailing blackberries and dewberries, but rarely on red and black raspberries. In the United States, rosette occurs from New Jersey to Illinois and southwest to Texas and i...

  18. Double layers without current

    SciTech Connect

    Perkins, F.W.; Sun, Y.C.

    1980-11-01

    The steady-state solution of the nonlinear Vlasov-Poisson equations is reduced to a nonlinear eigenvalue problem for the case of double-layer (potential drop) boundary conditions. Solutions with no relative electron-ion drifts are found. The kinetic stability is discussed. Suggestions for creating these states in experiments and computer simulations are offered.

  19. Double resonator cantilever accelerometer

    DOEpatents

    Koehler, Dale R.

    1984-01-01

    A digital quartz accelerometer includes a pair of spaced double-ended tuning forks fastened at one end to a base and at the other end through a spacer mass. Transverse movement of the resonator members stresses one and compresses the other, providing a differential frequency output which is indicative of acceleration.

  20. Double resonator cantilever accelerometer

    DOEpatents

    Koehler, D.R.

    1982-09-23

    A digital quartz accelerometer includes a pair of spaced double-ended tuning forks fastened at one end to a base and at the other end through a spacer mass. Transverse movement of the resonator members stresses one and compresses the other, providing a differential frequency output which is indicative of acceleration.

  1. Double Trouble (Abstract)

    NASA Astrophysics Data System (ADS)

    Simonsen, M.

    2015-12-01

    (Abstract only) Variable stars with close companions can be difficult to accurately measure and characterize. The companions can create misidentifications, which in turn can affect the perceived magnitudes, amplitudes, periods, and colors of the variable stars. We will show examples of these Double Trouble stars and the impact their close companions have had on our understanding of some of these variable stars.

  2. Weathering the Double Whammy.

    ERIC Educational Resources Information Center

    Wellman, Jane V.

    2002-01-01

    Discusses how governing boards can help their institutions weather the "double-whammy" of doing more with less: identify the institution's short-term and long-term challenges; refocus the institution's mission, planning, and programming; assess and integrate the institution's tuition, aid, and outreach strategies; redouble the institution's…

  3. Sun Packs Double Punch

    NASA Video Gallery

    On August 3, the sun packed a double punch, emitting a M6.0-class flare at 9:43 am EDT. This video is of the second, slightly stronger M9.3-class flare at 11:41 pm EDT. Both flares had significant ...

  4. Double-Entry Bookkeeping.

    ERIC Educational Resources Information Center

    Snyder, Herbert

    1999-01-01

    Explains the principles and mechanics of double-entry bookkeeping as a part of the accounting cycle to produce a functioning set of accounting records. Suggests that libraries need to have accurate and timely information about their spending to gain financial control and protect against fraud and abuse. (LRW)

  5. A matterless double slit

    NASA Astrophysics Data System (ADS)

    King, Ben; di Piazza, Antonino; Keitel, Christoph H.

    2010-02-01

    Double slits provide incoming particles with a choice. Those that survive passage through the slits have chosen from two possible paths, which interfere to distribute them in a wave-like manner. Such wave-particle duality continues to be challenged and investigated in a broad range of disciplines with electrons, neutrons, helium atoms, C60 fullerenes, Bose-Einstein condensates and biological molecules. All variants have hitherto involved material constituents. We present a matterless double-slit scenario in which photons generated from virtual electron-positron pair annihilation in head-on collisions of a probe laser field with two ultra-intense laser beams form a double-slit interference pattern. Such electromagnetic fields are predicted to induce material-like behaviour in vacuum, supporting elastic scattering between photons. Our double-slit scenario presents, on the one hand, a realizable method with which to observe photon-photon scattering and, on the other hand, demonstrates the possibility of both controlling light with light and non-locally investigating features of the quantum vacuum structure.

  6. Double Marking Revisited

    ERIC Educational Resources Information Center

    Brooks, Val

    2004-01-01

    In 2002, the Qualifications and Curriculum Authority (QCA) published the report of an independent panel of experts into maintaining standards at Advanced Level (A-Level). One of its recommendations was for: limited experimental double marking of scripts in subjects such as English to determine whether the strategy would significantly reduce errors…

  7. [Double ricochet marks].

    PubMed

    Sellier, K

    1987-01-01

    When bullets are flying stably and ricochet on a surface, only one mark is produced. In contrast yawing bullets can produce a double mark if the angle of incidence is sufficiently small (less than or equal to 5 degrees). Distances up to 15 cm were seen between the two marks. PMID:3660953

  8. Teaching the Double Layer.

    ERIC Educational Resources Information Center

    Bockris, J. O'M.

    1983-01-01

    Suggests various methods for teaching the double layer in electrochemistry courses. Topics addressed include measuring change in absolute potential difference (PD) at interphase, conventional electrode potential scale, analyzing absolute PD, metal-metal and overlap electron PDs, accumulation of material at interphase, thermodynamics of electrified…

  9. Design for Double Rainbow

    ERIC Educational Resources Information Center

    Thomas, Lisa Carlucci

    2011-01-01

    Rare is the inspirational, spontaneous, transformative moment shared among 20 million people. In the summer of 2010, people around the world were moved by the sighting of a double rainbow--almost a triple rainbow--"all the way across the sky" in Yosemite National Park. Caught on video and posted to by YouTube by Paul Vasquez in January 2010, the…

  10. Double-clad nuclear fuel safety rod

    DOEpatents

    McCarthy, William H.; Atcheson, Donald B.; Vaidyanathan, Swaminathan

    1984-01-01

    A device for shutting down a nuclear reactor during an undercooling or overpower event, whether or not the reactor's scram system operates properly. This is accomplished by double-clad fuel safety rods positioned at various locations throughout the reactor core, wherein melting of a secondary internal cladding of the rod allows the fuel column therein to shift from the reactor core to place the reactor in a subcritical condition.

  11. Double Degrees: Double the Trouble or Twice the Return?

    ERIC Educational Resources Information Center

    Russell, A. Wendy; Dolnicar, Sara; Ayoub, Marina

    2008-01-01

    Double degrees (also called joint or combined degrees)--programs of study combining two bachelor degrees--are increasingly popular in Australian universities, particularly among women. A case study using qualitative and quantitative surveys of current and past double degree students is presented. The study indicates that double degrees benefit…

  12. Tests on Double Layer Metalization

    NASA Technical Reports Server (NTRS)

    Woo, D. S.

    1983-01-01

    28 page report describes experiments in fabrication of integrated circuits with double-layer metalization. Double-layer metalization requires much less silicon "real estate" and allows more flexibility in placement of circuit elements than does single-layer metalization.

  13. Astrometric Measurements of Five Double Stars Report of February 2014

    NASA Astrophysics Data System (ADS)

    Carro, Joseph

    2014-07-01

    From my residence in Paso Robles, California, the position angles and separations of five double stars were measured. The two objectives of this project were to measure the position angles and separations of the aforementioned stars, and to learn the techniques necessary to conduct this research.

  14. Measuring the Double Helix

    SciTech Connect

    Mathew-Fenn, R.S.; Das, R.; Harbury, P.A.B.

    2009-05-26

    DNA is thought to behave as a stiff elastic rod with respect to the ubiquitous mechanical deformations inherent to its biology. To test this model at short DNA lengths, we measured the mean and variance of end-to-end length for a series of DNA double helices in solution, using small-angle x-ray scattering interference between gold nanocrystal labels. In the absence of applied tension, DNA is at least one order of magnitude softer than measured by single-molecule stretching experiments. Further, the data rule out the conventional elastic rod model. The variance in end-to-end length follows a quadratic dependence on the number of base pairs rather than the expected linear dependence, indicating that DNA stretching is cooperative over more than two turns of the DNA double helix. Our observations support the idea of long-range allosteric communication through DNA structure.

  15. Double meningocele. Case report.

    PubMed

    Durmaz, R; Arslantaş, A; Ozön, Y H; Tel, E

    2000-01-01

    The coexistence of two distinct meningoceles of the spine is a very unusual event. We report a three-day-old boy with double meningoceles at the thoracic and lumbar levels. The connection between the stalk of the thoracic meningocele and the spinal cord, as seen on magnetic resonance imaging, showed a neurological involvement in this lesion. Our case is only the third without association of congenital anomalies or neurofibromatosis to be reported to date. PMID:11196754

  16. The double massa intermedia

    PubMed Central

    Baydin, Serhat; Gungor, Abuzer; Baran, Oguz; Tanriover, Necmettin; Rhoton, Albert L.

    2016-01-01

    Background: To describe the rare finding of a double massa intermedia (MI). Typically, the MI (interthalamic adhesion) is a single bridge of gray matter connecting the medial surfaces of the thalami. Methods: Twelve formalin- and alcohol-fixed human third ventricles were examined from superior to inferior by fiber dissection technique under ×6 to ×40 magnifications and with the endoscope. Results: In all hemispheres, the anterior and posterior commissure were defined. The MI, which bridges the medial surfaces of the thalami, was defined in all hemispheres. In one hemisphere, there was a second bridge between the thalami, located posteroinferior to the common MI. Endoscopic view confirmed that there was a second MI in this specimen. The MI usually traverses the third ventricle posterior to the foramen of Monro and connects the paired thalami. The MI is an important landmark during endoscopic and microscopic surgeries of the third ventricle. Although a double MI is very rare, surgeons should be aware of the possibility in their surgical planning. Conclusion: The surgeon should be aware of the possibility of a double MI to avoid confusion during third ventricle surgery. PMID:27127695

  17. Double face sealing device

    NASA Technical Reports Server (NTRS)

    Weddendorf, Bruce (Inventor)

    1991-01-01

    A double face sealing device is disclosed for mounting between two surfaces to provide an air-tight and fluid-tight seal between a closure member bearing one of the surfaces and a structure or housing bearing the other surface which extends around the opening or hatchway to be closed. The double face sealing device includes a plurality of sections or segments mounted to one of the surfaces, each having a main body portion, a pair of outwardly extending and diverging, cantilever, spring arms, and a pair of inwardly extending and diverging, cantilever, spring arms, an elastomeric cover on the distal, free ends of the outwardly extending and diverging spring arms, and an elastomeric cover on the distal, free, ends of the outwardly extending and diverging spring arms, and an elastomeric cover on the distal, free ends of the inwardly extending and diverging spring arms. The double face sealing device has application or use in all environments requiring a seal, but is particularly useful to seal openings or hatchways between compartments of spacecraft or aircraft.

  18. Colloidal Double Quantum Dots

    PubMed Central

    2016-01-01

    Conspectus Pairs of coupled quantum dots with controlled coupling between the two potential wells serve as an extremely rich system, exhibiting a plethora of optical phenomena that do not exist in each of the isolated constituent dots. Over the past decade, coupled quantum systems have been under extensive study in the context of epitaxially grown quantum dots (QDs), but only a handful of examples have been reported with colloidal QDs. This is mostly due to the difficulties in controllably growing nanoparticles that encapsulate within them two dots separated by an energetic barrier via colloidal synthesis methods. Recent advances in colloidal synthesis methods have enabled the first clear demonstrations of colloidal double quantum dots and allowed for the first exploratory studies into their optical properties. Nevertheless, colloidal double QDs can offer an extended level of structural manipulation that allows not only for a broader range of materials to be used as compared with epitaxially grown counterparts but also for more complex control over the coupling mechanisms and coupling strength between two spatially separated quantum dots. The photophysics of these nanostructures is governed by the balance between two coupling mechanisms. The first is via dipole–dipole interactions between the two constituent components, leading to energy transfer between them. The second is associated with overlap of excited carrier wave functions, leading to charge transfer and multicarrier interactions between the two components. The magnitude of the coupling between the two subcomponents is determined by the detailed potential landscape within the nanocrystals (NCs). One of the hallmarks of double QDs is the observation of dual-color emission from a single nanoparticle, which allows for detailed spectroscopy of their properties down to the single particle level. Furthermore, rational design of the two coupled subsystems enables one to tune the emission statistics from single

  19. Colloidal Double Quantum Dots.

    PubMed

    Teitelboim, Ayelet; Meir, Noga; Kazes, Miri; Oron, Dan

    2016-05-17

    Pairs of coupled quantum dots with controlled coupling between the two potential wells serve as an extremely rich system, exhibiting a plethora of optical phenomena that do not exist in each of the isolated constituent dots. Over the past decade, coupled quantum systems have been under extensive study in the context of epitaxially grown quantum dots (QDs), but only a handful of examples have been reported with colloidal QDs. This is mostly due to the difficulties in controllably growing nanoparticles that encapsulate within them two dots separated by an energetic barrier via colloidal synthesis methods. Recent advances in colloidal synthesis methods have enabled the first clear demonstrations of colloidal double quantum dots and allowed for the first exploratory studies into their optical properties. Nevertheless, colloidal double QDs can offer an extended level of structural manipulation that allows not only for a broader range of materials to be used as compared with epitaxially grown counterparts but also for more complex control over the coupling mechanisms and coupling strength between two spatially separated quantum dots. The photophysics of these nanostructures is governed by the balance between two coupling mechanisms. The first is via dipole-dipole interactions between the two constituent components, leading to energy transfer between them. The second is associated with overlap of excited carrier wave functions, leading to charge transfer and multicarrier interactions between the two components. The magnitude of the coupling between the two subcomponents is determined by the detailed potential landscape within the nanocrystals (NCs). One of the hallmarks of double QDs is the observation of dual-color emission from a single nanoparticle, which allows for detailed spectroscopy of their properties down to the single particle level. Furthermore, rational design of the two coupled subsystems enables one to tune the emission statistics from single photon

  20. Design of a high-precision double crystal tunable monochromator

    SciTech Connect

    Shleifer, M.; Sharma, S.; Woodle, M.; Rotela, E.; Brite, C.

    1993-11-01

    This paper describes a UHV-compatible double crystal monochromator with independent drives for 2 linear and 2 angular crystal motions. Precise angular crystal positioning is achieved by using a spindle with a double gimbal mechanism, which converts linear motion of 0.1 micron to an angular motion of 0.042 arcsec. In order to decrease thermal distortions, the crystal intercepting white beam, is watercooled.

  1. Pattern Freezing Process Free Litho-Litho-Etch Double Patterning

    NASA Astrophysics Data System (ADS)

    Ando, Tomoyuki; Takeshita, Masaru; Takasu, Ryoichi; Yoshii, Yoshihiro; Iwashita, Jun; Matsumaru, Shogo; Abe, Sho; Iwai, Takeshi

    2009-06-01

    Double patterning technology based on existing ArF immersion lithography is considered as the most viable option for complementary metal oxide semiconductor (CMOS) node of 32 nm and below. Most of double patterning approaches previously described requires intermediate processing step such as hard mask etching, spacer material deposition, and resist pattern freezing. The requirement of these additional steps is now leading way to requests for throughput reduction and low cost for production for double patterning technology applications. In this paper, litho-litho-etch (LLE) double patterning without any intermediate processing steps is investigated to achieve narrow pitch resist imaging. The LLE options examined in this work are combinations of positive tone-negative tone and positive tone-positive tone photoresist double patterning process. These are the alternative processes in pattern freezing process free LLE double patterning. The goals of this work are to determine witch of these approaches is the most viable for future application and to confirm the patterning potential for 32 nm and below half pitch resist imaging.

  2. The Double Star mission

    NASA Astrophysics Data System (ADS)

    Liu, Z. X.; Escoubet, C. P.; Pu, Z.; Laakso, H.; Shi, J. K.; Shen, C.; Hapgood, M.

    2005-11-01

    The Double Star Programme (DSP) was first proposed by China in March, 1997 at the Fragrant Hill Workshop on Space Science, Beijing, organized by the Chinese Academy of Science. It is the first mission in collaboration between China and ESA. The mission is made of two spacecraft to investigate the magnetospheric global processes and their response to the interplanetary disturbances in conjunction with the Cluster mission. The first spacecraft, TC-1 (Tan Ce means "Explorer"), was launched on 29 December 2003, and the second one, TC-2, on 25 July 2004 on board two Chinese Long March 2C rockets. TC-1 was injected in an equatorial orbit of 570x79000 km altitude with a 28° inclination and TC-2 in a polar orbit of 560x38000 km altitude. The orbits have been designed to complement the Cluster mission by maximizing the time when both Cluster and Double Star are in the same scientific regions. The two missions allow simultaneous observations of the Earth magnetosphere from six points in space. To facilitate the comparison of data, half of the Double Star payload is made of spare or duplicates of the Cluster instruments; the other half is made of Chinese instruments. The science operations are coordinated by the Chinese DSP Scientific Operations Centre (DSOC) in Beijing and the European Payload Operations Service (EPOS) at RAL, UK. The spacecraft and ground segment operations are performed by the DSP Operations and Management Centre (DOMC) and DSOC in China, using three ground station, in Beijing, Shanghai and Villafranca.

  3. Positive position control of robotic manipulators

    NASA Technical Reports Server (NTRS)

    Baz, A.; Gumusel, L.

    1989-01-01

    The present, simple and accurate position-control algorithm, which is applicable to fast-moving and lightly damped robot arms, is based on the positive position feedback (PPF) strategy and relies solely on position sensors to monitor joint angles of robotic arms to furnish stable position control. The optimized tuned filters, in the form of a set of difference equations, manipulate position signals for robotic system performance. Attention is given to comparisons between this PPF-algorithm controller's experimentally ascertained performance characteristics and those of a conventional proportional controller.

  4. The Double Chooz Experiment

    NASA Astrophysics Data System (ADS)

    Pfahler, Patrick; Double Chooz Collaboration

    2012-07-01

    Double Chooz is a reactor bar nue-disappearance experiment situated at the commercial nuclear power plant of Chooz in northern France. The experiment aims for the revelation of the last unknown mixing angle Θ13 as a part of the neutrino mixing matrix or the improvement of the upper limit for sin2(2Θ13), which is currently < 0.14 (90% CL). A newly developed gadolinium-loaded liquid scintillator as target allows the detection of electron-anti-neutrinos (bar nue) using the inverse beta decay and its distinct decay pattern (bar nue + p → e+ +n). Double Chooz uses two identical detectors at different distances in order to reduce systematic uncertainties. This will allow, after a data taking phase of 4 years, an improvement on sin2(2Θ13) down to < 0.03 (90% CL). The first (far) detector has successfully been installed and filled, and takes data since April of 2011. A preliminary analysis of first 120 days revealed about 4000 Neutrino-candidates and a stable detector-setup with low backgrounds. The commissioning of the second (near) detector is expected for the beginning of 2013 and will provide maximum sensitivity for the experiment.

  5. T-cell subpopulations express a different pattern of dopaminergic markers in intra- and extra-thymic compartments.

    PubMed

    Mignini, F; Sabbatini, M; Capacchietti, M; Amantini, C; Bianchi, E; Artico, M; Tammaro, A

    2013-01-01

    An involvement of dopamine in regulation of the immune function has been assessed and dopaminergic system has been found widely represented in thymus. Nevertheless detail on the characterization of dopaminergic system in assisting thymocytes development and lymphocytes mature physiology are still lacking. The present study was designed to characterize dopamine plasma membrane transporter (DAT), vesicular dopamine transporters (VMAT)-1 and -2, and dopamine D1-like and D2-like receptors in rat thymocytes, splenocytes and peripheral blood mononuclear cells. Western blot and RT-PCR analyses, performed on these cells, showed an expression of dopamine transporters and receptors during thymocyte development (when of CD4 and CD8 markers are differently expressed). Furthermore FACS analysis, indicates that DAT and dopamine D1-like receptors are expressed at high levels in thymocytes, splenocytes, and peripheral lymphocytes. The percentage of CD4+ CD8+ (double-positive) thymocytes expressing dopaminergic markers was significantly higher compared to the percentage of double-negative ones. The percentage of CD8+ single positive cells expressing dopaminergic markers was significantly higher than that of CD4+ cells. The results suggest that the dopaminergic system plays a role in the thymus microenvironment during T-cell development. The more pronounced expression of dopaminergic markers in CD8+ subsets suggests that dopamine plays a role in development of cytotoxic T-cells. Our findings indicate dopaminergic system to have a role during the maturation and selection of lymphocytes, and support its involvement in the active phases of immune response. PMID:23830396

  6. Langmuir probe measurements of double-layers in a pulsed discharge

    NASA Technical Reports Server (NTRS)

    Levine, J. S.; Crawford, F. W.

    1980-01-01

    Langmuir probe measurements were carried out which confirm the occurrence of double-layers in an argon positive column. Pulsing the discharge current permitted probe measurements to be performed in the presence of the double-layer. Supplementary evidence, obtained from DC and pulsed discharges, indicated that the double-layers formed in the two modes of operation were similar. The double-layers observed were weak and stable; their relation to other classes of double-layers are discussed, and directions for future work are suggested.

  7. Double layers and electrostatic shocks

    NASA Technical Reports Server (NTRS)

    Hershkowitz, N.

    1981-01-01

    It is shown that it is useful to define double layers and shocks so that the ion phase spaces of double layers are the mirror image (about zero ion velocity) of the ion phase spaces for laminar electrostatic shocks. The distinguishing feature is the direction of the free ion velocity. It is also shown that double layers can exist without the presence of trapped ions. The Bohm condition for double layers, that the ion drift velocity on the high potential side must be greater than the ion sound velocity, is shown to be related to a requirement of a lower limit on the Mach number of laminar electrostatic shocks

  8. Colored Flag by Double Refraction.

    ERIC Educational Resources Information Center

    Reid, Bill

    1994-01-01

    Describes various demonstrations that illustrate double refraction and rotation of the plane of polarization in stressed, transparent plastics, with the consequent production of colored designs. (ZWH)

  9. Dual double field theory

    NASA Astrophysics Data System (ADS)

    Bergshoeff, Eric A.; Hohm, Olaf; Penas, Victor A.; Riccioni, Fabio

    2016-06-01

    We present the dual formulation of double field theory at the linearized level. This is a classically equivalent theory describing the duals of the dilaton, the Kalb-Ramond field and the graviton in a T-duality or O( D, D) covariant way. In agreement with previous proposals, the resulting theory encodes fields in mixed Young-tableau representations, combining them into an antisymmetric 4-tensor under O( D, D). In contrast to previous proposals, the theory also requires an antisymmetric 2-tensor and a singlet, which are not all pure gauge. The need for these additional fields is analogous to a similar phenomenon for "exotic" dualizations, and we clarify this by comparing with the dualizations of the component fields. We close with some speculative remarks on the significance of these observations for the full non-linear theory yet to be constructed.

  10. Neutrinoless Double Beta Decay

    NASA Astrophysics Data System (ADS)

    Cremonesi, Oliviero

    2016-05-01

    After more than 3/4 of century from its proposal, Neutrinoless Double Beta Decay (NLDBD) is still missing observation and continues to represent the only practical method for investigating the Dirac/Majorana nature of neutrinos. In case neutrinos would be Majorana particles, NLDBD would provide unique informations on their properties (absolute mass scale and Majorana phases). Boosted by the discovery of neutrino oscillations, a number of experiments with improved sensitivity have been proposed in the past decade. Some of them have recently started operation and others are ready to start. They will push the experimental sensitivity on the decay halflife beyond 1026 year, starting to analyze the region of the inverted mass hierarchy. The status and perspectives of the ongoing experimental effort are reviewed. Uncertainties coming from the calculation othe decay nuclear matrix elements (NME) as well as the recently suggested possibility of a relevant quenching of the axial coupling constant are also discussed.

  11. Double layer secure sketch

    NASA Astrophysics Data System (ADS)

    Li, Cai

    2012-09-01

    Secure sketch has been applied successfully in a wide variety of applications like cryptography, biometric authentication systems and so on. All of these secure sketches have properties in common namely error-tolerance and small entropy loss. The former ensures an input set w' can unlock the system if w' is substantially overlapped with a template set w while the latter means it is hard for an adversary to get the information of w even with the knowledge of s, which is produced by w and stored in the system publicly. In their constructions, they all consider w as a set of atomic elements. However, in the real word, it is very likely the elements in the template set are sets as well. In this paper, we propose a double layer secure sketch to address this issue.

  12. Doubled Color Codes

    NASA Astrophysics Data System (ADS)

    Bravyi, Sergey

    Combining protection from noise and computational universality is one of the biggest challenges in the fault-tolerant quantum computing. Topological stabilizer codes such as the 2D surface code can tolerate a high level of noise but implementing logical gates, especially non-Clifford ones, requires a prohibitively large overhead due to the need of state distillation. In this talk I will describe a new family of 2D quantum error correcting codes that enable a transversal implementation of all logical gates required for the universal quantum computing. Transversal logical gates (TLG) are encoded operations that can be realized by applying some single-qubit rotation to each physical qubit. TLG are highly desirable since they introduce no overhead and do not spread errors. It has been known before that a quantum code can have only a finite number of TLGs which rules out computational universality. Our scheme circumvents this no-go result by combining TLGs of two different quantum codes using the gauge-fixing method pioneered by Paetznick and Reichardt. The first code, closely related to the 2D color code, enables a transversal implementation of all single-qubit Clifford gates such as the Hadamard gate and the π / 2 phase shift. The second code that we call a doubled color code provides a transversal T-gate, where T is the π / 4 phase shift. The Clifford+T gate set is known to be computationally universal. The two codes can be laid out on the honeycomb lattice with two qubits per site such that the code conversion requires parity measurements for six-qubit Pauli operators supported on faces of the lattice. I will also describe numerical simulations of logical Clifford+T circuits encoded by the distance-3 doubled color code. Based on a joint work with Andrew Cross.

  13. Double Nail of the Little Toe

    PubMed Central

    Haneke, Eckart

    2016-01-01

    A rudimentary accessory or double nail of the little toe is not rare, although only described three times before. Most cases are accidentally detected and only few patients seek help because they have discomfort or pain. Some have a positive family history, but most patients cannot give any information concerning heredity. Clinically, the nail of the little toe is abnormally wide and is split or shows a longitudinal depression corresponding to a slight protuberance of the cuticle. Histopathology shows a complete though short nail. The treatment of choice is segmental excision of the entire accessory nail unit with mobilization of the lateral skin and primary suture. PMID:27386457

  14. Double umbilical cord blood transplant is effective therapy for relapsed or refractory Hodgkin lymphoma.

    PubMed

    Thompson, Philip A; Perera, Travis; Marin, David; Oran, Betul; Popat, Uday; Qazilbash, Muzaffar; Shah, Nina; Parmar, Simrit; Rezvani, Katayoun; Olson, Amanda; Kebriaei, Partow; Anderlini, Paolo; Rondon, Gabriela; Alousi, Amin; Ciurea, Stefan; Champlin, Richard E; Bajel, Ashish; Szer, Jeffrey; Shpall, Elizabeth J; Ritchie, David; Hosing, Chitra M

    2016-07-01

    A sub-group of patients with Hodgkin Lymphoma (HL) who relapse after autologous stem cell transplant can achieve long-term disease-free-survival after allogeneic stem cell transplant (alloSCT). There is limited information regarding the tolerability and efficacy of double umbilical cord blood transplant (dUCBT) for relapsed/refractory HL. We analyzed 27 consecutive, heavily pre-treated patients receiving dUCBT for relapsed/refractory HL at two centers from 2003-2014. The majority of patients relapsed <6 months after autologous stem cell transplant. A total of 15 patients received myeloablative (most commonly melphalan, fludarabine, thiotepa and anti-thymocyte globulin [ATG]) and 12 non-myeloablative conditioning regimens (fludarabine, cyclophosphamide, 200cGy total body irradiation +/- ATG). All patients engrafted; median time to neutrophil and platelet engraftment was 17 and 37 days, respectively. Overall response rate was 68%; 58% achieved complete remission. Median progression-free survival (PFS) was 12.2 months; median overall survival was 27 months. Cumulative incidences of relapse and of non-relapse mortality at 5 years were 30% and 37.9%, respectively; 5-year PFS was 31.3% (95%CI 10.1-52.5). There was a trend toward inferior PFS in patients with lymph node size ≥2 cm at the time of alloSCT (p = 0.07) and toward inferior survival in patients with chemorefractory disease pre-alloSCT (p = 0.12). dUCBT is feasible in patients with heavily pre-treated HL and can achieve long-term disease-free survival in approximately 30% of patients. PMID:26472485

  15. The double-mode Cepheids

    NASA Astrophysics Data System (ADS)

    Balona, L. A.

    1985-06-01

    Recent observational and theoretical results on double-mode Cepheids are reviewed. The likelihood that recently proposed candidate Cepheids are indeed Cepheids is evaluated. Periods, period ratios, and semi-amplitudes of the light and radial velocity variations of double-mode Cepheids are given. The physical and pulsational properties of double-mode Cepheids are discussed, reviewing evidence that these stars are Population I objects of high mass and that they all have the same mean effective temperature. The discovery of strong H-alpha emission occurring at seemingly random phases is addressed. Attempts to resolve the mass discrepancy problem of double-mode Cepheids, which results from observations showing that these Cepheids are indistinguishable from normal Cepheids of similar period, are reviewed along with attempts to find the cause of double-mode pulsation.

  16. Positional Plagiocephaly (Flattened Head)

    MedlinePlus

    ... Simple practices like changing a baby's sleep position, holding your baby, and providing lots of "tummy time" ... devices to keep your baby in one position. Alternate positions in the crib. Consider how you lay ...

  17. Latest Double Chooz results

    NASA Astrophysics Data System (ADS)

    Lasserre, Thierry; Double Chooz Collaboration

    2016-05-01

    I report the latest results from the Double Chooz experiment on the θ13 neutrino mixing angle. Two detectors are located at distances of 400 m and 1050 m from the reactor cores of the Chooz nuclear power station (France) to measure the disappearance of electron antineutrinos. The far detector has been taking data since 2011, accumulating a live time of 467.90 days (66.5 GW-ton-year). In this article we focus on the latest measurement using neutrino-induced neutron capture on hydrogen. A new analysis improved the signal efficiency and reduced the backgrounds and systematic uncertainties, leading to sin2 2θ 13 = 0.095+0.039 -0.038. When combined with the Gadolinium-based analysis this leads to sin2 2θ13 = 0.088+0.33 -0.033. The distortion from the prediction above a visible energy of 4 MeV is confirmed. The near detector started data taking in 2014 and first results shall be reported in 2016.

  18. Supported double membranes

    PubMed Central

    Murray, David H.; Tamm, Lukas K.; Kiessling, Volker

    2009-01-01

    Planar model membranes, like supported lipid bilayers and surface-tethered vesicles, have been proven to be useful tools for the investigation of complex biological functions in a significantly less complex membrane environment. In this study, we introduce a supported double membrane system that should be useful for studies that target biological processes in the proximity of two lipid bilayers such as the periplasm of bacteria and mitochondria or the small cleft between pre-and postsynaptic neuronal membranes. Large unilamellar vesicles (LUV) were tethered to a preformed supported bilayer by a biotin-streptavidin tether. We show from single particle tracking (SPT) experiments that these vesicle are mobile above the plane of the supported membrane. At higher concentrations, the tethered vesicles fuse to form a second continuous bilayer on top of the supported bilayer. The distance between the two bilayers was determined by fluorescence interference contrast (FLIC) microscopy to be between 16 and 24 nm. The lateral diffusion of labeled lipids in the second bilayer was very similar to that in supported membranes. SPT experiments with reconstituted syntaxin-1A show that the mobility of transmembrane proteins was not improved when compared with solid supported membranes. PMID:19236921

  19. Laser double Doppler flowmeter

    NASA Astrophysics Data System (ADS)

    Poffo, L.; Goujon, J.-M.; Le Page, R.; Lemaitre, J.; Guendouz, M.; Lorrain, N.; Bosc, D.

    2014-05-01

    The Laser Doppler flowmetry (LDF) is a non-invasive method for estimating the tissular blood flow and speed at a microscopic scale (microcirculation). It is used for medical research as well as for the diagnosis of diseases related to circulatory system tissues and organs including the issues of microvascular flow (perfusion). It is based on the Doppler effect, created by the interaction between the laser light and tissues. LDF measures the mean blood flow in a volume formed by the single laser beam, that penetrate into the skin. The size of this measurement volume is crucial and depends on skin absorption, and is not directly reachable. Therefore, current developments of the LDF are focused on the use of always more complex and sophisticated signal processing methods. On the other hand, laser Double Doppler Flowmeter (FL2D) proposes to use two laser beams to generate the measurement volume. This volume would be perfectly stable and localized at the intersection of the two laser beams. With FL2D we will be able to determine the absolute blood flow of a specific artery. One aimed application would be to help clinical physicians in health care units.

  20. Pion double charge exchange reactions leading to double pionic atoms

    SciTech Connect

    Nieves, J.; Oset, E.; Vincente-Vacas, M.J. ); Hirenzaki, S.; Toki, H. )

    1992-10-20

    In this paper, the authors study theoretically pion double charge exchange reactions leading to double pionic atoms. The reaction cross-sections with two pions in the deeper bound pionic orbits in [sup 208]Pb are calculated with realistic pionic atom wave functions and distortion effects. The cross-sections are found to be d[sup 2] [sigma]/dEd[Omega] [approx] 10[sup [minus] 3] [minus] 10[sup [minus] 4] [mu]b/srMeV, which are only a small fraction of the double charge exchange.

  1. Want Positive Behavior? Use Positive Language

    ERIC Educational Resources Information Center

    Wood, Chip; Freeman-Loftis, Babs

    2012-01-01

    Positive adult language is the professional use of words and tone of voice to enable students to learn in an engaged, active way. This includes learning social skills. To guide children toward choosing and maintaining positive behaviors, adults need to carefully choose the words and tone of voice used when speaking to them. Learning to use…

  2. Positive Classroom Environments = Positive Academic Results

    ERIC Educational Resources Information Center

    Wilson-Fleming, LaTerra; Wilson-Younger, Dylinda

    2012-01-01

    This article discusses the effects of a positive classroom environment and its impact on student behavior and achievement. It also provides strategies for developing expectations for student achievement and the importance of parental involvement. A positive classroom environment is essential in keeping behavior problems to a minimum. There are a…

  3. Positive Education: Positive Psychology and Classroom Interventions

    ERIC Educational Resources Information Center

    Seligman, Martin E. P.; Ernst, Randal M.; Gillham, Jane; Reivich, Karen; Linkins, Mark

    2009-01-01

    Positive education is defined as education for both traditional skills and for happiness. The high prevalence worldwide of depression among young people, the small rise in life satisfaction, and the synergy between learning and positive emotion all argue that the skills for happiness should be taught in school. There is substantial evidence from…

  4. α/β–T Cell Receptor (TCR)+CD4−CD8− (NKT) Thymocytes Prevent Insulin-dependent Diabetes Mellitus in Nonobese Diabetic (NOD)/Lt Mice by the Influence of Interleukin (IL)-4 and/or IL-10

    PubMed Central

    Hammond, Kirsten J.L.; Poulton, Lynn D.; Palmisano, Linda J.; Silveira, Pablo A.; Godfrey, Dale I.; Baxter, Alan G.

    1998-01-01

    We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in α/β-T cell receptor (TCR)+CD4−CD8− NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM in NOD mice was studied by the infusion of thymocyte subsets into young female NOD mice. A single intravenous injection of 106 CD4−/lowCD8− or CD4−CD8− thymocytes from female (BALB/c × NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. Insulitis was still present in some recipient mice, although the cell infiltrates were principally periductal and periislet, rather than the intraislet pattern characteristic of insulitis in unmanipulated NOD mice. Protection was not associated with the induction of “allogenic tolerance” or systemic autoimmunity. Accelerated IDDM occurs after injection of splenocytes from NOD donors into irradiated adult NOD recipients. When α/β-TCR+ and α/β-TCR− subsets of CD4−CD8− thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the α/β-TCR+ population was protective, confirming that NKT cells were responsible for this activity. The protective effect in the induced model of IDDM was neutralized by anti–IL-4 and anti–IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. These results have significant implications for the pathogenesis and potential prevention of IDDM in humans. PMID:9529321

  5. Double Radio Sources: Two Approaches

    NASA Astrophysics Data System (ADS)

    Valtonen, M. J.; Heinämäki, P.

    2000-02-01

    The theory of double radio sources is considered from two different points of view: the so called unified models and the slingshot model. First, observations and theory are discussed in 11 areas: (1) the dependence or independence of small-scale and large-scale jets from each other; (2) stability and existence of large-scale jets; (3) radio hot spots inside the lobes of double radio sources; (4) the relation of double-lobed quasars to radio galaxies; (5) polarization and other asymmetries between the two lobes and correlations among them; (6) the speeds of advance of radio lobes; (7) giant radio sources; (8) one-sided double radio sources; (9) multiple-sided double radio sources; (10) the origin of the Fanaroff-Riley classes of radio morphology; and (11) the origin of distance asymmetries of the radio lobes. Then five steps in building up a double radio source theory are discussed: (1) theory of galaxy mergers; (2) theory of black hole mergers; (3) theory of black hole interactions and ejections; (4) theory of radio lobe formation and evolution; and (5) radio jet theory. Finally, recent X-ray observations by ROSAT are discussed from the point of view of double radio source theory.

  6. Double-Knudsen-Cell Apparatus Measures Alloy-Component Activities

    NASA Technical Reports Server (NTRS)

    Jacobson, Nathan S.; Moore, Warren A.

    1995-01-01

    Double-Knudsen-cell apparatus provides molecular beam from selected one of two Knudsen cells. Both cells maintained at same temperature. Molecular beam directed into mass spectrometer for measurement of vapor pressure of selected material component. Designed to minimize undesired thermal gradients, provides appropriate translation to place selected cell in position for sampling, and minimizes mixing of molecular beams from cells.

  7. A Simple Double-Source Model for Interference of Capillaries

    ERIC Educational Resources Information Center

    Hou, Zhibo; Zhao, Xiaohong; Xiao, Jinghua

    2012-01-01

    A simple but physically intuitive double-source model is proposed to explain the interferogram of a laser-capillary system, where two effective virtual sources are used to describe the rays reflected by and transmitted through the capillary. The locations of the two virtual sources are functions of the observing positions on the target screen. An…

  8. Advanced double layer capacitors

    NASA Technical Reports Server (NTRS)

    Sarangapani, S.; Lessner, P.; Forchione, J.; Laconti, A. B.

    1989-01-01

    There is a need for large amounts of power to be delivered rapidly in a number of airborne and space systems. Conventional, portable power sources, such as batteries, are not suited to delivering high peak power pulses. The charge stored at the electrode-electrolyte double layer is, however, much more assessible on a short time scale. Devices exploiting this concept were fabricated using carbon and metal oxides (Pinnacle Research) as the electrodes and sulfuric acid as the electrolyte. The approach reported, replaces the liquid sulfuric acid electrolyte with a solid ionomer electrolyte. The challenge is to form a solid electrode-solid ionomer electrolyte composite which has a high capacitance per geometric area. The approach to maximize contact between the electrode particles and the ionomer was to impregnate the electrode particles using a liquid ionomer solution and to bond the solvent-free structure to a solid ionomer membrane. Ruthenium dioxide is the electrode material used. Three strategies are being pursued to provide for a high area electrode-ionomer contact: mixing of the RuOx with a small volume of ionomer solution followed by filtration to remove the solvent, and impregnation of the ionomer into an already formed RuOx electrode. RuOx powder and electrodes were examined by non-electrochemical techniques. X-ray diffraction has shown that the material is almost pure RuO2. The electrode structure depends on the processing technique used to introduce the Nafion. Impregnated electrodes have Nafion concentrated near the surface. Electrodes prepared by the evaporation method show large aggregates of crystals surrounded by Nafion.

  9. Measurements with Reticle Micrometer Performed by a New Double Stars Observing Group from Poland

    NASA Astrophysics Data System (ADS)

    Biskupski, Marcin; Banacka, Natalia; Cupryjak, Justyna; Malinowska, Malgorzata; Bujel, Kamil; Koltek, Zdzislaw; Mazur, Jaroslaw; Muskala, Marcin; Plotkowski, Lukasz; Prowans, Barlomiej; Szkaplewicz, Pawel

    2016-04-01

    Measurements of 19 double stars using a reticle micrometer eyepiece are reported. The observational program was held in spring and summer of 2015 as an extended workshop for a new double stars observing group from Szczecin, Poland. The goal of the program was to learn how to measure position angle and separation using a reticle micrometer eyepiece.

  10. Three step double layers in the laboratory

    NASA Astrophysics Data System (ADS)

    Bailey, Andrew, III; Hershkowitz, Noah

    1988-01-01

    A new class of stationary double layer structure, with three or more distinct steps, is demonstrated in the laboratory. A large monotonic potential increase results from a series of smaller double layers. In many respects, these double layer structures resemble those inferred from satellite measurements of auroral double layers. This new class of double layer appears to depend on turbulence for its existence and to be a hybrid structure, intermediate between anomalous resistivity and BGK double layers.

  11. Species doubling and effective Lagrangians

    SciTech Connect

    Creutz, M.; Tytgat, M.

    1996-09-01

    Coupling gauge fields to the chiral currents from an effective Lagrangian for pseudoscalar mesons naturally gives rise to a species doubling phenomenon similar to that seen with fermionic fields in lattice gauge theory. 17 refs.

  12. A Double Pendulum "Art Machine"

    ERIC Educational Resources Information Center

    Romer, R. H.

    1970-01-01

    Describes a double pendulum apparatus and its mode of operation to produce a great variety of figures similar to Lissajous figures. The author suggests that several advanced physics topics can be studied with the aid of this instrument. Bibliography. (LC)

  13. Entanglement purification with double selection

    SciTech Connect

    Fujii, Keisuke; Yamamoto, Katsuji

    2009-10-15

    We investigate an entanglement purification protocol with double-selection process, which works under imperfect local operations. Compared with the usual protocol with single selection, this double-selection method has higher noise thresholds for the local operations and quantum communication channels and achieves higher fidelity of purified states. It also provides a yield comparable to that of the usual protocol with single selection. We discuss on general grounds how some of the errors which are introduced by local operations are left as intrinsically undetectable. The undetectable errors place a general upper bound on the purification fidelity. The double selection is a simple method to remove all the detectable errors in the first order, so that the upper bound on the fidelity is achieved in the low-noise regime. The double selection is further applied to purification of multipartite entanglement such as two-colorable graph states.

  14. Simulation of auroral double layers

    NASA Technical Reports Server (NTRS)

    Hubbard, R. F.; Joyce, G.

    1979-01-01

    Some basic properties of plasma double layers are deduced from a particle-in-cell computer simulation and related to parallel electric-field structures above the auroral regions. The simulation results on the processes leading to double-layer formation are examined, particularly in relation to the transient stage and double-layer structure and stability. It is concluded that: (1) a large potential difference applied to a finite-length plasma will be concentrated in a shocklike localized region instead of occurring over the entire length of the system; (2) the initial stage in double-layer formation is dominated by a large-potential pulse propagating in the direction of the induced electrostatic drift; (3) the entire potential is dropped over a specific scale length once the double layer has formed; and (4) this scale length is expected to be of the order of 1 km for a double layer above a discrete auroral arc with a potential of 10 kV and the electric-field vector parallel to the magnetic-field vector.

  15. Double the Rubble

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This artist's conception shows the closest known planetary system to our own, called Epsilon Eridani. Observations from NASA's Spitzer Space Telescope show that the system hosts two asteroid belts, in addition to previously identified candidate planets and an outer comet ring.

    Epsilon Eridani is located about 10 light-years away in the constellation Eridanus. It is visible in the night skies with the naked eye.

    The system's inner asteroid belt appears as the yellowish ring around the star, while the outer asteroid belt is in the foreground. The outermost comet ring is too far out to be seen in this view, but comets originating from it are shown in the upper right corner.

    Astronomers think that each of Epsilon Eridani's asteroid belts could have a planet orbiting just outside it, shepherding its rocky debris into a ring in the same way that Jupiter helps keep our asteroid belt confined. The planet near the inner belt was previously identified in 2000 via the radial velocity, or 'star wobble,' technique, while the planet near the outer belt was inferred when Spitzer discovered the belt.

    The inner belt orbits at a distance of about 3 astronomical units from its star or about the same position as the asteroid belt in our own solar system (an astronomical unit is the distance between Earth and our sun). The second asteroid belt lies at about 20 astronomical units from the star, or a position comparable to Uranus in our solar system. The outer comet ring orbits from 35 to 90 astronomical units from the star; our solar system's analogous Kuiper Belt extends from about 30 to 50 astronomical units from the sun.

  16. The double burden.

    PubMed

    Faurholt-Jepsen, Daniel

    2013-07-01

    parameters. The population was followed up during treatment (2 and 5 months) to assess treatment outcome as well as after one year to assess their survival status. Based on data from 1,250 tuberculosis patients and 350 neighbourhood controls, we found that 38 and 21%, respectively, had impaired glycaemia, and that the prevalence of diabetes was 17 and 9% among tuberculosis patients and controls, respectively. This difference in prevalence between patients and controls was equivalent to an adjusted odds ratio of more than four, indicating a strong association between tuberculosis and diabetes. Furthermore, we found that diabetes was associated with tuberculosis among both participants with or without HIV co-infection. Despite the strong association, diabetes had only moderate clinical implications when the tuberculosis patients initiated the tuberculosis treatment; the patients with diabetes co-morbidity had a minor elevation in the immune response and more frequently reported to have fever. Furthermore, diabetes did not seem to delay time to sputum conversion during treatment. Nevertheless, diabetes co-morbidity led to impaired treatment outcome with slower recovery of weight and haemoglobin and a more than four times higher mortality rate within the initial phase of tuberculosis treatment. In conclusion, in the African region, the double burden of tuberculosis and diabetes is becoming a major health problem. Although the tuberculosis incidence has stabilized during the last decade, the increasing incidence of diabetes will possibly interfere with tuberculosis control and may, consequently, make the tuberculosis incidence increase again. Future research strategies should focus on enhanced diagnostic tools to identify tuberculosis patients with diabetes co-morbidity, and on the role of disease-disease, drug-disease and drug-drug interactions between tuberculosis and diabetes diseases and treatments. PMID:23809978

  17. Resonant double photoionization of lithium studied with medium energy resolution

    NASA Astrophysics Data System (ADS)

    Wehlitz, R.; Juranić, P. N.

    2006-10-01

    We have measured the relative photoionization cross section for the formation of Li2+ ions between 148 and 161eV photon energy with higher photon-energy resolution than in previous Li2+ studies. This energy region is characterized by double and triple excitations that lead to strong enhancements in the Li2+ cross section. As a result, the double-to-single photoionization ratio shows a dramatic resonance structure not seen before. We have determined the resonance positions and widths using Fano-profile fits to the Li2+ data and compare them to previously published values and a calculated Li2+ cross-section curve.

  18. Negative differential photovoltage in a biased double heterojunction

    NASA Astrophysics Data System (ADS)

    Žukauskas, A.; Meškauskas, D.; Jakštas, V.; Vitta, P.

    2013-02-01

    We report on negative differential photovoltage (DPV), which is observed under modulated photoexcitation of a double heterojunction, when the common positive photovoltage increment due to photocurrent modulation is suppressed by high bias current. The negative DPV was shown to be due to the effect of photoconductivity on the series resistance of the heterojunction and due to the modulation of junction temperature. In AlGaInP double heterojunction light-emitting diodes, the magnitudes of negative DPV in the range of -10 μV correspond to the estimated variation of series resistance and junction temperature as low as ˜10-3 Ω and ˜10-2 K, respectively.

  19. Woods-Saxon Equivalent to a Double Folding Potential

    NASA Astrophysics Data System (ADS)

    Freitas, A. S.; Marques, L.; Zhang, X. X.; Luzio, M. A.; Guillaumon, P.; Condori, R. Pampa; Lichtenthäler, R.

    2016-02-01

    A Woods-Saxon equivalent to a double folding potential in the nuclear surface region is obtained for the heavy-ion scattering potential. The Woods-Saxon potential has fixed geometry and was used as a bare potential in the analysis of elastic scattering angular distributions of several stable systems. A new analytical formula for the position and height of the Coulomb barrier is presented, which reproduces the results obtained using double folding potentials. This simple formula has been applied to estimate the fusion cross section above the Coulomb barrier. A comparison with experimental data is presented.

  20. Sharing a Faculty Position.

    ERIC Educational Resources Information Center

    O'Kane, Patricia K.; Meyer, Mary

    1982-01-01

    Describes the experience of two nursing faculty members who shared an assistant professor of nursing position. Discusses positive and negative aspects of the experience and notes that a unified and creative approach must be taken for it to succeed. (JOW)

  1. The double loop mattress suture

    PubMed Central

    Biddlestone, John; Samuel, Madan; Creagh, Terry; Ahmad, Tariq

    2014-01-01

    An interrupted stitch type with favorable tissue characteristics will reduce local wound complications. We describe a novel high-strength, low-tension repair for the interrupted closure of skin, cartilage, and muscle, the double loop mattress stitch, and compare it experimentally with other interrupted closure methods. The performance of the double loop mattress technique in porcine cartilage and skeletal muscle is compared with the simple, mattress, and loop mattress interrupted sutures in both a novel porcine loading chamber and mechanical model. Wound apposition is assessed by electron microscopy. The performance of the double loop mattress in vivo was confirmed using a series of 805 pediatric laparotomies/laparoscopies. The double loop mattress suture is 3.5 times stronger than the loop mattress in muscle and 1.6 times stronger in cartilage (p ≤ 0.001). Additionally, the double loop mattress reduces tissue tension by 66% compared with just 53% for the loop mattress (p ≤ 0.001). Wound gapping is equal, and wound eversion appears significantly improved (p ≤ 0.001) compared with the loop mattress in vitro. In vivo, the double loop mattress performs as well as the loop mattress and significantly better than the mattress stitch in assessments of wound eversion and dehiscence. There were no episodes of stitch extrusion in our series of patients. The mechanical advantage of its intrinsic pulley arrangement gives the double loop mattress its favorable properties. Wound dehiscence is reduced because this stitch type is stronger and exerts less tension on the tissue than the mattress stitch. We advocate the use of this novel stitch wherever a high-strength, low-tension repair is required. These properties will enhance wound repair, and its application will be useful to surgeons of all disciplines. PMID:24698436

  2. Positive battery plate

    NASA Technical Reports Server (NTRS)

    Rowlette, John R. (Inventor)

    1985-01-01

    The power characteristics of a lead acid battery are improved by incorporating a dispersion of 1 to 10% by weight of a thermodynamically stable conductivity additive, such as conductive tin oxide coated glass fibers (34) of filamentary glass wool (42) in the positive active layer (32) carried on the grid (30) of the positive plate (16). Positive plate potential must be kept high enough to prevent reduction of the tin oxide to tin by utilizing an oversized, precharged positive paste.

  3. Double metric, generalized metric, and α' -deformed double field theory

    NASA Astrophysics Data System (ADS)

    Hohm, Olaf; Zwiebach, Barton

    2016-03-01

    We relate the unconstrained "double metric" of the "α' -geometry" formulation of double field theory to the constrained generalized metric encoding the spacetime metric and b -field. This is achieved by integrating out auxiliary field components of the double metric in an iterative procedure that induces an infinite number of higher-derivative corrections. As an application, we prove that, to first order in α' and to all orders in fields, the deformed gauge transformations are Green-Schwarz-deformed diffeomorphisms. We also prove that to first order in α' the spacetime action encodes precisely the Green-Schwarz deformation with Chern-Simons forms based on the torsionless gravitational connection. This seems to be in tension with suggestions in the literature that T-duality requires a torsionful connection, but we explain that these assertions are ambiguous since actions that use different connections are related by field redefinitions.

  4. Precise Point Positioning in the Airborne Mode

    NASA Astrophysics Data System (ADS)

    El-Mowafy, Ahmed

    2011-01-01

    The Global Positioning System (GPS) is widely used for positioning in the airborne mode such as in navigation as a supplementary system and for geo-referencing of cameras in mapping and surveillance by aircrafts and Unmanned Aerial Vehicles (UAV). The Precise Point Positioning (PPP) approach is an attractive positioning approach based on processing of un-differenced observations from a single GPS receiver. It employs precise satellite orbits and satellite clock corrections. These data can be obtained via the internet from several sources, e.g. the International GNSS Service (IGS). The data can also broadcast from satellites, such as via the LEX signal of the new Japanese satellite system QZSS. The PPP can achieve positioning precision and accuracy at the sub-decimetre level. In this paper, the functional and stochastic mathematical modelling used in PPP is discussed. Results of applying the PPP method in an airborne test using a small fixed-wing aircraft are presented. To evaluate the performance of the PPP approach, a reference trajectory was established by differential positioning of the same GPS observations with data from a ground reference station. The coordinate results from the two approaches, PPP and differential positioning, were compared and statistically evaluated. For the test at hand, positioning accuracy at the cm-to-decimetre was achieved for latitude and longitude coordinates and doubles that value for height estimation.

  5. The Positivity Scale

    ERIC Educational Resources Information Center

    Caprara, Gian Vittorio; Alessandri, Guido; Eisenberg, Nancy; Kupfer, A.; Steca, Patrizia; Caprara, Maria Giovanna; Yamaguchi, Susumu; Fukuzawa, Ai; Abela, John

    2012-01-01

    Five studies document the validity of a new 8-item scale designed to measure "positivity," defined as the tendency to view life and experiences with a positive outlook. In the first study (N = 372), the psychometric properties of Positivity Scale (P Scale) were examined in accordance with classical test theory using a large number of college…

  6. Prone positioning for surgery.

    PubMed

    Bowers, Mark

    2012-05-01

    The role of the registered perioperative practitioner (Operating Department Practitioner or Registered Nurse) includes the responsibility for safely positioning patients for surgery. The prone position is in common use for a variety of surgical procedures. The formal term for this surgical position is ventral decubitus (meaning laying face down). PMID:22720505

  7. 32 CFR 199.8 - Double coverage.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Double coverage. 199.8 Section 199.8 National... CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.8 Double coverage. (a... insurance plans do not exceed the total charges. (b) Double coverage plan. A double coverage plan is one...

  8. 32 CFR 199.8 - Double coverage.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Double coverage. 199.8 Section 199.8 National... CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.8 Double coverage. (a... insurance plans do not exceed the total charges. (b) Double coverage plan. A double coverage plan is one...

  9. 32 CFR 199.8 - Double coverage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Double coverage. 199.8 Section 199.8 National... CIVILIAN HEALTH AND MEDICAL PROGRAM OF THE UNIFORMED SERVICES (CHAMPUS) § 199.8 Double coverage. Link to an... charges. (b) Double coverage plan. A double coverage plan is one of the following: (1) Insurance plan....

  10. Some dynamical properties of very strong double layers in a triple plasma device

    NASA Technical Reports Server (NTRS)

    Carpenter, T.; Torven, S.

    1987-01-01

    Dynamical properties of very strong double layers seen in a differentially pumped triple plasma device are reported. These double layers are V-shaped. The following findings are discussed: (1) Disruptions in the double layer potential and in the plasma current occur when an inductance is placed in series with the bias supply between the sources in the external circuit. These disruptions, which can be highly periodic, are the result of a negative resistance region. (2) When reactances in the circuit are minimized, the double layer exhibits a jitter motion in position approximately equal to the double layer thickness. (3) When the bias between the sources is rapidly turned on, the initial phase in the double layer formation is the occurrence of a constant electric field for the first few microseconds. First the apparatus used in all of the work is discussed and then each of the three phenomena are considered.

  11. Anti-spacer double patterning

    NASA Astrophysics Data System (ADS)

    Hyatt, Michael; Huang, Karen; DeVilliers, Anton; Slezak, Mark; Liu, Zhi

    2014-03-01

    With extreme UV not ready for HVM for the 20nm and 14nm nodes, double patterning options that extend the use of 193nm immersion lithography beyond the optical resolution limits, such as LELE (Litho-Etch-Litho-Etch) and SADP (Self Aligned Double Patterning), are being used for critical layers for these nodes. LELE requires very stringent overlay capability of the optical exposure tool. The spacer scheme of SADP starts with a conformal film of material around the mandrels and etched along the mandrel sidewalls to form patterns with doubled frequency. SADP, while having the advantage of being a self-aligned process, adds a number of process steps and strict control of the mandrel profile is required. In this paper, we will demonstrate a novel technique - ASDP (Anti-Spacer Double Patterning), which uses only spin-on materials to achieve self-aligned double patterning. After initial resist patterning, an Anti-Spacer Generator (ASG) material is coated on the resist pattern to create the developable spacer region. Another layer of material is then coated and processed to generate the second pattern in between the first resist pattern. We were able to define 37.5nm half pitch pattern features using this technique as well as sub-resolution features for an asymmetric pattern. In this paper we will review the capability of the process in terms of CD control and LWR (line width roughness) and discuss the limitations of the process.

  12. Plasmoid instability in double current sheets

    SciTech Connect

    Nemati, M. J.; Wang, Z. X. Wei, L.; Selim, B. I.

    2015-01-15

    The linear behavior of plasmoid instability in double current sheet configurations, namely, double plasmoid mode (DPM), is analytically and numerically investigated within the framework of a reduced magnetohydrodynamic model. Analytical analysis shows that if the separation of double current sheets is sufficiently small [κx{sub s}≪κ{sup 2/9}S{sub L}{sup 1/3}], the growth rate of DPMs scales as κ{sup 2/3}S{sub L}{sup 0} in the non-constant-ψ regime, where κ=kL{sub CS}/2 is the wave vector measured by the half length of the system L{sub CS}/2, 2x{sub s} is the separation between two resonant surfaces, and S{sub L}=L{sub CS}V{sub A}/2η is Lundquist number with V{sub A} and η being Alfven velocity and resistivity, respectively. If the separation is very large [κx{sub s}≫κ{sup 2/9}S{sub L}{sup 1/3}], the growth rate scales as κ{sup −2/5}S{sub L}{sup 2/5} in the constant-ψ regime. Furthermore, it is also analytically found that the maximum wave number scales as x{sub s}{sup −9/7}S{sub L}{sup 3/7} at the transition position between these two regimes, and the corresponding maximum growth rate scales as x{sub s}{sup −6/7}S{sub L}{sup 2/7} there. The analytically predicted scalings are verified in some limits through direct numerical calculations.

  13. Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus.

    PubMed

    Hesnard, Leslie; Legoux, François; Gautreau, Laetitia; Moyon, Melinda; Baron, Olivier; Devilder, Marie-Claire; Bonneville, Marc; Saulquin, Xavier

    2016-03-01

    In the thymus, a T-cell repertoire able to confer protection against infectious and noninfectious agents in a peptide-dependent, self-MHC-restricted manner is selected. Direct detection of Ag-specific thymocytes, and analysis of the impact of the expression of the MHC-restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer-based enrichment protocol to analyze the ex vivo frequency and activation-phenotype of human thymocytes specific for self, viral and tumor-antigens presented by HLA-A*0201 (A2) in individuals expressing or not this allele. Ag-specific thymocytes were quantified within both CD4CD8 double or single-positive compartments in every donor. Our data indicate that the maturation efficiency of Ag-specific thymocytes is poorly affected by HLA-A2 expression, in terms of frequencies. Nevertheless, A2-restricted T-cell lines from A2(+) donors reacted to A2(+) cell lines in a highly peptide-specific fashion, whereas their alloreactive counterparts showed off-target activity. This first ex vivo analysis of human antigen-specific thymocytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process. PMID:26635029

  14. Current-free double layers in helicon sources

    NASA Astrophysics Data System (ADS)

    Su, Yu-Jeng; Shaing, K. C.

    2011-10-01

    A model for the formation of a stationary current-free double layer in collisionless plasmas expanding in a magnetic nozzle is presented. The model consists of the dynamics of cold ions, isothermal hot electrons and fere-isothermal, i.e. almost isothermal, cold electrons. It can determine the position and amplitude of the double layer including the jump in cold electron temperature across the layer. The magnitude of the jump is consistent with experimental observations. Plasmas are accelerated mainly by the magnetic nozzle and the contribution from the double layer is small. The important effects of the ion charge state Z on the flow speed at the nozzle throat and at the exit are also discussed. It is found that the Mach number at the magnetic nozzle throat is \\sqrt Z which can be tested in experiments. The exit velocity also scales as \\sqrt Z . To increase the thrust power, the ion charge state Z could be an important parameter.

  15. Measuring Double Stars with the Modified Video Drift Method

    NASA Astrophysics Data System (ADS)

    Iverson, Ernest W.; Nugent, Richard L.

    2015-05-01

    The usefulness of a common CCTV video camera for measuring the position angle and separation of a double star is limited by the camera sensitivity and telescope aperture. The video drift method is enhanced by using an integrating camera but frame integrations longer than 0.132 seconds (4 frames) are impractical. This is due to the target stars elongating (streaking) and moving in incremental steps. A simple modification to the Video Drift Method and corresponding VidPro analysis program significantly increases the magnitude at which double stars can be measured. Double stars down to magnitude +16 have been measured with a 14-inch (35.6-cm) telescope using this method compared to magnitude +12 using the original video drift method under comparable seeing conditions.

  16. Mechanical seal having a double-tier mating ring

    DOEpatents

    Khonsari, Michael M.; Somanchi, Anoop K.

    2005-09-13

    An apparatus and method to enhance the overall performance of mechanical seals in one of the following ways: by reducing seal face wear, by reducing the contact surface temperature, or by increasing the life span of mechanical seals. The apparatus is a mechanical seal (e.g., single mechanical seals, double mechanical seals, tandem mechanical seals, bellows, pusher mechanical seals, and all types of rotating and reciprocating machines) comprising a rotating ring and a double-tier mating ring. In a preferred embodiment, the double-tier mating ring comprises a first and a second stationary ring that together form an agitation-inducing, guided flow channel to allow for the removal of heat generated at the seal face of the mating ring by channeling a coolant entering the mating ring to a position adjacent to and in close proximity with the interior surface area of the seal face of the mating ring.

  17. The frequency selectivity of double H-shaped metallic structures

    NASA Astrophysics Data System (ADS)

    Bu, Xiaoxia; Zhao, Guozhong

    2013-12-01

    This paper presents the design and numerical simulation of the double H-shaped metallic periodic structure based on finite difference time domain (FDTD) method in terahertz frequency range. The double H-shaped structure unit cell consists of two H structures overlapped in the same plane. Numerical simulation results show that the double H-shaped structure results in a distinct and strong transmission trap in 0.2~3.0THz range. The position and the full wave at half maximum (FWHM) of transmission trap are changed with different structure size. The surface current distribution of structure is numerical simulated, which clarifies the frequency selection mechanism of the transmission spectra.

  18. New double soft emission theorems

    NASA Astrophysics Data System (ADS)

    Cachazo, Freddy; He, Song; Yuan, Ellis Ye

    2015-09-01

    We study the behavior of the tree-level S-matrix of a variety of theories as two particles become soft. By analogy with the recently found subleading soft theorems for gravitons and gluons, we explore subleading terms in double soft emissions. We first consider double soft scalar emissions and find subleading terms that are controlled by the angular momentum operator acting on hard particles. The order of the subleading theorems depends on the presence or not of color structures. Next we obtain a compact formula for the leading term in a double soft photon emission. The theories studied are a special Galileon, Dirac-Born-Infeld, Einstein-Maxwell-Scalar, nonlinear sigma model and Yang-Mills-Scalar. We use the recently found Cachazo-He-Yuan representation of these theories in order to give a simple proof of the leading order part of all these theorems.

  19. Double field theory inspired cosmology

    SciTech Connect

    Wu, Houwen; Yang, Haitang E-mail: hyanga@scu.edu.cn

    2014-07-01

    Double field theory proposes a generalized spacetime action possessing manifest T-duality on the level of component fields. We calculate the cosmological solutions of double field theory with vanishing Kalb-Ramond field. It turns out that double field theory provides a more consistent way to construct cosmological solutions than the standard string cosmology. We construct solutions for vanishing and non-vanishing symmetry preserving dilaton potentials. The solutions assemble the pre- and post-big bang evolutions in one single line element. Our results show a smooth evolution from an anisotropic early stage to an isotropic phase without any special initial conditions in contrast to previous models. In addition, we demonstrate that the contraction of the dual space automatically leads to both an inflation phase and a decelerated expansion of the ordinary space during different evolution stages.

  20. Double patterning compliant logic design

    NASA Astrophysics Data System (ADS)

    Ma, Yuangsheng; Sweis, Jason; Bencher, Chris; Deng, Yunfei; Dai, Huixiong; Yoshida, Hidekazu; Gisuthan, Bimal; Kye, Jongwook; Levinson, Harry J.

    2011-04-01

    Double patterning technology (DPT) is the only solution to enable the scaling for advanced technology nodes before EUV or any other advanced patterning techniques become available. In general, there are two major double patterning techniques: one is Litho-Etch-Litho-Etch (LELE), and the other is sidewall spacer technology, a Self-Aligned Double Patterning technique (SADP). While numerous papers have previously demonstrated these techniques on wafer process capabilities and processing costs, more study needs to be done in the context of standard cell design flow to enable their applications in mass production. In this paper, we will present the impact of DPT on logic designs, and give a thorough discussion on how to make DPT-compliant constructs, placement and routing using examples with Cadence's Encounter Digital Implementation System (EDI System).

  1. Double ionization of atomic cadmium

    SciTech Connect

    Linusson, P.; Fritzsche, S.; Eland, J. H. D.; Hedin, L.; Karlsson, L.; Feifel, R.

    2011-02-15

    We have recorded the double photoionization spectrum of atomic Cd at four different photon energies in the range 40-200 eV. The main channel is single ionization and subsequent decay of excited Cd{sup +} states, some involving Coster-Kronig processes, whereas direct double ionization is found to be weak. The decay of the excited Cd{sup +} states shows a strong selectivity, related to the configuration of the final state. Double ionization leading to the Cd{sup 2+} ground state is investigated in some detail and is found to proceed mainly through ionization and decay of 4d correlation satellites. The most prominent autoionization peaks have been identified with the aid of quantum-mechanical calculations.

  2. Jobs: women's double burden.

    PubMed

    1995-01-01

    Whereas international conventions and national laws provide equal opportunities for women in employment, the reality of women's lives keeps a disproportionate number of women unemployed, underemployed, and living in poverty. The UN itself, which officially is working toward equity among its employees, has a staff composed of just 32.6% women, and women comprise only 10.5% of the top end of the hierarchy. In areas where women's labor force participation has increased dramatically, women typically earn 30-40% less than men doing the same job or else their employment is limited to "traditional female" service positions. The fact that women and girls have received an inadequate education makes it extremely difficult to break the barriers of discrimination in developing countries. The empowerment of women will break the education barrier, and, when that falls, many other barriers will follow suit. Efforts are already underway to break structural barriers caused by economic and social policies. For example, a more flexible pattern of work has been proposed which will include the voluntary assumption of flexible hours, job-sharing, and part-time work. The concept of work is also being broadened to include the important human services that women traditionally provide on a volunteer basis. This will lead to a valuation of women's contribution to society which can be added to calculations of gross domestic product. Women also need protection as they attempt to eke out a living in the informal sector which has been the traditional avenue for women to earn money. This sector is not protected by law and is subject to extortion by officials and by male competitors. A variety of measures is under consideration to increase the protection of informal sector workers. Women also need protection in the conventional work place, especially as they enter fields traditionally reserved for men. These questions are important even in the context of global unemployment because these issues

  3. Attosecond Double-Slit Experiment

    SciTech Connect

    Lindner, F.; Schaetzel, M.G.; Baltuska, A.; Goulielmakis, E.; Walther, H.; Krausz, F.; Milosevic, D.B.; Bauer, D.; Becker, W.; Paulus, G.G.

    2005-07-22

    A new scheme for a double-slit experiment in the time domain is presented. Phase-stabilized few-cycle laser pulses open one to two windows (slits) of attosecond duration for photoionization. Fringes in the angle-resolved energy spectrum of varying visibility depending on the degree of which-way information are measured. A situation in which one and the same electron encounters a single and a double slit at the same time is observed. The investigation of the fringes makes possible interferometry on the attosecond time scale. From the number of visible fringes, for example, one derives that the slits are extended over about 500 as.

  4. Double stranded nucleic acid biochips

    DOEpatents

    Chernov, Boris; Golova, Julia

    2006-05-23

    This invention describes a new method of constructing double-stranded DNA (dsDNA) microarrays based on the use of pre-synthesized or natural DNA duplexes without a stem-loop structure. The complementary oligonucleotide chains are bonded together by a novel connector that includes a linker for immobilization on a matrix. A non-enzymatic method for synthesizing double-stranded nucleic acids with this novel connector enables the construction of inexpensive and robust dsDNA/dsRNA microarrays. DNA-DNA and DNA-protein interactions are investigated using the microarrays.

  5. Double-Chooz Neutrino Experiment

    NASA Astrophysics Data System (ADS)

    Palomares, Carmen; Double Chooz Collaboration

    2011-12-01

    The Double Chooz experiment will use the electron anti-neutrinos produced by the Chooz nuclear power station to search for a non-vanishing value of the θ13 neutrino mixing angle. Double Chooz will be the first of a new generation of neutrino experiments using identical detectors at different distances from the neutrino source to reduce the systematic errors due to the uncertainties on the neutrino flux and to the detector acceptance. The far detector will be operative by the beginning of 2011. Installation of the near detector will occur in 2012.

  6. Simultaneous positive and negative external mechanical work in human walking.

    PubMed

    Donelan, J Maxwell; Kram, Rodger; Kuo, Arthur D

    2002-01-01

    In human walking, the center of mass motion is similar to an inverted pendulum. Viewing double support as a transition from one inverted pendulum to the next, we hypothesized that the leading leg performs negative work to redirect the center of mass velocity, while simultaneously, the trailing leg performs positive work to replace the lost energy. To test this hypothesis, we developed a method to quantify the external mechanical work performed by each limb (individual limbs method). Traditional measures of external mechanical work use the sum of the ground reaction forces acting on the limbs (combined limbs method) allowing for the mathematical cancellation of simultaneous positive and negative work during multiple support periods. We expected to find that the traditional combined limbs method underestimates external mechanical work by a substantial amount. We used both methods to measure the external mechanical work performed by humans walking over a range of speeds. We found that during double support, the legs perform a substantial amount of positive and negative external work simultaneously. The combined limbs measures of positive and negative external work were approximately 33% less than those calculated using the individual limbs method. At all speeds, the trailing leg performs greater than 97% of the double support positive work while the leading leg performs greater than 94% of the double support negative work. PMID:11747890

  7. Development of a Double Crystal Monochromator

    SciTech Connect

    Kupp, T.; Blank, B.; Deyhim, A.; Fuoss, P.H.; Benson, C.A.; Robinson, I.K.

    2010-11-16

    A high-precision water-cooled, small offset, double crystal monochromator has been developed for the Advanced Photon Source (APS) UNICAT Sector 34 beamline. The design incorporates the supports and gravity feed water cooling of two diamond or silicon crystals correctly positioned about a common rotation axis so that the incident and diffracted beam do not walk off the edges of the crystals within the energy range 6-15KeV (30{sup o} < q < 11.6{sup o}). In the 34ID implementation, the first crystal sees unfocussed pink beam from an undulator. The second crystal has a {+-}5{sup o} motorized tilt motion around an axis parallel to its face and around the beam direction. In this paper preliminary measurement data obtained from Advanced Photon Source and the detail of the instrument design are presented.

  8. Development of a Double Crystal Monochromator

    SciTech Connect

    Kupp, Tom; Blank, Basil; Deyhim, Alex; Benson, Curtis; Robinson, Ian; Fuoss, Paul

    2004-05-12

    A high-precision water-cooled, small offset, double crystal monochromator has been developed for the Advanced Photon Source (APS) UNICAT Sector 34 beamline. The design incorporates the supports and gravity feed water cooling of two diamond or silicon crystals correctly positioned about a common rotation axis so that the incident and diffracted beam do not walk off the edges of the crystals within the energy range 6-15KeV (30 deg.

  9. The effect of a magnetic field gradient on anode double layers

    NASA Technical Reports Server (NTRS)

    Song, B.; Merlino, R. L.; D'Angelo, N.

    1992-01-01

    In experiments on anode (ionization) double layers in nonuniform magnetic fields it has been noted that the magnetic field gradient seems to stabilize the double layer position. This effect is further investigated in a Q machine in which the magnetic field geometry could be varied. It is found that the position of the double layers, along the axis of the device, could be controlled by changing the magnetic geometry. This effect is accounted for in a physical model which takes into account the effect of ion reflection by the magnetic mirror force in the region of magnetic field nonuniformity. This model is also able to account for variation of the double layer position when the neutral gas pressure is varied.

  10. Double wall vacuum tubing and method of manufacture

    DOEpatents

    Stahl, Charles R.; Gibson, Michael A.; Knudsen, Christian W.

    1989-01-01

    An evacuated double wall tubing is shown together with a method for the manufacture of such tubing which includes providing a first pipe of predetermined larger diameter and a second pipe having an O.D. substantially smaller than the I.D. of the first pipe. An evacuation opening is then in the first pipe. The second pipe is inserted inside the first pipe with an annular space therebetween. The pipes are welded together at one end. A stretching tool is secured to the other end of the second pipe after welding. The second pipe is then prestressed mechanically with the stretching tool an amount sufficient to prevent substantial buckling of the second pipe under normal operating conditions of the double wall pipe. The other ends of the first pipe and the prestressed second pipe are welded together, preferably by explosion welding, without the introduction of mechanical spacers between the pipes. The annulus between the pipes is evacuated through the evacuation opening, and the evacuation opening is finally sealed. The first pipe is preferably of steel and the second pipe is preferably of titanium. The pipes may be of a size and wall thickness sufficient for the double wall pipe to be structurally load bearing or may be of a size and wall thickness insufficient for the double wall pipe to be structurally load bearing, and the double wall pipe positioned with a sliding fit inside a third pipe of a load-bearing size.

  11. Beam position monitor

    DOEpatents

    Alkire, Randy W.; Rosenbaum, Gerold; Evans, Gwyndaf

    2003-07-22

    An apparatus for determining the position of an x-ray beam relative to a desired beam axis. Where the apparatus is positioned along the beam path so that a thin metal foil target intersects the x-ray beam generating fluorescent radiation. A PIN diode array is positioned so that a portion of the fluorescent radiation is intercepted by the array resulting in an a series of electrical signals from the PIN diodes making up the array. The signals are then analyzed and the position of the x-ray beam is determined relative to the desired beam path.

  12. Interval polynomial positivity

    NASA Technical Reports Server (NTRS)

    Bose, N. K.; Kim, K. D.

    1989-01-01

    It is shown that a univariate interval polynomial is globally positive if and only if two extreme polynomials are globally positive. It is shown that the global positivity property of a bivariate interval polynomial is completely determined by four extreme bivariate polynomials. The cardinality of the determining set for k-variate interval polynomials is 2k. One of many possible generalizations, where vertex implication for global positivity holds, is made by considering the parameter space to be the set dual of a boxed domain.

  13. Biphoton double-slit experiment

    SciTech Connect

    Brida, G.; Cagliero, E.; Falzetta, G.; Genovese, M.; Gramegna, M.; Predazzi, E.

    2003-09-01

    In this paper we present a double-slit experiment where two indistinguishable photons produced by type-I parametric down-conversion are each sent to a well-defined slit. Data about the diffraction and interference patterns for coincidences are presented and discussed. An analysis of these data allows a test of standard quantum mechanics against the de Broglie-Bohm theory.

  14. A Double-Minded Fractal

    ERIC Educational Resources Information Center

    Simoson, Andrew J.

    2009-01-01

    This article presents a fun activity of generating a double-minded fractal image for a linear algebra class once the idea of rotation and scaling matrices are introduced. In particular the fractal flip-flops between two words, depending on the level at which the image is viewed. (Contains 5 figures.)

  15. The double well mass filter

    SciTech Connect

    Gueroult, Renaud; Fisch, Nathaniel J.; Rax, Jean-Marcel

    2014-02-15

    Various mass filter concepts based on rotating plasmas have been suggested with the specific purpose of nuclear waste remediation. We report on a new rotating mass filter combining radial separation with axial extraction. The radial separation of the masses is the result of a “double-well” in effective radial potential in rotating plasma with a sheared rotation profile.

  16. Double heterojunction bipolar phototransistor model

    NASA Astrophysics Data System (ADS)

    Horak, Michal

    2003-07-01

    An analytical mathematical model of the double heterojunction NpN bipolar phototransistor with abrupt heterojunctions in three terminal configuration is presented. The thermionic-filed emission and diffusion of injected carriers is considered and the Ebers-Moll type relations for the collector and emitter current are obtained. Several steady state characteristics of the phototransistor structure are calculated (optical gain, quantum efficiency, responsivity).

  17. The double well mass filter

    DOE PAGESBeta

    Gueroult, Renaud; Rax, Jean -Marcel; Fisch, Nathaniel J.

    2014-02-03

    Various mass filter concepts based on rotating plasmas have been suggested with the specific purpose of nuclear waste remediation. We report on a new rotating mass filter combining radial separation with axial extraction. Lastly, the radial separation of the masses is the result of a “double-well” in effective radial potential in rotating plasma with a sheared rotation profile.

  18. Time of flight diffraction imaging for double-probe technique.

    PubMed

    Chang, Young-Fo; Hsieh, Cheng-I

    2002-06-01

    Due to rapid progress in microelectronics and computer technologies, the system evolving from analog to digital, and a programmable and flexible synthetic aperture focusing technique (SAFT) for the single-probe pulse-echo imaging technique of ultrasonic nondestructive testing (NDT) becomes feasible. The double-probe reflection technique usually is used to detect the nonhorizontal flaws in the ultrasonic NDT. Because there is an offset between the transmitter and receiver, the position and size of the flaw cannot be directly read from the image. Therefore, a digital signal processing (DSP) imaging method is proposed to process the ultrasonic image obtained by double-probe reflection technique. In the imaging, the signal is redistributed on an ellipsoid with the transmitter and receiver positions as focuses, and the traveltime sum for the echo from the ellipsoid to the focuses as the traveltime of signal. After redistributing all the signals, the useful signals can be constructively added in some point in which the reflected point is; otherwise, the signals will be destructively added. Therefore, the image resolution of the flaw can be improved and the position and size of the flaw can be estimated directly from the processed image. Based on the experimental results, the steep flaw (45 degrees) cannot be detected by the pulse echo technique but can be detected by the double-probe method, and the double-probe B-scan image of 30 degrees tilted crack is clearer than the pulse echo B-scan image. However, the flaw image departs from its true position greatly. After processing, the steep flaw image can be moved to its true position. When the flaws are not greater than the probe largely, the sizes of the flaws are difficult to be discriminated in both pulse echo and double-probe B-scan images. In the processed double-probe B-scan image, the size of the flaws can be estimated successfully, and the images of the flaws are close to their true shape. PMID:12075969

  19. Keepers of the double stars

    NASA Astrophysics Data System (ADS)

    Tenn, Joseph S.

    2013-03-01

    Astronomers have long tracked double stars in efforts to find those that are gravitationally-bound binaries and then to determine their orbits. Early catalogues by the Herschels, Struves, and others began with their own discoveries. In 1906 court reporter and amateur astronomer Sherburne Wesley Burnham published a massive double star catalogue containing data from many observers on more than 13,000 systems. Lick Observatory astronomer Robert Grant Aitken produced a much larger catalogue in 1932 and coordinated with Robert Innes of Johannesburg, who catalogued the southern systems. Aitken maintained and expanded Burnham's records of observations on handwritten file cards, and eventually turned them over to the Lick Observatory, where astrometrist Hamilton Jeffers further expanded the collection and put all the observations on punched cards. With the aid of Frances M. "Rete" Greeby he made two catalogues: an Index Catalogue with basic data about each star, and a complete catalogue of observations, with one observation per punched card. He enlisted Willem van den Bos of Johannesburg to add southern stars, and together they published the Index Catalogue of Visual Double Stars, 1961.0. As Jeffers approached retirement he became greatly concerned about the disposition of the catalogues. He wanted to be replaced by another "double star man," but Lick Director Albert E. Whitford had the new 120-inch reflector, the world's second largest telescope, and he wanted to pursue modern astrophysics instead. Jeffers was vociferously opposed to turning over the card files to another institution, and especially against their coming under the control of Kaj Strand of the United States Naval Observatory. In the end the USNO got the files and has maintained the records ever since, first under Charles Worley, and, since 1997, under Brian Mason. Now called the Washington Double Star Catalog (WDS), it is completely online and currently contains more than 1,200,000 measures of more than 125

  20. "Positive Discipline": Beginnings Workshop.

    ERIC Educational Resources Information Center

    Stephens, Karen; And Others

    1992-01-01

    Four articles in this special section discuss (1) ideas for making discipline a positive experience for child care staff and children (Karen Stephens); (2) scenarios illustrating the power of adult messages to children (Karen Stephens); (3) classroom environments that facilitate positive discipline (Marjorie K. Kostelnik); and (4) strategies for…

  1. Positioning and locking apparatus

    DOEpatents

    Hayward, M.L.; Harper, W.H.

    1985-06-19

    A positioning and locking apparatus including a fixture having a rotatable torque ring provided with a plurality of cam segments for automatically guiding a container into a desired location within the fixture. Rotation of the ring turns the container into a final position in pressure sealing relation against a hatch member.

  2. Positioning and locking apparatus

    DOEpatents

    Hayward, M.L.; Harper, W.H.

    1987-06-30

    A positioning and locking apparatus are disclosed including a fixture having a rotatable torque ring provided with a plurality of cam segments for automatically guiding a container into a desired location within the fixture. Rotation of the ring turns the container into a final position in pressure sealing relation against a hatch member. 6 figs.

  3. Positioning and locking apparatus

    DOEpatents

    Hayward, Milton L.; Harper, William H.

    1987-01-01

    A positioning and locking apparatus including a fixture having a rotatable torque ring provided with a plurality of cam segments for automatically guiding a container into a desired location within the fixture. Rotation of the ring turns the container into a final position in pressure sealing relation against a hatch member.

  4. A laboratory investigation of potential double layers

    NASA Technical Reports Server (NTRS)

    Leung, Philip

    1987-01-01

    In a triple plasma device, the injection of electron current from the source chamber to the target chamber causes the formation of a potential double layer. At a low current density, the space charge of the injected current produces a virtual cathode-type potential double layer. This double layer is stable, and various wave instabilities are observed to associate with this double layer. As the current density is increased, the double layer becomes unstable, and a moving double layer results. As the current density is increased further, the enhanced ionization causes the neutralization of the space charge of the electron beam, and the beam plasma discharge is ignited.

  5. A laboratory investigation of potential double layers

    NASA Technical Reports Server (NTRS)

    Leung, Philip

    1987-01-01

    In a triple plasma device, the injection of electron current from the source chamber to the target chamber causes the formation of a potential double layer. At a low current density, the space charge of the injected current produces a virtual cathode-type potential double layer. This double layer is stable and various wave instabilities are observed to associate with this double layer. As the current density is increased, the double layer becomes unstable and a moving double layer results. As the current density is increased further, the enhanced ionization causes the neutralization of the space charge of the electron beam and the 'beam plasma discharge' is ignited.

  6. Double Photoionization into Double Core-Hole States in Xe

    SciTech Connect

    Hikosaka, Y.; Kaneyasu, T.; Shigemasa, E.; Lablanquie, P.; Penent, F.; Eland, J. H. D.; Aoto, T.; Ito, K.

    2007-05-04

    Double photoionization (DPI) leading to double core-hole states of Xe{sup 2+} 4d{sup -2} has been studied using a magnetic bottle time-of-flight spectrometer. The assignments of the Xe{sup 2+} 4d{sup -2} states are confirmed by the Auger lines extracted from fourfold coincidences including two photoelectrons and two Auger electrons. It is estimated that the core-core DPI into Xe{sup 2+} 4d{sup -2} at a photon energy of 301.6 eV has a favored cross section of about 0.3 MB. The intense core-core DPI is due to mixing of the 4d{sup -2} continuum with the 4p single photoionization, which is manifested in the relative intensities of the Xe{sup 2+} 4d{sup -2} components.

  7. Double photoionization into double core-hole states in Xe.

    PubMed

    Hikosaka, Y; Lablanquie, P; Penent, F; Kaneyasu, T; Shigemasa, E; Eland, J H D; Aoto, T; Ito, K

    2007-05-01

    Double photoionization (DPI) leading to double core-hole states of Xe2+ 4d(-2) has been studied using a magnetic bottle time-of-flight spectrometer. The assignments of the Xe2+ 4d(-2) states are confirmed by the Auger lines extracted from fourfold coincidences including two photoelectrons and two Auger electrons. It is estimated that the core-core DPI into Xe2+ 4d(-2) at a photon energy of 301.6 eV has a favored cross section of about 0.3 MB. The intense core-core DPI is due to mixing of the 4d(-2) continuum with the 4p single photoionization, which is manifested in the relative intensities of the Xe2+ 4d(-2) components. PMID:17501570

  8. Combined GPS and GALILEO instantaneous precise positioning

    NASA Astrophysics Data System (ADS)

    Wielgosz, P.; Paziewski, J.; Stepniak, K.

    2011-12-01

    This presentation provides results of the research aimed at precise positioning using single-epoch GPS and Galileo observations. The main goal was to develop algorithms that allow obtaining reliable centimeter-level position when using just a single epoch of pseudorange and carrier phase GPS and Galileo data in a single functional model. The presented algorithms are based on relative precise positioning using double-differenced observations in both single baseline and network mode. Fast and reliable ambiguity resolution is the key for rapid and single-epoch precise positioning. In order to support ambiguity resolution using small amount of data, special emphasis was put on mitigation of ionospheric and tropospheric delays. The functional model was based on constrained least squares estimation. The LAMBDA method was applied for ambiguity resolution and a multi-criteria statistical tests are used for ambiguity validation. These algorithms were implemented in GINPOS software developed at the University of Warmia and Mazury in Olsztyn. The results of combined GPS+Galileo processing were compared to the solutions obtained using GPS-only and Galileo-only data. Since there are just two test Galileo satellites on orbit, Spirent multi-GNSS simulator was used to obtain Galileo and GPS signals. The processed baselines reached up to 35-70 km. The results based on the simulated data show that even though single-epoch precise positioning is possible with GPS only, adding Galileo data increases availability and reliability of the user position.

  9. Evidence for susceptibility of intrathymic T-cell precursors and their progeny carrying T-cell antigen receptor phenotypes TCR alpha beta + and TCR gamma delta + to human immunodeficiency virus infection: a mechanism for CD4+ (T4) lymphocyte depletion.

    PubMed Central

    Schnittman, S M; Denning, S M; Greenhouse, J J; Justement, J S; Baseler, M; Kurtzberg, J; Haynes, B F; Fauci, A S

    1990-01-01

    Individuals infected by the human immunodeficiency virus type 1 (HIV-1) demonstrate progressive depletion and qualitative dysfunction of the helper T4 (CD4+) cell population. Mechanisms proposed for attrition of CD4+ T cells include direct cytopathicity of these mature cells following infection as well as infection of early T-lymphocyte progenitors. The latter mechanism could lead to failure to regenerate mature functioning CD4+ T cells. The present study determines the susceptibility of thymocytes at various stages of maturity to infection with HIV-1. Various normal thymocyte populations were inoculated with HIV-1, including unfractionated (UF), CD3- CD4- CD8- ["triple negative" (TN)], CD4+ CD8+ ["double positive" (DP)] thymocytes, and thymocyte populations obtained by limited dilution cloning. Cultures were studied for the presence of HIV-1 DNA by polymerase chain reaction in addition to examination for reverse transcriptase activity. We determined that transformed T-cell and thymocyte cell lines completely lacking CD4 were not susceptible to infection by HIV-1, whereas all of the following lines were: UF thymocytes (70-90% CD4hi+); DP thymocytes (99% CD4hi+); TN thymocytes (0% CD4hi+); and TCR alpha beta +, TCR gamma delta +, or CD16+ CD3- (natural killer) thymocyte clones expressing variable levels of CD4 and representing the progeny of TN thymocytes. [TCR alpha beta + and TCR gamma delta + refer to the chains of the T-cell antigen receptor (TCR), and CD4hi refers to a strong rightward shift (greater than 30 linear channels) of the CD4 curve on flow cytometric analysis compared with control.] Monoclonal antibodies (mAbs) to CD4 (T4a epitope) but not to CD3 (T3) were capable of blocking infection of mature and immature CD4hi+ thymocytes. Moreover, anti-CD4(T4a) mAbs also inhibited infection of CD4hi- TN thymocytes, indicating that these T-cell precursors--despite their apparent "triple negativity" (CD3- CD4hi- CD8-)--expressed sufficient CD4 molecules to become

  10. Double-clad nuclear-fuel safety rod

    DOEpatents

    McCarthy, W.H.; Atcheson, D.B.

    1981-12-30

    A device for shutting down a nuclear reactor during an undercooling or overpower event, whether or not the reactor's scram system operates properly. This is accomplished by double-clad fuel safety rods positioned at various locations throughout the reactor core, wherein melting of a secondary internal cladding of the rod allows the fuel column therein to shift from the reactor core to place the reactor in a subcritical condition.

  11. Inverse Beta Decay Reconstruction in the Double Chooz Monte Carlo

    NASA Astrophysics Data System (ADS)

    Norrick, Anne

    2010-02-01

    The Double Chooz Experiment will search for neutrino oscillations using the ``Inverse Beta-Decay'' (IBD) interactions of electron antineutrinos from a nuclear reactor in Chooz, France. The experiment needs to isolate IBD events by detecting and reconstructing the positions and deposited energies of the outgoing positron and neutron. Methods for isolating this process will be described. In addition, results of simulation studies of two different reconstruction algorithms will be presented and their performances compared. )

  12. Double layers and double wells in arbitrary degenerate plasmas

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2016-06-01

    Using the generalized hydrodynamic model, the possibility of variety of large amplitude nonlinear excitations is examined in electron-ion plasma with arbitrary electron degeneracy considering also the ion temperature effect. A new energy-density relation is proposed for plasmas with arbitrary electron degeneracy which reduces to the classical Boltzmann and quantum Thomas-Fermi counterparts in the extreme limits. The pseudopotential method is employed to find the criteria for existence of nonlinear structures such as solitons, periodic nonlinear structures, and double-layers for different cases of adiabatic and isothermal ion fluids for a whole range of normalized electron chemical potential, η0, ranging from dilute classical to completely degenerate electron fluids. It is observed that there is a Mach-speed gap in which no large amplitude localized or periodic nonlinear excitations can propagate in the plasma under consideration. It is further revealed that the plasma under investigation supports propagation of double-wells and double-layers the chemical potential and Mach number ranges of which are studied in terms of other plasma parameters. The Mach number criteria for nonlinear waves are shown to significantly differ for cases of classical with η0 < 0 and quantum with η0 > 0 regimes. It is also shown that the localized structure propagation criteria possess significant dissimilarities for plasmas with adiabatic and isothermal ions. Current research may be generalized to study the nonlinear structures in plasma containing positrons, multiple ions with different charge states, and charged dust grains.

  13. Study on integrated vehicle navigation system of "Beidou" Double-Star/DR

    NASA Astrophysics Data System (ADS)

    Liu, Hong; Liu, Jianye; Zhai, Linpei; Xiu, Jihong

    2005-12-01

    Vehicle navigation is the corn element of Intelligent Transport System. The integrated system of "Beidou" Double-star/DR is studied in this paper according to the present state of vehicle navigation in our country. "Beidou" Double-star navigation position system is one regional satellite position system built up by our country, which can provide rapidly not only highly precision position and brevity telegram service. However, when the vehicles go around the tall buildings, high mountain area, wayside trees and in the tunnels, all signal may not be received. If the satellite navigation position system is used only, the precision will be reduced. Therefore, this paper proposes a nonlinear self-adaptive Kalman filter model and its algorithm for a Double-star/DR integrated navigation system in land vehicles, and verifies effectively the algorithm and scheme through the means of simulation. Next, this paper introduces map match approach. The roads are segmented and character information is brought out. Then, proper search rules and map match algorithm are adopted. According to the current vehicle position information that Double-Star/DR system provides, the nearest road can be found in the map database. The vehicle position will be matched and displayed on the road. The result of the experiment shows that the Double-Star/DR integrated algorithm and map match can improve reliability and the precision of vehicle navigation system efficiently.

  14. CRANE POSITIONING APPARATUS

    DOEpatents

    Landsiedel, F.W.; Wolff, H.

    1960-06-28

    An apparatus is described for automatically accomplishing the final accurate horizontal positioning of a crane after the latter has been placed to within 1/8 in. of its selected position. For this purpose there is provided a tiltable member on the crane mast for lowering into contact with a stationary probe. Misalignment of the tiltable member, with respect to the probe as the member is lowered, causes tilting of the latter to actuate appropriate switches that energize motors for bringing the mast into proper position. When properly aligned the member is not tilted and a central switch is actuated to indicate the final alignment of the crane.

  15. Monocular Elevation Deficiency - Double Elevator Palsy

    MedlinePlus

    ... Eye Terms Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? ...

  16. Monocular Elevation Deficiency - Double Elevator Palsy

    MedlinePlus

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  17. Bifurcation structure of successive torus doubling

    NASA Astrophysics Data System (ADS)

    Sekikawa, Munehisa; Inaba, Naohiko; Yoshinaga, Tetsuya; Tsubouchi, Takashi

    2006-01-01

    The authors discuss the “embryology” of successive torus doubling via the bifurcation theory, and assert that the coupled map of a logistic map and a circle map has a structure capable of generating infinite number of torus doublings.

  18. Fluorescent optical position sensor

    DOEpatents

    Weiss, Jonathan D.

    2005-11-15

    A fluorescent optical position sensor and method of operation. A small excitation source side-pumps a localized region of fluorescence at an unknown position along a fluorescent waveguide. As the fluorescent light travels down the waveguide, the intensity of fluorescent light decreases due to absorption. By measuring with one (or two) photodetectors the attenuated intensity of fluorescent light emitted from one (or both) ends of the waveguide, the position of the excitation source relative to the waveguide can be determined by comparing the measured light intensity to a calibrated response curve or mathematical model. Alternatively, excitation light can be pumped into an end of the waveguide, which generates an exponentially-decaying continuous source of fluorescent light along the length of the waveguide. The position of a photodetector oriented to view the side of the waveguide can be uniquely determined by measuring the intensity of the fluorescent light emitted radially at that location.

  19. Benign positional vertigo

    MedlinePlus

    ... Clinical practice guideline: Benign paroxysmal positional vertigo. Otolaryngol Head Neck Surg . 2008;139(5 Suppl 4):S47-S81. ... BH, Lund V, et al, eds. Cummings Otolaryngology: Head & Neck Surgery . 6th ed. Philadelphia, PA: Elsevier Mosby; 2015: ...

  20. Five-photon double ionization of helium

    NASA Astrophysics Data System (ADS)

    Li, Y.; Pindzola, M. S.; Colgan, J.

    2016-03-01

    A time-dependent close-coupling method is used to calculate the five-photon double ionization of He. It is found that the generalized cross section used in the past for two-photon double ionization of He cannot be extended to five-photon double ionization of He. Therefore only five-photon double ionization probabilities that depend on specific radiation field pulses can be calculated.

  1. Minimal Doubling and Point Splitting

    SciTech Connect

    Creutz, M.

    2010-06-14

    Minimally-doubled chiral fermions have the unusual property of a single local field creating two fermionic species. Spreading the field over hypercubes allows construction of combinations that isolate specific modes. Combining these fields into bilinears produces meson fields of specific quantum numbers. Minimally-doubled fermion actions present the possibility of fast simulations while maintaining one exact chiral symmetry. They do, however, introduce some peculiar aspects. An explicit breaking of hyper-cubic symmetry allows additional counter-terms to appear in the renormalization. While a single field creates two different species, spreading this field over nearby sites allows isolation of specific states and the construction of physical meson operators. Finally, lattice artifacts break isospin and give two of the three pseudoscalar mesons an additional contribution to their mass. Depending on the sign of this mass splitting, one can either have a traditional Goldstone pseudoscalar meson or a parity breaking Aoki-like phase.

  2. Double Lambda and Xi hypernuclei

    NASA Astrophysics Data System (ADS)

    Nakazawa, Kazuma

    2014-09-01

    Nuclei with double strangeness (S = -2) provide the key information to understand Baryon-Baryon interaction under the SU(3)f symmetry. Therefore we have carried out the experiments at KEK for quarter a century. Recently, the interaction in S = -2 sector is noted to derive the information of the EOS of neutron star. The Lambda-Lambda interaction has been presented to be weak attractive by NAGARA event which showed the production and decay of 6He double-hypernucleus. The event also presented the lower mass limit of H dibaryon. In other five events, we obtained the knowledge about an excitation level of 10Be double-hypernucleus under the consistency with NAGARA event. Moreover, very recently, we have discovered a Xi-14N system which was deeply bound far from the atomic 3D level (0.17 MeV) for a captured Xi hyperon. Since a 8Li nucleus was associated with the decay of one of twin-hypernuclei, the event was uniquely identified as Xi- + 14N ==> 10BeL + 5HeL. The system was selected from 8 million pictures on the test running for development of ``Overall Scanning'' to be used in the coming experiment. This is the first evidence of Xi hypernucleus to be bound and it is impacting for the study of Xi-N interaction. At J-PARC facility, for the further study of hyperon-hyperon interaction, we plan to perform the E07 experiment at J-PARC. In the workshop, we will review the above knowledge obtained by the experiments at KEK-PS, and discuss developed technologies to detected 102 or more double-hypernuclei in the E07 experiment at J-PARC. Nuclei with double strangeness (S = -2) provide the key information to understand Baryon-Baryon interaction under the SU(3)f symmetry. Therefore we have carried out the experiments at KEK for quarter a century. Recently, the interaction in S = -2 sector is noted to derive the information of the EOS of neutron star. The Lambda-Lambda interaction has been presented to be weak attractive by NAGARA event which showed the production and decay of 6He

  3. Hierarchy in a double braneworld

    SciTech Connect

    Guerrero, Rommel; Rodriguez, R. Omar; Melfo, Alejandra; Pantoja, Nelson

    2006-10-15

    We show that the hierarchy between the Planck and the weak scales can follow from the tendency of gravitons and fermions to localize at different edges of a thick double wall embedded in an AdS{sub 5} spacetime without reflection symmetry. This double wall is a stable BPS thick-wall solution with two subwalls located at its edges; fermions are coupled to the scalar field through Yukawa interactions, but the lack of reflection symmetry forces them to be localized in one of the subwalls. We show that the graviton zero-mode wave function is suppressed in the fermion edge by an exponential function of the distance between the subwalls, and that the massive modes decouple so that Newtonian gravity is recuperated.

  4. Naturally Inspired Firefly Controller For Stabilization Of Double Inverted Pendulum

    NASA Astrophysics Data System (ADS)

    Srikanth, Kavirayani; Nagesh, Gundavarapu

    2015-12-01

    A double inverted pendulum plant as an established model that is analyzed as part of this work was tested under the influence of time delay, where the controller was fine tuned using a firefly algorithm taking into considering the fitness function of variation of the cart position and to minimize the cart position displacement and still stabilize it effectively. The naturally inspired algorithm which imitates the fireflies definitely is an energy efficient method owing to the inherent logic of the way the fireflies respond collectively and has shown that critical time delays makes the system healthy.

  5. Video image position determination

    DOEpatents

    Christensen, Wynn; Anderson, Forrest L.; Kortegaard, Birchard L.

    1991-01-01

    An optical beam position controller in which a video camera captures an image of the beam in its video frames, and conveys those images to a processing board which calculates the centroid coordinates for the image. The image coordinates are used by motor controllers and stepper motors to position the beam in a predetermined alignment. In one embodiment, system noise, used in conjunction with Bernoulli trials, yields higher resolution centroid coordinates.

  6. Optimal Centroid Position Estimation

    SciTech Connect

    Candy, J V; McClay, W A; Awwal, A S; Ferguson, S W

    2004-07-23

    The alignment of high energy laser beams for potential fusion experiments demand high precision and accuracy by the underlying positioning algorithms. This paper discusses the feasibility of employing online optimal position estimators in the form of model-based processors to achieve the desired results. Here we discuss the modeling, development, implementation and processing of model-based processors applied to both simulated and actual beam line data.

  7. Double Chooz and recent results

    NASA Astrophysics Data System (ADS)

    Meregaglia, A.; Double Chooz Collaboration

    2016-07-01

    The reactor bar{{ν}}e^{} disappearance experiment Double Chooz, located in France near the power plant of Chooz, has as main goal the measurement of the θ_{{13}}^{} mixing angle. For the first time, in 2011, the experimental results gave an indication for a non-zero value of such an oscillation parameter. The mixing angle was successively measured using only the far detector finding the best fit value of sin2(2 θ_{{13}}^{}) = 0.090+0.033-0.029 . The near detector started data taking in December 2014 and it will allow to reduce the systematic errors so far dominated by the reactor flux uncertainty. In this paper a review of the experiment is presented focusing on the so-called Gadolinium-III results (DOUBLE CHOOZ COLLABORATION (ABE Y. et al.), JHEP, 10 (2014) 086; 02 (2015) 074). Furthermore additional physics measurements are presented such as the capability of Double Chooz to identify the ortho-positronium state on event by event basis.

  8. Pair extended coupled cluster doubles

    SciTech Connect

    Henderson, Thomas M.; Scuseria, Gustavo E.; Bulik, Ireneusz W.

    2015-06-07

    The accurate and efficient description of strongly correlated systems remains an important challenge for computational methods. Doubly occupied configuration interaction (DOCI), in which all electrons are paired and no correlations which break these pairs are permitted, can in many cases provide an accurate account of strong correlations, albeit at combinatorial computational cost. Recently, there has been significant interest in a method we refer to as pair coupled cluster doubles (pCCD), a variant of coupled cluster doubles in which the electrons are paired. This is simply because pCCD provides energies nearly identical to those of DOCI, but at mean-field computational cost (disregarding the cost of the two-electron integral transformation). Here, we introduce the more complete pair extended coupled cluster doubles (pECCD) approach which, like pCCD, has mean-field cost and reproduces DOCI energetically. We show that unlike pCCD, pECCD also reproduces the DOCI wave function with high accuracy. Moreover, pECCD yields sensible albeit inexact results even for attractive interactions where pCCD breaks down.

  9. Revisiting double Dirac delta potential

    NASA Astrophysics Data System (ADS)

    Ahmed, Zafar; Kumar, Sachin; Sharma, Mayank; Sharma, Vibhu

    2016-07-01

    We study a general double Dirac delta potential to show that this is the simplest yet still versatile solvable potential to introduce double wells, avoided crossings, resonances and perfect transmission (T = 1). Perfect transmission energies turn out to be the critical property of symmetric and anti-symmetric cases wherein these discrete energies are found to correspond to the eigenvalues of a Dirac delta potential placed symmetrically between two rigid walls. For well(s) or barrier(s), perfect transmission (or zero reflectivity, R(E)) at energy E=0 is non-intuitive. However, this has been found earlier and called the ‘threshold anomaly’. Here we show that it is a critical phenomenon and we can have 0≤slant R(0)\\lt 1 when the parameters of the double delta potential satisfy an interesting condition. We also invoke a zero-energy and zero curvature eigenstate (\\psi (x)={Ax}+B) of the delta well between two symmetric rigid walls for R(0)=0. We resolve that the resonant energies and the perfect transmission energies are different and they arise differently.

  10. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  11. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  12. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  13. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  14. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  15. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  16. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  17. 46 CFR 171.105 - Double bottoms.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Double bottoms. 171.105 Section 171.105 Shipping COAST... VESSELS CARRYING PASSENGERS Additional Subdivision Requirements § 171.105 Double bottoms. (a) This section... over 165 feet (50 meters) and under 200 feet (61 meters) in LBP must have a double bottom that...

  18. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  19. 7 CFR 3560.460 - Double damages.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Double damages. 3560.460 Section 3560.460 Agriculture... Actions § 3560.460 Double damages. (a) Action to recover assets or income. (1) The Agency may request to... United States entered under this section, the Attorney General may recover double the value of the...

  20. Double-diffusive inner core translation

    NASA Astrophysics Data System (ADS)

    Deguen, Renaud; Alboussière, Thierry; Labrosse, Stéphane

    2015-04-01

    The hemispherical asymmetry of the inner core has recently been interpreted as resulting form a high-viscosity mode of inner core convection, consisting in a translation of the inner core. With melting on one hemisphere and crystallization on the other one, inner core translation would impose a strongly asymmetric buoyancy flux at the bottom of the outer core, with likely strong implications for the dynamics of the outer core and the geodynamo. The main requirement for convective instability in the inner core is an adverse radial density gradient. While older estimates of the inner core thermal conductivity favored a superadiabatic temperature gradient and the existence of thermal convection, the much higher values recently proposed make thermal convection unlikely. Compositional convection might be a viable alternative to thermal convection: an unstable compositional gradient may arise in the inner core either because the light elements present in the core are predicted to become increasingly incompatible as the inner core grows (Gubbins et al. 2013), or because of a possibly positive feedback of the development of the F-layer on inner core convection. Though the magnitude of the destabilizing effect of the compositional field is predicted to be similar to or smaller than the stabilizing effect of the thermal field, the huge difference between thermal and chemical diffusivities implies that double-diffusive instabilities may still arise even if the net density decreases upward. We propose here a theoretical (linear stability analysis) and numerical study of double diffusive convection in the inner core, focusing on the translation mode, and discuss in what conditions inner core translation can develop.

  1. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2011)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2011-11-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  2. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2010)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2009-10-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  3. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2010)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2010-11-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  4. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2012)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2012-11-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  5. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2014)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2016-07-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  6. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2014)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2015-11-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  7. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2013)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2013-11-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  8. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2014)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2014-11-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  9. VizieR Online Data Catalog: The Washington Visual Double Star Catalog (Mason+ 2001-2014)

    NASA Astrophysics Data System (ADS)

    Mason, B. D.; Wycoff, G. L.; Hartkopf, W. I.; Douglass, G. G.; Worley, C. E.

    2016-08-01

    The Washington Visual Double Star Catalog (WDS) is the successor to the Index Catalogue of Visual Double Stars, 1961.0 (IDS; Jeffers and van den Bos, Publ. Lick Obs. 21). Three earlier double star catalogs in XXth century, those by Burnham (BDS, 1906, "General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), Innes (SDS, 1927, "Southern Double Star Catalogue -19 to -90 degrees", Union Observatory, Johannesburg, South Africa), and Aitken (ADS, 1932 "New General Catalogue of Double Stars within 121 degrees of the North Pole", Carnegie Institution of Washington), each covered only a portion of the sky. Both the IDS and the WDS cover the entire sky, and the WDS is intended to contain all known visual double stars for which at least one differential measure has been published. The WDS is continually updated as published data become available. Prior to this, three major updates have been published (Worley and Douglass 1984, "Washington Visual Double Star Catalog, 1984.0", U.S. Naval Observatory, Washington; Worley and Douglass 1997A&AS..125..523W, Cat. I/237; Mason, Wycoff, Hartkopf, Douglass and Worley 2001AJ....122.3466M; and Mason et al. 2006.5). The Washington Double Star Catalog (WDS) has seen numerous changes since the last major release of the catalog. The application of many techniques and considerable industry over the past few years has yielded significant gains in both the number of systems and the number of measures. Is is maintained by the US Naval Observatory, and represents the world's principal database of astrometric double and multiple star information. The WDS contains positions (J2000), discoverer designations, epochs, position angles, separations, magnitudes, spectral types, proper motions, and, when available, Durchmusterung numbers and notes for the components of the systems. (3 data files).

  10. Local positioning system

    SciTech Connect

    Kyker, R.

    1995-07-25

    Navigation systems have been vital to transportation ever since man took to the air and sea. Early navigation systems utilized the sextant to navigate by starlight as well as the magnetic needle compass. As electronics and communication technologies improved, inertial navigation systems were developed for use in ships and missile delivery. These systems consisted of electronic compasses, gyro-compasses, accelerometers, and various other sensors. Recently, systems such as LORAN and the Global Positioning System (GPS) have utilized the properties of radio wave propagation to triangulate position. The Local Positioning System (LPS), described in this paper, is an implementation of a limited inertial navigation system designed to be used on a bicycle. LPS displays a cyclist`s current position relative to a starting location. This information is displayed in Cartesian-like coordinates. To accomplish this, LPS relies upon two sensors, an electronic compass sensor and a distance sensor. The compass sensor provides directional information while the distance sensor provides the distance traveled. This information yields a distance vector for each point in time which when summed produces the cyclist`s current position. LPS is microprocessor controlled and is designed for a range of less than 90 miles.

  11. Beyond Positive Psychology?

    PubMed Central

    McNulty, James K.; Fincham, Frank D.

    2014-01-01

    The field of positive psychology rests on the assumption that certain psychological traits and processes are inherently beneficial for well-being. We review evidence that challenges this assumption. First, we review data from 4 independent longitudinal studies of marriage revealing that 4 ostensibly positive processes—forgiveness, optimistic expectations, positive thoughts, and kindness—can either benefit or harm well-being depending on the context in which they operate. Although all 4 processes predicted better relationship well-being among spouses in healthy marriages, they predicted worse relationship well-being in more troubled marriages. Then, we review evidence from other research that reveals that whether ostensibly positive psychological traits and processes benefit or harm well-being depends on the context of various noninterpersonal domains as well. Finally, we conclude by arguing that any movement to promote well-being may be most successful to the extent that it (a) examines the conditions under which the same traits and processes may promote versus threaten well-being, (b) examines both healthy and unhealthy people, (c) examines well-being over substantial periods of time, and (d) avoids labeling psychological traits and processes as positive or negative. PMID:21787036

  12. The positivity scale.

    PubMed

    Caprara, Gian Vittorio; Alessandri, Guido; Eisenberg, Nancy; Kupfer, A; Steca, Patrizia; Caprara, Maria Giovanna; Yamaguchi, Susumu; Fukuzawa, Ai; Abela, John

    2012-09-01

    Five studies document the validity of a new 8-item scale designed to measure positivity, defined as the tendency to view life and experiences with a positive outlook. In the first study (N = 372), the psychometric properties of Positivity Scale (P Scale) were examined in accordance with classical test theory using a large number of college participants. In Study 2, the unidimensionality of the P Scale was corroborated with confirmatory factor analysis in 2 independent samples (N₁ = 322; N₂ = 457). In Study 3, P Scale invariance across sexes and its relations with self-esteem, life satisfaction, optimism, positive negative affect, depression, and the Big Five provided further evidence of the internal and construct validity of the new measure in a large community sample (N = 3,589). In Study 4, test-retest reliability of the P Scale was found in a sample of college students (N = 262) who were readministered the scale after 5 weeks. In Study 5, measurement invariance and construct validity of P Scale were further supported across samples in different countries and cultures, including Italy (N = 689), the United States (N = 1,187), Japan (N = 281), and Spain (N = 302). Psychometric findings across diverse cultural context attest to the robustness of the P Scale and to positivity as a basic disposition. PMID:22250591

  13. Double Cusp Observed By The Cluster Spacecraft

    NASA Astrophysics Data System (ADS)

    Escoubet, C. P.; Bosqued, J. M.; Berchem, J.; Anderson, P. C.; Fehringer, M.; Laakso, H.; Reme, H.

    The polar cusp is characterised by a direct entry of solar wind plasma into the magne- tosphere. Depending on the orientation of the interplanetary magnetic field (IMF), Bz positive or negative, the precipitation of the ions in the cusp presents a dispersion in energy directed poleward or equatorward. In addition the polar cusp moves in latitude according to the IMF, from about 75 deg. ILAT for Bz negative to about 82 deg. ILAT for Bz positive. The Cluster spacecraft are crossing the mid-altitude polar cusp, in a "string of pearl" configuration, and are therefore the ideal tool to study the motion and evolution of the cusp on time scale of a few minutes up to 45 min. On 30 August 2001, the four Cluster spacecraft crossed the mid-altitude polar cusp (4-6 Re) around 12.5 H local time with SC4 entering the cusp at 1532 UT, SC2 following 1.5 min later, SC1, 3 min later and finally SC3, 45 min later. SC4 and SC1 observed a typical poleward dispersion associated with Bz negative. SC3 observed first the same disper- sion starting at about 74 deg. ILAT, however at 81 deg. ILAT a second dispersion was observed. The IMF was southward during the dispersion and became slightly positive during the second dispersion. Two hypothesis can be proposed, a fast motion of the cusp poleward during the SC3 crossing or a double injection in the cusp. Preliminary analysis of DMSP satellites, although not exactly in the same sector, indicates that the cusp moved poleward around that time. Cluster observations will be compared with the results from a global MHD simulation model to investigate the geometry of the reconnection between the IMF and the Earth magnetic field.

  14. Positive quadrature formulas III

    NASA Astrophysics Data System (ADS)

    Peherstorfer, Franz

    2008-12-01

    First we discuss briefly our former characterization theorem for positive interpolation quadrature formulas (abbreviated qf), provide an equivalent characterization in terms of Jacobi matrices, and give links and applications to other qf, in particular to Gauss-Kronrod quadratures and recent rediscoveries. Then for any polynomial t_n which generates a positive qf, a weight function (depending on n ) is given with respect to which t_n is orthogonal to mathbb{P}_{n-1} . With the help of this result an asymptotic representation of the quadrature weights is derived. In general the asymptotic behaviour is different from that of the Gaussian weights. Only under additional conditions do the quadrature weights satisfy the so-called circle law. Corresponding results are obtained for positive qf of Radau and Lobatto type.

  15. Automated stereotactic positioning system.

    PubMed

    Goerss, S J; Kelly, P J; Kall, B A

    1987-01-01

    An automated stereotactic machine has been interfaced to a surgical computer to complete a totally interactive surgical system capable of locating tumor volumes. Stepper motors, activated by the host computer, drive a three-dimensional slide to position the patient's head with respect to a fixed arc, locating the surgical target. Linear encoders on each axis create a closed-loop positioning system and a digital display for visual inspection of the slide's position. The 160-mm arc directs all instrumentation to its isocenter, regardless of the two angular settings, providing maximum freedom in selecting a safe trajectory to the target. Phantom test points compatible with computerized tomographic and magnetic resonance imaging were repeatedly scanned to determine the overall system accuracy, which approached 0.6 mm, depending on the spatial resolution of the image. This stereotactic device may be used to perform stereotactic laser craniotomies, biopsies, 192Ir implants for interstitial radiation, third ventriculostomies and functional procedures. PMID:3329830

  16. [Mammaplasty: the "love position"].

    PubMed

    Petit, F; Paraskevas, A; Lantieri, L

    2004-02-01

    The authors describe a new position of the patient that enables the surgeon to perform a bilateral and synchronous mammaplasty, without switching sides. The patient is first raised in the sitting position, then the thigh and leg holders of the operating table are spread out to a 45-60 degrees angle. The surgeon stands in between the thighs, where he faces the chest and can operate on the breasts. The entire operation is performed by the surgeon, approaching both breasts simultaneously without the need for switching positions. The direct and central access, along with the continuing visual control of the shaping, turns the operation into a simple and faster one with better control of the cosmetic result. PMID:15013529

  17. Taking a Position

    NASA Technical Reports Server (NTRS)

    1999-01-01

    "TerrAvoid" and "Position Integrity" combine Global Positioning Satellite (GPS) data with high-resolution maps of the Earth's topography. Dubbs & Severino, Inc., based in Irvine, California, has developed software that allows the system to be run on a battery-powered laptop in the cockpit. The packages, designed primarily for military sponsors and now positioned to hit the consumer market in coming months, came about as the result of the Jet Propulsion Laboratory's Technology Affiliates Program. Intended to give American industry assistance from NASA experts and to facilitate business use of intellectual property developed for the space program, the Technology Affiliates Program introduced the start-up company of Dubbs & Severino to JPL's Dr. Nevin Bryant four years ago. GeoTIFF is now in the public domain, and its use for commercial product development has evolved into an industry standard over the last year.

  18. Uncharged positive electrode composition

    DOEpatents

    Kaun, Thomas D.; Vissers, Donald R.; Shimotake, Hiroshi

    1977-03-08

    An uncharged positive-electrode composition contains particulate lithium sulfide, another alkali metal or alkaline earth metal compound other than sulfide, e.g., lithium carbide, and a transition metal powder. The composition along with a binder, such as electrolytic salt or a thermosetting resin is applied onto an electrically conductive substrate to form a plaque. The plaque is assembled as a positive electrode within an electrochemical cell opposite to a negative electrode containing a material such as aluminum or silicon for alloying with lithium. During charging, lithium alloy is formed within the negative electrode and transition metal sulfide such as iron sulfide is produced within the positive electrode. Excess negative electrode capacity over that from the transition metal sulfide is provided due to the electrochemical reaction of the other than sulfide alkali metal or alkaline earth metal compound.

  19. Turbine nozzle positioning system

    DOEpatents

    Norton, Paul F.; Shaffer, James E.

    1996-01-30

    A nozzle guide vane assembly having a preestablished rate of thermal expansion is positioned in a gas turbine engine and being attached to conventional metallic components. The nozzle guide vane assembly includes an outer shroud having a mounting leg with an opening defined therein, a tip shoe ring having a mounting member with an opening defined therein, a nozzle support ring having a plurality of holes therein and a pin positioned in the corresponding opening in the outer shroud, opening in the tip shoe ring and the hole in the nozzle support ring. A rolling joint is provided between metallic components of the gas turbine engine and the nozzle guide vane assembly. The nozzle guide vane assembly is positioned radially about a central axis of the gas turbine engine and axially aligned with a combustor of the gas turbine engine.

  20. Turbine nozzle positioning system

    DOEpatents

    Norton, P.F.; Shaffer, J.E.

    1996-01-30

    A nozzle guide vane assembly having a preestablished rate of thermal expansion is positioned in a gas turbine engine and being attached to conventional metallic components. The nozzle guide vane assembly includes an outer shroud having a mounting leg with an opening defined therein, a tip shoe ring having a mounting member with an opening defined therein, a nozzle support ring having a plurality of holes therein and a pin positioned in the corresponding opening in the outer shroud, opening in the tip shoe ring and the hole in the nozzle support ring. A rolling joint is provided between metallic components of the gas turbine engine and the nozzle guide vane assembly. The nozzle guide vane assembly is positioned radially about a central axis of the gas turbine engine and axially aligned with a combustor of the gas turbine engine. 9 figs.

  1. THE SEXUAL DOUBLE STANDARD AND ADOLESCENT PEER ACCEPTANCE.

    PubMed

    Kreager, Derek A; Staff, Jeremy

    2009-06-01

    The belief that women and men are held to different standards of sexual conduct is pervasive in contemporary American society. According to the sexual double standard, boys and men are rewarded and praised for heterosexual sexual contacts, whereas girls and women are derogated and stigmatized for similar behaviors. Although widely held by the general public, research findings on the sexual double standard remain equivocal, with qualitative studies and early attitudinal surveys generally finding evidence of the double standard and more recent experimental vignette designs often failing to find similar results. In this study, we extend prior research by directly measuring the social status of sexually permissive youth. We use data collected from the National Longitudinal Study of Adolescent Health to relate adolescents' self-reported numbers of sexual partners to a network measure of peer acceptance. Results suggest that the association between lifetime sexual partnerships and peer status varies significantly by gender, such that greater numbers of sexual partners are positively correlated with boys' peer acceptance, but negatively correlated with girls' peer acceptance. Moreover, the relationship between boys' sexual behaviors and peer acceptance is moderated by socioeconomic origins; sexually permissive boys from disadvantaged backgrounds are predicted to have more friendships than permissive boys from more advantaged backgrounds. Our results thus support the existence of an adolescent sexual double standard and suggest that sexual norms vary by both gender and socioeconomic origins. PMID:25484478

  2. THE SEXUAL DOUBLE STANDARD AND ADOLESCENT PEER ACCEPTANCE*

    PubMed Central

    Kreager, Derek A.; Staff, Jeremy

    2014-01-01

    The belief that women and men are held to different standards of sexual conduct is pervasive in contemporary American society. According to the sexual double standard, boys and men are rewarded and praised for heterosexual sexual contacts, whereas girls and women are derogated and stigmatized for similar behaviors. Although widely held by the general public, research findings on the sexual double standard remain equivocal, with qualitative studies and early attitudinal surveys generally finding evidence of the double standard and more recent experimental vignette designs often failing to find similar results. In this study, we extend prior research by directly measuring the social status of sexually permissive youth. We use data collected from the National Longitudinal Study of Adolescent Health to relate adolescents’ self-reported numbers of sexual partners to a network measure of peer acceptance. Results suggest that the association between lifetime sexual partnerships and peer status varies significantly by gender, such that greater numbers of sexual partners are positively correlated with boys’ peer acceptance, but negatively correlated with girls’ peer acceptance. Moreover, the relationship between boys’ sexual behaviors and peer acceptance is moderated by socioeconomic origins; sexually permissive boys from disadvantaged backgrounds are predicted to have more friendships than permissive boys from more advantaged backgrounds. Our results thus support the existence of an adolescent sexual double standard and suggest that sexual norms vary by both gender and socioeconomic origins. PMID:25484478

  3. Nucleosome Positioning and Epigenetics

    NASA Astrophysics Data System (ADS)

    Schwab, David; Bruinsma, Robijn

    2008-03-01

    The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation.

  4. Simulation of plasma double-layer structures

    NASA Technical Reports Server (NTRS)

    Borovsky, J. E.; Joyce, G.

    1982-01-01

    Electrostatic plasma double layers are numerically simulated by means of a magnetized 2 1/2 dimensional particle in cell method. The investigation of planar double layers indicates that these one dimensional potential structures are susceptible to periodic disruption by instabilities in the low potential plasmas. Only a slight increase in the double layer thickness with an increase in its obliqueness to the magnetic field is observed. Weak magnetization results in the double layer electric field alignment of accelerated particles and strong magnetization results in their magnetic field alignment. The numerical simulations of spatially periodic two dimensional double layers also exhibit cyclical instability. A morphological invariance in two dimensional double layers with respect to the degree of magnetization implies that the potential structures scale with Debye lengths rather than with gyroradii. Electron beam excited electrostatic electron cyclotron waves and (ion beam driven) solitary waves are present in the plasmas adjacent to the double layers.

  5. Positive: HIV Affirmative Counseling.

    ERIC Educational Resources Information Center

    Kain, Craig D.

    At the end of the 1980s, counselors largely lacked an integrated approach to counseling people living with HIV disease. This book describes the experience of counseling this group of persons. The major premise here is that counselors who counsel HIV-positive clients must come to understand and affirm their clients' experiences. The text defines a…

  6. Nursing Research: Position Statement.

    ERIC Educational Resources Information Center

    Copp, Laurel; And Others

    The role of the American Association of Colleges of Nursing (AACN) in encouraging research through the programs and activities of the member schools is discussed. It is suggested that the dean or administrative head of a college of nursing is in a position to influence nursing research activities. The principal role of the academic dean in…

  7. Creating Positive Task Constraints

    ERIC Educational Resources Information Center

    Mally, Kristi K.

    2006-01-01

    Constraints are characteristics of the individual, the task, or the environment that mold and shape movement choices and performances. Constraints can be positive--encouraging proficient movements or negative--discouraging movement or promoting ineffective movements. Physical educators must analyze, evaluate, and determine the effect various…

  8. Positions of minor planets

    NASA Astrophysics Data System (ADS)

    Gressmann, M.

    A continuation of Gressman's (1980) observations is given using the Schmidt-camera 34/40 cm, f = 76. Topocentric positions of several minor planets are presented, and reference stars are obtained from the AGK(3), and applied to the two-star method to avoid any major errors. Parallax constants are also given, along with coordinates for the epoch 1950.0.

  9. Magnetic beam position monitor

    SciTech Connect

    Varfolomeev, A.A.; Ivanchenkov, S.N.; Khlebnikov, A.S.

    1995-12-31

    Many nondestructive beam position monitors are known. However, these devices can not be used for DC particle beam diagnostics. We investigated a method of beam diagnostics applicable for the operative control of DC high power e-beam inside closed waveguide. A design of the detector for determination of{open_quote} center of mass {close_quote} position of DC particle beam was developed. It was shown that the monitor can be used as a nondestructive method for the beam position control in resonators. Magnetic field of the particle beam outside a resonator is used. The detector consists of the steel yokes and magnetic field sensors. The sensors measure magnetic fluxes in the steel yokes fixed outside the resonator. When the particle beam changes its position, these magnetic fluxes also change. Beam displacement sensitivity of the monitor depends on the steel yoke dimensions. The detector sensitivity is equal to 1 Gauss/mm for the conditions adequate to the FOM-FEM project.

  10. Review of HRP Positions

    SciTech Connect

    Center for Reliability Studies

    2007-01-01

    The Department of Energy (DOE) Human Reliability Program (HRP), published as 10 CFR Part 712, is currently being reviewed and revised to address concerns identified during its implementation. Although these ''page changes'' primarily incorporate clarification of terms and language, the following discussion relates to broadening the definition of positions that require HRP certification that is found in {section}712.10.

  11. Immunizations. Position Statement. Revised

    ERIC Educational Resources Information Center

    Bobo, Nichole; Garrett, Jennifer; Teskey, Carmen; Duncan, Kay; Strasser, Kathy; Burrows-Mezu, Alicia L.

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that immunizations are essential to primary prevention of disease from infancy through adulthood. Promotion of immunizations by the registered professional school nurse (hereinafter referred to as school nurse) is central to the public health focus of school nursing practice…

  12. Positive Attitude Toward Learning.

    ERIC Educational Resources Information Center

    Bethalto Community Unit District 8, IL.

    Project Positive Attitude Toward Learning (PATL) grew out of an identified need by the Bethalto Community Unit No. 8 schools to improve student self-concept and attitudes toward school. The basic approach used in project PATL is to change teacher behavior which, in turn, causes change to take place in student behavior. The mechanism for affecting…

  13. Positive Discipline. (Revised Edition).

    ERIC Educational Resources Information Center

    Nelsen, Jane

    Understanding why children do not behave the way they used to, and why both controlling and overly-permissive discipline styles are ineffective, is the first step for parents and teachers who are facing child-discipline problems. This book describes a program of positive discipline principles aimed at assisting parents and teachers in…

  14. A Positive Report Card.

    ERIC Educational Resources Information Center

    Hellman, Sally G.

    A high school English teacher found that one easy way to keep the idea of positive reinforcement foremost in her mind when she works with students was to use writing portfolios. A Portfolio Assessment project was designed in which portfolios were used in two sophomore and two junior regular English classes. A flexible plan was developed for using…

  15. Position feedback control system

    DOEpatents

    Bieg, Lothar F.; Jokiel, Jr., Bernhard; Ensz, Mark T.; Watson, Robert D.

    2003-01-01

    Disclosed is a system and method for independently evaluating the spatial positional performance of a machine having a movable member, comprising an articulated coordinate measuring machine comprising: a first revolute joint; a probe arm, having a proximal end rigidly attached to the first joint, and having a distal end with a probe tip attached thereto, wherein the probe tip is pivotally mounted to the movable machine member; a second revolute joint; a first support arm serially connecting the first joint to the second joint; and coordinate processing means, operatively connected to the first and second revolute joints, for calculating the spatial coordinates of the probe tip; means for kinematically constraining the articulated coordinate measuring machine to a working surface; and comparator means, in operative association with the coordinate processing means and with the movable machine, for comparing the true position of the movable machine member, as measured by the true position of the probe tip, with the desired position of the movable machine member.

  16. INTERMITTENT POSITIVE PRESSURE BREATHING

    EPA Science Inventory

    Efficacy of long-term intermittent positive pressure breathing (IPPB) treatment when used as an adjunct to the overall care of ambulatory outpatients with chronic obstructive pulmonary disease. The evaluation compared the use of IPPB with use of a powered nebulizer.

  17. Delegation. Position Statement. Revised

    ERIC Educational Resources Information Center

    Board, Connie; Bushmiaer, Margo; Davis-Alldritt, Linda; Fekaris, Nina; Morgitan, Judith; Murphy, M. Kathleen; Yow, Barbara

    2010-01-01

    It is the position of the National Association of School Nurses (NASN) that the delegation of nursing tasks in the school setting can be a valuable tool for the school nurse, when based on the nursing definition of delegation and in compliance with state nursing regulations and guidance. Delegation in school nursing is a complex process in which…

  18. Schoolwide Positive Behavior Supports

    ERIC Educational Resources Information Center

    Flannery, K. Brigid; Guest, Elise M.; Horner, Robert H.

    2010-01-01

    Schools are complex communities that play a major role in the social fabric of culture. Effective schools provide access to both good instruction and a social culture that supports engagement, community, and success. Over the past 10 years, more than 11,000 elementary, middle level, and high schools have adopted schoolwide positive behavior…

  19. The Teacher's Social Position.

    ERIC Educational Resources Information Center

    Ziiatdinova, Fliura Gazizovna

    1990-01-01

    Discusses a survey conducted in the Tatar Republic of the Soviet Union involving over 800 teachers, students, and parents. Reports that the study investigated opinions about teachers' social position. Indicates widespread agreement concerning the teaching profession's low prestige. Explores reasons for the profession's low prestige through an…

  20. Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

    PubMed

    Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

    1984-12-01

    Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia. PMID:6150555