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Sample records for response factor srf

  1. Hyperosmotic stress strongly potentiates serum response factor (SRF)-dependent transcriptional activity in ehrlich lettré ascites cells through a mechanism involving p38 mitogen-activated protein kinase

    Gorbatenko, Andrej; Wiwel, Maria; Klingberg, Henrik

    2011-01-01

    Long-term osmotic stress results in altered gene transcription, however, with the exception of the TonE/TonEBP system, the underlying mechanisms are poorly understood. We previously showed that upon osmotic shrinkage of Ehrlich Lettré Ascites (ELA) fibroblasts, the MEK1-ERK1/2 pathway is transien......Long-term osmotic stress results in altered gene transcription, however, with the exception of the TonE/TonEBP system, the underlying mechanisms are poorly understood. We previously showed that upon osmotic shrinkage of Ehrlich Lettré Ascites (ELA) fibroblasts, the MEK1-ERK1/2 pathway......) and cAMP response element-binding protein (CREB) are differentially regulated in ELA cells. SRF Ser103 phosphorylation and SRF-dependent transcriptional activity were strongly augmented 5–30¿min and 24¿h, respectively, after hyperosmotic stress (50% increase in extracellular ionic strength), in a p38...... dephosphorylated within 5¿min of shrinkage. MSK1 phosphorylation recovered within 30¿min in a p38-MAPK-dependent manner. CREB was transiently dephosphorylated after shrinkage in a manner exacerbated by p38 MAPK inhibition or MSK1 knockdown, but unaffected by inhibition of RSK. In conclusion, in ELA cells...

  2. Regulation of cardiac microRNAs by serum response factor

    Wei Jeanne Y

    2011-02-01

    Full Text Available Abstract Serum response factor (SRF regulates certain microRNAs that play a role in cardiac and skeletal muscle development. However, the role of SRF in the regulation of microRNA expression and microRNA biogenesis in cardiac hypertrophy has not been well established. In this report, we employed two distinct transgenic mouse models to study the impact of SRF on cardiac microRNA expression and microRNA biogenesis. Cardiac-specific overexpression of SRF (SRF-Tg led to altered expression of a number of microRNAs. Interestingly, downregulation of miR-1, miR-133a and upregulation of miR-21 occurred by 7 days of age in these mice, long before the onset of cardiac hypertrophy, suggesting that SRF overexpression impacted the expression of microRNAs which contribute to cardiac hypertrophy. Reducing cardiac SRF level using the antisense-SRF transgenic approach (Anti-SRF-Tg resulted in the expression of miR-1, miR-133a and miR-21 in the opposite direction. Furthermore, we observed that SRF regulates microRNA biogenesis, specifically the transcription of pri-microRNA, thereby affecting the mature microRNA level. The mir-21 promoter sequence is conserved among mouse, rat and human; one SRF binding site was found to be in the mir-21 proximal promoter region of all three species. The mir-21 gene is regulated by SRF and its cofactors, including myocardin and p49/Strap. Our study demonstrates that the downregulation of miR-1, miR-133a, and upregulation of miR-21 can be reversed by one single upstream regulator, SRF. These results may help to develop novel therapeutic interventions targeting microRNA biogenesis.

  3. Relationship between serum response factor and androgen receptor in prostate cancer.

    Prencipe, Maria; O'Neill, Amanda; O'Hurley, Gillian; Nguyen, Lan K; Fabre, Aurelie; Bjartell, Anders; Gallagher, William M; Morrissey, Colm; Kay, Elaine W; Watson, R William

    2015-11-01

    Serum response factor (SRF) is an important transcription factor in castrate-resistant prostate cancer (CRPC). Since CRPC is associated with androgen receptor (AR) hypersensitivity, we investigated the relationship between SRF and AR. Transcriptional activity was assessed by luciferase assay. Cell proliferation was measured by MTT and flow cytometry. Protein expression in patients was assessed by immunohistochemistry. To investigate AR involvement in SRF response to androgen, AR expression was down-regulated using siRNA. This resulted in the abrogation of SRF induction post-DHT. Moreover, DHT stimulation failed to induce SRF transcriptional activity in AR-negative PC346 DCC cells, which was only restored following AR over-expression. Next, SRF expression was down-regulated by siRNA, resulting in AR increased transcriptional activity in castrate-resistant LNCaP Abl cells but not in the parental LNCaP. This negative feedback loop in the resistant cells was confirmed by immunohistochemistry which showed a negative correlation between AR and SRF expression in CRPC bone metastases and a positive correlation in androgen-naïve prostatectomies. Cell proliferation was next assessed following SRF inhibition, demonstrating that SRF inhibition is more effective than AR inhibition in castrate-resistant cells. Our data support SRF as a promising therapeutic target in combination with current treatments. © 2015 Wiley Periodicals, Inc.

  4. Enrichment of conserved synaptic activity-responsive element in neuronal genes predicts a coordinated response of MEF2, CREB and SRF.

    Fernanda M Rodríguez-Tornos

    Full Text Available A unique synaptic activity-responsive element (SARE sequence, composed of the consensus binding sites for SRF, MEF2 and CREB, is necessary for control of transcriptional upregulation of the Arc gene in response to synaptic activity. We hypothesize that this sequence is a broad mechanism that regulates gene expression in response to synaptic activation and during plasticity; and that analysis of SARE-containing genes could identify molecular mechanisms involved in brain disorders. To search for conserved SARE sequences in the mammalian genome, we used the SynoR in silico tool, and found the SARE cluster predominantly in the regulatory regions of genes expressed specifically in the nervous system; most were related to neural development and homeostatic maintenance. Two of these SARE sequences were tested in luciferase assays and proved to promote transcription in response to neuronal activation. Supporting the predictive capacity of our candidate list, up-regulation of several SARE containing genes in response to neuronal activity was validated using external data and also experimentally using primary cortical neurons and quantitative real time RT-PCR. The list of SARE-containing genes includes several linked to mental retardation and cognitive disorders, and is significantly enriched in genes that encode mRNA targeted by FMRP (fragile X mental retardation protein. Our study thus supports the idea that SARE sequences are relevant transcriptional regulatory elements that participate in plasticity. In addition, it offers a comprehensive view of how activity-responsive transcription factors coordinate their actions and increase the selectivity of their targets. Our data suggest that analysis of SARE-containing genes will reveal yet-undescribed pathways of synaptic plasticity and additional candidate genes disrupted in mental disease.

  5. Regulation of Serum Response Factor and Adiponectin by PPARγ Agonist Docosahexaenoic Acid

    Clayton Johnson

    2011-01-01

    Full Text Available Recent studies indicate that significant health benefits involving the regulation of signaling proteins result from the consumption of omega-3 polyunsaturated fatty acids (ω-3 PUFAs. Serum response factor (SRF is involved in transcriptional regulation of muscle growth and differentiation. SRF levels are increased in the aging heart muscle. It has not been examined whether SRF is made by adipocytes and whether SRF secretion by adipocytes is modulated by PPARγ agonist DHA. Adiponectin is made exclusively by adipocytes. We and others have previously reported that PUFAs such as DHA increase adiponectin levels and secretion in adipocytes. Here we show that DHA downregulates SRF with a simultaneous upregulation of adiponectin and that both these responses are reversible by PPARγ antagonist. Furthermore, there appears to be a direct relationship between DHA exposure and increased levels of membrane-associated high-density adiponectin, as well as lower levels of membrane-associated SRF. Thus, we find that the levels of SRF and adiponectin are inversely related in response to treatment with PPARγ agonist DHA. Decreased levels of SRF along with increase in membrane-associated adiponectin could in part mediate the health benefits of DHA.

  6. Quantum efficiency temporal response and lifetime of a GaAs cathode in SRF electron gun

    Wang, E.; Ben-Zvi, I.; Kewisch, J.; Burrill, A.; Rao, T.; Wu, Q.; Holmes, D.

    2010-05-23

    RF electron guns with a strained super lattice GaAs cathode can generate polarized electron beam of higher brightness and lower emittance than do DC guns, due to their higher field gradient at the cathode's surface. In a normal conducting RF gun, the extremely high vaccum required by these cathodes can not be met. We report on an experiment with a superconducting SRF gun, which can maintain a vacuum of nearly 10-12 torr because of cryo-pumping at the temperature of 4.2K. With conventional activation, we obtained a QE of 3% at 532 nm, with lifetime of nearly 3 days in the preparation chamber. We plan to use this cathode in a 1.3 GHz 1/2 cell SRF gun to study its performance. In addition, we studied the multipacting at the location of cathode. A new model based on the Forkker-Planck equation which can estimate the bunch length of the electron beam is discussed in this paper. Future particle accelerators such as eRHIC and ILC require high brightness, high current polarized electrons Recently, using a superlattice crystal, the maximum polarization of 95% was reached. Activation with Cs,O lowers the electron affinity and makes it energetically possible for all the electrons excited in to the conduction band and reach the surface to escape into the vacuum. Presently the polarized electron sources are based on DC gun, such as that at the CEBAF at Jlab. In these devices, the life time of the cathode is extended due to the reduced back bombardment in their UHV conditions. However, the low accelerating gradient of the DC guns lead to poor longitudinal emittance. The higher accelerating gradient of the RF gun generates low emittance beams. Superconducting RF guns combine the excellent vacuum conditions of the DC guns with the higher accelerating gradients of the RF guns and provide potentially a long lived cathode with very low transverse and longitudinal emittance. In our work at BNL, we successfully activated the GaAs. The quantum efficient is 3% at 532 nm and is

  7. Quantum efficiency temporal response and lifetime of a GaAs cathode in SRF electron gun

    Wang, E.; Ben-Zvi, I.; Kewisch, J.; Burrill, A.; Rao, T.; Wu, Q.; Holmes, D.

    2010-01-01

    RF electron guns with a strained super lattice GaAs cathode can generate polarized electron beam of higher brightness and lower emittance than do DC guns, due to their higher field gradient at the cathode's surface. In a normal conducting RF gun, the extremely high vaccum required by these cathodes can not be met. We report on an experiment with a superconducting SRF gun, which can maintain a vacuum of nearly 10-12 torr because of cryo-pumping at the temperature of 4.2K. With conventional activation, we obtained a QE of 3% at 532 nm, with lifetime of nearly 3 days in the preparation chamber. We plan to use this cathode in a 1.3 GHz 1/2 cell SRF gun to study its performance. In addition, we studied the multipacting at the location of cathode. A new model based on the Forkker-Planck equation which can estimate the bunch length of the electron beam is discussed in this paper. Future particle accelerators such as eRHIC and ILC require high brightness, high current polarized electrons Recently, using a superlattice crystal, the maximum polarization of 95% was reached. Activation with Cs,O lowers the electron affinity and makes it energetically possible for all the electrons excited in to the conduction band and reach the surface to escape into the vacuum. Presently the polarized electron sources are based on DC gun, such as that at the CEBAF at Jlab. In these devices, the life time of the cathode is extended due to the reduced back bombardment in their UHV conditions. However, the low accelerating gradient of the DC guns lead to poor longitudinal emittance. The higher accelerating gradient of the RF gun generates low emittance beams. Superconducting RF guns combine the excellent vacuum conditions of the DC guns with the higher accelerating gradients of the RF guns and provide potentially a long lived cathode with very low transverse and longitudinal emittance. In our work at BNL, we successfully activated the GaAs. The quantum efficient is 3% at 532 nm and is expected

  8. Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes

    Kim, Eunha; Tyagi, Richa; Lee, Joo-Young; Park, Jina; Kim, Young-ran; Beon, Jiyoon; Chen, Po Yu; Cha, Jiyoung Y.; Snyder, Solomon H.; Kim, Seyun

    2013-01-01

    Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic protein. It displays both inositol phosphate kinase and phosphatidylinositol kinase catalytic activities. Noncatalytically, IPMK stabilizes the mammalian target of rapamycin complex 1 and acts as a transcriptional coactivator for CREB-binding protein/E1A binding protein p300 and tumor suppressor protein p53. Serum response factor (SRF) is a major transcription factor for a wide range of immediate early genes. We report that IPMK, in a noncatalytic role, is a transcriptional coactivator for SRF mediating the transcription of immediate early genes. Stimulation by serum of many immediate early genes is greatly reduced by IPMK deletion. IPMK stimulates expression of these genes, an influence also displayed by catalytically inactive IPMK. IPMK acts by binding directly to SRF and thereby enhancing interactions of SRF with the serum response element of diverse genes. PMID:24248338

  9. SRF for neutrino factories

    Padamsee, H.

    2003-01-01

    The Neutrino Factory calls for nearly 500 meters of 200 MHz SRF cavities to provide 7.5 GV. Such a facility is more demanding than the largest SRF installation to date, i.e., LEP-II, where 500 m of niobium-coated copper cavities provided more than 3 GV of acceleration. Based on the high real estate gradient desired to minimize muon loss, superconducting cavities are selected to provide active gradients of 15 - 17 MV/m, and a real estate gradient of 7.5 MV/m. At such high gradients, the peak RF power demand for copper cavities would become prohibitively expensive. By virtue of low losses, SC cavities can be filled slowly (rise time 3 ms) reducing the peak power demand to roughly half MW per cell. (author)

  10. Superconducting Radiofrequency (SRF) Acceleration Technology

    Federal Laboratory Consortium — SRF cavities enable accelerators to increase particle beam energy levels while minimizing the use of electrical power by all but eliminating electrical resistance....

  11. Integration of growth factor signals at the c-fos serum response element.

    Price, M A; Hill, C; Treisman, R

    1996-04-29

    A transcription factor ternary complex composed of serum response factor (SRF) and a second factor, ternary complex factor (TCF), mediates the response of the c-fos Serum Response Element to growth factors and mitogens. In NIH3T3 fibroblasts, TCF binding is required for transcriptional activation by the SRE in response to activation of the Ras-Raf-ERK pathway. We compared the properties of three members of the TCF family, Elk-1, SAP-1 and SAP-2 (ERP/NET). Although all the proteins contain sequences required for ternary complex formation with SRF, only Elk-1 and SAP-1 appear to interact with the c-fos SRE efficiently in vivo. Each TCF contains a C-terminal activation domain capable of transcriptional activation in response to activation of the Ras-Raf-ERK pathway, and this is dependent on the integrity of S/T-P motifs conserved between all the TCF family members. In contrast, activation of the SRE by whole serum and the mitogenic phospholipid LPA requires SRF binding alone. Constitutively activated members of the Rho subfamily of Ras-like GTPases are also capable of inducing activation of the SRE in the absence of TCF; unlike activated Ras itself, these proteins do not activate the TCFs in NIH3T3 cells. At the SRE, SRF- and TCF-linked signalling pathways act synergistically to potentiate transcription.

  12. Analysis list: Srf [Chip-atlas[Archive

    Full Text Available Srf Blood,Embryonic fibroblast,Muscle + mm9 http://dbarchive.biosciencedbc.jp/kyush...u-u/mm9/target/Srf.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Srf.5.tsv http://dbarchive.bioscience...dbc.jp/kyushu-u/mm9/target/Srf.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Srf.Blood....tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Srf.Embryonic_fibroblast....tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Srf.Muscle.tsv http://dbarchive.biosciencedbc.jp/kyu

  13. CW SRF systems with ingot niobium and their applications

    Myneni, Ganapati

    2011-01-01

    Continuous wave (CW) superconducting radio frequency (SRF) accelerator systems are needed not only for discovery science initiatives through out the world but they are also expected to find applications in a wide variety of programs including advanced reactor cycles using thorium as nuclear fuel, commercial and university compact linacs and FEL's. However these state of the art particle accelerator systems are very expensive to build and consume significant power in their operations. In the present world economic, energy sustainability and global warming concerns, we must improve the efficiency of the CW SRF accelerator systems considerably and in a cost effective manner. In this presentation I will review the current status of the CW SRF systems including the recent advances in improving the quality factor of the SRF cavities at very much reduced costs with simplified process procedures. (author)

  14. Myocardin-related transcription factors are required for cardiac development and function

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2015-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the d...

  15. The Role of CREB, SRF, and MEF2 in Activity-Dependent Neuronal Plasticity in the Visual Cortex.

    Pulimood, Nisha S; Rodrigues, Wandilson Dos Santos; Atkinson, Devon A; Mooney, Sandra M; Medina, Alexandre E

    2017-07-12

    The transcription factors CREB (cAMP response element binding factor), SRF (serum response factor), and MEF2 (myocyte enhancer factor 2) play critical roles in the mechanisms underlying neuronal plasticity. However, the role of the activation of these transcription factors in the different components of plasticity in vivo is not well known. In this study, we tested the role of CREB, SRF, and MEF2 in ocular dominance plasticity (ODP), a paradigm of activity-dependent neuronal plasticity in the visual cortex. These three proteins bind to the synaptic activity response element (SARE), an enhancer sequence found upstream of many plasticity-related genes (Kawashima et al., 2009; Rodríguez-Tornos et al., 2013), and can act cooperatively to express Arc , a gene required for ODP (McCurry et al., 2010). We used viral-mediated gene transfer to block the transcription function of CREB, SRF, and MEF2 in the visual cortex, and measured visually evoked potentials in awake male and female mice before and after a 7 d monocular deprivation, which allowed us to examine both the depression component (Dc-ODP) and potentiation component (Pc-ODP) of plasticity independently. We found that CREB, SRF, and MEF2 are all required for ODP, but have differential effects on Dc-ODP and Pc-ODP. CREB is necessary for both Dc-ODP and Pc-ODP, whereas SRF and MEF2 are only needed for Dc-ODP. This finding supports previous reports implicating SRF and MEF2 in long-term depression (required for Dc-ODP), and CREB in long-term potentiation (required for Pc-ODP). SIGNIFICANCE STATEMENT Activity-dependent neuronal plasticity is the cellular basis for learning and memory, and it is crucial for the refinement of neuronal circuits during development. Identifying the mechanisms of activity-dependent neuronal plasticity is crucial to finding therapeutic interventions in the myriad of disorders where it is disrupted, such as Fragile X syndrome, Rett syndrome, epilepsy, major depressive disorder, and autism

  16. Egr-1 and serum response factor are involved in growth factors- and serum-mediated induction of E2-EPF UCP expression that regulates the VHL-HIF pathway.

    Lim, Jung Hwa; Jung, Cho-Rok; Lee, Chan-Hee; Im, Dong-Soo

    2008-11-01

    E2-EPF ubiquitin carrier protein (UCP) has been shown to be highly expressed in common human cancers and target von Hippel-Lindau (VHL) for proteosomal degradation in cells, thereby stabilizing hypoxia-inducible factor (HIF)-1alpha. Here, we investigated cellular factors that regulate the expression of UCP gene. Promoter deletion assay identified binding sites for early growth response-1 (Egr-1) and serum response factor (SRF) in the UCP promoter. Hepatocyte or epidermal growth factor (EGF), or phorbol 12-myristate 13-acetate induced UCP expression following early induction of Egr-1 expression in HeLa cells. Serum increased mRNA and protein levels of SRF and UCP in the cell. By electrophoretic mobility shift and chromatin immunoprecipitation assays, sequence-specific DNA-binding of Egr-1 and SRF to the UCP promoter was detected in nuclear extracts from HeLa cells treated with EGF and serum, respectively. Overexpression of Egr-1 or SRF increased UCP expression. RNA interference-mediated depletion of endogenous Egr-1 or SRF impaired EGF- or serum-mediated induction of UCP expression, which was required for cancer cell proliferation. Systemic delivery of EGF into mice also increased UCP expression following early induction of Egr-1 expression in mouse liver. The induced UCP expression by the growth factors or serum increased HIF-1alpha protein level under non-hypoxic conditions, suggesting that the Egr-1/SRF-UCP-VHL pathway is in part responsible for the increased HIF-1alpha protein level in vitro and in vivo. Thus, growth factors and serum induce expression of Egr-1 and SRF, respectively, which in turn induces UCP expression that positively regulates cancer cell growth.

  17. Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration.

    Somogyi, Kálmán; Rørth, Pernille

    2004-07-01

    Cells migrating through a tissue exert force via their cytoskeleton and are themselves subject to tension, but the effects of physical forces on cell behavior in vivo are poorly understood. Border cell migration during Drosophila oogenesis is a useful model for invasive cell movement. We report that this migration requires the activity of the transcriptional factor serum response factor (SRF) and its cofactor MAL-D and present evidence that nuclear accumulation of MAL-D is induced by cell stretching. Border cells that cannot migrate lack nuclear MAL-D but can accumulate it if they are pulled by other migrating cells. Like mammalian MAL, MAL-D also responds to activated Diaphanous, which affects actin dynamics. MAL-D/SRF activity is required to build a robust actin cytoskeleton in the migrating cells; mutant cells break apart when initiating migration. Thus, tension-induced MAL-D activity may provide a feedback mechanism for enhancing cytoskeletal strength during invasive migration.

  18. MicroRNA-125b Affects Vascular Smooth Muscle Cell Function by Targeting Serum Response Factor

    Zhibo Chen

    2018-04-01

    Full Text Available Background/Aims: Increasing evidence links microRNAs to the pathogenesis of peripheral vascular disease. We recently found microRNA-125b (miR-125b to be one of the most significantly down‑regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO of the lower extremities. However, its function in the process of ASO remains unclear. This study aimed to investigate the expression, regulatory mechanisms, and functions of miR-125b in the process of ASO. Methods: Using the tissue explants adherent method, vascular smooth muscle cells (VSMCs were prepared for this study. A rat carotid artery balloon injury model was constructed to simulate the development of vascular neointima, and a lentiviral transduction system was used to overexpress serum response factor (SRF or miR-125b. Quantitative real‑time PCR (qRT‑PCR was used to detect the expression levels of miR‑125b and SRF mRNA. Western blotting was performed to determine the expression levels of SRF and Ki67. In situ hybridization analysis was used to analyze the location and expression levels of miR-125b. CCK-8 and EdU assays were used to assess cell proliferation, and transwell and wound closure assays were performed to measure cell migration. Flow cytometry was used to evaluate cell apoptosis, and a dual-luciferase reporter assay was conducted to examine the effects of miR‑125b on SRF. Immunohistochemistry and immunofluorescence analyses were performed to analyze the location and expression levels of SRF and Ki67. Results: miR-125b expression was decreased in ASO arteries and platelet-derived growth factor (PDGF-BB-stimulated VSMCs. miR-125b suppressed VSMC proliferation and migration but promoted VSMC apoptosis. SRF was determined to be a direct target of miR-125b. Exogenous miR-125b expression modulated SRF expression and inhibited vascular neointimal formation in balloon-injured rat carotid arteries. Conclusions: These findings demonstrate a specific role of the mi

  19. Devices for SRF material characterization

    Goudket, Philippe; Xiao, B.; Junginger, T.; Helmholtz-Zentrum Berlin

    2016-01-01

    The surface resistance Rs of superconducting materials can be obtained by measuring the quality factor of an elliptical cavity excited in a transverse magnetic mode (TM010). The value obtained has however to be taken as averaged over the whole surface. A more convenient way to obtain Rs, especially of materials which are not yet technologically ready for cavity production, is to measure small samples instead. These can be easily man ufactured at low cost, duplicated and placed in film deposition and surface analytical tools. A commonly used design for a device to measure Rs consists of a cylindrical cavity excited in a transverse electric (TE110) mode with the sample under test serving as one replaceable endplate. Such a cavity has two drawbacks. For reasonably small samples the resonant frequency will be larger than frequencies of interest concerning SRF application and it requires a reference sample of known Rs. In this article we review several devices which have been designed to overcome these limitations, reaching sub - nΩ resolution in some cases. Some of these devices also comprise a parameter space in frequency and temperature which is inaccessible to standard cavity tests, making them ideal tools to test theoretical surface resistance models.

  20. Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses.

    Chevigny, Mylène; Guérin-Montpetit, Karine; Vargas, Amandine; Lefebvre-Lavoie, Josiane; Lavoie, Jean-Pierre

    2015-07-01

    Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, a spontaneously occurring asthma-like disease of horses, and in controls. Six horses with heaves and five aged-matched controls kept in the same environment were studied. Nuclear protein expression of SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial biopsies obtained during disease remission and after 1 and 30 days of naturally occurring antigenic exposure using immunohistochemistry and immunofluorescence techniques. Nuclear expression of SRF (P = 0.03, remission vs. 30 days) and MYOCD (P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of horses with heaves during disease exacerbation, while MYOCD (P = 0.04, remission vs. 30 days) decreased in the central airways of control horses. No changes were observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM observed in equine asthmatic airways, while the remodeling of the central airways is more static or involves different transcription factors. Copyright © 2015 the American Physiological Society.

  1. Multipacting studies in elliptic SRF cavities

    Prakash, Ram; Jana, Arup Ratan; Kumar, Vinit

    2017-09-01

    Multipacting is a resonant process, where the number of unwanted electrons resulting from a parasitic discharge rapidly grows to a larger value at some specific locations in a radio-frequency cavity. This results in a degradation of the cavity performance indicators (e.g. the quality factor Q and the maximum achievable accelerating gradient Eacc), and in the case of a superconducting radiofrequency (SRF) cavity, it leads to a quenching of superconductivity. Numerical simulations are essential to pre-empt the possibility of multipacting in SRF cavities, such that its design can be suitably refined to avoid this performance limiting phenomenon. Readily available computer codes (e.g.FishPact, MultiPac,CST-PICetc.) are widely used to simulate the phenomenon of multipacting in such cases. Most of the contemporary two dimensional (2D) codes such as FishPact, MultiPacetc. are unable to detect the multipacting in elliptic cavities because they use a simplistic secondary emission model, where it is assumed that all the secondary electrons are emitted with same energy. Some three-dimensional (3D) codes such as CST-PIC, which use a more realistic secondary emission model (Furman model) by following a probability distribution for the emission energy of secondary electrons, are able to correctly predict the occurrence of multipacting. These 3D codes however require large data handling and are slower than the 2D codes. In this paper, we report a detailed analysis of the multipacting phenomenon in elliptic SRF cavities and development of a 2D code to numerically simulate this phenomenon by employing the Furman model to simulate the secondary emission process. Since our code is 2D, it is faster than the 3D codes. It is however as accurate as the contemporary 3D codes since it uses the Furman model for secondary emission. We have also explored the possibility to further simplify the Furman model, which enables us to quickly estimate the growth rate of multipacting without

  2. Tunneling study of SRF cavity-grade niobium

    Proslier, T.; Zasadzinski, J.; Cooley, L.; Pellin, M.; Norem, J.; Elam, J.; Antonine, C. Z.; Rimmer, R.; Kneisel, P.

    2009-01-01

    Niobium, with its very high H C1 , has been used in superconducting radio frequency (SRF) cavities for accelerator systems for 40 years with continual improvement. The quality factor of cavities (Q) is governed by the surface impedance R BCS , which depends on the quasiparticle gap, delta, and the superfluid density. Both of these parameters are seriously affected by surface imperfections (metallic phases, dissolved oxygen, magnetic impurities). Loss mechanism and surface treatments of Nb cavities found to improve the Q factor are still unsolved mysteries. We present here an overview of the capabilities of the point contact tunneling spectroscopy and Atomic layer deposition methods and how they can help understanding the High field Q-drop and the mild baking effect. Tunneling spectroscopy was performed on Nb pieces from the same processed material used to fabricate SRF cavities. Air exposed, electropolished Nb exhibited a surface superconducting gap Delta = 1.55 meV, characteristic of clean, bulk Nb, however the tunneling density of states (DOS) was broadened significantly. Nb pieces treated with the same mild baking used to improve the Q-slope in SRF cavities revealed a much sharper DOS. Good fits to the DOS are obtained using Shiba theory suggesting that magnetic scattering of quasiparticles is the origin of the degraded surface superconductivity and the Q-slope problem of Nb SRF cavities

  3. Easing Gently into OpenSRF, Part 2

    Dan Scott

    2010-01-01

    The Open Service Request Framework (or OpenSRF, pronounced "open surf") is an inter-application message passing architecture built on XMPP (aka "jabber"). The Evergreen open source library system is built on an OpenSRF architecture to support loosely coupled individual components communicating over an OpenSRF messaging bus. This article introduces OpenSRF, demonstrates how to build OpenSRF services through simple code examples, explains the technical foundations on which OpenSRF is built, and...

  4. Easing Gently into OpenSRF, Part 1

    Dan Scott

    2010-01-01

    The Open Service Request Framework (or OpenSRF, pronounced "open surf") is an inter-application message passing architecture built on XMPP (aka "jabber"). The Evergreen open source library system is built on an OpenSRF architecture to support loosely coupled individual components communicating over an OpenSRF messaging bus. This article introduces OpenSRF, demonstrates how to build OpenSRF services through simple code examples, explains the technical foundations on which OpenSRF is built, and...

  5. Thin Film Approaches to the SRF Cavity Problem: Fabrication and Characterization of Superconducting Thin Films

    Beringer, Douglas B.

    Superconducting Radio Frequency (SRF) cavities are responsible for the acceleration of charged particles to relativistic velocities in most modern linear accelerators, such as those employed at high-energy research facilities like Thomas Jefferson National Laboratory's CEBAF and the LHC at CERN. Recognizing SRF as primarily a surface phenomenon enables the possibility of applying thin films to the interior surface of SRF cavities, opening a formidable tool chest of opportunities by combining and designing materials that offer greater benefit. Thus, while improvements in radio frequency cavity design and refinements in cavity processing techniques have improved accelerator performance and efficiency - 1.5 GHz bulk niobium SRF cavities have achieved accelerating gradients in excess of 35 MV/m - there exist fundamental material bounds in bulk superconductors limiting the maximally sustained accelerating field gradient (approximately 45 MV/m for Niobium) where inevitable thermodynamic breakdown occurs. With state of the art niobium based cavity design fast approaching these theoretical limits, novel material innovations must be sought in order to realize next generation SRF cavities. One proposed method to improve SRF performance is to utilize thin film superconducting-insulating-superconducting (SIS) multilayer structures to effectively magnetically screen a bulk superconducting layer such that it can operate at higher field gradients before suffering critically detrimental SRF losses. This dissertation focuses on the production and characterization of thin film superconductors for such SIS layers for radio-frequency applications.

  6. Magnesium Diboride thin Films, multilayers, and coatings for SRF cavities

    Xi, Xiaoxing [Temple Univ., Philadelphia, PA (United States)

    2017-08-17

    Superconducting radio frequency (SRF) cavities currently use low-temperature superconductor niobium, and the Nb SRF cavities have approached the performance levels predicted theoretically. Compared to Nb, MgB2 becomes superconducting at a much higher temperature and promises a better RF performance in terms of higher quality factor Q and higher acceleration capability. An MgB2 SRF technology can significantly reduce the operating costs of particle accelerators when these potentials are realized. This project aimed to advance the development of an MgB2 SRF technology. It had two main objectives: (1) materials issues of MgB2 thin films and multilayers related to their applications in SRF cavities; and (2) coating single-cell cavities for testing at RF frequencies. The key technical thrust of the project is the deposition of high quality clean MgB2 films and coatings by the hybrid physical-chemical vapor deposition (HPCVD) technique, which was developed in my group. We have achieved technical progress in each of the two areas. For the first objective, we have confirmed that MgB2 thin film coatings can be used to effectively enhance the vortex penetration field of an SRF cavity. A vortex is a normal region in the shape of spaghetti that threads through a superconductor. Its existence is due to an applied magnetic field that is greater than a so-called lower critical field, Hc1. Once a vortex enters the superconductor, its movement leads to loss. This has been shown to be the reason for an SRF cavity to break down. Thus, enhancing the magnetic field for a vortex to enter the superconductor that forms the SRF cavity has be a goal of intense research. To this end, Gurevich proposed that a coating of thin superconductor layer can impede the vortex entrance. In this project, we have done two important experiment to test this concept. One, we showed that the enhancement of Hc1 can be

  7. RF Power Requirements for PEFP SRF Cavity Test

    Kim, Han Sung; Seol, Kyung Tae; Kwon, Hyeok Jung; Cho, Yong Sub

    2011-01-01

    For the future extension of the PEFP (Proton Engineering Frontier Project) Proton linac, preliminary study on the SRF (superconducting radio-frequency) cavity is going on including a five-cell prototype cavity development to confirm the design and fabrication procedures and to check the RF and mechanical properties of a low-beta elliptical cavity. The main parameters of the cavity are like followings. - Frequency: 700 MHz - Operating mode: TM010 pi mode - Cavity type: Elliptical - Geometrical beta: 0.42 - Number of cells: 5 - Accelerating gradient: 8 MV/m - Epeak/Eacc: 3.71 - Bpeak/Eacc: 7.47 mT/(MV/m) - R/Q: 102.3 ohm - Epeak: 29.68 MV/m (1.21 Kilp.) - Geometrical factor: 121.68 ohm - Cavity wall thickness: 4.3 mm - Stiffening structure: Double ring - Effective length: 0.45 m For the test of the cavity at low temperature of 4.2 K, many subsystems are required such as a cryogenic system, RF system, vacuum system and radiation shielding. RF power required to generate accelerating field inside cavity depends on the RF coupling parameters of the power coupler and quality factor of the SRF cavity and the quality factor itself is affected by several factors such as operating temperature, external magnetic field level and surface condition. Therefore, these factors should be considered to estimate the required RF power for the SRF cavity test

  8. Locally expressed IGF1 propeptide improves mouse heart function in induced dilated cardiomyopathy by blocking myocardial fibrosis and SRF-dependent CTGF induction

    Melissa Touvron

    2012-07-01

    Cardiac fibrosis is critically involved in the adverse remodeling accompanying dilated cardiomyopathies (DCMs, which leads to cardiac dysfunction and heart failure (HF. Connective tissue growth factor (CTGF, a profibrotic cytokine, plays a key role in this deleterious process. Some beneficial effects of IGF1 on cardiomyopathy have been described, but its potential role in improving DCM is less well characterized. We investigated the consequences of expressing a cardiac-specific transgene encoding locally acting IGF1 propeptide (muscle-produced IGF1; mIGF1 on disease progression in a mouse model of DCM [cardiac-specific and inducible serum response factor (SRF gene disruption] that mimics some forms of human DCM. Cardiac-specific mIGF1 expression substantially extended the lifespan of SRF mutant mice, markedly improved cardiac functions, and delayed both DCM and HF. These protective effects were accompanied by an overall improvement in cardiomyocyte architecture and a massive reduction of myocardial fibrosis with a concomitant amelioration of inflammation. At least some of the beneficial effects of mIGF1 transgene expression were due to mIGF1 counteracting the strong increase in CTGF expression within cardiomyocytes caused by SRF deficiency, resulting in the blockade of fibroblast proliferation and related myocardial fibrosis. These findings demonstrate that SRF plays a key role in the modulation of cardiac fibrosis through repression of cardiomyocyte CTGF expression in a paracrine fashion. They also explain how impaired SRF function observed in human HF promotes fibrosis and adverse cardiac remodeling. Locally acting mIGF1 efficiently protects the myocardium from these adverse processes, and might thus represent a therapeutic avenue to counter DCM.

  9. SRF Clean Rooms and Cryomodule Assembly

    Federal Laboratory Consortium — Three primary cleanroom facilities used for the SRF cryomodule production program are available. All 3 clean rooms have class 10 and class 100 areas. The largest is...

  10. Frequency-tunable SRF cavities for microwave opto-mechanics

    Castelli, Alessandro; Martinez, Luis; Pate, Jacob; Thompson, Johnathon; Chiao, Raymond; Sharping, Jay

    Three dimensional SRF (Superconducting Radio Frequency) cavities are known for achieving high quality factors (Q =109 or higher) but suffer from limited frequency tunability once fabricated and cooled to superconducting temperatures. Our end-wall design allows for numerous applications of cavity tuning at temperatures as low as 40 millikelvin. Using a bimorphic piezoelectric transducer, we demonstrate approximately 15 MHz of resonance tunability for the TE011 mode at cryogenic temperatures in a cylindrical reactor grade niobium (Nb) cavity (10% of the range at room temperature). This range doubles when using tunable end-walls on both cavity ends. We report on techniques for improving the Q of multi-component cavities including the use of concave end-walls to reduce fields near the cylinder ends and indium O-rings to reduce resistive losses at the gaps. Three-dimensional SRF cavities of this type have potential applications to quantum information science, precision displacement metrology, and quantum electro-dynamics.

  11. Influence of SrF_2-doping in AlN ceramics on scintillation and dosimeter properties

    Kojima, Kaori; Okada, Go; Fukuda, Kentaro; Yanagida, Takayuki

    2016-01-01

    In this study, we synthesized undoped AlN and SrF_2-doped AlN (AlN-SrF_2) ceramics by Spark Plasma Sintering (SPS), and we characterized their optical, scintillation and dosimeter properties. The prepared undoped AlN ceramic had gray color and visually non-transparent whereas, with an addition of SrF_2, the transparency improved and became translucent. The measured in-line transmittance was approximately 0.2% at wavelengths longer than 500 nm. While the addition of SrF_2 decreased the scintillation intensity, the decay time was significantly fastened, which is a great advantage for fast photon counting-based measurements. Both the thermally-stimulated luminescence (TSL) and optically-stimulated luminescence (OSL) showed good linear response from the milli-gray range to over 10 Gy. The sensitivity seems to decrease by an addition of SrF_2 as it suppresses structural defect centers which are responsible for dosimeter properties. However, the main TSL glow peak position shifts to higher temperature with the addition of SrF_2, which indicates that inclusion of SrF_2 improves the TSL signal stability. - Highlights: • We synthesized undoped and SrF_2-doped AlN ceramics by Spark Plasma Sintering. • We evaluated scintillator and dosimeter properties of undoped and SrF_2-doped AlN. • By doping with SrF_2, the decay time is shortened. • By doping with SrF_2, the stability of TSL and OSL is improved.

  12. CEBAF's SRF cavity manufacturing experience

    Benesch, J.F.; Reece, C.E.

    1994-01-01

    Construction of the Continuous Electron Beam Accelerator Facility (CEBAF) recirculating linac represents the largest scale application of superconducting rf (SRF) technology to date. The accelerating structures in CEBAF are 169 pairs of 1.5 GHz superconducting rf cavities -- 9 pairs in an injector and 80 pairs each in two linacs. The beam is to be recirculated up to five passes through each linac. Data is presented on mechanical tolerances achieved by the industrial fabricator of the rf cavities (Siemens). Liquid helium leak rates integrated over 22 vacuum seals have been measured on over 110 cavity pairs. A roughly normal distribution of the log 10 (leak rate) is seen, centered about a rate of 10 -10.4 torr-l/s. Over 140 pairs of the cavities have been assembled and have completed rf testing at 2.0 K. Among these, 54% demonstrated usable accelerating gradients greater than 10 MV/m. Although the rf performance characteristics well exceed the CEBAF baseline requirements of 5 MV/m at Q 0 = 2.4x10 9 , the usual limiting phenomena are encountered: field emission, quenching, and occasional multipacting. A discussion of the occurrence conditions and severity of these phenomena during production cavity testing is presented. The frequency with which performance is limited by quenching suggests that additional material advances may be required for applications which require the reliable achievement of accelerating gradients of more than 15 MV/m

  13. Thin Film Approaches to the SRF Cavity Problem Fabrication and Characterization of Superconducting Thin Films

    Beringer, Douglas [College of William and Mary, Williamsburg, VA (United States)

    2017-08-01

    Superconducting Radio Frequency (SRF) cavities are responsible for the acceleration of charged particles to relativistic velocities in most modern linear accelerators, such as those employed at high-energy research facilities like Thomas Jefferson National Laboratory’s CEBAF and the LHC at CERN. Recognizing SRF as primarily a surface phenomenon enables the possibility of applying thin films to the interior surface of SRF cavities, opening a formidable tool chest of opportunities by combining and designing materials that offer greater performance benefit. Thus, while improvements in radio frequency cavity design and refinements in cavity processing techniques have improved accelerator performance and efficiency – 1.5 GHz bulk niobium SRF cavities have achieved accelerating gradients in excess of 35 MV/m – there exist fundamental material bounds in bulk superconductors limiting the maximally sustained accelerating field gradient (≈ 45 MV/m for Nb) where inevitable thermodynamic breakdown occurs. With state of the art Nb based cavity design fast approaching these theoretical limits, novel material innovations must be sought in order to realize next generation SRF cavities. One proposed method to improve SRF performance is to utilize thin film superconducting-insulating-superconducting (SIS) multilayer structures to effectively magnetically screen a bulk superconducting layer such that it can operate at higher field gradients before suffering critically detrimental SRF losses. This dissertation focuses on the production and characterization of thin film superconductors for such SIS layers for radio frequency applications. Correlated studies on structure, surface morphology and superconducting properties of epitaxial Nb and MgB2 thin films are presented.

  14. Protonation Effect of Tyrosine in a Segment of the SRF Transcription Factor: A Combined Optical Spectroscopy, Molecular Dynamics, and Density Functional Theory Calculation Study

    Profantová, B.; Profant, V.; Zíma, V.; Kopecký, V. Jr.; Bednárová, Lucie; Zentz, Ch.; Baumruk, V.; Turpin, P. Y.; Štěpánek, J.

    2013-01-01

    Roč. 117, č. 50 (2013), s. 16086-16095 ISSN 1520-6106 R&D Projects: GA ČR GA202/09/0193 Institutional support: RVO:61388963 Keywords : MADS box * protein secondary structure * tyrosine * pHtransition * Raman spectroscopy Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.377, year: 2013

  15. Study of RF flux penetration on Nb for SRF Applications

    Oripov, Bakhrom; Anlage, Steven

    Superconducting Radio Frequency (SRF) cavities are being widely used in new generation particle accelerators. Based on the needs of the SRF community to identify defects on Nb surfaces, a novel near-field magnetic field microwave microscope was successfully built using a magnetic writer from a conventional perpendicular magnetic recording hard-disk drive. Using our probe, we performed microwave measurement of both third P3f\\ (Pf,T) and fifth P5f (Pf,T) harmonic responses and its dependence on temperature and rf input power by applying a strong and localized RF magnetic field on high quality Nb films. Our preliminary results show significant difference in low-field and high-field harmonic responses. Above a temperature-dependent onset field H1 periodic structures in the harmonic response vs rf field amplitude data emerges. Similar behavior is observed in both bulk Nb and thin film Nb samples. We attribute this periodic response to vortex nonlinearity. Using our microscope, we are able to measure a local lower critical field for vortex formation Hc,v (in arbitrary units), and compare the Hc,v's of samples produced with different techniques and chemical treatments. This work is funded by US Department of Energy through Grant # DE-SC0012036T and CNAM.

  16. Sample preparation and biomass determination of SRF model mixture using cryogenic milling and the adapted balance method

    Schnöller, Johannes, E-mail: johannes.schnoeller@chello.at; Aschenbrenner, Philipp; Hahn, Manuel; Fellner, Johann; Rechberger, Helmut

    2014-11-15

    Highlights: • An alternative sample comminution procedure for SRF is tested. • Proof of principle is shown on a SRF model mixture. • The biogenic content of the SRF is analyzed with the adapted balance method. • The novel method combines combustion analysis and a data reconciliation algorithm. • Factors for the variance of the analysis results are statistically quantified. - Abstract: The biogenic fraction of a simple solid recovered fuel (SRF) mixture (80 wt% printer paper/20 wt% high density polyethylene) is analyzed with the in-house developed adapted balance method (aBM). This fairly new approach is a combination of combustion elemental analysis (CHNS) and a data reconciliation algorithm based on successive linearisation for evaluation of the analysis results. This method shows a great potential as an alternative way to determine the biomass content in SRF. However, the employed analytical technique (CHNS elemental analysis) restricts the probed sample mass to low amounts in the range of a few hundred milligrams. This requires sample comminution to small grain sizes (<200 μm) to generate representative SRF specimen. This is not easily accomplished for certain material mixtures (e.g. SRF with rubber content) by conventional means of sample size reduction. This paper presents a proof of principle investigation of the sample preparation and analysis of an SRF model mixture with the use of cryogenic impact milling (final sample comminution) and the adapted balance method (determination of biomass content). The so derived sample preparation methodology (cutting mills and cryogenic impact milling) shows a better performance in accuracy and precision for the determination of the biomass content than one solely based on cutting mills. The results for the determination of the biogenic fraction are within 1–5% of the data obtained by the reference methods, selective dissolution method (SDM) and {sup 14}C-method ({sup 14}C-M)

  17. Modeling the interaction of a heavily beam loaded SRF cavity with its low-level RF feedback loops

    Liu, Zong-Kai; Wang, Chaoen; Chang, Lung-Hai; Yeh, Meng-Shu; Chang, Fu-Yu; Chang, Mei-Hsia; Chang, Shian-Wen; Chen, Ling-Jhen; Chung, Fu-Tsai; Lin, Ming-Chyuan; Lo, Chih-Hung; Yu, Tsung-Chi

    2018-06-01

    A superconducting radio frequency (SRF) cavity provides superior stability to power high intensity light sources and can suppress coupled-bunch instabilities due to its smaller impedance for higher order modes. Because of these features, SRF cavities are commonly used for modern light sources, such as the TLS, CLS, DLS, SSRF, PLS-II, TPS, and NSLS-II, with an aggressive approach to operate the light sources at high beam currents. However, operating a SRF cavity at high beam currents may result with unacceptable stability problems of the low level RF (LLRF) system, due to drifts of the cavity resonant frequency caused by unexpected perturbations from the environment. As the feedback loop gets out of control, the cavity voltage may start to oscillate with a current-dependent characteristic frequency. Such situations can cause beam abort due to the activation of the interlock protection system, i.e. false alarm of quench detection. This malfunction of the light source reduces the reliability of SRF operation. Understanding this unstable mechanism to prevent its appearance becomes a primary task in the pursuit of highly reliable SRF operation. In this paper, a Pedersen model, including the response of the LLRF system, was used to simulate the beam-cavity interaction of a SRF cavity under heavy beam loading. Causes for the onset of instability at high beam current will be discussed as well as remedies to assure the design of a stable LLRF system.

  18. Resonance control in SRF cavities at FNAL

    Schappert, W.; Pischalnikov, Y.; /Fermilab; Scorrano, M.; /INFN, Pisa

    2011-03-01

    The Lorentz force can dynamically detune pulsed Superconducting RF cavities. Considerable additional RF power can be required to maintain the accelerating gradient if no effort is made to compensate for this detuning. Compensation systems using piezo actuators have been used successfully at DESY and elsewhere to control Lorentz Force Detuning (LFD). Recently, Fermilab has developed an adaptive compensation system for cavities in the Horizontal Test Stand, in the SRF Accelerator Test Facility, and for the proposed Project X.

  19. Additive manufacturing method for SRF components of various geometries

    Rimmer, Robert; Frigola, Pedro E; Murokh, Alex Y

    2015-05-05

    An additive manufacturing method for forming nearly monolithic SRF niobium cavities and end group components of arbitrary shape with features such as optimized wall thickness and integral stiffeners, greatly reducing the cost and technical variability of conventional cavity construction. The additive manufacturing method for forming an SRF cavity, includes atomizing niobium to form a niobium powder, feeding the niobium powder into an electron beam melter under a vacuum, melting the niobium powder under a vacuum in the electron beam melter to form an SRF cavity; and polishing the inside surface of the SRF cavity.

  20. Strategies for waveguide coupling for SRF cavities

    Doolittle, L.R.

    1998-01-01

    Despite widespread use of coaxial couplers in SRF cavities, a single, simple waveguide coupling can be used both to transmit generator power to a cavity, and to remove a large class of Higher Order Modes (HOMs, produced by the beam). There are balances and tradeoffs to be made, such as the coupling strength of the various frequencies, the transverse component of the coupler fields on the beam axis, and the magnitude of the surface fields and currents. This paper describes those design constraints, categories of solutions, and examples from the CEBAF Energy Upgrade studies

  1. Fabrication of elliptical SRF cavities

    Singer, W.

    2017-03-01

    The technological and metallurgical requirements of material for high-gradient superconducting cavities are described. High-purity niobium, as the preferred metal for the fabrication of superconducting accelerating cavities, should meet exact specifications. The content of interstitial impurities such as oxygen, nitrogen, and carbon must be below 10 μg g-1. The hydrogen content should be kept below 2 μg g-1 to prevent degradation of the quality factor (Q-value) under certain cool-down conditions. The material should be free of flaws (foreign material inclusions or cracks and laminations) that can initiate a thermal breakdown. Traditional and alternative cavity mechanical fabrication methods are reviewed. Conventionally, niobium cavities are fabricated from sheet niobium by the formation of half-cells by deep drawing, followed by trim machining and electron beam welding. The welding of half-cells is a delicate procedure, requiring intermediate cleaning steps and a careful choice of weld parameters to achieve full penetration of the joints. A challenge for a welded construction is the tight mechanical and electrical tolerances. These can be maintained by a combination of mechanical and radio-frequency measurements on half-cells and by careful tracking of weld shrinkage. The main aspects of quality assurance and quality management are mentioned. The experiences of 800 cavities produced for the European XFEL are presented. Another cavity fabrication approach is slicing discs from the ingot and producing cavities by deep drawing and electron beam welding. Accelerating gradients at the level of 35-45 MV m-1 can be achieved by applying electrochemical polishing treatment. The single-crystal option (grain boundary free) is discussed. It seems that in this case, high performance can be achieved by a simplified treatment procedure. Fabrication of the elliptical resonators from a seamless pipe as an alternative is briefly described. This technology has yielded good

  2. Status and future prospects of SRF gun developments

    Teichert, Jochen

    2006-01-01

    While the concepts of DC and normal-conducting photo-injectors are well proofed, the SRF gun development still possesses a high risk. Challenges are the thermal and contaminant isolation needed between the cathode and superconducting cavity, the choice of the right photocathode and its life time, the difficulty of coupling high-average power into the gun, and beam excitation of higher order cavity modes. But in combination with SRF linacs, the SRF guns are the best solution for high current and CW operation. Thus, several R and D projects of SRF gun have been launched. The talk will give an overview of the history and progress of the SRF gun development. In more detail the technical concept, performance, and status of the Rossendorf superconducting RF gun project, a collaboration of BESSY, DESY, MBI and FZR, will be presented. (author)

  3. Diagnostics Beamline for the SRF Gun Project

    Kamps, T; Goldammer, K; Krämer, Dietrich; Kuske, P; Kuszynski, J; Lipka, D; Marhauser, F; Quast, T; Richter, R

    2005-01-01

    A superconducting rf photo electron injector (SRF gun) is currently under construction by a collaboration between BESSY, DESY, FZR and MBI. The project aims at the design and setup of an CW SRF gun including a diagnostics beamline for the ELBE FEL and to address R&D issues on low emittance injectors for future light sources such as the BESSY FEL. Of critical importance for the injector performance is the control of the electron beam parameters. For this reason a compact diagnostics beamline is under development serving a multitude of operation settings ranging from low-charge (77pC), low-emittance (1 pi mm mrad) mode to high-charge (2.5nC) operation of the gun. For these operation modes beam dynamics simulations are resulting in boundary conditions for the beam instrumentation. Proven and mature technology is projected wherever possible, for example for current and beam position monitoring. The layout of the beam profile and emittance measurement systems is described. For the bunch length, which varies be...

  4. Small-Molecule Inhibition of Rho/MKL/SRF Transcription in Prostate Cancer Cells: Modulation of Cell Cycle, ER Stress, and Metastasis Gene Networks

    Chris R. Evelyn

    2016-05-01

    Full Text Available Metastasis is the major cause of cancer deaths and control of gene transcription has emerged as a critical contributing factor. RhoA- and RhoC-induced gene transcription via the actin-regulated transcriptional co-activator megakaryocytic leukemia (MKL and serum response factor (SRF drive metastasis in breast cancer and melanoma. We recently identified a compound, CCG-1423, which blocks Rho/MKL/SRF-mediated transcription and inhibits PC-3 prostate cancer cell invasion. Here, we undertook a genome-wide expression study in PC-3 cells to explore the mechanism and function of this compound. There was significant overlap in the genes modulated by CCG-1423 and Latrunculin B (Lat B, which blocks the Rho/MKL/SRF pathway by preventing actin polymerization. In contrast, the general transcription inhibitor 5,6-dichloro-1-β-d-ribofuranosyl-1H-benzimidazole (DRB showed a markedly different pattern. Effects of CCG-1423 and Lat B on gene expression correlated with literature studies of MKL knock-down. Gene sets involved in DNA synthesis and repair, G1/S transition, and apoptosis were modulated by CCG-1423. It also upregulated genes involved in endoplasmic reticulum stress. Targets of the known Rho target transcription factor family E2F and genes related to melanoma progression and metastasis were strongly suppressed by CCG-1423. These results confirm the ability of our compound to inhibit expression of numerous Rho/MKL-dependent genes and show effects on stress pathways as well. This suggests a novel approach to targeting aggressive cancers and metastasis.

  5. BNL 703 MHz SRF cryomodule demonstration

    Burrill, A.; Ben-Zvi, I.; Calaga, R.; Dalesio, L.; Dottavio, T.; Gassner, D.; Hahn, H.; Hoff, L.; Kayran, D.; Kewisch, J.; Lambiase, R.; Lederle, D.; Litvinenko, V.; Mahler, G.; McIntyre, G.

    2009-01-01

    This paper will present the preliminary results of the testing of the 703 MHz SRF cryomodule designed for use in the ampere class ERL under construction at Brookhaven National Laboratory. The preliminary cavity tests, carried out at Thomas Jefferson Laboratory, demonstrated cavity performance of 20 MV/m with a Qo of 1 x 10 10 , results we expect to reproduce in the horizontal configuration. This test of the entire string assembly will allow us to evaluate all of the additional cryomodule components not previously tested in the VTA and will prepare us for our next milestone test which will be delivery of electrons from our injector through the cryomodule to the beam dump. This will also be the first demonstration of an accelerating cavity designed for use in an ampere class ERL, a key development which holds great promise for future machines

  6. A Family of L-band SRF Cavities for High Power Proton Driver Applications

    Rimmer, Robert; Marhauser, Frank

    2009-01-01

    Recent global interest in high duty factor or CW superconducting linacs with high average beam power highlights the need for robust and reliable SRF structures capable of delivering high average RF power to the beam with moderate HOM damping, low interception of halo and good efficiency. Potential applications include proton or H- drivers for spallation neutron sources, neutrino physics, waste transmutation, subcritical reactors, and high-intensity high-energy physics experiments. We describe a family of SRF cavities with a range of Betas capable of transporting beam currents in excess of 10 mA CW with large irises for minimal interception of halo and HOM and power couplers capable of supporting high average power operation. Goals include an efficient cell shape, high packing factor for efficient real-estate gradient and strong HOM damping to ensure stable beam operation,

  7. HOM frequency control of SRF cavity in high current ERLs

    Xu, Chen; Ben-Zvi, Ilan

    2018-03-01

    The acceleration of high-current beam in Superconducting Radio Frequency (SRF) cavities is a challenging but essential for a variety of advanced accelerators. SRF cavities should be carefully designed to minimize the High Order Modes (HOM) power generated in the cavities by the beam current. The reduction of HOM power we demonstrate in a particular case can be quite large. This paper presents a method to systematically control the HOM resonance frequencies in the initial design phase to minimize the HOM power generation. This method is expected to be beneficial for the design of high SRF cavities addressing a variety of Energy Recovery Linac (ERL) applications.

  8. A SRF niobium cylindrical cavity with a large silicon nitride niobium-coated membrane as one end-wall

    Martinez, Luis; Castelli, Alessandro; Pate, Jacob; Thompson, Johnathon; Delmas, William; Sharping, Jay; Chiao, Raymond; Chiao Team; Sharping Team

    The development of large silicon nitride membranes and niobium film deposition techniques motivate new architectures in opto-mechanics and microwave devices that can exploit the extremely high Q's obtainable with superconducting radio frequency (SRF) niobium cavities. We present a X-band SRF cylindrical cavity-membrane system in which one end-wall of the cavity is replaced by a niobium coated centimeter-sized silicon nitride membrane. We report moderately high Q factors above 10 million. Experimental results characterizing the system and potential future applications for such schemes in microwave devices and optomechanics are discussed.

  9. Mass, energy and material balances of SRF production process. Part 1: SRF produced from commercial and industrial waste.

    Nasrullah, Muhammad; Vainikka, Pasi; Hannula, Janne; Hurme, Markku; Kärki, Janne

    2014-08-01

    This paper presents the mass, energy and material balances of a solid recovered fuel (SRF) production process. The SRF is produced from commercial and industrial waste (C&IW) through mechanical treatment (MT). In this work various streams of material produced in SRF production process are analyzed for their proximate and ultimate analysis. Based on this analysis and composition of process streams their mass, energy and material balances are established for SRF production process. Here mass balance describes the overall mass flow of input waste material in the various output streams, whereas material balance describes the mass flow of components of input waste stream (such as paper and cardboard, wood, plastic (soft), plastic (hard), textile and rubber) in the various output streams of SRF production process. A commercial scale experimental campaign was conducted on an MT waste sorting plant to produce SRF from C&IW. All the process streams (input and output) produced in this MT plant were sampled and treated according to the CEN standard methods for SRF: EN 15442 and EN 15443. The results from the mass balance of SRF production process showed that of the total input C&IW material to MT waste sorting plant, 62% was recovered in the form of SRF, 4% as ferrous metal, 1% as non-ferrous metal and 21% was sorted out as reject material, 11.6% as fine fraction, and 0.4% as heavy fraction. The energy flow balance in various process streams of this SRF production process showed that of the total input energy content of C&IW to MT plant, 75% energy was recovered in the form of SRF, 20% belonged to the reject material stream and rest 5% belonged with the streams of fine fraction and heavy fraction. In the material balances, mass fractions of plastic (soft), plastic (hard), paper and cardboard and wood recovered in the SRF stream were 88%, 70%, 72% and 60% respectively of their input masses to MT plant. A high mass fraction of plastic (PVC), rubber material and non

  10. Observation of Stable Low Surface Resistance in Large-Grain Niobium SRF Cavities

    Geng, Rongli [Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States); Huang, Shichun [Institute of Modern Physics (IMP)/Chinese Academy of Sciences (CAS), Lanzhou (China)

    2016-05-01

    Low surface resistance, or high unloaded quality factor (Q0), superconducting radio frequency (SRF) cavities are being pursued actively nowadays as their application in large-scale CW SRF accelerators can save capital and operational cost in cryogenics. There are different options in realization of such cavities. One of them is the large-grain (LG) niobium cavity. In this contribution, we present new experimental results in evaluation of LG niobium cavities cooled down in the presence of an external magnetic field. High Q0 values are achieved even with an ambient magnetic field of up to 100 mG. More over, it is observed that these high Q0 values are super-robust against repeated quench, literally not affected at all after the cavity being deliberately quenched for hundreds of times in the presence of an ambient magnetic field of up to 200 mG.

  11. Dealing with a large installation of SRF cavities: Characterizing limitations and exploiting operational flexibility

    C. Reece; B. Madre; L. Doolittle; J. Delayen

    1999-01-01

    Linacs using a large number of SRF cavities can have an awkwardly large number of degrees of freedom for operational setup. The cost and robustness of operation as a function of operating gradient is a particular characteristic of each cavity system and the intended beamloading. A systematic characterization of these limitations has been developed which yields a valuable guide for development resource allocation. In addition, a software tool has been developed which enables the CEBAF machine operator to conveniently exploit the flexibility that results from the many degrees of freedom in response to changing programmatic needs. The two CEBAF SRF linacs each have about 160 independently-controlled SRF cavities. The software utility (LEM++) establishes the operationally optimum gradient in each cavity in response to the operator providing only three of the following four parameters: linac voltage, anticipated beam current, rf cryoheat load, and net rf trip rate. The utility is now fully operational at CEBAF. The methods employed and particular features useful for operations will be presented. The interactive process that has brought the software to its current form will also be discussed. The analysis scheme used to characterize the limitations of the ensemble of cavities will be presented as well

  12. Mass, energy and material balances of SRF production process. Part 2: SRF produced from construction and demolition waste.

    Nasrullah, Muhammad; Vainikka, Pasi; Hannula, Janne; Hurme, Markku; Kärki, Janne

    2014-11-01

    In this work, the fraction of construction and demolition waste (C&D waste) complicated and economically not feasible to sort out for recycling purposes is used to produce solid recovered fuel (SRF) through mechanical treatment (MT). The paper presents the mass, energy and material balances of this SRF production process. All the process streams (input and output) produced in MT waste sorting plant to produce SRF from C&D waste are sampled and treated according to CEN standard methods for SRF. Proximate and ultimate analysis of these streams is performed and their composition is determined. Based on this analysis and composition of process streams their mass, energy and material balances are established for SRF production process. By mass balance means the overall mass flow of input waste material stream in the various output streams and material balances mean the mass flow of components of input waste material stream (such as paper and cardboard, wood, plastic (soft), plastic (hard), textile and rubber) in the various output streams of SRF production process. The results from mass balance of SRF production process showed that of the total input C&D waste material to MT waste sorting plant, 44% was recovered in the form of SRF, 5% as ferrous metal, 1% as non-ferrous metal, and 28% was sorted out as fine fraction, 18% as reject material and 4% as heavy fraction. The energy balance of this SRF production process showed that of the total input energy content of C&D waste material to MT waste sorting plant, 74% was recovered in the form of SRF, 16% belonged to the reject material and rest 10% belonged to the streams of fine fraction and heavy fraction. From the material balances of this process, mass fractions of plastic (soft), paper and cardboard, wood and plastic (hard) recovered in the SRF stream were 84%, 82%, 72% and 68% respectively of their input masses to MT plant. A high mass fraction of plastic (PVC) and rubber material was found in the reject material

  13. Modified SRF Photoinjector for the ELBE at HZDR

    Murcek, P; Buettig, H; Michel, P; Teichert, J; Xiang, R; Kneisel, P

    2012-01-01

    The superconducting radio frequency photoinjector (SRF photoinjector) with Cs2Te cathode has been successfully operated under the collaboration of HZB, DESY, HZDR, and MBI.[1] In order to improve the gradient of the gun cavity and the beam quality, a new modified SRF gun (SRF-gun 2008) has been designed. The main updates of the new cavity design for the new photoinjector were publisched before. (ID THPPO022 on the SRF09 Berlin.) This cavity is being fabricated in Jefferson Lab. In this paper the new ideas of the further parts of the SRF-gun 2008 will be presented. The most important issue is the special design of half-cell and choke filter. The cathode cooler is also slightly changed, which simplifies the installation of the cathode cooler in the cavity. The next update is the separation of input and output of the liquid nitrogen supply, for the purpose of the stability of the nitrogen pressure as well as the better possibility of temperature measurement. Another key point is the implementation of the superco...

  14. SRF and RF systems for LEReC Linac

    Belomestnykh, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., NY (United States); Ben-Zvi, I. [Brookhaven National Lab. (BNL), Upton, NY (United States); Stony Brook Univ., NY (United States); Brutus, J. C. [Brookhaven National Lab. (BNL), Upton, NY (United States); Fedotov, A. [Brookhaven National Lab. (BNL), Upton, NY (United States); McIntyre, G. [Brookhaven National Lab. (BNL), Upton, NY (United States); Polizzo, S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Smith, K. [Brookhaven National Lab. (BNL), Upton, NY (United States); Than, R. [Brookhaven National Lab. (BNL), Upton, NY (United States); Tuozzolo, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Veshcherevich, V. [Cornell Univ., Ithaca, NY (United States); Wu, Q. [Brookhaven National Lab. (BNL), Upton, NY (United States); Xiao, B. [Brookhaven National Lab. (BNL), Upton, NY (United States); Xu, W. [Brookhaven National Lab. (BNL), Upton, NY (United States); Zaltsman, A. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-05-03

    The Low Energy RHIC electron Cooling (LEReC) is under development at BNL to improve RHIC luminosity at low energies. It will consist of a short electron linac and two cooling sections, one for blue and one for yellow rings. For the first stage of the project, LEReC-I, we will install a 704 MHz superconducting RF cavity and three normal conducting cavities operating at 9 MHz, 704 MHz and 2.1 GHz. The SRF cavity will boost the electron beam energy up to 2 MeV. The warm cavities will be used to correct the energy spread introduced in the SRF cavity. The paper describes layouts of the SRF and RF systems, their parameters and status.

  15. Electron color centers in SrF2-Na crystals

    Kachan, S.I.; Chornij, Z.P.

    2006-01-01

    A radiation-induced memory effect in SrF 2 -Na crystals is studied. It was shown that optical bleaching of M + A color centers at 80 K in SrF 2 -Na crystals causes the core of an M + A -center to transform into the V + a Me + V + a configuration, in which all three point defects are arranged diagonally in the cube cell. Reirradiation of an optically bleached crystal by X-rays generates F D centers in it. The F D →M + A transformation in SrF 2 -Na crystals occurs at T = 135 K, in contrast to the F A →M + A transformations, which take place at T > 200 K [ru

  16. SRF technology at accel for worldwide accelerator projects

    Bauer, S.; Griep, B.; Peiniger, M.; Pekeler, M.; Piel, C.; Stein, P. vom; Vogel, H.

    2003-01-01

    Within the last two years activities at ACCEL for international accelerator projects using superconducting cavities have steadily increased. We report on our production work for CERN (HOM couplers for LHC cavities), DESY (TESLA cavities and couplers), Forschungszentrum Juelich (turn key low beta SRF module), SRRC, CLS and Cornell (turn key 500 MHz SRF modules. The production a superconducting Landau accelerator module for BESSY has started recently. In addition studies are under way for a superconducting 40 MeV proton/deuteron linac and for superconducting low beta multi gap structures. (author)

  17. Simulation Study Using an Injection Phase-locked Magnetron as an Alternative Source for SRF Accelerators

    Wang, Haipeng [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Plawski, Tomasz E. [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States); Rimmer, Robert A. [Thomas Jefferson National Accelerator Facility, Newport News, VA (United States)

    2015-09-01

    As a drop-in replacement for the CEBAF CW klystron system, a 1497 MHz, CW-type high-efficiency magnetron using injection phase lock and amplitude variation is attractive. Amplitude control using magnetic field trimming and anode voltage modulation has been studied using analytical models and MATLAB/Simulink simulations. Since the 1497 MHz magnetron has not been built yet, previously measured characteristics of a 2.45GHz cooker magnetron are used as reference. The results of linear responses to the amplitude and phase control of a superconducting RF (SRF) cavity, and the expected overall benefit for the current CEBAF and future MEIC RF systems are presented in this paper.

  18. Pengaruh variasi rasio HAF/SRF terhadap sifat vulkanisat NBR

    Ihda Novia Indrajati

    2012-12-01

    Full Text Available The objectives of the research were to study the effect of HAF/SRF black ratio and the loading of sulfur on vulcanization characteristic, swelling behaviour and compression set of NBR vulcanizates. The ratio of HAF/SRF were 0/70; 10/60; 20/50; 30/40; 35/35; 40/30; 50/20 and 70/0 phr, respectively. The observation of this research consist of curing characteristic, morphology property and swelling equilibrium. Curing characteristic was determined from cure rate index (CRI, vulcanizates morphology was studied by SEM and swelling equilibrium was conducted by immersion test using benzene. The data were analyzed qualitatively to see the respond of the variable on physical properties. The curing characteristic of double filler vulcanizates was higher than those with single filler. Solvent uptake for double filler present in between to those with HAF or SRF. All of vulcanizates indicate the anomalous mass tranfer, with n>0,5 and constant k showed the same trend. The intrinsic diffusivity (D*, sorption and permeation coefficient showed similar trend and the maximum was obtained by the ratio HAF/SRF 0/70.

  19. Oncogenic N-Ras Stimulates SRF-Mediated Transactivation via H3 Acetylation at Lysine 9

    Sun-Ju Yi

    2018-01-01

    Full Text Available Signal transduction pathways regulate the gene expression by altering chromatin dynamics in response to mitogens. Ras proteins are key regulators linking extracellular stimuli to a diverse range of biological responses associated with gene regulation. In mammals, the three ras genes encode four Ras protein isoforms: H-Ras, K-Ras4A, K-Ras4B, and N-Ras. Although emerging evidence suggests that Ras isoforms differentially regulate gene expressions and are functionally nonredundant, the mechanisms underlying Ras specificity and Ras signaling effects on gene expression remain unclear. Here, we show that oncogenic N-Ras acts as the most potent regulator of SRF-, NF-κB-, and AP-1-dependent transcription. N-Ras-RGL2 axis is a distinct signaling pathway for SRF target gene expression such as Egr1 and JunB, as RGL2 Ras binding domain (RBD significantly impaired oncogenic N-Ras-induced SRE activation. By monitoring the effect of Ras isoforms upon the change of global histone modifications in oncogenic Ras-overexpressed cells, we discovered that oncogenic N-Ras elevates H3K9ac/H3K23ac levels globally in the chromatin context. Importantly, chromatin immunoprecipitation (ChIP assays revealed that H3K9ac is significantly enriched at the promoter and coding regions of Egr1 and JunB. Collectively, our findings define an undocumented role of N-Ras in modulating of H3 acetylation and in gene regulation.

  20. Analysis Of Post-Wet-Chemistry Heat Treatment Effects On Nb SRF Surface Resistance

    Dhakal, Pashupati; Ciovati, Gianluigi; Kneisel, Peter K.; Myneni, Ganapati Rao

    2014-01-01

    Most of the current research in superconducting radio frequency (SRF) cavities is focused on ways to reduce the construction and operating cost of SRF-based accelerators as well as on the development of new or improved cavity processing techniques. The increase in quality factors is the result of the reduction of the surface resistance of the materials. A recent test on a 1.5 GHz single cell cavity made from ingot niobium of medium purity and heat treated at 1400 °C in a ultra-high vacuum induction furnace resulted in a residual resistance of ∼ 1nΩ and a quality factor at 2.0 K increasing with field up to ∼ 5A-10 10 at a peak magnetic field of 90 mT. In this contribution, we present some results on the investigation of the origin of the extended Q 0 -increase, obtained by multiple HF rinses, oxypolishing and heat treatment of A ''all NbA'' cavities

  1. The effects of Eu-concentrations on the luminescent properties of SrF2:Eu nanophosphor

    Yagoub, M.Y.A.; Swart, H.C.; Noto, L.L.; O’Connel, J.H.; Lee, M.E.; Coetsee, E.

    2014-01-01

    SrF 2 :Eu nanophosphors were successfully synthesized by the hydrothermal method. The structure of the nanophosphors was investigated with x-ray diffraction. The average crystallite size calculated using the Scherrer equation was in the range of 7.0 nm. The photoluminescence of Eu doped as-prepared SrF 2 nanophosphors were studied using different excitation sources. The samples showed emission from both the Eu oxidation states, Eu 2+ and Eu 3+ . At low Eu concentrations the emission from Eu 2+ centered at 416 nm was more dominant. While the narrow band of Eu 3+ emission intensity increased with an increase in the Eu concentration. High resolution x-ray photoelectron spectroscopy results indicated that the Eu was indeed in both Eu 2+ and Eu 3+ valance states. The presence of Eu 2+ and Eu 3+ in the system largely enhanced the response of the Eu 3+ under ultraviolet excitation. The time of flight-secondary ion mass spectrometry results suggested that the energy transfer between two ions was likely to occur. The relative photoluminescence intensity of the Eu 2+ rapidly decreased with an increasing laser beam irradiating time. This result would make the current Eu 2+ doped SrF 2 samples unsuitable candidates for several applications, such as white light-emitting diodes and wavelength conversion films for silicon photovoltaic cells. - Highlights: • SrF 2 : Eu nanophosphors were successfully synthesised (hydrothermal technique). • PL and XPS results showed enhanced absorption response of Eu 3+ UV excitation. • Eu concentrations more than 5 mol% improved fluorescence emission. • TOF-SIMS results suggested that the energy transfer from Eu 2+ to Eu 3+ is dominant

  2. Recent Developments in SRF Cavity Science and Performance

    G. Ciovati

    2006-08-10

    The performances of SRF cavities made of high purity bulk niobium have been improving in the last few years and surface magnetic fields (Bp) close to the thermodynamic critical field of niobium have been achieved in a few cases. The recommendation made in 2004 in favor of SRF as the technology of choice for the International Linear Collider (ILC), requires improving the reliability of multi-cell cavities operating at accelerating gradients (Eacc) of the order of 35 MV/m. Additionally, a better understanding of the present limitations to cavity performance, such as the high-field Q-drop is needed. This contribution presents some recent developments in SRF cavity science and performance. Among the most significant advances of the last few years, new cavity shapes with lower ratio Bp/Eacc were designed and tested. Cavities made of large-grain niobium became available, promising lower cost at comparable performance to standard fine-grain ones and several tests on single-cell cavities were done to gain a better understanding of high-field losses. In addition, studies to improve the reliability of electropolishing are being carried out by several research groups.

  3. Apparatus and method for plasma processing of SRF cavities

    Upadhyay, J.; Im, Do; Peshl, J.; Bašović, M.; Popović, S.; Valente-Feliciano, A.-M.; Phillips, L.; Vušković, L.

    2016-05-01

    An apparatus and a method are described for plasma etching of the inner surface of superconducting radio frequency (SRF) cavities. Accelerator SRF cavities are formed into a variable-diameter cylindrical structure made of bulk niobium, for resonant generation of the particle accelerating field. The etch rate non-uniformity due to depletion of the radicals has been overcome by the simultaneous movement of the gas flow inlet and the inner electrode. An effective shape of the inner electrode to reduce the plasma asymmetry for the coaxial cylindrical rf plasma reactor is determined and implemented in the cavity processing method. The processing was accomplished by moving axially the inner electrode and the gas flow inlet in a step-wise way to establish segmented plasma columns. The test structure was a pillbox cavity made of steel of similar dimension to the standard SRF cavity. This was adopted to experimentally verify the plasma surface reaction on cylindrical structures with variable diameter using the segmented plasma generation approach. The pill box cavity is filled with niobium ring- and disk-type samples and the etch rate of these samples was measured.

  4. Heat load of a GaAs photocathode in an SRF electron gun

    Wang Erdong; Zhao Kui; Jorg Kewisch; Ilan Ben-Zvi; Andrew Burrill; Trivini Rao; Wu Qiong; Animesh Jain; Ramesh Gupta; Doug Holmes

    2011-01-01

    A great deal of effort has been made over the last decades to develop a better polarized electron source for high energy physics. Several laboratories operate DC guns with a gallium arsenide photocathode, which yield a highly polarized electron beam. However, the beam's emittance might well be improved by using a superconducting radio frequency (SRF) electron gun, which delivers beams of a higher brightness than that from DC guns because the field gradient at the cathode is higher. SRF guns with metal and CsTe cathodes have been tested successfully. To produce polarized electrons, a Gallium-Arsenide photo-cathode must be used: an experiment to do so in a superconducting RF gun is under way at BNL. Since a bulk gallium arsenide (GaAs) photocathode is normal conducting, a problem arises from the heat load stemming from the cathode. We present our measurements of the electrical resistance of GaAs at cryogenic temperatures, a prediction of the heat load and verification by measuring the quality factor of the gun with and without the cathode at 2 K. We simulate heat generation and flow from the GaAs cathode using the ANSYS program. By following the findings with the heat load model, we designed and fabricated a new cathode holder (plug) to decrease the heat load from GaAs. (authors)

  5. Phase and Frequency Locked Magnetrons for SRF Sources

    Neubauer, Michael [Muons, Inc.; Johnson, Rolland

    2014-09-12

    There is great potential for a magnetron power source that can be controlled both in phase and frequency. Such a power source could revolutionize many particle accelerator systems that require lower capital cost and/or higher power efficiency. Beyond the accelerator community, phase and frequency locked magnetons could improve radar systems around the world and make affordable phased arrays for wireless power transmission for solar powered satellites. This joint project of Muons, Inc., Fermilab, and L-3 CTL was supported by an STTR grant monitored by the Nuclear Physics Office of the DOE Office of Science. The object of the program was to incorporate ferrite materials into the anode of a magnetron and, with appropriate biasing of the ferrites, to maintain frequency lock and to allow for frequency adjustment of the magnetron without mechanical tuners. If successful, this device would have a dual use both as a source for SRF linacs and for military applications where fast tuning of the frequency is a requirement. In order to place the materials in the proper location, several attributes needed to be modeled. First the impact of the magnetron’s magnetic field needed to be shielded from the ferrites so that they were not saturated. And second, the magnetic field required to change the frequency of the magnetron at the ferrites needed to be shielded from the region containing the circulating electrons. ANSYS calculations of the magnetic field were used to optimize both of these parameters. Once the design for these elements was concluded, parts were fabricated and a complete test assembly built to confirm the predictions of the computer models. The ferrite material was also tested to determine its compatibility with magnetron tube processing temperatures. This required a vacuum bake out of the chosen material to determine the cleanliness of the material in terms of outgassing characteristics, and a subsequent room temperature test to verify that the characteristics of

  6. Testing a GaAs cathode in SRF gun

    Wang, E.; Kewisch, J.; Ben-Zvi, I.; Burrill, A.; Rao, T.; Wu, Q.; Holmes, D.

    2011-01-01

    RF electron guns with a strained superlattice GaAs cathode are expected to generate polarized electron beams of higher brightness and lower emittance than do DC guns, due to their higher field gradient at the cathode's surface and lower cathode temperature. We plan to install a bulk GaAs:Cs in a SRF gun to evaluate the performance of both the gun and the cathode in this environment. The status of this project is: In our 1.3 GHz 1/2 cell SRF gun, the vacuum can be maintained at nearly 10 -12 Torr because of cryo-pumping at 2K. With conventional activation of bulk GaAs, we obtained a QE of 10% at 532 nm, with lifetime of more than 3 days in the preparation chamber and have shown that it can survive in transport from the preparation chamber to the gun. The beam line has been assembled and we are exploring the best conditions for baking the cathode under vacuum. We report here the progress of our test of the GaAs cathode in the SRF gun. Future particle accelerators, such as eRHIC and the ILC require high-brightness, high-current polarized electrons. Strained superlattice GaAs:Cs has been shown to be an efficient cathode for producing polarized electrons. Activation of GaAs with Cs,O(F) lowers the electron affinity and makes it energetically possible for all the electrons, excited into the conduction band that drift or diffuse to the emission surface, to escape into the vacuum. Presently, all operating polarized electron sources, such as the CEBAF, are DC guns. In these devices, the excellent ultra-high vacuum extends the lifetime of the cathode. However, the low field gradient on the photocathode's emission surface of the DC guns limits the beam quality. The higher accelerating gradients, possible in the RF guns, generate a far better beam. Until recently, most RF guns operated at room temperature, limiting the vacuum to ∼10 -9 Torr. This destroys the GaAs's NEA surface. The SRF guns combine the excellent vacuum conditions of DC guns and the high accelerating

  7. Elemental balance of SRF production process: solid recovered fuel produced from municipal solid waste.

    Nasrullah, Muhammad; Vainikka, Pasi; Hannula, Janne; Hurme, Markku; Oinas, Pekka

    2016-01-01

    In the production of solid recovered fuel (SRF), certain waste components have excessive influence on the quality of product. The proportion of rubber, plastic (hard) and certain textiles was found to be critical as to the elemental quality of SRF. The mass flow of rubber, plastic (hard) and textiles (to certain extent, especially synthetic textile) components from input waste stream into the output streams of SRF production was found to play the decisive role in defining the elemental quality of SRF. This paper presents the mass flow of polluting and potentially toxic elements (PTEs) in SRF production. The SRF was produced from municipal solid waste (MSW) through mechanical treatment (MT). The results showed that of the total input chlorine content to process, 55% was found in the SRF and 30% in reject material. Of the total input arsenic content, 30% was found in the SRF and 45% in fine fraction. In case of cadmium, lead and mercury, of their total input content to the process, 62%, 38% and 30%, respectively, was found in the SRF. Among the components of MSW, rubber material was identified as potential source of chlorine, containing 8.0 wt.% of chlorine. Plastic (hard) and textile components contained 1.6 and 1.1. wt.% of chlorine, respectively. Plastic (hard) contained higher lead and cadmium content compared with other waste components, i.e. 500 mg kg(-1) and 9.0 mg kg(-1), respectively. © The Author(s) 2015.

  8. EFFECTIVENESS OF FERTILIZER SRF-N D AND H ON RICE GROWTH AND RESULTS

    Nasruddin Razak

    2014-02-01

    Full Text Available Study aims are to know effectiveness level of SRF-N (D & H on growth and yield of lowland rice, and gets fertilizer dosage that gave highest yield of lowland rice. Twelve 12 treatments added with recommendation dosage and farmer treatment. Experiment arranged in RCBD three replications. Result: SRF-N significantly effect growth and yield of lowland rice. Applied SRF-N type H with dosage 350 kg per ha which combined SP-36 and KCl gave higher dry grind grain compared to other treatments of SRF. Proposes SRF-H 280 kg and SRF-D 500 kg per ha. Treatment of farmer way with dosage Urea 300 kg, SP-36 100 kg, and KCl 50 kg per ha, gave higher dry grind grain (8.14 t DGG per ha compared to other treatments including recommendation dosage (7.65 t DGG per ha. Effectiveness of SRF-N type H with dosage 350 kg (two times applications on produce of grain, is 0.97 times compared to recommendation. Need to study more of SRF-H 350 kg and 280 kg per ha, and SRF-H 500 kg per ha (two times application which combined with P and K recommendation on different location and planting season to obtain accurate data in order to obtain locationspecific fertilizer recommendation

  9. RF control studies for moderate beamtime coupling between SRF cavities

    Doolittle, L.R.; Wang, D.X.

    1998-01-01

    When an SRF accelerator is designed, there is motivation to move the cavities close together on the beamline. Assuming the beamline apertures are not shrunk as well, this compaction (which will increase the overall accelerating gradient and/or lower the dynamic cryogenic heat load) increases the inter-cavity coupling. Within certain limits, the control system can compensate for this coupling by retuning each of the cavities. This paper describes constraints on the RF system, tuners, couplers, and control systems that are required to provide stable operation of cavities in the presence of inter-cavity coupling that exceeds the loaded bandwidth of an individual cavity

  10. JLab SRF Cavity Fabrication Errors, Consequences and Lessons Learned

    Marhauser, Frank

    2011-01-01

    Today, elliptical superconducting RF (SRF) cavities are preferably made from deep-drawn niobium sheets as pursued at Jefferson Laboratory (JLab). The fabrication of a cavity incorporates various cavity cell machining, trimming and electron beam welding (EBW) steps as well as surface chemistry that add to forming errors creating geometrical deviations of the cavity shape from its design. An analysis of in-house built cavities over the last years revealed significant errors in cavity production. Past fabrication flaws are described and lessons learned applied successfully to the most recent in-house series production of multi-cell cavities.

  11. Mobile communications technology: The singular factor responsible ...

    This paper investigated the factors responsible for the growth of Internet usage on the African continent. The principal finding was that increasing growth of Internet usage is also down to one singular factor: mobile communications technology. The proliferation of mobile phone usage in Africa has resulted in the sustained ...

  12. Technology challenges for SRF guns as ERL sources in view of Rossendorf work

    Janssen, Dietmar; Buettig, Hartmut; Evtushenko, Pavel; Lehnert, Ulf; Michel, Peter; Moeller, Karsten; Murcek, Petr; Schneider, Christof; Schurig, Rico; Staufenbiel, Friedrich; Teichert, Jochen; Xiang, Rong; Stephan, Juergen; Lehmann, Wolf-Dietrich; Kamps, Thorsten; Lipka, Dirk; Volkov, Vladimir; Will, Ingo

    2006-01-01

    After successful tests of a SRF gun with a superconducting half-cell cavity a new SRF photoinjector for cw operation at the ELBE linac is under development. The paper discuss the design of the injector, the technological challenges of different components, the status of manufacturing and the expected parameters

  13. Investigations of Residual Stresses and Mechanical Properties of Single Crystal Niobium for SRF Cavities

    Gnäupel-Herold, Thomas; Myneni, Ganapati Rao; Ricker, Richard E.

    2007-08-01

    This work investigates properties of large grained, high purity niobium with respect to the forming of superconducting radio frequency (SRF) cavities from such large grained sheets. The yield stresses were examined using tensile specimens that were essentially single crystals in orientations evenly distributed in the standard projection triangle. No distinct yield anisotropy was found, however, vacuum annealing increased the yield strength by a factor 2…3. The deep drawing forming operation of the half cells raises the issues of elastic shape changes after the release of the forming tool (springback) and residual stresses, both of which are indicated to be negligible. This is a consequence of the low yield stress (sheet metal forming). However, the significant anisotropy of the transversal plastic strains after uniaxial deformation points to potentially critical thickness variations for large grained / single crystal half cells, thus raising the issue of controlling grain orientation or using single crystal sheet material.

  14. Studies of HOMs in chains of SRF cavities using state-space concatenation scheme

    Galek, Tomasz; Heller, Johann; Flisgen, Thomas; Brackebusch, Korinna; Rienen, Ursula van [Institut fuer Allgemeine Elektrotechnik, Universitaet Rostock (Germany)

    2016-07-01

    The design of modern superconducting radio frequency cavities for acceleration of charged particle bunches requires intensive numerical simulations, as they typically arise as modules of several multi-cell cavities. A wide variety of parameters vital to the proper operation of accelerating cavities must be optimized and studied. One of the most important issues concerning the SRF cavities is the influence of the higher order modes on the beam quality, in this contribution. For TESLA-like structures with 1.3 GHz accelerating mode, higher order modes are calculated up to 4 GHz, the external quality factor and the shunt/geometrical impedance spectra are analyzed. To compute properties of complete RF modules the state-space concatenation scheme is used. The aspects of the concatenation scheme and its application to the bERLinPro's chain of cavities is discussed.

  15. SRF Performance of CEBAF After Thermal Cycle to Ambient Temperature

    Robert Rimmer; Jay Benesch; Joseph Preble; Charles Reece

    2005-01-01

    In September 2003, in the wake of Hurricane Isabel, JLab was without power for four days after a tree fell on the main power lines feeding the site. This was long enough to lose insulating vacuum in the cryomodules and cryogenic systems resulting in the whole accelerator warming up and the total loss of the liquid helium inventory. This thermal cycle stressed many of the cryomodule components causing several cavities to become inoperable due to helium to vacuum leaks. At the same time the thermal cycle released years of adsorbed gas from the cold surfaces. Over the next days and weeks this gas was pumped away, the insulating vacuum was restored and the machine was cooled back down and re-commissioned. In a testament to the robustness of SRF technology, only a small loss in energy capability was apparent, although individual cavities had quite different field-emission characteristics compared to before the event. In Summer 2004 a section of the machine was again cycled to room temperature during the long maintenance shutdown. We report on the overall SRF performance of the machine after these major disturbances and on efforts to characterize and optimize the new behavior for high-energy running

  16. Optimizing SRF Gun Cavity Profiles in a Genetic Algorithm Framework

    Hofler, Alicia; Evtushenko, Pavel; Marhauser, Frank

    2009-01-01

    Automation of DC photoinjector designs using a genetic algorithm (GA) based optimization is an accepted practice in accelerator physics. Allowing the gun cavity field profile shape to be varied can extend the utility of this optimization methodology to superconducting and normal conducting radio frequency (SRF/RF) gun based injectors. Finding optimal field and cavity geometry configurations can provide guidance for cavity design choices and verify existing designs. We have considered two approaches for varying the electric field profile. The first is to determine the optimal field profile shape that should be used independent of the cavity geometry, and the other is to vary the geometry of the gun cavity structure to produce an optimal field profile. The first method can provide a theoretical optimal and can illuminate where possible gains can be made in field shaping. The second method can produce more realistically achievable designs that can be compared to existing designs. In this paper, we discuss the design and implementation for these two methods for generating field profiles for SRF/RF guns in a GA based injector optimization scheme and provide preliminary results.

  17. NB Coating Developments with HIPIMS for SRF Applications

    Terenziani, G; Junginger, T; Santillana, I A; Ehiasarian, A P

    2013-01-01

    In the last few years the interest of the thin film science and technology community on High Impulse Power Magnetron Sputtering (HIPIMS) coatings has steadily increased. HIPIMS literature shows that better thin film morphology, denser and smoother films can be achieved when compared with standard dc Magnetron Sputtering (dcMS) coating technology [1]. Furthermore the capability of HIPIMS to produce a high quantity of ionized species [2,3] can allow conformal coatings also for complex geometries. A study is under way at CERN to apply this technology for the Nb coating of SRF 1.3-1.5 GHz Cu cavities, and in parallel at SHU the plasma physics and its correlation with film morphology are being investigated [2]. Recent results achieved with this technique are presented in the paper.

  18. Vibrational Stability of SRF Accelerator Test Facility at Fermilab

    McGee, M.W.; Volk, J.T.; /Fermilab

    2009-05-01

    Recently developed, the Superconducting Radio Frequency (SRF) Accelerator Test Facilities at Fermilab support the International Linear Collider (ILC), High Intensity Neutrino Source (HINS), a new high intensity injector (Project X) and other future machines. These facilities; Meson Detector Building (MDB) and New Muon Lab (NML) have very different foundations, structures, relative elevations with respect to grade level and surrounding soil composition. Also, there are differences in the operating equipment and their proximity to the primary machine. All the future machines have stringent operational stability requirements. The present study examines both near-field and ambient vibration in order to develop an understanding of the potential contribution of near-field sources (e.g. compressors, ultra-high and standard vacuum equipment, klystrons, modulators, utility fans and pumps) and distant noise sources to the overall system displacements. Facility vibration measurement results and methods of possible isolation from noise sources are presented and discussed.

  19. Operational optimization of large-scale SRF accelerators

    J. R. Delayen; L. R. Doolittle; C. E. Reece

    1999-01-01

    Unlike other types of accelerator subsystems, because of the flexibility in setting the gradient in each cavity, an SRF linac has many operational degrees of freedom. The overall linac has an operational envelope (beam voltage and current) that depends on acceptable reliability, cryogenic capacity, and RF power budget. For economic and end-user physics reasons, one typically wants to run as close to the edge of the operational envelope as possible. With about 160 cavities in each of the CEBAF linacs. The authors have been forced to treat this problem in a very general way, and satisfy other non-fundamental needs as energy lock and rapid recovery from failures. They present a description of the relevant diverse constraints and the solution developed for CEBAF

  20. SRF Cavity Surface Topography Characterization Using Replica Techniques

    C. Xu, M.J. Kelley, C.E. Reece

    2012-07-01

    To better understand the roll of topography on SRF cavity performance, we seek to obtain detailed topographic information from the curved practical cavity surfaces. Replicas taken from a cavity interior surface provide internal surface molds for fine Atomic Force Microscopy (AFM) and stylus profilometry. In this study, we confirm the replica resolution both on surface local defects such as grain boundary and etching pits and compare the surface uniform roughness with the aid of Power Spectral Density (PSD) where we can statistically obtain roughness parameters at different scales. A series of sampling locations are at the same magnetic field chosen at the same latitude on a single cell cavity to confirm the uniformity. Another series of sampling locations at different magnetic field amplitudes are chosen for this replica on the same cavity for later power loss calculation. We also show that application of the replica followed by rinsing does not adversely affect the cavity performance.

  1. Hydroforming SRF Three-cell Cavity from Seamless Niobium Tube

    Yamanaka, Masashi [KEK, Tsukuba; Dohmae, Takeshi [KEK, Tsukuba; Hocker, Andy [Fermilab; Inoue, Hitoshi [KEK, Tsukuba; Park, Gunn-Tae [KEK, Tsukuba; Tajima, Tsuyoshi [Los Alamos; Umemori, Kensei [KEK, Tsukuba

    2016-06-01

    We are developing the manufacturing method for superconducting radio frequency (SRF) cavities by using a hydroforming instead of using conventional electron beam welding. We expect higher reliability and reduced cost with hydroforming. For successful hydroforming, high-purity seamless niobium tubes with good formability as well as advancing the hydroforming technique are necessary. Using a seamless niobium tube from ATI Wah Chang, we were able to successfully hydroform a 1.3 GHz three-cell TESLA-like cavity and obtained an Eacc of 32 MV/m. A barrel polishing process was omitted after the hydroforming. The vertical test was carried out with very rough inside surface. We got amazing and interesting result.

  2. Turn-key SRF accelerators to drive subcritical reactors

    Johnson, Rolland P.

    2011-01-01

    Large particle accelerator projects, both accomplished and proposed, have been used to engage US industry through contracts and grants to develop efficient capabilities to design, develop, produce, and deliver entire accelerator systems or any needed subsystems. Staffed in many cases by experienced scientists and engineers from National Laboratories and Universities, existing companies could extend their portfolios to offer turn-key accelerators with parameters to match the needs of ADS. If the reactors were based on molten salt fuel such that trip rate requirements were relaxed, the developments needed for a multi-MW proton accelerator for ADS would be minimal. Turn-key SRF proton linacs for ADS operation can be ordered now to enable GW-level power generation from natural thorium, natural uranium, or nuclear waste from conventional reactors. (author)

  3. Activities on cryostats and SRF cavities at the I.P.N. Orsay laboratory

    Buelher, S.; Caruette, A.; Fouaidy, M.; Junquera, T.

    1993-01-01

    The main effort of the SRF community at Orsay during the last five years was concentrated on the MACSE project (study, construction, assembly and test of 3 cryostats), participation to the TESLA project and R and D activities in close collaboration with the Saclay SRF group. 3 major topics are outlined and briefly discussed: cryogenics, scanning surface thermometers for diagnostics on SRF cavities and thermal behaviour analysis of HOM couplers. The main results obtained in this frame since the 5th SC workshop at Hamburg in 1991 are presented. (authors) 12 refs., 17 figs., 6 tabs

  4. Personal factors of moral responsibility in adolescence

    Sergey V. Molchanov

    2017-12-01

    Full Text Available Background. Responsibility as a measure of individual freedom comes only under the condition of freedom of choice and the ability to anticipate and take into account the consequences of acts. Therefore, personal factors play a key role in taking moral responsibility. Scholars have studied the personal bases of responsibility that comprises autonomy, independence, confidence, the locus of control, the motivation to achieve a goal, the level of aspiration. However, the role of the moral self and moral identity in the determination of responsibility is not sufficiently studied. Objective. The objective of the research is to study the relationship between the moral identity of the individual and the willingness to accept moral responsibility in adolescence. Proceeding from the general hypothesis about the essential role of moral identity in adopting and actualising themoral responsibility, two specific hypotheses are articulated, specifying the role of values and moral self-esteem in taking moral responsibility. Design. An empirical study of adolescents aged 13–17 years was conducted. Subjects are students of educational institutions of general education in Moscow (a total of 314 subjects. The study poses the challenges of studying the readiness to accept moral responsibility by adolescents in the situation of a moral dilemma, the connection of the moral and value orientation of adolescents and the willingness to accept moral responsibility, the connection of self-esteem of moral qualities and the readiness of adolescents to accept moral responsibility. The methodology for assessing moral responsibility in the situation of solving the moral dilemma «Moral Situations from Real Life» (MORS, a modified version of M. Rokich’s method for evaluating value orientations, the method of structured moral self-esteem (A.I. Podolsky, P. Heymans, O.A. Karabanova are used. Conclusion. The results revealed the influence of the participants’ moral dilemma

  5. Factors affecting seismic response of submarine slopes

    G. Biscontin

    2006-01-01

    Full Text Available The response of submerged slopes on the continental shelf to seismic or storm loading has become an important element in the risk assessment for offshore structures and 'local' tsunami hazards worldwide. The geological profile of these slopes typically includes normally consolidated to lightly overconsolidated soft cohesive soils with layer thickness ranging from a few meters to hundreds of meters. The factor of safety obtained from pseudo-static analyses is not always a useful measure for evaluating the slope response, since values less than one do not necessarily imply slope failure with large movements of the soil mass. This paper addresses the relative importance of different factors affecting the response of submerged slopes during seismic loading. The analyses use a dynamic finite element code which includes a constitutive law describing the anisotropic stress-strain-strength behavior of normally consolidated to lightly overconsolidated clays. The model also incorporates anisotropic hardening to describe the effect of different shear strain and stress histories as well as bounding surface principles to provide realistic descriptions of the accumulation of the plastic strains and excess pore pressure during successive loading cycles. The paper presents results from parametric site response analyses on slope geometry and layering, soil material parameters, and input ground motion characteristics. The predicted maximum shear strains, permanent deformations, displacement time histories and maximum excess pore pressure development provide insight of slope performance during a seismic event.

  6. The New 2nd-Generation SRF RandD Facility at Jefferson Lab: TEDF

    Reece, Charles E.; Reilly, Anthony V.

    2012-01-01

    The US Department of Energy has funded a near-complete renovation of the SRF-based accelerator research and development facilities at Jefferson Lab. The project to accomplish this, the Technical and Engineering Development Facility (TEDF) Project has completed the first of two phases. An entirely new 3,100 m 2 purpose-built SRF technical work facility has been constructed and was occupied in summer of 2012. All SRF work processes with the exception of cryogenic testing have been relocated into the new building. All cavity fabrication, processing, thermal treatment, chemistry, cleaning, and assembly work is collected conveniently into a new LEED-certified building. An innovatively designed 800 m2 cleanroom/chemroom suite provides long-term flexibility for support of multiple RandD and construction projects as well as continued process evolution. The characteristics of this first 2nd-generation SRF facility are described

  7. Ion Exchange Temperature Testing with SRF Resin - 12088

    Russell, R.L.; Rinehart, D.E.; Brown, G.N.; Peterson, R.A. [Pacific Northwest National Laboratory, Richland, WA 99352 (United States)

    2012-07-01

    Ion exchange using the Spherical Resorcinol-Formaldehyde (SRF) resin has been selected by the U.S. Department of Energy's Office of River Protection for use in the Pretreatment Facility of the Hanford Tank Waste Treatment and Immobilization Plant (WTP) and for potential application in an at-tank deployment for removing Cs-137. Recent proposed changes to the WTP ion exchange process baseline indicate that higher temperatures (50 deg. C) to alleviate post-filtration precipitation issues prior to reaching the ion exchange columns may be required. Therefore, it is important to understand the behavior of SRF resin performance under the conditions expected with the new equipment and process changes. This research examined the impact of elevated temperature on resin loading and resin degradation during extended solution flow at elevated temperature (45 deg., 50 deg., 55 deg., 60 deg., 65 deg., 75 deg. C). Testing for extended times at elevated temperatures showed that the resin does degrade and loading capacity is reduced at and above 45 deg. C. Above 60 deg. C the resin appears to not load at all. It was observed that the resin disintegrated at 75 deg. C until not much was left and partially disintegrated at 65 deg. C, which caused the column to plug in both tests after ∼336 hours. The results indicate that WTP will lose resin loading capacity if the ion exchange process is performed above 25 deg. C, and the resin will disintegrate above 65 deg. C. Therefore, WTP will have a restricted operating range of temperatures to perform the ion exchange process with this resin. PNNL and WTP are currently evaluating the operating limits of the resin in further detail. Aging in 0.5 M HNO{sub 3} also caused the resin to lose capacity above 25 deg. C and to completely dissolve at 55 deg. C. Again, WTP will have a restricted operating range of temperatures when eluting the resin with nitric acid in order to maintain resin loading capacity and avoid disintegration of the resin

  8. SRF Performance of CEBAF After Thermal Cycle to Ambient Temperature

    Rimmer, Robert; Preble, Joseph P; Reece, Charles E

    2005-01-01

    In September 2003, in the wake of Hurricane Isabel, JLab was without power for four days after a tree fell on the main power lines feeding the site. This was long enough to lose insulating vacuum in the cryomodules and cryogenic systems resulting in the whole accelerator warming up and the total loss of the liquid helium inventory. This thermal cycle stressed many of the cryomodule components causing several cavities to become inoperable due to helium to vacuum leaks. At the same time the thermal cycle released years of adsorbed gas from the cold surfaces. Over the next days and weeks this gas was pumped away, the insulating vacuum was restored and the machine was cooled back down and re-commissioned. In a testament to the robustness of SRF technology, only a small loss in energy capability was apparent, although individual cavities had quite different field-emission characteristics compared to before the event. In Summer 2004 a section of the machine was again cycled to room temperature during the long maint...

  9. Superionic conductors with the fluorite structure: a) Measurement of the ionic conductivity of SrF2 at high temperatures, b) Study of the thermodynamic properties at CaF2 by numerical simulation

    Evangelakis, Georges

    1989-01-01

    In this work we present the results of an experimental study concerning the superionic conductivity of SrF 2 and those obtained by an investigation of the thermodynamical properties of CaF 2 using molecular dynamics simulation in the superionic region. The conductivity measurements in SrF 2 have been performed at high temperatures (700-1350 K) and various frequencies (10 Hz-10 MHz). At each temperature a frequency dependence of the conductivity has been detected. The analysis of the results using complex impedance diagrams revealed that this dependence is not an intrinsic property of the material but is related to electrodes effects. The apparent activation energies associated to the different parts of the intrinsic and extrinsic conductivity regions have been determined. Unfortunately no clear conclusion relative to the conduction mechanism can be made there from. Computer simulations by molecular dynamics have been performed in CaF 2 modeled using a rigid ion potential. The diffusion coefficient, the specific heat, structure factors, mean square displacements of both anions and cations, as well as the temperature dependence of these quantities have been calculated. The good agreement found between calculated quantities and experimental results justified us in using the crude approximation of a rigid on potential. A direct computation of the superionic conductivity has been obtained for the first time using non-equilibrium molecular dynamics in the linear response regime. From the independent calculation of the diffusion coefficient and the conductivity, the Havens ratio has been deduced, Hr 0.34, in the superionic region. Its value suggests that the superionic conductivity of CaF 2 is due to a collective and correlated mechanism, a fact which has been confirmed by the MD trajectory analysis. (author) [fr

  10. Fundamental damper power calculation of the 56 MHz SRF cavity for RHIC

    Wu, Q.; Bellavia, S.; Ben-Zvi, I.; Grau, M.; Miglionico, G.; Pai, C.

    2011-01-01

    At each injection period during RHIC's operation, the beam's frequency sweeps across a wide range, and some of its harmonics will cross the frequency of the 56MHz SRF cavity. To avoid excitation of the cavity at these times, we designed a fundamental damper for the quarter-wave resonator to damp the cavity heavily. The power extracted by the fundamental damper should correspond to the power handling ability of the system at all stages. In this paper, we discuss the power output from the fundamental damper when it is fully extracted, inserted, and any intermediate point. A Fundamental Damper (FD) will greatly reduce the cavity's Q factor to ∼300 during the acceleration phase of the beam. However, when the beam is at store and the FD is removed, the cavity is excited by both the yellow and the blue beams at 2 x 0.3A to attain the required 2MV voltage across its gap. The cavity then is operated to increase the luminosity of the RHIC experiments. Table 1 lists the parameters of the FD. Figure 1 shows the configuration of the FD fully inserted into the 56MHz SRF cavity; this complete insertion is defined as the start location (0cm) of FD simulation, an assumption we make throughout this paper. The power consumed by the cavity while maintaining the beam's energy and its orbit is compensated by the 28MHz accelerating cavities in the storage ring. The power dissipation of the external load is dynamic with respect to the position of the FD during its extraction. As a function of the external Q and the EM field in the cavity, the power should peak with the FD at a certain vertical location. Our calculation of the power extracted is detailed in the following sections. Figure 2 plots the frequency change in the cavity, and the external Q against the changes in position of the FD. The location of the FD is selected carefully such that the frequency will approach the designed working point from the lower side only. The loaded Q of the cavity is 223 when the FD is fully

  11. Deep drawing experiences of niobium disk for PEFP SRF cavity prototype

    Kim, Han Sung; An, Sun; Zhang, Liping; Tang, Yazhe; Li, Ying Min; Kwon, Hyeok Jung; Cho, Yong Sub

    2009-01-01

    A superconducting radio frequency (SRF) cavity with a geometrical beta of 0.42 has been designed to accelerate a proton beam after 100 MeV for an extension of Proton Engineering Frontier Project (PEFP). The designed cavity shape is an elliptical and the resonant frequency is 700 MHz. In order to confirm the RF and mechanical properties of the cavity, two prototypes of copper cavities have been fabricated and tested. Based on the experiences gained with the copper prototypes, two niobium prototypes have been designed. One is two-cell cavity and the other is five cell cavity. The two-cell cavity is for finalizing the niobium cavity production procedure and testing the cavity RF properties at a low temperature and moderate power level. The five-cell cavity is for checking the production quality and testing vertical test system in the future. Both of them are under fabrication. Through the fabrication of the niobium prototype, several issues such as deep drawing, electron beam welding and surface treatment will be addressed. The drawing of the PEPF SRF low beta cavity is shown in Fig. 1. Major parameters for the cavity are like following. - Frequency: 700 MHz - Operating mode: TM010 pi mode - Cavity type: Elliptical - Geometrical beta: 0.42 - Number of cells: 5 per cavity - Accelerating gradient: 8 MV/m - Epeak/Eacc: 3.71 - Bpeak/Eacc: 7.47 mT/(MV/m) - R/Q: 102.3 ohm - Epeak: 29.68 MV/m - Field flatness: 1.56 % - Cell to cell coupling: 1.41 % - Geometrical factor: 121.68 ohm - Cavity wall thickness: 4.3 mm - Lorentz force detuning: 0.4 Hz/(MV/m)2 - Stiffening structure: Double ring - Effective length: 0.45 m - External Q of FPC: 8.0E5 ±20 % - HOM load: less than 2 W - HOM Qext requirement: less than 3.0E5 At present, all the niobium disk and plates for cavity and NbTi flanges for beam pipe flange are prepared

  12. Discovery of Salmonella Virulence Factors Translocated via Outer Membrane Vesicles to Murine Macrophages.

    Yoon, Hyunjin; Ansong, Charles; Adkins, Joshua N.; Heffron, Fred

    2011-06-01

    We have previously shown that the regulators SpvR, FruR, IHF, PhoP/PhoQ, SsrA/SsrB, SlyA, Hnr, RpoE, SmpB, CsrA, RpoS, Crp, OmpR/EnvZ, and Hfq are essential for Salmonella Typhimurium virulence in mice. Here we use quantitative LC-MS-based proteomics profiling of in-frame deletion mutants of these 14 regulators to identify proteins that are coordinately regulated by these virulence regulators and are thus presumably novel factors contributing to Salmonella pathogenesis. Putative candidate proteins from proteomics analysis were determined, which exhibited similar abundance profiles to those of Salmonella pathogenicity island (SPI)-2 type III secretion system (TTSS) proteins. A subset of 5 proteins including STM0082, STM1548, PdgL, STM1633, and STM3595 was selected for further analysis. All 5 proteins were expressed inside macrophage cells and STM0082 (SrfN) was secreted into host cytoplasm. Furthermore, deletion of STM0082 attenuated virulence in mice when administered intraperitoneally as determined by competitive index. srfN transcription was positively regulated by SsrAB, however, secretion was independent of SPI-2 TTSS as well as SPI-1 TTSS and flagella. Proteins including PagK and STM2585A, which are positively regulated by PhoP/PhoQ, have sec signal peptides as predicted for SrfN and were secreted into macrophage cytoplasm regardless of SPI-2 TTSS. Isolation of outer membrane vesicles (OMVs) revealed the presence of SrfN, PagK, and STM2585A inside vesicle compartments. This result is the first case showing delivery of virulence effectors via OMVs in S. Typhimurium. Moreover, Hfq regulation of SrfN translation suggests that small non-coding RNAs may be responsible for regulating effector protein expression.

  13. G-actin sequestering protein thymosin-β4 regulates the activity of myocardin-related transcription factor

    Morita, Tsuyoshi; Hayashi, Ken’ichiro

    2013-01-01

    Highlights: •Tβ4 competed with MRTF-A for G-actin binding. •Tβ4 activated the MRTF–SRF signaling pathway. •Tβ4 increased the endogenous expression of SRF-dependent genes. -- Abstract: Myocardin-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). MRTFs contain three copies of the RPEL motif at their N-terminus, and they bind to monomeric globular actin (G-actin). Previous studies illustrate that G-actin binding inhibits MRTF activity by preventing the MRTFs nuclear accumulation. In the living cells, the majority of G-actin is sequestered by G-actin binding proteins that prevent spontaneous actin polymerization. Here, we demonstrate that the most abundant G-actin sequestering protein thymosin-β4 (Tβ4) was involved in the regulation of subcellular localization and activity of MRTF-A. Tβ4 competed with MRTF-A for G-actin binding; thus, interfering with G-actin–MRTF-A complex formation. Tβ4 overexpression induced the MRTF-A nuclear accumulation and activation of MRTF–SRF signaling. The activation rate of MRTF-A by the Tβ4 mutant L17A, whose affinity for G-actin is very low, was lower than that by wild-type Tβ4. In contrast, the β-actin mutant 3DA, which has a lower affinity for Tβ4, more effectively suppressed MRTF-A activity than wild-type β-actin. Furthermore, ectopic Tβ4 increased the endogenous expression of SRF-dependent actin cytoskeletal genes. Thus, Tβ4 is an important MRTF regulator that controls the G-actin–MRTFs interaction

  14. G-actin sequestering protein thymosin-β4 regulates the activity of myocardin-related transcription factor

    Morita, Tsuyoshi, E-mail: tsuyo@nbiochem.med.osaka-u.ac.jp; Hayashi, Ken’ichiro

    2013-08-02

    Highlights: •Tβ4 competed with MRTF-A for G-actin binding. •Tβ4 activated the MRTF–SRF signaling pathway. •Tβ4 increased the endogenous expression of SRF-dependent genes. -- Abstract: Myocardin-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). MRTFs contain three copies of the RPEL motif at their N-terminus, and they bind to monomeric globular actin (G-actin). Previous studies illustrate that G-actin binding inhibits MRTF activity by preventing the MRTFs nuclear accumulation. In the living cells, the majority of G-actin is sequestered by G-actin binding proteins that prevent spontaneous actin polymerization. Here, we demonstrate that the most abundant G-actin sequestering protein thymosin-β4 (Tβ4) was involved in the regulation of subcellular localization and activity of MRTF-A. Tβ4 competed with MRTF-A for G-actin binding; thus, interfering with G-actin–MRTF-A complex formation. Tβ4 overexpression induced the MRTF-A nuclear accumulation and activation of MRTF–SRF signaling. The activation rate of MRTF-A by the Tβ4 mutant L17A, whose affinity for G-actin is very low, was lower than that by wild-type Tβ4. In contrast, the β-actin mutant 3DA, which has a lower affinity for Tβ4, more effectively suppressed MRTF-A activity than wild-type β-actin. Furthermore, ectopic Tβ4 increased the endogenous expression of SRF-dependent actin cytoskeletal genes. Thus, Tβ4 is an important MRTF regulator that controls the G-actin–MRTFs interaction.

  15. Factors influencing induction of adaptive response

    Misonoh, Jun; Ojima, Mitsuaki; Yonezawa, Morio

    2000-01-01

    Exposure to low doses of X-rays makes ICR mice resistant to subsequent sublethal irradiation and decrease mortality from hematopoietic death. Many factors, however, influence the induction of radioresistance. For instances, in ICR mice, the priming irradiation with 0.50 Gy was effective in the induction of radioresistance, when it is given at 6-week old, 2 weeks prior to subsequent sublethal irradiation. One hundred-fifty kV X-ray filtered off the soft component through 1.0 mm aluminum and 0.2 mm copper induces radioadaptive response as well as the harder radiation such as 260 kV X-ray filtered through 0.5 mm aluminum and 0.3 mm copper. Dose rate of priming irradiation also seemed to influence the induction of radioresistance. Priming irradiation with 0.50 Gy at 0.50 Gy/min and 0.25 Gy/min induced adaptive response, while same 0.50 Gy given at 0.063 Gy/min didn't. To make the matter complicated, when mice were pre-irradiated with 0.50 Gy at 0.013 Gy/min in the irradiation cell which was 1.2 x 1.2 x 1.4 times larger than the usual one, adaptive response was induced again. These results suggested that mice felt more uncomfortable when they were packing in the irradiation cell with little free space even for several minutes than when they were placed in the cell with much free space for about 40 minutes, and such a stress might give the mice some resistance to the subsequent sublethal irradiation. (author)

  16. Development of Vertical Buffered Electropolishing for Its Post-Treatment Technology on 1.5 GHz Niobium SRF Cavities

    Jin Song; Lu Xiang-Yang; Lin Lin; Zhao Kui; Wu, A. T.; Rimmer, R. A.

    2011-01-01

    We report the latest research development of vertical buffered electropolishing on its post-treatment procedure as well as the effects of several major post-treatment techniques for buffered electropolishing (BEP) processed 1.5 GHz niobium (Nb) superconducting radio frequency (SRF) cavities. With the established post-treatment procedure, an accelerating gradient of 28.4 MV/m is obtained on a single cell cavity of the cebaf shape. This is the best result in the history of BEP development. The cavity is limited by quench with a high quality factor over 1.2 × 10 10 at the quench point. Analyses from optical inspection and temperature-mapping show that the quench should be originated from the pits that were already present on the cavity before this BEP treatment. All of these factors indicate that this procedure will have a great potential to produce better results if cavities without intrinsic performance limiting imperfections are used. (nuclear physics)

  17. Development of Nb$_3$Sn coatings by magnetron sputtering for SRF cavities

    Rosaz, G.; Leaux, F.; Motschmann, F.; Mydlarz, Z.; Taborelli, M.; Vollenberg, W.

    2016-01-01

    Cost and energy savings are an integral requirement in the design of future particle accelerators. Very low losses SRF accelerating systems, together with high-efficiency cryogenics systems, have the potential of low running costs. The association to the capital cost reduction allowed by thin films coated copper cavities may represent the best overall cost-performance compromise. This strategy has been applied for instance in LEP, the LHC and HIE-ISOLDE with the niobium thin films technology. New materials must be considered to improve the quality factor of the cavities, such as Nb$_{3}$Sn, which could also ideally operate at higher temperature thus allowing further energy savings. The study considers the possibility to coat a copper resonator with an Nb$_{3}$Sn layer by means of magnetron sputtering using an alloyed target. We present the impact of the process parameters on the as-deposited layer stoichiometry. The latter is in good agreement with previous results reported in the literature and can be tuned ...

  18. Heat load of a P-doped GaAs photocathode in SRF electron gun

    Wang, E.; Ben-Zvi, I.; Kewisch, J.; Burrill, A.; Rao, T.; Wu, Q.; Jain, A.; Gupta, R.; Holmes, D.

    2010-01-01

    Many efforts were made over the last decades to develop a better polarized electron source for the high energy physics. Several laboratories operate DC guns with the Gallium-Arsenide photo-cathode, which yield a highly polarized electron beam. However, the beam's emittance might well be improved using a Superconducting RF electron gun, which delivers beams of higher brightness than DC guns does, because the field gradient at the cathode is higher. SRF guns with metal cathodes and CsTe cathodes have been tested successfully. To produce polarized electrons, a Gallium-Arsenide photo-cathode must be used: an experiment to do so in a superconducting RF gun is under way at BNL. Since the cathode will be normal conducting, the problem about the heat load stemming from the cathode arises. We present our measurements of the electrical resistance of GaAs at cryogenic temperatures, a prediction of the heat load and the verification by measuring the quality factor of the gun with and without cathode.

  19. Investigations of Residual Stresses and Mechanical Properties of Single Crystal Niobium for SRF Cavities

    Gnaeupel-Herold, Thomas; Myneni, Ganapati Rao; Ricker, Richard E.

    2007-01-01

    This work investigates properties of large grained, high purity niobium with respect to the forming of superconducting radio frequency (SRF) cavities from such large grained sheets. The yield stresses were examined using tensile specimens that were essentially single crystals in orientations evenly distributed in the standard projection triangle. No distinct yield anisotropy was found, however, vacuum annealing increased the yield strength by a factor 2...3. The deep drawing forming operation of the half cells raises the issues of elastic shape changes after the release of the forming tool (springback) and residual stresses, both of which are indicated to be negligible. This is a consequence of the low yield stress (< 100 MPa) and the large thickness (compared to typical thicknesses in sheet metal forming). However, the significant anisotropy of the transversal plastic strains after uniaxial deformation points to potentially critical thickness variations for large grained / single crystal half cells, thus raising the issue of controlling grain orientation or using single crystal sheet material

  20. Geometric optimization of the 56 MHz SRF cavity and its frequency table

    Chang, X.; Ben-Zvi, I.

    2008-01-01

    It is essential to know the frequency of a Superconducting Radio Frequency (SRF) cavity at its 'just being fabricated' stage because frequency is the key parameter in constructing the cavity. In this paper, we report our work on assessing it. We can estimate the frequency change from stage to stage theoretically and/or by simulation. At the operating stage, the frequency can be calculated accurately, and, from this value, we obtain the frequencies at other stages. They are listed in a table that serves to check the processes from stage to stage. Equally important is optimizing the geometric shape of the SRF cavity so that the peak electric-field and peak magnetic-field are as low as possible. It is particularly desirable in the 56MHz SRF cavity of RHIC to maximize the frequency sensitivity of the slow tuner. After undertaking such optimization, our resultant peak electric-field is only 44.1MV/m, and the peak magnetic-field is 1049G at 2.5MV of voltage across the cavity gap. To quench superconductivity in an SRF cavity, it is reported that the limit of the peak magnetic-field is 1800G (1), and that of the peak electric-field is more than l00MV/m for a SRF cavity (2). Our simulations employed the codes Superfish and Microwave Studio

  1. 40 CFR 1065.845 - Response factor determination.

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Response factor determination. 1065... POLLUTION CONTROLS ENGINE-TESTING PROCEDURES Testing With Oxygenated Fuels § 1065.845 Response factor... each FID analyzer's alcohol/carbonyl response factor (such as RF MeOH) after FID optimization to...

  2. Root Causes of Field Emitters in SRF Cavities Placed in CEBAF Tunnel

    Geng, Rongli

    2016-05-01

    It has been suspected that appearance of new field emitters can occur in SRF cavities after their placement in accelerator tunnel for long term beam operation. This apparently has been the case for CEBAF. However, no physical evidence has been shown in the past. In this contribution, we will report on the recent results concerning the root cause of field emitters in SRF cavities placed in CEBAF tunnel. We will discuss these results in the context of high-reliability and low-cryogenic-loss operation of CEBAF.

  3. New Insights into the Limitations on the Efficiency and Achievable Gradients in Nb3Sn SRF Cavities

    Hall, Daniel Leslie

    The A15 superconductor Nb3Sn has shown great promise to replace niobium as the material of choice for the construction of superconducting radio-frequency (SRF) accelerator cavities. It promises, at least on paper, greater efficiency and higher accelerating gradients, with the potential to enable the construction of smaller yet more powerful accelerators than can be constructed using niobium. Although the state-of-the-art performance of cavities coated with Nb3Sn has shown great potential, the achievable limits in cavity quality factor Q0 and accelerating gradient Eacc are still below that expected given theoretical limits. In this work we present and discuss results of experiments carried out to understand the current limitations on Q0 and Eacc, and propose methods to improve these further. We will conclude with an outlook to the future, and the prospects that Nb3Sn could enable.

  4. Industrialization of the nitrogen-doping preparation for SRF cavities for LCLS-II

    Gonnella, D.; Aderhold, S.; Burrill, A.; Daly, E.; Davis, K.; Grassellino, A.; Grimm, C.; Khabiboulline, T.; Marhauser, F.; Melnychuk, O.; Palczewski, A.; Posen, S.; Ross, M.; Sergatskov, D.; Sukhanov, A.; Trenikhina, Y.; Wilson, K. M.

    2018-03-01

    The Linac Coherent Light Source II (LCLS-II) is a new state-of-the-art coherent X-ray source being constructed at SLAC National Accelerator Laboratory. It employs 280 superconducting radio frequency (SRF) cavities in order operate in continuous wave (CW) mode. To reduce the overall cryogenic cost of such a large accelerator, nitrogen-doping of the SRF cavities is being used. Nitrogen-doping has consistently been shown to increase the efficiency of SRF cavities operating in the 2.0 K regime and at medium fields (15-20 MV/m) in vertical cavity tests and horizontal cryomodule tests. While nitrogen-doping's efficacy for improvement of cavity performance was demonstrated at three independent labs, Fermilab, Jefferson Lab, and Cornell University, transfer of the technology to industry for LCLS-II production was not without challenges. Here we present results from the beginning of LCLS-II cavity production. We discuss qualification of the cavity vendors and the first cavities from each vendor. Finally, we demonstrate that nitrogen-doping has been successfully transferred to SRF cavity vendors, resulting in consistent production of cavities with better cryogenic efficiency than has ever been achieved for a large-scale accelerator.

  5. Myocardin-related transcription factors are required for cardiac development and function

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2016-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

  6. AN APPRAISAL OF FACTORS RESPONSIBLE FOR ERRORS IN ...

    Osondu

    2013-01-11

    Jan 11, 2013 ... management and clients are the main factors responsible for them. However, the collective .... planning/programming, stress, repetitive tasks. (Shelton, 1999) ... concurrent working control, communications) and global factors ...

  7. Factors Responsible for Domestic Water Contamination | Idika ...

    This study was therefore designed to identify the factors that influenced domestic water contamination in our rural communities and recommend some intervention measures that can reduce this high morbidity and mortality due to diarrhoeal diseases in Nigeria. Water samples from the water sources serving six rural ...

  8. Factors influencing societal response of nanotechnology : an expert stakeholder analysis

    Gupta, N.; Fischer, A.R.H.; Lans, van der, I.A.; Frewer, L.J.

    2012-01-01

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured i...

  9. Factors influencing societal response of nanotechnology: an expert stakeholder analysis

    Gupta, Nidhi; Fischer, Arnout R. H.; van der Lans, Ivo A.; Frewer, Lynn J.

    2012-01-01

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured i...

  10. In-Orbit Spectral Response Function Correction and Its Impact on Operational Calibration for the Long-Wave Split-Window Infrared Band (12.0 μm of FY-2G Satellite

    Qiang Guo

    2017-06-01

    Full Text Available During the early stage of the G satellite of the Fengyun-2 series (FY-2G, severe cold biases up to ~2.3 K occur in its measurements in the 12.0 μm (IR2 band, which demonstrate time- and scene-dependent characteristics. Similar cold biases in water vapor and carbon dioxide absorption bands of other satellites are considered to be caused by either ice contamination (physical method or spectral response function (SRF shift (empirical method. Simulations indicate that this cold bias of FY-2G indeed suffers from equivalent SRF shift as a whole towards the longer wavelength direction. To overcome it, a novel approach combining both physical and empirical methods is proposed. With the possible ice thicknesses tested before launch, the ice contamination effect is alleviated, while the shape of the SRF can be modified in a physical way. The remaining unknown factors for cold bias are removed by shifting the convolved SRF with an ice transmittance spectrum. Two parameters, i.e., the ice thickness (5 μm and the shifted value (+0.15 μm, are estimated by inter-calibration with reference instruments, and the modification coefficient is also calculated (0.9885 for the onboard blackbody calibration. Meanwhile, the updated SRF was released online on 23 March 2016. For the period between July 2015 and December 2016, the monthly biases of the FY-2G IR2 band remain oscillating around zero, the majorities (~89% of which are within ±1.0 K, while its mean monthly absolute bias is around 0.6 K. Nevertheless, the cold bias phenomenon of the IR2 band no longer exists. The combination method can be referred by other corrections for cold biases.

  11. Relational factors in psychopathological responses to childbirth.

    Cigoli, Vittorio; Gilli, Gabriella; Saita, Emanuela

    2006-06-01

    Childbirth can represent for women the time of greatest vulnerability experience, often associated with being out of control, loneliness or sadness. One hundred and sixty women who had 'normal' births were assessed within 48 hours on potential predictive measures and at 3-6 months post-partum for PTSD. Symptoms of depression, anxiety, perceived and desired support by family members, friends, medical personnel were also assessed. t-Test and chi-square were used to analyze, differences between 'risk group' and 'non-risk group'. Few women (1.25%) showed questionnaire responses suggesting clinically significant levels on PTSD; other women (28.75%) reported clinically significant symptoms for at least one subscale. Being at the first delivery experience, together with perceptions of low levels of support from family members and medical personnel, were found to be related to experience of post-traumatic stress symptoms. Anxiety for the child and previous depression are also related to such symptoms. Moreover, anxiety and depression are related to a difficult recognition of the support received, as well as to the desire for more support, in the care of the newborn, from medical professionals.

  12. Optimization of Pulsed Operation of the Superconducting Radio-Frequency (SRF) Cavities at the Spallation Neutron Source (SNS)

    Kim, Sang-Ho; Campisi, Isidoro E.

    2007-01-01

    In order to address the optimization in a pulsed operation, a systematic computational analysis has been made in comparison with operational experiences in superconducting radio-frequency (SRF) cavities at the Spallation Neutron Source (SNS). From the analysis it appears that the SNS SRF cavities can be operated at temperatures higher than 2.1 K, a fact resulting from both the pulsed nature of the superconducting cavities, the specific configuration of the existing cryogenic plant and the operating frequency

  13. Progress in the Development of SRF Cavity Tuners Based on Magnetic Smart Materials

    C. Joshi; A. Pappo; D. Upham; J. Preble

    2001-01-01

    Energen, Inc. has developed and demonstrated an SRF cavity tuning mechanism based on magnetic smart materials. Magnetic ''smart'' materials change their shape in a reversible and repeatable manner when exposed to a small magnetic field. A fine-tuning mechanism with a 2 kHz tuning range on a nominal resonant frequency of 1.497 GHz. was successfully demonstrated in 1999 [1]. Since then, Energen has been developing a tuning mechanism based on its linear stepper motors. These stepper motors are designed to deliver high-force precision linear motion of tens of millimeters at cryogenic temperatures. A locking mechanism built into the stepper motor enables the tuner to be locked into position when the power is turned off. This new tuning technology will eliminate the mechanical feeds through the vacuum jacket and reduce the complexity of the cryostat design and assembly. Performance and capabilities of a prototype SRF cavity tuner will be reported

  14. Flange joint system for SRF cavities utilizing high force spring clamps for low particle generation

    None

    2017-09-05

    A flange joint system for SRF cavities. The flange joint system includes a set of high force spring clamps that produce high force on the simple flanges of Superconducting Radio Frequency (SRF) cavities to squeeze conventional metallic seals. The system establishes the required vacuum and RF-tight seal with minimum particle contamination to the inside of the cavity assembly. The spring clamps are designed to stay within their elastic range while being forced open enough to mount over the flange pair. Upon release, the clamps have enough force to plastically deform metallic seal surfaces and continue to a new equilibrium sprung dimension where the flanges remain held against one another with enough preload such that normal handling will not break the seal.

  15. Evaluation Of Silicon Diodes As IN-SITU Cryogenic Field Emission Detectors For SRF Cavity Development

    Palczewski, Ari; Geng, Rongli

    2012-01-01

    We performed in-situ cryogenic testing of four silicon diodes as possible candidates for field emission (FE) monitors of superconducting radio frequency (SRF) cavities during qualification testing and in accelerator cryo-modules. We evaluated diodes from 2 companies - from Hamamatsu corporation model S1223-01; and from OSI Optoelectronics models OSD35-LR-A, XUV-50C, and FIL-UV20. The measurements were done by placing the diodes in superfluid liquid helium near the top of a field emitting 9-cell cavity during its vertical test. For each diode, we will discuss their viability as a 2K cryogenic detector for FE mapping of SRF cavities and the directionality of S1223-01 in such environments. We will also present calibration curves between the diodes and JLab's standard radiation detector placed above the Dewar's top plate.

  16. WAVEGUIDE COUPLER KICK TO BEAM BUNCH AND CURRENT DEPENDENCY ON SRF CAVITIES

    Genfa Wu; Haipeng Wang; Charles Reece; Robert Rimmer

    2008-01-01

    JLAB SRF cavities employ waveguide type fundamental power couplers (FPC). The FPC design for the 7-cell upgrade cavities was optimized to minimize the dipole field kick. For continuous wave (CW) operation, the forwarding RF power will be at different magnitude to drive the different beam current and cavity gradient. This introduces some deviation from optimized FPC field for varying beam loading. This article analyzes the beam behavior both in centroid kick and head-tail kick under different beam loading conditions

  17. How to Achieve the Best SRF Performance: (Practical) Limitations and Possible Solutions

    Antoine, Claire Z

    2014-01-01

    This chapter presents in the first part the requirement for the surface preparation of RF Niobium cavities and its justification in term s of physical origin of limitation (e.g. cleanliness and field emission, influence of the surface treatments, morphology and surface damage, etc.). In the second part we discuss the different models describing the ultimate limits of SRF cavities, and we present one of the possible ways to overcome Niobium monopoly toward higher performances

  18. How to Achieve the Best SRF Performance: (Practical) Limitations and Possible Solutions

    Antoine, Claire Z [IRFU, Saclay (France)

    2014-07-01

    This chapter presents in the first part the requirement for the surface preparation of RF Niobium cavities and its justification in term s of physical origin of limitation (e.g. cleanliness and field emission, influence of the surface treatments, morphology and surface damage, etc.). In the second part we discuss the different models describing the ultimate limits of SRF cavities, and we present one of the possible ways to overcome Niobium monopoly toward higher performances.

  19. Quench dynamics in SRF cavities: can we locate the quench origin with 2nd sound?

    Maximenko, Yulia; Segatskov, Dmitri A.

    2011-01-01

    A newly developed method of locating quenches in SRF cavities by detecting second-sound waves has been gaining popularity in SRF laboratories. The technique is based on measurements of time delays between the quench as determined by the RF system and arrival of the second-sound wave to the multiple detectors placed around the cavity in superfluid helium. Unlike multi-channel temperature mapping, this approach requires only a few sensors and simple readout electronics; it can be used with SRF cavities of almost arbitrary shape. One of its drawbacks is that being an indirect method it requires one to solve an inverse problem to find the location of a quench. We tried to solve this inverse problem by using a parametric forward model. By analyzing the data we found that the approximation where the second-sound emitter is a near-singular source does not describe the physical system well enough. A time-dependent analysis of the quench process can help us to put forward a more adequate model. We present here our current algorithm to solve the inverse problem and discuss the experimental results.

  20. Development of optical inspection system of L-band SRF cavity

    Tajima, Yujiro; Iwashita, Yoshihisa; Hayano, Hitoshi

    2008-01-01

    The International Linear Collider (ILC) will require about 15,000 1.3 GHz superconducting radio frequency (SRF) accelerating cavities with high accelerating gradient (>35 MV/m) in its main linac. The high yield (80%) of successful high gradient cavities is necessary. Both of the yield and the accelerating gradient of SRF cavities does not reach the required level at present. We think that the gradient of the SRF cavities is limited by irregularities on the interior surface of the cavities, for example, fine dusts (1μm), balls (100μm) and pits (100μm): electrons emitted from the fine dusts by the tunnel effect are accelerated in the electric field, and consume the stored energy of the cavities (Field Emission). The balls and pits cause a breakdown by a magnetic field enhancement or a thermal current concentration (Thermal Breakdown). To prevent these problems the interior surface are treated by polishing and rinsing. The relation between the surface states and the gradient limitations, however, is still not clarified. To study the relation, we are developing an optical inspection system of the interior surface. (author)

  1. Gas Generation Testing of Spherical Resorcinol-Formaldehyde (sRF) Resin

    Colburn, Heather A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bryan, Samuel A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Camaioni, Donald M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mahoney, Lenna A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Adami, Susan R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2018-01-19

    This report describes gas generation testing of the spherical resorcinol-formaldehyde (sRF) resin that was conducted to support the technology maturation of the LAWPS facility. The current safety basis for the LAWPS facility is based primarily on two studies that had limited or inconclusive data sets. The two studies indicated a 40% increase in hydrogen generation rate of water (as predicted by the Hu model) with sRF resin over water alone. However, the previous studies did not test the range of conditions (process fluids and temperatures) that are expected in the LAWPS facility. Additionally, the previous studies did not obtain replicate test results or comparable liquid-only control samples. All of the testing described in this report, conducted with water, 0.45M nitric acid, and waste simulants with and without sRF resin, returned hydrogen generation rates that are within the current safety basis for the facility of 1.4 times the Hu model output for water.

  2. G-actin sequestering protein thymosin-β4 regulates the activity of myocardin-related transcription factor.

    Morita, Tsuyoshi; Hayashi, Ken'ichiro

    2013-08-02

    Myocardin-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). MRTFs contain three copies of the RPEL motif at their N-terminus, and they bind to monomeric globular actin (G-actin). Previous studies illustrate that G-actin binding inhibits MRTF activity by preventing the MRTFs nuclear accumulation. In the living cells, the majority of G-actin is sequestered by G-actin binding proteins that prevent spontaneous actin polymerization. Here, we demonstrate that the most abundant G-actin sequestering protein thymosin-β4 (Tβ4) was involved in the regulation of subcellular localization and activity of MRTF-A. Tβ4 competed with MRTF-A for G-actin binding; thus, interfering with G-actin-MRTF-A complex formation. Tβ4 overexpression induced the MRTF-A nuclear accumulation and activation of MRTF-SRF signaling. The activation rate of MRTF-A by the Tβ4 mutant L17A, whose affinity for G-actin is very low, was lower than that by wild-type Tβ4. In contrast, the β-actin mutant 3DA, which has a lower affinity for Tβ4, more effectively suppressed MRTF-A activity than wild-type β-actin. Furthermore, ectopic Tβ4 increased the endogenous expression of SRF-dependent actin cytoskeletal genes. Thus, Tβ4 is an important MRTF regulator that controls the G-actin-MRTFs interaction. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Characterization of a Cytokinin Response Factor in Arabidopsis thaliana

    Ketelsen, Bernd

    2012-01-01

    The papers of this thesis are not available in Munin: 1. Bernd Ketelsen, Rainer Schwacke, Kirsten Krause and Karsten Fischer: 'Transcriptional activation by Cytokinin Response Factor 5 is governed by an acidic Cterminus containing two conserved domains' (manuscript) 2. Bernd Ketelsen, Stian Olsen, Kirsten Krause and Karsten Fischer: 'Cytokinin responsive factor 5 (CRF5) is involved in root development, hormonal crosstalk and sugar metabolism in Arabidopsis thaliana' (manuscript) 3. Bernd K...

  4. Risk factors for discordant immune response among HIV-infected ...

    Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study. ... Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs) to determine associations between discordant immune response and clinical and demographic ...

  5. Short Rotation Forestry (SRF in a Mediterranean Environment Under Limited Energy Inputs

    Antonio Sergio De Franchi

    2010-10-01

    Full Text Available The aim of this work is comparing the two year performance (diameter, total height and mortality of twenty tree and shrub species in a semi arid environment. The research also wants to supply recommendation on the agronomic cropping techniques in areas where rainfall is the main limiting factor and water use is strictly limited. Woody biomass is gaining increasing importance for energy production in Italy. During the last five years, roughly 5000 ha of Short Rotation Forestry (SRF have been planted, mostly in northern Italy, especially using poplar clones. However, in Southern Italy, due to the poor rainfall and the lack of knowledge existing on the species to use, few groves have been established. The studied groves were set in December 2005 in a Mediterranean area where the total year rainfall is not higher than 600 mm (mostly in autumn and winter. Twenty species (Salix cinerea, Ulmus carpinifolia, Corylus avellana, Spartium junceum, Acer saccharinum, Morus alba, Saphora japonica, Eleagnus angustifolia, Fraxinus angustifolia (var oxicarpa, Sambucus nigra, Robinia pseudoacacia, Populus nigra, Albizia julibrissis, Populus alba, Salix alba, Ailanthus altissima, Alnus cordata, Ficus carica, Eucalyptus camaldulensis, Celtis australis were planted in “collection” plots and set in singular plots on single rows (3 m X 0.5 m spacing. Six species (R. pseudoacacia, P. nigra, P. alba, S. nigra, E. camaldulensis, and A. altissima were planted in eighteen random “experimental” split-plots, using single and twin rows (0.5 m spacing between plants. Plots had a rectangular plant spacing (3 m between singular and twin rows, 0.5 m on each row. Plant density was roughly 6670 cuttings ha-1 in “collection” plots with singular rows and 10950 cuttings ha-1 in “experimental” plots using single and twin rows. The expected harvest interval ranges from 2 to 5 years, depending on the first results. In the “collection” plots, the first results showed

  6. Short Rotation Forestry (SRF in a Mediterranean Environment Under Limited Energy Inputs

    Stella Lovelli

    2010-12-01

    Full Text Available The aim of this work is comparing the two year performance (diameter, total height and mortality of twenty tree and shrub species in a semi arid environment. The research also wants to supply recommendation on the agronomic cropping techniques in areas where rainfall is the main limiting factor and water use is strictly limited. Woody biomass is gaining increasing importance for energy production in Italy. During the last five years, roughly 5000 ha of Short Rotation Forestry (SRF have been planted, mostly in northern Italy, especially using poplar clones. However, in Southern Italy, due to the poor rainfall and the lack of knowledge existing on the species to use, few groves have been established. The studied groves were set in December 2005 in a Mediterranean area where the total year rainfall is not higher than 600 mm (mostly in autumn and winter. Twenty species (Salix cinerea, Ulmus carpinifolia, Corylus avellana, Spartium junceum, Acer saccharinum, Morus alba, Saphora japonica, Eleagnus angustifolia, Fraxinus angustifolia (var oxicarpa, Sambucus nigra, Robinia pseudoacacia, Populus nigra, Albizia julibrissis, Populus alba, Salix alba, Ailanthus altissima, Alnus cordata, Ficus carica, Eucalyptus camaldulensis, Celtis australis were planted in “collection” plots and set in singular plots on single rows (3 m X 0.5 m spacing. Six species (R. pseudoacacia, P. nigra, P. alba, S. nigra, E. camaldulensis, and A. altissima were planted in eighteen random “experimental” split-plots, using single and twin rows (0.5 m spacing between plants. Plots had a rectangular plant spacing (3 m between singular and twin rows, 0.5 m on each row. Plant density was roughly 6670 cuttings ha-1 in “collection” plots with singular rows and 10950 cuttings ha-1 in “experimental” plots using single and twin rows. The expected harvest interval ranges from 2 to 5 years, depending on the first results. In the “collection” plots, the first results showed

  7. Factors affecting the runoff response of watersheds to precipitation

    DROZDOVÁ, Martina

    2013-01-01

    This bachelor thesis is focused on the factors that affect the drainage basin of the response. It contains a literature review, which deals with the hydrological cycle characteristics of precipitation, surface runoff and flood and erosion protection. The aim of the work is to evaluate the factors that adversely affect the runoff from the catchment.

  8. Factors influencing societal response of nanotechnology : an expert stakeholder analysis

    Gupta, N.; Fischer, A.R.H.; Lans, van der I.A.; Frewer, L.J.

    2012-01-01

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an

  9. Novel and easy access to highly luminescent Eu and Tb doped ultra-small CaF2, SrF2 and BaF2 nanoparticles - structure and luminescence.

    Ritter, Benjamin; Haida, Philipp; Fink, Friedrich; Krahl, Thoralf; Gawlitza, Kornelia; Rurack, Knut; Scholz, Gudrun; Kemnitz, Erhard

    2017-02-28

    A universal fast and easy access at room temperature to transparent sols of nanoscopic Eu 3+ and Tb 3+ doped CaF 2 , SrF 2 and BaF 2 particles via the fluorolytic sol-gel synthesis route is presented. Monodisperse quasi-spherical nanoparticles with sizes of 3-20 nm are obtained with up to 40% rare earth doping showing red or green luminescence. In the beginning luminescence quenching effects are only observed for the highest content, which demonstrates the unique and outstanding properties of these materials. From CaF 2 :Eu10 via SrF 2 :Eu10 to BaF 2 :Eu10 a steady increase of the luminescence intensity and lifetime occurs by a factor of ≈2; the photoluminescence quantum yield increases by 29 to 35% due to the lower phonon energy of the matrix. The fast formation process of the particles within fractions of seconds is clearly visualized by exploiting appropriate luminescence processes during the synthesis. Multiply doped particles are also available by this method. Fine tuning of the luminescence properties is achieved by variation of the Ca-to-Sr ratio. Co-doping with Ce 3+ and Tb 3+ results in a huge increase (>50 times) of the green luminescence intensity due to energy transfer Ce 3+ → Tb 3+ . In this case, the luminescence intensity is higher for CaF 2 than for SrF 2 , due to a lower spatial distance of the rare earth ions.

  10. Hypoxia activates muscle-restricted coiled-coil protein (MURC) expression via transforming growth factor-β in cardiac myocytes.

    Shyu, Kou-Gi; Cheng, Wen-Pin; Wang, Bao-Wei; Chang, Hang

    2014-03-01

    The expression of MURC (muscle-restricted coiled-coil protein), a hypertrophy-regulated gene, increases during pressure overload. Hypoxia can cause myocardial hypertrophy; however, how hypoxia affects the regulation of MURC in cardiomyocytes undergoing hypertrophy is still unknown. The aim of the present study was to test the hypothesis that hypoxia induces MURC expression in cardiomyocytes during hypertrophy. The expression of MURC was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia and in an in vivo model of AMI (acute myocardial infarction) to induce myocardial hypoxia in adult rats. MURC protein and mRNA expression were significantly enhanced by hypoxia. MURC proteins induced by hypoxia were significantly blocked after the addition of PD98059 or ERK (extracellular-signal-regulated kinase) siRNA 30 min before hypoxia. Gel-shift assay showed increased DNA-binding activity of SRF (serum response factor) after hypoxia. PD98059, ERK siRNA and an anti-TGF-β (transforming growth factor-β) antibody abolished the SRF-binding activity enhanced by hypoxia or exogenous administration of TGF-β. A luciferase promoter assay demonstrated increased transcriptional activity of SRF in cardiomyocytes by hypoxia. Increased βMHC (β-myosin heavy chain) and BNP (B-type natriuretic peptide) protein expression and increased protein synthesis was identified after hypoxia with the presence of MURC in hypertrophic cardiomyocytes. MURC siRNA inhibited the hypertrophic marker protein expression and protein synthesis induced by hypoxia. AMI in adult rats also demonstrated increased MURC protein expression in the left ventricular myocardium. In conclusion, hypoxia in cultured rat neonatal cardiomyocytes increased MURC expression via the induction of TGF-β, SRF and the ERK pathway. These findings suggest that MURC plays a role in hypoxia-induced hypertrophy in cardiomyocytes.

  11. ABFs, a family of ABA-responsive element binding factors.

    Choi, H; Hong, J; Ha, J; Kang, J; Kim, S Y

    2000-01-21

    Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

  12. Assessment of seismic design response factors of concrete wall buildings

    Mwafy, Aman

    2011-03-01

    To verify the seismic design response factors of high-rise buildings, five reference structures, varying in height from 20- to 60-stories, were selected and designed according to modern design codes to represent a wide range of concrete wall structures. Verified fiber-based analytical models for inelastic simulation were developed, considering the geometric nonlinearity and material inelasticity of the structural members. The ground motion uncertainty was accounted for by employing 20 earthquake records representing two seismic scenarios, consistent with the latest understanding of the tectonic setting and seismicity of the selected reference region (UAE). A large number of Inelastic Pushover Analyses (IPAs) and Incremental Dynamic Collapse Analyses (IDCAs) were deployed for the reference structures to estimate the seismic design response factors. It is concluded that the factors adopted by the design code are adequately conservative. The results of this systematic assessment of seismic design response factors apply to a wide variety of contemporary concrete wall buildings with various characteristics.

  13. Seismic analysis response factors and design margins of piping systems

    Shieh, L.C.; Tsai, N.C.; Yang, M.S.; Wong, W.L.

    1985-01-01

    The objective of the simplified methods project of the Seismic Safety Margins Research Program is to develop a simplified seismic risk methodology for general use. The goal is to reduce seismic PRA costs to roughly 60 man-months over a 6 to 8 month period, without compromising the quality of the product. To achieve the goal, it is necessary to simplify the calculational procedure of the seismic response. The response factor approach serves this purpose. The response factor relates the median level response to the design data. Through a literature survey, we identified the various seismic analysis methods adopted in the U.S. nuclear industry for the piping system. A series of seismic response calculations was performed. The response factors and their variabilities for each method of analysis were computed. A sensitivity study of the effect of piping damping, in-structure response spectra envelop method, and analysis method was conducted. In addition, design margins, which relate the best-estimate response to the design data, are also presented

  14. Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic Response

    Vrushali A. Pathak

    2016-01-01

    Full Text Available Anemia is the primary clinical manifestation of malarial infections and is responsible for the substantial rate of morbidity. The pathophysiology discussed till now catalogued several causes for malarial anemia among which ineffective erythropoiesis being remarkable one occurs silently in the bone marrow. A systematic literature search was performed and summarized information on erythropoietic response upon malaria infection and the factors responsible for the same. This review summarizes the clinical and experimental studies on patients, mouse models, and in vitro cell cultures reporting erythropoietic changes upon malaria infection as well as factors accountable for the same. Inadequate erythropoietic response during malaria infection may be the collective effect of various mediators generated by host immune response as well as parasite metabolites. The interplay between various modulators causing the pathophysiology needs to be explored further. Globin gene expression profiling upon malaria infection should also be looked into as abnormal production of globin chains could be a possible contributor to ineffective erythropoiesis.

  15. Apparatus and process for passivating an SRF cavity

    Myneni, Ganapati Rao; Wallace, John P

    2014-12-02

    An apparatus and process for the production of a niobium cavity exhibiting high quality factors at high gradients is provided. The apparatus comprises a first chamber positioned within a second chamber, an RF generator and vacuum pumping systems. The process comprises placing the niobium cavity in a first chamber of the apparatus; thermally treating the cavity by high temperature in the first chamber while maintaining high vacuum in the first and second chambers; and applying a passivating thin film layer to a surface of the cavity in the presence of a gaseous mixture and an RF field. Further a niobium cavity exhibiting high quality factors at high gradients produced by the method of the invention is provided.

  16. Comparison of coal/solid recovered fuel (SRF) with coal/refuse derived fuel (RDF) in a fluidised bed reactor

    Wagland, S.T.; Kilgallon, P.; Coveney, R.; Garg, A.; Smith, R.; Longhurst, P.J.; Pollard, S.J.T.; Simms, N.

    2011-01-01

    An experimental study was undertaken to compare the differences between municipal solid waste (MSW) derived solid recovered fuel (SRF) (complying with CEN standards) and refuse derived fuel (RDF). Both fuels were co-combusted with coal in a 50 kW fluidised bed combustor and the metal emissions were compared. Synthetic SRF was prepared in the laboratory by grinding major constituents of MSW such as paper, plastic, textile and wood. RDF was obtained from a local mechanical treatment plant. Heavy metal emissions in flue gas and ash samples from the (coal + 10% SRF) fuel mixture were found to be within the acceptable range and were generally lower than that obtained for coal + 10% RDF fuel mixture. The relative distribution of heavy metals in ash components and the flue gas stream shows the presence of a large fraction (up to 98%) of most of the metals in the ash (except Hg and As). Thermo-gravimetric (TG) analysis of SRF constituents was performed to understand the behaviour of fuel mixtures in the absence and presence of air. The results obtained from the experimental study will enhance the confidence of fuel users towards using MSW-derived SRF as an alternative fuel.

  17. Spectroscopic properties of Er3+ and Yb3+ co-doped glass ceramics containing SrF2 nanocrystals

    Qiao Xvsheng; Fan Xianping; Wang Minquan; Zhang Xianghua

    2009-01-01

    The spectroscopic properties of Er 3+ /Yb 3+ co-doped 50SiO 2 -10Al 2 O 3 -20ZnF 2 -20SrF 2 glass and glass ceramic containing SrF 2 nanocrystals were investigated. The formation of SrF 2 nanocrystals in the glass ceramic was confirmed by XRD. The oscillator strengths for several transitions of the Er 3+ ions in the glass ceramic have been obtained and the Judd-Ofelt parameters were then determined. The XRD result and Judd-Ofelt parameters suggested that Er 3+ and Yb 3+ ions had efficiently enriched in the SrF 2 nanocrystals in the glass ceramic. The lifetime of excited states has been used to reveal the surroundings of luminescent Er 3+ and Yb 3+ and energy transfer (ET) mechanism between Er 3+ and Yb 3+ . Much stronger upconversion luminescence and longer lifetime of the Er 3+ /Yb 3+ co-doped glass ceramic were observed in comparison with the Er 3+ /Yb 3+ co-doped glass, which could be ascribed to more efficient ET from Yb 3+ to Er 3+ due to the enrichment of Yb 3+ and Er 3+ and the shortening of the distance between lanthanide ions in the precipitated SrF 2 nanocrystals.

  18. Convergence Improvement of Response Matrix Method with Large Discontinuity Factors

    Yamamoto, Akio

    2003-01-01

    In the response matrix method, a numerical divergence problem has been reported when extremely small or large discontinuity factors are utilized in the calculations. In this paper, an alternative response matrix formulation to solve the divergence problem is discussed, and properties of iteration matrixes are investigated through eigenvalue analyses. In the conventional response matrix formulation, partial currents between adjacent nodes are assumed to be discontinuous, and outgoing partial currents are converted into incoming partial currents by the discontinuity factor matrix. Namely, the partial currents of the homogeneous system (i.e., homogeneous partial currents) are treated in the conventional response matrix formulation. In this approach, the spectral radius of an iteration matrix for the partial currents may exceed unity when an extremely small or large discontinuity factor is used. Contrary to this, an alternative response matrix formulation using heterogeneous partial currents is discussed in this paper. In the latter approach, partial currents are assumed to be continuous between adjacent nodes, and discontinuity factors are directly considered in the coefficients of a response matrix. From the eigenvalue analysis of the iteration matrix for the one-group, one-dimensional problem, the spectral radius for the heterogeneous partial current formulation does not exceed unity even if an extremely small or large discontinuity factor is used in the calculation; numerical stability of the alternative formulation is superior to the conventional one. The numerical stability of the heterogeneous partial current formulation is also confirmed by the two-dimensional light water reactor core analysis. Since the heterogeneous partial current formulation does not require any approximation, the converged solution exactly reproduces the reference solution when the discontinuity factors are directly derived from the reference calculation

  19. Assumptions of Corporate Social Responsibility as Competitiveness Factor

    Zaneta Simanaviciene

    2017-09-01

    Full Text Available The purpose of this study was to examine the assumptions of corporate social responsibility (CSR as competitiveness factor in economic downturn. Findings indicate that factors affecting the quality of the micro-economic business environment, i.e., the sophistication of enterprise’s strategy and management processes, the quality of the human capital resources, the increase of product / service demand, the development of related and supporting sectors and the efficiency of natural resources, and competitive capacities of enterprise impact competitiveness at a micro-level. The outcomes suggest that the implementation of CSR elements, i.e., economic, environmental and social responsibilities, gives good opportunities to increase business competitiveness.

  20. SRF cavity testing using a FPGA Self Excited Loop

    Ben-Zvi, Ilan

    2018-01-01

    This document provides a detailed description of procedures for very-high precision calibration and testing of superconducting RF cavities using digital Low-Level RF (LLRF) electronics based on Field Programmable Gate Arrays (FPGA). The use of a Self-Excited Loop with an innovative procedure for fast turn-on allows the measurement of the forward, reflected and transmitted power from a single port of the directional coupler in front of the cavity, thus eliminating certain measurement errors. Various procedures for measuring the quality factor as a function of cavity fields are described, including a single RF pulse technique. Errors are estimated for the measurements.

  1. Tumor necrosis factor blockers influence macrophage responses to Mycobacterium tuberculosis

    HARRIS, JAMES; HARRIS, JAMES

    2008-01-01

    PUBLISHED umor necrosis factor (TNF)?? is a proinflammatory cytokine that mediates inflammation in response to various pathogens, including Mycobacterium tuberculosis, but is also a key factor in the pathogenesis of rheumatoid arthritis and other autoimmune diseases. Three TNF???suppressing drugs have been approved to treat selected autoimmune diseases; 2 are monoclonal antibodies against TNF?? (adalimumab and infliximab), and the other is a soluble TNF receptor/Fc fusion protein (etanerce...

  2. Buffer Chemical Polishing and RF Testing of the 56 MHz SRF Cavity

    Burrill,A.

    2009-01-01

    The 56 MHz cavity presents a unique challenge in preparing it for RF testing prior to construction of the cryomodule. This challenge arises due to the physical dimensions and subsequent weight of the cavity, and is further complicated by the coaxial geometry, and the need to properly chemically etch and high pressure rinse the entire inner surface prior to RF testing. To the best of my knowledge, this is the largest all niobium SRF cavity to be chemically etched and subsequently tested in a vertical dewar at 4K, and these processes will be the topic of this technical note.

  3. Design and commissioning of Fermilab's vertical test stand for ILC SRF cavities.

    Ozelis, Joseph P.; Carcagno, Ruben; Ginsburg, Camille M.; Huang, Yuenian; Norris, Barry; Peterson, Thomas; Poloubotko, Valeri; Rabehl, roger; Rakhno, Igor; Reid, Clark; Sergatskov, Dmitri A.; /Fermilab

    2007-06-01

    As part of its ILC program, Fermilab is developing a facility for vertical testing of SRF cavities. It operates at a nominal temperature of 2K, using a cryoplant that can supply LHe in excess of 20g/sec and provide bath pumping capacity of 125W at 2K. The below-grade cryostat consists of a vacuum vessel and LHe vessel, equipped with magnetic shielding to reduce the ambient magnetic field to <10mG. Internal fixed and external movable radiation shielding ensures that exposure to personnel is minimized. The facility features an integrated personnel safety system consisting of RF switches, interlocks, and area radiation monitors.

  4. Design and commissioning of Fermilab's vertical test stand for ILC SRF cavities

    Ozelis, Joseph P.; Carcagno, Ruben; Ginsburg, Camille M.; Huang, Yuenian; Norris, Barry; Peterson, Thomas; Poloubotko, Valeri; Rabehl, roger; Rakhno, Igor; Reid, Clark; Sergatskov, Dmitri A.

    2007-01-01

    As part of its ILC program, Fermilab is developing a facility for vertical testing of SRF cavities. It operates at a nominal temperature of 2K, using a cryoplant that can supply LHe in excess of 20g/sec and provide bath pumping capacity of 125W at 2K. The below-grade cryostat consists of a vacuum vessel and LHe vessel, equipped with magnetic shielding to reduce the ambient magnetic field to <10mG. Internal fixed and external movable radiation shielding ensures that exposure to personnel is minimized. The facility features an integrated personnel safety system consisting of RF switches, interlocks, and area radiation monitors

  5. Laser excited fluorescence spectrum of Ho3+:SrF2 single crystal

    Lal, Bansi; Ramachandra Rao, D.

    1980-01-01

    The fluorescence spectrum of Ho 3+ : SrF 2 single crystal excited by the various lines of an Ar + laser, is reported. The three fluorescence groups recorded in the region 5300-7700 A, correspond to the transitions from ( 5 F 4 , 5 S 2 ) to 5 I 8 , 5 F 5 to 5 I 8 , 5 F 3 to 5 I 7 and ( 5 F 4 , 5 S 2 ) to 5 I 7 . Marked changes in the total integrated intensity of the various fluorescence groups with the change in the exciting wavelength are observed. (author)

  6. Key factors driving corporate social responsibility of Vietnamese firms

    Kabir, Mohammed Rezaul; Thai Minh, H.

    2016-01-01

    We examine the impact of firm, corporate governance and managerial characteristics on the corporate social responsibility (CSR) activities of Vietnamese listed firms. Our results show that export-oriented firms engage in more CSR activities. As for corporate governance factors, we observe that

  7. Analysis of Factors Responsible for Low Utilization of Mechanical ...

    The study is concerned with identifying the problems of low utilization of plant and equipment by the indigenous building construction firms in Nigeria. The methodology involved the use of a well structured questionnaire complemented with an oral interview. The results revealed that (15) factors were responsible for low ...

  8. Physiological response of carnation to radiation and some other factors

    Abdel - Baky, M.M.

    1986-01-01

    This study was carried out to investigate the physiological response of carnation plant (Dianthus caryophyllus c v. William sim) to gamma rays irradiation and some other factors namely: gibberellic acid and alar (B - 9 or daminozide) as growth regulators and potassium and boron as nutrients. The obtained results would be summarized

  9. Factors Responsible for Students' Involvement in Internet Fraud as ...

    Internet fraud is one of the most rapidly increasing forms of cybercrime. It has become rampant among students generally because they make use of different Internet devices in schools. The purpose of this study was to examine the factors responsible for students' involvement in Internet fraud as expressed by tertiary ...

  10. Chenodeoxycholic acid stimulated fibroblast growth factor 19 response

    Borup, C; Wildt, S; Rumessen, J J

    2017-01-01

    BACKGROUND: Bile acid diarrhoea is underdiagnosed and better diagnostic tests are needed. Fasting serum fibroblast growth factor-19 (FGF19) has insufficient diagnostic value, but this may be improved by stimulation. AIM: To explore if an impaired FGF19 response identifies primary bile acid...

  11. Fibrinolytic response to tumor necrosis factor in healthy subjects

    van der Poll, T.; Levi, M. [=Marcel M.; Büller, H. R.; van Deventer, S. J.; de Boer, J. P.; Hack, C. E.; ten Cate, J. W.

    1991-01-01

    Tumor necrosis factor (TNF) may be involved in the disturbance of the procoagulant-fibrinolytic balance in septicemia, leading to microvascular thrombosis. To assess the dynamics of the fibrinolytic response to TNF in humans, we performed a crossover saline-controlled study in six healthy men,

  12. gender and school types as factors responsible for job stress

    Emeka Egbochuku

    public Universities should be looked into so that all factors responsible for stress might be .... universities in Malaysia, university academic staffs faced more problems .... adjustment with different coping styles. .... in college students: The role of rumination and stress. ... International Journal of Stress Management, 8, 285–29.

  13. Bayes Factor Covariance Testing in Item Response Models.

    Fox, Jean-Paul; Mulder, Joris; Sinharay, Sandip

    2017-12-01

    Two marginal one-parameter item response theory models are introduced, by integrating out the latent variable or random item parameter. It is shown that both marginal response models are multivariate (probit) models with a compound symmetry covariance structure. Several common hypotheses concerning the underlying covariance structure are evaluated using (fractional) Bayes factor tests. The support for a unidimensional factor (i.e., assumption of local independence) and differential item functioning are evaluated by testing the covariance components. The posterior distribution of common covariance components is obtained in closed form by transforming latent responses with an orthogonal (Helmert) matrix. This posterior distribution is defined as a shifted-inverse-gamma, thereby introducing a default prior and a balanced prior distribution. Based on that, an MCMC algorithm is described to estimate all model parameters and to compute (fractional) Bayes factor tests. Simulation studies are used to show that the (fractional) Bayes factor tests have good properties for testing the underlying covariance structure of binary response data. The method is illustrated with two real data studies.

  14. Dynamics of ethylene production in response to compatible Nod factor

    Reid, Dugald; Liu, Huijun; Kelly, Simon

    2018-01-01

    Establishment of symbiotic nitrogen-fixation in legumes is regulated by the plant hormone ethylene, but it has remained unclear whether and how its biosynthesis is regulated by the symbiotic pathway. We established a sensitive ethylene detection system for Lotus japonicus and found that ethylene...... production increased as early as six hours after inoculation with Mesorhizobium loti. This ethylene response was dependent on Nod factor production by compatible rhizobia. Analyses of nodulation mutants showed that perception of Nod factor was required for ethylene emission, while downstream transcription...... factors including CYCLOPS, NIN and ERN1 were not required for this response. Activation of the nodulation signalling pathway in spontaneously nodulating mutants was also sufficient to elevate ethylene production. Ethylene signalling is controlled by EIN2, which is duplicated in L. japonicus. We obtained...

  15. Performance of 3.9 GHz SRF cavities at Fermilab's ILCTA_MDB nhorizontal test stand

    Harms, Elvin; Hocker, Andy; /Fermilab

    2008-08-01

    Fermilab is building a cryomodule containing four 3.9 GHz superconducting radio frequency (SRF) cavities for the Free electron LASer in Hamburg (FLASH) facility at the Deutsches Elektronen-SYnchrotron (DESY) laboratory. Before assembling the cavities into the cryomodule, each individual cavity is tested at Fermilab's Horizontal Test Stand (HTS). The HTS provides the capability to test fully-dressed SRF cavities at 1.8 K with high-power pulsed RF in order to verify that the cavities achieve performance requirements under these conditions. The performance at the HTS of the 3.9 GHz cavities built for FLASH is presented here.

  16. Design, Fabrication and Testing of Medium-Beta 650 MHz SRF Cavity Prototypes for Project-X

    Marhauser, F.; Clemens, W.A.; Henry, J.; Kneisel, P.; Martin, R.; Rimmer, R.A.; Slack, G.; Turlington, L.; Williams, R.S.

    2011-01-01

    A new type of superconducting radio frequency (SRF) cavity shape with a shallow equator dome to reduce electron impact energies for suppressing multipacting barriers has been proposed. The shape is in consideration for the first time in the framework of Project-X to design a potential multi-cell cavity candidate for the medium-beta section of the SRF proton CW linac operating at 650 MHz. Rationales covering the design of the multi-cell cavity, the manufacture, post-processing and high power testing of two single-cell prototypes are presented.

  17. Design of 650 MHz, β=0.61, 5-cell SRF cavity and development of single cell niobium cavity

    Seth, Sudeshna; Som, Sumit; Bhattacharyya, Pranab

    2015-01-01

    In India, DAE laboratories and other institutes are now actively involved in research and development activities on SRF cavities and associated technologies for the proposed high current, high energy proton linear accelerators like ISNS/IADS and also for the FERMILAB PIP-II program under Indian institutions-Fermilab collaboration (IIFC). As part of the above activities, VECC, Kolkata, has been involved in the design, analysis and development of a 650 MHz, β=0.61, 5-cell elliptical shape Superconducting RF linac cavity. RF design involves optimization of the geometry to get acceptable values of field enhancement factors (magnetic and electric), R/Q , Geometric factor, coupling factor and field flatness. This paper describes the RF design using 2-D superfish and 3-D CST Microwave studio and multipacting analysis using 2-D Multipac2.1 and 3-D CST Particle Studio. A prototype 1-cell aluminum cavity and a prototype 5-cell copper cavity have been fabricated using die-punch assembly designed for fabrication of elliptical half-cells to check the procedures for forming and to make sure the desired frequency and field flatness could be obtained. RF characterization has been carried out for both the prototypes using Vector Network Analyzer and Bead pull measurement set up.The fabrication of a single-cell niobium cavity has been carried out indigenously and with the help of Electron Beam Welding (EBW) facility at IUAC, New Delhi. CMM measurement and RF characterization of the niobium half cells and full cell cavities have been carried out. This paper describes the development and measurement of prototype cavities and single cell niobium cavity. (author)

  18. Development efforts on helium vessel for 5 cell - 650 MHz SRF cavity at RRCAT

    Kumar, Abhay; Kumar, Pankaj; Sandha, R.S.; Dutta, Subhajit; Soni, Rakesh; Dwivedi, Jishnu; Thakurta, A.C.; Bhatnagar, V.K.; Mundra, G.

    2011-01-01

    The work focuses on the development of helium vessel which houses a 5 cell - 650 MHz SRF niobium cavity and serves as a helium bath to maintain the cavity at 2 K. The vessel has provision for changing the axial length of the cavity for tuning purpose by using a tuning mechanism and a large bellow. Titanium has been chosen as a material of construction of the vessel due to its coefficient of thermal expansion being close to that of niobium. Efforts have been initiated to understand the functional requirements, design requirements, acceptance criteria for design and analysis, non-destructive examination requirements, inspection and testing requirements, manufacturing technology of the titanium vessel and its integration with the SRF cavity. The welding assumes a special significance as titanium is highly reactive and ductility of the weld joint is lost in the presence of air and other impurities. A trial vessel has been conceptualised having typical sizes and geometries. The manufacturing features of vessel are based on ASME B and PV Code, Section VIII Division-1 and manufacturing of this vessel has been started at an Indian industry. Quality assurance plan for this work is developed. The paper describes the work done at RRCAT on the functional and integration requirements, overall design requirements, design methodology to achieve code conformance, manufacturing technology and QAP being used in the development of helium vessel. (author)

  19. Effect of cathode shape on vertical buffered electropolishing for niobium SRF cavities

    Jin, S.; Wu, A. T.; Lu, X. Y.; Rimmer, R. A.; Lin, L.; Zhao, K.; Mammosser, J.; Gao, J.

    2013-09-01

    This paper reports the research results of the effect of cathode shape during vertical buffered electropolishing (BEP) by employing a demountable single cell niobium (Nb) superconducting radio frequency (SRF) cavity. Several different cathode shapes such as, for instance, bar, ball, ellipsoid, and wheels of different diameters have been tested. Detailed electropolishing parameters including I-V characteristic, removal rate, surface roughness, and polishing uniformity at different locations inside the demountable cavity are measured. Similar studies are also done on conventional electropolishing (EP) for comparison. It is revealed that cathode shape has dominant effects for BEP especially on the obtaining of a suitable polishing condition and a uniform polishing rate in an Nb SRF single cell cavity. EP appears to have the same tendency. This paper demonstrates that a more homogeneous polishing result can be obtained by optimizing the electric field distribution inside the cavity through the modification of the cathode shape given the conditions that temperature and electrolyte flow are kept constant. Electric field distribution and electrolyte flow patterns inside the cavity are simulated via Poisson-Superfish and Solidworks respectively. With the optimal cathode shape, BEP shows a much faster polishing rate of ∼2.5 μm/min and is able to produce a smoother surface finish in the treatments of single cell cavities in comparison with EP.

  20. SQUID-based Nondestructive Testing Instrument of Dished Niobium Sheets for SRF Cavities

    Q. S. Shu; I. Ben-Zvi; G. Cheng; I. M. Phipps; J. T. Susta; P. Kneisel; G. Myneni; J. Mast; R. Selim

    2007-01-01

    Currently available technology can only inspect flat sheets and allow the elimination of defective flat sheets before the expensive forming and machining of the SRF cavity half-cells, but it does not eliminate the problem of remaining or uncovered surface impurities after partial chemical etching of the half-cells, nor does it detect any defects that may have been added during the fabrication of the half-cells. AMAC has developed a SQUID scanning system based on eddy current technique that allows the scanning of curved Nb samples that are welded to make superconducting RF cavity half-cells. AMAC SQUID scanning system successfully located the defects (Ta macro particles about 100 mm diameter) in a flat Nb sample (top side) and was able to also locate the defects in a cylindrical surface sample (top side). It is more significant that the system successfully located the defects on the backside of the flat sample and curved sample or 3-mm from the top surface. The 3-D SQUID-based Nondestructive instrument will be further optimized and improved in making SRF cavities and allow inspection and detection during cavity manufacturing for achieving highest accelerating fields

  1. Multipacting in a coaxial coupler with bias voltage for SRF operation with a large beam current

    Liu, Z.-K.; Wang, Ch.; Chang, F.-Y.; Chang, L.-H.; Chang, M.-H.; Chen, L.-J.; Chung, F.-T.; Lin, M.-C.; Lo, C.-H.; Tsai, C.-L.; Tsai, M.-H.; Yeh, M.-S.; Yu, T.-C.

    2016-09-01

    A superconducting radio-frequency (SRF) module is commonly used for a high-energy accelerator; its purpose is to provide energy to the particle beam. Because of the low power dissipation and smaller impedance of a higher-order mode for this module, it can provide more power to the particle beam with better stability through decreasing the couple bunch instability. A RF coupler is necessary to transfer the high power from a RF generator to the cavity. A coupler of coaxial type is a common choice. With high-power operation, it might suffer from multipacting, which is a resonance phenomenon due to re-emission of secondary electrons. Applying a bias voltage between inner and outer conductors of the coaxial coupler might increase or decrease the strength of the multipacting effect. We studied the effect of a bias voltage on multipacting using numerical simulation to track the motion of the electrons. The simulation results and an application for SRF operation with a large beam current are presented in this paper.

  2. Effect of cathode shape on vertical buffered electropolishing for niobium SRF cavities

    Jin, S.; Wu, A.T.; Lu, X.Y.; Rimmer, R.A.; Lin, L.; Zhao, K.; Mammosser, J.; Gao, J.

    2013-01-01

    This paper reports the research results of the effect of cathode shape during vertical buffered electropolishing (BEP) by employing a demountable single cell niobium (Nb) superconducting radio frequency (SRF) cavity. Several different cathode shapes such as, for instance, bar, ball, ellipsoid, and wheels of different diameters have been tested. Detailed electropolishing parameters including I–V characteristic, removal rate, surface roughness, and polishing uniformity at different locations inside the demountable cavity are measured. Similar studies are also done on conventional electropolishing (EP) for comparison. It is revealed that cathode shape has dominant effects for BEP especially on the obtaining of a suitable polishing condition and a uniform polishing rate in an Nb SRF single cell cavity. EP appears to have the same tendency. This paper demonstrates that a more homogeneous polishing result can be obtained by optimizing the electric field distribution inside the cavity through the modification of the cathode shape given the conditions that temperature and electrolyte flow are kept constant. Electric field distribution and electrolyte flow patterns inside the cavity are simulated via Poisson–Superfish and Solidworks respectively. With the optimal cathode shape, BEP shows a much faster polishing rate of ∼2.5 μm/min and is able to produce a smoother surface finish in the treatments of single cell cavities in comparison with EP.

  3. Factors influencing societal response of nanotechnology: an expert stakeholder analysis

    Gupta, Nidhi, E-mail: nidhi.gupta@wur.nl; Fischer, Arnout R. H., E-mail: arnout.fischer@wur.nl; Lans, Ivo A. van der, E-mail: Ivo.vanderLans@wur.nl [Wageningen University, Marketing and Consumer Behaviour Group (Netherlands); Frewer, Lynn J., E-mail: lynn.frewer@newcastle.ac.uk [Newcastle University, School of Agriculture, Food and Rural Development (United Kingdom)

    2012-05-15

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured interviews with experts on nanotechnology from North West Europe were conducted using repertory grid methodology in conjunction with generalized Procrustes analysis to examine the psychological constructs underlying societal uptake of 15 key applications of nanotechnology drawn from different areas (e.g. medicine, agriculture and environment, chemical, food, military, sports, and cosmetics). Based on expert judgement, the main factors influencing societal response to different applications of nanotechnology will be the extent to which applications are perceived to be beneficial, useful, and necessary, and how 'real' and physically close to the end-user these applications are perceived to be by the public.

  4. Factors influencing societal response of nanotechnology: an expert stakeholder analysis

    Gupta, Nidhi; Fischer, Arnout R. H.; Lans, Ivo A. van der; Frewer, Lynn J.

    2012-01-01

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured interviews with experts on nanotechnology from North West Europe were conducted using repertory grid methodology in conjunction with generalized Procrustes analysis to examine the psychological constructs underlying societal uptake of 15 key applications of nanotechnology drawn from different areas (e.g. medicine, agriculture and environment, chemical, food, military, sports, and cosmetics). Based on expert judgement, the main factors influencing societal response to different applications of nanotechnology will be the extent to which applications are perceived to be beneficial, useful, and necessary, and how 'real' and physically close to the end-user these applications are perceived to be by the public.

  5. Factors influencing societal response of nanotechnology: an expert stakeholder analysis

    Gupta, Nidhi; Fischer, Arnout R. H.; van der Lans, Ivo A.; Frewer, Lynn J.

    2012-05-01

    Nanotechnology can be described as an emerging technology and, as has been the case with other emerging technologies such as genetic modification, different socio-psychological factors will potentially influence societal responses to its development and application. These factors will play an important role in how nanotechnology is developed and commercialised. This article aims to identify expert opinion on factors influencing societal response to applications of nanotechnology. Structured interviews with experts on nanotechnology from North West Europe were conducted using repertory grid methodology in conjunction with generalized Procrustes analysis to examine the psychological constructs underlying societal uptake of 15 key applications of nanotechnology drawn from different areas (e.g. medicine, agriculture and environment, chemical, food, military, sports, and cosmetics). Based on expert judgement, the main factors influencing societal response to different applications of nanotechnology will be the extent to which applications are perceived to be beneficial, useful, and necessary, and how 'real' and physically close to the end-user these applications are perceived to be by the public.

  6. Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness.

    Nakagawa, S; Pawelek, P; Grinnell, F

    1989-06-01

    To learn more about the relationship between extracellular matrix organization, cell shape, and cell growth control, we studied DNA synthesis by fibroblasts in collagen gels that were either attached to culture dishes or floating in culture medium during gel contraction. After 4 days of contraction, the collagen density (initially 1.5 mg/ml) reached 22 mg/ml in attached gels and 55 mg/ml in floating gels. After contraction, attached collagen gels were well organized; collagen fibrils were aligned in the plane of cell spreading; and fibroblasts had an elongated, bipolar morphology. Floating collagen gels, however, were unorganized; collagen fibrils were arranged randomly; and fibroblasts had a stellate morphology. DNA synthesis by fibroblasts in contracted collagen gels was suppressed if the gels were floating in medium but not if the gels were attached, and inhibition was independent of the extent of gel contraction. Therefore, growth of fibroblasts in contracted collagen gels could be regulated by differences in extracellular matrix organization and cell shape independently of extracellular matrix density. We also compared the responses of fibroblasts in contracted collagen gels and monolayer culture to peptide growth factors including fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, and interleukin 1. Cells in floating collagen gels were generally unresponsive to any of the growth factors. Cells in attached collagen gels and monolayer culture were affected similarly by fibroblast growth factor but not by the others. Our results indicate that extracellular matrix organization influenced not only cell growth, but also fibroblast responsiveness to peptide growth factors.

  7. WRKY transcription factors in plant responses to stresses.

    Jiang, Jingjing; Ma, Shenghui; Ye, Nenghui; Jiang, Ming; Cao, Jiashu; Zhang, Jianhua

    2017-02-01

    The WRKY gene family is among the largest families of transcription factors (TFs) in higher plants. By regulating the plant hormone signal transduction pathway, these TFs play critical roles in some plant processes in response to biotic and abiotic stress. Various bodies of research have demonstrated the important biological functions of WRKY TFs in plant response to different kinds of biotic and abiotic stresses and working mechanisms. However, very little summarization has been done to review their research progress. Not just important TFs function in plant response to biotic and abiotic stresses, WRKY also participates in carbohydrate synthesis, senescence, development, and secondary metabolites synthesis. WRKY proteins can bind to W-box (TGACC (A/T)) in the promoter of its target genes and activate or repress the expression of downstream genes to regulate their stress response. Moreover, WRKY proteins can interact with other TFs to regulate plant defensive responses. In the present review, we focus on the structural characteristics of WRKY TFs and the research progress on their functions in plant responses to a variety of stresses. © 2016 Institute of Botany, Chinese Academy of Sciences.

  8. Biogastronomy: Factors that determine the biological response to meal ingestion.

    Pribic, T; Azpiroz, F

    2018-02-02

    The biological response to a meal includes physiological changes, primarily related to the digestive process, and a sensory experience, involving sensations related to the homeostatic control of food consumption, eg, satiety and fullness, with a hedonic dimension, ie associated with changes in digestive well-being and mood. The responses to a meal include a series of events before, during and after ingestion. While much attention has been paid to the events before and during ingestion, relatively little is known about the postprandial sensations, which are key to the gastronomical experience. The aim of this narrative review is to provide a comprehensive overview and to define the framework to investigate the factors that determine the postprandial experience. Based on a series of proof-of-concept studies and related information, we propose that the biological responses to a meal depend on the characteristics of the meal, primarily its palatability and composition, and the responsiveness of the guest, which may be influenced by multiple previous and concurrent conditioning factors. This information provides the scientific backbone to the development of personalized gastronomy. © 2018 John Wiley & Sons Ltd.

  9. Comparative analysis of the ternary complex factors Elk-1, SAP-1a and SAP-2 (ERP/NET).

    Price, M A; Rogers, A E; Treisman, R

    1995-06-01

    A transcription factor ternary complex composed of Serum Response Factor (SRF) and Ternary Complex Factor (TCF) mediates the response of the c-fos Serum Response Element (SRE) to growth factors and mitogens. Three Ets domain proteins, Elk-1, SAP-1 and ERP/NET, have been reported to have the properties of TCF. Here we compare Elk-1 and SAP-1a with the human ERP/NET homologue SAP-2. All three TCF RNAs are ubiquitously expressed at similar relative levels. All three proteins contain conserved regions that interact with SRF and the c-fos SRE with comparable efficiency, but in vitro complex formation by SAP-2 is strongly inhibited by its C-terminal sequences. Similarly, only Elk-1 and SAP-1a efficiently bind the c-fos SRE in vivo; ternary complex formation by SAP-2 is weak and is substantially unaffected by serum stimulation or v-ras co-expression. All three TCFs contain C-terminal transcriptional activation domains that are phosphorylated following growth factor stimulation. Activation requires conserved S/T-P motifs found in all the TCF family members. Each TCF activation domain can be phosphorylated in vitro by partially purified ERK2, and ERK activation in vivo is sufficient to potentiate transcriptional activation.

  10. Snakebite Prognostic Factors: Leading Factors of Weak Therapeutic Response Following Snakebite Envenomation

    Bita Dadpour

    2012-12-01

    Full Text Available Background: The goal of antivenom administration for snake-bitten patients is to achieve therapeutic response (initial control, which means reversal of the venom-induced effects through neutralizing the venom. The aim of this study was to identify snakebite prognostic factors of weak therapeutic response prior to antivenom administration. Methods: This was a retrospective study of patients with viperidae snakebite envenomation who were admitted to Mashhad Toxicology Centre during 2007-2011. Demographic features, clinical manifestations and snakebite severity score (SSS were collected prior to antivenom administration. Total number of antivenom vials administered to achieve therapeutic response and duration of hospitalization were also recorded. Potential factors in snakebite prognosis were analyzed by comparing in two groups of achieving therapeutic response with less than 5 vials and over 5 to calculate odds ratio.  Results: Total of 108 patients (male/female: 85/23 with mean (SD age of 34.5 (17.0 were studied. The most common manifestations included fang marks (100%, pain (100%, ecchymosis (89%, swelling (83%, blister formation (48% and thrombocytopenia (25%. In univariate analysis, thrombocytopenia (P=0.01, spontaneous bleeding (P=0.02, coagulopathic disturbances (P=0.007, swelling (P=0.003, progressive swelling (P=0.005, ecchymosis (P=0.05 and respiratory distress (P= 0.05 were significantly correlated to weak therapeutic response. Swelling and spontaneous bleeding were the strongest snakebite prognostic factors, as respectively they put the patients at 12.4 and 10.4 fold risks for difficult achievement of therapeutic response. Conclusions: In snakebite, some clinical manifestations in the first hours of admission and prior to antivenom administration are associated with weak therapeutic response. Identifying these prognostic factors, can assist health care providers to better estimate the patient’s needs and predict the final

  11. Development of a high brightness, high current SRF photo-electron source for ERL applications

    Neumann, Axel [Helmholtz-Zentrum Berlin (Germany); Collaboration: bERLinPro Team

    2016-07-01

    Energy recovery linacs (ERL) offer the potential to combine major beam properties of the two main domains of particle accelerators: The low emittance of linear accelerators and the high average beam current of storage rings, while also allowing to compress to short bunches below the ps regime. This makes among other applications ERLs an ideal candidate for future light sources. The beam properties of the ERL are given by the performance of the injection section and hence of the beam source. Helmholtz-Zentrum Berlin is currently designing and building a high average current all superconducting CW driven ERL as a prototype to demonstrate low normalized beam emittance of 1 mm*mrad at 100 mA and short pulses of about 2 ps. In this contribution we discuss the development of this class of a high brightness, high current SRF photo-electron source and present recent commissioning results. Also, alternative approaches at other laboratories are shortly reviewed.

  12. Optimizing Centrifugal Barrel Polishing For Mirror Finish SRF Cavity And RF Tests At Jefferson Lab

    Palczewski, Ari; Geng, Rongli; Tian, Hui

    2012-01-01

    We performed Centrifugal Barrel Polishing (CBP) on a 1.3 GHz fine grain TESLA single cell cavity and 1.5 GHz fine grain CEBAF high gradient superconducting radio frequency (SRF) single cell cavity following a modified recipe originally developed at Fermi National Accelerator Lab (FNAL). We were able to obtain a mirror like surface similar to that obtained at FNAL, while reducing the number of CBP steps and total processing time. This paper will discuss the change in surface and subsequent cavity performance post CBP, after a 800 C bake (no pre-bake chemistry) and minimal controlled electro-polishing (10 micron). In addition to Q vs. E ACC thermometry mapping with preheating characteristics and optical inspection of the cavity after CBP will also be shown.

  13. Tuner control system of Spoke012 SRF cavity for C-ADS injector I

    Liu, Na; Sun, Yi; Wang, Guang-Wei; Mi, Zheng-Hui; Lin, Hai-Ying; Wang, Qun-Yao; Liu, Rong; Ma, Xin-Peng

    2016-09-01

    A new tuner control system for spoke superconducting radio frequency (SRF) cavities has been developed and applied to cryomodule I of the C-ADS injector I at the Institute of High Energy Physics, Chinese Academy of Sciences. We have successfully implemented the tuner controller based on Programmable Logic Controller (PLC) for the first time and achieved a cavity tuning phase error of ±0.7° (about ±4 Hz peak to peak) in the presence of electromechanical coupled resonance. This paper presents preliminary experimental results based on the PLC tuner controller under proton beam commissioning. Supported by Proton linac accelerator I of China Accelerator Driven sub-critical System (Y12C32W129)

  14. SRF Accelerator Technology Transfer Experience from the Achievement of the SNS Cryomodule Production Run

    Hogan, John; Daly, Edward; Drury, Michael A; Fischer, John; Hiatt, Tommy; Kneisel, Peter; Mammosser, John; Preble, Joseph P; Whitlatch, Timothy; Wilson, Katherine; Wiseman, Mark

    2005-01-01

    This paper will discuss the technology transfer aspect of superconducting RF expertise, as it pertains to cryomodule production, beginning with the original design requirements through testing and concluding with product delivery to the end user. The success of future industrialization, of accelerator systems, is dependent upon a focused effort on accelerator technology transfer. Over the past twenty years the Thomas Jefferson National Accelerator Facility (Jefferson Lab) has worked with industry to successfully design, manufacture, test and commission more superconducting RF cryomodules than any other entity in the United States. The most recent accomplishment of Jefferson Lab has been the successful production of twenty-four cryomodules designed for the Spallation Neutron Source (SNS). Jefferson Lab was chosen, by the United States Department of Energy, to provide the superconducting portion of the SNS linac due to its reputation as a primary resource for SRF expertise. The successful partnering with, and d...

  15. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

    Buddemeier, B R; Dillon, M B

    2009-01-21

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

  16. Jasmonate-responsive transcription factors regulating plant secondary metabolism.

    Zhou, Meiliang; Memelink, Johan

    2016-01-01

    Plants produce a large variety of secondary metabolites including alkaloids, glucosinolates, terpenoids and phenylpropanoids. These compounds play key roles in plant-environment interactions and many of them have pharmacological activity in humans. Jasmonates (JAs) are plant hormones which induce biosynthesis of many secondary metabolites. JAs-responsive transcription factors (TFs) that regulate the JAs-induced accumulation of secondary metabolites belong to different families including AP2/ERF, bHLH, MYB and WRKY. Here, we give an overview of the types and functions of TFs that have been identified in JAs-induced secondary metabolite biosynthesis, and highlight their similarities and differences in regulating various biosynthetic pathways. We review major recent developments regarding JAs-responsive TFs mediating secondary metabolite biosynthesis, and provide suggestions for further studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Regulation of bitter taste responses by tumor necrosis factor.

    Feng, Pu; Jyotaki, Masafumi; Kim, Agnes; Chai, Jinghua; Simon, Nirvine; Zhou, Minliang; Bachmanov, Alexander A; Huang, Liquan; Wang, Hong

    2015-10-01

    Inflammatory cytokines are important regulators of metabolism and food intake. Over production of inflammatory cytokines during bacterial and viral infections leads to anorexia and reduced food intake. However, it remains unclear whether any inflammatory cytokines are involved in the regulation of taste reception, the sensory mechanism governing food intake. Previously, we showed that tumor necrosis factor (TNF), a potent proinflammatory cytokine, is preferentially expressed in a subset of taste bud cells. The level of TNF in taste cells can be further induced by inflammatory stimuli. To investigate whether TNF plays a role in regulating taste responses, in this study, we performed taste behavioral tests and gustatory nerve recordings in TNF knockout mice. Behavioral tests showed that TNF-deficient mice are significantly less sensitive to the bitter compound quinine than wild-type mice, while their responses to sweet, umami, salty, and sour compounds are comparable to those of wild-type controls. Furthermore, nerve recording experiments showed that the chorda tympani nerve in TNF knockout mice is much less responsive to bitter compounds than that in wild-type mice. Chorda tympani nerve responses to sweet, umami, salty, and sour compounds are similar between TNF knockout and wild-type mice, consistent with the results from behavioral tests. We further showed that taste bud cells express the two known TNF receptors TNFR1 and TNFR2 and, therefore, are potential targets of TNF. Together, our results suggest that TNF signaling preferentially modulates bitter taste responses. This mechanism may contribute to taste dysfunction, particularly taste distortion, associated with infections and some chronic inflammatory diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Cadmium, cobalt and lead cause stress response, cell cycle deregulation and increased steroid as well as xenobiotic metabolism in primary normal human bronchial epithelial cells which is coordinated by at least nine transcription factors

    Glahn, Felix; Wiese, Jan; Foth, Heidi [Martin-Luther-University, Halle-Wittenberg, Institute of Environmental Toxicology, Halle/Saale (Germany); Schmidt-Heck, Wolfgang; Guthke, Reinhard [Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Jena (Germany); Zellmer, Sebastian; Gebhardt, Rolf [University of Leipzig, Institute of Biochemistry, Medical Faculty, Leipzig (Germany); Golka, Klaus; Degen, Gisela H.; Hermes, Matthias; Schormann, Wiebke; Brulport, Marc; Bauer, Alexander; Bedawy, Essam [IfADo, Leibniz Research Centre for Working Environment and Human Factors, Dortmund (Germany); Hergenroeder, Roland [ISAS, Institute for Analytical Sciences, Dortmund (Germany); Lehmann, Thomas [Translational Centre for Regenerative Medicine, Leipzig (Germany); Hengstler, Jan G. [IfADo, Leibniz Research Centre for Working Environment and Human Factors, Dortmund (Germany)

    2008-08-15

    Workers occupationally exposed to cadmium, cobalt and lead have been reported to have increased levels of DNA damage. To analyze whether in vivo relevant concentrations of heavy metals cause systematic alterations in RNA expression patterns, we performed a gene array study using primary normal human bronchial epithelial cells. Cells were incubated with 15{mu}g/l Cd(II), 25{mu}g/l Co(II) and 550{mu}g/l Pb(II) either with individual substances or in combination. Differentially expressed genes were filtered out and used to identify enriched GO categories as well as KEGG pathways and to identify transcription factors whose binding sites are enriched in a given set of promoters. Interestingly, combined exposure to Cd(II), Co(II) and Pb(II) caused a coordinated response of at least seven stress response-related transcription factors, namely Oct-1, HIC1, TGIF, CREB, ATF4, SRF and YY1. A stress response was further corroborated by up regulation of genes involved in glutathione metabolism. A second major response to heavy metal exposure was deregulation of the cell cycle as evidenced by down regulation of the transcription factors ELK-1 and the Ets transcription factor GABP, as well as deregulation of genes involved in purine and pyrimidine metabolism. A third and surprising response was up regulation of genes involved in steroid metabolism, whereby promoter analysis identified up regulation of SRY that is known to play a role in sex determination. A forth response was up regulation of xenobiotic metabolising enzymes, particularly of dihydrodiol dehydrogenases 1 and 2 (AKR1C1, AKR1C2). Incubations with individual heavy metals showed that the response of AKR1C1 and AKR1C2 was predominantly caused by lead. In conclusion, we have shown that in vivo relevant concentrations of Cd(II), Co(II) and Pb(II) cause a complex and coordinated response in normal human bronchial epithelial cells. This study gives an overview of the most responsive genes. (orig.)

  19. FACTORS RESPONSIBLE FOR CONSUMER’S ATTITUDE TOWARDS ADVERGAMES

    Ghirvu Alina

    2013-07-01

    Full Text Available Internet technology, as well as development of mobile phone was fast adopted by people for recreational, economical and business reasons. The Internet technology development and the new communication systems made marketers to orientate their promotional campaigns and efforts towards new ways of reaching their actual and potential client. They started to use new and innovative ways to get public’s interest and to encourage purchase. In this context, Internet offered a complex environment to support the development of innovative brand strategies. One of the emerging new techniques in advertising is advergaming. Advergames represent the use of video game interactive technology for delivering brand messages to public. They are electronic games accessible on companies own websites, on social media sites and on application which can be downloaded on mobile devices. For marketers is important to understand the way that advergames work and what consumer’s attitude towards this practice is. The formation of attitude depends on a series of factors which are common to all types of advertisements based on Internet technology. These factors responsible for consumers’ attitude towards online advertising and implicit for attitude formation over advergames are informative component, entertainment, source credibility and irritation. Beside these four elements, there are additional criterions which consumers use for evaluating advertising in video games: the viral component, interactivity and telepresence. For marketers it is important to understand these factors and to find practical ways for using them for a better brand communication and for higher result of advertising campaigns which include the use of advergames as part of the promotional strategy. The present paper is looking to make a description of the factors influencing consumer’s attitude formation towards advergames, in conjunction with the Internet environment and the specific features of

  20. Cooperative binding of transcription factors promotes bimodal gene expression response.

    Pablo S Gutierrez

    Full Text Available In the present work we extend and analyze the scope of our recently proposed stochastic model for transcriptional regulation, which considers an arbitrarily complex cis-regulatory system using only elementary reactions. Previously, we determined the role of cooperativity on the intrinsic fluctuations of gene expression for activating transcriptional switches, by means of master equation formalism and computer simulation. This model allowed us to distinguish between two cooperative binding mechanisms and, even though the mean expression levels were not affected differently by the acting mechanism, we showed that the associated fluctuations were different. In the present generalized model we include other regulatory functions in addition to those associated to an activator switch. Namely, we introduce repressive regulatory functions and two theoretical mechanisms that account for the biphasic response that some cis-regulatory systems show to the transcription factor concentration. We have also extended our previous master equation formalism in order to include protein production by stochastic translation of mRNA. Furthermore, we examine the graded/binary scenarios in the context of the interaction energy between transcription factors. In this sense, this is the first report to show that the cooperative binding of transcription factors to DNA promotes the "all-or-none" phenomenon observed in eukaryotic systems. In addition, we confirm that gene expression fluctuation levels associated with one of two cooperative binding mechanism never exceed the fluctuation levels of the other.

  1. Ethylene response factor AtERF72 negatively regulates Arabidopsis thaliana response to iron deficiency.

    Liu, Wei; Li, Qiwei; Wang, Yi; Wu, Ting; Yang, Yafei; Zhang, Xinzhong; Han, Zhenhai; Xu, Xuefeng

    2017-09-23

    Ethylene regulates the plant's response to stress caused by iron (Fe) deficiency. However, specific roles of ERF proteins in response to Fe deficiency remain poorly understood. Here, we investigated the role of ERF72 in response to iron deficiency in Arabidopsis thaliana. In this study, the levels of the ethylene response factor AtERF72 increased in leaves and roots induced under the iron deficient conditions. erf72 mutant plants showed increased growth compared to wild type (WT) when grown in iron deficient medium for 5 d. erf72 mutants had increased root H + velocity and the ferric reductase activity, and increase in the expression of the iron deficiency response genes iron-regulated transporter 1 (IRT1) and H + -ATPase (HA2) levels in iron deficient conditions. Compared to WT plants, erf72 mutants retained healthy chloroplast structure with significantly higher Fe and Mg content, and decreased chlorophyll degradation gene pheophorbide a oxygenase (PAO) and chlorophyllase (CLH1) expression when grown in iron deficient media. Yeast one-hybrid analysis showed that ERF72 could directly bind to the promoter regions of iron deficiency responses genes IRT1, HA2 and CLH1. Based on our results, we suggest that ethylene released from plants under iron deficiency stress can activate the expression of ERF72, which responds to iron deficiency in the negative regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Insulin and insulin-like growth factor receptors and responses

    Roth, R.A.; Steele-Perkins, G.; Hari, J.; Stover, C.; Pierce, S.; Turner, J.; Edman, J.C.; Rutter, W.J.

    1988-01-01

    Insulin is a member of a family of structurally related hormones with diverse physiological functions. In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. Each of these three polypeptide hormones has its own distinct receptor. The structures of each of these receptors have now been deduced from analyses of isolated cDNA clones. To study further the responses mediated through these three different receptors, the authors have been studying cells expressing the proteins encoded by these three cDNAs. The isolated cDNAs have been transfected into Chinese hamster ovary (CHO) cells, and the resulting transfected cell lines have been characterized as to the ligand-binding activities and signal-transducing activities of the expressed proteins

  3. Fundamental Study of Micro-Defects in Electropolished EB-Welded and Hydroformed SRF Accelerating Structures

    Sumption, Mike

    2014-08-29

    In the area of niobium elecropolishing fundamentals, we focused on understanding the influence of the surface topology, and geometry (with effects from gravity included. The formation of a viscous film is essential for the electropolishing process to take place. The exact nature and composition of the film formed on niobium is still unknown because of its solubility in the electrolyte. Extensive pitting may take place at surface where a stable film cannot form. This has to be taken into consideration while determining the speed with which the SRF cavities are rotated while EP. Hydrodynamic aspects must be taken into consideration while optimizing the polishing parameters. There is improvement in surface finish with polishing time. There is a huge change in surface quality when the EP time is increased from 2 hours to 4 hours but not much change takes place when the time is further increased to 6 hours. So keeping the economic points in view, about 100 um defect layer removal may be sufficient to get the desired performance. In the area of Electropolishing of untreated and treated niobium with Weld Joints we studied untreated and treated Nb, especially for the heat affected areas next to welded bumps, electropolished for different durations. The electropolishing of the untreated Nb caused the formation of pits on the surface at about 15 min but they disappeared when the electropolishing duration was more than 15 min. Electropolishing for 120 min smoothened the surface of untreated Nb by levelling the surface, but the severe formation of pits on the whole surface was found after 240 min. The treatment of Nb significantly changed the Nb surface morphology which was covered by grains of different size that looked light or dark in the optical microscope. The treated Nb was susceptible to pitting during the entire electropolishing starting from 15 min and the dark grains had more susceptibility to pitting than the light grains. In addition, electropolishing for 240 min

  4. Experimental and Numerical Analysis of Hydroformed Tubular Materials for Superconducting Radio Frequency (SRF) Cavities

    Kim, Hyun Sung

    Superconducting radio frequency (SRF) cavities represent a well established technology benefiting from some 40 years of research and development. An increasing demand for electron and positron accelerators leads to a continuing interest in improved cavity performance and fabrication techniques. Therefore, several seamless cavity fabrication techniques have been proposed for eliminating the multitude of electron-beam welded seams that contribute to the introduction of performance-reducing defects. Among them, hydroforming using hydraulic pressure is a promising fabrication technique for producing the desired seamless cavities while at the same time reducing manufacturing cost. This study focused on experimental and numerical analysis of hydroformed niobium (Nb) tubes for the successful application of hydroforming technique to the seamless fabrication of multi-cell SRF cavities for particle acceleration. The heat treatment, tensile testing, and bulge testing of Cu and Nb tubes has been carried out to both provide starting data for models of hydroforming of Nb tube into seamless SRF cavities. Based on the results of these experiments, numerical analyses using finite element modeling were conducted for a bulge deformation of Cu and Nb. In the experimental part of the study samples removed from representative tubes were prepared for heat treatment, tensile testing, residual resistance ratio (RRR) measurement, and orientation imaging electron microscopy (OIM). After being optimally heat treated Cu and Nb tubes were subjected to hydraulic bulge testing and the results analyzed. For numerical analysis of hydroforming process, two different simulation approaches were used. The first model was the macro-scale continuum model using the constitutive equations (stress-strain relationship) as an input of the simulation. The constitutive equations were obtained from the experimental procedure including tensile and tube bulge tests in order to investigate the influence of loading

  5. Surface polishing of niobium for superconducting radio frequency (SRF) cavity applications

    Zhao, Liang [College of William and Mary, Williamsburg, VA (United States)

    2014-08-01

    Niobium cavities are important components in modern particle accelerators based on superconducting radio frequency (SRF) technology. The interior of SRF cavities are cleaned and polished in order to produce high accelerating field and low power dissipation on the cavity wall. Current polishing methods, buffered chemical polishing (BCP) and electro-polishing (EP), have their advantages and limitations. We seek to improve current methods and explore laser polishing (LP) as a greener alternative of chemical methods. The topography and removal rate of BCP at different conditions (duration, temperature, sample orientation, flow rate) was studied with optical microscopy, scanning electron microscopy (SEM), and electron backscatter diffraction (EBSD). Differential etching on different crystal orientations is the main contributor to fine grain niobium BCP topography, with gas evolution playing a secondary role. The surface of single crystal and bi-crystal niobium is smooth even after heavy BCP. The topography of fine grain niobium depends on total removal. The removal rate increases with temperature and surface acid flow rate within the rage of 0~20 °C, with chemical reaction being the possible dominate rate control mechanism. Surface flow helps to regulate temperature and avoid gas accumulation on the surface. The effect of surface flow rate on niobium EP was studied with optical microscopy, atomic force microscopy (AFM), and power spectral density (PSD) analysis. Within the range of 0~3.7 cm/s, no significant difference was found on the removal rate and the macro roughness. Possible improvement on the micro roughness with increased surface flow rate was observed. The effect of fluence and pulse accumulation on niobium topography during LP was studied with optical microscopy, SEM, AFM, and PSD analysis. Polishing on micro scale was achieved within fluence range of 0.57~0.90 J/cm2, with pulse accumulation adjusted accordingly. Larger area treatment was proved possible by

  6. R&D progress in SRF surface preparation with centrifugal barrel polishing (cbp) for both Nb and Cu

    Palczewski, Ari [JLAB

    2013-09-01

    Centrifugal Barrel polishing (CBP) is becoming a common R&D tool for SRF cavity preparation around the world. During the CBP process a cylindrically symmetric SRF cavity is filled with relatively cheap and environmentally friendly abrasive and sealed. The cavity is then spun around a cylindrically symmetric axis at high speeds uniformly conditioning the inner surface. This uniformity is especially relevant for SRF application because many times a single manufacturing defects limits cavity?s performance well below it?s theoretical limit. In addition CBP has created surfaces with roughness?s on the order of 10?s of nm which create a unique surface for wet chemistry or thin film deposition. CBP is now being utilized at Jefferson Laboratory, Fermi Laboratory and Cornell University in the US, Deutsches Elektronen-Synchrotron in Germany, Laboratori Nazionali di Legnaro in Italy, and Raja Ramanna Centre for Advanced Technology in India. In this talk we will present current CBP research from each lab including equipment, baseline recipes, cavity removal rates and subsequent cryogenic cavity tests on niobium as well as copper cavities where available.

  7. Maximum Potential Hydrogen Gas Retention in the sRF Resin Ion Exchange Column for the LAWPS Process

    Gauglitz, Phillip A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wells, Beric E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Bottenus, Courtney LH [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Schonewill, Philip P. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2018-01-22

    The Low-Activity Waste Pretreatment System (LAWPS) is being developed to provide treated supernatant liquid from the Hanford tank farms directly to the Low-Activity Waste (LAW) Vitrification Facility at the Hanford Tank Waste Treatment and Immobilization Plant. The design and development of the LAWPS is being conducted by Washington River Protection Solutions, LLC. A key process in LAWPS is the removal of radioactive Cs in ion exchange (IX) columns filled with spherical resorcinol-formaldehyde (sRF) resin. One accident scenario being evaluated is the loss of liquid flow through the sRF resin bed after it has been loaded with radioactive Cs and hydrogen gas is being generated by radiolysis. In normal operations, the generated hydrogen is expected to remain dissolved in the liquid and be continuously removed by liquid flow. For an accident scenario with a loss of flow, hydrogen gas can be retained within the IX column both in the sRF resin and below the bottom screen that supports the resin within the column. The purpose of this report is to summarize calculations that estimate the upper-bound volume of hydrogen gas that can be retained in the column and potentially be released to the headspace of the IX column or to process equipment connected to the IX column and, thus, pose a flammability hazard.

  8. A generalized linear factor model approach to the hierarchical framework for responses and response times.

    Molenaar, Dylan; Tuerlinckx, Francis; van der Maas, Han L J

    2015-05-01

    We show how the hierarchical model for responses and response times as developed by van der Linden (2007), Fox, Klein Entink, and van der Linden (2007), Klein Entink, Fox, and van der Linden (2009), and Glas and van der Linden (2010) can be simplified to a generalized linear factor model with only the mild restriction that there is no hierarchical model at the item side. This result is valuable as it enables all well-developed modelling tools and extensions that come with these methods. We show that the restriction we impose on the hierarchical model does not influence parameter recovery under realistic circumstances. In addition, we present two illustrative real data analyses to demonstrate the practical benefits of our approach. © 2014 The British Psychological Society.

  9. NECAP 4.1: NASA's Energy Cost Analysis Program thermal response factor routine

    Weise, M. R.

    1982-08-01

    A thermal response factor is described and calculation sequences and flowcharts for RESFAC2 are provided. RESFAC is used by NASA's (NECAP) to calculate hourly heat transfer coefficients (thermal response factors) for each unique delayed surface. NECAP uses these response factors to compute each spaces' hourly heat gain/loss.

  10. Materials and surface aspects in the development of SRF Niobium cavities

    Antoine, C

    2012-01-01

    Foreword from author; When I joined the CEA Saclay SRF group in 1989, my initial background was physical chemistry and surface science, which I completed later on with solid state physics and metallurgy. Most accelerator physicists at that time had training in RF, plasma physics, nuclear or particle physics. We were very few with a background in material science. Working with people with a different background than yours reveals to be both challenging and funny: you can impress them with things you consider basic while they simply do not believe you for other things you consider so well admitted that you do not even remember where it comes from. At the end it obliges you to reconsider your basics and re-question many results, which opens many new and sometimes unexpected paths. Like usual in science, answering one question rises many new ones, and trying to improve cavities performance led to fascinating physics problems. Exploring some of these problems often requires techniques and expertise that are far be...

  11. Improving the work function of the niobium surface of SRF cavities by plasma processing

    Tyagi, P.V.; Doleans, M.; Hannah, B.; Afanador, R.; McMahan, C.; Stewart, S.; Mammosser, J.; Howell, M.; Saunders, J.; Degraff, B.; Kim, S.-H.

    2016-01-01

    Highlights: • An in situ plasma processing for SNS SRF cavities has been developed to remove hydrocarbons from cavity surface. • Reactive oxygen plasma is very effective to remove hydrocarbons from niobium top surface. • Reactive oxygen plasma processing increases the work function of niobium surface in the range of 0.5–1.0 eV. • It was observed that hydrocarbons can migrate at plasma cleaned top surface from near surface regions when waiting in vacuum at room temperature. • Multiple cycles of plasma processing with waiting periods in between was found beneficial to mitigate such hydrocarbons migration at plasma cleaned surface. - Abstract: An in situ plasma processing technique using chemically reactive oxygen plasma to remove hydrocarbons from superconducting radio frequency cavity surfaces at room temperature has been developed at the spallation neutron source, at Oak Ridge National Laboratory. To understand better the interaction between the plasma and niobium surface, surface studies on small samples were performed. In this article, we report the results from those surface studies. The results show that plasma processing removes hydrocarbons from top surface and improves the surface work function by 0.5–1.0 eV. Improving the work function of RF surface of cavities can help to improve their operational performance.

  12. Full Characterization at Low Temperature of Piezoelectric Actuators Used for SRF Cavities Active Tuning

    Fouaidy, Mohammed; Chatelet, Frederic; Hammoudi, Nourredine; Martinet, Guillaume; Olivier, Aurelia; Saugnac, Herve

    2005-01-01

    In the frame of the CARE project activities, supported by EU, IPN Orsay participate to the development of a fast cold tuning system for SRF cavities operating at a temperature T=2 K. The study is aimed at full characterization of piezoelectric actuators at low temperature. A new experimental facility was developed for testing various prototypes piezoelectric actuators and successfully operated for T in the range 1.8 K-300 K. Different parameters were investigated as function of T: piezoelectric actuator displacement vs. applied voltage V, capacitance vs. T, dielectric and thermal properties vs. T and finally heating DT due to dielectric losses vs. modulating voltage Vmod and frequency. We observed a decrease of the Full Range Displacement (FRD or DX) of the actuator from ~40μm @ 300K down to 1.8μm-3μm @ 1.8K, depending on both material and fabrication process of the piezostacks. Besides, both material and fabrication process have a strong influence on the shape of the characteris...

  13. Surface studies of niobium chemically polished under conditions for superconducting radio frequency (SRF) cavity production

    Tian, Hui; Reece, Charles E.; Kelley, Michael J.; Wang, Shancai; Plucinski, Lukasz; Smith, Kevin E.; Nowell, Matthew M.

    2006-11-01

    The performance of niobium superconducting radiofrequency (SRF) accelerator cavities is strongly impacted by the topmost several nanometers of the active (interior) surface, especially as influenced by the final surface conditioning treatments. We examined the effect of the most commonly employed treatment, buffered chemical polishing (BCP), on polycrystalline niobium sheet over a range of realistic solution flow rates using electron back scatter diffraction (EBSD), stylus profilometry, atomic force microscopy, laboratory XPS and synchrotron (variable photon energy) XPS, seeking to collect statistically significant datasets. We found that the predominant general surface orientation is (1 0 0), but others are also present and at the atomic-level details of surface plane orientation are more complex. The post-etch surface exhibits micron-scale roughness, whose extent does not change with treatment conditions. The outermost surface consists of a few-nm thick layer of niobium pentoxide, whose thickness increases with solution flow rate to a maximum of 1.3-1.4 times that resulting from static solution. The standard deviation of the roughness measurements is ±30% and that of the surface composition is ±5%.

  14. A novel approach to characterizing the surface topography of niobium superconducting radio frequency (SRF) accelerator cavities

    Tian, Hui; Ribeill, Guilhem; Xu, Chen; Reece, Charles E.; Kelley, Michael J.

    2011-03-01

    As superconducting niobium radio-frequency (SRF) cavities approach fundamental material limits, there is increased interest in understanding the details of topographical influences on realized performance limitations. Micro- and nano-roughness are implicated in both direct geometrical field enhancements as well as complications of the composition of the 50 nm surface layer in which the super-currents typically flow. Interior surface chemical treatments such as buffered chemical polishing (BCP) and electropolishing (EP) used to remove mechanical damage leave surface topography, including pits and protrusions of varying sharpness. These may promote RF magnetic field entry, locally quenching superconductivity, so as to degrade cavity performance. A more incisive analysis of surface topography than the widely used average roughness is needed. In this study, a power spectral density (PSD) approach based on Fourier analysis of surface topography data acquired by both stylus profilometry and atomic force microscopy (AFM) is introduced to distinguish the scale-dependent smoothing effects, resulting in a novel qualitative and quantitative description of Nb surface topography. The topographical evolution of the Nb surface as a function of different steps of well-controlled EP is discussed. This study will greatly help to identify optimum EP parameter sets for controlled and reproducible surface levelling of Nb for cavity production.

  15. Surface studies of niobium chemically polished under conditions for superconducting radio frequency (SRF) cavity production

    Tian Hui [Thomas Jefferson National Accelerator Facility and College of William and Mary (United States); Reece, Charles E. [Thomas Jefferson National Accelerator Facility and College of William and Mary (United States); Kelley, Michael J. [Thomas Jefferson National Accelerator Facility and College of William and Mary (United States)]. E-mail: mkelley@jlab.org; Wang Shancai [Department of Physics, Boston University (United States); Plucinski, Lukasz [Department of Physics, Boston University (United States); Smith, Kevin E. [Department of Physics, Boston University (United States); Nowell, Matthew M. [EDAX TSL (United States)

    2006-11-30

    The performance of niobium superconducting radiofrequency (SRF) accelerator cavities is strongly impacted by the topmost several nanometers of the active (interior) surface, especially as influenced by the final surface conditioning treatments. We examined the effect of the most commonly employed treatment, buffered chemical polishing (BCP), on polycrystalline niobium sheet over a range of realistic solution flow rates using electron back scatter diffraction (EBSD), stylus profilometry, atomic force microscopy, laboratory XPS and synchrotron (variable photon energy) XPS, seeking to collect statistically significant datasets. We found that the predominant general surface orientation is (1 0 0), but others are also present and at the atomic-level details of surface plane orientation are more complex. The post-etch surface exhibits micron-scale roughness, whose extent does not change with treatment conditions. The outermost surface consists of a few-nm thick layer of niobium pentoxide, whose thickness increases with solution flow rate to a maximum of 1.3-1.4 times that resulting from static solution. The standard deviation of the roughness measurements is {+-}30% and that of the surface composition is {+-}5%.

  16. Surface Studies of Niobium Chemically Polished Under Conditions for Superconducting Radio Frequency (SRF) Cavity Production

    Tian,H.; Reece, C.; Kelley, M.; Wang, S.; Plucinski, L.; Smith, K.; Nowell, M.

    2006-01-01

    The performance of niobium superconducting radiofrequency (SRF) accelerator cavities is strongly impacted by the topmost several nanometers of the active (interior) surface, especially as influenced by the final surface conditioning treatments. We examined the effect of the most commonly employed treatment, buffered chemical polishing (BCP), on polycrystalline niobium sheet over a range of realistic solution flow rates using electron back scatter diffraction (EBSD), stylus profilometry, atomic force microscopy, laboratory XPS and synchrotron (variable photon energy) XPS, seeking to collect statistically significant datasets. We found that the predominant general surface orientation is (1 0 0), but others are also present and at the atomic-level details of surface plane orientation are more complex. The post-etch surface exhibits micron-scale roughness, whose extent does not change with treatment conditions. The outermost surface consists of a few-nm thick layer of niobium pentoxide, whose thickness increases with solution flow rate to a maximum of 1.3-1.4 times that resulting from static solution. The standard deviation of the roughness measurements is {+-}30% and that of the surface composition is {+-}5%.

  17. A novel approach to characterizing the surface topography of niobium superconducting radio frequency (SRF) accelerator cavities

    Tian Hui; Ribeill, Guilhem; Xu Chen; Reece, Charles E.; Kelley, Michael J.

    2011-01-01

    As superconducting niobium radio-frequency (SRF) cavities approach fundamental material limits, there is increased interest in understanding the details of topographical influences on realized performance limitations. Micro- and nano-roughness are implicated in both direct geometrical field enhancements as well as complications of the composition of the 50 nm surface layer in which the super-currents typically flow. Interior surface chemical treatments such as buffered chemical polishing (BCP) and electropolishing (EP) used to remove mechanical damage leave surface topography, including pits and protrusions of varying sharpness. These may promote RF magnetic field entry, locally quenching superconductivity, so as to degrade cavity performance. A more incisive analysis of surface topography than the widely used average roughness is needed. In this study, a power spectral density (PSD) approach based on Fourier analysis of surface topography data acquired by both stylus profilometry and atomic force microscopy (AFM) is introduced to distinguish the scale-dependent smoothing effects, resulting in a novel qualitative and quantitative description of Nb surface topography. The topographical evolution of the Nb surface as a function of different steps of well-controlled EP is discussed. This study will greatly help to identify optimum EP parameter sets for controlled and reproducible surface levelling of Nb for cavity production.

  18. SRF cavity alignment detection method using beam-induced HOM with curved beam orbit

    Hattori, Ayaka; Hayano, Hitoshi

    2017-09-01

    We have developed a method to obtain mechanical centers of nine cell superconducting radio frequency (SRF) cavities from localized dipole modes, that is one of the higher order modes (HOM) induced by low-energy beams. It is to be noted that low-energy beams, which are used as alignment probes, are easy to bend in fringe fields of accelerator cavities. The estimation of the beam passing orbit is important because only information about the beam positions measured by beam position monitors outside the cavities is available. In this case, the alignment information about the cavities can be obtained by optimizing the parameters of the acceleration components over the beam orbit simulation to consistently represent the position of the beam position monitors measured at every beam sweep. We discuss details of the orbit estimation method, and estimate the mechanical center of the localized modes through experiments performed at the STF accelerator. The mechanical center is determined as (x , y) =(0 . 44 ± 0 . 56 mm , - 1 . 95 ± 0 . 40 mm) . We also discuss the error and the applicable range of this method.

  19. Characterization of Nb SRF cavity materials by white light interferometry and replica techniques

    Xu, Chen [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States); The Applied Science Department, The College of William and Mary, Williamsburg, VA 23185 (United States); Reece, Charles [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States); Kelley, Michael, E-mail: mkelley@jlab.org [Thomas Jefferson National Accelerator Facility, Newport News, VA 23606 (United States); The Applied Science Department, The College of William and Mary, Williamsburg, VA 23185 (United States)

    2013-06-01

    Much work has shown that the topography of the interior surface is an important contributor to the performance of Nb superconducting radiofrequency (SRF) accelerator cavities. Micron-scale topography is implicated in non-linear loss mechanisms that limit the useful accelerating gradient range and impact cryogenic cost. Aggressive final chemical treatments in cavity production seek to reliably obtain “smoothest” surfaces with superior performance. Process development suffers because the cavity interior surface cannot be viewed directly without cutting out pieces, rendering the cavities unavailable for further study. Here we explore replica techniques as an alternative, providing imprints of cavity internal surface that can be readily examined. A second matter is the topography measurement technique used. Atomic force microscopy (AFM) has proven successful, but too time intensive for routine use in this application. We therefore introduce white light interferometry (WLI) as an alternative approach. We examined real surfaces and their replicas, using AFM and WLI. We find that the replica/WLI is promising to provide the large majority of the desired information, recognizing that a trade-off is being made between best lateral resolution (AFM) and the opportunity to examine much more surface area (WLI).

  20. Longitudinal conductivity of LaF3/SrF2 multilayer heterostructures.

    Vergentev, Tikhon; Banshchikov, Alexander; Filimonov, Alexey; Koroleva, Ekaterina; Sokolov, Nikolay; Wurz, Marc Christopher

    2016-01-01

    LaF 3 /SrF 2 multilayer heterostructures with thicknesses of individual layers in the range 5-100 nm have been grown on MgO(100) substrates using molecular beam epitaxy. The longitudinal conductivity of the films has been measured using impedance spectroscopy in the frequency range 10 -1 -10 6  Hz and a temperature range 300-570 K. The ionic DC conductivities have been determined from Nyquist impedance diagrams and activation energies from the Arrhenius-Frenkel equation. An increase of the DC conductivity has been observed to accompany decreased layer thickness for various thicknesses as small as 25 nm. The greatest conductivity has been shown for a multilayer heterostructure having thicknesses of 25 nm per layer. The structure has a conductivity two orders of magnitude greater than pure LaF 3 bulk material. The increasing conductivity can be understood as a redistribution of charge carriers through the interface due to differing chemical potentials of the materials, by strong lattice-constant mismatch, and/or by formation of a solid La 1-x Sr x F 3-x solution at the interface during the growth process.

  1. Characterization of an SRF gun: a 3D full wave simulation

    Wang, E.; Ben-Zvi, I.; Wang, J.

    2011-01-01

    We characterized a BNL 1.3GHz half-cell SRF gun is tested for GaAs photocathode. The gun already was simulated several years ago via two-dimensional (2D) numerical codes (i.e., Superfish and Parmela) with and without the beam. In this paper, we discuss our investigation of its characteristics using a three dimensional (3D) full-wave code (CST STUDIO SUITE(trademark)).The input/pickup couplers are sited symmetrically on the same side of the gun at an angle of 180 o . In particular, the inner conductor of the pickup coupler is considerably shorter than that of the input coupler. We evaluated the cross-talk between the beam (trajectory) and the signal on the input coupler compared our findings with published results based on analytical models. The CST STUDIO SUITE(trademark) also was used to predict the field within the cavity; particularly, a combination of transient/eigenmode solvers was employed to accurately construct the RF field for the particles, which also includes the effects of the couplers. Finally, we explored the beam's dynamics with a particle in cell (PIC) simulation, validated the results and compare them with 2D code result.

  2. Defect model of a tetragonal Sm sup 3 sup + center found from EPR measurements in CaF sub 2 and SrF sub 2 crystals

    Zheng Wen Chen; Wu Shao Yi; Tang Sheng

    2003-01-01

    The EPR parameters (g factors g sub p sub a sub r sub a sub l sub l sub e sub l , g sub p sub e sub r sub p sub e sub n sub d sub i sub c sub u sub l sub a sub r sub t sub o and hyperfine structure constants A sub p sub a sub r sub a sub l sub l sub e sub l , A sub p sub e sub r sub p sub e sub n sub d sub i sub c sub u sub l sub a sub r sub t sub o) of a tetragonal (C sub 4 sub v) Sm sup 3 sup + center in CaF sub 2 and SrF sub 2 crystals are calculated by considering the crystal-field J-mixing among the ground sup 6 H sub 5 sub / sub 2 , the first excited sup 6 H sub 7 sub / sub 2 and second excited sup 6 H sub 9 sub / sub 2 state multiplets. In the calculations the free-ion and crystal-field parameters of the tetragonal Sm sup 3 sup + -F sup - center obtained from polarized laser-selective excitation spectroscopy are used. The calculated results suggest that the tetragonal Sm sup 3 sup + -F sup - center is the Sm sup 3 sup + center found by later EPR measurements. The g factors g sub p sub a sub r sub a sub...

  3. Cytokinin response factors regulate PIN-FORMED auxin transporters

    Šimášková, M.; O'Brien, J.A.; Khan, M.; Van Noorden, G.; Ötvös, K.; Vieten, A.; De Clercq, E.; Van Haperen, J.M.A.; Cuesta, C.; Hoyerová, Klára; Vanneste, S.; Marhavý, P.; Wabnik, K.; Van Breusegem, F.; Nowack, M.; Murphy, A.; Friml, J.; Weijers, D.; Beeckman, T.; Benková, E.

    2015-01-01

    Roč. 6, NOV (2015), s. 8717 ISSN 2041-1723 Institutional support: RVO:61389030 Keywords : ARABIDOPSIS -THALIANA * ROOT-MERISTEM * TRANSCRIPTION FACTORS Subject RIV: ED - Physiology Impact factor: 11.329, year: 2015

  4. Extreme and Local 3rd Harmonic Response of Niobium (Nb) Superconductor

    Oripov, Bakhrom; Tai, Tamin; Anlage, Steven

    Superconducting Radio Frequency (SRF) cavities are being widely used in new generation particle accelerators. These SRF cavities are based on bulk Nb. Based on the needs of the SRF community to identify defects on Nb surfaces, a novel near-field magnetic microwave microscope was successfully built using a magnetic writer from a conventional magnetic recording hard-disk drive1. This magnetic writer can create an RF magnetic field, localized and strong enough to drive Nb into the vortex state. This probe enables us to locate defects through scanning and mapping of the local electrodynamic response in the multi-GHz frequency range. Recent measurements have shown that 3rd harmonic nonlinear response is far more sensitive to variations in input power and temperature then linear response, thus we mainly study the 3rd harmonic response. Moreover, the superconductor is usually the only source for nonlinear response in our setup, thus there is less chance of having noise or background signal. Understanding the mechanism responsible for this non-linear response is important for improving the performance of SRF cavities. Besides Nb we also study various other superconductors such as MgB2 and the cuprate Bi-Sr-Ca-Cu-O (BSCCO) for potential applications in SRF cavities. This work is funded by US Department of Energy through Grant # DE-SC0012036T and CNAM.

  5. Bayes factor covariance testing in item response models

    Fox, J.P.; Mulder, J.; Sinharay, Sandip

    2017-01-01

    Two marginal one-parameter item response theory models are introduced, by integrating out the latent variable or random item parameter. It is shown that both marginal response models are multivariate (probit) models with a compound symmetry covariance structure. Several common hypotheses concerning

  6. Bayes Factor Covariance Testing in Item Response Models

    Fox, Jean-Paul; Mulder, Joris; Sinharay, Sandip

    2017-01-01

    Two marginal one-parameter item response theory models are introduced, by integrating out the latent variable or random item parameter. It is shown that both marginal response models are multivariate (probit) models with a compound symmetry covariance structure. Several common hypotheses concerning

  7. How media factors affect audience responses to brand placement

    van Reijmersdal, E.; Smit, E.; Neijens, P.

    2010-01-01

    This study investigates the influence of media factors on brand placement effects in a real-life setting. Although many studies on brand placement have been conducted, insights into context effects on brand placement reactions are scarce. The impact of objective and subjective media context factors

  8. Energy, environmental and operation aspects of a SRF-fired fluidized bed waste-to-energy plant.

    De Gisi, Sabino; Chiarelli, Agnese; Tagliente, Luca; Notarnicola, Michele

    2018-03-01

    A methodology based on the ISO 14031:2013 guideline has been developed and applied to a full-scale fluidized bed waste to energy plant (WtE) burning solid recovered fuel (SRF). With reference to 3years of operation, the data on energy and environmental performance, on raw materials consumptions such as sand and diesel fuel, accidental reasons of plant shutdown, have been acquired and analyzed. The obtained results have allowed to quantify the energy and environmental performance of the WtE plant under investigation by varying the amount and mixings of the inlet waste, available in form of thickened and fluff (similar to coriander) SRF. In terms of the energy performance, the fluidized bed technology applied to the SRF was able to guarantee an adequate production of electricity (satisfying the market demands), showing a relative flexibility with respect to the inlet waste. In terms of net energy production efficiency, the plant showed values in the range of 13.8-14.9% in line with similar installations. In terms of the environmental performance, the adoption of a cleaning system based on SNCR (Selective Non Catalitic Reduction)+semi-dry scrubbing+Fabric filter generated emissions usually well below the limits set by the EU Directive 2000/76/EC as well as the Italian Law 46/2014 (more restrictive) with reference to all the key parameters. In terms of the plant shutdown, the majority of problems focused on the combustion chamber and boiler due to the erosion of the refractory material of the furnace as well as to the breaking of the superheaters of the boiler. In contrast, the mechanical and electrical causes, along with those related to the control and instrumentation system, were of secondary importance. The sand bed de-fluidization was also among the leading causes of a frequent plant shutdown. In particular, results showed how although the SRF presents standard characteristics, the use of different mixtures may affect the number of plant shutdowns. The full

  9. Mechanical Responses and Physical Factors of the Fingertip Pulp

    N. Sakai

    2006-01-01

    Full Text Available The images of the mechanical responses were analysed when the fingertip was pressed against a plateau plate, and the influence of the contact angle on the loading pressure and the mechanical responses was investigated. As a result, as the contact angle was smaller, the change ratios due to the loading pressure were significantly larger in the contact length, the contact width and the distortion of lateral-view area. These parameters were thought to be useful in clinical medicine as indices for the degrees of mechanical responses of the fingertip. The length of the central axis and the maximum width of the fingertip were inappropriate as the parameters to represent the mechanical responses of the fingertip. The maximum width of the fingertip scarcely changed. This does not reflect the compressibility of the fingertip, and the fingertip as a whole extended along the central axis and in the vertical direction, and the change was not reflected in the maximum width.

  10. Ab Initio Study of Chemical Reactions of Cold SrF and CaF Molecules with Alkali-Metal and Alkaline-Earth-Metal Atoms: The Implications for Sympathetic Cooling.

    Kosicki, Maciej Bartosz; Kędziera, Dariusz; Żuchowski, Piotr Szymon

    2017-06-01

    We investigate the energetics of the atom exchange reaction in the SrF + alkali-metal atom and CaF + alkali-metal atom systems. Such reactions are possible only for collisions of SrF and CaF with the lithium atoms, while they are energetically forbidden for other alkali-metal atoms. Specifically, we focus on SrF interacting with Li, Rb, and Sr atoms and use ab initio methods to demonstrate that the SrF + Li and SrF + Sr reactions are barrierless. We present potential energy surfaces for the interaction of the SrF molecule with the Li, Rb, and Sr atoms in their energetically lowest-lying electronic spin states. The obtained potential energy surfaces are deep and exhibit profound interaction anisotropies. We predict that the collisions of SrF molecules in the rotational or Zeeman excited states most likely have a strong inelastic character. We discuss the prospects for the sympathetic cooling of SrF and CaF molecules using ultracold alkali-metal atoms.

  11. A naturally occurring single nucleotide polymorphism in the Salmonella SPI-2 type III effector srfH/sseI controls early extraintestinal dissemination.

    Joshua M Thornbrough

    Full Text Available CD18 expressing phagocytes associated with the gastro-intestinal (GI epithelium can shuttle Salmonella directly into the bloodstream within a few minutes following microbial ingestion. We have previously demonstrated that Salmonella controls the CD18 pathway to deeper tissue, manipulating the migratory properties of infected cells as an unappreciated component of its pathogenesis. We have observed that one type III effector, SrfH (also called SseI that Salmonella secretes into infected phagocytes manipulates the host protein TRIP6 to stimulate their migration. Paradoxically, SrfH was shown in another study to subvert a different host protein, IQGAP1, in a manner that inhibits the productive motility of such cells, perhaps to avoid interactions with T cells. Here, we resolve the discrepancy. We report that one naturally occurring allele of srfH promotes the migration of infected phagocytes into the bloodstream, while another naturally occurring allele that differs by only a single nucleotide polymorphism (SNP does not. This SNP determines if the protein contains an aspartic acid or a glycine residue at position 103 and may determine if SrfH binds TRIP6. SrfH Gly103 is a rare allele, but is present in the highly invasive strain Salmonella enterica serovar Typhimurium UK-1 (stands for universal killer. It is also present in the genome of the only sequenced strain belonging to the emerging pandemic Salmonella enterica serovar 4, [5],12,i:-, which is frequently associated with septicemia. Finally, we present evidence that suggests that Gifsy-2, the bacteriophage upon which srfH resides, is present in a clinical isolate of the human-specific pathogen, Salmonella enterica serovar Typhi. These observations may have interesting implications for our understanding of Salmonella pathogenesis.

  12. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise

    J.E. van Loon (Janine ); M.A.H. Sonneveld (Michelle); S.F.E. Praet (Stephan); M.P.M. de Maat (Moniek); F.W.G. Leebeek (Frank)

    2014-01-01

    textabstractBackground: Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the

  13. NAC Transcription Factors in Stress Responses and Senescence

    O'Shea, Charlotte

    Plant-specific NAM/ATAF/CUC (NAC) transcription factors have recently received considerable attention due to their significant roles in plant development and stress signalling. This interest has resulted in a number of physiological, genetic and cell biological studies of their functions. Some...... of these studies have also revealed emerging gene regulatory networks and protein-protein interaction networks. However, structural studies relating structure to function are lagging behind. Structure-function analysis of the NAC transcription factors has therefore been the main focus of this PhD thesis...... not involve significant folding-upon-binding but fuzziness or an extended ANAC046 region. The ANAC046 regulatory domain functions as an entropic chain with a bait for interactions with for example RCD1. RCD1 interacts with transcription factors from several different families, and the large stress...

  14. A Two-Level Sensorless MPPT Strategy Using SRF-PLL on a PMSG Wind Energy Conversion System

    Amina Echchaachouai

    2017-01-01

    Full Text Available In this paper, a two-level sensorless Maximum Power Point Tracking (MPPT strategy is presented for a variable speed Wind Energy Conversion System (WECS. The proposed system is composed of a wind turbine, a direct-drive Permanent Magnet Synchronous Generator (PMSG and a three phase controlled rectifier connected to a DC load. The realised generator output power maximization analysis justifies the use of the Field Oriented Control (FOC giving the six Pulse Width Modulation (PWM signals to the active rectifier. The generator rotor speed and position required by the FOC and the sensorless MPPT are estimated using a Synchronous Reference Frame Phase Locked Loop (SRF-PLL. The MPPT strategy used consists of two levels, the first level is a power regulation loop and the second level is an extremum seeking bloc generating the coefficient gathering the turbine characteristics. Experimental results validated on a hardware test setup using a DSP digital board (dSPACE 1104 are presented. Figures illustrating the estimated speed and angle confirm that the SRF-PLL is able to give an estimated speed and angle which closely follow the real ones. Also, the power at the DC load and the power at the generator output indicate that the MPPT gives optimum extracted power. Finally, other results show the effectiveness of the adopted approach in real time applications.

  15. Cryogenic rf test of the first SRF cavity etched in an rf Ar/Cl2 plasma

    Upadhyay, J.; Palczewski, A.; Popović, S.; Valente-Feliciano, A.-M.; Im, Do; Phillips, H. L.; Vušković, L.

    2017-12-01

    An apparatus and a method for etching of the inner surfaces of superconducting radio frequency (SRF) accelerator cavities are described. The apparatus is based on the reactive ion etching performed in an Ar/Cl2 cylindrical capacitive discharge with reversed asymmetry. To test the effect of the plasma etching on the cavity rf performance, a 1497 MHz single cell SRF cavity was used. The single cell cavity was mechanically polished and buffer chemically etched and then rf tested at cryogenic temperatures to provide a baseline characterization. The cavity's inner wall was then exposed to the capacitive discharge in a mixture of Argon and Chlorine. The inner wall acted as the grounded electrode, while kept at elevated temperature. The processing was accomplished by axially moving the dc-biased, corrugated inner electrode and the gas flow inlet in a step-wise manner to establish a sequence of longitudinally segmented discharges. The cavity was then tested in a standard vertical test stand at cryogenic temperatures. The rf tests and surface condition results, including the electron field emission elimination, are presented.

  16. Cryogenic rf test of the first SRF cavity etched in an rf Ar/Cl2 plasma

    J. Upadhyay

    2017-12-01

    Full Text Available An apparatus and a method for etching of the inner surfaces of superconducting radio frequency (SRF accelerator cavities are described. The apparatus is based on the reactive ion etching performed in an Ar/Cl2 cylindrical capacitive discharge with reversed asymmetry. To test the effect of the plasma etching on the cavity rf performance, a 1497 MHz single cell SRF cavity was used. The single cell cavity was mechanically polished and buffer chemically etched and then rf tested at cryogenic temperatures to provide a baseline characterization. The cavity’s inner wall was then exposed to the capacitive discharge in a mixture of Argon and Chlorine. The inner wall acted as the grounded electrode, while kept at elevated temperature. The processing was accomplished by axially moving the dc-biased, corrugated inner electrode and the gas flow inlet in a step-wise manner to establish a sequence of longitudinally segmented discharges. The cavity was then tested in a standard vertical test stand at cryogenic temperatures. The rf tests and surface condition results, including the electron field emission elimination, are presented.

  17. Religious beliefs, coping skills and responsibility to family as factors ...

    Background. Deliberate self-harm (DSH) ranges from behaviours aiming to communicate distress or relieve tension, but where suicide is not intended, to suicide. Not all individuals are prone to DSH, which suggests that there are factors that protect against it. Identifying these could play an important role in the management ...

  18. Factors affecting the remotely sensed response of coniferous forest plantations

    Danson, F.M.; Curran, P.J.

    1993-01-01

    Remote sensing of forest biophysical properties has concentrated upon forest sites with a wide range of green vegetation amount and thereby leaf area index and canopy cover. However, coniferous forest plantations, an important forest type in Europe, are managed to maintain a large amount of green vegetation with little spatial variation. Therefore, the strength of the remotely sensed signal will, it is hypothesized, be determined more by the structure of this forest than by its cover. Airborne Thematic Mapper (ATM) and SPOT-1 HRV data were used to determine the effects of this structural variation on the remotely sensed response of a coniferous forest plantation in the United Kingdom. Red and near infrared radiance were strongly and negatively correlated with a range of structural properties and with the age of the stands but weakly correlated with canopy cover. A composite variable, related to the volume of the canopy, accounted for over 75% of the variation in near infrared radiance. A simple model that related forest structural variables to the remotely sensed response was used to understand and explain this response from a coniferous forest plantation

  19. Plant community mediation of ecosystem responses to global change factors

    Churchill, A. C.

    2017-12-01

    Human alteration of the numerous environmental drivers affecting ecosystem processes is unprecedented in the last century, including changes in climate regimes and rapid increases in the availability of biologically active nitrogen (N). Plant communities may offer stabilizing or amplifying feedbacks mediating potential ecosystem responses to these alterations, and my research seeks to examine the conditions associated with when plant feedbacks are important for ecosystem change. My dissertation research focused on the unintended consequences of N deposition into natural landscapes, including alpine ecosystems which are particularly susceptible to adverse environmental impacts. In particular, I examined alpine plant and soil responses to N deposition 1) across multiple spatial scales throughout the Southern Rocky Mountains, 2) among diverse plant communities associated with unique environmental conditions common in the alpine of this region, and 3) among ecosystem pools of N contributing to stabilization of N inputs within those communities. I found that communities responded to inputs of N differently, often associated with traits of dominant plant species but these responses were intimately linked with the abiotic conditions of each independent community. Even so, statistical models predicting metrics of N processing in the alpine were improved by encompassing both abiotic and biotic components of the main community types.

  20. Factors responsible for the growth of small business

    JA Döckel

    2015-01-01

    Full Text Available Entrepreneurial conduct holds the key to economic growth. Thus those business that show growth and development are considered entrepreneurial, implying that SMME policy initiatives should focus on businesses with growth potential, and not the small business sector as a whole.  The success of a small business seems to depend on the intentions of the owner, together with factors associated with the ability of, and opportunity for, the specific business to grow.  The aim of this article is to make use of a multiple linear regression model to determine the variables that impact positively on business growth.  In addition to demand factors, it was established that smaller and younger businesses are the ones that grow faster. A successful business also shows a positive correlation between business management skills and entrepreneurial conduct.

  1. Factor Responsible for Examination Malpractices as Expressed by Undergraduates of Osun State University, Nigeria

    Yusuf; Adeoti, Florence; Olufunke, Yinusa Rasheedat; Ruth, Bamgbose Oluwayemisi

    2015-01-01

    The study investigated perception of undergraduates on factors responsible for examination malpractices. The study is a descriptive study; a sample of two hundred (200) undergraduates formed the participants for the study. A questionnaire titled: "Factor responsible for examination malpractices was used for data collection. Data collected…

  2. Introductory analysis of sustainable consumption and production : Factors of corporate social responsibility management in Japan

    八木, 迪幸; 國部, 克彦

    2017-01-01

    As an introductory analysis of sustainable consumption and production, this paper examines what factors influence corporate social responsibility management in Japan. Following some underlying theories (management control system; the neo-institutional theory; performance measurement systems; the stakeholder theory; the resource dependence theory), this paper conducts empirical studies using firm-level data. The first three studies examine what factors encourage corporate social responsibility...

  3. DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

    Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

  4. A method to adjust radiation dose-response relationships for clinical risk factors

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

    Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

  5. Off-centre dynamic Jahn-Teller effect studied by electron spin relaxation of Cu2+ ions in SrF2 crystal

    Hoffmann, S.K.

    2000-01-01

    Temperature cw-EPR and pulsed EPR electron spin echo experiments were performed for a low concentration of Cu 2+ ions in cubic SrF 2 crystals. The well resolved EPR spectrum at low temperatures (below 30 K) with parameters g parallel = 2.493, g perpendicular = 2.083, A parallel = 121, A perpendicular = 8.7, A parallel ( 19 F) = 135, A parallel ( 19 F) = 33.0 (A-values in 10 -4 cm -1 ) is transformed continuously into a single broad line above 225 K on heating, due to the g-factor shift and EPR line broadening. These data along with the angular variation EPR data are described in terms of a pseudo-Jahn-Teller effect of (T 2g +A 2u )x(a 1g +e g +t 1u ) type producing six off-centre positions of the Cu 2+ ion in the fluorine cube. Above 30 K a two-step averaging g -factor process occurs and is governed by vibronic dynamics between potential wells of the off-centre positions. This dynamics governs the electron spin relaxation in the whole temperature range. The electron spin-lattice relaxation rate 1/T 1 grows rapidly by six orders of magnitude in the temperature range 30-100 K and is determined by the Orbach-type process with excitations to two excited vibronic levels of energy 83 and 174 cm -1 . For higher temperatures the relaxation is dominated by overbarrier jumps leading to the isotropic EPR spectrum above 225 K. The phase memory time T M has the rigid lattice value 3.5 μs determined by nuclear spectral diffusion and its temperature variation is governed by the vibronic dynamics indicating that the excitations between vibronic levels produce a dephasing of the electron spin precessional motion. (author)

  6. Transcription Factor Functional Protein-Protein Interactions in Plant Defense Responses

    Murilo S. Alves

    2014-03-01

    Full Text Available Responses to biotic stress in plants lead to dramatic reprogramming of gene expression, favoring stress responses at the expense of normal cellular functions. Transcription factors are master regulators of gene expression at the transcriptional level, and controlling the activity of these factors alters the transcriptome of the plant, leading to metabolic and phenotypic changes in response to stress. The functional analysis of interactions between transcription factors and other proteins is very important for elucidating the role of these transcriptional regulators in different signaling cascades. In this review, we present an overview of protein-protein interactions for the six major families of transcription factors involved in plant defense: basic leucine zipper containing domain proteins (bZIP, amino-acid sequence WRKYGQK (WRKY, myelocytomatosis related proteins (MYC, myeloblastosis related proteins (MYB, APETALA2/ ETHYLENE-RESPONSIVE ELEMENT BINDING FACTORS (AP2/EREBP and no apical meristem (NAM, Arabidopsis transcription activation factor (ATAF, and cup-shaped cotyledon (CUC (NAC. We describe the interaction partners of these transcription factors as molecular responses during pathogen attack and the key components of signal transduction pathways that take place during plant defense responses. These interactions determine the activation or repression of response pathways and are crucial to understanding the regulatory networks that modulate plant defense responses.

  7. Design, Construction, and Initial Test of High Spatial Resolution Thermometry Arrays for Detection of Surface Temperature Profiles on SRF Cavities in Super Fluid Helium

    Ari Palczewski, Rongli Geng, Grigory Eremeev

    2011-07-01

    We designed and built two high resolution (0.6-0.55mm special resolution [1.1-1.2mm separation]) thermometry arrays prototypes out of the Allen Bradley 90-120 ohm 1/8 watt resistor to measure surface temperature profiles on SRF cavities. One array was designed to be physically flexible and conform to any location on a SRF cavity; the other was modeled after the common G-10/stycast 2850 thermometer and designed to fit on the equator of an ILC (Tesla 1.3GHz) SRF cavity. We will discuss the advantages and disadvantages of each array and their construction. In addition we will present a case study of the arrays performance on a real SRF cavity TB9NR001. TB9NR001 presented a unique opportunity to test the performance of each array as it contained a dual (4mm separation) cat eye defect which conventional methods such as OST (Oscillating Superleak second-sound Transducers) and full coverage thermometry mapping were unable to distinguish between. We will discuss the new arrays ability to distinguish between the two defects and their preheating performance.

  8. Evaluation of response factors for seismic probabilistic safety assessment of nuclear power plants

    Ebisawa, K.; Abe, K.; Muramatsu, K.; Itoh, M.; Kohno, K.; Tanaka, T.

    1994-01-01

    This paper presents a method for evaluating 'response factors' of components in nuclear power plants for use in a seismic probabilistic safety assessment (PSA). The response factor here is a measure of conservatism included in response calculations in seismic design analysis of components and is defined as a ratio of conservative design resonse to actual response. This method has the following characteristic features: (1) The components are classified into several groups based on the differences in their location and in the vibration models used in design response analyses; (2) the response factors are decomposed into subfactors corresponding to the stages of the seismic response analyses in the design practices; (3) the response factors for components are calculated as products of subfactors; (4) the subfactors are expressed either as a single value or as a function of parameters that influence the response of components. This paper describes the outline of this method and results from an application to a sample problem in which response factors were quantified for examples of components selected from the groups. (orig.)

  9. Sociodemographic factors responsible for blindness in diabetic Egyptian patients

    Abueleinen KGI

    2011-11-01

    Full Text Available Khaled Gamal Ibraheem Abueleinen1, Hany El-Mekawey1, Yasser Sayed Saif2, Amr Khafagy1, Hoda Ibrahim Rizk3, Eman M Eltahlawy41Department of Ophthalmology, Cairo University, Cairo, Egypt; 2Department of Ophthalmology, Beni-Suef University, Beni-Suef, Egypt; 3Department of Public Health, Cairo University, Cairo, Egypt; 4Public Health and Community Medicine National Research Center, Cairo, EgyptPurpose: To evaluate factors behind the delay in diagnosis and treatment among Egyptian patients who present with complicated diabetic retinopathy.Methods: Observational cross-sectional study of diabetic patients with advanced diabetic retinopathy. Patients were asked to answer a questionnaire to assess the impact of several sociodemographic factors.Results: A total of 397 patients agreed to take the questionnaire. Diabetic vitreous hemorrhage was the most common ocular complication and was found in 359 patients (90.4%. A total of 158 (39.8% patients knew that diabetes mellitus can be sight threatening, while 240 (60.2% were not aware until they developed sight threatening complication. A total of 179 patients (45.1% had early retirement because of visual loss related to diabetes mellitus. Multivariate logistic regression has shown that education, internist, contact with other patients, and media were respectively significant in predicting the awareness of patients about the sight-threatening effect of diabetic retinopathy.Conclusion: Patient education regarding diabetes and diabetic eye disease is essential for early detection and compliance with treatment. Illiteracy has a significant impact on development of sight-threatening diabetic complications. The internist is the first line of prophylaxis. Media has to participate more in patient education.Keywords: blindness, education, laser photocoagulation, macular edema, vitreous hemorrhage

  10. FTIR spectroscopic studies of bacterial cellular responses to environmental factors, plant-bacterial interactions and signalling

    Kamnev, Alexander A.

    2008-01-01

    Modern spectroscopic techniques are highly useful in studying diverse processes in microbial cells related to or incited by environmental factors. Spectroscopic data for whole cells, supramolecular structures or isolated cellular constituents can reflect structural and/or compositional changes occurring in the course of cellular metabolic responses to the effects of pollutants, environmental conditions (stress factors); nutrients, signalling molecules (communication factors), etc. This inform...

  11. Class and compassion: socioeconomic factors predict responses to suffering.

    Stellar, Jennifer E; Manzo, Vida M; Kraus, Michael W; Keltner, Dacher

    2012-06-01

    Previous research indicates that lower-class individuals experience elevated negative emotions as compared with their upper-class counterparts. We examine how the environments of lower-class individuals can also promote greater compassionate responding-that is, concern for the suffering or well-being of others. In the present research, we investigate class-based differences in dispositional compassion and its activation in situations wherein others are suffering. Across studies, relative to their upper-class counterparts, lower-class individuals reported elevated dispositional compassion (Study 1), as well as greater self-reported compassion during a compassion-inducing video (Study 2) and for another person during a social interaction (Study 3). Lower-class individuals also exhibited heart rate deceleration-a physiological response associated with orienting to the social environment and engaging with others-during the compassion-inducing video (Study 2). We discuss a potential mechanism of class-based influences on compassion, whereby lower-class individuals' are more attuned to others' distress, relative to their upper-class counterparts.

  12. Different responses of influenza epidemic to weather factors among Shanghai, Hong Kong, and British Columbia.

    Wang, Xi-Ling; Yang, Lin; He, Dai-Hai; Chiu, Alice Py; Chan, Kwok-Hung; Chan, King-Pan; Zhou, Maigeng; Wong, Chit-Ming; Guo, Qing; Hu, Wenbiao

    2017-06-01

    Weather factors have long been considered as key sources for regional heterogeneity of influenza seasonal patterns. As influenza peaks coincide with both high and low temperature in subtropical cities, weather factors may nonlinearly or interactively affect influenza activity. This study aims to assess the nonlinear and interactive effects of weather factors with influenza activity and compare the responses of influenza epidemic to weather factors in two subtropical regions of southern China (Shanghai and Hong Kong) and one temperate province of Canada (British Columbia). Weekly data on influenza activity and weather factors (i.e., mean temperature and relative humidity (RH)) were obtained from pertinent government departments for the three regions. Absolute humidity (AH) was measured by vapor pressure (VP), which could be converted from temperature and RH. Generalized additive models were used to assess the exposure-response relationship between weather factors and influenza virus activity. Interactions of weather factors were further assessed by bivariate response models and stratification analyses. The exposure-response curves of temperature and VP, but not RH, were consistent among three regions/cities. Bivariate response model revealed a significant interactive effect between temperature (or VP) and RH (P weather factors in developing a universal model to explain seasonal outbreaks of influenza. However, further research is needed to assess the association between weather factors and influenza activity in a wider context of social and environmental conditions.

  13. Mechanical design and engineering of the 3.9 GHZ, 3rd harmonic SRF system at Fermilab

    Don Mitchell

    2004-01-01

    The mechanical development of the 3.9 GHz, 3rd Harmonic SRF System is summarized to include: the development of a full scale copper prototype cavity structure; the design of the niobium 3 cell and niobium 9 cell structures; the design of the helium vessel and cryostat; the HOM coupler design; and a preliminary look at the main coupler design. The manufacturing processes for forming, rolling, and e-beam welding the HOM coupler, cavity cells, and end tubes are also described. Due to the exotic materials and manufacturing processes used in this type of device, a cost estimate for the material and fabrication is provided. The 3rd harmonic design is organized via a web-based data management approach

  14. An update on the study of high-gradient elliptical SRF cavities at 805 MHz for proton and other applications

    Tajima, Tsuyoshi [Los Alamos National Laboratory; Haynes, Brian [Los Alamos National Laboratory; Krawczyk, Frank [Los Alamos National Laboratory; Madrid, Mike [Los Alamos National Laboratory; Roybal, Ray [Los Alamos National Laboratory; Simakov, Evgenya [Los Alamos National Laboratory; Clemens, Bob [TJNAF; Macha, Jurt [TJNAF; Manus, Bob [TJNAF; Rimmer, Bob [TJNAF; Rimmer, Bob [TJNAF; Turlington, Larry [TJNAF

    2010-09-09

    An update on the study of 805 MHz elliptical SRF cavities that have been optimized for high gradient will be presented. An optimized cell shape, which is still appropriate for easy high pressure water rinsing, has been designed with the ratios of peak magnetic and electric fields to accelerating gradient being 3.75 mT/(MV/m) and 1.82, respectively. A total of 3 single-cell cavities have been fabricated. Two of the 3 cavities have been tested so far. The second cavity achieved an E{sub acc} of {approx}50 MV/m at Q{sub 0} of 1.4 x 10{sup 10}. This result demonstrates that 805 MHz cavities can, in principle, achieve as high as, or could even be better than, 1.3 GHz high-gradient cavities.

  15. Mechanical design and engineering of the 3.9 GHZ, 3rd harmonic SRF system at Fermilab

    Don Mitchell et al.

    2004-08-05

    The mechanical development of the 3.9 GHz, 3rd Harmonic SRF System is summarized to include: the development of a full scale copper prototype cavity structure; the design of the niobium 3 cell and niobium 9 cell structures; the design of the helium vessel and cryostat; the HOM coupler design; and a preliminary look at the main coupler design. The manufacturing processes for forming, rolling, and e-beam welding the HOM coupler, cavity cells, and end tubes are also described. Due to the exotic materials and manufacturing processes used in this type of device, a cost estimate for the material and fabrication is provided. The 3rd harmonic design is organized via a web-based data management approach.

  16. Improvement of the operational performance of SRF cavities via in situ helium processing and waveguide vacuum processing

    Reece, C.E.; Drury, M.; Rao, M.G.; Nguyen-Tuong, V.

    1997-01-01

    The useful performance range of the superconducting rf (SRF) cavities in the CEBAF accelerator at Jefferson Lab is frequently limited by electron field emission and derived phenomena. Improvements are required to support future operation of the accelerator at higher than 5 GeV. Twelve operational cryomodules have been successfully processed to higher useful operating gradients via rf-helium processing. Progress against field emission was evidenced by improved high-field Q, reduced x-ray production and greatly reduced incidence of arcing at the cold ceramic window. There was no difficulty reestablishing beamline vacuum following the processing. Cavities previously limited to 4-6 MV/m are now operating stably at 6-9 MV/m. By applying a pulsed-rf processing technique, we have also improved the pressure stability of the thermal transition region of the input waveguide for several cavities

  17. Screening and ranking framework (SRF) for geologic CO2 storagesite selection on the basis of HSE risk

    Oldenburg, Curtis M.

    2006-11-27

    A screening and ranking framework (SRF) has been developedto evaluate potential geologic carbon dioxide (CO2) storage sites on thebasis of health, safety, and environmental (HSE) risk arising from CO2leakage. The approach is based on the assumption that CO2 leakage risk isdependent on three basic characteristics of a geologic CO2 storage site:(1) the potential for primary containment by the target formation; (2)the potential for secondary containment if the primary formation leaks;and (3) the potential for attenuation and dispersion of leaking CO2 ifthe primary formation leaks and secondary containment fails. Theframework is implemented in a spreadsheet in which users enter numericalscores representing expert opinions or published information along withestimates of uncertainty. Applications to three sites in Californiademonstrate the approach. Refinements and extensions are possible throughthe use of more detailed data or model results in place of propertyproxies.

  18. A heteroscedastic generalized linear model with a non-normal speed factor for responses and response times.

    Molenaar, Dylan; Bolsinova, Maria

    2017-05-01

    In generalized linear modelling of responses and response times, the observed response time variables are commonly transformed to make their distribution approximately normal. A normal distribution for the transformed response times is desirable as it justifies the linearity and homoscedasticity assumptions in the underlying linear model. Past research has, however, shown that the transformed response times are not always normal. Models have been developed to accommodate this violation. In the present study, we propose a modelling approach for responses and response times to test and model non-normality in the transformed response times. Most importantly, we distinguish between non-normality due to heteroscedastic residual variances, and non-normality due to a skewed speed factor. In a simulation study, we establish parameter recovery and the power to separate both effects. In addition, we apply the model to a real data set. © 2017 The Authors. British Journal of Mathematical and Statistical Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

  19. Host transcription factors in the immediate pro-inflammatory response to the parasitic mite Psoroptes ovis.

    Stewart T G Burgess

    Full Text Available BACKGROUND: Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, results in the rapid development of cutaneous inflammation and leads to the crusted skin lesions characteristic of the disease. We described previously the global host transcriptional response to infestation with P. ovis, elucidating elements of the inflammatory processes which lead to the development of a rapid and profound immune response. However, the mechanisms by which this response is instigated remain unclear. To identify novel methods of intervention a better understanding of the early events involved in triggering the immune response is essential. The objective of this study was to gain a clearer understanding of the mechanisms and signaling pathways involved in the instigation of the immediate pro-inflammatory response. RESULTS: Through a combination of transcription factor binding site enrichment and pathway analysis we identified key roles for a number of transcription factors in the instigation of cutaneous inflammation. In particular, defined roles were elucidated for the transcription factors NF-kB and AP-1 in the orchestration of the early pro-inflammatory response, with these factors being implicated in the activation of a suite of inflammatory mediators. CONCLUSIONS: Interrogation of the host temporal response to P. ovis infestation has enabled the further identification of the mechanisms underlying the development of the immediate host pro-inflammatory response. This response involves key regulatory roles for the transcription factors NF-kB and AP-1. Pathway analysis demonstrated that the activation of these transcription factors may be triggered following a host LPS-type response, potentially involving TLR4-signalling and also lead to the intriguing possibility that this could be triggered by a P. ovis allergen.

  20. Emotional Responses to Suicidal Patients: Factor Structure, Construct, and Predictive Validity of the Therapist Response Questionnaire-Suicide Form

    Shira Barzilay

    2018-04-01

    Full Text Available BackgroundMental health professionals have a pivotal role in suicide prevention. However, they also often have intense emotional responses, or countertransference, during encounters with suicidal patients. Previous studies of the Therapist Response Questionnaire-Suicide Form (TRQ-SF, a brief novel measure aimed at probing a distinct set of suicide-related emotional responses to patients found it to be predictive of near-term suicidal behavior among high suicide-risk inpatients. The purpose of this study was to validate the TRQ-SF in a general outpatient clinic setting.MethodsAdult psychiatric outpatients (N = 346 and their treating mental health professionals (N = 48 completed self-report assessments following their first clinic meeting. Clinician measures included the TRQ-SF, general emotional states and traits, therapeutic alliance, and assessment of patient suicide risk. Patient suicidal outcomes and symptom severity were assessed at intake and one-month follow-up. Following confirmatory factor analysis of the TRQ-SF, factor scores were examined for relationships with clinician and patient measures and suicidal outcomes.ResultsFactor analysis of the TRQ-SF confirmed three dimensions: (1 affiliation, (2 distress, and (3 hope. The three factors also loaded onto a single general factor of negative emotional response toward the patient that demonstrated good internal reliability. The TRQ-SF scores were associated with measures of clinician state anger and anxiety and therapeutic alliance, independently of clinician personality traits after controlling for the state- and patient-specific measures. The total score and three subscales were associated in both concurrent and predictive ways with patient suicidal outcomes, depression severity, and clinicians’ judgment of patient suicide risk, but not with global symptom severity, thus indicating specifically suicide-related responses.ConclusionThe TRQ-SF is a brief and reliable measure with a

  1. Emotional Responses to Suicidal Patients: Factor Structure, Construct, and Predictive Validity of the Therapist Response Questionnaire-Suicide Form.

    Barzilay, Shira; Yaseen, Zimri S; Hawes, Mariah; Gorman, Bernard; Altman, Rachel; Foster, Adriana; Apter, Alan; Rosenfield, Paul; Galynker, Igor

    2018-01-01

    Mental health professionals have a pivotal role in suicide prevention. However, they also often have intense emotional responses, or countertransference, during encounters with suicidal patients. Previous studies of the Therapist Response Questionnaire-Suicide Form (TRQ-SF), a brief novel measure aimed at probing a distinct set of suicide-related emotional responses to patients found it to be predictive of near-term suicidal behavior among high suicide-risk inpatients. The purpose of this study was to validate the TRQ-SF in a general outpatient clinic setting. Adult psychiatric outpatients ( N  = 346) and their treating mental health professionals ( N  = 48) completed self-report assessments following their first clinic meeting. Clinician measures included the TRQ-SF, general emotional states and traits, therapeutic alliance, and assessment of patient suicide risk. Patient suicidal outcomes and symptom severity were assessed at intake and one-month follow-up. Following confirmatory factor analysis of the TRQ-SF, factor scores were examined for relationships with clinician and patient measures and suicidal outcomes. Factor analysis of the TRQ-SF confirmed three dimensions: (1) affiliation, (2) distress, and (3) hope. The three factors also loaded onto a single general factor of negative emotional response toward the patient that demonstrated good internal reliability. The TRQ-SF scores were associated with measures of clinician state anger and anxiety and therapeutic alliance, independently of clinician personality traits after controlling for the state- and patient-specific measures. The total score and three subscales were associated in both concurrent and predictive ways with patient suicidal outcomes, depression severity, and clinicians' judgment of patient suicide risk, but not with global symptom severity, thus indicating specifically suicide-related responses. The TRQ-SF is a brief and reliable measure with a 3-factor structure. It demonstrates

  2. Enhanceosomes as integrators of hypoxia inducible factor (HIF) and other transcription factors in the hypoxic transcriptional response.

    Pawlus, Matthew R; Hu, Cheng-Jun

    2013-09-01

    Hypoxia is a prevalent attribute of the solid tumor microenvironment that promotes the expression of genes through posttranslational modifications and stabilization of alpha subunits (HIF1α and HIF2α) of hypoxia-inducible factors (HIFs). Despite significant similarities, HIF1 (HIF1α/ARNT) and HIF2 (HIF2α/ARNT) activate common as well as unique target genes and exhibit different functions in cancer biology. More surprisingly, accumulating data indicates that the HIF1- and/or HIF2-mediated hypoxia responses can be oncogenic as well as tumor suppressive. While the role of HIF in the hypoxia response is well established, recent data support the concept that HIF is necessary, but not sufficient for the hypoxic response. Other transcription factors that are activated by hypoxia are also required for the HIF-mediated hypoxia response. HIFs, other transcription factors, co-factors and RNA poll II recruited by HIF and other transcription factors form multifactorial enhanceosome complexes on the promoters of HIF target genes to activate hypoxia inducible genes. Importantly, HIF1 or HIF2 requires distinct partners in activating HIF1 or HIF2 target genes. Because HIF enhanceosome formation is required for the gene activation and distinct functions of HIF1 and HIF2 in tumor biology, disruption of the HIF1 or HIF2 specific enhanceosome complex may prove to be a beneficial strategy in tumor treatment in which tumor growth is specifically dependent upon HIF1 or HIF2 activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Factors effecting Corporate Social Responsibility disclosure ratings:an empirical study of Finnish listed companies

    Roitto, A. (Artturi)

    2013-01-01

    Abstract As Corporate Social Responsibility (CSR) disclosure is becoming more common practise amongst companies, it is valuable to understand the underlying factors involved. The Goal of this thesis is to examine if the factors suggested by previous studies seem to have significance in a Finnish sample composed of 31 listed companies. As an ancillary research question linkage between Corporate Governance recommendation devi...

  4. Age and other perioperative risk factors for postoperative systemic inflammatory response syndrome after cardiac surgery

    Dieleman, J. M.; Peelen, L. M.; Coulson, T. G.; Tran, L.; Reid, C. M.; Smith, Jennifer A.; Myles, P. S.; Pilcher, C.D.

    2017-01-01

    Background The inflammatory response to surgery varies considerably between individual patients. Age might be a substantial factor in this variability. Our objective was to examine the association of patient age and other potential risk factors with the occurrence of a postoperative systemic

  5. Auxin Response Factors (ARFs are potential mediators of auxin action in tomato response to biotic and abiotic stress (Solanum lycopersicum.

    Sarah Bouzroud

    Full Text Available Survival biomass production and crop yield are heavily constrained by a wide range of environmental stresses. Several phytohormones among which abscisic acid (ABA, ethylene and salicylic acid (SA are known to mediate plant responses to these stresses. By contrast, the role of the plant hormone auxin in stress responses remains so far poorly studied. Auxin controls many aspects of plant growth and development, and Auxin Response Factors play a key role in the transcriptional activation or repression of auxin-responsive genes through direct binding to their promoters. As a mean to gain more insight on auxin involvement in a set of biotic and abiotic stress responses in tomato, the present study uncovers the expression pattern of SlARF genes in tomato plants subjected to biotic and abiotic stresses. In silico mining of the RNAseq data available through the public TomExpress web platform, identified several SlARFs as responsive to various pathogen infections induced by bacteria and viruses. Accordingly, sequence analysis revealed that 5' regulatory regions of these SlARFs are enriched in biotic and abiotic stress-responsive cis-elements. Moreover, quantitative qPCR expression analysis revealed that many SlARFs were differentially expressed in tomato leaves and roots under salt, drought and flooding stress conditions. Further pointing to the putative role of SlARFs in stress responses, quantitative qPCR expression studies identified some miRNA precursors as potentially involved in the regulation of their SlARF target genes in roots exposed to salt and drought stresses. These data suggest an active regulation of SlARFs at the post-transcriptional level under stress conditions. Based on the substantial change in the transcript accumulation of several SlARF genes, the data presented in this work strongly support the involvement of auxin in stress responses thus enabling to identify a set of candidate SlARFs as potential mediators of biotic and abiotic

  6. Regulation of Cancer Cell Responsiveness to Ionizing Radiation Treatment by Cyclic AMP Response Element Binding Nuclear Transcription Factor

    Francesca D’Auria

    2017-05-01

    Full Text Available Cyclic AMP response element binding (CREB protein is a member of the CREB/activating transcription factor (ATF family of transcription factors that play an important role in the cell response to different environmental stimuli leading to proliferation, differentiation, apoptosis, and survival. A number of studies highlight the involvement of CREB in the resistance to ionizing radiation (IR therapy, demonstrating a relationship between IR-induced CREB family members’ activation and cell survival. Consistent with these observations, we have recently demonstrated that CREB and ATF-1 are expressed in leukemia cell lines and that low-dose radiation treatment can trigger CREB activation, leading to survival of erythro-leukemia cells (K562. On the other hand, a number of evidences highlight a proapoptotic role of CREB following IR treatment of cancer cells. Since the development of multiple mechanisms of resistance is one key problem of most malignancies, including those of hematological origin, it is highly desirable to identify biological markers of responsiveness/unresponsiveness useful to follow-up the individual response and to adjust anticancer treatments. Taking into account all these considerations, this mini-review will be focused on the involvement of CREB/ATF family members in response to IR therapy, to deepen our knowledge of this topic, and to pave the way to translation into a therapeutic context.

  7. The small ethylene response factor ERF96 is involved in the regulation of the abscisic acid response in Arabidopsis

    Xiaoping eWang

    2015-11-01

    Full Text Available Ethylene regulates many aspects of plant growth and development including seed germination, leaf senescence, and fruit ripening, and of plant responses to environmental stimuli including both biotic and abiotic stresses. Ethylene Response Factors (ERFs are plant-specific transcription factors and are a subfamily of the AP2 (APETALA2/ERF transcription factor family. The function of many members in this large gene family remains largely unknown. ERF96, a member of the Group IX ERF family transcription factors, has recently been shown to be a transcriptional activator that is involved in plant defense response in Arabidopsis. Here we provide evidence that ERF96 is a positive regulator of abscisic acid (ABA responses. Bioinformatics analysis indicated that there are a total four small ERFs in Arabidopsis including ERF95, ERF96, ERF97 and ERF98, and that ERF96 forms a cluster with ERF95 and ERF97. By using quantitative RT-PCR, we found that ERF96 is expressed in all tissues and organs examined except roots, with relatively high expression in flowers and seeds. Results from the protoplast transfection assay results indicated that the EDLL motif-containing C-terminal domain is responsible for ERF96’s transcriptional activity. Although loss-of-function mutant of ERF96 was morphologically similar to wild type plants, transgenic plants overexpressing ERF96 had smaller rosette size and were delayed in flowering time. In ABA sensitivity assays, we found that ERF96 overexpression plants were hypersensitive to ABA in terms of ABA inhibition of seed germination, early seedling development and root elongation. Consistent with these observations, elevated transcript levels of some ABA-responsive genes including RD29A, ABI5, ABF3, ABF4, P5CS and COR15A were observed in the transgenic plants in the presence of ABA. However, in the absence of ABA treatment, the transcript levels of these ABA-responsive genes remained largely unchanged. Our experiments also showed

  8. Tissue factor-dependent vascular endothelial growth factor production by human fibroblasts in response to activated factor VII.

    Ollivier, V; Bentolila, S; Chabbat, J; Hakim, J; de Prost, D

    1998-04-15

    The transmembrane protein tissue factor (TF) is the cell surface receptor for coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has been identified as a regulator of angiogenesis, tumor growth, and metastasis. This study was designed to link the binding of FVII(a) to its receptor, TF, with the subsequent triggering of angiogenesis through vascular endothelial growth factor (VEGF) production by human lung fibroblasts. We report that incubation of fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked immunosorbent assay, was time- and concentration-dependent. VEGF secretion was maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and represented a threefold induction of the basal VEGF level. Reverse transcriptase-polymerase chain reaction analysis of VEGF detected three mRNA species of 180, 312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A 2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12 and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a pool of antibodies against TF, pointing to the involvement of this receptor. On specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production. Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold stimulating effect. Protein tyrosine kinase and protein kinase C are involved in signal transduction leading to VEGF production, as shown by the inhibitory effects of genistein and GF 109203X. The results of this study indicate that TF is essential for VIIa-induced VEGF production by human fibroblasts and that its role is mainly linked to the proteolytic activity of the TF-VIIa complex.

  9. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

    Hajar Mazahery

    2015-06-01

    Full Text Available Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OHD concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OHD concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OHD response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OHD, aging, body mass index(BMI/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation and environment (season are other contributing factors. With the exception of baseline 25(OHD, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.

  10. Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation.

    Mazahery, Hajar; von Hurst, Pamela R

    2015-06-25

    Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.

  11. Pilot Evaluation of Angiogenesis Signaling Factor Response after Transcatheter Arterial Embolization for Hepatocellular Carcinoma.

    Ronald, James; Nixon, Andrew B; Marin, Daniele; Gupta, Rajan T; Janas, Gemini; Chen, Willa; Suhocki, Paul V; Pabon-Ramos, Waleska; Sopko, David R; Starr, Mark D; Brady, John C; Hurwitz, Herbert I; Kim, Charles Y

    2017-10-01

    Purpose To identify changes in a broad panel of circulating angiogenesis factors after bland transcatheter arterial embolization (TAE), a purely ischemic treatment for hepatocellular carcinoma (HCC). Materials and Methods This prospective HIPAA-compliant study was approved by the institutional review board. Informed written consent was obtained from all participants prior to entry into the study. Twenty-five patients (21 men; mean age, 61 years; range, 30-81 years) with Liver Imaging Reporting and Data System category 5 or biopsy-proven HCC and who were undergoing TAE were enrolled from October 15, 2014, through December 2, 2015. Nineteen plasma angiogenesis factors (angiopoietin 2; hepatocyte growth factor; platelet-derived growth factor AA and BB; placental growth factor; vascular endothelial growth factor A and D; vascular endothelial growth factor receptor 1, 2, and 3; osteopontin; transforming growth factor β1 and β2; thrombospondin 2; intercellular adhesion molecule 1; interleukin 6 [IL-6]; stromal cell-derived factor 1; tissue inhibitor of metalloproteinases 1; and vascular cell adhesion molecule 1 [VCAM-1]) were measured by using enzyme-linked immunosorbent assays at 1 day, 2 weeks, and 5 weeks after TAE and were compared with baseline levels by using paired Wilcoxon tests. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Angiogenesis factor levels were compared between responders and nonresponders by mRECIST criteria by using unpaired Wilcoxon tests. Results All procedures were technically successful with no complications. Fourteen angiogenesis factors showed statistically significant changes following TAE, but most changes were transient. IL-6 was upregulated only 1 day after the procedure, but showed the largest increases of any factor. Osteopontin and VCAM-1 demonstrated sustained upregulation at all time points following TAE. At 3-month follow-up imaging, 11 patients had responses to TAE

  12. Fabrication and Final Field Tuning of Copper Cavity Models for a High-Current SRF ERL at 703.75 MHz

    Cole, Michael; Burger, Al; Falletta, Michael; Holmes, Douglas; Peterson, Ed; Wong, Robert

    2005-01-01

    Advanced Energy Systems is currently under contract to BNL to fabricate a five cell superconducting cavity and cryomodule for the RHIC eCooler SRF Energy Recovery Linac (ERL) program.* The cavity is designed and optimized for ampere class SRF ERL service. As part of this program, we have fabricated two low power copper models of the RF cavities. During the fabrication process a series of frequency measurements were made and compared to the frequency expected at that point in the fabrication process. Where possible, the cavity was modified either before or during, the next fabrication step to tune the cavity frequency toward the target frequency. Following completion of the cavities they were tuned for field flatness and frequency. This paper will review the measurements made, frequency tuning performed, and discuss discrepancies between the expected and measured results. We will also review the as fabricated field profiles and the results of the tuning steps. Further, the cost and benefits of extensive in pro...

  13. Investigation into the MgF2-NiF2, CaF2-NiF2, SrF2-NiF2 systems

    Ikrami, D.D.; Petrov, S.V.; Fedorov, P.P.; Ol'khovaya, L.A.; Luginina, A.A.; AN SSSR, Moscow. Inst. Fizicheskikh Problem; AN SSSR, Moscow. Inst. Kristallografii)

    1984-01-01

    Using the methods of differential thermal and X-ray phase analyses the systems MgF 2 -NiF 2 , CaF 2 -NiF 2 , SrF 2 -NiF 2 have been studied. In the system SrF 2 -NiF 2 the only orthorhombic compounds SrNiF 4 (a=14.43; b=3.93; c=5.66 (+-0.01 A)) is formed. SrNiF 4 density constitutes: dsub(X-ray)=4.60+-0.01 g/cm 3 , dsub(exp.)=4.60+-0.03 g/cm 3 . Refraction indices are as follows SrNiF 4 :Ng=1.500; Nsub(m)=1.497; Nsub(p)=1.479. SrNiF 4 magnetic ordering temperature Tsub(N) approximately 100 K

  14. Simulation and Analysis of Spectral Response Function and Bandwidth of Spectrometer

    Zhenyu Gao

    2016-01-01

    Full Text Available A simulation method for acquiring spectrometer’s Spectral Response Function (SRF based on Huygens Point Spread Function (PSF is suggested. Taking into account the effects of optical aberrations and diffraction, the method can obtain the fine SRF curve and corresponding spectral bandwidth at any nominal wavelength as early as in the design phase. A prism monochromator is proposed for illustrating the simulation procedure. For comparison, a geometrical ray-tracing method is also provided, with bandwidth deviations varying from 5% at 250 nm to 25% at 2400 nm. Further comparison with reported experiments shows that the areas of the SRF profiles agree to about 1%. However, the weak scattered background light on the level of 10−4 to 10−5 observed by experiment could not be covered by this simulation. This simulation method is a useful tool for forecasting the performance of an underdesigned spectrometer.

  15. High responders and low responders: factors associated with individual variation in response to standardized training.

    Mann, Theresa N; Lamberts, Robert P; Lambert, Michael I

    2014-08-01

    The response to an exercise intervention is often described in general terms, with the assumption that the group average represents a typical response for most individuals. In reality, however, it is more common for individuals to show a wide range of responses to an intervention rather than a similar response. This phenomenon of 'high responders' and 'low responders' following a standardized training intervention may provide helpful insights into mechanisms of training adaptation and methods of training prescription. Therefore, the aim of this review was to discuss factors associated with inter-individual variation in response to standardized, endurance-type training. It is well-known that genetic influences make an important contribution to individual variation in certain training responses. The association between genotype and training response has often been supported using heritability estimates; however, recent studies have been able to link variation in some training responses to specific single nucleotide polymorphisms. It would appear that hereditary influences are often expressed through hereditary influences on the pre-training phenotype, with some parameters showing a hereditary influence in the pre-training phenotype but not in the subsequent training response. In most cases, the pre-training phenotype appears to predict only a small amount of variation in the subsequent training response of that phenotype. However, the relationship between pre-training autonomic activity and subsequent maximal oxygen uptake response appears to show relatively stronger predictive potential. Individual variation in response to standardized training that cannot be explained by genetic influences may be related to the characteristics of the training program or lifestyle factors. Although standardized programs usually involve training prescribed by relative intensity and duration, some methods of relative exercise intensity prescription may be more successful in creating

  16. Hepatitis B viral factors and treatment responses in chronic hepatitis B

    Chih-Lin Lin

    2013-06-01

    Full Text Available Baseline and on-treatment hepatitis B viral factors are reported to affect treatment responses. A lower baseline hepatitis B virus (HBV DNA level is a strong predictor of the response to antiviral therapy. HBV genotype A/B patients have better responses to interferon-based therapy than those with genotypes C/D. Regarding the association of HBV mutants with responses to antiviral therapy, current evidence is limited. On-treatment viral suppression is the most important predictor of response to nucleoside analogs. On-treatment hepatitis B surface antigen decline is significantly associated with response to pegylated interferon. In the future, individualized therapy should be based on treatment efficacy, adverse effects, baseline and on-treatment predictors of antiviral therapy.

  17. Boundary condition effect on response modification factor of X-braced steel frames

    Walid A. Attia

    2018-04-01

    Full Text Available Design of the structures to resist seismic force depends on the theory of dissipation in elastic energy that already exists in response modification factor “R-factor”. The main problem in codes gives a constant value for R-factor, since change in boundary conditions of building change in behavior of braced steel frame structures and that effects on R-factor. This study is an attempt to assess overstrength, ductility and response modification factor of X-braced steel frame under change in boundary conditions, as change in the direction of strong axis of column and connection support type of column besides variation in storey and bays numbers to be 21 frames and each frame has 8 different boundary conditions as sum of 168 cases for analysis. These frames were analyzed by using nonlinear static “pushover” analysis. As results of this study change in support type and direction of strong axis of column give large change in value of R-factor; the minimum value was 4.37 and maximum value 10.97. Minimum value is close to code value that’s mean the code is more conservative in suggesting of R-factor and gives a large factor of safety. Change in the location of bracing gives change in value of R-factor for all boundary conditions. Change in direction of strong axis of columns and support type didn’t give change in value of fundamental period, all boundary conditions. Keywords: Response modification factor, Ductility reduction factor, Overstrength factor, Boundary conditions, Brace frame, Nonlinear static analysis “Pushover”

  18. Dyadic confirmatory factor analysis of the inflammatory bowel disease family responsibility questionnaire.

    Greenley, Rachel Neff; Reed-Knight, Bonney; Blount, Ronald L; Wilson, Helen W

    2013-09-01

    Evaluate the factor structure of youth and maternal involvement ratings on the Inflammatory Bowel Disease Family Responsibility Questionnaire, a measure of family allocation of condition management responsibilities in pediatric inflammatory bowel disease. Participants included 251 youth aged 11-18 years with inflammatory bowel disease and their mothers. Item-level descriptive analyses, subscale internal consistency estimates, and confirmatory factor analyses of youth and maternal involvement were conducted using a dyadic data-analytic approach. Results supported the validity of 4 conceptually derived subscales including general health maintenance, social aspects, condition management tasks, and nutrition domains. Additionally, results indicated adequate support for the factor structure of a 21-item youth involvement measure and strong support for a 16-item maternal involvement measure. Additional empirical support for the validity of the Inflammatory Bowel Disease Family Responsibility Questionnaire was provided. Future research to replicate current findings and to examine the measure's clinical utility is warranted.

  19. Elevated-CO2 Response of Stomata and Its Dependence on Environmental Factors

    Xu, Zhenzhu; Jiang, Yanling; Jia, Bingrui; Zhou, Guangsheng

    2016-01-01

    Stomata control the flow of gases between plants and the atmosphere. This review is centered on stomatal responses to elevated CO2 concentration and considers other key environmental factors and underlying mechanisms at multiple levels. First, an outline of general responses in stomatal conductance under elevated CO2 is presented. Second, stomatal density response, its development, and the trade-off with leaf growth under elevated CO2 conditions are depicted. Third, the molecular mechanism regulating guard cell movement at elevated CO2 is suggested. Finally, the interactive effects of elevated CO2 with other factors critical to stomatal behavior are reviewed. It may be useful to better understand how stomata respond to elevated CO2 levels while considering other key environmental factors and mechanisms, including molecular mechanism, biochemical processes, and ecophysiological regulation. This understanding may provide profound new insights into how plants cope with climate change. PMID:27242858

  20. Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination.

    Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

    2012-03-01

    Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy

    Young, Robin J; Litière, Saskia; Lia, Michela

    2017-01-01

    BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) 62012 study was a Phase III trial of doxorubicin versus doxorubicin-ifosfamide chemotherapy in 455 patients with advanced soft tissue sarcoma (STS). Analysis of the main study showed that combination chemotherapy...... improved tumor response and progression-free survival, but differences in overall survival (OS) were not statistically significant. We analyzed factors prognostic for tumor response and OS, and assessed histological subgroup and tumor grade as predictive factors to identify patients more likely to benefit...... patients had improved tumor response compared to other histological subgroups, whilst patients with metastases other than lung, liver or bone had a poorer response [odds ratio (OR) 0.42, 95% confidence interval (CI) 0.23-0.78; p = 0.006]. Patients with bone metastases had reduced OS [hazard ratio (HR) 1...

  2. The Role of Trauma-Specific Irrational Beliefs and Sociodemographic Risk Factors in Posttraumatic Stress Responses

    Hyland, Philip; Shevlin, Mark; Adamson, Gary; Boduszek, Daniel

    2013-01-01

    Posttraumatic stress responses have been linked to a range of social-cognitive and sociodemographic factors. Rational Emotive Behaviour Therapy suggests that responding to a traumatic life event with a set of irrational beliefs should play a crucial role in predicting the development of posttraumatic stress disorder (PTSD: Ellis, 2001). The current study assessed the role of trauma-specific irrational beliefs in the prediction of clinically relevant posttraumatic stress responses, while contr...

  3. Factors behind response strategies of incumbent firms to disruptive innovation: case of TV broadcasting industry

    Markevičiūtė, Imantė

    2017-01-01

    Disruptive technologies and business models are fundamentally changing the established ‘rules of the game’ in many industries. Thus, finding an adequate response becomes a matter of survival to companies touched by disruptive innovation. The current research is attempting to reveal the factors determining the response strategy of local incumbent TV broadcasters to global disruptive innovation. In order to do so, these research objectives are pursued in order to answer the research question: t...

  4. Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

    Harris Pratsinis

    2015-01-01

    Full Text Available Intervertebral disc (IVD degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D organotypic milieu, comprising characteristic molecules of IVD’s extracellular matrix. In particular, annulus fibrosus (AF cells were cultured inside collagen type-I gels, while nucleus pulposus (NP cells in chondroitin sulfate A (CSA supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF, basic Fibroblast Growth Factor (bFGF, and Insulin-Like Growth Factor-I (IGF-I were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration.

  5. Modified 3½-Cell SC Cavity Made of Large Grain Niobium for the FZD SRF Photoinjector

    Murcek, P; Michel, P; Moeller, K; Arnold, A; Teichert, J; Xiang, R; Freitag, M; Kneisel, P

    2010-01-01

    An SRF photoinjector has been successfully tested in FZD under the collaboration of BESSY, DESY, FZD, and MBI. In order to improve the gun cavity quality and thus reach a higher gradient, a new 3+1/2 superconducting cavity is being fabricated in cooperation with JLab. The modified cavity is made of large grain niobium, composed of one filter choke, one special designed half-cell (gun-cell) and three TESLA cavities. In this paper, the main updates of the new cavity design will be explained in detail. The deformation of the filter choke and the gun-cell, which is caused by pressure fluctuation in the He-line and also by the effect of the Lorentz force, will be minimized by stiffening between the filter choke and the gun-cell. Meanwhile, the cathode hole in the choke and gun-cell is enlarged for better rinsing. To simplify assembly, the NbTi pick-up will be welded directly on the wall of filter choke.

  6. Time to treatment as an important factor for the response to methotrexate in juvenile idiopathic arthritis.

    Albers, H M; Wessels, J A M; van der Straaten, R J H M; Brinkman, D M C; Suijlekom-Smit, L W A; Kamphuis, S S M; Girschick, H J; Wouters, C; Schilham, M W; le Cessie, S; Huizinga, T W J; Ten Cate, R; Guchelaar, H J

    2009-01-15

    Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug in juvenile idiopathic arthritis (JIA). Currently, individual response to MTX cannot be reliably predicted. Identification of clinical and genetic factors that influence the response to MTX could be helpful in realizing the optimal treatment for individual patients. A cohort of 128 JIA patients treated with MTX were studied retrospectively. Eleven clinical parameters and genotypes of 6 single nucleotide polymorphisms in 5 genes related to the mechanism of action of MTX were compared between MTX responders and nonresponders using a multivariate regression analysis. The time from diagnosis to start of MTX treatment, physician's global assessment at baseline, and the starting dose were significantly associated with the response to MTX at 6 months after initiation. Patients with a shorter time from diagnosis to start of MTX and a higher disease activity according to the physician but with a lower MTX dose showed an increased response. The effect of the starting dose on MTX response seemed to be mainly due to the influence of the systemic JIA subtype. The time from diagnosis to start of MTX treatment and physician's global assessment at baseline were highly correlated. Therefore, the precise effect size of each independent variable could not be determined. In children with JIA, the time from diagnosis to start of MTX appears to be an important factor for MTX response. Our results suggest that an earlier start of MTX treatment will lead to an increased response.

  7. Familial factors responsible for persistent crying-induced asthma: a case report.

    Weinstein, A G

    1987-10-01

    Crying behavior of the asthmatic child may induce wheezing symptoms. This may be a clinical problem for families with asthmatic children who exhibit frequent and persistent crying behavior. This case report identifies behaviors by the child and parents that may be responsible for continual crying. Child factors include (1) "spoiled" personality, (2) poor self-image, (3) biologic sensitivity to foods, medication, and environmental allergens producing irritability. Parental factors include poor disciplinary practices secondary to (1) disrupted home life, (2) guilt, and (3) overprotective behavior. Identification of these factors may be helpful in establishing clinical management strategies to reduce crying-induced asthma.

  8. Capsicum annuum WRKY transcription factor d (CaWRKYd) regulates hypersensitive response and defense response upon Tobacco mosaic virus infection.

    Huh, Sung Un; Choi, La Mee; Lee, Gil-Je; Kim, Young Jin; Paek, Kyung-Hee

    2012-12-01

    WRKY transcription factors regulate biotic, abiotic, and developmental processes. In terms of plant defense, WRKY factors have important roles as positive and negative regulators via transcriptional regulation or protein-protein interaction. Here, we report the characterization of the gene encoding Capsicum annuum WRKY transcription factor d (CaWRKYd) isolated from microarray analysis in the Tobacco mosaic virus (TMV)-P(0)-inoculated hot pepper plants. CaWRKYd belongs to the WRKY IIa group, a very small clade in the WRKY subfamily, and WRKY IIa group has positive/negative regulatory roles in Arabidopsis and rice. CaWRKYd transcripts were induced by various plant defense-related hormone treatments and TMV-P(0) inoculation. Silencing of CaWRKYd affected TMV-P(0)-mediated hypersensitive response (HR) cell death and accumulation of TMV-P(0) coat protein in local and systemic leaves. Furthermore, expression of some pathogenesis-related (PR) genes and HR-related genes was reduced in the CaWRKYd-silenced plants compared with TRV2 vector control plants upon TMV-P(0) inoculation. CaWRKYd was confirmed to bind to the W-box. Thus CaWRKYd is a newly identified Capsicum annuum WRKY transcription factor that appears to be involved in TMV-P(0)-mediated HR cell death by regulating downstream gene expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. Functional analysis of jasmonate-responsive transcription factors in Arabidopsis thaliana

    Zarei, Adel

    2007-01-01

    The aim of the studies described in this thesis was the functional analysis of JA-responsive transcription factors in Arabidopsis with an emphasis on the interaction with the promoters of their target genes. In short, the following new results were obtained. The promoter of the PDF1.2 gene contains

  10. 41 CFR 101-25.202 - Factors to be used to determine assignment of purchase responsibility.

    2010-07-01

    ... experience of agency purchasing and contracting officials and their operating units with due regard to... determine assignment of purchase responsibility. 101-25.202 Section 101-25.202 Public Contracts and Property... PROCUREMENT 25-GENERAL 25.2-Interagency Purchase Assignments § 101-25.202 Factors to be used to determine...

  11. Parasitism can be a confounding factor in assessing the response of zebra mussels to water contamination

    Minguez, Laëtitia; Buronfosse, Thierry; Beisel, Jean-Nicolas; Giambérini, Laure

    2012-01-01

    Biological responses measured in aquatic organisms to monitor environmental pollution could be also affected by different biotic and abiotic factors. Among these environmental factors, parasitism has often been neglected even if infection by parasites is very frequent. In the present field investigation, the parasite infra-communities and zebra mussel biological responses were studied up- and downstream a waste water treatment plant in northeast France. In both sites, mussels were infected by ciliates and/or intracellular bacteria, but prevalence rates and infection intensities were different according to the habitat. Concerning the biological responses differences were observed related to the site quality and the infection status. Parasitism affects both systems but seemed to depend mainly on environmental conditions. The influence of parasites is not constant, but remains important to consider it as a potential confounding factor in ecotoxicological studies. This study also emphasizes the interesting use of integrative indexes to synthesize data set. Highlights: ► Study of potential bias associated with the use of infected zebra mussels in ecotoxicological studies. ► Presence of infected mussels on banks and channels, up- and downstream a waste water treatment plant. ► Parasitism influence on biological responses dependent of mussel population history. ► Integrative index, an interesting tool to synthesize the set of biological data. - Parasitism influence on the host physiology would be strongly dependent on environmental conditions but remains a potential confounding factor in ecotoxicological studies.

  12. Risk factors of virologic failure and slow response to art among HIV ...

    Risk factors of virologic failure and slow response to art among HIV-infected children and adolescents in Nairobi. J. M. Kabogo, S. Gupta, A. K. Maina, M. Ochwoto, R. W. Omange, R. N. Musoke, R. W. Lihana, E. Muniu, F. W. Wamunyokoli, B. Liang, E. M. Songok ...

  13. Using the Bayes Factors to Evaluate Person Fit in the Item Response Theory

    Pan, Tianshu; Yin, Yue

    2017-01-01

    In this article, we propose using the Bayes factors (BF) to evaluate person fit in item response theory models under the framework of Bayesian evaluation of an informative diagnostic hypothesis. We first discuss the theoretical foundation for this application and how to analyze person fit using BF. To demonstrate the feasibility of this approach,…

  14. Linear Ordinary Differential Equations with Constant Coefficients. Revisiting the Impulsive Response Method Using Factorization

    Camporesi, Roberto

    2011-01-01

    We present an approach to the impulsive response method for solving linear constant-coefficient ordinary differential equations based on the factorization of the differential operator. The approach is elementary, we only assume a basic knowledge of calculus and linear algebra. In particular, we avoid the use of distribution theory, as well as of…

  15. General biological character of mammal adaptive potential in the response to diverse extreme environmental factors

    Graevskaya, B.M.; Zolotareva, N.N.

    1986-01-01

    Method for evaluating individual response and its prediction to extreme effect was developed. Experiments with different mammal types show that ranking (dominancy or subordination) are tightly related to radiosensitivity. It is confirmed that organism sensitivity, independen of effect factors, is determined with homeostasis capacity characterizing mammal genotype. Variation limits of ogranism mobilization possibilities depending on species differences were determined as well

  16. Epigenetic and genetic factors in the cellular response to radiations and DNA-damaging chemicals

    Williams, J.R.; D'Arpa, P.

    1981-01-01

    DNA-damaging agents are widely used as therapeutic tools for a variety of disease states. Many such agents are considered to produce detrimental side effects. Thus, it is important to evaluate both therapeutic efficacy and potential risk. DNA-damaging agents can be so evaluated by comparison to agents whose therapeutic benefit and potential hazards are better known. We propose a framework for such comparison, demonstrating that a simple transformation of cytotoxicity-dose response patterns permits a facile comparison of variation between cells exposed to a single DNA-damaging agent or to different cytotoxic agents. Further, by transforming data from experiments which compare responses of 2 cell populations to an effects ratio, different patterns for the changes in cytotoxicity produced by epigenetic and genetic factors were compared. Using these transformations, we found that there is a wide variation (a factor of 4) between laboratories for a single agent (UVC) and only a slightly larger variation (factor of 6) between normal cell response for different types of DNA-damaging agents (x-ray, UVC, alkylating agents, crosslinking agents). Epigenetic factors such as repair and recovery appear to be a factor only at higher dose levels. Comparison in the cytotoxic effect of a spectrum of DNA-damaging agents in xeroderma pigmentosum, ataxia telangiectasia, and Fanconi's anemia cells indicates significantly different patterns, implying that the effect, and perhaps the nature, of these genetic conditions are quite different

  17. Factors Promoting Environmental Responsibility in European SMEs: The Effect on Performance

    Francisco J. Sáez-Martínez

    2016-09-01

    Full Text Available There is increasing social and political awareness of the importance of developing environmental responsibility at a corporate level. When focusing on issues of responsibility, large companies are frequently perceived to be more responsible for driving climate change and resource depletion. However, small and medium enterprises (SMEs contribute significantly to the use of resources such as material and energy and produce approximately 64% of the pollution in Europe. Drawing on evidence from “The Eurobarometer 381 Survey on SMEs, Resource Efficiency and Green Markets”, we analyze the environmental responsibility of European SMEs, studying their compliance with environmental legislation and how several factors drive environmental orientation among SMEs. Our sample consists of 3647 SMEs operating in 38 countries. Only around a fifth of the firms go beyond environmental regulations, showing the highest levels of environmental responsibility. We conduct OLS regressions to analyze the factors that affect a positive environmental attitude among European SMEs (internal drivers being more significant than external ones and then, to observe the positive effect of environmental responsibility and firm’s experience in offering green services/products on performance, although a conjoint effect was not found. Implications for practitioners, academics, and policy-makers are outlined.

  18. Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factorresponsiveness

    Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua; Warner-Blankenship, Matthew; Lyons, Karen M.; Varga, John

    2008-01-01

    Background: The matricellular protein connective tissue growth factor (CCN2) has been implicated in pathological fibrosis, but its physiologic role remains elusive. In vitro, transforming growth factor-β (TGF-β) induces CCN2 expression in mesenchymal cells. Because CCN2 can enhance profibrotic responses elicited by TGF-β, it has been proposed that CCN2 functions as an essential downstream signaling mediator for TGF-β. To explore this notion, we characterized TGF-β-induced activation of fibroblasts from CCN2-null (CCN2 -/- ) mouse embryos. Methods: The regulation of CCN2 expression was examined in vivo in a model of fibrosis induced by bleomycin. Cellular TGF-β signal transduction and regulation of collagen gene expression were examined in CCN2 -/- MEFs by immunohistochemistry, Northern, Western and RT-PCR analysis, immunocytochemistry and transient transfection assays. Results: Bleomycin-induced skin fibrosis in the mouse was associated with substantial CCN2 up-regulation in lesional fibroblasts. Whereas in vitro proliferation rate of CCN2 -/- MEFs was markedly reduced compared to wild type MEFs, TGF-β-induced activation of the Smad pathways, including Smad2 phosphorylation, Smad2/3 and Smad4 nuclear accumulation and Smad-dependent transcriptional responses, were unaffected by loss of CCN2. The stimulation of COL1A2 and fibronectin mRNA expression and promoter activity, and of corresponding protein levels, showed comparable time and dose-response in wild type and CCN2 -/- MEFs, whereas stimulation of alpha smooth muscle actin and myofibroblast transdifferentiation showed subtle impairment in MEFs lacking CCN2. Conclusion: Whereas endogenous CCN2 plays a role in regulation of proliferation and TGF-β-induced myofibroblast transdifferentiation, it appears to be dispensable for Smad-dependent stimulation of collagen and extracellular matrix synthesis in murine embryonic fibroblasts

  19. PSO-based optimization of PI regulator and VA loading of a SRF ...

    DR OKE

    minimum real power injection (Yashomani et al, 2007) of the MC-DVR has also been ... distribution system are carried out and results are presented. .... operating point, the average dc-link voltage} will also get perturbed by a small amount .... For above optimal Kp and Ki values step response characteristics. Rise time.

  20. [Identification of an auxin response factor-like protein cDNA from mango cotyledon section].

    Xiao, Jie-Ning; Huang, Xue-Lin; Huang, Xia; Li, Xiao-Ju

    2004-01-01

    Auxin-responsive elements (AuxRE) interact with a new class of plant-specific transcription factors, auxin response factors (ARFs). Some of ARFs have been shown to repress or activate expression of genes with an AuxRE promotor element. In Arabidopsis, ARFs play important roles in early embryo development and vascular strand formation (ARF5), floral patterning (ARF3) and photo- and gravitropic responses (ARF7). Two cut surfaces (distal and proximal) of mango (Mangifera indica L. var. Zi-Hua) cotyledon showed different patterns of adventitious root formation, with only the proximal cut surface, but not the distal one, could be induced to form the roots. Thus, the mango cotyledon is a good system for studying adventitious root formation. A cDNA fragment homologous to the Arabidopsis auxin response factor-like protein and relates to adventitious root formation from the cut sections were isolated using suppressive subtractive hybridization (SSH). Two cDNA clones, designated as MiARF1 (mango auxin response factor 1 gene, GenBank accession number AY255705) and MiARF2 (mango auxin response factor 2 gene, GenBank accession number is AY300808), were identified by 3'RACE. MiARF1, 3 272bp long, contains an open reading frame (ORF) of 2 523bp, 5'UTR of 285bp and 3'UTR of 464bp, MiARF2, 1 474bp long, contains an ORF of 981bp, 5' UTR of 285bp and 3'UTR of 208bp. The deduced MiARF1 and MiARF2 are homologues of auxin response factor (ARF) family of transcriptional regulators, and show high similarity to ARF of Arabidopsis in conserved domains. The motifs of MiARF1 EL-WHACAGPL in DBD (DNA binding domain) and GDDPW in IV domain are identical to that of ARF-like protein of Arabidopsis. MiARF2 is identical to MiARF1 in a large part of DBD, but lacks a carboxyl-terminal domain containing conserved motifs III and IV. Virtual Northern blot showed that the expression of MiARF2 was high in rooting tissue of cultured cotyledon sections but low in non-rooting tissue, and the MiARF1 was

  1. A systems biology perspective on the role of WRKY transcription factors in drought responses in plants.

    Tripathi, Prateek; Rabara, Roel C; Rushton, Paul J

    2014-02-01

    Drought is one of the major challenges affecting crop productivity and yield. However, water stress responses are notoriously multigenic and quantitative with strong environmental effects on phenotypes. It is also clear that water stress often does not occur alone under field conditions but rather in conjunction with other abiotic stresses such as high temperature and high light intensities. A multidisciplinary approach with successful integration of a whole range of -omics technologies will not only define the system, but also provide new gene targets for both transgenic approaches and marker-assisted selection. Transcription factors are major players in water stress signaling and some constitute major hubs in the signaling webs. The main transcription factors in this network include MYB, bHLH, bZIP, ERF, NAC, and WRKY transcription factors. The role of WRKY transcription factors in abiotic stress signaling networks is just becoming apparent and systems biology approaches are starting to define their places in the signaling network. Using systems biology approaches, there are now many transcriptomic analyses and promoter analyses that concern WRKY transcription factors. In addition, reports on nuclear proteomics have identified WRKY proteins that are up-regulated at the protein level by water stress. Interactomics has started to identify different classes of WRKY-interacting proteins. What are often lacking are connections between metabolomics, WRKY transcription factors, promoters, biosynthetic pathways, fluxes and downstream responses. As more levels of the system are characterized, a more detailed understanding of the roles of WRKY transcription factors in drought responses in crops will be obtained.

  2. Factors affecting the United Nations' response to natural disasters: what determines the allocation of the Central Emergency Response Fund?

    Robinson, Tyler D; Oliveira, Thiago M; Kayden, Stephanie

    2017-10-01

    Natural disasters can overwhelm the domestic response of a country, leaving it dependent on external humanitarian relief. The Central Emergency Response Fund (CERF) of the United Nations centralises humanitarian funding and thus allows for a rapid response. This study combined data to analyse the factors that affected the allocation of CERF funding to countries that suffered a natural disaster between 2007 and 2013. It generated descriptive statistics and information on relative risks, and performed regressions of CERF funding across countries. There were 4,346 disasters in total in 188 countries between 2007 and 2013. CERF provided USD 2.98 billion to 87 countries, comprising 3.3 per cent of their total humanitarian funding. CERF more frequently supplied aid to countries in North Africa and the Middle East, and to those that had suffered geophysical disasters. Appropriately, it funds vulnerable countries experiencing severe natural disasters, yet its funding may be affected by variables beyond severity and vulnerability. Further investigation is warranted, therefore. © 2017 The Author(s). Disasters © Overseas Development Institute, 2017.

  3. The functions of WHIRLY1 and REDOX-RESPONSIVE TRANSCRIPTION FACTOR 1 in cross tolerance responses in plants: a hypothesis.

    Foyer, Christine H; Karpinska, Barbara; Krupinska, Karin

    2014-04-19

    Chloroplasts are important sensors of environment change, fulfilling key roles in the regulation of plant growth and development in relation to environmental cues. Photosynthesis produces a repertoire of reductive and oxidative (redox) signals that provide information to the nucleus facilitating appropriate acclimation to a changing light environment. Redox signals are also recognized by the cellular innate immune system allowing activation of non-specific, stress-responsive pathways that underpin cross tolerance to biotic-abiotic stresses. While these pathways have been intensively studied in recent years, little is known about the different components that mediate chloroplast-to-nucleus signalling and facilitate cross tolerance phenomena. Here, we consider the properties of the WHIRLY family of proteins and the REDOX-RESPONSIVE TRANSCRIPTION FACTOR 1 (RRTF1) in relation to chloroplast redox signals that facilitate the synergistic co-activation of gene expression pathways and confer cross tolerance to abiotic and biotic stresses. We propose a new hypothesis for the role of WHIRLY1 as a redox sensor in chloroplast-to-nucleus retrograde signalling leading to cross tolerance, including acclimation and immunity responses. By virtue of its association with chloroplast nucleoids and with nuclear DNA, WHIRLY1 is an attractive candidate coordinator of the expression of photosynthetic genes in the nucleus and chloroplasts. We propose that the redox state of the photosynthetic electron transport chain triggers the movement of WHIRLY1 from the chloroplasts to the nucleus, and draw parallels with the regulation of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1).

  4. Factors involved in nurses' responses to burnout: a grounded theory study

    Nikravesh Mansoure

    2004-11-01

    Full Text Available Abstract Background Intense and long-standing problems in burn centers in Tehran have led nurses to burnout. This phenomenon has provoked serious responses and has put the nurses, patients and the organization under pressure. The challenge for managers and nurse executives is to understand the factors which would reduce or increase the nurses' responses to burnout and develop delivery systems that promote positive adaptation and facilitate quality care. This study, as a part of more extensive research, aims to explore and describe the nurses' perceptions of the factors affecting their responses to burnout. Methods Grounded theory was used as the method. Thirty- eight participants were recruited. Data were generated by unstructured interviews and 21 sessions of participant observations. Constant comparison was used for data analysis. Results Nurses' and patients' personal characteristics and social support influenced nurses' responses to burnout. Personal characteristics of the nurses and patients, especially when interacting, had a more powerful effect. They altered emotional, attitudinal, behavioral and organizational responses to burnout and determined the kind of caring behavior. Social support had a palliative effect and altered emotional responses and some aspects of attitudinal responses. Conclusions The powerful effect of positive personal characteristics and its sensitivity to long standing and intense organizational pressures suggests approaches to executing stress reduction programs and refreshing the nurses' morale by giving more importance to ethical aspects of caring. Moreover, regarding palliative effect of social support and its importance for the nurses' wellbeing, nurse executives are responsible for promoting a work environment that supports nurses and motivates them.

  5. Modeling silicon diode energy response factors for use in therapeutic photon beams.

    Eklund, Karin; Ahnesjö, Anders

    2009-10-21

    Silicon diodes have good spatial resolution, which makes them advantageous over ionization chambers for dosimetry in fields with high dose gradients. However, silicon diodes overrespond to low-energy photons, that are more abundant in scatter which increase with large fields and larger depths. We present a cavity-theory-based model for a general response function for silicon detectors at arbitrary positions within photon fields. The model uses photon and electron spectra calculated from fluence pencil kernels. The incident photons are treated according to their energy through a bipartition of the primary beam photon spectrum into low- and high-energy components. Primary electrons from the high-energy component are treated according to Spencer-Attix cavity theory. Low-energy primary photons together with all scattered photons are treated according to large cavity theory supplemented with an energy-dependent factor K(E) to compensate for energy variations in the electron equilibrium. The depth variation of the response for an unshielded silicon detector has been calculated for 5 x 5 cm(2), 10 x 10 cm(2) and 20 x 20 cm(2) fields in 6 and 15 MV beams and compared with measurements showing that our model calculates response factors with deviations less than 0.6%. An alternative method is also proposed, where we show that one can use a correlation with the scatter factor to determine the detector response of silicon diodes with an error of less than 3% in 6 MV and 15 MV photon beams.

  6. Modeling silicon diode energy response factors for use in therapeutic photon beams

    Eklund, Karin; Ahnesjoe, Anders

    2009-01-01

    Silicon diodes have good spatial resolution, which makes them advantageous over ionization chambers for dosimetry in fields with high dose gradients. However, silicon diodes overrespond to low-energy photons, that are more abundant in scatter which increase with large fields and larger depths. We present a cavity-theory-based model for a general response function for silicon detectors at arbitrary positions within photon fields. The model uses photon and electron spectra calculated from fluence pencil kernels. The incident photons are treated according to their energy through a bipartition of the primary beam photon spectrum into low- and high-energy components. Primary electrons from the high-energy component are treated according to Spencer-Attix cavity theory. Low-energy primary photons together with all scattered photons are treated according to large cavity theory supplemented with an energy-dependent factor K(E) to compensate for energy variations in the electron equilibrium. The depth variation of the response for an unshielded silicon detector has been calculated for 5 x 5 cm 2 , 10 x 10 cm 2 and 20 x 20 cm 2 fields in 6 and 15 MV beams and compared with measurements showing that our model calculates response factors with deviations less than 0.6%. An alternative method is also proposed, where we show that one can use a correlation with the scatter factor to determine the detector response of silicon diodes with an error of less than 3% in 6 MV and 15 MV photon beams.

  7. Evaluating response modification factor (R for some types of steel structure

    Doralba Valencia Restrepo

    2008-01-01

    Full Text Available Response modification factor (R, tabulated in the Colombian Design Code as NSR-98, is used in this paper for eva-luating internal member forces produced by design earthquake action on steel structures and the inconsistencies pre-sent when designing structures when 1% drift limits must be complied with. The article presents the design of 45 frames corresponding to the seismic resistance system of 5 buildings: 15 special moment frames (SMF, 15 special concentrically-braced frames (CBF and 15 eccentrically-braced frames (EBF. External loads and their combination were used in estimating internal loads and rigidity demands (1% drift were evaluated in line with NSR-98 requi-rements. Member strength requirements were evaluated by using the AISC-2005 seismic provisions for steel structu-red buildings. Modal pushover analysis was used for evaluating the response modification factor for the 45 given frames at different structural performance levels. It was found that this factor was not constant for any of the three structural systems (SMF, CBF and EBF suggested by NSR-98 and that the values of the response modification factor found in the present investigation were smaller than those tabulated in this design code governing everyday structural design. This would lead to significant errors being made in evaluating design forces, not only in the structures but in the support elements (base-plates, foundations, shear walls and any structures attached to buildings constructed in line with the seismic resistance system.

  8. Religious beliefs, coping skills and responsibility to family as factors protecting against deliberate self-harm

    K Kannan

    2010-12-01

    Full Text Available Background. Deliberate self-harm (DSH ranges from behaviours aiming to communicate distress or relieve tension, but where suicide is not intended, to actual suicide. Not all individuals are prone to DSH, which suggests that there are factors that protect against it. Identifying these could play an important role in the management and prevention of DSH. Objectives. This study examined whether religious beliefs, coping skills and responsibility to family serve as factors protecting against DSH in Kota Kinabalu, Sabah, Malaysia. Method. A cross-sectional comparative study assessed DSH patients consecutively admitted or directly referred to Queen Elizabeth General Hospital and Hospital Mesra Bukit Padang during the period December 2006 - April 2007. DSH patients (N=42 were matched with controls (N=42 for gender, age, religion, race, occupation and marital status. The DSH and control groups were compared using psychosocial tests that assess coping skills, religious beliefs and responsibility to family. Results. There were significant differences in religious beliefs (p=0.01 and responsibility to family (p=0.03 between the DSH patients and the control group. There were also significant differences in coping skills, DSH patients tending to use emotion-orientated coping (p=0.01 as opposed to task- and avoidance-orientated coping. Conclusion. Consistent with international studies, coping skills (i.e. task-orientated skills, religious beliefs and responsibility to family were more evident in patients who did not attempt DSH than in those who did. These findings imply that treating DSH should not start only at the point of contact. Protective factors such as religious beliefs, responsibility to family and coping strategies can be inculcated from a very young age. However, caution is required in generalising the results owing to limitations of the study. Further extensive research on religious and psychotherapeutic interventions and prospective studies on

  9. Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients

    Zhiming Lin

    2015-01-01

    Full Text Available Objectives. To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. Methods. Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. Results. Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P=0.005, CRP (AUC = 0.75; P=0.017, and ASDAS (AUC = 0.778, P=0.007 significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P=0.040 significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ2=6.87, P=0.009, and wald χ2=5.171, P=0.023. Conclusions. Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients.

  10. Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage

    Logan, Ian R.; McNeill, Hesta V.; Cook, Susan; Lu, Xiaohong; Meek, David W.; Fuller-Pace, Frances V.; Lunec, John; Robson, Craig N.

    2009-01-01

    Here we define an important role for heat shock factor 1 (HSF1) in the cellular response to genotoxic agents. We demonstrate for the first time that HSF1 can complex with nuclear p53 and that both proteins are co-operatively recruited to p53-responsive genes such as p21. Analysis of natural and synthetic cis elements demonstrates that HSF1 can enhance p53-mediated transcription, whilst depletion of HSF1 reduces the expression of p53-responsive transcripts. We find that HSF1 is required for optimal p21 expression and p53-mediated cell-cycle arrest in response to genotoxins while loss of HSF1 attenuates apoptosis in response to these agents. To explain these novel properties of HSF1 we show that HSF1 can complex with DNA damage kinases ATR and Chk1 to effect p53 phosphorylation in response to DNA damage. Our data reveal HSF1 as a key transcriptional regulator in response to genotoxic compounds widely used in the clinical setting, and suggest that HSF1 will contribute to the efficacy of these agents. PMID:19295133

  11. Factors affecting responses of infants with respiratory distress syndrome to exogenous surfactant therapy.

    Ho, N K

    1993-02-01

    Approximately 20% to 30% of infants with respiratory distress syndrome (RDS) do not respond to surfactant replacement therapy. Unfortunately there is no uniform definition of 'response' or 'non-response' to surfactant therapy. Response was based on improvement in a/A PO2 and/or mean airway pressure (MAP) by some and on improvement in FIO2 and/or MAP by others. Even the point of time at which evaluation of response was done is different in various reports. There is an urgent need to adopt an uniform definition. Most premature babies are surfactant deficient which is the aetiological factor of RDS. Generally good antenatal care and perinatal management are essential in avoidance of premature birth. Babies with lung hypoplasia and who are extremely premature (less than 24 weeks of gestation) do not respond well to exogenous surfactant replacement because of structural immaturity. Prompt management of asphyxiated birth and shock are necessary as there may be negative response to surfactant replacement. Foetal exposure to glucocorticoids improves responsiveness to postnatal administration of surfactant. Antenatal steroid therapy has become an important part of management of RDS with surfactant replacement. The premature lungs with high alveolar permeability tend to develop pulmonary oedema. With the presence of plasma-derived surfactant inhibitors, the response to exogenous surfactant may be affected. These inhibitors may also be released following ventilator barotrauma. The standard of neonatal intensive care such as ventilatory techniques has an important bearing on the outcome of the RDS babies.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. The ethylene response factor AtERF4 negatively regulates the iron deficiency response in Arabidopsis thaliana.

    Wei Liu

    Full Text Available Iron (Fe deficiency is one of many conditions that can seriously damage crops. Low levels of photosynthesis can lead to the degradation of chlorophyll content and impaired respiration in affected plants, which together cause poor growth and reduce quality. Although ethylene plays an important role in responses to Fe deficiency, a limited number of studies have been carried out on ethylene response factor (ERFs as components of plant regulation mechanisms. Thus, this study aimed to investigate the role of AtERF4 in plant responses to Fe deficiency. Results collected when Arabidopsis thaliana was grown under Fe deficient conditions as well as in the presence of 1-aminocyclopropane-1-carboxylic acid (ACC revealed that leaf chlorosis did not occur over short timescales and that chloroplast structural integrity was retained. At the same time, expression of the chlorophyll degradation-related genes AtPAO and AtCLH1 was inhibited and net H+ root flux was amplified. Our results show that chlorophyll content was enhanced in the mutant erf4, while expression of the chlorophyll degradation gene AtCLH1 was reduced. Ferric reductase activity in roots was also significantly higher in the mutant than in wild type plants, while erf4 caused high levels of expression of the genes AtIRT1 and AtHA2 under Fe deficient conditions. We also utilized yeast one-hybrid technology in this study to determine that AtERF4 binds directly to the AtCLH1 and AtITR1 promoter. Observations show that transient over-expression of AtERF4 resulted in rapid chlorophyll degradation in the leaves of Nicotiana tabacum and the up-regulation of gene AtCLH1 expression. In summary, AtERF4 plays an important role as a negative regulator of Fe deficiency responses, we hypothesize that AtERF4 may exert a balancing effect on plants subject to nutrition stress.

  13. Hysteresis responses of evapotranspiration to meteorological factors at a diel timescale: patterns and causes.

    Han Zheng

    Full Text Available Evapotranspiration (ET is an important component of the water cycle in terrestrial ecosystems. Understanding the ways in which ET changes with meteorological factors is central to a better understanding of ecological and hydrological processes. In this study, we used eddy covariance measurements of ET from a typical alpine shrubland meadow ecosystem in China to investigate the hysteresis response of ET to environmental variables including air temperature (Ta, vapor pressure deficit (VPD and net radiation (Rn at a diel timescale. Meanwhile, the simulated ET by Priestly-Taylor equation was used to interpret the measured ET under well-watered conditions. Pronounced hysteresis was observed in both Ta and VPD response curves of ET. At a similar Ta and VPD, ET was always significantly depressed in the afternoon compared with the morning. But the hysteresis response of ET to Rn was not evident. Similar hysteresis patterns were also observed in the Ta/VPD response curves of simulated ET. The magnitudes of the measured and simulated hysteresis loops showed similar seasonal variation, with relatively smaller values occurring from May to September, which agreed well with the lifetime of plants and the period of rainy season at this site. About 62% and 23% of changes in the strength of measured ET-Ta and ET-VPD loops could be explained by the changes in the strength of simulated loops, respectively. Thus, the time lag between Rn and Ta/VPD is the most important factor generating and modulating the ET-Ta/VPD hysteresis, but plants and water status also contribute to the hysteresis response of ET. Our research confirmed the different hysteresis in the responses of ET to meteorological factors and proved the vital role of Rn in driving the diel course of ET.

  14. Baseline factors that influence ASAS 20 response in patients with ankylosing spondylitis treated with etanercept.

    Davis, John C; Van der Heijde, Désirée M F M; Dougados, Maxime; Braun, Jurgen; Cush, John J; Clegg, Daniel O; Inman, Robert D; de Vries, Todd; Tsuji, Wayne H

    2005-09-01

    To examine the baseline demographic and disease characteristics that might influence improvement as measured by the Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) in patients with ankylosing spondylitis (AS). A multicenter Phase 3 study was performed to compare the safety and efficacy of 24 weeks of etanercept 25 mg subcutaneous injection twice weekly (n = 138) and placebo (n = 139) in patients with AS. The ASAS 20 was measured at multiple time points. Using a significance level of 0.05, a repeated measures logistic regression model was used to determine which baseline factors influenced response in the etanercept-treated patients during the 24-week double blind portion of the trial. The following baseline factors were used in the model: demographic and disease severity variables, concomitant medications, extra-articular manifestations, and HLA-B27 status. The predictive capability of the model was then tested on the patients receiving placebo after they had received open-label etanercept treatment. Baseline factors that were significant predictors of an ASAS 20 response in etanercept-treated patients were C-reactive protein (CRP), back pain score, and Bath Ankylosing Spondylitis Functional Index (BASFI) score. Although clinical response to etanercept was seen at all levels of baseline disease activity, responses were consistently more likely with higher CRP levels or back pain scores and less likely with increased BASFI scores at baseline. Higher CRP values and back pain scores and lower BASFI scores at baseline were significant predictors of a higher ASAS 20 response in patients with AS receiving etanercept but predictive value was of insufficient magnitude to determine treatment in individual patients.

  15. Modifying chemotherapy response by targeted inhibition of eukaryotic initiation factor 4A

    Cencic, R; Robert, F; Galicia-Vázquez, G; Malina, A; Ravindar, K; Somaiah, R; Pierre, P; Tanaka, J; Deslongchamps, P; Pelletier, J

    2013-01-01

    Translation is regulated predominantly at the initiation phase by several signal transduction pathways that are often usurped in human cancers, including the PI3K/Akt/mTOR axis. mTOR exerts unique administration over translation by regulating assembly of eukaryotic initiation factor (eIF) 4F, a heterotrimeric complex responsible for recruiting 40S ribosomes (and associated factors) to mRNA 5′ cap structures. Hence, there is much interest in targeted therapies that block eIF4F activity to assess the consequences on tumor cell growth and chemotherapy response. We report here that hippuristanol (Hipp), a translation initiation inhibitor that selectively inhibits the eIF4F RNA helicase subunit, eIF4A, resensitizes Eμ-Myc lymphomas to DNA damaging agents, including those that overexpress eIF4E—a modifier of rapamycin responsiveness. As Mcl-1 levels are significantly affected by Hipp, combining its use with the Bcl-2 family inhibitor, ABT-737, leads to a potent synergistic response in triggering cell death in mouse and human lymphoma and leukemia cells. Suppression of eIF4AI using RNA interference also synergized with ABT-737 in murine lymphomas, highlighting eIF4AI as a therapeutic target for modulating tumor cell response to chemotherapy

  16. Study of Nb-Cu 1.3 GHz SRF cavity resonators for future particle accelerators

    Amelin, Kirill

    2017-01-01

    Niobium-coated superconducting radio-frequency cavities have a number of advantages over cavities made from bulk niobium. Cavities coated with high-power impulse magnetron sputtering are tested at CERN in order to optimize the coating and study the Q-slope that limits the performance. To accurately measure the quality factor as a function of accelerating field, it is important to have good matching between an input antenna and a cavity impedance. To improve the matching, a variable coupler that changes the length of the antenna can be used. We have shown that the Q-factor of the input antenna can be changed between $10^7-10^{11}$ by moving the antenna, which should allow to achieve critical coupling with a cavity. This technology could be used in future measurements, so that reflections are always minimized.

  17. Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia

    de Pont, A. C. J. M.; Moons, A. H. M.; de Jonge, E.; Meijers, J. C. M.; Vlasuk, G. P.; Rote, W. E.; Büller, H. R.; van der Poll, T.; Levi, M. [=Marcel M.

    2004-01-01

    The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa. mechanistically distinct from tissue factor

  18. Obstructive Jaundice in Hepatocellular Carcinoma: Response after Percutaneous Transhepatic Biliary Drainage and Prognostic Factors

    Lee, Joon Woo; Han, Joon Koo; Kim, Tae Kyoung; Choi, Byung Ihn; Park, Seong Ho; Ko, Young Hwan; Yoon, Chang Jin; Yeon, Kyung-Mo

    2002-01-01

    Purpose: To evaluate the therapeutic effect of percutaneous transhepatic biliary drainage (PTBD) in patients with obstructive jaundice caused by biliary involvement of hepatocellular carcinomas (HCC) and to determine the prognostic factors. Methods: We retrospectively analyzed the data of 22 consecutive patients (M:F = 20:2, mean age 52.8 years).Inclusion criteria were the patient having obstructive jaundice caused by HCC that invaded the bile ducts and having at least 4 weeks of follow-up data after the PTBD. We defined 'good response' and 'poor response' as whether the level of total bilirubin decreased more than 50% in 4 weeks or not. Total bilirubin level (T-bil),Child-Pugh score and the location of biliary obstruction for the two groups were compared. In addition, the interval between clinical onset of jaundice and PTBD, the degree of parenchymal atrophy and the size of the primary tumor were compared. Results: Of the 22 patients, 13 (59.1%) showed good response. T-bil was significantly lower in the good response group than in the poor (14.2 ± 6 mg/dlvs 25.9 ± 13.8 mg/dl, p = .017). In the five patients with T-bil 20 mg/dl, only three (33%)showed good response. Although statistically not significant, patients with Child score <10 showed better results [good response rate of 66.7% (12/18)] than patients with Child score ?10 [good response rate of 25% (1/4)]. Involvement of secondary confluence of the bile duct also served as a poor prognostic factor (p =0.235). The interval between clinical onset of jaundice and PTBD, the presence of parenchymal atrophy and the size of the tumor did not show significant effect. Conclusion: Early and effective biliary drainage might be necessary in this group of patients with limited hepatic function

  19. PLZF regulates fibroblast growth factor responsiveness and maintenance of neural progenitors.

    Gaber, Zachary B; Butler, Samantha J; Novitch, Bennett G

    2013-10-01

    Distinct classes of neurons and glial cells in the developing spinal cord arise at specific times and in specific quantities from spatially discrete neural progenitor domains. Thus, adjacent domains can exhibit marked differences in their proliferative potential and timing of differentiation. However, remarkably little is known about the mechanisms that account for this regional control. Here, we show that the transcription factor Promyelocytic Leukemia Zinc Finger (PLZF) plays a critical role shaping patterns of neuronal differentiation by gating the expression of Fibroblast Growth Factor (FGF) Receptor 3 and responsiveness of progenitors to FGFs. PLZF elevation increases FGFR3 expression and STAT3 pathway activity, suppresses neurogenesis, and biases progenitors towards glial cell production. In contrast, PLZF loss reduces FGFR3 levels, leading to premature neuronal differentiation. Together, these findings reveal a novel transcriptional strategy for spatially tuning the responsiveness of distinct neural progenitor groups to broadly distributed mitogenic signals in the embryonic environment.

  20. Roles of Arabidopsis WRKY3 and WRKY4 Transcription Factors in Plant Responses to Pathogens

    Fan Baofang

    2008-06-01

    Full Text Available Abstract Background Plant WRKY DNA-binding transcription factors are involved in plant responses to biotic and abiotic responses. It has been previously shown that Arabidopsis WRKY3 and WRKY4, which encode two structurally similar WRKY transcription factors, are induced by pathogen infection and salicylic acid (SA. However, the role of the two WRKY transcription factors in plant disease resistance has not been directly analyzed. Results Both WRKY3 and WRKY4 are nuclear-localized and specifically recognize the TTGACC W-box sequences in vitro. Expression of WRKY3 and WRKY4 was induced rapidly by stress conditions generated by liquid infiltration or spraying. Stress-induced expression of WRKY4 was further elevated by pathogen infection and SA treatment. To determine directly their role in plant disease resistance, we have isolated T-DNA insertion mutants and generated transgenic overexpression lines for WRKY3 and WRKY4. Both the loss-of-function mutants and transgenic overexpression lines were examined for responses to the biotrophic bacterial pathogen Pseudomonas syringae and the necrotrophic fungal pathogen Botrytis cinerea. The wrky3 and wrky4 single and double mutants exhibited more severe disease symptoms and support higher fungal growth than wild-type plants after Botrytis infection. Although disruption of WRKY3 and WRKY4 did not have a major effect on plant response to P. syringae, overexpression of WRKY4 greatly enhanced plant susceptibility to the bacterial pathogen and suppressed pathogen-induced PR1 gene expression. Conclusion The nuclear localization and sequence-specific DNA-binding activity support that WRKY3 and WRKY4 function as transcription factors. Functional analysis based on T-DNA insertion mutants and transgenic overexpression lines indicates that WRKY3 and WRKY4 have a positive role in plant resistance to necrotrophic pathogens and WRKY4 has a negative effect on plant resistance to biotrophic pathogens.

  1. Behavioral factors predicting response to employment-based reinforcement of cocaine abstinence in methadone patients

    Holtyn, August F.; Washington, Wendy Donlin; Knealing, Todd W.; Wong, Conrad J.; Kolodner, Ken; Silverman, Kenneth

    2016-01-01

    We sought to identify behavioral factors associated with response to an employment-based intervention, in which participants had to provide drug-free urine samples to gain access to paid employment. The present secondary analysis included data from a randomized clinical trial. The trial evaluated whether employment-based reinforcement could decrease cocaine use in community methadone patients. Participants (N=56) in the trial worked in a model workplace for 4 hr every weekday and earned about...

  2. Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor

    Jeong, Wooyoung; Bazer, Fuller W.; Song, Gwonhwa; Kim, Jinyoung

    2016-01-01

    The low oxygen environment in the uterine environment requires pre-implantation embryos to adapt to oxygen deficiency. Hypoxia-inducible factor (HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1α were explored using porcine trophectoderm (pTr) cells. The results indicated that expression of HIF-1α and HIF-1β mRNAs was not affected by low concentrations of oxygen; however, hypoxic conditions markedly increased the abundance of HIF-1α protein, especially in nuclei of pTr cells. Even under normoxic conditions, the abundance of HIF-1α protein increased in response to EGF. This EGF-mediated increase in HIF-1α protein was blocked through inhibition of translation by cycloheximide. The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1α protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Both hypoxia and EGF induced proliferation of pTr cells. This ability of EGF to stimulate proliferation of pTr cells was suppressed by EGFR siRNA, but not HIF-1α siRNA, but a significant decrease in EGF-induced HIF-1α protein occurred when pTr cells were transfected with HIF-1α siRNA. The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal–conceptus interface can increase the abundance of HIF-1α protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. - Highlights: • HIF-1α expression is up-regulated in pTr cells under low oxygen concentrations. • EGF induces HIF-1α accumulation in pTr cells. • EGF-induced HIF-1α accumulation is blocked by de

  3. Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor

    Jeong, Wooyoung [Department of Animal Resources Science, Dankook University, Cheonan (Korea, Republic of); Bazer, Fuller W. [Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A& M University, College Station, TX (United States); Song, Gwonhwa, E-mail: ghsong@korea.ac.kr [Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Kim, Jinyoung, E-mail: jinyoungkim@dankook.ac.kr [Department of Animal Resources Science, Dankook University, Cheonan (Korea, Republic of)

    2016-01-08

    The low oxygen environment in the uterine environment requires pre-implantation embryos to adapt to oxygen deficiency. Hypoxia-inducible factor (HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1α were explored using porcine trophectoderm (pTr) cells. The results indicated that expression of HIF-1α and HIF-1β mRNAs was not affected by low concentrations of oxygen; however, hypoxic conditions markedly increased the abundance of HIF-1α protein, especially in nuclei of pTr cells. Even under normoxic conditions, the abundance of HIF-1α protein increased in response to EGF. This EGF-mediated increase in HIF-1α protein was blocked through inhibition of translation by cycloheximide. The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1α protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Both hypoxia and EGF induced proliferation of pTr cells. This ability of EGF to stimulate proliferation of pTr cells was suppressed by EGFR siRNA, but not HIF-1α siRNA, but a significant decrease in EGF-induced HIF-1α protein occurred when pTr cells were transfected with HIF-1α siRNA. The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal–conceptus interface can increase the abundance of HIF-1α protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. - Highlights: • HIF-1α expression is up-regulated in pTr cells under low oxygen concentrations. • EGF induces HIF-1α accumulation in pTr cells. • EGF-induced HIF-1α accumulation is blocked by de

  4. Genome wide analysis of stress responsive WRKY transcription factors in Arabidopsis thaliana

    Shaiq Sultan

    2016-04-01

    Full Text Available WRKY transcription factors are a class of DNA-binding proteins that bind with a specific sequence C/TTGACT/C known as W-Box found in promoters of genes which are regulated by these WRKYs. From previous studies, 43 different stress responsive WRKY transcription factors in Arabidopsis thaliana, identified and then categorized in three groups viz., abiotic, biotic and both of these stresses. A comprehensive genome wide analysis including chromosomal localization, gene structure analysis, multiple sequence alignment, phylogenetic analysis and promoter analysis of these WRKY genes was carried out in this study to determine the functional homology in Arabidopsis. This analysis led to the classification of these WRKY family members into 3 major groups and subgroups and showed evolutionary relationship among these groups on the base of their functional WRKY domain, chromosomal localization and intron/exon structure. The proposed groups of these stress responsive WRKY genes and annotation based on their position on chromosomes can also be explored to determine their functional homology in other plant species in relation to different stresses. The result of the present study provides indispensable genomic information for the stress responsive WRKY transcription factors in Arabidopsis and will pave the way to explain the precise role of various AtWRKYs in plant growth and development under stressed conditions.

  5. Chemical risk factors responsible for the formation of wedge-shaped lesions

    Perić Dejan

    2015-01-01

    Full Text Available Introduction: Non-carious tooth substances loss pose a major health problem of a modern man. The literature often collectively describes all non-carious lesions and is therefore difficult to compare results obtained by different authors. Chemical factors are one of the predisposing factors responsible for the formation of wedge-shaped erosions. Aim: Examination of chemical risk factors as one of the predisposing causes responsible for the formation of wedge-shaped lesions. Method: We examined 62 patients with wedge-shaped erosions (mean age 45.52 ± 12.03 years, 58.1% of men and 60 patients without erosions in the control group (mean age 34.40 ± 9.28 years, 60% men . The entire examination was completed by using a questionnaire at the Dental Clinic of the University of Pristina - Kosovska Mitrovica. salivary pH was measured by the pH meter. Results: The results show that the wedge-shaped lesions often occur equally in both men and women. Considerably often it might appear in older people but can also occur in teenagers. Patients with wedge-shaped erosion have increased acidity of saliva, a heightened sense of acid in the mouth and consume a lot more carbonated drinks compared to patients without erosions. Conclusion: Wedge-shaped lesions are more common in people older than 40 years. Taking into account the results obtained in this study it can be concluded that the chemical risk factors truly fall within the predisposing factors that may be responsible for the creation of wedge-shaped erosions.

  6. Structure, function and networks of transcription factors involved in abiotic stress responses

    Lindemose, Søren; O'Shea, Charlotte; Jensen, Michael Krogh

    2013-01-01

    Transcription factors (TFs) are master regulators of abiotic stress responses in plants. This review focuses on TFs from seven major TF families, known to play functional roles in response to abiotic stresses, including drought, high salinity, high osmolarity, temperature extremes...... and the phytohormone ABA. Although ectopic expression of several TFs has improved abiotic stress tolerance in plants, fine-tuning of TF expression and protein levels remains a challenge to avoid crop yield loss. To further our understanding of TFs in abiotic stress responses, emerging gene regulatory networks based...... on TFs and their direct targets genes are presented. These revealed components shared between ABA-dependent and independent signaling as well as abiotic and biotic stress signaling. Protein structure analysis suggested that TFs hubs of large interactomes have extended regions with protein intrinsic...

  7. Immune responses to influenza virus and its correlation to age and inherited factors

    Azadeh Bahadoran

    2016-11-01

    Full Text Available Influenza viruses belong to the family Orthomyxoviridae of enveloped viruses and are an important cause of respiratory infections worldwide. The influenza virus is able to infect a wide variety species as diverse as poultry, marine, pigs, horses and humans. Upon infection with influenza virus the innate immunity plays a critical role in efficient and rapid control of viral infections as well as in adaptive immunity initiation. The humoral immune system produces antibodies against different influenza antigens, of which the HA-specific antibody is the most important for neutralization of the virus and thus prevention of illness. Cell mediated immunity including CD4+ helper T cells and CD8+ cytotoxic T cells are the other arms of adaptive immunity induced upon influenza virus infection. The complex inherited factors and age related changes are associated with the host immune responses. Here, we review the different components of immune responses against influenza virus. Additionally, the correlation of the immune response to age and inherited factors has been discussed. These determinations lead to a better understanding of the limitations of immune responses for developing improved vaccines to control influenza virus infection.

  8. Factors influencing response to ingenol mebutate therapy for actinic keratosis of face and scalp

    Skroza, Nevena; Proietti, Ilaria; Bernardini, Nicoletta; Balduzzi, Veronica; Mambrin, Alessandra; Marchesiello, Anna; Tolino, Ersilia; Zuber, Sara; La Torre, Giuseppe; Potenza, Concetta

    2017-01-01

    AIM To determine factors independently influencing response to ingenol mebutate therapy and assess efficacy on clinical setting of non-hypertrophic non-hyperkeratotic actinic keratosis (AK). METHODS Consecutive patients affected by non-hypertrophic non-hyperkeratotic AKs of the face or scalp were enrolled to receive ingenol mebutate 0.015% gel on a selected skin area of 25 cm2 for 3 consecutive days. Local skin reactions were calculated at each follow up visit using a validated composite score. Efficacy was evaluated by the comparison of clinical and dermoscopic pictures before the treatment and at day 57, and classified as complete, partial and poor response. RESULTS A number of 130 patients were enrolled, of which 101 (77.7%) were treated on the face, while 29 (22.3%) on the scalp. The great majority of our study population (n = 119, 91.5%) reached at least a 75% clearance of AKs and, in particular, 58 patients (44.6%) achieved a complete response while 61 (46.9%) a partial one. Logistic backward multivariate analysis showed that facial localization, level of local skin reaction (LSR) at day 2, the highest LSR values and level of crusts at day 8 were factors independently associated with the achievement of a complete response. CONCLUSION Ingenol mebutate 0.015% gel, when properly applied, is more effective on the face than on the scalp and efficacy is directly associated to LSR score. PMID:29067277

  9. Annealing to Mitigate Pitting in Electropolished Niobium Coupons and SRF Cavities

    Cooley, L.D.; Hahn, E.; Hicks, D.; Romanenko, A.; Schuessler, R.; Thompson, C.; /Fermilab

    2011-06-08

    Ongoing studies at Fermilab investigate whether dislocations and other factors instigate pitting during cavity electropolishing (EP), despite careful processing controls and the inherent leveling mechanism of EP itself. Here, cold-worked niobium coupons, which exhibited increased tendencies for pitting in our past study, were annealed in a high vacuum furnace and subsequently processed by EP. Laser confocal scanning microscopy and special defect counting algorithms were used to assess the population of pits formed. Hardness measurements indicated that annealing for 2 hours at 800 C produced recovery, whereas annealing for 12 hours at 600 C did not, as is consistent with known changes for cavities annealed in a similar way. The 800 C anneal was effective in some cases but not others, and we discuss reasons why tendencies for pitting remain. We discuss implications for cavities and continued work to understand pitting.

  10. Energy response of detectors to alpha/beta particles and compatibility of the equivalent factors

    Lin Bingxing; Li Guangxian; Lin Lixiong

    2011-01-01

    By measuring detect efficiency and equivalent factors of alpha/beta radiation with different energies on three types of detectors, this paper compares compatibility of their equivalent factors and discusses applicability of detectors to measuring total alpha/beta radiation. The result shows the relationship between efficiency of alpha/beta radiation and their energies on 3 types of detectors, such as scintillation and proportional and semiconductor counters, are overall identical. Alpha count efficiency display exponential relation with alpha-particle energy. While beta count efficiency display logarithm relation with beta-particle energy, but the curves appears deflection at low energy. Comparison test of energy response also shows that alpha and beta equivalent factors of scintillation and proportional counters have a good compatibility, and alpha equivalent factors of the semiconductor counters are in good agreement with those of the above two types of counters, but beta equivalent factors have obvious difference, or equivalent factors of low energy beta-particle are lower than those of other detectors. So, the semiconductor counter can not be used for measuring total radioactivity or for the measurements for the purpose of food safety. (authors)

  11. Influential Factors and Strategy of Sustainable Product Development under Corporate Social Responsibility in Taiwan

    Jui-Che Tu

    2013-01-01

    Full Text Available This study aimed to adopt the perspective of corporate social responsibility (CSR to explore the intention of sustainable product development in Taiwan, as well as leading to the creation of influential factors that affect corporate sustainable product development intention. In this research, the induction analysis was conducted to understand the implementation of sustainable product development, and this was supplemented with questionnaire surveys and in-depth interviews to evaluate developmental intention. In addition, principal component analysis was used for factor analysis and content analysis in the 6 W expression method, leading to the creation of the influential factors. The research results have demonstrated that the factors affecting the intention of corporate sustainable product development include having a sustainable design and a development purpose, a corporate development purpose, sustainable development concepts, a sustainable design value, a sustainability concept, and a manufacturing process quality. For sustainable product development, corporate social responsibility needs to be most concerned with the added value of products, regulation requirements, and accommodation of the industrial chain, costs, and quality.

  12. Soluble factors from biofilm of Candida albicans and Staphylococcus aureus promote cell death and inflammatory response.

    de Carvalho Dias, Kassia; Barbugli, Paula Aboud; de Patto, Fernanda; Lordello, Virginia Barreto; de Aquino Penteado, Letícia; Medeiros, Alexandra Ivo; Vergani, Carlos Eduardo

    2017-06-30

    The objective of this study was to better understand the effects of soluble factors from biofilm of single- and mixed-species Candida albicans (C. albicans) and methicillin-sensitive Staphylococcus aureus (MSSA) cultures after 36 h in culture on keratinocytes (NOK-si and HaCaT) and macrophages (J774A.1). Soluble factors from biofilms of C. albicans and MSSA were collected and incubated with keratinocytes and macrophages, which were subsequently evaluated by cell viability assays (MTT). Lactate dehydrogenase (LDH) enzyme release was measured to assess cell membrane damage to keratinocytes. Cells were analysed by brightfield microscopy after 2 and 24 h of exposure to the soluble factors from biofilm. Cell death was detected by labelling apoptotic cells with annexin V and necrotic cells with propidium iodide (PI) and was visualized via fluorescence microscopy. Soluble factors from biofilm were incubated with J774A.1 cells for 24 h; the subsequent production of NO and the cytokines IL-6 and TNF-α was measured by ELISA. The cell viability assays showed that the soluble factors of single-species C. albicans cultures were as toxic as the soluble factors from biofilm of mixed cultures, whereas the soluble factors of MSSA cultures were less toxic than those of C. albicans or mixed cultures. The soluble factors from biofilm of mixed cultures were the most toxic to the NOK-si and HaCaT cells, as confirmed by analyses of PI labelling and cell morphology. Soluble factors from biofilm of single-species MSSA and mixed-species cultures induced the production of IL-6, NO and TNF-α by J744A.1 macrophages. The production of IL-6 and NO induced by the soluble factors from biofilm of mixed cultures was lower than that induced by the soluble factors from biofilm of single-species MSSA cultures, whereas the soluble factors from biofilm of C. albicans cultures induced only low levels of NO. Soluble factors from 36-h-old biofilm of C. albicans and MSSA cultures promoted cell death and

  13. Compensating microphonics in SRF cavities to ensure beam stability for future free electron lasers

    Neumann, Axel

    2008-07-21

    In seeded High-Gain-Harmonic-Generation free electron lasers or energy recovery linear accelerators the requirements for the bunch-to-bunch timing and energy jitter of the beam are in the femtosecond and per mill regime. This implies the ability to control the cavity radiofrequency (RF) field to an accuracy of 0.02 in phase and up to 1.10{sup -4} in amplitude. For the planned BESSY-FEL it is envisaged to operate 144 superconducting 1.3 GHz cavities of the 2.3 GeV driver linac in continuous wave mode and at a low beam current. The cavity resonance comprises a very narrow bandwidth of the order of tens of Hertz. Such cavities have been characterized under accelerator like conditions in the HoBiCaT test facility. It was possible to measure the error sources affecting the field stability in continuous wave (CW) operation. Microphonics, the main error source for a mechanical detuning of the cavities, lead to an average fluctuation of the cavity resonance of 1-5 Hz rms. Furthermore, the static and dynamic Lorentz force detuning and the helium pressure dependance of the cavity resonance have been measured. Single cavity RF control and linac bunch-to-bunch longitudinal phase space modeling containing the measured properties showed, that it is advisable to find means to minimize the microphonics detuning by mechanical tuning. Thus, several fast tuning systems have been tested for CW operation. These tuners consist of a motor driven lever for slow and coarse tuning and a piezo that is integrated into the tuner support for fast and fine tuning. Regarding the analysis of the detuning spectrum an adaptive feedforward method based on the least-mean-square filter algorithm has been developed for fast cavity tuning. A detuning compensation between a factor of two and up to a factor of seven has been achieved. Modeling the complete system including the fast tuning scheme, showed that the requirements of the BESSY-FEL are attainable. (orig.)

  14. Compensating microphonics in SRF cavities to ensure beam stability for future free electron lasers

    Neumann, Axel

    2008-01-01

    In seeded High-Gain-Harmonic-Generation free electron lasers or energy recovery linear accelerators the requirements for the bunch-to-bunch timing and energy jitter of the beam are in the femtosecond and per mill regime. This implies the ability to control the cavity radiofrequency (RF) field to an accuracy of 0.02 in phase and up to 1.10 -4 in amplitude. For the planned BESSY-FEL it is envisaged to operate 144 superconducting 1.3 GHz cavities of the 2.3 GeV driver linac in continuous wave mode and at a low beam current. The cavity resonance comprises a very narrow bandwidth of the order of tens of Hertz. Such cavities have been characterized under accelerator like conditions in the HoBiCaT test facility. It was possible to measure the error sources affecting the field stability in continuous wave (CW) operation. Microphonics, the main error source for a mechanical detuning of the cavities, lead to an average fluctuation of the cavity resonance of 1-5 Hz rms. Furthermore, the static and dynamic Lorentz force detuning and the helium pressure dependance of the cavity resonance have been measured. Single cavity RF control and linac bunch-to-bunch longitudinal phase space modeling containing the measured properties showed, that it is advisable to find means to minimize the microphonics detuning by mechanical tuning. Thus, several fast tuning systems have been tested for CW operation. These tuners consist of a motor driven lever for slow and coarse tuning and a piezo that is integrated into the tuner support for fast and fine tuning. Regarding the analysis of the detuning spectrum an adaptive feedforward method based on the least-mean-square filter algorithm has been developed for fast cavity tuning. A detuning compensation between a factor of two and up to a factor of seven has been achieved. Modeling the complete system including the fast tuning scheme, showed that the requirements of the BESSY-FEL are attainable. (orig.)

  15. Problems with the factor analysis of items: Solutions based on item response theory and item parcelling

    Gideon P. De Bruin

    2004-10-01

    Full Text Available The factor analysis of items often produces spurious results in the sense that unidimensional scales appear multidimensional. This may be ascribed to failure in meeting the assumptions of linearity and normality on which factor analysis is based. Item response theory is explicitly designed for the modelling of the non-linear relations between ordinal variables and provides a strong alternative to the factor analysis of items. Items may also be combined in parcels that are more likely to satisfy the assumptions of factor analysis than do the items. The use of the Rasch rating scale model and the factor analysis of parcels is illustrated with data obtained with the Locus of Control Inventory. The results of these analyses are compared with the results obtained through the factor analysis of items. It is shown that the Rasch rating scale model and the factoring of parcels produce superior results to the factor analysis of items. Recommendations for the analysis of scales are made. Opsomming Die faktorontleding van items lewer dikwels misleidende resultate op, veral in die opsig dat eendimensionele skale as meerdimensioneel voorkom. Hierdie resultate kan dikwels daaraan toegeskryf word dat daar nie aan die aannames van lineariteit en normaliteit waarop faktorontleding berus, voldoen word nie. Itemresponsteorie, wat eksplisiet vir die modellering van die nie-liniêre verbande tussen ordinale items ontwerp is, bied ’n aantreklike alternatief vir die faktorontleding van items. Items kan ook in pakkies gegroepeer word wat meer waarskynlik aan die aannames van faktorontleding voldoen as individuele items. Die gebruik van die Rasch beoordelingskaalmodel en die faktorontleding van pakkies word aan die hand van data wat met die Lokus van Beheervraelys verkry is, gedemonstreer. Die resultate van hierdie ontledings word vergelyk met die resultate wat deur ‘n faktorontleding van die individuele items verkry is. Die resultate dui daarop dat die Rasch

  16. Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

    Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

    2011-01-01

    Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

  17. Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses.

    Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

    2017-05-04

    Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs , including DnARF1 , DnARF4 , and DnARF6 , were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1 , DnARF4 , and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale . To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment.

  18. Development of new geomagnetic storm ground response scaling factors for utilization in hazard assessments

    Pulkkinen, A. A.; Bernabeu, E.; Weigel, R. S.; Kelbert, A.; Rigler, E. J.; Bedrosian, P.; Love, J. J.

    2017-12-01

    Development of realistic storm scenarios that can be played through the exposed systems is one of the key requirements for carrying out quantitative space weather hazards assessments. In the geomagnetically induced currents (GIC) and power grids context, these scenarios have to quantify the spatiotemporal evolution of the geoelectric field that drives the potentially hazardous currents in the system. In response to the Federal Energy Regulatory Commission (FERC) order 779, a team of scientists and engineers that worked under the auspices of North American Electric Reliability Corporation (NERC), has developed extreme geomagnetic storm and geoelectric field benchmark(s) that use various scaling factors that account for geomagnetic latitude and ground structure of the locations of interest. These benchmarks, together with the information generated in the National Space Weather Action Plan, are the foundation for the hazards assessments that the industry will be carrying out in response to the FERC order and under the auspices of the National Science and Technology Council. While the scaling factors developed in the past work were based on the best available information, there is now significant new information available for parts of the U.S. pertaining to the ground response to external geomagnetic field excitation. The significant new information includes the results magnetotelluric surveys that have been conducted over the past few years across the contiguous US and results from previous surveys that have been made available in a combined online database. In this paper, we distill this new information in the framework of the NERC benchmark and in terms of updated ground response scaling factors thereby allowing straightforward utilization in the hazard assessments. We also outline the path forward for improving the overall extreme event benchmark scenario(s) including generalization of the storm waveforms and geoelectric field spatial patterns.

  19. Suppression of the UV-sensitive phenotype of Escherichia coli recF mutants by recA(Srf) and recA(Tif) mutations requires recJ+

    Thoms, B.; Wackernagel, W.

    1988-01-01

    Mutations in recA, such as recA801(Srf) (suppressor of RecF) or recA441(Tif) (temperature-induced filamentation) partially suppress the deficiency in postreplication repair of UV damage conferred by recF mutations. We observed that spontaneous recA(Srf) mutants accumulated in cultures of recB recC sbcB sulA::Mu dX(Ap lac) lexA51 recF cells because they grew faster than the parental strain. We show that in a uvrA recB+ recC+ genetic background there are two prerequisites for the suppression by recA(Srf) of the UV-sensitive phenotype of recF mutants. (i) The recA(Srf) protein must be provided in increased amounts either by SOS derepression or by a recA operator-constitutive mutation in a lexA(Ind) (no induction of SOS functions) genetic background. (ii) The gene recJ, which has been shown previously to be involved in the recF pathway of recombination and repair, must be functional. The level of expression of recJ in a lexA(Ind) strain suffices for full suppression. Suppression by recA441 at 30 degrees C also depends on recJ+. The hampered induction by UV of the SOS gene uvrA seen in a recF mutant was improved by a recA(Srf) mutation. This improvement did not require recJ+. We suggest that recA(Srf) and recA(Tif) mutant proteins can operate in postreplication repair independent of recF by using the recJ+ function

  20. Interleukin-6, vascular endothelial growth factor and transforming growth factor beta 1 in canine steroid responsive meningitis-arteritis

    Maiolini Arianna

    2013-02-01

    Full Text Available Abstract Background Steroid Responsive Meningitis-Arteritis (SRMA is a common cause of inflammation of the canine central nervous system (CNS. To investigate if transforming growth factor beta 1 (TGF-β1, interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF are involved in the production of excessive immunoglobulin A (IgA, the induction of acute phase proteins and in the development of a systemic necrotizing vasculitis, characteristic of SRMA, these three signalling proteins were evaluated. Results Cerebrospinal fluid (CSF and serum samples of dogs during the acute phase of SRMA (SRMA were tested for IL-6, VEGF and TGF- β1. Results were compared to those of dogs affected with SRMA during treatment (SRMA Th and during relapse (SRMA R, to dogs with other meningoencephalomyelitides (ME, with miscellaneous non-inflammatory diseases of the CNS (CNS-Mix, with idiopathic epilepsy (IE, with systemic inflammatory diseases (Syst. Infl. and with healthy dogs (Healthy. Concentrations of IL-6 and VEGF in CSF were significantly elevated in the SRMA group compared to the other disease categories (p 1 were increased in SRMA group, but statistically significant differences were found only in comparison with Healthy and CNS-Mix groups. No differences were detected in the serum concentrations of TGF-β1 between the different groups. In untreated SRMA patients, a positive correlation (rSpear = 0.3549; P = 0.0337 between concentrations of TGF-β1 and IgA concentration was found in CSF, while concentrations of IL-6 and VEGF in CSF positively correlated with the degree of pleocytosis (rSpear = 0.8323; P Spear = 0.5711; P = 0.0166, respectively. Conclusions Our results suggest that these three signalling proteins are biomarkers of disease activity in SRMA. VEGF might play an important role in the development of a systemic arteritis. TGF-β1 is considered to be involved in the excessive IgA production, while IL-6 in the pleocytosis

  1. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.

    Janine E van Loon

    Full Text Available Physical stress triggers the endothelium to release von Willebrand Factor (VWF from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise.105 healthy individuals (18-35 years were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag levels, VWF collagen binding (VWF:CB levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599, Syntaxin-2 (STX2, rs7978987 and VWF (promoter, rs7965413 were determined.The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001. VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001. The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001. We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001, which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase.VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.

  2. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise.

    van Loon, Janine E; Sonneveld, Michelle A H; Praet, Stephan F E; de Maat, Moniek P M; Leebeek, Frank W G

    2014-01-01

    Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. 105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (pexercise (median increase 43% and 12%, both pexercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter.

  3. Characterization of mechanical behavior of an epithelial monolayer in response to epidermal growth factor stimulation

    Yang, Ruiguo; Chen, Jennifer Y.; Xi, Ning; Lai, King Wai Chiu; Qu, Chengeng; Fung, Carmen Kar Man; Penn, Lynn S.; Xi, Jun

    2012-01-01

    Cell signaling often causes changes in cellular mechanical properties. Knowledge of such changes can ultimately lead to insight into the complex network of cell signaling. In the current study, we employed a combination of atomic force microscopy (AFM) and quartz crystal microbalance with dissipation monitoring (QCM-D) to characterize the mechanical behavior of A431 cells in response to epidermal growth factor receptor (EGFR) signaling. From AFM, which probes the upper portion of an individual cell in a monolayer of cells, we observed increases in energy dissipation, Young's modulus, and hysteresivity. Increases in hysteresivity imply a shift toward a more fluid-like mechanical ordering state in the bodies of the cells. From QCM-D, which probes the basal area of the monolayer of cells collectively, we observed decreases in energy dissipation factor. This result suggests a shift toward a more solid-like state in the basal areas of the cells. The comparative analysis of these results indicates a regionally specific mechanical behavior of the cell in response to EGFR signaling and suggests a correlation between the time-dependent mechanical responses and the dynamic process of EGFR signaling. This study also demonstrates that a combination of AFM and QCM-D is able to provide a more complete and refined mechanical profile of the cells during cell signaling. -- Highlights: ► The EGF-induced cellular mechanical response is regionally specific. ► The EGF-induced cellular mechanical response is time and dose dependent. ► A combination of AFM and QCM-D provides a more complete mechanical profile of cells.

  4. Climate and terrain factors explaining streamflow response and recession in Australian catchments

    A. I. J. M. van Dijk

    2010-01-01

    Full Text Available Daily streamflow data were analysed to assess which climate and terrain factors best explain streamflow response in 183 Australian catchments. Assessed descriptors of catchment response included the parameters of fitted baseflow models, and baseflow index (BFI, average quick flow and average baseflow derived by baseflow separation. The variation in response between catchments was compared with indicators of catchment climate, morphology, geology, soils and land use. Spatial coherence in the residual unexplained variation was investigated using semi-variogram techniques. A linear reservoir model (one parameter; recession coefficient produced baseflow estimates as good as those obtained using a non-linear reservoir (two parameters and for practical purposes was therefore considered an appropriate balance between simplicity and explanatory performance. About a third (27–34% of the spatial variation in recession coefficients and BFI was explained by catchment climate indicators, with another 53% of variation being spatially correlated over distances of 100–150 km, probably indicative of substrate characteristics not captured by the available soil and geology data. The shortest recession half-times occurred in the driest catchments and were attributed to intermittent occurrence of fast-draining (possibly perched groundwater. Most (70–84% of the variation in average baseflow and quick flow was explained by rainfall and climate characteristics; another 20% of variation was spatially correlated over distances of 300–700 km, possibly reflecting a combination of terrain and climate factors. It is concluded that catchment streamflow response can be predicted quite well on the basis of catchment climate alone. The prediction of baseflow recession response should be improved further if relevant substrate properties were identified and measured.

  5. Haemodynamic responses and changes of haemostatic risk factors in cold-adapted humans.

    De Lorenzo, F; Kadziola, Z; Mukherjee, M; Saba, N; Kakkar, V V

    1999-09-01

    Epidemiological studies have shown an increase in acute myocardial infarctions or deaths due to myocardial infarction in colder weather; the mechanisms most likely involve increased blood levels of haemostatic risk factors, and increases in arterial blood pressure and heart rate. We studied the relationship between cold adaptation, haemostatic risk factors and haemodynamic variables. Cold adaptation was obtained by a programme of immersion of the whole body up to the neck in a water-filled bath, the temperature of which was gradually decreased from 22 degrees C to 14 degrees C, time of exposure being increased from 5 to 20 min over a period of 90 days. We studied 428 patients (44% men) and measured blood levels of fibrinogen, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator antigen (t-PA), plasma viscosity, von Willebrand factor, D-dimer and platelet count, both at baseline and after 90 days of daily immersion. There were significant reductions in von Willebrand factor (-3%; p cold adaptation (-310; p = 0.004). Cold adaptation, compared with exposure to cold weather, induces different haemodynamic responses and changes of blood levels of haemostatic risk factors.

  6. Continuously tunable cw lasing near 2.75 μm in diode-pumped Er3+ : SrF2 and Er3+ : CaF2 crystals

    Basiev, Tasoltan T; Orlovskii, Yu V; Polyachenkova, M V; Fedorov, Pavel P; Kuznetsov, S V; Konyushkin, V A; Osiko, Vyacheslav V; Alimov, Olimkhon K; Dergachev, Alexey Yu

    2006-01-01

    CW lasing is obtained in Er 3+ (5%) : CaF 2 and Er 3+ (5%) : SrF 2 crystals near 2.75 μm with 0.4 and 2 W of output powers, respectively, upon transverse diode laser pumping into the upper 4 I 11/2 laser level of erbium ions at 980 nm. Continuous tuning of the laser wavelength between 2720 and 2760 nm is realised in the Er 3+ : SrF 2 crystal. (special issue devoted to the 90th anniversary of a.m. prokhorov)

  7. Factors determining immunological response to vaccination against tick-borne encephalitis virus in older individuals.

    Lindblom, Pontus; Wilhelmsson, Peter; Fryland, Linda; Matussek, Andreas; Haglund, Mats; Sjöwall, Johanna; Vene, Sirkka; Nyman, Dag; Forsberg, Pia; Lindgren, Per-Eric

    2014-01-01

    We performed a cross-sectional study including 533 individuals (median age 61) from the highly TBE endemic Åland Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 12 health-related factors. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the individual and the number of vaccine doses were the two most important factors determining the immunological response to vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same immunological response. Participants previously vaccinated against other flaviviruses had lower odds of being seropositive for neutralizing TBEV antibodies on average, while participants with self-reported asthma had higher odds of being seropositive. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.

  8. Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

    Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

    2017-12-12

    Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

  9. Identification, isolation and expression analysis of auxin response factor (ARF) genes in Solanum lycopersicum.

    Wu, Jian; Wang, Feiyan; Cheng, Lin; Kong, Fuling; Peng, Zhen; Liu, Songyu; Yu, Xiaolin; Lu, Gang

    2011-11-01

    Auxin response factors (ARFs) encode transcriptional factors that bind specifically to the TGTCTC-containing auxin response elements found in the promoters of primary/early auxin response genes that regulate plant development. In this study, investigation of the tomato genome revealed 21 putative functional ARF genes (SlARFs), a number comparable to that found in Arabidopsis (23) and rice (25). The full cDNA sequences of 15 novel SlARFs were isolated and delineated by sequencing of PCR products. A comprehensive genome-wide analysis of this gene family is presented, including the gene structures, chromosome locations, phylogeny, and conserved motifs. In addition, a comparative analysis between ARF family genes in tomato and maize was performed. A phylogenetic tree generated from alignments of the full-length protein sequences of 21 OsARFs, 23 AtARFs, 31 ZmARFs, and 21 SlARFs revealed that these ARFs were clustered into four major groups. However, we could not find homologous genes in rice, maize, or tomato with AtARF12-15 and AtARF20-23. The expression patterns of tomato ARF genes were analyzed by quantitative real-time PCR. Our comparative analysis will help to define possible functions for many of these newly isolated ARF-family genes in plant development.

  10. Neural Responses to Injury: Prevention, Protection and Repair; Volume 7: Role Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury

    Bazan, Nicolas

    1996-01-01

    ...: Prevention, Protection, and Repair, Subproject: Role of Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury, are as follows: Species Rat(Albino Wistar), Number Allowed...

  11. TCP Transcription Factors at the Interface between Environmental Challenges and the Plant's Growth Responses.

    Danisman, Selahattin

    2016-01-01

    Plants are sessile and as such their reactions to environmental challenges differ from those of mobile organisms. Many adaptions involve growth responses and hence, growth regulation is one of the most crucial biological processes for plant survival and fitness. The plant-specific TEOSINTE BRANCHED 1, CYCLOIDEA, PCF1 (TCP) transcription factor family is involved in plant development from cradle to grave, i.e., from seed germination throughout vegetative development until the formation of flowers and fruits. TCP transcription factors have an evolutionary conserved role as regulators in a variety of plant species, including orchids, tomatoes, peas, poplar, cotton, rice and the model plant Arabidopsis. Early TCP research focused on the regulatory functions of TCPs in the development of diverse organs via the cell cycle. Later research uncovered that TCP transcription factors are not static developmental regulators but crucial growth regulators that translate diverse endogenous and environmental signals into growth responses best fitted to ensure plant fitness and health. I will recapitulate the research on TCPs in this review focusing on two topics: the discovery of TCPs and the elucidation of their evolutionarily conserved roles across the plant kingdom, and the variety of signals, both endogenous (circadian clock, plant hormones) and environmental (pathogens, light, nutrients), TCPs respond to in the course of their developmental roles.

  12. A review of major factors influencing plant responses to recreation impacts

    Kuss, Fred R.

    1986-09-01

    This article reviews some of the more important factors found to influence the susceptibility of plants to trampling impacts associated with recreational use of natural areas. A three-way interaction mediates plant responses to impacts: plant x environment x stress level(s). Plant responses vary in part according to the genetic constitution of the plant, life and growth form, the adaptive flexibility of the plant, and anatomical differences inherent to growth habit and morphology. Other factors that influence plant sensitivities to impacts are the habitat environments in which plants grow, since a number of conditions such as moisture excesses or deficiencies, nitrogen or oxygen starvation, late frosts, etc., cause physiological injury and may increase plant sensitivity to impacts. Among the environmental factors that may increase or lessen plant sensitivities to impacts are soil moisture levels, canopy density, elevation, aspect, microclimate, soil drainage, texture, fertility and productivity. Seasonal influences also bear consideration since environmental changes and phonological and physiological events are mediated by time of year. Stresses are caused by both direct and indirect forms of impact and vary according to season of use, frequency and amount of use, and the type of activity. These interactions are further complicated by evidence that inter- and intraspecific competition, antagonism, and commensalism may influence differences in the sensitivity of plant communities to impacts.

  13. Prevalence and risk factors of clopidogrel non-response among Saudi patients undergoing coronary angiography

    Haitham I. Sakr

    2016-02-01

    Full Text Available Objectives: To estimate the prevalence of clopidogrel non-response and identify its risk factors among Saudi patients. Methods: This cross-sectional study was conducted at Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia between January and June 2013, to assess the degree of platelet inhibition using the VerifyNow assay (Accumetrics, San Diego, CA, USA after receiving clopidogrel standard loading dose. Clopidogrel resistance was defined as ≤15% platelet inhibition or greater than 213 P2Y12 reaction units (PRU. Results: Three hundred and four patients were included in the study. The mean age was 60.3 ± 11.4 years, and 73% were males. Clopidogrel doses were 300 mg (57%, 600 mg (27%, and 75 mg (16%. All patients used aspirin (81 mg in 94%. Approximately 66% (200/304 showed in vitro clopidogrel non-response, 54% had low platelet inhibitions, and 61% had high post-loading PRU. Using multivariate regression analysis that included all significant characteristics; only diabetes (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.30-4.27, p=0.005 and higher preloading PRU (OR: 2.39, 95% CI: 1.40-4.11, p=0.002 remained significantly associated with higher clopidogrel non-response while myocardial infarction (OR: 0.34, 95% CI: 0.15-0.81, p=0.014 remained significantly associated with lower clopidogrel non-response. The associations of morbid obesity and diuretics use with higher clopidogrel non-response were slightly attenuated. Conclusion: Our findings indicate a high rate of clopidogrel in-vitro non-response among Saudi patients undergoing coronary angiography.

  14. The effect of dietary fiber and other factors on insulin response: role in obesity.

    Ullrich, I H; Albrink, M J

    1985-07-01

    Epidemiologic evidence favors the hypothesis that obesity may result from the fiber-depleted diet of industrialized societies. Since hyperinsulinemia is a universal characteristic and perhaps causal of obesity, the possibility is considered that dietary factors causing excess insulin secretion might lead to obesity. Dietary glucose causes a slightly greater insulin rise than cooked starch containing an equal amount of carbohydrate, and high fiber starchy foods cause a much lesser insulin response than does glucose in solution. Doubling the dose of carbohydrate in a meal causes only a small increase in glucose response but a large increase in insulin response. Dietary fiber could act by displacing some of the carbohydrate that would normally be absorbable in the small intestine, or could translocate the carbohydrate to a point lower in the intestinal tract where less effect on insulin secretion would be observed. Evidence is presented that a higher fiber diet is associated with a higher concentration of fasting circulating free fatty acids, a lesser post-cibal decrease in circulating free fatty acids and triglycerides and less chronic increase in fasting triglycerides than a low fiber diet. These differences are associated with a lesser insulin response to high fiber meals. The extreme fluctuations between the fed and fasted states seen with low fiber diets are thus dampened by high fiber diets. The less complete inhibition of lipolysis during the fed state, and more intense lipolysis during fasting, suggested by the above data, might tend to prevent obesity. The mechanisms of the lesser insulin response to high rather than low fiber meals are not known, but the possibility that dietary fiber decreases the GIP response is considered.

  15. Large grain CBMM Nb ingot slices: An ideal test bed for exploring the microstructure-electromagnetic property relationships relevant to SRF

    Sung, Zu-Hawn; Lee, Peter J.; Polyanskii, Anatolii; Balachandran, Shreyas; Chetri, Santosh; Larbalestier, David C.; Wang, Mingmin; Compton, Christopher; Bieler, Thomas R.

    2015-01-01

    High purity (RRR > 200), large grain (> 5-10 cm) niobium ingot slices have been successfully used to fabricate radio frequency (RF) cavities for particle accelerators. They offer significantly reduced fabrication cost by eliminating processing steps and furthermore they provide the opportunity to study the influence of individual grain boundaries in SRF Nb. Here we summarize our measurements of grain boundary (GB) effects on the superconducting properties of large grain high purity niobium sheet manufactured by CBMM. We show by magneto-optical (MO) imaging that GBs allow premature flux penetration, but only when they are oriented close to the direction of the magnetic field. However, even low angle GBs produced by minor deformations commensurate with half-cell forming produce localized flux penetration. The transport properties of grain boundaries were investigated by direct transport across them and evidence for preferential vortex flow along the GBs of SRF Nb was observed for the first time. Using transmission electron microscopy (TEM) and micro crystallographic analysis with electron backscattered diffraction (EBSD), we were able to quantitatively characterize surface substructures that can lead to localized thermal breakdown of superconductivity. Important to these studies was the development of sample preparation techniques that made the cutout single, bi-crystal and tri-crystal Nb coupons as representative as possible of the surface properties of cavities manufactured by standard techniques

  16. Case study of an MBT plant producing SRF for cement kiln co-combustion, coupled with a bioreactor landfill for process residues.

    Grosso, Mario; Dellavedova, Stefano; Rigamonti, Lucia; Scotti, Sergio

    2016-01-01

    The paper describes the performances of the energy recovery pathway from the residual waste based on the production of a Solid Recovered Fuel (SRF) to be exploited via co-combustion in a cement kiln. The SRF is produced in a single stream Mechanical-Biological Treatment plant, where bio-drying of the waste is followed by mechanical refining in order to fulfil the quality requirements by the cement kilns. Peculiar of this MBT is the fact that sorting residues are disposed in a nearby landfill, managed according to a bioreactor approach, where landfill gas is collected for electric energy recovery. A detailed mass and energy balance of the system is presented based on one year operational data, followed by its Life Cycle Assessment. Results show that the system is energetically and environmentally effective, with most of the impacts being more than compensated by the savings of materials and energy. Major role in determining such outcome is the displacement of petcoke in the cement kiln, both in terms of its fossil CO2 emissions and of its life cycle impacts, including the trans-oceanic transport. To check the robustness of the results, two sensitivity analyses are performed on the landfill gas collection efficiency and on the avoided electric energy mix. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. The quasi-equilibrium response of MOS structures: Quasi-static factor

    Okeke, M.; Balland, B.

    1984-07-01

    The dynamic response of a MOS structure driven into a non-equilibrium behaviour by a voltage ramp is presented. In contrast to Khun's quasi-static technique it is shown that any ramp-driven MOS structure has some degree of non-equilibrium. A quasi staticity factor μAK which serves as a measure of the degree of quasi-equilibrium, has been introduced for the first time. The mathematical model presented in the paper allows a better explanation of the experimental recordings. It is shown that this model could be used to analyse the various features of the response of the structure and that such physical parameters as the generation-rate, trap activation energy, and the effective capture constants could be obtained.

  18. Respiratory sinus arrhythmia responses to cognitive tasks: effects of task factors and RSA indices.

    Overbeek, Thérèse J M; van Boxtel, Anton; Westerink, Joyce H D M

    2014-05-01

    Many studies show that respiratory sinus arrhythmia (RSA) decreases while performing cognitive tasks. However, there is uncertainty about the role of contaminating factors such as physical activity and stress-inducing task variables. Different methods to quantify RSA may also contribute to variable results. In 83 healthy subjects, we studied RSA responses to a working memory task requiring varying levels of cognitive control and a perceptual attention task not requiring strong cognitive control. RSA responses were quantified in the time and frequency domain and were additionally corrected for differences in mean interbeat interval and respiration rate, resulting in eight different RSA indices. The two tasks were clearly differentiated by heart rate and facial EMG reference measures. Cognitive control induced inhibition of RSA whereas perceptual attention generally did not. However, the results show several differences between different RSA indices, emphasizing the importance of methodological variables. Age and sex did not influence the results. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Consumer factors predicting level of treatment response to illness management and recovery.

    White, Dominique A; McGuire, Alan B; Luther, Lauren; Anderson, Adrienne I; Phalen, Peter; McGrew, John H

    2017-12-01

    This study aims to identify consumer-level predictors of level of treatment response to illness management and recovery (IMR) to target the appropriate consumers and aid psychiatric rehabilitation settings in developing intervention adaptations. Secondary analyses from a multisite study of IMR were conducted. Self-report data from consumer participants of the parent study (n = 236) were analyzed for the current study. Consumers completed prepost surveys assessing illness management, coping, goal-related hope, social support, medication adherence, and working alliance. Correlations and multiple regression analyses were run to identify self-report variables that predicted level of treatment response to IMR. Analyses revealed that goal-related hope significantly predicted level of improved illness self-management, F(1, 164) = 10.93, p consumer-level predictors of level of treatment response have not been explored for IMR. Although 2 significant predictors were identified, study findings suggest more work is needed. Future research is needed to identify additional consumer-level factors predictive of IMR treatment response in order to identify who would benefit most from this treatment program. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Decision-related factors in pupil old/new effects: Attention, response execution, and false memory.

    Brocher, Andreas; Graf, Tim

    2017-07-28

    In this study, we investigate the effects of decision-related factors on recognition memory in pupil old/new paradigms. In Experiment 1, we used an old/new paradigm with words and pseudowords and participants made lexical decisions during recognition rather than old/new decisions. Importantly, participants were instructed to focus on the nonword-likeness of presented items, not their word-likeness. We obtained no old/new effects. In Experiment 2, participants discriminated old from new words and old from new pseudowords during recognition, and they did so as quickly as possible. We found old/new effects for both words and pseudowords. In Experiment 3, we used materials and an old/new design known to elicit a large number of incorrect responses. For false alarms ("old" response for new word), we found larger pupils than for correctly classified new items, starting at the point at which response execution was allowed (2750ms post stimulus onset). In contrast, pupil size for misses ("new" response for old word) was statistically indistinguishable from pupil size in correct rejections. Taken together, our data suggest that pupil old/new effects result more from the intentional use of memory than from its automatic use. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Kruppel-like factor 15 is required for the cardiac adaptive response to fasting.

    Sugi, Keiki; Hsieh, Paishiun N; Ilkayeva, Olga; Shelkay, Shamanthika; Moroney, Bridget; Baadh, Palvir; Haynes, Browning; Pophal, Megan; Fan, Liyan; Newgard, Christopher B; Prosdocimo, Domenick A; Jain, Mukesh K

    2018-01-01

    Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand. Here we show that cardiac KLF15 is required for the normal cardiac response to fasting. Specifically, we find that cardiac function is impaired upon fasting in systemic and cardiac specific Klf15-null mice. Further, cardiac specific Klf15-null mice display a fasting-dependent accumulation of long chain acylcarnitine species along with a decrease in expression of the carnitine translocase Slc25a20. Treatment with a diet high in short chain fatty acids relieves the KLF15-dependent long chain acylcarnitine accumulation and impaired cardiac function in response to fasting. Our observations establish KLF15 as a critical mediator of the cardiac adaptive response to fasting through its regulation of myocardial lipid utilization.

  2. Weak Satiety Responsiveness Is a Reliable Trait Associated with Hedonic Risk Factors for Overeating among Women.

    Dalton, Michelle; Hollingworth, Sophie; Blundell, John; Finlayson, Graham

    2015-09-04

    Some individuals exhibit a weak satiety response to food and may be susceptible to overconsumption. The current study identified women showing consistently low or high satiety responses to standardised servings of food across four separate days and compared them on behavioural, psychological and physiological risk factors for overeating and future weight gain. In a crossover design, 30 female participants (age: 28.0 ± 10.6; body mass index (BMI): 23.1 ± 3.0) recorded sensations of hunger in the post-prandial period following four graded energy level breakfasts. Satiety quotients were calculated to compare individuals on satiety responsiveness across conditions. Body composition, resting metabolic rate (RMR), energy intake, food reward and craving, and eating behaviour traits were assessed under controlled laboratory conditions. A distinct low satiety phenotype (LSP) was identified with good consistency across separate study days. These individuals had a higher RMR, greater levels of disinhibition and reported feeling lower control over food cravings. Further, they consumed more energy and exhibited greater wanting for high-fat food. The inverse pattern of characteristics was observed in those exhibiting a consistently high satiety phenotype (HSP). Weak satiety responsiveness is a reliable trait identifiable using the satiety quotient. The LSP was characterised by distinct behavioural and psychological characteristics indicating a risk for overeating, compared to HSP.

  3. Weak Satiety Responsiveness Is a Reliable Trait Associated with Hedonic Risk Factors for Overeating among Women

    Michelle Dalton

    2015-09-01

    Full Text Available Some individuals exhibit a weak satiety response to food and may be susceptible to overconsumption. The current study identified women showing consistently low or high satiety responses to standardised servings of food across four separate days and compared them on behavioural, psychological and physiological risk factors for overeating and future weight gain. In a crossover design, 30 female participants (age: 28.0 ± 10.6; body mass index (BMI: 23.1 ± 3.0 recorded sensations of hunger in the post-prandial period following four graded energy level breakfasts. Satiety quotients were calculated to compare individuals on satiety responsiveness across conditions. Body composition, resting metabolic rate (RMR, energy intake, food reward and craving, and eating behaviour traits were assessed under controlled laboratory conditions. A distinct low satiety phenotype (LSP was identified with good consistency across separate study days. These individuals had a higher RMR, greater levels of disinhibition and reported feeling lower control over food cravings. Further, they consumed more energy and exhibited greater wanting for high-fat food. The inverse pattern of characteristics was observed in those exhibiting a consistently high satiety phenotype (HSP. Weak satiety responsiveness is a reliable trait identifiable using the satiety quotient. The LSP was characterised by distinct behavioural and psychological characteristics indicating a risk for overeating, compared to HSP.

  4. Malignant lymphoma. Prognostic factors and response to treatment of 473 patients at the National Cancer Institute

    Anderson, T.; DeVita, V.T. Jr.; Simon, R.M.; Berard, C.W.; Canellos, G.P.; Garvin, A.J.; Young, R.C.

    1982-01-01

    Treatment results were reviewed in 473 consecutively staged and treated patients at the National Cancer Institute over a 22-year period from 1953 to 1975. Responses correlated with histologic pattern and stage of disease. Complete responses to radiotherapy were frequent in nodular lymphoma patients. Similar treatment regimens were less effective in diffuse lymphoma patients. Using chemotherapy or combined modality approaches, complete responses were obtained in a high proportion of advanced nodular disease patients. Patients with nodular lymphoma tend to have higher complete response rates and longer survivals than their counterparts with diffuse histologic types. Patients with nodular lymphocytic lymphoma had a better survival than those with mixed or ''histiocytic'' histologic types. Patients with diffuse well differentiated lymphocytic lymphoma survived significantly longer than patients with other diffuse histologic types. Percentage and prominence of nodularity were not of prognostic significance in those patients with combined nodular and diffuse patterns of disease. When compared by histologic type, patient sex did not appear to be an important prognostic factor. The presence of B-symptoms was associated with a poorer survival in patients with nodular disease and in patients with diffuse disease. Over the years of this study, survival appears to have improved in each histologic subtype except diffuse poorly differentiated lymphoma

  5. Psychometric properties of the Epworth Sleepiness Scale: A factor analysis and item-response theory approach.

    Pilcher, June J; Switzer, Fred S; Munc, Alec; Donnelly, Janet; Jellen, Julia C; Lamm, Claus

    2018-04-01

    The purpose of this study is to examine the psychometric properties of the Epworth Sleepiness Scale (ESS) in two languages, German and English. Students from a university in Austria (N = 292; 55 males; mean age = 18.71 ± 1.71 years; 237 females; mean age = 18.24 ± 0.88 years) and a university in the US (N = 329; 128 males; mean age = 18.71 ± 0.88 years; 201 females; mean age = 21.59 ± 2.27 years) completed the ESS. An exploratory-factor analysis was completed to examine dimensionality of the ESS. Item response theory (IRT) analyses were used to provide information about the response rates on the items on the ESS and provide differential item functioning (DIF) analyses to examine whether the items were interpreted differently between the two languages. The factor analyses suggest that the ESS measures two distinct sleepiness constructs. These constructs indicate that the ESS is probing sleepiness in settings requiring active versus passive responding. The IRT analyses found that overall, the items on the ESS perform well as a measure of sleepiness. However, Item 8 and to a lesser extent Item 6 were being interpreted differently by respondents in comparison to the other items. In addition, the DIF analyses showed that the responses between German and English were very similar indicating that there are only minor measurement differences between the two language versions of the ESS. These findings suggest that the ESS provides a reliable measure of propensity to sleepiness; however, it does convey a two-factor approach to sleepiness. Researchers and clinicians can use the German and English versions of the ESS but may wish to exclude Item 8 when calculating a total sleepiness score.

  6. [Rapid Response obstetrics Team at Instituto Mexicano del Seguro Social,enabling factors].

    Dávila-Torres, Javier; González-Izquierdo, José de Jesús; Ruíz-Rosas, Roberto Aguli; Cruz-Cruz, Polita Del Rocío; Hernández-Valencia, Marcelino

    2015-01-01

    There are barriers and enablers for the implementation of Rapid Response Teams in obstetric hospitals. The enabling factors were determined at Instituto Mexicano del Seguro Social (IMSS) MATERIAL AND METHODS: An observational, retrospective study was conducted by analysing the emergency obstetric reports sent by mobile technology and e-mail to the Medical Care Unit of the IMSS in 2013. Frequency and mean was obtained using the Excel 2010 program for descriptive statistics. A total of 164,250 emergency obstetric cases were reported, and there was a mean of 425 messages per day, of which 32.2% were true obstetric emergencies and required the Rapid Response team. By e-mail, there were 73,452 life threatening cases (a mean of 6 cases per day). A monthly simulation was performed in hospitals (480 in total). Enabling factors were messagés synchronisation among the participating personnel,the accurate record of the obstetrics, as well as the simulations performed by the operational staff. The most common emergency was pre-eclampsia-eclampsia with 3,351 reports, followed by obstetric haemorrhage with 2,982 cases. The enabling factors for the implementation of a rapid response team at IMSS were properly timed communication between the central delegation teams, as they allowed faster medical and administrative management and participation of hospital medical teams in the process. Mobile technology has increased the speed of medical and administrative management in emergency obstetric care. However, comparative studies are needed to determine the statistical significance. Published by Masson Doyma México S.A.

  7. AP2/ERF Transcription Factors Involved in Response to Tomato Yellow Leaf Curly Virus in Tomato

    Ying Huang

    2016-07-01

    Full Text Available Tomato yellow leaf curly virus (TYLCV, transmitted by the whitefly (, causes leaf curling and yellowing, plant dwarfism, and growth inhibition in tomato ( L.. The APETALA2 (AP2 and ethylene response factor (ERF transcription factor (TF family, the largest plant-specific TF family, was identified to function in plant development and pathogen defense. Our study aimed to analyze the mechanism underlying the function of ERF (SlERF TFs in response to TYLCV infection and improve useful information to increase the resistance to TYLCV in tomato. A total of 22 tomato AP2/ERF TFs in response to TYLCV were identified according to transcriptome database. Five ERF-B3 TFs were identified in cultivars Hongbeibei (highly resistant, Zheza-301, Zhefen-702 (both resistant, Jinpeng-1, and Xianke-6 (both susceptible. Interaction network indicated that SlERF TFs could interact with mitogen-activated protein kinase (MAPK. Expression profiles of five ERF-B3 genes (, , , , and were detected by quantitative real-time–polymerase chain reaction (qRT-PCR after TYLCV infection in five tomato cultivars. expression was upregulated in five tomato cultivars. The expressions of three genes (, , and were upregulated in Zheza-301 and Zhefen-702. and expressions were downregulated in Hongbeibei and Xianke-6, respectively. Yeast one-hybrid showed that the GCC-box binding ability of ERF-B3 TFs differed in resistant and susceptible tomato cultivars. Expression profiles were related to the GCC-box binding ability of SlERF TFs in resistant and susceptible tomato cultivars. The defense mechanism underlying the tomato’s response to TYLCV involved a complicated network, which provided important information for us in breeding and genetic analysis.

  8. Effects of epidermal growth factor receptor kinase inhibition on radiation response in canine osteosarcoma cells.

    Mantovani, Fernanda B; Morrison, Jodi A; Mutsaers, Anthony J

    2016-05-31

    Radiation therapy is a palliative treatment modality for canine osteosarcoma, with transient improvement in analgesia observed in many cases. However there is room for improvement in outcome for these patients. It is possible that the addition of sensitizing agents may increase tumor response to radiation therapy and prolong quality of life. Epidermal growth factor receptor (EGFR) expression has been documented in canine osteosarcoma and higher EGFR levels have been correlated to a worse prognosis. However, effects of EGFR inhibition on radiation responsiveness in canine osteosarcoma have not been previously characterized. This study examined the effects of the small molecule EGFR inhibitor erlotinib on canine osteosarcoma radiation responses, target and downstream protein expression in vitro. Additionally, to assess the potential impact of treatment on tumor angiogenesis, vascular endothelial growth factor (VEGF) levels in conditioned media were measured. Erlotinib as a single agent reduced clonogenic survival in two canine osteosarcoma cell lines and enhanced the impact of radiation in one out of three cell lines investigated. In cell viability assays, erlotinib enhanced radiation effects and demonstrated single agent effects. Erlotinib did not alter total levels of EGFR, nor inhibit downstream protein kinase B (PKB/Akt) activation. On the contrary, erlotinib treatment increased phosphorylated Akt in these osteosarcoma cell lines. VEGF levels in conditioned media increased after erlotinib treatment as a single agent and in combination with radiation in two out of three cell lines investigated. However, VEGF levels decreased with erlotinib treatment in the third cell line. Erlotinib treatment promoted modest enhancement of radiation effects in canine osteosarcoma cells, and possessed activity as a single agent in some cell lines, indicating a potential role for EGFR inhibition in the treatment of a subset of osteosarcoma patients. The relative radioresistance of

  9. How Do Various Maize Crop Models Vary in Their Responses to Climate Change Factors?

    Bassu, Simona; Brisson, Nadine; Grassini, Patricio; Durand, Jean-Louis; Boote, Kenneth; Lizaso, Jon; Jones, James W.; Rosenzweig, Cynthia; Ruane, Alex C.; Adam, Myriam; hide

    2014-01-01

    Potential consequences of climate change on crop production can be studied using mechanistic crop simulation models. While a broad variety of maize simulation models exist, it is not known whether different models diverge on grain yield responses to changes in climatic factors, or whether they agree in their general trends related to phenology, growth, and yield. With the goal of analyzing the sensitivity of simulated yields to changes in temperature and atmospheric carbon dioxide concentrations [CO2], we present the largest maize crop model intercomparison to date, including 23 different models. These models were evaluated for four locations representing a wide range of maize production conditions in the world: Lusignan (France), Ames (USA), Rio Verde (Brazil) and Morogoro (Tanzania). While individual models differed considerably in absolute yield simulation at the four sites, an ensemble of a minimum number of models was able to simulate absolute yields accurately at the four sites even with low data for calibration, thus suggesting that using an ensemble of models has merit. Temperature increase had strong negative influence on modeled yield response of roughly -0.5 Mg ha(sup 1) per degC. Doubling [CO2] from 360 to 720 lmol mol 1 increased grain yield by 7.5% on average across models and the sites. That would therefore make temperature the main factor altering maize yields at the end of this century. Furthermore, there was a large uncertainty in the yield response to [CO2] among models. Model responses to temperature and [CO2] did not differ whether models were simulated with low calibration information or, simulated with high level of calibration information.

  10. Assessing the Role of ETHYLENE RESPONSE FACTOR Transcriptional Repressors in Salicylic Acid-Mediated Suppression of Jasmonic Acid-Responsive Genes

    Caarls, Lotte; van der Does, Adriana; Hickman, Richard; Jansen, Wouter; van Verk, Marcel; Proietti, Silvia; Lorenzo, Oscar; Solano, Roberto; Pieterse, Corné M J; Van Wees, Saskia C M

    2017-01-01

    Salicylic acid (SA) and jasmonic acid (JA) cross-communicate in the plant immune signaling network to finely regulate induced defenses. In Arabidopsis, SA antagonizes many JA-responsive genes, partly by targeting the ETHYLENE RESPONSE FACTOR (ERF)-type transcriptional activator ORA59. Members of the

  11. Sex, Receptors and Attachment: A Review of Individual Factors Influencing Response to Oxytocin

    Kai S Macdonald

    2013-01-01

    Full Text Available As discussed in the larger review in this special issue (MacDonald and Feifel, intranasal oxytocin (IN OT is demonstrating a growing potential as a therapeutic agent in psychiatry. Importantly, research suggests that a variety of individual factors may influence a person’s response to OT. In this mini-review, I provides a review of three: (1 sex and hormonal status; (2 genetic variation in aspects of the OT system (i.e. OT receptors; and (3 attachment history. Each of these factors will be important to monitor as we strive to develop a richer understanding of OT's role in human development, brain-based disease, and the potential for individualized, OT-targeted treatments.

  12. Nonlinear Local Bending Response and Bulging Factors for Longitudinal and Circumferential Cracks in Pressurized Cylindrical Shells

    Young, Richard D.; Rose, Cheryl A.; Starnes, James H., Jr.

    2000-01-01

    Results of a geometrically nonlinear finite element parametric study to determine curvature correction factors or bulging factors that account for increased stresses due to curvature for longitudinal and circumferential cracks in unstiffened pressurized cylindrical shells are presented. Geometric parameters varied in the study include the shell radius, the shell wall thickness, and the crack length. The major results are presented in the form of contour plots of the bulging factor as a function of two nondimensional parameters: the shell curvature parameter, lambda, which is a function of the shell geometry, Poisson's ratio, and the crack length; and a loading parameter, eta, which is a function of the shell geometry, material properties, and the applied internal pressure. These plots identify the ranges of the shell curvature and loading parameters for which the effects of geometric nonlinearity are significant. Simple empirical expressions for the bulging factor are then derived from the numerical results and shown to predict accurately the nonlinear response of shells with longitudinal and circumferential cracks. The numerical results are also compared with analytical solutions based on linear shallow shell theory for thin shells, and with some other semi-empirical solutions from the literature, and limitations on the use of these other expressions are suggested.

  13. Postprandial lipemia: factoring in lipemic response for ranking foods for their healthiness.

    Dias, Cintia Botelho; Moughan, Paul J; Wood, Lisa G; Singh, Harjinder; Garg, Manohar L

    2017-09-18

    One of the limitations for ranking foods and meals for healthiness on the basis of the glycaemic index (GI) is that the GI is subject to manipulation by addition of fat. Postprandial lipemia, defined as a rise in circulating triglyceride containing lipoproteins following consumption of a meal, has been recognised as a risk factor for the development of cardiovascular disease and other chronic diseases. Many non-modifiable factors (pathological conditions, genetic background, age, sex and menopausal status) and life-style factors (physical activity, smoking, alcohol and medication use, dietary choices) may modulate postprandial lipemia. The structure and the composition of a food or a meal consumed also plays an important role in the rate of postprandial appearance and clearance of triglycerides in the blood. However, a major difficulty in grading foods, meals and diets according to their potential to elevate postprandial triglyceride levels has been the lack of a standardised marker that takes into consideration both the general characteristics of the food and the food's fat composition and quantity. The release rate of lipids from the food matrix during digestion also has an important role in determining the postprandial lipemic effects of a food product. This article reviews the factors that have been shown to influence postprandial lipemia with a view to develop a novel index for ranking foods according to their healthiness. This index should take into consideration not only the glycaemic but also lipemic responses.

  14. Radiation damage of hemopoietic tissue: circulating stem cells and growth factor responses

    Wagemaker, G.

    1997-01-01

    Briefly, evidence in rodents and nonhuman primates demonstrated two types of immature cells to be involved in regeneration following total body irradiation (X-rays). These cell populations can be separated and there is good responses differ. Related to these observations, experimental growth factor therapy has been ineffective at doses larger than 6-7 Gy X-rays and was shown to be optimally effective at the mid-lethal dose of 5 Gy. Consequently, at relatively high doses of radiation, treatment should initially be directed at reconstitution of growth factor responding stem cell subsets rather than at accelerated production of mature blood cells. Following cytotoxic insult to bone marrow, hemopoietic reconstitution is characterized by an increased fraction of stem cells that enters circulation. This might reflect a physiological mechanism to regulate the activities of the scattered bone marrow sites. In experimental studies with nonhuman primates, we showed that the number of circulating immature cells are proportional to those in the bone marrow and can be used for quantitative evaluation of residual stem cells numbers and to monitor the effectiveness of growth factor therapy at the immature cell level. The latter observations enables the design of growth factor treatment schedules for radiation induced myelosuppression in which thrombopenia is reduced and the recovery of immature bone marrow cells is promoted. (N.C.)

  15. Human response to wind turbine noise - perception, annoyance and moderating factors

    Pedersen, Eja

    2007-05-15

    The aims of this thesis were to describe and gain an understanding of how people who live in the vicinity of wind turbines are affected by wind turbine noise, and how individual, situational and visual factors, as well as sound properties, moderate the response. Methods A cross-sectional study was carried out in a flat, mainly rural area in Sweden, with the objective to estimate the prevalence of noise annoyance and to examine the dose-response relationship between A-weighted sound pressure levels (SPLs) and perception of and annoyance with wind turbine noise. Subjective responses were obtained through a questionnaire (n = 513; response rate: 68%) and outdoor, A-weighted SPLs were calculated for each respondent. To gain a deeper understanding of the observed noise annoyance, 15 people living in an area were interviewed using open-ended questions. The interviews were analysed using the comparative method of Grounded Theory (GT). An additional cross-sectional study, mainly exploring the influence of individual and situational factors, was carried out in seven areas in Sweden that differed with regard to terrain (flat or complex) and degree of urbanization (n = 765; response rate: 58%). To further explore the impact of visual factors, data from the two cross-sectional studies were tested with structural equation modelling. A proposed model of the influence of visual attitude on noise annoyance, also comprising the influence of noise level and general attitude, was tested among respondents who could see wind turbines versus respondents who could not see wind turbines from their dwelling, and respondents living in flat versus complex terrain. Dose-response relationships were found both for perception of noise and for noise annoyance in relation to A-weighted SPLs. The risk of annoyance was enhanced among respondents who could see at least one turbine from their dwelling and among those living in a rural in comparison with a suburban area. Noise from wind turbines was

  16. Human response to wind turbine noise - perception, annoyance and moderating factors

    Pedersen, Eja

    2007-05-01

    The aims of this thesis were to describe and gain an understanding of how people who live in the vicinity of wind turbines are affected by wind turbine noise, and how individual, situational and visual factors, as well as sound properties, moderate the response. Methods A cross-sectional study was carried out in a flat, mainly rural area in Sweden, with the objective to estimate the prevalence of noise annoyance and to examine the dose-response relationship between A-weighted sound pressure levels (SPLs) and perception of and annoyance with wind turbine noise. Subjective responses were obtained through a questionnaire (n = 513; response rate: 68%) and outdoor, A-weighted SPLs were calculated for each respondent. To gain a deeper understanding of the observed noise annoyance, 15 people living in an area were interviewed using open-ended questions. The interviews were analysed using the comparative method of Grounded Theory (GT). An additional cross-sectional study, mainly exploring the influence of individual and situational factors, was carried out in seven areas in Sweden that differed with regard to terrain (flat or complex) and degree of urbanization (n = 765; response rate: 58%). To further explore the impact of visual factors, data from the two cross-sectional studies were tested with structural equation modelling. A proposed model of the influence of visual attitude on noise annoyance, also comprising the influence of noise level and general attitude, was tested among respondents who could see wind turbines versus respondents who could not see wind turbines from their dwelling, and respondents living in flat versus complex terrain. Dose-response relationships were found both for perception of noise and for noise annoyance in relation to A-weighted SPLs. The risk of annoyance was enhanced among respondents who could see at least one turbine from their dwelling and among those living in a rural in comparison with a suburban area. Noise from wind turbines was

  17. Clinical factors associated with the humoral immune response to influenza vaccination in chronic obstructive pulmonary disease

    Nath KD

    2013-12-01

    Full Text Available Karthik D Nath,1,2 Julie G Burel,1 Viswanathan Shankar,3 Antonia L Pritchard,1 Michelle Towers,2 David Looke,1,2 Janet M Davies,1 John W Upham1,2 1The University of Queensland (School of Medicine, Brisbane, QLD, Australia; 2Princess Alexandra Hospital, Brisbane, QLD, Australia; 3Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA Background and objective: Individuals with chronic obstructive pulmonary disease (COPD are at a high risk of developing significant complications from infection with the influenza virus. It is therefore vital to ensure that prophylaxis with the influenza vaccine is effective in COPD. The aim of this study was to assess the immunogenicity of the 2010 trivalent influenza vaccine in persons with COPD compared to healthy subjects without lung disease, and to examine clinical factors associated with the serological response to the vaccine. Methods: In this observational study, 34 subjects (20 COPD, 14 healthy received the 2010 influenza vaccine. Antibody titers at baseline and 28 days post-vaccination were measured using the hemagglutination inhibition assay (HAI assay. Primary endpoints included seroconversion (≥4-fold increase in antibody titers from baseline and the fold increase in antibody titer after vaccination. Results: Persons with COPD mounted a significantly lower humoral immune response to the influenza vaccine compared to healthy participants. Seroconversion occurred in 90% of healthy participants, but only in 43% of COPD patients (P=0.036. Increasing age and previous influenza vaccination were associated with lower antibody responses. Antibody titers did not vary significantly with cigarette smoking, presence of other comorbid diseases, or COPD severity. Conclusion: The humoral immune response to the 2010 influenza vaccine was lower in persons with COPD compared to non-COPD controls. The antibody response also declined with increasing age and in those with

  18. Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

    Mitchell, Jere H

    2017-06-01

    During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

  19. Factor XI Deficiency Alters the Cytokine Response and Activation of Contact Proteases during Polymicrobial Sepsis in Mice.

    Charles E Bane

    Full Text Available Sepsis, a systemic inflammatory response to infection, is often accompanied by abnormalities of blood coagulation. Prior work with a mouse model of sepsis induced by cecal ligation and puncture (CLP suggested that the protease factor XIa contributed to disseminated intravascular coagulation (DIC and to the cytokine response during sepsis. We investigated the importance of factor XI to cytokine and coagulation responses during the first 24 hours after CLP. Compared to wild type littermates, factor XI-deficient (FXI-/- mice had a survival advantage after CLP, with smaller increases in plasma levels of TNF-α and IL-10 and delayed IL-1β and IL-6 responses. Plasma levels of serum amyloid P, an acute phase protein, were increased in wild type mice 24 hours post-CLP, but not in FXI-/- mice, supporting the impression of a reduced inflammatory response in the absence of factor XI. Surprisingly, there was little evidence of DIC in mice of either genotype. Plasma levels of the contact factors factor XII and prekallikrein were reduced in WT mice after CLP, consistent with induction of contact activation. However, factor XII and PK levels were not reduced in FXI-/- animals, indicating factor XI deficiency blunted contact activation. Intravenous infusion of polyphosphate into WT mice also induced changes in factor XII, but had much less effect in FXI deficient mice. In vitro analysis revealed that factor XIa activates factor XII, and that this reaction is enhanced by polyanions such polyphosphate and nucleic acids. These data suggest that factor XI deficiency confers a survival advantage in the CLP sepsis model by altering the cytokine response to infection and blunting activation of the contact (kallikrein-kinin system. The findings support the hypothesis that factor XI functions as a bidirectional interface between contact activation and thrombin generation, allowing the two processes to influence each other.

  20. Identification and network-enabled characterization of auxin response factor genes in Medicago truncatula

    David J. Burks

    2016-12-01

    Full Text Available The Auxin Response Factor (ARF family of transcription factors is an important regulator of environmental response and symbiotic nodulation in the legume Medicago truncatula. While previous studies have identified members of this family, a recent spurt in gene expression data coupled with genome update and reannotation calls for a reassessment of the prevalence of ARF genes and their interaction networks in M. truncatula. We performed a comprehensive analysis of the M. truncatula genome and transcriptome that entailed search for novel ARF genes and the co-expression networks. Our investigation revealed 8 novel M. truncatula ARF (MtARF genes, of the total 22 identified, and uncovered novel gene co-expression networks as well. Furthermore, the topological clustering and single enrichment analysis of several network models revealed the roles of individual members of the MtARF family in nitrogen regulation, nodule initiation, and post-embryonic development through a specialized protein packaging and secretory pathway. In summary, this study not just shines new light on an important gene family, but also provides a guideline for identification of new members of gene families and their functional characterization through network analyses.

  1. Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

  2. The metal-responsive transcription factor-1 contributes to HIF-1 activation during hypoxic stress

    Murphy, Brian J.; Sato, Barbara G.; Dalton, Timothy P.; Laderoute, Keith R.

    2005-01-01

    Hypoxia-inducible factor-1 (HIF-1), the major transcriptional regulator of the mammalian cellular response to low oxygen (hypoxia), is embedded within a complex network of signaling pathways. We have been investigating the importance of another stress-responsive transcription factor, MTF-1, for the adaptation of cells to hypoxia. This article reports that MTF-1 plays a central role in hypoxic cells by contributing to HIF-1 activity. Loss of MTF-1 in transformed Mtf1 null mouse embryonic fibroblasts (MEFs) results in an attenuation of nuclear HIF-1α protein accumulation, HIF-1 transcriptional activity, and expression of an established HIF-1 target gene, glucose transporter-1 (Glut1). Mtf1 null (Mtf1 KO) MEFs also have constitutively higher levels of both glutathione (GSH) and the rate-limiting enzyme involved in GSH synthesis-glutamate cysteine ligase catalytic subunit-than wild type cells. The altered cellular redox state arising from increased GSH may perturb oxygen-sensing mechanisms in hypoxic Mtf1 KO cells and decrease the accumulation of HIF-1α protein. Together, these novel findings define a role for MTF-1 in the regulation of HIF-1 activity

  3. Factores sociales de riesgo para la falta de cumplimiento terapéutico en pacientes con tuberculosis en Pontevedra Social risk factors for noncompliance with tuberculosis treatment in Pontevedra [Spain

    Luis Anibarro

    2004-02-01

    Full Text Available Objetivo: Conocer la prevalencia y características de los factores sociales de riesgo (FSR para la falta de cumplimiento terapéutico entre los enfermos de tuberculosis de Pontevedra. Métodos: Análisis descriptivo de los enfermos de tuberculosis con FSR diagnosticados entre 1996 y 2002. Se consideró FSR la presencia de aislamiento social (alcoholismo, uso de drogas por vía parenteral, presidiario, sin domicilio fijo-sin techo, inadaptación social o la inmigración. Se calculó la prevalencia y la tendencia anual de los FSR, la situación final de los pacientes y la influencia de la administración directamente observada del tratamiento en la situación final. Resultados: De los 775 casos de TB, 156 pacientes (20,1% tenían algún FSR, 86 pacientes presentaban alcoholismo, 41 eran usuarios de drogas por vía parenteral, 24 eran inmigrantes, 14 no tenían domicilio fijo, 11 se consideraron con inadaptación social y 10 eran presidiarios. La presencia de FSR entre los enfermos de tuberculosis no mostró una tendencia a aumentar o disminuir durante el período de estudio, excepto por el incremento de inmigrantes (χ2 para la tendencia lineal = 12,24; p = 0,005. La proporciσn de pacientes con situaciσn final satisfactoria (curaciσn bacteriolσgica o tratamiento finalizado fue significativamente mayor en el grupo de pacientes sin FSR (el 90,4 frente al 70,8%; p Objetive: To determine the prevalence and characteristics of social risk factors (SRF for noncompliance with treatment in patients with tuberculosis (TB in Pontevedra. Methods: We performed a descriptive analysis of patients with TB and SRF diagnosed between 1996 and 2002. A patient was considered as having SRF if he or she was socially isolated (alcoholism, intravenous drug use, prison inmate, homelessness or social maladjustment or was an immigrant. The prevalence, annual trend of SRF and patient outcomes were calculated. The influence of direct observation of treatment

  4. Transcriptome-wide identification of Camellia sinensis WRKY transcription factors in response to temperature stress.

    Wu, Zhi-Jun; Li, Xing-Hui; Liu, Zhi-Wei; Li, Hui; Wang, Yong-Xin; Zhuang, Jing

    2016-02-01

    Tea plant [Camellia sinensis (L.) O. Kuntze] is a leaf-type healthy non-alcoholic beverage crop, which has been widely introduced worldwide. Tea is rich in various secondary metabolites, which are important for human health. However, varied climate and complex geography have posed challenges for tea plant survival. The WRKY gene family in plants is a large transcription factor family that is involved in biological processes related to stress defenses, development, and metabolite synthesis. Therefore, identification and analysis of WRKY family transcription factors in tea plant have a profound significance. In the present study, 50 putative C. sinensis WRKY proteins (CsWRKYs) with complete WRKY domain were identified and divided into three Groups (Group I-III) on the basis of phylogenetic analysis results. The distribution of WRKY family transcription factors among plantae, fungi, and protozoa showed that the number of WRKY genes increased in higher plant, whereas the number of these genes did not correspond to the evolutionary relationships of different species. Structural feature and annotation analysis results showed that CsWRKY proteins contained WRKYGQK/WRKYGKK domains and C2H2/C2HC-type zinc-finger structure: D-X18-R-X1-Y-X2-C-X4-7-C-X23-H motif; CsWRKY proteins may be associated with the biological processes of abiotic and biotic stresses, tissue development, and hormone and secondary metabolite biosynthesis. Temperature stresses suggested that the candidate CsWRKY genes were involved in responses to extreme temperatures. The current study established an extensive overview of the WRKY family transcription factors in tea plant. This study also provided a global survey of CsWRKY transcription factors and a foundation of future functional identification and molecular breeding.

  5. An inflammation-responsive transcription factor in the pathophysiology of osteoarthritis.

    Ray, Alpana; Ray, Bimal K

    2008-01-01

    A number of risk factors including biomechanical stress on the articular cartilage imposed by joint overloading due to obesity, repetitive damage of the joint tissues by injury of the menisci and ligaments, and abnormal joint alignment play a significant role in the onset of osteoarthritis (OA). Genetic predisposition can also lead to the formation of defective cartilage matrix because of abnormal gene expression in the cartilage-specific cells. Another important biochemical event in OA is the consequence of inflammation. It has been shown that synovial inflammation triggers the synthesis of biological stimuli such as cytokines and growth factors which subsequently reach the chondrocyte cells of the articular cartilage activating inflammatory events in the chondrocytes leading to cartilage destruction. In addition to cartilage degradation, hypertrophy of the subchondral bone and osteophyte formation at the joint margins also takes place in OA. Both processes involve abnormal expression of a number of genes including matrix metalloproteinases (MMPs) for cartilage degradation and those associated with bone formation during osteophyte development. To address how diverse groups of genes are activated in OA chondrocyte, we have studied their induction mechanism. We present evidence for abundant expression of an inflammation-responsive transcription factor, SAF-1, in moderate to severely damaged OA cartilage tissues. In contrast, cells in normal cartilage matrix contain very low level of SAF-1 protein. SAF-1 is identified as a major regulator of increased synthesis of MMP-1 and -9 and pro-angiogenic factor, vascular endothelial growth factor (VEGF). While VEGF by stimulating angiogenesis plays a key role in new bone formation in osteophyte, increase of MMP-1 and -9 is instrumental for cartilage erosion in the pathogenesis of OA. Increased expression in degenerated cartilage matrix and in the osteophytes indicate for a key regulatory role of SAF-1 in directing catabolic

  6. Germination Response of Four Alien Congeneric Amaranthus Species to Environmental Factors.

    Hao, Jian-Hua; Lv, Shuang-Shuang; Bhattacharya, Saurav; Fu, Jian-Guo

    2017-01-01

    Seed germination is the key step for successful establishment, growth and further expansion of population especially for alien plants with annual life cycle. Traits like better adaptability and germination response were thought to be associated with plant invasion. However, there are not enough empirical studies correlating adaptation to environmental factors with germination response of alien invasive plants. In this study, we conducted congeneric comparisons of germination response to different environmental factors such as light, pH, NaCl, osmotic and soil burials among four alien amaranths that differ in invasiveness and have sympatric distribution in Jiangsu Province, China. The data were used to create three-parameter sigmoid and exponential decay models, which were fitted to cumulative germination and emergence curves. The results showed higher maximum Germination (Gmax), shorter time for 50% germination (G50) and the rapid slope (Grate) for Amaranthus blitum (low-invasive) and A. retroflexus (high-invasive) compare to intermediately invasive A. spinosus and A. viridis in all experimental regimes. It indicated that germination potential does not necessarily constitute a trait that can efficiently distinguish highly invasive and low invasive congeners in four Amaranthus species. However, it was showed that the germination performances of four amaranth species were more or less correlated with their worldwide distribution area. Therefore, the germination performance can be used as a reference indicator, but not an absolute trait for invasiveness. Our results also confirmed that superior germination performance in wide environmental conditions supplementing high seed productivity in highly invasive A. retroflexus might be one of the reasons for its prolific growth and wide distribution. These findings lay the foundation to develop more efficient weed management practice like deep burial of seeds by turning over soil and use of tillage agriculture to control

  7. Sae regulator factor impairs the response to photodynamic inactivation mediated by Toluidine blue in Staphylococcus aureus.

    Gándara, Lautaro; Mamone, Leandro; Dotto, Cristian; Buzzola, Fernanda; Casas, Adriana

    2016-12-01

    Photodynamic inactivation (PDI) involves the combined use of light and a photosensitizer, which, in the presence of oxygen, originates cytotoxic species capable of inactivating bacteria. Since the emergence of multi-resistant bacterial strains is becoming an increasing public health concern, PDI becomes an attractive choice. The aim of this work was to study the differential susceptibility to Toluidine blue (TB) mediated PDI (TB-PDI) of S. aureus mutants (RN6390 and Newman backgrounds) for different key regulators of virulence factors related to some extent to oxidative stress. Complete bacteria eradication of planktonic cultures of RN6390 S. aureus photosensitized with 13μM TB was obtained upon illumination with a low light dose of 4.2J/cm 2 from a non-coherent light source. Similarly, complete cell death was achieved applying 1.3μM TB and 19J/cm 2 light dose, showing that higher light doses can lead to equal cell death employing low photosensitizer concentrations. Interestingly, RN6390 in planktonic culture responded significantly better to TB-PDI than the Newman strain. We showed that deficiencies in rsbU, mgrA (transcription factors related to stress response) or agr (quorum sensing system involved in copper resistance to oxidative stress) did not modify the response of planktonic S. aureus to PDI. On the other hand, the two component system sae impaired the response to TB-PDI through a mechanism not related to the Eap adhesin. More severe conditions were needed to inactivate S. aureus biofilms (0.5mM TB, 157J/cm 2 laser light). In mutant sae biofilms, strain dependant differential susceptibilities are not noticed. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. [Cryptogenic West syndrome: Clinical profile, response to treatment and prognostic factors].

    Calderón Romero, María; Arce Portillo, Elena; López Lobato, Mercedes; Muñoz Cabello, Beatriz; Blanco Martínez, Bárbara; Madruga Garrido, Marcos; Alonso Luego, Olga

    2017-12-06

    West syndrome (WS) is an age-dependent epileptic encephalopathy in which the prognosis varies according to the, not always identified, underlying origin. To define the profile of cryptogenic (a least studied isolated sub-group) WS, in Spain. To study its outcome, response to different treatments, and to establish prognostic factors. The study included a review of the medical records of 16 patients diagnosed with cryptogenic WS during the period, 2000-2015. The mean follow-up time was 6.6 years, with a minimum of 2 years. The large majority (11/16) were male. The mean age at onset was 6 months, and 6/16 had a family history of idiopathic epilepsy. The first line treatment with vigabatrin had an electrical-clinical response in 5/16 patients, with the remaining cases responding to adrenocorticotropic hormone (ACTH). Almost half (44%) of the patients progressed to other types of epilepsy, with no difference between those treated with vigabatrin or ACTH. A greater number of adverse effects were obtained with ACTH, with no retinal involvement being observed with vigabatrin. The aetiological cause was found in 2/16. Being female, late onset, and early control of the hypsarrhythmia, were factors of a good prognosis. The overall prognosis of cryptogenic WS was more serious than expected. Although the incidence of Lennox-Gastaut syndrome was low, the progression to focal epilepsy was the most common, with it appearing within the first 2 years of the diagnosis. The initial response to vigabatrin was lower than expected, but the long-term result was comparable to ACTH. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  9. Effect of environmental and material factors on the response of nanocomposite foam impact sensors

    Bird, Evan; Merrell, Jake; Rosquist, Parker; Martineau, Adin; Bowden, Anton; Seeley, Matthew; Fullwood, David

    2018-05-01

    Nanocomposite foam (NCF) is a multifunctional material that can be used to measure impact. Interactions between the flexible polymer matrix and conductive particles dispersed throughout it produce a voltage signal under dynamic strain, which correlates to the magnitude of impact. Though promising in applications requiring both impact sensing and energy absorption, NCF’s voltage response has been observed to suffer from significant signal drift. This paper investigates several causes of variance in the response of NCF sensors to consistent impacts. These effects can be classified into three general types: recoverable transient effects (such as those relating to viscoelasticity or capacitive charging), environmental drift (due to humidity and temperature), and permanent signal decay from material degradation. The motivation for the study arises from various potential repeat-impact applications where periodic recalibration of the sensor would be difficult (such as a gait-tracking insole in use for a marathon event). A cyclic drop testing machine was used to apply consistent impacts to NCF, and drift resulting from each factor (in ranges typical of an insole environment) was experimentally isolated. Models representing each factor’s contribution to signal drift are presented. Of the factors investigated, humidity and temperature caused the most significant drift, with permanent material degradation accounting for only minor decay in voltage response. Transient effects were also observed, with a characteristic ‘warm-up’ (or ‘charging’) time required for the NCF to achieve steady-state; this phenomenon, and the related ‘recovery’ time for the material to return to its original state, were determined. The resultant data can be leveraged to implement a correction algorithm or other drift-compensating method to retain an NCF sensor’s accuracy in both long and short data collection scenarios.

  10. Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

    Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

    2015-07-01

    Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

  11. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

    Blumberg, Jeffrey B.; Vita, Joseph A.; Chen, C. -Y. Oliver

    2015-01-01

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages. PMID:26633488

  12. Development of novel metabolite-responsive transcription factors via transposon-mediated protein fusion.

    Younger, Andrew K D; Su, Peter Y; Shepard, Andrea J; Udani, Shreya V; Cybulski, Thaddeus R; Tyo, Keith E J; Leonard, Joshua N

    2018-02-01

    Naturally evolved metabolite-responsive biosensors enable applications in metabolic engineering, ranging from screening large genetic libraries to dynamically regulating biosynthetic pathways. However, there are many metabolites for which a natural biosensor does not exist. To address this need, we developed a general method for converting metabolite-binding proteins into metabolite-responsive transcription factors-Biosensor Engineering by Random Domain Insertion (BERDI). This approach takes advantage of an in vitro transposon insertion reaction to generate all possible insertions of a DNA-binding domain into a metabolite-binding protein, followed by fluorescence activated cell sorting to isolate functional biosensors. To develop and evaluate the BERDI method, we generated a library of candidate biosensors in which a zinc finger DNA-binding domain was inserted into maltose binding protein, which served as a model well-studied metabolite-binding protein. Library diversity was characterized by several methods, a selection scheme was deployed, and ultimately several distinct and functional maltose-responsive transcriptional biosensors were identified. We hypothesize that the BERDI method comprises a generalizable strategy that may ultimately be applied to convert a wide range of metabolite-binding proteins into novel biosensors for applications in metabolic engineering and synthetic biology. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. The AP2/ERF Transcription Factor DRNL Modulates Gynoecium Development and Affects Its Response to Cytokinin

    Yolanda Durán-Medina

    2017-10-01

    Full Text Available The gynoecium is the female reproductive system in flowering plants. It is a complex structure formed by different tissues, some that are essential for reproduction and others that facilitate the fertilization process and nurture and protect the developing seeds. The coordinated development of these different tissues during the formation of the gynoecium is important for reproductive success. Both hormones and genetic regulators guide the development of the different tissues. Auxin and cytokinin in particular have been found to play important roles in this process. On the other hand, the AP2/ERF2 transcription factor BOL/DRNL/ESR2/SOB is expressed at very early stages of aerial organ formation and has been proposed to be a marker for organ founder cells. In this work, we found that this gene is also expressed at later stages during gynoecium development, particularly at the lateral regions (the region related to the valves of the ovary. The loss of DRNL function affects gynoecium development. Some of the mutant phenotypes present similarities to those observed in plants treated with exogenous cytokinins, and AHP6 has been previously proposed to be a target of DRNL. Therefore, we explored the response of drnl-2 developing gynoecia to cytokinins, and found that the loss of DRNL function affects the response of the gynoecium to exogenously applied cytokinins in a developmental-stage-dependent manner. In summary, this gene participates during gynoecium development, possibly through the dynamic modulation of cytokinin homeostasis and response.

  14. Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

    Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

    2016-01-01

    IMPORTANCE Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and lacks effective disease modifying therapies. In 2001 we initiated a clinical trial of Nerve Growth Factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in AD patients. We present post-mortem findings in 10 subjects with survival times ranging from 1 to 10 years post-treatment. OBJECTIVE To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND PARTICIPANTS 10 patients with early AD underwent NGF gene therapy using either ex vivo or in vivo gene transfer. The brains of all eight patients in the first Phase 1 ex vivo trial and two patients in a subsequent Phase 1 in vivo trial were examined. MAIN OUTCOME MEASURES Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In two cases, NGF protein levels were measured by ELISA. RESULTS Degenerating neurons in the AD brain respond to NGF. All patients exhibited a trophic response to NGF, in the form of axonal sprouting toward the NGF source. Comparing treated and non-treated sides of the brain in three patients that underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P>0.05). Activation of cellular signaling and functional markers were present in two patients that underwent AAV2-mediated NGF gene transfer. Neurons exhibiting tau pathology as well as neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes with resulting activation of cell signaling. No adverse pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE These findings indicate that

  15. Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease.

    Tuszynski, Mark H; Yang, Jennifer H; Barba, David; U, Hoi-Sang; Bakay, Roy A E; Pay, Mary M; Masliah, Eliezer; Conner, James M; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H

    2015-10-01

    Alzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment. To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. Patients in this anatomicopathological study were enrolled in clinical trials from March 2001 to October 2012 at the University of California, San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in vivo trial were examined. Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In 2 patients, NGF protein levels were measured by enzyme-linked immunosorbent assay. Among 10 patients, degenerating neurons in the AD brain responded to NGF. All patients exhibited a trophic response to NGF in the form of axonal sprouting toward the NGF source. Comparing treated and nontreated sides of the brain in 3 patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P < .05). Activation of cellular signaling and functional markers was present in 2 patients who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic

  16. Analysis of clinical factors for pathological complete response after preoperative neoadjuvant chemoradiotherapy for rectal cancer

    Ayiguli Hare; Palida Apizi; Iskandar Abulimiti; Zhang Jinrong; Tian Hanhan

    2014-01-01

    Objective: To evaluate the clinical factors associated with pathological complete response (pCR) after preoperative neoadjuvant chemoradiotherapy for rectal cancer. Methods: A retrospective analysis was performed on the clinical data of 116 patients with rectal cancer, who underwent neoadjuvant chemoradiotherapy followed by radical surgery from January 2009 to December 2012. All patients received pelvic intensity-modulated radiotherapy (50 Gy/25 fractions) with concurrent fluorouracil based chemotherapy and then underwent radical surgery 4-8 weeks later. The clinical factors associated with pCR or non-pCR were analyzed by Logistic regression. Results: Of the 116 patients, 20 (17.2%) achieved a pCR after neoadjuvant chemoradiotherapy. The univariate analysis showed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum carcinoembryonic antigen (CEA) level, T stage, N stage, distance from the anal verge, degree of tumor differentiation, and maximum tumor diameter were associated with pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. The multivariate analysis revealed that percentage of circumference of the rectal tube invaded by the tumor, preoperative serum CEA level,and T stage were predictive factors for pCR or non-pCR after neoadjuvant chemoradiotherapy for rectal cancer. Conclusions: Non-circumferential tumor (percentage of circumference of the rectal tube invaded by the tumor <75 %), low CEA level, and early T stage before treatment may be associated with pCR after neoadjuvant chemoradiotherapy for rectal cancer. (authors)

  17. Sequence and expression analyses of ethylene response factors highly expressed in latex cells from Hevea brasiliensis.

    Piyanuch Piyatrakul

    Full Text Available The AP2/ERF superfamily encodes transcription factors that play a key role in plant development and responses to abiotic and biotic stress. In Hevea brasiliensis, ERF genes have been identified by RNA sequencing. This study set out to validate the number of HbERF genes, and identify ERF genes involved in the regulation of latex cell metabolism. A comprehensive Hevea transcriptome was improved using additional RNA reads from reproductive tissues. Newly assembled contigs were annotated in the Gene Ontology database and were assigned to 3 main categories. The AP2/ERF superfamily is the third most represented compared with other transcription factor families. A comparison with genomic scaffolds led to an estimation of 114 AP2/ERF genes and 1 soloist in Hevea brasiliensis. Based on a phylogenetic analysis, functions were predicted for 26 HbERF genes. A relative transcript abundance analysis was performed by real-time RT-PCR in various tissues. Transcripts of ERFs from group I and VIII were very abundant in all tissues while those of group VII were highly accumulated in latex cells. Seven of the thirty-five ERF expression marker genes were highly expressed in latex. Subcellular localization and transactivation analyses suggested that HbERF-VII candidate genes encoded functional transcription factors.

  18. Changes in antagonistic activity of lactic acid bacteria induced by their response to technological factors

    Dovile Jonkuviene

    2015-12-01

    Full Text Available This study examined the changes in antagonistic activity of selected lactic acid bacteria (LAB in response to technological factors used in food production. The antimicrobial activity of 12 selected LAB strains was assessed against the bacterial and fungal strains using the agar well diffusion method. Sodium chloride (NaCl 6.5–8.0%, glucose 20-30% and pH 4.0, pH 8.0 and higher were the most crucial factors in reducing the spectra of the microorganisms antagonized. Heating at 80 °C or 100 °C had a greater negative impact than 63 °C on the antifungal activity of LAB. Freezing at –72 °C eliminated the antifungal activity, or it changed from fungicidal to fungistatic. Although each LAB demonstrated the ability to retain antimicrobial activity induced by various technological factors, Lactococcus lactis 768/5 was superior in retaining high antimicrobial activity against tested indicator strains.

  19. pH modulates the binding of early growth response protein 1 transcription factor to DNA.

    Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

    2013-08-01

    The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

  20. Divergent responses of tropical cyclone genesis factors to strong volcanic eruptions at different latitudes

    Yan, Qing; Zhang, Zhongshi; Wang, Huijun

    2018-03-01

    To understand the behaviors of tropical cyclones (TCs), it is very important to explore how TCs respond to anthropogenic greenhouse gases and natural forcings. Volcanic eruptions are a major natural forcing mechanism because they inject sulphate aerosols into the stratosphere, which modulate the global climate by absorbing and scattering solar radiation. The number of Atlantic hurricanes is thought to be reduced following strong tropical eruptions, but whether the response of TCs varies with the locations of the volcanoes and the different ocean basins remains unknown. Here, we use the Community Earth System Model-Last Millennium Ensemble to investigate the response of the large-scale environmental factors that spawn TCs to strong volcanic eruptions at different latitudes. A composite analysis indicates that tropical and northern hemisphere volcanic eruptions lead to significantly unfavorable conditions for TC genesis over the whole Pacific basin and the North Atlantic during the 3 years post-eruption, relative to the preceding 3 years. Southern hemisphere volcanic eruptions result in obviously unfavorable conditions for TC formation over the southwestern Pacific, but more favorable conditions over the North Atlantic. The mean response over the Indian Ocean is generally muted and insignificant. It should be noted that volcanic eruptions impact on environmental conditions through both the direct effect (i.e. on radiative forcing) and the indirect effect (i.e. on El Niño-Southern Oscillation), which is not differentiated in this study. In addition, the spread of the TC genesis response is considerably large for each category of eruptions over each ocean basin, which is also seen in the observational/proxy-based records. This large spread is attributed to the differences in stratospheric aerosol distributions, initial states and eruption intensities, and makes the short-term forecast of TC activity following the next large eruption challenging.

  1. Transcriptome-wide identification of bread wheat WRKY transcription factors in response to drought stress.

    Okay, Sezer; Derelli, Ebru; Unver, Turgay

    2014-10-01

    The WRKY superfamily of transcription factors was shown to be involved in biotic and abiotic stress responses in plants such as wheat (Triticum aestivum L.), one of the major crops largely cultivated and consumed all over the world. Drought is an important abiotic stress resulting in a considerable amount of loss in agronomical yield. Therefore, identification of drought responsive WRKY members in wheat has a profound significance. Here, a total of 160 TaWRKY proteins were characterized according to sequence similarity, motif varieties, and their phylogenetic relationships. The conserved sequences of the TaWRKYs were aligned and classified into three main groups and five subgroups. A novel motif in wheat, WRKYGQR, was identified. To putatively determine the drought responsive TaWRKY members, publicly available RNA-Seq data were analyzed for the first time in this study. Through in silico searches, 35 transcripts were detected having an identity to ten known TaWRKY genes. Furthermore, relative expression levels of TaWRKY16/TaWRKY16-A, TaWRKY17, TaWRKY19-C, TaWRKY24, TaWRKY59, TaWRKY61, and TaWRKY82 were measured in root and leaf tissues of drought-tolerant Sivas 111/33 and susceptible Atay 85 cultivars. All of the quantified TaWRKY transcripts were found to be up-regulated in root tissue of Sivas 111/33. Differential expression of TaWRKY16, TaWRKY24, TaWRKY59, TaWRKY61 and TaWRKY82 genes was discovered for the first time upon drought stress in wheat. These comprehensive analyses bestow a better understanding about the WRKY TFs in bread wheat under water deficit, and increased number of drought responsive WRKYs would contribute to the molecular breeding of tolerant wheat cultivars.

  2. Transcriptional responses of metallothionein gene to different stress factors in Pacific abalone (Haliotis discus hannai).

    Lee, Sang Yoon; Nam, Yoon Kwon

    2016-11-01

    A novel metallothionein (MT) gene from the Pacific abalone H. discus hannai was characterized and its mRNA expression patterns (tissue distribution, developmental expression and differential expression in responsive to various in vivo stimulatory treatments) were examined. Abalone MT shares conserved structural features with previously known gastropod orthologs at both genomic (i.e., tripartite organization) and amino acid (conserved Cys motifs) levels. The 5'-flanking regulatory region of abalone MT gene displayed various transcription factor binding motifs particularly including ones related with metal regulation and stress/immune responses. Tissue distribution and basal expression patterns of MT mRNAs indicated a potential association between ovarian MT expression and sexual maturation. Developmental expression pattern suggested the maternal contribution of MT mRNAs to embryonic and early larval developments. Abalone MT mRNAs could be significantly induced by various heavy metals in different tissues (gill, hepatopancreas, muscle and hemocyte) in a tissue- and/or metal-dependent fashion. In addition, the abalone MT gene was highly modulated in responsive to other non-metal, stimulatory treatments such as immune challenge (LPS, polyI:C and bacterial injections), hypoxia (decrease from normoxia 8 ppm-2 ppm), thermal elevation (increase from 20 °C to 30 °C), and xenobiotic exposure (250 ppb of 17α-ethynylestradiol and 0.25 ppb of 2,3,7,8-tetrachlorodibenzodioxin) where differential expression patterns were toward either up- or down-regulation depending on types of stimulations and tissues examined. Taken together, our results highlight that MT is a multifunctional effector playing in wide criteria of cellular pathways especially associated with development and stress responses in this abalone species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Emotional Responses to Suicidal Patients: Factor Structure, Construct, and Predictive Validity of the Therapist Response Questionnaire-Suicide Form

    Shira Barzilay; Zimri S. Yaseen; Zimri S. Yaseen; Mariah Hawes; Bernard Gorman; Rachel Altman; Adriana Foster; Alan Apter; Paul Rosenfield; Igor Galynker; Igor Galynker

    2018-01-01

    BackgroundMental health professionals have a pivotal role in suicide prevention. However, they also often have intense emotional responses, or countertransference, during encounters with suicidal patients. Previous studies of the Therapist Response Questionnaire-Suicide Form (TRQ-SF), a brief novel measure aimed at probing a distinct set of suicide-related emotional responses to patients found it to be predictive of near-term suicidal behavior among high suicide-risk inpatients. The purpose o...

  4. Expression of jasmonic ethylene responsive factor gene in transgenic poplar tree leads to increased salt tolerance.

    Li, Yiliang; Su, Xiaohua; Zhang, Bingyu; Huang, Qinjun; Zhang, Xianghua; Huang, Rongfeng

    2009-02-01

    The stress resistance of plants can be enhanced by regulating the expression of multiple downstream genes associated with stress resistance. We used the Agrobacterium method to transfer the tomato jasmonic ethylene responsive factors (JERFs) gene that encodes the ethylene response factor (ERF) like transcription factor to the genome of a hybrid poplar (Populus alba x Populus berolinensis). Eighteen resistant plants were obtained, of which 13 were identified by polymerase chain reaction (PCR), reverse transcriptase PCR and Southern blot analyses as having incorporated the JERFs gene and able to express it at the transcriptional level. Salinity tests were conducted in a greenhouse with 0, 100, 200 and 300 mM NaCl. In the absence of NaCl, the transgenic plants were significantly taller than the control plants, but no statistically significant differences in the concentrations of proline and chlorophyll were observed. With increasing salinity, the extent of damage was significantly less in transgenic plants than that in control plants, and the reductions in height, basal diameter and biomass were less in transgenic plants than those in control plants. At 200 and 300 mM NaCl concentrations, transgenic plants were 128.9% and 98.8% taller, respectively, and had 199.8% and 113.0% more dry biomass, respectively, than control plants. The saline-induced reduction in leaf water content and increase in root/crown ratio were less in transgenic plants than in control plants. Foliar proline concentration increased more in response to salt treatment in transgenic plants than in control plants. Foliar Na(+) concentration was higher in transgenic plants than in control plants. In the coastal area in Panjin of Liaoning where the total soil salt concentration is 0.3%, a salt tolerance trial of transgenic plants indicated that 3-year-old transgenic plants were 14.5% and 33.6% taller than the control plants at two field sites. The transgenic plants at the two field sites were growing

  5. Male endocrine response to seasonally varying environmental and social factors in a neotropical primate, Cebus capucinus.

    Schoof, Valérie A M; Bonnell, Tyler R; Jack, Katharine M; Ziegler, Toni E; Melin, Amanda D; Fedigan, Linda M

    2016-04-01

    Circannual variation in reproduction is pervasive in birds and mammals. In primates, breeding seasonality is variable, with seasonal birth peaks occurring even in year-round breeders. Environmental seasonality is reportedly an important contributor to the observed variation in reproductive seasonality. Given that food availability is the primary factor constraining female reproduction, predictions concerning responsiveness to environmental seasonality focus on females, with studies of males focusing primarily on social factors. We examined the influence of both environmental and social factors on male fecal testosterone (fT) and glucocorticoids (fGC) in moderately seasonally breeding white-faced capuchin monkeys (Cebus capucinus) in Costa Rica. Over 17 months, we collected 993 fecal samples from 14 males in three groups. We used LMM to simultaneously examine the relative effects of photoperiod, fruit biomass, rainfall, temperature, female reproductive status (i.e., number of periovulatory periods, POPs), and male age and dominance rank on monthly fT and fGC levels. Male age and rank had large effects on fT and fGC. Additionally, some hormone variation was explained by environmental factors: photoperiod in the previous month (i.e., lagged photoperiod) was the best environmental predictor of monthly fT levels, whereas fGC levels were best explained by lagged photoperiod, fruit biomass, and rainfall. POPs predicted monthly fT and fGC, but this effect was reduced when all variables were considered simultaneously, possibly because lagged photoperiod and POP were highly correlated. Males may use photoperiod as a cue predicting circannual trends in the temporal distribution of fertile females, while also fine-tuning short-term hormone increases to the actual presence of ovulatory females, which may occur at any time during the year. © 2016 Wiley Periodicals, Inc.

  6. Protein Kinases and Transcription Factors Activation in Response to UV-Radiation of Skin: Implications for Carcinogenesis

    Laurence A. Marchat; Elena Aréchaga Ocampo; Mavil López Casamichana; Carlos Pérez-Plasencia; César López-Camarillo; Elizbeth Álvarez-Sánchez

    2011-01-01

    Solar ultraviolet (UV) radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF-?B, AP-1, and NRF2...

  7. Corporate Social-Environmental Responsibility as an Attraction and Retention Factor for Young Professionals

    Marcos Cohen

    2017-01-01

    Full Text Available This research investigates if company social-environmental responsibility (SER is an attraction and retention factor for young professionals in two studies. The first study, an experiment, investigates whether such practices influence the attraction exerted by the company as a prospect employer among undergraduate students, considering different wage and professional development conditions. The second study, a survey, investigates the impact of company SER on voluntary turnover among trainees, controlling for individual differences and satisfaction with income, growth and interests. The results suggest that SER is an important element in the attractiveness exercised by companies as they recruit young professionals, and in the retention of trainees, since it is statistically associated with the likelihood of them leaving their companies after disputed selection processes and expensive training programs.

  8. The role of nuclear factor κB in the cellular response to different radiation qualities

    Koch, Kristina

    2013-04-11

    Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

  9. The role of nuclear factor κB in the cellular response to different radiation qualities

    Koch, Kristina

    2013-01-01

    Radiation is currently one of the most important limiting factors for manned space flight. During such missions, there is a constant exposure to low doses of galactic cosmic radiation and in particular high-energy heavy ions. Together this is associated with an increased cancer risk which currently cannot be sufficiently reduced by shielding. As such, cellular radiation response needs to be further studied in order to improve risk estimation and develop appropriate countermeasures. It has been shown that exposure of human cells to accelerated heavy ions, in fluences that can be reached during long-term missions, leads to activation of the Nuclear Factor κB (NF-κB) pathway. Heavy ions with a linear energy transfer (LET) of 90 to 300 keV/μm were most effective in activating NF-κB. NF-κB as an important modulating factor in the cellular radiation response could improve cellular survival after heavy ion exposure, thereby influencing the cancer risk of astronauts. The NF-κB pathway may be a potential pharmacological target in the mitigation of radiation response during space missions; such as the prevention of massive cell death after high dose irradiation (acute effects), in addition to neoplastic cell transformation during chronic low-dose exposure (late effects). The aim of this work was to examine the role of NF-κB in the cellular response to space-relevant radiation. Firstly, NF-κB activation in human embryonic kidney cells (HEK) after exposure to different radiation qualities and quantities was investigated. Key elements of different NF-κB sub-pathways were chemically inhibited to analyze their role in NF-κB activation induced by low and high LET ionizing radiation. Finally a cell line, stably transfected with a plasmid coding for a short-hairpin RNA (shRNA) for a knockdown of the NF-κB subunit RelA, was established to assess the role of RelA in the cellular response to space-relevant radiation. The knockdown was verified on several levels and the cell

  10. Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney

    Sheng, Lili; Yang, Min; Ding, Wei [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Zhang, Minmin [Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China); Niu, Jianying [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Qiao, Zhongdong [School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gu, Yong, E-mail: yonggu@vip.163.com [Department of Nephrology, Shanghai Fifth People' s Hospital, Fudan University, Shanghai 200240 (China); Department of Nephrology, Shanghai Huashan Hospital, Fudan University, Shanghai 200240 (China)

    2016-08-01

    Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights: • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.

  11. Agent-based modeling of oxygen-responsive transcription factors in Escherichia coli.

    Hao Bai

    2014-04-01

    Full Text Available In the presence of oxygen (O2 the model bacterium Escherichia coli is able to conserve energy by aerobic respiration. Two major terminal oxidases are involved in this process - Cyo has a relatively low affinity for O2 but is able to pump protons and hence is energetically efficient; Cyd has a high affinity for O2 but does not pump protons. When E. coli encounters environments with different O2 availabilities, the expression of the genes encoding the alternative terminal oxidases, the cydAB and cyoABCDE operons, are regulated by two O2-responsive transcription factors, ArcA (an indirect O2 sensor and FNR (a direct O2 sensor. It has been suggested that O2-consumption by the terminal oxidases located at the cytoplasmic membrane significantly affects the activities of ArcA and FNR in the bacterial nucleoid. In this study, an agent-based modeling approach has been taken to spatially simulate the uptake and consumption of O2 by E. coli and the consequent modulation of ArcA and FNR activities based on experimental data obtained from highly controlled chemostat cultures. The molecules of O2, transcription factors and terminal oxidases are treated as individual agents and their behaviors and interactions are imitated in a simulated 3-D E. coli cell. The model implies that there are two barriers that dampen the response of FNR to O2, i.e. consumption of O2 at the membrane by the terminal oxidases and reaction of O2 with cytoplasmic FNR. Analysis of FNR variants suggested that the monomer-dimer transition is the key step in FNR-mediated repression of gene expression.

  12. Sialadenitis after radioiodine therapy. Analysis of factors that influence the response to medical treatment.

    Geres, Alejandra E; Mereshian, Paula Szafryk; Fernández, Silvia; Rey Caro, Daniel Gonzalo; Castro, Ricardo; Podio, Ricardo; Ojeda, Silvia

    2015-12-01

    To assess the incidence of 131I-induced sialadenitis (SD) in patients with differentiated thyroid cancer (DTC), to analyze clinical and other factors related to metabolic radiotherapy that may predict the lack of response to conventional medical therapy (CMT), and to determine the effectiveness of intraductal steroid instillation in patients failing CMT. Fifty-two patients with DTC, 45 females (86.5%) and 7 males (13.5%) with a mean age of 44.21±13.3 years (r=17-74) who received ablation therapy with 131I after total thyroidectomy. Patients with diseases and/or medication causing xerostomia were excluded. Patients underwent salivary gland scintigraphy with 99Tc (10mCi). Eighteen patients (34.62%) had SD and received antibiotics, antispasmodics, and oral steroids for 15 days. They were divided into two groups: responders to medical therapy (n=12, age 44.3±14.4 years, 2 men [17%], 10 women [83%], cumulative dose 225±167.1 mCi) and non-responders to medical treatment, who underwent steroid instillation into the Stensen's duct (n=6 [33%], 2 men [33%], 4 women [67%], age 50±13.8 years, cumulative dose 138.3±61.7 mCi). Scintigraphy showed damage to the parotid and submaxillary glands. Incidence of 131I-induced sialadenitis was similar to that reported by other authors. Age, mean cumulative dose of 131I, and involvement of parotid and submaxillary glands did not condition response to CMT; however, male sex was a conditioning factor. Symptom persistence for more than 15 days makes instillation into the Stensen's duct advisable. This is an effective and safe method to avoid surgical excision of salivary glands. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  13. TMJ response to mandibular advancement surgery: an overview of risk factors

    VALLADARES-NETO, José; CEVIDANES, Lucia Helena; ROCHA, Wesley Cabral; ALMEIDA, Guilherme de Araújo; de PAIVA, João Batista; RINO-NETO, José

    2014-01-01

    Objective In order to understand the conflicting information on temporomandibular joint (TMJ) pathophysiologic responses after mandibular advancement surgery, an overview of the literature was proposed with a focus on certain risk factors. Methods A literature search was carried out in the Cochrane, PubMed, Scopus and Web of Science databases in the period from January 1980 through March 2013. Various combinations of keywords related to TMJ changes [disc displacement, arthralgia, condylar resorption (CR)] and aspects of surgical intervention (fixation technique, amount of advancement) were used. A hand search of these papers was also carried out to identify additional articles. Results A total of 148 articles were considered for this overview and, although methodological troubles were common, this review identified relevant findings which the practitioner can take into consideration during treatment planning: 1- Surgery was unable to influence TMJ with preexisting displaced disc and crepitus; 2- Clicking and arthralgia were not predictable after surgery, although there was greater likelihood of improvement rather than deterioration; 3- The amount of mandibular advancement and counterclockwise rotation, and the rigidity of the fixation technique seemed to influence TMJ position and health; 4- The risk of CR increased, especially in identified high-risk cases. Conclusions Young adult females with mandibular retrognathism and increased mandibular plane angle are susceptible to painful TMJ, and are subject to less improvement after surgery and prone to CR. Furthermore, thorough evidenced-based studies are required to understand the response of the TMJ after mandibular advancement surgery. PMID:24626243

  14. Genome-wide identification of soybean WRKY transcription factors in response to salt stress.

    Yu, Yanchong; Wang, Nan; Hu, Ruibo; Xiang, Fengning

    2016-01-01

    Members of the large family of WRKY transcription factors are involved in a wide range of developmental and physiological processes, most particularly in the plant response to biotic and abiotic stress. Here, an analysis of the soybean genome sequence allowed the identification of the full complement of 188 soybean WRKY genes. Phylogenetic analysis revealed that soybean WRKY genes were classified into three major groups (I, II, III), with the second group further categorized into five subgroups (IIa-IIe). The soybean WRKYs from each group shared similar gene structures and motif compositions. The location of the GmWRKYs was dispersed over all 20 soybean chromosomes. The whole genome duplication appeared to have contributed significantly to the expansion of the family. Expression analysis by RNA-seq indicated that in soybean root, 66 of the genes responded rapidly and transiently to the imposition of salt stress, all but one being up-regulated. While in aerial part, 49 GmWRKYs responded, all but two being down-regulated. RT-qPCR analysis showed that in the whole soybean plant, 66 GmWRKYs exhibited distinct expression patterns in response to salt stress, of which 12 showed no significant change, 35 were decreased, while 19 were induced. The data present here provide critical clues for further functional studies of WRKY gene in soybean salt tolerance.

  15. Manipulation of Auxin Response Factor 19 affects seed size in the woody perennial Jatropha curcas

    Sun, Yanwei; Wang, Chunming; Wang, Ning; Jiang, Xiyuan; Mao, Huizhu; Zhu, Changxiang; Wen, Fujiang; Wang, Xianghua; Lu, Zhijun; Yue, Genhua; Xu, Zengfu; Ye, Jian

    2017-01-01

    Seed size is a major determinant of seed yield but few is known about the genetics controlling of seed size in plants. Phytohormones cytokinin and brassinosteroid were known to be involved in the regulation of herbaceous plant seed development. Here we identified a homolog of Auxin Response Factor 19 (JcARF19) from a woody plant Jatropha curcas and genetically demonstrated its functions in controlling seed size and seed yield. Through Virus Induced Gene Silencing (VIGS), we found that JcARF19 was a positive upstream modulator in auxin signaling and may control plant organ size in J. curcas. Importantly, transgenic overexpression of JcARF19 significantly increased seed size and seed yield in plants Arabidopsis thaliana and J. curcas, indicating the importance of auxin pathway in seed yield controlling in dicot plants. Transcripts analysis indicated that ectopic expression of JcARF19 in J. curcas upregulated auxin responsive genes encoding essential regulators in cell differentiation and cytoskeletal dynamics of seed development. Our data suggested the potential of improving seed traits by precisely engineering auxin signaling in woody perennial plants. PMID:28102350

  16. Homeodomain Transcription Factor Msx-2 Regulates Uterine Progenitor Cell Response to Diethylstilbestrol.

    Yin, Yan; Lin, Congxing; Zhang, Ivy; Fisher, Alexander V; Dhandha, Maulik; Ma, Liang

    The fate of mouse uterine epithelial progenitor cells is determined between postnatal days 5 to 7. Around this critical time window, exposure to an endocrine disruptor, diethylstilbestrol (DES), can profoundly alter uterine cytodifferentiation. We have shown previously that a homeo domain transcription factor MSX-2 plays an important role in DES-responsiveness in the female reproductive tract (FRT). Mutant FRTs exhibited a much more severe phenotype when treated with DES, accompanied by gene expression changes that are dependent on Msx2 . To better understand the role that MSX-2 plays in uterine response to DES, we performed global gene expression profiling experiment in mice lacking Msx2 By comparing this result to our previously published microarray data performed on wild-type mice, we extracted common and differentially regulated genes in the two genotypes. In so doing, we identified potential downstream targets of MSX-2, as well as genes whose regulation by DES is modulated through MSX-2. Discovery of these genes will lead to a better understanding of how DES, and possibly other endocrine disruptors, affects reproductive organ development.

  17. Thriving on Pressure: A Factor Mixture Analysis of Sport Performers' Responses to Competitive Encounters.

    Brown, Daniel J; Arnold, Rachel; Standage, Martyn; Fletcher, David

    2017-12-01

    Although considerable research exists on performers' responses to sporting encounters, little is known about thriving in sport contexts. The current study examined if distinct response patterns existed between sport performers who thrived in competitive encounters compared with those who did not. Participants were 535 sport performers (134 women; M age  = 23.60 years, SD age  = 8.08; M competing  = 11.84 years, SD competing  = 7.11). Results of factor mixture analysis supported a four-profile solution comprising a thriving group (n = 146), a low-functioning group (n = 38), and two groups characterized by scores marginally above (n = 131) and below (n = 209) the sample mean. Profile membership was found to be predicted by personal enablers (viz., personal resilient qualities, psychological skills use) and process variables (viz., basic psychological need satisfaction and frustration, challenge appraisal). This examination of thriving in sport performers offers significant implications for research and practice.

  18. Wavelet-based blind identification of the UCLA Factor building using ambient and earthquake responses

    Hazra, B; Narasimhan, S

    2010-01-01

    Blind source separation using second-order blind identification (SOBI) has been successfully applied to the problem of output-only identification, popularly known as ambient system identification. In this paper, the basic principles of SOBI for the static mixtures case is extended using the stationary wavelet transform (SWT) in order to improve the separability of sources, thereby improving the quality of identification. Whereas SOBI operates on the covariance matrices constructed directly from measurements, the method presented in this paper, known as the wavelet-based modified cross-correlation method, operates on multiple covariance matrices constructed from the correlation of the responses. The SWT is selected because of its time-invariance property, which means that the transform of a time-shifted signal can be obtained as a shifted version of the transform of the original signal. This important property is exploited in the construction of several time-lagged covariance matrices. The issue of non-stationary sources is addressed through the formation of several time-shifted, windowed covariance matrices. Modal identification results are presented for the UCLA Factor building using ambient vibration data and for recorded responses from the Parkfield earthquake, and compared with published results for this building. Additionally, the effect of sensor density on the identification results is also investigated

  19. Transcription factors and plant response to drought stress: Current understanding and future directions

    Rohit Joshi

    2016-07-01

    Full Text Available Increasing vulnerability of plants to a variety of stresses such as drought, salt and extreme temperatures poses a global threat to sustained growth and productivity of major crops. Of these stresses, drought represents a considerable threat to plant growth and development. In view of this, developing staple food cultivars with improved drought tolerance emerges as the most sustainable solution towards improving crop productivity in a scenario of climate change. In parallel, unraveling the genetic architecture and the targeted identification of molecular networks using modern OMICS analyses, that can underpin drought tolerance mechanisms, is urgently required. Importantly, integrated studies intending to elucidate complex mechanisms can bridge the gap existing in our current knowledge about drought stress tolerance in plants. It is now well established that drought tolerance is regulated by several genes, including transcription factors (TFs that enable plants to withstand unfavorable conditions, and these remain potential genomic candidates for their wide application in crop breeding. These TFs represent the key molecular switches orchestrating the regulation of plant developmental processes in response to a variety of stresses. The current review aims to offer a deeper understanding of TFs engaged in regulating plant’s response under drought stress and to devise potential strategies to improve plant tolerance against drought.

  20. Chemotaxis of primitive hematopoietic cells in response to stromal cell–derived factor-1

    Jo, Deog-Yeon; Rafii, Shahin; Hamada, Tsuneyoshi; Moore, Malcolm A.S.

    2000-01-01

    Stromal cell–derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34+ hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area–forming cells (CAFCs) and long-term culture–initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34+ cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34+ cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20–50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo. PMID:10619866

  1. Promiscuous Diffusible Signal Factor Production and Responsiveness of the Xylella fastidiosa Rpf System

    Michael Ionescu

    2016-07-01

    Full Text Available Cell density-dependent regulation of gene expression in Xylella fastidiosa that is crucial to its switching between plant hosts and insect vectors is dependent on RpfF and its production of 2-enoic acids known as diffusible signal factor (DSF. We show that X. fastidiosa produces a particularly large variety of similar, relatively long-chain-length 2-enoic acids that are active in modulating gene expression. Both X. fastidiosa itself and a Pantoea agglomerans surrogate host harboring X. fastidiosa RpfF (XfRpfF is capable of producing a variety of both saturated and unsaturated free fatty acids. However, only 2-cis unsaturated acids were found to be biologically active in X. fastidiosa. X. fastidiosa produces, and is particularly responsive to, a novel DSF species, 2-cis-hexadecanoic acid that we term XfDSF2. It is also responsive to other, even longer 2-enoic acids to which other taxa such as Xanthomonas campestris are unresponsive. The 2-enoic acids that are produced by X. fastidiosa are strongly affected by the cellular growth environment, with XfDSF2 not detected in culture media in which 2-tetradecenoic acid (XfDSF1 had previously been found. X. fastidiosa is responsive to much lower concentrations of XfDSF2 than XfDSF1. Apparently competitive interactions can occur between various saturated and unsaturated fatty acids that block the function of those agonistic 2-enoic fatty acids. By altering the particular 2-enoic acids produced and the relative balance of free enoic and saturated fatty acids, X. fastidiosa might modulate the extent of DSF-mediated quorum sensing.

  2. FACTORS RESPONSIBLE FOR SLOW ADOPTION OF PUBLIC PRIVATE PARTNERSHIP (PPPS IN NIGERIA

    Amir Hussin B. Baharuddin

    2011-12-01

    Full Text Available The growth and development of any nation is greatly dependent on the availability of basic social infrastructure like good road, efficient power supply, buildings, ports, rails etcetera. Over fifty years after independent Nigeria is still in a very undesirable state of infrastructural development; variety of broad-based opinion surveys in recent years have shown that prominent infrastructure deficiencies are responsible for the country’s disappointing economic performance. This paper is designed to unfold factors responsible for the slow adoption of public private partnership PPPs in Nigeria and proffer workable solutions that could help revised the current trend. A questionnaire survey was conducted seeking the opinions of one hundred (100 experienced professionals within the industry comprising architects, engineers, quantity surveyors, project managers and contractors. Out of 100 questionnaires sent out, 61 came back resulting in a response rate of 61%. The result shows that high rate of corruption in government, high cost of participation and lack of adequate security have all combined to slow the uptake and use of PPPs for the provision of public infrastructures and services. In order to improve the use of PPPs to provide the much needed infrastructures to enhance economic growth and well-being of the growing population of the country, it was found that the elimination of corruption in government, the building of strong financial institutions, improvement in security and improving the knowledge of professionals in the PPP procurement strategy would greatly assist the country to overcome the dearth of public services and enhance economic growth.

  3. Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

    Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

    2017-08-01

    Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

  4. Transcription factor assisted loading and enhancer dynamics dictate the hepatic fasting response

    Goldstein, Ido; Baek, Songjoon; Presman, Diego M.; Paakinaho, Ville; Swinstead, Erin E.; Hager, Gordon L.

    2017-01-01

    Fasting elicits transcriptional programs in hepatocytes leading to glucose and ketone production. This transcriptional program is regulated by many transcription factors (TFs). To understand how this complex network regulates the metabolic response to fasting, we aimed at isolating the enhancers and TFs dictating it. Measuring chromatin accessibility revealed that fasting massively reorganizes liver chromatin, exposing numerous fasting-induced enhancers. By utilizing computational methods in combination with dissecting enhancer features and TF cistromes, we implicated four key TFs regulating the fasting response: glucocorticoid receptor (GR), cAMP responsive element binding protein 1 (CREB1), peroxisome proliferator activated receptor alpha (PPARA), and CCAAT/enhancer binding protein beta (CEBPB). These TFs regulate fuel production by two distinctly operating modules, each controlling a separate metabolic pathway. The gluconeogenic module operates through assisted loading, whereby GR doubles the number of sites occupied by CREB1 as well as enhances CREB1 binding intensity and increases accessibility of CREB1 binding sites. Importantly, this GR-assisted CREB1 binding was enhancer-selective and did not affect all CREB1-bound enhancers. Single-molecule tracking revealed that GR increases the number and DNA residence time of a portion of chromatin-bound CREB1 molecules. These events collectively result in rapid synergistic gene expression and higher hepatic glucose production. Conversely, the ketogenic module operates via a GR-induced TF cascade, whereby PPARA levels are increased following GR activation, facilitating gradual enhancer maturation next to PPARA target genes and delayed ketogenic gene expression. Our findings reveal a complex network of enhancers and TFs that dynamically cooperate to restore homeostasis upon fasting. PMID:28031249

  5. Hypoxia Inducible Factor 1α Promotes Endogenous Adaptive Response in Rat Model of Chronic Cerebral Hypoperfusion

    Ying Yang

    2017-01-01

    Full Text Available Hypoxia inducible factor 1α (HIF-1α, a pivotal regulator of gene expression in response to hypoxia and ischemia, is now considered to regulate both pro-survival and pro-death responses depending on the duration and severity of the stress. We previously showed that chronic global cerebral hypoperfusion (CCH triggered long-lasting accumulation of HIF-1α protein in the hippocampus of rats. However, the role of the stabilized HIF-1α in CCH is obscure. Here, we knock down endogenous HIF-1α to determine whether and how HIF-1α affects the disease processes and phenotypes of CCH. Lentivirus expressing HIF-1α small hairpin RNA was injected into the bilateral hippocampus and bilateral ventricles to knock down HIF-1α gene expression in the hippocampus and other brain areas. Permanent bilateral common carotid artery occlusions, known as 2-vessel occlusions (2VOs, were used to induce CCH in rats. Angiogenesis, oxidative stress, histopathological changes of the brain, and cognitive function were tested. Knockdown of HIF-1α prior to 2VO significantly exacerbates the impairment of learning and memory after four weeks of CCH. Mechanically, reduced cerebral angiogenesis, increased oxidative damage, and increased density of astrocytes and microglia in the cortex and some subregions of hippocampus are also shown after four weeks of CCH. Furthermore, HIF-1α knockdown also disrupts upregulation of regulated downstream genes. Our findings suggest that HIF-1α-protects the brain from oxidative stress and inflammation response in the disease process of CCH. Accumulated HIF-1α during CCH mediates endogenous adaptive processes to defend against more severe hypoperfusion injury of the brain, which may provide a therapeutic benefit.

  6. A macroepigenetic approach to identify factors responsible for the autism epidemic in the United States

    Dufault Renee

    2012-04-01

    Full Text Available Abstract The number of children ages 6 to 21 in the United States receiving special education services under the autism disability category increased 91% between 2005 to 2010 while the number of children receiving special education services overall declined by 5%. The demand for special education services continues to rise in disability categories associated with pervasive developmental disorders. Neurodevelopment can be adversely impacted when gene expression is altered by dietary transcription factors, such as zinc insufficiency or deficiency, or by exposure to toxic substances found in our environment, such as mercury or organophosphate pesticides. Gene expression patterns differ geographically between populations and within populations. Gene variants of paraoxonase-1 are associated with autism in North America, but not in Italy, indicating regional specificity in gene-environment interactions. In the current review, we utilize a novel macroepigenetic approach to compare variations in diet and toxic substance exposure between these two geographical populations to determine the likely factors responsible for the autism epidemic in the United States.

  7. Review of research on identification of factors influencing social response to technological risks

    Otway, H.J.

    1977-01-01

    Many countries are experiencing a period in which traditional values are being questioned. The social response to plans for further technological development has often taken the form of demands for a closer examination of the associated benefits and risks, and consideration of social values in public planning and decision processes. A theoretical framework for interdisciplinary risk assessment studies is presented to allow the balancing of complex technical data with measures of the corresponding social values. The cognitive limitations which affect rationality in intuitive decision-making are summarized as background for the introduction of formal decision methodologies. Methods for obtaining value measures are reviewed and an attitude-based method is developed in detail; this model allows identification of the relative importance of the technical, psychological and social factors which underlie attitudes and indicates which factors differentiate between social groups. A pilot application to nuclear power indicated that, for the subjects tested, attitudes pro and con were primarily determined by strongly differing beliefs about the benefits of nuclear power. Symbolic aspects of the nuclear controversy are reviewed, including psychological associations with nuclear weapons. It is suggested that nuclear energy is providing a forum to evaluate a wide range of social issues, perhaps playing a symbolic role in a dialogue about the shape and direction of a technologically-determined future. (author)

  8. Rice homeobox transcription factor HOX1a positively regulates gibberellin responses by directly suppressing EL1.

    Wen, Bi-Qing; Xing, Mei-Qing; Zhang, Hua; Dai, Cheng; Xue, Hong-Wei

    2011-11-01

    Homeobox transcription factors are involved in various aspects of plant development, including maintenance of the biosynthesis and signaling pathways of different hormones. However, few direct targets of homeobox proteins have been identified. We here show that overexpression of rice homeobox gene HOX1a resulted in enhanced gibberellin (GA) response, indicating a positive effect of HOX1a in GA signaling. HOX1a is induced by GA and encodes a homeobox transcription factor with transcription repression activity. In addition, HOX1a suppresses the transcription of early flowering1 (EL1), a negative regulator of GA signaling, and further electrophoretic mobility shift assay and chromatin immunoprecipitation analysis revealed that HOX1a directly bound to the promoter region of EL1 to suppress its expression and stimulate GA signaling. These results demonstrate that HOX1a functions as a positive regulator of GA signaling by suppressing EL1, providing informative hints on the study of GA signaling. © 2011 Institute of Botany, Chinese Academy of Sciences.

  9. Considering the context: social factors in responses to drugs in humans.

    de Wit, Harriet; Sayette, Michael

    2018-04-01

    Drugs are typically used in social settings. Here, we consider two factors that may contribute to this observation: (i) the presence of other people may enhance the positive mood effects of a drug, and conversely, (ii) drugs may enhance the value of social stimuli. We review evidence from controlled laboratory studies with human volunteers, which investigated either of these interactions between social factors and responses to drugs. We examine the bidirectional effects of social stimuli and single doses of alcohol, stimulants, opioids, and cannabis. All four classes of drugs interact with social contexts, but the nature of these interactions varies across drugs, and depends on whether the context is positive or negative. Alcohol and stimulant drugs enhance the attractiveness of social stimuli and the desire to socialize, and social contexts, in turn, enhance these drugs' effects. In contrast, opioids and cannabis have subtler effects on social interactions and their effects are less influenced by the presence of others. Overall, there is stronger evidence that drugs enhance positive social contexts than that they dampen the negativity of unpleasant social settings. Controlled research is needed to understand the interactions between drugs of abuse and social contexts, to model and understand the determinants of drug use outside the laboratory.

  10. Factors responsible for formation of severity of inflammatory parodontal diseases in adolescent girls with menstrual dysfunction

    Ye. A. Kliuchka

    2017-06-01

    Full Text Available Determining the factors of formation of severity of parodontal inflammatory diseases (PID in adolescent girls with menstrual dysfunction (MD makes it possible to determine the predictors of severity of PID and, on this basis, to develop differentiated methods for their prevention. The aim. To determine the factors responsible for formation of PID severity in adolescent girls with MD. The materials and methods. The following data were studied in adolescent girls with MD with varying severity of PID: obstetric and genealogical anamnesis, lifestyles of adolescents, indices of oral hygiene, dental status, densitometry, content of CA ++ and sIgA in saliva, lysozyme and urease activity in saliva, cytobiophysical potential of buccal epithelium nuclei. The findings. In patients with more severe course of PID, in comparison to milder course of PID, there was determined a more significant degree of weakened heredity in relation to chronic dental and somatic pathology, unfavorable course of pregnancy and childbirth, violations of a healthy lifestyle and oral hygiene in adolescents, anomalies in the development of dentoalveolar system, dysbiosis of oral cavity, reduced local and systemic immunoresistance. Conclusion: The determined predictors of the severity of PID in adolescent girls with MD make it possible to develop differentiated methods for their prevention.

  11. Banana ethylene response factors are involved in fruit ripening through their interactions with ethylene biosynthesis genes.

    Xiao, Yun-yi; Chen, Jian-ye; Kuang, Jiang-fei; Shan, Wei; Xie, Hui; Jiang, Yue-ming; Lu, Wang-jin

    2013-05-01

    The involvement of ethylene response factor (ERF) transcription factor (TF) in the transcriptional regulation of ethylene biosynthesis genes during fruit ripening remains largely unclear. In this study, 15 ERF genes, designated as MaERF1-MaERF15, were isolated and characterized from banana fruit. These MaERFs were classified into seven of the 12 known ERF families. Subcellular localization showed that MaERF proteins of five different subfamilies preferentially localized to the nucleus. The 15 MaERF genes displayed differential expression patterns and levels in peel and pulp of banana fruit, in association with four different ripening treatments caused by natural, ethylene-induced, 1-methylcyclopropene (1-MCP)-delayed, and combined 1-MCP and ethylene treatments. MaERF9 was upregulated while MaERF11 was downregulated in peel and pulp of banana fruit during ripening or after treatment with ethylene. Furthermore, yeast-one hybrid (Y1H) and transient expression assays showed that the potential repressor MaERF11 bound to MaACS1 and MaACO1 promoters to suppress their activities and that MaERF9 activated MaACO1 promoter activity. Interestingly, protein-protein interaction analysis revealed that MaERF9 and -11 physically interacted with MaACO1. Taken together, these results suggest that MaERFs are involved in banana fruit ripening via transcriptional regulation of or interaction with ethylene biosynthesis genes.

  12. Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

    Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

    2005-01-01

    Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell......Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... intracellular signaling. This cytokine exerts its functions via interaction with two receptors: type-1 receptor (TNFR1) and type-2 receptor (TNFR2). In this work, the inflammatory response after a freeze injury (cryolesion) in the cortex was studied in wild-type (WT) animals and in mice lacking TNFR1 (TNFR1 KO...... signaling also affected the expression of apoptosis/cell death-related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected...

  13. Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

    St Denny, I.H.; Glinka, K.G.; Nemecek, G.M.; Stuetz, A.

    1987-01-01

    Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5μM T in fibroblast incubation media was associated with increased [ 3 H]thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6μM reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 μM. Neither the uptake of [ 3 H]thymidine nor the specific binding of 125 I-PDGF to fibroblast receptors was significantly affected by 10 μM T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism

  14. Inhibition of the mitogenic response to platelet-derived growth factor by terbinafine

    St. Denny, I.H.; Glinka, K.G.; Nemecek, G.M. (Sandoz Research Institute, East Hanover, NJ (USA)); Stuetz, A. (Sandoz Forschungsinstitut, Vienna (Austria))

    1987-05-01

    Terbinafine (T;(E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic which inhibits fungal squalene epoxidase activity, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated mitogenesis. The inclusion of 1.5-5{mu}M T in fibroblast incubation media was associated with increased ({sup 3}H)thymidine incorporation into DNA in the presence and absence of PDGF. However, T at concentrations above 6{mu}M reduced DNA synthesis in control and PDGF-exposed cultures to nearly undetectable levels. Under a phase-contrast microscope, fibroblasts appeared morphologically normal at T concentrations as high as 25 {mu}M. Neither the uptake of ({sup 3}H)thymidine nor the specific binding of {sup 125}I-PDGF to fibroblast receptors was significantly affected by 10 {mu}M T. Furthermore, concentrations of T which antagonized the mitogenic response to PDGF also interfered with fibroblast growth factor-induced mitogenesis. Together, these data suggest that T has the ability to inhibit the in vitro action of PDGF via a post-receptor mechanism.

  15. A network of paralogous stress response transcription factors in the human pathogen Candida glabrata.

    Jawad eMerhej

    2016-05-01

    Full Text Available The yeast Candida glabrata has become the second cause of systemic candidemia in humans. However, relatively few genome-wide studies have been conducted in this organism and our knowledge of its transcriptional regulatory network is quite limited. In the present work, we combined genome-wide chromatin immunoprecipitation (ChIP-seq, transcriptome analyses and DNA binding motif predictions to describe the regulatory interactions of the seven Yap (Yeast AP1 transcription factors of C. glabrata. We described a transcriptional network containing 255 regulatory interactions and 309 potential target genes. We predicted with high confidence the preferred DNA binding sites for 5 of the 7 CgYaps and showed a strong conservation of the Yap DNA binding properties between S. cerevisiae and C. glabrata. We provided reliable functional annotation for 3 of the 7 Yaps and identified for Yap1 and Yap5 a core regulon which is conserved in S. cerevisiae, C. glabrata and C. albicans. We uncovered new roles for CgYap7 in the regulation of iron-sulfur cluster biogenesis, for CgYap1 in the regulation of heme biosynthesis and for CgYap5 in the repression of GRX4 in response to iron starvation. These transcription factors define an interconnected transcriptional network at the cross-roads between redox homeostasis, oxygen consumption and iron metabolism.

  16. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2010-01-01

    OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

  17. On the application of CaF2:Eu and SrF2:Eu phosphors in LED based phototherapy lamp

    Belsare, P. D.; Moharil, S. V.; Joshi, C. P.; Omanwar, S. K.

    2013-06-01

    In the last few years the interest of scientific community has been increased towards solid state lighting based on LEDs because of their superior advantages over the conventional fluorescent lamps. As the GaN based LEDs are easily available efforts of the researchers are now on making the new phosphors which are excitable in the near UV region (360-400nm) for solid state lighting. This paper reports the photoluminescence characteristics of CaF2:Eu and SrF2:Eu phosphor prepared by wet chemical method. The violet emission of these phosphors with near UV excitation can be useful in making a phototherapy lamp based on LEDs for treating various skin diseases like acne vulgaris and hyperbilirubinemia.

  18. One- and two-photon spectra of Nd3+ clusters in CaF2 and SrF2 crystals

    Basiev, Tasoltan T; Voronov, Valerii V; Glotova, M Yu; Papashvili, A G; Karasik, Aleksandr Ya

    2003-01-01

    The polarised two-photon (IR) and one-photon (visible) luminescence excitation spectra of Nd 3+ nanoclusters in CaF 2 and SrF 2 crystals are measured at 10 K using a F - 2 :LiF colour centre laser tunable in spectral ranges 1090 - 1230 nm and 545 - 615 nm with an emission linewidth of ∼0.02 - 0.03 cm -1 , an average output power of ∼55 mW, and a pulse repetition rate of 10 Hz. The two-photon excitation spectra at the 4 I 9/2 → 4 G 5/2 transition reveal the structure, which is absent upon one-photon excitation, which can be explained by different selection rules for some Stark - Stark transitions upon one- and two-photon absorption. (special issue devoted to the memory of academician a m prokhorov)

  19. Calculation of the hyperfine constants of Vk center in CaF2, SrF2 and BaF2

    Bufaical, R.F.

    1975-03-01

    The magnetic hyperfine constants of the V sub(K) center in CaF 2 , SrF 2 and BaF 2 have been calculated, assuming a phenomenological model, based on the F 2 central molecule, to describe the wave function of the defect. The introduction of covalence, with the ions neighboring the central molecule, have shown that this is a better description for the defect than a simple central molecule model. It was also shown that the results for the hyperfine constants are strongly dependent on the relaxations of these neighboring ions, which have been determined by fitting the experimental data. The present results are compared with other previous calculations where similar and different methods have been used. A better description for the wave function of the defect is suggested

  20. Calculation of the hyperfine constants of the V sub (K) center in CaF2, SrF2 e BaF2

    Bufaical, R.F.

    1975-03-01

    The magnetic hyperfine constants of the V sub(K) center in CaF 2 , SrF 2 and BaF 2 have been calculated, assuming a phenomenological model, based on the F - 2 'central molecule', to describe the wave function of the defect. The introduction of covalence with the ions neighboring the 'central molecule', has shown that this is a better description for the defect than a simple 'central molecule' model. It was also shown that the results for the hyperfine constants are strongly dependent on the relaxations of these neighboring ions, which have been determined by fitting the experimental data. The present results are compared with other previous calculations where similar and different methods have been used. A better description for the wave function of the defect is suggested. (author) [pt

  1. Biological Factors Contributing to the Response to Cognitive Training in Mild Cognitive Impairment.

    Peter, Jessica; Schumacher, Lena V; Landerer, Verena; Abdulkadir, Ahmed; Kaller, Christoph P; Lahr, Jacob; Klöppel, Stefan

    2018-01-01

    In mild cognitive impairment (MCI), small benefits from cognitive training were observed for memory functions but there appears to be great variability in the response to treatment. Our study aimed to improve the characterization and selection of those participants who will benefit from cognitive intervention. We evaluated the predictive value of disease-specific biological factors for the outcome after cognitive training in MCI (n = 25) and also considered motivation of the participants. We compared the results of the cognitive intervention group with two independent control groups of MCI patients (local memory clinic, n = 20; ADNI cohort, n = 302). The primary outcome measure was episodic memory as measured by verbal delayed recall of a 10-word list. Episodic memory remained stable after treatment and slightly increased 6 months after the intervention. In contrast, in MCI patients who did not receive an intervention, episodic memory significantly decreased during the same time interval. A larger left entorhinal cortex predicted more improvement in episodic memory after treatment and so did higher levels of motivation. Adding disease-specific biological factors significantly improved the prediction of training-related change compared to a model based simply on age and baseline performance. Bootstrapping with resampling (n = 1000) verified the stability of our finding. Cognitive training might be particularly helpful in individuals with a bigger left entorhinal cortex as individuals who did not benefit from intervention showed 17% less volume in this area. When extended to alternative treatment options, stratification based on disease-specific biological factors is a useful step towards individualized medicine.

  2. Trait-specific responses of wild bee communities to landscape composition, configuration and local factors.

    Sebastian Hopfenmüller

    Full Text Available Land-use intensification and loss of semi-natural habitats have induced a severe decline of bee diversity in agricultural landscapes. Semi-natural habitats like calcareous grasslands are among the most important bee habitats in central Europe, but they are threatened by decreasing habitat area and quality, and by homogenization of the surrounding landscape affecting both landscape composition and configuration. In this study we tested the importance of habitat area, quality and connectivity as well as landscape composition and configuration on wild bees in calcareous grasslands. We made detailed trait-specific analyses as bees with different traits might differ in their response to the tested factors. Species richness and abundance of wild bees were surveyed on 23 calcareous grassland patches in Southern Germany with independent gradients in local and landscape factors. Total wild bee richness was positively affected by complex landscape configuration, large habitat area and high habitat quality (i.e. steep slopes. Cuckoo bee richness was positively affected by complex landscape configuration and large habitat area whereas habitat specialists were only affected by the local factors habitat area and habitat quality. Small social generalists were positively influenced by habitat area whereas large social generalists (bumblebees were positively affected by landscape composition (high percentage of semi-natural habitats. Our results emphasize a strong dependence of habitat specialists on local habitat characteristics, whereas cuckoo bees and bumblebees are more likely affected by the surrounding landscape. We conclude that a combination of large high-quality patches and heterogeneous landscapes maintains high bee species richness and communities with diverse trait composition. Such diverse communities might stabilize pollination services provided to crops and wild plants on local and landscape scales.

  3. Social responsibility of the state and business as a factor of competitiveness and economic growth

    Fylyppova Iryna H.

    2014-01-01

    Full Text Available The role of social factors in economic development of countries and nations cannot be ignored today. However, the goal of this article is not a proof of this already evident fact; the main hypothesis of the article is that the level of social responsibility of the state and business is directly reflected in competitiveness of the national economy and prospects of economic growth. The authors proceed from three quite evident assumptions: first – development of entrepreneurship is the basic factor of competitiveness in the market economy; second – competitiveness is a condition of export oriented economic growth; third – all the above listed “ingredients”, including economic growth, “close” on one key indicator – labour productivity, and the main problem lies in clear identification of the cause-effect relations between them. Thus, labour productivity is the nucleus of the “competitiveness – economic growth” system. The authors consider labour productivity as a function of three arguments: physical, human and social capital. Moreover, the first two arguments are a passive potential of the economic system and characterise the level of development of productive forces and only the social capital, which reflects the level of development of production relations, characterises real possibilities of the economic system with respect to realisation of its passive potential, that is, is the active potential of the system. The production function of social labour, identified in such a way, is, in fact, a characteristic of the social method of production. While studying influence of social factors upon development of entrepreneurship, competitiveness and economic growth, the authors reveal internal contradiction of the existing social method of production.

  4. Trait-specific responses of wild bee communities to landscape composition, configuration and local factors.

    Hopfenmüller, Sebastian; Steffan-Dewenter, Ingolf; Holzschuh, Andrea

    2014-01-01

    Land-use intensification and loss of semi-natural habitats have induced a severe decline of bee diversity in agricultural landscapes. Semi-natural habitats like calcareous grasslands are among the most important bee habitats in central Europe, but they are threatened by decreasing habitat area and quality, and by homogenization of the surrounding landscape affecting both landscape composition and configuration. In this study we tested the importance of habitat area, quality and connectivity as well as landscape composition and configuration on wild bees in calcareous grasslands. We made detailed trait-specific analyses as bees with different traits might differ in their response to the tested factors. Species richness and abundance of wild bees were surveyed on 23 calcareous grassland patches in Southern Germany with independent gradients in local and landscape factors. Total wild bee richness was positively affected by complex landscape configuration, large habitat area and high habitat quality (i.e. steep slopes). Cuckoo bee richness was positively affected by complex landscape configuration and large habitat area whereas habitat specialists were only affected by the local factors habitat area and habitat quality. Small social generalists were positively influenced by habitat area whereas large social generalists (bumblebees) were positively affected by landscape composition (high percentage of semi-natural habitats). Our results emphasize a strong dependence of habitat specialists on local habitat characteristics, whereas cuckoo bees and bumblebees are more likely affected by the surrounding landscape. We conclude that a combination of large high-quality patches and heterogeneous landscapes maintains high bee species richness and communities with diverse trait composition. Such diverse communities might stabilize pollination services provided to crops and wild plants on local and landscape scales.

  5. A review of research on the identification of factors influencing the social response to technological risks

    Otway, H.J.

    1977-01-01

    Many countries are experiencing a period in which traditional values are being questioned; plans for technological development are being met by a variety of individual and group demands for a closer examination of the associated benefits and risks and a consideration of social values and concerns in the regulatory process. This has created conditions of conflict with some groups sponsoring proposals intended to fulfill perceived social needs while other groups, with different perceptions of society's needs, work actively in opposition. Only in recent years, as the rate of technological innovation has increased, has significant attention been given to the rapid rate of social and cultural change and the associated risks which have emerged. The degree to which an individual responds to these changes is related to his perception of their importance in his life; likewise, the repsonse to risk situations, on the individual and societal level, is based upon how the risks are perceived. The social response to the introduction of nuclear power provides an interesting case in point: here several studies have indicated that nuclear power plants might be considered ''safe''; however, nuclear power is nevertheless being opposed in many countries by those who perceive it as an unacceptable source of risk. This paper reviews research oriented toward understanding the response to technological risks through identification of the specific technical, social and psychological factors which influence their perception. Several such factors have been identified which relate to the risk object, the individual at risk, and the risk situation in which the individual encounters this object. Nuclear power was found to be characterised by more of the factors tending to increase risk perception than was any other technology. It is hypothesized that, in part due to its high ''risk visibility'' and an unconscious psychological coupling with the death imagery of nuclear weapons, nuclear energy

  6. Aged blood factors decrease cellular responses associated with delayed gingival wound repair.

    María Paz Saldías

    A.X phosphorylated at Ser139. Moreover, we detected an increased frequency of γ-H2A.X-positive cells in aged rat gingival tissues. The present study suggests that serum factors present in middle-aged and aged individuals may be responsible, at least in part, for the altered responses observed during wound healing in aging.

  7. Participation and factors associated with late or non-response to an online survey in primary care.

    Aerny-Perreten, Nicole; Domínguez-Berjón, Ma Felicitas; Esteban-Vasallo, María D; García-Riolobos, Carmen

    2015-08-01

    Online surveys have several advantages, but a low response rate is common and it is uncertain how results are affected. Response inducement techniques can be used to overcome this problem. The objectives of this study were to describe the percentage of change in the response rate after reminders and to analyse the characteristics associated with non-response and late response based on the survey results, as well as by applying archival and extrapolation techniques. In the Autonomous Community of Madrid, an online questionnaire about cancer prevention was sent to a random sample of primary care health professionals (3586 physicians and nurses). Two reminders were sent later. The percentage of change in response rates after reminders, global and by demographic and health care characteristics of participants; and factors associated with non-response and late response were analysed using response rates and odds ratios (ORs). After the reminders, the response rate increased from 22.6% to 32.9% and to 39.4%. Non-response was associated with age [OR: 3.14; confidence interval (CI) 95%: 2.23-4.42 for aged >60 years], gender and functional area. Further, a higher response rate after reminders was observed in professionals with heavier workloads (OR: 1.46; CI 95%: 1.08-1.97) and in those who stated a lower relevance of cancer prevention in primary care. After electronic reminders, the response rate increased, especially among professionals with the highest workloads and a minor interest in the survey topic. However, possible bias associated with non-response remains and the factors behind this should be examined in future research. © 2015 John Wiley & Sons, Ltd.

  8. Expression profiling of AUXIN RESPONSE FACTOR genes during somatic embryogenesis induction in Arabidopsis.

    Wójcikowska, Barbara; Gaj, Małgorzata D

    2017-06-01

    Extensive modulation of numerous ARF transcripts in the embryogenic culture of Arabidopsis indicates a substantial role of auxin signaling in the mechanism of somatic embryogenesis induction. Somatic embryogenesis (SE) is induced by auxin in plants and auxin signaling is considered to play a key role in the molecular mechanism that controls the embryogenic transition of plant somatic cells. Accordingly, the expression of AUXIN RESPONSE FACTOR (ARF) genes in embryogenic culture of Arabidopsis was analyzed. The study revealed that 14 of the 22 ARFs were transcribed during SE in Arabidopsis. RT-qPCR analysis indicated that the expression of six ARFs (ARF5, ARF6, ARF8, ARF10, ARF16, and ARF17) was significantly up-regulated, whereas five other genes (ARF1, ARF2, ARF3, ARF11, and ARF18) were substantially down-regulated in the SE-induced explants. The activity of ARFs during SE was also monitored with GFP reporter lines and the ARFs that were expressed in areas of the explants engaged in SE induction were detected. A functional test of ARFs transcribed during SE was performed and the embryogenic potential of the arf mutants and overexpressor lines was evaluated. ARFs with a significantly modulated expression during SE coupled with an impaired embryogenic response of the relevant mutant and/or overexpressor line, including ARF1, ARF2, ARF3, ARF5, ARF6, ARF8, and ARF11 were indicated as possibly being involved in SE induction. The study provides evidence that embryogenic induction strongly depends on ARFs, which are key regulators of the auxin signaling. Some clues on the possible functions of the candidate ARFs, especially ARF5, in the mechanism of embryogenic transition are discussed. The results provide guidelines for further research on the auxin-related functional genomics of SE and the developmental plasticity of somatic cells.

  9. Physical attractiveness and sex as modulatory factors of empathic brain responses to pain

    Jankowiak-Siuda, Kamila; Rymarczyk, Krystyna; Żurawski, Łukasz; Jednoróg, Katarzyna; Marchewka, Artur

    2015-01-01

    Empathy is a process that comprises affective sharing, imagining, and understanding the emotions and mental states of others. The brain structures involved in empathy for physical pain include the anterior insula (AI), and the anterior cingulate cortex (ACC). High empathy may lead people to undertake pro-social behavior. It is important to understand how this process can be changed, and what factors these empathic responses depend on. Physical attractiveness is a major social and evolutional cue, playing a role in the formation of interpersonal evaluation. The aim of the study was to determine how attractiveness affects the level of empathy both in relation to self-rated behavior and in terms of activation of specific empathy-related brain regions. Twenty-seven subjects (14 female and 13 male) were studied using functional magnetic resonance imaging (fMRI) method while they were watching short video scenes involving physically more and less attractive men and women who exhibited pain responses. In the absence of behavioral effects in compassion ratings, we observed stronger activation in empathic brain structures (ACC; AI) for less attractive men and for attractive women than for attractive men. Evolutionary psychology studies suggest that beauty is valued more highly in females than males, which might lead observers to empathize more strongly with the attractive woman than the men. Attractive mens’ faces are typically associated with enhanced masculine facial characteristics and are considered to possess fewer desirable personality traits compared with feminized faces. This could explain why more empathy was shown to less attractive men. In conclusion, the study showed that the attractiveness and sex of a model are important modulators of empathy for pain. PMID:26441569

  10. Inoculation Policies in Response to Terrorist or WMD Attacks: Additional Factors to Consider

    Leitner, P. M.

    2007-01-01

    When viewed on its own merits, the debate over who should be inoculated during a period of biological emergency is a rather straightforward public policy decision. The classic public policy 'balancing act' decision-making model is defaulted to as issues of fairness, efficiency, cost-effectiveness, adequacy of supply, mission performance, and constituencies are arrayed and adjudicated. This mainstream approach is appropriate as far as it goes but it also exemplifies a series of structural and perceptual weaknesses when applied to wartime or localized terrorism scenarios. In fact, the establishment of a vaccination policy appropriate to a flu pandemic falls squarely within this mainstream debate. Although the notion of a pandemic carries an assumption of a great many fatalities it does not possess the fear quotient, uncertainty, horror, unnaturalness, or inevitability of a bio-terror or biological warfare incident. As a result, the reliability and responsiveness of key personnel responding to a flu pandemic should be less of an issue than it will be in the event of an intentional man-made biological incident. The principal policy weakness in instances an intentional bio-attack stems from a generalized failure, or refusal, to systematically study the behavior of key personnel, first-responders, soldiers, or critical senior leadership during severe crises occurring in their own backyards. In other words, when the 'balloon goes up' how many of your responders and critical personnel will show up for work? This presentation considers many of the 'unaddressed' factors that experience has shown may have a determinative effect upon the efficacy of a response to a biological incident. Lessons are drawn from experiences of US forces station in the former West Germany, US Defense Department Continuity of Operations Programs, Hurricane Katrina, and the 9/11 attacks on the United States. (author)

  11. Physical attractiveness and sex as modulatory factors of empathic brain responses to pain.

    Jankowiak-Siuda, Kamila; Rymarczyk, Krystyna; Żurawski, Łukasz; Jednoróg, Katarzyna; Marchewka, Artur

    2015-01-01

    Empathy is a process that comprises affective sharing, imagining, and understanding the emotions and mental states of others. The brain structures involved in empathy for physical pain include the anterior insula (AI), and the anterior cingulate cortex (ACC). High empathy may lead people to undertake pro-social behavior. It is important to understand how this process can be changed, and what factors these empathic responses depend on. Physical attractiveness is a major social and evolutional cue, playing a role in the formation of interpersonal evaluation. The aim of the study was to determine how attractiveness affects the level of empathy both in relation to self-rated behavior and in terms of activation of specific empathy-related brain regions. Twenty-seven subjects (14 female and 13 male) were studied using functional magnetic resonance imaging (fMRI) method while they were watching short video scenes involving physically more and less attractive men and women who exhibited pain responses. In the absence of behavioral effects in compassion ratings, we observed stronger activation in empathic brain structures (ACC; AI) for less attractive men and for attractive women than for attractive men. Evolutionary psychology studies suggest that beauty is valued more highly in females than males, which might lead observers to empathize more strongly with the attractive woman than the men. Attractive mens' faces are typically associated with enhanced masculine facial characteristics and are considered to possess fewer desirable personality traits compared with feminized faces. This could explain why more empathy was shown to less attractive men. In conclusion, the study showed that the attractiveness and sex of a model are important modulators of empathy for pain.

  12. Physical attractiveness and sex as modulatory factors of empathic brain responses to pain

    Kamila Jankowiak Siuda

    2015-09-01

    Full Text Available Empathy is a process that comprises affective sharing, imagining, and understanding the emotions and mental states of others. The brain structures involved in empathy for physical pain include the anterior insula (AI, and the anterior cingulate cortex (ACC. High empathy may lead people to undertake pro-social behaviour. It is important to understand how this process can be changed, and what factors these empathic responses depend on. Physical attractiveness is a major social and evolutional cue, playing a role in the formation of interpersonal evaluation. The aim of the study was to determine how attractiveness affects the level of empathy both in relation to self-rated behaviour and in terms of activation of specific empathy-related brain regions. Twenty-seven subjects (14 female and 13 male were studied using fMRI method while they were watching short video scenes involving physically more and less attractive men and women who exhibited pain responses. In the absence of behavioural effects in compassion ratings, we observed stronger activation in empathic brain structures (ACC; AI for less attractive men and for attractive women than for attractive men. Evolutionary psychology studies suggest that beauty is valued more highly in females than males, which might lead observers to empathize more strongly with the attractive woman than the men. Attractive mens’ faces are typically associated with enhanced masculine facial characteristics and are considered to possess fewer desirable personality traits compared with feminized faces. This could explain why more empathy was shown to less attractive men. In conclusion, the study showed that the attractiveness and sex of a model are important modulators of empathy for pain.

  13. Inoculation Policies in Response to BW Attacks: Additional Factors to Consider

    Leitner, P. M.

    2007-01-01

    When viewed on its own merits, the debate over who should be inoculated during a period of biological emergency is a rather straightforward public policy decision. The classic public policy 'balancing act' decision-making model is defaulted to as issues of fairness, efficiency, cost-effectiveness, adequacy of supply, mission performance, and constituencies are arrayed and adjudicated. This mainstream approach is appropriate as far as it goes but it also exemplifies a series of structural and perceptual weaknesses when applied to wartime or localized terrorism scenarios. In fact, the establishment of a vaccination policy appropriate to a flu pandemic falls squarely within this mainstream debate. Although the notion of a pandemic carries an assumption of a great many fatalities it does not possess the fear quotient, uncertainty, horror, unnaturalness, or inevitability of a bio-terror or biological warfare incident. As a result, the reliability and responsiveness of key personnel responding to a flu pandemic should be less of an issue than it will be in the event of an intentional man-made biological incident. The principal policy weakness in instances an intentional bio-attack stems from a generalized failure, or refusal, to systematically study the behavior of key personnel, first-responders, soldiers, or critical senior leadership during severe crises occurring in their own backyards. In other words, when the 'balloon goes up' how many of your responders and critical personnel will show up for work? This presentation considers many of the 'unaddressed' factors that experience has shown may have a determinative effect upon the efficacy of a response to a biological incident. Lessons are drawn from experiences of US forces station in the former West Germany, US Defense Department Continuity of Operations Programs, Hurricane Katrina, and the 9/11 attacks on the United States. (author)

  14. Factors influencing identification of and response to intimate partner violence: a survey of physicians and nurses

    Wathen C Nadine

    2007-01-01

    Full Text Available Abstract Background Intimate partner violence against women (IPV has been identified as a serious public health problem. Although the health care system is an important site for identification and intervention, there have been challenges in determining how health care professionals can best address this issue in practice. We surveyed nurses and physicians in 2004 regarding their attitudes and behaviours with respect to IPV, including whether they routinely inquire about IPV, as well as potentially relevant barriers, facilitators, experiential, and practice-related factors. Methods A modified Dillman Tailored Design approach was used to survey 1000 nurses and 1000 physicians by mail in Ontario, Canada. Respondents were randomly selected from professional directories and represented practice areas pre-identified from the literature as those most likely to care for women at the point of initial IPV disclosure: family practice, obstetrics and gynecology, emergency care, maternal/newborn care, and public health. The survey instrument had a case-based scenario followed by 43 questions asking about behaviours and resources specific to woman abuse. Results In total, 931 questionnaires were returned; 597 by nurses (59.7% response rate and 328 by physicians (32.8% response rate. Overall, 32% of nurses and 42% of physicians reported routinely initiating the topic of IPV in practice. Principal components analysis identified eight constructs related to whether routine inquiry was conducted: preparedness, self-confidence, professional supports, abuse inquiry, practitioner consequences of asking, comfort following disclosure, practitioner lack of control, and practice pressures. Each construct was analyzed according to a number of related issues, including clinician training and experience with woman abuse, area of practice, and type of health care provider. Preparedness emerged as a key construct related to whether respondents routinely initiated the topic of

  15. The leaf-level emission factor of volatile isoprenoids: caveats, model algorithms, response shapes and scaling

    Ü. Niinemets

    2010-06-01

    Full Text Available In models of plant volatile isoprenoid emissions, the instantaneous compound emission rate typically scales with the plant's emission potential under specified environmental conditions, also called as the emission factor, ES. In the most widely employed plant isoprenoid emission models, the algorithms developed by Guenther and colleagues (1991, 1993, instantaneous variation of the steady-state emission rate is described as the product of ES and light and temperature response functions. When these models are employed in the atmospheric chemistry modeling community, species-specific ES values and parameter values defining the instantaneous response curves are often taken as initially defined. In the current review, we argue that ES as a characteristic used in the models importantly depends on our understanding of which environmental factors affect isoprenoid emissions, and consequently need standardization during experimental ES determinations. In particular, there is now increasing consensus that in addition to variations in light and temperature, alterations in atmospheric and/or within-leaf CO2 concentrations may need to be included in the emission models. Furthermore, we demonstrate that for less volatile isoprenoids, mono- and sesquiterpenes, the emissions are often jointly controlled by the compound synthesis and volatility. Because of these combined biochemical and physico-chemical drivers, specification of ES as a constant value is incapable of describing instantaneous emissions within the sole assumptions of fluctuating light and temperature as used in the standard algorithms. The definition of ES also varies depending on the degree of aggregation of ES values in different parameterization schemes (leaf- vs. canopy- or region-scale, species vs. plant functional type levels and various

  16. Longitudinal tests of competing factor structures for the Rosenberg Self-Esteem Scale: traits, ephemeral artifacts, and stable response styles.

    Marsh, Herbert W; Scalas, L Francesca; Nagengast, Benjamin

    2010-06-01

    Self-esteem, typically measured by the Rosenberg Self-Esteem Scale (RSE), is one of the most widely studied constructs in psychology. Nevertheless, there is broad agreement that a simple unidimensional factor model, consistent with the original design and typical application in applied research, does not provide an adequate explanation of RSE responses. However, there is no clear agreement about what alternative model is most appropriate-or even a clear rationale for how to test competing interpretations. Three alternative interpretations exist: (a) 2 substantively important trait factors (positive and negative self-esteem), (b) 1 trait factor and ephemeral method artifacts associated with positively or negatively worded items, or (c) 1 trait factor and stable response-style method factors associated with item wording. We have posited 8 alternative models and structural equation model tests based on longitudinal data (4 waves of data across 8 years with a large, representative sample of adolescents). Longitudinal models provide no support for the unidimensional model, undermine support for the 2-factor model, and clearly refute claims that wording effects are ephemeral, but they provide good support for models positing 1 substantive (self-esteem) factor and response-style method factors that are stable over time. This longitudinal methodological approach has not only resolved these long-standing issues in self-esteem research but also has broad applicability to most psychological assessments based on self-reports with a mix of positively and negatively worded items.

  17. The external Q factor of a dual-feed coupling for superconducting radio frequency cavities: Theoretical and experimental studies

    Dai, J.; Belomestnykh, S.; Ben-Zvi, I.; Xu, Wencan

    2013-11-01

    We propose a theoretical model based on network analysis to study the external quality factor (Q factor) of dual-feed coupling for superconducting radio-frequency (SRF) cavities. Specifically, we apply our model to the dual-feed 704 MHz half-cell SRF gun for Brookhaven National Laboratory's prototype Energy Recovery Linac (ERL). The calculations show that the external Q factor of this dual-feed system is adjustable from 104 to 109 provided that the adjustment range of a phase shifter covers 0°-360°. With a period of 360°, the external Q factor of the coupling system changes periodically with the phase difference between the two coupling arms. When the RF phase of both coupling arms is adjusted simultaneously in the same direction, the external Q factor of the system also changes periodically, but with a period of 180°.

  18. Abiotic and biotic factors responsible for antimonite oxidation in Agrobacterium tumefaciens GW4

    Li, Jingxin; Yang, Birong; Shi, Manman; Yuan, Kai; Guo, Wei; Wang, Qian; Wang, Gejiao

    2017-03-01

    Antimonite [Sb(III)]-oxidizing bacteria can transform the toxic Sb(III) into the less toxic antimonate [Sb(V)]. Recently, the cytoplasmic Sb(III)-oxidase AnoA and the periplasmic arsenite [As(III)] oxidase AioAB were shown to responsible for bacterial Sb(III) oxidation, however, disruption of each gene only partially decreased Sb(III) oxidation efficiency. This study showed that in Agrobacterium tumefaciens GW4, Sb(III) induced cellular H2O2 content and H2O2 degradation gene katA. Gene knock-out/complementation of katA, anoA, aioA and anoA/aioA and Sb(III) oxidation and growth experiments showed that katA, anoA and aioA were essential for Sb(III) oxidation and resistance and katA was also essential for H2O2 resistance. Furthermore, linear correlations were observed between cellular H2O2 and Sb(V) content in vivo and chemical H2O2 and Sb(V) content in vitro (R2 = 0.93 and 0.94, respectively). These results indicate that besides the biotic factors, the cellular H2O2 induced by Sb(III) also catalyzes bacterial Sb(III) oxidation as an abiotic oxidant. The data reveal a novel mechanism that bacterial Sb(III) oxidation is associated with abiotic (cellular H2O2) and biotic (AnoA and AioAB) factors and Sb(III) oxidation process consumes cellular H2O2 which contributes to microbial detoxification of both Sb(III) and cellular H2O2.

  19. The emission factor of volatile isoprenoids: stress, acclimation, and developmental responses

    Ü. Niinemets

    2010-07-01

    Full Text Available The rate of constitutive isoprenoid emissions from plants is driven by plant emission capacity under specified environmental conditions (ES, the emission factor and by responsiveness of the emissions to instantaneous variations in environment. In models of isoprenoid emission, ES has been often considered as intrinsic species-specific constant invariable in time and space. Here we analyze the variations in species-specific values of ES under field conditions focusing on abiotic stresses, past environmental conditions and developmental processes. The reviewed studies highlight strong stress-driven, adaptive (previous temperature and light environment and growth CO2 concentration and developmental (leaf age variations in ES values operating at medium to long time scales. These biological factors can alter species-specific ES values by more than an order of magnitude. While the majority of models based on early concepts still ignore these important sources of variation, recent models are including some of the medium- to long-term controls. However, conceptually different strategies are being used for incorporation of these longer-term controls with important practical implications for parameterization and application of these models. This analysis emphasizes the need to include more biological realism in the isoprenoid emission models and also highlights the gaps in knowledge that require further experimental work to reduce the model uncertainties associated with biological sources of variation.

  20. Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses.

    Twu, Olivia; Dessí, Daniele; Vu, Anh; Mercer, Frances; Stevens, Grant C; de Miguel, Natalia; Rappelli, Paola; Cocco, Anna Rita; Clubb, Robert T; Fiori, Pier Luigi; Johnson, Patricia J

    2014-06-03

    The human-infective parasite Trichomonas vaginalis causes the most prevalent nonviral sexually transmitted infection worldwide. Infections in men may result in colonization of the prostate and are correlated with increased risk of aggressive prostate cancer. We have found that T. vaginalis secretes a protein, T. vaginalis macrophage migration inhibitory factor (TvMIF), that is 47% similar to human macrophage migration inhibitory factor (HuMIF), a proinflammatory cytokine. Because HuMIF is reported to be elevated in prostate cancer and inflammation plays an important role in the initiation and progression of cancers, we have explored a role for TvMIF in prostate cancer. Here, we show that TvMIF has tautomerase activity, inhibits macrophage migration, and is proinflammatory. We also demonstrate that TvMIF binds the human CD74 MIF receptor with high affinity, comparable to that of HuMIF, which triggers activation of ERK, Akt, and Bcl-2-associated death promoter phosphorylation at a physiologically relevant concentration (1 ng/mL, 80 pM). TvMIF increases the in vitro growth and invasion through Matrigel of benign and prostate cancer cells. Sera from patients infected with T. vaginalis are reactive to TvMIF, especially in males. The presence of anti-TvMIF antibodies indicates that TvMIF is released by the parasite and elicits host immune responses during infection. Together, these data indicate that chronic T. vaginalis infections may result in TvMIF-driven inflammation and cell proliferation, thus triggering pathways that contribute to the promotion and progression of prostate cancer.

  1. Promiscuous Diffusible Signal Factor Production and Responsiveness of the Xylella fastidiosa Rpf System.

    Ionescu, Michael; Yokota, Kenji; Antonova, Elena; Garcia, Angelica; Beaulieu, Ellen; Hayes, Terry; Iavarone, Anthony T; Lindow, Steven E

    2016-07-19

    Cell density-dependent regulation of gene expression in Xylella fastidiosa that is crucial to its switching between plant hosts and insect vectors is dependent on RpfF and its production of 2-enoic acids known as diffusible signal factor (DSF). We show that X. fastidiosa produces a particularly large variety of similar, relatively long-chain-length 2-enoic acids that are active in modulating gene expression. Both X. fastidiosa itself and a Pantoea agglomerans surrogate host harboring X. fastidiosa RpfF (XfRpfF) is capable of producing a variety of both saturated and unsaturated free fatty acids. However, only 2-cis unsaturated acids were found to be biologically active in X. fastidiosa X. fastidiosa produces, and is particularly responsive to, a novel DSF species, 2-cis-hexadecanoic acid that we term XfDSF2. It is also responsive to other, even longer 2-enoic acids to which other taxa such as Xanthomonas campestris are unresponsive. The 2-enoic acids that are produced by X. fastidiosa are strongly affected by the cellular growth environment, with XfDSF2 not detected in culture media in which 2-tetradecenoic acid (XfDSF1) had previously been found. X. fastidiosa is responsive to much lower concentrations of XfDSF2 than XfDSF1. Apparently competitive interactions can occur between various saturated and unsaturated fatty acids that block the function of those agonistic 2-enoic fatty acids. By altering the particular 2-enoic acids produced and the relative balance of free enoic and saturated fatty acids, X. fastidiosa might modulate the extent of DSF-mediated quorum sensing. X. fastidiosa, having a complicated lifestyle in which it moves and multiplies within plants but also must be vectored by insects, utilizes DSF-based quorum sensing to partition the expression of traits needed for these two processes within different cells in this population based on local cellular density. The finding that it can produce a variety of DSF species in a strongly

  2. Factors other than hepatitis B virus responsible for hepatocellular carcinomas in lower social class

    Pervez, T.; Anwar, M.S.

    2002-01-01

    Objective: To find out the role of other etiological agents besides hepatitis B virus in the genesis of Hepatocellular carcinoma (HCC) in our social classes. Design: A hospital-based observational study. Place and Duration of Study: The study was conducted in oncology department of services Hospital, Lahore from December 1997 to February 2001. Patients and Methods: One hundred patients of hepatocellular carcinoma ware divided into three groups based on monthly income. Lower socioeconomic group had monthly income less than 3,000 Pakistani rupees. Middle socioeconomic group had monthly income between 3,000-1,000 Pakistani rupees and upper socioeconomic group heard monthly income of more than 10,000 Pakistani rupees. Percentages of HCC patients positive for HbsAg in different socioeconomic groups in our population were compared to assess the social class difference, the possibility and correlation of other factors present in our classes for the formation of hepatocellular carcinoma besides hepatitis B virus. Results: We found that there was no significant difference in HbsAg positively in different classes. Conclusion: If HBV was only responsible for this disease than there should have been consistency in the outcome. But as there is a higher prevalence of HCC in poor class, this reflects that other etiological agents are also operating. This needs further evaluation. (author)

  3. Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine.

    Calipari, Erin S; Godino, Arthur; Peck, Emily G; Salery, Marine; Mervosh, Nicholas L; Landry, Joseph A; Russo, Scott J; Hurd, Yasmin L; Nestler, Eric J; Kiraly, Drew D

    2018-01-16

    Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine's behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential.

  4. Factors responsible for the emergence of arboviruses; strategies, challenges and limitations for their control.

    Liang, Guodong; Gao, Xiaoyan; Gould, Ernest A

    2015-03-01

    Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.

  5. HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

    Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

    2017-08-01

    Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

  6. Sex differences in stress responses: a critical role for corticotropin-releasing factor.

    Bangasser, Debra A; Wiersielis, Kimberly R

    2018-03-01

    Rates of post-traumatic stress disorder, panic disorder, and major depression are higher in women than in men. Another shared feature of these disorders is that dysregulation of the stress neuropeptide, corticotropin-releasing factor (CRF), is thought to contribute to their pathophysiology. Therefore, sex differences in responses to CRF could contribute to this sex bias in disease prevalence. Here, we review emerging data from non-human animal models that reveal extensive sex differences in CRF functions ranging from its presynaptic regulation to its postsynaptic efficacy. Specifically, detailed are sex differences in the regulation of CRF-containing neurons and the amount of CRF that they produce. We also describe sex differences in CRF receptor expression, distribution, trafficking, and signaling. Finally, we highlight sex differences in the processes that mitigate the effects of CRF. In most cases, the identified sex differences can lead to increased stress sensitivity in females. Thus, the relevance of these differences for the increased risk of depression and anxiety disorders in women compared to men is also discussed.

  7. Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection.

    Venkatasubramanian, Sambasivan; Tripathi, Deepak; Tucker, Torry; Paidipally, Padmaja; Cheekatla, Satyanarayana; Welch, Elwyn; Raghunath, Anjana; Jeffers, Ann; Tvinnereim, Amy R; Schechter, Melissa E; Andrade, Bruno B; Mackman, Nizel; Idell, Steven; Vankayalapati, Ramakrishna

    2016-02-01

    Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TF(Δ) ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL-10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2-like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)-2 and MMP-9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Transcription factors and stress response gene alterations in human keratinocytes following Solar Simulated Ultra Violet Radiation.

    Marais, Thomas L Des; Kluz, Thomas; Xu, Dazhong; Zhang, Xiaoru; Gesumaria, Lisa; Matsui, Mary S; Costa, Max; Sun, Hong

    2017-10-19

    Ultraviolet radiation (UVR) from sunlight is the major effector for skin aging and carcinogenesis. However, genes and pathways altered by solar-simulated UVR (ssUVR), a mixture of UVA and UVB, are not well characterized. Here we report global changes in gene expression as well as associated pathways and upstream transcription factors in human keratinocytes exposed to ssUVR. Human HaCaT keratinocytes were exposed to either a single dose or 5 repetitive doses of ssUVR. Comprehensive analyses of gene expression profiles as well as functional annotation were performed at 24 hours post irradiation. Our results revealed that ssUVR modulated genes with diverse cellular functions changed in a dose-dependent manner. Gene expression in cells exposed to a single dose of ssUVR differed significantly from those that underwent repetitive exposures. While single ssUVR caused a significant inhibition in genes involved in cell cycle progression, especially G2/M checkpoint and mitotic regulation, repetitive ssUVR led to extensive changes in genes related to cell signaling and metabolism. We have also identified a panel of ssUVR target genes that exhibited persistent changes in gene expression even at 1 week after irradiation. These results revealed a complex network of transcriptional regulators and pathways that orchestrate the cellular response to ssUVR.

  9. Evaluation of protection factors of a breath-responsive-powered air-purifying respirator

    Nakagawa, Masahiro; Nojima, Shun; Fujii, Katsutoshi; Shishido, Nobuhito; Sakai, Toshiya; Umehara, Takashi; Shimizu, Isamu

    2012-01-01

    It is essential to wear an air-purifying respirator in the radiation works in a contaminated atmosphere. A breath-responsive-powered air-purifying respirator (BR-PAPR) has been recently developed. However, no research has yet been conducted to determine the protection factor (PF) of the BR-PAPR in actual workplaces. In this study, the PFs of the BR-PAPR were measured by a man-test apparatus and compared with those of a non-powered full face mask. The PFs were measured under three different situations; normal wearing condition, clogging the filter and leaving a gap between the face and the mask. Under these situations, it was found that the PFs of the BR-PAPR are higher than those of the non-powered full face mask. PFs greater than 4,000 were obtained for 95% of the subjects who wear the BR-PAPR, and PFs over 6,667, the upper limit of the man-test apparatus, were obtained for 49% of them. The questionnaire survey was conducted for workers. The results showed that the workers feel a reduced burden when they wear the BR-PAPR. The results of this study showed high protection performance and operation efficiency of the BR-PAPR. (author)

  10. Near-UV radiation acts as a beneficial factor for physiological responses in cucumber plants.

    Mitani-Sano, Makiko; Tezuka, Takafumi

    2013-11-05

    Effects of near-UV radiation on the growth and physiological activity of cucumber plants were investigated morphologically, physiologically and biochemically using 3-week-old seedlings grown under polyvinyl chloride films featuring transmission either above 290 nm or above 400 nm in growth chambers. The hypocotyl length and leaf area of cucumber seedlings were reduced but the thickness of leaves was enhanced by near-UV radiation, due to increased upper/lower epidermis thickness, palisade parenchyma thickness and volume of palisade parenchyma cells. Photosynthetic and respiratory activities were also promoted by near-UV radiation, associated with general enhancement of physiological/biochemical responses. Particularly, metabolic activities in the photosynthetic system of chloroplasts and the respiratory system of mitochondria were analyzed under the conditions of visible light with and without near-UV radiation. For example, the activities of NAD(P)-dependent enzymes such as glyceraldehyde-3-phosphate dehydrogenase (G3PDH) in chloroplasts and isocitrate dehydrogenase (ICDH) in mitochondria were elevated, along with levels of pyridine nucleotides (nicotinamide coenzymes) [NAD(H) and NADP(H)] and activity of NAD kinase (NADP forming enzyme). Taken together, these data suggest that promotion of cucumber plant growth by near-UV radiation involves activation of carbon and nitrogen metabolism in plants. The findings of this research showed that near-UV radiation reaching the Earth's surface is a beneficial factor for plant growth. Copyright © 2013. Published by Elsevier B.V.

  11. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

    Taub, Mary, E-mail: biochtau@buffalo.edu

    2016-03-11

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10{sup −5} M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  12. Cancer drug troglitazone stimulates the growth and response of renal cells to hypoxia inducible factors

    Taub, Mary

    2016-01-01

    Troglitazone has been used to suppress the growth of a number of tumors through apoptosis and autophagy. However, previous in vitro studies have employed very high concentrations of troglitazone (≥10"−"5 M) in order to elicit growth inhibitory effects. In this report, when employing lower concentrations of troglitazone in defined medium, troglitazone was observed to stimulate the growth of primary renal proximal tubule (RPT) cells. Rosiglitazone, like troglitazone, is a thiazolidinedione (TZD) that is known to activate Peroxisome Proliferator Activated Receptor Υ (PPARΥ). Notably, rosiglitazone also stimulates RPT cell growth, as does Υ-linolenic acids, another PPARΥ agonist. The PPARΥ antagonist GW9662 inhibited the growth stimulatory effect of troglitazone. In addition, troglitazone stimulated transcription by a PPAR Response Element/Luciferase construct. These results are consistent with the involvement of PPARΥ as a mediator of the growth stimulatory effect of troglitazone. In a number of tumor cells, the expression of hypoxia inducible factor (HIF) is increased, promoting the expression of HIF inducible genes, and vascularization. Troglitazone was observed to stimulate transcription by a HIF/luciferase construct. These observations indicate that troglitazone not only promotes growth, also the survival of RPT cells under conditions of hypoxia. - Highlights: • Troglitazone and rosiglitazone stimulate renal proximal tubule cell growth. • Troglitazone and linolenic acid stimulate growth via PPARϒ. • Linolenic acid stimulates growth in the presence of fatty acid free serum albumin. • Rosiglitazone stimulates transcription by a HRE luciferase construct.

  13. A review of the prevalence and factors responsible for mal-nutrition in Pakistan

    Hafsa Hina

    2015-01-01

    Full Text Available Problems occupying special attention identified by the World Health Organization also include Childhood malnutrition (Beagle hole et al., 1993. Development goals are also program by the United Nations to halve the problem of under nutrition (Alderman et al., 2005. Despite of the involvement of international organizations still under nutrition has a main contribution to the high mortality rate of the children in the most part of the world (Caulfield et al., 2004. Poverty plays a main part in the high prevalence of childhood under nutrition. The child is said to be under-weight when its weight is lower than the weight of the reference rage for that age. The weight for height deficiency is known as wasting, while height for age deficiency as stunting. Wasting may be due to acute food shortage while prolonged food deprivation can cause stunting (Cosminsky et al., 1993; de Onis et al., 2000; Fernandez et al., 2002; and Zere & McIntyre, 2003. The factors responsible for the predisposition of children to mal nutrition vary and ranges from political instability to the economical status of the area (de Onis et al., 2000. Therefore protocols developed for the preventive measures of mal-nutrition should be multifaceted. 

  14. Multinomial Response Models, for Modeling and Determining Important Factors in Different Contraceptive Methods in Women

    E Haji Nejad

    2001-06-01

    Full Text Available Difference aspects of multinomial statistical modelings and its classifications has been studied so far. In these type of problems Y is the qualitative random variable with T possible states which are considered as classifications. The goal is prediction of Y based on a random Vector X ? IR^m. Many methods for analyzing these problems were considered. One of the modern and general method of classification is Classification and Regression Trees (CART. Another method is recursive partitioning techniques which has a strange relationship with nonparametric regression. Classical discriminant analysis is a standard method for analyzing these type of data. Flexible discriminant analysis method which is a combination of nonparametric regression and discriminant analysis and classification using spline that includes least square regression and additive cubic splines. Neural network is an advanced statistical method for analyzing these types of data. In this paper properties of multinomial logistics regression were investigated and this method was used for modeling effective factors in selecting contraceptive methods in Ghom province for married women age 15-49. The response variable has a tetranomial distibution. The levels of this variable are: nothing, pills, traditional and a collection of other contraceptive methods. A collection of significant independent variables were: place, age of women, education, history of pregnancy and family size. Menstruation age and age at marriage were not statistically significant.

  15. Behavioral factors predicting response to employment-based reinforcement of cocaine abstinence in methadone patients.

    Holtyn, August F; Washington, Wendy Donlin; Knealing, Todd W; Wong, Conrad J; Kolodner, Ken; Silverman, Kenneth

    2016-06-01

    We sought to identify behavioral factors associated with response to an employment-based intervention, in which participants had to provide drug-free urine samples to gain access to paid employment. The present secondary analysis included data from a randomized clinical trial. The trial evaluated whether employment-based reinforcement could decrease cocaine use in community methadone patients. Participants (N=56) in the trial worked in a model workplace for 4 hr every weekday and earned about $10 per hr. After a 4-week baseline, participants were randomly assigned to an Abstinence & Work (n = 28) or Work Only (n = 28) condition and could work for an additional 26 weeks. Abstinence & Work participants had to provide cocaine-negative urine samples to work and maintain maximum pay. Work Only participants only had to work to earn pay. For Work Only participants, cocaine abstinence during baseline and the intervention period were significantly ( r s = .72, p workplace attendance was marginally correlated ( r s = .32, p = .098) with cocaine abstinence during the intervention period. Furthermore, participants who provided over 60% cocaine-negative urine samples during the intervention period (i.e., responders) had significantly higher baseline rates of opiate abstinence ( p workplace attendance ( p = .042) than non-responders. Employment-based reinforcement of cocaine abstinence may be improved by increasing opiate abstinence and workplace attendance prior to initiating the cocaine-abstinence intervention.

  16. Using Interactive Response Systems in Economics: utility and factors influencing students’ attitudes

    Lydia Bares López

    2017-04-01

    Full Text Available The European Higher Education Area (EHEA involves changing traditional methods to promote innovative teaching experiences. This paper has two main aims: a to show evidence of the use of Interactive Response Systems (IRS to identify gaps in the understanding of the course contents and b to investigate factors influencing students’ attitudes towards the use of IRS. The experience was developed through a collective tutoring session in the subject of Economics using IRS. Economics is a first-year subject in the Degree of Business Administration and Management offered by the University of Cadiz, which includes contents of Microeconomics and Macroeconomics and uses economic models to explain the function of the economy and the behaviour of economic agents. Results show that IRS technique allows detecting gaps in learning and comprehension. From our econometric estimations, we also identify two strongly significant variables affecting students’ attitudes towards IRS: gender and received explanations regarding the use of IRS. Variables such as first enrolment in the subject and the number of hours devoted to studying have a positive and significant effect on the attitude to IRS, but at a lower level of significance (from 5% to 10%.

  17. MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.

    Pereira, Cynthia Brito Lins; Leal, Mariana Ferreira; Abdelhay, Eliana Saul Furquim Werneck; Demachki, Sâmia; Assumpção, Paulo Pimentel; de Souza, Mirian Carvalho; Moreira-Nunes, Caroline Aquino; Tanaka, Adriana Michiko da Silva; Smith, Marília Cardoso; Burbano, Rommel Rodríguez

    2017-06-01

    Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response. We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently. The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

    Lang, Charles H; Frost, Robert A

    2002-05-01

    The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

  19. Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype

    da Silveira, W A; Palma, P V B; Sicchieri, R D

    2017-01-01

    Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis...... of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies....... and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression...

  20. Tumor Necrosis Factor-α Produced in Cardiomyocytes Mediates a Predominant Myocardial Inflammatory Response to Stretch in Early Volume Overload

    Chen, Yuanwen; Pat, Betty; Zheng, Junying; Cain, Laura; Powell, Pamela; Shi, Ke; Sabri, Abdelkarim; Husain, Ahsan; Dell’Italia, Louis J

    2010-01-01

    Acute stretch caused by volume overload (VO) of aorto-caval fistula (ACF) induces a variety of myocardial responses including mast cell accumulation, matrix metalloproteinase (MMP) activation and collagen degradation, all of which are critical in dictating long term left ventricle (LV) outcome to VO. Meanwhile, these responses can be part of myocardial inflammation dictated by tumor necrosis factor-α (TNF-α) which is elevated after acute ACF. However, it is unknown whether TNF-α mediates a ma...

  1. Youth suicide attempts and the dose-response relationship to parental risk factors: a population-based study

    Christiansen, E; Goldney, R D; Beautrai, A L

    2011-01-01

    BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suic......BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...

  2. Increased Contractile Response to Noradrenaline Induced By Factors Associated with the Metabolic Syndrome in Cultured Small Mesenteric Arteries

    Blædel, Martin; Sams, Anette; Boonen, Harrie C M

    2016-01-01

    UNLABELLED: This study investigated the effect of the metabolic syndrome associated risk factors hyperglycemia (glucose [Glc]), hyperinsulinemia (insulin [Ins]) and low-grade inflammation (tumor necrosis factor α [TNFα]) on the vasomotor responses of resistance arteries. Isolated small mesenteric...... arteries from 3-month-old Sprague-Dawley rats, were suspended for 21-23 h in tissue cultures containing either elevated Glc (30 mmol/l), Ins (100 nmol/l), TNFα (100 ng/ml) or combinations thereof. After incubation, the vascular response to noradrenaline (NA), phenylephrine, isoprenaline and NA...... in vascular tone....

  3. Dose response and factors related to interstitial pneumonitis after bone marrow transplant

    Sampath, Sagus; Schultheiss, Timothy E.; Wong, Jeffrey

    2005-01-01

    Purpose: Total body irradiation (TBI) and chemotherapy are common components of conditioning regimens for bone marrow transplantation. Interstitial pneumonitis (IP) is a known regimen-related complication. Using published data of IP in a multivariate logistic regression, this study sought to identify the parameters in the bone marrow transplantation conditioning regimen that were significantly associated with IP and to establish a radiation dose-response function. Methods and Materials: A retrospective review was conducted of articles that reported IP incidence along with lung dose, fractionation, dose rate, and chemotherapy regimen. In the final analysis, 20 articles (n = 1090 patients), consisting of 26 distinct TBI/chemotherapy regimens, were included in the analysis. Multivariate logistic regression was performed to determine dosimetric and chemotherapeutic factors that influenced the incidence of IP. Results: A logistic model was generated from patients receiving daily fractions of radiation. In this model, lung dose, cyclophosphamide dose, and the addition of busulfan were significantly associated with IP. An incidence of 3%-4% with chemotherapy-only conditioning regimens is estimated from the models. The α/β value of the linear-quadratic model was estimated to be 2.8 Gy. The dose eliciting a 50% incidence, D 50 , for IP after 120 mg/kg of cyclophosphamide was 8.8 Gy; in the absence of chemotherapy, the estimated D 50 is 10.6 Gy. No dose rate effect was observed. The use of busulfan as a substitute for radiation is equivalent to treating with 14.8 Gy in 4 fractions with 50% transmission blocks shielding the lung. The logistic regression failed to find a model that adequately fit the multiple-fraction-per-day data. Conclusions: Dose responses for both lung radiation dose and cyclophosphamide dose were identified. A conditioning regimen of 12 Gy TBI in 6 daily fractions induces an IP incidence of about 11% in the absence of lung shielding. Shielding the lung

  4. Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials.

    George, Angela; Kristeleit, Rebecca; Rafii, Saeed; Michie, Caroline O; Bowen, Rebecca; Michalarea, Vasiliki; van Hagen, Tom; Wong, Mabel; Rallis, Grigorios; Molife, L Rhoda; Lopez, Juanita; Banerji, Udai; Banerjee, Susana N; Gore, Martin E; de Bono, Johann S; Kaye, Stan B; Yap, Timothy A

    2017-05-01

    Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug development unit may represent a viable alternative; however, there is currently little evidence for patient outcomes in such patients. To address this, we undertook a retrospective review of patients with AOC allocated to phase I trials in the Drug Development Unit at Royal Marsden Hospital (RMH) between June 1998 and October 2010. A total of 200 AOC patients with progressive disease were allocated to ≥1 trial each, with a total of 281 allocations. Of these, 135 (68%) patients commenced ≥1 trial (mean 1.4 [1-8]), totaling 216 allocated trials; 65 (32%) patients did not start due to deterioration resulting from rapidly progressive disease (63 patients) or patient choice (2 patients). Response Evaluation Criteria in Solid Tumours (RECIST) complete/partial responses (CR/PR) were observed in 43 (20%) of those starting trials, including those on poly(ADP-ribose) polymerase (PARP) inhibitors (18/79 [23%]), antiangiogenics (9/65 [14%]) and chemotherapy combinations (14/43 [33%]). Factors associated with CR/PR included: fewer prior treatments, platinum-sensitive disease, CR/PR with prior therapy, (the United States-based) Eastern Cooperative Oncology Group (ECOG) performance status score, fewer metastatic sites, higher albumin and haemoglobin levels, lower white cell counts and baseline CA125 levels, germline BRCA1/2 mutations and better RMH Prognostic Score. Mean survival was 32° months for patients who achieved CR/PR. Treatments were generally well tolerated. Most patients with AOC (134/200 [67%]) received ≥1 subsequent line of therapy after phase I trials. Our data suggest that phase I trial referrals should be considered earlier in the AOC treatment pathway and before the onset of rapid disease progression particularly with the emergence of

  5. Staphylococcus aureus Esx Factors Control Human Dendritic Cell Functions Conditioning Th1/Th17 Response

    Melania Cruciani

    2017-07-01

    Full Text Available The opportunistic pathogen Staphylococcus aureus (S. aureus is a major cause of nosocomial- and community-acquired infections. In addition, many antibiotic-resistant strains are emerging worldwide, thus, there is an urgent unmet need to pinpoint novel therapeutic and prophylactic strategies. In the present study, we characterized the impact of infection with the pandemic methicillin-resistant USA300 S. aureus strain on human primary dendritic cells (DC, key initiators and regulators of immune responses. In particular, among staphylococcal virulence factors, the function of EsxA and EsxB, two small acidic dimeric proteins secreted by the type VII-like secretion system Ess (ESAT-6-like secretion system, was investigated in human DC setting. A comparative analysis of bacterial entry, replication rate as well as DC maturation, apoptosis, signaling pathway activation and cytokine production was performed by using wild type (wt USA300 and three isogenic mutants carrying the deletion of esxA (ΔesxA, esxB (ΔesxB, or both genes (ΔesxAB. The S. aureus mutant lacking only the EsxA protein (ΔesxA stimulated a stronger pro-apoptotic phenotype in infected DC as compared to wt USA300, ΔesxAB, and ΔesxB strains. When the mutant carrying the esxB deletion (ΔesxB was analyzed, a higher production of both regulatory and pro-inflammatory mediators was found in the infected DC with respect to those challenged with the wt counterpart and the other esx mutants. In accordance with these data, supernatant derived from ΔesxB-infected DC promoted a stronger release of both IFN-γ and IL-17 from CD4+ T cells as compared with those conditioned with supernatants derived from wild type USA300-, ΔesxAB-, and ΔesxA-infected cultures. Although, the interaction of S. aureus with human DC is not yet fully understood, our data suggest that both cytokine production and apoptotic process are modulated by Esx factors, thus indicating a possible role of these proteins in the

  6. Dealing with extreme response style in cross-cultural research: A restricted latent class factor approach

    Morren, M.H.; Gelissen, J.P.T.M.; Vermunt, J.K.

    2011-01-01

    Cross-cultural comparison of attitudes using rating scales may be seriously biased by response styles. This paper deals with statistical methods for detection of and correction for extreme response style (ERS), which is one of the well-documented response styles. After providing an overview of

  7. CREB binding protein is a required coactivator for Smad-dependent, transforming growth factor β transcriptional responses in endothelial cells

    Topper, James N.; DiChiara, Maria R.; Brown, Jonathan D.; Williams, Amy J.; Falb, Dean; Collins, Tucker; Gimbrone, Michael A.

    1998-01-01

    The transforming growth factor-β (TGF-β) superfamily of growth factors and cytokines has been implicated in a variety of physiological and developmental processes within the cardiovascular system. Smad proteins are a recently described family of intracellular signaling proteins that transduce signals in response to TGF-β superfamily ligands. We demonstrate by both a mammalian two-hybrid and a biochemical approach that human Smad2 and Smad4, two essential Smad proteins involved in mediating TG...

  8. Factors affecting the response of the bubble detector BD-100 and a comparison of its response to CR-39

    Ipe, N.E.; Busick, D.D.; Pollock, R.W.

    1987-08-01

    The BD-100 is a bubble detector available commercially from Chalk River Nuclear Laboratories, Canada for neutron dosimetry. According to the manufacturer, the BD-100 detects neutrons over an energy range of 100 keV to 14 MeV and the dose equivalent response is independent of energy. The sensitivity of the detector is dependent upon its temperature at the time of irradiation. The sensitized detector self-nucleates upon sharp impact and when heated to temperatures of 48 0 C or greater. The BD-100 is insensitive to low energy gamma rays but responds to 6 MeV photons. The sensitivity (bubbles/μSv) of the BD-100 was found to be energy dependent when exposed to standard neutron sources with average energies ranging from 0.5 to 4.5 MeV. The bubbles formed upon irradiation continued to grow in size with time. The response of electrochemically etched CR-39 to the same neutron sources is also reported for comparison

  9. Sustainable Entrepreneurship Orientation: A Reflection on Status-Quo Research on Factors Facilitating Responsible Managerial Practices

    Sascha Kraus

    2018-02-01

    Full Text Available With the global financial system having undergone vast changes since the financial crisis of 2007, scientific research concerning the investor’s point of view on sustainable investments has drastically increased. However, there remains a lack of research focused on the entrepreneur’s angle regarding sustainable oriented investments. The aim of this paper is to contribute to the understanding of sustainable financial markets by bringing together entrepreneurial and financial research. This paper provides a structured literature review, based on which the authors identify three relevant levels that they believe have an effect on the successful implementation of managerial sustainable practices; these are the individual, the firm, and the contextual levels. The results show that on the individual level sustainable entrepreneurs tend to derive their will to act more sustainably from their personal values or traits. On the organizational level, though, it can be concluded that an small and medium sized enterprise’s internal culture and the reconfiguration of resources are critical determinants for adopting a sustainable entrepreneurial orientation. Finally, on the contextual level, researchers have focused on a better understanding of how entrepreneurs can help society and the environment through sustainable entrepreneurship, and how they can act as role models or change agents in light of the fact that the choice of investing or financing based on sustainability is still in its infancy. By providing an overview on facilitating factors for responsible managerial practices on the entrepreneur’s side, this research contributes to a better understanding for both theory and practice on how sustainable practices can be implemented and facilitated.

  10. Accessory factors of cytoplasmic viral RNA sensors required for antiviral innate immune response

    Hiroyuki eOshiumi

    2016-05-01

    Full Text Available Type I interferon (IFN induces many antiviral factors in host cells. RIG-I-like receptors (RLRs are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and thus cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway.

  11. Prevention and Reversal of Antibody Responses Against Factor IX in Gene Therapy for Hemophilia B

    Sushrusha eNayak

    2011-12-01

    Full Text Available Intramuscular (IM administration of an adeno-associated viral (AAV vector represents a simple and safe method of gene transfer for treatment of the X-linked bleeding disorder hemophilia B (factor IX, F.IX, deficiency. However, the approach is hampered by an increased risk of immune responses against F.IX. Previously, we demonstrated that the drug cocktail of immune suppressants rapamycin, IL-10, and a specific peptide (encoding a dominant CD4+ T cell epitope caused an induction of regulatory T cells (Treg with a concomitant apoptosis of antigen-specific effector T cells (J. Thromb. Haemost. 7:1523, 2009. This protocol was effective in preventing inhibitory antibody formation against human F.IX (hF.IX in muscle gene transfer to C3H/HeJ hemophilia B mice (with targeted F9 gene deletion. Here, we show that this protocol can also be used to reverse inhibitor formation. IM injection of AAV1-hF.IX vector resulted in inhibitors of on average 8-10 BU within 1 month. Subsequent treatment with the tolerogenic cocktail accomplished a rapid reduction of hF.IX-specific antibodies to <2 BU, which lasted for >4.5 months. Systemic hF.IX expression increased from undetectable to >200 ng/ml, and coagulation times improved. In addition, we developed an alternative prophylactic protocol against inhibitor formation that did not require knowledge of T cell epitopes, consisting of daily oral administration of rapamycin for 1-month combined with frequent, low-dose intravenous injection of hF.IX protein. Experiments in T cell receptor transgenic mice showed that the route and dosing schedule of drug administration substantially affected Treg induction. When combined with intravenous antigen administration, oral delivery of rapamycin had to be performed daily in order to induce Treg, which were suppressive and phenotypically comparable to natural Treg.

  12. Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation.

    Harb, H; González-de-la-Vara, M; Thalheimer, L; Klein, U; Renz, H; Rose, M; Kruse, J; Potaczek, D P; Peters, E M J

    2017-12-01

    To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions. Copyright © 2017. Published by Elsevier Ltd.

  13. Multi-factor challenge/response approach for remote biometric authentication

    Al-Assam, Hisham; Jassim, Sabah A.

    2011-06-01

    Although biometric authentication is perceived to be more reliable than traditional authentication schemes, it becomes vulnerable to many attacks when it comes to remote authentication over open networks and raises serious privacy concerns. This paper proposes a biometric-based challenge-response approach to be used for remote authentication between two parties A and B over open networks. In the proposed approach, a remote authenticator system B (e.g. a bank) challenges its client A who wants to authenticate his/her self to the system by sending a one-time public random challenge. The client A responds by employing the random challenge along with secret information obtained from a password and a token to produce a one-time cancellable representation of his freshly captured biometric sample. The one-time biometric representation, which is based on multi-factor, is then sent back to B for matching. Here, we argue that eavesdropping of the one-time random challenge and/or the resulting one-time biometric representation does not compromise the security of the system, and no information about the original biometric data is leaked. In addition to securing biometric templates, the proposed protocol offers a practical solution for the replay attack on biometric systems. Moreover, we propose a new scheme for generating a password-based pseudo random numbers/permutation to be used as a building block in the proposed approach. The proposed scheme is also designed to provide protection against repudiation. We illustrate the viability and effectiveness of the proposed approach by experimental results based on two biometric modalities: fingerprint and face biometrics.

  14. The cytokinin response factors modulate root and shoot growth and promote leaf senescence in Arabidopsis

    Raines, T.; Shanks, C.; Cheng, C.Y.; McPherson, D.; Argueso, C.T.; Kim, H.J.; Franco-Zorrilla, J.M.; Lopez-Vidriero, I.; Solano, R.; Vaňková, Radomíra; Schaller, G.E.; Kieber, J.J.

    2016-01-01

    Roč. 85, č. 1 (2016), s. 134-147 ISSN 0960-7412 Institutional support: RVO:61389030 Keywords : cytokinin * two-component signaling * transcription factors Subject RIV: EF - Botanics Impact factor: 5.901, year: 2016

  15. The influence of product- and person-related factors on consumer hedonic responses to soy products

    Fenko, Anna; Backhaus, Birte W.; van Hoof, Joris Jasper

    2015-01-01

    Consumers in Western countries increasingly appreciate health benefits of soy products. However, several barriers prevent full acceptance of these products. This study investigates the effects of product-related factors (perceived familiarity and expected healthiness) and person-related factors

  16. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. The NAC transcription factor family in maritime pine (Pinus Pinaster): molecular regulation of two genes involved in stress responses.

    Pascual, Ma Belén; Cánovas, Francisco M; Ávila, Concepción

    2015-10-24

    NAC transcription factors comprise a large plant-specific gene family involved in the regulation of diverse biological processes. Despite the growing number of studies on NAC transcription factors in various species, little information is available about this family in conifers. The goal of this study was to identify the NAC transcription family in maritime pine (Pinus pinaster), to characterize ATAF-like genes in response to various stresses and to study their molecular regulation. We have isolated two maritime pine NAC genes and using a transient expression assay in N. benthamiana leaves estudied the promoter jasmonate response. In this study, we identified 37 NAC genes from maritime pine and classified them into six main subfamilies. The largest group includes 12 sequences corresponding to stress-related genes. Two of these NAC genes, PpNAC2 and PpNAC3, were isolated and their expression profiles were examined at various developmental stages and in response to various types of stress. The expression of both genes was strongly induced by methyl jasmonate (MeJA), mechanical wounding, and high salinity. The promoter regions of these genes were shown to contain cis-elements involved in the stress response and plant hormonal regulation, including E-boxes, which are commonly found in the promoters of genes that respond to jasmonate, and binding sites for bHLH proteins. Using a transient expression assay in N. benthamiana leaves, we found that the promoter of PpNAC3 was rapidly induced upon MeJA treatment, while this response disappeared in plants in which the transcription factor NbbHLH2 was silenced. Our results suggest that PpNAC2 and PpNAC3 encode stress-responsive NAC transcription factors involved in the jasmonate response in pine. Furthermore, these data also suggest that the jasmonate signaling pathway is conserved between angiosperms and gymnosperms. These findings may be useful for engineering stress tolerance in pine via biotechnological approaches.

  18. Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes.

    Pondman, Kirsten M; Pednekar, Lina; Paudyal, Basudev; Tsolaki, Anthony G; Kouser, Lubna; Khan, Haseeb A; Shamji, Mohamed H; Ten Haken, Bennie; Stenbeck, Gudrun; Sim, Robert B; Kishore, Uday

    2015-11-01

    Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Global self-esteem and method effects: competing factor structures, longitudinal invariance, and response styles in adolescents.

    Urbán, Róbert; Szigeti, Réka; Kökönyei, Gyöngyi; Demetrovics, Zsolt

    2014-06-01

    The Rosenberg Self-Esteem Scale (RSES) is a widely used measure for assessing self-esteem, but its factor structure is debated. Our goals were to compare 10 alternative models for the RSES and to quantify and predict the method effects. This sample involves two waves (N =2,513 9th-grade and 2,370 10th-grade students) from five waves of a school-based longitudinal study. The RSES was administered in each wave. The global self-esteem factor with two latent method factors yielded the best fit to the data. The global factor explained a large amount of the common variance (61% and 46%); however, a relatively large proportion of the common variance was attributed to the negative method factor (34 % and 41%), and a small proportion of the common variance was explained by the positive method factor (5% and 13%). We conceptualized the method effect as a response style and found that being a girl and having a higher number of depressive symptoms were associated with both low self-esteem and negative response style, as measured by the negative method factor. Our study supported the one global self-esteem construct and quantified the method effects in adolescents.

  20. Global self-esteem and method effects: competing factor structures, longitudinal invariance and response styles in adolescents

    Urbán, Róbert; Szigeti, Réka; Kökönyei, Gyöngyi; Demetrovics, Zsolt

    2013-01-01

    The Rosenberg Self-Esteem Scale (RSES) is a widely used measure for assessing self-esteem, but its factor structure is debated. Our goals were to compare 10 alternative models for RSES; and to quantify and predict the method effects. This sample involves two waves (N=2513 ninth-grade and 2370 tenth-grade students) from five waves of a school-based longitudinal study. RSES was administered in each wave. The global self-esteem factor with two latent method factors yielded the best fit to the data. The global factor explained large amount of the common variance (61% and 46%); however, a relatively large proportion of the common variance was attributed to the negative method factor (34 % and 41%), and a small proportion of the common variance was explained by the positive method factor (5% and 13%). We conceptualized the method effect as a response style, and found that being a girl and having higher number of depressive symptoms were associated with both low self-esteem and negative response style measured by the negative method factor. Our study supported the one global self-esteem construct and quantified the method effects in adolescents. PMID:24061931

  1. Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma

    Salas, Sebastien; Deville, Jean-Laurent; Giorgi, Roch; Pignon, Thierry; Bagarry, Danielle; Barrau, Karine; Zanaret, Michel; Giovanni, Antoine; Bourgeois, Aude; Favre, Roger; Duffaud, Florence

    2008-01-01

    Background and purpose: This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. Methods and materials: Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. Results: All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p = 0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p = 0.04). The factors influencing OS in univariate analysis were Alb (p = 0.008), CRP (p = 0.004), orosomucoid (p = 0.01) and NRI (p = 0.01), response to radio-chemotherapy (p < 0.001) and staging (p = 0.04). In multivariate analysis, only the response to radio-chemotherapy (p < 0.001) remained significant. Conclusions: This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials

  2. Factor VIIa response to a fat-rich meal does not depend on fatty acid composition: A randomized controlled trial

    Mennen, L.; Maat, M. de; Meijer, G.; Zock, P.; Grobbee, D.; Kok, F.; Kluft, C.; Schouten, E.

    1998-01-01

    A fat-rich meal increases activated factor VII (FVIIa), but it is not clear whether this increase depends on the fatty acid composition of the meal. Therefore, we studied the FVIIa response to fat-rich meals with different fatty acid composition in a randomized controlled crossover trial and

  3. Regulator-dependent mechanisms of C3b processing by factor i allow differentiation of immune responses

    Xue, Xiaoguang|info:eu-repo/dai/nl/413576841; Wu, Jin|info:eu-repo/dai/nl/304829552; Ricklin, Daniel; Forneris, Federico|info:eu-repo/dai/nl/341358622; Di Crescenzio, Patrizia; Schmidt, Christoph Q.; Granneman, Joke|info:eu-repo/dai/nl/304839396; Sharp, Thomas H; Lambris, John D; Gros, Piet|info:eu-repo/dai/nl/075243016

    2017-01-01

    The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of

  4. A Fresh Look at Linear Ordinary Differential Equations with Constant Coefficients. Revisiting the Impulsive Response Method Using Factorization

    Camporesi, Roberto

    2016-01-01

    We present an approach to the impulsive response method for solving linear constant-coefficient ordinary differential equations of any order based on the factorization of the differential operator. The approach is elementary, we only assume a basic knowledge of calculus and linear algebra. In particular, we avoid the use of distribution theory, as…

  5. Electron paramagnetic resonance and optical spectroscopy of Yb sup 3 sup + ions in SrF sub 2 and BaF sub 2; an analysis of distortions of the crystal lattice near Yb sup 3 sup +

    Falin, M L; Latypov, V A; Leushin, A M

    2003-01-01

    SrF sub 2 and BaF sub 2 crystals, doped with the Yb sup 3 sup + ions, have been investigated by electron paramagnetic resonance and optical spectroscopy. As-grown crystals of SrF sub 2 and BaF sub 2 show the two paramagnetic centres for the cubic (T sub c) and trigonal (T sub 4) symmetries of the Yb sup 3 sup + ions. Empirical diagrams of the energy levels were established and the potentials of the crystal field were determined. Information was obtained on the SrF sub 2 and BaF sub 2 phonon spectra from the electron-vibrational structure of the optical spectra. The crystal field parameters were used to analyse the crystal lattice distortions in the vicinity of the impurity ion and the F sup - ion compensating for the excess positive charge in T sub 4. Within the frames of a superposition model, it is shown that three F sup - ions from the nearest surrounding cube, located symmetrically with respect to the C sub 3 axis from the side of the ion-compensator, approach the impurity ion and cling to the axis of the...

  6. ETHYLENE RESPONSE FACTOR 96 positively regulates Arabidopsis resistance to necrotrophic pathogens by direct binding to GCC elements of jasmonate - and ethylene-responsive defence genes.

    Catinot, Jérémy; Huang, Jing-Bo; Huang, Pin-Yao; Tseng, Min-Yuan; Chen, Ying-Lan; Gu, Shin-Yuan; Lo, Wan-Sheng; Wang, Long-Chi; Chen, Yet-Ran; Zimmerli, Laurent

    2015-12-01

    The ERF (ethylene responsive factor) family is composed of transcription factors (TFs) that are critical for appropriate Arabidopsis thaliana responses to biotic and abiotic stresses. Here we identified and characterized a member of the ERF TF group IX, namely ERF96, that when overexpressed enhances Arabidopsis resistance to necrotrophic pathogens such as the fungus Botrytis cinerea and the bacterium Pectobacterium carotovorum. ERF96 is jasmonate (JA) and ethylene (ET) responsive and ERF96 transcripts accumulation was abolished in JA-insensitive coi1-16 and in ET-insensitive ein2-1 mutants. Protoplast transactivation and electrophoresis mobility shift analyses revealed that ERF96 is an activator of transcription that binds to GCC elements. In addition, ERF96 mainly localized to the nucleus. Microarray analysis coupled to chromatin immunoprecipitation-PCR of Arabidopsis overexpressing ERF96 revealed that ERF96 enhances the expression of the JA/ET defence genes PDF1.2a, PR-3 and PR-4 as well as the TF ORA59 by direct binding to GCC elements present in their promoters. While ERF96-RNAi plants demonstrated wild-type resistance to necrotrophic pathogens, basal PDF1.2 expression levels were reduced in ERF96-silenced plants. This work revealed ERF96 as a key player of the ERF network that positively regulates the Arabidopsis resistance response to necrotrophic pathogens. © 2015 John Wiley & Sons Ltd.

  7. Tomato NAC transcription factor SlSRN1 positively regulates defense response against biotic stress but negatively regulates abiotic stress response.

    Bo Liu

    Full Text Available Biotic and abiotic stresses are major unfavorable factors that affect crop productivity worldwide. NAC proteins comprise a large family of transcription factors that play important roles in plant growth and development as well as in responses to biotic and abiotic stresses. In a virus-induced gene silencing-based screening to identify genes that are involved in defense response against Botrytis cinerea, we identified a tomato NAC gene SlSRN1 (Solanum lycopersicum Stress-related NAC1. SlSRN1 is a plasma membrane-localized protein with transactivation activity in yeast. Expression of SlSRN1 was significantly induced by infection with B. cinerea or Pseudomonas syringae pv. tomato (Pst DC3000, leading to 6-8 folds higher than that in the mock-inoculated plants. Expression of SlSRN1 was also induced by salicylic acid, jasmonic acid and 1-amino cyclopropane-1-carboxylic acid and by drought stress. Silencing of SlSRN1 resulted in increased severity of diseases caused by B. cinerea and Pst DC3000. However, silencing of SlSRN1 resulted in increased tolerance against oxidative and drought stresses. Furthermore, silencing of SlSRN1 accelerated accumulation of reactive oxygen species but attenuated expression of defense genes after infection by B. cinerea. Our results demonstrate that SlSRN1 is a positive regulator of defense response against B. cinerea and Pst DC3000 but is a negative regulator for oxidative and drought stress response in tomato.

  8. Apple MdACS6 Regulates Ethylene Biosynthesis During Fruit Development Involving Ethylene-Responsive Factor.

    Li, Tong; Tan, Dongmei; Liu, Zhi; Jiang, Zhongyu; Wei, Yun; Zhang, Lichao; Li, Xinyue; Yuan, Hui; Wang, Aide

    2015-10-01

    Ethylene biosynthesis in plants involves different 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes. The regulation of each ACS gene during fruit development is unclear. Here, we characterized another apple (Malus×domestica) ACS gene, MdACS6. The transcript of MdACS6 was observed not only in fruits but also in other tissues. During fruit development, MdACS6 was initiated at a much earlier stage, whereas MdACS3a and MdACS1 began to be expressed at 35 d before harvest and immediateley after harvest, respectively. Moreover, the enzyme activity of MdACS6 was significantly lower than that of MdACS3a and MdACS1, accounting for the low ethylene biosynthesis in young fruits. Overexpression of MdACS6 (MdACS6-OE) by transient assay in apple showed enhanced ethylene production, and MdACS3a was induced in MdACS6-OE fruits but not in control fruits. In MdACS6 apple fruits silenced by the virus-induced gene silencing (VIGS) system (MdACS6-AN), neither ethylene production nor MdACS3a transcript was detectable. In order to explore the mechanism through which MdACS3a was induced in MdACS6-OE fruits, we investigated the expression of apple ethylene-responsive factor (ERF) genes. The results showed that the expression of MdERF2 was induced in MdACS6-OE fruits and inhibited in MdACS6-AN fruits. Yeast one-hybrid assay showed that MdERF2 protein could bind to the promoter of MdACS3a. Moreover, down-regulation of MdERF2 in apple flesh callus led to a decrease of MdACS3a expression, demonstrating the regulation of MdERF2 on MdACS3a. The mechanism through which MdACS6 regulates the action of MdACS3a was discussed. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Factors responsible for the patchy distribution of natural soil water repellency in Mediterranean semiarid forest

    Lozano, E.; Jiménez-Pinilla, P.; Mataix-Solera, J.; González-Pérez, J. A.; García-Orenes, F.; Torres, M. P.; Arcenegui, V.; Mataix-Beneyto, J.

    2012-04-01

    Soil water repellency (WR) is commonly observed in forest areas showing wettable and water repellent patches with high spatial variability. This has important hydrological implications; in semiarid areas where water supply is limited, even slight WR may play an important role in infiltration patterns and distribution of water into the soil (Mataix-Solera et al., 2007). It has been proposed that the origin of WR is the release of organic compounds from different plants species and sources (due to waxes and other organic substances in their tissues; Doerr et al., 1998). However, the relationship between WR and plants may not always be a direct one: a group of fungi (mainly mycorrhizal fungi) and microorganisms could be also responsible for WR. The aim of this research is to study the relationships between WR in soils under different plant cover with selected soil properties and the quantity of fungi and their exudates. The study area is located in Southeast Spain, "Sierra de la Taja" near Pinoso (Alicante)), with a semiarid Mediterranean climate (Pm=260mm). Samples were taken in September 2011, when WR is normally strongest after summer drought. Soil samples were collected from the first 2.5cm of the mineral A horizon at microsites beneath each of the four most representative species (Pinus halepensis, Rosmarinus officinalis, Quercus. rotundifolia and Cistus albidus; n=15 per specie) and 5 samples from bare soil with no influence of any species. Different soil parameters were analyzed; water content, soil organic mater content (SOM), pH, WR, easily extractable glomalin (EEG), total mycelium and extractable lipids. The occurrence of WR was higher under P. halepensis (87% of samples) and Q. rotundifolia (60% of samples). Positive significant correlations were found between WR and SOM content for all species, with the best correlations for Pinus and Quercus (r=0.855**, r= 0.934** respectively). In addition, negative significant correlations were found between WR and p

  10. Risk factors for discordant immune response among HIV-infected patients initiating antiretroviral therapy: A retrospective cohort study

    B P Muzah

    2012-10-01

    Full Text Available Background. The therapeutic goal of antiretroviral therapy (ART is sustained immune recovery and viral suppression. However, some patients experience poor CD4 cell count responses despite achieving viral suppression. Such discordant immune responses have been associated with poor clinical outcomes. Objective. We aimed to determine the prevalence of discordant immune response and explore associated factors in a retrospective cohort of patients attending 2 large public sector clinics, during the 6 months following ART initiation. Methods. Data were analysed from 810 HIV-infected adults initiated on first-line ART at 2 clinics in Johannesburg, between 1 November 2008 and 31 December 2009. Multivariate logistic regression models were used to estimate adjusted odds ratios (AORs to determine associations between discordant immune response and clinical and demographic factors. Results. At ART initiation, 65% (n=592 of participants were female, with a mean age of 38.5 years. Median baseline CD4 cell count was 155 cells/mm3, 70% (n=645 of patients had a haemoglobin level >11 g/dl and 88% (n=803 were initiated on stavudine-lamivudine-efavirenz/nevirapine (D4T-3TC-EFV/NVP. Six months after ART initiation, 24% (n=220 of patients had a discordant immune response and 7% (n=67 a discordant virological response. On multivariate analysis, baseline CD cell count ≥200 cells/mm3 (AOR 3.02; 95% confidence interval (CI 2.08 - 4.38; p

  11. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

    Sun, Xingmin; Hirota, Simon A.

    2014-01-01

    Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

  12. Developing a Scale for Culturally Responsive Practice: Validation, Relationship with School Organizational Factors, and Application

    Han, Jae-Bum

    2017-01-01

    The primary goal of this dissertation is to develop and provide preliminary validation for a new measure of culturally responsive practice. This instrument, which is called the Culturally Responsive Practice Scale (CRPS), includes items that reflect ways that teachers teach multicultural students in their classrooms. To accomplish the goal, three…

  13. Anoxia-responsive regulation of the FoxO transcription factors in freshwater turtles, Trachemys scripta elegans.

    Krivoruchko, Anastasia; Storey, Kenneth B

    2013-11-01

    The forkhead class O (FoxO) transcription factors are important regulators of multiple aspects of cellular metabolism. We hypothesized that activation of these transcription factors could play crucial roles in low oxygen survival in the anoxia-tolerant turtle, Trachemys scripta elegans. Two FoxOs, FoxO1 and FoxO3, were examined in turtle tissues in response to 5 and 20h of anoxic submergence using techniques of RT-PCR, western immunoblotting and DNA-binding assays to assess activation. Transcript levels of FoxO-responsive genes were also quantified using RT-PCR. FoxO1 was anoxia-responsive in the liver, with increases in transcript levels, protein levels, nuclear levels and DNA-binding of 1.7-4.8fold in response to anoxia. Levels of phosphorylated FoxO1 also decreased to 57% of control values in response to 5h of anoxia, indicating activation. FoxO3 was activated in the heart, kidney and liver in response to anoxia, with nuclear levels increasing by 1.5-3.7fold and DNA-binding activity increasing by 1.3-2.9fold. Transcript levels of two FoxO-target genes, p27kip1 and catalase, also rose by 2.4-2.5fold in the turtle liver under anoxia. The results suggest that the FoxO transcription factors are activated in response to anoxia in T. scripta elegans, potentially contributing to the regulation of stress resistance and metabolic depression. This study provides the first demonstration of activation of FoxOs in a natural model for vertebrate anoxia tolerance, further improving understanding of how tissues can survive without oxygen. © 2013.

  14. Dual DNA binding property of ABA insensitive 3 like factors targeted to promoters responsive to ABA and auxin.

    Nag, Ronita; Maity, Manas Kanti; Dasgupta, Maitrayee

    2005-11-01

    The ABA responsive ABI3 and the auxin responsive ARF family of transcription factors bind the CATGCATG (Sph) and TGTCTC core motifs in ABA and auxin response elements (ABRE and AuxRE), respectively. Several evidences indicate ABI3s to act downstream to auxin too. Because DNA binding domain of ABI3s shows significant overlap with ARFs we enquired whether auxin responsiveness through ABI3s could be mediated by their binding to canonical AuxREs. Investigations were undertaken through in vitro gel mobility shift assays (GMSA) using the DNA binding do