Sample records for c5ar chimeras reveal

  1. C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid

    DEFF Research Database (Denmark)

    Hornum, Lars; Hansen, Anker Jon; Tornehave, Ditte


    synovial fluid was significantly inhibited by anti-C5aR. The data support that the C5a-C5aR axis may be driving the infiltration of inflammatory cells into the synovial fluid and synovium in both rheumatoid and psoriatic arthritis, and suggest that C5a or C5aR may be a promising treatment target in both...... a Boyden chamber. Appropriate statistical tests were applied for comparisons. C5aR+ cells were detected in most rheumatoid arthritis, in all psoriatic arthritis, but not in non-inflammatory control synovia. C5aR+ cells were primarily neutrophils and macrophages. C5aR+ macrophages were mainly found...

  2. Complement factor 5a receptor chimeras reveal the importance of lipid-facing residues in transport competence

    DEFF Research Database (Denmark)

    Klco, Jeffery M; Sen, Saurabh; Hansen, Jakob L


    . Despite relatively conservative substitutions, the lipid-facing chimeras (TM1, TM2, TM4, TM5, TM6 or TM7) were retained in the endoplasmic reticulum/cis-Golgi network. With the exception of the TM7 chimera that did not bind ligand, the lipid-facing chimeras bound ligand with low affinity, but similar...... oligomerization studies demonstrated energy transfer between the wild-type complement factor 5a receptor and the lipid-facing chimeras, suggesting that the lipid-facing residues within a single TM segment are not essential for oligomerization. These studies highlight the importance of the lipid-facing residues...

  3. Complement C5a-C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB/c mice. (United States)

    Zhang, Jia-xiang; Zha, Wan-sheng; Ye, Liang-ping; Wang, Feng; Wang, Hui; Shen, Tong; Wu, Chang-hao; Zhu, Qi-xing


    We have previously shown complement activation as a possible mechanism for trichloroethylene (TCE) sensitization, leading to multi-organ damage including the kidneys. In particular, excessive deposition of C5 and C5b-9-the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE-sensitized BALB/c mice. BALB/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up-regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE-induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro-inflammatory cytokines IL-2, TNF-α and IFN-γ in the kidney tissue (P < 0.05); this was accompanied by increased expression of P-p38, P-ERK and P-JNK proteins (P < 0.05). Pretreatment with the C5aR antagonist attenuated the increase of expression of P-p38, P-ERK and P-JNK proteins (P < 0.05) and also consistently reduced the TCE sensitization-induced increase of IL-2, TNF-α and IFN-γ (P < 0.05). These data identify C5a binding to C5aR, MAP kinase activation, and inflammatory cytokine release as a novel mechanism for complement-mediated renal injury by sensitization with TCE or other environmental chemicals. Copyright © 2015 John Wiley & Sons, Ltd.

  4. The C5a/C5aR1 axis controls the development of experimental allergic asthma independent of LysM-expressing pulmonary immune cells.

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    Anna V Wiese

    Full Text Available C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1. Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs and monocyte-derived DCs (moDCs during the allergic effector phase using a floxed green fluorescent protein (GFP-C5aR1 knock-in mouse. Here, we determined the role of C5aR1 signaling in neutrophils, moDCs and macrophages for the pulmonary recruitment of such cells and the importance of C5aR1-mediated activation of LysM-expressing cells for the development of allergic asthma. We used LysM-C5aR1 KO mice with a specific deletion of C5aR1 in LysMCre-expressing cells and confirmed the specific deletion of C5aR1 in neutrophils, macrophages and moDCs in the airways and/or the lung tissue. We found that alveolar macrophage numbers were significantly increased in LysM-C5aR1 KO mice. Induction of ovalbumin (OVA-driven experimental allergic asthma in GFP-C5aR1fl/fl and LysM-C5aR1 KO mice resulted in strong but similar airway resistance, mucus production and Th2/Th17 cytokine production. In contrast, the number of airway but not of pulmonary neutrophils was lower in LysM-C5aR1 KO as compared with GFP-C5aR1fl/fl mice. The recruitment of macrophages, cDCs, moDCs, T cells and type 2 innate lymphoid cells was not altered in LysM-C5aR1 KO mice. Our findings demonstrate that C5aR1 is critical for steady state control of alveolar macrophage numbers and the transition of neutrophils from the lung into the airways in OVA-driven allergic asthma. However, C5aR1 activation of LysM-expressing cells plays a surprisingly minor role in the recruitment and activation of such cells and the development of the allergic phenotype in OVA-driven experimental

  5. Differential contribution of complement receptor C5aR in myeloid and non-myeloid cells in chronic ethanol-induced liver injury in mice. (United States)

    McCullough, Rebecca L; McMullen, Megan R; Das, Dola; Roychowdhury, Sanjoy; Strainic, Michael G; Medof, M Edward; Nagy, Laura E


    Complement is implicated in the development of alcoholic liver disease. C3 and C5 contribute to ethanol-induced liver injury; however, the role of C5a receptor (C5aR) on myeloid and non-myeloid cells to progression of injury is not known. C57BL/6 (WT), global C5aR-/-, myeloid-specific C5aR-/-, and non-myeloid-specific C5aR-/- mice were fed a Lieber-DeCarli diet (32%kcal EtOH) for 25 days. Cultured hepatocytes were challenged with ethanol, TNFα, and C5a. Chronic ethanol feeding increased expression of pro-inflammatory mediators in livers of WT mice; this response was completely blunted in C5aR-/- mice. However, C5aR-/- mice were not protected from other measures of hepatocellular damage, including ethanol-induced increases in hepatic triglycerides, plasma alanine aminotransferase and hepatocyte apoptosis. CYP2E1 and 4-hydroxynonenal protein adducts were induced in WT and C5aR-/- mice. Myeloid-specific C5aR-/- mice were protected from ethanol-induced increases in hepatic TNFα, whereas non-myeloid-specific C5aR-/- displayed increased hepatocyte apoptosis and inflammation after chronic ethanol feeding. In cultured hepatocytes, cytotoxicity induced by challenge with ethanol and TNFα was completely eliminated by treatment with C5a in cells from WT, but not C5aR-/- mice. Further, treatment with C5a enhanced activation of pro-survival signal AKT in hepatocytes challenged with ethanol and TNFα. Taken together, these data reveal a differential role for C5aR during ethanol-induced liver inflammation and injury, with C5aR on myeloid cells contributing to ethanol-induced inflammatory cytokine expression, while non-myeloid C5aR protects hepatocytes from death after chronic ethanol feeding. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Association of Immune and Metabolic Receptors C5aR and C5L2 with Adiposity in Women (United States)

    Rezvani, Reza; Gupta, Abhishek; Marceau, Picard; Tchernof, André


    Adipose tissue receptors C5aR and C5L2 and their heterodimerization/functionality and interaction with ligands C5a and acylation stimulating protein (ASP) have been evaluated in cell and rodent studies. Their contribution to obesity factors in humans remains unclear. We hypothesized that C5a receptors, classically required for host defense, are also associated with adiposity. Anthropometry and fasting blood parameters were measured in 136 women divided by body mass index (BMI): normal/overweight (≤30 kg/m2; n = 34), obese I (≤45 kg/m2; n = 33), obese II (≤51 kg/m2; n = 33), and obese III (≤80 kg/m2; n = 36). Subcutaneous and omental adipose tissue C5aR and C5L2 expression were analysed. C5L2 expression was comparable between subcutaneous and omental across all BMI groups. Plasma ASP and ASP/omental C5L2 expression increased with BMI (P correlations between C5L2/C5aR and waist circumference, HDL-C, and adiponectin. Tissue and BMI differences in receptors and ligands, particularly in omental, suggest relationship to metabolic disturbances and highlight adipose-immune interactions. PMID:24523571

  7. Influences of atom Ar on Ar at C60 + Ar at C60 collisions

    International Nuclear Information System (INIS)

    Zhao Qiang; Zhou Hongyu; Zhang Fengshou


    A semi-emperical molecular dynamics model was developed. The central collisions of C 60 + C 60 and Ar at C 60 + Ar at C 60 at the same incident energy were investigated within this model. The fullerene dimers could be formed by a self-assembly of C 60 fullerene, and the new fullerene structure like 'peanut' could be formed by a self-assembly of Ar at C 60 . It was found that atom Ar had a great effect on the collision of Ar at C 60 + Ar at C 60 . (authors)

  8. Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury

    NARCIS (Netherlands)

    Poppelaars, Felix; van Werkhoven, Maaike B; Kotimaa, Juha; Veldhuis, Zwanida J; Ausema, Albertina; Broeren, Stefan G M; Damman, Jeffrey; Hempel, Julia C.; Leuvenink, Henri G D; Daha, Mohamed R; van Son, Willem J; van Kooten, Cees; van Os, Ronald P; Hillebrands, Jan-Luuk; Seelen, Marc A

    The complement system, and specifically C5a, is involved in renal ischemia-reperfusion (IR) injury. The 2 receptors for complement anaphylatoxin C5a (C5aR1 and C5aR2) are expressed on leukocytes as well as on renal epithelium. Extensive evidence shows that C5aR1 inhibition protects kidneys from IR

  9. Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

    Directory of Open Access Journals (Sweden)

    Reza Rezvani


    Full Text Available Objective. Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation. We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2 would be associated with pre- or postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predict metabolic profiles after weight loss surgery. Materials and Methods. Fasting plasma (hormone, lipid, and enzyme analysis and liver biopsies (RT-PCR gene expression were obtained from 91 women during surgery. Results. Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women (P<0.01 and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (all P<0.05. While plasma ASP was lower in pre- versus postmenopausal women (P<0.01, the hepatic C5L2/C5aR mRNA ratio was increased (P<0.001 and correlated positively with estrone (P<0.01 and estradiol (P<0.001 and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (all P<0.05. Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT, P<0.05, AST and GGT, P<0.001 2-way-ANOVA. Conclusion. C5L2-C5aR association with other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.

  10. Growth promotion of genetically modified hematopoietic progenitors using an antibody/c-Mpl chimera. (United States)

    Kawahara, Masahiro; Chen, Jianhong; Sogo, Takahiro; Teng, Jinying; Otsu, Makoto; Onodera, Masafumi; Nakauchi, Hiromitsu; Ueda, Hiroshi; Nagamune, Teruyuki


    Thrombopoietin is a potent cytokine that exerts proliferation of hematopoietic stem cells (HSCs) through its cognate receptor, c-Mpl. Therefore, mimicry of c-Mpl signaling by a receptor recognizing an artificial ligand would be attractive to attain specific expansion of genetically modified HSCs. Here we propose a system enabling selective expansion of genetically modified cells using an antibody/receptor chimera that can be activated by a specific antigen. We constructed an antibody/c-Mpl chimera, in which single-chain Fv (ScFv) of an anti-fluorescein antibody was tethered to the extracellular D2 domain of the erythropoietin receptor and transmembrane/cytoplasmic domains of c-Mpl. When the chimera was expressed in interleukin (IL)-3-dependent pro-B cell line Ba/F3, genetically modified cells were selectively expanded in the presence of fluorescein-conjugated BSA (BSA-FL) as a specific antigen. Furthermore, highly purified mouse HSCs transduced with the retrovirus carrying antibody/c-Mpl chimera gene proliferated in vitro in response to BSA-FL, and the cells retained in vivo long-term repopulating abilities. These results demonstrate that the antibody/c-Mpl chimera is capable of signal transduction that mimics wild-type c-Mpl signaling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Chimera patterns in the Kuramoto–Battogtokh model

    International Nuclear Information System (INIS)

    Smirnov, Lev; Osipov, Grigory; Pikovsky, Arkady


    Kuramoto and Battogtokh (2002 Nonlinear Phenom. Complex Syst . 5 380) discovered chimera states represented by stable coexisting synchrony and asynchrony domains in a lattice of coupled oscillators. After a reformulation in terms of a local order parameter, the problem can be reduced to partial differential equations. We find uniformly rotating, spatially periodic chimera patterns as solutions of a reversible ordinary differential equation, and demonstrate a plethora of such states. In the limit of neutral coupling they reduce to analytical solutions in the form of one- and two-point chimera patterns as well as localized chimera solitons. Patterns at weakly attracting coupling are characterized by virtue of a perturbative approach. Stability analysis reveals that only the simplest chimeras with one synchronous region are stable. (letter)

  12. Chimera patterns in the Kuramoto-Battogtokh model (United States)

    Smirnov, Lev; Osipov, Grigory; Pikovsky, Arkady


    Kuramoto and Battogtokh (2002 Nonlinear Phenom. Complex Syst. 5 380) discovered chimera states represented by stable coexisting synchrony and asynchrony domains in a lattice of coupled oscillators. After a reformulation in terms of a local order parameter, the problem can be reduced to partial differential equations. We find uniformly rotating, spatially periodic chimera patterns as solutions of a reversible ordinary differential equation, and demonstrate a plethora of such states. In the limit of neutral coupling they reduce to analytical solutions in the form of one- and two-point chimera patterns as well as localized chimera solitons. Patterns at weakly attracting coupling are characterized by virtue of a perturbative approach. Stability analysis reveals that only the simplest chimeras with one synchronous region are stable.

  13. Growth control of genetically modified cells using an antibody/c-Kit chimera. (United States)

    Kaneko, Etsuji; Kawahara, Masahiro; Ueda, Hiroshi; Nagamune, Teruyuki


    Gene therapy has been regarded as an innovative potential treatment against serious congenital diseases. However, applications of gene therapy remain limited, partly because its clinical success depends on therapeutic gene-transduced cells acquiring a proliferative advantage. To address this problem, we have developed the antigen-mediated genetically modified cell amplification (AMEGA) system, which uses chimeric receptors to enable the selective proliferation of gene-transduced cells. In this report, we describe mimicry of c-Kit signaling and its application to the AMEGA system. We created an antibody/c-Kit chimera in which the extracellular domain of c-Kit is replaced with an anti-fluorescein single-chain Fv antibody fragment and the extracellular D2 domain of the erythropoietin receptor. A genetically modified mouse pro-B cell line carrying this chimera showed selective expansion in the presence of fluorescein-conjugated BSA (BSA-FL) as a growth inducer. By further engineering the transmembrane domain of the chimera to reduce interchain interaction we attained stricter ligand-dependency. Since c-Kit is an important molecule in the expansion of hematopoietic stem cells (HSCs), this antibody/c-Kit chimera could be a promising tool for gene therapy targeting HSCs. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Tissue Destruction in Bullous Pemphigoid Can Be Complement Independent and May Be Mitigated by C5aR2

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    Christian M. Karsten


    Full Text Available Bullous pemphigoid (BP, the most frequent autoimmune bullous disorder, is a paradigmatic autoantibody-mediated disease associated with autoantibodies against BP180 (type XVII collagen, Col17. Several animal models have been developed that reflect important clinical and immunological features of human BP. Complement activation has been described as a prerequisite for blister formation, however, the recent finding that skin lesions can be induced by anti-Col17 F(ab′2 fragments indicates complement-independent mechanisms to contribute to blister formation in BP. Here, C5−/− mice injected with anti-Col17 IgG showed a reduction of skin lesions by about 50% associated with significantly less skin-infiltrating neutrophils compared to wild-type mice. Reduction of skin lesions and neutrophil infiltration was seen independently of the employed anti-Col17 IgG dose. Further, C5ar1−/− mice were protected from disease development, whereas the extent of skin lesions was increased in C5ar2−/− animals. Pharmacological inhibition of C5a receptor 1 (C5aR1 by PMX53 led to reduced disease activity when applied in a prophylactic setting. In contrast, PMX-53 treatment had no effect when first skin lesions had already developed. While C5aR1 was critically involved in neutrophil migration in vitro, its role for Col17-anti-Col17 IgG immune complex-mediated release of reactive oxygen species from neutrophils was less pronounced. Our data demonstrate that complement-dependent and -independent mechanisms coexist in anti-Col17-autoantibody-mediated tissue destruction. C5aR1 and C5aR2 seem to play opposing roles in this process with C5aR1 exerting its primary effect in recruiting inflammatory cells to the skin during the early phase of the disease. Further studies are required to fully understand the role of C5aR2 in autoantibody-mediated skin inflammation.

  15. Whole-exome sequencing of a patient with severe and complex hemostatic abnormalities reveals a possible contributing frameshift mutation in C3AR1

    DEFF Research Database (Denmark)

    Leinøe, Eva; Nielsen, Ove Juul; Jønson, Lars


    -threatening coagulation disorder causing recurrent venous thromboembolic events, severe thrombocytopenia, and subdural hematomas. Whole-exome sequencing revealed a frameshift mutation (C3AR1 c.355-356dup, p.Asp119Alafs*19) resulting in a premature stop codon in C3AR1 (Complement Component 3a Receptor 1). Based...

  16. PyChimera: use UCSF Chimera modules in any Python 2.7 project. (United States)

    Rodríguez-Guerra Pedregal, Jaime; Maréchal, Jean-Didier


    UCSF Chimera is a powerful visualization tool remarkably present in the computational chemistry and structural biology communities. Built on a C++ core wrapped under a Python 2.7 environment, one could expect to easily import UCSF Chimera's arsenal of resources in custom scripts or software projects. Nonetheless, this is not readily possible if the script is not executed within UCSF Chimera due to the isolation of the platform. UCSF ChimeraX, successor to the original Chimera, partially solves the problem but yet major upgrades need to be undergone so that this updated version can offer all UCSF Chimera features. PyChimera has been developed to overcome these limitations and provide access to the UCSF Chimera codebase from any Python 2.7 interpreter, including interactive programming with tools like IPython and Jupyter Notebooks, making it easier to use with additional third-party software. PyChimera is LGPL-licensed and available at or Supplementary data are available at Bioinformatics online.

  17. Etching Enhancement Followed by Nitridation on Low-k SiOCH Film in Ar/C5F10O Plasma (United States)

    Miyawaki, Yudai; Shibata, Emi; Kondo, Yusuke; Takeda, Keigo; Kondo, Hiroki; Ishikawa, Kenji; Okamoto, Hidekazu; Sekine, Makoto; Hori, Masaru


    The etching rates of low-dielectric-constant (low-k), porous SiOCH (p-SiOCH) films were increased by nitrogen-added Ar/C5F10O plasma etching in dual-frequency (60 MHz/2 MHz)-excited parallel plate capacitively coupled plasma. Previously, perfluoropropyl vinyl ether [C5F10O] provided a very high density of CF3+ ions [Nagai et al.: Jpn. J. Appl. Phys. 45 (2006) 7100]. Surface nitridation on the p-SiOCH surface exposed to Ar/N2 plasma led to the etching of larger amounts of p-SiOCH in Ar/C5F10O plasma, which depended on the formation of bonds such as =C(sp2)=N(sp2)- and -C(sp)≡N(sp).

  18. Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury. (United States)

    Bosmann, Markus; Grailer, Jamison J; Ruemmler, Robert; Russkamp, Norman F; Zetoune, Firas S; Sarma, J Vidya; Standiford, Theodore J; Ward, Peter A


    We investigated how complement activation promotes tissue injury and organ dysfunction during acute inflammation. Three models of acute lung injury (ALI) induced by LPS, IgG immune complexes, or C5a were used in C57BL/6 mice, all models requiring availability of both C5a receptors (C5aR and C5L2) for full development of ALI. Ligation of C5aR and C5L2 with C5a triggered the appearance of histones (H3 and H4) in bronchoalveolar lavage fluid (BALF). BALF from humans with ALI contained H4 histone. Histones were absent in control BALF from healthy volunteers. In mice with ALI, in vivo neutralization of H4 with IgG antibody reduced the intensity of ALI. Neutrophil depletion in mice with ALI markedly reduced H4 presence in BALF and was highly protective. The direct lung damaging effects of extracellular histones were demonstrated by airway administration of histones into mice and rats (Sprague-Dawley), which resulted in ALI that was C5a receptor-independent, and associated with intense inflammation, PMN accumulation, damage/destruction of alveolar epithelial cells, together with release into lung of cytokines/chemokines. High-resolution magnetic resonance imaging demonstrated lung damage, edema and consolidation in histone-injured lungs. These studies confirm the destructive C5a-dependent effects in lung linked to appearance of extracellular histones.

  19. Low-k SiOCH Film Etching Process and Its Diagnostics Employing Ar/C5F10O/N2 Plasma (United States)

    Nagai, Mikio; Hayashi, Takayuki; Hori, Masaru; Okamoto, Hidekazu


    We proposed an environmental harmonic etching gas of C5F10O (CF3CF2CF2OCFCF2), and demonstrated the etching of low-k SiOCH films employing a dual-frequency capacitively coupled etching system. Dissociative ionization cross sections for the electron impact ionizations of C5F10O and c-C4F8 gases have been measured by quadrupole mass spectroscopy (QMS). The dissociative ionization cross section of CF3+ from C5F10O gas was much higher than those of other ionic species, and 10 times higher than that of CF3+ from C4F8 gas. CF3+ is effective for increasing the etching rate of SiO2. As a result, the etching rate of SiOCH films using Ar/C5F10O/N2 plasma was about 1000 nm/min, which is much higher than that using Ar/C4F8/N2 plasma. The behaviours of fluorocarbon radicals in Ar/C5F10O/N2 plasma, which were measured by infrared diode laser absorption spectroscopy, were similar to those in Ar/C4F8/N2 plasma. The densities of CF and CF3 radicals were markedly decreased with increasing N2 flow rate. Etching rate was controlled by N2 flow rate. A vertical profile of SiOCH with a high etching rate and less microloading was realized using Ar/C5F10O/N2 plasma chemistry.

  20. Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

    DEFF Research Database (Denmark)

    Windrem, Martha S.; Osipovitch, Mikhail; Liu, Zhengshan


    with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal...... astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial...

  1. C3a Enhances the Formation of Intestinal Organoids through C3aR1

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    Naoya Matsumoto


    Full Text Available C3a is important in the regulation of the immune response as well as in the development of organ inflammation and injury. Furthermore, C3a contributes to liver regeneration but its role in intestinal stem cell function has not been studied. We hypothesized that C3a is important for intestinal repair and regeneration. Intestinal organoid formation, a measure of stem cell capacity, was significantly limited in C3-deficient and C3a receptor (C3aR 1-deficient mice while C3a promoted the growth of organoids from normal mice by supporting Wnt-signaling but not from C3aR1-deficient mice. Similarly, the presence of C3a in media enhanced the expression of the intestinal stem cell marker leucine-rich repeat G-protein-coupled receptor 5 (Lgr5 and of the cell proliferation marker Ki67 in organoids formed from C3-deficient but not from C3aR1-deficient mice. Using Lgr5.egfp mice we showed significant expression of C3 in Lgr5+ intestinal stem cells whereas C3aR1 was expressed on the surface of various intestinal cells. C3 and C3aR1 expression was induced in intestinal crypts in response to ischemia/reperfusion injury. Finally, C3aR1-deficient mice displayed ischemia/reperfusion injury comparable to control mice. These data suggest that C3a through interaction with C3aR1 enhances stem cell expansion and organoid formation and as such may have a role in intestinal regeneration.

  2. Chimera states in mechanical oscillator networks

    DEFF Research Database (Denmark)

    Martens, Erik Andreas; Thutupalli, Shashi; Fourrière, Antoine


    of identical oscillators, numerous theoretical studies in recent years have revealed the intriguing possibility of "chimera states," in which the symmetry of the oscillator population is broken into a synchronous part and an asynchronous part. However, a striking lack of empirical evidence raises the question...... of whether chimeras are indeed characteristic of natural systems. This calls for a palpable realization of chimera states without any fine-tuning, from which physical mechanisms underlying their emergence can be uncovered. Here, we devise a simple experiment with mechanical oscillators coupled...... in a hierarchical network to show that chimeras emerge naturally from a competition between two antagonistic synchronization patterns. We identify a wide spectrum of complex states, encompassing and extending the set of previously described chimeras. Our mathematical model shows that the self-organization observed...

  3. Importance of M2-M3 loop in governing properties of genistein at the α7 nicotinic acetylcholine receptor inferred from α7/5-HT3A chimera. (United States)

    Grønlien, Jens Halvard; Ween, Hilde; Thorin-Hagene, Kirsten; Cassar, Steven; Li, Jinhe; Briggs, Clark A; Gopalakrishnan, Murali; Malysz, John


    Genistein and 5-hydroxyindole (5-HI) potentiate the α7 nicotinic acetylcholine receptor current by primarily increasing peak amplitude, a property of type I α7 positive allosteric modulation. In this study, the effects of these two compounds were investigated at two different α7/5-HT(3) chimeras (chimera 1, comprising of extracellular α7 N-terminus fused to the remainder of 5-HT(3A), and chimera 2 containing an additional α7 encoded M2-M3 loop), and wild-type α7 and 5-HT(3A) receptors. Agonist-evoked responses, examined by expression of the chimeras in Xenopus laevis oocytes or HEK-293 cells, revealed that currents decayed slower and compounds {rank order: N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987)~2-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-5-phenyl-1,3,4-oxadiazole (NS6784)>acetylcholine>choline} were more potent in chimera 2 than chimera 1 or α7 receptors. In chimera 2, genistein and 5-HI potentiated agonist-evoked responses (EC(50): 4-5 μM for genistein and 300-500 μM for 5-HI) and at higher concentrations evoked current directly consistent with ago-allosteric modulation. At chimera 1 and 5-HT(3A) receptors, neither compound directly evoked any current and 5-HI, only at chimera 1, was able to potentiate agonist-evoked responses. Genistein and 5-HI did not inhibit the binding of the α7 agonist [(3)H](1S,4S)-2,2-dimethyl-5-(6-phenylpyridazin-3-yl)-5-aza-2-azoniabicyclo[2.2.1] heptane ([(3)H]A-585539) to rat brain or chimera 2. In summary, this study supports the role of the M2-M3 loop being critical for the positive allosteric effect of genistein, but not 5-HI, and in agonist-evoked response fine-tuning. The identification of distinct α7 receptor modulatory sites offers unique opportunities for developing CNS therapeutics and understanding its pharmacology. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Amplitude chimeras and chimera death in dynamical networks

    International Nuclear Information System (INIS)

    Zakharova, Anna; Kapeller, Marie; Schöll, Eckehard


    We find chimera states with respect to amplitude dynamics in a network of Stuart- Landau oscillators. These partially coherent and partially incoherent spatio-temporal patterns appear due to the interplay of nonlocal network topology and symmetry-breaking coupling. As the coupling range is increased, the oscillations are quenched, amplitude chimeras disappear and the network enters a symmetry-breaking stationary state. This particular regime is a novel pattern which we call chimera death. It is characterized by the coexistence of spatially coherent and incoherent inhomogeneous steady states and therefore combines the features of chimera state and oscillation death. Additionally, we show two different transition scenarios from amplitude chimera to chimera death. Moreover, for amplitude chimeras we uncover the mechanism of transition towards in-phase synchronized regime and discuss the role of initial conditions. (paper)

  5. Cloning, expression, cellular distribution, and role in chemotaxis of a C5a receptor in rainbow trout: the first identification of a C5a receptor in a nonmammalian species (United States)

    Boshra, Hani; Li, Jun; Peters, Rodney; Hansen, John; Matlapudi, Anjan; Sunyer, J. Oriol


    C3a, C4a, and C5a anaphylatoxins generated during complement activation play a key role in inflammation. C5a is the most potent of the three anaphylatoxins in eliciting biological responses. The effects of C5a are mediated by its binding to C5a receptor (C5aR, CD88). To date, C5aR has only been identified and cloned in mammalian species, and its evolutionary history remains ill-defined. To gain insights into the evolution, conserved structural domains, and functions of C5aR, we have cloned and characterized a C5aR in rainbow trout, a teleost fish. The isolated cDNA encoded a 350-aa protein that showed the highest sequence similarity to C5aR from other species. Genomic analysis revealed the presence of one continuous exon encoding the entire open reading frame. Northern blot analysis showed significant expression of the trout C5a receptor (TC5aR) message in PBLs and kidney. Flow cytometric analysis showed that two Abs generated against two different areas of the extracellular N-terminal region of TC5aR positively stained the same leukocyte populations from PBLs. B lymphocytes and granulocytes comprised the majority of cells recognized by the anti-TC5aR. More importantly, these Abs inhibited chemotaxis of PBLs toward a chemoattractant fraction purified from complement-activated trout serum. Our data suggest that the split between C5aR and C3aR from a common ancestral molecule occurred before the emergence of teleost fish. Moreover, we demonstrate that the overall structure of C5aR as well as its role in chemotaxis have remained conserved for >300 million years.

  6. Niemann-Pick C1 (NPC1/NPC1-like1 Chimeras Define Sequences Critical for NPC1’s Function as a Filovirus Entry Receptor

    Directory of Open Access Journals (Sweden)

    Esther Ndungo


    Full Text Available We recently demonstrated that Niemann-Pick C1 (NPC1, a ubiquitous 13-pass cellular membrane protein involved in lysosomal cholesterol transport, is a critical entry receptor for filoviruses. Here we show that Niemann-Pick C1-like1 (NPC1L1, an NPC1 paralog and hepatitis C virus entry factor, lacks filovirus receptor activity. We exploited the structural similarity between NPC1 and NPC1L1 to construct and analyze a panel of chimeras in which NPC1L1 sequences were replaced with cognate sequences from NPC1. Only one chimera, NPC1L1 containing the second luminal domain (C of NPC1 in place of its own, bound to the viral glycoprotein, GP. This engineered protein mediated authentic filovirus infection nearly as well as wild-type NPC1, and more efficiently than did a minimal NPC1 domain C-based receptor recently described by us. A reciprocal chimera, NPC1 containing NPC1L1’s domain C, was completely inactive. Remarkably, an intra-domain NPC1L1-NPC1 chimera bearing only a ~130-amino acid N–terminal region of NPC1 domain C could confer substantial viral receptor activity on NPC1L1. Taken together, these findings account for the failure of NPC1L1 to serve as a filovirus receptor, highlight the central role of the luminal domain C of NPC1 in filovirus entry, and reveal the direct involvement of N–terminal domain C sequences in NPC1’s function as a filovirus receptor.

  7. Chimera states in mechanical oscillator networks. (United States)

    Martens, Erik Andreas; Thutupalli, Shashi; Fourrière, Antoine; Hallatschek, Oskar


    The synchronization of coupled oscillators is a fascinating manifestation of self-organization that nature uses to orchestrate essential processes of life, such as the beating of the heart. Although it was long thought that synchrony and disorder were mutually exclusive steady states for a network of identical oscillators, numerous theoretical studies in recent years have revealed the intriguing possibility of "chimera states," in which the symmetry of the oscillator population is broken into a synchronous part and an asynchronous part. However, a striking lack of empirical evidence raises the question of whether chimeras are indeed characteristic of natural systems. This calls for a palpable realization of chimera states without any fine-tuning, from which physical mechanisms underlying their emergence can be uncovered. Here, we devise a simple experiment with mechanical oscillators coupled in a hierarchical network to show that chimeras emerge naturally from a competition between two antagonistic synchronization patterns. We identify a wide spectrum of complex states, encompassing and extending the set of previously described chimeras. Our mathematical model shows that the self-organization observed in our experiments is controlled by elementary dynamical equations from mechanics that are ubiquitous in many natural and technological systems. The symmetry-breaking mechanism revealed by our experiments may thus be prevalent in systems exhibiting collective behavior, such as power grids, optomechanical crystals, or cells communicating via quorum sensing in microbial populations.

  8. A C-terminal segment of the V{sub 1}R vasopressin receptor is unstructured in the crystal structure of its chimera with the maltose-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Adikesavan, Nallini Vijayarangan; Mahmood, Syed Saad; Stanley, Nithianantham; Xu, Zhen; Wu, Nan [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Thibonnier, Marc [Department of Medicine, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States); Shoham, Menachem, E-mail: [Department of Biochemistry, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4935 (United States)


    The 1.8 Å crystal structure of an MBP-fusion protein with the C-terminal cytoplasmic segment of the V1 vasopressin receptor reveals that the receptor segment is unstructured. The V{sub 1} vascular vasopressin receptor (V{sub 1}R) is a G-protein-coupled receptor (GPCR) involved in the regulation of body-fluid osmolality, blood volume and blood pressure. Signal transduction is mediated by the third intracellular loop of this seven-transmembrane protein as well as by the C-terminal cytoplasmic segment. A chimera of the maltose-binding protein (MBP) and the C-terminal segment of V{sub 1}R has been cloned, expressed, purified and crystallized. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 51.10, b = 66.56, c = 115.72 Å, β = 95.99°. The 1.8 Å crystal structure reveals the conformation of MBP and part of the linker region of this chimera, with the C-terminal segment being unstructured. This may reflect a conformational plasticity in the C-terminal segment that may be necessary for proper function of V{sub 1}R.

  9. Baicalein suppresses the androgen receptor (AR)-mediated prostate cancer progression via inhibiting the AR N-C dimerization and AR-coactivators interaction. (United States)

    Xu, Defeng; Chen, Qiulu; Liu, Yalin; Wen, Xingqiao


    Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression. PCa cells including LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with baicalein and luciferase assay was used to evaluate their effect on the AR transactivation. Cell growth and IC 50 were determined by MTT assay after 48 hrs treatment. RT-PCR was used to evaluate the mRNA levels of AR target genes including PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR and PSA protein expression. The natural product of baicalein can selectively inhibit AR transactivation with little effect on the other nuclear receptors, including ERα, and GR. At a low concentration, 2.5 μM of baicalein effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Mechanism dissection suggest that baicalein can suppress AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive LNCaP cells and castration resistant CWR22Rv1 cells, that may involve the inhibiting the AR N/C dimerization and AR-coactivators interaction. Baicalein may be developed as an effective anti-AR therapy via its ability to inhibit AR transactivation and AR-mediated PCa cell growth.

  10. Deficiency in early development of the thymus-dependent cells in irradiation chimeras attributable to recipient's environment

    International Nuclear Information System (INIS)

    Iwabuchi, C.; Iwabuchi, K.; Kobayashi, S.; Ogasawara, K.; Negishi, I.; Wang, B.Y.; Wambua, P.P.; Arase, H.; Fukushi, N.; Itoh, Y.


    Bone marrow chimeras were prepared using reciprocal combinations of AKR and C3H mice. When C3H mice were recipients, the number of thymocytes recoverable from such chimeras (C3H recipient chimeras) was small as compared with that from chimeras for which AKR mice were used as recipients (AKR recipient chimeras) regardless of donor strain. The thymocytes from C3H recipient chimeras showed a profound deficiency in generating proliferative responses to stimulation by anti-CD3 mAb (2C11) or anti-TCR (alpha, beta) mAb (H57-597), even though the expression of CD3 and TCR molecules fell within the same range as that in AKR recipient chimeras. Furthermore, after stimulation with immobilized 2C11, the proportion of IL-2R+ cells in the thymocytes from C3H recipient chimeras was much less than that in AKR recipient chimeras. However, no significant difference in proliferative responses to 2C11 plus PMA, in influx of Ca2+ after stimulation with 2C11 or IL-2 production in response to 2C11 plus PMA or PMA plus A23187 was demonstrated between C3H and AKR recipient chimeras. These findings suggest that the thymocytes from C3H recipient chimeras have a deficiency in the signal transduction system as compared with chimeras for which AKR mice are the recipients. The thymic stromal component involved in this difference in the C3H recipient chimeras is discussed


    Directory of Open Access Journals (Sweden)



    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.


    Directory of Open Access Journals (Sweden)



    Full Text Available In a mutant ES cells↔ wild-type embryo chimera, ES cells behave more like epiblastcells. They can contribute to the primitive ectoderm layers, which give rise to all theembryonic tissues and some extraembryonic tissues (Beddington and Robertson,1989, but not to trophectoderm or primitive endoderm. Using transgenic ES celllines, aggregated with cleavage stage host embryo, ES cells can integrate randomlyin the embryo proper. If they will be take part in the formation of ICM (inner cellmass, it will be possible to obtain germline chimera animals. To generate ES cells↔ cleavage stage host embryo chimeras, we used (CD-1 mice as donors of hostembryos as well as recipients of manipulated embryos. For chimera production, weused fluorescent-labeled ES cell line (CD1/EGFP, because in this case we canfollow the fate of ES cells during the embryonic development. We produced thechimers using “aggregation chimera technique”. 8 cells stage zona pellucida free,mouse embryos were aggregated in an aggregation plates, with a clump of ES cells(10 – 15 cells. The chimera embryos were cultivated for 24 hours in the incubator(at 37 °C, 5% CO2 in air. The chimera blastocysts resulted after cultivation, weretransferred to the uterus of the 2.5-dpc pseudo pregnant females.

  13. Smallest chimera states (United States)

    Maistrenko, Yuri; Brezetsky, Serhiy; Jaros, Patrycja; Levchenko, Roman; Kapitaniak, Tomasz


    We demonstrate that chimera behavior can be observed in small networks consisting of three identical oscillators, with mutual all-to-all coupling. Three different types of chimeras, characterized by the coexistence of two coherent oscillators and one incoherent oscillator (i.e., rotating with another frequency) have been identified, where the oscillators show periodic (two types) and chaotic (one type) behaviors. Typical bifurcations at the transitions from full synchronization to chimera states and between different types of chimeras have been described. Parameter regions for the chimera states are obtained in the form of Arnold tongues, issued from a singular parameter point. Our analysis suggests that chimera states can be observed in small networks relevant to various real-world systems.

  14. Quantum chimera states

    International Nuclear Information System (INIS)

    Viennot, David; Aubourg, Lucile


    We study a theoretical model of closed quasi-hermitian chain of spins which exhibits quantum analogues of chimera states, i.e. long life classical states for which a part of an oscillator chain presents an ordered dynamics whereas another part presents a disordered dynamics. For the quantum analogue, the chimera behaviour deals with the entanglement between the spins of the chain. We discuss the entanglement properties, quantum chaos, quantum disorder and semi-classical similarity of our quantum chimera system. The quantum chimera concept is novel and induces new perspectives concerning the entanglement of multipartite systems. - Highlights: • We propose a spin chain model with long range couplings having purely quantum states similar to the classical chimera states. • The quantum chimera states are characterized by the coexistence of strongly entangled and non-entangled spins in the same chain. • The quantum chimera states present some characteristics of quantum chaos.

  15. Quantum chimera states

    Energy Technology Data Exchange (ETDEWEB)

    Viennot, David, E-mail:; Aubourg, Lucile


    We study a theoretical model of closed quasi-hermitian chain of spins which exhibits quantum analogues of chimera states, i.e. long life classical states for which a part of an oscillator chain presents an ordered dynamics whereas another part presents a disordered dynamics. For the quantum analogue, the chimera behaviour deals with the entanglement between the spins of the chain. We discuss the entanglement properties, quantum chaos, quantum disorder and semi-classical similarity of our quantum chimera system. The quantum chimera concept is novel and induces new perspectives concerning the entanglement of multipartite systems. - Highlights: • We propose a spin chain model with long range couplings having purely quantum states similar to the classical chimera states. • The quantum chimera states are characterized by the coexistence of strongly entangled and non-entangled spins in the same chain. • The quantum chimera states present some characteristics of quantum chaos.

  16. Periclinal chimera technique: new plant breeding approach. (United States)

    Gakpetor, P M; Mohammed, H; Moreti, D; Nassar, N M A


    Plant interspecific periclinal chimeras are a mosaic formed by tissues from two species. They are manipulated here as an efficient plant breeding tool for cassava root yields. In this study, plants synthesized from two chimeras, designated as chimera 2 and chimera 4, were characterized morphologically and cytologically to unravel the origin of their tissue layers (L2 and L3). Root yield of the two chimeras was also evaluated. Chimera 2 that was developed from graft union between Manihot fortalezensis (F) as scion and M. esculenta (E) as rootstock and the same in chimera 4 was developed from grafting triploid cassava cultivar (2n = 54) (C) as scion and M. pohlii (P) (2n = 36) as rootstock. A new method of inducing interspecific chimeras without using hormones was also tested in this study. Five combinations between four cassava cultivars on one side and M. fortalezensis and an interspecific hybrid (M. glaziovii x M. esculenta) on the other side were experimented to determine compatibility between the parents. Wild species always gave L2 and L3, independent of being used as rootstock or scion. L3 is responsible for producing pericycle. Thus, its performance was different in each chimera due to specific epigenetic interaction. Of 48 grafts, it was obtained one chimera giving a percentage of 2.1% that is little lower than using hormones but much efficient to use. Chimera induction efficiency in this investigation was the same when using hormones. Thus, our new, less labor, and more cost-effective technique is as much efficient as hormones and is much potential to employ as an effective plant breeding method boosting cassava root yield.

  17. A chimera embryo assay reveals a decrease in embryonic cellular proliferation induced by sperm from X-irradiated male mice

    International Nuclear Information System (INIS)

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Raabe, O.; Overstreet, J.W.


    Male mice were divided into three experimental groups and a control group. Mice in the experimental groups received one of three doses of acute X irradiation (1.73, 0.29, and 0.05 Gy) and together with the control unirradiated mice were then mated weekly to unirradiated female mice for a 9-week experimental period. Embryos were recovered from the weekly matings at the four-cell stage and examined by the chimera assay for proliferative disadvantage. Aggregation chimeras were constructed of embryos from female mice mated to irradiated males (experimental embryos) and embryos from females mated to unexposed males (control embryos) and contained either one experimental embryo and one control embryo (heterologous chimera) or two control embryos (control chimera). The control embryo in heterologous chimeras and either embryo in control chimeras were prelabeled with the vital dye fluorescein isothiocyanate (FITC), and the chimeras were cultured for 40 h and viewed under phase-contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution from the FITC-labeled embryo. Experimental and control embryos that were cultured singly were also examined for embryo cell number at the end of the 40-h culture period. In control chimeras, the mean ratio of the unlabeled cells:total chimera cell number (henceforth referred to as ''mean ratio'') was 0.50 with little or no weekly variation over the 9-week experimental period. During Weeks 4-7, the mean ratios of heterologous chimeras differed significantly from the mean ratio of control chimeras with the greatest differences occurring during Week 7 (0.41 for chimeras of 0.05 Gy dose group, 0.40 for chimeras of the 0.29 Gy dose group, and 0.17 for chimeras of the 1.73 Gy dose group)

  18. Inducing and destruction of chimeras and chimera-like states by an external harmonic force (United States)

    Shepelev, I. A.; Vadivasova, T. E.


    We study the phenomena of chimera destruction and inducing of chimera-like states in an ensemble of nonlocally coupled chaotic Rössler oscillators under an external harmonic force. The localized harmonic influence can lead to both destruction and changing of the spatial topology of chimeras. At the same time this influence can cause the emergence of stable chimera-like states (induced chimeras) for the regime of partial coherent chaos. Induced chimeras are also observed for the global influence. We show the possibility of controlling the chimera-like state topology by varying the parameters of localized external harmonic influence.

  19. The mathematics behind chimera states (United States)

    Omel’chenko, O. E.


    Chimera states are self-organized spatiotemporal patterns of coexisting coherence and incoherence. We give an overview of the main mathematical methods used in studies of chimera states, focusing on chimera states in spatially extended coupled oscillator systems. We discuss the continuum limit approach to these states, Ott-Antonsen manifold reduction, finite size chimera states, control of chimera states and the influence of system design on the type of chimera state that is observed.

  20. The Crystal Structure of a Maxi/Mini-Ferritin Chimera Reveals Guiding Principles for the Assembly of Protein Cages

    Energy Technology Data Exchange (ETDEWEB)

    Cornell, Thomas A. [Department; Division; Srivastava, Yogesh [Genome; Jauch, Ralf [Genome Institute of Singapore, Singapore; Genome; Fan, Rongli [Division; Orner, Brendan P. [Department; Division


    Cage proteins assemble into nanoscale structures with large central cavities. They play roles, including those as virus capsids and chaperones, and have been applied to drug delivery and nanomaterials. Furthermore, protein cages have been used as model systems to understand and design protein quaternary structure. Ferritins are ubiquitous protein cages that manage iron homeostasis and oxidative damage. Two ferritin subfamilies have strongly similar tertiary structure yet distinct quaternary structure: maxi-ferritins normally assemble into 24-meric, octahedral cages with C-terminal E-helices centered around 4-fold symmetry axes, and mini-ferritins are 12-meric, tetrahedral cages with 3-fold axes defined by C-termini lacking E-domains. To understand the role E-domains play in ferritin quaternary structure, we previously designed a chimera of a maxi-ferritin E-domain fused to the C-terminus of a mini-ferritin. The chimera is a 12-mer cage midway in size between those of the maxi- and mini-ferritin. The research described herein sets out to understand (a) whether the increase in size over a typical mini-ferritin is due to a frozen state where the E-domain is flipped out of the cage and (b) whether the symmetrical preference of the E-domain in the maxi-ferritin (4-fold axis) overrules the C-terminal preference in the mini-ferritin (3-fold axis). With a 1.99 Å resolution crystal structure, we determined that the chimera assembles into a tetrahedral cage that can be nearly superimposed with the parent mini-ferritin, and that the E-domains are flipped external to the cage at the 3-fold symmetry axes.

  1. Simple and complex chimera states in a nonlinearly coupled oscillatory medium (United States)

    Bolotov, Maxim; Smirnov, Lev; Osipov, Grigory; Pikovsky, Arkady


    We consider chimera states in a one-dimensional medium of nonlinear nonlocally coupled phase oscillators. In terms of a local coarse-grained complex order parameter, the problem of finding stationary rotating nonhomogeneous solutions reduces to a third-order ordinary differential equation. This allows finding chimera-type and other inhomogeneous states as periodic orbits of this equation. Stability calculations reveal that only some of these states are stable. We demonstrate that an oscillatory instability leads to a breathing chimera, for which the synchronous domain splits into subdomains with different mean frequencies. Further development of instability leads to turbulent chimeras.

  2. Cellular basis of the immunohematologic defects observed in short-term semiallogeneic B6C3F1→C3H chimeras: evidence for host-versus-graft reaction initiated by radioresistant T cells

    International Nuclear Information System (INIS)

    Aizawa, S.; Sado, T.; Kamisaku, H.; Kubo, E.


    Lethally irradiated C3Hf mice reconstituted with a relatively low dose (2 x 10 6 ) of B6C3F 1 bone marrow cells (B6C3F 1 →C3Hf chimeras) frequently manifest immunohematologic deficiencies during the first month following injection of bone marrow cells. They show slow recovery of antibody-forming potential to sheep red blood cells (SRBC) as compared to that observed in syngeneic (C3Hf→C3Hf or B6C3F 1 →B6C3F 1 ) chimeras. They also show a deficiency of B-cell activity as assessed by antibody response to SRBC following further reconstitution with B6C3F 1 -derived thymus cells 1 week after injection of bone marrow cells. A significant fraction of B6C3F 1 →C3Hf chimeras was shown to manifest a sudden loss of cellularity of spleens during the second week following injection of bone marrow cells even though cellularity was restored to the normal level within 1 week. The splenic mononuclear cells recovered from such chimeras almost invariably showed strong cytotoxicity against target cells expressing donor-type specific H-2 antigens (H-2/sup b/) when assesed by 51 Cr-release assay in vitro. The effector cells responsible for the observed anti-donor specific cytotoxicity were shown to be residual host-derived T cells. These results indicate strongly that residual host T cells could develop anti-donor specific cytotoxicity even after exposure to a supralethal dose (1050 R) of radiation and that the immunohematologic disturbances observed in shortterm F 1 to parent bone marrow chimeras (B6C3F 1 →C3Hf) were due to host-versus-graft reaction (HVGR) initiated by residual host T cells. The implication of these findings on the radiobiological nature of the residual T cells and the persistence of potentially anti-donor reactive T-cell clones in long-surviving allogeneic bone marrow chimeras was discussed

  3. Chimeras of Bet v 1 and Api g 1 reveal heterogeneous IgE responses in patients with birch pollen allergy. (United States)

    Gepp, Barbara; Lengger, Nina; Bublin, Merima; Hemmer, Wolfgang; Breiteneder, Heimo; Radauer, Christian


    Characterization of IgE-binding epitopes of allergens and determination of their patient-specific relevance is crucial for the diagnosis and treatment of allergy. We sought to assess the contribution of specific surface areas of the major birch pollen allergen Bet v 1.0101 to binding IgE of individual patients. Four distinct areas of Bet v 1 representing in total 81% of its surface were grafted onto the scaffold of its homolog, Api g 1.0101, to yield the chimeras Api-Bet-1 to Api-Bet-4. The chimeras were expressed in Escherichia coli and purified. IgE binding of 64 sera from Bet v 1-sensitized subjects with birch pollen allergy was determined by using direct ELISA. Specificity was assessed by means of inhibition ELISA. rApi g 1.0101, Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4 bound IgE from 44%, 89%, 80%, 78%, and 48% of the patients, respectively. By comparing the amount of IgE binding to the chimeras and to rApi g 1.0101, 81%, 70%, 75%, and 45% of the patients showed significantly enhanced IgE binding to Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4, respectively. The minority (8%) of the sera revealed enhanced IgE binding exclusively to a single chimera, whereas 31% showed increased IgE binding to all 4 chimeras compared with rApi g 1.0101. The chimeras inhibited up to 70% of IgE binding to rBet v 1.0101, confirming the specific IgE recognition of the grafted regions. The Bet v 1-specific IgE response is polyclonal, and epitopes are spread across the entire Bet v 1 surface. Furthermore, the IgE recognition profile of Bet v 1 is highly patient specific. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

  4. COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine. (United States)

    Bosia, Marta; Lorenzi, Cristina; Pirovano, Adele; Guglielmino, Carmelo; Cocchi, Federica; Spangaro, Marco; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto


    Clozapine is still considered the gold standard for treatment-resistant schizophrenia patients; however, up to 40% of patients do not respond adequately. Identifying potential predictors of clinical response to this last-line antipsychotic could represent an important goal for treatment. Among these, functional polymorphisms involved in dopamine system modulation, known to be disrupted in schizophrenia, may play a role. We examined the COMT Val158Met polymorphism, which plays a key role in dopamine regulation at the prefrontal level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity involved in the interaction between the serotonin and dopamine systems. 107 neuroleptic-refractory, biologically unrelated Italian patients (70 males and 37 females) with a DSM-IV diagnosis of schizophrenia who were being treated with clozapine were recruited. Psychopathology was assessed by the Positive and Negative Symptoms Scale (PANSS) at the beginning of treatment, and at weeks 8 and 12. Genomic DNA was extracted from venous blood samples. COMT rs4680 (Val158Met) and 5-HT1A-R rs6295 (-1019 C/G) polymorphisms were analyzed by PCR-based restriction fragment length and direct sequencing, respectively. We found a significant effect of COMT and 5-HT1A-R on the PANSS Negative Subscale variation, with greater improvement among COMT Val/Val and 5-HT1A-R G/G subjects. The findings support the hypothesis that COMT rs4680 and 5-HT1A-R rs6295 polymorphisms could influence the negative symptom response to clozapine, probably through modulation of the dopaminergic system.

  5. Chimera states in bursting neurons


    Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.


    We study the existence of chimera states in pulse-coupled networks of bursting Hindmarsh-Rose neurons with nonlocal, global and local (nearest neighbor) couplings. Through a linear stability analysis, we discuss the behavior of stability function in the incoherent (i.e. disorder), coherent, chimera and multi-chimera states. Surprisingly, we find that chimera and multi-chimera states occur even using local nearest neighbor interaction in a network of identical bursting neurons alone. This is i...

  6. Tolerance, immunocompetence, and secondary disease in fully allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Rayfield, L.S.; Brent, L.


    The aim of this study was to ascertain the extent to which secondary disease and mortality in fully allogeneic chimeras (C57BL leads to CBA) is caused (if at all) by a delayed graft-versus-host reaction. Adult CBA males were thymectomized, irradiated, and reconstituted with T-lymphocyte-depleted C57BL or CBA bone marrow cells (BMC), followed three weeks after irradiation by implantation under the kidney capsule of thymic lobes from C57BL or CBA fetal or adult donors. These mice were observed for the development of secondary disease for periods in excess of 250 days, and they were examined at 5 weeks or 4 months for T lymphocyte reactivity and tolerance to alloantigens, using the cell-mediated lympholysis assay (CML). The following results were obtained. First, removal of T lymphocytes with anti-Thy 1 antibody and complement from allogeneic bone marrow did not prevent wasting and eventual death, although it prolonged the lifespan of mice substantially. Second, T lymphocytes generated from bone marrow-derived precursor cells became tolerant of the histocompatibility antigens of the thymus donor strain but remained normally reactive to third-party antigens. Third, allogeneic radiation chimeras did not survive as well as animals reconstituted with syngeneic cells, even when they were demonstrably tolerant in CML. Fourth, C57BL BMC maturing in a CBA host equipped with a C57BL thymus graft did not become tolerant of host antigens, indicating that extra-thymic tolerance does not occur in fully allogeneic--as opposed to semiallogeneic--chimeras. It is argued that the function of B lymphocytes and/or accessory cells is impaired in fully allogeneic radiation chimeras, and that the mortality observed was directly related to the resulting immunodeficiency. The relevance of the results described in this paper to clinical bone marrow transplantation is discussed

  7. Estrogen enhances expression of the complement C5a receptor and the C5a-agonist evoked calcium influx in hormone secreting neurons of the hypothalamus. (United States)

    Farkas, Imre; Varju, Patricia; Szabo, Emese; Hrabovszky, Erik; Okada, Noriko; Okada, Hidechika; Liposits, Zsolt


    In the present study we examined presence of the complement C5a receptor (C5aR) in hypothalamic neurosecretory neurons of the rodent brain and effect of estrogen on C5aR expression. Whole cell patch clamp measurements revealed that magnocellular neurons in the supraoptic and paraventricular nuclei of hypothalamic slices of the rats responded to the C5aR-agonist PL37-MAP peptide with calcium ion current pulses. Gonadotropin-releasing hormone (GnRH) producing neurons in slices of the preoptic area of the mice also reacted to the peptide treatment with inward calcium current. PL37-MAP was able to evoke the inward ion current of GnRH neurons in slices from ovariectomized animals. The amplitude of the inward pulses became higher in slices obtained from 17beta-estradiol (E2) substituted mice. Calcium imaging experiments demonstrated that PL37-MAP increased the intracellular calcium content in the culture of the GnRH-producing GT1-7 cell line in a concentration-dependent manner. Calcium imaging also showed that E2 pretreatment elevated the PL37-MAP evoked increase of the intracellular calcium content in the GT1-7 cells. The estrogen receptor blocker Faslodex in the medium prevented the E2-evoked increase of the PL37-MAP-triggered elevation of the intracellular calcium content in the GT1-7 cells demonstrating that the effect of E2 might be related to the presence of estrogen receptor. Real-time PCR experiments revealed that E2 increased the expression of C5aR mRNA in GT1-7 neurons, suggesting that an increased C5aR synthesis could be involved in the estrogenic modulation of calcium response. These data indicate that hypothalamic neuroendocrine neurons can integrate immune and neuroendocrine functions. Our results may serve a better understanding of the inflammatory and neurodegeneratory diseases of the hypothalamus and the related neuroendocrine and autonomic compensatory responses.

  8. Allogeneic radiation chimeras induced in SPF mice

    International Nuclear Information System (INIS)

    Sado, Toshihiko; Kamisaku, Hitoko


    During the past two decades much has been learned concerning the immunobiology of bone marrow chimeras induced in experimental animals as well as in man. However, from the basic as well as clinical points of view, there still remain many unsolved questions yet to be resolved. In this presentation, we discussed some of our recent results on the immunobiology of radiation chimeras induced in specific-pathogen-free (SPF) mice. These included the following: (a) contribution of graft versus host reaction (GVHR) as well non- GVHR mediated immunologic mechanism(s) to the expression of immunologic dysfunctions observed in allogeneic and certain semiallogeneic chimeras, (b) existence of immunoregulatory mechanism as a basis for the apparent lack of immunologic reactivity (tolerance) to the host- as well as to the donor-type alloantigens in situ in successful allogeneic bone marrow chimeras, and (c) the effect of microflora of the environment on the stability of such immunoregulatory mechanisms and its possible mechanism of action. (auth.)

  9. Lessons from Interspecies Mammalian Chimeras. (United States)

    Suchy, Fabian; Nakauchi, Hiromitsu


    As chimeras transform from beasts of Greek mythology into tools of contemporary bioscience, secrets of developmental biology and evolutionary divergence are being revealed. Recent advances in stem cell biology and interspecies chimerism have generated new models with extensive basic and translational applications, including generation of transplantable, patient-specific organs.

  10. Mechanism of chimera formation during the Multiple Displacement Amplification reaction

    Directory of Open Access Journals (Sweden)

    Stockwell Timothy B


    Full Text Available Abstract Background Multiple Displacement Amplification (MDA is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

  11. Serine integrase chimeras with activity in E. coli and HeLa cells

    Directory of Open Access Journals (Sweden)

    Alfonso P. Farruggio


    Full Text Available In recent years, application of serine integrases for genomic engineering has increased in popularity. The factor-independence and unidirectionality of these large serine recombinases makes them well suited for reactions such as site-directed vector integration and cassette exchange in a wide variety of organisms. In order to generate information that might be useful for altering the specificity of serine integrases and to improve their efficiency, we tested a hybridization strategy that has been successful with several small serine recombinases. We created chimeras derived from three characterized members of the serine integrase family, phiC31, phiBT1, and TG1 integrases, by joining their amino- and carboxy-terminal portions. We found that several phiBT1-phiC31 (BC and phiC31-TG1 (CT hybrid integrases are active in E. coli. BC chimeras function on native att-sites and on att-sites that are hybrids between those of the two donor enzymes, while CT chimeras only act on the latter att-sites. A BC hybrid, BC{−1}, was also active in human HeLa cells. Our work is the first to demonstrate chimeric serine integrase activity. This analysis sheds light on integrase structure and function, and establishes a potentially tractable means to probe the specificity of the thousands of putative large serine recombinases that have been revealed by bioinformatics studies.

  12. Proteomic Analysis Reveals the Leaf Color Regulation Mechanism in Chimera Hosta "Gold Standard" Leaves. (United States)

    Yu, Juanjuan; Zhang, Jinzheng; Zhao, Qi; Liu, Yuelu; Chen, Sixue; Guo, Hongliang; Shi, Lei; Dai, Shaojun


    Leaf color change of variegated leaves from chimera species is regulated by fine-tuned molecular mechanisms. Hosta "Gold Standard" is a typical chimera Hosta species with golden-green variegated leaves, which is an ideal material to investigate the molecular mechanisms of leaf variegation. In this study, the margin and center regions of young and mature leaves from Hosta "Gold Standard", as well as the leaves from plants after excess nitrogen fertilization were studied using physiological and comparative proteomic approaches. We identified 31 differentially expressed proteins in various regions and development stages of variegated leaves. Some of them may be related to the leaf color regulation in Hosta "Gold Standard". For example, cytosolic glutamine synthetase (GS1), heat shock protein 70 (Hsp70), and chloroplastic elongation factor G (cpEF-G) were involved in pigment-related nitrogen synthesis as well as protein synthesis and processing. By integrating the proteomics data with physiological results, we revealed the metabolic patterns of nitrogen metabolism, photosynthesis, energy supply, as well as chloroplast protein synthesis, import and processing in various leaf regions at different development stages. Additionally, chloroplast-localized proteoforms involved in nitrogen metabolism, photosynthesis and protein processing implied that post-translational modifications were crucial for leaf color regulation. These results provide new clues toward understanding the mechanisms of leaf color regulation in variegated leaves.

  13. Recurrence quantification analysis of chimera states

    International Nuclear Information System (INIS)

    Santos, M.S.; Szezech, J.D.; Batista, A.M.; Caldas, I.L.; Viana, R.L.; Lopes, S.R.


    Chimera states, characterised by coexistence of coherence and incoherence in coupled dynamical systems, have been found in various physical systems, such as mechanical oscillator networks and Josephson-junction arrays. We used recurrence plots to provide graphical representations of recurrent patterns and identify chimera states. Moreover, we show that recurrence plots can be used as a diagnostic of chimera states and also to identify the chimera collapse. - Highlights: • Chimera states have been found in various physical systems. • Recurrence plots is a graphical method useful to locate recurring patterns. • We used recurrence plots to identify the chimera states. • We show also the recurrence plots can identify the chimera collapse

  14. Recurrence quantification analysis of chimera states

    Energy Technology Data Exchange (ETDEWEB)

    Santos, M.S. [Pós-Graduação em Ciências/Física, Universidade Estadual de Ponta Grossa, 84030-900, Ponta Grossa, PR (Brazil); Szezech, J.D., E-mail: [Departamento de Matemática e Estatística, Universidade Estadual de Ponta Grossa, 84030-900, Ponta Grossa, PR (Brazil); Batista, A.M., E-mail: [Departamento de Matemática e Estatística, Universidade Estadual de Ponta Grossa, 84030-900, Ponta Grossa, PR (Brazil); Caldas, I.L. [Instituto de Física, Universidade de São Paulo, 05315-970, São Paulo, SP (Brazil); Viana, R.L.; Lopes, S.R. [Departamento de Física, Universidade Federal do Paraná, 81531-990, Curitiba, PR (Brazil)


    Chimera states, characterised by coexistence of coherence and incoherence in coupled dynamical systems, have been found in various physical systems, such as mechanical oscillator networks and Josephson-junction arrays. We used recurrence plots to provide graphical representations of recurrent patterns and identify chimera states. Moreover, we show that recurrence plots can be used as a diagnostic of chimera states and also to identify the chimera collapse. - Highlights: • Chimera states have been found in various physical systems. • Recurrence plots is a graphical method useful to locate recurring patterns. • We used recurrence plots to identify the chimera states. • We show also the recurrence plots can identify the chimera collapse.

  15. A phase one AR/C system design (United States)

    Kachmar, Peter M.; Polutchko, Robert J.; Matusky, Martin; Chu, William; Jackson, William; Montez, Moises


    The Phase One AR&C System Design integrates an evolutionary design based on the legacy of previous mission successes, flight tested components from manned Rendezvous and Proximity Operations (RPO) space programs, and additional AR&C components validated using proven methods. The Phase One system has a modular, open architecture with the standardized interfaces proposed for Space Station Freedom system architecture.

  16. Mechanisms of tolerance in murine radiation bone marrow chimeras. I. Nonspecific suppression of alloreactivity by spleen cells from early, but not late, chimeras

    International Nuclear Information System (INIS)

    Auchincloss, H. Jr.; Sachs, D.H.


    Allogeneic chimeras were prepared using lethally irradiated B6 hosts and untreated marrow from exsanguinated BALB/c donors. For about two months after reconstitution, chimeras had very weak antihost cell-mediated lymphocytotoxicity (CML) reactivity and little third-party alloreactivity. During this time a cell population capable of suppressing CML reactivity against both host and third-party alloantigens (i.e., antigen-nonspecific) was demonstrated in chimera spleens by in vitro mixing experiments. The putative suppressor cells were Thy-1-negative and radiation-sensitive. Subsequently, mature chimeras showed host tolerance and strong third-party alloreactivity. At this point suppressor mechanisms could no longer be demonstrated. These data are consistent with a clonal elimination hypothesis in that they do not provide evidence to indicate that maintenance of specific immune tolerance is mediated by an active suppressor mechanism

  17. Gargoyles, Grotesques, & Chimeras (United States)

    Wilbert, Nancy Corrigan


    Gargoyles, grotesques, and chimeras are scary, mythical (and sometimes humorous) creatures that have functional, decorative, and spiritual significance in medieval architecture. In this article, the author describes how her ceramics students created contemporary versions of gargoyles, chimeras, and grotesque faces. (Contains 1 online resource.)

  18. Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis. (United States)

    Hsu, Cheng-Lung; Liu, Jai-Shin; Wu, Po-Long; Guan, Hong-Hsiang; Chen, Yuh-Ling; Lin, An-Chi; Ting, Huei-Ju; Pang, See-Tong; Yeh, Shauh-Der; Ma, Wen-Lung; Chen, Chung-Jung; Wu, Wen-Guey; Chang, Chawnshang


    Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Angular distributions of projectiles following electron capture from C60 by 2.5-keV Ar8+

    International Nuclear Information System (INIS)

    Walch, B.; Thumm, U.; Stoeckli, M.; Cocke, C.L.; Klawikowski, S.


    Experimental measurements of the projectile angular distributions for 2.5-keV Ar 8+ ions capturing one to five electrons from a gas-phase C 60 target are presented. The number of captured electrons was determined by demanding a coincidence between the scattered projectile and a charge-state-analyzed intact C 60 recoil ion. The results are compared to calculations based on a dynamical classical overbarrier model. Good agreement is obtained only if the influence on the projectile trajectory by the large polarizability of the C 60 target is taken into account, thereby making the collective dielectric response of the cluster target observable in a scattering experiment. copyright 1998 The American Physical Society

  20. DNAzyme-mediated recovery of small recombinant RNAs from a 5S rRNA-derived chimera expressed in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Willson Richard C


    Full Text Available Abstract Background Manufacturing large quantities of recombinant RNAs by overexpression in a bacterial host is hampered by their instability in intracellular environment. To overcome this problem, an RNA of interest can be fused into a stable bacterial RNA for the resulting chimeric construct to accumulate in the cytoplasm to a sufficiently high level. Being supplemented with cost-effective procedures for isolation of the chimera from cells and recovery of the recombinant RNA from stabilizing scaffold, this strategy might become a viable alternative to the existing methods of chemical or enzymatic RNA synthesis. Results Sequence encoding a 71-nucleotide recombinant RNA was inserted into a plasmid-borne deletion mutant of the Vibrio proteolyticus 5S rRNA gene in place of helix III - loop C segment of the original 5S rRNA. After transformation into Escherichia coli, the chimeric RNA (3×pen aRNA was expressed constitutively from E. coli rrnB P1 and P2 promoters. The RNA chimera accumulated to levels that exceeded those of the host's 5S rRNA. A novel method relying on liquid-solid partitioning of cellular constituents was developed for isolation of total RNA from bacterial cells. This protocol avoids toxic chemicals, and is therefore more suitable for large scale RNA purification than traditional methods. A pair of biotinylated 8-17 DNAzymes was used to bring about the quantitative excision of the 71-nt recombinant RNA from the chimera. The recombinant RNA was isolated by sequence-specific capture on beads with immobilized complementary deoxyoligonucleotide, while DNAzymes were recovered by biotin affinity chromatography for reuse. Conclusions The feasibility of a fermentation-based approach for manufacturing large quantities of small RNAs in vivo using a "5S rRNA scaffold" strategy is demonstrated. The approach provides a route towards an economical method for the large-scale production of small RNAs including shRNAs, siRNAs and aptamers for use

  1. Multiple scroll wave chimera states (United States)

    Maistrenko, Volodymyr; Sudakov, Oleksandr; Osiv, Oleksiy; Maistrenko, Yuri


    We report the appearance of three-dimensional (3D) multiheaded chimera states that display cascades of self-organized spatiotemporal patterns of coexisting coherence and incoherence. We demonstrate that the number of incoherent chimera domains can grow additively under appropriate variations of the system parameters generating thereby head-adding cascades of the scroll wave chimeras. The phenomenon is derived for the Kuramoto model of N 3 identical phase oscillators placed in the unit 3D cube with periodic boundary conditions, parameters being the coupling radius r and phase lag α. To obtain the multiheaded chimeras, we perform the so-called `cloning procedure' as follows: choose a sample single-headed 3D chimera state, make appropriate scale transformation, and put some number of copies of them into the unit cube. After that, start numerical simulations with slightly perturbed initial conditions and continue them for a sufficiently long time to confirm or reject the state existence and stability. In this way it is found, that multiple scroll wave chimeras including those with incoherent rolls, Hopf links and trefoil knots admit this sort of multiheaded regeneration. On the other hand, multiple 3D chimeras without spiral rotations, like coherent and incoherent balls, tubes, crosses, and layers appear to be unstable and are destroyed rather fast even for arbitrarily small initial perturbations.

  2. Immune tolerance in radiation chimeras

    International Nuclear Information System (INIS)

    Awaya, Kazuhiko; Kuniki, Hiromichi; Neki, Miyuki


    Establishment of immune tolerance in radiation chimeras and the mechanism of maintaining it were discussed from certain points. Semiallogeneic radiation chimeras are mostly of long-living, and the hematopoietic organ of this individual consists mainly of the cells derived from the marrow donor, i. e., F 1 -type cells. F 1 -type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F 1 -skin graft maintains to be fresh as long as the host is alive, showing immune tolerance effective through its life. In establishment and maintenance of this immune tolerance, the suppressing mechanism of host-type or F 1 -type seems to be involved. The allogeneic radiation chimera has very poor long-survival rate compared with that of the semiallogeneic radiation chimera. To raise this survival rate, efforts are now being made from the immunological point of view. (Ueda, J.)

  3. Molecular characterization of the gerbil C5a receptor and identification of a transmembrane domain V amino acid that is crucial for small molecule antagonist interaction. (United States)

    Waters, Stephen M; Brodbeck, Robbin M; Steflik, Jeremy; Yu, Jianying; Baltazar, Carolyn; Peck, Amy E; Severance, Daniel; Zhang, Lu Yan; Currie, Kevin; Chenard, Bertrand L; Hutchison, Alan J; Maynard, George; Krause, James E


    Anaphylatoxin C5a is a potent inflammatory mediator associated with pathogenesis and progression of several inflammation-associated disorders. Small molecule C5a receptor (C5aR) antagonist development is hampered by species-specific receptor biology and the associated inability to use standard rat and mouse in vivo models. Gerbil is one rodent species reportedly responsive to small molecule C5aR antagonists with human C5aR affinity. We report the identification of the gerbil C5aR cDNA using a degenerate primer PCR cloning strategy. The nucleotide sequence revealed an open reading frame encoding a 347-amino acid protein. The cloned receptor (expressed in Sf9 cells) bound recombinant human C5a with nanomolar affinity. Alignment of the gerbil C5aR sequence with those from other species showed that a Trp residue in transmembrane domain V is the only transmembrane domain amino acid unique to small molecule C5aR antagonist-responsive species (i.e. gerbil, human, and non-human primate). Site-directed mutagenesis was used to generate human and mouse C5aRs with a residue exchange of this Trp residue. Mutation of Trp to Leu in human C5aR completely eliminated small molecule antagonist-receptor interaction. In contrast, mutation of Leu to Trp in mouse C5aR enabled small molecule antagonist-receptor interaction. This crucial Trp residue is located deeper within transmembrane domain V than residues reportedly involved in C5a- and cyclic peptide C5a antagonist-receptor interaction, suggesting a novel interaction site(s) for small molecule antagonists. These data provide insight into the basis for small molecule antagonist species selectivity and further define sites critical for C5aR activation and function.

  4. Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex

    International Nuclear Information System (INIS)

    Onoe, K.; Yasumizu, R.; Oh-Ishi, T.; Kakinuma, M.; Good, R.A.; Morikawa, K.


    Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient

  5. Structure of 10Be and 16C nuclei via break-up reactions studied with the 4π Chimera array (United States)

    Dell'Aquila, D.; Acosta, L.; Amorini, F.; Andolina, R.; Auditore, L.; Berceanu, I.; Cardella, G.; Chatterjiee, M. B.; De Filippo, E.; Francalanza, L.; Gnoffo, B.; Grzeszczuk, A.; Lanzalone, G.; Lombardo, I.; Martorana, N.; Minniti, T.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Pop, A.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Rosato, E.; Russotto, P.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.


    The study of cluster states in neutron-rich Be and C isotopes is a subject of interest in Nuclear Physics. These states should be characterized by high deformation where α-clusters are bounded by valence neutrons. We performed a spectroscopic study of 10Be and 16C isotopes via projectile break-up reactions, by using radioactive beams produced at the INFN-LNS FRIBs facility and the Chimera 4π array. The possible evidence of a new 10Be state at 13.5 MeV excitation energy was found in the 6He+4He disintegration channel. The spectroscopy of 16C was studied via the 6He+10Be break-up channel; in this case we found the indication of a possible new state at about 20.6 MeV.

  6. Synthetic of Zr2Al3C5 material

    International Nuclear Information System (INIS)

    Leela-Adisorn, U.; Yamaguchi, A.


    Synthesis method of Zr 2 Al 3 C 5 via solid state reaction between Al, ZrC and carbon powder was studied. Al-ZrC-C compact with equivalent mol ratio of Zr 2 Al 3 C 5 was heated up to 1600 C in Ar atmosphere for 1 h and 4 h but ZrC phase still existed as major phase with very small amount of Zr 2 Al 3 C 5 . Because ZrC started to oxidize at low temperature under very low oxygen partial pressure, the same mol ratio of Al-ZrC-C compact was heated at 1600 C in vacuum for 1 h as parallel test. After firing in vacuum, some carbon still exist with small amount of AlZrC 2 occurred with Zr 2 Al 3 C 5 as a main phase, but no ZrC was found. Different result from firing in Ar atmosphere and in vacuum had been discussed here. It was believed that very small amount of impurities in Ar had some effect on the formation of Al-Zr-C compound. The effect of very small amount of impurities in Ar was studied by thermal analysis (DTA/TG) and XRD. It was found that very small amount of impurities in Ar has effect on the reaction between Al, ZrC and carbon by diffusion through the surface and form Zr-C-O-N solid solution. This solid solution cannot differentiate from ZrC by XRD. With help of thermal analysis method (DTA/TG), Zr-C-O-N solid solution can be differentiated from ZrC. Therefore, synthesis of Al-Zr-C compound should be done in vacuum. Zr 2 Al 3 C 5 can be prepared from mixture of Al-ZrC-C with excess amount of Al at 1600 C for 1 h. (orig.)

  7. Enstore with Chimera namespace provider

    International Nuclear Information System (INIS)

    Litvintsev, Dmitry; Moibenko, Alexander; Oleynik, Gene; Zalokar, Michael


    Enstore is a mass storage system developed by Fermilab that provides distributed access and management of data stored on tapes. It uses a namespace service, PNFS, developed by DESY to provide a filesystem-like view of the stored data. PNFS is a legacy product and is being replaced by a new implementation, called Chimera, which is also developed by DESY. Chimera offers multiple advantages over PNFS in terms of performance and functionality. The Enstore client component, encp, has been modified to work with Chimera, as well as with any other namespace provider. We performed high load end-to-end acceptance test of Enstore with the Chimera namespace. This paper describes the modifications to Enstore, the test procedure and the results of the acceptance testing.

  8. Non-identical multiplexing promotes chimera states (United States)

    Ghosh, Saptarshi; Zakharova, Anna; Jalan, Sarika


    We present the emergence of chimeras, a state referring to coexistence of partly coherent, partly incoherent dynamics in networks of identical oscillators, in a multiplex network consisting of two non-identical layers which are interconnected. We demonstrate that the parameter range displaying the chimera state in the homogeneous first layer of the multiplex networks can be tuned by changing the link density or connection architecture of the same nodes in the second layer. We focus on the impact of the interconnected second layer on the enlargement or shrinking of the coupling regime for which chimeras are displayed in the homogeneous first layer. We find that a denser homogeneous second layer promotes chimera in a sparse first layer, where chimeras do not occur in isolation. Furthermore, while a dense connection density is required for the second layer if it is homogeneous, this is not true if the second layer is inhomogeneous. We demonstrate that a sparse inhomogeneous second layer which is common in real-world complex systems can promote chimera states in a sparse homogeneous first layer.

  9. Nonspecific suppressor elements in murine allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.


    Spleen cells from long-term mouse allogeneic radiation chimeras were tested for their ability to modulate the graft-versus-host (GVH) or plaque-forming cell (PFC) response of normal lymphocytes transplanted in lethally x-irradiated recipients. In vivo GVH proliferation of normal lymphocytes (syngeneic to donor cells of the chimera) against antigens of host-type in which the chimeric state had been established was reduced by chimera cells. Inhibition varied, some chimeras suppressing GVH more than others and a few not suppressing at all. The suppressive effect was abrogated if the chimera cells were treated with anti-THETA; treatment with anti-IgM did not eliminate this activity. When mixtures of normal donor lymphocytes and chimera cells were given to irradiated recipients genetically different from host or donor, reduction of donor cell GVH also occurred. Further, chimera cells reduced the GVH activity of normal host cells in irradiated recipients differing from the host at one H-2 locus and from the donor at minor histocompatibility loci. The modulating effect of spleen cells from chimeras on the PFC response by normal lymphocytes also varied. Six chimeras induced a 25 to 90% suppression, two enhanced the response, and one showed no effect. Where suppression occurred, treatment of chimera cells with anti-THETA most often, but not always, restored PFC production. Our results show that the suppressive action of splenic lymphoid cells by chimeras is highly nonspecific and variable in expression. We suggest that tolerance in chimeras may be mediated by nonspecific suppressor elements leading to unresponsiveness to a variety of antigens including SRBC

  10. Allogeneic radiation chimeras respond to TNP-modified donor and host targets

    International Nuclear Information System (INIS)

    Lattime, E.C.; Gershon, H.E.; Stutman, O.


    Tolerance to major histocompatibility antigens as well as the ability to mount a cytotoxic response to hapten-modified cells of bone marrow donor and host origin was studied in allogeneic radiation chimeras. Lethally irradiated (C57BL/6 x DBA/2)F1 hosts reconstituted with anti-Thy 1.2 + C-treated bone marrow from (C57BL/6 x CBA)F1 mice showed tolerance to the MHC antigens of the three parental strains as measured by MLC and CML assay. The chimeras responded normally to unrelated allogeneic cells. Chimeric animals generated a cytotoxic response to hapten-modified cells of both donor (CBA) and host (DBA/2) haplotypes, as well as to C57BL/6, demonstrating that tolerance to the hapten-presenting host haplotype is sufficient to allow a cytotoxic antihapten response, and that processing through a semiallogeneic host environment does not affect the ability to generate a response to hapten in conjunction with self-determinants. Chimeras failed to mount a cytotoxic response to hapten presented on nontolerated allogeneic spleen cells

  11. Mobility-induced persistent chimera states (United States)

    Petrungaro, Gabriela; Uriu, Koichiro; Morelli, Luis G.


    We study the dynamics of mobile, locally coupled identical oscillators in the presence of coupling delays. We find different kinds of chimera states in which coherent in-phase and antiphase domains coexist with incoherent domains. These chimera states are dynamic and can persist for long times for intermediate mobility values. We discuss the mechanisms leading to the formation of these chimera states in different mobility regimes. This finding could be relevant for natural and technological systems composed of mobile communicating agents.

  12. Solvable model for chimera states of coupled oscillators. (United States)

    Abrams, Daniel M; Mirollo, Rennie; Strogatz, Steven H; Wiley, Daniel A


    Networks of identical, symmetrically coupled oscillators can spontaneously split into synchronized and desynchronized subpopulations. Such chimera states were discovered in 2002, but are not well understood theoretically. Here we obtain the first exact results about the stability, dynamics, and bifurcations of chimera states by analyzing a minimal model consisting of two interacting populations of oscillators. Along with a completely synchronous state, the system displays stable chimeras, breathing chimeras, and saddle-node, Hopf, and homoclinic bifurcations of chimeras.

  13. Construction of RNA-Quantum Dot Chimera for Nanoscale Resistive Biomemory Application. (United States)

    Lee, Taek; Yagati, Ajay Kumar; Pi, Fengmei; Sharma, Ashwani; Choi, Jeong-Woo; Guo, Peixuan


    RNA nanotechnology offers advantages to construct thermally and chemically stable nanoparticles with well-defined shape and structure. Here we report the development of an RNA-QD (quantum dot) chimera for resistive biomolecular memory application. Each QD holds two copies of the pRNA three-way junction (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor. The fixed quantity of two RNAs per QD was achieved by immobilizing the pRNA-3WJ with a Sephadex aptamer for resin binding. Two thiolated pRNA-3WJ serve as two feet of the chimera that stand on the gold plate. The RNA nanostructure served as both an insulator and a mediator to provide defined distance between the QD and gold. Immobilization of the chimera nanoparticle was confirmed with scanning tunneling microscopy. As revealed by scanning tunneling spectroscopy, the conjugated pRNA-3WJ-QD chimera exhibited an excellent electrical bistability signal for biomolecular memory function, demonstrating great potential for the development of resistive biomolecular memory and a nano-bio-inspired electronic device for information processing and computing.

  14. Chimera states in three dimensions

    International Nuclear Information System (INIS)

    Maistrenko, Yuri; Sudakov, Oleksandr; Osiv, Oleksiy; Maistrenko, Volodymyr


    The chimera state is a recently discovered dynamical phenomenon in arrays of nonlocally coupled oscillators, that displays a self-organized spatial pattern of coexisting coherence and incoherence. In this paper, the first evidence of three-dimensional chimera states is reported for the Kuramoto model of phase oscillators in 3D grid topology with periodic boundary conditions. Systematic analysis of the dependence of the spatiotemporal dynamics on the range and strength of coupling shows that there are two principal classes of the chimera patterns which exist in large domains of the parameter space: (I) oscillating and (II) spirally rotating. Characteristic examples from the first class include coherent as well as incoherent balls, tubes, crosses, and layers in incoherent or coherent surrounding; the second class includes scroll waves with incoherent, randomized rolls of different modality and dynamics. Numerical simulations started from various initial conditions indicate that the states are stable over the integration time. Videos of the dynamics of the chimera states are presented in supplementary material. It is concluded that three-dimensional chimera states, which are novel spatiotemporal patterns involving the coexistence of coherent and incoherent domains, can represent one of the inherent features of nature. (paper)

  15. The Dependence of Chimera States on Initial Conditions

    International Nuclear Information System (INIS)

    Feng Yue-E; Li Hai-Hong


    A chimera state consisting of both coherent and incoherent groups is a fascinating spatial pattern in non-locally coupled identical oscillators. It is thought that random initial conditions hardly evolve to chimera states. In this work, we study the dependence of chimera states on initial conditions. We show that random initial conditions may lead to chimera states and the chance of realizing chimera states becomes increasing when the model parameters are moving away from the boundary of their stable regime. (paper)

  16. Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

    International Nuclear Information System (INIS)

    Pierpaoli, W.


    Haemopoietic radiation chimeras across the H-2 barrier (BALB/cC57B1/6; H-2sup(d) → H-2sup(b) chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57B1/6 mice was injected i.p. into established chimeras (H-2sup(d) → H-2sup(b)). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/cC57B1/6 or C57B1/6 → BALB/c chimeras. However, inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/cC57B1/6 chimeras failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2sup(d) → H-2sup(b) chimeras displayed complete resistance to inoculation of leukaemogenic H-2sup(b) restricted RadLV while all H-2sup(b) → H-2sup(b), syngeneically reconstituted mice developed disseminated leukaemia. (author)

  17. H-2 restriction of the T cell response to chemically induced tumors: evidence from F1 → parent chimeras

    International Nuclear Information System (INIS)

    Lannin, D.R.; Yu, S.; McKhann, C.F.


    It has been well established that T cells that react to tumor antigen on virus-induced tumors must share H-2D or H-2K specificities with the tumor. It has been impossible to perform similar studies with chemically induced tumors because each chemically induced tumor expresses a unique tumor antigen that cannot be studied in association with other H-2 types. This study provies evidence that H-2 recognition is also necessary for recognition of chemically induced tumors. We have found that F 1 → parent chimeras preferentially recognize chemically induced tumors of parental H-2 type. C3H/HeJ and C57BL/6 mice were lethally irradiated and restored with (C3H x C57BL/6) F 1 hybrid bone marrow. The F 1 → C3H chimera but not the F 1 → C57BL/6 chimera was able to respond to a C3H fibrosarcoma in mixed lymphocyte-tumor cell culture and also to neutralize the tumor in an in vivo tumor neutralization assay. On the other hand, the F 1 → C57BL/6 chimera but not the F 1 → C3H chimera was able to kill the C57BL/6 lymphoma EL4 in an in vitro cytotoxicity assay. Both chimeras were tolerant to C3H and C57BL/6 alloantigens but could respond normally to Con A and to BALB/c spleen cells in mixed lymphocyte cultures and cytotoxicity assay

  18. Engineering human cytochrome P450 enzymes into catalytically self-sufficient chimeras using molecular Lego. (United States)

    Dodhia, Vikash Rajnikant; Fantuzzi, Andrea; Gilardi, Gianfranco


    The membrane-bound human cytochrome P450s have essential roles in the metabolism of endogenous compounds and drugs. Presented here are the results on the construction and characterization of three fusion proteins containing the N-terminally modified human cytochrome P450s CYP2C9, CY2C19 and CYP3A4 fused to the soluble NADPH-dependent oxidoreductase domain of CYP102A1 from Bacillus megaterium. The constructs, CYP2C9/BMR, CYP2C19/BMR and CYP3A4/BMR are well expressed in Escherichia coli as holo proteins. The chimeras can be purified in the absence of detergent and the purified enzymes are both active and correctly folded in the absence of detergent, as demonstrated by circular dichroism and functional studies. Additionally, in comparison with the parent P450 enzyme, these chimeras have greatly improved solubility properties. The chimeras are catalytically self-sufficient and present turnover rates similar to those reported for the native enzymes in reconstituted systems, unlike previously reported mammalian cytochrome P450 fusion proteins. Furthermore the specific activities of these chimeras are not dependent on the enzyme concentration present in the reaction buffer and they do not require the addition of accessory proteins, detergents or phospholipids to be fully active. The solubility, catalytic self-sufficiency and wild-type like activities of these chimeras would greatly simplify the studies of cytochrome P450 mediated drug metabolism in solution.

  19. C5a receptor deficiency alters energy utilization and fat storage.

    Directory of Open Access Journals (Sweden)

    Christian Roy

    Full Text Available To investigate the impact of whole body C5a receptor (C5aR deficiency on energy metabolism and fat storage.Male wildtype (WT and C5aR knockout (C5aRKO mice were fed a low fat (CHOW or a high fat high sucrose diet-induced obesity (DIO diet for 14 weeks. Body weight and food intake were measured weekly. Indirect calorimetry, dietary fatload clearance, insulin and glucose tolerance tests were also evaluated. Liver, muscle and adipose tissue mRNA gene expression were measured by RT-PCR.At week one and 12, C5aRKO mice on DIO had increased oxygen consumption. After 12 weeks, although food intake was comparable, C5aRKO mice had lower body weight (-7% CHOW, -12% DIO as well as smaller gonadal (-38% CHOW, -36% DIO and inguinal (-29% CHOW, -30% DIO fat pads than their WT counterparts. Conversely, in WT mice, C5aR was upregulated in DIO vs CHOW diets in gonadal adipose tissue, muscle and liver, while C5L2 mRNA expression was lower in C5aRKO on both diet. Furthermore, blood analysis showed lower plasma triglyceride and non-esterified fatty acid levels in both C5aRKO groups, with faster postprandial triglyceride clearance after a fatload. Additionally, C5aRKO mice showed lower CD36 expression in gonadal and muscle on both diets, while DGAT1 expression was higher in gonadal (CHOW and liver (CHOW and DIO and PPARγ was increased in muscle and liver.These observations point towards a role (either direct or indirect for C5aR in energy expenditure and fat storage, suggesting a dual role for C5aR in metabolism as well as in immunity.

  20. Enhancing UCSF Chimera through web services. (United States)

    Huang, Conrad C; Meng, Elaine C; Morris, John H; Pettersen, Eric F; Ferrin, Thomas E


    Integrating access to web services with desktop applications allows for an expanded set of application features, including performing computationally intensive tasks and convenient searches of databases. We describe how we have enhanced UCSF Chimera (, a program for the interactive visualization and analysis of molecular structures and related data, through the addition of several web services ( By streamlining access to web services, including the entire job submission, monitoring and retrieval process, Chimera makes it simpler for users to focus on their science projects rather than data manipulation. Chimera uses Opal, a toolkit for wrapping scientific applications as web services, to provide scalable and transparent access to several popular software packages. We illustrate Chimera's use of web services with an example workflow that interleaves use of these services with interactive manipulation of molecular sequences and structures, and we provide an example Python program to demonstrate how easily Opal-based web services can be accessed from within an application. Web server availability: © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Chimera and phase-cluster states in populations of coupled chemical oscillators (United States)

    Tinsley, Mark R.; Nkomo, Simbarashe; Showalter, Kenneth


    Populations of coupled oscillators may exhibit two coexisting subpopulations, one with synchronized oscillations and the other with unsynchronized oscillations, even though all of the oscillators are coupled to each other in an equivalent manner. This phenomenon, discovered about ten years ago in theoretical studies, was then further characterized and named the chimera state after the Greek mythological creature made up of different animals. The highly counterintuitive coexistence of coherent and incoherent oscillations in populations of identical oscillators, each with an equivalent coupling structure, inspired great interest and a flurry of theoretical activity. Here we report on experimental studies of chimera states and their relation to other synchronization states in populations of coupled chemical oscillators. Our experiments with coupled Belousov-Zhabotinsky oscillators and corresponding simulations reveal chimera behaviour that differs significantly from the behaviour found in theoretical studies of phase-oscillator models.

  2. Chimera states in bipartite networks of FitzHugh-Nagumo oscillators (United States)

    Wu, Zhi-Min; Cheng, Hong-Yan; Feng, Yuee; Li, Hai-Hong; Dai, Qiong-Lin; Yang, Jun-Zhong


    Chimera states consisting of spatially coherent and incoherent domains have been observed in different topologies such as rings, spheres, and complex networks. In this paper, we investigate bipartite networks of nonlocally coupled FitzHugh-Nagumo (FHN) oscillators in which the units are allocated evenly to two layers, and FHN units interact with each other only when they are in different layers. We report the existence of chimera states in bipartite networks. Owing to the interplay between chimera states in the two layers, many types of chimera states such as in-phase chimera states, antiphase chimera states, and out-of-phase chimera states are classified. Stability diagrams of several typical chimera states in the coupling strength-coupling radius plane, which show strong multistability of chimera states, are explored.

  3. Tools for integrated sequence-structure analysis with UCSF Chimera

    Directory of Open Access Journals (Sweden)

    Huang Conrad C


    Full Text Available Abstract Background Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual aspects of such work, there is a need for interactive visualization tools that: (a provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit; (c can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals. Results The molecular graphics program UCSF Chimera includes a suite of tools for interactive analyses of sequences and structures. Structures automatically associate with sequences in imported alignments, allowing many kinds of crosstalk. A novel method is provided to superimpose structures in the absence of a pre-existing sequence alignment. The method uses both sequence and secondary structure, and can match even structures with very low sequence identity. Another tool constructs structure-based sequence alignments from superpositions of two or more proteins. Chimera is designed to be extensible, and mechanisms for incorporating user-specific data without Chimera code development are also provided. Conclusion The tools described here apply to many problems involving comparison and analysis of protein structures and their sequences. Chimera includes complete documentation and is intended for use by a wide range of scientists, not just those in the computational disciplines. UCSF Chimera is free for non-commercial use and is

  4. Greengenes: Chimera-checked 16S rRNA gene database and workbenchcompatible in ARB

    Energy Technology Data Exchange (ETDEWEB)

    DeSantis, T.Z.; Hugenholtz, P.; Larsen, N.; Rojas, M.; Brodie,E.L; Keller, K.; Huber, T.; Dalevi, D.; Hu, P.; Andersen, G.L.


    A 16S rRNA gene database ( addresses limitations of public repositories by providing chimera-screening, standard alignments and taxonomic classification using multiple published taxonomies. It was revealed that incongruent taxonomic nomenclature exists among curators even at the phylum-level. Putative chimeras were identified in 3% of environmental sequences and 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages within the Archaea and Bacteria.

  5. The Complement C3a-C3aR Axis Promotes Development of Thoracic Aortic Dissection via Regulation of MMP2 Expression. (United States)

    Ren, Weihong; Liu, Yan; Wang, Xuerui; Piao, Chunmei; Ma, Youcai; Qiu, Shulan; Jia, Lixin; Chen, Boya; Wang, Yuan; Jiang, Wenjian; Zheng, Shuai; Liu, Chang; Dai, Nan; Lan, Feng; Zhang, Hongjia; Song, Wen-Chao; Du, Jie


    Thoracic aortic dissection (TAD), once ruptured, is devastating to patients, and no effective pharmaceutical therapy is available. Anaphylatoxins released by complement activation are involved in a variety of diseases. However, the role of the complement system in TAD is unknown. We found that plasma levels of C3a, C4a, and C5a were significantly increased in patients with TAD. Elevated circulating C3a levels were also detected in the developmental process of mouse TAD, which was induced by β-aminopropionitrile monofumarate (BAPN) treatment, with enhanced expression of C1q and properdin in mouse dissected aortas. These findings indicated activation of classical and alternative complement pathways. Further, expression of C3aR was obviously increased in smooth muscle cells of human and mouse dissected aortas, and knockout of C3aR notably inhibited BAPN-induced formation and rupture of TAD in mice. C3aR antagonist administered pre- and post-BAPN treatment attenuated the development of TAD. We found that C3aR knockout decreased matrix metalloproteinase 2 (MMP2) expression in BAPN-treated mice. Additionally, recombinant C3a stimulation enhanced MMP2 expression and activation in smooth muscle cells that were subjected to mechanical stretch. Finally, we generated MMP2-knockdown mice by in vivo MMP2 short hairpin RNA delivery using recombinant adeno-associated virus and found that MMP2 deficiency significantly reduced the formation of TAD. Therefore, our study suggests that the C3a - C3aR axis contributes to the development of TAD via regulation of MMP2 expression. Targeting the C3a-C3aR axis may represent a strategy for inhibiting the formation of TAD. Copyright © 2018 by The American Association of Immunologists, Inc.

  6. Mechanisms of appearance of amplitude and phase chimera states in ensembles of nonlocally coupled chaotic systems (United States)

    Bogomolov, Sergey A.; Slepnev, Andrei V.; Strelkova, Galina I.; Schöll, Eckehard; Anishchenko, Vadim S.


    We explore the bifurcation transition from coherence to incoherence in ensembles of nonlocally coupled chaotic systems. It is firstly shown that two types of chimera states, namely, amplitude and phase, can be found in a network of coupled logistic maps, while only amplitude chimera states can be observed in a ring of continuous-time chaotic systems. We reveal a bifurcation mechanism by analyzing the evolution of space-time profiles and the coupling function with varying coupling coefficient and formulate the necessary and sufficient conditions for realizing the chimera states in the ensembles.

  7. Bioassays for TSH Receptor Autoantibodies, from FRTL-5 Cells to TSH Receptor-LH/CG Receptor Chimeras: The Contribution of Leonard D. Kohn. (United States)

    Giuliani, Cesidio; Saji, Motoyasu; Bucci, Ines; Napolitano, Giorgio


    Since the discovery 60 years ago of the "long-acting thyroid stimulator" by Adams and Purves, great progress has been made in the detection of thyroid-stimulating hormone (TSH) receptor (TSHR) autoantibodies (TRAbs) in Graves' disease. Today, commercial assays are available that can detect TRAbs with high accuracy and provide diagnostic and prognostic evaluation of patients with Graves' disease. The present review focuses on the development of TRAbs bioassays, and particularly on the role that Leonard D. Kohn had in this. Indeed, 30 years ago, the Kohn group developed a bioassay based on the use of FRTL-5 cells that was characterized by high reproducibility, feasibility, and diagnostic accuracy. Using this FRTL-5 bioassay, Kohn and his colleagues were the first to develop monoclonal antibodies (moAbs) against the TSHR. Furthermore, they demonstrated the multifaceted functional nature of TRAbs in patients with Graves' disease, with the identification of stimulating and blocking TRAbs, and even antibodies that activated pathways other than cAMP. After the cloning of the TSHR, the Kohn laboratory constructed human TSHR-rat luteinizing hormone/chorionic gonadotropin receptor chimeras. This paved the way to a new bioassay based on the use of non-thyroid cells transfected with the Mc4 chimera. The new Mc4 bioassay is characterized by high diagnostic and prognostic accuracy, greater than for other assays. The availability of a commercial kit based on the Mc4 chimera is spreading the use of this assay worldwide, indicating its benefits for these patients with Graves' disease. This review also describes the main contributions made by other researchers in TSHR molecular biology and TRAbs assay, especially with the development of highly potent moAbs. A comparison of the diagnostic accuracies of the main TRAbs assays, as both immunoassays and bioassays, is also provided.

  8. Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice. (United States)

    Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis


    The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells.

  9. Chimera States in Mechanical Oscillator Networks


    Martens, Erik Andreas; Thutupalli, Shashi; Fourrière, Antoine; Hallatschek, Oskar


    The synchronization of coupled oscillators is a fascinating manifestation of self-organization that nature uses to orchestrate essential processes of life, such as the beating of the heart. Although it was long thought that synchrony and disorder were mutually exclusive steady states for a network of identical oscillators, numerous theoretical studies in recent years have revealed the intriguing possibility of “chimera states,” in which the symmetry of the oscillator population is broken into...

  10. Refining the intrinsic chimera flap: a review. (United States)

    Agarwal, Jayant P; Agarwal, Shailesh; Adler, Neta; Gottlieb, Lawrence J


    Reconstruction of complex tissue deficiencies in which each missing component is in a different spatial relationship to each other can be particularly challenging, especially in patients with limited recipient vessels. The chimera flap design is uniquely suited to reconstruct these deformities. Chimera flaps have been previously defined in many ways with 2 main categories: prefabricated or intrinsic. Herein we attempt to clarify the definition of a true intrinsic chimeric flap and provide examples of how these constructs provide a method for reconstruction of complex defects. The versatility of the intrinsic chimera flap and its procurement from 7 different vascular systems is described. A clarification of the definition of a true intrinsic chimera flap is described. In addition, construction of flaps from the lateral femoral circumflex, deep circumflex iliac, inferior gluteal, peroneal, subscapular, thoracodorsal, and radial arterial systems is described to showcase the versatility of these chimera flaps. A true intrinsic chimera flap must consist of more than a single tissue type. Each of the tissue components receives its blood flow from separate vascular branches or perforators that are connected to a single vascular source. These vascular branches must be of appropriate length to allow for insetting with 3-dimensional spatial freedom. There are a multitude of sites from which true intrinsic chimera flaps may be harvested.

  11. Quantum walk on a chimera graph (United States)

    Xu, Shu; Sun, Xiangxiang; Wu, Jizhou; Zhang, Wei-Wei; Arshed, Nigum; Sanders, Barry C.


    We analyse a continuous-time quantum walk on a chimera graph, which is a graph of choice for designing quantum annealers, and we discover beautiful quantum walk features such as localization that starkly distinguishes classical from quantum behaviour. Motivated by technological thrusts, we study continuous-time quantum walk on enhanced variants of the chimera graph and on diminished chimera graph with a random removal of vertices. We explain the quantum walk by constructing a generating set for a suitable subgroup of graph isomorphisms and corresponding symmetry operators that commute with the quantum walk Hamiltonian; the Hamiltonian and these symmetry operators provide a complete set of labels for the spectrum and the stationary states. Our quantum walk characterization of the chimera graph and its variants yields valuable insights into graphs used for designing quantum-annealers.

  12. Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

    DEFF Research Database (Denmark)

    Laursen, Nick Stub; Andersen, Kasper Røjkjær; Braren, Ingke


    with a protease subunit (Bb or C2a). We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. The structures reveal a parallel two-point attachment between C5 and CVF, where the presence of SSL7 only...

  13. The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance. (United States)

    Phieler, Julia; Chung, Kyoung-Jin; Chatzigeorgiou, Antonios; Klotzsche-von Ameln, Anne; Garcia-Martin, Ruben; Sprott, David; Moisidou, Maria; Tzanavari, Theodora; Ludwig, Barbara; Baraban, Elena; Ehrhart-Bornstein, Monika; Bornstein, Stefan R; Mziaut, Hassan; Solimena, Michele; Karalis, Katia P; Economopoulou, Matina; Lambris, John D; Chavakis, Triantafyllos


    Obese adipose tissue (AT) inflammation contributes critically to development of insulin resistance. The complement anaphylatoxin C5a receptor (C5aR) has been implicated in inflammatory processes and as regulator of macrophage activation and polarization. However, the role of C5aR in obesity and AT inflammation has not been addressed. We engaged the model of diet-induced obesity and found that expression of C5aR was significantly upregulated in the obese AT, compared with lean AT. In addition, C5a was present in obese AT in the proximity of macrophage-rich crownlike structures. C5aR-sufficient and -deficient mice were fed a high-fat diet (HFD) or a normal diet (ND). C5aR deficiency was associated with increased AT weight upon ND feeding in males, but not in females, and with increased adipocyte size upon ND and HFD conditions in males. However, obese C5aR(-/-) mice displayed improved systemic and AT insulin sensitivity. Improved AT insulin sensitivity in C5aR(-/-) mice was associated with reduced accumulation of total and proinflammatory M1 macrophages in the obese AT, increased expression of IL-10, and decreased AT fibrosis. In contrast, no difference in β cell mass was observed owing to C5aR deficiency under an HFD. These results suggest that C5aR contributes to macrophage accumulation and M1 polarization in the obese AT and thereby to AT dysfunction and development of AT insulin resistance.

  14. Chimera States in Neural Oscillators (United States)

    Bahar, Sonya; Glaze, Tera


    Chimera states have recently been explored both theoretically and experimentally, in various coupled nonlinear oscillators, ranging from phase-oscillator models to coupled chemical reactions. In a chimera state, both coherent and incoherent (or synchronized and desynchronized) states occur simultaneously in populations of identical oscillators. We investigate chimera behavior in a population of neural oscillators using the Huber-Braun model, a Hodgkin-Huxley-like model originally developed to characterize the temperature-dependent bursting behavior of mammalian cold receptors. One population of neurons is allowed to synchronize, with each neuron receiving input from all the others in its group (global within-group coupling). Subsequently, a second population of identical neurons is placed under an identical global within-group coupling, and the two populations are also coupled to each other (between-group coupling). For certain values of the coupling constants, the neurons in the two populations exhibit radically different synchronization behavior. We will discuss the range of chimera activity in the model, and discuss its implications for actual neural activity, such as unihemispheric sleep.

  15. Samsun İli Salıpazarı İlçesi Arıcılığının ve Arıcı-Birlik İlişkilerinin İncelenmesi

    Directory of Open Access Journals (Sweden)

    Murat Emir


    Full Text Available Bu araştırma, Samsun ili Salıpazarı ilçesindeki arıcıların sosyo-ekonomik ve üretim yapısı ile arıcı-birlik ilişkilerini ortaya koymayı amaçlamıştır. Araştırma verileri sistematik örnekleme metoduyla seçilmiş 30 arıcıdan 2014-2015 üretim yılı esas alınarak anket yoluyla ve alan çalışmasındaki gözlemlerle elde edilmiştir. Arıcıların sosyo-ekonomik yapısı, klasik ekonomik analizle ortaya konulmuştur. Verilerin analizinde tanımlayıcı istatistikler kullanılmıştır.  Araştırma sonuçlarına göre; arıcılar, arıcılığı ek gelir amaçlı, kısa mesafeli göçer veya sabit arıcılık olarak yapmaktadırlar. Ortalama 52 yaşında olan arıcılar, 15 yıllık arıcılık deneyimine sahip olup, 8 yıl örgün eğitim görmüşlerdir. İlçede arıcıların ortalama 90 kolonisi olup, koloni başına bal veriminin 15 kg olduğu saptanmıştır. Son yıllarda azalan verimin en önemli nedeni olarak yöre şartlarına uyum sağlamayan arı ırkları gösterilmiştir. Arıcıların %93’ü Varroa destructor ile mücadele ettiğini belirtmiştir. İlçede süzme çiçek balı 25-50 TL kg-1 satılırken; kestane balı 55-90 TL kg-1 arasında pazarlanmaktadır. Arıcıların %80’i birlik faaliyetlerini yararlı bulmaktadır. İlçe gençleri meslek yüksekokullarında açılacak arıcılık bölümlerinde eğitilerek arıcılığa özendirilmeli ve arıcı ortalama yaşı düşürülerek yeni neslin arıcılık mesleğini sahiplenmesi sağlanmalıdır. Varroa destructor mücadelesi için entegre ilaçlama yapılmalıdır. Birliklerin düzenleneceği eğitimlerde, pazarlama, ana arı yetiştiriciliği, arı hastalıkları ve tedavi yöntemleri konularına yer verilmesi ve bu eğitimlerin uygulamalı olması ilçe ve ülke arıcılığında var olan yanlış uygulamaların azaltılmasına katkı sağlayabilecektir.

  16. Generation of an adenovirus-parvovirus chimera with enhanced oncolytic potential. (United States)

    El-Andaloussi, Nazim; Bonifati, Serena; Kaufmann, Johanna K; Mailly, Laurent; Daeffler, Laurent; Deryckère, François; Nettelbeck, Dirk M; Rommelaere, Jean; Marchini, Antonio


    In this study, our goal was to generate a chimeric adenovirus-parvovirus (Ad-PV) vector that combines the high-titer and efficient gene transfer of adenovirus with the anticancer potential of rodent parvovirus. To this end, the entire oncolytic PV genome was inserted into a replication-defective E1- and E3-deleted Ad5 vector genome. As we found that parvoviral NS expression inhibited Ad-PV chimera production, we engineered the parvoviral P4 early promoter, which governs NS expression, by inserting into its sequence tetracycline operator elements. As a result of these modifications, P4-driven expression was blocked in the packaging T-REx-293 cells, which constitutively express the tetracycline repressor, allowing high-yield chimera production. The chimera effectively delivered the PV genome into cancer cells, from which fully infectious replication-competent parvovirus particles were generated. Remarkably, the Ad-PV chimera exerted stronger cytotoxic activities against various cancer cell lines, compared with the PV and Ad parental viruses, while being still innocuous to a panel of tested healthy primary human cells. This Ad-PV chimera represents a novel versatile anticancer agent which can be subjected to further genetic manipulations in order to reinforce its enhanced oncolytic capacity through arming with transgenes or retargeting into tumor cells.

  17. Synthesis of periclinal chimera in cassava. (United States)

    Nassar, N M A; Bomfim, N


    We provide the first report on the synthesis of a very productive interspecific periclinal chimera of cassava, with large and edible roots. The epidermal tissue of the chimera was formed by the cultivated species Manihot esculenta (E), and the subepidermis and internal tissue were formed by the wild species, Manihot fortalezensis (F). We used cytogenetics and morphological analyses to determine the origins of all tissues. These results may offer potential for the development of new lines for crop improvement based on the use of chimera composed of different combinations of wild species and cultivars.

  18. Clustered chimera states in systems of type-I excitability

    International Nuclear Information System (INIS)

    Vüllings, Andrea; Omelchenko, Iryna; Hövel, Philipp; Hizanidis, Johanne


    The chimera state is a fascinating phenomenon of coexisting synchronized and desynchronized behaviour that was discovered in networks of nonlocally coupled identical phase oscillators over ten years ago. Since then, chimeras have been found in numerous theoretical and experimental studies and more recently in models of neuronal dynamics as well. In this work, we consider a generic model for a saddle-node bifurcation on a limit cycle representative of neural excitability type I. We obtain chimera states with multiple coherent regions (clustered chimeras/multi-chimeras) depending on the distance from the excitability threshold, the range of nonlocal coupling and the coupling strength. A detailed stability diagram for these chimera states and other interesting coexisting patterns (like traveling waves) is presented. (paper)

  19. Generalized synchronization between chimera states (United States)

    Andrzejak, Ralph G.; Ruzzene, Giulia; Malvestio, Irene


    Networks of coupled oscillators in chimera states are characterized by an intriguing interplay of synchronous and asynchronous motion. While chimera states were initially discovered in mathematical model systems, there is growing experimental and conceptual evidence that they manifest themselves also in natural and man-made networks. In real-world systems, however, synchronization and desynchronization are not only important within individual networks but also across different interacting networks. It is therefore essential to investigate if chimera states can be synchronized across networks. To address this open problem, we use the classical setting of ring networks of non-locally coupled identical phase oscillators. We apply diffusive drive-response couplings between pairs of such networks that individually show chimera states when there is no coupling between them. The drive and response networks are either identical or they differ by a variable mismatch in their phase lag parameters. In both cases, already for weak couplings, the coherent domain of the response network aligns its position to the one of the driver networks. For identical networks, a sufficiently strong coupling leads to identical synchronization between the drive and response. For non-identical networks, we use the auxiliary system approach to demonstrate that generalized synchronization is established instead. In this case, the response network continues to show a chimera dynamics which however remains distinct from the one of the driver. Hence, segregated synchronized and desynchronized domains in individual networks congregate in generalized synchronization across networks.

  20. A New Approximate Chimera Donor Cell Search Algorithm (United States)

    Holst, Terry L.; Nixon, David (Technical Monitor)


    The objectives of this study were to develop chimera-based full potential methodology which is compatible with overflow (Euler/Navier-Stokes) chimera flow solver and to develop a fast donor cell search algorithm that is compatible with the chimera full potential approach. Results of this work included presenting a new donor cell search algorithm suitable for use with a chimera-based full potential solver. This algorithm was found to be extremely fast and simple producing donor cells as fast as 60,000 per second.

  1. Time-delayed feedback control of coherence resonance chimeras (United States)

    Zakharova, Anna; Semenova, Nadezhda; Anishchenko, Vadim; Schöll, Eckehard


    Using the model of a FitzHugh-Nagumo system in the excitable regime, we investigate the influence of time-delayed feedback on noise-induced chimera states in a network with nonlocal coupling, i.e., coherence resonance chimeras. It is shown that time-delayed feedback allows for the control of the range of parameter values where these chimera states occur. Moreover, for the feedback delay close to the intrinsic period of the system, we find a novel regime which we call period-two coherence resonance chimera.

  2. Status of T- and B-cell cooperation in radiation chimeras: evidence for a suppressor effect

    International Nuclear Information System (INIS)

    Gengozian, N.; Urso, P.


    Absolute tolerance may not be in operation in the allogeneic bone marrow chimera, but rather a dynamic state involving interaction not only between the donor and host but also among the donor-lymphoid cells themselves may exist. Whether this observation made in one allogeneic chimera, CD2F 1 → C3BF 1 , will be true for other chimeras (different strain combinations, species) remains to be shown. Thus, the tempo, mode, and requirement for the generation of suppressor T cells are factors that may vary for any specific allogeneic bone marrow transplant. Finally, the manner and degree to which the tolerance-inducing mechanism may affect T- and B-cell functions of the chimera with respect to third-party antigens are yet to be determined

  3. Antibody responses in allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Coico, R.F.


    The construction of long-lived allogeneic radiation chimeras, free of graft-versus-host disease, has been achieved using serologic elimination of Thy 1 + cells from donor bone marrow. Humoral immune function was not restored in these animals as evidenced by lack of primary antibody responses to a T cell-dependent antigen, namely, sheep erythrocytes (SRBC) both in vivo and in vitro. No evidence for a suppressor cell-mediated mechanism was found. Using separated chimera spleen cell populations and specific helper cell soluble mediators, the functional capabilities of chimera B cells, T cells, and macrophages were assessed. These findings suggested that the failure of chimeras to produce antibody is not the result of impaired B cell, T cell, or macrophage function, but rather, that it is due to ineffective cellular interactions. Physiologic cellular interactions depend upon the sharing of major histocompatibility complex (MHC) determinants between interacting cells. However, the self-recognition repertoire of developing T cells may be influenced by the environment which these cells differentiate such that they learn to recognize host MHC determinants as self. These findings support the interpretation that the immunologic hyporeactivity of allogeneic bone marrow chimeras reflects the role of the host environment in restricting the interactive capabilities of donor-derived cells

  4. Identification of excess 40Ar by the 40Ar/39Ar age spectrum technique

    International Nuclear Information System (INIS)

    Lanphere, M.A.; Dalrymple, G.B.


    40 Ar/ 39 Ar incremental heating experiments on igneous plagioclase, biotite, and pyroxene that contain known amounts of excess 40 Ar indicate that saddle-shaped age spectra are diagnostic of excess 40 Ar in igneous minerals as well as in igneous rocks. The minima in the age spectra approach but do not reach the crystallization age. Neither the age spectrum diagram nor the 40 Ar/ 36 Ar versus 39 Ar/ 36 Ar isochron diagram reliably reveal the crystallization age in such samples. (Auth.)

  5. Substrate recognition by complement convertases revealed in the C5-cobra venom factor complex

    DEFF Research Database (Denmark)

    Laursen, Nick Stub; Andersen, Kasper Røjkjær; Braren, Ingke


    with a protease subunit (Bb or C2a). We determined the crystal structures of the C3b homologue cobra venom factor (CVF) in complex with C5, and in complex with C5 and the inhibitor SSL7 at 4.3 Å resolution. The structures reveal a parallel two-point attachment between C5 and CVF, where the presence of SSL7 only...... slightly affects the C5-CVF interface, explaining the IgA dependence for SSL7-mediated inhibition of C5 cleavage. CVF functions as a relatively rigid binding scaffold inducing a conformational change in C5, which positions its cleavage site in proximity to the serine protease Bb. A general model...

  6. Thermal significance of potassium feldspar K-Ar ages inferred from /sup 40/Ar//sup 39/Ar age spectrum results

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, T.M.; McDougall, I. (Australian National Univ., Canberra. Research School of Earth Sciences)


    /sup 40/Ar//sup 39/Ar age spectrum analyses of three microcline separates from the Separation Point Batholith, northwest Nelson, New Zealand, which cooled slowly through the temperature zone of partial radiogenic /sup 40/Ar accumulation are characterized by a linear age increase over the first 65 percent of gas release with the lowest ages corresponding to the time that the samples cooled below about 100/sup 0/C. The last 35 percent of /sup 39/Ar released from the microclines yields plateau ages which reflect the different bulk mineral ages, and correspond to cooling temperatures between about 130 to 160/sup 0/C. Theoretical calculations confirm the likelihood of diffusion gradients in feldspars cooling at rates =< 5/sup 0/C-Ma/sup -1/. Diffusion parameters calculated from the /sup 39/Ar release yield an activation energy, E = 28.8 +- 1.9 kcal-mol/sup -1/, and a frequency factor/grain size parameter, D/sub 0//l/sup 2/ = 5.6sub(-3.9)sup(+14) sec/sup -1/. This Arrhenius relationship corresponds to a closure temperature of 132 +- 13/sup 0/C which is very similar to the independently estimated temperature. From the observed diffusion compensation correlation, this D/sub 0//l/sup 2/ implies an average diffusion half-width of about 3, similar to the half-width of the perthite lamellae in the feldspars. The results are discussed.

  7. Chimera Grid Tools (United States)

    Chan, William M.; Rogers, Stuart E.; Nash, Steven M.; Buning, Pieter G.; Meakin, Robert


    Chimera Grid Tools (CGT) is a software package for performing computational fluid dynamics (CFD) analysis utilizing the Chimera-overset-grid method. For modeling flows with viscosity about geometrically complex bodies in relative motion, the Chimera-overset-grid method is among the most computationally cost-effective methods for obtaining accurate aerodynamic results. CGT contains a large collection of tools for generating overset grids, preparing inputs for computer programs that solve equations of flow on the grids, and post-processing of flow-solution data. The tools in CGT include grid editing tools, surface-grid-generation tools, volume-grid-generation tools, utility scripts, configuration scripts, and tools for post-processing (including generation of animated images of flows and calculating forces and moments exerted on affected bodies). One of the tools, denoted OVERGRID, is a graphical user interface (GUI) that serves to visualize the grids and flow solutions and provides central access to many other tools. The GUI facilitates the generation of grids for a new flow-field configuration. Scripts that follow the grid generation process can then be constructed to mostly automate grid generation for similar configurations. CGT is designed for use in conjunction with a computer-aided-design program that provides the geometry description of the bodies, and a flow-solver program.

  8. Double-well chimeras in 2D lattice of chaotic bistable elements (United States)

    Shepelev, I. A.; Bukh, A. V.; Vadivasova, T. E.; Anishchenko, V. S.; Zakharova, A.


    We investigate spatio-temporal dynamics of a 2D ensemble of nonlocally coupled chaotic cubic maps in a bistability regime. In particular, we perform a detailed study on the transition ;coherence - incoherence; for varying coupling strength for a fixed interaction radius. For the 2D ensemble we show the appearance of amplitude and phase chimera states previously reported for 1D ensembles of nonlocally coupled chaotic systems. Moreover, we uncover a novel type of chimera state, double-well chimera, which occurs due to the interplay of the bistability of the local dynamics and the 2D ensemble structure. Additionally, we find double-well chimera behavior for steady states which we call double-well chimera death. A distinguishing feature of chimera patterns observed in the lattice is that they mainly combine clusters of different chimera types: phase, amplitude and double-well chimeras.

  9. Numerical analysis of the chimera states in the multilayered network model (United States)

    Goremyko, Mikhail V.; Maksimenko, Vladimir A.; Makarov, Vladimir V.; Ghosh, Dibakar; Bera, Bidesh K.; Dana, Syamal K.; Hramov, Alexander E.


    We numerically study the interaction between the ensembles of the Hindmarsh-Rose (HR) neuron systems, arranged in the multilayer network model. We have shown that the fully identical layers, demonstrated individually different chimera due to the initial mismatch, come to the identical chimera state with the increase of inter-layer coupling. Within the multilayer model we also consider the case, when the one layer demonstrates chimera state, while another layer exhibits coherent or incoherent dynamics. It has been shown that the interactions chimera-coherent state and chimera-incoherent state leads to the both excitation of chimera as from the ensemble of fully coherent or incoherent oscillators, and suppression of initially stable chimera state

  10. Targeting nanodisks via a single chain variable antibody - Apolipoprotein chimera

    International Nuclear Information System (INIS)

    Iovannisci, David M.; Beckstead, Jennifer A.; Ryan, Robert O.


    Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As currently formulated, ND possess limited targeting capability. In this study, we constructed a single chain variable antibody (scFv).apolipoprotein chimera and assessed the ability of this fusion protein to form ND and recognize the antigen to which the scFv is directed. Data obtained revealed that α-vimentin scFv.apolipoprotein A-I is functional in ND formation and antigen recognition, opening the door to the use of such chimeras in targeting drug-enriched ND to specific tissues.

  11. Implementing real-time robotic systems using CHIMERA II (United States)

    Stewart, David B.; Schmitz, Donald E.; Khosla, Pradeep K.


    A description is given of the CHIMERA II programming environment and operating system, which was developed for implementing real-time robotic systems. Sensor-based robotic systems contain both general- and special-purpose hardware, and thus the development of applications tends to be a time-consuming task. The CHIMERA II environment is designed to reduce the development time by providing a convenient software interface between the hardware and the user. CHIMERA II supports flexible hardware configurations which are based on one or more VME-backplanes. All communication across multiple processors is transparent to the user through an extensive set of interprocessor communication primitives. CHIMERA II also provides a high-performance real-time kernel which supports both deadline and highest-priority-first scheduling. The flexibility of CHIMERA II allows hierarchical models for robot control, such as NASREM, to be implemented with minimal programming time and effort.

  12. Bistable Chimera Attractors on a Triangular Network of Oscillator Populations

    DEFF Research Database (Denmark)

    Martens, Erik Andreas


    . This triangular network is the simplest discretization of a continuous ring of oscillators. Yet it displays an unexpectedly different behavior: in contrast to the lone stable chimera observed in continuous rings of oscillators, we find that this system exhibits two coexisting stable chimeras. Both chimeras are......, as usual, born through a saddle-node bifurcation. As the coupling becomes increasingly local in nature they lose stability through a Hopf bifurcation, giving rise to breathing chimeras, which in turn get destroyed through a homoclinic bifurcation. Remarkably, one of the chimeras reemerges by a reversal...

  13. 77 FR 65602 - Chimera Energy Corporation; Order of Suspension of Trading (United States)


    ... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] Chimera Energy Corporation; Order of... lack of current and accurate information concerning the securities of Chimera Energy Corporation (``Chimera'') because of questions regarding the accuracy of statements by Chimera in press releases to...

  14. Breathing chimera in a system of phase oscillators (United States)

    Bolotov, M. I.; Smirnov, L. A.; Osipov, G. V.; Pikovsky, A. S.


    Chimera states consisting of synchronous and asynchronous domains in a medium of nonlinearly coupled phase oscillators have been considered. Stationary inhomogeneous solutions of the Ott-Antonsen equation for a complex order parameter that correspond to fundamental chimeras have been constructed. The direct numerical simulation has shown that these structures under certain conditions are transformed to oscillatory (breathing) chimera regimes because of the development of instability.

  15. Phylogenetic analysis of bacterial and archaeal arsC gene sequences suggests an ancient, common origin for arsenate reductase

    Directory of Open Access Journals (Sweden)

    Dugas Sandra L


    Full Text Available Abstract Background The ars gene system provides arsenic resistance for a variety of microorganisms and can be chromosomal or plasmid-borne. The arsC gene, which codes for an arsenate reductase is essential for arsenate resistance and transforms arsenate into arsenite, which is extruded from the cell. A survey of GenBank shows that arsC appears to be phylogenetically widespread both in organisms with known arsenic resistance and those organisms that have been sequenced as part of whole genome projects. Results Phylogenetic analysis of aligned arsC sequences shows broad similarities to the established 16S rRNA phylogeny, with separation of bacterial, archaeal, and subsequently eukaryotic arsC genes. However, inconsistencies between arsC and 16S rRNA are apparent for some taxa. Cyanobacteria and some of the γ-Proteobacteria appear to possess arsC genes that are similar to those of Low GC Gram-positive Bacteria, and other isolated taxa possess arsC genes that would not be expected based on known evolutionary relationships. There is no clear separation of plasmid-borne and chromosomal arsC genes, although a number of the Enterobacteriales (γ-Proteobacteria possess similar plasmid-encoded arsC sequences. Conclusion The overall phylogeny of the arsenate reductases suggests a single, early origin of the arsC gene and subsequent sequence divergence to give the distinct arsC classes that exist today. Discrepancies between 16S rRNA and arsC phylogenies support the role of horizontal gene transfer (HGT in the evolution of arsenate reductases, with a number of instances of HGT early in bacterial arsC evolution. Plasmid-borne arsC genes are not monophyletic suggesting multiple cases of chromosomal-plasmid exchange and subsequent HGT. Overall, arsC phylogeny is complex and is likely the result of a number of evolutionary mechanisms.

  16. Assay using embryo aggregation chimeras for the detection of nonlethal changes in X-irradiated mouse preimplantation embryos

    International Nuclear Information System (INIS)

    Obasaju, M.F.; Wiley, L.M.; Oudiz, D.J.; Miller, L.; Samuels, S.J.; Chang, R.J.; Overstreet, J.W.


    We have developed a short-term in vitro assay for the detection of sublethal effects produced by very low levels of ionizing radiation. The assay utilizes mouse embryo aggregation chimeras consisting of one irradiated embryo paired with an unirradiated embryo whose blastomeres have been labeled with fluorescein isothiocyanate (FITC). X irradiation (from 0.05 to 2 Gy) and chimera construction were performed with four-cell stage embryos, and the chimeras were cultured for 40 h to the morula stage. The morulae were partially dissociated with calcium-free culture medium and viewed under phase contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution of irradiated (unlabeled) and control (FITC labeled) embryos per chimera. In chimeras where neither embryo was irradiated, the ratio of the unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.50 (17.8 +/- 5.6 cells per unlabeled embryo and 17.4 +/- 5.5 cells per FITC-labeled partner embryo). However, in chimeras formed after the unlabeled embryos were irradiated with as little as 0.05 Gy, the ratio of unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.43 (P less than 0.01). The apparent decreases in cell proliferation were not observed in irradiated embryos that were merely cocultured with control embryos, regardless of whether the embryos were zona enclosed or zona free. We conclude that very low levels of radiation induce sublethal changes in cleaving embryos that are expressed as a proliferative disadvantage within two cell cycles when irradiated embryos are in direct cell-to-cell contact with unirradiated embryos

  17. Persistent chimera states in nonlocally coupled phase oscillators


    Suda, Yusuke; Okuda, Koji


    Chimera states in the systems of nonlocally coupled phase oscillators are considered stable in the continuous limit of spatially distributed oscillators. However, it is reported that in the numerical simulations without taking such limit, chimera states are chaotic transient and finally collapse into the completely synchronous solution. In this Rapid Communication, we numerically study chimera states by using the coupling function different from the previous studies and obtain the result that...

  18. High-resolution Auger spectroscopy on 79 MeV Ar5+, 89 MeV Ar6+, and 136 MeV Ar7+ ions after excitation by helium

    International Nuclear Information System (INIS)

    Schneider, T.


    In this thesis the atomic structure of highly excited Ar 6+ and Ar 7+ ions was studied. For this 79 MeV Ar 5+ , 89 MeV Ar 6+ , and 136 MeV Ar 7+ ions of a heavy ion accelerator were excited by a He gas target to autoionizing states and the Auger electrons emitted in the decay were measured in highly-resolving state. The spectra were taken under an observational angle of zero degree relative to the beam axis in order to minimize the kinematical broadening of the Auger lines. (orig./HSI) [de

  19. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

    Directory of Open Access Journals (Sweden)

    Chloë R McDonald


    Full Text Available The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.

  20. Chimera states in nonlocally coupled phase oscillators with biharmonic interaction (United States)

    Cheng, Hongyan; Dai, Qionglin; Wu, Nianping; Feng, Yuee; Li, Haihong; Yang, Junzhong


    Chimera states, which consist of coexisting domains of coherent and incoherent parts, have been observed in a variety of systems. Most of previous works on chimera states have taken into account specific form of interaction between oscillators, for example, sinusoidal coupling or diffusive coupling. Here, we investigate chimera dynamics in nonlocally coupled phase oscillators with biharmonic interaction. We find novel chimera states with features such as that oscillators in the same coherent cluster may split into two groups with a phase difference around π/2 and that oscillators in adjacent coherent clusters may have a phase difference close to π/2. The different impacts of the coupling ranges in the first and the second harmonic interactions on chimera dynamics are investigated based on the synchronous dynamics in globally coupled phase oscillators. Our study suggests a new direction in the field of chimera dynamics.

  1. Düzce İlinde Arıcılığın Yapısı ve Arıcılık Faaliyetleri Üzerine Bir Araştırma

    Directory of Open Access Journals (Sweden)



    Full Text Available Düzce ili zengin florası ve eşsiz arı ekotipi nedeniyle büyük bir arıcılık potansiyeline sahiptir. Bu çalışma Düzce ilinde arıcılığın genel yapısını ve arıcılık faaliyetlerini ortaya koymak amacıyla gerçekleştirilmiştir. Araştırma kapsamında 412 arıcıya ulaşılmıştır. Yüz yüze yapılan görüşmeler ve anket çalışması ile mevcut durum ortaya konulmuştur. Elde edilen sonuçlara göre ankete katılan arıcıların yaş ortalamasının 50 olduğu, % 73,10’unun ilköğretim, % 14,10’unun lise mezunu, % 20,90’ının ana gelir kaynağı olarak arıcılık yaptığı; % 59,20’sinin Arı Yetiştiricileri Birliği’ne, % 24,50’sinin Bal Üreticileri Birliği’ne üye olduğu; % 61,50’sinin yerel bölge arısını, % 34,70’inin de Kafkas arı ırkını kullandıkları; % 46,80’inin gezginci arıcılık yaptığı, tercih edilen bitki çeşitliliğinin sırasıyla ayçiçeği (% 62,96 kestane (% 54,32 kır çiçekleri (% 22,22, kanola (% 11,73 ve ormangülü (% 11,73 olduğu, kovan başına verimin 2010 ve 2011 yıllarına göre sırasıyla 9 ve 8 kg arasında değiştiği saptanmıştır. En fazla süzme bal üretimi yapılmakta bunu polen ve propolis takip etmektedir. Bu araştırmada, Düzce arıcılığının genel yapısı ve arıcılık problemleri tespit edilmiş ve çözüm önerileri sunulmuştur

  2. Optimal design of tweezer control for chimera states (United States)

    Omelchenko, Iryna; Omel'chenko, Oleh E.; Zakharova, Anna; Schöll, Eckehard


    Chimera states are complex spatio-temporal patterns which consist of coexisting domains of spatially coherent and incoherent dynamics in systems of coupled oscillators. In small networks, chimera states usually exhibit short lifetimes and erratic drifting of the spatial position of the incoherent domain. A tweezer feedback control scheme can stabilize and fix the position of chimera states. We analyze the action of the tweezer control in small nonlocally coupled networks of Van der Pol and FitzHugh-Nagumo oscillators, and determine the ranges of optimal control parameters. We demonstrate that the tweezer control scheme allows for stabilization of chimera states with different shapes, and can be used as an instrument for controlling the coherent domains size, as well as the maximum average frequency difference of the oscillators.

  3. Ar-39/Ar-40 systematics of Allende inclusions

    International Nuclear Information System (INIS)

    Herzog, G.F.; Rutgers University, New Brunswick, NJ); Bence, A.E.


    A laser microprobe was used to measure the Ar isotopic contents of individual mineral grains in four neutron-irradiated Allende samples: two coarse-grained Ca-Al-rich inclusions, one fine-grained Ca-Al-rich inclusion, and one sample with matrix and miscellaneous chondrules. The following K-Ar ages (G.y.) were obtained after degassing low Ar retentive sites by preheating the samples for one hour at 675 C: matrix, 3.5 + or - 0.2 three miscellaneous chondrules, 4.4 + or - 0.1, 4.0 + or - 0.1, and 4.4 + or - 0.1 and the fine-grained inclusion, 4.5 + or - 0.2. The minerals in the coarse-grained Ca-Al-rich inclusions have ubiquitous chlorine, less than 10 ppm K and apparent ages ranging upwards from 4.6 G.y. to well over 10 G.y. Possible explanations for these apparent ages are atmospheric contamination, the decay of K-40 prior to the formation of the solar system, and the trapping of radiogenic Ar-40 lost by the matrix

  4. α-Peptide/ß-Peptoid Chimeras

    DEFF Research Database (Denmark)

    Olsen, Christian Adam; Bonke, Gitte; Vedel, Line


    We describe the synthesis and characterization of the first generation of oligomers consisting of alternating repeats of a-amino acids and chiral N-alkyl-ß-alanine (ß-peptoid) residues. These chimeras are stable toward proteolysis, non-hemolytic, and possess antibacterial activity comparable...... to well-known antimicrobial agents. Moreover, the chimeras exhibit length-dependent, concentration-dependent, solvent-dependent, and ion-strength-dependent ellipticity, indicating the presence of a secondary structure in solution. Thus, a-peptide/ß-peptoid oligomers represent a promising novel...

  5. A Novel Role for C5a in B-1 Cell Homeostasis

    Directory of Open Access Journals (Sweden)

    Katharina Bröker


    Full Text Available B-1 cells constitute a unique subpopulation of lymphocytes residing mainly in body cavities like the peritoneal cavity (PerC but are also found in spleen and bone marrow (BM. As innate-like B cells, they mediate first line immune defense through low-affinity natural IgM (nIgM antibodies. PerC B-1 cells can egress to the spleen and differentiate into nIgM antibody-secreting plasma cells that recognize conserved exogenous and endogenous cellular structures. Homing to and homeostasis within the PerC are regulated by the chemokine CXCL13 released by PerC macrophages and stroma cells. However, the exact mechanisms underlying the regulation of CXCL13 and B-1 homeostasis are not fully explored. B-1 cells play important roles in the inflammatory response to infection, autoimmunity, ischemia/reperfusion injury, obesity, and atherosclerosis. Remarkably, this list of inflammatory entities has a strong overlap with diseases that are regulated by complement suggesting a link between B-1 cells and the complement system. Interestingly, up to now, no data exist regarding the role of complement in B-1 cell biology. Here, we demonstrate for the first time that C5a regulates B-1 cell steady-state dynamics within the peritoneum, the spleen, and the BM. We found decreased B-1a cell numbers in the peritoneum and the spleen of C5aR1−/− mice associated with increased B1-a and B1-b numbers in the spleen and high serum titers of nIgM antibodies directed against phosphorylcholine and several pneumococcal polysaccharides. Similarly, peritoneal B-1a cells were decreased in the peritoneum and splenic B-1a and B-1b cells were increased in C5aR2−/− mice. The decrease in peritoneal B-1 cell numbers was associated with decreased peritoneal CXCL13 levels in C5aR1−/− and C5aR2−/− mice. In search for mechanisms, we found that combined TLR2 and IL-10 receptor activation in PerC macrophages induced strong CXCL13 production, which was significantly reduced in cells

  6. Cyclic adenosine 3',5'-monophosphate (cAMP) enhances cAMP-responsive element binding (CREB) protein phosphorylation and phospho-CREB interaction with the mouse steroidogenic acute regulatory protein gene promoter. (United States)

    Clem, Brian F; Hudson, Elizabeth A; Clark, Barbara J


    Steroidogenic acute regulatory protein (StAR) transcription is regulated through cAMP-protein kinase A-dependent mechanisms that involve multiple transcription factors including the cAMP-responsive element binding protein (CREB) family members. Classically, binding of phosphorylated CREB to cis-acting cAMP-responsive elements (5'-TGACGTCA-3') within target gene promoters leads to recruitment of the coactivator CREB binding protein (CBP). Herein we examined the extent of CREB family member phosphorylation on protein-DNA interactions and CBP recruitment with the StAR promoter. Immunoblot analysis revealed that CREB, cAMP-responsive element modulator (CREM), and activating transcription factor (ATF)-1 are expressed in MA-10 mouse Leydig tumor cells, yet only CREB and ATF-1 are phosphorylated. (Bu)2cAMP treatment of MA-10 cells increased CREB phosphorylation approximately 2.3-fold within 30 min but did not change total nuclear CREB expression levels. Using DNA-affinity chromatography, we now show that CREB and ATF-1, but not CREM, interact with the StAR promoter, and this interaction is dependent on the activator protein-1 (AP-1) cis-acting element within the cAMP-responsive region. In addition, (Bu)2cAMP-treatment increased phosphorylated CREB (P-CREB) association with the StAR promoter but did not influence total CREB interaction. In vivo chromatin immunoprecipitation assays demonstrated CREB binding to the StAR proximal promoter is independent of (Bu)2cAMP-treatment, confirming our in vitro analysis. However, (Bu)2cAMP-treatment increased P-CREB and CBP interaction with the StAR promoter, demonstrating for the first time the physical role of P-CREB:DNA interactions in CBP recruitment to the StAR proximal promoter.

  7. Symmetries of Chimera States (United States)

    Kemeth, Felix P.; Haugland, Sindre W.; Krischer, Katharina


    Symmetry broken states arise naturally in oscillatory networks. In this Letter, we investigate chaotic attractors in an ensemble of four mean-coupled Stuart-Landau oscillators with two oscillators being synchronized. We report that these states with partially broken symmetry, so-called chimera states, have different setwise symmetries in the incoherent oscillators, and in particular, some are and some are not invariant under a permutation symmetry on average. This allows for a classification of different chimera states in small networks. We conclude our report with a discussion of related states in spatially extended systems, which seem to inherit the symmetry properties of their counterparts in small networks.

  8. Is repulsion good for the health of chimeras? (United States)

    Jalan, Sarika; Ghosh, Saptarshi; Patra, Bibhabasu


    Yes! Very much so. A chimera state refers to the coexistence of a coherent-incoherent dynamical evolution of identically coupled oscillators. We investigate the impact of multiplexing of a layer having repulsively coupled oscillators on the occurrence of chimeras in the layer having attractively coupled identical oscillators. We report that there exists an enhancement in the appearance of the chimera state in one layer of the multiplex network in the presence of repulsive coupling in the other layer. Furthermore, we show that a small amount of inhibition or repulsive coupling in one layer is sufficient to yield the chimera state in another layer by destroying its synchronized behavior. These results can be used to obtain insight into dynamical behaviors of those systems where both attractive and repulsive couplings exist among their constituents.

  9. Chimera regimes in a ring of oscillators with local nonlinear interaction (United States)

    Shepelev, Igor A.; Zakharova, Anna; Vadivasova, Tatiana E.


    One of important problems concerning chimera states is the conditions of their existence and stability. Until now, it was assumed that chimeras could arise only in ensembles with nonlocal character of interactions. However, this assumption is not exactly right. In some special cases chimeras can be realized for local type of coupling [1-3]. We propose a simple model of ensemble with local coupling when chimeras are realized. This model is a ring of linear oscillators with the local nonlinear unidirectional interaction. Chimera structures in the ring are found using computer simulations for wide area of values of parameters. Diagram of the regimes on plane of control parameters is plotted and scenario of chimera destruction are studied when the parameters are changed.

  10. Metaphysical and ethical perspectives on creating animal-human chimeras. (United States)

    Eberl, Jason T; Ballard, Rebecca A


    This paper addresses several questions related to the nature, production, and use of animal-human (a-h) chimeras. At the heart of the issue is whether certain types of a-h chimeras should be brought into existence, and, if they are, how we should treat such creatures. In our current research environment, we recognize a dichotomy between research involving nonhuman animal subjects and research involving human subjects, and the classification of a research protocol into one of these categories will trigger different ethical standards as to the moral permissibility of the research in question. Are a-h chimeras entitled to the more restrictive and protective ethical standards applied to human research subjects? We elucidate an Aristotelian-Thomistic metaphysical framework in which to argue how such chimeras ought to be defined ontologically. We then examine when the creation of, and experimentation upon, certain types of a-h chimeras may be morally permissible.

  11. The chimera state in colloidal phase oscillators with hydrodynamic interaction (United States)

    Hamilton, Evelyn; Bruot, Nicolas; Cicuta, Pietro


    The chimera state is the incongruous situation where coherent and incoherent populations coexist in sets of identical oscillators. Using driven non-linear oscillators interacting purely through hydrodynamic forces at low Reynolds number, previously studied as a simple model of motile cilia supporting waves, we find concurrent incoherent and synchronised subsets in small arrays. The chimeras seen in simulation display a "breathing" aspect, reminiscent of uniformly interacting phase oscillators. In contrast to other systems where chimera has been observed, this system has a well-defined interaction metric, and we know that the emergent dynamics inherit the symmetry of the underlying Oseen tensor eigenmodes. The chimera state can thus be connected to a superposition of eigenstates, whilst considering the mean interaction strength within and across subsystems allows us to make a connection to more generic (and abstract) chimeras in populations of Kuramoto phase oscillators. From this work, we expect the chimera state to emerge in experimental observations of oscillators coupled through hydrodynamic forces.

  12. Characterization of host lymphoid cells in antibody-facilitated bone marrow chimeras

    International Nuclear Information System (INIS)

    McCarthy, S.A.; Griffith, I.J.; Gambel, P.; Francescutti, L.H.; Wegmann, T.G.


    The authors have produced stable murine antibody-facilitated (AF) chimeras by the simultaneous injection of P1 bone marrow cells and anti-P2 monoclonal antibody into normal (unirradiated) adult (P1 X P2)F1 recipients. These AF chimeras are healthy, long-lived, and exhibit no overt signs of graft-versus-host disease. They are immunocompetent and tolerant of host, P2-encoded alloantigens. Donor cell engraftment and takeover, monitored by glucosephosphate isomerase isozyme patterns, is usually complete (greater than 95%) in the peripheral blood, bone marrow, and hemopoietic stem cell compartments of long-term (greater than 3 months posttransplantation) AF chimeras. The authors report here, however, that splenic, lymph node, and thymic leukocytes of AF chimeras represent donor/host chimeric populations. Spleen cell populations of AF chimeras exhibit substantial chimera-to-chimera variation in the preponderant residual host cell type(s) present. Interpretations of the implications of these findings are discussed

  13. Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    Urso, P.; Gengozian, N.


    The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

  14. H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s)

    International Nuclear Information System (INIS)

    Noguchi, M.; Onoe, K.; Ogasawara, M.; Iwabuchi, K.; Geng, L.; Ogasawara, K.; Good, R.A.; Morikawa, K.


    To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented

  15. Connecting the Kuramoto Model and the Chimera State (United States)

    Kotwal, Tejas; Jiang, Xin; Abrams, Daniel M.


    Since its discovery in 2002, the chimera state has frequently been described as a counterintuitive, puzzling phenomenon. The Kuramoto model, in contrast, has become a celebrated paradigm useful for understanding a range of phenomena related to phase transitions, synchronization, and network effects. Here we show that the chimera state can be understood as emerging naturally through a symmetry-breaking bifurcation from the Kuramoto model's partially synchronized state. Our analysis sheds light on recent observations of chimera states in laser arrays, chemical oscillators, and mechanical pendula.

  16. Ar-Ar_Redux: rigorous error propagation of 40Ar/39Ar data, including covariances (United States)

    Vermeesch, P.


    Rigorous data reduction and error propagation algorithms are needed to realise Earthtime's objective to improve the interlaboratory accuracy of 40Ar/39Ar dating to better than 1% and thereby facilitate the comparison and combination of the K-Ar and U-Pb chronometers. Ar-Ar_Redux is a new data reduction protocol and software program for 40Ar/39Ar geochronology which takes into account two previously underappreciated aspects of the method: 1. 40Ar/39Ar measurements are compositional dataIn its simplest form, the 40Ar/39Ar age equation can be written as: t = log(1+J [40Ar/39Ar-298.5636Ar/39Ar])/λ = log(1 + JR)/λ Where λ is the 40K decay constant and J is the irradiation parameter. The age t does not depend on the absolute abundances of the three argon isotopes but only on their relative ratios. Thus, the 36Ar, 39Ar and 40Ar abundances can be normalised to unity and plotted on a ternary diagram or 'simplex'. Argon isotopic data are therefore subject to the peculiar mathematics of 'compositional data', sensu Aitchison (1986, The Statistical Analysis of Compositional Data, Chapman & Hall). 2. Correlated errors are pervasive throughout the 40Ar/39Ar methodCurrent data reduction protocols for 40Ar/39Ar geochronology propagate the age uncertainty as follows: σ2(t) = [J2 σ2(R) + R2 σ2(J)] / [λ2 (1 + R J)], which implies zero covariance between R and J. In reality, however, significant error correlations are found in every step of the 40Ar/39Ar data acquisition and processing, in both single and multi collector instruments, during blank, interference and decay corrections, age calculation etc. Ar-Ar_Redux revisits every aspect of the 40Ar/39Ar method by casting the raw mass spectrometer data into a contingency table of logratios, which automatically keeps track of all covariances in a compositional context. Application of the method to real data reveals strong correlations (r2 of up to 0.9) between age measurements within a single irradiation batch. Propertly taking

  17. Petascale supernova simulation with CHIMERA

    Energy Technology Data Exchange (ETDEWEB)

    Messer, O E B [National Center for Computational Sciences, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6008 (United States); Bruenn, S W [Department of Physics, Florida Atlantic University, 777 W Glades Road, Boca Raton, FL 33431-0991 (United States); Blondin, J M [Department of Physics, North Carolina State University, Raleigh, NC 27695-8202 (United States); Hix, W R [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Mezzacappa, A [Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6354 (United States); Dirk, C J [Department of Physics, Florida Atlantic University, 777 W Glades Road, Boca Raton, FL 33431-0991 (United States)


    CHIMERA is a multi-dimensional radiation hydrodynamics code designed to study core-collapse supernovae. The code is made up of three essentially independent parts: a hydrodynamics module, a nuclear burning module, and a neutrino transport solver combined within an operator-split approach. We describe some major algorithmic facets of the code and briefly discuss some recent results. The multi-physics nature of the problem, and the specific implementation of that physics in CHIMERA, provide a rather straightforward path to effective use of multi-core platforms in the near future.

  18. Preliminary results of Digital Pulse Shape Acquisition from Chimera

    International Nuclear Information System (INIS)

    Alderighi, D.M.; Sechi, G.; Anzalone, A.; Cavallaro, S.; Giustolisi, F.; Laguidara, E.; Lanzalone, G.; Porto, F.; Bassini, R.; Boiano, C.; Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L.; Cardella, G.; Defilippo, S.E.; Lanzano, G.; Paganod, A.; Papa, M.; Pirrone, S.; Politi, G.; Geraci, E.


    A 100 MS/s 14-bit Sampling Analog-to-Digital converter has been used to perform digital pulse-shape acquisition of signals collected from CHIMERA telescopes. The signals from a typical CHIMERA detection cell have been collected using both a standard CHIMERA electronic chain up to the amplifier, and a very simple analog front end, basically reduced to the preamplifier. The preliminary on-beam results are presented. (authors)

  19. Preliminary results of Digital Pulse Shape Acquisition from Chimera

    Energy Technology Data Exchange (ETDEWEB)

    Alderighi, D.M.; Sechi, G. [INFN Milano and IASF, CNR, Milano (France); Anzalone, A.; Cavallaro, S.; Giustolisi, F.; Laguidara, E.; Lanzalone, G.; Porto, F. [Catania Univ., LNS and Dipartimento di Fisica (France); Bassini, R.; Boiano, C.; Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L. [Milano Univ., INFN and Dipartimento di Fisica (Italy); Cardella, G.; Defilippo, S.E.; Lanzano, G.; Paganod, A.; Papa, M.; Pirrone, S.; Politi, G. [Catania Univ., INFN and Dipartimento di Fisica (Italy); Geraci, E. [Bologna Univ., INFN and Dipartimento di Fisica (Italy)


    A 100 MS/s 14-bit Sampling Analog-to-Digital converter has been used to perform digital pulse-shape acquisition of signals collected from CHIMERA telescopes. The signals from a typical CHIMERA detection cell have been collected using both a standard CHIMERA electronic chain up to the amplifier, and a very simple analog front end, basically reduced to the preamplifier. The preliminary on-beam results are presented. (authors)

  20. Chimera states in networks of logistic maps with hierarchical connectivities (United States)

    zur Bonsen, Alexander; Omelchenko, Iryna; Zakharova, Anna; Schöll, Eckehard


    Chimera states are complex spatiotemporal patterns consisting of coexisting domains of coherence and incoherence. We study networks of nonlocally coupled logistic maps and analyze systematically how the dilution of the network links influences the appearance of chimera patterns. The network connectivities are constructed using an iterative Cantor algorithm to generate fractal (hierarchical) connectivities. Increasing the hierarchical level of iteration, we compare the resulting spatiotemporal patterns. We demonstrate that a high clustering coefficient and symmetry of the base pattern promotes chimera states, and asymmetric connectivities result in complex nested chimera patterns.

  1. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C


    -allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...... preserved, the allosteric enhancement of chemokine binding was disrupted. In summary, the Trojan horse chimera revealed that orthosteric and allosteric sites could be structurally separated and still act together with transmission of agonism and antagonism across the different receptor units....

  2. Feldspar 40Ar/39Ar dating of ICDP PALEOVAN cores (United States)

    Engelhardt, Jonathan Franz; Sudo, Masafumi; Stockhecke, Mona; Oberhänsli, Roland


    Volcaniclastic fall deposits in ICDP drilling cores from Lake Van, Turkey, contain sodium-rich sanidine and calcium-rich anorthoclase, which both comprise a variety of textural zoning and inclusions. An age model records the lake's history and is based on climate-stratigraphic correlations, tephrostratigraphy, paleomagnetics, and earlier 40Ar/39Ar analyses (Stockhecke et al., 2014b). Results from total fusion and stepwise heating 40Ar/39Ar analyses presented in this study allow for the comparison of radiometric constraints from texturally diversified feldspar and the multi-proxy lacustrine age model and vice versa. This study has investigated several grain-size fractions of feldspar from 13 volcaniclastic units. The feldspars show textural features that are visible in cathodoluminescence (CL) or back-scattered electron (BSE) images and can be subdivided into three dominant zoning-types: (1) compositional zoning, (2) round pseudo-oscillatory zoning and (3) resorbed and patchy zoning (Ginibre et al., 2004). Round pseudo-oscillatory zoning records a sensitive alternation of Fe and Ca that also reflects resorption processes. This is only visible in CL images. Compositional zoning reflects anticorrelated anorthite and orthoclase contents and is visible in BSE. Eleven inverse isochron ages from total fusion and three from stepwise heating analyses fit the age model. Four experiments resulted in older inverse isochron ages that do not concur with the model within 2σ uncertainties and that deviate from 1 ka to 17 ka minimum. C- and R-type zoning are interpreted as representing growth in magma chamber cupolas, as wall mushes, or in narrow conduits. Persistent compositions of PO-type crystals and abundant surfaces recording dissolution features correspond to formation within a magma chamber. C-type zoning and R-type zoning have revealed an irregular incorporation of melt and fluid inclusions. These two types of zoning in feldspar are interpreted as preferentially

  3. Allogeneic unresponsiveness to orthotopic cardiac transplants in DL-A-identical radiation chimeras

    International Nuclear Information System (INIS)

    Boyd, A.D.; Spencer, F.C.; Hirose, H.; Engelman, R.M.; Cannon, F.D.; Ferrebee, J.W.; Rapaport, F.T.


    Nine Cooperstown beagles of known DL-A genotypes were exposed to supralethal total-body irradiation and received bone-marrow allografts from DL-A-identical donors. Four to 5 months later, the resulting chimeras received orthotopic cardiac allografts from their corresponding donors of marrow. Six chimeras died of operative complications in the immediate postoperative period. The other 3 chimeras survived from 173 to 547 days; 1 dog died at 173 days as a result of right-sided heart failure, secondary to stenosis at the site of the pulmonary artery anastomosis. The other two recipients continue to be active and healthy at 545 and 547 days. The results indicate that dogs can be rendered specifically tolerant to orthotopic cardiac allografts by supralethal total-body irradiation and the transplantation of marrow obtained from the prospective allograft donor

  4. Single-crystal 40Ar/39Ar incremental heating reveals bimodal sanidine ages in the Bishop Tuff (United States)

    Andersen, N. L.; Jicha, B. R.; Singer, B. S.


    The 650 km3 Bishop Tuff (BT) is among the most studied volcanic deposits because it is an extensive marker bed deposited just after the Matuyama-Brunhes boundary. Reconstructions of the vast BT magma reservoir from which high-silica rhyolite erupted have long influenced thinking about how large silicic magma systems are assembled, crystallized, and mixed. Yet, the longevity of the high silica rhyolitic melt and exact timing of the eruption remain controversial due to recent conflicting 40Ar/39Ar sanidine vs. SIMS and ID-TIMS U-Pb zircon dates. We have undertaken 21 40Ar/39Ar incremental heating ages on 2 mm BT sanidine crystals from pumice in 3 widely separated outcrops of early-erupted fall and flow units. Plateau ages yield a bimodal distribution: a younger group has a mean of 766 ka and an older group gives a range between 772 and 782 ka. The younger population is concordant with the youngest ID-TIMS and SIMS U-Pb zircon ages recently published, as well as the astronomical age of BT in marine sediment. Of 21 crystals, 17 yield older, non-plateau, steps likely affected by excess Ar that would bias traditional 40Ar/39Ar total crystal fusion ages. The small spread in older sanidine ages, together with 25+ kyr of pre-eruptive zircon growth, suggest that the older sanidines are not partially outgassed xenocrysts. A bimodal 40Ar/39Ar age distribution implies that some fraction of rhyolitic melt cooled below the Ar closure temperature at least 10 ky prior to eruption. We propose that rapid "thawing" of a crystalline mush layer released older crystals into rhyolitic melt from which sanidine also nucleated and grew immediately prior to the eruption. High precision 40Ar/39Ar dating can thus provide essential information on thermo-physical processes at the millenial time scale that are critical to interpreting U-Pb zircon age distributions that are complicated by large uncertainties associated with zircon-melt U-Th systematics.

  5. Chimera States in Two Populations with Heterogeneous Phase-lag

    DEFF Research Database (Denmark)

    Martens, Erik Andreas; Bick, Christian; Panaggio, Mark


    The simplest network of coupled phase-oscillators exhibiting chimera states is given by two populations with disparate intra- and inter-population coupling strengths. We explore the effects of heterogeneous coupling phase-lags between the two populations. Such heterogeneity arises naturally......-uniform synchronization, including in-phase and anti-phase synchrony, full incoherence (splay state), chimera states with phase separation of 0 or π between populations, and states where both populations remain desynchronized. These desynchronized states exhibit stable, oscillatory, and even chaotic dynamics. Moreover......, we identify the bifurcations through which chimera and desynchronized states emerge. Stable chimera states and desynchronized solutions, which do not arise for homogeneous phase-lag parameters, emerge as a result of competition between synchronized in-phase, anti-phase equilibria, and fully...

  6. Temperature and pressure effects on 40Ar-39Ar systematics

    International Nuclear Information System (INIS)

    Ozima, M.; Kaneoka, I.; Yanagisawa, M.


    The effects of thermal and compressional treatment on 40 Ar- 39 Ar systematics have been investigated on three artificially heated biotite samples (heated for 1 hour at 700 0 C and 860 0 C in air and 700 0 C in vacuum respectively) and uniaxially compressed granite (p=1400 bar) and basalt samples (p=1660 bar). The 40 Ar- 39 Ar results for the disturbed samples are compared with those for undisturbed samples. Except for the vacuum-heating case, the effects of the disturbances may be interpreted as the combined effect of a partial loss of radiogenic 40 Ar from the sample and an incorporation of air Ar into the sample. Common diagnostic effects are (1) reduction of the total fusion age, (2) distortion of the age spectrum and, if the degree of the partial Ar loss is small (3) approximate preservation of the isochron age, and (4) reduction of the intercept value ( 40 Ar/ 36 Ar) in the isochron plot. The features observed in the age spectra of artificially disturbed samples are rather common in geologically disturbed samples, suggesting that the artificial disturbances simulate the effects of geological disturbances on 40 Ar- 39 Ar systematics. (Auth.)

  7. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.


    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis.

  8. Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.


    The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis

  9. Chimera states in coupled Kuramoto oscillators with inertia

    International Nuclear Information System (INIS)

    Olmi, Simona


    The dynamics of two symmetrically coupled populations of rotators is studied for different values of the inertia. The system is characterized by different types of solutions, which all coexist with the fully synchronized state. At small inertia, the system is no more chaotic and one observes mainly quasi-periodic chimeras, while the usual (stationary) chimera state is not anymore observable. At large inertia, one observes two different kind of chaotic solutions with broken symmetry: the intermittent chaotic chimera, characterized by a synchronized population and a population displaying a turbulent behaviour, and a second state where the two populations are both chaotic but whose dynamics adhere to two different macroscopic attractors. The intermittent chaotic chimeras are characterized by a finite life-time, whose duration increases as a power-law with the system size and the inertia value. Moreover, the chaotic population exhibits clear intermittent behavior, displaying a laminar phase where the two populations tend to synchronize, and a turbulent phase where the macroscopic motion of one population is definitely erratic. In the thermodynamic limit, these states survive for infinite time and the laminar regimes tends to disappear, thus giving rise to stationary chaotic solutions with broken symmetry contrary to what observed for chaotic chimeras on a ring geometry

  10. Chimera states in coupled Kuramoto oscillators with inertia

    Energy Technology Data Exchange (ETDEWEB)

    Olmi, Simona, E-mail: [CNR - Consiglio Nazionale delle Ricerche - Istituto dei Sistemi Complessi, via Madonna del Piano 10, I-50019 Sesto Fiorentino (Italy); INFN Sez. Firenze, via Sansone, 1 - I-50019 Sesto Fiorentino (Italy)


    The dynamics of two symmetrically coupled populations of rotators is studied for different values of the inertia. The system is characterized by different types of solutions, which all coexist with the fully synchronized state. At small inertia, the system is no more chaotic and one observes mainly quasi-periodic chimeras, while the usual (stationary) chimera state is not anymore observable. At large inertia, one observes two different kind of chaotic solutions with broken symmetry: the intermittent chaotic chimera, characterized by a synchronized population and a population displaying a turbulent behaviour, and a second state where the two populations are both chaotic but whose dynamics adhere to two different macroscopic attractors. The intermittent chaotic chimeras are characterized by a finite life-time, whose duration increases as a power-law with the system size and the inertia value. Moreover, the chaotic population exhibits clear intermittent behavior, displaying a laminar phase where the two populations tend to synchronize, and a turbulent phase where the macroscopic motion of one population is definitely erratic. In the thermodynamic limit, these states survive for infinite time and the laminar regimes tends to disappear, thus giving rise to stationary chaotic solutions with broken symmetry contrary to what observed for chaotic chimeras on a ring geometry.

  11. Chimera states in coupled Kuramoto oscillators with inertia. (United States)

    Olmi, Simona


    The dynamics of two symmetrically coupled populations of rotators is studied for different values of the inertia. The system is characterized by different types of solutions, which all coexist with the fully synchronized state. At small inertia, the system is no more chaotic and one observes mainly quasi-periodic chimeras, while the usual (stationary) chimera state is not anymore observable. At large inertia, one observes two different kind of chaotic solutions with broken symmetry: the intermittent chaotic chimera, characterized by a synchronized population and a population displaying a turbulent behaviour, and a second state where the two populations are both chaotic but whose dynamics adhere to two different macroscopic attractors. The intermittent chaotic chimeras are characterized by a finite life-time, whose duration increases as a power-law with the system size and the inertia value. Moreover, the chaotic population exhibits clear intermittent behavior, displaying a laminar phase where the two populations tend to synchronize, and a turbulent phase where the macroscopic motion of one population is definitely erratic. In the thermodynamic limit, these states survive for infinite time and the laminar regimes tends to disappear, thus giving rise to stationary chaotic solutions with broken symmetry contrary to what observed for chaotic chimeras on a ring geometry.

  12. Using CHIMERA detector at LNS for gamma-particle coincidences

    Directory of Open Access Journals (Sweden)

    Cardella G.


    Full Text Available We have recently evaluated the quality of γ-ray angular distributions that can be extracted in particle-gamma coincidence measurements using the CHIMERA detector at LNS. γ-rays have been detected using the CsI(Tl detectors of the spherical part of the CHIMERA array. Very clean γ-rays angular distributions were extracted in reactions induced by different stable beams impinging on 12C thin targets. The results evidenced an effect of projectile spin flip on the γ-rays angular distributions. γ-particle coincidence measurements were also performed in reactions induced by neutron rich exotic beams produced through in-flight fragmentation at LNS. In recent experiments also the Farcos array was used to improve energy and angular resolution measurements of the detected charged particles. Results obtained with both stable and radioactive beams are reported.

  13. Chimera states: Effects of different coupling topologies (United States)

    Bera, Bidesh K.; Majhi, Soumen; Ghosh, Dibakar; Perc, Matjaž


    Collective behavior among coupled dynamical units can emerge in various forms as a result of different coupling topologies as well as different types of coupling functions. Chimera states have recently received ample attention as a fascinating manifestation of collective behavior, in particular describing a symmetry breaking spatiotemporal pattern where synchronized and desynchronized states coexist in a network of coupled oscillators. In this perspective, we review the emergence of different chimera states, focusing on the effects of different coupling topologies that describe the interaction network connecting the oscillators. We cover chimera states that emerge in local, nonlocal and global coupling topologies, as well as in modular, temporal and multilayer networks. We also provide an outline of challenges and directions for future research.

  14. Chimera states in a Hodgkin-Huxley model of thermally sensitive neurons (United States)

    Glaze, Tera A.; Lewis, Scott; Bahar, Sonya


    Chimera states occur when identically coupled groups of nonlinear oscillators exhibit radically different dynamics, with one group exhibiting synchronized oscillations and the other desynchronized behavior. This dynamical phenomenon has recently been studied in computational models and demonstrated experimentally in mechanical, optical, and chemical systems. The theoretical basis of these states is currently under active investigation. Chimera behavior is of particular relevance in the context of neural synchronization, given the phenomenon of unihemispheric sleep and the recent observation of asymmetric sleep in human patients with sleep apnea. The similarity of neural chimera states to neural "bump" states, which have been suggested as a model for working memory and visual orientation tuning in the cortex, adds to their interest as objects of study. Chimera states have been demonstrated in the FitzHugh-Nagumo model of excitable cells and in the Hindmarsh-Rose neural model. Here, we demonstrate chimera states and chimera-like behaviors in a Hodgkin-Huxley-type model of thermally sensitive neurons both in a system with Abrams-Strogatz (mean field) coupling and in a system with Kuramoto (distance-dependent) coupling. We map the regions of parameter space for which chimera behavior occurs in each of the two coupling schemes.

  15. Deterministic and stochastic control of chimera states in delayed feedback oscillator

    Energy Technology Data Exchange (ETDEWEB)

    Semenov, V. [Department of Physics, Saratov State University, Astrakhanskaya Str. 83, 410012 Saratov (Russian Federation); Zakharova, A.; Schöll, E. [Institut für Theoretische Physik, TU Berlin, Hardenbergstraße 36, 10623 Berlin (Germany); Maistrenko, Y. [Institute of Mathematics and Center for Medical and Biotechnical Research, NAS of Ukraine, Tereschenkivska Str. 3, 01601 Kyiv (Ukraine)


    Chimera states, characterized by the coexistence of regular and chaotic dynamics, are found in a nonlinear oscillator model with negative time-delayed feedback. The control of these chimera states by external periodic forcing is demonstrated by numerical simulations. Both deterministic and stochastic external periodic forcing are considered. It is shown that multi-cluster chimeras can be achieved by adjusting the external forcing frequency to appropriate resonance conditions. The constructive role of noise in the formation of a chimera states is shown.

  16. Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals. (United States)

    Wang, Kefeng; Sun, Yin; Tao, Wei; Fei, Xiang; Chang, Chawnshang


    Increasing evidence has demonstrated that the androgen receptor (AR) plays important roles to promote the metastasis of clear cell renal cell carcinoma (ccRCC). The detailed mechanisms, especially how AR functions via altering the circular RNAs (circRNAs) remain unclear. Here we identified a new circRNA (named as circHIAT1) whose expression was lower in ccRCCs than adjacent normal tissues. Targeting AR could suppress ccRCC cell progression via increasing circHIAT1 expression. ChIP assay and luciferase assay demonstrated that AR suppressed circHIAT1 expression via regulating its host gene, Hippocampus Abundant Transcript 1 (HIAT1) expression at the transcriptional level. The consequences of AR-suppressed circHIAT1 resulted in deregulating miR-195-5p/29a-3p/29c-3p expressions, which increased CDC42 expression to enhance ccRCC cell migration and invasion. Increasing this newly identified signal via circHIAT1 suppressed AR-enhanced ccRCC cell migration and invasion. Together, these results suggested that circHIAT1 functioned as a metastatic inhibitor to suppress AR-enhanced ccRCC cell migration and invasion. Targeting this newly identified AR-circHIAT1-mediated miR-195-5p/29a-3p/29c-3p/CDC42 signals may help us develop potential new therapies to better suppress ccRCC metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. State-specific transport properties of electronically excited Ar and C (United States)

    Istomin, V. A.; Kustova, E. V.


    In the present study, a theoretical model of state-resolved transport properties in electronically excited atomic species developed earlier is applied to argon and carbon atomic species. It is shown that for Ar and C, similarly to the case of atomic nitrogen and oxygen, the Slater-like models can be applied to calculate diameters of electronically excited atoms. Using the Slater-like model it is shown that for half-filled N (2 px1py1pz1) and full-filled Ar (3 px2py2pz2) electronic shells the growth of atomic radius goes slowly compared to C (2 px1py1) and O (2 px2py1pz1). The effect of collision diameters on the transport properties of Ar and C is evaluated. The influence of accounted number of electronic levels on the transport coefficients is examined for the case of Boltzmann distributions over electronic energy levels. It is emphasized that in the temperature range 1000-14000 K, for Boltzmann-like distributions over electronic states the number of accounted electronic levels do not influence the transport coefficients. Contrary to this, for higher temperatures T > 14000 K this effect becomes of importance, especially for argon.

  18. Antiviral T cell competence and restriction specificity of mixed allogeneic (P1 + P2----P1) irradiation chimeras

    International Nuclear Information System (INIS)

    Rueedi, E.S.; Sykes, M.; Ildstad, S.T.; Chester, C.H.; Althage, A.; Hengartner, H.; Sachs, D.H.; Zinkernagel, R.M.


    Mixed irradiation bone marrow chimeras were prepared by reconstituting lethally irradiated C57BL/10 (B10) or B10.D2 mice with T cell-depleted bone marrow cells of B10 plus B10.D2 origin. These chimeras were healthy and survived well under conventional housing conditions and after experimental laboratory infections. Of a total of 17 chimeras tested, 2 died spontaneously or from the injected virus. Twelve of fifteen chimeras mounted a measurable cytotoxic T cell response to virus. Despite approximately equal percentages of B10 and B10.D2 lymphocytes in chimeras, cytotoxic T cell responses to vaccinia virus and lymphocytic choriomeningitis virus were mediated variably by either syngeneic or allogeneic donor lymphocytes; thus the H-2 type of effector T cells frequently did not correspond to the 50:50 distribution of spleen or peripheral blood lymphocytes. Cytotoxic responses were restricted exclusively to recipient H-2 type. All mixed chimeras examined were able to mount a good IgG response to vesicular stomatitis virus. These results confirm previous data suggesting that such mixed chimeras are healthy and immunocompetent and demonstrate strict recipient-determined restriction specificity of effector T cells; they also suggest that if T help is necessary for induction of virus-specific cytotoxic T cells, it does not require host-restricted interactions between helper T cells and precursor cytotoxic T cells

  19. Spiral wave chimera states in large populations of coupled chemical oscillators (United States)

    Totz, Jan Frederik; Rode, Julian; Tinsley, Mark R.; Showalter, Kenneth; Engel, Harald


    The coexistence of coherent and incoherent dynamics in a population of identically coupled oscillators is known as a chimera state1,2. Discovered in 20023, this counterintuitive dynamical behaviour has inspired extensive theoretical and experimental activity4-15. The spiral wave chimera is a particularly remarkable chimera state, in which an ordered spiral wave rotates around a core consisting of asynchronous oscillators. Spiral wave chimeras were theoretically predicted in 200416 and numerically studied in a variety of systems17-23. Here, we report their experimental verification using large populations of nonlocally coupled Belousov-Zhabotinsky chemical oscillators10,18 in a two-dimensional array. We characterize previously unreported spatiotemporal dynamics, including erratic motion of the asynchronous spiral core, growth and splitting of the cores, as well as the transition from the chimera state to disordered behaviour. Spiral wave chimeras are likely to occur in other systems with long-range interactions, such as cortical tissues24, cilia carpets25, SQUID metamaterials26 and arrays of optomechanical oscillators9.

  20. Identification and characterization of NDT 9513727 [N,N-bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-imidazole-5-methanamine], a novel, orally bioavailable C5a receptor inverse agonist. (United States)

    Brodbeck, Robbin M; Cortright, Daniel N; Kieltyka, Andrzej P; Yu, Jianying; Baltazar, Carolyn O; Buck, Marianne E; Meade, Robin; Maynard, George D; Thurkauf, Andrew; Chien, Du-Shieng; Hutchison, Alan J; Krause, James E


    The complement system represents an innate immune mechanism of host defense that has three effector arms, the C3a receptor, the C5a receptor (C5aR), and the membrane attack complex. Because of its inflammatory and immune-enhancing properties, the biological activity of C5a and its classical receptor have been widely studied. Because specific antagonism of the C5aR could have therapeutic benefit without affecting the protective immune response, the C5aR continues to be a promising target for pharmaceutical research. The lack of specific, potent and orally bioavailable small-molecule antagonists has limited the clinical investigation of the C5aR. We report the discovery of NDT 9513727 [N,N-bis(1,3-benzodioxol-5-ylmethyl)-1-butyl-2,4-diphenyl-1H-imidazole-5-methanamine], a small-molecule, orally bioavailable, selective, and potent inverse agonist of the human C5aR. NDT 9513727 was discovered based on the integrated use of in vitro affinity and functional assays in conjunction with medicinal chemistry. NDT 9513727 inhibited C5a-stimulated responses, including guanosine 5'-3-O-(thio)triphosphate binding, Ca(2+) mobilization, oxidative burst, degranulation, cell surface CD11b expression and chemotaxis in various cell types with IC(50)s from 1.1 to 9.2 nM, respectively. In C5a competition radioligand binding experiments, NDT 9513727 exhibited an IC(50) of 11.6 nM. NDT 9513727 effectively inhibited C5a-induced neutropenia in gerbil and cynomolgus macaque in vivo. The findings suggest that NDT 9513727 may be a promising new entity for the treatment of human inflammatory diseases.

  1. Stable amplitude chimera states in a network of locally coupled Stuart-Landau oscillators (United States)

    Premalatha, K.; Chandrasekar, V. K.; Senthilvelan, M.; Lakshmanan, M.


    We investigate the occurrence of collective dynamical states such as transient amplitude chimera, stable amplitude chimera, and imperfect breathing chimera states in a locally coupled network of Stuart-Landau oscillators. In an imperfect breathing chimera state, the synchronized group of oscillators exhibits oscillations with large amplitudes, while the desynchronized group of oscillators oscillates with small amplitudes, and this behavior of coexistence of synchronized and desynchronized oscillations fluctuates with time. Then, we analyze the stability of the amplitude chimera states under various circumstances, including variations in system parameters and coupling strength, and perturbations in the initial states of the oscillators. For an increase in the value of the system parameter, namely, the nonisochronicity parameter, the transient chimera state becomes a stable chimera state for a sufficiently large value of coupling strength. In addition, we also analyze the stability of these states by perturbing the initial states of the oscillators. We find that while a small perturbation allows one to perturb a large number of oscillators resulting in a stable amplitude chimera state, a large perturbation allows one to perturb a small number of oscillators to get a stable amplitude chimera state. We also find the stability of the transient and stable amplitude chimera states and traveling wave states for an appropriate number of oscillators using Floquet theory. In addition, we also find the stability of the incoherent oscillation death states.

  2. Plant chimeras: The good, the bad, and the 'Bizzaria'. (United States)

    Frank, Margaret H; Chitwood, Daniel H


    Chimeras - organisms that are composed of cells of more than one genotype - captured the human imagination long before they were formally described and used in the laboratory. These organisms owe their namesake to a fire-breathing monster from Greek mythology that has the head of a lion, the body of a goat, and the tail of a serpent. The first description of a non-fictional chimera dates back to the middle of the seventeenth century when the Florentine gardener Pietro Nati discovered an adventitious shoot growing from the graft junction between sour orange (Citrus aurantium) and citron (Citrus medica). This perplexing chimera that grows with sectors phenotypically resembling each of the citrus progenitors inspired discussion and wonder from the scientific community and was fittingly named the 'Bizzaria'. Initially, the 'Bizzaria' was believed to be an asexual hybrid that formed from a cellular fusion between the grafted parents; however, in-depth cellular analyses carried out centuries later demonstrated that the 'Bizzaria', along with other chimeras, owe their unique sectored appearance to a conglomeration of cells from the two donors. Since this pivotal discovery at the turn of the twentieth century, chimeras have served both as tools and as unique biological phenomena that have contributed to our understanding of plant development at the cellular, tissue, and organismal level. Rapid advancements in genome sequencing technologies have enabled the establishment of new model species with novel morphological and developmental features that enable the generation of chimeric organisms. In this review, we show that genetic mosaic and chimera studies provide a technologically simple way to delve into the organismal, genetic, and genomic inner workings underlying the development of diverse model organisms. Moreover, we discuss the unique opportunity that chimeras present to explore universal principles governing intercellular communication and the coordination of

  3. Progress in Grid Generation: From Chimera to DRAGON Grids (United States)

    Liou, Meng-Sing; Kao, Kai-Hsiung


    Hybrid grids, composed of structured and unstructured grids, combines the best features of both. The chimera method is a major stepstone toward a hybrid grid from which the present approach is evolved. The chimera grid composes a set of overlapped structured grids which are independently generated and body-fitted, yielding a high quality grid readily accessible for efficient solution schemes. The chimera method has been shown to be efficient to generate a grid about complex geometries and has been demonstrated to deliver accurate aerodynamic prediction of complex flows. While its geometrical flexibility is attractive, interpolation of data in the overlapped regions - which in today's practice in 3D is done in a nonconservative fashion, is not. In the present paper we propose a hybrid grid scheme that maximizes the advantages of the chimera scheme and adapts the strengths of the unstructured grid while at the same time keeps its weaknesses minimal. Like the chimera method, we first divide up the physical domain by a set of structured body-fitted grids which are separately generated and overlaid throughout a complex configuration. To eliminate any pure data manipulation which does not necessarily follow governing equations, we use non-structured grids only to directly replace the region of the arbitrarily overlapped grids. This new adaptation to the chimera thinking is coined the DRAGON grid. The nonstructured grid region sandwiched between the structured grids is limited in size, resulting in only a small increase in memory and computational effort. The DRAGON method has three important advantages: (1) preserving strengths of the chimera grid; (2) eliminating difficulties sometimes encountered in the chimera scheme, such as the orphan points and bad quality of interpolation stencils; and (3) making grid communication in a fully conservative and consistent manner insofar as the governing equations are concerned. To demonstrate its use, the governing equations are

  4. Assessing reprogramming by chimera formation and tetraploid complementation. (United States)

    Li, Xin; Xia, Bao-long; Li, Wei; Zhou, Qi


    Pluripotent stem cells can be evaluated by pluripotent markers expression, embryoid body aggregation, teratoma formation, chimera contribution and even more, tetraploid complementation. Whether iPS cells in general are functionally equivalent to normal ESCs is difficult to establish. Here, we present the detailed procedure for chimera formation and tetraploid complementation, the most stringent criterion, to assessing pluripotency.

  5. Pharmacological characterisation of α6β4* nicotinic acetylcholine receptors assembled from three different α6/α3 subunit chimeras in tsA201 cells

    DEFF Research Database (Denmark)

    Jensen, Anne Bjørnskov; Hoestgaard-Jensen, Kirsten; Jensen, Anders A.


    by their inefficient functional expression in vitro. In the present study we have characterized and compared the pharmacological properties displayed by α6β4 and α6β4β3 nicotinic acetylcholine receptors assembled in tsA201 cells from the classical α6/α3 chimera (C1) and two novel α6/α3 chimeras (C6F223L and C16F223L...... should be made keeping the molecular modifications in the α6 surrogate subunits in mind, this study sheds light on the pharmacological properties of α6β4⁎ nicotinic acetylcholine receptors and demonstrates the applicability of the C6F223L and C16F223L chimeras for studies of these receptors....

  6. Resistance to infection with Eimeria vermiformis in mouse radiation chimeras is determined by donor bone-marrow cells

    International Nuclear Information System (INIS)

    Joysey, H.S.; Wakelin, D.; Rose, M.E.


    The course of infection with Eimeria vermiformis was determined in BALB/b, BALB/c, and C57BL/10ScSn (B10) mice and in radiation chimeras prepared from the H-2-compatible BALB/b and B10 mice. The BALB strains, irrespective of H-2 haplotype, were resistant, the B10 mice were susceptible, and in the chimeras infection was characterized by the genotype of the donated bone-marrow cells and not by the phenotype of the recipient. Thus, the genetic control of relative resistance or susceptibility to infection with this parasite is expressed through bone-marrow-derived cells

  7. Chimera states and the interplay between initial conditions and non-local coupling (United States)

    Kalle, Peter; Sawicki, Jakub; Zakharova, Anna; Schöll, Eckehard


    Chimera states are complex spatio-temporal patterns that consist of coexisting domains of coherent and incoherent dynamics. We study chimera states in a network of non-locally coupled Stuart-Landau oscillators. We investigate the impact of initial conditions in combination with non-local coupling. Based on an analytical argument, we show how the coupling phase and the coupling strength are linked to the occurrence of chimera states, flipped profiles of the mean phase velocity, and the transition from a phase- to an amplitude-mediated chimera state.

  8. Chimera states in two-dimensional networks of locally coupled oscillators (United States)

    Kundu, Srilena; Majhi, Soumen; Bera, Bidesh K.; Ghosh, Dibakar; Lakshmanan, M.


    Chimera state is defined as a mixed type of collective state in which synchronized and desynchronized subpopulations of a network of coupled oscillators coexist and the appearance of such anomalous behavior has strong connection to diverse neuronal developments. Most of the previous studies on chimera states are not extensively done in two-dimensional ensembles of coupled oscillators by taking neuronal systems with nonlinear coupling function into account while such ensembles of oscillators are more realistic from a neurobiological point of view. In this paper, we report the emergence and existence of chimera states by considering locally coupled two-dimensional networks of identical oscillators where each node is interacting through nonlinear coupling function. This is in contrast with the existence of chimera states in two-dimensional nonlocally coupled oscillators with rectangular kernel in the coupling function. We find that the presence of nonlinearity in the coupling function plays a key role to produce chimera states in two-dimensional locally coupled oscillators. We analytically verify explicitly in the case of a network of coupled Stuart-Landau oscillators in two dimensions that the obtained results using Ott-Antonsen approach and our analytical finding very well matches with the numerical results. Next, we consider another type of important nonlinear coupling function which exists in neuronal systems, namely chemical synaptic function, through which the nearest-neighbor (locally coupled) neurons interact with each other. It is shown that such synaptic interacting function promotes the emergence of chimera states in two-dimensional lattices of locally coupled neuronal oscillators. In numerical simulations, we consider two paradigmatic neuronal oscillators, namely Hindmarsh-Rose neuron model and Rulkov map for each node which exhibit bursting dynamics. By associating various spatiotemporal behaviors and snapshots at particular times, we study the chimera

  9. Subtype Specific Differences in NS5A Domain II Reveals Involvement of Proline at Position 310 in Cyclosporine Susceptibility of Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Israr-ul H. Ansari


    Full Text Available Hepatitis C virus (HCV is susceptible to cyclosporine (CsA and other cyclophilin (CypA inhibitors, but the genetic basis of susceptibility is controversial. Whether genetic variation in NS5A alters cell culture susceptibility of HCV to CypA inhibition is unclear. We constructed replicons containing NS5A chimeras from genotypes 1a, 2a and 4a to test how variation in carboxy terminal regions of NS5A altered the genotype 1b CsA susceptibility. All chimeric replicons including genotype 1b Con1LN-wt replicon exhibited some cell culture sensitivity to CsA with genotype 4a being most sensitive and 1a the least. The CypA binding pattern of truncated NS5A genotypes correlated with the susceptibility of these replicons to CsA. The Con1LN-wt replicon showed increased susceptibility towards CsA when proline at position 310P was mutated to either threonine or alanine. Furthermore, a 15 amino acid long peptide fused N terminally to GFP coding sequences confirmed involvement of proline at 310 in CypA binding. Our findings are consistent with CypA acting on multiple prolines outside of the previously identified CypA binding sites. These results suggest multiple specific genetic variants between genotype 1a and 1b in the C-terminus of NS5A alter the CsA susceptibility of replicons, and some variants may oppose the effects of others.

  10. Development of cassava periclinal chimera may boost production. (United States)

    Bomfim, N; Nassar, N M A


    Plant periclinal chimeras are genotypic mosaics arranged concentrically. Trials to produce them to combine different species have been done, but pratical results have not been achieved. We report for the second time the development of a very productive interspecific periclinal chimera in cassava. It has very large edible roots up to 14 kg per plant at one year old compared to 2-3 kg in common varieties. The epidermal tissue formed was from Manihot esculenta cultivar UnB 032, and the subepidermal and internal tissue from the wild species, Manihot fortalezensis. We determined the origin of tissues by meiotic and mitotic chromosome counts, plant anatomy and morphology. Epidermal features displayed useful traits to deduce tissue origin: cell shape and size, trichome density and stomatal length. Chimera roots had a wholly tuberous and edible constitution with smaller starch granule size and similar distribution compared to cassava. Root size enlargement might have been due to an epigenetic effect. These results suggest a new line of improved crop based on the development of interspecific chimeras composed of different combinations of wild and cultivated species. It promises boosting cassava production through exceptional root enlargement.

  11. Chaotic weak chimeras and their persistence in coupled populations of phase oscillators

    International Nuclear Information System (INIS)

    Bick, Christian; Ashwin, Peter


    Nontrivial collective behavior may emerge from the interactive dynamics of many oscillatory units. Chimera states are chaotic patterns of spatially localized coherent and incoherent oscillations. The recently-introduced notion of a weak chimera gives a rigorously testable characterization of chimera states for finite-dimensional phase oscillator networks. In this paper we give some persistence results for dynamically invariant sets under perturbations and apply them to coupled populations of phase oscillators with generalized coupling. In contrast to the weak chimeras with nonpositive maximal Lyapunov exponents constructed so far, we show that weak chimeras that are chaotic can exist in the limit of vanishing coupling between coupled populations of phase oscillators. We present numerical evidence that positive Lyapunov exponents can persist for a positive measure set of this inter-population coupling strength. (paper)

  12. Recent results of CHIMERA activity

    Directory of Open Access Journals (Sweden)

    Pagano A.


    Full Text Available The experimental activity of CHIMERA in recent years has been characterized by a steady progress in the detection technique and data analysis. Since 2008 the detector system benefits of new implementations: a new reaction chamber, a new charged particle identification in silicon detector made by an extended pulse shape method and an efficient system for the identification of exotic beams produced by projectile-like fragmentation (In-flight method. These implementations appear to be promising tools in view of further exclusive experiments in the field of isospin physics. The coupling of CHIMERA with other equipments (such as interferometers and highly segmented arrays, magnetic elements, neutron detectors, etc. is also envisaged in order to extend the studies of the reaction mechanism in heavy ion physics.

  13. "cAMP sponge": a buffer for cyclic adenosine 3', 5'-monophosphate.

    Directory of Open Access Journals (Sweden)

    Konstantinos Lefkimmiatis

    Full Text Available BACKGROUND: While intracellular buffers are widely used to study calcium signaling, no such tool exists for the other major second messenger, cyclic AMP (cAMP. METHODS/PRINCIPAL FINDINGS: Here we describe a genetically encoded buffer for cAMP based on the high-affinity cAMP-binding carboxy-terminus of the regulatory subunit RIbeta of protein kinase A (PKA. Addition of targeting sequences permitted localization of this fragment to the extra-nuclear compartment, while tagging with mCherry allowed quantification of its expression at the single cell level. This construct (named "cAMP sponge" was shown to selectively bind cAMP in vitro. Its expression significantly suppressed agonist-induced cAMP signals and the downstream activation of PKA within the cytosol as measured by FRET-based sensors in single living cells. Point mutations in the cAMP-binding domains of the construct rendered the chimera unable to bind cAMP in vitro or in situ. Cyclic AMP sponge was fruitfully applied to examine feedback regulation of gap junction-mediated transfer of cAMP in epithelial cell couplets. CONCLUSIONS: This newest member of the cAMP toolbox has the potential to reveal unique biological functions of cAMP, including insight into the functional significance of compartmentalized signaling events.

  14. 40Ar/39Ar age of the Rotoiti Breccia and Rotoehu Ash, Okataina Volcanic Complex, New Zealand, and identification of heterogeneously distributed excess 40Ar in supercooled crystals

    DEFF Research Database (Denmark)

    Flude, Stephanie; Storey, Michael


    Co-magmatic granitoid clasts erupted as part of the Rotoiti Ignimbrite (Rotoehu Tephra) contain euhedral K-feldspar and biotite crystals that protrude into miarolytic cavities and show textural evidence for growth in super-cooled conditions and are thus interpreted as growing during eruption. 40Ar...... that appear to be largely unaffected by excess 40Ar. This population gives a statistically robust weighted mean age of 47.4 ± 1.5 ka (1σ, n = 13) and an indistinguishable inverse isochron age of 50 ± 3 ka for this historically difficult to date eruption. The weighted mean age is significantly younger than...... previous age estimates of the Rotoiti eruption obtained by K/Ar and 40Ar/39Ar dating of bracketing lavas, but is indistinguishable from recent 14C and (U–Th)/He dates and estimates based on orbital tuning and sedimentation rates constrained by 14C ages....

  15. U-series in zircon and 40Ar/39Ar geochronology reveal the most recent stage of a supervolcanic cycle in the Altiplano-Puna Volcanic Complex, Central Andes (United States)

    Tierney, C.; de Silva, S. L.; Schmitt, A. K.; Jicha, B.; Singer, B. S.


    The ignimbrite flare up that produced the Altiplano-Puna Volcanic Complex of the Central Andes is characterized by episodic supervolcanism over a ~10 Ma time-span that climaxed about 4Ma. Since peak activity, the temporal and spatial record of volcanism suggests a waning of the system with only one other supervolcanic eruption at 2.6Ma. The most recent phase of volcanism from the APVC comprises a series of late Pleistocene domes that share a general petrochemical resemblance to the ignimbrites. New U-series data on zircons and high precision 40Ar/39Ar age determinations reveal that these effusive eruptions represent a temporally coherent magmatic episode. The five largest domes (Chao, Chillahuita, Chanka, Chascon-Runtu Jarita, and Tocopuri) have a combined volume >40 km3, and are distributed over an elliptical area of over 3000km2 centered at 22°S 68°W. They are crystal rich (>50%) dacites to rhyolites. New 40Ar/39Ar age determinations on biotite for the domes range range from 108±6 to 190±50 ka. However, 40Ar/39Ar ages from sanidine for some of the domes are more precise and span from 87±4 to 97±2 ka. We therefore interpret the eruption age of all these domes to be ~90 - 100 ka. This is consistent with SIMS U-series crystallization ages from the rims of 66 zircon crystals from four of the domes that reveal a fairly continuous spread of ages from ~90 ka to >300 ka with potentially common peaks in zircon ages at 100 ka and ~200 ka. U-Pb dating on the interiors of some of these zircon crystals indicates crystallization ages of up to 1.5 Ma. The common peaks of zircon crystallization between domes suggest that magma that fed these domes shared a larger regional source. Furthermore, the large volume of this potential source and the crystal-rich nature of the lava imply that this source was likely a large body of crystal-mush. The continuous nature of the zircon rim age population indicates that the residence time of this magma body was likely >200kyr. Potential

  16. Computing Flows Using Chimera and Unstructured Grids (United States)

    Liou, Meng-Sing; Zheng, Yao


    DRAGONFLOW is a computer program that solves the Navier-Stokes equations of flows in complexly shaped three-dimensional regions discretized by use of a direct replacement of arbitrary grid overlapping by nonstructured (DRAGON) grid. A DRAGON grid (see figure) is a combination of a chimera grid (a composite of structured subgrids) and a collection of unstructured subgrids. DRAGONFLOW incorporates modified versions of two prior Navier-Stokes-equation-solving programs: OVERFLOW, which is designed to solve on chimera grids; and USM3D, which is used to solve on unstructured grids. A master module controls the invocation of individual modules in the libraries. At each time step of a simulated flow, DRAGONFLOW is invoked on the chimera portion of the DRAGON grid in alternation with USM3D, which is invoked on the unstructured subgrids of the DRAGON grid. The USM3D and OVERFLOW modules then immediately exchange their solutions and other data. As a result, USM3D and OVERFLOW are coupled seamlessly.

  17. Pulse shape method for the Chimera silicon detectors

    Energy Technology Data Exchange (ETDEWEB)

    Pagano, A.; Arena, N.; Cardella, G.; D' Andrea, M.; Filippo, E. de; Fichera, F.; Giudice, N.; Guardone, N.; Grimaldi, A.; Nicotra, D.; Papa, M.; Pirrone, S.; Politi, G.; Rapicavoli, C.; Rizza, G.; Russotto, P.; Sacca, G.; Urso, S.; Lanzano, G. [Catania Univ., INFN Catania and Dipartimento di Fisica e Astronomia (Italy); Alderighi, M.; Sechi, G. [INFN Milano and Istituto di Fisica Cosmica CNR, Milano (Italy); Amorini, F.; Anzalone, A.; Cali, C.; Campagna, V.; Cavallaro, S.; Di Stefano, A.; Giustolisi, F.; La Guidara, E.; Lanzalone, G.; Maiolino, C.; Porto, F.; Rizzo, F.; Salamone, S. [Catania Univ., INFN-LNS and Dipartimento di Fisica e Astronomia (Italy); Auditore, L.; Trifiro, A.; Trimarchi, M. [Messina Univ., INFN and Dipartimento di Fisica (Italy); Bassini, R.; Boiano, C.; Guazzoni, P.; Russo, S.; Sassi, M.; Zetta, L. [Milano Univ., INFN Milano and Dipartimento di Fisica (Italy); Blicharska, J.; Grzeszczuk, A. [Silesia Univ., Institute of Physics, Katowice (Poland); Chatterjee, M.B. [Saha Institute Of Nuclear Physics, Kolkata (India); Geraci, E.; Zipper, W. [Bologna Univ., INFN Bologna and Dipartimento di Fisica (Italy); Rosato, E.; Vigilante, M. [Napoli Univ., INFN and Dipartimento di Fisica (Italy); Schroder, W.U.; T-ke, J. [Rochester Univ., Dept. of Chemistry, Rochester, N.Y. (United States)


    Since January 2003, the 4{pi} CHIMERA (Charged Heavy Ions Mass and Energy Resolving Array) detector in its full configuration has successfully been operated at the 'Catania Laboratori Nazionali del Sud' (LNS) accelerator facility. The detector has been used with a variety of beams from the Superconducting Cyclotron in heavy-ion reaction studies at Fermi bombarding energies. Future experiments with a focus on isospin physics at Fermi energies, planned for both primary and less intense secondary particle beams, suggest the development of new and more versatile experimental particle identification methods. Recent achievements in implementing specific pulse shape particle identification methods for CHIMERA silicon detectors are reported. They suggest an upgrade of the present charge and mass identification capability of CHIMERA by a simple extension of the method. (authors)

  18. Targeted chimera delivery to ovarian cancer cells by heterogeneous gold magnetic nanoparticle (United States)

    Chen, Yao; Xu, Mengjiao; Guo, Yi; Tu, Keyao; Wu, Weimin; Wang, Jianjun; Tong, Xiaowen; Wu, Wenjuan; Qi, Lifeng; Shi, Donglu


    Efficient delivery of small interfering RNAs (siRNAs) to the targeted cells has remained a significant challenge in clinical applications. In the present study, we developed a novel aptamer-siRNA chimera delivery system mediated by cationic Au-Fe3O4 nanoparticles (NPs). The chimera constructed by VEGF RNA aptamer and Notch3 siRNA was bonded with heterogeneous Au-Fe3O4 nanoparticles by electrostatic interaction. The obtained complex exhibited much higher silencing efficiency against Notch3 gene compared with chimera alone and lipofectamine-siRNA complex, and improved the antitumor effects of the loaded chimera. Moreover, the efficient delivery of the chimera by Au-Fe3O4 NPs could reverse multi-drug resistance (MDR) of ovarian cancer cells against the chemotherapeutic drug cisplatin, indicating its potential capability for future targeted cancer therapy while overcoming MDR.

  19. A Navier-Strokes Chimera Code on the Connection Machine CM-5: Design and Performance (United States)

    Jespersen, Dennis C.; Levit, Creon; Kwak, Dochan (Technical Monitor)


    We have implemented a three-dimensional compressible Navier-Stokes code on the Connection Machine CM-5. The code is set up for implicit time-stepping on single or multiple structured grids. For multiple grids and geometrically complex problems, we follow the 'chimera' approach, where flow data on one zone is interpolated onto another in the region of overlap. We will describe our design philosophy and give some timing results for the current code. A parallel machine like the CM-5 is well-suited for finite-difference methods on structured grids. The regular pattern of connections of a structured mesh maps well onto the architecture of the machine. So the first design choice, finite differences on a structured mesh, is natural. We use centered differences in space, with added artificial dissipation terms. When numerically solving the Navier-Stokes equations, there are liable to be some mesh cells near a solid body that are small in at least one direction. This mesh cell geometry can impose a very severe CFL (Courant-Friedrichs-Lewy) condition on the time step for explicit time-stepping methods. Thus, though explicit time-stepping is well-suited to the architecture of the machine, we have adopted implicit time-stepping. We have further taken the approximate factorization approach. This creates the need to solve large banded linear systems and creates the first possible barrier to an efficient algorithm. To overcome this first possible barrier we have considered two options. The first is just to solve the banded linear systems with data spread over the whole machine, using whatever fast method is available. This option is adequate for solving scalar tridiagonal systems, but for scalar pentadiagonal or block tridiagonal systems it is somewhat slower than desired. The second option is to 'transpose' the flow and geometry variables as part of the time-stepping process: Start with x-lines of data in-processor. Form explicit terms in x, then transpose so y-lines of data are

  20. C-14 and Ar-39 content in a ground water aquifer in the Saarland - comparison of two ground water isotope dating methods

    International Nuclear Information System (INIS)

    Forster, M.


    For the Ar-39 groundwater ages found an age comparison is made with ground waters investigated for C-14, Kr-85 and H-3 contents. The location of investigation is a sandstone aquifer of Southern Saarland. The underground production of Ar-39 the hydrological applicability. In granite, the average concentration of U, Th, K, and Cl with an average porosity of 1% and complete diffusion of the isotopes Ar-39 and Cl-36 produced underground can be as high as 10 5 % for Ar-39 moderated and 16% Cl-36 moderated in the interstitial water. (DG) [de

  1. Chimera: Experiencing Language Arts. (United States)

    Paul, Rebecca K.


    Describes the production of a dramatic musical, Chimera: A Journey to Redoubtia, at Chapman Elementary School in Anchor Point, Alaska. Student participation in the project, and students' rewards from participation, are detailed. Benefits of the integration of dramatics into the language arts curriculum are listed. (BB)

  2. In vitro induction of mutation and separation of chimeras in Gerbera jamesonii

    International Nuclear Information System (INIS)

    Jerzy, M.; Zalewska, M.; Garczewska, A.


    Using ex vitro leaves as objects to be irradiated and to induce variation in sixteen Gerbera jamesonii cultivars, reproduced from adventitious buds, resulted in obtaining the mutants which inflorescence color was uniformly changed and which newly acquired traits recurred in the second generation of plants reproduced vegetatively from the isolated shoot tips. However, chimeras appeared among the vM 1 plants exposed to various doses of gamma rays (5-25 Gy and they constituted almost half of the mutated plants. A further propagation of chimeras from leaf explants forming adventitious shoots significantly increased the number of solid mutants with uniformly changed inflorescence color in the vM 1 generation. (author)

  3. A microdose study of ¹⁴C-AR-709 in healthy men: pharmacokinetics, absolute bioavailability and concentrations in key compartments of the lung. (United States)

    Lappin, G; Boyce, M J; Matzow, T; Lociuro, S; Seymour, M; Warrington, S J


    To explore, in a microdose (phase-0) study, the pharmacokinetics, bioavailability and concentrations in key compartments of the lung, of AR-709, a novel diaminopyrimidine antibiotic for the treatment of respiratory infection. Four healthy men each received two single, 100 μg microdoses of ¹⁴C-AR-709, 7 days apart: the first was administered intravenously (IV), the second orally. Plasma pharmacokinetics of ¹⁴C and unchanged AR-709 were obtained by high-performance liquid chromatography and accelerator mass spectrometry (AMS). Next, 15 healthy men received a single, 100 μg microdose of ¹⁴C-AR-709 IV. Plasma, bronchoalveolar lavage fluid, alveolar macrophages and bronchial mucosal biopsy samples were analysed by AMS. After IV administration, clearance of AR-709 was 496 mL/min, volume of distribution was 1,700 L and the absolute oral bioavailability was 2.5 %. Excretion in urine was negligible. At 8-12 h after IV dosing, ¹⁴C concentrations in lung samples were 15- (bronchial mucosa) to 200- (alveolar macrophages) fold higher than in plasma. In alveolar macrophages, ¹⁴C was still mostly associated with AR-709 at 12 h after dosing. The results of this microdose study indicate that AR-709 attains concentrations appreciably higher within the lung than in plasma. Its low oral bioavailability however, precludes oral administration. Although IV administration would appear to be an effective route of administration, this would limit the use of AR-709 to a clinical setting and would therefore be economically unsustainable. If further clinical development were to be undertaken, therefore, an alternative route of administration would be necessary.

  4. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. (United States)

    Göttlicher, M; Widmark, E; Li, Q; Gustafsson, J A


    Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have been shown to activate PPAR (peroxisome proliferator-activated receptor), a member of the steroid nuclear receptor superfamily. We have cloned the cDNA from the rat that is homologous to that from the mouse [Issemann, I. & Green, S. (1990) Nature (London) 347, 645-650], which encodes a 97% similar protein with a particularly well-conserved putative ligand-binding domain. To search for physiologically occurring activators, we established a transcriptional transactivation assay by stably expressing in CHO cells a chimera of rat PPAR and the human glucocorticoid receptor that activates expression of the placental alkaline phosphatase reporter gene under the control of the mouse mammary tumor virus promoter. Testing of compounds related to lipid metabolism or peroxisomal proliferation revealed that 150 microM concentrations of arachidonic or linoleic acid but not of dehydroepiandrosterone, cholesterol, or 25-hydroxy-cholesterol, activate the receptor chimera. In addition, saturated fatty acids induce the reporter gene. Shortening the chain length to n = 6 or introduction of an omega-terminal carboxylic group abolished the activation potential of the fatty acid. In conclusion, the present results indicate that fatty acids can regulate gene expression mediated by a member of the steroid nuclear receptor superfamily. Images PMID:1316614

  5. CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene. (United States)

    Christenson, L K; Johnson, P F; McAllister, J M; Strauss, J F


    Two putative CCAAT/enhancer-binding protein (C/EBP) response elements were identified in the proximal promoter of the human steroidogenic acute regulatory protein (StAR) gene, which encodes a key protein-regulating steroid hormone synthesis. Expression of C/EBPalpha and -beta increased StAR promoter activity in COS-1 and HepG2 cells. Cotransfection of C/EBPalpha or -beta and steroidogenic factor 1, a transcription factor required for cAMP regulation of StAR expression, into COS-1 augmented 8-bromoadenosine 3':5'-cyclic monophosphate (8-Br-cAMP)-stimulated promoter activity. When the putative C/EBP response elements were mutated, individually or together, a pronounced decline in basal StAR promoter activity in human granulosa-lutein cells resulted, but the fold stimulation of promoter activity by 8-Br-cAMP was unaffected. Recombinant C/EBPalpha and -beta bound to the two identified sequences but not the mutated elements. Human granulosa-lutein cell nuclear extracts also bound these elements but not the mutated sequences. An antibody to C/EBPbeta, but not C/EBPalpha, supershifted the nuclear protein complex associated with the more distal element. The complex formed by nuclear extracts with the proximal element was not supershifted by either antibody. Western blot analysis revealed the presence of C/EBPalpha and C/EBPbeta in human granulosa-lutein cell nuclear extracts. C/EBPbeta levels were up-regulated 3-fold by 8-Br-cAMP treatment. Our studies demonstrate a role for C/EBPbeta as well as yet to be identified proteins, which can bind to C/EBP response elements, in the regulation of StAR gene expression and suggest a mechanism by which C/EBPbeta participates in the cAMP regulation of StAR gene transcription.

  6. Incremental heating of Bishop Tuff sanidine reveals preeruptive radiogenic Ar and rapid remobilization from cold storage (United States)

    Andersen, Nathan L.; Jicha, Brian R.; Singer, Brad S.; Hildreth, Wes


    Accurate and precise ages of large silicic eruptions are critical to calibrating the geologic timescale and gauging the tempo of changes in climate, biologic evolution, and magmatic processes throughout Earth history. The conventional approach to dating these eruptive products using the 40Ar/39Ar method is to fuse dozens of individual feldspar crystals. However, dispersion of fusion dates is common and interpretation is complicated by increasingly precise data obtained via multicollector mass spectrometry. Incremental heating of 49 individual Bishop Tuff (BT) sanidine crystals produces 40Ar/39Ar dates with reduced dispersion, yet we find a 16-ky range of plateau dates that is not attributable to excess Ar. We interpret this dispersion to reflect cooling of the magma reservoir margins below ˜475 °C, accumulation of radiogenic Ar, and rapid preeruption remobilization. Accordingly, these data elucidate the recycling of subsolidus material into voluminous rhyolite magma reservoirs and the effect of preeruptive magmatic processes on the 40Ar/39Ar system. The youngest sanidine dates, likely the most representative of the BT eruption age, yield a weighted mean of 764.8 ± 0.3/0.6 ka (2σ analytical/full uncertainty) indicating eruption only ˜7 ky following the Matuyama‑Brunhes magnetic polarity reversal. Single-crystal incremental heating provides leverage with which to interpret complex populations of 40Ar/39Ar sanidine and U-Pb zircon dates and a substantially improved capability to resolve the timing and causal relationship of events in the geologic record.

  7. Mechanisms of tolerance in murine radiation bone marrow chimeras. II. Absence of nonspecific suppression in mature chimeras

    International Nuclear Information System (INIS)

    Auchincloss, H. Jr.; Sachs, D.H.


    Spleen cells from a series of allogeneic bone marrow chimeras were sensitized in vitro with stimulator cells from major histocompatibility complex recombinant strains of mice. The combinations were chosen such that both tolerated (host or donor) and nontolerated (third-party) antigens were present on the same stimulator cells in order to determine whether the tolerated host antigens might elicit nonspecific suppressor mechanisms affecting the cell-mediated lympholysis (CML) response to the nontolerated antigens. No evidence for such nonspecific suppression was obtained in several types of assays. Therefore, if suppressor mechanisms exist that mediate such tolerance in mature allogeneic chimeras then these mechanisms must be highly antigen-specific

  8. Chimera-like states in structured heterogeneous networks (United States)

    Li, Bo; Saad, David


    Chimera-like states are manifested through the coexistence of synchronous and asynchronous dynamics and have been observed in various systems. To analyze the role of network topology in giving rise to chimera-like states, we study a heterogeneous network model comprising two groups of nodes, of high and low degrees of connectivity. The architecture facilitates the analysis of the system, which separates into a densely connected coherent group of nodes, perturbed by their sparsely connected drifting neighbors. It describes a synchronous behavior of the densely connected group and scaling properties of the induced perturbations.

  9. Kinetics of Ar isotopes during neutron irradiation: 39Ar loss from minerals as a source of error in 40Ar/39Ar dating

    International Nuclear Information System (INIS)

    Hess, J.C.; Lippolt, H.J.


    The loss of 39 Ar from minerals in the course of neutron activation for 40 Ar/ 39 Ar dating is studied by directly measuring the loss rates in vacuum-sealed ampoules. Biotite shows 39 Ar losses between 0.1% and 16%. These losses are predominantly due to diffusion processes from K-poor alteration-phase intergrowths in the biotites at the elevated temperatures during the irradiation. Estimates for the irradiation temperatures range from 150 0 to 180 0 C. Direct 39 Ar recoil loss from biotite seems to be minor compared to difussion loss of recoil-implanted 39 Ar. Precise 40 Ar/ 39 Ar dating of biotites therefore requires the measurement of the 39 Ar losses during irradiation. Glauconite loses not only neutron-induced Ar isotopes ( 39 Ar: 20-22%, 37 Ar: 17-19%) but also radiogenic 40 Ar(∼9%). Slight 39 Ar losses are also observed for light micas (0.2% and 0.35%), hornblendes (0.1%) and sanidines (200 and 700 ppm). 25 refs.; 4 figs.; 6 tabs

  10. Expression of AR, 5αR1 and 5αR2 in bladder urothelial carcinoma and relationship to clinicopathological factors. (United States)

    Hata, Shuko; Ise, Kazue; Azmahani, Abdullah; Konosu-Fukaya, Sachiko; McNamara, Keely May; Fujishima, Fumiyoshi; Shimada, Keiji; Mitsuzuka, Koji; Arai, Yoichi; Sasano, Hironobu; Nakamura, Yasuhiro


    Bladder urothelial carcinoma is increasing in incidence with age and its prognosis could become worse when accompanied with metastasis. Effective treatment of these advanced patients is required and it becomes important to understand its underlying biology of this neoplasm, especially with regard to its biological pathways. A potential proposed pathway is androgen receptor (AR)-mediated intracellular signaling but the details have remained relatively unexplored. The expression of AR, 5α-reductase type1 (5αR1) and 5α-reductase type2 (5αR2) were examined in the bladder cancer cell line T24 and surgical pathology specimens. We also evaluated the status of androgen related cell proliferation and migration using the potent, non-aromatizable androgen agonist 5α-dihydrotestosterone (DHT). DHT treatment significantly increased AR mRNA expression level, but not those of 5αR1 and 5αR2 in T24 cells. DHT also suppressed cellular migration with weaker and opposite effects on cell proliferation. A significant inverse correlation was detected between pT stage and AR, 5αR1 and 5αR2 immunoreactivity. Inverse correlations detected between tumor grade and AR/androgen metabolizing enzyme also suggested that the loss of AR and androgen-producing enzymes could be associated with tumor progression. Effects of DHT on cells also suggest that androgens may regulate cellular behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Construction and characterization of the interdomain chimeras using Cry11Aa and Cry11Ba from Bacillus thuringiensis and identification of a possible novel toxic chimera. (United States)

    Sun, Yunjun; Zhao, Qiang; Zheng, Dasheng; Ding, Xuezhi; Wang, Jingfang; Hu, Quanfang; Yuan, Zhiming; Park, Hyun-Woo; Xia, Liqiu


    Three structural domains of mosquitocidal Cry11Aa and Cry11Ba from Bacillus thuringiensis were exchanged to produce interdomain chimeras [BAA (11Ba/11Aa/11Aa), ABA (11Aa/11Ba/11Aa), AAB (11Aa/11Aa/11Ba), ABB (11Aa/11Ba/11Ba), BAB (11Ba/11Aa/11Ba), BBA (11Ba/11Ba/11Aa]. Chimeras BAB, BAA, BBA, and AAB formed inclusion bodies in the crystal-negative B. thuringiensis host and produced expected protein bands on SDS-PAGE gel. However, no inclusion body or target protein could be found for chimeras ABA and ABB. In bioassays using the fourth-instar larvae of Culex quinquefasciatus and Aedes aegypti, AAB had ~50 % lethal concentrations of 4.8 and 2.2 μg ml(-1), respectively; however, the rest of chimeras were not toxic. This study thus helps to understand the domain-function relationships of the Cry11Aa and Cry11Ba toxins. The toxic chimera, AAB, might be a candidate for mosquito control as its amino acid sequence is different from the two parental toxins.

  12. Anti-bacterial immunity to Listeria monocytogenes in allogeneic bone marrow chimera in mice

    International Nuclear Information System (INIS)

    Onoe, K.; Good, R.A.; Yamamoto, K.


    Protection and delayed-type hypersensitivity (DTH) to the facultative intracellular bacterium Listeria monocytogenes (L.m.) were studied in allogeneic and syngeneic bone marrow chimeras. Lethally irradiated AKR (H-2k) mice were successfully reconstituted with marrow cells from C57BL/10 (B10) (H-2b), B10 H-2-recombinant strains or syngeneic mice. Irradiated AKR mice reconstituted with marrow cells from H-2-compatible B10.BR mice, [BR----AKR], as well as syngeneic marrow cells, [AKR----AKR], showed a normal level of responsiveness to the challenge stimulation with the listeria antigens when DTH was evaluated by footpad reactions. These mice also showed vigorous activities in acquired resistance to the L.m. By contrast, chimeric mice that had total or partial histoincompatibility at the H-2 determinants between donor and recipient, [B10----AKR], [B10.AQR----AKR], [B10.A(4R)----AKR], or [B10.A(5R)----AKR], were almost completely unresponsive in DTH and antibacterial immunity. However, when [B10----AKR] H-2-incompatible chimeras had been immunized with killed L.m. before challenge with live L.m., these mice manifested considerable DTH and resistance to L.m. These observations suggest that compatibility at the entire MHC between donor and recipient is required for bone marrow chimeras to be able to manifest DTH and protection against L.m. after a short-term immunization schedule. However, this requirement is overcome by a preceding or more prolonged period of immunization with L.m. antigens. These antigens, together with marrow-derived antigen-presenting cells, can then stimulate and expand cell populations that are restricted to the MHC (H-2) products of the donor type

  13. Interordinal chimera formation between medaka and zebrafish for analyzing stem cell differentiation. (United States)

    Hong, Ni; Chen, Songlin; Ge, Ruowen; Song, Jianxing; Yi, Meisheng; Hong, Yunhan


    Chimera formation is a standard test for pluripotency of stem cells in vivo. Interspecific chimera formation between distantly related organisms offers also an attractive approach for propagating endangered species. Parameters influencing interspecies chimera formation have remained poorly elucidated. Here, we report interordinal chimera formation between medaka and zebrafish, which separated ∼320 million years ago and exhibit a more than 2-fold difference in developmental speed. We show that, on transplantation into zebrafish blastulae, both noncultivated blastomeres and long-term cultivated embryonic stem (ES) cells of medaka adopted the zebrafish developmental program and differentiated into physiologically functional cell types including pigment cells, blood cells, and cardiomyocytes. We also show that medaka ES cells express differentiation gene markers during chimeric embryogenesis. Therefore, the evolutionary distance and different embryogenesis speeds do not produce donor-host incompatibility to compromise chimera formation between medaka and zebrafish, and molecular markers are valuable for analyzing lineage commitment and cell differentiation in interspecific chimeric embryos.

  14. Chimera states in a population of identical oscillators under planar ...

    Indian Academy of Sciences (India)

    finding, observed in both a collection of van der Pol oscillators and chaotic Rössler oscillators, fur- ther simplifies the existence criterion for chimeras, thereby broadens the range of their applicability to real-world situations. Keywords. Synchronization; chimera; Rössler system; van der Pol oscillator. PACS Nos 05.45.

  15. Chimera States in Continuous Media: Existence and Distinctness (United States)

    Nicolaou, Zachary G.; Riecke, Hermann; Motter, Adilson E.


    The defining property of chimera states is the coexistence of coherent and incoherent domains in systems that are structurally and spatially homogeneous. The recent realization that such states might be common in oscillator networks raises the question of whether an analogous phenomenon can occur in continuous media. Here, we show that chimera states can exist in continuous systems even when the coupling is strictly local, as in many fluid and pattern forming media. Using the complex Ginzburg-Landau equation as a model system, we characterize chimera states consisting of a coherent domain of a frozen spiral structure and an incoherent domain of amplitude turbulence. We show that in this case, in contrast with discrete network systems, fluctuations in the local coupling field play a crucial role in limiting the coherent regions. We suggest these findings shed light on new possible forms of coexisting order and disorder in fluid systems.

  16. Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice

    International Nuclear Information System (INIS)

    Noguchi, M.; Ogasawara, M.; Iwabuchi, K.; Osgasawara, K.; Ishihara, T.; Good, R.A.; Morikawa, K.; Onoe, K.


    The authors have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, the author analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that were provided by the thymuses of the recipient mice

  17. Interspecific in vitro assay for the chimera-forming ability of human pluripotent stem cells. (United States)

    Masaki, Hideki; Kato-Itoh, Megumi; Umino, Ayumi; Sato, Hideyuki; Hamanaka, Sanae; Kobayashi, Toshihiro; Yamaguchi, Tomoyuki; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Nakauchi, Hiromitsu


    Functional assay limitations are an emerging issue in characterizing human pluripotent stem cells (PSCs). With rodent PSCs, chimera formation using pre-implantation embryos is the gold-standard assay of pluripotency (competence of progeny to differentiate into all three germ layers). In human PSCs (hPSCs), however, this can only be monitored via teratoma formation or in vitro differentiation, as ethical concerns preclude generation of human-human or human-animal chimeras. To circumvent this issue, we developed a functional assay utilizing interspecific blastocyst injection and in vitro culture (interspecies in vitro chimera assay) that enables the development and observation of embryos up to headfold stage. The assay uses mouse pre-implantation embryos and rat, monkey and human PSCs to create interspecies chimeras cultured in vitro to the early egg-cylinder stage. Intra- and interspecific chimera assays with rodent PSC lines were performed to confirm the consistency of results in vitro and in vivo. The behavior of chimeras developed in vitro appeared to recapitulate that of chimeras developed in vivo; that is, PSC-derived cells survived and were integrated into the epiblast of egg-cylinder-stage embryos. This indicates that the interspecific in vitro chimera assay is useful in evaluating the chimera-forming ability of rodent PSCs. However, when human induced PSCs (both conventional and naïve-like types) were injected into mouse embryos and cultured, some human cells survived but were segregated; unlike epiblast-stage rodent PSCs, they never integrated into the epiblast of egg-cylinder-stage embryos. These data suggest that the mouse-human interspecies in vitro chimera assay does not accurately reflect the early developmental potential/process of hPSCs. The use of evolutionarily more closely related species as host embryos might be necessary to evaluate the developmental potency of hPSCs. © 2015. Published by The Company of Biologists Ltd.

  18. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats

    Directory of Open Access Journals (Sweden)

    Malgorzata S. Martin-Gronert


    Full Text Available Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC peptides within the arcuate nucleus of the hypothalamus (ARC. We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus of in utero growth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist.

  19. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats. (United States)

    Martin-Gronert, Malgorzata S; Stocker, Claire J; Wargent, Edward T; Cripps, Roselle L; Garfield, Alastair S; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S H; Cawthorne, Michael A; Arch, Jonathan R S; Heisler, Lora K; Ozanne, Susan E


    Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. © 2016. Published by The Company of Biologists Ltd.

  20. Reference binding energies of transition metal carbides by core-level x-ray photoelectron spectroscopy free from Ar+ etching artefacts (United States)

    Greczynski, G.; Primetzhofer, D.; Hultman, L.


    We report x-ray photoelectron spectroscopy (XPS) core level binding energies (BE's) for the widely-applicable groups IVb-VIb transition metal carbides (TMCs) TiC, VC, CrC, ZrC, NbC, MoC, HfC, TaC, and WC. Thin film samples are grown in the same deposition system, by dc magnetron co-sputtering from graphite and respective elemental metal targets in Ar atmosphere. To remove surface contaminations resulting from exposure to air during sample transfer from the growth chamber into the XPS system, layers are either (i) Ar+ ion-etched or (ii) UHV-annealed in situ prior to XPS analyses. High resolution XPS spectra reveal that even gentle etching affects the shape of core level signals, as well as BE values, which are systematically offset by 0.2-0.5 eV towards lower BE. These destructive effects of Ar+ ion etch become more pronounced with increasing the metal atom mass due to an increasing carbon-to-metal sputter yield ratio. Systematic analysis reveals that for each row in the periodic table (3d, 4d, and 5d) C 1s BE increases from left to right indicative of a decreased charge transfer from TM to C atoms, hence bond weakening. Moreover, C 1s BE decreases linearly with increasing carbide/metal melting point ratio. Spectra reported here, acquired from a consistent set of samples in the same instrument, should serve as a reference for true deconvolution of complex XPS cases, including multinary carbides, nitrides, and carbonitrides.

  1. Regulation of StAR by the N-terminal Domain and Coinduction of SIK1 and TIS11b/Znf36l1 in Single Cells. (United States)

    Lee, Jinwoo; Tong, Tiegang; Duan, Haichuan; Foong, Yee Hoon; Musaitif, Ibrahim; Yamazaki, Takeshi; Jefcoate, Colin


    The cholesterol transfer function of steroidogenic acute regulatory protein (StAR) is uniquely integrated into adrenal cells, with mRNA translation and protein kinase A (PKA) phosphorylation occurring at the mitochondrial outer membrane (OMM). The StAR C-terminal cholesterol-binding domain (CBD) initiates mitochondrial intermembrane contacts to rapidly direct cholesterol to Cyp11a1 in the inner membrane (IMM). The conserved StAR N-terminal regulatory domain (NTD) includes a leader sequence targeting the CBD to OMM complexes that initiate cholesterol transfer. Here, we show how the NTD functions to enhance CBD activity delivers more efficiently from StAR mRNA in adrenal cells, and then how two factors hormonally restrain this process. NTD processing at two conserved sequence sites is selectively affected by StAR PKA phosphorylation. The CBD functions as a receptor to stimulate the OMM/IMM contacts that mediate transfer. The NTD controls the transit time that integrates extramitochondrial StAR effects on cholesterol homeostasis with other mitochondrial functions, including ATP generation, inter-organelle fusion, and the major permeability transition pore in partnership with other OMM proteins. PKA also rapidly induces two additional StAR modulators: salt-inducible kinase 1 (SIK1) and Znf36l1/Tis11b. Induced SIK1 attenuates the activity of CRTC2, a key mediator of StAR transcription and splicing, but only as cAMP levels decline. TIS11b inhibits translation and directs the endonuclease-mediated removal of the 3.5-kb StAR mRNA. Removal of either of these functions individually enhances cAMP-mediated induction of StAR. High-resolution fluorescence in situ hybridization (HR-FISH) of StAR RNA reveals asymmetric transcription at the gene locus and slow RNA splicing that delays mRNA formation, potentially to synchronize with cholesterol import. Adrenal cells may retain slow transcription to integrate with intermembrane NTD activation. HR-FISH resolves individual 3.5-kb StAR

  2. Production of somatic chimera chicks by injection of bone marrow cells into recipient blastoderms. (United States)

    Heo, Young Tae; Lee, Sung Ho; Kim, Teoan; Kim, Nam Hyung; Lee, Hoon Taek


    Several types of cells, including blastoderm cells, primordial germ cells, and embryonic germ cells were injected into early-stage recipient embryos to produce chimera avians and to gain insights into cell development. However, a limited number of studies of avian adult stem cells have also been conducted. This study is, to the best of our knowledge, the first to evaluate chicken bone marrow cells' (chBMC) ability to differentiate into multiple cell lineages and capability to generate chimera chicks. We induced random differentiation of chBMCs in vitro and injected immunologically selected pluripotent cells in chBMCs into the blastoderms of recipient eggs. The multipotency of BMCs from the barred Plymouth rock (BPR) was confirmed via AP staining, RT-PCR, immunocytochemistry, and FACS using specific markers, such as Oct-4 and SSEA-1, 3 and 4. Isolated chBMCs were found to be able to induce in vitro differentiation to multiple cell lineages. Approximately 5,000 chBMCs were injected into the blastoderms of white leghorn (WL) recipients and proved able to contribute to the generation of somatic chimera chicks with a frequency of 2.7% (2 of 73). Confirmation of chimerism in hatched chicks was achieved via PCR analysis using D-loop-specific primers of BPR and WL. Our study demonstrated the successful production of chimera chicks using chBMC. Therefore, we propose that the use of adult chBMCs may constitute a new possible approach to the production of chimera poultry, and may provide helpful studies in avian developmental biology.

  3. Identification of an IL-1-induced gene expression pattern in AR+ PCa cells that mimics the molecular phenotype of AR- PCa cells. (United States)

    Thomas-Jardin, Shayna E; Kanchwala, Mohammed S; Jacob, Joan; Merchant, Sana; Meade, Rachel K; Gahnim, Nagham M; Nawas, Afshan F; Xing, Chao; Delk, Nikki A


    In immunosurveillance, bone-derived immune cells infiltrate the tumor and secrete inflammatory cytokines to destroy cancer cells. However, cancer cells have evolved mechanisms to usurp inflammatory cytokines to promote tumor progression. In particular, the inflammatory cytokine, interleukin-1 (IL-1), is elevated in prostate cancer (PCa) patient tissue and serum, and promotes PCa bone metastasis. IL-1 also represses androgen receptor (AR) accumulation and activity in PCa cells, yet the cells remain viable and tumorigenic; suggesting that IL-1 may also contribute to AR-targeted therapy resistance. Furthermore, IL-1 and AR protein levels negatively correlate in PCa tumor cells. Taken together, we hypothesize that IL-1 reprograms AR positive (AR + ) PCa cells into AR negative (AR - ) PCa cells that co-opt IL-1 signaling to ensure AR-independent survival and tumor progression in the inflammatory tumor microenvironment. LNCaP and PC3 PCa cells were treated with IL-1β or HS-5 bone marrow stromal cell (BMSC) conditioned medium and analyzed by RNA sequencing and RT-QPCR. To verify genes identified by RNA sequencing, LNCaP, MDA-PCa-2b, PC3, and DU145 PCa cell lines were treated with the IL-1 family members, IL-1α or IL-1β, or exposed to HS-5 BMSC in the presence or absence of Interleukin-1 Receptor Antagonist (IL-1RA). Treated cells were analyzed by western blot and/or RT-QPCR. Comparative analysis of sequencing data from the AR + LNCaP PCa cell line versus the AR - PC3 PCa cell line reveals an IL-1-conferred gene suite in LNCaP cells that is constitutive in PC3 cells. Bioinformatics analysis of the IL-1 regulated gene suite revealed that inflammatory and immune response pathways are primarily elicited; likely facilitating PCa cell survival and tumorigenicity in an inflammatory tumor microenvironment. Our data supports that IL-1 reprograms AR + PCa cells to mimic AR - PCa gene expression patterns that favor AR-targeted treatment resistance and cell survival. © 2018 Wiley

  4. 40Ar/(39)Ar geochronology and paleomagnetic stratigraphy of the Lukeino and lower Chemeron Formations at Tabarin and Kapcheberek, Tugen Hills, Kenya. (United States)

    Deino, Alan L; Tauxe, Lisa; Monaghan, Marc; Hill, Andrew


    (40)Ar/(39)Ar single-crystal laser-fusion dating, K-Ar dating, and paleomagnetic reversal stratigraphy have been used to determine the chronostratigraphy of the Kabarnet Trachyte, Lukeino Formation, Kaparaina Basalt Formation, and Chemeron Formation at the sites of Kapcheberek (BPRP#77) and Tabarin (BPRP#77) in the Tugen Hills, Kenya. The succession ranges in age from 6.56-3.8 Ma. The upper Lukeino Formation at Kapcherberek, including the fauna from the site BPRP#76, was deposited during chron C3r and can be constrained to the interval 5.88-5.72 Ma. The Chemeron Formation at Tabarin includes at the base an ignimbrite and associated basal air-fall tuff with a combined age of 5.31+/-0.03 Ma. Sedimentary and volcaniclastic rocks of the Chemeron Formation which unconformably overlie the ignimbrite record chrons C3n.2n through C2Ar. The combined(40)Ar/(39)Ar and paleomagnetic data constrain the age of this sequence to 4.63-3.837 Ma. The age of the Tabarin mandible fragment (KNM-TH 13150) and associated fauna at site BPRP#77 in the Chemeron Formation is 4.48-4.41 Ma, marginally older than similar early hominids from Aramis, Ethiopia. Basin subsidence appears to be defining an overall accumulation rate of about 17 cm/ka over the 2.7 Ma represented at Tabarin and Kapcheberek, despite episodes of rapid accumulation and hiatuses. Copyright 2002 Academic Press.

  5. Experimental observation of chimera and cluster states in a minimal globally coupled network

    Energy Technology Data Exchange (ETDEWEB)

    Hart, Joseph D. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Physics, University of Maryland, College Park, Maryland 20742 (United States); Bansal, Kanika [Department of Mathematics, University at Buffalo, SUNY Buffalo, New York 14260 (United States); US Army Research Laboratory, Aberdeen Proving Ground, Maryland 21005 (United States); Murphy, Thomas E. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Electrical and Computer Engineering, University of Maryland, College Park, Maryland 20742 (United States); Roy, Rajarshi [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States); Department of Physics, University of Maryland, College Park, Maryland 20742 (United States); Institute for Physical Science and Technology, University of Maryland, College Park, Maryland 20742 (United States)


    A “chimera state” is a dynamical pattern that occurs in a network of coupled identical oscillators when the symmetry of the oscillator population is broken into synchronous and asynchronous parts. We report the experimental observation of chimera and cluster states in a network of four globally coupled chaotic opto-electronic oscillators. This is the minimal network that can support chimera states, and our study provides new insight into the fundamental mechanisms underlying their formation. We use a unified approach to determine the stability of all the observed partially synchronous patterns, highlighting the close relationship between chimera and cluster states as belonging to the broader phenomenon of partial synchronization. Our approach is general in terms of network size and connectivity. We also find that chimera states often appear in regions of multistability between global, cluster, and desynchronized states.

  6. Hydroxyl radical yields in the tracks of high energy 13C6+ and 36Ar18+ ions in liquid water

    International Nuclear Information System (INIS)

    Baldacchino, G.; Vigneron, G.; Renault, J.P.; Le Caer, S.; Pin, S.; Mialocq, J.-C.; Balanzat, E.; Bouffard, S.


    This article reports the determination of the OH · radiolytic yields in water irradiated by high energy C 6+ and Ar 18+ ions with LET values of 32 ± 2 and 280 ± 10 eV nm -1 . The time evolution of the yields between 9 x 10 -11 and 9 x 10 -8 s was deduced using the scavenging method with SCN - and Br - and pulse radiolysis with pulses of 5 and 10 μs. The thiocyanate chemical system is less affected with the local high dose rates specific to the high LET particles than the bromide system. At 32 eV nm -1 with C 6+ ions, G(OH · ) reaches a maximum of 1.5 x 10 -7 mol J -1 at 1 ns and decreases at earlier times. With Ar 18+ ions of 280 eV nm -1 G(OH · ) is always increasing at early times up to 1.6 x 10 -7 mol J -1 at 9 x 10 -11 s. In this case the evolution of the hydroxyl radical yields agrees with the high local concentrations obtained with Ar 18+ and C 6+ ions and depicted in recent literature with the yields of the hydrated electron in the ns range

  7. Radiobiological research on carnation chimerae Dianthus Caryophyllus L

    International Nuclear Information System (INIS)

    Pereau-Leroy, Pierre.


    A radiobiological study of periclinal carnation chimerae is carried out by subjecting whole plants and cuttings at different physiological stages to cobalt 60 gamma radiation under different dose and dose rate conditions. The effects of these treatments are observed during cultivation of the treated plants and by microscopic examination of irradiated meristem sections. The destruction of meristem cells in proportions varying with the irradiation conditions leads to structural changes in the chimerae; the more frequent change is the formation of genetically homogeneous stalks from different genotypes existing in the irradiated plant. Treatment by ionizing radiations is thus a practical means of detecting periclinical chimerae which, as in the case of carnations, are very common in plants grown by vegetative propagation. However since more than two independent meristem cell groups are usually present it is not possible by this method alone to define the distribution of the differentent genotypes in these groups; additional genetic studies or cell labelling such as chlorophyll or genoma mutations are then necessary [fr

  8. Integration of the GET electronics for the CHIMERA and FARCOS devices (United States)

    De Filippo, E.; Acosta, L.; Auditore, L.; Boiano, C.; Cardella, G.; Castoldi, A.; D’Andrea, M.; De Luca, S.; Favela, F.; Fichera, F.; Giudice, N.; Gnoffo, B.; Grimaldi, A.; Guazzoni, C.; Lanzalone, G.; Librizzi, F.; Litrico, P.; Maiolino, C.; Maffesanti, S.; Martorana, NS; Pagano, A.; Pagano, EV; Papa, M.; Parsani, T.; Passaro, G.; Pirrone, S.; Politi, G.; Previdi, F.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Saccà, G.; Salemi, G.; Sciliberto, D.; Trifirò, A.; Trimarchi, M.


    A new front-end based on digital GET electronics has been adopted for the readout of the CsI(Tl) detectors of the CHIMERA 4π multi-detector and for the new modular Femtoscopy Array for Correlation and Spectroscopy (FARCOS). It is expected that the coupling of CHIMERA with the FARCOS array, featuring high angular and energy resolution, and the adoption of the new digital electronics will be well suited for improving specific future data analysis, with the full shape storage of the signals, in the field of heavy ion reactions with stable and exotic beams around the Fermi energies domain. Integration of the GET electronics with CHIMERA and FARCOS devices and with the local analog data acquisition will be briefly discussed. We present some results from previous experimental tests and from the first in-beam experiment (Hoyle-Gamma) with the coupled GET+CHIMERA data acquisition.

  9. Chimera-like states in a neuronal network model of the cat brain (United States)

    Santos, M. S.; Szezech, J. D.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Batista, A. M.; Viana, R. L.; Kurths, J.


    Neuronal systems have been modeled by complex networks in different description levels. Recently, it has been verified that networks can simultaneously exhibit one coherent and other incoherent domain, known as chimera states. In this work, we study the existence of chimera states in a network considering the connectivity matrix based on the cat cerebral cortex. The cerebral cortex of the cat can be separated in 65 cortical areas organised into the four cognitive regions: visual, auditory, somatosensory-motor and frontolimbic. We consider a network where the local dynamics is given by the Hindmarsh-Rose model. The Hindmarsh-Rose equations are a well known model of neuronal activity that has been considered to simulate membrane potential in neuron. Here, we analyse under which conditions chimera states are present, as well as the affects induced by intensity of coupling on them. We observe the existence of chimera states in that incoherent structure can be composed of desynchronised spikes or desynchronised bursts. Moreover, we find that chimera states with desynchronised bursts are more robust to neuronal noise than with desynchronised spikes.

  10. Spectroscopic analysis of visible and near UV light emitted by Ar7+ and Ar6+ ions produced in Ar8+-He and Ar8+-H2 collisions at 120 keV

    International Nuclear Information System (INIS)

    Boduch, P.; Chantepie, M.; Hennecart, D.; Husson, X.; Kucal, H.; Lecler, D.; Stolterfoht, N.; Druetta, M.; Fawcett, B.; Wilson, M.


    A spectroscopic analysis of light emitted in the 2000-6000A wavelength range by Ar 7+ and Ar 6+ ions produced in Ar 8+ -He and Ar 8+ -H 2 collisions at 120 keV is performed. Well resolved fine structure components of 5s-5p and 5p-5d transitions in Ar VIII following single electron capture are precisely measured. Predominant lines due to double electron capture are observed. In particular, strong lines observed both in Ar 8+ -He and Ar 8+ -H 2 collisions are attributed to Ryberg transitions 3snl-3sn'l' in Ar VII. Attempts at identifications are made for the transition 3dnl-3dn'l' (n=4, 5) with the help of ab initio calculations. Photon emission cross sections for individual lines are determined from the measured data. (orig.)

  11. Chimera states in complex networks: interplay of fractal topology and delay (United States)

    Sawicki, Jakub; Omelchenko, Iryna; Zakharova, Anna; Schöll, Eckehard


    Chimera states are an example of intriguing partial synchronization patterns emerging in networks of identical oscillators. They consist of spatially coexisting domains of coherent (synchronized) and incoherent (desynchronized) dynamics. We analyze chimera states in networks of Van der Pol oscillators with hierarchical connectivities, and elaborate the role of time delay introduced in the coupling term. In the parameter plane of coupling strength and delay time we find tongue-like regions of existence of chimera states alternating with regions of existence of coherent travelling waves. We demonstrate that by varying the time delay one can deliberately stabilize desired spatio-temporal patterns in the system.

  12. Role of C5 Activation Products in Sepsis

    Directory of Open Access Journals (Sweden)

    Peter A. Ward


    Full Text Available Complement activation products are known to be generated in the setting of both experimental and human sepsis. C5 activation products (C5a anaphylatoxin and the membrane attack complex [MAC] C5b-9 are generated during sepsis following infusion of endotoxin, or after cecal ligation and puncture (CLP, which produces polymicrobial sepsis. C5a reacts with its receptors C5aR and C5L2 in a manner that creates the “cytokine storm”, and is associated with development of multiorgan failure (MOF. A number of other complications arising from the interaction of C5a with its receptors include apoptosis of lymphoid cells, loss of innate immune functions of neutrophils (PMNs, polymorphonuclear leukocytes, cardiomyopathy, disseminated intravascular coagulation, and complications associated with MOF. Neutralization of C5a in vivo or absence/blockade of C5a receptors greatly reduces the adverse events in the setting of sepsis, markedly attenuates MOF, and greatly improves survival. Regarding the possible role of C5b-9 in sepsis, the literature is conflicting. Some studies suggest that C5b-9 is protective, while other studies suggest the contrary. Clearly, in human sepsis, C5a and its receptors may be logical targets for interception.

  13. A Knock-in Reporter for a Novel AR-Targeted Therapy (United States)


    AWARD NUMBER: W81XWH-15-1-0049 TITLE: A Knock -in Reporter for a Novel AR-Targeted Therapy PRINCIPAL INVESTIGATOR: Chunhong Yan, Ph.D...5a. CONTRACT NUMBER A Knock -in Reporter for a Novel AR-Targeted Therapy 5b. GRANT NUMBER W81XWH-15-1-0049 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...enhancer. While the knock -in reporter is expected to faithfully reproduce chemical responses of the endogenous AR gene, we carried out a pilot screen

  14. Graphene synthesis on SiC: Reduced graphitization temperature by C-cluster and Ar-ion implantation

    International Nuclear Information System (INIS)

    Zhang, R.; Li, H.; Zhang, Z.D.; Wang, Z.S.; Zhou, S.Y.; Wang, Z.; Li, T.C.; Liu, J.R.; Fu, D.J.


    Thermal decomposition of SiC is a promising method for high quality production of wafer-scale graphene layers, when the high decomposition temperature of SiC is substantially reduced. The high decomposition temperature of SiC around 1400 °C is a technical obstacle. In this work, we report on graphene synthesis on 6H–SiC with reduced graphitization temperature via ion implantation. When energetic Ar, C 1 and C 6 -cluster ions implanted into 6H–SiC substrates, some of the Si–C bonds have been broken due to the electronic and nuclear collisions. Owing to the radiation damage induced bond breaking and the implanted C atoms as an additional C source the graphitization temperature was reduced by up to 200 °C

  15. Inhibition of Apoptosis Overcomes Stage-Related Compatibility Barriers to Chimera Formation in Mouse Embryos. (United States)

    Masaki, Hideki; Kato-Itoh, Megumi; Takahashi, Yusuke; Umino, Ayumi; Sato, Hideyuki; Ito, Keiichi; Yanagida, Ayaka; Nishimura, Toshinobu; Yamaguchi, Tomoyuki; Hirabayashi, Masumi; Era, Takumi; Loh, Kyle M; Wu, Sean M; Weissman, Irving L; Nakauchi, Hiromitsu


    Cell types more advanced in development than embryonic stem cells, such as EpiSCs, fail to contribute to chimeras when injected into pre-implantation-stage blastocysts, apparently because the injected cells undergo apoptosis. Here we show that transient promotion of cell survival through expression of the anti-apoptotic gene BCL2 enables EpiSCs and Sox17 + endoderm progenitors to integrate into blastocysts and contribute to chimeric embryos. Upon injection into blastocyst, BCL2-expressing EpiSCs contributed to all bodily tissues in chimeric animals while Sox17 + endoderm progenitors specifically contributed in a region-specific fashion to endodermal tissues. In addition, BCL2 expression enabled rat EpiSCs to contribute to mouse embryonic chimeras, thereby forming interspecies chimeras that could survive to adulthood. Our system therefore provides a method to overcome cellular compatibility issues that typically restrict chimera formation. Application of this type of approach could broaden the use of embryonic chimeras, including region-specific chimeras, for basic developmental biology research and regenerative medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Density effects on high-n molecular Rydberg states: CH3I and C6H6 in H2 and Ar

    International Nuclear Information System (INIS)

    Asaf, U.; Felps, W.S.; Rupnik, K.; McGlynn, S.P.; Ascarelli, G.


    The absorption spectra of high-n Rydberg states of methyl iodide and benzene perturbed by varying number densities of hydrogen or argon, range 0.9x10 20 --10.5x10 20 cm -3 for H 2 and 0.6x10 20 --7.5x10 20 cm -3 for Ar, have been investigated. The high-n molecular states of both absorbers were found to shift linearly with the number density of atomic Ar and molecular H 2 scatterers. The Fermi formula modified by the Alekseev--Sobel'man polarization term provides an excellent fit of the shift data. The electron scattering lengths obtained are: 0.93 a 0 for H 2 and -1.63 a 0 for Ar using the CH 3 I absorber; and 0.99 a 0 for H 2 and -1.57 a 0 for Ar using the C 6 H 6 absorber. The electron scattering lengths for H 2 and Ar agree with the results of an empirical model that correlates scattering lengths and the polarizabilities α(spherical) for inert atoms and α 2 (nonspherical) for H 2 molecule

  17. Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites. (United States)

    Laverty, Duncan; Thomas, Philip; Field, Martin; Andersen, Ole J; Gold, Matthew G; Biggin, Philip C; Gielen, Marc; Smart, Trevor G


    γ-Aminobutyric acid receptors (GABA A Rs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABA A Rs is the α subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABA A R function requires high-resolution structures. Here we present the first atomic structures of a GABA A R chimera at 2.8-Å resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the α-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABA A Rs in neurological disorders.

  18. Thymectomized, irradiated, and bone marrow-reconstituted chimeras have normal cytolytic T lymphocyte precursors but a defect in lymphokine production

    International Nuclear Information System (INIS)

    Duprez, V.; Maziarz, R.; Weinberger, O.; Burakoff, S.J.


    A model system has been developed to study extrathymic T cell differentiation; mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1 + cells. After 8 wk, the spleen cells of these athymic, bone marrow-reconstituted chimeras contain Thy-1 + precytolytic T lymphocytes (CTL) that are able to respond to antigen only if supernatant from Con A-activated T cells is added to culture. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be immature T cells. Initial evaluation of the CTL repertoire of these athymic mice demonstrated that the CTL generated to trinitrophenyl-modified syngeneic cells are H-2-restricted, and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal mice but not in nude mice. In this report, the authors demonstrate a helper T cell defect in these thymectomized chimeras. These chimeras lack an Ly-1 + helper cell required for thymocytes to differentiate to CTL. Further studies revealed that when spleen cells from these thymectomized chimeras were stimulated with Con A, they produced normal levels of interleukin 2. However, these splenocytes were defective in the production of another factor needed for CTL differentiation

  19. properties of Cr(C,N) hard coatings deposited in Ar-C2H2-N2 plasma

    International Nuclear Information System (INIS)

    Macek, M.; Cekada, M.; Kek, D.; Panjan, P.


    Mechanical properties, microstructure and the average chemical composition of Cr(C,N) hard coatings deposited in Ar-C 2 H 2 -N 2 plasma strongly depends on the partial pressure of the reactive gases (N 2 , C 2 H 2 ) and on the type of the deposition equipment. In this study we report on the properties of Cr(C,N) hard coatings deposited by means of the triode ion plating in the BAI 730 apparatus and those prepared by sputter deposition in Balzers Sputron in the pressure range from 0.12 Pa (pure Ar) up to 0.35 Pa with different ratios (0-100%) between C 2 H 2 and N 2 . At first mechanical properties (microhardness and adhesion) of coatings were analyzed on the common way. Internal stress was measured by the radius of substrate curvature. Chemical composition of coatings was analyzed by means of AES while the Raman and XPS spectroscopy was used to determined the nature of carbon bonding in the Cr(C,N) films. Microstructure was determined by XRD as well as by means of TEM and TED. Chemical state of various elements in the coating has been studied by XPS. The ratio of the carbide bond (C-Cr) against the C-C and C-H bonds was calculated. The existence of the graphite phase in some Cr(C,N) coatings was confirmed by Raman spectroscopy. (Authors)

  20. Chimera states in a multilayer network of coupled and uncoupled neurons (United States)

    Majhi, Soumen; Perc, Matjaž; Ghosh, Dibakar


    We study the emergence of chimera states in a multilayer neuronal network, where one layer is composed of coupled and the other layer of uncoupled neurons. Through the multilayer structure, the layer with coupled neurons acts as the medium by means of which neurons in the uncoupled layer share information in spite of the absence of physical connections among them. Neurons in the coupled layer are connected with electrical synapses, while across the two layers, neurons are connected through chemical synapses. In both layers, the dynamics of each neuron is described by the Hindmarsh-Rose square wave bursting dynamics. We show that the presence of two different types of connecting synapses within and between the two layers, together with the multilayer network structure, plays a key role in the emergence of between-layer synchronous chimera states and patterns of synchronous clusters. In particular, we find that these chimera states can emerge in the coupled layer regardless of the range of electrical synapses. Even in all-to-all and nearest-neighbor coupling within the coupled layer, we observe qualitatively identical between-layer chimera states. Moreover, we show that the role of information transmission delay between the two layers must not be neglected, and we obtain precise parameter bounds at which chimera states can be observed. The expansion of the chimera region and annihilation of cluster and fully coherent states in the parameter plane for increasing values of inter-layer chemical synaptic time delay are illustrated using effective range measurements. These results are discussed in the light of neuronal evolution, where the coexistence of coherent and incoherent dynamics during the developmental stage is particularly likely.

  1. Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo. (United States)

    Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M; Melendy, Thomas; Archambault, Jacques


    integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Requirement for the E1 Helicase C-Terminal Domain in Papillomavirus DNA Replication In Vivo (United States)

    Bergvall, Monika; Gagnon, David; Titolo, Steve; Lehoux, Michaël; D'Abramo, Claudia M.


    for the structural integrity of the helicase domain, followed by an acidic region (AR) and a C-terminal tail (C-tail) that have been shown to regulate the oligomerization of BPV1 E1 in vitro. Characterization of E1 chimeras revealed that, while the function of the AR could be transferred from BPV1 E1 to HPV11 E1, that of the C-tail could not. These results suggest that the E1 CTD performs multiple functions in DNA replication, some of them in a virus type-specific manner. PMID:26739052

  3. C[sub 10]-O[sub eq]-N-(4-azido-5-[sup 125]iodo salicyloyl)-[beta]-alanyl-[beta] alanyl ryanodine (Az-[beta]AR), a novel photo-affinity ligand for the ryanodine binding site

    Energy Technology Data Exchange (ETDEWEB)

    Bidasee, K.R.; Besch, H.R. Jr.; Kwon, Sangyeol; Emmick, J.T.; Besch, K.T.; Gerzon, Koert; Humerickhouse, R.A. (Indiana Univ., Indianapolis, IN (United States). School of Medicine)


    A high affinity, photoactivatable, radio-iodinated ligand for the ryanodine binding site(s) of the sarcoplasmic reticulum calcium-release channel, C[sub 10]-O[sub e]-N-(4-azido-5-[sup 125]iodo salicyloyl)-[beta]-alanyl-[beta]-alanyl ryanodine (Az-[beta]AR), was synthesized at a specific activity of 1400mCi/mmol. (Author).

  4. The effects of acid treatment and sample preparation on 40Ar/39Ar ages (United States)

    Morgan, L. E.; Davidheiser, B.; Kuiper, K.; Wijbrans, J. R.


    Practitioners of K-Ar and 40Ar/39Ar geochronology regularly use dilute acids (typically 5-10% hydrofluoric acid (HF)) to clean mineral grains prior to irradiation (in the case of 40Ar/39Ar), and analysis (e.g. Evernden and Curtis, 1965; Dalrymple, 1967). This treatment has been shown to reduce contamination from atmospheric Ar, which consists largely of 40Ar and thus must be differentiated from radiogenic 40Ar* (Evernden and Curtis, 1965). Acid treatments can also remove fine grained material attached to mineral grains, such as glass shards or devitrified glass, which can affect analyses and is difficult to remove by other means (Evernden and Curtis, 1965). Such treatments were originally examined for their efficacy in reducing atmospheric argon contamination (Dalrymple, 1967) but were not assessed for the possibility of leaching Ar* or K differentially, which would affect both K-Ar and 40Ar/39Ar ages. Indeed, Evernden and Curtis (1965) state that they are simply removing the "outer portions of the crystals" and apparently do not account for the potential for leaching of 40Ar* or K from the mass of their host mineral. Moreover, the capabilities of the K-Ar system in the 1960s was limited to a precision of ca. 3-4% on samples of 1-3 Ma (Cox and Dalrymple, 1967). Effects of smaller magnitude could not have been detected at the time. As the developments of the 40Ar/39Ar system and modern mass spectrometer technology have allowed for precision to approach 0.1%, the potential effects of acid treatment during sample preparation warrant revisiting. Additionally, the use of Calgon for sample disintegration has not previously been quantitatively assessed but is used extensively in some laboratories. Here we present a series of experiments from co-irradiated Fish Canyon sanidine (FCs) and Mes-4 (Kuiper et al., 2008). FCs is used as the mineral standard following standard procedures. Mes-4 splits were treated with H2O (10 minutes, ultrasonic), Calgon (10%, overnight at 50°C

  5. Control of βAR- and N-methyl-D-aspartate (NMDA Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.

    Directory of Open Access Journals (Sweden)

    Andrew Chay


    Full Text Available Norepinephrine, a neuromodulator that activates β-adrenergic receptors (βARs, facilitates learning and memory as well as the induction of synaptic plasticity in the hippocampus. Several forms of long-term potentiation (LTP at the Schaffer collateral CA1 synapse require stimulation of both βARs and N-methyl-D-aspartate receptors (NMDARs. To understand the mechanisms mediating the interactions between βAR and NMDAR signaling pathways, we combined FRET imaging of cAMP in hippocampal neuron cultures with spatial mechanistic modeling of signaling pathways in the CA1 pyramidal neuron. Previous work implied that cAMP is synergistically produced in the presence of the βAR agonist isoproterenol and intracellular calcium. In contrast, we show that when application of isoproterenol precedes application of NMDA by several minutes, as is typical of βAR-facilitated LTP experiments, the average amplitude of the cAMP response to NMDA is attenuated compared with the response to NMDA alone. Models simulations suggest that, although the negative feedback loop formed by cAMP, cAMP-dependent protein kinase (PKA, and type 4 phosphodiesterase may be involved in attenuating the cAMP response to NMDA, it is insufficient to explain the range of experimental observations. Instead, attenuation of the cAMP response requires mechanisms upstream of adenylyl cyclase. Our model demonstrates that Gs-to-Gi switching due to PKA phosphorylation of βARs as well as Gi inhibition of type 1 adenylyl cyclase may underlie the experimental observations. This suggests that signaling by β-adrenergic receptors depends on temporal pattern of stimulation, and that switching may represent a novel mechanism for recruiting kinases involved in synaptic plasticity and memory.

  6. Reevaluation of the Solar Wind 36Ar/38Ar Ratio (United States)

    Becker, R. H.; Schlutter, D. J.; Rider, P. E.; Pepin, R. O.


    The isotopic composition of solar wind (SW) argon is an important parameter in the modeling of the evolution of the terrestrial planet atmospheres. Anders and Grevesse assumed a 36Ar/38Ar ratio for SW of 5.31, essentially equal to that of air. Considerable evidence has since developed which indicates that this ratio is too low. Benkert et al. have reported their best estimate for the recent SW as 5.48 +/- 0.05, determined from measurements of lunar soil 71501. Based on Ar data obtained from surface oxidation of a metal separate from the Weston meteorite and from an uncontrolled etch of lunar sample 67701, reported by our group previously, we consider even this value to be too low. Since values of 5.75 to 5.85 were reported by Black for initial low temperature (fairly high SW 36Ar/38Ar ratio (in the range of ~5.6 to ~5.7), we decided to analyze Kapoeta for its light solar wind gases using the acid-etching techniques developed in our laboratory based on the CSSE procedure of Benkert et al.

  7. Chimeras in a network of three oscillator populations with varying network topology

    DEFF Research Database (Denmark)

    Martens, Erik Andreas


    this system as a model system, we discuss for the first time the influence of network topology on the existence of so-called chimera states. In this context, the network with three populations represents an interesting case because the populations may either be connected as a triangle, or as a chain, thereby......-like. By showing that chimera states only exist for a bounded set of parameter values, we demonstrate that their existence depends strongly on the underlying network structures, and conclude that chimeras exist on networks with a chain-like character....

  8. Robust Weak Chimeras in Oscillator Networks with Delayed Linear and Quadratic Interactions (United States)

    Bick, Christian; Sebek, Michael; Kiss, István Z.


    We present an approach to generate chimera dynamics (localized frequency synchrony) in oscillator networks with two populations of (at least) two elements using a general method based on a delayed interaction with linear and quadratic terms. The coupling design yields robust chimeras through a phase-model-based design of the delay and the ratio of linear and quadratic components of the interactions. We demonstrate the method in the Brusselator model and experiments with electrochemical oscillators. The technique opens the way to directly bridge chimera dynamics in phase models and real-world oscillator networks.

  9. CAPRRESI: Chimera Assembly by Plasmid Recovery and Restriction Enzyme Site Insertion. (United States)

    Santillán, Orlando; Ramírez-Romero, Miguel A; Dávila, Guillermo


    Here, we present chimera assembly by plasmid recovery and restriction enzyme site insertion (CAPRRESI). CAPRRESI benefits from many strengths of the original plasmid recovery method and introduces restriction enzyme digestion to ease DNA ligation reactions (required for chimera assembly). For this protocol, users clone wildtype genes into the same plasmid (pUC18 or pUC19). After the in silico selection of amino acid sequence regions where chimeras should be assembled, users obtain all the synonym DNA sequences that encode them. Ad hoc Perl scripts enable users to determine all synonym DNA sequences. After this step, another Perl script searches for restriction enzyme sites on all synonym DNA sequences. This in silico analysis is also performed using the ampicillin resistance gene (ampR) found on pUC18/19 plasmids. Users design oligonucleotides inside synonym regions to disrupt wildtype and ampR genes by PCR. After obtaining and purifying complementary DNA fragments, restriction enzyme digestion is accomplished. Chimera assembly is achieved by ligating appropriate complementary DNA fragments. pUC18/19 vectors are selected for CAPRRESI because they offer technical advantages, such as small size (2,686 base pairs), high copy number, advantageous sequencing reaction features, and commercial availability. The usage of restriction enzymes for chimera assembly eliminates the need for DNA polymerases yielding blunt-ended products. CAPRRESI is a fast and low-cost method for fusing protein-coding genes.

  10. Influence of residual Ar+ in Ar cluster ion beam for DLC film formation

    International Nuclear Information System (INIS)

    Kitagawa, Teruyuki; Miyauchi, Kazuya; Toyoda, Noriaki; Kanda, Kazuhiro; Ikeda, Tokumi; Tsubakino, Harushige; Matsuo, Jiro; Matsui, Shinji; Yamada, Isao


    In order to study the influences of residual Ar monomer ion (Ar + ) on sp 2 content and hardness of diamond like carbon (DLC) films formed by Ar cluster ion beam assisted deposition, Ar cluster ion, Ar + and their mixed ions (Ar cluster ion and Ar + ) bombardments were performed during evaporation of C 60 . From near edge X-ray absorption fine structure (NEXAFS) and Raman spectroscopy measurements, lower sp 2 content in the carbon films was obtained with Ar cluster ion bombardment than that with Ar + and mixed ion. Furthermore higher hardness and smooth surface were shown with Ar cluster ion bombardments. Therefore it was important to reduce Ar + in Ar cluster ion beams to obtain hard DLC films with flat surface

  11. Contrasting feature in the repopulation of host-type T cells in the spleens of F1----P and P----F1 radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Hirokawa, K.; Sado, T.; Kubo, S.; Kamisaku, H.; Utsuyama, M.


    The regeneration and persistence of host- and donor-derived T cells were examined in the thymus as well as the spleen of mouse radiation bone marrow chimeras of two semiallogeneic combinations (F1----P, P----F1) with different Thy-1 markers on T cells of donor and host origins. An unexpectedly large number of host-type T cells were recovered from the spleens of F1----P chimeras, amounting to as high as 45 and 25% of total T cells at 6 and 14 weeks after bone marrow transplantation (BMT), respectively. To the contrary, the residual host-type T cells in the spleens of P----F1 chimeras disappeared quickly, resulting in less than 0.1% of total T cells at 6 weeks after BMT. It was also revealed that the number of host-type T cells in the spleens of F1----P chimeras decreased in proportion to increase of radiation dose given to the recipients

  12. Ar-37 in the Atmospheric and Sub-Soil Gases

    International Nuclear Information System (INIS)

    Purtschert, R.; Raghoo, L.S.


    On-site inspection of the radioactive noble gas isotope 37Ar is a definitive and unambiguous indicator of an underground nuclear explosion. 37Ar is produced underground by neutron activation of calcium by the reaction 40Ca(n,α)37Ar. In the atmosphere, 37Ar is produced by the spallation reaction 40Ar(n,4n)37Ar. Periodic measurements over the last six years on air collected in Bern revealed a background level in the order of 1-5 mBq/m 3 air in agreement with former findings and theoretical calculations. Those calculations also indicated that the intrusion of stratospheric air masses may lead to elevated tropospheric 37Ar concentrations up to 8-10 mBq/m 3 air. Selected samples taken up to now in the vicinity of nuclear power plants revealed no significant deviation from the natural background. In order to distinguish between natural and artificially elevated 37Ar the location-specific 37Ar activity range in soils, rocks and the atmosphere were identified. From CARIBIC flights, a passenger aircraft with a special air freight container filled with scientific equipment in the cargo compartment, tropospheric air samples were analyzed for 37Ar and 85Kr. The natural 37Ar production in soils and the rock basement underlying the alluvium is investigated by means of in situ measurements of different isotopes, theoretical calculations and irradiation experiments on selected rock samples. This will help resolve the temporal evolution and/or constancy of the natural 37Ar background and allow for an interpretation in terms of the identification of clandestine nuclear explosions. (author)

  13. Transcriptome-wide mapping of 5-methylcytidine RNA modifications in bacteria, archaea, and yeast reveals m5C within archaeal mRNAs.

    Directory of Open Access Journals (Sweden)

    Sarit Edelheit


    Full Text Available The presence of 5-methylcytidine (m(5C in tRNA and rRNA molecules of a wide variety of organisms was first observed more than 40 years ago. However, detection of this modification was limited to specific, abundant, RNA species, due to the usage of low-throughput methods. To obtain a high resolution, systematic, and comprehensive transcriptome-wide overview of m(5C across the three domains of life, we used bisulfite treatment on total RNA from both gram positive (B. subtilis and gram negative (E. coli bacteria, an archaeon (S. solfataricus and a eukaryote (S. cerevisiae, followed by massively parallel sequencing. We were able to recover most previously documented m(5C sites on rRNA in the four organisms, and identified several novel sites in yeast and archaeal rRNAs. Our analyses also allowed quantification of methylated m(5C positions in 64 tRNAs in yeast and archaea, revealing stoichiometric differences between the methylation patterns of these organisms. Molecules of tRNAs in which m(5C was absent were also discovered. Intriguingly, we detected m(5C sites within archaeal mRNAs, and identified a consensus motif of AUCGANGU that directs methylation in S. solfataricus. Our results, which were validated using m(5C-specific RNA immunoprecipitation, provide the first evidence for mRNA modifications in archaea, suggesting that this mode of post-transcriptional regulation extends beyond the eukaryotic domain.

  14. A Universal Aptamer Chimera for the Delivery of Functional microRNA-126. (United States)

    Rohde, Jan-H; Weigand, Julia E; Suess, Beatrix; Dimmeler, Stefanie


    microRNAs (miRs) regulate vascular diseases such as atherosclerosis and cancer. miR-126 is important for endothelial cell signaling and promotes angiogenesis, protects against atherosclerosis, and reduces breast cancer cell growth and metastasis. The overexpression of miR-126, therefore, may be an attractive therapeutic strategy for the treatment of cardiovascular disease or cancer. Here we report a novel strategy to deliver miR-126 to endothelial and breast cancer cells. We tested three different strategies to deliver miR-126 by linking the miR to an aptamer for the ubiquitously expressed transferrin receptor (transferrin receptor aptamer, TRA). Linking the precursor of miR-126 (pre-miR-126) to the TRA by annealing of a complementary stick led to efficient uptake and processing of miR-126, resulting in the delivery of 1.6×10(6)±0.3×10(6) copies miR-126-3p per ng RNA in human endothelial cells and 7.4×10(5)±2×10(5) copies miR-126-3p per ng in MCF7 breast cancer cells. The functionality of the active TRA-miR-126 chimera was further demonstrated by showing that the chimera represses the known miR-126 target VCAM-1 and improved endothelial cell sprouting in a spheroid assay. Moreover, the TRA-miR-126 chimera reduced proliferation and paracrine endothelial cell recruitment of breast cancer cells to a similar extent as miR-126-3p mimics introduced by conventional liposome-based transfection. Together, this data demonstrates that pre-miR-126 can be delivered by a non-specific aptamer to exert biological functions in two different cell models. The use of the TRA-miR-126 chimera or the combination of the delivery strategy with other endothelial or tumor specific aptamers may provide an interesting therapeutic option to treat vascular disease or cancers.

  15. Recombination reduction at the c-Si/RCA oxide interface through Ar-H2 plasma treatment (United States)

    Landheer, Kees; Bronsveld, Paula C. P.; Poulios, Ioannis; Tichelaar, Frans D.; Kaiser, Monja; Schropp, Ruud E. I.; Rath, Jatin K.


    An Ar-H2 plasma treatment was applied on an ultrathin RCA oxide to create well-passivated silicon wafers with symmetric c-Si/SiOx:H/a-Si:H passivation layer stacks. The effective lifetime of these samples increased from 10 μs to 4 ms after annealing at 200 °C through Ar-H2 plasma treatment of the oxide. The results indicate that the plasma treatment can modify the RCA oxide and this enables atomic hydrogen diffusion at low annealing temperature, leading to a well passivated c-Si/SiOx:H interface. This might provide new possibilities to use wet chemical oxides in c-Si solar cells, for example as tunnel contacts.

  16. Diversity of chimera-like patterns from a model of 2D arrays of neurons with nonlocal coupling (United States)

    Tian, Chang-Hai; Zhang, Xi-Yun; Wang, Zhen-Hua; Liu, Zong-Hua


    Chimera states have been studied in 1D arrays, and a variety of different chimera states have been found using different models. Research has recently been extended to 2D arrays but only to phase models of them. Here, we extend it to a nonphase model of 2D arrays of neurons and focus on the influence of nonlocal coupling. Using extensive numerical simulations, we find, surprisingly, that this system can show most types of previously observed chimera states, in contrast to previous models, where only one or a few types of chimera states can be observed in each model. We also find that this model can show some special chimera-like patterns such as gridding and multicolumn patterns, which were previously observed only in phase models. Further, we present an effective approach, i.e., removing some of the coupling links, to generate heterogeneous coupling, which results in diverse chimera-like patterns and even induces transformations from one chimera-like pattern to another.

  17. Basins of Attraction for Chimera States

    DEFF Research Database (Denmark)

    Martens, Erik Andreas; Panaggio, Mark; Abrams, Daniel


    Chimera states---curious symmetry-broken states in systems of identical coupled oscillators---typically occur only for certain initial conditions. Here we analyze their basins of attraction in a simple system comprised of two populations. Using perturbative analysis and numerical simulation we...

  18. Intermittent chaotic chimeras for coupled rotators

    DEFF Research Database (Denmark)

    Olmi, Simona; Martens, Erik Andreas; Thutupalli, Shashi


    Two symmetrically coupled populations of N oscillators with inertia m display chaotic solutions with broken symmetry similar to experimental observations with mechanical pendulums. In particular, we report evidence of intermittent chaotic chimeras, where one population is synchronized and the other...

  19. Effect of Ti and C particle sizes on reaction behavior of thermal explosion reaction of Cu−Ti−C system under Ar and air atmospheres

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Yunhong; Zhao, Qian; Li, Xiujuan; Zhang, Zhihui, E-mail:; Ren, Luquan


    The thermal explosion (TE) reaction behavior of Cu−Ti−C systems with different Ti and C particle sizes was investigated under air and Ar atmospheres. It was found that increasing the Ti and C particle sizes leads to higher ignition temperatures under both atmospheres and that the maximum combustion temperature decreases with increasing C particle size. The TE reaction is much easier to activate (i.e., it has a lower ignition temperature) in air because of the heat released from Ti oxidation and nitridation and Cu oxidation reactions on the Cu−Ti−C compact surface. TiC ceramic particles are successfully prepared in the bulk Cu−Ti−C compacts under both air and Ar atmospheres through a dissolution-diffusion-precipitation mechanism. Differential thermal and thermodynamic analyses show that the TE reaction ignition process in air is mainly controlled by the Ti particle size. - Highlights: • Variation of Ti and C particle sizes affects thermal reaction (TE) behaviors. • Ignition temperature under air is much lower than that under Ar atmosphere. • Heat of oxidation and nitridation reactions reduces ignition temperature under air.

  20. On the application of Chimera/unstructured hybrid grids for conjugate heat transfer (United States)

    Kao, Kai-Hsiung; Liou, Meng-Sing


    A hybrid grid system that combines the Chimera overset grid scheme and an unstructured grid method is developed to study fluid flow and heat transfer problems. With the proposed method, the solid structural region, in which only the heat conduction is considered, can be easily represented using an unstructured grid method. As for the fluid flow region external to the solid material, the Chimera overset grid scheme has been shown to be very flexible and efficient in resolving complex configurations. The numerical analyses require the flow field solution and material thermal response to be obtained simultaneously. A continuous transfer of temperature and heat flux is specified at the interface, which connects the solid structure and the fluid flow as an integral system. Numerical results are compared with analytical and experimental data for a flat plate and a C3X cooled turbine cascade. A simplified drum-disk system is also simulated to show the effectiveness of this hybrid grid system.

  1. Androgen Receptor-Mediated Growth Suppression of HPr-1AR and PC3-Lenti-AR Prostate Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Young-Chae Kim

    Full Text Available The androgen receptor (AR mediates the developmental, physiologic, and pathologic effects of androgens including 5α-dihydrotestosterone (DHT. However, the mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells are not well understood, though they are central to prostate development, homeostasis, and neoplasia. Here, we identify androgen-responsive genes that restrain cell cycle progression and proliferation of human prostate epithelial cell lines (HPr-1AR and PC3-Lenti-AR, and we investigate the mechanisms through which AR regulates their expression. DHT inhibited proliferation of HPr-1AR and PC3-Lenti-AR, and cell cycle analysis revealed a prolonged G1 interval. In the cell cycle, the G1/S-phase transition is initiated by the activity of cyclin D and cyclin-dependent kinase (CDK complexes, which relieve growth suppression. In HPr-1AR, cyclin D1/2 and CDK4/6 mRNAs were androgen-repressed, whereas CDK inhibitor, CDKN1A, mRNA was androgen-induced. The regulation of these transcripts was AR-dependent, and involved multiple mechanisms. Similar AR-mediated down-regulation of CDK4/6 mRNAs and up-regulation of CDKN1A mRNA occurred in PC3-Lenti-AR. Further, CDK4/6 overexpression suppressed DHT-inhibited cell cycle progression and proliferation of HPr-1AR and PC3-Lenti-AR, whereas CDKN1A overexpression induced cell cycle arrest. We therefore propose that AR-mediated growth suppression of HPr-1AR involves cyclin D1 mRNA decay, transcriptional repression of cyclin D2 and CDK4/6, and transcriptional activation of CDKN1A, which serve to decrease CDK4/6 activity. AR-mediated inhibition of PC3-Lenti-AR proliferation occurs through a similar mechanism, albeit without down-regulation of cyclin D. Our findings provide insight into AR-mediated regulation of prostate epithelial cell proliferation.

  2. Ar-40/Ar-39 age determinations for the Rotoiti eruption, New Zealand (United States)

    Flude, S.; Storey, M.


    The contemporaneous Rotoiti and Earthquake Flat ignimbrites, erupted from the Taupo Volcanic zone, New Zealand, form a distinctive tephrostratigraphic horizon in the Southern Pacific. Radioisotopic dating results for these eruptions remain controversial, with published ages ranging from 35.1 × 2.8 ka [1] to 71 × 6 ka [2], with 61.0 × 1.5 ka [3] often being cited as the most widely accepted age. These eruptions are difficult to date as their age is near the limit for various radiometric dating techniques, which are complicated by a large proportion of inherited material (xenocrysts) and a lack of phases suitable for dating. Glass-bearing plutonic blocks erupted with the Rotoiti and Earthquake Flat ignimbrites have previously been interpreted as deriving from a slowly cooled and incompletely solidified magma body that was sampled by the eruptions. They contain large vugs lined with euhedral quartz, sanidine and biotite crystals, indicating that these crystals grew in a gas or aqueous fluid rich environment and are interpreted to have formed shortly before or during eruption. Here we will present Ar-40/Ar-39 ages for sanidines and biotites extracted from vugs in lithic blocks erupted as part of the Earthquake Flat ignimbrite. We show that, even for vug-lining material, inherited ages remain a problem and are the likely source of the wide variation in published radiometric ages. Nevertheless, many of the Ar-40/Ar-39 ages are much younger than the 61 ka age [3] and are more consistent with the recent stratigraphic, C-14 and U-238/Th-230+(U-Th)/He ages that have been suggested (e.g. [4,5]). 1. Whitehead, N. & Ditchburn, R. New Zealand Journal of Geology and Geophysics 37, 381-383 (1994). 2. Ota, Y., Omura, A. & Iwata, H. New Zealand Journal of Geology and Geophysics 32, 327-331 (1989). 3. Wilson, C. J. N. et al. Quaternary Science Reviews 26, 1861-1870 (2007). 4. Molloy, C., Shane, P. & Augustinus, P. Geological Society of America Bulletin 121, 1666-1677 (2009). 5

  3. Astronomically calibrated 40Ar/39Ar age for the Toba supereruption and global synchronization of late Quaternary records (United States)

    Storey, Michael; Roberts, Richard G.; Saidin, Mokhtar


    The Toba supereruption in Sumatra, ∼74 thousand years (ka) ago, was the largest terrestrial volcanic event of the Quaternary. Ash and sulfate aerosols were deposited in both hemispheres, forming a time-marker horizon that can be used to synchronize late Quaternary records globally. A precise numerical age for this event has proved elusive, with dating uncertainties larger than the millennial-scale climate cycles that characterized this period. We report an astronomically calibrated 40Ar/39Ar age of 73.88 ± 0.32 ka (1σ, full external errors) for sanidine crystals extracted from Toba deposits in the Lenggong Valley, Malaysia, 350 km from the eruption source and 6 km from an archaeological site with stone artifacts buried by ash. If these artifacts were made by Homo sapiens, as has been suggested, then our age indicates that modern humans had reached Southeast Asia by ∼74 ka ago. Our 40Ar/39Ar age is an order-of-magnitude more precise than previous estimates, resolving the timing of the eruption to the middle of the cold interval between Dansgaard-Oeschger events 20 and 19, when a peak in sulfate concentration occurred as registered by Greenland ice cores. This peak is followed by a ∼10 °C drop in the Greenland surface temperature over ∼150 y, revealing the possible climatic impact of the eruption. Our 40Ar/39Ar age also provides a high-precision calibration point for other ice, marine, and terrestrial archives containing Toba sulfates and ash, facilitating their global synchronization at unprecedented resolution for a critical period in Earth and human history beyond the range of 14C dating.

  4. Four-cluster chimera state in non-locally coupled phase oscillator systems with an external potential

    International Nuclear Information System (INIS)

    Zhu Yun; Zheng Zhi-Gang; Yang Jun-Zhong


    Dynamics of a one-dimensional array of non-locally coupled Kuramoto phase oscillators with an external potential is studied. A four-cluster chimera state is observed for the moderate strength of the external potential. Different from the clustered chimera states studied before, the instantaneous frequencies of the oscillators in a synchronized cluster are different in the presence of the external potential. As the strength of the external potential increases, a bifurcation from the two-cluster chimera state to the four-cluster chimera states can be found. These phenomena are well predicted analytically with the help of the Ott—Antonsen ansatz. (general)

  5. Investigation of a van der Waals complex with C 1 symmetry: the free-jet rotational spectrum of 1,2-difluoroethane-Ar (United States)

    Melandri, Sonia; Velino, Biagio; Favero, Paolo G.; Dell'Erba, Adele; Caminati, Walther


    The van der Waals complex between Ar and 1,2-difluoroethane has been investigated by free-jet absorption millimeter-wave spectroscopy in the frequency range 60-78 GHz. The analysis of the spectroscopic constants derived from the rotational spectrum allowed the determination of the dimer's structure. 1,2-Difluoroethane is in the gauche conformation and the Ar atom is in a position stabilized by the interaction with one fluorine and the two carbon atoms. The distance between Ar and the center of mass (CM) of the monomer is 3.968 Å, the angle between the Ar-CM line and the C-C bond is 65° and the dihedral angle Ar-CM-C-C is 99°. From centrifugal distortion effects the dissociation energy of the complex has been estimated to be 2.1 kJ/mol.

  6. Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance

    International Nuclear Information System (INIS)

    Weiden, P.L.; Storb, R.; Tsoi, M.S.; Graham, T.C.; Lerner, K.G.; Thomas, E.D.


    Canine radiation chimeras were used to investigate further mechanism(s) responsible for maintaining the stable chimeric state. In an attempt to elucidate the nature of this postulated active mechanism, the cytotoxicity of donor lymphocytes for fibroblasts of the chimera and the presence or absence of serum-blocking factors were assessed in vitro by using a cellular inhibition (CI) assay. The presence of serum-blocking factors did not protect against the development of significant GVHD in two chimeras (fatal in one). GVHD did not occur in four other chimeras after infusion of cytotoxic donor lymphocytes despite the absence of serum-blocking factors. These and previous results suggest that serum-blocking factors are not the mechanism suppressing the development of GVHD in canine radiation chimeras, and raise the possibility that a suppressor cell population may be responsible for preventing GVHD

  7. Suppressed phenylalanine ammonia-lyase activity after heat shock in transgenic Nicotiana plumbaginifolia containing an Arabidopsis HSP18.2-parsley PAL2 chimera gene. (United States)

    Moriwaki, M; Yamakawa, T; Washino, T; Kodama, T; Igarashi, Y


    The activity of phenylalanine ammonia-lyase (PAL; EC after heat shock (HS) in leaves and buds of transgenic Nicotiana plumbaginifolia containing an Arabidopsis HSP18.2 promoter-parsley phenylalanine ammonia-lyase 2 (HSP18.2-PAL2) chimera gene was examined. Immediately after HS treatment at 44 degrees C for 5 h, the PAL activity in both transgenic and normal (untransformed) plants was 35-38% lower than that before HS. At normal temperature (25-26 degrees C), the PAL activity recovered within 5 h of ending the HS treatment in normal plants, but not until 12-24 h in transgenic plants containing the HSP18.2-PAL2 gene. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the presence of parsley PAL2 mRNA in transgenic plants, which remained for 8-12 h following 5-h HS at 44 degrees C; the mRNA was not observed before HS. The content of chlorogenic acid (CGA; 3-caffeoylquinic acid) decreased drastically 8-12 h after HS in transgenic plants, but only slightly in normal plants. Thus, the decrease in PAL activity accompanied by expression of the parsley PAL2 gene after HS treatment corresponded to the decrease in CGA synthesis. These results might be attributed to post-transcriptional degradation of endogenous PAL mRNA triggered by transcription of the transgene.

  8. Secondary Disease in Radiation Chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Congdon, C. C. [Biology Division, Oak Ridge National Laboratory, Oak Ridge, TN (United States)


    A review of research dealing directly or indirectly with the development of bidirectional tolerance in radiation chimeras has been made, emphasizing some of the contemporary research on this subject in Oak Ridge and Knoxville. By controlling such factors as cell dose, age of donor animal and day of cell injection, it was possible to achieve bidirectional tolerance. Attempts to reduce bidirectional tolerance in favour of increasing the graft-versus-host reaction were less successful. Hypoxic caging demonstrated a new approach to achieving bidirectional tolerance through physiological competition for growth. Graft-versus-host reactions have a lower growth priority than marrow regeneration or erythropoietic hyperplasia. Study of pathologic processes, immunologic capability and the-biochemical lesions in radiation chimeras all lead to new ideas that involve bidirectional tolerance. The investigations on dose rate in radiation suppression of the immune response and on LD{sub 50} (30- to 90-day)values after injection of different numbers of marrow cells all have a bearing on control of the host-versus-graft response and therefore are important in understanding bidirectional tolerance. (author)

  9. Major Histocompatibilty Complex-Restricted Adaptive Immune Responses to CT26 Colon Cancer Cell Line in Mixed Allogeneic Chimera. (United States)

    Lee, K W; Choi, B; Kim, Y M; Cho, C W; Park, H; Moon, J I; Choi, G-S; Park, J B; Kim, S J


    Although the induction of mixed allogeneic chimera shows promising clinical tolerance results in organ transplantation, its clinical relevance as an anti-cancer therapy is yet unknown. We introduced a mixed allogenic chimera setting with the use of a murine colon cancer cell line, CT26, by performing double bone marrow transplantation. We analyzed donor- and recipient-restricted anti-cancer T-cell responses, and phenotypes of subpopulations of T cells. The protocol involves challenging 1 × 10 5 cells of CT26 cells intra-hepatically on day 50 after bone marrow transplantation, and, by use of CT26 lysates and an H-2L d -restricted AH1 pentamer, flow cytometric analysis was performed to detect the generation of cancer-specific CD4 + and CD8 + T cells at various time points. We found that immunocompetence against tumors depends heavily on cancer-specific CD8 + T-cell responses in a major histocompatibility complex-restricted manner; the evidence was further supported by the increase of interferon-γ-secreting CD4 + T cells. Moreover, we demonstrated that during the effector immune response to CT26 cancer challenge, there was a presence of central memory cells (CD62L hi CCR7 + ) as well as effector memory cells (CD62L lo CCR7 - ). Moreover, mixed allogeneic chimeras (BALB/c to C56BL/6 or vice versa) showed similar or heightened immune responses to CT26 cells compared with that of wild-type mice. Our results suggest that the responses of primary immunocompetency and of pre-existing memory T cells against allogeneic cancer are sustained and preserved long-term in a mixed allogeneic chimeric environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Age measurements of potassium-bearing sulfide minerals by the 40Ar/39Ar technique

    International Nuclear Information System (INIS)

    Czamanske, G.K.; Lanphere, M.A.; Erd, R.C.; Blake, M.C. Jr.


    K-Ar ages have been determined for sulfide minerals for the first time. The occurrence of adequate amounts of potassium-bearing sulfides with ideal compositions K 3 Fe 10 S 14 (approximately 10 wt.% K) and KFe 2 S 3 (approximately 16 wt.% K) in samples from a mafic alkalic diatreme at Coyote Peak, California, prompted an attempt to date these materials. K 3 Fe 10 S 14 , a massive mineral with conchoidal fracture, gives an age of 29.4 +- 0.5 m.y. ( 40 Ar/ 39 Ar), indistinguishable from the 28.3 +- 0.4 m.y. ( 40 Ar/ 39 Ar) and 30.2 +- 1.0 m.y. (conventional K-Ar) ages obtained for associated phlogopite (8.7 wt.% K). KFe 2 S 3 , a bladed, fibrous sulfide, gives a younger age, 26.5 +- 0.5 m.y. ( 40 Ar/ 39 Ar), presumably owing to Ar loss. (Auth.)

  11. Chimera Type Behavior in Nonlocal Coupling System with Two Different Inherent Frequencies (United States)

    Lin, Larry; Li, Ping-Cheng; Tseng, Hseng-Che


    From the research of Kuramoto and Strogatz, arrays of identical oscillators can display a remarkable pattern, named chimera state, in which phase-locked oscillators coexist with drifting ones in nonlocal coupling oscillator system. We consider further in this study, two groups of oscillators with different inherent frequencies and arrange them in a ring. When the difference of the inherent frequencies is within some specific parameter range, oscillators of nonlocal coupling system show two distinct chimera states. When the parameter value exceeds some threshold value, two chimera states disappear. They show different features. The statistical dynamic behavior of the system can be described by Kuramoto theory.

  12. Photoionization study of HgAr

    International Nuclear Information System (INIS)

    Linn, S.H.; Brom, J.M. Jr.; Tzeng, W.; Ng, C.Y.


    Photoionization efficiency data for HgAr + have been obtained in the region of 680--1240 A. The ionization energy of HgAr was determined to be 10.217 +- 0.012 eV. This value allows the calculation of the dissociation energy of HgAr + to be 0.228 +- 0.017 eV. The relative probabilities for the formation of HgAr + via the reactions Ar* x Hg or Hg* x Ar→ HgAr + +e - with Ar* and Hg* prepared in high Rydberg states in the energy range of 10.22--15.79 eV were estimated. Although the radii for the 3d and 5s Rydberg ortitals of Ar have similar values, the probabilities for the formation of HgAr + from Hg x Ar* with Ar* in the 5s[3/2] 0 1 and 5s'[1/2] 0 1 Rydberg states are substantially greater than those when the Ar* excited atoms are in the 3d[1/2] 0 1 , 3s[3/2] 0 1 , and 3d'[3/2] 0 1 Rydberg levels. The ratio for the cross sections for the formation of HgAr + from Hg x Ar* with Ar* formed in the 3d[1/2] 0 1 and 4d[1/2] 0 1 states, as well as that with Ar* prepared in the 5d[1/2] 0 1 and 6d[1/2] 0 1 states, were found to be consistent with the predictions of the previous impact parameter calculations

  13. The 40Ar/39Ar and U/Pb dating of young rhyolites in the Kos-Nisyros volcanic complex, Eastern Aegean Arc, Greece: Age discordance due to excess 40Ar in biotite (United States)

    Bachmann, O.; Schoene, B.; Schnyder, C.; Spikings, R.


    High-precision dating of Quaternary silicic magmas in the active Kos-Nisyros volcanic center (Aegean Arc, Greece) by both 40Ar/39Ar on biotite and U/Pb on zircon reveals a complex geochronological story. U/Pb ID-TIMS multi and single-grain zircon analyses from 3 different units (Agios Mammas and Zini domes, Kefalos Serie pyroclasts) range in age from 0.3 to 0.5 to 10-20 Ma. The youngest dates provide the maximum eruption age, while the oldest zircons indicate inheritance from local continental crust (Miocene and older). Step-heating 40Ar/39Ar experiments on 1-3 crystals of fresh biotite yielded highly disturbed Ar-release patterns with plateau ages typically older than most U/Pb ages. These old plateau ages are probably not a consequence of inheritance from xenocrystic biotites because Ar diffuses extremely fast at magmatic temperatures and ratios are reset within a few days. On the basis of (1) elevated and/or imprecise 40Ar/36Ar ratios, (2) shapes of the Ar release spectra, and (3) a high mantle 3He flux in the Kos-Nisyros area, we suggest that biotite crystals retained some mantle 40Ar that led to the observed, anomalously old ages. In contrast, sanidine crystals from the only sanidine-bearing unit in the Kos-Nisyros volcanic center (the caldera-forming Kos Plateau Tuff) do not appear to store any excess 40Ar relative to atmospheric composition. The eastern edge of the Aegean Arc is tectonically complex, undergoing rapid extension and located close to a major structural boundary. In such regions, which are characterized by high fluxes of mantle volatiles, 40Ar/39Ar geochronology on biotite can lead to erroneous results due to the presence of excess 40Ar and should be checked either against 40Ar/39Ar sanidine or U/Pb zircon ages.

  14. Transcriptome mapping of pAR060302, a blaCMY-2-positive broad-host-range IncA/C plasmid. (United States)

    Lang, Kevin S; Danzeisen, Jessica L; Xu, Wayne; Johnson, Timothy J


    The multidrug resistance-encoding plasmids belonging to the IncA/C incompatibility group have recently emerged among Escherichia coli and Salmonella enterica strains in the United States. These plasmids have a unique genetic structure compared to other enterobacterial plasmid types, a broad host range, and a propensity to acquire large numbers of antimicrobial resistance genes via their accessory regions. Using E. coli strain DH5α harboring the prototype IncA/C plasmid pAR060302, we sought to define the baseline transcriptome of IncA/C plasmids under laboratory growth and in the face of selective pressure. The effects of ampicillin, florfenicol, or streptomycin exposure were compared to those on cells left untreated at logarithmic phase using Illumina platform-based RNA sequencing (RNA-Seq). Under growth in Luria-Bertani broth lacking antibiotics, much of the backbone of pAR060302 was transcriptionally inactive, including its putative transfer regions. A few plasmid backbone genes of interest were highly transcribed, including genes of a putative toxin-antitoxin system and an H-NS-like transcriptional regulator. In contrast, numerous genes within the accessory regions of pAR060302 were highly transcribed, including the resistance genes floR, bla(CMY-2), aadA, and aacA. Treatment with ampicillin or streptomycin resulted in no genes being differentially expressed compared to controls lacking antibiotics, suggesting that many of the resistance-associated genes are not differentially expressed due to exposure to these antibiotics. In contrast, florfenicol treatment resulted in the upregulation of floR and numerous chromosomal genes. Overall, the transcriptome mapping of pAR060302 suggests that it mitigates the fitness costs of carrying resistance-associated genes through global regulation with its transcriptional regulators.

  15. Characterization of a novel androgen receptor (AR) coregulator RIPK1 and related chemicals that suppress AR-mediated prostate cancer growth via peptide and chemical screening. (United States)

    Hsu, Cheng-Lung; Liu, Jai-Shin; Lin, Ting-Wei; Chang, Ying-Hsu; Kuo, Yung-Chia; Lin, An-Chi; Ting, Huei-Ju; Pang, See-Tong; Lee, Li-Yu; Ma, Wen-Lung; Lin, Chun-Cheng; Wu, Wen-Guey


    Using bicalutamide-androgen receptor (AR) DNA binding domain-ligand binding domain as bait, we observed enrichment of FxxFY motif-containing peptides. Protein database searches revealed the presence of receptor-interacting protein kinase 1 (RIPK1) harboring one FxxFY motif. RIPK1 interacted directly with AR and suppressed AR transactivation in a dose-dependent manner. Domain mapping experiments showed that the FxxFY motif in RIPK1 is critical for interactions with AR and the death domain of RIPK1 plays a crucial role in its inhibitory effect on transactivation. In terms of tissue expression, RIPK1 levels were markedly higher in benign prostate hyperplasia and non-cancerous tissue regions relative to the tumor area. With the aid of computer modeling for screening of chemicals targeting activation function 2 (AF-2) of AR, we identified oxadiazole derivatives as good candidates and subsequently generated a small library of these compounds. A number of candidates could effectively suppress AR transactivation and AR-related functions in vitro and in vivo with tolerable toxicity via inhibiting AR-peptide, AR-coregulator and AR N-C interactions. Combination of these chemicals with antiandrogen had an additive suppressive effect on AR transcriptional activity. Our collective findings may pave the way in creating new strategies for the development and design of anti-AR drugs.

  16. Cumulative carbon emissions budgets consistent with 1.5 °C global warming (United States)

    Tokarska, Katarzyna B.; Gillett, Nathan P.


    The Paris Agreement1 commits ratifying parties to pursue efforts to limit the global temperature increase to 1.5 °C relative to pre-industrial levels. Carbon budgets2-5 consistent with remaining below 1.5 °C warming, reported in the IPCC Fifth Assessment Report (AR5)2,6,8, are directly based on Earth system model (Coupled Model Intercomparison Project Phase 5)7 responses, which, on average, warm more than observations in response to historical CO2 emissions and other forcings8,9. These models indicate a median remaining budget of 55 PgC (ref. 10, base period: year 1870) left to emit from January 2016, the equivalent to approximately five years of emissions at the 2015 rate11,12. Here we calculate warming and carbon budgets relative to the decade 2006-2015, which eliminates model-observation differences in the climate-carbon response over the historical period9, and increases the median remaining carbon budget to 208 PgC (33-66% range of 130-255 PgC) from January 2016 (with mean warming of 0.89 °C for 2006-2015 relative to 1861-188013-18). There is little sensitivity to the observational data set used to infer warming that has occurred, and no significant dependence on the choice of emissions scenario. Thus, although limiting median projected global warming to below 1.5 °C is undoubtedly challenging19-21, our results indicate it is not impossible, as might be inferred from the IPCC AR5 carbon budgets2,8.

  17. Exhumation history of the NW Indian Himalaya revealed by fission track and 40Ar/39Ar ages (United States)

    Schlup, Micha; Steck, Albrecht; Carter, Andrew; Cosca, Michael; Epard, Jean-Luc; Hunziker, Johannes


    New fission track and Ar/Ar geochronological data provide time constraints on the exhumation history of the Himalayan nappes in the Mandi (Beas valley) — Tso Morari transect of the NW Indian Himalaya. Results from this and previous studies suggest that the SW-directed North Himalayan nappes were emplaced by detachment from the underthrusted upper Indian crust by 55 Ma and metamorphosed by ca. 48–40 Ma. The nappe stack was subsequently exhumed to shallow upper crustal depths (

  18. Detection of Hepatitis C core antibody by dual-affinity yeast chimera and smartphone-based electrochemical sensing. (United States)

    Aronoff-Spencer, Eliah; Venkatesh, A G; Sun, Alex; Brickner, Howard; Looney, David; Hall, Drew A


    Yeast cell lines were genetically engineered to display Hepatitis C virus (HCV) core antigen linked to gold binding peptide (GBP) as a dual-affinity biobrick chimera. These multifunctional yeast cells adhere to the gold sensor surface while simultaneously acting as a "renewable" capture reagent for anti-HCV core antibody. This streamlined functionalization and detection strategy removes the need for traditional purification and immobilization techniques. With this biobrick construct, both optical and electrochemical immunoassays were developed. The optical immunoassays demonstrated detection of anti-HCV core antibody down to 12.3pM concentrations while the electrochemical assay demonstrated higher binding constants and dynamic range. The electrochemical format and a custom, low-cost smartphone-based potentiostat ($20 USD) yielded comparable results to assays performed on a state-of-the-art electrochemical workstation. We propose this combination of synthetic biology and scalable, point-of-care sensing has potential to provide low-cost, cutting edge diagnostic capability for many pathogens in a variety of settings. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Stopping power measurements for 4-5MeV/nucleon 16O, 40Ar, 63Cu and 84Kr in C, Al, Ni, Ag and Au

    International Nuclear Information System (INIS)

    Bimbot, R.; Della Negra, S.; Gardes, D.; Gauvin, H.; Fleury, A.; Hubert, F.


    The stopping powers for (4 and 5 MeV/nucleon) 16 O, 40 Ar, 63 Cu and 84 Kr have been measured in C, Al, Ni, Ag and Au media. The experimental technique consists in measuring accurately the energy of protons elastically scattered at zero degree by the incident and degraded beams. The experimental results have been compared with stopping powers calculated in different ways. Discrepancies as large as 30% have been observed for the heaviest ions in light media (C, Al), the experimental values being higher than the calculated ones. Moreover, this comparison indicates that, from these calculations, no agreement can be obtained in the whole range of incident ions and stopping media. On the contrary, a quantitative agreement was obtained by a new calculation mode which takes into account the variation of the moving ion effective charge with the atomic number of the stopping medium

  20. Advances in Chimera Grid Tools for Multi-Body Dynamics Simulations and Script Creation (United States)

    Chan, William M.


    This viewgraph presentation contains information about (1) Framework for multi-body dynamics - Geometry Manipulation Protocol (GMP), (2) Simulation procedure using Chimera Grid Tools (CGT) and OVERFLOW-2 (3) Further recent developments in Chimera Grid Tools OVERGRID, Grid modules, Script library and (4) Future work.

  1. Double-chimera proteins to enhance recruitment of endothelial cells and their progenitor cells. (United States)

    Behjati, M; Kazemi, M; Hashemi, M; Zarkesh-Esfahanai, S H; Bahrami, E; Hashemi-Beni, B; Ahmadi, R


    Enhanced attraction of selective vascular reparative cells is of great importance in order to increase vascular patency after endovascular treatments. We aimed to evaluate efficient attachment of endothelial cells and their progenitors on surfaces coated with mixture of specific antibodies, L-selectin and VE-cadherin, with prohibited platelet attachment. The most efficient conditions for coating of L-selectin-Fc chimera and VE-cadherin-Fc chimera proteins were first determined by protein coating on ELISA plates. The whole processes were repeated on titanium substrates, which are commonly used to coat stents. Endothelial progenitor cells (EPCs) and human umbilical vein endothelial cells (HUVECs) were isolated and characterized by flow cytometry. Cell attachment, growth, proliferation, viability and surface cytotoxicity were evaluated using nuclear staining and MTT assay. Platelet and cell attachment were evaluated using scanning electron microscopy. Optimal concentration of each protein for surface coating was 50 ng/ml. The efficacy of protein coating was both heat and pH independent. Calcium ions had significant impact on simultaneous dual-protein coating (P<0.05). Coating stability data revealed more than one year stability for these coated proteins at 4°C. L-selectin and VE-cadherin (ratio of 50:50) coated surface showed highest EPC and HUVEC attachment, viability and proliferation compared to single protein coated and non-coated titanium surfaces (P<0.05). This double coated surface did not show any cytotoxic effect. Surfaces coated with L-selectin and VE-cadherin are friendly surface for EPC and endothelial cell attachment with less platelet attachment. These desirable factors make the L-selectin and VE-cadherin coated surfaces perfect candidate endovascular device. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Chimera states in an ensemble of linearly locally coupled bistable oscillators (United States)

    Shchapin, D. S.; Dmitrichev, A. S.; Nekorkin, V. I.


    Chimera states in a system with linear local connections have been studied. The system is a ring ensemble of analog bistable self-excited oscillators with a resistive coupling. It has been shown that the existence of chimera states is not due to the nonidentity of oscillators and noise, which is always present in real experiments, but is due to the nonlinear dynamics of the system on invariant tori with various dimensions.

  3. Multiclustered chimeras in large semiconductor laser arrays with nonlocal interactions (United States)

    Shena, J.; Hizanidis, J.; Hövel, P.; Tsironis, G. P.


    The dynamics of a large array of coupled semiconductor lasers is studied numerically for a nonlocal coupling scheme. Our focus is on chimera states, a self-organized spatiotemporal pattern of coexisting coherence and incoherence. In laser systems, such states have been previously found for global and nearest-neighbor coupling, mainly in small networks. The technological advantage of large arrays has motivated us to study a system of 200 nonlocally coupled lasers with respect to the emerging collective dynamics. Moreover, the nonlocal nature of the coupling allows us to obtain robust chimera states with multiple (in)coherent domains. The crucial parameters are the coupling strength, the coupling phase and the range of the nonlocal interaction. We find that multiclustered chimera states exist in a wide region of the parameter space and we provide quantitative characterization for the obtained spatiotemporal patterns. By proposing two different experimental setups for the realization of the nonlocal coupling scheme, we are confident that our results can be confirmed in the laboratory.

  4. Epigenetic modulation of AR gene expression in prostate cancer DU145 cells with the combination of sodium butyrate and 5'-Aza-2'-deoxycytidine. (United States)

    Fialova, Barbora; Luzna, Petra; Gursky, Jan; Langova, Katerina; Kolar, Zdenek; Trtkova, Katerina Smesny


    The androgen receptor (AR) plays an essential role in the development and progression of prostate cancer. Castration-resistant prostate cancer (CRPC) is a consequence of androgen deprivation therapy. Unchecked CRPC followed by metastasis is lethal. Some CRPCs show decreased AR gene expression due to epigenetic mechanisms such as DNA methylation and histone deacetylation. The aim of this study was to epigenetically modulate the methylated state of the AR gene leading to targeted demethylation and AR gene expression in androgen-independent human prostate cancer DU145 cell line, representing the CRPC model with very low or undetectable AR levels. The cell treatment was based on single and combined applications of two epigenetic inhibitors, sodium butyrate (NaB) as histone deacetylases inhibitor and 5'-Aza-2'-deoxycytidine (Aza-dC) as DNA methyltransferases inhibitor. We found that the Aza-dC in combination with NaB may help reduce the toxicity of higher NaB concentrations in cancer cells. In normal RWPE-1 cells and even stronger in cancer DU145 cells, the combined treatment induced both AR gene expression on the mRNA level and increased histone H4 acetylation in AR gene promoter. Also activation and maintenance of G2/M cell cycle arrest and better survival in normal RWPE-1 cells compared to cancer DU145 cells were observed after the treatments. These results imply the selective toxicity effect of both inhibitors used and their potentially more effective combined use in the epigenetic therapy of prostate cancer patients.

  5. Microstructural evolution by heating at 1673-2373 K in ultra-fine grained W-(0.25-1.5)%TiC consolidates

    International Nuclear Information System (INIS)

    Hidaka, M.; Sakamoto, T.; Kobayashi, S.; Nakai, K.; Kurishita, H.; Arakawa, H.


    Full text of publication follows: Ultra-fine grained (UFG) W-TiC consolidates with nearly full densification are expected to be very promising for their use as divertors and structural materials exposed to irradiation environments because they exhibit good resistance to irradiations with fast neutrons, helium-ions and hydrogen-ions. In view of exposure to high heat loading on divertors, it is necessary to examine microstructural evolution due to high temperature heating in UFG W-TiC consolidates, which is closely related to recrystallization embrittlement. The objective of this study is to clarify how the microstructures in UFG W-TiC consolidates change with annealing at 1673-2373 K, with emphasis on the effects of TiC additions and nano-sized Ar bubbles retained in UFG W-TiC consolidates fabricated by mechanical alloying (MA) in an Ar atmosphere. UFG W-(0.25, 0.5, 0.8, 1.1, 1.5)%TiC (in wt%) consolidates were fabricated by powder metallurgical methods utilizing MA with 3MPDA (three mutually perpendicular directions agitation) bail mill in an atmosphere of purified H 2 (MA-H 2 ) or Ar (MA-Ar), followed by hot isostatic pressing (HIP) at 1623 K. Thin foils for transmission electron microscopy (TEM) observations were prepared from each of the as-HIPed consolidates and subjected to annealing in vacuum at temperatures from 1673 to 2373 K for 3.6 ks by radio-frequency induction heating. TEM examinations and EDX analyses were made using a JEM-2000FX and JEM-4000FX operating at 200 and 400 kV, respectively. It is shown that the as-HIPed specimens exhibit equiaxed grain sizes of 40 to 200 nm which decrease with increasing TiC addition, but the grain size tends to saturate around 1 wt% TiC addition. The nano-sized Ar bubbles in W-TiC with MA-Ar are observed in approximately half of the grains and provide a significant grain refinement effect: The grain size in W-TiC with MA-Ar is approximately half of that with MA-H 2 . Such Ar bubbles are retained even after heating at

  6. Pig StAR: mRNA expression and alternative splicing in testis and Leydig cells, and association analyses with testicular morphology traits. (United States)

    Zhang, Yanghai; Cui, Yang; Zhang, Xuelian; Wang, Yimin; Gao, Jiayang; Yu, Ting; Lv, Xiaoyan; Pan, Chuanying


    Steroidogenic acute regulatory protein (StAR), primarily expressed in Leydig cells (LCs) in the mammalian testes, is essential for testosterone biosynthesis and male fertility. However, no previous reports have explored the expression profiles, alternative splicing and genetic variations of StAR gene in pig. The aim of current study was to explore the expression profiles in different tissues and different types of testicular cells (LCs; spermatogonial stem cells, SSCs; Sertoli cells, SCs), to identify different splice variants and their expression levels, as well as to detect the indel polymorphism in pig StAR gene. Expression analysis results revealed that StAR was widely expressed in all tested tissues and the expression level in testis was significantly higher than that in other tissues (P StAR mRNA expression level was significantly higher in LCs than others (P StAR-a, StAR-b and StAR-c, were first found in pig. Further study showed StAR-a was highly expressed in both testis and LCs when compared with other variants (P StAR-a was the primary variant at StAR gene post-transcription and may facilitate the combination and transportation of cholesterol with StAR. In addition, a 5-bp duplicated deletion (NC_010457.5:g.5524-5528 delACTTG) was verified in the porcine StAR gene, which was closely related to male testicular morphology traits (P StAR gene might be a positive allele. Briefly, the current findings suggest that StAR and StAR-a play imperative roles in male fertility and the 5-bp indel can be a potential DNA marker for the marker-assisted selection in boar. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. 37Ar and 39Ar in meteorites and the spatial cosmic ray gradient

    International Nuclear Information System (INIS)

    Heusser, G.; Schaeffer, O.A.


    Cosmic-ray-produced 37 Ar (tsub(1/2) = 35 days), and 39 Ar (tsub(1/2) = 269 years) in the Fe-Ni phase of meteorites have been studied in connection with their implications for the radial gradient of cosmic ray particles. For the chondrite, Canon City, which fell on October 27, 1973, 20.1 +- 1.5 dpm/kg FeNi of 37 Ar and 22.5 +- 1.4 dpm/kg FeNi of 39 Ar was found. Usually, the 37 Ar/ 39 Ar ratio is used to deduce a spatial gradient. However, 37 Ar data reported in the literature are inconsistent. They fluctuate much more than could be accounted for by different orbits and the anticipated correlation with the cosmic ray neutron registrations is rather weak. Consequently, the 37 Ar/ 39 Ar-derived gradient has a low confidence level. On the other hand, 39 Ar activities group close to a mean value of 22.5 dpm/kg FeNi and appear to be almost independent of the different meteoroid orbits. A comparison of measured 39 Ar activities in meteorites with those calculated for orbits obtained from fireball data shows that a gradient of 10%/Au or less is reconcilable with the experimental findings. The average gradient (E > 200 MeV) during the last 500 years was probably not much larger than that measured presently by the Pioneer 10 and 11, and Helios spacecrafts. (Auth.)

  8. Single electron capture by state-prepared Ar2+ projectiles in Ar

    International Nuclear Information System (INIS)

    Puerta, J.; Huber, B.A.


    Electron capture by state-selected Ar 2+ projectiles in Ar has been studied at low collision energies ( 2+ ions are measured explaining existing discrepancies of partial and total cross sections in the Ar 2+ /Ar collision system. Although highly excited metastable ions ( 5 D 4 0 , 3 F 4 0 ) represent a minor contamination of a non-prepared Ar 2+ beam (proportional1%), their contributions are found to dominate the capture process due to cross section values larger than 10 -15 cm 2 . (orig.)

  9. Immune responsiveness and incidence of reticulum cell sarcoma in long-term syngeneic radiation chimeras

    International Nuclear Information System (INIS)

    Adorini, L.; Gorini, G.; Covelli, V.; Ballardin, E.; di Michele, A.; Bassani, B.; Metalli, P.; Doria, G.


    Long-term syngeneic radiation chimeras displayed a very low incidence of reticulum cell sarcoma as compared with control mice. Immune reactivity of these animals was studied in vivo by anti-dinitrophenyl antibody titer and affinity and in vitro by mitotic responsiveness to phytohemagglutinin, concanavalin A and lipopolysaccharide. Antibody titer and affinity as well as the response to T lectins were found to be increased in chimeras. These results were attributed to increased function of mature T2 cells, which could explain the reduced incidence of reticulum cell sarcoma in chimeras

  10. Application of a Chimera Full Potential Algorithm for Solving Aerodynamic Problems (United States)

    Holst, Terry L.; Kwak, Dochan (Technical Monitor)


    A numerical scheme utilizing a chimera zonal grid approach for solving the three dimensional full potential equation is described. Special emphasis is placed on describing the spatial differencing algorithm around the chimera interface. Results from two spatial discretization variations are presented; one using a hybrid first-order/second-order-accurate scheme and the second using a fully second-order-accurate scheme. The presentation is highlighted with a number of transonic wing flow field computations.

  11. The Chimera II Real-Time Operating System for advanced sensor-based control applications (United States)

    Stewart, David B.; Schmitz, Donald E.; Khosla, Pradeep K.


    Attention is given to the Chimera II Real-Time Operating System, which has been developed for advanced sensor-based control applications. The Chimera II provides a high-performance real-time kernel and a variety of IPC features. The hardware platform required to run Chimera II consists of commercially available hardware, and allows custom hardware to be easily integrated. The design allows it to be used with almost any type of VMEbus-based processors and devices. It allows radially differing hardware to be programmed using a common system, thus providing a first and necessary step towards the standardization of reconfigurable systems that results in a reduction of development time and cost.

  12. Influence of halogen substitution in the ligand sphere on the antitumor and antibacterial activity of half-sandwich ruthenium(II) complexes [RuX(η{sup 6}-arene)(C{sub 5}H{sub 4}N-2-cH=N-Ar)]{sup +}

    Energy Technology Data Exchange (ETDEWEB)

    Gichumbi, Joel M.; Omondi, Bernard; Friedrich, Holger B. [School of Chemistry, University of KwaZulu-Natal, Durban (South Africa); Lazarus, Geraldine; Singh, Moganavelli; Shaikh, Nazia; Chenia, Hafizah Y. [School of Life Sciences, University of KwaZulu-Natal, Durban (South Africa)


    New complexes [(η{sup 6}-p-cymene)Ru(C{sub 5}H{sub 4}N-2-CH=N-Ar)X]PF{sub 6} [X = Br (1), I (2); Ar = 4-fluorophenyl (a), 4-chlorophenyl (b), 4-bromophenyl (c), 4-iodophenyl (d), 2,5-dichlorophenyl (e)] were prepared, as well as 3a-3e (X = Cl) and the new complexes [(η{sup 6}-arene)RuCl(N-N)]PF{sub 6} [arene = C{sub 6}H{sub 5}OCH{sub 2}CH{sub 2}OH, N-N = 2,2{sup '}-bipyridine (4), 2,6-(dimethylphenyl)-pyridin-2-yl-methylene amine (5), 2,6-(diisopropylphenyl)-pyridin-2-yl-methylene amine (6); arene = p-cymene, N-N = 4-(aminophenyl)-pyridin-2-yl-methylene amine (7)]. X-ray diffraction studies were performed for 1a, 1b, 1c, 1d, 2b, 5, and 7. Cytotoxicities of 1a-1d and 2 were established versus human cancer cells epithelial colorectal adenocarcinoma (Caco-2) (IC{sub 50}: 35.8-631.0 μM), breast adenocarcinoma (MCF7) (IC{sub 50}: 36.3-128.8.0 μM), and hepatocellular carcinoma (HepG2) (IC{sub 50}: 60.6-439.8 μM), 3a-3e were tested against HepG2 and Caco-2, and 4-7 were tested against Caco-2. 1-7 were tested against non-cancerous human epithelial kidney cells. 1 and 2 were more selective towards tumor cells than the anticancer drug 5-fluorouracil (5-FU), but 3a-3e (X = Cl) were not selective. 1 and 2 had good activity against MCF7, some with lower IC{sub 50} than 5-FU. Complexes with X = Br or I had moderate activity against Caco-2 and HepG2, but those with Cl were inactive. Antibacterial activities of 1a, 2b, 3a, and 7 were tested against antibacterial susceptible and resistant Gram-negative and -positive bacteria. 1a, 2b, and 3a showed activity against methicillin-resistant S. aureus (MIC = 31-2000 μg.mL{sup -1}). (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  13. A Phase 1 Study of 4 Live, Recombinant Human Cytomegalovirus Towne/Toledo Chimera Vaccines in Cytomegalovirus-Seronegative Men. (United States)

    Adler, Stuart P; Manganello, Anne-Marie; Lee, Ronzo; McVoy, Michael A; Nixon, Daniel E; Plotkin, Stanley; Mocarski, Edward; Cox, Josephine H; Fast, Patricia E; Nesterenko, Pavlo A; Murray, Susan E; Hill, Ann B; Kemble, George


     Human cytomegalovirus (HCMV) infection causes disease in newborns and transplant recipients. A HCMV vaccine (Towne) protects transplant recipients.  The genomes of Towne and the nonattenuated Toledo strain were recombined, yielding 4 Towne/Toledo chimera vaccines. Each of 36 HCMV-seronegative men received 1 subcutaneous dose of 10, 100, or 1000 plaque-forming units (PFU) in cohorts of 3. Safety and immunogenicity were evaluated over 12 weeks after immunization and for 52 weeks for those who seroconverted.  There were no serious local or systemic reactions. No subject had HCMV in urine or saliva. For chimera 3, none of 9 subjects seroconverted. For chimera 1, 1 of 9 seroconverted (the seroconverter received 100 PFU). For chimera 2, 3 subjects seroconverted (1 received 100 PFU, and 2 received 1000 PFU). For chimera 4, 7 subjects seroconverted (1 received 10 PFU, 3 received 100 PFU, and 3 received 1000 PFU). All 11 seroconverters developed low but detectable levels of neutralizing activity. CD4 + T-cell responses were detectable in 1 subject (who received 100 PFU of chimera 4). Seven subjects receiving chimera 2 or 4 had detectable CD8 + T-cell responses to IE1; 3 responded to 1-2 additional antigens.  The Towne/Toledo chimera vaccine candidates were well tolerated and were not excreted. Additional human trials of chimeras 2 and 4 are appropriate.  NCT01195571. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail

  14. Structure and properties of TiC, VC, and TiC/VC thin films deposited by pulsed laser deposition

    International Nuclear Information System (INIS)

    Krzanowski, J.E.; Leuchtner, R.E.


    A study has been conducted on the mechanical, tribological and chemical properties of pulsed laser deposited (PLD) TiC, VC and TiC/VC thin films. The TiC films were deposited at 375 C and 5 mTorr Ar, while the TiC/VC films were deposited from a composite target at 475 C at pressures of base vacuum and 50 mTorr Ar. XRD analysis revealed the films had the expected B1 structure, although XPS analysis showed a significant oxygen content. Tribological studies were conducted using a ball-on-disk test, and the wear behavior depended on the surface condition and film composition. One TiC/VC film exhibited little wear but caused significant ball wear, indicating mixed carbide films are promising candidates for wear-resistant coatings

  15. Particle gamma correlations in {sup 12}C measured with the CsI(Tl) based detector array CHIMERA

    Energy Technology Data Exchange (ETDEWEB)

    Cardella, G., E-mail: [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Acosta, L. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Amorini, F. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Auditore, L. [INFN Gruppo collegato di Messina and Dip. di Fisica e Scienze della Terra, Università di Messina (Italy); Berceanu, I. [Institute for Physics and Nuclear Engineering, Bucharest (Romania); Castoldi, A. [INFN Sezione di Milano e Politecnico Milano (Italy); De Filippo, E. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Dell' Aquila, D. [Dipartimento di scienze Fisiche, Università Federico II and INFN Sezione di Napoli (Italy); Francalanza, L. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Dip. di Fisica e Astronomia, Università di Catania, Via S. Sofia, Catania (Italy); Gnoffo, B. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Guazzoni, C. [INFN Sezione di Milano e Politecnico Milano (Italy); Lanzalone, G. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Facoltà di Ingegneria e Architettura, Università Kore, Enna (Italy); Lombardo, I. [Dipartimento di scienze Fisiche, Università Federico II and INFN Sezione di Napoli (Italy); Minniti, T.; Morgana, E.; Norella, S. [INFN Gruppo collegato di Messina and Dip. di Fisica e Scienze della Terra, Università di Messina (Italy); Pagano, A. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); Pagano, E.V. [INFN - Laboratori Nazionali del Sud, Via S. Sofia, Catania (Italy); Dip. di Fisica e Astronomia, Università di Catania, Via S. Sofia, Catania (Italy); Papa, M.; Pirrone, S. [INFN - Sezione di Catania, Via S. Sofia, 95123 Catania (Italy); and others


    The gamma decay of the first excited 4.44 MeV 2+level of {sup 12}C, populated by inelastic scattering of proton and {sup 16}O beams at various energies was studied in order to test γ-ray detection efficiency and the quality of angular distribution information given by the CsI(Tl) detectors of the 4π CHIMERA array. The γ-decay was measured in coincidence with ejectile scattered particles in an approximately 4π geometry allowing to extract the angular distribution in the reference frame of recoiling {sup 12}C target. The typical sin{sup 2} (2θ) behavior of angular distribution was observed in the case of {sup 16}O beam. Besides that, for the proton beam, in order to explain the observed distribution, the addition of an incoherent flat contribution was required. This latter is the effect of proton spin flip events allowing the population of M=±1 magnetic substates, that is not possible in reactions induced by {sup 16}O beam. A comparison with previously collected data, obtained measuring only in and out of plane proton-γ-ray coincidences, confirms the good quality of the angular distribution information given by the apparatus. Possible applications with radioactive beams are outlined.

  16. 40Ar/ 39Ar and paleomagnetic results from Liberia and the Precambrian APW data base for the West African Shield (United States)

    Onstott, T. C.; Dorbor, J.

    Lower amphibolite to granulite facies metamorphic rocks in Nimba County, Liberia have yielded 2.2-2.9 Ga RbSr whole rock ages, indicating that they are part of the Archean Liberian age province. We report a 2040 Ma 4040Ar/ 39Ar plateau date on hornblende from an amphibolite in this region, and suggest that these rocks were also severelyreworked during the Eburnean (˜2.0 Ga) metamorphic episode. 40Ar/ 39Ar analyses of biotite and feldspars from neighboring schists also indicate the presence of two mild thermal events, at 1.5 Ga and 0.6 Ga. Paleomagnetic analyses of samples from these same metamorphic rocks reveal three components of magnetization. The predominant and most stable component (273°E, 21°N) is considered to have been acquired as a result of pos Eburnean uplift and cooling at ˜ 2.0 Ga, whereas the two less stable components with poles at 235°E, 43°N and 16°E, 36°N, probably correlate with the 1.5 Ga and 0.6 Ga thermal pulses, respectively. Rock units from southern Liberia also yield two secondary magnetizations, one at 247°E, 37°N and the other at 104°E, 5°N, and a 1.5 Ga 40Ar/ 39Ar date on plagioclase. Comparison of the paleomagnetic poles corresponding to the ˜2.0 Ga Eburnean component with published paleomagnetic data for West Africa is not consistent with prior interpretations of the polar wander path for West Africa. Our paleomagnetic data, when compared to poles of comparable age from the Kalahari Shield, still suggest that some form of displacement has occurred between the Kalahari and West African Shields since 2.0 Ga.

  17. 40Ar/39Ar and K-Ar dating of altered glassy volcanic rocks: the Dabi Volcanics, P.N.G

    International Nuclear Information System (INIS)

    Walker, D.A.; McDougall, I.


    K-Ar and 40 Ar/ 39 Ar ages have been determined for altered submarine tholeiitic and boninite (high-Mg andesite) lavas from the Dabi Volcanics, Cape Vogel Peninsula, Papua New Guinea. 40 Ar/ 39 Ar whole rock total fusion and plateau ages identify a Late Paleocene age for the tholeiitic lavas (58.9 +- 1.1 Ma), and also for the boninitic lavas (58.8 +- 0.8 Ma). Apparent K-Ar ages for the same samples range from 27.2 +- 0.7 to 63.9 +- 4.5 Ma, and young K-Ar ages for glassy boninites are probably due to variable radiogenic 40 Ar( 40 Ar*) loss. These new ages effectively reconcile previously ambiguous age data for the Dabi Volcanics, and indicate contemporaneous tholeiitic and boninitic volcanism occurring in southeast PNG during the Late Paleocene. Smectites, developed as alteration products after glass in oceanic lavas commonly do not retain 39 Ar during or subsequent to irradiation, but in some cases may contain 40 Ar*. The results are discussed. (author)

  18. Inherited effects from irradiated mouse immature oocytes detected in aggregation embryo chimeras

    International Nuclear Information System (INIS)

    Straume, T.; Raabe, O.G.; Walsh, K.J.; Wiley, L.M.


    Data obtained using the mouse-preimplantation-embryo-chimera assay are presented that show a transmitted effect following low-dose irradiation of immature oocytes in vivo. Six-week-old female mice were irradiated using 137 Cs-γ-rays (0.05 Gy, 0.15 Gy, and unexposed controls). At 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 weeks post exposure, the mice were mated and aggregation chimeras made from the 4-cell embryos. Three independent experiments have now been carried out, all showing a significant embryonic cell-proliferation disadvantage of the embryos obtained from the females treated 7 weeks previously, i.e., embryos from oocytes that were immature at the time of radiation exposure. No effect was detected at 1-6 weeks when embryos were obtained from maturing oocytes. Also, the effect was not seen at 8, 9, 10, 11, and 12 weeks post exposure. The implications of these results are discussed in the light of previous studies on mouse oocytes

  19. Survival of allografts from bone marrow donors in temporary dog radiation chimeras

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.

    Complete radiation chimeras accept indefinitely a skin or a kidney graft from the bone marrow (BM) donor. The advantages of this method of inducing graft acceptance are that it does not require the use of toxic post-operative immunosuppressive agents and that the immune reactivity against antigens other than the ones carried by the BM donor remains intact. The disadvantages of this approach are that supralethal total body irradiation (TBI) causes toxicity and that allogeneic BM cells can cause lethal Graft versus Host reactions. Attempts were made to diminish the significance of these disadvantages by using lower dose TBI and giving fewer BM cells. It is shown that, in dogs, 7.5 Gy TBI followed by 4 X 10 8 BM -1 body weight of a DLA identical sibling leads to the development of complete radiation chimeras. The exclusive presence of donor type haemopoiesis can be demonstrated by determinations of 'informative' genetic markers, i.e., markers that show different genotypes in donor and recipient. (Auth.)

  20. Anticipatory Governance: Bioethical Expertise for Human/Animal Chimeras (United States)

    Harvey, Alison; Salter, Brian


    The governance demands generated by the use of human/animal chimeras in scientific research offer both a challenge and an opportunity for the development of new forms of anticipatory governance through the novel application of bioethical expertise. Anticipatory governance can be seen to have three stages of development whereby bioethical experts move from a reactive to a proactive stance at the edge of what is scientifically possible. In the process, the ethicists move upstream in their engagement with the science of human-to-animal chimeras. To what extent is the anticipatory coestablishment of the principles and operational rules of governance at this early stage in the development of the human-to-animal research field likely to result in a framework for bioethical decision making that is in support of science? The process of anticipatory governance is characterised by the entwining of the scientific and the philosophical so that judgements against science are also found to be philosophically unfounded, and conversely, those activities that are permissible are deemed so on both scientific and ethical grounds. Through what is presented as an organic process, the emerging bioethical framework for human-to-animal chimera research becomes a legitimating framework within which ‘good’ science can safely progress. Science gives bioethical expertise access to new governance territory; bioethical expertise gives science access to political acceptability. PMID:23576848

  1. Chimera at the phase-flip transition of an ensemble of identical nonlinear oscillators (United States)

    Gopal, R.; Chandrasekar, V. K.; Senthilkumar, D. V.; Venkatesan, A.; Lakshmanan, M.


    A complex collective emerging behavior characterized by coexisting coherent and incoherent domains is termed as a chimera state. We bring out the existence of a new type of chimera in a nonlocally coupled ensemble of identical oscillators driven by a common dynamic environment. The latter facilitates the onset of phase-flip bifurcation/transitions among the coupled oscillators of the ensemble, while the nonlocal coupling induces a partial asynchronization among the out-of-phase synchronized oscillators at this onset. This leads to the manifestation of coexisting out-of-phase synchronized coherent domains interspersed by asynchronous incoherent domains elucidating the existence of a different type of chimera state. In addition to this, a rich variety of other collective behaviors such as clusters with phase-flip transition, conventional chimera, solitary state and complete synchronized state which have been reported using different coupling architectures are found to be induced by the employed couplings for appropriate coupling strengths. The robustness of the resulting dynamics is demonstrated in ensembles of two paradigmatic models, namely Rössler oscillators and Stuart-Landau oscillators.

  2. Timing and processes for exhumation of HP/LT rocks of the southern Brooks Range (AK): Insight from combined geochemistry and 40Ar/39Ar thermochronology of white mica (United States)

    O'Brien, T.; Miller, E. L.; Grove, M. J.; Hayden, L. A.


    The obduction of an island arc onto the Arctic Alaska continental margin in the Jura-Cretaceous led to southward subduction of continental crust and high-pressure/low-temperature (HP/LT) epidote-blueschist facies metamorphism in the southern Brooks Range (BR). A regionally developed greenschist facies normal-sense shear zone system along the southern margin of the BR suggests that extensional faulting had an influential role in the exhumation of the metamorphic core. To better constrain the exhumation history of the metamorphic core of the BR, samples were collected from a N-S transect through the metamorphic core of the orogen. Electron microprobe (EMP) analyses of white micas reveal that they are composed of phengite (Si > 3.0 pfu) or a combination of phengite + paragonite. Si-content of phengites reveal a southward increase in Si from 3.1 to 3.4 pfu (corresponding to an increase in pressure). Si-contents in higher-P phengites are scattered, reflecting subsequent muscovite growth. The Si trend is matched by a southward increase in the 40Ar/39Ar total gas ages of white micas. Phengite from the north are characterized by younger ages (~115 Ma) and flatter 40Ar/39Ar spectra. Farther south, phengites and paragonites yield older 40Ar/39Ar ages. These samples yield convex, staircase 40Ar/39Ar spectra that initiate ~115-120 Ma and flatten-out ~130-138 Ma. Modeling using MacArgon proposes that an initial cooling of HP/LT metamorphism occurred ~130-138 Ma, recorded in the high-Si phengites and paragonites. Following initial cooling, modeling suggests HP/LT rocks stalled in the greenschist facies field before subsequent exhumation, resulting in the staircase 40Ar/39Ar spectra. Flatter 40Ar/39Ar spectra recorded by the northern samples and modeling of 40Ar/39Ar results from the southern samples suggest that these rocks from metamorphic core of the BR were exhumed to temperatures < 300°C by ~115 Ma.

  3. On mechanism of Ar(3p54p) states excitation in low-energy Ar-Ar collisions

    International Nuclear Information System (INIS)

    Kurskov, S Y; Kashuba, A S


    The present work is devoted to study of Ar(3p 5 4p) states excitation in binary low-energy Ar-Ar collisions. The results of the experimental investigation of excitation cross sections of Ar I 4p'[l/2] 1 , 4p'[3/2] 1 , 4p'[3/2] 2 and 4p[3/2] 2 levels in the collision energy range from threshold up to 500 eV (cm) and degree of polarization for 4s[3/2] 2 0 -4p'[l/2] 1 and 4s[3/2] 2 0 -4p[3/2] 2 transitions in this energy range are represented.

  4. Characterization of a C3a receptor in rainbow trout and Xenopus: the first identification of C3a receptors in nonmammalian species (United States)

    Boshra, Hani; Wang, Tiehui; Hove-Madsen, Leif; Hansen, John D.; Li, Jun; Matlapudi, Anjun; Secombes, Christopher J.; Tort, Lluis; Sunyer, J. Oriol


    Virtually nothing is known about the structure, function, and evolutionary origins of the C3aR in nonmammalian species. Because C3aR and C5aR are thought to have arisen from the same common ancestor, the recent characterization of a C5aR in teleost fish implied the presence of a C3aR in this animal group. In this study we report the cloning of a trout cDNA encoding a 364-aa molecule (TC3aR) that shows a high degree of sequence homology and a strong phylogenetic relationship with mammalian C3aRs. Northern blotting demonstrated that TC3aR was expressed primarily in blood leukocytes. Flow cytometric analysis and immunofluorescence microscopy showed that Abs raised against TC3aR stained to a high degree all blood B lymphocytes and, to a lesser extent, all granulocytes. More importantly, these Abs inhibited trout C3a-mediated intracellular calcium mobilization in trout leukocytes. A fascinating structural feature of TC3aR is the lack of a significant portion of the second extracellular loop (ECL2). In all C3aR molecules characterized to date, the ECL2 is exceptionally large when compared with the same region of C5aR. However, the exact function of the extra portion of ECL2 is unknown. The lack of this segment in TC3aR suggests that the extra piece of ECL2 was not necessary for the interaction of the ancestral C3aR with its ligand. Our findings represent the first C3aR characterized in nonmammalian species and support the hypothesis that if C3aR and C5aR diverged from a common ancestor, this event occurred before the emergence of teleost fish.

  5. Mechanistic Characterization of GS-9190 (Tegobuvir), a Novel Nonnucleoside Inhibitor of Hepatitis C Virus NS5B Polymerase▿ (United States)

    Shih, I-hung; Vliegen, Inge; Peng, Betty; Yang, Huiling; Hebner, Christy; Paeshuyse, Jan; Pürstinger, Gerhard; Fenaux, Martijn; Tian, Yang; Mabery, Eric; Qi, Xiaoping; Bahador, Gina; Paulson, Matthew; Lehman, Laura S.; Bondy, Steven; Tse, Winston; Reiser, Hans; Lee, William A.; Schmitz, Uli; Neyts, Johan; Zhong, Weidong


    GS-9190 (Tegobuvir) is a novel imidazopyridine inhibitor of hepatitis C virus (HCV) RNA replication in vitro and has demonstrated potent antiviral activity in patients chronically infected with genotype 1 (GT1) HCV. GS-9190 exhibits reduced activity against GT2a (JFH1) subgenomic replicons and GT2a (J6/JFH1) infectious virus, suggesting that the compound's mechanism of action involves a genotype-specific viral component. To further investigate the GS-9190 mechanism of action, we utilized the susceptibility differences between GT1b and GT2a by constructing a series of replicon chimeras where combinations of 1b and 2a nonstructural proteins were encoded within the same replicon. The antiviral activities of GS-9190 against the chimeric replicons were reduced to levels comparable to that of the wild-type GT2a replicon in chimeras expressing GT2a NS5B. GT1b replicons in which the β-hairpin region (amino acids 435 to 455) was replaced by the corresponding sequence of GT2a were markedly less susceptible to GS-9190, indicating the importance of the thumb subdomain of the polymerase in this effect. Resistance selection in GT1b replicon cells identified several mutations in NS5B (C316Y, Y448H, Y452H, and C445F) that contributed to the drug resistance phenotype. Reintroduction of these mutations into wild-type replicons conferred resistance to GS-9190, with the number of NS5B mutations correlating with the degree of resistance. Analysis of GS-9190 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of GS-9190 is different from other nonnucleoside inhibitors. Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain. PMID:21746939

  6. Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras

    International Nuclear Information System (INIS)

    Sharrow, S.O.; Mathieson, B.J.; Singer, A.


    The phenotypic appearance of cell surface antigens on murine thymocytes from long-term radiation bone marrow chimeras was analyzed using indirect immunofluorescence and flow microfluorometry. Cells maturing in the thymi of these mice were typed for MHC (Kk, I-Ak, H-2b, Kb, and Ib) and non-MHC (Lty 1, Ly 9, and TL) determinants. All cells were of donor origin as determined by non-MHC (Ly) phenotype in P1 leads to P2, P1 x P2 leads to P1, and P1 leads to P2 radiation chimeras. In contrast, the MHC phenotypes of these thymocytes were markedly affected by the host environment. Specifically, H-2 and I-A determinants of both parental phenotypes were detected on thymocytes from P1 leads to P1 x P2 chimeras; I-A determinants of host phenotype were present, whereas I-A determinants of donor phenotype were reduced on thymocytes from P1 x P2 leads to P1 chimeras; and thymocytes from P1 leads to P2 chimeras possessed H-2 and I-A determinants of host phenotype but showed reduction of donor I-A phenotype determinants. The appearance of host cell surface H-2 and I-A determinants on thymocytes from chimeras closely parallels the functional recognition of MHC determinants by T cells from chimeric mice and thus may be significantly related to the development of the self-recognition repertoire by maturing T cells

  7. Experimental and theoretical studies of the C{sub 6}H{sub 5} + C{sub 6}H{sub 6} reaction

    Energy Technology Data Exchange (ETDEWEB)

    Park, J.; Burova, S.; Rodgers, A.S.; Lin, M.C.


    The absolute rate constants for the C{sub 6}H{sub 5} + C{sub 6}H{sub 6} and C{sub 6}D{sub 6} reactions have been measured by cavity ringdown spectrometry at temperatures between 298 and 495 K at a constant 40 Torr Ar pressure. The new results, which reveal no detectable kinetic isotopic effect, can be represented by the Arrhenius equation, {kappa}{sub 1} = 10{sup (11.91{+-}0.13)} exp[{minus}(2,102 {+-} 106)/T] cm{sup 3}/(mol s). Low-temperature data for the addition/stabilization process, C{sub 6}H{sub 5} + C{sub 6}H{sub 6} {r{underscore}arrow} C{sub 12}H{sub 11}, can be correlated with those obtained in a low-pressure, high-temperature Knudsen cell study for the addition/displacement reaction, C{sub 6}H{sub 5} + C{sub 6}H{sub 6} {r{underscore}arrow} C{sub 12}H{sub 10} + H, by the RRKM theory using the molecular and transition-state parameters computed at the B3LYP/6-311G(d,p) level of theory. Combination of these two sets of data gives {kappa}{sub 1} = 10{sup (11.98{+-}0.03)} exp[{minus}(2168 {+-} 34)/T] cm{sup 3}/(mol s) covering the temperature range 298--1,330 K. The RRKM theory also correlates satisfactorily the forward reaction data with the high-temperature shock-tube result for the reverse H-for-C{sub 6}H{sub 5} substitution process with 2.7 and 4.7 kcal/mol barriers for the entrance (C{sub 6}H{sub 5} + C{sub 6}H{sub 6}) and reverse (H + C{sub 12}H{sub 10}) reactions, respectively. For modeling applications, the authors have calculated the forward reaction rate constants for the formation of the two competing products, H + C{sub 12}H{sub 10} and C{sub 12}H{sub 11}, at several pressures covering 300 K {lt} T {lt} 2,500 K.

  8. A flavor of 40Ar-39Ar geochronology research at lIT Bombay

    International Nuclear Information System (INIS)

    Pande, Kanchan


    Geochronology based on radiogenic isotopes has become an invaluable tool in earth sciences. Several radioactive parent-daughter systems of varying half-lives such as Rb-Sr, Sm-Nd, K-Ar have been traditionally used by researchers for determining the timing of geological and planetary processes. 40 Ar- 39 Ar dating, a variant of the K-Ar system, is a well-established and versatile method of determining the eruptive ages of volcanic rocks and the ∼150-500° C thermal histories of a variety of more slowly cooled igneous and metamorphic rocks. In the 40 Ar- 39 Ar method the sample is irradiated by fast neutrons in a nuclear reactor to convert some of 39 K into 39 Ar. The fixed natural ratio 39 K/ 40 K provides estimate for the parent 40 K by measuring 39 Ar. In order to know the conversion factor of 39 K to 39 Ar and to take care of other nuclear interfering reactions a sample of known K-Ar age is irradiated along with the unknown. The age of the unknown is then derived by comparison with the monitor sample of known age

  9. Comparative evaluation of the IPCC AR5 CMIP5 versus the AR4 CMIP3 model ensembles for regional precipitation and their extremes over South America (United States)

    Tolen, J.; Kodra, E. A.; Ganguly, A. R.


    The assertion that higher-resolution experiments or more sophisticated process models within the IPCC AR5 CMIP5 suite of global climate model ensembles improves precipitation projections over the IPCC AR4 CMIP3 suite remains a hypothesis that needs to be rigorously tested. The questions are particularly important for local to regional assessments at scales relevant for the management of critical infrastructures and key resources, particularly for the attributes of sever precipitation events, for example, the intensity, frequency and duration of extreme precipitation. Our case study is South America, where precipitation and their extremes play a central role in sustaining natural, built and human systems. To test the hypothesis that CMIP5 improves over CMIP3 in this regard, spatial and temporal measures of prediction skill are constructed and computed by comparing climate model hindcasts with the NCEP-II reanalysis data, considered here as surrogate observations, for the entire globe and for South America. In addition, gridded precipitation observations over South America based on rain gage measurements are considered. The results suggest that the utility of the next-generation of global climate models over the current generation needs to be carefully evaluated on a case-by-case basis before communicating to resource managers and policy makers.

  10. Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma (United States)

    Grosso, Ana R; Leite, Ana P; Carvalho, Sílvia; Matos, Mafalda R; Martins, Filipa B; Vítor, Alexandra C; Desterro, Joana MP; Carmo-Fonseca, Maria; de Almeida, Sérgio F


    Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer. DOI: PMID:26575290

  11. What's Wrong with Human/Nonhuman Chimera Research? (United States)

    Hyun, Insoo


    The National Institutes of Health (NIH) is poised to lift its funding moratorium on research involving chimeric human/nonhuman embryos, pending further consideration by an NIH steering committee. The kinds of ethical concerns that seem to underlie this research and chimera research more generally can be adequately addressed.

  12. H{sub 2}-Ar dilution for improved c-Si quantum dots in P-doped SiN{sub x}:H thin film matrix

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jia [Shaanxi Engineering Lab for Advanced Energy Technology, School of Materials Science and Engineering, Shaanxi Normal University, Xi’an 710119 (China); Zhang, Weijia, E-mail: [Center of Condensed Matter and Material Physics, School of Physics and Nuclear Energy Engineering, Beihang University, Beijing, 100191 (China); Liu, Shengzhong, E-mail: [Shaanxi Engineering Lab for Advanced Energy Technology, School of Materials Science and Engineering, Shaanxi Normal University, Xi’an 710119 (China); State key Laboratory of Catalysis, iChEM, Dalian Institute of Chemical Physics, Dalian National Laboratory for Clean Energy, Chinese Academy of Sciences, Dalian 116023 (China)


    Highlights: • Phosphorous-doped SiN{sub x}:H thin films containing c-Si QDs were prepared by PECVD in H{sub 2}-Ar mixed dilution under low temperature. • QD density and QD size can be controlled by tuning H{sub 2}/Ar flow ratio. • The sample prepared at the H{sub 2}/Ar flow ratio of 100/100 possesses both wide band gap and excellent conductivity. • Detail discussion has been presented for illustrating the influence of H{sub 2}/Ar mixed dilution on the crystallization process and P-doping. - Abstract: Phosphorus-doped hydrogenated silicon nitride (SiN{sub x}:H) thin films containing crystalline silicon quantum dot (c-Si QD) was prepared by plasma enhanced chemical vapor deposition (PECVD) using hydrogen-argon mixed dilution. The effects of H{sub 2}/Ar flow ratio on the structural, electrical and optical characteristics of as-grown P-doped SiN{sub x}:H thin films were systematically investigated. Experimental results show that crystallization is promoted by increasing the H{sub 2}/Ar flow ratio in dilution, while the N/Si atomic ratio is higher for thin film deposited with argon-rich dilution. As the H{sub 2}/Ar flow ratio varies from 100/100 to 200/0, the samples exhibit excellent conductivity owing to the large volume fraction of c-Si QDs and effective P-doping. By adjusting the H{sub 2}/Ar ratio to 100/100, P-doped SiN{sub x}:H thin film containing tiny and densely distributed c-Si QDs can be obtained. It simultaneously possesses wide optical band gap and high dark conductivity. Finally, detailed discussion has been made to analyze the influence of H{sub 2}-Ar mixed dilution on the properties of P-doped SiN{sub x}:H thin films.

  13. Origin of hemopoietic stromal progenitor cells in chimeras

    International Nuclear Information System (INIS)

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.


    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice

  14. /sup 40/Ar//sup 39/Ar and K-Ar dating of altered glassy volcanic rocks: the Dabi Volcanics, P. N. G

    Energy Technology Data Exchange (ETDEWEB)

    Walker, D.A. (Australian National Univ., Canberra. Dept. of Geology); McDougall, I. (Australian National Univ., Canberra. Research School of Earth Sciences)


    K-Ar and /sup 40/Ar//sup 39/Ar ages have been determined for altered submarine tholeiitic and boninite (high-Mg andesite) lavas from the Dabi Volcanics, Cape Vogel Peninsula, Papua New Guinea. /sup 40/Ar//sup 39/Ar whole rock total fusion and plateau ages identify a Late Paleocene age for the tholeiitic lavas (58.9 +- 1.1 Ma), and also for the boninitic lavas (58.8 +- 0.8 Ma). Apparent K-Ar ages for the same samples range from 27.2 +- 0.7 to 63.9 +- 4.5 Ma, and young K-Ar ages for glassy boninites are probably due to variable radiogenic /sup 40/Ar(/sup 40/Ar*) loss. These new ages effectively reconcile previously ambiguous age data for the Dabi Volcanics, and indicate contemporaneous tholeiitic and boninitic volcanism occurring in southeast PNG during the Late Paleocene. Smectites, developed as alteration products after glass in oceanic lavas commonly do not retain /sup 39/Ar during or subsequent to irradiation, but in some cases may contain /sup 40/Ar*. The results are discussed.

  15. Three-dimensional chimera patterns in networks of spiking neuron oscillators (United States)

    Kasimatis, T.; Hizanidis, J.; Provata, A.


    We study the stable spatiotemporal patterns that arise in a three-dimensional (3D) network of neuron oscillators, whose dynamics is described by the leaky integrate-and-fire (LIF) model. More specifically, we investigate the form of the chimera states induced by a 3D coupling matrix with nonlocal topology. The observed patterns are in many cases direct generalizations of the corresponding two-dimensional (2D) patterns, e.g., spheres, layers, and cylinder grids. We also find cylindrical and "cross-layered" chimeras that do not have an equivalent in 2D systems. Quantitative measures are calculated, such as the ratio of synchronized and unsynchronized neurons as a function of the coupling range, the mean phase velocities, and the distribution of neurons in mean phase velocities. Based on these measures, the chimeras are categorized in two families. The first family of patterns is observed for weaker coupling and exhibits higher mean phase velocities for the unsynchronized areas of the network. The opposite holds for the second family, where the unsynchronized areas have lower mean phase velocities. The various measures demonstrate discontinuities, indicating criticality as the parameters cross from the first family of patterns to the second.

  16. Global Warming Induced Changes in Rainfall Characteristics in IPCC AR5 Models (United States)

    Lau, William K. M.; Wu, Jenny, H.-T.; Kim, Kyu-Myong


    Changes in rainfall characteristic induced by global warming are examined from outputs of IPCC AR5 models. Different scenarios of climate warming including a high emissions scenario (RCP 8.5), a medium mitigation scenario (RCP 4.5), and 1% per year CO2 increase are compared to 20th century simulations (historical). Results show that even though the spatial distribution of monthly rainfall anomalies vary greatly among models, the ensemble mean from a sizable sample (about 10) of AR5 models show a robust signal attributable to GHG warming featuring a shift in the global rainfall probability distribution function (PDF) with significant increase (>100%) in very heavy rain, reduction (10-20% ) in moderate rain and increase in light to very light rains. Changes in extreme rainfall as a function of seasons and latitudes are also examined, and are similar to the non-seasonal stratified data, but with more specific spatial dependence. These results are consistent from TRMM and GPCP rainfall observations suggesting that extreme rainfall events are occurring more frequently with wet areas getting wetter and dry-area-getting drier in a GHG induced warmer climate.

  17. What's Wrong with Human/Nonhuman Chimera Research?

    Directory of Open Access Journals (Sweden)

    Insoo Hyun


    Full Text Available The National Institutes of Health (NIH is poised to lift its funding moratorium on research involving chimeric human/nonhuman embryos, pending further consideration by an NIH steering committee. The kinds of ethical concerns that seem to underlie this research and chimera research more generally can be adequately addressed.

  18. Application of Chimera Composite Grid Scheme to Ship Appendages

    National Research Council Canada - National Science Library

    Lin, Cheng-Wen


    .... The chimera scheme of grid generation uses a system of relatively simple grids. The grids each define a particular component of the overall geometry, making the initial grid generation much simpler...

  19. Studies on the mechanism of stable graft--host tolerance in canine and human radiation chimeras

    International Nuclear Information System (INIS)

    Storb, R.; Tsoi, M.S.; Weiden, P.L.; Graham, T.C.; Thomas, E.D.


    In studies with dogs, marrow donors were immunized against their chimeras by repeated skin grafts which they rejected. Lymphocytes from chimeras and donors were tested for cell inhibition by exposure to skin fibroblasts from chimeras and donors. Results were not compatible with the concept that tolerance in radiation chimeras is maintained by serum-blocking factors. They provide circumstantial evidence against the possibility that the stable chimeric state is the result of the deletion of a close or inactivation of donor lymphocytes specifically responsive for host antigens. They are most consistent with the possibility that a suppressor-cell population is responsible for the maintenance of tolerance. Human recipients of marrow transplants were tested with the cell inhibition assay. Although the incidence of positive cell inhibition and blocking was somewhat higher than in the dog, results were not compatible with the concept that serum blocking is the sole mechanism for maintaining the stable chimeric state in human patients

  20. Electron scattering from 36Ar and 40Ar

    International Nuclear Information System (INIS)

    Finn, J.M.


    The argon isotopes, 36 Ar and 40 Ar, have been investigated using electron scattering at the high-resolution Linac facilities of the National Bureau of Standards. Both elastic scattering and scattering to low-lying states have been observed. A high-pressure, low-volume gas target cell was designed and developed for this experiment. The cell features a transmission geometry and has resolution comparable to solid targets. Spectra were obtained at incident beam energies ranging from 65 to 115 MeV at scattering angles of 92.5 0 and 110 0 . Values obtained for the rms charge radii are 3.327 +- 0.015 and 3.393 +- 0.015 fm for 36 Ar and 40 Ar respectively. A sensitive measurement was made of the difference in the two radii yielding a value of Δ r = 0.079 +- 0.006 fm. The inelastic levels observed are the 1.97 (2 + ) and 4.18 MeV (3 - ) levels in 36 Ar, and the 1.46 (2 + ), 2.52 (2 + ), 3.21 (2 + ), and 3.68 MeV (3 - ) levels in 40 Ar. A Tassie model analysis was made of the inelastic transitions in the DWBA approximation and transition strengths of these levels were extracted

  1. Defining the biomechanical and biological threshold of murine mild traumatic brain injury using CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration). (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Bashir, Asma; Wilkinson, Anna; Stukas, Sophie; Martens, Kris M; Whyte, Tom; Abebe, Zelalem A; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L


    CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a recently described animal model of traumatic brain injury (TBI) that primarily produces diffuse axonal injury (DAI) characterized by white matter inflammation and axonal damage. CHIMERA was specifically designed to reliably generate a variety of TBI severities using precise and quantifiable biomechanical inputs in a nonsurgical user-friendly platform. The objective of this study was to define the lower limit of single impact mild TBI (mTBI) using CHIMERA by characterizing the dose-response relationship between biomechanical input and neurological, behavioral, neuropathological and biochemical outcomes. Wild-type male mice were subjected to a single CHIMERA TBI using six impact energies ranging from 0.1 to 0.7J, and post-TBI outcomes were assessed over an acute period of 14days. Here we report that single TBI using CHIMERA induces injury dose- and time-dependent changes in behavioral and neurological deficits, axonal damage, white matter tract microgliosis and astrogliosis. Impact energies of 0.4J or below produced no significant phenotype (subthreshold), 0.5J led to significant changes for one or more phenotypes (threshold), and 0.6 and 0.7J resulted in significant changes in all outcomes assessed (mTBI). We further show that linear head kinematics are the most robust predictors of duration of unconsciousness, severity of neurological deficits, white matter injury, and microgliosis following single TBI. Our data extend the validation of CHIMERA as a biofidelic animal model of DAI and establish working parameters to guide future investigations of the mechanisms underlying axonal pathology and inflammation induced by mechanical trauma. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  2. Effects of shock pressure on 40Ar-39Ar radiometric age determinations

    International Nuclear Information System (INIS)

    Davis, P.K.


    The relation of shock to the drop in the 40 *Ar/ 39 *Ar ratio seen at high release temperatures in some neutron-irradiated lunar samples is investigated through measurements of the 40 *Ar/ 39 *Ar ratio in gas samples released by stepwise heating of rock samples previously subjected to shock, either in the laboratory or in nature. Explosives were used to shock solid pieces and powder of a basalt from a diabase dike in Liberia to calculated pressures of 65, 150 and 270 kbar. These, an unshocked sample of the powder, two naturally shocked samples from the Brent impact crater in Canada, one unshocked sample from near the crater, and appropriate monitors were irradiated. Ar from stepwise heating was analyzed. The unshocked basalt shows a good 40 *Ar/ 39 *Ar plateau at age 198 +-9 m.y. in agreement with a previous result of 186 +- 2 m.y. The shocked samples contain varying amounts of implanted atmospheric Ar, the isotopes of which have experienced mass fractionation. This effect is small enough in four samples so that the linearity of their graphs of 39 *Ar/ 40 Ar vs 36 Ar/ 40 Ar is evidence of a plateau. The ages of these samples are then 201 +- 10, 205 +- 12 and 201 +-9 m.y. It appears that the shock has had little effect on the 40 Ar- 39 Ar age spectrum, although the release patterns of the 39 *Ar are shifted downward by the order of 200 0 C. Shock implantation of Ar was at lower shock pressure, in the presence of less Ar, and into a less porous material than previously demonstrated. The Brent Crater samples do not all show good plateaus, but do indicate an age of 420 m.y. for the crater event and 795 +- 24 m.y. for the rock formation, in agreement with previous results. None of the 40 *Ar/ 39 *Ar profiles shows a drop at high temperature, but a possible role of shock implantation of Ar is indicated in the production of this effect. Further experiments are suggested. (author)

  3. Chemical degradation of selected Zn-based corrosion products induced by C{sub 60} cluster, Ar cluster and Ar{sup +} ion sputtering in the focus of X-ray photoelectron spectroscopy (XPS)

    Energy Technology Data Exchange (ETDEWEB)

    Steinberger, R., E-mail: [Christian Doppler Laboratory for Microscopic and Spectroscopic Material Characterization, Center for Surface and Nanoanalytics, Johannes Kepler University Linz, Altenberger Straße 69, 4040 Linz (Austria); Sicking, J., E-mail: [Bayer AG, Engineering & Technology, Applied Physics, Chempark Building E 41, 51368 Leverkusen (Germany); Weise, J., E-mail: [Institut für Experimentelle Physik, TU Bergakademie Freiberg, Leipziger Straße 23, 09599 Freiberg (Germany); Duchoslav, J., E-mail: [Christian Doppler Laboratory for Microscopic and Spectroscopic Material Characterization, Center for Surface and Nanoanalytics, Johannes Kepler University Linz, Altenberger Straße 69, 4040 Linz (Austria); Greunz, T., E-mail: [Christian Doppler Laboratory for Microscopic and Spectroscopic Material Characterization, Center for Surface and Nanoanalytics, Johannes Kepler University Linz, Altenberger Straße 69, 4040 Linz (Austria); Meyer, D.C., E-mail: [Institut für Experimentelle Physik, TU Bergakademie Freiberg, Leipziger Straße 23, 09599 Freiberg (Germany); Stifter, D., E-mail: [Christian Doppler Laboratory for Microscopic and Spectroscopic Material Characterization, Center for Surface and Nanoanalytics, Johannes Kepler University Linz, Altenberger Straße 69, 4040 Linz (Austria)


    Highlights: • XPS investigations for various sputter concepts on Zn-based corrosions products. • Direct comparison of induced chemical damage for ion and cluster sputtering. • Azimuthal rotation or heavy projectile bombardment was not found to be beneficial. • Ar cluster etching is rated as unsuitable for surface cleaning or depth profiling. • C{sub 60} and Ar{sup +} are applicable for sputtering when degradation is carefully considered. - Abstract: Monoatomic ion sputtering is a common concept for surface sensitive analysis methods to clean surfaces prior investigation or to obtain information from deeper regions. However, severe damage of the materials – linked to preferential sputtering, ion implantation, atomic mixing and in worst case chemical degradation – can affect the validity of the analysis. Hence, the impact of C{sub 60} cluster etching, furthermore, of Ar{sup +} ion bombardment with and without azimuthal sample rotation and also the application of heavy projectiles (Xe{sup +} ions) was investigated to find a concept, which is less destructive or with less critical influence on the chemical nature of the investigated materials. In this work the focus is set on hydrozincite and zinc oxide, two common corrosion products of Zn-based coatings. As a main point, all the obtained results from (i) Ar{sup +} ion, (ii) Ar cluster, and (iii) C{sub 60} cluster etching on the degradation kinetics of hydrozincite were compared with respect to the reached sputter depth. In addition, the sputter rate of all three methods was experimentally determined for ZnO. In total, fully non-destructive conditions could not be found, but valuable knowledge on the type and rate of degradation, which is essential to choose the most suited sputter concept.

  4. Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP. (United States)

    Sarkar, Sukumar; Brautigan, David L; Larner, James M


    Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer. Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation. Aurora A kinase is activated by 2-ME in the S-phase as well as during mitosis, and phosphorylates CHIP at S273. Prostate cancer cells expressing an S273A mutant of CHIP have attenuated AR degradation upon 2-ME treatment compared with cells expressing wild-type CHIP, supporting the idea that CHIP phosphorylation by Aurora A activates its E3 ligase activity for the AR. These results reveal a novel 2-ME→Aurora A→CHIP→AR pathway that promotes AR degradation via the proteasome that may offer novel therapeutic opportunities for prostate cancer. Mol Cancer Res; 15(8); 1063-72. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. 10- 12 gadus vecu bērnu ar atkārtotu nesekmību iemācītās bezpalīdzības saistība ar vecāku iemācīto bezpalīdzību


    Lamstere, Jolanta


    Darbā tika pētīta iemācītās bezpalīdzības saistība bērniem ar vecāku iemācīto bezpalīdzību. Pētījuma gaitā tika izvirzīti pētījuma jautājumi: vai pastāv statistiski nozīmīgas sakarības starp iemācītās bezpalīdzības rādītājiem 10- 12 gadus veciem bērniem ar atkārtotu nesekmību un viņu vecāku iemācītās bezpalīdzības rādītājiem; vai pastāv statistiski nozīmīgas atšķirības starp iemācītās bezpalīdzības rādītājiem bērniem ar atkārtotu nesekmību un sekmīgiem bērniem; vai pastāv statistiski nozīmīga...

  6. La Chimera di Dino Campana e Altre Chimere

    Directory of Open Access Journals (Sweden)

    Lucia Wataghin


    Full Text Available O presente artigo contém considerações sobre resultados e problemáticas da reutilização de materiais da tradição literária em um dos mais celebrados poemas de Dino Campana, La Chimera.

  7. Navier-Stokes Computations of Sabot Discard Using Chimera Scheme

    National Research Council Canada - National Science Library

    Ferry, E


    .... Numerical flow field computations have been made for various orientations and locations of sabots using an unsteady, zonal Navier-Stokes code and the Chimera composite grid discretization technique at M = 4.0 and alpha = 0...

  8. Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol hydrobromide

    Directory of Open Access Journals (Sweden)

    Amber L. Thompson


    Full Text Available X-ray crystallographic analysis of the title hydrobromide salt, C10H20N+·Br−, of (1R,2S,3R,5R,8aR-3-hydroxymethyl-5-methyloctahydroindolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxylated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae leaves. In the crystal structure, molecules are linked by intermolecular O—H...Br and N—H...Br hydrogen bonds, forming double chains around the twofold screw axes along the b-axis direction. Intramolecular O—H...O interactions occur.

  9. Alignment and orientation of Ar+ in He+-Ar collisions

    International Nuclear Information System (INIS)

    Moudry, B.W.; Yenen, O.; Jaecks, D.H.


    We have measured the alignment and orientation parameters of the 2 F 7/2 0 and 2 F 5/2 0 states of Ar + formed in the two-electron process; He + +Ar→He(1s 2 )+Ar + (3p 4 4p'). These have been measured at a collision energy of 0.25 keV/amu and for scattering angles ranging from 0.94 to 3.75 . First, by comparing the orientation prameter for the Ar + [(3p 4 [ 1 D]4p' 2 F 7/2 0 ] and the Ar + [(3p 4 [ 1 D]4p' 2 F 5/2 0 ] states, we have experimentally determined the importance of the spin-dependent interactions for the present collision system, by testing the Percival-Seaton hypothesis of spin independence. If the Percival-Seaton hypothesis holds for this system, the orientation parameter should be J-independent. Secondly, the magnitude of the orientation prameter can be interpreted as resulting from the collective circulation of the unexcited 3p 4 electrons and the excited 4p electron. The direction of this collective circulation is compared to the propensity rule for colliding di-atom systems. (orig.)

  10. Chimera states in Gaussian coupled map lattices (United States)

    Li, Xiao-Wen; Bi, Ran; Sun, Yue-Xiang; Zhang, Shuo; Song, Qian-Qian


    We study chimera states in one-dimensional and two-dimensional Gaussian coupled map lattices through simulations and experiments. Similar to the case of global coupling oscillators, individual lattices can be regarded as being controlled by a common mean field. A space-dependent order parameter is derived from a self-consistency condition in order to represent the collective state.

  11. Chimera: construction of chimeric sequences for phylogenetic analysis

    NARCIS (Netherlands)

    Leunissen, J.A.M.


    Chimera allows the construction of chimeric protein or nucleic acid sequence files by concatenating sequences from two or more sequence files in PHYLIP formats. It allows the user to interactively select genes and species from the input files. The concatenated result is stored to one single output

  12. 40Ar/39Ar age and thermal history of the Kirin chondrite

    International Nuclear Information System (INIS)

    Wang, S.; McDougall, I.; Tetley, N.; Harrison, T.M.


    The Kirin meteorite, a large (> 2800 kg) H5 chondrite, fell in Kirin Province, China in 1976. A sample from each of the two largest fragments (K-1. K-2) yield 40 Ar/ 39 Ar total fusion ages of 3.63 +- 0.02 b.y. and 2.78 +- 0.02 b.y. respectively. 40 Ar/ 40 Ar age spectra show typical diffusional argon loss profiles. Maximum apparent ages of 4.36 b.y. (K-1) and approx. 4.0 b.y. (K-2) are interpreted as possible minimum estimates for the age of crystallization of the parent body. (orig./ME)

  13. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes. (United States)

    Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell


    Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Application of Chimera Grid Scheme to Combustor Flowfields at all Speeds (United States)

    Yungster, Shaye; Chen, Kuo-Huey


    A CFD method for solving combustor flowfields at all speeds on complex configurations is presented. The approach is based on the ALLSPD-3D code which uses the compressible formulation of the flow equations including real gas effects, nonequilibrium chemistry and spray combustion. To facilitate the analysis of complex geometries, the chimera grid method is utilized. To the best of our knowledge, this is the first application of the chimera scheme to reacting flows. In order to evaluate the effectiveness of this numerical approach, several benchmark calculations of subsonic flows are presented. These include steady and unsteady flows, and bluff-body stabilized spray and premixed combustion flames.

  15. Phe783, Thr797, and Asp804 in transmembrane hairpin M5-M6 of Na+,K+-ATPase play a key role in ouabain binding. (United States)

    Qiu, Li Yan; Koenderink, Jan B; Swarts, Herman G P; Willems, Peter H G M; De Pont, Jan Joep H H M


    Ouabain is a glycoside that binds to and inhibits the action of Na+,K+-ATPase. Little is known, however, about the specific requirements of the protein surface for glycoside binding. Using chimeras of gastric H+,K+-ATPase and Na+,K+-ATPase, we demonstrated previously that the combined presence of transmembrane hairpins M3-M4 and M5-M6 of Na+,K+-ATPase in a backbone of H+,K+-ATPase (HN34/56) is both required and sufficient for high affinity ouabain binding. Since replacement of transmembrane hairpin M3-M4 by the N terminus up to transmembrane segment 3 (HNN3/56) resulted in a low affinity ouabain binding, hairpin M5-M6 seems to be essential for ouabain binding. To assess which residues of M5-M6 are required for ouabain action, we divided this transmembrane hairpin in seven parts and individually replaced these parts by the corresponding sequences of H+,K+-ATPase in chimera HN34/56. Three of these chimeras failed to bind ouabain following expression in Xenopus laevis oocytes. Altogether, these three chimeras contained 7 amino acids that were specific for Na+,K+-ATPase. Individual replacement of these 7 amino acids by the corresponding amino acids in H+,K+-ATPase revealed a dramatic loss of ouabain binding for F783Y, T797C, and D804E. As a proof of principle, the Na+,K+-ATPase equivalents of these 3 amino acids were introduced in different combinations in chimera HN34. The presence of all 3 amino acids appeared to be required for ouabain action. Docking of ouabain onto a three-dimensional-model of Na+,K+-ATPase suggests that Asp804, in contrast to Phe783 and Thr797, does not actually form part of the ouabain-binding pocket. Most likely, the presence of this amino acid is required for adopting of the proper conformation for ouabain binding.

  16. Fluorocarbon assisted atomic layer etching of SiO{sub 2} and Si using cyclic Ar/C{sub 4}F{sub 8} and Ar/CHF{sub 3} plasma

    Energy Technology Data Exchange (ETDEWEB)

    Metzler, Dominik; Oehrlein, Gottlieb S., E-mail: [Department of Materials Science and Engineering, and Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20740 (United States); Li, Chen [Department of Physics, and Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20740 (United States); Engelmann, Sebastian; Bruce, Robert L.; Joseph, Eric A. [IBM T. J. Watson Research Center, Yorktown Heights, New York 10598 (United States)


    The need for atomic layer etching (ALE) is steadily increasing as smaller critical dimensions and pitches are required in device patterning. A flux-control based cyclic Ar/C{sub 4}F{sub 8} ALE based on steady-state Ar plasma in conjunction with periodic, precise C{sub 4}F{sub 8} injection and synchronized plasma-based low energy Ar{sup +} ion bombardment has been established for SiO{sub 2} [Metzler et al., J. Vac. Sci. Technol. A 32, 020603 (2014)]. In this work, the cyclic process is further characterized and extended to ALE of silicon under similar process conditions. The use of CHF{sub 3} as a precursor is examined and compared to C{sub 4}F{sub 8}. CHF{sub 3} is shown to enable selective SiO{sub 2}/Si etching using a fluorocarbon (FC) film build up. Other critical process parameters investigated are the FC film thickness deposited per cycle, the ion energy, and the etch step length. Etching behavior and mechanisms are studied using in situ real time ellipsometry and x-ray photoelectron spectroscopy. Silicon ALE shows less self-limitation than silicon oxide due to higher physical sputtering rates for the maximum ion energies used in this work, ranged from 20 to 30 eV. The surface chemistry is found to contain fluorinated silicon oxide during the etching of silicon. Plasma parameters during ALE are studied using a Langmuir probe and establish the impact of precursor addition on plasma properties.

  17. The 40Ar/39Ar and K/Ar dating of lavas from the Hilo 1-km core hole, Hawaii Scientific Drilling Project (United States)

    Sharp, W.D.; Turrin, B.D.; Renne, P.R.; Lanphere, M.A.


    Mauna Kea lava flows cored in the HilIo hole range in age from <200 ka to about 400 ka based on 40Ar/39Ar incremental heating and K-Ar analyses of 16 groundmass samples and one coexisting plagioclase. The lavas, all subaerially deposited, include a lower section consisting only of tholeiitic basalts and an upper section of interbedded alkalic, transitional tholeiitic, and tholeiitic basalts. The lower section has yielded predominantly complex, discordant 40Ar/39Ar age spectra that result from mobility of 40Ar and perhaps K, the presence of excess 40Ar, and redistribution of 39Ar by recoil. Comparison of K-Ar ages with 40Ar/39Ar integrated ages indicates that some of these samples have also lost 39Ar. Nevertheless, two plateau ages of 391 ?? 40 and 400 ?? 26 ka from deep in the hole, combined with data from the upper section, show that the tholeiitic section accumulated at an average rate of about 7 to 8 m/kyr and has an mean recurrence interval of 0.5 kyr/flow unit. Samples from the upper section yield relatively precise 40Ar/39Ar plateau and isotope correlation ages of 326 ?? 23, 241 ?? 5, 232 ?? 4, and 199 ?? 9 ka for depths of -415.7 m to -299.2 m. Within their uncertainty, these ages define a linear relationship with depth, with an average accumulation rate of 0.9 m/kyr and an average recurrence interval of 4.8 kyr/flow unit. The top of the Mauna Kea sequence at -280 m must be older than the plateau age of 132 ?? 32 ka, obtained for the basal Mauna Loa flow in the corehole. The upward decrease in lava accumulation rate is a consequence of the decreasing magma supply available to Mauna Kea as it rode the Pacific plate away from its magma source, the Hawaiian mantle plume. The age-depth relation in the core hole may be used to test and refine models that relate the growth of Mauna Kea to the thermal and compositional structure of the mantle plume.

  18. Microstructure and mechanical properties of TiC0.5 reinforced copper matrix composites

    International Nuclear Information System (INIS)

    Li, Mengqi; Zhai, Hongxiang; Huang, Zhenying; Liu, Xiaohan; Zhou, Yang; Li, Shibo; Li, Cuiwei


    Cu–Al alloy matrix composites containing in-situ TiC 0.5 particles were fabricated by sintering of a mixture of Cu and Ti 2 AlC powders at 1150 °C for 60 min in Ar atmosphere. The micron-sized Ti 2 AlC particles were decomposed into submicron TiC 0.5 grains during the sintering process, meanwhile, Al atoms entered into Cu to form Cu–Al alloy matrix. It was shown that the Cu–Al alloy matrix also consisted of ultrafine grains. Compression tests indicate TiC 0.5 particles can improve mechanical properties significantly, and the ductility maintains at a comparatively high level. The fracture strength of 40Ti 2 AlC/Cu sample reaches 1126 MPa with 12.8% fracture strain. The 20Ti 2 AlC/Cu and 30Ti 2 AlC/Cu samples keep undamaged even after the strain of 26.7%

  19. Small angle Ar2+ + Ar collisions

    International Nuclear Information System (INIS)

    Stevens, J.J.


    Electron capture in Ar 2+ + Ar is studied at low keV energies. Using Ar 2+ + He collisions as a calibration, it is shown that the dominant single electron capture process is endothermic and of the type Ar 2+ ( 3 P) + ArAr + ( 2 P) + Ar + (3s 2 3p 4 nI), with nI primarily being 3d and 4p. Weaker exothermic processes are also found and are due mainly to the existence of long-lived highly-excited states in the incident Ar 2+ beam. The direct scattering and double electron capture processes are also studied. Direct scattering occurs with no target excitation. Differential cross sections are presented for the collision processes. The single electron capture results are interpreted using a simple model in which a strongly attractive intermediate state couples with incident and outgoing channels

  20. Effects of liver depression and psychological stress on human uterine leiomyoma cells by an AR-cAMP-PKA signal transduction pathway. (United States)

    Xia, Tian; Li, Shuang; Ma, Ruihong; Guan, Sufen; Li, Jiacui; Li, Hongqin; Zhang, Hexin; Lin, Qiu; Zhao, Zhimei; Wang, Baojuan


    Based on the emotional theory of Traditional Chinese Medicine, and combined with the modern medicine theory of psychological stress, a research model of human uterine leiomyoma cells (ULM) was cultured in vitro to determine the effectiveness of adrenergic receptor (AR) agonists in human ULM cell growth. In addition, we studied the functional influence of "liver depression and psychological stress theory" on fibroid formation by intervening in the AR-cAMP-PKA signaling pathway. The intention was to establish a new method to prevent and cure fibroids through "liver depression and psychological stress theory" and provide an experimental basis for the Traditional Chinese Medicine emotional theory. Primary human ULM cells were enriched by collagenase digestion. Immunohistochemistry and hematoxylin and eosin (HE) staining were used for cytological identification. Using this model, we studied intervention using specific AR agonists on ULM cells to observe the influence of "liver depression and psychological stress theory" on estrogen receptor (ER), progesterone receptor (PR), vascular endothelial growth factor (VEGF) and fibroblast growth factors (FGF). Norepinephrine (NE) and epinephrine (E) are adrenergic receptor agonists. They promoted ULM cell proliferation and increased the levels of ER, PR, VEGF and FGF. In contrast, isoproterenol (ISO) inhibited ULM cell proliferation and decreased the levels of ER, PR, VEGF and FGF. The protein expression of cAMP and PKA in ULM cells was reduced and the levels of ER, PR, VEGF and FGF were increased when co-treatment with the α-AR blocker (phentolamine). The β-AR blocker (metoprolol) displayed an opposite effect. AR agonists modulated ER, PR, VEGF and FGF levels in ULM cells in an AR-cAMP-PKA-dependent signaling pathways to influence fibroid occurrence and development. Copyright © 2017. Published by Elsevier B.V.

  1. Deletion of the complement C5a receptor alleviates the severity of acute pneumococcal otitis media following influenza A virus infection in mice.

    Directory of Open Access Journals (Sweden)

    Hua Hua Tong

    Full Text Available There is considerable evidence that influenza A virus (IAV promotes adherence, colonization, and superinfection by S. pneumoniae (Spn and contributes to the pathogenesis of otitis media (OM. The complement system is a critical innate immune defense against both pathogens. To assess the role of the complement system in the host defense and the pathogenesis of acute pneumococcal OM following IAV infection, we employed a well-established transtympanically-induced mouse model of acute pneumococcal OM. We found that antecedent IAV infection enhanced the severity of acute pneumococcal OM. Mice deficient in complement C1qa (C1qa-/- or factor B (Bf -/- exhibited delayed viral and bacterial clearance from the middle ear and developed significant mucosal damage in the eustachian tube and middle ear. This indicates that both the classical and alternative complement pathways are critical for the oto-immune defense against acute pneumococcal OM following influenza infection. We also found that Spn increased complement activation following IAV infection. This was characterized by sustained increased levels of anaphylatoxins C3a and C5a in serum and middle ear lavage samples. In contrast, mice deficient in the complement C5a receptor (C5aR demonstrated enhanced bacterial clearance and reduced severity of OM. Our data support the concept that C5a-C5aR interactions play a significant role in the pathogenesis of acute pneumococcal OM following IAV infection. It is possible that targeting the C5a-C5aR axis might prove useful in attenuating acute pneumococcal OM in patients with influenza infection.

  2. Spectroscopic and electric dipole properties of Sr+Ar and SrAr systems including high excited states (United States)

    Hamdi, Rafika; Abdessalem, Kawther; Dardouri, Riadh; Al-Ghamdi, Attieh A.; Oujia, Brahim; Gadéa, Florent Xavier


    The spectroscopic properties of the fundamental and several excited states of Sr+Ar and SrAr, Van der Waals systems are investigated by employing an ab initio method in a pseudo-potential approach. The potential energy curves and the spectroscopic parameters are displayed for the 1-10 2Σ+, 1-6 2Π and 1-3 2Δ electronic states of the Sr+Ar molecule and for the 1-6 1Σ+, 1-4 3Σ+, 1-3 1,3Π and 1-3 1,3Δ states of the neutral molecule SrAr. In addition, from these curves, the vibrational levels and their energy spacing are deduced for Σ+, Π and Δ symmetries. The spectra of the permanent and transition dipole moments are studied for the 1,3Σ+ states of SrAr, which are considered to be two-electron systems and 2Σ+ states of the single electron Sr+Ar ion. The spectroscopic parameters obtained for each molecular system are compared with previous theoretical and experimental works. A significant correlation revealed the accuracy of our results.

  3. Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs

    Directory of Open Access Journals (Sweden)

    David Juan


    Full Text Available Summary: Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs. : 5-hydroxymethylcytosine (5hmC plays a key role in the epigenomic communication network of embryonic stem cells. Juan et al. build a communication network based in co-localization of epigenomic data and literature. The analysis of the network and its components reveals that proteins reading and editing 5hmC co-evolve and serve as links between diverse molecular processes.

  4. Analysis list: Ar [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Ar Gonad,Kidney,Prostate + mm9,,,http://dbarchive.bioscience

  5. Chimera states in multi-strain epidemic models with temporary immunity (United States)

    Bauer, Larissa; Bassett, Jason; Hövel, Philipp; Kyrychko, Yuliya N.; Blyuss, Konstantin B.


    We investigate a time-delayed epidemic model for multi-strain diseases with temporary immunity. In the absence of cross-immunity between strains, dynamics of each individual strain exhibit emergence and annihilation of limit cycles due to a Hopf bifurcation of the endemic equilibrium, and a saddle-node bifurcation of limit cycles depending on the time delay associated with duration of temporary immunity. Effects of all-to-all and non-local coupling topologies are systematically investigated by means of numerical simulations, and they suggest that cross-immunity is able to induce a diverse range of complex dynamical behaviors and synchronization patterns, including discrete traveling waves, solitary states, and amplitude chimeras. Interestingly, chimera states are observed for narrower cross-immunity kernels, which can have profound implications for understanding the dynamics of multi-strain diseases.

  6. Multi-dimensional simulations of core-collapse supernova explosions with CHIMERA (United States)

    Messer, O. E. B.; Harris, J. A.; Hix, W. R.; Lentz, E. J.; Bruenn, S. W.; Mezzacappa, A.


    Unraveling the core-collapse supernova (CCSN) mechanism is a problem that remains essentially unsolved despite more than four decades of effort. Spherically symmetric models with otherwise high physical fidelity generally fail to produce explosions, and it is widely accepted that CCSNe are inherently multi-dimensional. Progress in realistic modeling has occurred recently through the availability of petascale platforms and the increasing sophistication of supernova codes. We will discuss our most recent work on understanding neutrino-driven CCSN explosions employing multi-dimensional neutrino-radiation hydrodynamics simulations with the Chimera code. We discuss the inputs and resulting outputs from these simulations, the role of neutrino radiation transport, and the importance of multi-dimensional fluid flows in shaping the explosions. We also highlight the production of 48Ca in long-running Chimera simulations.

  7. Jahn-Teller effect in van der Waals complexes; Ar-C6H6 + and Ar-C6D6 +.

    NARCIS (Netherlands)

    Avoird, A. van der; Lotrich, VF


    The two asymptotically degenerate potential energy surfaces of argon interacting with the X (2)E(1g) ground state benzene(+) cation were calculated ab initio from the interaction energy of the neutral Ar-benzene complex given by Koch et al. [J. Chem. Phys. 111, 198 (1999)] and the difference of the

  8. Electronic-state distribution of Ar* produced from Ar+(2P3/2)/2e- collisional radiative recombination in an argon flowing afterglow

    International Nuclear Information System (INIS)

    Tsuji, Masaharu; Matsuzaki, Toshinori; Tsuji, Takeshi


    The Ar + /2e - collisional radiative recombination has been studied by observing UV and visible emissions of Ar* in an Ar flowing afterglow. In order to clarify recombination mechanism, the Ar + ( 2 P 3/2 ) spin-orbit component was selected by using a filter gas of the Ar + ( 2 P 1/2 ) component. Spectral analysis indicated that 34 Ar*(4p, 4d, 5p, 5d, 6s, 6p, 6d, 4p ' , 4d ' , 5p ' , 5d ' , 6s ' ) states in the 13.08-15.33 eV range are produced. The electronic-state distribution decreased with an increase in the excitation energy of Ar*, which was expressed by a Boltzmann electronic temperature of 0.54 eV. The formation ratios of the 4p: 4d + 5p + 5d + 6s + 6p + 6d: 4p ' : 4d ' + 5p ' + 5d ' + 6s ' states were 43%, 2.8%, 54%, and 0.31%, respectively. The high formation ratio of the 4p ' state having an Ar + ( 2 P 1/2 ) ion core in the Ar + ( 2 P 3/2 )/2e - recombination indicated that such a two-electron process as an electron transfer to an inner 3p orbital followed by excitation of a 3p electron to an outer 4p orbital occurs significantly. The higher formation ratios of 4d + 5p + 5d + 6s + 6p + 6d than those of 4d ' + 5p ' + 5d ' + 6s ' led us to conclude the formation of these upper states dominantly proceeds through one electron transfer to an outer nl orbital of Ar + ( 2 P 3/2 )

  9. Construction of an Aptamer-SiRNA Chimera-Modified Tissue-Engineered Blood Vessel for Cell-Type-Specific Capture and Delivery. (United States)

    Chen, Wen; Zeng, Wen; Sun, Jiansen; Yang, Mingcan; Li, Li; Zhou, Jingting; Wu, Yangxiao; Sun, Jun; Liu, Ge; Tang, Rui; Tan, Ju; Zhu, Chuhong


    The application of tissue-engineered blood vessels (TEBVs) is the main developmental direction of vascular replacement therapy. Due to few and/or dysfunctional endothelial progenitor cells (EPCs), it is difficult to successfully construct EPC capture TEBVs in diabetes. RNA has a potential application in cell protection and diabetes treatment, but poor specificity and low efficiency of RNA transfection in vivo limit the application of RNA. On the basis of an acellular vascular matrix, we propose an aptamer-siRNA chimera-modified TEBV that can maintain a satisfactory patency in diabetes. This TEBV consists of two parts, CD133-adenosine kinase (ADK) chimeras and a TEBV scaffold. Our results showed that CD133-ADK chimeras could selectively capture the CD133-positive cells in vivo, and then captured cells can internalize the bound chimeras to achieve RNA self-transfection. Subsequently, CD133-ADK chimeras were cut into ADK siRNA by a dicer, resulting in depletion of ADK. An ADK-deficient cell may act as a bioreactor that sustainably releases adenosine. To reduce nonspecific RNA transfection, we increased the proportion of HAuCl4 during the material preparation, through which the transfection capacity of polyethylenimine (PEI)/polyethylene glycol (PEG)-capped gold nanoparticles (PEI/PEG-AuNPs) was significantly decreased and the ability of TEBV to resist tensile and liquid shear stress was greatly enhanced. PEG and 2'-O-methyl modification was used to enhance the in vivo stability of RNA chimeras. At day 30 postgrafting, the patency rate of CD133-ADK chimera-modified TEBVs reached 90% in diabetic rats and good endothelialization was observed.

  10. Bovine and human lactoferricin peptides: chimeras and new cyclic analogs. (United States)

    Arias, Mauricio; McDonald, Lindsey J; Haney, Evan F; Nazmi, Kamran; Bolscher, Jan G M; Vogel, Hans J


    Lactoferrin (LF) is an important antimicrobial and immune regulatory protein present in neutrophils and most exocrine secretions of mammals. The antimicrobial activity of LF has been related to the presence of an antimicrobial peptide sequence, called lactoferricin (LFcin), located in the N-terminal region of the protein. The antimicrobial activity of bovine LFcin is considerably stronger than the human version. In this work, chimera peptides combining segments of bovine and human LFcin were generated in order to study their antimicrobial activity and mechanism of action. In addition, the relevance of the conserved disulfide bridge and the resulting cyclic structure of both LFcins were analyzed by using "click chemistry" and sortase A-catalyzed cyclization of the peptides. The N-terminal region of bovine LFcin (residues 17-25 of bovine LF) proved to be very important for the antimicrobial activity of the chimera peptides against E. coli, when combined with the C-terminal region of human LFcin. Similarly the cyclic bovine LFcin analogs generated by "click chemistry" and sortase A preserved the antimicrobial activity of the original peptide, showing the significance of these two techniques in the design of cyclic antimicrobial peptides. The mechanism of action of bovine LFcin and its active derived peptides was strongly correlated with membrane leakage in E. coli and up to some extent with the ability to induce vesicle aggregation. This mechanism was also preserved under conditions of high ionic strength (150 mM NaCl) illustrating the importance of these peptides in a more physiologically relevant system.

  11. In silico Analysis and Experimental Validation of Lignan Extracts from Kadsura longipedunculata for Potential 5-HT1AR Agonists.

    Directory of Open Access Journals (Sweden)

    Yaxin Zheng

    Full Text Available Kadsura longipedunculata (KL has been widely used for the treatment of insomnia in traditional Chinese medicine. The aim of this study was to explore the mechanism of the sedative and hypnotic effects of KL.The content of KL was evaluated by HPLC-TOF-MS, and a potential target was found and used to construct its 3D structure to screen for potential ligands among the compounds in KL by using bioinformatics analysis, including similarity ensemble approach (SEA docking, homology modeling, molecular docking and ligand-based pharmacophore. The PCPA-induced insomnia rat model was then applied to confirm the potential targets related to the sedative effects of KL by performing the forced swimming test (FST, the tail suspension test (TST and the measurement of target-related proteins using western blotting and immunofluorescence.Bioinformatics analysis showed that most of lignan compounds in KL were optimal ligands for the 5-HT1A receptor (5-HT1AR, and they were found to be potential targets related to sedative effects; the main lignan content of KL extracts was characterized by HPLC-TOF-MS, with 7 proposed lignans detected. Administration of KL could significantly reduce FST and TST immobility time in the PCPA-induced 5HT-depleted insomnia rat model. The expressions of proteins related to the 5-HT1AR pathway were regulated by extracts of KL in a concentration-dependent manner, indicating that extracts of KL had 5-HT1AR agonist-like effects.In silico analysis and experimental validation together demonstrated that lignan extracts from KL can target 5-HT1AR in insomniac rats, which could shed light on its use as a potential 5-HT1AR agonist drug.

  12. Formation of germline chimera Gaok chicken used circulation primordial germ cells (circulation PGCs fresh and thawed

    Directory of Open Access Journals (Sweden)

    Kostaman T


    Full Text Available Formation of germline chimeras by transfer of chicken primordial germ cells (PGCs is one of the effective techniques for preservation and regeneration of genetic resources in chickens. This study attempted to form germline chimeras of Gaok chicken buy purifying circulated PGCs of donor embryo before it is transferred to the recipient (White Leghorn chickens=WL and studied the ability of recipient embryo on survival in incubators, and hatchability. This study used 200 fertile eggs of Gaok and 90 fertile WL breed all of the eggs was incubated at 380C and 60% humidity in a portable incubator. PGCs-circulation of the blood collected Gaok embryos at stage 14-16 were taken from the dorsal aorta, and then purified by centrifugation method using nycodenz. PGCs-circulation results further purification frozen in liquid nitrogen before being transferred to the recipient embryo. The results showed that for the development of embryos transferred to the fresh circulation of PGCs-circulation as many as 25 cells can survive up to day 14, while one of the transferred of 50 and 100 cells into recipient embryos was hatched (10%. On the contrari recipient embryos that are transferred to the frozen PGCs-circulation the embryos development was shorter, and only survived until day 10th (treatment 25 cells, day 14th (treatment of 50 cells and day 17th (treatment of 100 cells. It is concluded that the amount of PGCs-circulation embryos transferred to the recipient is one factor that influence the success of the development germline chimeras.

  13. Radiobiological researches on Dianthus caryophyllus L. carnation chimeras

    International Nuclear Information System (INIS)

    Pereau-Leroy, Pierre


    This research thesis reports a radiobiological study of Dianthus periclinal chimeras performed by submitting plants and plant cuttings at different physiological stages to cobalt-60 gamma irradiation under different dose conditions and rates. The effects of these treatments are studied while growing the so-processed plants and by microscopic examination of sections of irradiated meristems [fr

  14. Comparison of male chimeric mice generated from microinjection of JM8.N4 embryonic stem cells into C57BL/6J and C57BL/6NTac blastocysts. (United States)

    Fielder, Thomas J; Yi, Charles S; Masumi, Juliet; Waymire, Katrina G; Chen, Hsiao-Wen; Wang, Shuling; Shi, Kai-Xuan; Wallace, Douglas C; MacGregor, Grant R


    To identify ways to improve the efficiency of generating chimeric mice via microinjection of blastocysts with ES cells, we compared production and performance of ES-cell derived chimeric mice using blastocysts from two closely related and commonly used sub-strains of C57BL/6. Chimeras were produced by injection of the same JM8.N4 (C57BL/6NTac) derived ES cell line into blastocysts of mixed sex from either C57BL/6J (B6J) or C57BL/6NTac (B6NTac) mice. Similar efficiency of production and sex-conversion of chimeric animals was observed with each strain of blastocyst. However, B6J chimeric males had fewer developmental abnormalities involving urogenital and reproductive tissues (1/12, 8%) compared with B6NTac chimeric males (7/9, 78%). The low sample size did not permit determination of statistical significance for many parameters. However, in each category analyzed the B6J-derived chimeric males performed as well, or better, than their B6NTac counterparts. Twelve of 14 (86%) B6J male chimeras were fertile compared with 6 of 11 (55%) B6NTac male chimeras. Ten of 12 (83%) B6J chimeric males sired more than 1 litter compared with only 3 of 6 (50%) B6NTac chimeras. B6J male chimeras produced more litters per productive mating (3.42 ± 1.73, n = 12) compared to B6NTac chimeras (2.17 ± 1.33, n = 6). Finally, a greater ratio of germline transmitting chimeric males was obtained using B6J blastocysts (9/14; 64%) compared with chimeras produced using B6NTac blastocysts (4/11; 36%). Use of B6J host blastocysts for microinjection of ES cells may offer improvements over blastocysts from B6NTac and possibly other sub-strains of C57BL/6 mice.

  15. 40Ar/36Ar in MORB glasses: Constraints on atmosphere and mantle evolution

    International Nuclear Information System (INIS)

    Sarda, P.; Staudacher, T.; Allegre, C.J.; Paris-7 Univ., 75


    Argon isotopic composition measurements of MORB glassy samples from the Pacific, Atlantic and Indian Oceans are performed. There is a very large scatter in the 40 Ar/ 36 Ar ratio, from 980 up to 24,400 for bulk rock analyses, which is mainly due to atmospheric contamination: Using the stepwise heating technique, very high ratios are obtained, from 15,000 up to 25,250 which is the highest 40 Ar/ 36 Ar ratio ever measured in MORB. We establish a negative correlation between the highest 40 Ar/ 36 Ar results from stepwise heating and 87 Sr/ 86 Sr ratios, which is perfectly consistent with a two-layered mantle structure. From both 40 Ar and 129 Xe MORB systematics a model is proposed for the kinetics of degassing: a very early and extensive burst, with a time constant of approx.= 4 My, is followed by a slower process of present day type, with a time constant of approx.= 0.5 Gy. The mean age of the atmosphere is so determined to be around 4.4 Gy. (orig./WB)

  16. Purification and characterization of Yersinia enterocolitica and Yersinia pestis LcrV-cholera toxin A(2)/B chimeras. (United States)

    Tinker, Juliette K; Davis, Chadwick T; Arlian, Britni M


    Yersinia pestis is a virulent human pathogen and potential biological weapon. Despite a long history of research on this organism, there is no licensed vaccine to protect against pneumonic forms of Y. pestis disease. In the present study, plasmids were constructed to express cholera toxin A(2)/B chimeric molecules containing the LcrV protective antigen from Yersinia enterocolitica and Y. pestis. These chimeras were expressed and purified to high yields from the supernatant of transformed Escherichia coli. Western and GM(1) ELISA assays were used to characterize the composition, receptor-binding and relative stability of the LcrV-CTA(2)/B chimera in comparison to cholera toxin. In addition, we investigated the ability of the Y. pestis LcrV-CTA(2)/B chimera to bind to and internalize into cultured epithelial cells and macrophages by confocal microscopy. These studies indicate that the uptake and trafficking of the LcrV antigen from the chimera is comparable to the trafficking of native toxin. Together these findings report that stable, receptor-binding, non-toxic LcrV-cholera toxin A(2)/B chimeras can be expressed at high levels in E. coli and purified from the supernatant. In addition, the internalization of antigen in vitro reported here supports the development of these molecules as novel mucosal vaccine candidates. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Sequential analysis of the virus-immune responder characteristics of thymocytes from F1→parent radiation chimeras

    International Nuclear Information System (INIS)

    Korngold, R.; Doherty, P.C.


    The virus-immune responder characteristics of thymocytes, spleen and lymph node (LN) cells from (P 1 x P 2 )F 1 →P 1 radiation chimeras have been examined sequentially at weekly intervals. Adoptively-transferred thymocytes generate strong cytotoxic thymus-derived lymphocyte (CTL) responses from 28 to 100 days after reconstitution with bone marrow, which are almost invariably restricted to recognition of virus presented in the context of P 1 . This pattern of H-2 restriction is also maintained for spleen and LN cells from the [(H-2sup(kxd)F 1 →H-2sup(k)] and [(H-2sup(kxb)F 1 →H-2sup(k)] combinations but there is random emergence of reactivity to H-2sup(k)+virus for peripheral lymphoid cells from [(H-2sup(kxb)F 1 →H-2sup(b)] chimeras. Treatment of established [(P 1 xP 2 )]F 1 →P 1 ] chimeras with a low dose of cyclophosphamide (Cy) did not lead to the emergence of significant CTL effector function for P2 + virus. Also, administration of a large dose of Cy prior to irradiation of the chimera recipients did not modify the H-2 restriction profile of the chimera, though the level of CTL responsiveness associated with the appropriate H-2 type was apparently enhanced. (Auth.)

  18. 40Ar/39Ar geochronology and volume estimates of the Tasmantid Seamounts: Support for a change in the motion of the Australian plate (United States)

    Crossingham, Tracey J.; Vasconcelos, Paulo M.; Cunningham, Toby; Knesel, Kurt M.


    New volume estimates and 40Ar/39Ar ages for the Tasmantid Seamounts are reported to investigate the origin of volcanism and potential links between volcanism and changes in the speed and direction of migration of the Australian plate during the Cenozoic. The results show that the average extrusive volume of individual volcanoes along the seamount chain is 2587 ± 3078 km3 (1 s), and that volumes generally increase towards the south. An exception, the Britannia Guyot, located in the middle of the seamount chain, is the most voluminous (11,374 km3). Nineteen new 40Ar/39Ar ages, from Wreck to Gascoyne, show that the emplacement of the Tasmantid Seamounts occurred between 33.2 ± 1.5 and 6.5 ± 0.6 Ma. A single linear regression applied to the age versus latitude data, assuming volcanism to be caused by plate migration over a stationary hotspot, reveals a plate migration rate of 62 ± 2 kmMa- 1 (R2 = 0.97; n = 27) between 33 and 6 Ma. However, the bend in the seamount track, corresponding with the period of largest eruptive volumes, suggests three distinct segments in the Tasmantid age versus latitude data. The northern segment is consistent with a plate migration rate of 75 ± 10 kmMa- 1 (R2 = 0.88; n = 10) and the southern segment reveals a plate migration rate of 64 ± 4 kmMa- 1 (R2 = 0.94; n = 17). The period between these two segments, from 25 to 19 Ma, overlaps with the period of slow migration and change in the direction of the Australian plate derived from the age versus latitude distribution of continental central volcanoes. The new Tasmantid Seamount results support the interpretation that there were changes in the velocity and direction to Australia's northward trajectory, possibly resulting from a series of collisional events.

  19. Chemical changes in titanate surfaces induced by Ar+ ion bombardment

    International Nuclear Information System (INIS)

    Gonzalez-Elipe, A.R.; Fernandez, A.; Espinos, J.P.; Munuera, G.; Sanz, J.M.


    The reduction effects and compositional changes induced by 3.5 keV Ar + bombardment of several titanates (i.e. SrTiO 3 , Al 2 TiO 5 and NiTiO 3 ) have been quantitatively investigated by XPS. In all the samples studied here the original Ti 4+ species were reduced to lower oxidation states (i.e. Ti 3+ and Ti 2+ ), although to a lesser extent than in pure TiO 2 . On the contrary, whereas Sr 2+ and Al 3+ seem to remain unaffected by Ar + bombardment, in agreement with the behaviour of the respective oxides (i.e. SrO and Al 2 O 3 ), Ni 2+ appears more easily reducible to Ni o in NiTiO 3 than in NiO. In addition, other specific differences were observed between the titanates, which reveal the existence of interesting chemical effects related to the presence of the different counter-ions in the titanates. In the case of Al 2 TiO 5 , its Ar + -induced decomposition to form TiO 2 + Al 2 O 3 could be followed by XPS. (Author)

  20. Germline competence of mouse ES and iPS cell lines: Chimera technologies and genetic background. (United States)

    Carstea, Ana Claudia; Pirity, Melinda K; Dinnyes, Andras


    In mice, gene targeting by homologous recombination continues to play an essential role in the understanding of functional genomics. This strategy allows precise location of the site of transgene integration and is most commonly used to ablate gene expression ("knock-out"), or to introduce mutant or modified alleles at the locus of interest ("knock-in"). The efficacy of producing live, transgenic mice challenges our understanding of this complex process, and of the factors which influence germline competence of embryonic stem cell lines. Increasingly, evidence indicates that culture conditions and in vitro manipulation can affect the germline-competence of Embryonic Stem cell (ES cell) lines by accumulation of chromosome abnormalities and/or epigenetic alterations of the ES cell genome. The effectiveness of ES cell derivation is greatly strain-dependent and it may also influence the germline transmission capability. Recent technical improvements in the production of germline chimeras have been focused on means of generating ES cells lines with a higher germline potential. There are a number of options for generating chimeras from ES cells (ES chimera mice); however, each method has its advantages and disadvantages. Recent developments in induced pluripotent stem (iPS) cell technology have opened new avenues for generation of animals from genetically modified somatic cells by means of chimera technologies. The aim of this review is to give a brief account of how the factors mentioned above are influencing the germline transmission capacity and the developmental potential of mouse pluripotent stem cell lines. The most recent methods for generating specifically ES and iPS chimera mice, including the advantages and disadvantages of each method are also discussed.

  1. Vector analyzing power and cross section for the reactions 40Ar(d(pol),p)41Ar and 40Ar(d(pol),t)39Ar

    International Nuclear Information System (INIS)

    Sen, S.; Darden, S.E.; Yoh, W.A.; Berners, E.D.


    Angular distributions of vector analyzing power and cross section for the reactions 40 Ar(d,p) 41 Ar and 40 Ar(d,t) 39 Ar have been measured at an incident deuteron energy of 14.83 MeV. The bound-state data in the (d,p) reaction and the (d,t) data are compared to DWBA calculations. The data for the neutron-unbound states are analyzed in the framework of the DWBA using (i) a form factor for weakly bound neutron and (ii) a resonance form factor, following the approach of Vincent and Fortune. The j-dependence of the (d,p) vector analyzing power permits definite spin-parity assignments to be made for 19 neutron-bound and 4 neutron unbound states in 41 Ar with excitation energy up to 6.57 MeV. Tentative Jsup(π) assignments have been made for 3 states. The l-value for the 5.62 MeV states has been determined. Data for the observed unbound states are found to be equally well reproduced by the type (i) calculations as by the type (ii) calculations. The (d,t) vector cnalyzing power data show definite J-dependence although not as strongly as in the (d,p) reaction. For relatively weakly excited states a pre-knowledge of the l-value of the transition is desirable for an unambiguous spin assignment. In general, the J-dependence in the (d,t) vector analyzing power can be utilized for definitive Jsup(π) assignments. On this basis, Jsub(π) values have been assigned for seven states in 39 Ar with excitation energies up to 4.47MeV excitation. Possible spin values for three other states are suggested. Spectroscopic factors fo the states in 41 Ar and 39 Ar have been extracted and are in fair agreement with those obtained by other workers. (Auth.)

  2. Chaos in Dirac Electron Optics: Emergence of a Relativistic Quantum Chimera. (United States)

    Xu, Hong-Ya; Wang, Guang-Lei; Huang, Liang; Lai, Ying-Cheng


    We uncover a remarkable quantum scattering phenomenon in two-dimensional Dirac material systems where the manifestations of both classically integrable and chaotic dynamics emerge simultaneously and are electrically controllable. The distinct relativistic quantum fingerprints associated with different electron spin states are due to a physical mechanism analogous to a chiroptical effect in the presence of degeneracy breaking. The phenomenon mimics a chimera state in classical complex dynamical systems but here in a relativistic quantum setting-henceforth the term "Dirac quantum chimera," associated with which are physical phenomena with potentially significant applications such as enhancement of spin polarization, unusual coexisting quasibound states for distinct spin configurations, and spin selective caustics. Experimental observations of these phenomena are possible through, e.g., optical realizations of ballistic Dirac fermion systems.

  3. Chaos in Dirac Electron Optics: Emergence of a Relativistic Quantum Chimera (United States)

    Xu, Hong-Ya; Wang, Guang-Lei; Huang, Liang; Lai, Ying-Cheng


    We uncover a remarkable quantum scattering phenomenon in two-dimensional Dirac material systems where the manifestations of both classically integrable and chaotic dynamics emerge simultaneously and are electrically controllable. The distinct relativistic quantum fingerprints associated with different electron spin states are due to a physical mechanism analogous to a chiroptical effect in the presence of degeneracy breaking. The phenomenon mimics a chimera state in classical complex dynamical systems but here in a relativistic quantum setting—henceforth the term "Dirac quantum chimera," associated with which are physical phenomena with potentially significant applications such as enhancement of spin polarization, unusual coexisting quasibound states for distinct spin configurations, and spin selective caustics. Experimental observations of these phenomena are possible through, e.g., optical realizations of ballistic Dirac fermion systems.

  4. Enhancement of sp3 hybridized C in amorphous carbon films by Ar ion bombardment and Si incorporation

    International Nuclear Information System (INIS)

    Jung, Hae-Suk; Park, Hyung-Ho; Mendieta, I.R.; Smith, D.A.


    We report an effective method of increasing the sp 3 hybridization fraction in sputtered amorphous carbon (a-C) film by the combination of Ar ion bombardment and Si incorporation. In the deposition of an a-C film, Ar ion bombardment by controlling the applied bias voltage plays a role in creating high stress in film and causes the local bonding configuration to change to a sp 3 hybridized bond. Simultaneously, the incorporated Si in an a-C network breaks the sp 2 hybridized bonded ring and promotes the formation of a sp 3 hybridized bond. This enhancement of the sp 3 hybridized bonding characteristic is maximized for an a-C film with 23 at. % of Si and 100-150 V of applied bias voltage. In this region, the increase of resistivity, optical band gap, and mechanical hardness of a-C is attributed to the reduction of the sp 2 hybridized bonded ring and increased fraction of the sp 3 hybridized bond. However, at a higher bias voltage above 150 V, the enhancement effect is reduced due to the resputtering and thermally activated reconversion of a sp 3 to a sp 2 hybridized bond

  5. Book Review: Evolution's Chimera: Bats and the Marvel of ...

    African Journals Online (AJOL)

    Abstract. Book Title: Evolution's Chimera: Bats and the Marvel of Evolutionary Adaptation. Book Author: David Jacobs. 2016, University of Cape Town Press, Juta and Company (Pty) Ltd, PO Box 14373, Lansdowne 7779, Cape Town, South Africa Softcover, 204 pages. ISBN 978-1-77582-212-7. Price R299 ...

  6. Use of fragmentation beams at LNS with CHIMERA detector

    Directory of Open Access Journals (Sweden)

    Gianí R.


    Full Text Available The recent intensity upgrade of the LNS fragmentation beam is discussed. The available beams, the tagging procedures and details on the beam quality are reported. The experimental program started with the CHIMERA detector using such beams is also discussed with preliminary results and future perspectives.

  7. Identification of thermotectonics events by 40Ar/39Ar methodology, in Jauru, Pontes e Lacerda and Rio Alegre Terrane - southwest portion of Amazon Craton

    International Nuclear Information System (INIS)

    Paulo, Valeria Guimaraes de


    The southwest portion of Amazon Craton, subject of these work, correspond to the southwest region of Mato Grosso State and is inserted on Rio Negro-Juruena, Rondoniana-San Ignacio and Sunsas-Aguapei geochronologic Provinces. This region is surrounded by three big terranes: Jauru, Pontes e Lacerda and Rio Alegre. The main aim of this study is to use the ages of termochronologic events obtained by 40 Ar/ 39 Ar methodology, including data of literature, to contribute with the study of the geotectonic evolution on this region. Twenty samples were analyzed and 40 Ar/ 39 Ar ages found for the Jauru Terrane vary of 1539 ± 3 Ma to 1338 ± 3 Ma, for the Pontes e Lacerda Terrane the interval obtained was of 946,1 ± 0,8 Ma to 890 ± 2 Ma and for Rio Alegre Terrane the ages are between 1407 ± 3 Ma to 1321 ± 2 Ma. U/Pb, Rb/Sr and Sm/Nd data from previous works, together with 40 Ar/ 39 Ar results allowed to obtain cooling average rates to each terrane. The Jauru Terrane units cooling age is equivalent to 1,52 Ga. The cooling average rates found to Alto Jauru Greenstone belt rocks is 2,4 deg C - 1,0 Ma and to Magmatic Arc Cachoeirinha is 10,8 deg C - 1,0 Ma. Stabilization age obtained for Pontes and Lacerda Terrane is about 900 Ma coherent with the cooling age of the Sunsas Aguapei Event (1,0 - 0,9 Ga) and cooling average rates calculate were the lower, equivalent to 1,0 deg C - 1,0 Ma. Cooling age found in Rio Alegre Terrane was 1,35 Ga, possibility correspond to collision age these terrane with Amazonian protoCraton and cooling average rates of 5,0 deg C - 1,0 Ma. Finally, younger age found of 900 Ma, coherent to the Sunsas - Aguapei Event, probably represent the last regional event that affected these rocks, characterizing the stabilization period of the southwest portion of Amazon Craton. (author)

  8. Chimeras Reveal a Single Lipid-Interface Residue that Controls MscL Channel Kinetics as well as Mechanosensitivity

    Directory of Open Access Journals (Sweden)

    Li-Min Yang


    Full Text Available MscL, the highly conserved bacterial mechanosensitive channel of large conductance, serves as an osmotic “emergency release valve,” is among the best-studied mechanosensors, and is a paradigm of how a channel senses and responds to membrane tension. Although all homologs tested thus far encode channel activity, many show functional differences. We tested Escherichia coli and Staphylococcus aureus chimeras and found that the periplasmic region of the protein, particularly E. coli I49 and the equivalent S. aureus F47 at the periplasmic lipid-aqueous interface of the first transmembrane domain, drastically influences both the open dwell time and the threshold of channel opening. One mutant shows a severe hysteresis, confirming the importance of this residue in determining the energy barriers for channel gating. We propose that this site acts similarly to a spring for a clasp knife, adjusting the resistance for obtaining and stabilizing an open or closed channel structure.

  9. Liquid phase interaction in TiC0,5N0,5-TiNi-Mo and TiC0,5N0,5-TiNi-Ti-Mo

    International Nuclear Information System (INIS)

    Askarova, L.Kh; Grigorov, I.G.; Zajnulin, Yu.G.


    Using the methods of X ray diffraction analysis, electron microscopy and X ray spectrum microanalysis a study was made into specific features of phase and structure formation in alloys TiC 0,5 N 0,5 -TiNi-Mo and TiC 0,5 N 0,5 -TiNi-Mo in the presence of a liquid phase at temperatures of 1380-1600 deg C. It is revealed that the physical and chemical processes taking place during the liquid-phase sintering result in the formation of a three-phase alloy consisting of nonstoichiometric titanium carbonitride TiC 0.5-x N 0.5-x , a molybdenum base solid solution of titanium, nickel and carbon Mo(Ti, Ni, C) and one of two intermetallic compounds, either TiNi or Ni 3 Ti. Metallic element concentration in individual phase constituents of the alloy is determined by means of X ray spectrum microanalysis

  10. The celecoxib derivatives AR-12 and AR-14 induce autophagy and clear prion-infected cells from prions. (United States)

    Abdulrahman, Basant A; Abdelaziz, Dalia; Thapa, Simrika; Lu, Li; Jain, Shubha; Gilch, Sabine; Proniuk, Stefan; Zukiwski, Alexander; Schatzl, Hermann M


    Prion diseases are fatal infectious neurodegenerative disorders that affect both humans and animals. The autocatalytic conversion of the cellular prion protein (PrP C ) into the pathologic isoform PrP Sc is a key feature in prion pathogenesis. AR-12 is an IND-approved derivative of celecoxib that demonstrated preclinical activity against several microbial diseases. Recently, AR-12 has been shown to facilitate clearance of misfolded proteins. The latter proposes AR-12 to be a potential therapeutic agent for neurodegenerative disorders. In this study, we investigated the role of AR-12 and its derivatives in controlling prion infection. We tested AR-12 in prion infected neuronal and non-neuronal cell lines. Immunoblotting and confocal microscopy results showed that AR-12 and its analogue AR-14 reduced PrP Sc levels after only 72 hours of treatment. Furthermore, infected cells were cured of PrP Sc after exposure of AR-12 or AR-14 for only two weeks. We partially attribute the influence of the AR compounds on prion propagation to autophagy stimulation, in line with our previous findings that drug-induced stimulation of autophagy has anti-prion effects in vitro and in vivo. Taken together, this study demonstrates that AR-12 and the AR-14 analogue are potential new therapeutic agents for prion diseases and possibly protein misfolding disorders involving prion-like mechanisms.

  11. Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

    International Nuclear Information System (INIS)

    Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.


    Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

  12. Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Morecki, S.; Weigensberg, M.; Bar, S.; Weiss, L.


    Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones

  13. Using quantitative real-time PCR to detect chimeras in transgenic tobacco and apricot and to monitor their dissociation

    Directory of Open Access Journals (Sweden)

    Burgos Lorenzo


    Full Text Available Abstract Background The routine generation of transgenic plants involves analysis of transgene integration into the host genome by means of Southern blotting. However, this technique cannot distinguish between uniformly transformed tissues and the presence of a mixture of transgenic and non-transgenic cells in the same tissue. On the other hand, the use of reporter genes often fails to accurately detect chimerical tissues because their expression can be affected by several factors, including gene silencing and plant development. So, new approaches based on the quantification of the amount of the transgene are needed urgently. Results We show here that chimeras are a very frequent phenomenon observed after regenerating transgenic plants. Spatial and temporal analyses of transformed tobacco and apricot plants with a quantitative, real-time PCR amplification of the neomycin phosphotransferase (nptII transgene as well as of an internal control (β-actin, used to normalise the amount of target DNA at each reaction, allowed detection of chimeras at unexpected rates. The amount of the nptII transgene differed greatly along with the sub-cultivation period of these plants and was dependent on the localisation of the analysed leaves; being higher in roots and basal leaves, while in the apical leaves it remained at lower levels. These data demonstrate that, unlike the use of the gus marker gene, real-time PCR is a powerful tool for detection of chimeras. Although some authors have proposed a consistent, positive Southern analysis as an alternative methodology for monitoring the dissociation of chimeras, our data show that it does not provide enough proof of uniform transformation. In this work, however, real-time PCR was applied successfully to monitor the dissociation of chimeras in tobacco plants and apricot callus. Conclusions We have developed a rapid and reliable method to detect and estimate the level of chimeras in transgenic tobacco and apricot

  14. Gas separation techniques with liquid Ar for production of 11C ions

    International Nuclear Information System (INIS)

    Hojo, Satoru; Honma, Toshihiro; Kanazawa, Mitsutaka; Muramatsu, Masayuki; Sakamoto, Yukio; Sugiura, Akinori; Suzuki, Naokata; Noda, Koji


    Heavy-ion cancer therapy with 12 C-beam has been carried out at HIMAC (Heavy Ion Medical Accelerator in Chiba) in NIRS (National Institute of Radiological Sciences) since 1994. One of the feasibility study in HIMAC is to use a positron emitter beam such as 11 C-beam for the cancer therapy. A nuclear reaction, 14 N (p,α) 11 C will be applied in the present study; it can be expected to obtain a considerably large number of 11 C-particles by utilizing the commonly used short-lives RI production techniques for PET (Positron Emission Tomography). The amount of 11 C gas is limited in this technique. The 11 CO 2 gas was produced from N 2 gas that is irradiated high-energy proton beam. Therefore, CO 2 gas separation from N 2 gas is very important. The gas-separation techniques with cryogenic system utilizing a liquid Ar were tested by dummy gas (N 2 + 12 CO 2 ). Details of the gas-separation techniques and measurement of CO 2 partial pressure are discussed. (author)

  15. Spectroanalytical investigations on inductively coupled N2/Ar and Ar/Ar high frequency plasmas

    International Nuclear Information System (INIS)

    Malinowski, P.; Mazurkiewicz, M.; Nickel, H.


    In order to improve the detection limits of trace elements in corrosion products of metallic materials, the inductively coupled plasma excitation source (ICP) was applied for spectroscopic analysis. Besides optimizing the working conditions for the mentioned materials, the fundamental research clearing the excitation processes in ICP was carried out. Basicly, two plasma systems were investigated: the nitrogen cooled N 2 /Ar- and pure Ar/Ar-plasma. The computed detection limits for 8 chosen elements are between 0.1 and 50 μg ml -1 in both plasmas. The advantage of ion lines was clearly present; in N 2 /Ar-plasma it was larger than in Ar/Ar-plasma. The excitation temperatures measured with help of ArI, FeI and ZnI lines rise with increasing power and decreasing distance from the induction coil. The distribution of Zn excitation temperature in N 2 /Ar-plasma as well as the measured N + 2 rotational and CN vibrational temperatures indicate, that the toroidal structure of Ar/Ar-plasma is not analogue to the N 2 /Ar-plasma. The values of the various excitation temperatures (Ar, Fe, Zn) and the differences between the excitation, vibration, rotation and ionization temperatures (Tsub(i) > Tsub(n) = Tsub(vib) > Tsub(rot)) indicate an absence of thermal equilibrium in the concerned system. (orig.)

  16. Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses. (United States)

    Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald


    Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Effects of antibiotic resistance (AR) and microbiota shifts on Campylobacter jejuni-mediated diseases. (United States)

    Brooks, Phillip T; Mansfield, Linda S


    Campylobacter jejuni is an important zoonotic pathogen recently designated a serious antimicrobial resistant (AR) threat. While most patients with C. jejuni experience hemorrhagic colitis, serious autoimmune conditions can follow including inflammatory bowel disease (IBD) and the acute neuropathy Guillain Barré Syndrome (GBS). This review examines inter-relationships among factors mediating C. jejuni diarrheal versus autoimmune disease especially AR C. jejuni and microbiome shifts. Because both susceptible and AR C. jejuni are acquired from animals or their products, we consider their role in harboring strains. Inter-relationships among factors mediating C. jejuni colonization, diarrheal and autoimmune disease include C. jejuni virulence factors and AR, the enteric microbiome, and host responses. Because AR C. jejuni have been suggested to affect the severity of disease, length of infections and propensity to develop GBS, it is important to understand how these interactions occur when strains are under selection by antimicrobials. More work is needed to elucidate host-pathogen interactions of AR C. jejuni compared with susceptible strains and how AR C. jejuni are maintained and evolve in animal reservoirs and the extent of transmission to humans. These knowledge gaps impair the development of effective strategies to prevent the emergence of AR C. jejuni in reservoir species and human populations.

  18. 40Ar/39Ar dating and paleo-magnetism of traps from Ethiopia, Deccan and Siberia

    International Nuclear Information System (INIS)

    Hofmann, C.


    Recent studies have shown that major flood basalt provinces have been emplaced as short events (∼ 1 Myr), more or less synchronous with climatic crises and mass extinctions. We present new geochronologic ( 40 Ar/ 39 Ar) and magneto-stratigraphic results for the Ethiopian traps, one of the last remaining flood basalts for which little of such data were available. The ages obtained in a 2000 m thick section are indistinguishable. Moreover, magneto-stratigraphy reveals a simple 3-chron reverse-normal-reverse sequence. Although magnetic chrons cannot be yet unambiguously identified, there is more likelihood for the normal sub-chron in the main basaltic pile to correspond to 11N, supporting a brief duration (less than 1.5 Ma). The Ethiopian traps erupted near 30 Ma at or near the time of the cold and dry climate, major Antarctic ice sheet advance, and the largest sea-level drop in the Tertiary. Bhandari et al. (GRL, 1995) have discovered inter-traps sediments with a triple iridium anomaly in a series of seven basaltic lava flows in the Kutch area of the North Western Deccan traps of India. Plagioclases from three flows above the iridium bearing sediments yield 39 Ar/ 40 Ar plateau ages near 65.0 Ma: these flows have unambiguously reversed magnetic polarity interpreted as chron 29R. As a preliminary summary, evidence of the KTB asteroid impact is confirmed in the Deccan traps, showing that they are coeval events in a general sense (in a Ma long window) though clearly with vastly different time constants. This is compatible with paleontologic evidence of two scales of extinctions, one quasi-instantaneous and the other on the order of 10 5 to 10 6 yrs. Clearly, the impact cannot have caused trap eruptions. On the other hand, the exact age and significance of the lower flows more altered remains to be analyzed further as they pertained to the much debated question of duration of Deccan trap volcanism. (author)

  19. A test of the 40Ar/39Ar age spectrum technique on some terrestrial materials (United States)

    Lanphere, M.A.; Brent, Dalrymple G.


    40Ar/39Ar age spectra were determined for 10 terrestrial rock and mineral samples whose geologic history is known from independent evidence. The spectra for six mineral and whole rock samples, including biotite, feldspar, hornblende, muscovite, and granodiorite, that have experienced post-crystallization heating did not reveal the age of crystallization in any obvious way. Minima in the spectra, however, give reasonable maximum ages for reheating and high-temperature maxima can be interpreted as minimum crystallization ages. High-temperature ages of microcline and albite that have not been reheated are approximately 10% younger than the known crystallization age. Apparently there are no domains in these feldspars that have retained radiogenic 40Ar quantitatively. Spectra from two diabase samples that contain significant quantities of excess argon might mistakenly be interpreted as spectra from reheated samples and do not give the age of emplacement. The 40Ar/39Ar age spectrum technique may be a potentially valuable tool for the study of geologic areas with complex histories, but the interpretation of age spectra from terrestrial samples seems to be more difficult than suggested by some previous studies. ?? 1971.

  20. Solvable model of spiral wave chimeras. (United States)

    Martens, Erik A; Laing, Carlo R; Strogatz, Steven H


    Spiral waves are ubiquitous in two-dimensional systems of chemical or biological oscillators coupled locally by diffusion. At the center of such spirals is a phase singularity, a topological defect where the oscillator amplitude drops to zero. But if the coupling is nonlocal, a new kind of spiral can occur, with a circular core consisting of desynchronized oscillators running at full amplitude. Here, we provide the first analytical description of such a spiral wave chimera and use perturbation theory to calculate its rotation speed and the size of its incoherent core.

  1. Solvable Model of Spiral Wave Chimeras

    DEFF Research Database (Denmark)

    Martens, Erik Andreas; Laing, Carlo R.; Strogatz, Steven H.


    Spiral waves are ubiquitous in two-dimensional systems of chemical or biological oscillators coupled locally by diffusion. At the center of such spirals is a phase singularity, a topological defect where the oscillator amplitude drops to zero. But if the coupling is nonlocal, a new kind of spiral...... can occur, with a circular core consisting of desynchronized oscillators running at full amplitude. Here, we provide the first analytical description of such a spiral wave chimera and use perturbation theory to calculate its rotation speed and the size of its incoherent core....

  2. Ar-Ar dating techniques for terrestrial meteorite impacts (United States)

    Kelley, S. P.


    The ages of the largest (>100 km) known impacts on Earth are now well characterised. However the ages of many intermediate sized craters (20-100 km) are still poorly known, often the only constraints are stratigraphic - the difference between the target rock age and the age of crater filling sediments. The largest impacts result in significant melt bodies which cool to form igneous rocks and can be dated using conventional radiometric techniques. Smaller impacts give rise to thin bands of melted rock or melt clasts intimately mixed with country rock clasts in breccia deposits, and present much more of a challenge to dating. The Ar-Ar dating technique can address a wide variety of complex and heterogeneous samples associated with meteorite impacts and obtain reasonable ages. Ar-Ar results will be presented from a series of terrestrial meteorite impact craters including Boltysh (65.17±0.64 Ma, Strangways (646±42 Ma), and St Martin (220±32 Ma) and a Late Triassic spherule bed, possibly representing distal deposits from Manicouagan (214±1 Ma) crater. Samples from the Boltysh and Strangways craters demonstrate the importance of rapid cooling upon the retention of old ages in glassy impact rocks. A Late Triassic spherule bed in SW England is cemented by both carbonate and K-feldspar cements allowing Ar-Ar dating of fine grained cement to place a mimimum age upon the age of the associated impact. An age of 214.7±2.5 Ma places the deposit with errors of the age of the Manicouagan impact, raising the possibility that it may represent a distal deposit (the deposit lay around 2000 km away from the site of the Manicouagan crater during the Late Triassic). Finally the limits of the technique will be demonstrated using an attempt to date melt rocks from the St Martin Crater in Canada.

  3. Temporal intermittency and the lifetime of chimera states in ensembles of nonlocally coupled chaotic oscillators (United States)

    Semenova, N. I.; Strelkova, G. I.; Anishchenko, V. S.; Zakharova, A.


    We describe numerical results for the dynamics of networks of nonlocally coupled chaotic maps. Switchings in time between amplitude and phase chimera states have been first established and studied. It has been shown that in autonomous ensembles, a nonstationary regime of switchings has a finite lifetime and represents a transient process towards a stationary regime of phase chimera. The lifetime of the nonstationary switching regime can be increased to infinity by applying short-term noise perturbations.

  4. Dating method with /sup 39/Ar

    Energy Technology Data Exchange (ETDEWEB)

    Loosli, H H [Bern Univ. (Switzerland). Physikalisches Inst.


    The principles of a dating method based on the cosmic-ray-produced radioisotope /sup 39/Ar are given. Technical requirements such as background and standard gas samples and gas proportional counting systems are described. With samples extracted from Greenland ice it can be demonstrated that /sup 39/Ar ages agree with ages obtained by other methods. First results on ocean water samples show that with this isotope valuable information on ocean mixing and circulation can be expected. /sup 39/Ar results on groundwater samples disagree for some aquifers with conventional /sup 14/C ages; possible explanations are discussed, especially underground production of /sup 39/Ar.

  5. Incomplete development of the spleen and the deformity in the chimeras between asplenic mutant (Dominant hemimelia) and normal mice. (United States)

    Suto, J; Wakayama, T; Imamura, K; Goto, S; Fukuta, K


    The semidominant gene Dh (Dominant hemimelia) induces skeletal and visceral abnormalities of various degrees and failure of the spleen in mice. The homozygous individual (Dh/Dh) seems to be lethal. The present experiment was designed to investigate the ability Dh cells to form a spleen and the genesis of the hind limb malformations by Dh/Dh and Dh/+ cells in chimeric mice. The Dh/Dh and Dh/+ embryos were produced in the F2 progeny of a cross between inbred strains of Dh/+ and DDD mice. They were aggregated with C3H/He or C57BL/6 embryos to make chimeras. Identification of Dh/Dh or Dh/+ embryos was carried out by Pep-3, and chimerism was analyzed by Gpi-1. Of 25 chimeras carrying the Dh gene, four mice formed a small spleen, two mice had a vestigial spleen, and the others no spleen. The tissues of the incompletely developed spleens were normal histologically and Dh cells were involved in the tissues of the spleen. In the chimeric mice, hindlimb malformation by the Dh gene was reduced in severity and the lethality of the homozygote (Dh/Dh) was rescued.

  6. No Bursts Detected from FRB121102 in Two 5 hr Observing Campaigns with the Robert C. Byrd Green Bank Telescope (United States)

    Price, Danny C.; Gajjar, Vishal; Rosenthal, Lee; Hallinan, Gregg; Croft, Steve; DeBoer, David; Hellbourg, Greg; Isaacson, Howard; Lebofsky, Matt; Lynch, Ryan; MacMahon, David H. E.; Men, Yunpeng; Xu, Yonghua; Liu, Zhiyong; Lee, Kejia; Siemion, Andrew


    Here, we report non-detection of radio bursts from Fast Radio Burst FRB 121102 during two 5-hour observation sessions on the Robert C. Byrd 100-m Green Bank Telescope in West Virginia, USA, on December 11, 2017, and January 12, 2018. In addition, we report non-detection during an abutting 10-hour observation with the Kunming 40-m telescope in China, which commenced UTC 10:00 January 12, 2018. These are among the longest published contiguous observations of FRB 121102, and support the notion that FRB 121102 bursts are episodic. These observations were part of a simultaneous optical and radio monitoring campaign with the the Caltech HIgh- speed Multi-color CamERA (CHIMERA) instrument on the Hale 5.1-m telescope.

  7. Microstructure and mechanical properties of TiC{sub 0.5} reinforced copper matrix composites

    Energy Technology Data Exchange (ETDEWEB)

    Li, Mengqi; Zhai, Hongxiang, E-mail:; Huang, Zhenying; Liu, Xiaohan; Zhou, Yang; Li, Shibo; Li, Cuiwei


    Cu–Al alloy matrix composites containing in-situ TiC{sub 0.5} particles were fabricated by sintering of a mixture of Cu and Ti{sub 2}AlC powders at 1150 °C for 60 min in Ar atmosphere. The micron-sized Ti{sub 2}AlC particles were decomposed into submicron TiC{sub 0.5} grains during the sintering process, meanwhile, Al atoms entered into Cu to form Cu–Al alloy matrix. It was shown that the Cu–Al alloy matrix also consisted of ultrafine grains. Compression tests indicate TiC{sub 0.5} particles can improve mechanical properties significantly, and the ductility maintains at a comparatively high level. The fracture strength of 40Ti{sub 2}AlC/Cu sample reaches 1126 MPa with 12.8% fracture strain. The 20Ti{sub 2}AlC/Cu and 30Ti{sub 2}AlC/Cu samples keep undamaged even after the strain of 26.7%.

  8. The titanium tris-anilide cation [Ti(N[(t)Bu]Ar)3](+) stabilized as its perfluoro-tetra-phenylborate salt: structural characterization and synthesis in connection with redox activity of 4,4'-bipyridine dititanium complexes. (United States)

    Spinney, Heather A; Clough, Christopher R; Cummins, Christopher C


    This work explores the reduction of 4,4'-bipyridine using two equivalents of the titanium(iii) complex Ti(N[(t)Bu]Ar)3 resulting in formation of a black, crystalline complex, (4,4'-bipy){Ti(N[(t)Bu]Ar)3}2, for which an X-ray structure determination is reported. The neutral, black, 4,4'-bipyridine-bridged bimetallic was found to be redox active, with mono- and di-anions being accessible electrochemically, and with the mono- and di-cations also being accessible chemically, and isolable, at least when using the weakly coordinating anion [B(C6F5)4](-) as the counter-ion. It proved possible to crystallize the salt [(4,4'-bipy){Ti(N[(t)Bu]Ar)3}2][B(C6F5)4]2 for a single-crystal X-ray structure investigation; in this instance it was revealed that the aromaticity of the 4,4'-bipyridine ligand, that had been disrupted upon reduction, had been regained. A rare cationic d(0) metal tris-amide complex, shown by X-ray crystallography to contain an intriguing pyramidal TiN3 core geometry, namely {Ti(N[(t)Bu]Ar)3}(+), could also be isolated when using [B(C6F5)4] as the essentially non-interacting counter-ion. This highly reactive cation should be considered as a potential intermediate in the plethora of reactions wherein Ti(N[(t)Bu]Ar)3 has been shown to effect the reduction of substrates including halogenated organic molecules, carbonyl compounds, organic nitriles, and metal complexes.

  9. Multimodal actions of the phytochemical sulforaphane suppress both AR and AR-V7 in 22Rv1 cells: Advocating a potent pharmaceutical combination against castration-resistant prostate cancer. (United States)

    Khurana, Namrata; Kim, Hogyoung; Chandra, Partha K; Talwar, Sudha; Sharma, Pankaj; Abdel-Mageed, Asim B; Sikka, Suresh C; Mondal, Debasis


    Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1). MTT cell viability, wound-heal assay, and colony forming unit (CFU) measurements revealed that 22Rv1 cells are resistant to the anti-androgen, enzalutamide (ENZ). However, co-exposure to SFN sensitized these cells to the potent anticancer effects of ENZ (PAR-FL and AR-V7 levels, and immunofluorescence microscopy (IFM) depicted decreased AR in both cytoplasm and nucleus with SFN treatment. SFN increased both ubiquitination and proteasomal activity in 22Rv1 cells. Studies using a protein synthesis inhibitor (cycloheximide) or a proteasomal inhibitor (MG132) indicated that SFN increases both ubiquitin-mediated aggregation and subsequent proteasomal-degradation of AR proteins. Previous studies reported that SFN inhibits the chaperone activity of heat-shock protein 90 (Hsp90) and induces the nuclear factor erythroid-2-like 2 (Nrf2) transcription factor. Therefore, we investigated whether the Hsp90 inhibitor, ganetespib (G) or the Nrf2 activator, bardoxolone methyl (BM) can similarly suppress AR levels in 22Rv1 cells. Low doses of G and BM, alone or in combination, decreased both AR-FL and AR-V7 levels, and combined exposure to G+BM sensitized 22Rv1 cells to ENZ. Therefore, adjunct treatment with the phytochemical SFN or a safe pharmaceutical combination of G+BM may be effective against CRPC cells, especially those expressing AR-V7.

  10. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

    Directory of Open Access Journals (Sweden)

    Dhananjay R Namjoshi

    Full Text Available Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE, a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS. How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  11. Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion. (United States)

    Namjoshi, Dhananjay R; Cheng, Wai Hang; Carr, Michael; Martens, Kris M; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L


    Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

  12. Analysis of the hormone-binding domain of steroid receptors using chimeras generated by homologous recombination

    International Nuclear Information System (INIS)

    Martinez, Elisabeth D.; Pattabiraman, Nagarajan; Danielsen, Mark


    The glucocorticoid receptor and the mineralocorticoid receptor are members of the steroid receptor family that exhibit ligand cross-reactivity. Specificity of steroid receptor action is investigated in the present work by the construction and characterization of chimeras between the glucocorticoid receptor and the mineralocorticoid receptor. We used an innovative approach to make novel steroid receptor proteins in vivo that in general, contrary to our expectations, show increased ligand specificity compared to the parental receptors. We describe a receptor that is specific for the potent synthetic glucocorticoid triamcinolone acetonide and does not bind aldosterone. A further set of chimeras has an increased ability to discriminate between ligands, responding potently to mineralocorticoids and only very weakly to synthetic glucocorticoids. A chimera with the fusion site in the hinge highlights the importance of the region between the DNA-binding and the hormone-binding domains since, unlike both the glucocorticoid and mineralocorticoid receptors, it only responds to mineralocorticoids. One chimera has reduced specificity in that it acts as a general corticoid receptor, responding to glucocorticoids and mineralocorticoids with similar potency and efficacy. Our data suggest that regions of the glucocorticoid and mineralocorticoid receptor hormone-binding domains are functionally non-reciprocal. We present transcriptional, hormone-binding, and structure-modeling evidence that suggests that receptor-specific interactions within and across domains mediate aspects of specificity in transcriptional responses to steroids

  13. Studies on the mechanism of the self restriction of T cell responses in radiation chimeras

    International Nuclear Information System (INIS)

    Fink, P.J.; Bevan, M.J.


    Recent experiments with murine radiation chimeras have shown that F 1 T cells that mature in an H-2 homozygous thymus, as is the case in [F 1 → Parent 1] chimeras, are restricted to recognizing foreign antigen in the context of Parent 1 H-2 antigens. Conflicting results on the stringency of self H-2 restriction of T cells from normal mice have suggested that the thymic restriction in chimeras may be due to active suppression of parent 2-restricted T cell clones. We have therefore conducted 3 sets of experiments to test for suppression of maturing T cells that could mediate thymic tutoring of H-2-restriction specificity in chimeras. In 2 sets of experiments, we found no evidence that suppressor cells could be exported from 1 thymus and act either intrathymically on thymocytes in a 2nd thymus or extrathymically on recent thymic emigrants. We believe current data support a role for the thymus in positive as well as negative selection of maturing thymocytes on the basis of self recognition, in the absence of any suppression. Our results do not support the concept that suppression is responsible for the difference in the degree of self preference in the T cells of chimeric mice relative to cell populations obtained from neonatally tolerant mice or from normal mice after acute negative selection


    Directory of Open Access Journals (Sweden)



    Full Text Available The aim of this study was to examine the factors, which influence the chimeraforming potential of mouse embryonic stem cells (ES cells. In our work, we examinethe chimera producing ability of R1 and R1/E mouse ES cell lines. We found that thepassage number affects chimera-forming capability of the ES cells. With theincreasing of the passage number, it could be getting less chimera animal, and onlythe R1/E ES cell line derived cells could contribute to the germ cells. At first, wecompared the marker of pluripotency using immunostaining and RT PCR, but wecould not find any difference between the R1 and R1/E cell in this way. Atchromosome analysis, we found, that the number of aneuploid cells, in R1 ES cellline, dramatically increased after 10 passages. We thought that the reason is thatduring the cell division Y chromosome could not arrange correctly between the twonewly derived progeny cells. To prove our conception, we made X and YchromosomeFISH analyses. We found, that the aneuploid R1 and R1/E ES cellscontain only one X and one Y chromosome, so not the loss of Y chromosome causethe problem at the germ cell formation. At last, we made the karyotypeanalysis of R1 and R1/E ES cells at different passages. The karyotype analysisdemonstrated that in the case of R1 ES cell line, the 41 and 42-chromosomecontaining cells hold trisomy. With the increasing of the passages number, thenumber of trisomy containing aneuploid cells increased. The aneuploid ES cells cancontribute to the different tissuses of chimera animals, but cannot form viable germcells.


    Directory of Open Access Journals (Sweden)



    Full Text Available The aim of this study was to examine the factors, which influence the chimeraforming potential of mouse embryonic stem cells (ES cells. In our work, we examinethe chimera producing ability of R1 and R1/E mouse ES cell lines. We found that thepassage number affects chimera-forming capability of the ES cells. With theincreasing of the passage number, it could be getting less chimera animal, and onlythe R1/E ES cell line derived cells could contribute to the germ cells. At first, wecompared the marker of pluripotency using immunostaining and RT PCR, but wecould not find any difference between the R1 and R1/E cell in this way. Atchromosome analysis, we found, that the number of aneuploid cells, in R1 ES cellline, dramatically increased after 10 passages. We thought that the reason is thatduring the cell division Y chromosome could not arrange correctly between the twonewly derived progeny cells. To prove our conception, we made X and YchromosomeFISH analyses. We found, that the aneuploid R1 and R1/E ES cellscontain only one X and one Y chromosome, so not the loss of Y chromosome causethe problem at the germ cell formation. At last, we made the karyotypeanalysis of R1 and R1/E ES cells at different passages. The karyotype analysisdemonstrated that in the case of R1 ES cell line, the 41 and 42-chromosomecontaining cells hold trisomy. With the increasing of the passages number, thenumber of trisomy containing aneuploid cells increased. The aneuploid ES cells cancontribute to the different tissuses of chimera animals, but cannot form viable germcells.

  16. {sup 40}Ar/{sup 39}Ar dating and paleo-magnetism of traps from Ethiopia, Deccan and Siberia; Datation {sup 40}Ar/{sup 39}Ar et paleomagnetisme des traps d'Ethiopie, du Deccan et de Siberie

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, C


    Recent studies have shown that major flood basalt provinces have been emplaced as short events ({approx} 1 Myr), more or less synchronous with climatic crises and mass extinctions. We present new geochronologic ({sup 40}Ar/{sup 39}Ar) and magneto-stratigraphic results for the Ethiopian traps, one of the last remaining flood basalts for which little of such data were available. The ages obtained in a 2000 m thick section are indistinguishable. Moreover, magneto-stratigraphy reveals a simple 3-chron reverse-normal-reverse sequence. Although magnetic chrons cannot be yet unambiguously identified, there is more likelihood for the normal sub-chron in the main basaltic pile to correspond to 11N, supporting a brief duration (less than 1.5 Ma). The Ethiopian traps erupted near 30 Ma at or near the time of the cold and dry climate, major Antarctic ice sheet advance, and the largest sea-level drop in the Tertiary. Bhandari et al. (GRL, 1995) have discovered inter-traps sediments with a triple iridium anomaly in a series of seven basaltic lava flows in the Kutch area of the North Western Deccan traps of India. Plagioclases from three flows above the iridium bearing sediments yield {sup 39}Ar/{sup 40}Ar plateau ages near 65.0 Ma: these flows have unambiguously reversed magnetic polarity interpreted as chron 29R. As a preliminary summary, evidence of the KTB asteroid impact is confirmed in the Deccan traps, showing that they are coeval events in a general sense (in a Ma long window) though clearly with vastly different time constants. This is compatible with paleontologic evidence of two scales of extinctions, one quasi-instantaneous and the other on the order of 10{sup 5} to 10{sup 6} yrs. Clearly, the impact cannot have caused trap eruptions. On the other hand, the exact age and significance of the lower flows more altered remains to be analyzed further as they pertained to the much debated question of duration of Deccan trap volcanism. (author)

  17. Aluminum chloride- and norepinephrine-induced immunotoxicity on splenic lymphocytes by activating β2-AR/cAMP/PKA/NF-κB signal pathway in rats. (United States)

    Xiu, Chunyu; Ren, Limin; Li, Miao; Liu, Shiming; Zhu, Yanzhu; Liu, Jianyu; Li, Yanfei


    We found in our previous research that aluminum (Al) exposure induced immunotoxicity on spleen and increased norepinephrine (NE) content in serum from rats. However, it is unclear how NE is involved in the AlCl3 immunotoxicity on rats. Therefore, this experiment was designed to explore the mechanism of AlCl3 and NE-induced immunotoxicity on the splenic lymphocytes. Eighty male Wistar rats were orally exposed to AlCl3 (0, 64, 128, and 256 mg/kg BW) through drinking water for 120 days. Al contents in brain and spleen; NE contents in serum and in the hypothalamus; β2-AR density; cAMP content; β2-AR, PKA, and NF-κB mRNA expression levels; and protein expressions of PKA and nuclear NF-κB in splenic lymphocytes of AlCl3-treated rats were examined. The results showed that AlCl3 increased NE content in serum, the β2-AR density, the β2-AR and PKA (C-subunits) mRNA expression levels, cAMP content and the PKA (C-subunits) protein expression levels in lymphocytes, whereas, decreased NE content in the hypothalamus, the NF-κB (p65) mRNA expression level and nuclear NF-κB (p65) protein expression level in lymphocytes. These results indicated that the accumulated AlCl3 in spleen and the increased NE in serum induced the immunotoxicity on splenic lymphocytes by activating β2-AR/cAMP/PKA/NF-κB signal pathway in rats.

  18. Chimera patterns in two-dimensional networks of coupled neurons (United States)

    Schmidt, Alexander; Kasimatis, Theodoros; Hizanidis, Johanne; Provata, Astero; Hövel, Philipp


    We discuss synchronization patterns in networks of FitzHugh-Nagumo and leaky integrate-and-fire oscillators coupled in a two-dimensional toroidal geometry. A common feature between the two models is the presence of fast and slow dynamics, a typical characteristic of neurons. Earlier studies have demonstrated that both models when coupled nonlocally in one-dimensional ring networks produce chimera states for a large range of parameter values. In this study, we give evidence of a plethora of two-dimensional chimera patterns of various shapes, including spots, rings, stripes, and grids, observed in both models, as well as additional patterns found mainly in the FitzHugh-Nagumo system. Both systems exhibit multistability: For the same parameter values, different initial conditions give rise to different dynamical states. Transitions occur between various patterns when the parameters (coupling range, coupling strength, refractory period, and coupling phase) are varied. Many patterns observed in the two models follow similar rules. For example, the diameter of the rings grows linearly with the coupling radius.

  19. Polariton Chimeras: Bose-Einstein Condensates with Intrinsic Chaoticity and Spontaneous Long-Range Ordering (United States)

    Gavrilov, S. S.


    The system of cavity polaritons driven by a plane electromagnetic wave is found to undergo the spontaneous breaking of spatial symmetry, which results in a lifted phase locking with respect to the driving field and, consequently, in the possibility of internal ordering. In particular, periodic spin and intensity patterns arise in polariton wires; they exhibit strong long-range order and can serve as media for signal transmission. Such patterns have the properties of dynamical chimeras: they are formed spontaneously in perfectly homogeneous media and can be partially chaotic. The reported new mechanism of chimera formation requires neither time-delayed feedback loops nor nonlocal interactions.

  20. Chimera grids in the simulation of three-dimensional flowfields in turbine-blade-coolant passages (United States)

    Stephens, M. A.; Rimlinger, M. J.; Shih, T. I.-P.; Civinskas, K. C.


    When computing flows inside geometrically complex turbine-blade coolant passages, the structure of the grid system used can affect significantly the overall time and cost required to obtain solutions. This paper addresses this issue while evaluating and developing computational tools for the design and analysis of coolant-passages, and is divided into two parts. In the first part, the various types of structured and unstructured grids are compared in relation to their ability to provide solutions in a timely and cost-effective manner. This comparison shows that the overlapping structured grids, known as Chimera grids, can rival and in some instances exceed the cost-effectiveness of unstructured grids in terms of both the man hours needed to generate grids and the amount of computer memory and CPU time needed to obtain solutions. In the second part, a computational tool utilizing Chimera grids was used to compute the flow and heat transfer in two different turbine-blade coolant passages that contain baffles and numerous pin fins. These computations showed the versatility and flexibility offered by Chimera grids.

  1. Human-animal chimera: a neuro driven discussion? Comparison of three leading European research countries. (United States)

    Cabrera Trujillo, Laura Yenisa; Engel-Glatter, Sabrina


    Research with human-animal chimera raises a number of ethical concerns, especially when neural stem cells are transplanted into the brains of non-human primates (NHPs). Besides animal welfare concerns and ethical issues associated with the use of embryonic stem cells, the research is also regarded as controversial from the standpoint of NHPs developing cognitive or behavioural capabilities that are regarded as "unique" to humans. However, scientists are urging to test new therapeutic approaches for neurological diseases in primate models as they better mimic human physiology than all current animal models. As a response, various countries have issued reports on the topic. Our paper summarizes the ethical issues raised by research with human-animal brain chimeras and compares the relevant regulatory instruments and different recommendations issued in national reports from three important European research nations: Germany, Switzerland and the United Kingdom. We assess and discuss the focus and priorities set by the different reports, review various reasons for and perspectives on the importance of the brain in chimera research, and identify critical points in the reports that warrant further specification and debate.

  2. Decisive factors affecting plasma resistance and roughness formation in ArF photoresist

    Energy Technology Data Exchange (ETDEWEB)

    Jinnai, Butsurin; Uesugi, Takuji; Koyama, Koji; Samukawa, Seiji [Institute of Fluid Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577 (Japan); Kato, Keisuke; Yasuda, Atsushi; Maeda, Shinichi [Yokohama Research Laboratories, Mitsubishi Rayon Co., Ltd, 10-1 Daikoku-cho, Tsurumi-ku, Yokohama 230-0053 (Japan); Momose, Hikaru, E-mail: [Corporate Research Laboratories, Mitsubishi Rayon Co., Ltd, 2-1 Miyuki-cho, Otake, Hiroshima 739-0693 (Japan)


    Low plasma resistance and roughness formation in an ArF photoresist are serious issues in plasma processes. To resolve these issues, we investigated several factors that affect the roughness formation and plasma resistance in an ArF photoresist. We used our neutral beam process to categorize the effects of species from the plasma on the ArF photoresist into physical bombardment, chemical reactions and ultraviolet/vacuum ultraviolet (UV/VUV) radiation. The UV/VUV radiation drastically increased the etching rates of the ArF photoresist films, and, in contrast, chemical reactions increased the formation of surface roughness. FTIR analysis indicated that the UV/VUV radiation preferentially dissociates C-H bonds in the ArF photoresist, rather than C=O bonds, because of the dissociation energies of the bonds. This indicated that the etching rates of the ArF photoresist are determined by the UV/VUV radiation because this radiation can break C-H bonds, which account for the majority of structures in the ArF photoresist. In contrast, FTIR analysis showed that chemical species such as radicals and ions were likely to react with C=O bonds, in particular C=O bonds in the lactone groups of the ArF photoresist, due to the structural and electronic effects of the lactone groups. As a result, the etching rates of the ArF photoresist can vary in different bond structures, leading to increased surface roughness in the ArF photoresist.

  3. Transcription Profiling of Bacillus subtilis Cells Infected with AR9, a Giant Phage Encoding Two Multisubunit RNA Polymerases. (United States)

    Lavysh, Daria; Sokolova, Maria; Slashcheva, Marina; Förstner, Konrad U; Severinov, Konstantin


    Bacteriophage AR9 is a recently sequenced jumbo phage that encodes two multisubunit RNA polymerases. Here we investigated the AR9 transcription strategy and the effect of AR9 infection on the transcription of its host, Bacillus subtilis Analysis of whole-genome transcription revealed early, late, and continuously expressed AR9 genes. Alignment of sequences upstream of the 5' ends of AR9 transcripts revealed consensus sequences that define early and late phage promoters. Continuously expressed AR9 genes have both early and late promoters in front of them. Early AR9 transcription is independent of protein synthesis and must be determined by virion RNA polymerase injected together with viral DNA. During infection, the overall amount of host mRNAs is significantly decreased. Analysis of relative amounts of host transcripts revealed notable differences in the levels of some mRNAs. The physiological significance of up- or downregulation of host genes for AR9 phage infection remains to be established. AR9 infection is significantly affected by rifampin, an inhibitor of host RNA polymerase transcription. The effect is likely caused by the antibiotic-induced killing of host cells, while phage genome transcription is solely performed by viral RNA polymerases. IMPORTANCE Phages regulate the timing of the expression of their own genes to coordinate processes in the infected cell and maximize the release of viral progeny. Phages also alter the levels of host transcripts. Here we present the results of a temporal analysis of the host and viral transcriptomes of Bacillus subtilis infected with a giant phage, AR9. We identify viral promoters recognized by two virus-encoded RNA polymerases that are a unique feature of the phiKZ-related group of phages to which AR9 belongs. Our results set the stage for future analyses of highly unusual RNA polymerases encoded by AR9 and other phiKZ-related phages. Copyright © 2017 Lavysh et al.

  4. Regional elevation history from Ribeira belt based in K-Ar dating

    International Nuclear Information System (INIS)

    Zimbres, E.; Kawashita, K.; Motoki, A.


    The Ribeira orogenic belt, Brazilian cycle in metamorphism, has biotite K-Ar ages becoming young from the border (600 Ma) to the central axis (450 Ma), these ages are not related to rock type nor intrusive phase, but to occurrence area. The fact suggests that this wide-ranging age distribution is not due to later thermal events, e.g. post tectonic intrusion, but to slow cooling on the axis zone. The climax metamorphic condition have been estimated as 675 sup(0)C and 4 to 5 kb (18 km's depth). This temperature is much higher than that of biotite argon retention (310 sup(0)C). These data indicate that the biotite K-Ar clock have been set fairly after the climax during regional uplift at a depth much shallower that the metamorphism. Biotite clock setting depth (310 sup(0)C) is calculated as 7.5 km, using geothermal gradient of 30 sup(0)C/km. In this connection, uplift of 11.5 km from 600 Ma to 450 Ma (rate of 77 m/m.y.) is estimated. Fission track datings in apatite (110 Ma), combined with a present geothermal gradient (25 sup(0)C/km) indicate uplift of 3.5 km from 450 Ma to 110 Ma (16 m/m.y.) and 4 km from 110 Ma to the present (35 m/m.y.). (author)

  5. A chimeric prokaryotic pentameric ligand–gated channel reveals distinct pathways of activation (United States)

    Schmandt, Nicolaus; Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Stein, Richard A.; Bonner, Ross; Talley, Lauren; Parker, Mark D.; Mchaourab, Hassane S.; Yee, Vivien C.; Lodowski, David T.


    Recent high resolution structures of several pentameric ligand–gated ion channels have provided unprecedented details of their molecular architecture. However, the conformational dynamics and structural rearrangements that underlie gating and allosteric modulation remain poorly understood. We used a combination of electrophysiology, double electron–electron resonance (DEER) spectroscopy, and x-ray crystallography to investigate activation mechanisms in a novel functional chimera with the extracellular domain (ECD) of amine-gated Erwinia chrysanthemi ligand–gated ion channel, which is activated by primary amines, and the transmembrane domain of Gloeobacter violaceus ligand–gated ion channel, which is activated by protons. We found that the chimera was independently gated by primary amines and by protons. The crystal structure of the chimera in its resting state, at pH 7.0 and in the absence of primary amines, revealed a closed-pore conformation and an ECD that is twisted with respect to the transmembrane region. Amine- and pH-induced conformational changes measured by DEER spectroscopy showed that the chimera exhibits a dual mode of gating that preserves the distinct conformational changes of the parent channels. Collectively, our findings shed light on both conserved and divergent features of gating mechanisms in this class of channels, and will facilitate the design of better allosteric modulators. PMID:26415570

  6. (11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand

    DEFF Research Database (Denmark)

    Andersen, Valdemar L; Hansen, Hanne D; Herth, Matthias M


    ]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs...

  7. Mechanism of donor to host tolerance in rat bone marrow chimeras

    International Nuclear Information System (INIS)

    Tutschka, P.; Schwerdtfeger, R.; Slavin, R.; Santos, G.


    Lewis rats were conditioned with cyclophosphamide and grafted with AgB incompatible bone marrow. They were examined 250 days after transplantation and demonstrated to be healthy complete chimeras. Marrow cells from these chimeras were infused into lethally irradiated ACI, Lewis and BN recipients. Graft-versus-host disease occurred only in the BN rats. Other chimeric rats were given no treatment, busulfan, CY, or total body irradiation prior to the infusion of normal ACI BM. GvHD occurred only in animals given CY or TBI. Normal Lewis rats were conditioned with TBI and given ACI BM. In addition, they received whole blood, irradiated blood, or serum from chimeric rats. GvHD developed in all animals except those given unirradiated chimeric blood. These studies suggest that suppressor cell populations, sensitive to immunosuppression, are likely the fundamental mechanism of recovery from GvHD

  8. In vitro neoformation of grape chimeras (Vitis vinifera L.

    Directory of Open Access Journals (Sweden)

    Sandrine Verdisson


    Full Text Available Difference in grape sensitivity to Botrytis cinerea attacks between cultivars was explained by differences in the epidermic tissue of the fruit. Therefore, this work was conducted to create a grape periclinal chimera, whose fruits would combine the skin of a Botrytis tolerant cultivar with a pulp of an another cultivar admitted its good organoleptic quality and productivity. In a first time, graftings of two cultivars (Chardonnay and Pinot noir were conducted in vitro on 5 different media supplemented with various plant growth regulators. Adventitious shoots were only observed on medium containing BAP and GA3 from a mixed callus structure after four weeks of darkness followed by a light/dark regime. In a second time, RAPD analysis, conducted on these plants, showed their chimerical characteristics.

  9. Bacillus sp.CDB3 isolated from cattle dip-sites possesses two ars gene clusters

    Institute of Scientific and Technical Information of China (English)

    Somanath Bhat; Xi Luo; Zhiqiang Xu; Lixia Liu; Ren Zhang


    Contamination of soil and water by arsenic is a global problem.In Australia, the dipping of cattle in arsenic-containing solution to control cattle ticks in last centenary has left many sites heavily contaminated with arsenic and other toxicants.We had previously isolated five soil bacterial strains (CDB1-5) highly resistant to arsenic.To understand the resistance mechanism, molecular studies have been carried out.Two chromosome-encoded arsenic resistance (ars) gene clusters have been cloned from CDB3 (Bacillus sp.).They both function in Escherichia coli and cluster 1 exerts a much higher resistance to the toxic metalloid.Cluster 2 is smaller possessing four open reading frames (ORFs) arsRorf2BC, similar to that identified in Bacillus subtilis Skin element.Among the eight ORFs in cluster 1 five are analogs of common ars genes found in other bacteria, however, organized in a unique order arsRBCDA instead of arsRDABC.Three other putative genes are located directly downstream and designated as arsTIP based on the homologies of their theoretical translation sequences respectively to thioredoxin reductases, iron-sulphur cluster proteins and protein phosphatases.The latter two are novel of any known ars operons.The arsD gene from Bacillus species was cloned for the first time and the predict protein differs from the well studied E.coli ArsD by lacking two pairs of C-terrninal cysteine residues.Its functional involvement in arsenic resistance has been confirmed by a deletion experiment.There exists also an inverted repeat in the intergenic region between arsC and arsD implying some unknown transcription regulation.

  10. Magnetostratigraphy and 39Ar/40Ar studies of the Lana'i Long Volcanic Sequence (ca. 1.606+/-0.063 Ma), Hawaii, USA (United States)

    Herrero-Bervera, E.; Jicha, B.; Valet, J.


    Previous published work on Lanai indicated that the volcano was formed mainly during the Matuyama Chron (Herrero-Bervera et al., 2000). In order to constrain further the timing of the active phases of the Lanai volcano, we conducted a paleomagnetic and rock magnetic study involving a ~500-m vertical thick sequence of lava flows that were erupted between 0.76+/-0.66 Ma and 1.6+/-0.09 Ma according to previous K/Ar and 40Ar/39Ar dating (Leonhardt et al., 2009). Low-field susceptibility versus temperature (k-T) and SIRM experiments performed on a dozen flows indicate that magnetite dominates the remanent magnetization (575°C). In a few cases, a low-temperature mineral phase (300-400°C) could reflect the presence of titanomagnetite with low Ti content, but the presence of maghemite or pyrrhotite cannot be completely excluded. Additional investigations are in progress on this matter. All specimens were step-wise demagnetized by alternating fields from 5 to 100 mT. Companion specimens from the same samples were demagnetized at 15 temperature steps. The demagnetization diagrams obtained with each technique showed a stable direction of remanence. In all cases, the characteristic (ChRM) component was clearly defined from at least seven successive directions isolated during step-wise demagnetization. The succession of the mean directions calculated for each lava flow reveals the existence of at least one polarity interval. Based on radiometric dates, they were assigned to the Gilsa, "excursion" (1.606+/-0.063 Ma). Thus, the present results, along with the radiometric ages of the lavas, indicate that the tholeiitic flows that formed the Lanai volcano were erupted over a short time period, and only during the Matuyama Chron (0.780-2.58 Ma). No eruptions have occurred during the Brunhes Chron (0.78 Ma) as previously indicated from K-Ar data on lavas in the Maunalei Gulch. The excursional VGPs from the onset of the Gilsa excursion recorded on Lanai are situated near the

  11. Induction of chlorophyll chimeras and chlorophyll mutations in mungbean (Vigna radiata) cv. T44

    International Nuclear Information System (INIS)

    Singh, V.P.; Yadav, R.D.S.


    Uniform and healthy seeds of mungbean (Vigna radiata) cv. T44 were exposed to varying doses of gamma rays, ethyl methane sulphonate (EMS) and combination treatment of gamma rays with EMS. The data were recorded for seed germination, plant survival, frequency and spectrum of chlorophyll chimeras in M 1 and chlorophyll mutations in M 2 generation. Among all, the combination treatments were found most effective for inducing chlorophyll chimeras and chlorophyll mutations than the gamma rays or EMS alone. Of the mutants under reference, the albino, xantha and chlorina showed monogenic recessive while viridis exhibited digenic recessive inheritance. (author). 8 refs., 2 tabs

  12. Bacterial membrane activity of a-peptide/b-peptoid chimeras: Influence of amino acid composition and chain length on the activity against different bacterial strains

    DEFF Research Database (Denmark)

    Hein-Kristensen, Line; Knapp, Kolja M; Franzyk, Henrik


    and subsequent killing is usually not tested. In this report, six α-peptide/β-peptoid chimeras were examined for the effect of amino acid/peptoid substitutions and chain length on the membrane perturbation and subsequent killing of food-borne and clinical bacterial isolates. RESULTS: All six AMP analogues...... acid only had a minor effect on MIC values, whereas chain length had a profound influence on activity. All chimeras were less active against Serratia marcescens (MICs above 46 μM). The chimeras were bactericidal and induced leakage of ATP from Staphylococcus aureus and S. marcescens with similar time...... of onset and reduction in the number of viable cells. EDTA pre-treatment of S. marcescens and E. coli followed by treatment with chimeras resulted in pronounced killing indicating that disintegration of the Gram-negative outer membrane eliminated innate differences in susceptibility. Chimera chain length...

  13. 40Ar/39Ar Dating of Zn-Pb-Ag Mineralization in the Northern Brooks Range, Alaska (United States)

    Werdon, Melanie B.; Layer, Paul W.; Newberry, Rainer J.


    The 40Ar/39Ar laser step-heating method potentially can be used to provide absolute ages for a number of formerly undatable, low-temperature ore deposits. This study demonstrates the use of this method by determining absolute ages for Zn-Pb-Ag sediment-hosted massive sulfide deposits and vein-breccia occurrences found throughout a 300-km-long, east-west-trending belt in the northern Brooks Range, Alaska. Massive sulfide deposits are hosted by Mississippian to Pennsylvanian(?) black carbonaceous shale, siliceous mudstone, and lesser chert and carbonate turbidites of the Kuna Formation (e.g., Red Dog, Anarraaq, Lik (Su), and Drenchwater). The vein-breccia occurrences (e.g., Husky, Story Creek, West Kivliktort Mountain, Vidlee, and Kady) are hosted by a deformed but only weakly metamorphosed package of Upper Devonian to Lower Mississippian mixed continental and marine clastic rocks (the Endicott Group) that stratigraphically underlie the Kuna Formation. The vein-breccias are mineralogically similar to, but not spatially associated with, known massive sulfide deposits. The region's largest shale-hosted massive sulfide deposit is Red Dog; it has reserves of 148 Mt grading 16.6 percent zinc, 4.5 percent lead, and 77 g of silver per tonne. Hydrothermally produced white mica in a whole-rock sample from a sulfide-bearing igneous sill within the Red Dog deposit yielded a plateau age of 314.5 Ma. The plateau age of this whole-rock sample records the time at which temperatures cooled below the argon closure temperature of the white mica and is interpreted to represent the minimum age limit for massive sulfide-related hydrothermal activity in the Red Dog deposit. Sulfide-bearing quartz veins at Drenchwater crosscut a hypabyssal intrusion with a maximum biotite age of 337.0 Ma. Despite relatively low sulfide deposition temperatures in the vein-breccia occurrences (162°-251°C), detrital white mica in sandstone immediately adjacent to large vein-breccia zones was partially to

  14. Study of Flux Ratio of C60 to Ar Cluster Ion for Hard DLC Film deposition

    International Nuclear Information System (INIS)

    Miyauchi, K.; Toyoda, N.; Kanda, K.; Matsui, S.; Kitagawa, T.; Yamada, I.


    To study the influence of the flux ratio of C60 molecule to Ar cluster ion on (diamond like carbon) DLC film characteristics, DLC films deposited under various flux ratios were characterized with Raman spectrometry and Near Edge X-ray Absorption Fine Structure (NEXAFS). From results of these measurements, hard DLC films were deposited when the flux ratio of C60 to Ar cluster ion was between 0.7 and 4. Furthermore the DLC film with constant sp2 content was obtained in the range of the ratio from 0.7 to 4, which contents are lower values than that of conventional films such as RF plasma. DLC films deposited under the ratio from 1 to 4 had hardness from 40 to 45GPa. It was shown that DLC films with stable properties of low sp2 content and high hardness were formed even when the fluxes were varied from 1 to 4 during deposition. It was indicated that this process was useful in the view of industrial application

  15. Plastid and mitochondrion genomic sequences from Arctic Chlorella sp. ArM0029B (United States)


    Background Chorella is the representative taxon of Chlorellales in Trebouxiophyceae, and its chloroplast (cp) genomic information has been thought to depend only on studies concerning Chlorella vulgaris and GenBank information of C. variablis. Mitochondrial (mt) genomic information regarding Chlorella is currently unavailable. To elucidate the evolution of organelle genomes and genetic information of Chlorella, we have sequenced and characterized the cp and mt genomes of Arctic Chlorella sp. ArM0029B. Results The 119,989-bp cp genome lacking inverted repeats and 65,049-bp mt genome were sequenced. The ArM0029B cp genome contains 114 conserved genes, including 32 tRNA genes, 3 rRNA genes, and 79 genes encoding proteins. Chlorella cp genomes are highly rearranged except for a Chlorella-specific six-gene cluster, and the ArM0029B plastid resembles that of Chlorella variabilis except for a 15-kb gene cluster inversion. In the mt genome, 62 conserved genes, including 27 tRNA genes, 3 rRNA genes, and 32 genes encoding proteins were determined. The mt genome of ArM0029B is similar to that of the non-photosynthetic species Prototheca and Heicosporidium. The ArM0029B mt genome contains a group I intron, with an ORF containing two LAGLIDADG motifs, in cox1. The intronic ORF is shared by C. vulgaris and Prototheca. The phylogeny of the plastid genome reveals that ArM0029B showed a close relationship of Chlorella to Parachlorella and Oocystis within Chlorellales. The distribution of the cox1 intron at 721 support membership in the order Chlorellales. Mitochondrial phylogenomic analyses, however, indicated that ArM0029B shows a greater affinity to MX-AZ01 and Coccomyxa than to the Helicosporidium-Prototheca clade, although the detailed phylogenetic relationships among the three taxa remain to be resolved. Conclusions The plastid genome of ArM0029B is similar to that of C. variabilis. The mt sequence of ArM0029B is the first genome to be reported for Chlorella. Chloroplast

  16. 40Ar/39Ar dating of the Late Cretaceous

    International Nuclear Information System (INIS)

    Gaylor, Jonathan


    As part of the wider European GTS Next project, I propose new constraints on the ages of the Late Cretaceous, derived from a multitude of geochronological techniques, and successful stratigraphic interpretations from Canada and Japan. In the Western Canada Sedimentary Basin, we propose a new constraint on the age of the K/Pg boundary in the Red Deer River section (Alberta, Canada). We were able to cyclo-stratigraphically tune sediments in a non-marine, fluvial environment utilising high-resolution proxy records suggesting a 11-12 precession related cyclicity. Assuming the 40 Ar/ 39 Ar method is inter-calibrated with the cyclo-stratigraphy, the apparent age for C29r suggests that the K/Pg boundary falls between eccentricity maxima and minima, yielding an age of the C29r between 65.89 ± 0.08 and 66.30 ± 0.08 Ma. Assuming that the bundle containing the coal horizon represents a precession cycle, the K/Pg boundary is within the analytical uncertainty of the youngest zircon population achieving a revised age for the K/Pg boundary as 65.75 ± 0.06 Ma. The Campanian - Maastrichtian boundary is preserved in the sedimentary succession of the Horseshoe Canyon Formation and has been placed 8 m below Coal nr. 10. Cyclo-stratigraphic studies show that the formation of these depositional sequences (alternations) of all scales are influenced directly by sea-level changes due to precession but more dominated by eccentricity cycles proved in the cyclo-stratigraphic framework and is mainly controlled by sand horizons, which have been related by auto-cyclicity in a dynamic sedimentary setting. Our work shows that the Campanian - Maastrichtian boundary in the Western Canada Sedimentary Basin coincides with 2.5 eccentricity cycles above the youngest zircon age population at the bottom of the section and 4.9 Myr before the Cretaceous - Palaeogene boundary (K/Pg), and thus corresponds to an absolute age of 70.65 ± 0.09 Ma producing an 1.4 Myr younger age than recent published ages

  17. Single grains, thermal histories, and the 40Ar/39Ar method

    International Nuclear Information System (INIS)

    Wright, Norrie


    A key part in unraveling the history of the physical evolution of the earth is knowledge of the earth's thermal history. 40 Ar/ 39 Ar step heating of mineral samples provides a means of defining a local thermal history. to do this accurately the challenge is to extract meaningful diffusion parameters from a mineral's Arrhenius plot. In the case of biotite single grains, where the laboratory release of argon is a complex process, this can be a difficult task. (12 refs., 5 figs.)

  18. Resistance to BN myelogenous leukemia in rat radiation chimeras

    International Nuclear Information System (INIS)

    Singer, D.E.; Haynor, D.R.; Williams, R.M


    Lewis → LBNFl rat radiation chimeras showed marked resistance to transplanted BN myelogenous leukemia when compared to naive LBNFl, LBNFl → LBNFl, or BN → LBNFl. This occurred in the absence of overt graft versus host disease or of anti-BN response in mixed lymphocyte culture. Bone marrow specific antigens may serve as the target of the resistance mechanism. (author)

  19. Simultaneous measurement of the 37Ar and 39Ar activity

    International Nuclear Information System (INIS)

    Fisenko, A.V.


    A method for simultaneous measurement of 37 Ar and 39 Ar activities, based on the different radiation penetrabilities of these isotopes is described. Two versions are realized. In the first case, a two-section detector is used whose partition partially transmits 39 Ar β-radiation and fully absorbs 37 Ar Auger electrons. A mixture of 37 Ar and 39 Ar is introduced into an internal counter operating at anticoincidences with an external counter. In the second version, a scintillation detector is used as an external counter, while the 37 Ar- 39 Ar mixture is introduced into a gas counter with a thin cathode. The rated detection efficiency of 37 Ar radiation in both versions is 80%. When measurement duration is 500 h, the sensitivity is approximately 10 -14 and 6x10 -15 Ci for 39 Ar and 37 Ar respectively

  20. Determination of Ar metastable atom densities in Ar and Ar/H2 inductively coupled low-temperature plasmas

    International Nuclear Information System (INIS)

    Fox-Lyon, N; Knoll, A J; Oehrlein, G S; Franek, J; Demidov, V; Koepke, M; Godyak, V


    Ar metastable atoms are important energy carriers and surface interacting species in low-temperature plasmas that are difficult to quantify. Ar metastable atom densities (N Ar,m ) in inductively coupled Ar and Ar/H 2 plasmas were obtained using a model combining electrical probe measurements of electron density (N e ) and temperature (T e ), with analysis of spectrally resolved Ar plasma optical emission based on 3p → 1s optical emission ratios of the 419.8 nm line to the 420.1 nm line. We present the variation of N Ar,m as the Ar pressure and the addition of H 2 to Ar are changed comparatively to recent adsorption spectroscopy measurements. (paper)

  1. Numerical and analytical investigation of the chimera state excitation conditions in the Kuramoto-Sakaguchi oscillator network (United States)

    Frolov, Nikita S.; Goremyko, Mikhail V.; Makarov, Vladimir V.; Maksimenko, Vladimir A.; Hramov, Alexander E.


    In this paper we study the conditions of chimera states excitation in ensemble of non-locally coupled Kuramoto-Sakaguchi (KS) oscillators. In the framework of current research we analyze the dynamics of the homogeneous network containing identical oscillators. We show the chimera state formation process is sensitive to the parameters of coupling kernel and to the KS network initial state. To perform the analysis we have used the Ott-Antonsen (OA) ansatz to consider the behavior of infinitely large KS network.

  2. The contribution of human/non-human animal chimeras to stem cell research

    Directory of Open Access Journals (Sweden)

    Sonya Levine


    Full Text Available Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States.

  3. 40Ar-39Ar dating of hornfels dredged near the Japan trench

    International Nuclear Information System (INIS)

    Takigami, Yutaka; Fujioka, Kantaro


    During the KH 81-3 Cruise of the R/V Hakuho-Maru, biotite-bearing hornfelses were dredged from the landward slope of the Japan Trench. Bulk sample and separated biotite were dated by the 40 Ar- 39 Ar method and they showed 40 Ar- 39 Ar ages of 28.9±1.4 Ma and 28.5±1.4 Ma, respectively. This would indicate that biotite was formed at about 29 Ma by the thermal metamorphism which might have related with some magmatic activity. In this magmatic activity was caused by the subducting oceanic plate in the similar conditions at present, it seems to have occurred at a place too close to the present trench axis. This discrepancy could be explained by such processes as the change of the angle of the subducting plate, the moving of the trench axis by tectonic erosion and so on. However, more age data are required to solve this discrepancy. (author)

  4. 40Ar/39Ar geochronology of terrestrial pyroxene (United States)

    Ware, Bryant; Jourdan, Fred


    Geochronological techniques such as U/Pb in zircon and baddeleyite and 40Ar/39Ar on a vast range of minerals, including sanidine, plagioclase, and biotite, provide means to date an array of different geologic processes. Many of these minerals, however, are not always present in a given rock, or can be altered by secondary processes (e.g. plagioclase in mafic rocks) limiting our ability to derive an isotopic age. Pyroxene is a primary rock forming mineral for both mafic and ultramafic rocks and is resistant to alteration process but attempts to date this phase with 40Ar/39Ar has been met with little success so far. In this study, we analyzed pyroxene crystals from two different Large Igneous Provinces using a multi-collector noble gas mass spectrometer (ARGUS VI) since those machines have been shown to significantly improve analytical precision compared to the previous single-collector instruments. We obtain geologically meaningful and relatively precise 40Ar/39Ar plateau ages ranging from 184.6 ± 3.9 to 182.4 ± 0.8 Ma (2σ uncertainties of ±1.8-0.4%) and 506.3 ± 3.4 Ma for Tasmanian and Kalkarindji dolerites, respectively. Those data are indistinguishable from new and/or published U-Pb and 40Ar/39Ar plagioclase ages showing that 40Ar/39Ar dating of pyroxene is a suitable geochronological tool. Scrutinizing the analytical results of the pyroxene analyses as well as comparing them to the analytical result from plagioclase of the same samples indicate pure pyroxene was dated. Numerical models of argon diffusion in plagioclase and pyroxene support these observations. However, we found that the viability of 40Ar/39Ar dating approach of pyroxene can be affected by irradiation-induced recoil redistribution between thin pyroxene exsolution lamellae and the main pyroxene crystal, hence requiring careful petrographic observations before analysis. Finally, diffusion modeling show that 40Ar/39Ar of pyroxene can be used as a powerful tool to date the formation age of mafic

  5. Chimera states in brain networks: Empirical neural vs. modular fractal connectivity (United States)

    Chouzouris, Teresa; Omelchenko, Iryna; Zakharova, Anna; Hlinka, Jaroslav; Jiruska, Premysl; Schöll, Eckehard


    Complex spatiotemporal patterns, called chimera states, consist of coexisting coherent and incoherent domains and can be observed in networks of coupled oscillators. The interplay of synchrony and asynchrony in complex brain networks is an important aspect in studies of both the brain function and disease. We analyse the collective dynamics of FitzHugh-Nagumo neurons in complex networks motivated by its potential application to epileptology and epilepsy surgery. We compare two topologies: an empirical structural neural connectivity derived from diffusion-weighted magnetic resonance imaging and a mathematically constructed network with modular fractal connectivity. We analyse the properties of chimeras and partially synchronized states and obtain regions of their stability in the parameter planes. Furthermore, we qualitatively simulate the dynamics of epileptic seizures and study the influence of the removal of nodes on the network synchronizability, which can be useful for applications to epileptic surgery.

  6. What do we really know about 5-HT1A receptor signaling in neuronal cells?

    Directory of Open Access Journals (Sweden)



    Full Text Available Serotonin (5-HT is a neurotransmitter that plays an important role in neuronal plasticity. Variations in the levels of 5-HT at the synaptic cleft, expression or dysfunction of serotonin receptors may alter brain development and predispose to various mental diseases. Here, we review the transduction pathways described in various cell types transfected with recombinant 5-HT1A receptor (5-HT1AR, specially contrasting with those findings obtained in neuronal cells. The 5-HT1AR is detected in early stages of neural development and is located in the soma, dendrites and spines of hippocampal neurons. The 5-HT1AR differs from other serotonin receptors because it is coupled to different pathways, depending on the targeted cell. The signaling pathway associated with this receptor is determined by Gα isoforms and some cascades involve βγ signaling. The activity of 5-HT1AR usually promotes a reduction in neuronal excitability and firing, provokes a variation in cAMP and Ca2+, levels which may be linked to specific types of behavior and cognition. Furthermore, evidence indicates that 5-HT1AR induces neuritogesis and synapse formation, probably by modulation of the neuronal cytoskeleton through MAPK and PI3K-Akt signaling pathways. Advances in understanding the actions of 5-HT1AR and its association with different signaling pathways in the central nervous system will reveal their pivotal role in health and disease.

  7. Generation of axolotl hematopoietic chimeras

    Directory of Open Access Journals (Sweden)

    David Lopez


    Full Text Available Wound repair is an extremely complex process that requires precise coordination between various cell types including immune cells.  Unfortunately, in mammals this usually results in scar formation instead of restoration of the original fully functional tissue, otherwise known as regeneration.  Various animal models like frogs and salamanders are currently being studied to determine the intracellular and intercellular pathways, controlled by gene expression, that elicit cell proliferation, differentiation, and migration of cells during regenerative healing.  Now, the necessary genetic tools to map regenerative pathways are becoming available for the axolotl salamander, thus allowing comparative studies between scarring and regeneration.  Here, we describe in detail three methods to produce axolotl hematopoietic cell-tagged chimeras for the study of hematopoiesis and regeneration.

  8. Autoantibody detection in type 2 autoimmune hepatitis using a chimera recombinant protein. (United States)

    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Alvarez, Fernando


    Autoantibodies against cytochrome P450 2D6 (CYP2D6), known as anti-liver/kidney microsome type 1 (LKM1) and/or anti-human formiminotransferase cyclodeaminase, formally known as anti-liver cytosol type 1 (LC1) define type 2 autoimmune hepatitis (AIH). The aims of this work are to develop a sensitive and specific test to detect anti-LKM1 and/or anti-LC1 autoantibodies and to establish the prevalence of anti-LC1. Sera from children with type 2 AIH (n=48) and those from a control group (n=100) were evaluated for anti-LKM1 and anti-LC1 by Enzyme-Linked Immunosorbent Assay (ELISA) and Western blotting. Each serum sample was assayed for reactivity against formiminotransferase cyclodeaminase and CYP2D6 alone or as part of a recombinant chimera protein. By ELISA with recombinant chimera protein, 50 serum samples were positive, 48 from patients with type 2 AIH and 2 from patients with chronic hepatitis C. Twenty-five of 48 (52%) patients studied were positive for both CYP2D6 and LC1 autoantibodies. Anti-LC1, either as the only marker or associated with anti-LKM1, was positive in 34/48 (71%). By Western blotting, anti-LC1 was found in 27/48 (56%) patients. This ELISA technique has proven to be antigen-specific and more sensitive than Western blot for the detection of anti-LC1 and anti-LKM1 autoantibodies. The prevalence of anti-LC1 (71%) confirms it as an important immunomarker in type 2 AIH.

  9. A 3-D chimera grid embedding technique (United States)

    Benek, J. A.; Buning, P. G.; Steger, J. L.


    A three-dimensional (3-D) chimera grid-embedding technique is described. The technique simplifies the construction of computational grids about complex geometries. The method subdivides the physical domain into regions which can accommodate easily generated grids. Communication among the grids is accomplished by interpolation of the dependent variables at grid boundaries. The procedures for constructing the composite mesh and the associated data structures are described. The method is demonstrated by solution of the Euler equations for the transonic flow about a wing/body, wing/body/tail, and a configuration of three ellipsoidal bodies.

  10. 40Ar/39Ar studies of deep sea igneous rocks

    International Nuclear Information System (INIS)

    Seidemann, D.


    An attempt to date deep-sea igneous rocks reliably was made using the 40 Ar/ 39 Ar dating technique. It was determined that the 40 Ar/ 39 Ar incremental release technique could not be used to eliminate the effects of excess radiogenic 40 Ar in deep-sea basalts. Excess 40 Ar is released throughout the extraction temperature range and cannot be distinguished from 40 Ar generated by in situ 40 K decay. The problem of the reduction of K-Ar dates associated with sea water alteration of deep-sea igneous rocks could not be resolved using the 40 Ar/ 39 Ar technique. Irradiation induced 39 Ar loss and/or redistribution in fine-grained and altered igneous rocks results in age spectra that are artifacts of the experimental procedure and only partly reflect the geologic history of the sample. Therefore, caution must be used in attributing significance to age spectra of fine grained and altered deep-sea igneous rocks. Effects of 39 Ar recoil are not important for either medium-grained (or coarser) deep-sea rocks or glasses because only a small fraction of the 39 Ar recoils to channels of easy diffusion, such as intergranular boundaries or cracks, during the irradiation. (author)

  11. Stable Chimeras and Independently Synchronizable Clusters (United States)

    Cho, Young Sul; Nishikawa, Takashi; Motter, Adilson E.


    Cluster synchronization is a phenomenon in which a network self-organizes into a pattern of synchronized sets. It has been shown that diverse patterns of stable cluster synchronization can be captured by symmetries of the network. Here, we establish a theoretical basis to divide an arbitrary pattern of symmetry clusters into independently synchronizable cluster sets, in which the synchronization stability of the individual clusters in each set is decoupled from that in all the other sets. Using this framework, we suggest a new approach to find permanently stable chimera states by capturing two or more symmetry clusters—at least one stable and one unstable—that compose the entire fully symmetric network.

  12. Sedimentary cycles and volcanic ash beds in the Lower Pliocene lacustrine succession of Ptolemais (NW Greece): discrepancy between 40 Ar/39 Ar and astronomical ages

    NARCIS (Netherlands)

    Steenbrink, J.; Vugt, N. van; Hilgen, F.J.; Wijbrans, J.R.; Meulenkamp, J.E.


    A high-resolution cyclostratigraphy for the rhythmically bedded lignite-marl sequences of the Lower Pliocene Ptole-mais Formation is combined with 40 Ar= 39 Ar dating results of intercalated volcanic ash beds. Detailed field reconnaissance in three open-pit lignite mines reveals three end-member

  13. Geological Dating by 40 Ar - 39 Ar method

    International Nuclear Information System (INIS)

    Vollbert Romero, M.E.


    The isotope 40 K is radioactive, it decays to 40 Ar stable. The number of 40 Ar atoms produced from 40 K, permits to calculate the date of rocks and minerals. This dating technique is named 'Conventional K-Ar Dating Method'. The 40 Ar - 39 Ar dating method permits to calculate the age of rocks and minerals eliminating the limitation of the K-Ar method by calculating potassium and argon concentrations in a single measurement of the ratio of argon isotopes. In this work, the irradiation of the sample with fast neutrons in the nuclear reactor was established. 39 Ar is obtained from the induced reaction 39 K (n,p) 39 Ar. Thus the ration of 40 Ar - 39 Ar allows to obtain the date of rocks and minerals. This ratio was measured in a mass spectrometer. If the measurement of argon concentration in the sample is carried out at different increasing temperature values, it is possible to get information of paleotemperatures. The number of atoms 39 Ar is a function of the number 39 K atoms, irradiation time, neutrons flux, its energy E and the capture cross section σ of 39 K. These parameters are calculate indirectly by obtaining the so called 'J value ' by using a standard mineral with known age (HD-BI y Biot-133), this mineral is irradiated together with the unknown age sample. The values of 'J' obtained are in the interval of 2.85 a 3.03 (x 10 - 3)J/h. Rocks from 'Tres Virgenes' were dated by the method described in this work, showing an agreement with previous values of different authors. The age of this rocks are from Cenozoico era, mainly in the miocene period. (Author)

  14. Dual Functions of the C5a Receptor as a Connector for the K562 Erythroblast-Like Cell-THP-1 Macrophage-Like Cell Island and as a Sensor for the Differentiation of the K562 Erythroblast-Like Cell during Haemin-Induced Erythropoiesis

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura


    Full Text Available The transcriptional nuclear factor binding to the Y box of human leukocyte antigen genes (NF-Y for the C5a receptor (C5aR gene is active in erythroblasts. However, the roles of the C5aR in erythropoiesis are unclear. We have previously demonstrated that apoptotic cell-derived ribosomal protein S19 (RP S19 oligomers exhibit extraribosomal functions in promoting monocyte chemotaxis and proapoptosis via the C5aR without receptor internalisation. In contrast to the extraribosomal functions of the RP S19, a proapoptotic signal in pro-EBs, which is caused by mutations in the RP S19 gene, is associated with the inherited erythroblastopenia, Diamond-Blackfan anaemia. In this study, we detected C5aR expression and RP S19 oligomer generation in human erythroleukemia K562 cells during haemin-induced erythropoiesis. Under monocell culture conditions, the differentiation into K562 erythrocyte-like cells was enhanced following the overexpression of Wild-type RP S19. Conversely, the differentiation was repressed following the overexpression of mutant RP S19. An RP S19 oligomer inhibitor and a C5aR inhibitor blocked the association of the K562 basophilic EB-like cells and the THP-1 macrophage-like cells under coculture conditions. When bound to RP S19 oligomers, the C5aR may exhibit dual functions as a connector for the EB-macrophage island and as a sensor for EB differentiation in the bone marrow.

  15. Icing modelling in NSMB with chimera overset grids

    Energy Technology Data Exchange (ETDEWEB)

    Pena, D. [Ècole Polytechnique de Montréal (Canada); ICUBE, Strasbourg University (France); Deloze, T.; Laurendeau, E. [Ècole Polytechnique de Montréal (Canada); Hoarau, Y. [ICUBE, Strasbourg University (France)


    In aerospace Engineering, the accurate simulation of ice accretion is a key element to increase flight safety and avoid accidents related to icing effects. The icing code developed in the NSMB solver is based on an Eulerian formulation for droplets tracking, an iterative Messinger model using a modified water runback scheme for ice thickness calculation and mesh deformation to track the ice/air interface through time. The whole process is parallelized with MPI and applied with chimera grids.

  16. Study of the excitation mechanisms of the second positive system in the negative glow of a N2-Ar discharge

    International Nuclear Information System (INIS)

    Isola, L; Lopez, M; Gomez, B J


    In an Ar-N 2 discharge, the high excitation transfer from Ar( 3 P 2,0 ) to N 2 produces an overpopulation of the high rotational levels of the bands of the second positive system (SPS), and so the spectra interpretation is not straightforward. This paper presents a fit function for the SPS bands measured in Ar-N 2 , which allows us to study the excitation process contributions to the N 2 (C) level. The procedure was tested in the negative glow of a pulsed Ar-N 2 discharge at a pressure of 2.5 Torr, for different mixture concentrations. In this discharge, through the fitting, it was possible to calculate the variation of the N 2 (C) densities produced by different excitation processes as well as the variation of Ar metastable density.

  17. Selective Etching of Silicon in Preference to Germanium and Si0.5Ge0.5. (United States)

    Ahles, Christopher F; Choi, Jong Youn; Wolf, Steven; Kummel, Andrew C


    The selective etching characteristics of silicon, germanium, and Si 0.5 Ge 0.5 subjected to a downstream H 2 /CF 4 /Ar plasma have been studied using a pair of in situ quartz crystal microbalances (QCMs) and X-ray photoelectron spectroscopy (XPS). At 50 °C and 760 mTorr, Si can be etched in preference to Ge and Si 0.5 Ge 0.5 , with an essentially infinite Si/Ge etch-rate ratio (ERR), whereas for Si/Si 0.5 Ge 0.5 , the ERR is infinite at 22 °C and 760 mTorr. XPS data showed that the selectivity is due to the differential suppression of etching by a ∼2 ML thick C x H y F z layer formed by the H 2 /CF 4 /Ar plasma on Si, Ge, and Si 0.5 Ge 0.5 . The data are consistent with the less exothermic reaction of fluorine radicals with Ge or Si 0.5 Ge 0.5 being strongly suppressed by the C x H y F z layer, whereas, on Si, the C x H y F z layer is not sufficient to completely suppress etching. Replacing H 2 with D 2 in the feed gas resulted in an inverse kinetic isotope effect (IKIE) where the Si and Si 0.5 Ge 0.5 etch rates were increased by ∼30 times with retention of significant etch selectivity. The use of D 2 /CF 4 /Ar instead of H 2 /CF 4 /Ar resulted in less total carbon deposition on Si and Si 0.5 Ge 0.5 and gave less Ge enrichment of Si 0.5 Ge 0.5 . These results are consistent with the selectivity being due to the differential suppression of etching by an angstrom-scale carbon layer.

  18. Influence of annealing temperature on physical properties and photocatalytic ability of g-C3N4 nanosheets synthesized through urea polymerization in Ar atmosphere (United States)

    Mai Oanh, Le Thi; Hang, Lam Thi; Lai, Ngoc Diep; Phuong, Nguyen Thi; Thang, Dao Viet; Hung, Nguyen Manh; Danh Bich, Do; Minh, Nguyen Van


    The influences of annealing temperature on structure, morphology, vibration, optical properties and photocatalytic ability of g-C3N4 nanosheets synthesized from urea in Ar atmosphere were investigated in detail by using x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET), Fourier transform infrared spectroscopy (FTIR), UV-vis absorption, and photoluminescence (PL). It was found that the preparation temperature had a great effect on structure and physical properties of g-C3N4. As the processing temperature increased from 450 °C to 650 °C, the interlayer stacking distance of g-C3N4 decreased from 3.281 Å to 3.217 Å and the lattice parameter a decreased from 5.010 Å to 4.934 Å. This indicated a denser packing fashion of g-C3N4 at high annealing temperature. Moreover, the FTIR spectra and SEM images revealed a large fraction of small polymer segments containing only a few heptazine units as annealing temperature increased. BET result indicated an increasing specific surface area as preparation temperature increased. UV-vis absorption spectra showed a decrease of the band gap energy with increasing calcination temperature which agrees well with the measured PL spectra. It was demonstrated that samples annealed at 550 °C exhibited the strongest photocatalytic activity. A decomposition of 80% and 100% of rhodamine B was obtained within respectively 1 h and 2 h under Xenon lamp irradiation. Photocatalytic result could be adequately explained based on evidences of specific surface area, average pore volume and pore size, and recombination rate of photoinduced electron-hole pairs.

  19. The contribution of human/non-human animal chimeras to stem cell research. (United States)

    Levine, Sonya; Grabel, Laura


    Chimeric animals are made up of cells from two separate zygotes. Human/non-human animal chimeras have been used for a number of research purposes, including human disease modeling. Pluripotent stem cell (PSC) research has relied upon the chimera approach to examine the developmental potential of stem cells, to determine the efficacy of cell replacement therapies, and to establish a means of producing human organs. Based on ethical issues, this work has faced pushback from various sources including funding agencies. We discuss here the essential role these studies have played, from gaining a better understanding of human biology to providing a stepping stone to human disease treatments. We also consider the major ethical issues, as well as the current status of support for this work in the United States. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Numerical solution of the full potential equation using a chimera grid approach (United States)

    Holst, Terry L.


    A numerical scheme utilizing a chimera zonal grid approach for solving the full potential equation in two spatial dimensions is described. Within each grid zone a fully-implicit approximate factorization scheme is used to advance the solution one interaction. This is followed by the explicit advance of all common zonal grid boundaries using a bilinear interpolation of the velocity potential. The presentation is highlighted with numerical results simulating the flow about a two-dimensional, nonlifting, circular cylinder. For this problem, the flow domain is divided into two parts: an inner portion covered by a polar grid and an outer portion covered by a Cartesian grid. Both incompressible and compressible (transonic) flow solutions are included. Comparisons made with an analytic solution as well as single grid results indicate that the chimera zonal grid approach is a viable technique for solving the full potential equation.

  1. 40Ar/39Ar dating of the Mumbai tholeiites and Panvel flexure: intense 62.5 Ma onshore-offshore Deccan magmatism during India-Laxmi Ridge-Seychelles breakup (United States)

    Pande, Kanchan; Yatheesh, Vadakkeyakath; Sheth, Hetu


    Mumbai, located on the western Indian continental margin, exposes Danian-age Deccan magmatic units of diverse compositions, dipping seaward due to the Panvel flexure. The Ghatkopar-Powai tholeiitic sequence contains seaward-dipping (thus pre-flexure) flows and subvertical (thus post-flexure) dykes. We present new 40Ar/39Ar ages of 62.4 ± 0.7 and 62.4 ± 0.3 Ma (2σ) on two flows, and 62.2 ± 0.3, 62.8 ± 0.3 and 61.8 ± 0.2 Ma on three dykes, showing that this sequence is much younger than the main 66-65 Ma Deccan sequence in the Western Ghats escarpment. The mutually indistinguishable ages of the Ghatkopar-Powai tholeiites overlap with available 40Ar/39Ar ages of 62.6 ± 0.6 and 62.9 ± 0.2 Ma for the seaward-dipping Dongri rhyolite flow and 62.2 ± 0.6 Ma for the Saki Naka trachyte intrusion, both from the uppermost Mumbai stratigraphy. The weighted mean of these eight 40Ar/39Ar ages is 62.4 ± 0.1 Ma (2 SEM), relative to an MMhb-1 monitor age of 523.1 ± 2.6 Ma (2σ), and indicates essentially contemporaneous volcanism, intrusion and tectonic flexure. This age also coincides with the rift-to-drift transition of the Seychelles and Laxmi Ridge-India breakup and the emplacement of the Raman-Panikkar-Wadia seamount chain in the axial part of the Laxmi Basin. Pre-rift magmatism is seen in the 64.55 Ma Jogeshwari basalt in Mumbai and 63.5-63.0 Ma intrusions in the Seychelles. Post-rift magmatism is seen in the 60.8-60.9 Ma Manori trachyte and Gilbert Hill basalt intrusions in Mumbai and 60-61 Ma syenitic intrusions in the Seychelles. The Mumbai area thus preserves the pre-, syn- and post-rift onshore tectonomagmatic record of the breakup between the Seychelles and the Laxmi Ridge-India. Voluminous submarine volcanism forming the Raman, Panikkar and Wadia seamounts in the Laxmi Basin represents the offshore syn-rift magmatism.

  2. Experimental system to measure excitation cross-sections by electron impact. Measurements for ArI and ArII

    International Nuclear Information System (INIS)

    Blanco, F.; Sanchez, J.A.; Aguilera, J.A.; Campos, J.


    An experimental set-up to measure excitation cross-section of atomic and molecular levels by electron impact based on the optical method is reported. We also present some measurements on the excitation cross-section for ArI 5p'(1/2)0 level, and for simultaneous ionization and excitation of Ar leading to ArII levels belonging to the 3p 4 4p and 3p 4 4d configurations. (Author)

  3. Standardization of 40Ar-39Ar dating facility at KDMIPE, ONGC, Dehradun

    International Nuclear Information System (INIS)

    Rathore, S.S.; Singh, M.P.; Vijan, A.R.; Bansal, M.; Prabhu, B.N.; Misra, K.N.


    In the pursuit of acquiring state of the art technology, efforts were being made for last more than two years to establish 40 Ar- 39 Ar dating facility at KDMIPE. The 40 Ar- 39 Ar dating technique is an analytical conversion of the conventional K-Ar dating method. In this method, the sample to be dated is first irradiated in a nuclear reactor to transform a portion of 39 K to 39 Ar by the fast neutron reaction i.e. 39 K(n, p) 39 Ar. After irradiation, the sample is placed in an ultra-high vacuum system and the argon extracted from it by fusion is purified and analyzed isotopically in a mass spectrometer. The relative abundances of 40 Ar, 39 Ar, 37 Ar and 36 Ar are measured. The 40 Ar/ 39 Ar K is determined, where 40 Ar is the radiogenic argon, and 39 Ar K is the 39 Ar produced from 39 K during the irradiation. The 40 Ar/ 39 Ar K ratio is proportional to the 40 Ar/ 40 K ratio in the sample and, therefore, is proportional to age

  4. Parallel detection, quantification, and depth profiling of peptides with dynamic-secondary ion mass spectrometry (D-SIMS) ionized by C{sub 60}{sup +}-Ar{sup +} co-sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Chi-Jen [Department of Materials Science and Engineering, National Taiwan University, Taipei 106, Taiwan (China); Chang, Hsun-Yun; You, Yun-Wen; Liao, Hua-Yang [Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan (China); Kuo, Yu-Ting; Kao, Wei-Lun; Yen, Guo-Ji; Tsai, Meng-Hung [Department of Materials Science and Engineering, National Taiwan University, Taipei 106, Taiwan (China); Shyue, Jing-Jong, E-mail: [Department of Materials Science and Engineering, National Taiwan University, Taipei 106, Taiwan (China); Research Center for Applied Sciences, Academia Sinica, Taipei 115, Taiwan (China)


    Highlights: Black-Right-Pointing-Pointer Multiple peptides are detected and quantified at the same time without labeling. Black-Right-Pointing-Pointer C{sub 60}{sup +} ion is responsible for generating molecular-specific ions at high mass. Black-Right-Pointing-Pointer The co-sputtering yielded more steady depth profile and more well defined interface. Black-Right-Pointing-Pointer The fluence of auxiliary Ar{sup +} does not affect the quantification curve. Black-Right-Pointing-Pointer The damage from Ar{sup +} is masked by high sputtering yield of C{sub 60}{sup +}. - Abstract: Time-of-flight secondary ion mass spectrometry (ToF-SIMS) using pulsed C{sub 60}{sup +} primary ions is a promising technique for analyzing biological specimens with high surface sensitivities. With molecular secondary ions of high masses, multiple molecules can be identified simultaneously without prior separation or isotope labeling. Previous reports using the C{sub 60}{sup +} primary ion have been based on static-SIMS, which makes depth profiling complicated. Therefore, a dynamic-SIMS technique is reported here. Mixed peptides in the cryoprotectant trehalose were used as a model for evaluating the parameters that lead to the parallel detection and quantification of biomaterials. Trehalose was mixed separately with different concentrations of peptides. The peptide secondary ion intensities (normalized with respect to those of trehalose) were directly proportional to their concentration in the matrix (0.01-2.5 mol%). Quantification curves for each peptide were generated by plotting the percentage of peptides in trehalose versus the normalized SIMS intensities. Using these curves, the parallel detection, identification, and quantification of multiple peptides was achieved. Low energy Ar{sup +} was used to co-sputter and ionize the peptide-doped trehalose sample to suppress the carbon deposition associated with C{sub 60}{sup +} bombardment, which suppressed the ion intensities during the depth

  5. Production and evaluation of a recombinant chimeric vaccine against clostridium botulinum neurotoxin types C and D.

    Directory of Open Access Journals (Sweden)

    Luciana A F Gil

    Full Text Available Bovine botulism is a fatal disease that is caused by botulinum neurotoxins (BoNTs produced by Clostridium botulinum serotypes C and D and that causes great economic losses, with nearly 100% lethality during outbreaks. It has also been considered a potential source of human food-borne illness in many countries. Vaccination has been reported to be the most effective way to control bovine botulism. However, the commercially available toxoid-based vaccines are difficult and hazardous to produce. Neutralizing antibodies targeted against the C-terminal fragment of the BoNT heavy chain (HC are known to confer efficient protection against lethal doses of BoNTs. In this study, a novel recombinant chimera, consisting of Escherichia coli heat-labile enterotoxin B subunit (LTB, a strong adjuvant of the humoral immune response, fused to the HC of BoNT serotypes C and D, was produced in E. coli. Mice vaccinated with the chimera containing LTB and an equivalent molar ratio of the chimera without LTB plus aluminum hydroxide (Al(OH3 developed 2 IU/mL of antitoxins for both serotypes. Guinea pigs immunized with the recombinant chimera with LTB plus Al(OH3 developed a protective immune response against both BoNT/C (5 IU/mL and BoNT/D (10 IU/mL, as determined by a mouse neutralization bioassay with pooled sera. The results achieved with guinea pig sera fulfilled the requirements of commercial vaccines for prevention of botulism, as determined by the Brazilian Ministry of Agriculture, Livestock and Food, Supply. The presence of LTB was essential for the development of a strong humoral immune response, as it acted in synergism with Al(OH3. Thus, the vaccine described in this study is a strong candidate for the control of botulism in cattle.

  6. Complement C3a binding to its receptor as a negative modulator of Th2 response in liver injury in trichloroethylene-sensitized mice. (United States)

    Wang, Feng; Zha, Wan-sheng; Zhang, Jia-xiang; Li, Shu-long; Wang, Hui; Ye, Liang-ping; Shen, Tong; Wu, Chang-hao; Zhu, Qi-xing


    Trichloroethylene (TCE) is a major occupational health hazard and causes occupational medicamentosa-like dermatitis (OMLDT) and liver damage. Recent evidence suggests immune response as a distinct mode of action for TCE-induced liver damage. This study aimed to explore the role of the key complement activation product C3a and its receptor C3aR in TCE-induced immune liver injury. A mouse model of skin sensitization was induced by TCE in the presence and absence of the C3aR antagonist SB 290157. Liver function was evaluated by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in conjunction with histopathological characterizations. C3a and C3aR were detected by immunohistochemistry and C5b-9 was assessed by immunofluorescence. IFN-γ and IL4 expressions were determined by flow cytometry and ELISA. The total sensitization rate was 44.1%. TCE sensitization caused liver cell necrosis and inflammatory infiltration, elevated serum ALT and AST, expression of C3a and C3aR, and deposition of C5b-9 in the liver. IFN-γ and IL-4 expressions were up-regulated in spleen mononuclear cells and their serum levels were also increased. Pretreatment with SB 290157 resulted in more inflammatory infiltration in the liver, higher levels of AST, reduced C3aR expression on Kupffer cells, and decreased IL-4 levels while IFN-γ remained unchanged. These data demonstrate that blocking of C3a binding to C3aR reduces IL4, shifts IFN-γ and IL-4 balance, and aggravates TCE-sensitization induced liver damage. These findings reveal a novel mechanism whereby modulation of Th2 response by C3a binding to C3a receptor contributes to immune-mediated liver damage by TCE exposure. Copyright © 2014. Published by Elsevier Ireland Ltd.

  7. De novo generation of helper virus-satellite chimera RNAs results in disease attenuation and satellite sequence acquisition in a host-dependent manner. (United States)

    Pyle, J D; Scholthof, Karen-Beth G


    Panicum mosaic virus (PMV) is a helper RNA virus for satellite RNAs (satRNAs) and a satellite virus (SPMV). Here, we describe modifications that occur at the 3'-end of a satRNA of PMV, satS. Co-infections of PMV+satS result in attenuation of the disease symptoms induced by PMV alone in Brachypodium distachyon and proso millet. The 375 nt satS acquires ~100-200 nts from the 3'-end of PMV during infection and is associated with decreased abundance of the PMV RNA and capsid protein in millet. PMV-satS chimera RNAs were isolated from native infections of St. Augustinegrass and switchgrass. Phylogenetic analyses revealed that the chimeric RNAs clustered according to the host species from which they were isolated. Additionally, the chimera satRNAs acquired non-viral "linker" sequences in a host-specific manner. These results highlight the dynamic regulation of viral pathogenicity by satellites, and the selective host-dependent, sequence-based pressures for driving satRNA generation and genome compositions. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Androgen-Sensitized Apoptosis of HPr-1AR Human Prostate Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Congcong Chen

    Full Text Available Androgen receptor (AR signaling is crucial to the development and homeostasis of the prostate gland, and its dysregulation mediates common prostate pathologies. The mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells have been investigated in human and rodent adult prostate. However, the cellular stress response of human prostate epithelial cells is not well understood, though it is central to prostate health and pathology. Here, we report that androgen sensitizes HPr-1AR and RWPE-AR human prostate epithelial cells to cell stress agents and apoptotic cell death. Although 5α-dihydrotestosterone (DHT treatment alone did not induce cell death, co-treatment of HPr-1AR cells with DHT and an apoptosis inducer, such as staurosporine (STS, TNFt, or hydrogen peroxide, synergistically increased cell death in comparison to treatment with each apoptosis inducer by itself. We found that the synergy between DHT and apoptosis inducer led to activation of the intrinsic/mitochondrial apoptotic pathway, which is supported by robust cleavage activation of caspase-9 and caspase-3. Further, the dramatic depolarization of the mitochondrial membrane potential that we observed upon co-treatment with DHT and STS is consistent with increased mitochondrial outer membrane permeabilization (MOMP in the pro-apoptotic mechanism. Interestingly, the synergy between DHT and apoptosis inducer was abolished by AR antagonists and inhibitors of transcription and protein synthesis, suggesting that AR mediates pro-apoptotic synergy through transcriptional regulation of MOMP genes. Expression analysis revealed that pro-apoptotic genes (BCL2L11/BIM and AIFM2 were DHT-induced, whereas pro-survival genes (BCL2L1/BCL-XL and MCL1 were DHT-repressed. Hence, we propose that the net effect of these AR-mediated expression changes shifts the balance of BCL2-family proteins

  9. The ethics of killing human/great-ape chimeras for their organs: a reply to Shaw et al. (United States)

    Palacios-González, César


    The aim of this paper is to critically examine David Shaw, Wybo Dondorp, and Guido de Wert's arguments in favour of the procurement of human organs from human/nonhuman-primate chimeras, specifically from great-ape/human chimeras. My main claim is that their arguments fail and are in need of substantial revision. To prove this I first introduce the topic, and then reconstruct Shaw et al.'s position and arguments. Next, I show that Shaw et al.: (1) failed to properly apply the subsidiarity and proportionality principles; (2) neglected species overlapping cases in their ethical assessment; (3) ignored the ethics literature on borderline persons; and (4) misunderstood McMahan's two-tiered moral theory. These mistakes render an important part of their conclusions either false or problematic to the point that they would no longer endorse them. Finally I will briefly mention a possible multipolar solution to the human organ shortage problem that would reduce the need for chimeras' organs.

  10. Interatomic scattering in energy dependent photoelectron spectra of Ar clusters

    Energy Technology Data Exchange (ETDEWEB)

    Patanen, M.; Benkoula, S.; Nicolas, C.; Goel, A. [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex (France); Antonsson, E. [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex (France); Physikalische und Theoretische Chemie Institut für Chemie und Biochemie, Fachbereich Biologie, Chemie, Pharmazie, Freie Universität Berlin, Takustrasse 3, 14195 Berlin (Germany); Neville, J. J. [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex (France); Department of Chemistry, University of New Brunswick, Fredericton, New Brunswick E3B 6E2 (Canada); Miron, C., E-mail: [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex (France); Extreme Light Infrastructure - Nuclear Physics (ELI-NP), ‘Horia Hulubei’ National Institute for Physics and Nuclear Engineering, 30 Reactorului Street, RO-077125 Măgurele, Jud. Ilfov (Romania)


    Soft X-ray photoelectron spectra of Ar 2p levels of atomic argon and argon clusters are recorded over an extended range of photon energies. The Ar 2p intensity ratios between atomic argon and clusters’ surface and bulk components reveal oscillations similar to photoelectron extended X-ray absorption fine structure signal (PEXAFS). We demonstrate here that this technique allows us to analyze separately the PEXAFS signals from surface and bulk sites of free-standing, neutral clusters, revealing a bond contraction at the surface.

  11. Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells. (United States)

    Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G


    Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. 40Ar/39Ar dating and zircon chronochemistry for the Izu-Bonin rear arc, IODP site U1437 (United States)

    Schmitt, A. K.; Konrad, K.; Andrews, G. D.; Horie, K.; Brown, S. R.; Koppers, A. A. P.; Busby, C.; Tamura, Y.


    The scientific objective of IODP Expedition 350 drilling at Site U1437 (31°47.390'N, 139°01.580'E) was to reveal the "missing half of the subduction factory": the rear arc of a long-lived intraoceanic subduction zone. Site U1437 lies in a 50 km long and 20 km wide volcano-bounded basin, 90 km west of the Izu arc front, and is the only IODP site drilled in the rear arc. The Izu rear arc is dominated by Miocene basaltic to dacitic seamount chains, which strike at a high angle to the arc front. Radiometric dating targeted a single igneous unit (1390 mbsf), and fine to coarse volcaniclastic units for which we present zircon and 40Ar/39Ar (hornblende, plagioclase, and groundmass) age determinations. All zircons analyzed as grain separates were screened for contamination from drill-mud (Andrews et al., 2016) by analyzing trace elements and, where material was available, O and Hf isotope compositions. Igneous Unit 1 is a rhyolite sheet and yielded concordant in-situ and crystal separate U-Pb zircon ages (13.7±0.3 Ma; MSWD = 1.3; n = 40 spots), whereas the 40Ar/39Ar hornblende plateau age (12.9±0.3; MSWD = 1.1; n = 9 steps) is slightly younger, possibly reflecting pre-eruptive zircon crystallization, or alteration of hornblende. U-Pb zircon and 40Ar/39Ar plateau ages from samples above igneous Unit 1 are concordant with biostratigraphic and paleomagnetic ages (available to 1300 mbsf), but plagioclase and groundmass samples below 1300 m become younger with depth, hinting at post-depositional alteration. A single zircon from 1600 mbsf yielded a U-Pb age of 15.4±1.8 Ma; its trace element composition resembles other igneous zircons from U1437, and is tentatively interpreted as a Middle Miocene age for the lowermost lithostratigraphic unit VII. Oxygen and Hf isotopic values of igneous zircon indicate mantle origins, with some influence of assimilation of hydrothermally altered oceanic crust evident in sub-mantle oxygen isotopic compositions. Lessons from site U1437 are

  13. 40Ar/39Ar and K/Ar whole rock age constraints on the timing of regional deformation, South Coast of New South Wales, Lachlan Fold Belt, Southeastern Australia: problems and implications

    International Nuclear Information System (INIS)

    Phillips, D.; Fergusson, C.L.


    mellange and intensely cleaved slate have been analysed and have 40 Ar/ 39 Ar integrated ages of 422 ± 2 Ma (K/Ar: 424 ± 5 Ma) and 415 ± 2 Ma (K/Ar: 400 ± 5 Ma). The general consistency of these results accompanied by microstructural observation indicating a low abundance of detrital mica, show that in these samples recoil and inheritance problems appear to be less important. Thus they provide a more reliable upper constraint on the timing the regional deformation on the south coast of New South Wales, i.e. younger than ca. 420 Ma, consistent with previously recognised regional structural constraints. Elsewhere in the Lachlan Fold Belt 40 Ar/ 39 Ar ages on fine-grained slates have been used to provide concise constraints on the timing of deformation. The current results raise serious questions about the interpretation of these ages as representing on-going deformation and therefore tectonic models derived from these data should be treated with caution. Copyright (1999) Geological Society of Australia

  14. Novel type of chimera spiral waves arising from decoupling of a diffusible component

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Xiaodong; Yang, Tao; Liu, Yang; Zhao, Yuemin; Gao, Qingyu, E-mail:, E-mail: [College of Chemical Engineering, China University of Mining and Technology, Xuzhou 221008 (China); Epstein, Irving R., E-mail:, E-mail: [Department of Chemistry and Volen Center for Complex Systems, MS 015, Brandeis University, Waltham, Massachusetts 02454-9110 (United States)


    Spiral waves composed of coherent traveling waves surrounding a core containing stochastically distributed stationary areas are found in numerical simulations of a three-variable reaction-diffusion system with one diffusible species. In the spiral core, diffusion of this component (w) mediates transitions between dynamic states of the subsystem formed by the other two components, whose dynamics is more rapid than that of w. Diffusive coupling between adjacent sites can be “on” or “off” depending on the subsystem state. The incoherent structures in the spiral core are produced by this decoupling of the slow diffusive component from the fast non-diffusing subsystem. The phase diagram reveals that the region of incoherent behavior in chimera spirals grows drastically, leading to modulation and breakup of the spirals, in the transition zones between 1{sup n-1} and 1{sup n} local mixed-mode oscillations.

  15. The mass of sup 3 sup 2 Ar and sup 3 sup 3 Ar for fundamental tests

    CERN Document Server

    Blaum, K; Beck, D; Bollen, G; Herfurth, F; Kellerbauer, A G; Kluge, H J; Sauvan, E; Schwarz, S


    Masses of the short-lived radionuclides sup 3 sup 2 Ar (T sub 1 sub / sub 2 = 98 ms) sup 3 sup 3 Ar (T sub 1 sub / sub 2 = 173 ms) have been determined with the Penning trap mass spectrometer ISOLTRAP. Relative uncertainties of 6.0 x 10 sup - sup 8 (delta m = 1.8 keV) and 1.4 x 10 sup - sup 8 (delta m = 0.44 keV), respectively, have been achieved. At present, these new mass data serve as the most stringent test of the quadratic form of the isobaricmultiplet mass equation IMME. Furthermore, the improved accuracy for the mass of sup 3 sup 2 Ar yields a better constraint on scalar contributions to the weak interaction. New mass values have also been measured for sup 4 sup 4 Ar and sup 4 sup 5 Ar, and a 20 sigma deviation for sup 4 sup 4 Ar from the literature value was found and interpreted.

  16. Electron excitation cross sections for some Ar I 5d (J = 2) levels

    International Nuclear Information System (INIS)

    Blanco, F.; Sanchez, J.A.; Campos, J.


    Absolute excitation cross sections by electron impact for some 5d levels with J = 2 of Ar I have been measured by the optical method. Excitation functions for electron energies in the range from the excitation threshold to 1000 eV are also reported. A delayed coincidence analysis of the de-excitation at 100 eV electron energy allowed for the subtraction of radiative cascades. The resulting excitation cross sections are between 7.3 and 12x10 -20 cm 2 . (author)

  17. Complement 5a stimulates macrophage polarization and contributes to tumor metastases of colon cancer. (United States)

    Piao, Chunmei; Zhang, Wen-Mei; Li, Tao-Tao; Zhang, Cong-Cong; Qiu, Shulan; Liu, Yan; Liu, Sa; Jin, Ming; Jia, Li-Xin; Song, Wen-Chao; Du, Jie


    Inflammatory cells such as macrophages can play a pro-tumorigenic role in the tumor stroma. Tumor-associated macrophages (TAMs) generally display an M2 phenotype with tumor-promoting activity; however, the mechanisms regulating the TAM phenotype remain unclear. Complement 5a (C5a) is a cytokine-like polypeptide that is generated during complement system activation and is known to promote tumor growth. Herein, we investigated the role of C5a on macrophage polarization in colon cancer metastasis in mice. We found that deficiency of the C5a receptor (C5aR) severely impairs the metastatic ability of implanted colon cancer cells. C5aR was expressed on TAMs, which exhibited an M2-like functional profile in colon cancer liver metastatic lesions. Furthermore, C5a mediated macrophage polarization and this process relied substantially on activation of the nuclear factor-kappa B (NF-κB) pathway. Finally, analysis of human colon carcinoma indicated that C5aR expression is negatively associated with tumor differentiation grade. Our results demonstrate that C5aR has a central role in regulating the M2 phenotype of TAMs, which in turn, contributes to hepatic metastasis of colon cancer through NF-κB signaling. C5a is a potential novel marker for cancer prognosis and drugs targeting complement system activation, specifically the C5aR pathway, may offer new therapeutic opportunities for colon cancer management. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Test of GET Electronics for the CHIMERA and FARCOS multi-detectors (United States)

    De Luca, S.; Acosta, L.; Auditore, L.; Boiano, C.; Cardella, G.; Castoldi, A.; D'Andrea, M.; De Filippo, E.; Dell'Aquila, D.; Fichera, F.; Gnoffo, B.; Guazzoni, C.; Lanzalone, G.; Lombardo, I.; Martorana, N. S.; Minniti, T.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Saccà, G.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.


    In this paper we present the results of the tests on the new digital electronics GET (General Electronics for Tpc), which will be used for the readout of the CsI(Tl) detectors of CHIMERA (Charged Heavy Ion Mass and Energy Resolving Array) and for the new correlator FARCOS (Femtoscope ARray for COrrelations and Spectroscopy). The new electronics allows us to digitize the full waveform of the signals produced by the detector. Among its features it is worth noticing the compactness and low power consumption (5W for 256 channels). Tests have been performed with pulsers, radioactive sources and ion beams. With such electronics very good results in energy resolution and isotope separation of the detected fragments were obtained, by using both hardware and software filters.

  19. Navier-Stokes calculations on multi-element airfoils using a chimera-based solver (United States)

    Jasper, Donald W.; Agrawal, Shreekant; Robinson, Brian A.


    A study of Navier-Stokes calculations of flows about multielement airfoils using a chimera grid approach is presented. The chimera approach utilizes structured, overlapped grids which allow great flexibility of grid arrangement and simplifies grid generation. Calculations are made for two-, three-, and four-element airfoils, and modeling of the effect of gap distance between elements is demonstrated for a two element case. Solutions are obtained using the thin-layer form of the Reynolds averaged Navier-Stokes equations with turbulence closure provided by the Baldwin-Lomax algebraic model or the Baldwin-Barth one equation model. The Baldwin-Barth turbulence model is shown to provide better agreement with experimental data and to dramatically improve convergence rates for some cases. Recently developed, improved farfield boundary conditions are incorporated into the solver for greater efficiency. Computed results show good comparison with experimental data which include aerodynamic forces, surface pressures, and boundary layer velocity profiles.

  20. Smooth YBa2Cu3O7-x thin films prepared by pulsed laser deposition in O2/Ar atmosphere

    DEFF Research Database (Denmark)

    Kyhle, Anders; Skov, Johannes; Hjorth, Søren


    We report on pulsed laser deposition of YBa2Cu3O7-x in a diluted O2/Ar gas resulting in thin epitaxial films which are almost outgrowth-free. Films were deposited on SrTiO3 or MgO substrates around 800-degrees-C at a total chamber pressure of 1.0 mbar, varying the argon partial pressure from 0 to 0.......6 mbar. The density of boulders and outgrowths usual for laser deposited films varies strongly with Ar pressure: the outgrowth density is reduced from 1.4 x 10(7) to 4.5 x 10(5) cm-2 with increasing Ar partial pressure, maintaining a critical temperature T(c,zero) almost-equal-to 90 K and a transport...... critical current density J(c)(77 K) greater-than-or-equal-to 10(6) A/cm2 by extended oxygenation time during cool down....

  1. 40Ar/39Ar ages of adularia from the Golden Cross, Neavesville, and Komata epithermal deposits, Hauraki Goldfield, New Zealand

    International Nuclear Information System (INIS)

    Mauk, J.L.; Hall, C.M.


    New 40 Ar/ 39 Ar ages of adularia from three epithermal vein deposits in the Hauraki Goldfield constrain when these deposits formed. Adularia from veins at Neavesville has 40 Ar/ 39 Ar plateau and isochron ages of 6.89 ± 0.02 and 6.86 ± 0.02 Ma, respectively, similar to the 40 Ar/ 39 Ar plateau and isochron ages of adularia from veins at Golden Cross of 6.96 ± 0.04 and 6.93 ± 0.03 Ma, respectively. In contrast, Komata mineralisation formed at 5.99 ± 0.02 to 6.07 ± 0.03 Ma, based on the 40 Ar/ 39 Ar isochron and plateau ages of the adularia in these veins, similar to the previously reported 6.0 Ma age of mineralisation at Waihi/Favona. These preliminary data suggest that mineralisation in the Hauraki Goldfields occurred episodically. (author). 19 refs., 3 figs., 1 tab

  2. 40Ar/ 39Ar, K-Ar and 230Th- 238U dating of the Laschamp excursion: A radioisotopic tie-point for ice core and climate chronologies (United States)

    Singer, Brad S.; Guillou, Hervé; Jicha, Brian R.; Laj, Carlo; Kissel, Catherine; Beard, Brian L.; Johnson, Clark M.


    A brief period of enhanced 10Be flux that straddles the interstadial warm period known as Dansgaard-Oeschger event 10 in Greenland and its counterpart in Antarctica, the Antarctic Isotope Maximum 10 is but one consequence of the weakening of Earth's magnetic field associated with the Laschamp excursion. This 10Be peak measured in the GRIP ice core is dated at 41,250 y b2k (= before year 2000 AD) in the most recent GICC05 age model obtained from the NorthGRIP core via multi-parameter counting of annual layers. Uncertainty in the age of the 10Be peak is, however, no better than ± 1630 y at the 95% confidence level, reflecting accumulated error in identifying annual layers. The age of the Laschamp excursion [Guillou, H., Singer, B.S., Laj, C., Kissel, C., Scaillet, S., Jicha, B., 2004. On the age of the Laschamp geomagnetic excursion. Earth Planet. Sci. Lett. 227, 331-343.] is revised on the basis of new 40Ar/ 39Ar, unspiked K-Ar and 238U- 230Th data from three lava flows in the Massif Central, France, together with the 40Ar/ 39Ar age of a transitionally magnetized lava flow at Auckland, New Zealand. Combined, these data yield an age of 40,700 ± 950 y b2k, where the uncertainty includes both analytical and systematic ( 40K and 230Th decay constant) errors. Taking the radioisotopic age as a calibration tie point suggests that the layer-counting chronologies for the NorthGRIP and GISP2 ice cores are more accurate and precise than previously thought at depths corresponding to the Laschamp excursion.

  3. 39Ar/Ar measurements using ultra-low background proportional counters

    International Nuclear Information System (INIS)

    Hall, Jeter; Aalseth, Craig E.; Bonicalzi, Ricco M.; Brandenberger, Jill M.; Day, Anthony R.; Humble, Paul H.; Mace, Emily K.; Panisko, Mark E.; Seifert, Allen


    Age-dating groundwater and seawater using the 39 Ar/Ar ratio is an important tool to understand water mass-flow rates and mean residence time. Low-background proportional counters developed at Pacific Northwest National Laboratory use mixtures of argon and methane as counting gas. We demonstrate sensitivity to 39 Ar by comparing geological (ancient) argon recovered from a carbon dioxide gas well and commercial argon. The demonstrated sensitivity to the 39 Ar/Ar ratio is sufficient to date water masses as old as 1000 years. - Highlights: • 39 Ar/Ar age dating is important for understanding environmental water migration. • Ultra low background proportional counters have been developed. • 39 Ar is detected in atmospheric argon at a rate of 70.3 counts per day. The demonstrated background is 166 counts per day. • Age dating is possible for water with underground residence time of up to 1000 years.

  4. Enhanced sources of acoustic power surrounding AR 11429

    International Nuclear Information System (INIS)

    Donea, Alina; Hanson, Christopher


    Multi-frequency power maps of the local acoustic oscillations show acoustic enhancements (''acoustic-power halos'') at high frequencies surrounding large active region. Computational seismic holography reveals a high-frequency ''acoustic-emission halo'', or ''seismic glory'' surrounding large active regions. In this study, we have applied computational seismic holography to map the seismic seismic source density surrounding AR 11429. Studies of HMI/SDO Doppler data, shows that the ''acoustic halos'' and the ''seismic glories'' are prominent at high frequencies 5–8 mHz. We investigate morphological properties of acoustic-power and acoustic emission halos around an active region to see if they are spatially correlated. Details about the local magnetic field from vectormagnetograms of AR 11429 are included. We identify a 15'' region of seismic deficit power (dark moat) shielding the white-light boundary of the active region. The size of the seismic moat is related to region of intermediate magnetic field strength. The acoustic moat is circled by the halo of enhanced seismic amplitude as well as enhanced seismic emission. Overall, the results suggest that features are related. However, if we narrow the frequency band to 5.5 – 6.5 mHz, we find that the seismic source density dominates over the local acoustic power, suggesting the existence of sources that emit more energy downward into the solar interior than upward toward the solar surface.

  5. Chimeras taking shape: Potential functions of proteins encoded by chimeric RNA transcripts (United States)

    Frenkel-Morgenstern, Milana; Lacroix, Vincent; Ezkurdia, Iakes; Levin, Yishai; Gabashvili, Alexandra; Prilusky, Jaime; del Pozo, Angela; Tress, Michael; Johnson, Rory; Guigo, Roderic; Valencia, Alfonso


    Chimeric RNAs comprise exons from two or more different genes and have the potential to encode novel proteins that alter cellular phenotypes. To date, numerous putative chimeric transcripts have been identified among the ESTs isolated from several organisms and using high throughput RNA sequencing. The few corresponding protein products that have been characterized mostly result from chromosomal translocations and are associated with cancer. Here, we systematically establish that some of the putative chimeric transcripts are genuinely expressed in human cells. Using high throughput RNA sequencing, mass spectrometry experimental data, and functional annotation, we studied 7424 putative human chimeric RNAs. We confirmed the expression of 175 chimeric RNAs in 16 human tissues, with an abundance varying from 0.06 to 17 RPKM (Reads Per Kilobase per Million mapped reads). We show that these chimeric RNAs are significantly more tissue-specific than non-chimeric transcripts. Moreover, we present evidence that chimeras tend to incorporate highly expressed genes. Despite the low expression level of most chimeric RNAs, we show that 12 novel chimeras are translated into proteins detectable in multiple shotgun mass spectrometry experiments. Furthermore, we confirm the expression of three novel chimeric proteins using targeted mass spectrometry. Finally, based on our functional annotation of exon organization and preserved domains, we discuss the potential features of chimeric proteins with illustrative examples and suggest that chimeras significantly exploit signal peptides and transmembrane domains, which can alter the cellular localization of cognate proteins. Taken together, these findings establish that some chimeric RNAs are translated into potentially functional proteins in humans. PMID:22588898

  6. Contribution of Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells to Chimeras through Injection and Coculture of Embryos


    Guo, Jitong; Wu, Baojiang; Li, Shuyu; Bao, Siqin; Zhao, Lixia; Hu, Shuxiang; Sun, Wei; Su, Jie; Dai, Yanfeng; Li, Xihe


    Blastocyst injection and morula aggregation are commonly used to evaluate stem cell pluripotency based on chimeric contribution of the stem cells. To assess the protocols for generating chimeras from stem cells, 8-cell mouse embryos were either injected or cocultured with mouse embryonic stem cells and induced pluripotent stem cells, respectively. Although a significantly higher chimera rate resulted from blastocyst injection, the highest germline contribution resulted from injection of 8-cel...

  7. 40Ar/39Ar age calibration against counted annuallayers

    DEFF Research Database (Denmark)

    Storey, Michael; Stecher, Ole


    The 40Ar/39Ar method, based on the decay of the naturally occurring radioactive isotope 40K, is capable of producing ages with precision better than ± 0.1 %. However, accuracy is limited to no better than 1 % mainly due to the relatively large uncertainty in the 40K decay constants. One approach...... worth exploring for an improved absolute age basis for the 40Ar/39Ar system is through cross-calibration with counted annual layers (e.g. tree rings, varves and ice cores). North Atlantic Ash Zone (NAAZ) II is found within the dated part of the annual Greenland ice core record. NAAZ II has been...... correlated to the Icelandic peralkaline rhyolitic Thorsmörk ignimbrite. We will present preliminary 40Ar/39Ar results on the age of this eruption...

  8. Array-based assay detects genome-wide 5-mC and 5-hmC in the brains of humans, non-human primates, and mice. (United States)

    Chopra, Pankaj; Papale, Ligia A; White, Andrew T J; Hatch, Andrea; Brown, Ryan M; Garthwaite, Mark A; Roseboom, Patrick H; Golos, Thaddeus G; Warren, Stephen T; Alisch, Reid S


    Methylation on the fifth position of cytosine (5-mC) is an essential epigenetic mark that is linked to both normal neurodevelopment and neurological diseases. The recent identification of another modified form of cytosine, 5-hydroxymethylcytosine (5-hmC), in both stem cells and post-mitotic neurons, raises new questions as to the role of this base in mediating epigenetic effects. Genomic studies of these marks using model systems are limited, particularly with array-based tools, because the standard method of detecting DNA methylation cannot distinguish between 5-mC and 5-hmC and most methods have been developed to only survey the human genome. We show that non-human data generated using the optimization of a widely used human DNA methylation array, designed only to detect 5-mC, reproducibly distinguishes tissue types within and between chimpanzee, rhesus, and mouse, with correlations near the human DNA level (R(2) > 0.99). Genome-wide methylation analysis, using this approach, reveals 6,102 differentially methylated loci between rhesus placental and fetal tissues with pathways analysis significantly overrepresented for developmental processes. Restricting the analysis to oncogenes and tumor suppressor genes finds 76 differentially methylated loci, suggesting that rhesus placental tissue carries a cancer epigenetic signature. Similarly, adapting the assay to detect 5-hmC finds highly reproducible 5-hmC levels within human, rhesus, and mouse brain tissue that is species-specific with a hierarchical abundance among the three species (human > rhesus > mouse). Annotation of 5-hmC with respect to gene structure reveals a significant prevalence in the 3'UTR and an association with chromatin-related ontological terms, suggesting an epigenetic feedback loop mechanism for 5-hmC. Together, these data show that this array-based methylation assay is generalizable to all mammals for the detection of both 5-mC and 5-hmC, greatly improving the utility of mammalian model systems

  9. Investigations into the construction of the pentasubstituted ring C of Neosurugatoxin – a crystallographic study

    Directory of Open Access Journals (Sweden)

    Alan M. Jones


    Full Text Available The crystal structures of three cyclopenta[c]furans with various substituents at the 4-, 5- and 6-positions of the ring system are reported, namely, (±-(3aR,4S,5S,6aS-4-methyl-5-phenylhexahydro-1H-cyclopenta[c]furan-4,5-diol, C14H18O3, (I, (±-(3aR,4S,5S,6aS-4-benzyloxy-4-methyl-5-phenylhexahydro-1H-cyclopenta[c]furan-5-ol, C21H24O3, (II, and (±-(1aR,1bS,4aR,5S,5aR-5-benzyloxy-5-methyl-5a-phenylhexahydro-2H-oxireno[2′,3′:3,4]cyclopenta[1,2-c]furan, C21H22O3, (III. The dominant interaction in (I and (II is an O—H...O hydrogen bond across the bicyclic 5,5-ring system between the non-functionalized hydroxy group and the tetrahydrofuran O atom, which appears to influence the envelope conformations of the fused five-membered rings, whereas in (III, the rings have different conformations. A weak intramolecular C—H...O interaction appears to influence the degree of tilt of the phenyl ring attached to the 5-position and is different in (I compared to (II and (III.

  10. Characterization of novel StAR (steroidogenic acute regulatory protein mutations causing non-classic lipoid adrenal hyperplasia.

    Directory of Open Access Journals (Sweden)

    Christa E Flück

    Full Text Available CONTEXT: Steroidogenic acute regulatory protein (StAR is crucial for transport of cholesterol to mitochondria where biosynthesis of steroids is initiated. Loss of StAR function causes lipoid congenital adrenal hyperplasia (LCAH. OBJECTIVE: StAR gene mutations causing partial loss of function manifest atypical and may be mistaken as familial glucocorticoid deficiency. Only a few mutations have been reported. DESIGN: To report clinical, biochemical, genetic, protein structure and functional data on two novel StAR mutations, and to compare them with published literature. SETTING: Collaboration between the University Children's Hospital Bern, Switzerland, and the CIBERER, Hospital Vall d'Hebron, Autonomous University, Barcelona, Spain. PATIENTS: Two subjects of a non-consanguineous Caucasian family were studied. The 46,XX phenotypic normal female was diagnosed with adrenal insufficiency at the age of 10 months, had normal pubertal development and still has no signs of hypergonodatropic hypogonadism at 32 years of age. Her 46,XY brother was born with normal male external genitalia and was diagnosed with adrenal insufficiency at 14 months. Puberty was normal and no signs of hypergonadotropic hypogonadism are present at 29 years of age. RESULTS: StAR gene analysis revealed two novel compound heterozygote mutations T44HfsX3 and G221S. T44HfsX3 is a loss-of-function StAR mutation. G221S retains partial activity (∼30% and is therefore responsible for a milder, non-classic phenotype. G221S is located in the cholesterol binding pocket and seems to alter binding/release of cholesterol. CONCLUSIONS: StAR mutations located in the cholesterol binding pocket (V187M, R188C, R192C, G221D/S seem to cause non-classic lipoid CAH. Accuracy of genotype-phenotype prediction by in vitro testing may vary with the assays employed.

  11. Thoughts on the chimera method of simulation of three-dimensional viscous flow (United States)

    Steger, Joseph L.


    The chimera overset grid is reviewed and discussed relative to other procedures for simulating flow about complex configurations. It is argued that while more refinement of the technique is needed, current schemes are competitive to unstructured grid schemes and should ultimately prove more useful.

  12. Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin. (United States)

    Lin, Marvin; Yin, Na; Murphy, Barbara; Medof, M Edward; Segerer, Stephan; Heeger, Peter S; Schröppel, Bernd


    The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model. The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.

  13. Epigenetic Machinery Regulates Alternative Splicing of Androgen Receptor (AR) Gene in Castration-Resistant Prostate Cancer (CRPC) (United States)


    Splicing of Androgen Receptor (AR) Gene in Castration-Resistant Prostate Cancer (CRPC) 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jer...Epigenetic regulation of androgen receptor signaling in prostate cancer . Epigenetics. 5, 100-104. 2. Duan LL, Rai G , Roggero C, Zhang Q-J, Wei Q... Prostate Cancer (CRPC) PRINCIPAL INVESTIGATOR: Hsieh, Jer-Tsong CONTRACTING ORGANIZATION: University of Texas Southwestern Medical Center

  14. Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

    International Nuclear Information System (INIS)

    Ogasawara, M.; Iwabuchi, K.; Good, R.A.; Onoe, K.


    When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance

  15. Paleomagnetism and 40Ar / 39Ar Geochronology of Yemeni Oligocene volcanics: Implications for timing and duration of Afro-Arabian traps and geometry of the Oligocene paleomagnetic field (United States)

    Riisager, Peter; Knight, Kim B.; Baker, Joel A.; Ukstins Peate, Ingrid; Al-Kadasi, Mohamed; Al-Subbary, Abdulkarim; Renne, Paul R.


    A combined paleomagnetic and 40Ar / 39Ar study was carried out along eight stratigraphically overlapping sections in the Oligocene Afro-Arabian flood volcanic province in Yemen (73 sites). The composite section covers the entire volcanic stratigraphy in the sampling region and represents five polarity zones that are correlated to the geomagnetic polarity time scale based on 40Ar / 39Ar ages from this and previous studies. The resulting magnetostratigraphy is similar to that of the conjugate margin in Ethiopia. The earliest basaltic volcanism took place in a reverse polarity chron that appears to correspond to C11r, while the massive rhyolitic ignimbrite eruptions correlated to ash layers in Oligocene Indian Ocean sediment 2700 km away from the Afro-Arabian traps, appear to have taken place during magnetochron C11n. The youngest ignimbrite was emplaced during magnetochron C9n. Both 40Ar / 39Ar and paleomagnetic data suggest rapid Red Sea. By analyzing Afro-Arabian paleomagnetic data in conjunction with contemporaneous paleomagnetic poles available from different latitudes we argue that the Oligocene paleomagnetic field was dominated by the axial dipole with insignificant non-dipole field contributions.

  16. Study on proliferative responses to host Ia antigens in allogeneic bone marrow chimera in mice: sequential analysis of the reactivity and characterization of the cells involved in the responses

    International Nuclear Information System (INIS)

    Iwabuchi, K.; Ogasawara, K.; Ogasawara, M.; Yasumizu, R.; Noguchi, M.; Geng, L.; Fujita, M.; Good, R.A.; Onoe, K.


    Irradiation bone marrow chimeras were established by reconstitution of lethally irradiated AKR mice with C57BL/10 marrow cells to permit serial analysis of the developing reactivities of lymphocytes from such chimeras, [B10----AKR], against donor, host, or third party antigens. We found that substantial proliferative responses to Ia antigens of the recipient strain and also to third party antigens were generated by the thymocytes obtained from the irradiation chimeras at an early stage after bone marrow reconstitution. The majority of the responding thymocytes had surfaces lacking demonstrable peanut agglutinin receptors and were donor type Thy-1+, Ly-2-, and L3T4+ in both anti-recipient and anti-third party MLR. In anti-host responses, however, Ly-2+ thymocytes seemed to be at least partially involved. This capacity of thymus cells to mount a response to antigens of the recipient strain declined shortly thereafter, whereas the capacity to mount MLR against third party antigens persisted. The spleen cells of [B10----AKR] chimeras at the same time developed a more durable capability to exhibit anti-host reactivities and a permanent capability of reacting to third party allo-antigens. The stimulator antigens were Ia molecules on the stimulator cells in both anti-recipient and anti-third party MLR. The responding splenocytes were of donor origin and most of them had Thy-1+, Ly-1+2-, and L3T4+ phenotype

  17. Deposition and characterisation of multilayer hard coatings. Ti/TiNδ/TiCxNy/(TiC) a-C:H/(Ti) a-C:H

    International Nuclear Information System (INIS)

    Burinprakhon, T.


    Multilayer hard coatings containing Ti, TiNδ, TiC x N y , (TiC m ) a-C:H, (TiC n ) a-C:H, and (Ti) a-C:H were deposited on commercially pure titanium substrates by using an asymmetric bipolar pulsed-dc reactive magnetron sputtering of a titanium target, with Ar, Ar+N 2 , Ar+N 2 +CH 4 , and Ar+CH 4 gas mixtures. The microstructures, elemental compositions and bonding states of the interlayers and the coating surfaces were studied by using cross-sectional transmission electron microscopy (XTEM), electron energy loss spectroscopy (EELS), X-ray diffraction (XRD), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). The microstructure development of the multilayer coating was strongly influenced by target poisoning. As a result of the complete poisoning of the titanium target during the deposition of TiNδ and TiC x N y interlayers, the a-C:H interlayers containing graded titanium and nitrogen contents were found to develop successively to the TiC x N y interlayer without the formation of near-stoichiometric TiC. The (TiC m ) a-C:H interlayer consisted of nano-particles of distorted fcc crystal structure embedded in the a-C:H matrix. The (TiC n ) a-C:H and (Ti) a-C:H top layers were found to be a-C:H matrix without nano-particles. In the (Ti) a-C:H top layer there was no measurable amount of Ti observed, regardless of the variation of CH 4 concentration between 37.5 and 60 % flow rate in Ar+-CH4 gas mixture. The top layer (Ti) a-C:H was found to contain approximately 10 atomic % nitrogen, due to N 2 contamination during deposition caused by low conductance of N 2 through the nominally closed valve of the mass flow controller. The change of the CH 4 concentration during deposition of the top layer (Ti) a-C:H, however, showed a strong influence on the hydrogen content. The comparison of the fluorescence background of the Raman spectra revealed that hydrogen-less (Ti) a-C:H was deposited at a CH 4 concentration of less than 50 % flow rate in Ar. The hardness

  18. Fusion-fission in Ar-heavy nuclei collisions

    International Nuclear Information System (INIS)

    Zaric, Alexandre


    Fusion-fission products have been studied for three reactions: Ar + Au, Ar + Bi and Ar + U (5.25-7.5 MeV/u). By measuring symmetric fragmentation components (fission-like events), cross sections for fusion were deduced and compared with the prediction of static and dynamic models. With increasing projectile energy, the width of the mass distributions strongly increases for the two lighter systems. By contrast, for Ar + U it remains essentially constant at a very large value. These results clearly demonstrate that the large increase of the width of the mass distribution cannot be attributed simply to large values of the angular momentum. However, they can be explained by the occurrence of a different dissipative process, fast fission, which can be expected if there is no barrier to fission. For the reaction Ar + Au, the total kinetic-energy distributions were also studied in detail. In this case fast fission occurs only at high incident energy. The average total kinetic energy (TKE) was found to be constant with increasing energy. (author) [fr

  19. Clonal deletion: A mechanism of tolerance in mixed bone marrow chimeras

    International Nuclear Information System (INIS)

    Yu, J.C.; Webster, M.; Fox, I.J.


    The mechanism of antigen-specific immunologic unresponsiveness which results from lethal irradiation and mixed (syngeneic-allogeneic) bone marrow cell (BMC) reconstitution is unknown. To determine whether clonal deletion is the mechanism of tolerance in this model, monoclonal antibody (Mab) RR-4-4, specific for a T-cell receptor (V beta 6) reactive against the minor alloantigen MLsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thyl.2) were tolerized to AKR antigens (H-2k, Mlsa, Thyl.1) by whole body irradiation (950 R) and iv infusion of T-cell-depleted (TCD) B10 BMC + non-TCD AKR BMC. Chimerism and antigen-specific tolerance were documented by flow microfluorometry (FMF), skin grafting, mixed lymphocyte reaction, and cell-mediated lympholysis. When tolerant B10 mice (n = 15) had accepted AKR skin grafts for greater than 100 days, these animals were studied for the presence of host V beta 6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were V beta 6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed V beta 6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive V beta 6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice

  20. Transfer of C-terminal residues of human apolipoprotein A-I to insect apolipophorin III creates a two-domain chimeric protein with enhanced lipid binding activity. (United States)

    Horn, James V C; Ellena, Rachel A; Tran, Jesse J; Beck, Wendy H J; Narayanaswami, Vasanthy; Weers, Paul M M


    Apolipophorin III (apoLp-III) is an insect apolipoprotein (18kDa) that comprises a single five-helix bundle domain. In contrast, human apolipoprotein A-I (apoA-I) is a 28kDa two-domain protein: an α-helical N-terminal domain (residues 1-189) and a less structured C-terminal domain (residues 190-243). To better understand the apolipoprotein domain organization, a novel chimeric protein was engineered by attaching residues 179 to 243 of apoA-I to the C-terminal end of apoLp-III. The apoLp-III/apoA-I chimera was successfully expressed and purified in E. coli. Western blot analysis and mass spectrometry confirmed the presence of the C-terminal domain of apoA-I within the chimera. While parent apoLp-III did not self-associate, the chimera formed oligomers similar to apoA-I. The chimera displayed a lower α-helical content, but the stability remained similar compared to apoLp-III, consistent with the addition of a less structured domain. The chimera was able to solubilize phospholipid vesicles at a significantly higher rate compared to apoLp-III, approaching that of apoA-I. The chimera was more effective in protecting phospholipase C-treated low density lipoprotein from aggregation compared to apoLp-III. In addition, binding interaction of the chimera with phosphatidylglycerol vesicles and lipopolysaccharides was considerably improved compared to apoLp-III. Thus, addition of the C-terminal domain of apoA-I to apoLp-III created a two-domain protein, with self-association, lipid and lipopolysaccharide binding properties similar to apoA-I. The apoA-I like behavior of the chimera indicate that these properties are independent from residues residing in the N-terminal domain of apoA-I, and that they can be transferred from apoA-I to apoLp-III. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells. (United States)

    El-Heliebi, Amin; Hille, Claudia; Laxman, Navya; Svedlund, Jessica; Haudum, Christoph; Ercan, Erkan; Kroneis, Thomas; Chen, Shukun; Smolle, Maria; Rossmann, Christopher; Krzywkowski, Tomasz; Ahlford, Annika; Darai, Evangelia; von Amsberg, Gunhild; Alsdorf, Winfried; König, Frank; Löhr, Matthias; de Kruijff, Inge; Riethdorf, Sabine; Gorges, Tobias M; Pantel, Klaus; Bauernhofer, Thomas; Nilsson, Mats; Sedlmayr, Peter


    Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms. We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients. In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts. Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices. © 2017 American Association for Clinical Chemistry.

  2. Interaction of Thermus thermophilus ArsC enzyme and gold nanoparticles naked-eye assays speciation between As(III) and As(V)

    International Nuclear Information System (INIS)

    Politi, Jane; De Stefano, Luca; Spadavecchia, Jolanda; Casale, Sandra; Fiorentino, Gabriella; Antonucci, Immacolata


    The thermophilic bacterium Thermus thermophilus HB27 encodes chromosomal arsenate reductase (TtArsC), the enzyme responsible for resistance to the harmful effects of arsenic. We report on adsorption of TtArsC onto gold nanoparticles for naked-eye monitoring of biomolecular interaction between the enzyme and arsenic species. Synthesis of hybrid biological–metallic nanoparticles has been characterized by transmission electron microscopy (TEM), ultraviolet-visible (UV–vis), dynamic light scattering (DLS) and phase modulated infrared reflection absorption (PM-IRRAS) spectroscopies. Molecular interactions have been monitored by UV–vis and Fourier transform-surface plasmon resonance (FT-SPR). Due to the nanoparticles’ aggregation on exposure to metal salts, pentavalent and trivalent arsenic solutions can be clearly distinguished by naked-eye assay, even at 85 μM concentration. Moreover, the assay shows partial selectivity against other heavy metals. (paper)

  3. Study of the excitation mechanisms of the second positive system in the negative glow of a N{sub 2}-Ar discharge

    Energy Technology Data Exchange (ETDEWEB)

    Isola, L; Lopez, M; Gomez, B J, E-mail: [Instituto de Fisica Rosario (CONICET-UNR) 27 Febrero 210 Bis. (S2000EZP) Rosario (Argentina)


    In an Ar-N{sub 2} discharge, the high excitation transfer from Ar({sup 3}P{sub 2,0}) to N{sub 2} produces an overpopulation of the high rotational levels of the bands of the second positive system (SPS), and so the spectra interpretation is not straightforward. This paper presents a fit function for the SPS bands measured in Ar-N{sub 2}, which allows us to study the excitation process contributions to the N{sub 2}(C) level. The procedure was tested in the negative glow of a pulsed Ar-N{sub 2} discharge at a pressure of 2.5 Torr, for different mixture concentrations. In this discharge, through the fitting, it was possible to calculate the variation of the N{sub 2}(C) densities produced by different excitation processes as well as the variation of Ar metastable density.

  4. 40Ar-39Ar stepheating studies of clay concentrates from Irish orebodies

    International Nuclear Information System (INIS)

    Halliday, A.N.


    40 Ar- 39 Ar step heating analyses of clay concentrates from the Gortdrum and Tynagh orebodies (Ireland) previously dated by conventional K-Ar, indicate major losses of 39 Ar (32 to 45%) and rad. 40 Ar (25 to 35%) during the irradiation. The proportion of rad. 40 Ar loss, unlike that of 39 Ar, increases with J-value. The difference between 39 Ar and rad. 40 Ar proportion losses is related to the mineralogy and grain intimacy. These also affect the stepwise release patterns - the Gortdrum concentrates yield age spectra very consistent with 39 Ar recoil predictions, whereas the Tynagh concentrates in which the grains are intimately intergrown, show no clear evidence for 39 Ar recoil depletion in the K-rich phases. The difference is resolvable if illite argon release is not a simple volume diffusion type process under vacuum conditions. (author)

  5. Oxygen functionalization of MWCNTs in RF-dielectric barrier discharge Ar/O2 plasma (United States)

    Abdel-Fattah, E.; Ogawa, D.; Nakamura, K.


    The oxygenation of multi-wall carbon nanotubes (MWCNTs) was performed via a radio frequency dielectric barrier discharge (RF-DBD) in an Ar/{{\\text{H}}2}\\text{O} plasma mixture. The relative intensity of the Ar/{{\\text{O}}2} plasma species was characterized by optical emission spectroscopy (OES). The effects of treatment time, RF power and oxygen gas percentage on the chemical composition and surface morphology of MWCNTs were investigated by means of x-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy and field emission scanning electron microscopy (FE-SEM). The results of FTIR and XPS revealed the presence of oxygen-containing functional groups on the MWCNTs treated in an Ar/{{\\text{O}}2} plasma at an RF power of 50 W and pressure of 400 Pa. The amount of oxygen functional groups (C=O, C-O, and O-COO) also increased by increasing treatment time up to 6 min, but slightly decreased when treatment time was increased by 10 min. The increase of oxygen gas percentage in the plasma mixture does not affect the oxygen content in the treated MWCNTs. Meanwhile, MWCNTs treated at high power (80 W) showed a reduction in oxygen functional groups in comparison with low RF power conditions. The Raman analysis was consistent with the XPS and FTIR results. The integrity of the nanotube patterns also remained damaged as observed by FE-SEM images. The MWCNTs treated in RF-DBD using the Ar/{{\\text{O}}2} plasma mixture showed improved dispersibility in deionized water. A correlation between the OES data and the observed surface characterization for an improved understanding of the functionalization of MWCNTs in Ar/{{\\text{O}}2} plasma was presented.

  6. Assembly and Regulation of the Membrane Attack Complex Based on Structures of C5b6 and sC5b9

    Directory of Open Access Journals (Sweden)

    Michael A. Hadders


    Full Text Available Activation of the complement system results in formation of membrane attack complexes (MACs, pores that disrupt lipid bilayers and lyse bacteria and other pathogens. Here, we present the crystal structure of the first assembly intermediate, C5b6, together with a cryo-electron microscopy reconstruction of a soluble, regulated form of the pore, sC5b9. Cleavage of C5 to C5b results in marked conformational changes, distinct from those observed in the homologous C3-to-C3b transition. C6 captures this conformation, which is preserved in the larger sC5b9 assembly. Together with antibody labeling, these structures reveal that complement components associate through sideways alignment of the central MAC-perforin (MACPF domains, resulting in a C5b6-C7-C8β-C8α-C9 arc. Soluble regulatory proteins below the arc indicate a potential dual mechanism in protection from pore formation. These results provide a structural framework for understanding MAC pore formation and regulation, processes important for fighting infections and preventing complement-mediated tissue damage.

  7. VLA radio observations of AR Scorpii (United States)

    Stanway, E. R.; Marsh, T. R.; Chote, P.; Gänsicke, B. T.; Steeghs, D.; Wheatley, P. J.


    Aims: AR Scorpii is unique amongst known white dwarf binaries in showing powerful pulsations extending to radio frequencies. Here we aim to investigate the multi-frequency radio emission of AR Sco in detail, in order to constrain its origin and emission mechanisms. Methods: We present interferometric radio frequency imaging of AR Sco at 1.5, 5 and 9 GHz, analysing the total flux and polarization behaviour of this source at high time resolution (10, 3 and 3 s), across a full 3.6 h orbital period in each band. Results: We find strong modulation of the radio flux on the orbital period and the orbital sideband of the white dwarf's spin period (also known as the "beat" period). This indicates that, like the optical flux, the radio flux arises predominantly from on or near the inner surface of the M-dwarf companion star. The beat-phase pulsations of AR Sco decrease in strength with decreasing frequency. They are strongest at 9 GHz and at an orbital phase 0.5. Unlike the optical emission from this source, radio emission from AR Sco shows weak linear polarization but very strong circular polarization, reaching 30% at an orbital phase 0.8. We infer the probable existence of a non-relativistic cyclotron emission component, which dominates at low radio frequencies. Given the required magnetic fields, this also likely arises from on or near the M-dwarf. A table of the flux time series is only available at the CDS via anonymous ftp to ( or via

  8. Timing of Secondary Hydrothermal Alteration of the Luobusa Chromitites Constrained by Ar/Ar Dating of Chrome Chlorites

    Directory of Open Access Journals (Sweden)

    Wei Guo


    Full Text Available Chrome chlorites are usually found as secondary phases formed by hydrothermal alteration of chromite deposits and associated mafic/ultramafic rocks. Here, we report the 40Ar/39Ar age of chrome chlorites separated from the Luobusa massive chromitites which have undergone secondary alteration by CO2-rich hydrothermal fluids. The dating results reveal that the intermediate heating steps (from 4 to 10 of sample L7 generate an age plateau of 29.88 ± 0.42 Ma (MSWD = 0.12, plateau 39Ar = 74.6%, and the plateau data points define a concordant inverse isochron age of 30.15 ± 1.05 Ma (MSWD = 0.08, initial 40Ar/36Ar = 295.8 ± 9.7. The Ar release pattern shows no evidence of later degassing or inherited radiogenic component indicated by an atmospheric intercept, thus representing the age of the hydrothermal activity. Based on the agreement of this hydrothermal age with the ~30 Ma adakitic plutons exposed in nearby regions (the Zedong area, tens of kilometers west Luobusa and the extensive late Oligocene plutonism distributed along the southeastern Gangdese magmatic belt, it is suggested that the hydrothermal fluids are likely related to the ~30 Ma magmatism. The hydrothermal fluid circulation could be launched either by remote plutons (such as the Sangri granodiorite, the nearest ~30 Ma pluton west Luobusa or by a similar coeval pluton in the local Luobusa area (inferred, not found or reported so far. Our results provide important clues for when the listwanites in Luobusa were formed.

  9. K-Ar ages of the Auckland geomagnetic excursions

    International Nuclear Information System (INIS)

    Mochizuki, Nobutatsu; Tsunakawa, Hideo; Shibuya, Hidetoshi; Tagami, Takahiro; Ozawa, Ayako; Cassidy, John; Smith, E.M.


    K-Ar age determinations were made on two monogenetic volcanoes in the Auckland volcanic field, New Zealand, which have recorded the Auckland geomagnetic excursions. For the Wiri volcano with the north-down intermediate paleomagnetic direction, five samples gave a weighted mean age of 27±5 (1σ) ka. For the Hampton Park volcano with the west-up intermediate direction, three samples gave a weighted mean of 55±5(1σ) ka. Since these two K-Ar ages are distinguished at 2σ level, it is inferred that at least two geomagnetic excursions can be recognized in Auckland. The age of the Hampton Park is barely distinguished from the established age range of the Laschamp excursion (39-45 ka) at 2σ level. The age of the Wiri coincides with the age of c. 30 ka in which excursions have been found from sedimentary and volcanic records. The reported excursions from volcanic rocks show a VGP cluster in the central to northern Pacific region which is distinct from the VGP paths or clusters during polarity reversals. (author)

  10. In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation. (United States)

    Choi, Hyun Woo; Hong, Yean Ju; Kim, Jong Soo; Song, Hyuk; Cho, Ssang Gu; Bae, Hojae; Kim, Changsung; Byun, Sung June; Do, Jeong Tae


    Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of fetal brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell types whose differentiation protocols are not well established.

  11. Lipon thin films grown by plasma-enhanced metalorganic chemical vapor deposition in a N{sub 2}-H{sub 2}-Ar gas mixture

    Energy Technology Data Exchange (ETDEWEB)

    Meda, Lamartine, E-mail: [Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA, 70125 (United States); Maxie, Eleston E. [Excellatron Solid State LLC, 263 Decatur Street, Atlanta, GA 30312 (United States)


    Lithium phosphorus oxynitride (Lipon) thin films have been deposited by a plasma-enhanced metalorganic chemical vapor deposition method. Lipon thin films were deposited on approximately 0.2 {mu}m thick Au-coated alumina substrates in a N{sub 2}-H{sub 2}-Ar plasma at 13.56 MHz, a power of 150 W, and at 180 Degree-Sign C using triethyl phosphate [(CH{sub 2}CH{sub 3}){sub 3}PO{sub 4}] and lithium tert-butoxide [(LiOC(CH{sub 3}){sub 3}] precursors. Lipon growth rates ranged from 10 to 42 nm/min and thicknesses varied from 1 to 2.5 {mu}m. X-ray powder diffraction showed that the films were amorphous, and X-ray photoelectron spectroscopy (XPS) revealed approximately 4 at.% N in the films. The ionic conductivity of Lipon was measured by electrochemical impedance spectroscopy to be approximately 1.02 {mu}S/cm, which is consistent with the ionic conductivity of Lipon deposited by radio frequency magnetron sputtering of Li{sub 3}PO{sub 4} targets in either mixed Ar-N{sub 2} or pure N{sub 2} atmosphere. Attempts to deposit Lipon in a N{sub 2}-O{sub 2}-Ar plasma resulted in the growth of Li{sub 3}PO{sub 4} thin films. The XPS analysis shows no C and N atom peaks. Due to the high impedance of these films, reliable conductivity measurements could not be obtained for films grown in N{sub 2}-O{sub 2}-Ar plasma.

  12. Stimulation of StAR expression by cAMP is controlled by inhibition of highly inducible SIK1 via CRTC2, a co-activator of CREB. (United States)

    Lee, Jinwoo; Tong, Tiegang; Takemori, Hiroshi; Jefcoate, Colin


    In mouse steroidogenic cells the activation of cholesterol metabolism is mediated by steroidogenic acute regulatory protein (StAR). Here, we visualized a coordinated regulation of StAR transcription, splicing and post-transcriptional processing, which are synchronized by salt inducible kinase (SIK1) and CREB-regulated transcription coactivator (CRTC2). To detect primary RNA (pRNA), spliced primary RNA (Sp-RNA) and mRNA in single cells, we generated probe sets by using fluorescence in situ hybridization (FISH). These methods allowed us to address the nature of StAR gene expression and to visualize protein-nucleic acid interactions through direct detection. We show that SIK1 represses StAR expression in Y1 adrenal and MA10 testis cells through inhibition of processing mediated by CRTC2. Digital image analysis matches qPCR analyses of the total cell culture. Evidence is presented for spatially separate accumulation of StAR pRNA and Sp-RNA at the gene loci in the nucleus. These findings establish that cAMP, SIK and CRTC mediate StAR expression through activation